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Part 17-1. Infectious Diseases

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PART 17. Infectious Disease

Section 1. General Consideration

Chapter165. Fever

# Category of fever in children

    1) short duration fever with localizing sign

           ; Dx. by Hx. & P/Ex. with or without laboratory tests

    2) fever without localizing signs

           ; Hx.³ª P/Ex.¿¡ ÀÇÇØ¼­´Â Áø´ÜÇÏÁö ¾Ê°í, laboratory test¿¡ ÀÇÇØ Dx.

    3) FUO

# Thermoregulation

    1) hypothalamic thermoregulatory center controls BT

        ; peripheral cold & warm neuronal receptorÀÇ balancing signal¿¡ ÀÇÇØ control µÊ.

    2) another regulatory factor

           ; temperature of blood circulating in the hypothalamus

    3) normal core temperature

           ; 37¡É (¡¾1~1.5¡É)·Î set point µÇ¾î ÀÖÀ½.

        ; axillary temperature - core temperature º¸´Ù 1¡É Á¤µµ ³·´Ù. (by cutaneous vasoconstriction)

        ; *circardian rhythm - low at early morning, highest at 4:00~6:00 P.M.

# Heat generation & heat conservation

    ; balanced against heat loss

    1) heat generation

           ; cell metabolism¡è, cell activity¡è, involuntary shivering¡è

    2) heat conservation

           ; vasoconstriction, heat preference behavior

    3) heat loss

           ; obligate heat loss. (evaporation-radiation-convection-conducton)

           ; vasodilation, sweating, cold preferance behavior

# Cause of fever

    1) infection

    2) vaccines

    3) biologic agents : granulocyte-macrophage colony-stimulating factor, interferon, interleukins

    4) tissue injury : infarction, pul. embolism, trauma, intramuscular inj., burns

  5) malignancy : leukemia, lymphoma, hepatoma, metastatic disease

    6) drugs : drug fever, cocaine, amphotericin B

    7) immunologic-rheumatologic disorders : SLE, rheumatoid arthritis

    8) granulomatous diseases : sarcoidosis

    9) endocrine disorders : thyrotoxicosis, pheochromocytoma

  10) metabolic disorders : gout, uremia, Fabry disease, type 1 hyperlipidemia

  11) unknown or poorly understood entities : familial Mediterranean fever

  12) Factitious (self-induced) fever

# ¡ÚEtiology¿¡ °ü°è¾øÀÌ feverÀÇ final pathway

    ; production of endogenous pyrogens(PGE2)

    ; À̰ÍÀÌ hypothalamic temperature set-point¸¦ Á÷Á¢ º¯È­½ÃÅ´.

         ¡æ heat generation and heat conservation ( Fig 165-1 )

# Heat Production

    ; O2 consumption¡è, CO2 production¡è, cardiac output¡è

    ; *exacerbate cardiac insufficiency in patients with

           ¨ç heart disease

           ¨è chronic anemia (sickle cell disease)

           ¨é pulmonary insufficiency with chronic lung disease

           ¨ê metabolic instabilaty in children with DM or inborn errors of metabolism

# 6 Mo ~ 5 yrs

    ; nonspecific febrile illnessÀÇ ÇÑ part·Î seizure frequency¡è¡è

Fever Patterns

    ; remittent fever : daily elevated Temp. returning to the baseline but above normal

    ; intermittent fever : daily fever returning to the normal

    ; hectic fever : intermittent or remittent with Temp. excursion of£¾ *1.4¡É

    ; sustained or continuous fever : fluctuation of elevated Temp. of £¼ *0.3¡É

# fever patternÀÌ not diagnostic in most infectious processes

# ¡Úfever patternÀÌ Æ¯Â¡ÀûÀÎ disease

    ; malaria, Hodgkins ds. (Pel-Ebstein fever), cyclic neutropenia

Treatment

# ¡ÚAntipyretics Tx Benefit

    ; chr. cardiopul ds.  

    ; metabolic ds.

    ; neurologic ds.         

    ; risk for febrile seizure

2) antipyretic Tx.

  :     common infection ds.ÀÇ course¸¦ º¯È­½ÃŰÁö´Â ¸øÇÔ.

effect    controversal

# ¡ÚHyperpyrexia (> 41¡É)

    ; severe infection                           

    ; hypothalamic disorder

  ; CNS hemorrhage

4) pregnancy µ¿¾ÈÀÇ high fever

  :     teratogenic effect

5) antipyreticsÀÇ ±âÀü

  : hypothalamic cyclooxygenase inhibitor·Î ÀÛ¿ë

       PG E2 synthesis inhibition

Hyperthermia

; high BT not caused by hypothalamic thermoregulaton mechanism, due to

a. endogenous heat production Áõ°¡ (malig. hyperthermia. vigorous exercise, neuroleptic. malig. synd., hyperthyroidism )

b. heat loss °¨¼Ò (atropine intoxication)

c. prolonged exposure to high environmental temperature (heat stroke)

 

malignant hyperthermia

neuroleptic malig. synd.

AD disorder

   ¿øÀÎ :       a. Hx. of drug exposure

           b. previously affected family members

           c. exposure to high environmental temp.

           d. absence of the hypothalamic regulated circadian rhythm

       e. myopathic disorder

 

a. exposure to phenothiazine-like agent

 

    ¡Ø malignant hyperthermia¿Í ±¸ºÐ ¾ÈµÊ

    ¡Ø Tx. :        dantrolene

                   supportive care

 

Drug Fever

    ; ´Ù¸¥ fever ³ª´Â ¿øÀξøÀÌ drug administrationÀ¸·Î fever À¯¹ßµÇ°í drug discontinutionÀ¸·Î fever°¡ »ç¶óÁüÀ¸·Î¼­ Áø´ÜµÇ°í, Ư¡ÀûÀÎ fever patternÀ̳ª eosinophilia, rash, pruritus, drug allergy µî°ú Áö¼ÓÀûÀÎ °ü°è ¾øÀ½.

    ; at any time after therapy initiation (*median - 8 day, average - 21 days)

  ; average temp. range : 38 ¡­ 43¡É

Etiology

   a. antibiotics : penicilline, cephalosporine

   b. anticonvulsants : phenytoin, carbamazepine

   c. antineoplastic : bleomycin, daunorubicin, cytarabine, L-asparaginase

   d. cardiovascular : hydralazine, methyldopa(aldomet), quinidine

Treatment

    ; withdrawal of drug (°è¼Ó Ä¡·á½Ã ´Ù¸¥ ¾àÀ¸·Î ´ëÄ¡)

  ; *72½Ã°£³» fever resolve

# subsequent exposure to the drug °æ¿ì

    ; dose not necessarily reproduce a drug fever.

Rash With Fever

¡ÚEtiology

    ; direct inoculation ( anthrax or tularemia )

  ; hematogenous dissemination

         ( septisemia due to meningococci, Rickettsiae, other bacteria )

  ; contiguous spread from adjacent foci of infection ( impetigo, herpetic lesion )

  ; effect of toxin ( scarlet fever )

  ; Ag-Ab reaction ( rheumatic fever )

  ; delayed hypersensitivity ( erythema nodosum ) 

Chapter 166. Clinical use of the microbiology laboratory

Laboratory Finding Diagnosis Of Bacterial Infection

Gram stain

: useful in giving rapid result interpretating the subsequent cultural data

: esp. in resp. specimen

Special Cultures

: in blood agar. chocolate agar, eosin methylene blue, MacConkey agar

: capped syringe, special swab supplied in oxygen-free tube »ç¿ë

            for collection of anaerobes c/s

Blood Cultures

; 50~100§¢ bottle - 5~6§¢ blood äÃë

# ¢¾Why Repeated Culture ?

    ; infectionÀÇ Ä¡·á°¡ ¾î·Á¿î high risk patient°¡ AB Tx. ¹Þ°í ÀÖ´Â °æ¿ì Ä¡·áÀÇ ¼º°ø¿©ºÎ¸¦ º¸±â À§ÇØ

  ; repeated organismÀÌ nonpathogenic isolateÀ϶§ contaminationÀÇ ¿©ºÎ¸¦ º¸±â À§ÇØ

CSF examination

1) CSF stain : viral & bacterialÀÇ ±¸ºÐ¿¡´Â À¯ÀÍ, specific organismÀ» ã¾Æ³»Áö´Â ¸øÇÔ.

2) acute & rapid method for Dx

    : counterimmunoelectophoresis & agglutination of Ab-coated latex beads

3) specific Ag detect À§ÇØ antisera »ç¿ëµÇ´Â °æ¿ì

    ¨ç S. pneumoniae

    ¨è H. influenzae type b

    ¨é N. meningitidis

    ¨ê Streptococci (group B)

    ¨ë E. coli Kl

Urine Cultures

; collection by      ¨ç clean catched mid-stream

                           ¨è catheterization

                           ¨é suprapubic puncture

; catheter collection - £¾ 103/ml(reflect infection)

; clean catch urine

    - £¾105/ml : considered abnormal

    - 104~105/ml : possibly abnormal

    - *gram(-)¿¡ ±¹ÇÑ

    - gram(+), yeast, pt with diuresis or chronic PN , pt on AB ¿¡´Â ´Ù¸¥ ±âÁØ

Stool Cultures

1) rectal swab or stool specimens c/s

    a. identify common bact. pathogen : Salmonella, Shigella

    b. to determine the predominant flora of intestine

2) added pathogen

    a. Helicobacter pylori

    b. Y. enterocolitica

    c. C. difficle

    d. Aeromonas

    e. Plesiomonas

    f. Vibrio

    g. E. coli

Exudate and Transudate

           ¨ç c/s                  ¨è stain                                     ¨é glucose                            ¨ê cell counts

Nasopharyngeal, Throat & Skin Swab

# Most Efficient Method

    ; *dry rayon, dacron, calcium alginate swab

    ; dry µÇ±â Àü ½Å¼ÓÇÏ°Ô transport medium

¡ØÁÖ Pathogenic Organism

    ; Corynebacterium diphtheria

    ; Bordetella pertussis

    ; N. gonorrhea

¡Ø94°´ Pathognomic Or Nonpathognomic

    ; Strep. pyogenes

    ; N. meningitidis

    ; H. influenzae

  ; staphylococcus

Antibody-Based Techniques

# ¡Úclinical use of FA (fluorescent antibody)

    ; B. pertussis

    ; Legionella pneumophilia

    ; N. gonorrhea

    --> conjugated Ab

# M. Tuberculosis

    ; *no antibody used

    ; *acid-fast fluorescent stainingÀÌ Ziehl-Neelson or Kinyoun acid-fast staining¿¡ ºñÇØ more sensitive, but less specific

Antibiotic Sensitivity Tests

# most prevalent technique

    ; *agar disc diffusion method

       - inoculation 18~24hr ÈÄ¿¡ zone of inhibition of bacterial growth ÃøÁ¤

# MIC (minimal inhibitory concentration)

    ; organism¿¡ ´ëÇÑ Æ¯Á¤ÇÑ antibioticsÀÇ bacteriostatic concentration

# MBC (minimal bactericidal concentration)

  ; bacteriaÀÇ 99.9%¸¦ Á×ÀÏ ¼ö ÀÖ´Â antibioticsÀÇ lowest concentration Áï bactericidal end point

# it is important to measured conc. of drug needed to kill bacteria

¢ÀDNA probes

    ; Mycoplasma pneumonia, M. tuberculosis, M. aviumintracellulare, enteric organism

Laboratory Dx. Of Viruses

Rapid Viral Detection

1) smears of mucosal cell stained by immunologic reagents

        - identity the Ag of resp. virus ( RS virus, influenza )

2) ELISA

    ; specific antiserum ÀÌ¿ë

    ; *rota virus infection (infantile gastroenteritis), Hepatitis B surface Ag detect

Isolation

1) urine culture   

    ; ¡Ø89°´ most useful for isolation of CMV

    ; *good source of isolation of mumps. adenovirus

2) specimen should be transported at 4¡É

3) best throat specimen

       taken by vigorous throat swabbing, removing some superficial cells

4) ¡Ø°´ vesicular fluidÀÇ culture°¡ ÇÊ¿äÇÑ °æ¿ì

    ; vaccinia, varicella, herpes simplex, enterovirus

Viral Genome And Virion Detection

1) PCR : complementary nucleotides ÀÌ¿ë

        ¡æ detect viral gene sequences

2) electron microscopy ( EM )

        : direct visualization of virions within infected cells

Serologic Test

# Speciemen

    ; *Àû¾îµµ 2°³ÀÇ blood specimen ÇÊ¿ä

           - early acute phase (acute serum) & later 14-21 days (convalescent serum)

    ; *2nd specimenÀÌ earlier than 14 daysÀ̸é 3rd blood specimen 4~6wks later

# Etiologic Dx titer

    ; acute phase serum¿¡¼­ º¸´Ù convalescent serum¿¡¼­ 4¹è ÀÌ»ó ¡èÇØ¾ß ÇÑ´Ù.

# ¢ÞSingle specimenÀÌ Dx.À» supportÇÏ´Â °æ¿ì

    1) E-B Ab

    2) Young infant¿¡¼­ÀÇ Ab°¡ mother¿¡ ¾ø´Â °æ¿ì

    3) infant°¡ Ä¿°¨¿¡ µû¶ó¼­ infant¿Í mother¿¡¼­ Ab levelÀÌ µ¿ÀϽÃ

  4) Mumps ÀǽÉãÁ presence of Ab to the soluble (s) fraction of the mumps virus in the acute serum, when Ab to viral [V] Ag may be absent or very low

    ; Acute infection½Ã IgM viral specific Ab

    ; general population°ú ºñ±³ÇÏ¿© high Ab level

# methods for Ig M Ab detection

    ; diffcult to standardize

  ¡æ F (+) result°¡ common

  Ig G Ab assay : viral pathogen ¡æ induce humoral immunity (primary inf.ÈÄ ¼ö³â Áö¼Ó)

                                ¡æ useful for established immune status

Method for Detecting Ab

# *CF Ab : useful in recent inf. but less useful in past inf.

# Neutralizing Ab

    ; remain for life, early Ds.¿¡ serum ¾ò°Ô µÇ¸é Ab rise difficult

    - Neutralization test : c/s¿¡¼­º¸´Ù disadvantage

# HI Ab

    ; correlate fairly well with neutralizing ab.

    ; erythrocyte agglutination (+) viurs

           - *myxovirus, rubella, some enterovirus

    ; ¡Úuseful test for Parainfluenzae virus Ab

# fluorescent Ab detected by indirect fluorescent technique

# ¡ÚELISA & latex agglutination test

  ; *now most used

  ; viral Ag ÀÌ plastic well or to latex beads¿¡ attachµÇ¾î °Ë»çµÊ.

Section 2. Clinical Syndromes Caused by a Variety of Infectious Agents

Chapter 167. Fever without a Focus

Fever As A Manifestation Of Serious Bacterial Disease

Table 167-1

Fever Without A Focus

1) 36°³¿ùÀÌÇÏ¿¡¼­ ƯÈ÷ Áø´Ü¿¡ dilemmaÃÊ·¡

2) 3°³¿ùÀ̳»ÀÇ febrile infantÀÇ 40-60%°¡ viral pathogen

3) ¢ÀExclusion finding of Bacterial infection

    ; infants appear generally well

    ; previously healthy

  ; no evidence of skin, soft tissue, bone, joint, or ear infection

  ; total white blood cell count of > 5,000 or < 15,000 cells/¥ìL

    ; absolute band count of < 1,500 cells/¥ìL

  ; normal urinalysis

    --> negative predictive value´Â 98%ÀÌ»óÀ̸ç, bacetremia¿¡ ´ëÇØ¼­´Â 99%ÀÌ»óÀÌ´Ù.

4) 3°³¿ùÀÌÇÏÀÇ ill-appearing (toxic) febrile infant¿¡¼­ÀÇ ´ëÃ¥

  1. prompt hospitalization

  2. culture (blood, urine, CSF)

  3. immediate parenteral antimicrobial therapy

   : ceftriaxone or cefotamixe + ampicillin (for L. monocytogenes)

     ¡æ focal signs¾ø´Â ill-appearing patientsÀÇ initial therapy

¢ÀPC resistant Strept. pneumoniae¿¡ ÀÇÇÑ meningitis¿¡¼­´Â vancomycinÃß°¡.

Occult Bacteremia

1. bacteremia without an obvious focus of infection

2. occult bacteremia°¡Áø childrenÀÇ 85%¿¡¼­ culture»ó S. pneumoniae (+)

   ³ª¸ÓÁö positive culture¿¡¼­´Â H. influenzae type b, N. meningitidis, Salmonella species

3. ¢ÀIncreased Risk For Occult Bacteremia

 ¨ç temperature: 39.4¡ÉÀÌ»ó

 ¨è total WBC count: < 5,000 or > 15,000

 ¨é elevated absolute neutrophil count, band count, ESR, or C-reactive protein

4. 3-36°³¿ù infant¿¡¼­ temp. 39¡ÉÀÌ»ó, WBC > 15,000À϶§

    --> bacteremia incidence 13%

    --> *3-36°³¿ù»çÀÌ¿¡¼­ bacteremia incidence°¡ Áõ°¡ÇÏ´Â ÀÌÀ¯

           ; maturational immune deficiency

           ; decrease in opsonic IgG Ab against polysaccharide Ag. of bacteria

5. bacteremia Ä¡·á ¾Ê´Â °æ¿ì

 ¨ç resolve without sequelae

 ¨è persist

 ¨é produced localized inf. (meningitis, pn., cellulitis, septic arthritis)

6. H. influenzae¿¡ ÀÇÇÑ bacteremia°¡ S. pneumoniae¿¡ ÀÇÇÑ bacteremiaº¸´Ù ´õ ½ÉÇÑ bacterial infectionÀ» ÀÏÀ¸Å²´Ù.

    ; H. influenzae type b bacteremia´Â meningitis, epiglottitis, cellulitis, osteoarticular infection°°Àº focal infectionÀ» ¾ß±â. 5%¿¡¼­ occult bacteremiaº¸ÀδÙ.

7. pneumococcal bacteremia¿¡¼­ spontaneous resolutionµÇ´Â transient bacteremia incidence

  ; 30-40%

8. 3-36°³¿ùÀÇ toxic-appearing febrile child¿¡¼­ infectionÀÇ focal signÀÌ ¾ø¾îµµ severe bacterial diseaseÀÇ high risk°¡ ÀÖÀ¸¸é immediate antibiotic Tx.ÇÊ¿ä

# ¢ÀPractice guideline (published in Pediatrics & Annals of Emergency medicine in 1933)

  1) 3-36mo nontoxic infant with temp. < 39¡É

         ; obseved outpatients without diagnostic test or antibiotics medication

  2) non-toxic with rectal temp.¡Ã 39¡É

           ; two option

               - blood culture & empirical antimicrobial therapy

               - complete blood cell count

                           --> if WBC ¡Ã 15,000 cells/¥ìL, blood culture & empirical antimicrobial therapy

  3) others infants

           ; after blood culture, observed without antimicrobial therapy

10. ill appeared child¿¡¼­ fever°¡ °è¼ÓµÇ°í focus ¹ß°ßµÇÁö ¾Ê°Å³ª H. influenzae³ª N. meningitidis°¡ 1st blood culture»ó (+)ÀÎ °æ¿ì

  ; meningitis¿©ºÎ ±Ô¸í, repeat blood culture³»¸®°í ÀÔ¿øÇؼ­ ÀûÀýÇÑ antibiotic Tx.¸¦ ÇÑ´Ù.

Fever With Petechiae

; *Age¿Í °ü°è¾øÀÌ high risk for life-threatening bacterial infection

; 8-20%¿¡¼­ serious bacterial infection

; 7-10%¿¡¼­ meningococcal sepsis or meningitis

; H. influenzae type b´Â meningococcusº¸´Ù less common, serious bacterial illness¾ß±â

Fever In Patients With Sickle Cell Anemia

1) sickle cell anemia¿¡¼­ M/C cause of death : infection

2) 2¼¼ÀÌÇÏ¿¡¼­ infection incidence°¡Àå ³ô´Ù.

3) infectionÀÇ riskÁõ°¡ ¿øÀÎ

  1. functional asplenia

  2. defect in properdin pathway (alternate complement)

4) common pathogens

  1. pnuemococus (sepsis or meningitis)

  2. H. influenzae (meningitis)

  3. Salmonella (osteomyelitis)

  4. E. coli (pyelonephritis)

5) Tx.

½Å1. seriously ill, temp 40¡É¡è, WBC count < 5,000/¥ìL, or >30,000/¥ìL, pulm. infiltrates,

     sickle cell ds.ÀÇ Cx., severe pain

    : hospitalization

  2. other febrile infant : ceftriaxone IM & cultureÈÄ outpatient·Î manage

6) prevention of pneumococcal sepsis

   : long term Pc.(¸ÅÀÏ oral·Î ¶Ç´Â 3-4ÁÖ¸¶´Ù IM)À¸·Î adolescence±îÁö Tx.

   H. influenzae¿¡ ´ëÇØ¼­´Â daily oral amoxacillin

Hyperpyrexia

½Å *Temp. >41¡É

; uncommon

; temp 39.1-40.0¡É or 40.1-41.0¡Éº¸´Ù serious bacterial infectionÀÇ high rate°ü·Ã¼º ¾øÀ½.

FUO

# ¢ÀDefinition

 1) history of fever of more than 1wk duration (2-3wks if adolescent)

 2) ducumentation of fever by health care provider

 3) no apparent diagnosis 1wk after investigation was begun in either an inpatient or outpatient setting

# *Principal Causes Of FUO

  ; infection, connective tissue (autoimmune) disease

    ; other causes

           - neoplasms, drug fever

# FUO¿Í AIDS

    ; HIV-1 infection½Ãµµ fever(+), AIDSÇϳª·Î´Â FUO¿¡ ºÎÇÕÇÏÁö ¾Ê´Â´Ù.

    ; FUO¿Í AIDSÀִ ȯÀÚ¿¡¼­´Â common, unusual pathogenÀÇ opportunistic infectionÀ» ¶ÇÇÑ °¡Áü

# *6°³¿ùÀÌ»ó Áö¼ÓµÇ´Â FUOÀÇ ¿øÀÎ (children¿¡¼­´Â uncommon)

    ; granuolmatous or autoimmune diseaseÀǹÌ

¢¾Table 167-3

    ; ¢Þviral cause of FUO

           - cytomegalovirus, hepatitis, infectious mononucleosis, HIV

    ; *¡ãcommon autoimmune hypersensitivity disease

         - juvenile rheumatoid arthritis

Diagnostic Clues In The Child With Fever Of Unknown Origin

History

 1. 6¼¼ÀÌÇÏ

  : resp. or G-U tract infection

    localized infection (abscess, osteomyelitis)

    junvenile rheumatoid arthritis

    leukemia

 2. adolescent

  : Tbc

    inflammatory bowel disease

    autoimmune disease

    lymphoma

* Pica

  : Toxocara or infection of Toxoplasma gondii

* medication

  : over-the-count preparation & topical agent (atropine induced fever)

Physical Examination

# ¢Þsweat (-) in the presence of elevated or changing body temperature

    ; dehydration from vomiting, diarrhea, central or nephrogenic DI

    ; anhidrotic ectodermal dysplasia

    ; familial dysautonomia

    ; exposal to atropine

# Eye lesion

¨ç red, weeping eye

  : connective tissue disease ƯÈ÷ polyarteritis nodosa

¨è palpebral conjuctivitis

  : measle, coxsackie viral infection, Tbc, IM, lymphogranuloma venereum, cat-scratch or New-castle disease viral infection

¨é bulbar conjunctivitis

  : Kawasakie disease, leptospirosis

¨ê petechial conjunctival hemorrhage

  : endocarditis

¨ë uveitis

  : sarcoidosis, juvenile rheumatoid arthritis, SLE, Kawasaki disease, Behcet syndrome, vasculitis

¨ì chorioretinitis

    : CMV, toxoplasmosis, syphilis

¨í proptosis

  : orbital tumor, thyrotoxicosis, metastasis of neuroblastoma, orbital infection, Wegener granulomatosis, pseudotumor

# ¢ÀOphthalmoscopic examination of nailfold capillary abnormalities

  ; *dermatomyositis & systemic scleroderma°°Àº connective tissue disease

           - markedly dilated capillary pattern

        - Figure 167-1 A & B

# hypothalamic dysfunction¿¡ ÀÇÇÑ FUOÀÇ ¿øÀÎ

    ; failure of pupillary constriction due to abscence of the sphincter constrictor muscle

# ¡Ø°´ Fever Blister

    ; pneumococcal, streptococcal, malarial, rickettsial infection

    ; meningococcal meningitis

    ; rarely seen in meningococcemia, salmonella, staphylococcal infection

# repetitive chill & temp. spikes

    ; common in septicemia (ƯÈ÷, renal, liver or biliary, endocarditis, malaria, brucellosis, rat-bite fever, loculated pus)

Laboratory studies

1) *WBC & UA

 ¨ç *absolute neutrophil count < 5,000/mm3

    ; against fulminant bacterial infection other than typhoid fever

 ¨è *PMNL > 10,000/mm3 or nonsegmented PMNL > 500/mm3

    ; high chance of severe bacterial infection

2) Giemsa or Wright stain with blood smear

 : malaria, trypanosomiasis, babesiosis, relapsing fever

3) ESR

  ; *ESR(>30mm/hr, Westergen method)

           - inflammationÀ» ÀǹÌ

         - infectious, autoimmune, & malignant¿¡ ´ëÇÑ evaluation

  ; low ESR

       - juvenile rheumatoid arthritis, infectionÀÇ °¡´É¼ºÀ» ¹èÁ¦ÇÏÁö ¸øÇÔ

  ; ¡Ø94 ESR > 100

           - Tbc, Kawasaki disease, malignancy, autoimmue disease

4. Radioactive scan

 ¨ç galium citrate(67Ga)

   : tumor, abscessÀÇ inflammatory tissue (leukocyte)¿¡ localized

 ¨è 99mTc phosphate

   : X-ray¿¡¼­ bone lesionÁõ¸í ÇϱâÀü¿¡ osteomyelitis detect

 ¨é *Indium-III granulocyte or iodinated IgG

   : useful detecting localized pyogenic process

Treatment

¢Þ FUO¿¡¼­ ¹«ºÐº°ÇÑ antibiotic treatment°¡ À§ÇèÇÑ ÀÌÀ¯

    ; endocarditis, meningitis, parameningeal infection, osteomyelitisÀÇ Áø´ÜÀ» ¸ðÈ£ÇÏ°Ô ÇÑ´Ù.

    ; ±×·¯³ª, anti Tbc treatment´Â ¿¹¿Ü

Prognosis

    ; adultº¸´Ù better prognosis

    ; unclear etiology : 25%

Chapter 168 Sepsis & Shock

Bacteremia & Septicemia

# bacteremia

  ; disease¿¡ °ü°è¾øÀÌ ÀϽÃÀûÀ¸·Î blood culture¿¡¼­ bacteria°¡ recoveryµÇ´Â °æ¿ì

# septicemia

  ; acute disease¿Í °ü·ÃµÈ bacteremiaÀÇ severe formÀ¸·Î¼­ septic shockÀ¸·Î progressÇÒ ¼ö ÀÖ´Â °æ¿ì

# *BacteremiaÀÇ Á¤µµ

    ; transient or low grade (< 100 CFU/ml blood) bacteremia

    : follow instrumentation of resp., G-I, G-U tract

    ; *high grade (> 100-1000 CFU/ml blood) bacteremia

    : in sepsis condition may progress to septic shock

Epidemiology

1. Immunocompetent nonhospitalized patient

 ¨ç community acquired bacteremia-sepsis from local tissue infection

 ¨è colonization & local mucosal invasion by particulary virulent pathogen

    ; *S. pneumoniae, H. influenzae b, N. meningitidis

2. Hospitalized patient

 ¨ç catheter sepsis or surgical wound

  ; S. aureus, S. epidermidis

 ¨è immunocompromized neutropenic patient

    ; *E. coli, pseudomonas, Acinetobacter, Klebsiella-Enterobacter, Serratia

 ¨é polymicorbial sepsis

    ; in high risk patient with central venous catheterization, gastrointestinal disease, neutropenia, malignancy

3. Pseudobacteremia-associated with contaminated solution such as

    ; microbial disinfectant, heparinized flush solutions, intravenous infusions, albumin, cryoprecipitate, contaminated equipment

Pathogenesis Of Sepsis & The Systemic Inflammatory Response Syndrome (SIRS)

¢ÀFigure 168-1 & Figure 168-2

; bacterial products¿¡ ´ëÇÑ host response

    - gram-negative bacteria ¡æ endotoxin

  - gram-positive bacteria ¡æ lipoteichoic aicd-peptidoglycan complex

; blood stream³»·Î bacterial cell wall components°¡ releaseµÉ¶§, cytokines´Â Ȱ¼ºÈ­µÈ´Ù.

    - *TNF, IL-1, -6 & -8, platelet-activating factor (PAF), interferon-¥ã

# ¢ÀPhysiologic response by cytokines

   ¨ç activation of complement system

   ¨è activation of Hageman factor (factor XII)

   ¨é adrenocorticotrophic hormone & beta-endorphin release

   ¨ê stimulation of polymorphonuclear neutrophils

   ¨ë stimulation of the kallikrein-kinin system

½Å4. TNF & other inflammatory mediators

   ¨ç vascular permeability ¡è, diffuse capillary leakage

   ¨è vascular tone ¡é

   ¨é imbalance between perfusion & the increased metabolic requirements of tissue

½Å5. shock

   ¨ç def.

     : a systolic blood pr. below the 5th percentile for age or by cool extremities

   ¨è delayed capillary refill (> 2 sec.)

     : no considered a reliable indicator of decreased peripheral perfusion

  6. early (warm) septic shock : peripheral vascular resistance ¡é

  7. tissue oxygen consumptionÀº

     septic shock¿¡¼­ oxygen deliveryÃʰú

   ¨ç early peripheral vasodilation

   ¨è late vasoconstriction

   ¨é myocardial depression

   ¨ê hypotension

   ¨ë ventilatory insufficiency

   ¨ì anemia

  8. cardiac indexÁõ°¡: sepsis¿¡¼­

  9. pulmonary function: often severely impaired

Clinical Manifestation

 1. septic shockÀÇ primary sign & Sx.

  : fever, shaking chills, hypertension, tachycardia, hypothermia, cutaneous lesion (petechiae,

    ecchymoses, ecthyma gangrenosum, diffuse erythema, cellulitis), ÀǽÄÀå¾Ö (confusion,

    agitation, anxiety, excitation, lethargy, obtundation, coma)

 2. secondary Mx.

  : hypotension, cyanosis, systemic peripheral gangrene (purpura fulminans), oliguria or

    anuria, jaundice (direct-reacting hyperbilirubinemia), sign of heart failure

 3. cold shock

  ¨ç Ư¡

   : cold, clammy, cyanotic & pale extremities, unresponsive to verbal or painful stimuli

  ¨è evidence of a focus of infection such as

   : meningitis, pneumonia, arthritis, cellulitis, pyelonephritis, immunocompromised status

     (malignancy, T & B lymphocyte defect, prior splenectomy)

Laboratory Manifestation

1. postive blood culture

    ; gram, Wright, Methylene blue, acridine orange stain of the buffy coat or petechial lesion

2. metabolic acidosis

3. thrombocytopenia

4. anemia

5. PT ¡è, PTT ¡è

6. serum fibrinogen level ¡é

7. Pa O2 ¡è& Pa CO2 ¡é

8. ¡Ø90 neutrophilÀÇ morphology º¯È­

 ¨ç neutrophilÀÇ vacuolization

 ¨è toxic granulation

 ¨é Dohle body

 ¨ê elevated neutrophil & band

 ¨ë neutropenia

   ¨ç-¨é : bacterial sepsis

   ¨ê    : bacterial infection

   ¨ë    : ominous sign of fulminant septic shock

Treatment

¨ç community acquired ds. (H. influenzae, N. meningitidis, S. pneumoniae)

    ; ceftriaxone

¨è nosocomial sepsis

    ; cephalosporin (3rd) or extended gram (-) sepectrum PC + aminoglycoside

¨é S. pneumoniae°¡ PC resistant

    ; vancomycin Ãß°¡ 

# shock

 ¨ç fluid restriction (N/S, albumin, hetastarch, dextran sol.)

 ¨è IV sympathomimetic agent

    ; 1st - dopamine, dobutamine

    ; 2nd - epinephrine, NE, sodium nitropruside

# hypoxia

  ; PEEP (5-20 cm H2O)

# DIC

 ¨ç replace consumed coagulation factors

  : fresh frozen plasma, cryoprcipitate, platelets

 ¨è heparin

  : thromobosis, peripheral gangrene¿¡ ´ëÇØ

# overexuberant host response¸¦ ¸ñÀûÀ¸·Î

  ; IV Immunoglobulin, monoclonal IgM to endotoxin, granulocyte transfusion

# corticosteroid effect

    ; adult ¿¡¼­´Â not beneficial

    ; adrenal hemorrhage (Waterhouse-Fridrichsen syndrome)

    ; *meningitis caused by H. influenzae type b

Prognosis

; gram (-) enteric sepsis: 40-60%

# ¡ÚPoor Prognostic Sign In Meningococcal Sepsis

  ; hypotension

  ; coma

  ; leukopenia (< 5,000)

  ; thrombocytopenia (< 100,000)

  ; *low fibrinogen level (<150mg/dl)

  ; absence of meningismus

  ; absence of CSF pleocytosis with bacteria noted on gram stain of CSF

  ; *rapid appearance of petechia (in 1hr)

  ; hypothermia

# ±×¿Ü TNF, bacterial No./ml blood, endotoxin level

    : prognosis¿Í ¿¬°ü

Prevention

1. 2°³¿ù-4¼¼ÀÇ all children

  : immunization against H. influenzae type b

2. high risk pt

  : 2¼¼¿¡ *23-valent pneumococcal vaccine, quadrivalent meningococcal vaccine (group A, C, Y, W-135)

3. pneumococcal infection¿¡ ´ëÇÑ PC prophylaxis

  : splenic dysfunction (sickle cell anemia pt) & splenectomy

4. H. influenzae³ª meningococcal ds.¿¡ exposureµÈ pt.¿¡ close contactÇÑ °æ¿ì

  : Rifampin

Chapter 169. Infections Of The Central Nervous System

# CNSÀÇ acute infectionÀº children¿¡¼­ CNS ds ÀÇ Sx, SgÀ» µ¿¹ÝÇÑ feverÀÇ mc causeÀÌ´Ù.

# ÀϹÝÀûÀ¸·Î CNS infectionÀº viralÀÌ bacterialº¸´Ù more common

# etiology¿¡ °ü°è¾øÀÌ acute CNS infectionÀ» °¡Áø ȯÀÚ´Â similar syndromeÀ» °¡Áø´Ù. ;

  ( infortunately, most of these Sx are quite non-specific )

# common sx : headache, nausea, vomiting, anorexia, restlessness, irritability

  common sg : fever, photophobia, neck pain, rigidity, obtundation, stupor, coma, seizure, focal neurologic deficity

# signÀÇ severity¿Í constellationÀº specific pathogen, host,  infectionÀÇ anatomic distribution¿¡ ÀÇÇØ Á¤ÇØÁü

# diffuse CNS infection

  +- Menigitis : meninges

  +- encephalitis : brain parenchymal involvement

  ; ¸¹Àº ȯÀÚ¿¡¼­ anatomic barrier°¡ not distinctÇϱ⠶§¹®¿¡ meningeal, parenchymal involvement¼Ò°ßÀ» º¸À̸é meningoencephalitis¸¦ ²À »ý°¢ÇØ ÁÖ¾î¾ß ÇÑ´Ù.

# Brain absess :  best examples of  a focal infection of the CNS

               : neurological expression´Â absessÀÇ site¿Í extent¿¡ ÀÇÇØ °áÁ¤

# diffuse CNS infection Dx : careful examination of CSF obtained by lumbar punture

Table 169-1

¢Þ169.1 Acute Bacterial Meningitis The Neonatal Period

Etiology

# within 2mo

    ; *group B streptococci, gram(-) enteric bacilii, L. monocytogen

    ; *H. influenza(both nontypable and type b strains)

# 2mo-12yrs

    ; *H. influenza type B, S. pneumoniae, N. meningitidis

    ; H. influenza type bÀÇ vaciination »ç¿ëÀü¿¡´Â H. influenza°¡ far common      

# H. influenza vaccinated children & older unvaccinated children, adults

    ; *N. meningitidis or S. pneumoniae

# alteration of host defense

    ; P. aeruginosa, S. aureus, salmonella, S. epidermis, L. monocytogenes

# H. influenza type B

  ; 2¼¼ÀÌÇÏ¿¡ ÈçÇÏÁö¸¸ ¸ðµç ¿¬·É¿¡ ¿Ã ¼ö ÀÖ´Ù.

Epidemiology

# ¡ÚRisk factors for menigitis

    ; attenuated immunologic response to specific pathogen with young age

           - major risk factor

    - 1mo-12mo ¿¡¼­ greatest risk

           - 1mo-5yr »çÀÌ¿¡¼­ menigitis°¡ ÀüüÀÇ 95% Â÷Áö

    ; recent colonization with pathogenic bacteria

    ; invasive disease¸¦ °¡Áø »ç¶÷°ú close contact

    ; crowding

    ; poverty

    ; black race

    ; male sex

    ; possiblly absence of breast feeding for infant 2¡­5 mo of age

# Occult bacteremia¸¦ °¡Áø ȯÀÚ¿¡¼­ menigitisÀÇ risk°¡ Áõ°¡Çϴµ¥ À̶§ÀÇ etiology»ó odds ratio

 pneumococcus ( 85 ¹è )

 H. influenza type B ( 12 ¹è )

 meningococcus ( 1 )

# Epidemiology»ó À¯ÀÇÁ¡µé

    ; specipic host defence defect, d/t altered immunolglobulin in response to encapsulated pathogen

           ¡æ bacterial menigitis¡è

    ; defect of the complement system ( C5 - C6 )

         - associated with reccurent meningococcal infection

  ; defect of properdin system

           - associated with significant risk of lethal meningococcal infection

  ; splenic dysfunction or asplenia

           - assiciated with increased risk of pneumoccocal,

           - H. influenza type B and rarely meningococcal menigitis and sepsis

  ; T-lymphocyte defect

           - assiciated with increased risk of L. monocytogens

  ; cong, or acquired CSF communication across the mucocut. barrier

           - associated with increased risk of pneumococcal

  ; lumbosacral dermal sinus and meningomyelocele

           - associated with staphylococcal and enteric bacterial menigitis

  ; penetrating cranial trauma and CSF shunt infection

           - assiciated with increased risk of staphylococcal and other cutaneous bacteria

H. Influenzae Type b

; 80% normal children in throat or nasopharynx

    - H. influenza

    - 2-5% carry H. influenza type b

; H. influenzae type bÀÇ carriage´Â 1mo¡­4yrs ¶§ predominent

; invasive H. influenzae type B bacteremia and meningitis

    - unvaccinated children

    - ¡ã in infant 2 mo-2yr age

    - peak incidence 6-9mo. (caseÀÇ 50%°¡ 1¼¼ÀÌÇÏ)

; risk markedly increased among family or day care center contact pts

; other risk factor

  a. otitis media due to H. influenzae

    b. HIV infection

    c. CSF leakage

    d. occult bacteremia

Streptococcus Pneumoniae

    ; from family contact after birth

           - transient in 2-4mo

           - *if recent (£¼1mo) is risk factor for serious infection

    ; incidence : 1-3 / 100,000

    ; peak season - midwinter month

    ; risk factors

  a. black > white ( 5 ¡­ 36 ¹è )

      ( black and sickle cell anemia ½Ã 300 ¹è ÀÌ»ó )

    b. sickle cell anemiaÀÇ 4%°¡ 5¼¼ÀÌÇÏ¿¡¼­ pneumococcal menigitis, if no vaccination.

  c. otitis med

  d. sinusitis

  e. pneumonia

  f. CSF otorrhea or rhinorrhea

  g. chronic GVHD following BM transplantation

  h. splenetomy   

N. meningitidis

    ¨ç sporadic (group B.) epidemic (A and C)

    ¨è peak season ; winter and spring

    ¨é nasopharyngeal carriage ; 1-15% of adult

    ¨ê risk factors

              a. recent colonization places the nonimmune young children

              b. contact in a day care facility

                     colonized family member

                     ill patient with meningococcal infection

Pathology

# vascular and parenchymal cerebral change°¡ PMNÀÇ small arteriole, veinÀÇ subintimal regionÀ¸·ÎÀÇ infiltration¿¡ ÀÇÇØ ³ªÅ¸³ª°í vasospasm, vasculitis, thrombosis of small cortical necrosis, occlusion of major venous sinuses, necrotizing arteritis producing subarachnoid hemorrhage, rarely cerebral cortical necrosis°¡ autopy¿¡¼­  identifiable thrombosis¾øÀÌ ³ªÅ¸³­´Ù.

# cerebral infarctionÀÌ vascular occlusionÀÇ sequelae·Î ³ªÅ¸³­´Ù.

# spinal n. root infiltration ¡æ meningitis sign

# cranial n. infiltraion ¡æ optic, oculomotor, facial, auditory n.¿¡ cranial neuropathy  

# cranial N.ÀÇ Àå¾Ö by IICP

¨ç oculomotor N. palsy ; tentorial herniation µ¿¾È temporal lobe compression¿¡ ±âÀÎ

¨è abducence N. palsy ; nonlocalized sign of IICP

¨é ¥²-¥µ N. palsy ; by septic carvernous sinus thrombosis

# IICP mechanism

    ; cell death (cytotoxic cbr. edema)

    ; cytokine-induced increased capillary vascular permeability (vasogenic cbr. edema)

    ; increased hydrostatic pressure (interstitial cbr. edema)

    ; following obstructed reabsorption of CSF in the arachnoid villus or obstruction of the flow of fluid within or exiting from the ventricle.

    ; SIADH (excessive water retention ¡æ IICP¡è)

    ; brain extracellular spaceÀÇ hypotonicity

           --> cell swelling and lysis

           --> cytotoxic edema

# ICP°¡ Á¾Á¾ 300cmH20±îÁö ¿À¸£´Â °æ¿ìµµ ÀÖ°í, reduced cerebral blood flow --> cbr. perfusion pr. (mean arterial-intracranial pr.)°¡£¼50cmH20À̸é cbr. perfusionÀÌ futher compromised.

# herniationµµ meningitis ȯ¾ÆÀÇ ¾à 5%

    ; suggest

           a. marked IICP

           b. cerebral absess

           c. subdural empyema

# neonatal period Áö³­ ÈÄ¿¡´Â hydrocephalus´Â meningitisÀÇ uncommon acute complicationÀÌ´Ù.

# tentorial, falx, cerebellar herniation : rare

# ¶§¶§·Î brain base¿¡¼­ cisternÁÖÀ§ÀÇ arachnoid villiÀÇ adhersive thickening¿¡ ÀÇÇØ communicating hydrocephalus°¡ ÀϾ ¼ö ÀÖ´Ù. ---> CSF normal resorptionÀ» interfere.

# less often, foramina magendie, Luschka, aqueduct of SylviasÀÇ fibrosis and gliosis¿¡ ÀÇÇØ obstructive hydrocephalus°¡ developedµÈ´Ù.

# raised CSF proteinÀÇ ¿øÀÎ

    ¨ç BBBÀÇ vascular permeability Áõ°¡

    ¨è capillary or vein¿¡¼­ subdural space·Î albumin rich fluidÀÇ loss.

           ; subdural effusionÀÌ ±Ã±ØÀûÀ¸·Î ¿Ã ¼ö ÀÖ´Ù.( late phase¿¡ ¿Â´Ù )

# ¢ÀHypoglycorrhachiaÀÇ ¿øÀÎ (Reduced CSF Glucose Level)

    ; decreased glucose transport by cerebral tissue

  ; latter may produce a local lactic acidosis

# ¢¾Mechanism of Cbr cortex damage

    ; focal or diffuse effect of vascular occlusion(infarction, necrosis)

    ; hypoxia

    ; bacterial invasion (cerebritis)

    ; toxic encephalopathy (lactic acidosis)

    ; IICP

    ; ventriculitis

    ; transudation (subdural effusion)

--> impaired consciousness, seizure, hydrocephalus, cranial n. deficits, motor and sensory deficits, and later psychomotor retardation

Pathogenesis

; hematogeneous dissemination from distant site of infection

    - *¡ãcommon

    - usually precedes or concomitant bacteremia

    - nasopharynxÀÇ bacterial colonizationÀÌ usual sourse.

; H. influenza type b¿Í meningocci

    - epihterial cell¿¡ attach ¡æ circulaton

; N. meningitis

    - phagocytic vacule ¡æ epitherial cell ¿¡ ingestion

; entry to CSF

    - lateral ventricleÀÇ choroid plexus¸¦ ÅëÇØ

           --> extracerebral CSF¿Ísubarachnoid space

           --> rapidly multiply ( ¡ñ complement¿Í AbÀÇ CSF concentrationÀÌ bacterial proliferationÀ» ¾ïÁ¦Çϱ⿡´Â inadequate )

; gram(-) bact. cell wall lipopolysaccharide (endotoxin) & pneumococcal cell wall component (teicholic acid, peptidoglycan)ÀÌ marked inflamm. response¸¦ stimulation by production of

           ¨ç TNF

           ¨è interleukin I

           ¨é PGE2

           ¨ê cytokine inflammatory mediators

; subsequent inflammatory response

    ¡æ neutrophilic infiltration, increased vascular permeability, alteration of the BBB, vascular thrombosis

; excessive cytokine-induced inflammationÀº CSF°¡ sterilizedµÈ ÈÄ¿¡µµ °è¼ÓµÇ°í À̵éÀº pyogenic meningitisÀÇ chronic inflammatory sequelae¿¡ ºÎºÐÀûÀ¸·Î ¹Ý¿µ.

; infectionÀÇ contiguous focus·ÎºÎÅÍ bacterial invasion¿¡ ÀÇÇÑ menigitis´Â rare

  - paranasal sinusitis, OM, mastoiditis, orbital cellulitis ...

; occur during endocarditis, pneuminia, thrombophlebitis

; associated with severe burns, indwelling cathers or contaminated equipment

Clinical Manifestation

# sudden onset

    ¨ç shock, purpura, DIC, reduced level of consciousness°¡ rapidly progressive( esp, meningococcal spp.)

    ¨è 24hr³»¿¡ death

  ¨é H. influenzae type b and pneumococcal menigitis´Ârare

# ¼öÀϰ£ÀÇ URI or G-I Sx. ¼±Çà

# nonspecific findings

    ; fever (90-95%), anorexia, poor feeding, URI Sx., myalgia, arthralgia, tarchycardia, hypotension, various cutaneous sign : petechea, purpura, erythmatous macular rash

# Specific Signs

    1) meningeal irritation sign

           ¨ç nuchal rigidity

           ¨è back pain

           ¨é Kernig sign : hipÀ» 90¡Æflexion½ÃŲ »óÅ¿¡¼­ leg extension½Ã subsequent pain(+)

           ¨ê Brudzinski sign : supine¿¡¼­ neck flexion½Ã knee & hipÀÇ ºÒ¼öÀÇÀû flexion

           ; 12 ¡­ 18 mo Àü¿¡´Â not evident

    2) papilledema

           ; IICP ¶§

           ; uncomplicated meningitis½Ã´Â Àß ¾È³ªÅ¸³².

           ; ¢¾³ªÅ¸³­´Ù¸é

                   a. intracranial abscess

                       b. subdural empyema

                       c. occlusion of dural venous sinus µîÀÇ *chronic process suggest

    3) focal neurologic sign

           ; due to vascular occclusion or focal inflammation     

           ; 10¡­20%¿¡¼­ focal neurologic sign (+)

         ; *pneumococcal menigitis¿¡¼­ 30%À̻󿡼­ ³ªÅ¸³­´Ù

                   - due to vigorous inflammatory response.

    4) seizure in meningitis

           ; *due to cerebritis, infarction, electrolyte imbalance

           ; 20-30% of meningitis

           ; *more common in H. influenzae & pneumococcus than meningococcus

           ; *seizure persist after the 4th day of illness

                   - *poor prognosis

    5) IICP

           ; headache, emesis, bulging fontanel, diastasis of the sutures, oculomotor or abducens nerve paralysis, hypertension withbradycardia, apnea, hyperventilation, decorticate or decerebrate posturing, stupor, coma, herniation sign.

    6) Alteration of mental status

           ; *due to IICP, cerebritis, hypotension

           ; irritability, stupor, obtundation, coma

           ; comatose patient in meningitis

                   - poor px. sign.

                   - more often with pneumococcal or meningococcal than H. influenza

Complication

1) Neurologic Cx.

    ; seizure, IICP, cranial N. palsy, stroke, cbr. or cbll herniation transverse myelitis, ataxia, dural venous sinus thrombosis, subdural effusion

2) Subdural effusion

    ; *10-30%

           - 85-90% asymptomatic

    ; more common in young infant

    ; ¡Ø91 Symptomatic Subdural Effusion

           - bulging fontanel, diastasis of suture, emesis, seizure, fever, increased head circumference, abnormal results of cranial transillumination

         - aspiration

         - fever no indication of aspiration

    ; CT - confirm

3) Subdural empyema

    ; 1% of subdural effusion

4) SIADH

    ; occurs in majority of meningitis

    ; hyponatremic and reduced s-osmorality (30-50%)

           ¡æ exacerbate cerebral edema or independently hyponatremia seizure

    ; TxÀÇ late course¿¡ central diabetes inspidus°¡ hypothalamus or pituitary dysfunctionÀÇ °á°ú·Î ¿Â´Ù.

5) Fever

    ; more easily resolve in meningococcal and pneumococcal (90%) than H. influenza (70%)

           - by the 6th day of therapy

    ; prolonged fever (£¾10 days)

           - 15% of H. influenzae, 9% of pnumococcal, 6% of meningococcal

           - *cause

                   / intercurrent viral infection, nosocomial or 2¡Æbacterial infection, thrombophlebitis pericarditis drug reaction, arthritis

    ; *secondary fever

           - afebrile ÇØÁø ÈÄ¿¡ ´Ù½Ã fever ³ªÅ¸³ª´Â °æ¿ì

           - nosocomial infection

6) infectious pericarditis, arthritis                                                              

  ; due to bacterial dissemination or immune complex desposition

    ; occur earlier in the course of Tx than dose immune-mediated ds

7) ¡ÚThrombocytosis, Eosinophilia, Anemia

    ; *anemia

           - *¡ãcommon in H. influenzae

           - causes

                   / hemolysis

                   / BM suppression

8) DIC

    ; *¡ãoften associated with rapidly progressive pattern of presentation

    ; ¡ãcommonly in patient with *shock and prupura (purpura fulminans)

9) ¢¾Repeated episode of meningitis (3 pattern) :rare

    ; recrudescence

           - reappearence during therapy with appropriate AB

           - CSF

                   / *growth of bacteria & resistance of antibiotics

    ; relapse

           - occurs between 3days and 3wk after therapy

           - *persistent CNS infection (subdural empyema, ventriculitis, cerebral abscess) or other site infection (mastoid, cranial osteomyelitis, orbital infection)

           - *often asso. with inadequate choice, dose, duration of AB therapy

    ; recurrence          

           - new episode of meningitis due to reinfection

           - same bacterial species or andther pyogenic pathogen

           - ¡ÚSuggest

                   / acquired or congenital anatomic communication between CSF & mucocutaneous site

                   / defect in immune host defense

Differential Diagnosis

1) other organism meningitis

    ; Tb, Norcardia, Syphilis, lyme disease

  ; Fungus ( coccidioides, Histoplasma , Blastomyces )

    ; compromised host - candida , Cryptociccus, Aspergillus

    ; Parasite : Toxoplasma gondii, Cysticercus

    ; Virus( most frequently )

    ; noninfectious illness : malignancy, collagen vascular syndrome, toxin

2) focal infection of the CNS

    ; brain abscess, parenchymal infection ( ex. subdural empyema )

3) acute viral meningoencephalitis

    ; *most likely infection to be confused with bacterial meningitis.

    ; bacterial meningitisº¸´Ù less illÇÏ¿© DdxÇÏÁö¸¸, ±×·¸Áö ¾ÊÀº °æ¿ì°¡ ÀÖ¾î Èûµé´Ù.

4) ¡ÚPartially Treated Bacterial Meningitis

    ; 25-50% of bacterial meningitis children

    ; CSF¸¦ obtainÇϱâÀü¿¡ oral antibioticsÀÇ »ç¿ëÇÑ °æ¿ì

    ; effects

           - gram stain to less than 60%

           - reduce of incidence of growth of bacteria in CSF culture

    ; ¡Úno effects

           - *CSF glucose, protein, neutrophil profile, detection of bacterial antigen in CSF

Diagnosis

; confirm by CSF analysis

¨ç microorganism(+), gram s., c/s

¨è neutrophilic pleocytosis

¨é protein¡è

¨ê glucose¡é

# Lumbar puncture (LP)

    ; flexed lateral decubitus position

    ; L3-L4, L4-L5 intervertebral space

    ; ¡Ø95ÁÖ Cotnraindication

        - evidence of IICP

                   / bulging fontanel

                   / cranial nerve(III,VI) palsy with depressed level of consciousness

                   / hypertension & bradycardia with resp. abnormalities

           - severe cardiopulmonary compromised state requiring resuscitation for shock or in patients whom positioning for LP comprimise cardiopulmonary function

           - infection of skin overlying the site of the LP

    ; relative CIx

           - thrombocytopenia

           - *DIC or petechiae´Â CIxÀÌ µÇÁö ¾Ê°í, immunosuppressed patients with chronic thrombocytopeniaÀ» °¡Áø ȯÀÚÀÇ °æ¿ì transfusionÈÄ °¡´É

    ; ¡ÚLP¸¦ À§¿Í°°Àº °æ¿ì·Î ÀÎÇØ ¿¬±âÇÏ´õ¶óµµ empiric AB Tx.´Â Áï°¢ÀûÀ¸·Î ½ÃÀÛÇØ¾ß ÇÑ´Ù 

    ; CT scan »ó IICP, brain abscessÀÇ evidence°¡ ÀÖ´õ¶óµµ Ä¡·á°¡ delay µÇ¾î¼­´Â ¾ÈµÈ´Ù.

  ; *LP´Â IICP°¡ Tx. µÇ°í brain abscess°¡ excludedµÈ ÈÄ¿¡ ½Ç½ÃÇÑ´Ù.

# concurrent immunoelectrophoresis (CIE)

    ; *to identify Ag of ¨ç H. influenzae

                                ¨è S. pneumoniae

                                ¨é N. meningitidis type A, C, Y, W135

# ¡ÚLatex Particle Agglutination

    ; *¡ãpopular, widely used

  ; CSF¿¡¼­ most consistently detect

    ; antigenuriaµµ common

  ; serumÀº false positive°¡ ¸¹¾Æ good specimenÀÌ ¾Æ´Ï´Ù.

  ; Antibiotics Tx.¸¦ ÇÏ¿´´õ¶óµµ therapy½ÃÇà ¼öÀϳ»¿¡ AgÀ» detectÇÒ ¼ö ÀÖ´Ù.

    ; H. influenzae type B vaccinationÀ» ÃÖ±Ù¿¡ ¹ÞÀº ȯ¾Æ¿¡¼­´Â urine & serum¿¡¼­ Ag detection method¿¡¼­ false(+)

           - CSF¿¡¼­´Â ±×·± ÀÏÀÌ ¾ø´Ù.

# blood C/S

    ; *80¡­90% (+) in childhood meningitis

    ; menigitis°¡ ÀǽɵǴ ¸ðµç ȯ¾Æ¿¡¼­ ½ÃÇàÇØ¾ßÇÑ´Ù

  ; ƯÈ÷ °æÇèÀû Ç×»ýÁ¦¸¦ LPÀü¿¡ »ç¿ëÇÑ °æ¿ì  

# CSF leukocyte counts

    ; usually 1000¡è

           - neutrophilic predominance (75-95%)

    ; turbid £½ leukocyte counts £¾ 200¡­400

  ; Á¤»ó

           - *neonate : 30°³ÀÌÇÏ, older chikdren : 5¡­6°³ÀÌÇÏ

           - lymphocyte, monocyte°¡ ´ëºÎºÐ

    ; ¡Úlower CSF leukocyte (£¼250)

           - acute bact. meningitis ptÀÇ 20%

    ; ¡Úabsent pleocytosis

           - *overwhelming sepsis & severe meningitis

           - *poor prognostic sign

    ; pleocytosis with lymphocyte predominance

           - during early stage of acute bact, meningitis

    ; neutrophilic pleocytosis

           - during early stage of acute viral meningitis

    ; viral menigitis¿¡¼­ÀÇ shift to lymphocyte-monocyte predominance´Âinitial LPÈÄ 12¡­ 24hr ³»¿¡ ÀϾ´Ù

# Gram stain

    ; 70~90% (+)

# Traumatic LP

    ¨ç traumatic LP½Ã ´Ù¸¥ site¿¡ ´Ù½Ã ½ÃÇà½Ã óÀ½º¸´Ù ´ú hemorrhagic, CSF³» RBC´Â Æ÷ÇÔµÊ.

    ¨è gram stain, c/s, glucose level¿¡ ¿µÇâÀ» ÁÖÁö ¸øÇÔ.

        - ±×·¯³ª CSF leukocytosis and protein concentrationÀº ¿µÇâ (+)

Treatment

Initial AB Therapy

; illnessÀÇ innitial manifestationÀÇ nature¿¡ ÀÇÁ¸ÇÑ´Ù.

; LPÈÄ Áï°¢ÀûÀ¸·Î AB Tx

    - 24½Ã°£ À̳»¿¡ rapid progression without IICP

; *LP½ÃÇàÇÏÁö¾Ê°í, brain CTÀü¿¡ AB Tx, µ¿½Ã¿¡ IICP Tx

    - *IICP or focal neurologic finding (+)

; more protacted subacute course³ª 1-7 day periodÀÌ»ó ill

    - IICP, focal neurologic deficits¿¡´ëÇÑ evaluationÇØ¾ßÇÑ´Ù.

; initial (empiric) choice of Tx

    - H. influenza type B, S. pneumoniae, N. meningitidisÀÇantibioitic susceptibility

    - 3rd geneation cephalosporin

           / *ceftriaxone or cefotaxime

                   a. ceftriaxone : 100mg/kg/d qd or 50mg/kg/d q 12hrs

                   b. cefotaxime : 200mg/kg/d q 6hrs

           / ¢ÀÃÖ±Ù¿¡´Â PC resistant S. pneumoniae¶§¹®¿¡ vancomycin or rifampin¸¦ ÇÔ²² »ç¿ë.

    - ½ÇÁúÀûÀ¸·Î 24hrÀ̳»¿¡ CSF´Â sterilizationµÈ´Ù.

    - ¥â-lactam antibiotis¿¡ allergic pts

           / CM : 100 mg/kg/24hr div 6hrs

           / ¸¹Àº bacteria¿¡ bacteristatic agentÀÌÁö¸¸ H. influensae type b, S. pneumoniae, N.

           / ¢¾Adverse Effect

                   : aplastic anemia, shock-like gray infant syndrome,

                   : dose depent BM suppression  ¡Å drug moniteringÀÌ ÇÊ¿ä.

    - 1-2 MoÀÇ infant³ª T lymphocyte def. ó·³ L. moncytogenes°¡ ¿øÀαÕÀ¸·Î »ý°¢µÉ ¶§

           / Ampicillin + Ceftriaxone or Cefotaxime

           / Trimethoprime + Sulfamethoxazole IVµµ alternate Tx.

    - ¡Úlmmunocompromised & G(-) bact. meningitis

           / *ceftazidine£«aminoglycoside

Duration Of Antibiotic Theraphy.

# uncomplicate H. influenzae type B meningitis

    ; 7 -10 days

    ; ampicillin¿¡ Àß µè°í, ¥â-lactamase µîÀ» production ÇÏÁö ¾ÊÀ¸¸é initial AB¸¦ ampicillinÀ¸·Î change

# penicillin¿¡ relative resistantÇÑ S. pneumoniae (5¡­25%) menigitis

    ; CM

    ; ¸¸¾à C-M¿¡ resistanceÇϸé vancomycin

# uncomplicated penicillin senstive pneumococcal meningitis

    ; penicillin 30Ø¿U/kg/24hr #4 for 10-14 days

# choice for uncomplicated N. meningitidis meningitis

    ; penicillin 30Ø¿U/kg/24hr #4 for *5-7days

# ¡Ø90 causative organismÀ» ¹ß°ßÇÏÁö ¸øÇϰí CSF»ó bacterial infectionÀÇ evidence°¡ ÀÖ´Â °æ¿ì

    ; ceftriaxone, cefotaxime 7-10 days

# ¡Ø82 CT scan Ix

    a. focal sign (+)

    b. dose not respond to Tx.

    c. parameningeal focus may be present

    d. increased head circumference

    e. IICP sign

# routine repeated LP is not indicated

    ; ¡ÚLx. Of Repeat Exam. Of CSF

           a. some neonates

           b. patients with gram (-) bacillary meningitis

           c. not respond to conventional AB Tx. within 48-72hr

# Improvement of CSF profile (Ä¡·á¿¡ È¿°ú°¡ ÀÖ´Ù°í º¸¿©Áö´Â °æ¿ì)

    ; *Gram stainÀÌ (+) but sterile

    ; increased CSF glucose level

    ; appearance of lymphocyte-monocyte cells

# ¢ÀG(-) Bacillary Meningitis

    ;  3ÁÖ µ¿¾È or CSF sterilization 2ÁÖ ÈıîÁö »ç¿ë

    ; E. coli

           - cefotaxime, ceftriaxone¿¡ ´ëºÎºÐ sensitive

    ; P. aeruginosa

           - ceftazidine¿¡ ´ëºÎºÐ sensitive

# Side effect of AB Tx. for meningitis

    ; phlebitis, drug fever, rash, emesis, oral candidiasis, diarrhea, reversible gall bladder pseudolithiasis (ceftriaxone)

Supportive Care

# Repeated medical and neurological assessment are essential

    ; identify early sign of cardiovascular CNS, metabolic complication

# Neurologic assessment

    ; frequently *during first 72hr due to greatest risk of neurologic Cx.

           - ÀÌ ÈÄ¿¡´Â ÇÏ·ç¿¡ Çѹø¾¿ assesment ½ÃÇà      

           a. pupillary reflex

                   b. level of consciousness

                   c. motor strength

                   d. cranial n.sign

                   e. evaluation for seizure

# Important laboratory studies

                   a. BUN

                   b. s- Na, Cl, K, HCO3

                   c. urine output, SG

                   d. complete blood & plt counts

                   e. coagulation factor for petechiae, purpura, abn, bleeding

¡Ø96 NPO with ¥³ fluid administration (restricted)

    ; *1/2¡­1/3 of maintenance or 800-1000ml/m2/day

    ; IICP³ª SIADH °¡ ¾ø´Ù°í evaluationµÉ ¶§ ±îÁö

           - 1,500-1,700 m1/m2/D

    ; systemic hypotension½Ã fluid restrictionÀº not appropriate

           - ¿Ö³ÄÇϸé reduced BP·Î cerebral perfusion pressure°¡ 50cm H2OÀÌÇÏÀ̸é subsequient                             CNS ischemia°¡ ³ªÅ¸³²

# Septic shock µ¿¹Ý½Ã

    ; fluid resuscitation£«vasoactive agent

    (Na-Nitroprusside, dopamine, epinephrine)

    ; goal : blood flow³ª vital signÀ¸·ÎÀÇ O2 delivery¿¡ ¿µÇâÀ» ÁÖÁö ¾Ê°í IICP ¹æÁö 

# IICP Tx.

    ; endotracheal intubation & hyperventilation (PCO2£½25mmHg)

    ; ¥³ furosemide, Laxis(1mg/kg)

         - intracranial blood valumeÀÇ Áõ°¡ ¾øÀÌ venodilation, diuresis¸¦ ÅëÇØ brain swelling °¨¼Ò

    ; mannitol (0.5-1 g/kg) osmotherapy

           - brain°ú plasma »çÀÌÀÇ osmolar gradient¿¡ µû¶ó fluid°¡ CNS¿¡¼­  plasma·Î À̵¿½ÃÄÑ  osmotic diuresis ·Î ¹èÃâ½ÃÅ´.

¡Ø96 Seizures

    ; diazepam (0.1-0.2mg/kg/dose) or lorazepam (0.05mg/kg/dose) for immediate control of seizure

           - diazepamÀÌ respiratory supressionÀÌ lorazepam º¸´Ù ´õ ³ô´Ù.

    ; seizure ÀÇ immediate management ÈÄ phenytoin (15¡­ 20mg/kg, loading dose, 5mg/kg, maintenance dose)

    ; to reduce the likelihood of recurrence

# ¡ÚDexamethasone Tx (0.15mg/kg/dose q 6hrs ¡¿ 4 days)

    ; AB medication --> rapid killing of bacteria --> cell lysis·Î toxic producrs»ý¼º --> cytokine-mediated inflammatory response

    ; effects

           - less fever

           - lower CSF protein & lactate level reduction

           - reduction in permanent auditory n. damage (sensorineural hearing loss)

    ; ´ëºÎºÐ H. influenzae type b¿¡¼­´Â °á°ú°¡ ÀÖ¾úÁö¸¸ ´Ù¸¥ organism¿¡¼­µµ È¿°ú°¡ ÀÖÀ» °ÍÀ¸·Î »ý°¢µÊ

    ; »ç¿ë½Ã±â

           - *antibiotics Åõ¿© Á÷Àü¿¡ Åõ¿©ÇÏ´Â °ÍÀÌ maximum benefit

    ; Cx : G-I bleeding, hypertension, hyperglycemia, leukocytosis, rebound fever after last dose

Prevention

H. Influenzae Type B

# ¡ÚRifampin prophylaxis

    ; household contacts

           - *close family members less than 4yr no immunized fully°¡ ÀÖ´Â °æ¿ì

           - *people who lives in residence of index case or spent a minimum of 4hr for at least 5 of 7days proceding hospitalization

           - diagnosis°¡ confirmµÇ¸é Áï°¢ ½Ç½Ã

                   / 2nd index case°¡ 1st case ÀÔ¿ø ÀÏÁÖÀÏ À̳»¿¡ ³ªÅ¸³¯ È®·üÀÇ 50% ÀÌ»óÀ̱⠶§¹®

    ; day-care center contacts

           - less risk than houshold contacts

           - *2 or more index case and not fully immunized children under 2yrÀÌ ÀÖ´Â °æ¿ì

           - *>25hr/wk of close contact

    ; Dose

           - *20mg/kg/24hr once each day for 4 days (max. 600mg)

    ; Rifampin is contraindicated to pregnancy

  ; S/E - discolors the urine, swear red orange, stains contact lenses, reduce the serum concentrations of some drug

N. meningitidis

    ; ¡Ø83ÁÖ age³ª immunization ¿©ºÎ¿¡ °ü°è¾øÀÌ ¸ðµç meningococcal meningitis¿Í Á¢ÃËÇÑ »ç¶÷¿¡ prophylaxis ÇØ¾ß ÇÔ

    ; *rifampin 20mg/kg/dose #2 for 2 days (max. 600mg)

    ; vaccine

           - meningococcal quadrivalent vaccine for serogroups A, C, Y and W135

    - Indication

                   / *2¼¼ÀÌ»óÀÇ high risk children

                           : *asplenia, functional splenic dysfunction, terminal complement protein deficiency

Streptococcus pneumonia

    ; normal host´Â chemoprophylaxis¿Í vaccination°¡ ÇÊ¿ä¾ø´Ù

  ; high risk patiens´Â 23-valent pneumoccal vaccineÇÊ¿ä

  ; sickle cell anemia pt´Â chemoprophylaxisÇÊ¿ä ( PC, Amx, Bactrim )

Prognosis

# mortality rate in neonatal period

    ; 1-8%

  ; highest mortality rate in pneumococcal meningitis

# severe neurodevelopmental sequele ; 10-20%

# albeit subtle, neurobehavioral morbidity ; 50%

# ¡Ø89 Poor Prognostic Sign

    ; < 6 mo

    ; >106 CFU /ml in CSF

    ; seizures more than 4days into therapy

    ; coma or focal neurologic sign on presentation

# *Áø´Ü ÀüÀÇ SxÀÇ duration°ú outcome°ú´Â ¹«°ü

4) neurologic sequele

    ; hearing loss (sensorineural hearing loss), mental retardation, seizure, delay in acquisition of language, behavioral problem, visual impairment

    ; sensorineural hearing loss

           - ¡ã of bacterial meningitis

    - cause

                   / labyrinthitis following cochlear infection

                   / direct inflammation of auditory N

           - ºóµµ

                   / peumococcal menigitis : 30 %

               / menigococcal menigitis : 10 %

               / H. influenza type b menigitis : 5 ¡­ 20 %

           - Dexamethasone »ç¿ëÀÌ severe hearing loss incidence¸¦ °¨¼Ò½ÃŲ´Ù

    - dischargeÀü¿¡ ²À audiologic assesment

169.2 Viral Meningoencephalitis

; menigitis¿Í brain tissue¿¡ acute inflammatory process

; CSF : pleocytosis

; absence of microorganisms on Gram stain and Routine culture

; self limited ÀÌÁö¸¸ some case¿¡¼­ substantial morbidity¿Í mortality°¡ °üÂû

Etiology

; seasonal pattern (+)

; *enterovirus ( 80 % ÀÌ»ó)

; arbovirus, herpes virus ( common )

; Mumps ( vaccineÀÌ »ç¿ëµÇÁö¾Ê´Â Áö¿ª¿¡¼­ common )

Epidemiology

; ´ëºÎºÐÀÌ enterovirus¿¡ ÀÇÇØ ¾ß±âµÇ¹Ç·Î basic epidermiologic patternÀº prevalence¸¦ ¹Ý¿µÇÑ´Ù

; person to person spread

; IP : 4 ¡­ 6 days

; most case in temperate climates occur in the summer and fall.

Common Pathogen

1) arbovirus

    ; infected accidentally by an arthropod vector mosquito or tic (varemia)

    ; insect vector

2) enterovirus

    ; small RNA containing virus

    ; aseptic meningitis - severe encephaltis, death

  ; epidermics - newborns in nurseries

3) herpesvirus

    a. hespes simplex type 1 & 2

           ; HSV-1

                   - severe, sporadic encephalites in children, adult

               - brain involvement : focal

               - antiviral Tx(-) ; 70 % ¿¡¼­ coma, death

           ; HSV-2

                   - neonate ; diffuse brain involvement¸¦ °¡Áø severe encephalitis

                - delivery½Ã mother·Î ºÎÅÍ virus  

    b. varicella zoster virus (VZV)

       ; chicken pox¿Í ÀϽÃÀûÀ¸·Î, ¹ÐÁ¢ÇÏ°Ô °ü·ÃµÈ acute encephalitis ÀÏÀ¸Å´

    ; *most common manifestation - cerebellar ataxia, acute encephalitis

           ; spinal & cranial nerve root¿Í ganglia Â÷´Ü

                   - ³ªÁß¿¡ hespes zosterÀÇ ÇüÅ·Π³ªÅ¸³²

    c. cytomegalovirus (CMV)

        ; congeital infection or compromised hosts¿¡¼­ disseminated disease    

    ; normal infant , children : not

    d. Ebstein-Barr virus (EBV)

        ; myriad of CNS syndromes¿Í °ü°è ( see chapter 215 )

    e. respiratory virus, Rubella, Rubeolar¿¡ ÀÇÇØ¼­µµ meningoencephalitis¾ß±â

    f. Mumps meningoencephalitis : mildÇÏÁö¸¸ µå¹°°Ô 8¹ø CN¿¡ damage¸¦ ÁÖ¾î deafness ¾ß±â

Pathogenesis And Pathology

1) ingestion of enterovirus ¡æ lymphatics(multiplication) ¡æ mosquito or insect bite

         ¡æ to blood stream(seeding) : hematogenous spread

         ¡æ several organ infection(further viral multiplication)

         ¡æ secondary propagation of large amounts of virus

         ¡æ CNS invasion

         ¡æ neurologic disease evidence (+)

2) neurologic damage is caused

    a. direct invasion and destruction of neural tissue

                 by actively multiplying virus. : direct neural destruction

    b. viral Ag¿¡ ´ëÇÑ host reaction

                : demyelinization, vascular and perivascular destruction

              ¡ç host's vigorous tissue response°¡ induced

               : ´ëºÎºÐÀÇ neural destructionÀº ¾Æ¸¶ direct viral invasion¿¡ ÀÇÇØ ¾ß±â 

 3) brain tissue secretion

     <-- meningeal congestion and mononuclear infilteration, perivascular cuffs of lymphocytes and plasma cell myelobreakdown À» °¡Áø  perivascular tissue necrosis

       various stage¿¡¼­ neuronal disruption ---> neuronophagia, endothelial proliperation, necrosis.

4) marked demyelinization £« preservation of nurons & their axon

    "postinfections" or "allergic" encephalitis

5) cbr cortex

    a. Temporal lobe : severely affected by Herpes virus (intranuclear inclusion bodies)

    b. entire brain : Arbovirus

    c. basal structure : Rabies (Negri bodies)

  d. spiral cord, nerve roots, peripheala nerve : vaiable

Clinical Manifestation

# ¢¾Specific Form Or Complicating Manifestations Of Encephalitis

    ; Guillain-Barre Syn.

    ; Acute transverse myelitis

    ; Acute hemiplegia

    ; Acute cerebellar ataxia

# progression, severityÀÇ Á¤µµ´Â meningeal and parenchymal invovementÀÇ Á¤µµ¿Í  agent¿¡ ÀÇÇØ °áÁ¤  

# illnessÀÇ onsetÀº acuteÇϰí CNS Sx°ú signÀº ¸îÀϵ¿¾ÈÀÇ nonspecipic acute febrile illness µÚ¿¡ ¿Â´Ù

# headache, hyperesthesia : common sx, focal or generalized

# aldolesence : retrobulbar pain, fever, nausea, vomiting, neck pain, back pain, leg pain, photophobia, exanthemÀÌ CNS sign°ú µ¿¹ÝµÇ¾î ³ªÅ¸³ª±âµµ ÇÑ´Ù

 ( ƯÈ÷ echovirus, coxachivirus, VZA, mealses, rubella )

Laboratory Abnormality And Diagnosis

 1) CSF. : in viral encephalitis

    ¨ç color : clear

    ¨è leukocyte : 0 - several thousand

    ¨é cell type : PMNL (initial) ¡æ Monocyte ( 8 ¡­ 12 hr ÈÄ )

    ¨ê protein : N to slight¡è ¡æ brain destructionÀÌ extensiveÇϸé high : HSV encephalitisÀÇ late stage ¿¡.

¨ë glucose : N

         ( Mumps µî ÀϺο¡¼­´Â substantial depression of CSF glucose concentration )

2) serum specimen´Â illnessÀÇ early¿¡ ¾ò¾îÁ®¾ß Çϰí viral culture°¡

  not diagnoticÇÏ´Ù¸é 2-3wksÈÄ¿¡ ´Ù½Ã serologic study¸¦ ÇØ¾ßÇÑ´Ù                                       

<½Å>3) serologic method´Â too many potential serotypes¸¦ °¡Áø enterovirusÀÇ idenfication¿¡´Â not practicalÇÏÁö¸¸

       known circulating viral type¿¡ ÀÇÇØ ¾ß±âµÈ caseÀÇ confirm¿¡ È¿°úÀûÀÌ´Ù . ( nonenteroviral CNS infection )

<½Å>4) PCR: new technique

            not yet clinically available

<½Å>5) electroencehalogram

            neuroimaging studies

Diagnosis And Differential Diagnosis

bacterial infection ; mc ( H. influenza type b, S. peumoniae, N, meningitis )

                   other : Tuberculosis,

                          T. pallidum ( syphilis )

                          Borralia burgdorferi ( Lyme disease )

                          bacillus associated with cat-scratch ds

parameningeal bacterial infection : similar to viral CNS infection

                               : brain absess, subdural or epidural empyema

nonbacterial infectious agents : rickettsia, mycoplasma, protoza, fungus

CNS inflammation : malignancy, collagen-vascular disease, intracranial hemorrhage, drug, toxin

Prevention

polio, meales, mumps, rubella ÀÇ attenuated viral vaccineÀÌ effective

Rabies¿¡ ´ëÇÑ domestic animal vaccine programÀÌ rabies encephalitisÀÇ frequency¸¦ ³·Ãá´Ù  

Arbovirus¿¡ ´ëÇÑ vaccineÀº less successful

<½Å>   insect vectorÀÇ conrolÀÌ À̵é incidenc¸¦ reduce

Treatment

; bacterial cause°¡ excludeµÇ±â Àü¿¡ parenteral antibiotics therapy°¡ administeredµÇ¾î¾ß ÇÑ´Ù 

; Herpes simplex  encephalitis¿¡ acyclovir»ç¿ëÀ» Á¦¿ÜÇϰí´Â viral meningoencephalitisÀÇ tx´Â nonspecificÇÏ´Ù

3) mild infection ; symptomatic relief

  severe infection ; maintaining life and supporting organ system

4)      +-   headache, hyperesthesia ; rest

       |                             non-aspirin containing analgesics

       |                             room light ¡é

       |                             noise, visitor ¡é

       |    fever : acetaminophen

       +-   pain, vomiting ; codein, morpine, phenothiazine derivatives

       ¡æ °¡´ÉÇÏ´Ù¸é children¿¡¼­ sign, sxÀÇ misleadingÀ» ³ªÅ¸³¿À¸·Î À̵éÀÇ

           »ç¿ëÀ» ÃÖ¼ÒÈ­ÇÏ¿©¾ß ÇÑ´Ù

5) all patient with severe encephalitis sould be monitored carefully

6) intracranial pressuree monitoring Ix

       IICP evidence (+)

       epidural spaceÀÇ pressure transduderÀÇ placement (+)

7) all fluid, electrolyte medication˼ parenterally

8) glucose, Mg, Ca : must be maintained : seizure ¡é

9) supportive and rehabilitative effort : very important after recovery

 * motor incordination, convulsive disorder, squint, total or partial deafness, behavioral disturbance°¡ °ð ³ªÅ¸³­´Ù.

10) visual disturbance ; d/t chorioretinopathy and perceptual amblyopia

                        ; delayed appearance

11) viral meningoencephalities¿¡¼­ recoveryÈÄ grossly normal ÀÏÁö¶óµµ neurodevelopmental 

        and audiologic evaluationÀº ¹Ýµå½Ã routine follow up ÇØ¶ó

Prognosis

most children completely recover

px : º´ÀÇ severity, speicfic etiology, age¿¡ ÀÇÁ¸

 severeÇÑ case¿¡¼­ substantial parenchymal involvementÀÇ evidence°¡ ÀÖ´Ù¸é px´Â poor Çϰí

         intellectual, motor, psychiatric, epileptic, visual. auditory deficiiy°¡ ¿Ã ¼ö ÀÖ´Ù.

severe  sequelae : HSV ¿¡¼­ ¿¹°ß

infant¿¡¼­ older childrenº¸´Ù poor long-term outcome

 ; ÃÖ±ÙÀÇ data´Â ¾î·± observationÀ» ³í¹ÚÇÑ´Ù

 ±×·¯³ª enteroviral CNS infectionÀ» °¡Áø 2¼¼ÀÌÇÏÀÇ patientsÀÇ ¾à 10 %¿¡¼­ seizure, IICP, coma µî long term neurologic outcomes¸¦ °¡Áø´Ù.

Chapter 170. Pneumonia

# non-infectious cause

     ¨ç aspiration of food and/or gastric acid

     ¨è foreign bodies

     ¨é hydrocarbons

     ¨ê lipoid substance

     ¨ë hypersensitive reaction

     ¨ì drug or radiation induced peumonitis

# the common microbiologic cause

    1. resp. viruses

        : TMC cause of pneumonia during first several years of life

    2. mycoplasma pneumonia

        : predominant role in the school age & old child

    3. selected bacteria

        - ¼ýÀûÀ¸·Î´Â Áß¿äÇÏÁö ¾ÊÀ½

        - more severe inf.

        - most common bacteria

           ¨ç Streptococcus pneumoniae

           ¨è S. pyogens

           ¨é Staphylococcus aureus

           ¨ê Haemophylus influenza type b

        - use of effective vaccines

              --> less common with the widespread

# less common cause

     ¨ç non-respiratory viruses

     ¨è enteric Gram negative bacteria

     ¨é Mycobacteria

     ¨ê Chlamydia spp.

     ¨ë Rickettsia spp.

     ¨ì Coxillea

     ¨í Pneumocyst carinii

     ¨î fungus

# anatomic classification

     ¨ç lobar

     ¨è lobular

     ¨é alveolar

     ¨ê interstitial

Pneumonias Of Viral Origin

Etiology

# ¡ÚCommon Viruses

  ; Respiratory syncytial virus (RSV)

  ; parainfluenza viruses 1, 2, 3

  ; influenza viruses

  ; adenoviruses 3, 4, 7

# type & severity of illness

       : age, sex, season, crowding ¿¡ ÀÇÇØ ¿µÇâ

        ¨ç peak age

             bronchiolitis --> 1¼¼ ÀÌÇÏ

             viral pneumonia --> 2-3¼¼

        ¨è boy¡è

        ¨é winter¡è

Clinical Manifestation

    1. rhinitis, cough

        temp.¡é than bacterial pneumonia

        tachypnea with intercostal, subcostal, supracostal retraction

        nasal flaring

        severe inf.-->cyanosis & respiratory fatigue

    2. P/Ex.

      : rale & wheezing

Diagnosis

    1. X-ray (Fig 170-1)

        ¨ç diffuse infiltrate in perihilum

        ¨è transient lobar infiltrate

        ¨é hyperinflation

    2. WBC

        : sl. elevated (< 20.000), lymphocyte predominant

    3. ESR, CRP

        : normal or sl. elevated

    4. Definite Dx.

        : isolation of virus --> tissue culture (5-10 days)

    5. Serologic test

       - antibody to specific viral antigen ¡è

       - ¿ªÇÐÀû µµ±¸·Î »ç¿ë

Treatment

1. supportive Tx.

2. some patients --> hospitalization

   : IV fluid, oxygen, assisted ventilation

3.¡Ø96 oral amantadine ( or rimantadine)

   ¨ç influenza A --> prevention & Tx

   ¨è inf. ÀÇ onset 48hr³» »ç¿ëÇØ¾ß È¿°ú

4. aerosolized ribavirin

   ¨ç RSV

   ¨è expensive

Prognosis

    1. most children --> recovery with no sequelae

    2. Cx.

       ¨ç bronchiolitis obliterans

       ¨è unilat. hyperlucent lung

       ¨é fatal acute fulminant pneumonia

             - adenovirus 1, 3, 4, 7, 21ÀÌ °¡Àå À§Çè

Bacterial Pneumonia

General consideration

; *not a common infection

; ¡Ø89 TMC event disturbing the defense mechanism of lung

  - viral inf.

    ¨ç normal secretionÀÇ ¼º»ó º¯È­

    ¨è phagocytosisÀúÇØ

    ¨é modifies bacterial flora

           ¨êresp. passageÀÇ normal epithelial layer¸¦ disrupt

  - ¼öÀϳ» Á¾Á¾ bacterial pn.·Î ÁøÇà

; *Recurrent pneumonia

  ¨ç abnormalities of Ab production (e.g. agammaglobulinemia)

    ¨è cystic fibrosis

  ¨é cleft palate                 

    ¨ê cong. bronchiectasis

  ¨ë ciliary dyskinesia           

    ¨ì TEF

  ¨í abnormalities of PMNL     

    ¨î neutropenia

  ¨ï pul. blood flow ¡è          

    ¨ð deficient gag reflex

  ¨ñ iatrogenic factor --> trauma, anesthesia, aspiration

Pneumococcal Pneumonia

    # S. pneumoniae ==> TMC cause of bacterial inf. of the lung

1) Pathology & Pathogenesis

    1. upper airway or nasopharynx --> periphery of the lung

    2. reactive edema

       ¨ç support proliferation of the organism

       ¨è aid inspread into adjacent portion

3. one or more lobe, part of lobes --> involve

       cf) bronchopulmonary system --> uninvolved

      # infant

          ¨ç lobar pn. --> µå¹³

          ¨è bronchial distributionÀ» µû¶ó¼­ patchy or diffuse ds.

          ¨é small airways ÁÖÀ§·Î limited area consolidation

2) Cl/m

     : shaking chill, high fever, cough, chest pain in older children

   1. Infants

      a. mild URI Sx. for several day (stuffy nose, fretfulness, appetite ¡é)

         --> abrupt high fevr 39¡É ¡è, restlessness, apprehension

         --> respiratory distress

                : grunting, flaing of alae nasi,

                  retraction of supraclavicular, intercostal, subcostal area,

                  tachypnea, tachycardia

         --> air hunger & cyanosis

      b. P/E

         ¨ç dullness, B/S¡é, fine & crackling rale <-- affected side

         ¨è abd. distension : reflecting gastric dilatation or ileus

            liver enlargement : Rt. diaphragm downward displacement

                               superimposed cong. heart failure

            menigismus : esp. RUL pn.½Ã

         ¨é physical findingÀº illnessÀÇ clinical courseµ¿¾È Àß º¯ÇÏÁö ¾Ê´Â´Ù.

 

   2. Children & Adolescents

      a. brief mild URI

         ¨ç shaking chill, 40.5¡É fever

         ¨è drowsiness with intermittent restlessness

            tachypnea,

            dry, hacking unproductive cough

            anxiety, delirium

            circum-oral cyanosis

            splinting on the affected side

            knee drawn up to the chest

            lie on affected side

      b. P/Ex. : change during the course of illness

         ¨ç classic Sg. of consolidation (2-3day)

             - dullness, fremitus¡è, tubular B/S, disappearance of rales

         ¨è resolution

            - moist rales, productive cough with blood tinged mucus

         ¨é pleural effusion or empyema

             +-¥¡) visible lag in respiration on affected side

             |         with excursion¡è on opposite site

             | ¥¢) dullness over area of effusion

             | ¥£) fremitus & B/S ¡è

             +-¥¤) tubular breathing above fluid level & unaffected side

 

3) Lab/F

      a. ¨ç WBC : 15.000-40.000 (PMNL¿ì¼¼)

             cf) WBC 5.000ÀÌÇÏ --> poor Px.

         ¨è Hb. : normal or sl. decreased

         ¨é ABGA : hypoxemia without hypercapnea

     b. isolation of pneumococci

        ¨ç nasopharyngeal secretion

           cf) 10-15% of population --> uninfected carrers of S. pneumoniae

        ¨è pleural fluid from thoracentesis --> diagnostic

        ¨é bactetemia : 30% in pneumococcal pn.

4) X-ray finding (fig 170-1, 170-2)

       ¨ç lobar consolidation : infant or young children¿¡¼­´Â rare

       ¨è pleural reaction with fluid

       ¨é X-ray»ó complete resolution

            : 3-4wks after disappearance of all Sx.

5) DDx.

    1. other bacteria and viral pn.

    2. pneumona¿Í È¥µ¿ÇÒ ¼ö ÀÖ´Â condition

         ¨ç bronchioliotis          ¨è CHF

         ¨é bronchiectasisÀÇ ¾ÇÈ­  ¨ê FB aspiration

         ¨ë sequestered lobe       ¨ì atelectasis

         ¨í pulmonary abscess     ¨î allergic bronchitis

    3. RLL pn.¸¦ °¡Áø old children

         --> diaphragmatic irritaton

         --> reffered pain to the RLQ

         --> acute appendicitis¿Í È¥µ¿

    4. severe meningismus

         --> meningitis¿Í È¥µ¿

6) Cx.

    1. concomitant pneumococcal inf. & metastatic inf

          --> infrequent

    2. empyema --> infant

7) Px.

    1. preantibiotic era

         ¨ç mortality rate

             - infant & small children : 20-50%

             - older children : 3-5%

         ¨è high incidence chronic empyema

    2. ÀûÀýÇÑ antibiotics Tx.

          - mortality rate : 1% ÀÌÇÏ

8) Tx.

    1. drug of choice

          : Penicillin 10¸¸unit/kg/24hr

    2. decision of hospitalization

           ¨ç severity of illness                          ---+ ¿¡ ÀÇÁ¸

           ¨è ability of family to supply good nursing care --+

           ¨é young infant

               : hospitalization

                    ¥¡) for IV fluid & antibiotics

                    ¥¢) cilnical course --> more variable

           ¨ê pleural effusion or empyema

    3. oxygen with resp. distress

           ¨ç sedatives & analgesicsÀÇ ÇÊ¿ä °¨¼Ò

           ¨è cyanotic change°¡ ¿À±âÀü¿¡ °ø±Þ

Strptococcal Pneumonia

; Gr. A streptococci

; uncommon but predisposing state Á¸Àç

    - epidemic influenza, exanthemµî

; *3-5¼¼ more frequent

; *rare in infant

Pathology

1. lower respiratory infection : tracheitis, bronchitis, interstitial pneumonia

2. lobar pn.´Â µå¹³

3. *pleurisy ; ºñ±³Àû ÈçÇÔ

     --> serous, thinly purulent, fibrin¡é

4. lesion

     ¨ç necrosis of tracheobronchial mucosa

     ¨è formation of ragged ulcer

     ¨é large exudate

     ¨ê edema

     ¨ë localized hemorrage

Clinical Manifestation

; pneumococcal pn.¿Í À¯»ç

; sudden

; *high fever, chills, sg of respiratory distress

; at times, extreme prostration

Laboratory Finding

1. leukocytosis

2. ASLO Áõ°¡

3. *organism culture from pleural fluid/blood/lung aspirate --> definite Dx.

4. bacteremia : 10%

5. chest X-ray

    ¨ç diffuse bronchopneumonia

    ¨è often large pleural effusion

6. *complete resolution : 10ÁÖ ÀÌ»ó

Differential Diagnosis

      ¨ç staphylococcal pn.

      ¨è mycolasma pn.

Complication

      ¨ç *empyema : 20%

      ¨è septic foci on bone, joint

Treatment

    ; *Penicillin 10¸¸unit/kg/24hr iv for 2-3wk

        --> oral after clinical improvement

  ; empyema --> thoracentesis

Staphylococcal Pneumonia

; *rapid progressive inf. with prolonged morbidity & high mortality

; *more common in infant

Epidemiology

; viral URI ¼±Çà

; *30%°¡ 3°³¿ù ÀÌÇÏ, 70%°¡ 1¼¼ ÀÌÇÏ

; male ¡è

Pathogenesity & Pathology

¨ç confluent bronchopneumonia

¨è unilat. or prominent on one side

¨é extensive area of hemorrhagic necrosis & irregular cavitation

¨ê multiple abscess

    ; rupture of small subpleural abscess

        --> pyopneumothorax

    --> *bronchopleural fistula

Clinical Manifestation

1) Sx.

 ¨ç 1¼¼ ÀÌÇÏ : staphylococcal skin lesion ¶Ç´Â resp tr. infÀÇ Sx & Sg

 ¨è abrupt high fever, cough, resp. distress

           ; if undisturbed, lethergic, irritable, toxic --> severe dyspnea, shocklike state

 ¨é GI disturbance with vomiting, anorexia, diarrhea, abd. distention

   ==> *rapid progressionÀÌ Æ¯Â¡

2) P/Ex.

    ; early : diminished B/S, scattered rale, rhonchi

       --> affected lung

  ; effusion, empyema, pyopneumothorax, dullness on percussion

    ; marked diminished B/S & vocal fremitus

    ; lag in resp. excursion on affected side

    ; * young infant¿¡´Â tachypneaÁ¤µµ¿Í ¸ÂÁö ¾Ê´Â ºó¾àÇÑ ¼Ò°ß¶§¹®¿¡ misleading °¡´É

Laboratory Finding

1. WBC Áõ°¡

    ; *2¸¸ÀÌ»ó -- older infant & children

  ; *normal WBC in young infant

  ; 5.000 ÀÌÇϽà --> poor Px.

2. culture by tracheal aspiration, pleural tap, blood --> diagnostic

3. mild to moderate anemia

4. pleural fluid

     ¨ç exudate with PMNL 300- 100,000/mm3

     ¨è protein : 2.5g/dl ÀÌ»ó

     ¨é low glucose (blood¿¡ ºñÇØ)

Roentgenographic manifestation

1. Ãʱâ

    ; nonspecific bronchopneumonia

        --> *soon, patch infiltrate and limited extent or dense, homogeneous and involve entire lobe or hemithorax

    ; *Rt. lung : 65%

    ; bilat. - 20%ÀÌÇÏ

2. pleural effusion or empyema

3. pyopneumothorax

4. pneumatocele

    ; *clinical improvement procede X-ray finding

    ; *persist for months

# ¢Þover a few hrs, progression from bronchopn. to effusion or pyopneumothorax with/without pneumatocele

    --> suggestive staphylococcal pneumonia

Differential Diagnosis

1. early stage pneumonia´Â DDx.Çϱâ Èûµë

2. ¡ÚPossibility Of Dx.

  ; abrupt onset & rapid progression of Sx.

  ; Hx. of frunculosis

  ; recent hospital admission

  ; maternal breast abscess

3. ¢¾Empyema or pneumatocele À» ÃÊ·¡ÇÏ´Â bacterial pneumonia

  ¨ç staphylococcus                

    ¨è streptococcus

  ¨é klebsiella.                    

    ¨ê H. influenza

  ¨ë pneumococcal pneumonia.     

    ¨ì 1¡ÆTb pneumonia with cavitation

  ¨í aspiration of nonopaque FB --> pumonary abscess

¡Ø93ÁÖComplication.

  ; empyema, pyopneumothorax, pneumatocele

         - natural course·Î »ý°¢Çϱ⵵ ÇÑ´Ù.

    ; *sta. pericarditis, meningitis, osteomyelitis, multiple metastatic abscess

    ; ÇÑ±ÛÆÇ (p503)

           - Æó³ó¾ç, ³óÈä, ±â°üÁö È®ÀåÁõ, ÁßÀÌ¿°, ºÎºñµ¿¿°, ½É¸·¿°, ÆÐÇ÷Áõ, ³ú¸·¿°, °ñ¿°, º¹¸·¿°, »êÁõ, ³úÁõ

Prognosis

1. mortality 10-30%

    ; ¡Ø91 varies with

     ¨ç length of illness prior to hospitalization

     ¨è age of pt.

     ¨é adequacy of Tx.

     ¨ê other illness or Cx.

2. course : 6-10ÁÖ°£ ÀÔ¿ø

Treatment

- antibiotcs & drainage

- oxygen, semireclining position

- acute phase : IV hydration & nutrition

- blood transfusion, assist ventilation

1. ¢¾semisynthetic penicillinase-resistant PC (naficillin 200mg/kg/24hr) 

    ; IV immediately after culture (reportÀü±îÁö)

2. ¡Ø94 chest tube drainage

    ; *even if small effusion or empyema

  ; BPF °¨¼Ò, repeated pleural tapÀÇ Çʿ伺 °¨¼Ò

    ; largest caliber »ç¿ë

    ; *pyopneumothorax½Ã Áï°¢

    ; removal

        - *improvement & lung expansionµÇ±â ½ÃÀÛÇϸé Á¦°Å(ºñ·Ï ¼Ò·®ÀÇ pus°¡ drainµÇ´õ¶óµµ)

    - *5-7ÀÏÀÌ»óÀº ÇÏÁö ¾ÊÀ½

Haemophilus influenza Pneumonia

; nasopharyngeal infÈÄ

  --> epiglottitis, pneumonia, meningitis

; pneumonia : second in frequency

; *winter - spring

Clinical Manifestation

; *usually lobar pneumonia

; *Ư¡ÀûÀÎ X-ray finding¾øÀ½

   ¥¡) segmental infiltrate

   ¥¢) single or multiple lobe involvement

   ¥£) pleural effusion, pneumatocele

   ¥¤) disseminated pul. ds. & bronchopn.

; male ¡è

; *more insidious in onset

; *course is usually prolonged over several weeks

; febrile, tachypnea with nasal flaring & retraction

; P/Ex

    ¥¡) rale & tubular B/S

    ¥¢) localized dullness on pucussion

; pathology

 ¨ç PMNL or lymphocytic infl.

 ¨è extensive dustruction of epithelium of small airway

 ¨é interstitial infl.

 ¨ê marked or hemorrhagic edema

Differential Diagnosis

; Dx. --> isolation of organism from blood, pleural fluid & lung aspirate

; mod. leukocytosis with relative lymphopnea

; *latex agglutination test of urine

  - absence of positive cultureÀ϶§ À¯¿ë

; if atelectasis --> bronchoscopy·Î FB rule out

Complication

; frequent in young infant

     ¨ç bacteremia

     ¨è pericarditis

     ¨é cellulitis

     ¨ê empyema

     ¨ë meningitis ( # CSF exam.ÀÌ H. influenza pn.Áø´Ü½Ã ²À °í·ÁµÊ )

     ¨ì pyoarthrosis

Treatment

; ampicillin (100mg/kg/24hr), CM (100mg/kg/24hr) or ceftriaxone (100mg/kg/24hr)

      --> initial

; sensitive°¡ ³ª¿À¸é ampicillin´Üµ¶ °¡´É

; ¥¡) needle aspiration or closed chest drainage

         --> *initial AB¿¡ ¹ÝÀÀÀÌ ÁÁÀ¸¸é oral Tx. for 10- 14days

   ¥¢) open drainage --> infrequently need

; X-ray »ó complete resolution : 2-4ÁÖ

Carpter 171. Gastroenteritis (Àüü chapter°¡ »õ·Î »ý±è)

# Clinical manifestation

    ; organism°ú host¿¡ ÀÇÁ¸

# Presumptive Etiologic Diagnosis

 ¨ç epidemiologic clue

 ¨è clinical menifestation

 ¨é physical exam.

 ¨ê knowledge of the pathophysiologic mechanism of enteropathogen

# ¡ÚTwo Basic Type Of Acute Infectios Diarrhea

  1) inflammatory diarrhea by bacteria

     ¨ç invade the intestine directly

     ¨è produce cytotoxin

  2) noninflammatory diarrhea

     ¨ç enterotoxine production by some bacteria

     ¨è *destruction of villus cell by virus

     ¨é adherence and/or translocation by bacteria

# ¡ÚƯ¡

 ¨ç most self limited --> lab/study°¡ ºÒÇÊ¿äÇÑ °æ¿ì°¡ ¸¹´Ù.

 ¨è all patients require fluid & electrolyte treatment

 ¨é a few patients --> antimicrobial Tx.

Epidemiology

# Major Mechanism Of Transmission For Diarrheal Pathogen

  ; fecal-oral ( vehicles : food, water )

# ¡ÚSmall InoculationÀ¸·Î Inf.µÇ´Â Enterpathogen

    --> person-to-person contact

   ¨ç shigella

   ¨è enteric viruses

   ¨é G. lambria

   ¨ê cryptosporidium

   ¨ë E-coli 0157:H7

# Factors Rhat Increase Susceptibility To Infection

    ; young age, immune deficiency, measles, malnutrition, travel to the endemic area, lack of breast feeding, exposure to unsanitary codition, ingestion of contaminated food or water, level of maternal education, day care center attendance

Causative agents

Table 171-1

# chronic or persistent diarrhea

    ; lasting 14days or longer

    ; due to

           ¨ç infectious agent

               - G. lambria, Cryptosporidium, enteroaggregative or enteropathogenic E coli

           ¨è any enteropathogenic inf. of immunocompromised host

           ¨é residual symptom due to damaged intestine

Table 171-2 Noninfectious Causes Of Diarrhea

Bacterial Enteropathogen

     1. inflammatory diarrhea

         ¨ç Aeromonas spp.          ¨è Campylobacter jejuni

         ¨é Closstridium difficile      ¨ê enteroinvasive E coli

         ¨ë enterohemorrhagic E coli  ¨ì Plesimonas shigelloides

         ¨í salmonella spp            ¨î shigella spp.

         ¨ï Vibrio parahemolyticus.    ¨ð Yersinia enterocolitica

     2. noninflammatory diarrhea

         ¨ç enteropathogenic E coli

         ¨è enterotoxigenc E coli

         ¨é V cholerae

    # Antimicrobial TxÀÇ ¸ñÀû

         ¨ç shorten the clinical course

         ¨è causative agent ÀÇ  secretion °¨¼Ò

         ¨é complication °¨¼Ò

       Table 171-3

Parasitic Enteropathogen

     1. Á¾·ù

         ¨ç G. lambria --> TMC in U.S.A

         ¨è Cryptosporidium

         ¨é Entameba hystolytica

         ¨ê Strongyloides stercoralis

         ¨ë Isospora belli-----------------+ AIDS¿¡¼­ ¹ß°ß

         ¨ì Enterocytozoon bieneusi ------+

     2. Stool¿¡¼­ parasite, ova exam.ÀÇ Ix.

         ¨ç Hx. of recent travel to endemic area

         ¨è other enteropathogen¿¡ ´ëÇÑ stool culture --> negative

         ¨é 1 wk. ÀÌ»ó Áö¼ÓµÇ´Â diarrhea

         ¨ê immunocompromised Pt.

     3. Tx. --> Table 171-4

Viral enteropathogen

         ¨ç rota V

         ¨è enteric adenoV

         ¨é astrovirus

         ¨ê calicivirus

General approach to childhood

  A) Sx & Sg

    1. GI tract involvement

         : diarrhea, cramps & emesis

    2. systemic manifestation

         : fever, malaise, seizure

    3. extraintestinal inf.

        a) local spread

            : vulvovaginitis, UTI, keratoconjunctivitis

        b) remote spread

            : endocarditis, osteomyelitis, meningitis, pneumonia, hepatitis, peritonitis,

              chorioamnionitis, soft tissue inf. & septic thrombophlebitis

    4. immune-mediated extraintestinal manifestation

         --> Table 171-5

          : º¸Åë diarrhea ÇØ¼ÒÈÄ ÀϾ´Ù

B) Main objectives in the approach to a child with acute diarrhea

        ¨ç degree of dehydration --> fluid & electrolyte Tx.

        ¨è prevent spread of enteropathogen

        ¨é determine the etiologic agent & provide specific therpy

      # Table 171-6

Exam. of stool

   1. exam for mucus, blood, leukocyte

        --> colitis

     # fecal leukocyte

         ¨ç colonic mucosa¸¦ diffuseÇÏ°Ô invasion

         ¨è invasive or cytotoxine producing organism

   2. stool culture

       a) °¡´ÉÇÑ diseaseÃʱ⿡ ½ÃÇà

       # Hemolytic uremic syndrome

           ¨ç blood diarrhea

           ¨è fecal leukocytes

           ¨é immunocompromised Pt.

   3. modified Lab. procedure°¡ ÇÊ¿äÇÑ °æ¿ì

         ¨ç Y. enterocolitica       ¨è V parahemolyticus

         ¨é V cholera             ¨ê Aeromonas

         ¨ë C. difficle             ¨ì Comphylobacter

   4. serologic & toxin assay --> E coli subtype

   5. C difficile toxin --> diagnosis of antimicrobial- associated colitis

   6. Proctosigmoidoscopy

        ¨ç colitisÀÇ Sx. ÀÌ ½ÉÇÒ ¶§

        ¨è inflammatory enteritis synd.

Management Of Fluid, Electrolyte & Refeeding

# children

    ; more suseptible than adult to dehydration

        ¨ç assess the degree of dehydration

    ¨è ongoing loss

    ¨é daily requirement

Oral Hydration

    ; Tx. of choice

   1. Home remedies

       : decarbonated soda beverage, juices, tea µî --> not suitable

         ¨ç ºÎÀûÀýÇÑ high osmolality --> diarrhea ¾ÇÈ­

         ¨è low sodium conc. --> hyponatremia

         ¨é inappropriate carbohydrate to sodium ratio

   2. maintenance sol.

       --> Table 171-7

3. rehydrationÈÄ --> refeeding ½Ãµµ

       breast feeding Àº °¡´ÉÇÑ »¡¸® ½ÃÇà

Antidiarrheal Compound

# classification by their mechanism

  ¨ç alteration of intestinal motility

  ¨è adsorption of fluid or toxin

  ¨é alteration of intestial micreflora

  ¨ê alteration of fluid & electrolyte solution

Prevention

       ¨ç handwashing, gown -> soiling, glove

       ¨è education to patient & their family

       ¨é seperation

Acute Foodborne & Water-Borne Diseases

      # major cause of morbidity & mortality in all developed country

     1. diagnosis

         ¨ç °øÅëÀÇ À½½ÄÀ̳ª ¹°À» ¸ÔÀº »ç¶÷µé¿¡¼­ À¯»çÇÑ acute illness

         ¨è nausea, emesis, diarrhes, neurologic Sx.

     2. pathogenesis & severity of bacterial diseaseÀÇ ÀÇÁ¸ÀÎÀÚ

         ¨ç toxinÀ» »ý¼ºÇÏ´Â organism (S. aureus, B. cereus)

         ¨è »ý¼ºµÈ toxin

         ¨é invasive ¿©ºÎ

         ¨ê À½½Ä³» replication

     3. severity of disease due to viral, parasitic, chemical cause

           --> food, water¸¦ ÅëÇØ inoculation µÇ´Â ¾ç¿¡ ÀÇÁ¸

     4.

        ¨ç epidemiology·Î specific agent ÀǽÉ

        ¨è incubation period & clinical synd. --> DX

        ¨é specific Lab. testing --> confirm

     5. grouped by incubation period (Table 171-8)

         a) 1hr À̳» IP

             ¨ç chemical poisioning

             ¨è toxins form fish or shellfish

             ¨é proformed toxin of S. aureus, or B. cereus

 

         b) long IP

             ¨ç enterotoxin-producing bacteria

             ¨è invasive bacteria

             ¨é Norwalk V.

             ¨ê some form of mushroom poisioning

Clinical Syndrome

 (Table 171-8)

7. Tx. --> supportive

          ¿¹¿Ü) fetal

              ¨ç botulism

              ¨è paralytic shellfish poisioning

              ¨é long acting Mushroom poisioning

Chap.172  Osteomyelitis & Septic Arthritis

Osteomyelitis

   # hematogenous O.M : M.C in ¡Â 10 year children

Pathology & Pathogenesis

    1. virulent organism -> focal inf. in bone

                        -> suppuration & ischemic necrosis

                        -> fibrosis & bony repair

    2. entire bone involved : marrow, cortex, periosteum

    3. acute hematogenous O.M : localization of bloodborne bacteria

         * sta. aureus : adhesion to connective tissue elements in bone

         * local trauma -> thrombosis

                       -> inf.ÀÇ localized

         * source of bacteremia

           a. focal suppurative inf.

           b. inapparent, unidentified colonization or inf.

    4. inf. : begin in the metaphyseal region of long bone

            a. contain stagnant network of end arterioles & capillary

            b. lacks effective phagocytic cells

          : production of inflam. exudate

            -> septic thrombosis of vessels & compromised vascular supply

            -> ischemic bony infarction with local pain

            -> sufficient pus : intact periosteumÀ» elevation½Ã۱â À§ÇØ subperiosteal space¿¡ collectionµÊ

            -> disruption of the periosteal component of blood supply

                 & infarction of cortical bone

 

        * sequestrum

           : formation of necrotic bone area

              -> later stageµ¿¾È free foreign bodyÀ» Çü¼ºÇϱâ À§ÇØ underlying viable bone°ú              

                    seperationµÇ°Å³ª or gradual resorptionµÊ

        * involucrum

           : during the reparative phase of acute O.M

            elevated periosteumÀÇ osteogenic precursor cell

              -> new bone formation in the subperiosteal region

              -> infected focusÀ» enveloped

    5. in infants

       a. transphysial vessels -> traverse the cartilagenous growth plate

                             -> inf.ÀÌ marrow cavity, epiphysis·Î extend

                             -> pyarthrosis or septic arthritis

       b. ischemic necrosis of growth plate

          -> growth disturbance

    6. Brodie abscess

       : rim of sclerotic tissue·Î µÑ·¯½ÎÀÎ subacute or chronic localized abscess

       : ÁÖ·Î distal tibia

       : dull pain & local tenderness

       : spontaneous sterilization or chronic nidus of inf.

         -> surgical or long-term medical Tx.

Etiology

  1. sta. aureus : TMC

  2. H.influenza : 3yr ÀÌÇÏ

  3. group B strep & coliform : in neonate

  4. pseudomonas : puncture wound , intravenous drug users

  5. salmonella & Brucella : vertebral bone

                           esp. salmonella - in hemoglobinopathies pt.

  6. anaerobes : trauma, human bites, decubitus ulcer

  7. strep. pneumoniae, strep. pyogenes

  8. G(-)bacilli : salmonella, brucella, kingella, pseudomonas, serratia

  9. N.gonorrhea

  10. actinomycetes : spine, jaw

  11. mycobacteria , fungus

Clinical Manifestation

  1. in neonates

    a. iatrogenic procedureÈÄ (heel puncture, fetal scalp monitoring)

    b. pseudoparalysis : in infants

    c. common eti. : sta. , group B strep., coliforms

    d. multifocal disease(50%¡è)

    e. involved boneÀÇ ÀÎÁ¢ joint Àß Ä§¹ü

  2. in sickle cell disease

    a. vaso-occlusive crises

    b. multiple bone involve

    c. sta., salmonella

  3. vertebral O.M

    a. ÁÖ·Î 8¼¼ ÀÌ»óÀÇ children¿¡¼­ hematogenous inf.

    b. Sx. & Sg. : poorly localized

                  fever, back pain, abd. pain, referred pain in the thigh, gait disturbance

    c. percussion of the spinous process : point tenderness

      paraspinous m. spasm with limitation of movement

     ->more diagnostic

    d. eti. : sta. aureus, G(-)bacilli

    e. destruction of vert. body & paraspinous abscess

      -> spinal cord compressionµÇ¾î emergency op.

    4. pelvic O.M

    a. poorly localized

    b. pain : buttock, hip, knee

      gait disturbance

    c. afebrile

    d. sta. aureus, salmonella, mycobacteria

Diagnosis

  1. microbiologic studies

    a. blood culture : 50-60%

      bone aspiration or biopsyÀÇ material culture : increased positive

    b. if culture method impossible

        S. pneumoniae, H. influenza -> positive urine bacterial Ag test

    c. chronic draining O.M

       : boneÀÇ needle biopsy

    d. Tbc suspect

       : tuberculin skin test & chest X-ray

       : mycobacterial culture

  2. imaging studies

    1) X-ray

      a. negative in the 1st week

      b. deep soft-tissue swelling with obscuring of fat line

      c. vertebral OM : erosion and collapse of vert. body

      d. 10-14days : periosteal reaction(periosteal elevation, subperiosteal new bone formation)

                   : bony destruction (rarefaction, lysis)

    2) three-phase bone scan(99mTc-MDP)

      a. cellulitis without OM : initial phase - focal increased uptake

                               later phase (esp.bone phases) - decline

      b. OM : in all three phase (esp. bone phase) - localized uptake

      c. advantage

         : Á¶±â¿¡ involvedµÈ multiple siteÀ» detect

      d. gallium-67 citrate scan & labelled WBC scan

         : pelvic bone OM

    3) CT

    4) MRI

  3. marker of acute inflammation

    1) WBC Áõ°¡

    2) ESR  Áõ°¡

    3) CRP  Áõ°¡

Differential Diagnosis

  1. pyomyositis, cellulitis, bursitis, abscess, septic arthritis, diskitis

  2. trauma

  3. primary or secondary bony malig.

     : neuroblastoma, osteogenic & Ewing sarcoma

  4. leukemia, lymphoma

  5. bony infarction

  6. DDx. of pelvic OM

    1) arthritis(toxic & septic)

    2) retroperitoneal abscess

    3) avascular necrosis of femoral head

 

  # chronic recurrent multifocal OM (CROM)

   1. noninfectious, inflammatory condition

   2. multiple site involve, remission & exacerbations

   3. lack of isolation of etiologic agent

        "    response to empiric antimicrobial therapy

   4. female > male (2¹è)

   5. involve site

      a. metaphyses of tubular bone (prox. & distal tibia)

      b. sternal end of clavicle

      c. femur, fibula, radius, ulna, vertebra

   6. associated condition

      a. palmoplantar pustulosis

      b. Sweet synd.

      c. vertebral sclerosis

      d. psoriasis

   7. bony biopsy

     : acute inflammation, granulation tissue, noncaseating granuloma

     : pathogen culture(-)

   8. DDx

      a. multifocal acute or subacute pyogenic OM

      b. leukemia

      c. neuroblastoma

      d. histiocytosis X

   9. Px : excellent

      * exacerbationµ¿¾È NSAID & physiotherapy¿¡ response ÁÁÀ½

      * severe case : steroid

 

  # Diskitis

   1. involve site : intervertebral disk esp. L4-L5 & L3-L4 interspace

   2. 5¼¼ÀÌÇÏ Àß ¹ßº´ : disk-vertebral interface»óÀÇ catilaginous end plateÀÇ vasculature

                      -> involution with age

   3. etiology : sta. aureus(TMC)

   4. clinical manifestation : irritability, gradual onset of limb, refusal to sit, stand or walk

                             & low grade fever

 

 

   5. physical exam

      .normal or localized or diffuse spinal tenderness

      .muscles spasm with limitation of movement

   6. ESRÁõ°¡ , WBC normal

   7. X-ray finding

      +- disk space narrowing

      +- irregular erosion of adjacent vert. surface

        -> Sx onsetÈÄ 1-2ÁÖ¿¡ (-)

   8. Technetium & gallium scan

Treatment

¢ÞTable 172-1 & Table 172-2

# ¡ÚInitial Response To Tx

  ; resolution of systemic & local sg.

  ; decline in WBC, ESR, CRP

  ; resolution or at least lack of progression of radiologic changes

# duration

    ; *3-6wks recommand in uncomplicated case

    ; ESRÀÌ Á¤»óÀÌ µÉ¶§±îÁö Åõ¿©ÇÑ´Ù.

           - Á¤»óÀÌ µÇÁö ¾ÊÀº °æ¿ì¿¡´Â oral AB·Î ¹Ù²Ù¾î °è¼Ó Åõ¿©ÇÑ´Ù.

                   / dichloxacillin, oxacillin

                   / minor inf.½Ã Tx¿ë·®º¸´Ù 2-3¹è

                   / IV Ab, 1-2Mo --> oral Ab, 2-4Mo

# SBT(seurm bactericidal titer)

  ; acute OM        1 : 2 (peak 1 : 8)

  ; chronic OM     1 : 4 (peak 1 : 16)

# ¡ÚOp Indication

  ; removal of sequestra & sinus tract

  ; curretage of Brodie abscess

  ; irrigation with debridement of OM associated with foreign body, decubitus ulcer or open fx

Prognosis & Complication

  1. Px for uncomplicated OM : good

  2. Cx & sequale

     a. septic arthritis

     b. involvement of bone & cartilagenous growth plate

         -> bony deformity & altered growth

Septic Arthritis

Pathology & Pathogenesis

  1. hematogenous dissemination of bacteria

  2. contiguous spread of OM

  3. direct inoculation

¢ÞTable      172-3

Etiology

# H. influenza type b

  ; *¡ãcommon at 2mo-5yr

    ; 20-50%

    ; complicated by concurrent other disease

           - meningitis (10-30%)

       - cellulitis (10-30%)

    - otitis media (10%)

    - OM (5-10%)

    - pneumonia(5%)

# sta. aureus

  ; *¡ãcommon in neonates & at more than 5yr

    ; *2nd ¡ãcommon at 2mo-5yr

# neonatal septic arthritis

    . group B strep.

    . E. coli

    . candida albicans

    . S. pneumonia, neisseria spp., G(-) bacilli

# sexually active adolescent

    : N. gonorrhea

# streptobacillus moniliformis, spirillum minus, Borrelia burgdoferi, C. diphtheria

# chronic septic arthritis

    . Brucella

    . mycobacteria

    . fungi

Clinical Manifestation

  1. main feature

    : joint region¿¡ localizedµÈ acute inflammation

      -> pain, tenderness, swelling, erythema, decreased range of motion

  2. in neonate

    . irritability, poor feeding(few systemic sg.)

    . pseudoparalysis

    . diaper change -> pain

    . in infants : multiple jt. involve & contiguous OM

 

  3. older pts

    . pain : localized to the involved site

            but referred pain,  hip -> knee

                              pelvis -> back, hip, & ant. thigh

 

  4. antalgic position

    : intra-articular pr. & pain °¨¼Ò

         +- hip - flexion, abduction & external rotation

         |  knee & ankle - partial flexion

         |  shoulder - adduction & internal rotation

         +- elbow - midflexion

  5. antalgic gait

     pain -> gait disturbance(limp)

  6. pyogenic sacroilitis

     . fever

     . pain : hip, thigh, back, buttock

             -> movement½Ã aggrevated

     . diagnostic sg.

         - localized tenderness over the region of sacroiliac jt.

         - compression of the iliac wing -> pain Áõ°¡

  7. gonococcal septic arthritis

     . disseminated bacteremic inf.

     . monoarticular inf.

        : knee, shoulder, wrist, ankle, interphalangeal jt.

     . disseminated gonococcal inf.

        - female(4¹è)

        - during menstruation or 2nd or 3rd trimester of preg.

  8. Tb arthritis

     . chronic, simple jt. involve

     . knee, wrist, hip, interphalangeal, metacarpal jt., spine, ankle jt., synovial sheath

Diagnosis

  1. initial lab

      : ESR, CRP, WBC, neutrophil Áõ°¡

  2. blood culture : 30-40%(+)

  3. diagnostic arthrocentesis : suspect µÇ´Â all pt.

     * synovial fluid

        . grossly purulent fluid with WBC count > 10¸¸/¥ìL

            : not obtained

        . culture : 70-80%(+)

        . G. stain : 50%(+)

  4. serum or synovial Ag detective test

     : septic arthritis ·Î º¸±â¿¡´Â ºÒÃæºÐÇÑ nonspecific, nonlocalizing SxÀ¸·Î oral Abc.·Î partially treatµÈ

      ȯ¾Æ¿¡ »ç¿ë

  5. N. gonorrhea

     : recovery of synovial fluid -> difficult

       ¡Å blood, cervix, urethra, rectum, nasopharynx culture

Table 172-4

  6. X-ray

    . swelling with widening of the joint space

    . superficial & deep periarticular soft tissue swelling

    . displacement or loss of fat plane & edema of fat pads

    . hip joint : effusion

                -> lat. displacement of the femoral head or subluxation

    . septic arthritis °¡ 10-14ÀÏ ÀÌ»ó Áö¼Ó½Ã

       : osteoporosis or subluxation

    . OMµ¿¹Ý½Ã : periosteal elevation with or without lytic lesion

  7. U/S , CT & scan

  8. synovial biopsy, special stain & culture

     : chronic arthritis by M.tuberculosis or fungi -+

       sarcoidosis, rheumatologic reaction       -+- DDx °¡´É

Differential Diagnosis

  1. suppurative arthritis

    . OM, deep cellulitis, pyomyositis, psoas or retroperitoneal abscess, synovitis,

     septic bursitis, reactive arthritis

    . SLE, serum sickness, H-S purpura, Kawasaki disease, metabolic jt. disease

    . viral arthritis

      : interphalangeal-metacarpal jt.(TMC), knee, wrist, ankle, elbow jt.

 

  2. toxic synovitis

    . 5¼¼ ÀÌÇÏ, ÁÖ·Î hip

    . viral URIÈÄ

    . mild fever, limp, irritability

      extremity : mininal limitation of motion

    . ESR & WBC : normal

 

  3. migratory or recurrent polyarthritis

    . rheumatic fever

    . JRA

    . Lyme disease

    . serum sickness

    . DGI & Reiter synd.

       : DDx(Abc TxÈÄ)

           +- DGI : rapidly resolve

           +- Reiter : continuous jt Sx & development of new jt. effusion

Treatment

# ¢¾Principle

    ; AB therapy

    ; irrigation & drainage of the joint

  ; immobilization of the joint in a functional position

# ¡ÚDuration Of AB Tx

    ; *S. aureus - 4-6wks

  ; *strep. pneumoniae, H. influenza type b, group A streptococci - 14-21days

    ; gonococcus - 7-10 days

    ; neonate & immunocompromised host - longer duration

# fever : 3-5ÀÏ Áö¼Ó

             but more persist : Cx(abscess, loculation, OM) suspect

      jt. inflammation : 5-7Àϳ» resolve but jt. swelling : 10-14ÀÏ Áö¼Ó

   4. IV Abc Tx -> high dose oral Tx·Î changeÇÏ´Â ±âÁØ

      . remission of fever

      . reduction in inflammatory marker

      . synovial swelling °¨¼Ò

   5. S. aureus suspect

     : antistaphylococcal PC(methicillin, oxacillin, or nafcillin)

        -> iv route (not intra-articular)

   6. H. influenza type B

     : cephalosporin(ceftriaxone or cefuroxime)

       or CM + antista. PC

   7. G(-) enteric bacilli

     : antipseudomonal PC + aminoglycoside

   8. Kingella Kingae

     : PC

   9. N. gonorrhea

      . parenteral 3rd generation cephalosporin

         (ceftriaxone or cefoxitin)

      . susceptability test»ó PC¿¡ sensitiveÇÑ °æ¿ì

         : oral amoxicillin 3-5ÀÏ initiate

      . sexually active adolescent

         : doxycycline(for treat concurrent chlamydia trachomatis genital inf.)

   10. fungal arthritis

       : IV or intra-articular amphotericin B or 5-fluorocytosine

 

   11. open surgical drainage Ix

      . every case of septic arthritis of hip

      . most inf. involving the shoulder

      . recurrent purulent or culture (+) effusion or 7ÀÏ ÀÌ»ó Áö¼Ó½Ã

   12. emergent open drainage of hip ÀÇ Ix

      . reduce the intra-articular pr.

      . avoiding septic necrosis of the femoral head & the chance of permanent jt. damage

      . removal of necrotic bone & inflammatory mediators

   13. supportive Tx

      . Ä¡·á ù72½Ã°£ or synovial inflammation ¼Ò°ß improve µÉ ¶§ ±îÁö functional positionÀ¸·Î joint

          immobilization (splint)

         -> ÀÌÈÄ passive range of motion exercise

                a. maintain physiologic circulation of synovial fluid

                b. reduce the risk of contracture

      . for the upper limb

          shoulder - adduction & internal rotation

          elbow - midflexion

       . for the lower limb

          hip & ankle - extension

          ankle - neutral position

Prognosis

    - poor prognostic feature

        . young age(<6Mo)

        . delayed therapy(Sx ³ªÅ¸³­Áö 5ÀÏ °æ°ú)

        . sta. aureus, G(-), fungal pathogens

        . hip or shoulder jt. involve

        . associated OM with epiphyseal damage

Chapter 173. Infections In The Compromised Host

 

½Å* pts with a specific T-lymphocyte defect caused by HIV

   . neutropenia caused by antiviral drug

   . indwelling central lines, IV drug abuse

    -> breech of the integrity of the skin & mucous memb.

   . secondary malignancy

   . malnutrition

   . exposure to inf.(Tbc., sexually transmitted disease, hepatitis)

Compromised Host With Immunodeficiency

¡ÚTable 173-1

¡ÚTable 173-2

Clinical Manifestation

   * immunocompromised host ÀÇ inf.½Ã general clinical features

     a. any organism

        : immunocompromised host¿¡¼­ potentioal pathogen

     b. fever : sensitive & specific sg.

     c. fever¿Ü ´Ù¸¥ Sx & Sg¾øÀ» ¼öµµ ÀÖ´Ù

     d. skin & mucous memb.ÀÇ low microbial virulence & components of  normal flora

         : life-threatening inf.

     e. extreme granulocytopenia with absolute neutrophil count of 0.5 X 109cell/L or less

         : predictive of impending inf.

     f. 5¼¼ÀÌ»ó children¿¡¼­ CD4+ T lymhyocyte count 200/mm3ÀÌÇÏ (20%ÀÌÇÏ)

         : HIV infected pt.¿¡¼­ P. carinii pneumoniaÀÇ riskÁõ°¡

     g. mutiple inf. : common

     h. known & suspected bact. inf.

         : maximal tolerated dose·Î Áï½Ã Abc Ä¡·á

     i. inf. Tx·Î ÀÌ¿ëµÇ´Â drug : side effect °¡Áü

Infection In Pts With Immunodeficiency

Ab deficiency

    (1) X-linked agammaglobulinemia

       : S. aureus, H. influenza, strep. pneumoniaeµî¿¡ susceptible

       : viral & protozoal inf.

       : ÁÖ·Î upper & lower resp. tracts

          -> chronic & recurrent pul. inf.

          -> bronchiectasis

       : arthritis & pneumonitis -> mycoplasma

       : enteritis -> salmonella & campylobacter

    (2) selective Ig A defi.

       : viral inf.¿¡ ´ëÇÑ susceptability´Â no increase

    (3) hyper-IgM synd.

       : Ig G, Ig A & Ig E °¨¼Ò & neutropenia

       : agammagolbulinemiaÀÇ Æ¯Â¡ÀûÀÎ inf.¿Ü¿¡µµ P. carinii pneumonitisÀÇ riskÁõ°¡

    (4) IgG subclass defi.

       : sinopul. disease, menigitis, bacteremia, OM, pyoderma

       # IgG subclass 2 defi.

         : polysaccharide-encapsulated bact.(H. influenza, pneumococcus) & immunization with           

                                 polysaccharide bacterial vaccine¿¡ ´ëÇØ poor Ab response º¸ÀÓ

Defect in cell-mediated immunity

    a. cong. T-lymphocyte defi.

           +- T-lym. function °¨¼Ò

           +- protective by passive transfer of maternal IgG

            -> inf. after birth

       * early infections Cx

           : chronic mucocutaneous candidiasis, chronic rhinitis, otitis media, recurrent pn., & diarrhea

    b. acquired T-lymphocyte defect

      : AIDS (most common)

Combined B & T-lymphocyte defects

   . severe combined immunodefi. synd.(SCID)

     Wiskott-Aldrich synd.

     ataxia-telangiectasia

   . life-threatening inf.

     : surface systemic candidiasis, CMV inf., bact. inf., P-carinii pneumonitis

 

   . live-attenuated polio & measles vaccin

     : serious inf. ÃÊ·¡

Lymphocyte-phagocyte defects

     * leukocyte adhesion deficiency

         . delayed seperation of the umbilical cord

         . cellulitis

         . gingivitis

         . necrotic skin lesion

Complement deficiency

    . familial rheumatologic disorder

    . pneumococcemia, menigococcemia, gonococcemia

Phagocyte-Neutrophil Defects

    . S. aureus, G(-) bacilli, C. albicans

    . systemic bacterial inf. : sepsis, pneumonia, meningitis

    . pyogenic lymphadenitis, hepatic abscess, gingivitis, pn. & OM

    . risk of inf. Áõ°¡ : neutrophil count < 1,000

      * neutropenia

         a. cong. : cyclic neutropenia

                   severe infantile agranulocytosis

                   benign familial neutropenia

         b. acquired : antineutrophil Ab(autoimmune conditions, AIDS)

                    : drug reaction

                      (phenothiazine, sulfonamide, PC, CM, cancer chemotherapy)

                    : febrile viral illness

                    : BM deficiency

     ½Å* CGD - normal neutrophil count

              - deficient mechanism of bact. killing

     ½Å* hyper-IgE synd.

          : variable leukocyte function

    . clinical manifestation

       : severe neutropenia( < 500 neutrophil )

           - high risk of fulminant bact. sepsis

    . Tx

        a. depend on

            - microorganism responsible for the inf.

            - duration & severity of the neutropenia

            - possibility of BM recovery

            - associated impairment of host defense

        b. Abc

        c. corticosteroid : CGD pt¿¡¼­ granuloma resolve

        d. granulocyte transfusion

             - bact. or fungus : IV bactericidal Abc¿¡ unresponsiveÇÒ¶§

             - ´ÜÁ¡ : .expensive

                      .CM virus inf. riskÁõ°¡

                      .allosensitization to HLA Ag.

                      .GVH dis. in immunosuppressed pts

                      .amphotericin B °ú combine½Ã pul. infiltrate & hypoxia

                      .transfusion reaction

    . prevention

       ½ÅCGP pt. : broad spectrum Abc combination trimethoprim-sulfamethoxazole

                    -> improve phagocytic killing

                 : recombinent human interferon-¥ã

                    (50 ¥ìg/M2 subcutaneous 3ȸ/wk)

                     + oral trimethoprim-sulfamethoxazole

                    -> inf. rate °¨¼Ò

Defective Opsonization

     . splenectomy, cong. asplenia, splenic dysfunction from sickle cell dis.

        : bact. inf.Áõ°¡

           - strep. pneumoniae, H. influenza, salmonella

     . PC prophylaxis

        : sickle cell dis. & age 6MoÀÌ»ó

     . routine immunization ¿Ü¿¡µµ 2¼¼¶§ pneumococcal vacination

Infection With Organ & Tissue Transplantation

BM transplantation

Autologus BMT

      : 5-10%, ÁÖ·Î lung

Allogenic BMT

     a. inf. & GVH dis. : serious Cx.

     b. ÁÖ·Î G(-) bacilli & G(+) cocci

    ½Åc. table 173-3

          # transplantation ÈÄ 1Mo

          . granulocytopenia : profound

          . mucous memb. damage -> mucositis

          . indwelling catheter -> G(+) cocci, G(-) bacilli, fungus

          . RS virus pneumonitis

              : serious consequence

      # BMTÈÄ 30-100ÀÏ

          . granulocytopeniaº¸´Ù´Â immune systemÀÇ derangement¿¡ ÀÇÇØ

          . CM virus : no prophylaxis ½Ã 50-60% infected

          . interstitial pneumonia

               - common in leukemia pt.

               - BMTÈÄ 60Àϰ濡 occur

               - CM virus , P. carinii, RSV, idiopathic(30%)

 

      # BMT 100ÀÏ ÈÄÀÇ inf.

          . chronic G-V-H associated Ab deficiency

             -> pneumococcal sepsis or meningitis, sinopul. inf.

          . varicella-zoster virus reactivation

          . hemorrhagic cystitis

             : due to reactivation of papovavirus BK

          . rotaviral enteritis

          . pseudomembranous colitis(C. difficile)

          . human herpesvirus virus-6 inf.

    d. Tx of inf. after BMT

       1. depend on 

            . transplantationÈÄ °æ°úÇÑ ½Ã°£

            . neutropenia

            . acute or chronic G-V-H dis.

       2. approach : febrile neutropenia patient with malignancy ¿Í °°À½

                    - prompt institution of empiric bactericidal broad-spectrum antibiotics

                    - neutrophil count °¡ 500ÀÌ»ó µÉ ¶§±îÁö °è¼Ó

       3. acyclovir : herpes simplex, varicella-zoster viral inf.

       4. ganciclovir and CMV hyperimmune globulin

            : serious primary CMV pneumonia

    e. prevention

       1) IV gamma globulin

          fluorinated quinolones

          preventing acute graft-versus-host ds.

       2) prevention of CMV virus

            . avoiding administration of CMV-positive blood products and marrow

            . reducing the incidence of graft-versus-host ds. by acyclovir

            . allogenic BMTÈÄ 120ÀÏ µ¿¾È weekly blood, urine, throat culture

Liver transplant

  ½Å1) 1st Mo posttransplantation

       . highest risk of inf.

       . average 2.5 episode of inf.

   2) 2nd & 3rd Moµ¿¾È

       : inf. rate°¨¼Ò (0.35, 0.17 episodes)

   3) surgical procedure

       : biliary & liver·Î G-I tract microbial flora inf.Áõ°¡

   4) early inf.

       . G(-) enteric bacterial pneumonia

       . soft tissue and wound infections

       . intra-abdominal abscesses : enterococci, anaerobic, G(-) enteric-bacteria

       . peritonitis

       . disseminated candidiasis

       . cholangitis : "charcot triad" (fever, abd. pain, jaundice)

                   : liver rejection°ú ±¸ºÐ ÇÊ¿ä

                       by liver biopsy, Gram stain, culture

       . hepatic abscess : biliary or vascular obst.¶§¹®

                        (cf. cholangitis : biliary stricture or the use of ERCP¶§¹®)

       . ischemic injury to the bile ducts

           a. hepatic a. occlusion or bile duct anastomotic breakdown

           b. produce bile leakage and G(-) or candidial peritonitis

           c. detect by culture of the abd. drain

       . CM virus inf.

           a. 30-60% of children

           b. found in 1st 3Mo post-transplantation

           c. CMV hepatitis

               : up to 15% of transplanted children

           d. pneumonitis, gastroenteritis

       . EBVÀÇ reactivation

           a. mononucleosis-like synd.ÀÏÀ¸Å´

           b. late-onset lymphoproliferative synd.À¸·Î ÁøÇà

           c. immunosuppresive therapyÀÇ dosageÁÙÀÓÀ¸·Î improve

   5) Evaluation(of the febrile liver transplant recipient)

         . culture(blood, abd. drains)

         . chest roentgenography

         . abd. ultrasound and CT imaging

         . doppler assessment of hepatic artery blood flow

         . percutaneous liver biopsy : cholangitis ¿Í rejection±¸ºÐ

 

   6) Tx

      : broad-spectrum antibiotics and aspiration or drainage of abscesses

 

   7) prevention

        . prophylactic antibacterial agents

        . acyclovir, and trimethoprim-sulfamethoxazole (P. carinii)

        . avoiding neutropenia (due to azathioprine)

        . maintaining good surgical technique

Renal transplants

   1) inf. : major cause of death

     ½Å a. UTI  - TMC inf.

                - highest incidence (10%) during 1st Mo post-transplant

                - À̽ñ⿡ p. aeruginosa : MC cause

                - 1st Mo ÀÌÈÄ : E. coli MC

     ½Å b. CM virus inf.

            a) reduced by  . prophylactic antiviral drug

                           . CMV-Ab(-) blood products

                           . selection of seronegative organ donors

            b) MC clinical pattern

                 . 1-4Mo after transplantation

                 . fever, malaise, myalgia, arthralgia, leukopenia

            c) hepatitis, pneumonitis

       c. other herpes virus(H. simplex, varicella zoster, E-B virus)

          P. carinii, aspergillus spp., candidia, viral hepatitis

   2) Tx of inf.

       a. directed at the specific manifestation and the responsible microbiologic agent

       b. culture (urine, blood, sputum)´Â antibiotics ¾²±â Àü

       c. biopsy : rejection °ú inf.±¸ºÐ

   3) prevention

      a. Trimethoprime-sulfamethoxazole

          : pyelonephritis & P. carinii pneumonitisÀÇ incidenceÁÙÀÓ

      b. careful evalution of the urinary tract for abnormalities

        (urethral, ureteral, and vesicoureteral stricture, ureteral reflux, lymphocele, neurogenic bladder)

          : recurrent  urinary tract inf.ÀÇ ¿øÀÎ identify

Heart transplant

     # mediastinitis

        . infected surgical wound

           -> S. aureus, S. epidermidis, G(-) bacilli

        . fever, sternal tenderness, erythema, & purulent drainage with bone destruction

Infection In Patients With Cancer

     # inf. risk

         a. damage to the skin & mucous  memb.

         b. indwelling catheters

         c. malnutrition

         d. prolonged Abc usage

         e. hospitalization

     # anticancer Tx

        : one aspect of immue system ÀÌ»óÀ» involve

         a. corticosteroid & radiation

            : destruction of both T & B lymphocytes

         b. MTx & other antifols

            : inhibit DNA synthesis

         c. alkylating agent (cyclophosphamide)

            : block DNA replication

         d. 6-mercaptopurine

            : interfere with purine synthesis

Inf. In The Nongranulocytic Patients

    a. viral inf., P. carinii, toxoplasma gondii, fungus

    b. pneumococcal pn., otitis media, strep. pharyngitis, UTI

Inf. In The Gronulocytopenic Cancer Patients

   1) granulocyte count 500 cells/mm3 ÀÌÇÏ

       : high risk of serious inf.

   2) fever : only manifestation of inf.

           (due to granulcytopenia and poor inflammatory response)

Etiology

    ; G(+) cocci(most frequent), G(-) bacilli

  ; ¡ÚCoagulase(-) Staphylococci, S. Aureus, ¥á-Hemolytic Strep.

           - *¡ãfrequent in bood culture

      b. alpha-hemolytic streptococcal bacteremiaÁß¿¡¼­

         : acute septic shock synd. occur

            - adult resp. distress synd.°ú À¯»ç

            - cytarabine Åõ¿©½Ã MC manifestation

      c. P. aeruginosa, E. coli, Klebsiella pneumoniae

         : most common G(-) bacilli

      d. prolonged Abc Tx

         -> apportunistic fungal inf. (candida & aspergillus)

Clinical Manifestation

      a. G(-) sepsis

         : S. epidermidis, E. coli, pseudomonas inf.¿¡ ÀÇÇÑ septic shock (30-50% of episode) º¸´Ù severe

 

      b. oropharyngeal inf.

           . ulcerating stomatitis, gingivitis, periodontal lesion

           . mucositis : anaerobics, candida, herpes simplex

      c. esophagitis

      d. cutaneous sg. of disseminated inf.

           . ecthyma gangrenosum

           . nodule

           . gangrenous cellulitis

           . thrombotic arterial occlusion with dist. ischemia

      e. pneumonia in granulocytopenic cancer pts

           . stable

           . local rales, tachypnea, chest pain, ARDS

           . pul. infiltrate

              : abscent or faint

              : neutrophil count 500ÀÌ»ó µÉ¶§ obvious

              : noninfectious disorder ¿¡ ÀÇÇØ¼­µµ ³ªÅ¸³²

               ( hemorrhage, malig., emboli, edema, reaction to granulocyte transfusion,

                  radiation or CTx-induced pneumonitis )

 

          . G(-) enteric bacteria or fungus¿¡ ÀÇÇØ

               # aspergillus : wedge-shaped infiltrates

                            : typical of arterial invasion & subsequent thrombotic

                               pul. infarction

               # pul. cavitation

                   : aspergillosis

                   : mucormycosis

                   : G(-) enteric bact.(rare)

       f. sinusitis, hepatic & splenic candidiasis, severe diarrhea(C. difficile)

Diagnosis

       a. blood culture : peripheral vein & lumen of central venous catheter

       b. culture or biopsy : local cutaneous lesion

       c. chest X-ray : infiltrate, infarction, cavitation

       d. nasal secretion & sputum culture : aspergillus

       e. sinus X-ray & CT : aSx sinusitis

       f. esophageal endoscopy : odynophagia

           - esophageal lesion»ó pseudohyphae(+) : disseminated candidiasis

       g. serum CRP ¡Ã 40mg/h : bact. inf.

       h. lumbar puncture : meningitis

       i. fibrotic bronchoscopy, BAL, transbronchial biopsy, open lung biopsy

           : identify the microorganism responsible for pneumonia

Treatment

( of infants in febrile neutropenia cancer patient)

     (1) Prompt initiation of empiric broad-spectrum, bactericidal antibiotics

       a. monotherapy

         . ceftazidine, cefoperazone, or imipenem/cilastatin

         . ±×ÈÄ S. epidermidis ³ªÅ¸³¯ °æ¿ì

            : vancomycin ÷°¡

         . monotherapy´Â mild neutropenia(500-1,000 neutrophil)°æ¿ìÀ̸鼭 S. epidermidis°¡ pathogenÀ̶ó

          »ý°¢ µÇÁö ¾ÊÀ»¶§ »ç¿ë

       b. double beta-lactam therapy

         1. extended G(-) spectrum carboxy- or ureido-penicillin

             (ticarcillin with or without clavulanic acid, mezlocillin, piperacillin)

            and a cephalosporin

             (ceftazidine, cefoperazone, cefotaxime, ceftriaxone)

             - disadvantage

                . selection of resistant bacteria

                . possible antibiotic antagonism

                . poor antistaphylococcal coverage

         2. anti-pseudomonas beta-lactam penicillin or cephalosporin

               + aminoglycoside

             - avoid the risk of the emergence of resistent organism

             - synergistic

             - anaerobic coverage

             - disadvantage

                . nephrotoxicity

                . hypokalemia

                . ototoxicity

                . poor coverage of staphylococci

        c. triple drug regimen

            : extended G(-) spectrum penicillin or a cephalosporin

              + vancomycin

              + aminoglycoside(gentamicin, tobramycin, amikacin)

            - most beneficial in a risk of serious staphylococcal, enterococcal

               or bacterial multiple-resistant inf.

 

     (2) Duration and modification of antimicrobial therapy

        1) antibiotic Tx 72½Ã°£ ÈÄ afebrile ÇØÁö°í, bacterial source °¡ identifyµÇ´Â °æ¿ì

           - Tx. should be modified based on the antibiotic sensitivity

           - ±×·¯³ª spectrumÀÌ ³Ê¹« Á¼¾ÆÁö¸é bacteremia°¡ ³ªÅ¸³¯ risk°¡ ³ô±â ¶§¹®¿¡ broad spectrum

               antibiotic ¸¦ °è¼Ó »ç¿ëÇØ¾ß ÇÑ´Ù.

        2) antibiotic Tx´Â response°¡ ÁÁÀº (afebrile, negative repeat culture,

           free of signs and symptoms of inf.) pt.¿¡¼­ Àû¾îµµ 7Àϰ£ »ç¿ë

        3) antibiotics°¡ stopµÈÈÄ neutrophil count´Â 500À» ³Ñ¾î¾ß ÇÑ´Ù.

 

        4) high risk pt.

            - profound neutropenia, mucositis

            - signs of persistent inf.

            - central line tract inf.

            - bleeding

            - impending invasive procedure or chemotherapy

          °æ¿ì neutrophil count°¡ 500ÀÌ»ó µÉ ¶§ ±îÁö antibiotics¸¦ °è¼Ó »ç¿ëÇÏ´Â °ÍÀÌ benefitÇÏ´Ù.

        5) ¾î¶² cliniciansÀº defervescence or clinical well-being¿¡ »ó°ü¾øÀÌ fever¿Í

            neutropenia°¡ ÀÖ´Â ¸ðµç ȯÀÚ´Â neutrophil count°¡ 500ÀÌ»ó µÉ¶§±îÁö

            antibiotics¸¦ °è¼Ó »ç¿ëÇÏ¿©¾ß ÇÑ´Ù°í ±Ç°íÇÑ´Ù.

        6) febrile despite broad-spectrum antibiotic Tx and no pathogen is identified

            - reassess the patient's condition

          # etiology of persistent fever

              a. nonbacterial pathogen

                 : candida, aspergillus, toxoplasma, herpes simplex, cytomegalovirus, 

                   Epstein-Barr virus, enterovirus

              b. emergence of a second resistant species of bacteria

              c. inadequate serum or tissue antibiotics levels

              d. drug fever

              e. deep tissue (abscess) or catheter inf.

              f. fever resulting from the underlying malig.

 

        7) if no identified cause of fever is evident, the fever and neutropenia remains after 5-7days

              of antibiotics therapy,

            there is no progression or deterioration in the patient's condition and the patient appears

              clinically well.

            - the original antibiotics may be continued

        8) illÇÏ¿© º¸À̰ųª inf.ÀÇ manifestationÀÌ progressÇÒ °æ¿ì

            - vancomycin or 3rd generation cephalosporinÀ» ÷°¡

           (initial empiric regimen¿¡ µé¾îÀÖÁö ¾ÊÀº °æ¿ì)

        9) antibiotics¸¦ modificationÇÏ¿´´Âµ¥µµ ºÒ±¸Çϰí neutropenicÇϸ鼭 7ÀÏ °£ febrileÇѰæ¿ì

            1. intravenous amphotericin B¸¦ startÇÔ

               (33%¿¡¼­ invasive fungal ds. °¡Áü)

            2. amphotericin B¸¦ initiation Çϱâ Àü invasive candidiasis, aspergillosis, or mucormycosisÀÇ 

               source¸¦ °áÁ¤Çϱâ À§ÇØ ÇàÇÏ¿©¾ß ÇÒ evaluation

                - biopsy of lesion

                - several bl. and urine culture

                - chest and sinus roentgenograms repeated

                - abd. CT : to identify hepatic or splenic microabscess

                - opthalmologic examination

                     : to identify candidal ophthalmitis

           3. daily for 2wks (fungal inf.ÀÌ identify ¾ÈµÈ °æ¿ì)

                - ±× ÈÄ stopÇÏ¿© ȯÀÚ condition À» re-evaluate

           4. documented fungal inf. °æ¿ì

                - prolonged amphotericin B and aspiration or incision and drainage of cutaneous lesion

                   or deep abscess

           5. side effect : nephrotoxicity

              - ÁÙÀ̱â À§ÇØ nephrotoxic drugÀÇ »ç¿ëÀ» ÁÙÀÓ

            (aminoglycoside -> 3rd generation cephalosporin ´ëü,

              chemotherapeutic agent(cisplatin) »ç¿ë ÁÙÀÓ)

           6. new fungal agent (fluconazole)

              - effective

              - amphotericin ÀÌ not tolerate Çϰųª severe nephrotoxicity°¡ ÀÖ´Â °æ¿ì

      10) central venous catheter, implanted device¿¡ ÀÇÇÑ documented bacteremia

           ( catheter-related sepsis )

             - bacteremia¹ß»ý½Ã antibiotics¸¦ lineÀÇ sterilizationÀ» À§ÇØ lumen³»·Î ÁÖÀÔ

             - respond to systemic antibiotics

             - no need to remove the catheter

             - difficult to sterilize line inf.

                 . tract inf.

                 . sepsis due to Bacillus sp., fungi

                 . G(-) enteric bacteria

                 . multiple organism

       11) Empiric antiviral therapy for the febrile neutropenic patientÀÇ indication

           : typical mucocutaneous lesions suggestive of herpes simplex

             or varicella zoster

              -> intravenous acyclovir is the choice

   7) Prevention

        - difficult

       (1) method

           : reverse isolation, total protective environment

 

       (2) prophylactic antibiotics

           1) oral nonabsorbable

              - colistin, nystatin, and polymyxin

           2) oral absorbable

              - trimethoprim-sulfamethoxazole

                  : for P. carinii, G(-) enteric bacteria

                  # side effect

                    . delay bone marrow recovery

                    . drug rash

              - new fluorinated quinolones

       &nb