Part 17-1. Infectious Diseases

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.나 P/Ex.에 의해서는 진단하지 않고, laboratory test에 의해 Dx.

    3) FUO

# Thermoregulation

    1) hypothalamic thermoregulatory center controls BT

        ; peripheral cold & warm neuronal receptor의 balancing signal에 의해 control 됨.

    2) another regulatory factor

           ; temperature of blood circulating in the hypothalamus

    3) normal core temperature

           ; 37℃ (±1~1.5℃)로 set point 되어 있음.

        ; axillary temperature - core temperature 보다 1℃ 정도 낮다. (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↑, cell activity↑, involuntary shivering↑

    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

# ★Etiology에 관계없이 fever의 final pathway

    ; production of endogenous pyrogens(PGE2)

    ; 이것이 hypothalamic temperature set-point를 직접 변화시킴.

         → heat generation and heat conservation ( Fig 165-1 )

# Heat Production

    ; O2 consumption↑, CO2 production↑, cardiac output↑

    ; *exacerbate cardiac insufficiency in patients with

           ① heart disease

           ② chronic anemia (sickle cell disease)

           ③ pulmonary insufficiency with chronic lung disease

           ④ metabolic instabilaty in children with DM or inborn errors of metabolism

# 6 Mo ~ 5 yrs

    ; nonspecific febrile illness의 한 part로 seizure frequency↑↑

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＞ *1.4℃

    ; sustained or continuous fever : fluctuation of elevated Temp. of ＜ *0.3℃

# fever pattern이 not diagnostic in most infectious processes

# ★fever pattern이 특징적인 disease

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

Treatment

# ★Antipyretics Tx Benefit

    ; chr. cardiopul ds.  

    ; metabolic ds.

    ; neurologic ds.         

    ; risk for febrile seizure

2) antipyretic Tx.

  :     common infection ds.의 course를 변화시키지는 못함.

effect    controversal

# ★Hyperpyrexia (> 41℃)

    ; severe infection                           

    ; hypothalamic disorder

  ; CNS hemorrhage

4) pregnancy 동안의 high fever

  :     teratogenic effect

5) antipyretics의 기전

  : hypothalamic cyclooxygenase inhibitor로 작용

       PG E2 synthesis inhibition

Hyperthermia

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

a. endogenous heat production 증가 (malig. hyperthermia. vigorous exercise, neuroleptic. malig. synd., hyperthyroidism )

b. heat loss 감소 (atropine intoxication)

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

 

malignant hyperthermia	neuroleptic malig. synd.
AD disorder    원인 :       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       ※ malignant hyperthermia와 구분 안됨     ※ Tx. :        dantrolene                    supportive care

 

Drug Fever

    ; 다른 fever 나는 원인없이 drug administration으로 fever 유발되고 drug discontinution으로 fever가 사라짐으로서 진단되고, 특징적인 fever pattern이나 eosinophilia, rash, pruritus, drug allergy 등과 지속적인 관계 없음.

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

  ; average temp. range : 38 ∼ 43℃

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 (계속 치료시 다른 약으로 대치)

  ; *72시간내 fever resolve

# subsequent exposure to the drug 경우

    ; dose not necessarily reproduce a drug fever.

Rash With Fever

★Etiology

    ; 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 사용

            for collection of anaerobes c/s

Blood Cultures

; 50~100㎖ bottle - 5~6㎖ blood 채취

# ♥Why Repeated Culture ?

    ; infection의 치료가 어려운 high risk patient가 AB Tx. 받고 있는 경우 치료의 성공여부를 보기 위해

  ; repeated organism이 nonpathogenic isolate일때 contamination의 여부를 보기 위해

CSF examination

1) CSF stain : viral & bacterial의 구분에는 유익, specific organism을 찾아내지는 못함.

2) acute & rapid method for Dx

    : counterimmunoelectophoresis & agglutination of Ab-coated latex beads

3) specific Ag detect 위해 antisera 사용되는 경우

    ① S. pneumoniae

    ② H. influenzae type b

    ③ N. meningitidis

    ④ Streptococci (group B)

    ⑤ E. coli Kl

Urine Cultures

; collection by      ① clean catched mid-stream

                           ② catheterization

                           ③ suprapubic puncture

; catheter collection - ＞ 10³/ml(reflect infection)

; clean catch urine

    - ＞10⁵/ml : considered abnormal

    - 10⁴~10⁵/ml : possibly abnormal

    - *gram(-)에 국한

    - gram(+), yeast, pt with diuresis or chronic PN , pt on AB 에는 다른 기준

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

           ① c/s                  ② stain                                     ③ glucose                            ④ cell counts

Nasopharyngeal, Throat & Skin Swab

# Most Efficient Method

    ; *dry rayon, dacron, calcium alginate swab

    ; dry 되기 전 신속하게 transport medium

※주 Pathogenic Organism

    ; Corynebacterium diphtheria

    ; Bordetella pertussis

    ; N. gonorrhea

※94객 Pathognomic Or Nonpathognomic

    ; Strep. pyogenes

    ; N. meningitidis

    ; H. influenzae

  ; staphylococcus

Antibody-Based Techniques

# ★clinical use of FA (fluorescent antibody)

    ; B. pertussis

    ; Legionella pneumophilia

    ; N. gonorrhea

    --> conjugated Ab

# M. Tuberculosis

    ; *no antibody used

    ; *acid-fast fluorescent staining이 Ziehl-Neelson or Kinyoun acid-fast staining에 비해 more sensitive, but less specific

Antibiotic Sensitivity Tests

# most prevalent technique

    ; *agar disc diffusion method

       - inoculation 18~24hr 후에 zone of inhibition of bacterial growth 측정

# MIC (minimal inhibitory concentration)

    ; organism에 대한 특정한 antibiotics의 bacteriostatic concentration

# MBC (minimal bactericidal concentration)

  ; bacteria의 99.9%를 죽일 수 있는 antibiotics의 lowest concentration 즉 bactericidal end point

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

♣DNA 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 이용

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

Isolation

1) urine culture   

    ; ※89객 most useful for isolation of CMV

    ; *good source of isolation of mumps. adenovirus

2) specimen should be transported at 4℃

3) best throat specimen

       taken by vigorous throat swabbing, removing some superficial cells

4) ※객 vesicular fluid의 culture가 필요한 경우

    ; vaccinia, varicella, herpes simplex, enterovirus

Viral Genome And Virion Detection

1) PCR : complementary nucleotides 이용

        → detect viral gene sequences

2) electron microscopy ( EM )

        : direct visualization of virions within infected cells

Serologic Test

# Speciemen

    ; *적어도 2개의 blood specimen 필요

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

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

# Etiologic Dx titer

    ; acute phase serum에서 보다 convalescent serum에서 4배 이상 ↑해야 한다.

# ㉿Single specimen이 Dx.을 support하는 경우

    1) E-B Ab

    2) Young infant에서의 Ab가 mother에 없는 경우

    3) infant가 커감에 따라서 infant와 mother에서 Ab level이 동일시

  4) Mumps 의심時 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 infection시 IgM viral specific Ab

    ; general population과 비교하여 high Ab level

# methods for Ig M Ab detection

    ; diffcult to standardize

  → F (+) result가 common

  Ig G Ab assay : viral pathogen → induce humoral immunity (primary inf.후 수년 지속)

                                → 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.에 serum 얻게 되면 Ab rise difficult

    - Neutralization test : c/s에서보다 disadvantage

# HI Ab

    ; correlate fairly well with neutralizing ab.

    ; erythrocyte agglutination (+) viurs

           - *myxovirus, rubella, some enterovirus

    ; ★useful test for Parainfluenzae virus Ab

# fluorescent Ab detected by indirect fluorescent technique

# ★ELISA & latex agglutination test

  ; *now most used

  ; viral Ag 이 plastic well or to latex beads에 attach되어 검사됨.

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) 36개월이하에서 특히 진단에 dilemma초래

2) 3개월이내의 febrile infant의 40-60%가 viral pathogen

3) ♣Exclusion 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/μL

    ; absolute band count of < 1,500 cells/μL

  ; normal urinalysis

    --> negative predictive value는 98%이상이며, bacetremia에 대해서는 99%이상이다.

4) 3개월이하의 ill-appearing (toxic) febrile infant에서의 대책

  1. prompt hospitalization

  2. culture (blood, urine, CSF)

  3. immediate parenteral antimicrobial therapy

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

     → focal signs없는 ill-appearing patients의 initial therapy

♣PC resistant Strept. pneumoniae에 의한 meningitis에서는 vancomycin추가.

Occult Bacteremia

1. bacteremia without an obvious focus of infection

2. occult bacteremia가진 children의 85%에서 culture상 S. pneumoniae (+)

   나머지 positive culture에서는 H. influenzae type b, N. meningitidis, Salmonella species

3. ♣Increased Risk For Occult Bacteremia

 ① temperature: 39.4℃이상

 ② total WBC count: < 5,000 or > 15,000

 ③ elevated absolute neutrophil count, band count, ESR, or C-reactive protein

4. 3-36개월 infant에서 temp. 39℃이상, WBC > 15,000일때

    --> bacteremia incidence 13%

    --> *3-36개월사이에서 bacteremia incidence가 증가하는 이유

           ; maturational immune deficiency

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

5. bacteremia 치료 않는 경우

 ① resolve without sequelae

 ② persist

 ③ produced localized inf. (meningitis, pn., cellulitis, septic arthritis)

6. H. influenzae에 의한 bacteremia가 S. pneumoniae에 의한 bacteremia보다 더 심한 bacterial infection을 일으킨다.

    ; H. influenzae type b bacteremia는 meningitis, epiglottitis, cellulitis, osteoarticular infection같은 focal infection을 야기. 5%에서 occult bacteremia보인다.

7. pneumococcal bacteremia에서 spontaneous resolution되는 transient bacteremia incidence

  ; 30-40%

8. 3-36개월의 toxic-appearing febrile child에서 infection의 focal sign이 없어도 severe bacterial disease의 high risk가 있으면 immediate antibiotic Tx.필요

# ♣Practice guideline (published in Pediatrics & Annals of Emergency medicine in 1933)

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

         ; obseved outpatients without diagnostic test or antibiotics medication

  2) non-toxic with rectal temp.≥ 39℃

           ; two option

               - blood culture & empirical antimicrobial therapy

               - complete blood cell count

                           --> if WBC ≥ 15,000 cells/μL, blood culture & empirical antimicrobial therapy

  3) others infants

           ; after blood culture, observed without antimicrobial therapy

10. ill appeared child에서 fever가 계속되고 focus 발견되지 않거나 H. influenzae나 N. meningitidis가 1st blood culture상 (+)인 경우

  ; meningitis여부 규명, repeat blood culture내리고 입원해서 적절한 antibiotic Tx.를 한다.

Fever With Petechiae

; *Age와 관계없이 high risk for life-threatening bacterial infection

; 8-20%에서 serious bacterial infection

; 7-10%에서 meningococcal sepsis or meningitis

; H. influenzae type b는 meningococcus보다 less common, serious bacterial illness야기

Fever In Patients With Sickle Cell Anemia

1) sickle cell anemia에서 M/C cause of death : infection

2) 2세이하에서 infection incidence가장 높다.

3) infection의 risk증가 원인

  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.

신1. seriously ill, temp 40℃↑, WBC count < 5,000/μL, or >30,000/μL, pulm. infiltrates,

     sickle cell ds.의 Cx., severe pain

    : hospitalization

  2. other febrile infant : ceftriaxone IM & culture후 outpatient로 manage

6) prevention of pneumococcal sepsis

   : long term Pc.(매일 oral로 또는 3-4주마다 IM)으로 adolescence까지 Tx.

   H. influenzae에 대해서는 daily oral amoxacillin

Hyperpyrexia

신 *Temp. >41℃

; uncommon

; temp 39.1-40.0℃ or 40.1-41.0℃보다 serious bacterial infection의 high rate관련성 없음.

FUO

# ♣Definition

 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

# FUO와 AIDS

    ; HIV-1 infection시도 fever(+), AIDS하나로는 FUO에 부합하지 않는다.

    ; FUO와 AIDS있는 환자에서는 common, unusual pathogen의 opportunistic infection을 또한 가짐

# *6개월이상 지속되는 FUO의 원인 (children에서는 uncommon)

    ; granuolmatous or autoimmune disease의미

♥Table 167-3

    ; ㉿viral cause of FUO

           - cytomegalovirus, hepatitis, infectious mononucleosis, HIV

    ; *▲common autoimmune hypersensitivity disease

         - juvenile rheumatoid arthritis

Diagnostic Clues In The Child With Fever Of Unknown Origin

History

 1. 6세이하

  : 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

# ㉿sweat (-) 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

① red, weeping eye

  : connective tissue disease 특히 polyarteritis nodosa

② palpebral conjuctivitis

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

③ bulbar conjunctivitis

  : Kawasakie disease, leptospirosis

④ petechial conjunctival hemorrhage

  : endocarditis

⑤ uveitis

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

⑥ chorioretinitis

    : CMV, toxoplasmosis, syphilis

⑦ proptosis

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

# ♣Ophthalmoscopic examination of nailfold capillary abnormalities

  ; *dermatomyositis & systemic scleroderma같은 connective tissue disease

           - markedly dilated capillary pattern

        - Figure 167-1 A & B

# hypothalamic dysfunction에 의한 FUO의 원인

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

# ※객 Fever Blister

    ; pneumococcal, streptococcal, malarial, rickettsial infection

    ; meningococcal meningitis

    ; rarely seen in meningococcemia, salmonella, staphylococcal infection

# repetitive chill & temp. spikes

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

Laboratory studies

1) *WBC & UA

 ① *absolute neutrophil count < 5,000/mm³

    ; against fulminant bacterial infection other than typhoid fever

 ② *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)

           - inflammation을 의미

         - infectious, autoimmune, & malignant에 대한 evaluation

  ; low ESR

       - juvenile rheumatoid arthritis, infection의 가능성을 배제하지 못함

  ; ※94 ESR > 100

           - Tbc, Kawasaki disease, malignancy, autoimmue disease

4. Radioactive scan

 ① galium citrate(⁶⁷Ga)

   : tumor, abscess의 inflammatory tissue (leukocyte)에 localized

 ② ^99mTc phosphate

   : X-ray에서 bone lesion증명 하기전에 osteomyelitis detect

 ③ *Indium-III granulocyte or iodinated IgG

   : useful detecting localized pyogenic process

Treatment

㉿ FUO에서 무분별한 antibiotic treatment가 위험한 이유

    ; endocarditis, meningitis, parameningeal infection, osteomyelitis의 진단을 모호하게 한다.

    ; 그러나, anti Tbc treatment는 예외

Prognosis

    ; adult보다 better prognosis

    ; unclear etiology : 25%

Chapter 168 Sepsis & Shock

Bacteremia & Septicemia

# bacteremia

  ; disease에 관계없이 일시적으로 blood culture에서 bacteria가 recovery되는 경우

# septicemia

  ; acute disease와 관련된 bacteremia의 severe form으로서 septic shock으로 progress할 수 있는 경우

# *Bacteremia의 정도

    ; 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

 ① community acquired bacteremia-sepsis from local tissue infection

 ② colonization & local mucosal invasion by particulary virulent pathogen

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

2. Hospitalized patient

 ① catheter sepsis or surgical wound

  ; S. aureus, S. epidermidis

 ② immunocompromized neutropenic patient

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

 ③ 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)

♣Figure 168-1 & Figure 168-2

; bacterial products에 대한 host response

    - gram-negative bacteria → endotoxin

  - gram-positive bacteria → lipoteichoic aicd-peptidoglycan complex

; blood stream내로 bacterial cell wall components가 release될때, cytokines는 활성화된다.

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

# ♣Physiologic response by cytokines

   ① activation of complement system

   ② activation of Hageman factor (factor XII)

   ③ adrenocorticotrophic hormone & beta-endorphin release

   ④ stimulation of polymorphonuclear neutrophils

   ⑤ stimulation of the kallikrein-kinin system

신4. TNF & other inflammatory mediators

   ① vascular permeability ↑, diffuse capillary leakage

   ② vascular tone ↓

   ③ imbalance between perfusion & the increased metabolic requirements of tissue

신5. shock

   ① def.

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

   ② delayed capillary refill (> 2 sec.)

     : no considered a reliable indicator of decreased peripheral perfusion

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

  7. tissue oxygen consumption은

     septic shock에서 oxygen delivery초과

   ① early peripheral vasodilation

   ② late vasoconstriction

   ③ myocardial depression

   ④ hypotension

   ⑤ ventilatory insufficiency

   ⑥ anemia

  8. cardiac index증가: sepsis에서

  9. pulmonary function: often severely impaired

Clinical Manifestation

 1. septic shock의 primary sign & Sx.

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

    ecchymoses, ecthyma gangrenosum, diffuse erythema, cellulitis), 의식장애 (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

  ① 특징

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

  ② 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 ↑, PTT ↑

6. serum fibrinogen level ↓

7. Pa O2 ↑& Pa CO2 ↓

8. ※90 neutrophil의 morphology 변화

 ① neutrophil의 vacuolization

 ② toxic granulation

 ③ Dohle body

 ④ elevated neutrophil & band

 ⑤ neutropenia

   ①-③ : bacterial sepsis

   ④    : bacterial infection

   ⑤    : ominous sign of fulminant septic shock

Treatment

① community acquired ds. (H. influenzae, N. meningitidis, S. pneumoniae)

    ; ceftriaxone

② nosocomial sepsis

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

③ S. pneumoniae가 PC resistant

    ; vancomycin 추가 

# shock

 ① fluid restriction (N/S, albumin, hetastarch, dextran sol.)

 ② IV sympathomimetic agent

    ; 1st - dopamine, dobutamine

    ; 2nd - epinephrine, NE, sodium nitropruside

# hypoxia

  ; PEEP (5-20 cm H2O)

# DIC

 ① replace consumed coagulation factors

  : fresh frozen plasma, cryoprcipitate, platelets

 ② heparin

  : thromobosis, peripheral gangrene에 대해

# overexuberant host response를 목적으로

  ; IV Immunoglobulin, monoclonal IgM to endotoxin, granulocyte transfusion

# corticosteroid effect

    ; adult 에서는 not beneficial

    ; adrenal hemorrhage (Waterhouse-Fridrichsen syndrome)

    ; *meningitis caused by H. influenzae type b

Prognosis

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

# ★Poor 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

# 그외 TNF, bacterial No./ml blood, endotoxin level

    : prognosis와 연관

Prevention

1. 2개월-4세의 all children

  : immunization against H. influenzae type b

2. high risk pt

  : 2세에 *23-valent pneumococcal vaccine, quadrivalent meningococcal vaccine (group A, C, Y, W-135)

3. pneumococcal infection에 대한 PC prophylaxis

  : splenic dysfunction (sickle cell anemia pt) & splenectomy

4. H. influenzae나 meningococcal ds.에 exposure된 pt.에 close contact한 경우

  : Rifampin

Chapter 169. Infections Of The Central Nervous System

# CNS의 acute infection은 children에서 CNS ds 의 Sx, Sg을 동반한 fever의 mc cause이다.

# 일반적으로 CNS infection은 viral이 bacterial보다 more common

# etiology에 관계없이 acute CNS infection을 가진 환자는 similar syndrome을 가진다. ;

  ( 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

# sign의 severity와 constellation은 specific pathogen, host,  infection의 anatomic distribution에 의해 정해짐

# diffuse CNS infection

  +- Menigitis : meninges

  +- encephalitis : brain parenchymal involvement

  ; 많은 환자에서 anatomic barrier가 not distinct하기 때문에 meningeal, parenchymal involvement소견을 보이면 meningoencephalitis를 꼭 생각해 주어야 한다.

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

               : neurological expression는 absess의 site와 extent에 의해 결정

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

Table 169-1

㉿169.1 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 b의 vaciination 사용전에는 H. influenza가 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

  ; 2세이하에 흔하지만 모든 연령에 올 수 있다.

Epidemiology

# ★Risk factors for menigitis

    ; attenuated immunologic response to specific pathogen with young age

           - major risk factor

    - 1mo-12mo 에서 greatest risk

           - 1mo-5yr 사이에서 menigitis가 전체의 95% 차지

    ; recent colonization with pathogenic bacteria

    ; invasive disease를 가진 사람과 close contact

    ; crowding

    ; poverty

    ; black race

    ; male sex

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

# Occult bacteremia를 가진 환자에서 menigitis의 risk가 증가하는데 이때의 etiology상 odds ratio

 pneumococcus ( 85 배 )

 H. influenza type B ( 12 배 )

 meningococcus ( 1 )

# Epidemiology상 유의점들

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

           → bacterial menigitis↑

    ; 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 b의 carriage는 1mo∼4yrs 때 predominent

; invasive H. influenzae type B bacteremia and meningitis

    - unvaccinated children

    - ▲ in infant 2 mo-2yr age

    - peak incidence 6-9mo. (case의 50%가 1세이하)

; 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 (＜1mo) is risk factor for serious infection

    ; incidence : 1-3 / 100,000

    ; peak season - midwinter month

    ; risk factors

  a. black > white ( 5 ∼ 36 배 )

      ( black and sickle cell anemia 시 300 배 이상 )

    b. sickle cell anemia의 4%가 5세이하에서 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

    ① sporadic (group B.) epidemic (A and C)

    ② peak season ; winter and spring

    ③ nasopharyngeal carriage ; 1-15% of adult

    ④ 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 change가 PMN의 small arteriole, vein의 subintimal region으로의 infiltration에 의해 나타나고 vasospasm, vasculitis, thrombosis of small cortical necrosis, occlusion of major venous sinuses, necrotizing arteritis producing subarachnoid hemorrhage, rarely cerebral cortical necrosis가 autopy에서  identifiable thrombosis없이 나타난다.

# cerebral infarction이 vascular occlusion의 sequelae로 나타난다.

# spinal n. root infiltration → meningitis sign

# cranial n. infiltraion → optic, oculomotor, facial, auditory n.에 cranial neuropathy  

# cranial N.의 장애 by IICP

① oculomotor N. palsy ; tentorial herniation 동안 temporal lobe compression에 기인

② abducence N. palsy ; nonlocalized sign of IICP

③ Ⅲ-Ⅵ 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 → IICP↑)

    ; brain extracellular space의 hypotonicity

           --> cell swelling and lysis

           --> cytotoxic edema

# ICP가 종종 300cmH₂0까지 오르는 경우도 있고, reduced cerebral blood flow --> cbr. perfusion pr. (mean arterial-intracranial pr.)가＜50cmH₂0이면 cbr. perfusion이 futher compromised.

# herniation도 meningitis 환아의 약 5%

    ; suggest

           a. marked IICP

           b. cerebral absess

           c. subdural empyema

# neonatal period 지난 후에는 hydrocephalus는 meningitis의 uncommon acute complication이다.

# tentorial, falx, cerebellar herniation : rare

# 때때로 brain base에서 cistern주위의 arachnoid villi의 adhersive thickening에 의해 communicating hydrocephalus가 일어날 수 있다. ---> CSF normal resorption을 interfere.

# less often, foramina magendie, Luschka, aqueduct of Sylvias의 fibrosis and gliosis에 의해 obstructive hydrocephalus가 developed된다.

# raised CSF protein의 원인

    ① BBB의 vascular permeability 증가

    ② capillary or vein에서 subdural space로 albumin rich fluid의 loss.

           ; subdural effusion이 궁극적으로 올 수 있다.( late phase에 온다 )

# ♣Hypoglycorrhachia의 원인 (Reduced CSF Glucose Level)

    ; decreased glucose transport by cerebral tissue

  ; latter may produce a local lactic acidosis

# ♥Mechanism 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

    - *▲common

    - usually precedes or concomitant bacteremia

    - nasopharynx의 bacterial colonization이 usual sourse.

; H. influenza type b와 meningocci

    - epihterial cell에 attach → circulaton

; N. meningitis

    - phagocytic vacule → epitherial cell 에 ingestion

; entry to CSF

    - lateral ventricle의 choroid plexus를 통해

           --> extracerebral CSF와subarachnoid space

           --> rapidly multiply ( ∵ complement와 Ab의 CSF concentration이 bacterial proliferation을 억제하기에는 inadequate )

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

           ① TNF

           ② interleukin I

           ③ PGE2

           ④ cytokine inflammatory mediators

; subsequent inflammatory response

    → neutrophilic infiltration, increased vascular permeability, alteration of the BBB, vascular thrombosis

; excessive cytokine-induced inflammation은 CSF가 sterilized된 후에도 계속되고 이들은 pyogenic meningitis의 chronic inflammatory sequelae에 부분적으로 반영.

; infection의 contiguous focus로부터 bacterial invasion에 의한 menigitis는 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

    ① shock, purpura, DIC, reduced level of consciousness가 rapidly progressive( esp, meningococcal spp.)

    ② 24hr내에 death

  ③ H. influenzae type b and pneumococcal menigitis는rare

# 수일간의 URI or G-I Sx. 선행

# 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

           ① nuchal rigidity

           ② back pain

           ③ Kernig sign : hip을 90°flexion시킨 상태에서 leg extension시 subsequent pain(+)

           ④ Brudzinski sign : supine에서 neck flexion시 knee & hip의 불수의적 flexion

           ; 12 ∼ 18 mo 전에는 not evident

    2) papilledema

           ; IICP 때

           ; uncomplicated meningitis시는 잘 안나타남.

           ; ♥나타난다면

                   a. intracranial abscess

                       b. subdural empyema

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

    3) focal neurologic sign

           ; due to vascular occclusion or focal inflammation     

           ; 10∼20%에서 focal neurologic sign (+)

         ; *pneumococcal menigitis에서 30%이상에서 나타난다

                   - 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

    ; ※91 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%)

           → exacerbate cerebral edema or independently hyponatremia seizure

    ; Tx의 late course에 central diabetes inspidus가 hypothalamus or pituitary dysfunction의 결과로 온다.

5) Fever

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

           - by the 6th day of therapy

    ; prolonged fever (＞10 days)

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

           - *cause

                   / intercurrent viral infection, nosocomial or 2°bacterial infection, thrombophlebitis pericarditis drug reaction, arthritis

    ; *secondary fever

           - afebrile 해진 후에 다시 fever 나타나는 경우

           - 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) ★Thrombocytosis, Eosinophilia, Anemia

    ; *anemia

           - *▲common in H. influenzae

           - causes

                   / hemolysis

                   / BM suppression

8) DIC

    ; *▲often associated with rapidly progressive pattern of presentation

    ; ▲commonly in patient with *shock and prupura (purpura fulminans)

9) ♥Repeated 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

           - ★Suggest

                   / 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 meningitis보다 less ill하여 Ddx하지만, 그렇지 않은 경우가 있어 힘들다.

4) ★Partially Treated Bacterial Meningitis

    ; 25-50% of bacterial meningitis children

    ; CSF를 obtain하기전에 oral antibiotics의 사용한 경우

    ; effects

           - gram stain to less than 60%

           - reduce of incidence of growth of bacteria in CSF culture

    ; ★no effects

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

Diagnosis

; confirm by CSF analysis

① microorganism(+), gram s., c/s

② neutrophilic pleocytosis

③ protein↑

④ glucose↓

# Lumbar puncture (LP)

    ; flexed lateral decubitus position

    ; L3-L4, L4-L5 intervertebral space

    ; ※95주 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 petechiae는 CIx이 되지 않고, immunosuppressed patients with chronic thrombocytopenia을 가진 환자의 경우 transfusion후 가능

    ; ★LP를 위와같은 경우로 인해 연기하더라도 empiric AB Tx.는 즉각적으로 시작해야 한다 

    ; CT scan 상 IICP, brain abscess의 evidence가 있더라도 치료가 delay 되어서는 안된다.

  ; *LP는 IICP가 Tx. 되고 brain abscess가 excluded된 후에 실시한다.

# concurrent immunoelectrophoresis (CIE)

    ; *to identify Ag of ① H. influenzae

                                ② S. pneumoniae

                                ③ N. meningitidis type A, C, Y, W135

# ★Latex Particle Agglutination

    ; *▲popular, widely used

  ; CSF에서 most consistently detect

    ; antigenuria도 common

  ; serum은 false positive가 많아 good specimen이 아니다.

  ; Antibiotics Tx.를 하였더라도 therapy시행 수일내에 Ag을 detect할 수 있다.

    ; H. influenzae type B vaccination을 최근에 받은 환아에서는 urine & serum에서 Ag detection method에서 false(+)

           - CSF에서는 그런 일이 없다.

# blood C/S

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

    ; menigitis가 의심되는 모든 환아에서 시행해야한다

  ; 특히 경험적 항생제를 LP전에 사용한 경우  

# CSF leukocyte counts

    ; usually 1000↑

           - neutrophilic predominance (75-95%)

    ; turbid ＝ leukocyte counts ＞ 200∼400

  ; 정상

           - *neonate : 30개이하, older chikdren : 5∼6개이하

           - lymphocyte, monocyte가 대부분

    ; ★lower CSF leukocyte (＜250)

           - acute bact. meningitis pt의 20%

    ; ★absent 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 menigitis에서의 shift to lymphocyte-monocyte predominance는initial LP후 12∼ 24hr 내에 일어난다

# Gram stain

    ; 70~90% (+)

# Traumatic LP

    ① traumatic LP시 다른 site에 다시 시행시 처음보다 덜 hemorrhagic, CSF내 RBC는 포함됨.

    ② gram stain, c/s, glucose level에 영향을 주지 못함.

        - 그러나 CSF leukocytosis and protein concentration은 영향 (+)

Treatment

Initial AB Therapy

; illness의 innitial manifestation의 nature에 의존한다.

; LP후 즉각적으로 AB Tx

    - 24시간 이내에 rapid progression without IICP

; *LP시행하지않고, brain CT전에 AB Tx, 동시에 IICP Tx

    - *IICP or focal neurologic finding (+)

; more protacted subacute course나 1-7 day period이상 ill

    - IICP, focal neurologic deficits에대한 evaluation해야한다.

; initial (empiric) choice of Tx

    - H. influenza type B, S. pneumoniae, N. meningitidis의antibioitic 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

           / ♣최근에는 PC resistant S. pneumoniae때문에 vancomycin or rifampin를 함께 사용.

    - 실질적으로 24hr이내에 CSF는 sterilization된다.

    - β-lactam antibiotis에 allergic pts

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

           / 많은 bacteria에 bacteristatic agent이지만 H. influensae type b, S. pneumoniae, N.

           / ♥Adverse Effect

                   : aplastic anemia, shock-like gray infant syndrome,

                   : dose depent BM suppression  ∴ drug monitering이 필요.

    - 1-2 Mo의 infant나 T lymphocyte def. 처럼 L. moncytogenes가 원인균으로 생각될 때

           / Ampicillin + Ceftriaxone or Cefotaxime

           / Trimethoprime + Sulfamethoxazole IV도 alternate Tx.

    - ★lmmunocompromised & G(-) bact. meningitis

           / *ceftazidine＋aminoglycoside

Duration Of Antibiotic Theraphy.

# uncomplicate H. influenzae type B meningitis

    ; 7 -10 days

    ; ampicillin에 잘 듣고, β-lactamase 등을 production 하지 않으면 initial AB를 ampicillin으로 change

# penicillin에 relative resistant한 S. pneumoniae (5∼25%) menigitis

    ; CM

    ; 만약 C-M에 resistance하면 vancomycin

# uncomplicated penicillin senstive pneumococcal meningitis

    ; penicillin 30萬U/kg/24hr #4 for 10-14 days

# choice for uncomplicated N. meningitidis meningitis

    ; penicillin 30萬U/kg/24hr #4 for *5-7days

# ※90 causative organism을 발견하지 못하고 CSF상 bacterial infection의 evidence가 있는 경우

    ; ceftriaxone, cefotaxime 7-10 days

# ※82 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

    ; ★Lx. 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 (치료에 효과가 있다고 보여지는 경우)

    ; *Gram stain이 (+) but sterile

    ; increased CSF glucose level

    ; appearance of lymphocyte-monocyte cells

# ♣G(-) Bacillary Meningitis

    ;  3주 동안 or CSF sterilization 2주 후까지 사용

    ; E. coli

           - cefotaxime, ceftriaxone에 대부분 sensitive

    ; P. aeruginosa

           - ceftazidine에 대부분 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.

           - 이 후에는 하루에 한번씩 assesment 시행      

           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

※96 NPO with Ⅳ fluid administration (restricted)

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

    ; IICP나 SIADH 가 없다고 evaluation될 때 까지

           - 1,500-1,700 m1/m2/D

    ; systemic hypotension시 fluid restriction은 not appropriate

           - 왜냐하면 reduced BP로 cerebral perfusion pressure가 50cm H2O이하이면 subsequient                             CNS ischemia가 나타남

# Septic shock 동반시

    ; fluid resuscitation＋vasoactive agent

    (Na-Nitroprusside, dopamine, epinephrine)

    ; goal : blood flow나 vital sign으로의 O2 delivery에 영향을 주지 않고 IICP 방지 

# IICP Tx.

    ; endotracheal intubation & hyperventilation (PCO₂＝25mmHg)

    ; Ⅳ furosemide, Laxis(1mg/kg)

         - intracranial blood valume의 증가 없이 venodilation, diuresis를 통해 brain swelling 감소

    ; mannitol (0.5-1 g/kg) osmotherapy

           - brain과 plasma 사이의 osmolar gradient에 따라 fluid가 CNS에서  plasma로 이동시켜  osmotic diuresis 로 배출시킴.

※96 Seizures

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

           - diazepam이 respiratory supression이 lorazepam 보다 더 높다.

    ; seizure 의 immediate management 후 phenytoin (15∼ 20mg/kg, loading dose, 5mg/kg, maintenance dose)

    ; to reduce the likelihood of recurrence

# ★Dexamethasone Tx (0.15mg/kg/dose q 6hrs × 4 days)

    ; AB medication --> rapid killing of bacteria --> cell lysis로 toxic producrs생성 --> cytokine-mediated inflammatory response

    ; effects

           - less fever

           - lower CSF protein & lactate level reduction

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

    ; 대부분 H. influenzae type b에서는 결과가 있었지만 다른 organism에서도 효과가 있을 것으로 생각됨

    ; 사용시기

           - *antibiotics 투여 직전에 투여하는 것이 maximum benefit

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

Prevention

H. Influenzae Type B

# ★Rifampin prophylaxis

    ; household contacts

           - *close family members less than 4yr no immunized fully가 있는 경우

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

           - diagnosis가 confirm되면 즉각 실시

                   / 2nd index case가 1st case 입원 일주일 이내에 나타날 확률의 50% 이상이기 때문

    ; day-care center contacts

           - less risk than houshold contacts

           - *2 or more index case and not fully immunized children under 2yr이 있는 경우

           - *>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

    ; ※83주 age나 immunization 여부에 관계없이 모든 meningococcal meningitis와 접촉한 사람에 prophylaxis 해야 함

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

    ; vaccine

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

    - Indication

                   / *2세이상의 high risk children

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

Streptococcus pneumonia

    ; normal host는 chemoprophylaxis와 vaccination가 필요없다

  ; high risk patiens는 23-valent pneumoccal vaccine필요

  ; sickle cell anemia pt는 chemoprophylaxis필요 ( 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%

# ※89 Poor Prognostic Sign

    ; < 6 mo

    ; >10⁶ CFU /ml in CSF

    ; seizures more than 4days into therapy

    ; coma or focal neurologic sign on presentation

# *진단 전의 Sx의 duration과 outcome과는 무관

4) neurologic sequele

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

    ; sensorineural hearing loss

           - ▲ of bacterial meningitis

    - cause

                   / labyrinthitis following cochlear infection

                   / direct inflammation of auditory N

           - 빈도

                   / peumococcal menigitis : 30 %

               / menigococcal menigitis : 10 %

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

           - Dexamethasone 사용이 severe hearing loss incidence를 감소시킨다

    - discharge전에 꼭 audiologic assesment

169.2 Viral Meningoencephalitis

; menigitis와 brain tissue에 acute inflammatory process

; CSF : pleocytosis

; absence of microorganisms on Gram stain and Routine culture

; self limited 이지만 some case에서 substantial morbidity와 mortality가 관찰

Etiology

; seasonal pattern (+)

; *enterovirus ( 80 % 이상)

; arbovirus, herpes virus ( common )

; Mumps ( vaccine이 사용되지않는 지역에서 common )

Epidemiology

; 대부분이 enterovirus에 의해 야기되므로 basic epidermiologic pattern은 prevalence를 반영한다

; 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 % 에서 coma, death

           ; HSV-2

                   - neonate ; diffuse brain involvement를 가진 severe encephalitis

                - delivery시 mother로 부터 virus  

    b. varicella zoster virus (VZV)

       ; chicken pox와 일시적으로, 밀접하게 관련된 acute encephalitis 일으킴

    ; *most common manifestation - cerebellar ataxia, acute encephalitis

           ; spinal & cranial nerve root와 ganglia 차단

                   - 나중에 hespes zoster의 형태로 나타남

    c. cytomegalovirus (CMV)

        ; congeital infection or compromised hosts에서 disseminated disease    

    ; normal infant , children : not

    d. Ebstein-Barr virus (EBV)

        ; myriad of CNS syndromes와 관계 ( see chapter 215 )

    e. respiratory virus, Rubella, Rubeolar에 의해서도 meningoencephalitis야기

    f. Mumps meningoencephalitis : mild하지만 드물게 8번 CN에 damage를 주어 deafness 야기

Pathogenesis And Pathology

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

         → to blood stream(seeding) : hematogenous spread

         → several organ infection(further viral multiplication)

         → secondary propagation of large amounts of virus

         → CNS invasion

         → 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 Ag에 대한 host reaction

                : demyelinization, vascular and perivascular destruction

              ← host's vigorous tissue response가 induced

               : 대부분의 neural destruction은 아마 direct viral invasion에 의해 야기 

 3) brain tissue secretion

     <-- meningeal congestion and mononuclear infilteration, perivascular cuffs of lymphocytes and plasma cell myelobreakdown 을 가진  perivascular tissue necrosis

       various stage에서 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

# ♥Specific Form Or Complicating Manifestations Of Encephalitis

    ; Guillain-Barre Syn.

    ; Acute transverse myelitis

    ; Acute hemiplegia

    ; Acute cerebellar ataxia

# progression, severity의 정도는 meningeal and parenchymal invovement의 정도와  agent에 의해 결정  

# illness의 onset은 acute하고 CNS Sx과 sign은 몇일동안의 nonspecipic acute febrile illness 뒤에 온다

# headache, hyperesthesia : common sx, focal or generalized

# aldolesence : retrobulbar pain, fever, nausea, vomiting, neck pain, back pain, leg pain, photophobia, exanthem이 CNS sign과 동반되어 나타나기도 한다

 ( 특히 echovirus, coxachivirus, VZA, mealses, rubella )

Laboratory Abnormality And Diagnosis

 1) CSF. : in viral encephalitis

    ① color : clear

    ② leukocyte : 0 - several thousand

    ③ cell type : PMNL (initial) → Monocyte ( 8 ∼ 12 hr 후 )

    ④ protein : N to slight↑ → brain destruction이 extensive하면 high : HSV encephalitis의 late stage 에.

⑤ glucose : N

         ( Mumps 등 일부에서는 substantial depression of CSF glucose concentration )

2) serum specimen는 illness의 early에 얻어져야 하고 viral culture가

  not diagnotic하다면 2-3wks후에 다시 serologic study를 해야한다                                       

<신>3) serologic method는 too many potential serotypes를 가진 enterovirus의 idenfication에는 not practical하지만

       known circulating viral type에 의해 야기된 case의 confirm에 효과적이다 . ( nonenteroviral CNS infection )

<신>4) PCR: new technique

            not yet clinically available

<신>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 의 attenuated viral vaccine이 effective

Rabies에 대한 domestic animal vaccine program이 rabies encephalitis의 frequency를 낮춘다  

Arbovirus에 대한 vaccine은 less successful

<신>   insect vector의 conrol이 이들 incidenc를 reduce

Treatment

; bacterial cause가 exclude되기 전에 parenteral antibiotics therapy가 administered되어야 한다 

; Herpes simplex  encephalitis에 acyclovir사용을 제외하고는 viral meningoencephalitis의 tx는 nonspecific하다

3) mild infection ; symptomatic relief

  severe infection ; maintaining life and supporting organ system

4)      +-   headache, hyperesthesia ; rest

       |                             non-aspirin containing analgesics

       |                             room light ↓

       |                             noise, visitor ↓

       |    fever : acetaminophen

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

       → 가능하다면 children에서 sign, sx의 misleading을 나타냄으로 이들의

           사용을 최소화하여야 한다

5) all patient with severe encephalitis sould be monitored carefully

6) intracranial pressuree monitoring Ix

       IICP evidence (+)

       epidural space의 pressure transduder의 placement (+)

7) all fluid, electrolyte medication은 parenterally

8) glucose, Mg, Ca : must be maintained : seizure ↓

9) supportive and rehabilitative effort : very important after recovery

 * motor incordination, convulsive disorder, squint, total or partial deafness, behavioral disturbance가 곧 나타난다.

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

                        ; delayed appearance

11) viral meningoencephalities에서 recovery후 grossly normal 일지라도 neurodevelopmental 

        and audiologic evaluation은 반드시 routine follow up 해라

Prognosis

most children completely recover

px : 병의 severity, speicfic etiology, age에 의존

 severe한 case에서 substantial parenchymal involvement의 evidence가 있다면 px는 poor 하고

         intellectual, motor, psychiatric, epileptic, visual. auditory deficiiy가 올 수 있다.

severe  sequelae : HSV 에서 예견

infant에서 older children보다 poor long-term outcome

 ; 최근의 data는 어런 observation을 논박한다

 그러나 enteroviral CNS infection을 가진 2세이하의 patients의 약 10 %에서 seizure, IICP, coma 등 long term neurologic outcomes를 가진다.

Chapter 170. Pneumonia

# non-infectious cause

     ① aspiration of food and/or gastric acid

     ② foreign bodies

     ③ hydrocarbons

     ④ lipoid substance

     ⑤ hypersensitive reaction

     ⑥ 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

        - 숫적으로는 중요하지 않음

        - more severe inf.

        - most common bacteria

           ① Streptococcus pneumoniae

           ② S. pyogens

           ③ Staphylococcus aureus

           ④ Haemophylus influenza type b

        - use of effective vaccines

              --> less common with the widespread

# less common cause

     ① non-respiratory viruses

     ② enteric Gram negative bacteria

     ③ Mycobacteria

     ④ Chlamydia spp.

     ⑤ Rickettsia spp.

     ⑥ Coxillea

     ⑦ Pneumocyst carinii

     ⑧ fungus

# anatomic classification

     ① lobar

     ② lobular

     ③ alveolar

     ④ interstitial

Pneumonias Of Viral Origin

Etiology

# ★Common Viruses

  ; Respiratory syncytial virus (RSV)

  ; parainfluenza viruses 1, 2, 3

  ; influenza viruses

  ; adenoviruses 3, 4, 7

# type & severity of illness

       : age, sex, season, crowding 에 의해 영향

        ① peak age

             bronchiolitis --> 1세 이하

             viral pneumonia --> 2-3세

        ② boy↑

        ③ winter↑

Clinical Manifestation

    1. rhinitis, cough

        temp.↓ 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)

        ① diffuse infiltrate in perihilum

        ② transient lobar infiltrate

        ③ 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 ↑

       - 역학적 도구로 사용

Treatment

1. supportive Tx.

2. some patients --> hospitalization

   : IV fluid, oxygen, assisted ventilation

3.※96 oral amantadine ( or rimantadine)

   ① influenza A --> prevention & Tx

   ② inf. 의 onset 48hr내 사용해야 효과

4. aerosolized ribavirin

   ① RSV

   ② expensive

Prognosis

    1. most children --> recovery with no sequelae

    2. Cx.

       ① bronchiolitis obliterans

       ② unilat. hyperlucent lung

       ③ fatal acute fulminant pneumonia

             - adenovirus 1, 3, 4, 7, 21이 가장 위험

Bacterial Pneumonia

General consideration

; *not a common infection

; ※89 TMC event disturbing the defense mechanism of lung

  - viral inf.

    ① normal secretion의 성상 변화

    ② phagocytosis저해

    ③ modifies bacterial flora

           ④resp. passage의 normal epithelial layer를 disrupt

  - 수일내 종종 bacterial pn.로 진행

; *Recurrent pneumonia

  ① abnormalities of Ab production (e.g. agammaglobulinemia)

    ② cystic fibrosis

  ③ cleft palate                 

    ④ cong. bronchiectasis

  ⑤ ciliary dyskinesia           

    ⑥ TEF

  ⑦ abnormalities of PMNL     

    ⑧ neutropenia

  ⑨ pul. blood flow ↑          

    ⑩ deficient gag reflex

  ⑪ 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

       ① support proliferation of the organism

       ② aid inspread into adjacent portion

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

       cf) bronchopulmonary system --> uninvolved

      # infant

          ① lobar pn. --> 드뭄

          ② bronchial distribution을 따라서 patchy or diffuse ds.

          ③ small airways 주위로 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 ↓)

         --> abrupt high fevr 39℃ ↑, restlessness, apprehension

         --> respiratory distress

                : grunting, flaing of alae nasi,

                  retraction of supraclavicular, intercostal, subcostal area,

                  tachypnea, tachycardia

         --> air hunger & cyanosis

      b. P/E

         ① dullness, B/S↓, fine & crackling rale <-- affected side

         ② abd. distension : reflecting gastric dilatation or ileus

            liver enlargement : Rt. diaphragm downward displacement

                               superimposed cong. heart failure

            menigismus : esp. RUL pn.시

         ③ physical finding은 illness의 clinical course동안 잘 변하지 않는다.

 

   2. Children & Adolescents

      a. brief mild URI

         ① shaking chill, 40.5℃ fever

         ② 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

         ① classic Sg. of consolidation (2-3day)

             - dullness, fremitus↑, tubular B/S, disappearance of rales

         ② resolution

            - moist rales, productive cough with blood tinged mucus

         ③ pleural effusion or empyema

             +-ⅰ) visible lag in respiration on affected side

             |         with excursion↑ on opposite site

             | ⅱ) dullness over area of effusion

             | ⅲ) fremitus & B/S ↑

             +-ⅳ) tubular breathing above fluid level & unaffected side

 

3) Lab/F

      a. ① WBC : 15.000-40.000 (PMNL우세)

             cf) WBC 5.000이하 --> poor Px.

         ② Hb. : normal or sl. decreased

         ③ ABGA : hypoxemia without hypercapnea

     b. isolation of pneumococci

        ① nasopharyngeal secretion

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

        ② pleural fluid from thoracentesis --> diagnostic

        ③ bactetemia : 30% in pneumococcal pn.

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

       ① lobar consolidation : infant or young children에서는 rare

       ② pleural reaction with fluid

       ③ X-ray상 complete resolution

            : 3-4wks after disappearance of all Sx.

5) DDx.

    1. other bacteria and viral pn.

    2. pneumona와 혼동할 수 있는 condition

         ① bronchioliotis          ② CHF

         ③ bronchiectasis의 악화  ④ FB aspiration

         ⑤ sequestered lobe       ⑥ atelectasis

         ⑦ pulmonary abscess     ⑧ allergic bronchitis

    3. RLL pn.를 가진 old children

         --> diaphragmatic irritaton

         --> reffered pain to the RLQ

         --> acute appendicitis와 혼동

    4. severe meningismus

         --> meningitis와 혼동

6) Cx.

    1. concomitant pneumococcal inf. & metastatic inf

          --> infrequent

    2. empyema --> infant

7) Px.

    1. preantibiotic era

         ① mortality rate

             - infant & small children : 20-50%

             - older children : 3-5%

         ② high incidence chronic empyema

    2. 적절한 antibiotics Tx.

          - mortality rate : 1% 이하

8) Tx.

    1. drug of choice

          : Penicillin 10만unit/kg/24hr

    2. decision of hospitalization

           ① severity of illness                          ---+ 에 의존

           ② ability of family to supply good nursing care --+

           ③ young infant

               : hospitalization

                    ⅰ) for IV fluid & antibiotics

                    ⅱ) cilnical course --> more variable

           ④ pleural effusion or empyema

    3. oxygen with resp. distress

           ① sedatives & analgesics의 필요 감소

           ② cyanotic change가 오기전에 공급

Strptococcal Pneumonia

; Gr. A streptococci

; uncommon but predisposing state 존재

    - epidemic influenza, exanthem등

; *3-5세 more frequent

; *rare in infant

Pathology

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

2. lobar pn.는 드뭄

3. *pleurisy ; 비교적 흔함

     --> serous, thinly purulent, fibrin↓

4. lesion

     ① necrosis of tracheobronchial mucosa

     ② formation of ragged ulcer

     ③ large exudate

     ④ edema

     ⑤ localized hemorrage

Clinical Manifestation

; pneumococcal pn.와 유사

; sudden

; *high fever, chills, sg of respiratory distress

; at times, extreme prostration

Laboratory Finding

1. leukocytosis

2. ASLO 증가

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

4. bacteremia : 10%

5. chest X-ray

    ① diffuse bronchopneumonia

    ② often large pleural effusion

6. *complete resolution : 10주 이상

Differential Diagnosis

      ① staphylococcal pn.

      ② mycolasma pn.

Complication

      ① *empyema : 20%

      ② septic foci on bone, joint

Treatment

    ; *Penicillin 10만unit/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 선행

; *30%가 3개월 이하, 70%가 1세 이하

; male ↑

Pathogenesity & Pathology

① confluent bronchopneumonia

② unilat. or prominent on one side

③ extensive area of hemorrhagic necrosis & irregular cavitation

④ multiple abscess

    ; rupture of small subpleural abscess

        --> pyopneumothorax

    --> *bronchopleural fistula

Clinical Manifestation

1) Sx.

 ① 1세 이하 : staphylococcal skin lesion 또는 resp tr. inf의 Sx & Sg

 ② abrupt high fever, cough, resp. distress

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

 ③ GI disturbance with vomiting, anorexia, diarrhea, abd. distention

   ==> *rapid progression이 특징

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 infant에는 tachypnea정도와 맞지 않는 빈약한 소견때문에 misleading 가능

Laboratory Finding

1. WBC 증가

    ; *2만이상 -- older infant & children

  ; *normal WBC in young infant

  ; 5.000 이하시 --> poor Px.

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

3. mild to moderate anemia

4. pleural fluid

     ① exudate with PMNL 300- 100,000/mm³

     ② protein : 2.5g/dl 이상

     ③ low glucose (blood에 비해)

Roentgenographic manifestation

1. 초기

    ; nonspecific bronchopneumonia

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

    ; *Rt. lung : 65%

    ; bilat. - 20%이하

2. pleural effusion or empyema

3. pyopneumothorax

4. pneumatocele

    ; *clinical improvement procede X-ray finding

    ; *persist for months

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

    --> suggestive staphylococcal pneumonia

Differential Diagnosis

1. early stage pneumonia는 DDx.하기 힘듬

2. ★Possibility Of Dx.

  ; abrupt onset & rapid progression of Sx.

  ; Hx. of frunculosis

  ; recent hospital admission

  ; maternal breast abscess

3. ♥Empyema or pneumatocele 을 초래하는 bacterial pneumonia

  ① staphylococcus                

    ② streptococcus

  ③ klebsiella.                    

    ④ H. influenza

  ⑤ pneumococcal pneumonia.     

    ⑥ 1°Tb pneumonia with cavitation

  ⑦ aspiration of nonopaque FB --> pumonary abscess

※93주Complication.

  ; empyema, pyopneumothorax, pneumatocele

         - natural course로 생각하기도 한다.

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

    ; 한글판 (p503)

           - 폐농양, 농흉, 기관지 확장증, 중이염, 부비동염, 심막염, 패혈증, 뇌막염, 골염, 복막염, 산증, 뇌증

Prognosis

1. mortality 10-30%

    ; ※91 varies with

     ① length of illness prior to hospitalization

     ② age of pt.

     ③ adequacy of Tx.

     ④ other illness or Cx.

2. course : 6-10주간 입원

Treatment

- antibiotcs & drainage

- oxygen, semireclining position

- acute phase : IV hydration & nutrition

- blood transfusion, assist ventilation

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

    ; IV immediately after culture (report전까지)

2. ※94 chest tube drainage

    ; *even if small effusion or empyema

  ; BPF 감소, repeated pleural tap의 필요성 감소

    ; largest caliber 사용

    ; *pyopneumothorax시 즉각

    ; removal

        - *improvement & lung expansion되기 시작하면 제거(비록 소량의 pus가 drain되더라도)

    - *5-7일이상은 하지 않음

Haemophilus influenza Pneumonia

; nasopharyngeal inf후

  --> epiglottitis, pneumonia, meningitis

; pneumonia : second in frequency

; *winter - spring

Clinical Manifestation

; *usually lobar pneumonia

; *특징적인 X-ray finding없음

   ⅰ) segmental infiltrate

   ⅱ) single or multiple lobe involvement

   ⅲ) pleural effusion, pneumatocele

   ⅳ) disseminated pul. ds. & bronchopn.

; male ↑

; *more insidious in onset

; *course is usually prolonged over several weeks

; febrile, tachypnea with nasal flaring & retraction

; P/Ex

    ⅰ) rale & tubular B/S

    ⅱ) localized dullness on pucussion

; pathology

 ① PMNL or lymphocytic infl.

 ② extensive dustruction of epithelium of small airway

 ③ interstitial infl.

 ④ 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 culture일때 유용

; if atelectasis --> bronchoscopy로 FB rule out

Complication

; frequent in young infant

     ① bacteremia

     ② pericarditis

     ③ cellulitis

     ④ empyema

     ⑤ meningitis ( # CSF exam.이 H. influenza pn.진단시 꼭 고려됨 )

     ⑥ pyoarthrosis

Treatment

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

      --> initial

; sensitive가 나오면 ampicillin단독 가능

; ⅰ) needle aspiration or closed chest drainage

         --> *initial AB에 반응이 좋으면 oral Tx. for 10- 14days

   ⅱ) open drainage --> infrequently need

; X-ray 상 complete resolution : 2-4주

Carpter 171. Gastroenteritis (전체 chapter가 새로 생김)

# Clinical manifestation

    ; organism과 host에 의존

# Presumptive Etiologic Diagnosis

 ① epidemiologic clue

 ② clinical menifestation

 ③ physical exam.

 ④ knowledge of the pathophysiologic mechanism of enteropathogen

# ★Two Basic Type Of Acute Infectios Diarrhea

  1) inflammatory diarrhea by bacteria

     ① invade the intestine directly

     ② produce cytotoxin

  2) noninflammatory diarrhea

     ① enterotoxine production by some bacteria

     ② *destruction of villus cell by virus

     ③ adherence and/or translocation by bacteria

# ★특징

 ① most self limited --> lab/study가 불필요한 경우가 많다.

 ② all patients require fluid & electrolyte treatment

 ③ a few patients --> antimicrobial Tx.

Epidemiology

# Major Mechanism Of Transmission For Diarrheal Pathogen

  ; fecal-oral ( vehicles : food, water )

# ★Small Inoculation으로 Inf.되는 Enterpathogen

    --> person-to-person contact

   ① shigella

   ② enteric viruses

   ③ G. lambria

   ④ cryptosporidium

   ⑤ 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

           ① infectious agent

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

           ② any enteropathogenic inf. of immunocompromised host

           ③ residual symptom due to damaged intestine

Table 171-2 Noninfectious Causes Of Diarrhea

Bacterial Enteropathogen

     1. inflammatory diarrhea

         ① Aeromonas spp.          ② Campylobacter jejuni

         ③ Closstridium difficile      ④ enteroinvasive E coli

         ⑤ enterohemorrhagic E coli  ⑥ Plesimonas shigelloides

         ⑦ salmonella spp            ⑧ shigella spp.

         ⑨ Vibrio parahemolyticus.    ⑩ Yersinia enterocolitica

     2. noninflammatory diarrhea

         ① enteropathogenic E coli

         ② enterotoxigenc E coli

         ③ V cholerae

    # Antimicrobial Tx의 목적

         ① shorten the clinical course

         ② causative agent 의  secretion 감소

         ③ complication 감소

       Table 171-3

Parasitic Enteropathogen

     1. 종류

         ① G. lambria --> TMC in U.S.A

         ② Cryptosporidium

         ③ Entameba hystolytica

         ④ Strongyloides stercoralis

         ⑤ Isospora belli-----------------+ AIDS에서 발견

         ⑥ Enterocytozoon bieneusi ------+

     2. Stool에서 parasite, ova exam.의 Ix.

         ① Hx. of recent travel to endemic area

         ② other enteropathogen에 대한 stool culture --> negative

         ③ 1 wk. 이상 지속되는 diarrhea

         ④ immunocompromised Pt.

     3. Tx. --> Table 171-4

Viral enteropathogen

         ① rota V

         ② enteric adenoV

         ③ astrovirus

         ④ 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

          : 보통 diarrhea 해소후 일어난다

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

        ① degree of dehydration --> fluid & electrolyte Tx.

        ② prevent spread of enteropathogen

        ③ determine the etiologic agent & provide specific therpy

      # Table 171-6

Exam. of stool

   1. exam for mucus, blood, leukocyte

        --> colitis

     # fecal leukocyte

         ① colonic mucosa를 diffuse하게 invasion

         ② invasive or cytotoxine producing organism

   2. stool culture

       a) 가능한 disease초기에 시행

       # Hemolytic uremic syndrome

           ① blood diarrhea

           ② fecal leukocytes

           ③ immunocompromised Pt.

   3. modified Lab. procedure가 필요한 경우

         ① Y. enterocolitica       ② V parahemolyticus

         ③ V cholera             ④ Aeromonas

         ⑤ C. difficle             ⑥ Comphylobacter

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

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

   6. Proctosigmoidoscopy

        ① colitis의 Sx. 이 심할 때

        ② inflammatory enteritis synd.

Management Of Fluid, Electrolyte & Refeeding

# children

    ; more suseptible than adult to dehydration

        ① assess the degree of dehydration

    ② ongoing loss

    ③ daily requirement

Oral Hydration

    ; Tx. of choice

   1. Home remedies

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

         ① 부적절한 high osmolality --> diarrhea 악화

         ② low sodium conc. --> hyponatremia

         ③ inappropriate carbohydrate to sodium ratio

   2. maintenance sol.

       --> Table 171-7

3. rehydration후 --> refeeding 시도

       breast feeding 은 가능한 빨리 시행

Antidiarrheal Compound

# classification by their mechanism

  ① alteration of intestinal motility

  ② adsorption of fluid or toxin

  ③ alteration of intestial micreflora

  ④ alteration of fluid & electrolyte solution

Prevention

       ① handwashing, gown -> soiling, glove

       ② education to patient & their family

       ③ seperation

Acute Foodborne & Water-Borne Diseases

      # major cause of morbidity & mortality in all developed country

     1. diagnosis

         ① 공통의 음식이나 물을 먹은 사람들에서 유사한 acute illness

         ② nausea, emesis, diarrhes, neurologic Sx.

     2. pathogenesis & severity of bacterial disease의 의존인자

         ① toxin을 생성하는 organism (S. aureus, B. cereus)

         ② 생성된 toxin

         ③ invasive 여부

         ④ 음식내 replication

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

           --> food, water를 통해 inoculation 되는 양에 의존

     4.

        ① epidemiology로 specific agent 의심

        ② incubation period & clinical synd. --> DX

        ③ specific Lab. testing --> confirm

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

         a) 1hr 이내 IP

             ① chemical poisioning

             ② toxins form fish or shellfish

             ③ proformed toxin of S. aureus, or B. cereus

 

         b) long IP

             ① enterotoxin-producing bacteria

             ② invasive bacteria

             ③ Norwalk V.

             ④ some form of mushroom poisioning

Clinical Syndrome

 (Table 171-8)

7. Tx. --> supportive

          예외) fetal

              ① botulism

              ② paralytic shellfish poisioning

              ③ long acting Mushroom poisioning

Chap.172  Osteomyelitis & Septic Arthritis

Osteomyelitis

   # hematogenous O.M : M.C in ≤ 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.의 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 periosteum을 elevation시키기 위해 subperiosteal space에 collection됨

            -> disruption of the periosteal component of blood supply

                 & infarction of cortical bone

 

        * sequestrum

           : formation of necrotic bone area

              -> later stage동안 free foreign body을 형성하기 위해 underlying viable bone과              

                    seperation되거나 or gradual resorption됨

        * involucrum

           : during the reparative phase of acute O.M

            elevated periosteum의 osteogenic precursor cell

              -> new bone formation in the subperiosteal region

              -> infected focus을 enveloped

    5. in infants

       a. transphysial vessels -> traverse the cartilagenous growth plate

                             -> inf.이 marrow cavity, epiphysis로 extend

                             -> pyarthrosis or septic arthritis

       b. ischemic necrosis of growth plate

          -> growth disturbance

    6. Brodie abscess

       : rim of sclerotic tissue로 둘러싸인 subacute or chronic localized abscess

       : 주로 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 이하

  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 procedure후 (heel puncture, fetal scalp monitoring)

    b. pseudoparalysis : in infants

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

    d. multifocal disease(50%↑)

    e. involved bone의 인접 joint 잘 침범

  2. in sickle cell disease

    a. vaso-occlusive crises

    b. multiple bone involve

    c. sta., salmonella

  3. vertebral O.M

    a. 주로 8세 이상의 children에서 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 compression되어 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 biopsy의 material culture : increased positive

    b. if culture method impossible

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

    c. chronic draining O.M

       : bone의 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

         : 조기에 involved된 multiple site을 detect

      d. gallium-67 citrate scan & labelled WBC scan

         : pelvic bone OM

    3) CT

    4) MRI

  3. marker of acute inflammation

    1) WBC 증가

    2) ESR  증가

    3) CRP  증가

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 (2배)

   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

      * exacerbation동안 NSAID & physiotherapy에 response 좋음

      * severe case : steroid

 

  # Diskitis

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

   2. 5세이하 잘 발병 : disk-vertebral interface상의 catilaginous end plate의 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. ESR증가 , WBC normal

   7. X-ray finding

      +- disk space narrowing

      +- irregular erosion of adjacent vert. surface

        -> Sx onset후 1-2주에 (-)

   8. Technetium & gallium scan

Treatment

㉿Table 172-1 & Table 172-2

# ★Initial 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

    ; ESR이 정상이 될때까지 투여한다.

           - 정상이 되지 않은 경우에는 oral AB로 바꾸어 계속 투여한다.

                   / dichloxacillin, oxacillin

                   / minor inf.시 Tx용량보다 2-3배

                   / 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)

# ★Op 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

㉿Table      172-3

Etiology

# H. influenza type b

  ; *▲common 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

  ; *▲common in neonates & at more than 5yr

    ; *2nd ▲common 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 region에 localized된 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 감소

         +- 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

             -> movement시 aggrevated

     . diagnostic sg.

         - localized tenderness over the region of sacroiliac jt.

         - compression of the iliac wing -> pain 증가

  7. gonococcal septic arthritis

     . disseminated bacteremic inf.

     . monoarticular inf.

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

     . disseminated gonococcal inf.

        - female(4배)

        - 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 증가

  2. blood culture : 30-40%(+)

  3. diagnostic arthrocentesis : suspect 되는 all pt.

     * synovial fluid

        . grossly purulent fluid with WBC count > 10만/μL

            : not obtained

        . culture : 70-80%(+)

        . G. stain : 50%(+)

  4. serum or synovial Ag detective test

     : septic arthritis 로 보기에는 불충분한 nonspecific, nonlocalizing Sx으로 oral Abc.로 partially treat된

      환아에 사용

  5. N. gonorrhea

     : recovery of synovial fluid -> difficult

       ∴ 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 가 10-14일 이상 지속시

       : osteoporosis or subluxation

    . OM동반시 : 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 가능

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

    . 5세 이하, 주로 hip

    . viral URI후

    . 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 Tx후)

           +- DGI : rapidly resolve

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

Treatment

# ♥Principle

    ; AB therapy

    ; irrigation & drainage of the joint

  ; immobilization of the joint in a functional position

# ★Duration 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 : 3-5일 지속

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

      jt. inflammation : 5-7일내 resolve but jt. swelling : 10-14일 지속

   4. IV Abc Tx -> high dose oral Tx로 change하는 기준

      . remission of fever

      . reduction in inflammatory marker

      . synovial swelling 감소

   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 test상 PC에 sensitive한 경우

         : oral amoxicillin 3-5일 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 7일 이상 지속시

   12. emergent open drainage of hip 의 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

      . 치료 첫72시간 or synovial inflammation 소견 improve 될 때 까지 functional position으로 joint

          immobilization (splint)

         -> 이후 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 나타난지 5일 경과)

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

        . hip or shoulder jt. involve

        . associated OM with epiphyseal damage

Chapter 173. Infections In The Compromised Host

 

^신* 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

★Table 173-1

★Table 173-2

Clinical Manifestation

   * immunocompromised host 의 inf.시 general clinical features

     a. any organism

        : immunocompromised host에서 potentioal pathogen

     b. fever : sensitive & specific sg.

     c. fever외 다른 Sx & Sg없을 수도 있다

     d. skin & mucous memb.의 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. 5세이상 children에서 CD4⁺ T lymhyocyte count 200/mm³이하 (20%이하)

         : HIV infected pt.에서 P. carinii pneumonia의 risk증가

     g. mutiple inf. : common

     h. known & suspected bact. inf.

         : maximal tolerated dose로 즉시 Abc 치료

     i. inf. Tx로 이용되는 drug : side effect 가짐

Infection In Pts With Immunodeficiency

Ab deficiency

    (1) X-linked agammaglobulinemia

       : S. aureus, H. influenza, strep. pneumoniae등에 susceptible

       : viral & protozoal inf.

       : 주로 upper & lower resp. tracts

          -> chronic & recurrent pul. inf.

          -> bronchiectasis

       : arthritis & pneumonitis -> mycoplasma

       : enteritis -> salmonella & campylobacter

    (2) selective Ig A defi.

       : viral inf.에 대한 susceptability는 no increase

    (3) hyper-IgM synd.

       : Ig G, Ig A & Ig E 감소 & neutropenia

       : agammagolbulinemia의 특징적인 inf.외에도 P. carinii pneumonitis의 risk증가

    (4) IgG subclass defi.

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

       # IgG subclass 2 defi.

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

                                 polysaccharide bacterial vaccine에 대해 poor Ab response 보임

Defect in cell-mediated immunity

    a. cong. T-lymphocyte defi.

           +- T-lym. function 감소

           +- 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. 초래

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. 증가 : 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

     ^신* CGD - normal neutrophil count

              - deficient mechanism of bact. killing

     ^신* 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 pt에서 granuloma resolve

        d. granulocyte transfusion

             - bact. or fungus : IV bactericidal Abc에 unresponsive할때

             - 단점 : .expensive

                      .CM virus inf. risk증가

                      .allosensitization to HLA Ag.

                      .GVH dis. in immunosuppressed pts

                      .amphotericin B 과 combine시 pul. infiltrate & hypoxia

                      .transfusion reaction

    . prevention

       ^신CGP pt. : broad spectrum Abc combination trimethoprim-sulfamethoxazole

                    -> improve phagocytic killing

                 : recombinent human interferon-γ

                    (50 μg/M² subcutaneous 3회/wk)

                     + oral trimethoprim-sulfamethoxazole

                    -> inf. rate 감소

Defective Opsonization

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

        : bact. inf.증가

           - strep. pneumoniae, H. influenza, salmonella

     . PC prophylaxis

        : sickle cell dis. & age 6Mo이상

     . routine immunization 외에도 2세때 pneumococcal vacination

Infection With Organ & Tissue Transplantation

BM transplantation

Autologus BMT

      : 5-10%, 주로 lung

Allogenic BMT

     a. inf. & GVH dis. : serious Cx.

     b. 주로 G(-) bacilli & G(+) cocci

    ^신c. table 173-3

          # transplantation 후 1Mo

          . granulocytopenia : profound

          . mucous memb. damage -> mucositis

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

          . RS virus pneumonitis

              : serious consequence

      # BMT후 30-100일

          . granulocytopenia보다는 immune system의 derangement에 의해

          . CM virus : no prophylaxis 시 50-60% infected

          . interstitial pneumonia

               - common in leukemia pt.

               - BMT후 60일경에 occur

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

 

      # BMT 100일 후의 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 

            . transplantation후 경과한 시간

            . neutropenia

            . acute or chronic G-V-H dis.

       2. approach : febrile neutropenia patient with malignancy 와 같음

                    - prompt institution of empiric bactericidal broad-spectrum antibiotics

                    - neutrophil count 가 500이상 될 때까지 계속

       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 BMT후 120일 동안 weekly blood, urine, throat culture

Liver transplant

  ^신1) 1st Mo posttransplantation

       . highest risk of inf.

       . average 2.5 episode of inf.

   2) 2nd & 3rd Mo동안

       : inf. rate감소 (0.35, 0.17 episodes)

   3) surgical procedure

       : biliary & liver로 G-I tract microbial flora inf.증가

   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 rejection과 구분 필요

                       by liver biopsy, Gram stain, culture

       . hepatic abscess : biliary or vascular obst.때문

                        (cf. cholangitis : biliary stricture or the use of ERCP때문)

       . 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

       . EBV의 reactivation

           a. mononucleosis-like synd.일으킴

           b. late-onset lymphoproliferative synd.으로 진행

           c. immunosuppresive therapy의 dosage줄임으로 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 와 rejection구분

 

   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

     ^신 a. UTI  - TMC inf.

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

                - 이시기에 p. aeruginosa : MC cause

                - 1st Mo 이후 : E. coli MC

     ^신 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)는 antibiotics 쓰기 전

       c. biopsy : rejection 과 inf.구분

   3) prevention

      a. Trimethoprime-sulfamethoxazole

          : pyelonephritis & P. carinii pneumonitis의 incidence줄임

      b. careful evalution of the urinary tract for abnormalities

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

          : recurrent  urinary tract inf.의 원인 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 이상을 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 이하

       : 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

  ; ★Coagulase(-) Staphylococci, S. Aureus, α-Hemolytic Strep.

           - *▲frequent in bood culture

      b. alpha-hemolytic streptococcal bacteremia중에서

         : acute septic shock synd. occur

            - adult resp. distress synd.과 유사

            - cytarabine 투여시 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.에 의한 septic shock (30-50% of episode) 보다 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 500이상 될때 obvious

              : noninfectious disorder 에 의해서도 나타남

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

                  radiation or CTx-induced pneumonitis )

 

          . G(-) enteric bacteria or fungus에 의해

               # 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 lesion상 pseudohyphae(+) : disseminated candidiasis

       g. serum CRP ≥ 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

         . 그후 S. epidermidis 나타날 경우

            : vancomycin 첨가

         . monotherapy는 mild neutropenia(500-1,000 neutrophil)경우이면서 S. epidermidis가 pathogen이라

          생각 되지 않을때 사용

       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 72시간 후 afebrile 해지고, bacterial source 가 identify되는 경우

           - Tx. should be modified based on the antibiotic sensitivity

           - 그러나 spectrum이 너무 좁아지면 bacteremia가 나타날 risk가 높기 때문에 broad spectrum

               antibiotic 를 계속 사용해야 한다.

        2) antibiotic Tx는 response가 좋은 (afebrile, negative repeat culture,

           free of signs and symptoms of inf.) pt.에서 적어도 7일간 사용

        3) antibiotics가 stop된후 neutrophil count는 500을 넘어야 한다.

 

        4) high risk pt.

            - profound neutropenia, mucositis

            - signs of persistent inf.

            - central line tract inf.

            - bleeding

            - impending invasive procedure or chemotherapy

          경우 neutrophil count가 500이상 될 때 까지 antibiotics를 계속 사용하는 것이 benefit하다.

        5) 어떤 clinicians은 defervescence or clinical well-being에 상관없이 fever와

            neutropenia가 있는 모든 환자는 neutrophil count가 500이상 될때까지

            antibiotics를 계속 사용하여야 한다고 권고한다.

        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) ill하여 보이거나 inf.의 manifestation이 progress할 경우

            - vancomycin or 3rd generation cephalosporin을 첨가

           (initial empiric regimen에 들어있지 않은 경우)

        9) antibiotics를 modification하였는데도 불구하고 neutropenic하면서 7일 간 febrile한경우

            1. intravenous amphotericin B를 start함

               (33%에서 invasive fungal ds. 가짐)

            2. amphotericin B를 initiation 하기 전 invasive candidiasis, aspergillosis, or mucormycosis의 

               source를 결정하기 위해 행하여야 할 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.이 identify 안된 경우)

                - 그 후 stop하여 환자 condition 을 re-evaluate

           4. documented fungal inf. 경우

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

                   or deep abscess

           5. side effect : nephrotoxicity

              - 줄이기 위해 nephrotoxic drug의 사용을 줄임

            (aminoglycoside -> 3rd generation cephalosporin 대체,

              chemotherapeutic agent(cisplatin) 사용 줄임)

           6. new fungal agent (fluconazole)

              - effective

              - amphotericin 이 not tolerate 하거나 severe nephrotoxicity가 있는 경우

      10) central venous catheter, implanted device에 의한 documented bacteremia

           ( catheter-related sepsis )

             - bacteremia발생시 antibiotics를 line의 sterilization을 위해 lumen내로 주입

             - 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 patient의 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