¼±Åà - È­»ìǥŰ/¿£ÅÍŰ ´Ý±â - ESC

 

Part 17-2. Infectious Diseases

SECTION 3. Bacterial infections

Section 3. Bacterial Infections

Chapter 174. Staphylococcal Infection

174.1. Infection Due To Staphylococcus Aureus

Etiology

 : group I - group IV

 * Toxin released from S. aureus

¡ÚExotoxin

4 Immunological Distinct Hemolysin

   ¨ç ¥á-hemolysin: cell membrane¿¡ ÀÛ¿ë

                   tissue necrosis, injury to leukocyte, platelet aggregation, smooth m. spasm

   ¨è ¥â-hemolysin: degrade spingomyelin

                   ¡æ RBC hemolysis

   ¨é ¥ä-hemolysin: detergent like action

                   ¡æ membrane disruption

   ¨ê ¥ã-hemolysin: act on cell membrane

Leukocidin

   : phagocytic cellÀÇ phospholipid¿Í combineÇÏ¿© permeabilityÁõ°¡

     leakage of protein, eventual death of neutorphil & macrophage

Exfoliative Toxin A & B

    ; dermatologic localized (e.g. bullous impetigo) or generalized (e.g. scalded skin syndrome, scarletiniform eruption) complication

    ; A - chromosomal gene product

  ; B - plasmid gene product

Staphylococcal Enterotoxin

    ; type A, B, C1, C2, D, E

  ; Enterotoxin A or B ingestion

   ¨ç vomiting, diarrhea, profound hypotension

   ¨è enterotoxin A & enterotoxin B: associated with nonmenstrual TSS

TSS toxin-1 (TSST-1)

   ¨ç associated with TSS related to mensturation & focal staphyloccal inf.

   ¨è produce interleukin I & tumor necrosis factor

      : hypotension, fever multisystem involvement

Enzyme

  1. coagulase: S. aureus, S. epidermis, & other coagulase-negative staphylococcus±¸ºÐ

               ¡æ fibrinogen°ú interacting¿¡ ÀÇÇØ plasma clot

  2. catalase: inactivate H2O2, promoting intracellular survival

  3. penicillinase or beta-lactamase: inactivate penicilline at molecular level

  4. hyaluronidase: spreading factor

  5. lipase

  6. phosphodiesterase

Agglutinogen (Protein A)

  1. S. aureus´ëºÎºÐ Á¾¿¡¼­ °¡Áö°í ÀÖÀ½

  2. react with Fc fragment of IgG

  3. generate C'-derived chemotactic factor

     antiphagocytic activities

Capsular antigen 5, 8

    : 70%¿¡¼­ phagocyte¿¡ resistant

Cell Wall Peptidoglycan

  1. polysaccharide polymer

  2. endogenous pyrogen production from monocytes

  3. chemotactic effect

  4. C' activation

  5. endotoxin like effect

  6. opsonic antibody production stimulation

Loose Polysaccharide Capsule Or Slime Layer

Epidemiology

 1. »ýÈÄ 1ÁÖ³»¿¡ 20-30%ÀÇ neonate¿¡¼­ ant. nare¿¡ colonization

 2. transmission

  ¨ç direct contact or spread of heavy particle (6ftÀÌÇÏ)

  ¨è spread by fomite: rare

  ¨é autoinfection: common

  ¨ê minor infection (e.g., styes, pustules, paronychia)

 3. heavily colonized individuals, perianal carriers

   : ƯÈ÷ effectiveÇÑ disseminators

 4. neonate¿¡¼­ most common site of colonization

   : nasopharynx, skin, perineum, umbilical stump

Pathogenesis

 1. staphylococcal disease development is related to

    ¨ç infection¿¡ ´ëÇÑ hostÀÇ resistance

    ¨è virulance of the organism

 2. mucocutaneous barriers defect

    ¨ç by: trauma, surgery, foreign surfaces(e.g., sutures, shunts, intravascular catheters), burns

    ¨è S. aureus°¡ cell wallÀÇ teichoic acid¿¡ ÀÇÇØ mucosal cell adhesion.

     submucous, subcutaneous site¿¡ exposure´Â fibrinogen, fibronectin, laminin, collagen IV¿¡

     adhesionÁõ°¡

 3. protein A

    ¨ç S. aureus¿¡¼­´Â ³ª¿À°í S. epidermis¿¡¼­´Â »ý¼º ¾ÈµÊ

    ¨è bacteriaÀÇ outermost coat¿¡ À§Ä¡

    ¨é IgG1, IgG2, IgG4¿Í react

    ¨ê serum IgÀ» absorb

    ¨ë inhibiting phagocytosis

 4. G-I tract¿¡¼­ÀÇ S. aureusÀÇ infectionÀº other bacterial speciesÀÇ prevalence¿¡ ÀÇÇØ control µÇ´Âµ¥, ÀÌ

    balance°¡ Ç×»ýÁ¦Ä¡·áÁß ±úÁö¸é Staphylococcus°¡ proliferation & bowel wall invasion.

   G-I tract³»¿¡¼­ StaphylococcusÀÇ enterotoxinÀÇ elaboration. performed enterotoxinÀÇ ingestionÀ¸·Î

    tissue invasion¾øÀÌ diseaseÀ¯¹ß °¡´ÉÇÔ.

 5. antibody°¡ Á¸ÀçÇÑ´Ù°í ÇØ¼­ staphylococcal disease¸¦ ¾ðÁ¦³ª protectÇÒ¼ö ÀÖ´Â °ÍÀº ¾Æ´Ô

   : Áï healthy infant¿¡¼­ disseminated S. aureus ds.´Â viral inf.¼±ÇàÈÄ ¹ß»ýÇÒ¼ö ÀÖÀ½.

     viral infectionÀº neutrophil or respiratory epithelial cell function suppress.

 6. Staphylococcal infectionÀÇ risk°¡ Áõ°¡µÇ´Â °æ¿ì

  ¨ç C' systemÀÇ congenital or acquired defect

  ¨è defective chemotaxis (Job, Chediak-Higashi, Wiskott-Aldrich, & lazy leukocytes synd.)

  ¨é defective phagocytosis

  ¨ê defective humoral immunity (antibodies required for opsonization)

  ¨ë impaired intracellular bacterial capacity

 7. impaired mobilization of PMNL in

  ¨ç children with DKA

  ¨è healthy individual following ingestion of alcohol

Clinical Manifestion

 : most common located in the skin as a infection site

Newborn

    : general sepsis, meningitis, pneumonia, otitis media, conjunctivitis, ostemyelitis, & septic

      arthritis

Skin

    ; *impetigo contagiosa, ecthyma, bullous impetigo, folliculitis, hydradenitis, furuncles, carbuncles, SSSS(Ritter disease), syndrome resembling scarlet fever

    ; recurrent furunculitis

           - unknown etiology,

                          repeated pyoderma over several months to yrs.

                          should evaluate for immunity

Respiratory Tracts

  1. rare: URI, otitis media & sinusitis, suppurative parotitis, tonsillopharyngitis

          cystic fibrosis³ª WBC function defects°¡Áø ȯ¾Æ¿¡¼­ Staphylococcal sinusitis´Â

           common

  2. tracheitis: croup°ú À¯»ç

   ¨ç high fever, leukocytosis, upper airway obstruction evidence

   ¨è normal epiglottitis with subglottic narrowing

      thick purulent secretion within the trachea

       (direct laryngoscopy or bronchoscopy)

  3. pneumonia

   ¨ç 1¼¼ÀÌÇÏ¿¡¼­´Â ÀϽÃÀûÀ¸·Î acute bronchiolitisµ¿¹Ý

   ¨è high fever, abd. pain, tachypnea, dyspnea, localized or diffuse bronchopneumonia or

      lobar disease

   ¨é cause necrotizing penumonitis

      : empyema, pneumatocele, pyopneumothorax, bronchopleural fistula

   ¨ê nonproductive coughing

  4. sepsis

   ¨ç if appropriate antibiotic Tx.

      : blood culture may remain (+) for 24-48hr.

   ¨è fever decreased

      : median 22 hr (8-90hr)

   ¨é return of body temperature to normal

      : 58 hr (12-180hr)

   ¨ê DDx sepsis with endocarditis

     a. echocardiographic evidence of vegetation

     b. intravenous drug abuse

     c. presence of immune complex & antistaphylococcal antibody

     d. absence of primary focus of infection

Muscle

   ¨ç tropical pyomyositis: localized staphylococcal abscess in muscle, muscle enzymeÁõ°¡,

                          septicemia (-)

   ¨è multiple abscess in 30-40% of cases

Bone & Joints

CNS

    : meningitis associated with

     a. cranial trauma

        neurosurgery (e.g., craniotomy, CSF shunt placement)

     b. endocarditis, parameningeal foci (e.g., epidural or brain abscess), DM

        less frequently with malignancy

Heart

# *acute bacterial endocarditis

    ; native valve common cause

Kidney

: UTI is unusual

Toxic Shock Syndrome

Intestinal Tract

# Sta. enterocolitis

       : overgrowth of normal bowel flora by Sta.

         most common follow use of broad spectrum oral antibiotic Tx.

# peitonitis: CAPD pt.¿¡¼­ common

                 ¡æ catheter tunnel involve·Î

# food poisoning

    ; caused by enterotoxin ingestion

    ; 2-7hrÈÄ¿¡ sudden, severe vomiting

           --> *watery diarrhea : fever is absent or low

    ; *not persist longer than 12-24hr

Diagnosis

 1. isolation of the organism: skin lesions, abscess cavities, blood, CSF, or other site of inf.

 2. identification by Gram stain, coagulase, mannitol reactivity

Differential Diagnosis

 1. skin lesion by S. aureus & group A ¥â-hemolytic staphylococcus

 2. staphylococcal pneumonia & other bact. (Klebsiella, many anaerobes) origin pn.

 3. fluctant skin & soft tissue lesion

    lesion by: Mycobacterium, Francisella tularensis, various fungi, cat-scratch ds.

Prevention

# ¡ÚStrict Attention To Handwashing Technique

  ; *¡ãeffective measure for prevention of spread

2. used detergents

   : iodopher, chlorhexidine, hexachlorphene

 3. infectious disease control measures (Table 174-1)

 4. ICU¿¡¼­ stress ulcerÀÇ risk°ËÅäÀ§ÇØ H2-blockerº¸´Ù Sucralfate¸¦ ¾¸À¸·Î¼­ S. aureusÀÇ gastric

   colonizationÀ» °¨¼Ò½Ãų ¼ö ÀÖ´Ù. À̰ÍÀº sucralfate·Î natural gastric acidity¸¦ À¯Áö ÇÔÀ¸·Î½á

   2Â÷ÀûÀ¸·Î colonizationÀÇ °¨¼Ò¸¦ °¡Á®¿Â´Ù. ÀÌ·¯ÇÑ Â÷ÀÌ´Â pneumonia¿¡¼­µµ °¨¼Ò¸¦ °¡Á®¿Â´Ù.

 5. patient with recurrent staphylococcal frunculosis

    : Tx. with hexachlorophene & dicloxacilline or clindamycin to prevent recurrence

 6. food poisoning

Treatment

# ¡ÚChildren With Abscesses

    ; *AB alone is rarely effective

    ; *should be relieved by incision & drainage

# ¡ÚInitial AB

    ; penicillinase-resistant antibiotics

    ; methicillin, nafcilline

  ¨ç this stability°¡ large bacterial burdenÀÌ ÀÖÀ»¶§ ¥â-lactam antibioticsÀÇ antibacterial activity¸¦

     neutralize½ÃŰ´Â inoculum effect¿¡ ´ëÇØ °¡Àå Áß¿äÇÑ ¿ä¼Ò´Ù.

  ¨è general dose: 200mg/kg/24hr (IV in six divided doses)

 3. Staphylococcal pn.

  ¨ç 72½Ã°£ÀÌ»ó ¿­ÀÌ ¾ø°Å³ª ´Ù¸¥ infection signÀÌ ¾øÀ» ¶§±îÁö IV antibiotics ¼±ÅÃ

  ¨è ±×ÈÄ oral antibiotics¸¦ Àû¾îµµ 3ÁÖÀÌ»ó »ç¿ë

# ¡ÚMeningitis, Osteomyelitis, Endocarditis

  ; *IV Ä¡·á ³¡³ªµµ °è¼ÓÇØ¼­ PO·Î Ä¡·á¸¦ Áö¼ÓÇØ¾ß ÇÑ´Ù.

           - *Dicloxacillin 50-75mg/kg/24hr in four divided oral doses

                   / due to well absorption & quite effective

# skin & soft tissue infection & minor upper respiratory infection

  ¨ç managed by oral therapy alone or initial brief course of antibiotics provided parenterally,

        followed by oral medication

    : dicloxacillin (25-50mg/kg/24hr), oxacillin (100mg/kg/24hr), nafcillin (100mg/kg/24hr)

  ¨è amoxacillin (40mg/kg/24hr in three divided dose) + clavulonic acid

    : also effective

 6. very mild, localized skin infection

  ¨ç repeated cleasing with a mild antiseptic & use of topical antibiotics

    (bacitracin, mupirocin)

  ¨è penicillin should not be applied topically

  ¨é penicillin G: vitro¿¡¼­ S. aureus¿¡ ´ëÇØ sensitivityº¸À̸é infection Tx.¿¡ »ç¿ë

  ¨ê penicillin¿¡ sensitiveÇÑ pt.ÀÇ 5%¿¡¼­ cephalosporin¿¡ sensitive

# ¡ÚClindamycin, Lincomycin

  ; effective for skin, soft tissue, bone, joint infection

    ; *should not be used in endocarditis, brain abscess, meningitis

    ; clindamycin IV or oral: total daily dose - 30-40mg/kg/24hr #3-4

# vancomycin

  ¨ç penicillin¿¡ sensitiveÇÑ ptÀÇ endocarditis¿¡ »ç¿ë

  ¨è peak S-conc.: 25-40¥ìg/ml

  ¨é dosage: 10-15mg/kg/dose q 6hrs IV

 9. vancomycin or teicoplanin: semisynthetic penicillinÁ¾·ù¿¡ resistantÇÑ severe bacteremic

                              staphylococcal infection¿¡ »ç¿ë

 

 10. ciprofloxacin, other quinolone antibiotics

    : serious staphylococcal infection½Ã Áö¼ÓÀûÀÎ high cure rate¸¦ ¾òÀ» ¼ö ¾ø¾î¼­ should not be used

 11. staphylococcal infection of the CNS

  ¨ç IV methicillin or nafcillin

  ¨è in penicillin allergic pt: vancomycin, bactrim, imipenem

  ¨é surgery¶§¿¡´Â vancomycin¿¡ synergic effectÀ§ÇØ rifampinÃß°¡

Methicillin Resistant Staphylococcus Aureus: MRSA

   : become major nosocomial pathogen

 1. most MRSA belong to phage group II (type 77, 83A, 84, 85)

    ±×¿Ü, phage type I & nontypable strain¿¡¼­ reportµÊ

 2. MRSA stains

  ¨ç methicillin sensitiveÇÑ counterpart¿¡ ´ëÇØ¼­µµ virulentÇÑ effectº¸ÀÓ

  ¨è À̰æ¿ì

     : vancomycin (drug of choice) & teicoplaninÀÌ effective

  ¨é cepahlosporin°ú imipenem¿¡ ´ëÇØ¼­´Â resistant

     trimethoprim-sulfamethoxasole, ciprofloxacin¿¡´Â sensitive

 3. MRSA¹ß°ß½Ã °¨¿°¹ÞÀº ȯÀÚÀÇ °Ý¸®°¡ preventionÀÇ most effective method

Prognosis

 1. untreated staphylococcal septicemia: 80%ÀÌ»óÀÇ mortality

    ÀûÀýÇÑ antibiotic treatment·Î 20%ÀÌ»óÀÇ mortalityÁÙÀÓ

 2. grave prognostic sign

  ¨ç WBC < 5,000/mm3

  ¨è PMNL response < 50%

 3. prognosis¿¡ ¿µÇâÀ» ÁÖ´Â factors

  ¨ç nutrition

  ¨è immunologic competence

  ¨é presence or absence of other debilitating disease

174.2. Infection Due To Coagulase Negative Staphylococcus

 1. S. epidermis: CONS 11Á¾ Áß 1Á¾·ù

    : ½ÇÁ¦ avirulant commensal bacteriaÀ̳ª nosocomial infectionÀ» ¾Æ·¡ÀÇ °æ¿ì ÀÏÀ¸Å³ ¼ö ÀÖ´Ù.

  ¨ç indwelling foreign device

     a. IV catheters - sepsis

     b. hemodialysis shunts & grafts - sepsis

     c. CSF shunts - meningitis

     d. peritoneal dialysis catheters - peritonitis

     e. pacemaker wires & electrodes - pocket infection

     f. prosthetic cardiac valves - endocarditis

     g. urinary catheters - pyelonephritis

     h. prosthetic joints - arthritis

  ¨è surgical trauma

    : sternal ostoemyelitis, endophthalmitis

  ¨é immunocompromized state

    : malignancy, granulocytopenia, neonates

  ¨ê community acquired disease in patient with no underlying disease

    : UTI, osteomyelitis

Epidemiology

 1. CONS´Â skin, throat, mouth, vagina, urethraÀÇ normal inhibitant

 2. S. epidermis : skin°ú mucous membrane¿¡ Á¸ÀçÇÏ´Â staphylococciÀÇ 65-90%¸¦ Â÷ÁöÇÏ´Â most common & persistant species.

 3. CONSÀÇ epidemiologic purpose

    : identified organism by

  ¨ç phage typing

  ¨è antibiotic sensitivity

  ¨é slime layer production

  ¨ê molecular DNA method

    (chromosomal & phage DNA hybridization restriction enzyme analysis)

Pathogenesis

 * S. epidermis´Â exopolysaccharide production biofilm (slime) »ý»ê

    role 1. enhance adlhesion to foreign surface

        2. resist phagocytosis

        3. impair penetration of antibiotics

Clinical manifestation

 1) Clinical features

  1. bacteremia

  2. endocarditis

  3. central venous catheter infection

  4. central venous system CSF shunt

  5. UTI

 2) bacteremia

    : CONSÁß S. epidermis°¡ most common cause of nosocomial bacteremia

  1. neonate¿¡¼­ÀÇ S. epdermis bacteremia clinical manifestation

     : apnea, bradycardia, temperature instability, abdominal distension, hematochezia, cutaneous

       abscess, CSF pleocytosis (-) meningitis

       ÀûÀýÇÑ antibiotic Tx.¿¡µµ ºÒ±¸Çϰí (2ÁÖÀÌ»ó) persistant positive blood culture

  2. malignancy or BM transplantation ¹ÞÀº ȯÀÚÀÇ S. epidermis bacteremia

    : associated with neutropenia, central venous access (Hickman or Broviac catheters), & G-I obstruction

  3. º¸Åë overwhelming sepsis shock (-), indolent

 3) endocarditis

 4) central venous catheter infection

 5) central venous system CSF shunt

  1. S. epidermis: CSF shunt meningitisÀÇ most common pathogen

  2. most (70-80%) infection: ¼ö¼ú 2 mo.³»¿¡ ¹ßÇö

 6) UTI

  1. S. epidermis: asymptomatic UTI

                  most common pathogen for peritonitis in patients on continuous ambulatory

                   peritoneal diaylsis

  2. S. saprophyticus: symptomatic UTI, in previously healthy & sexually active teenage girls

Diagnosis

 * bacteremia¸¦ suspectÇÒ ¼ö ÀÖ´Â ¼Ò°ß

  1. blood culture»ó rapid growth (24½Ã°£À̳»)

  2. µ¿ÀÏÇÑ CONS¿¡ ´ëÇØ 2¹ø ÀÌ»óÀÇ blood cuture¿¡¼­ positive

  3. central venous catheterº¸´Ù peripheral venous blood culture¿¡¼­ quantitative colony count º¸ÀÏ ¶§

Treatment

 1. vancomycin

    : drug of choice for methicillin resistant S. epidermis

 2. quinolone & teicoplanin

    : some activity against CONS, vancomycin¿¡ rifampin, GMÃß°¡´Â efficacyÁõ°¡

 3. CONS infectionÀÌ foreign body, catheter valve, shuntµî°ú °ü·Ã½Ã cureÀ§ÇØ ¸ðµÎ Á¦°Å

    : central lineÀÇ »ç¿ëÀ» preserveÇϱâ À§ÇØ IV vancomycin Tx.¸¦ ½ÃµµÇϱ⵵ ÇÔ

 4. peritonitis in pt. in CAPD

    : dialysis catheter»ÌÁö ¾Ê°í IV or intraperitoneal antibiotics·Î Tx½Ã ¹ß»ýÇÒ ¼ö ÀÖ´Â

      another infection

Prognosis

  poor prognosis asso. with malignancy, neutropenia, infected prosthetic or native Ht. valve

174.3 Toxic Shock Syndrome

 * Á¤ÀÇ: acute multisystemic disease

   Ư¡: high fever, hypotonia, vomiting, abd. pain, diarrhea, myalgia, non focal neurologic

         abnormalities, erythematous rash

Etiology & Epidemiology

 1. many cases: tamponȤÀº vaginal devices (e.g., diaphragm, contraceptive sponge)»ç¿ëÇÏ´Â 15-25¼¼ÀÇ

                menstruating woman¿¡¼­ ¹ß»ý. S. aureusÀÇ toxin-producing strainÀÇ vaginal colonization

                ȤÀº infectionµ¿¹Ý

 2. nonmenstrual TSS associated with

    : wounds, nasal packing, sinusitis, tracheitis, pneumonia, empyema, abscess, burn,

      osteomyelitis, primary bacteremia

 3. antibiotic Tx. (-)¶§ menstural TSS¿¡¼­

    : original episode 3mo.À̳»¿¡ overall mortality rate - 3%

# phage group I sta. aureus

    ; major isolated strain from confirmed cases

    ; not invasive, not adhere to vaginal epithelium

    ; produce extracellular toxins : TSST-I

        --> *massive fluid loss from intravascular space

                - *by directly or by producing interleukin I & TNF

  ¨é TSST-I negative strainÀÌ TSS°¡Áø patient¿¡¼­ ¹ß°ßµÊ. À̰ÍÀº ´Ù¸¥ toxinÀÌ °ü°èÇÏ´Â °ÍÀ¸·Î ¿©°ÜÁü.

    Áï TSST-IÀÌ essentialÇÑ pathogenic factor´Â ¾Æ´Ô

    virtro study¿¡¼­ À̵é toxinµéÀº neutral pH, high Pco2, "aerobic" Pco2ÀÇ È¯°æ¿¡¼­ ¼±ÅÃÀûÀ¸·Î »ý»êµÇ´Âµ¥ 

    À̰ÍÀº menstruation tampon »ç¿ëÇÏ´Â vagina¿¡¼­ ¹ß°ßµÇ´Â conditionÀÌ´Ù.

Clinical Manifestation

¡ÚTable 174-2

 1. at onset

    : abrupt high fever, vomiting, diarrhea, sore throat, headache, myalgia

 2. diffuse erythematous macular rash (sunburn-like) within 24hr

    : petechia may developed on 3-4 day

 3. other Sx.

    : ÀǽÄÀå¾Ö, oliguria

      hypotension (shock or DIC¸¦ º¸ÀÌ´Â severe case·Î ¹ßÀü°¡´É)

 4. most frequent manifestation

    : diarrhea(98%) > myalgia(96%) > emesis(92%) > 40¡ÉÀÌ»óÀÇ fever(87%)

      > headache(72%) > sore throat(75%)

    * desquamation (ƯÈ÷ palm & sole)°ú ÇÔ²² 7-10ÀÏ ³»¿¡ recoverµÊ

       1-2moÈÄ hair & nail loss (+)

 5. the most frequent laboratory sign

    : Cr.¡è(69%) > thrombocytopenia (59%) > hypocalcemia (58%)

      > azotemia(57%) > hyperbilirubinemia (54%) > liver enzyme¡è(50%)

      > WBC>15,000 (48%)

      ¡æ no specific laboratory test

Differential diagnosis

 * Kawasaki disease

  1. À¯»çÁ¡

   ¨ç fever unresponsive to antibiotics

   ¨è hyperemia of mucous membrane

   ¨é erythematous rash with subsequent desquamation

  2. Kawasaki disease¿¡ ¾ø´Â ¼Ò°ß

   ¨ç diffuse myalgia

   ¨è vomiting

   ¨é abd. pain

   ¨ê diarrhea

   ¨ë azotemia

   ¨ì hypotension

   ¨í adult respiratory distress synd

   ¨î shock

   ¨ï age (Kawasaki´Â º¸Åë 5¼¼ÀÌÇÏ)

Prevention & Treatment

    : the low risk of acquired TSS (6.2 case/100,000)

 * management of adolescents suspected of having TSS

  1. careful removal of any retained tampon

  2. cardiovascular collapse¿¡ ´ëÇÑ aggressive fluid therapy

  3. inotropic agent for shock

  4. corticosteroid & IV immune globulin for severe case

  5. parenteral ¥â-lactamase resistant antistaphylococcal antibiotics

   ¨ç nafcilline, oxacilline, methicilline

   ¨è 150-200mg/kg/day # 4-6 ( x 10-14 days)

   ¨é not affected immediate outcome, but prevent reccurence in menstrual TSS

   ¨ê penicilline allergy: clindamycin, EM, rifampin, bactrim

 * culture

    menstrual TSS - from vagina

    nonmenstrual TSS - infected or colonized site

Chapter 175. Streptococcal Infections

 

 1. most common cause of bact. inf. in infancy & children

 2. Group A streptococci

  ¨ç most common bacterial cause of acute pharyngitis

  ¨è nonsuppurative sequelae: rheumatic fever, GN

 3. Group B ¥â-hemolytic streptococci

    : 3 mo.À̳»¿¡¼­ common

      bacteremia, meningitis, osteomyelitis, septic arthritisµî À¯¹ß

Etiology

¡ÚTable 175-1

# classification of streptococci

  ; by RBC hemolysis

        ¨ç ¥â-hemolysis: complete hemolysis

        ¨è ¥á-hemolysis: partial hemolysis

                 produce green color on sheep erythrocytes (Viridan group)

        ¨é¥ã-hemolysis: no hemolysis

    ; by C-carbohydrate in the cell wall (Lancefield classification)

           - A through H & K through V

# several antigenic proteins

    ; on outer layer of cell wall contain

  ; ¡ÚM protein (acquired immunity is directed)

        - *¡ãimportant

           - resistant to phagocytosis

           - *major virulence factor

    ; ¡Ølipoteichoic acid

           - *promotes colonization by binding to fibronectin on surface of epithelial cells

           - another virulence factor

    ; hyaluronic acid capsules

           - resists phagocytosis further facilitating virulence

 4. greatest clinical significance¸¦ °¡Áö´Â extracellular products

  ¨ç pyrogenic (formely erythrogenic) toxin (A, B & C)

     : responsible for the rash of scarlet fever & for shock in toxic shock-like illness

  ¨è streptolysin O

     : lyses RBC & toxic to neutrophils, platelets & mammalian heart muscle

  ¨é streptolysin S

     : largely cell bound & damage membranes of neutrophils & platelets

  ¨ê NADase

  ¨ë streptokinase (A & B)

  ¨ì DNase (A, B, C & D)

  ¨í hyaluronidase

  ¨î proteinase: associated with tissue destruction of severe invasive streptococcal disease

  ¨ï amylase

  ¨ð esterase

 5. Group A streptococcus infectionÀÇ diagnosis¿¡ À¯¿ëÇÑ antibody

    Ab to streptolysin O (ASO), DNase B, hyaluronidase, NADase, streptokinase

Group A Streptococci

Epidermiology

 1. normal inhabitant·Î nasopharynx¿¡ Á¸Àç

    colonization rate: 15-20%

# ¡ÚIncidence Depend On

    1) age of child

       ; *¡ãlowest incidenc among infant

                   - due to transplacental acquisitions of type-specific Ab & lack of pharyngeal receptor for streptococcal binding

       ; St. infection of skin

                   - *¡ãcommon in younger than 6yr

       ; St. pharyngitis

                   - *¡ãcommon at 5-15yr

       ; scarlet fever

                   - *uncommon less than 3yr

  2) season of the year

           ; St. pharyngitis

                   - higher in temperate climate

         - increased incidence & severity in cold weather

  3) climate & geographic location

           ; St. skin disease

                   - *prevalent in tropical climate, warmer weather in temperate climate

  4) degree of contact with infected individuals

# distruption of the cut. epithelium predispose to

    ¡æ streptococcal pyoderma & impetigo

    acquisiton from an infected individual is most common during

    ¡æ acute illness (3-5 days)

    decreased during the colonization stage

    colonization may preceed or follow (2-6wks) overt infection

# immunity

    ; type-specific

    ; *induced by carriage of organism or by overt infection

Pathogenesis

 1. inhalation or ingestion

    : streptococci attach to resp. epithelial cell by surface fibrils & cell wall lipoteichoic acid

      # fibrils + capsular hyaluronic acid: phagocytic reaction

 2. extracellular digestive enzyme

    : fasciliate the spread infection by

     ¨ç interfering with local thrombosis (streptolysins)

     ¨è pus formation (DNase)

     ¨é enhanced connective tissue digestion (hyaluronidase, proteinase)

 3. suppurative Cx. follow

  ¨ç local inflammation (peritonsillar, retropharyngeal abscess)

  ¨è direct extension (OM, sinusitis)

  ¨é lymphagitic spread (lymphadenitis)

  ¨ê bacteremia (sepsis, osteomyelitis, pneumonia)

 4. role of pyogenic toxin

  ¨ç hypersensitivity reaction (rash produced)

  ¨è exhibit pyogencicity, cytotoxicity

  ¨é enhance the effect of endotoxin

 5. streptococcal pyogenic exotoxin A

    : staphylococcal toxic shockÀÇ staphylococcal enterotoxin B¿Í ºÎºÐÀûÀ¸·Î amino acid »óµ¿°ü°è °¡Áü

Clinical manifestation

# ¡ãcommon infection sites

    ; respiratory tract, skin, soft tissue, blood

Scarlet Fever

    ; *pyrogenic(erythrogenic) exotoxins(A-C)Áß¿¡ Çϳª¸¦ »ý»êÇÏ´Â streptococci¿¡ ÀÇÇØ ¹ß»ý

    ; incubation period : 1-7 days average 3 days

Clinical Manifestation

    ; *fever, vomiting, headache, toxicity, pharyngitis & chills

           - fever

                   / *up to 39.6-40¡É on the 2nd day

                / if Tx.(-), normalized within 5-7days

         / if Tx.(+), normalized within 12-24hr

           - tonsil

            / hyperemic & edematous

                   / covered with gray white exudate

       - pharynx

            / inflamed, covered with membrane in severe case

           - tongue

               / wihite strawberry tongue

                   : Ãʱ⿡ red & edematous papillae project¿Í tongue dorsum¿¡ white coat (+)

               / red strawberry tongue, raspberry tongue

                   : ¼öÀÏÈÄ white coat desquamatedµÇ°í prominent papillae°¡ »êÀçÇØ ÀÖ´Â red tongueÁö¼Ó

    ; abdominal pain

    ; *rash within 12-48hr

           - red, punctate, finely papular, branches on pressure

           - texture of gooseflesh or coarse sandpaper

       - *initially appears in axilla, groin, neck and generalized within 24hr

7. forehead, cheek: flushing

     area around the mouth: pale (circumoral pallor)

  8. Pastia lines

     :antecubital fossaµî deep crease¿¡¼­ÀÇ hyperpigmentationºÎºÐ¿¡ pressure¸¦ °¡Çصµ blanch ³ªÅ¸³ªÁö ¾Ê´Â

        sign

  9. miliary sudamina

     : severe caseÀÇ abdomen, hand, feet¿¡ ³ªÅ¸³ª´Â small vesicular lesion

  10. desquamation

      : face ¡æ trunk ¡æ hand & feet

        1ÁÖ ¸»¿¡ ³ªÅ¸³ª¼­ ±æ°Ô´Â 6ÁÖ±îÁö Áö¼ÓµÇ´Â °æ¿ìµµ ÀÖ´Ù.

# ¡ÚOther Causes Of Scarlets Fevers

    ; infection of wounds (surgical scarlet fever)

  ; burn

  ; streptococcal skin infection

    ; certain strain of staphylococci infection producing exfoliative toxin

Differential Diagnosis

   ¨Í meales: conjunctivitis, photophobia, dry cough, Koplik's spot

   ¨Î rubella: mild, postauricular lymphadenopathy, throat cultrue (-)

   ¨Ï viral exanthem

   ¨Ð infectious mononucleosis: photophobia, rash, lymphadenopathy, splenomegaly, atypical

                 lymphocyte

   ¨Ñ exanthem by sereveral enterovirus: DDx course of disease, associated Sx. culture result

   ¨Ò roseolar: rash (+)·Î fever cessation

   ¨Ó Kawasaki disease: older age, conjunctival involvement (-), group A streptococciÀÇ

                        recovery in scarlet fever

   ¨Ô drug eruption

   ¨Õ toxic shock syndrome

   ¨Ö Arcanobacterium hemolyticum: adolescent, young adult

   ¨× severe sun burn

Skin Infection

Impetigo

    ; ¡ãcommon form

    ; superficial pyoderma

   ¨ç colonization of unbroken skin: pyoderma 10ÀÏÀü

   ¨è deeper soft tissue infectin ¿Ã¼ö ÀÖ´Ù.

   ¨é cellulitis

   ¨ê lymphangitis, lymphadenitis: common

   ¨ë soft tissue abscess (rare): contaminated needle·Î immunization½Ã ¿È.

Erysipelas

   ¨ç face & ext.: acute well-demarcated infection of the skin with lymphangitis involving

                  the face (asso. with pharyngitis) & extremities (wounds)

   ¨è erythematous indurated skin, advancing margin: raised firm border

   ¨é asso. with fever, vomiting, irritability

   ¨ê lymphatic barrier break·Î spreadµÇ¾î subcutaneous abscess, bacteremia, metastatic foci

      of infection°¡´É

   ¨ë streptococcal cellulitis¿Í µ¿¹ÝµÇ¾î bacteremia, death°¡ »ý±æ¼ö ÀÖÀ¸¸ç

      : rapid progressionÀ¸·Î penicillin¿¡ effect (-)¼öµµ ÀÖ´Ù.

Bacteremia

  1. local cutaneous & resp. infectionÀÏÀ¸Å´

  2. poorest prognosis: underlying malignancy (+) pt.

Vaginitis

    : in prepubertal girl

Diagnosis

; sore throatÀÖ´Â childrenÀÇ 30% ¡æ throat culture (+)

  - ÀÌÁß 50% ¡æ positive Ab response (active infection)

; St. pharyngitis ptÀÇ 50%¿¡¼­ tonsillar exudate (-)

# Throat Culture

    ; *most useful diagnostic method in acute tonsillitis or pharyngitis

    ; *normal inhibitant of nasopharynx in well children

           --> *hemolytic streptococci (+)°¡ È®ÁøÀº ¾ÈµÈ´Ù.

# rapid antigen detection test

    ; not sufficiently sensitive to be used without a back-upculture

# ASO titer

    ; untreated childrenÀÇ 80%À̻󿡼­ 166 todd unitÀÌ»ó Áõ°¡

     (°¨¿°¹ÞÀº ù 3-6ÁÖ»çÀÌ)

   1. very high ASO titer: rheumatic fever

   2. weakly (+) or not elevated: streptococcal pyoderma

   3. variable: glomerulonephritis

# Anti-DNase B

    : best serologic test for streptococcal pyoderma, infection¹ÞÀº 6-8ÁÖÈĺÎÅÍ Áõ°¡.

 4) pyoderma³ª pharyngitis¾ç°æ¿ì ¸ðµÎ¿¡¼­ antihyaluronidase titierÁõ°¡

    ASO titier´Â ºñ·ÊÇÏÁö ¾ÊÀ½

# 2 min, inexpensive streptozyme slide test

  1. multiple streptococcal extracellular Ag¿¡ ´ëÇÑ Ab detectÀ§ÇØ °³¹ß

  2. ´Ù¸¥ single testº¸´Ù ´õ ¸¹Àº ȯÀÚ¿¡¼­ Ab titer¡èº¼ ¼ö ÀÖ´Â À¯¿ëÇÔÀÌ ÀÖ´Ù.

  3. infection 7-10ÀÏ ³»¿¡ Ab detection °¡´É

  4. ´ÜÁ¡

     : not specific for Ab to extracellular product of group A streptococci

# ESR¡è & CRP¡è

    : DxÀ» establishÇϴµ¥ not helpful

Differential Diagnosis

Complication

 1. by extension of St. infection from the nasopharynx

    : sinusitis, otitis media, mastitis, cervical adenitis, bronchopeumonia

      retropharyngeal or parapharyngeal abscess

 2. hematogenous dissemination

    : meningitis, osteomyelitis, septic arthritis

 3. nonsuppurative late Cx.

    : rheumatic fever, glomerulonephritis

Prevention

 1. Sx onsetÀü¿¡ PCÅõ¿©·Î ´ëºÎºÐÀÇ °æ¿ì¿¡ prevention

    Á¤È®ÇÑ Ix.Àº unclear

 2. Institutional epidemics

  ¨ç oral PC G or V: 400,000 u/dose qid x 10 days

  ¨è 600,000 u benzathine PC + 600,000 u aqueous procaine PC

     : single IM

 3. carrier of group A ¥â-hemolytic St. management: conroversal

 4. available streptococcal vaccine: still not exist

 5. frequent viral resp. infectionÀ» °®´Â carrier´Â recurrent resp. inf.À¸·Î »ý°¢ÇÒ¼ö Àִµ¥ nonPc antibiotics

         (cephalosphorin, EM, clindamycin)´Â carrier state¸¦ ±ÙÀýÇϴµ¥ µµ¿ò

Treatment

# goal of therapy

    ; decrease Sx.

  ; prevent septic, suppurative, nonsuppurative Cx.

# *maintained for at least 10days

# children with streptococcal pharyngitis

  ; *PC 125-250mg/dose tid for 10days

           - penicillin G or penicillin V

    ; long-acting benzathine penicillin G single im

           < 60lb : 600.000 u

     > 60lb : 1,200,000 u

           - indication

                   / all noncompliant patient, those have nausea, vomiting or diarrhea

# allergy to penicillin

    ; EM 40mg/kg/24hr

  ; clindamycin 30mg/kg/24hr

  ; cefadroxil monohydrate 15mg/kg/24hr

# *TC, sulfonamide »ç¿ëÇØ¼­´Â ¾ÈµÊ

# Tx. failure

  1. due to

   ¨ç poor compliance

   ¨è reinfection

   ¨é the presence of ¥â-lactamase producing oral flora

   ¨ê presence of carrier state

  2. Ä¡·á°¡ ¸ðµÎ ³¡³­ µÚ¿¡µµ streptococci°è¼Ó ³²¾Æ ÀÖ´Â »óÅ·Π5-20%ÀÇ È¯¾Æ¿¡¼­ ³ªÅ¸³ª¸ç

     oral¿¡¼­°¡ IM¿¡¼­ º¸´Ù ³ô´Ù.

 6) repeat throat culture in risk situation

    : ÀÌÀü¿¡ rheumatic fever¸¦ ¾ÎÀº Hx.°¡ ÀÖ´Â patient

 7) persistance after 2nd course of antibiotic Tx.: carrier state

    * carrier state: rheumatic feverÀÇ risk°¡ ³·°í furthre Tx.´Â ÇÊ¿ä(-)

 8) IV Pc Tx.°¡ ²À À¯¿ëÇÑ °æ¿ì

  1. severe scarlet fever

  2. streptococcal bacteremia

  3. pneumonia

  4. meningitis

  5. deep soft tissue infection

  6. erysipelas

  7. streptococcal toxic shock syndrome

  8. Cx. of streptococcal phyryngitis

 9) in most severe infection

    : Pc 400,000 u/kg/24hr

½Å10) severe, necrotizing infection

    : complete bacterial killingÀ» À§ÇØ second antibiotic (e.g. clindamycin)ÀÇ Ãß°¡°¡ ÇÊ¿ä

175.1 Rheumatic fever

Etiology

; group A ¥â-hemolytic streptococcus

    - not all

    - some serotype : no recurrence

    - other serotype : 20-50% ÀÇ recurrence

; rheumatogenecity

           / M type 4

           / M type 1, 3, 5, 6 18, 24

; clinician assume that all group A streptococci cause rheumatic fever

¡Ø94,96 Epidermiology

; essentially epidermiology of Group A streptococcal pharyngitis

; *5-15 yr

    - *¡ãfrequently

    - ¡ãsusceptible to group A streptococcal infection

; also evidence in old age group &  outbreak in specific closed population such as military recruits

; increased cases in socially, economically disadvanced group

; ¡Ø94 increased incidence of fall, winter, early spring

; Group A streptococcal impetigo

    - RF (-), PSGN (+)

; ¡ØMajor Risk Factor

    - *streptococcal pharyngitis

; attack rate

    - 3% of untreated or inadequately treated infection patients

Pathogenesis

: unknown

      1. two basic theories

          toxic effect

         Group A streptococciÀÇ extracellular toxin¿¡ ÀÇÇØ target organ ( myocardium, valves, synovium, brain )           ¿¡ toxic effectÀÇ produced.

          abnormal immune response by the human host.

      2. streptolysin O°¡ animal¿¡¼­ cardiotoxic ÇÏÁö¸¸ in vivo toxic effect´Â È®¸³µÇÁö ¸øÇß´Ù.

      3. most popular hypothesis

         Group A streptococcus ÀÇ undefined component¿¡ ÀÇÇÑ human host ÀÇ abnormal immune response

          --> resulting Ab

          --> immunologic damage

          --> clinical manifestation.

      4. latent period : 1-3 wk

      5. Two streptococcal antigenÀº clinical manifestationÀ» ÀϾîŰ´Â abnormal immunologic responseÀÇ excellent           exampleÀÌ´Ù.

           Group specific polysaccharide of the Group A B-hemolytic streptococcal cell wallÀº human°ú bovineÀÇ             cardiac valve¿¡¼­ ¹ß°ßµÇ´Â glycoprotein°ú antigenically similar ÇÏ´Ù.

           : chronic Rheumatic valvular heart disease¸¦ °¡ÁøÀÌ¿¡¼­ acute nephritis³ª uncomplicated streptococcal               infection¿¡¼­ ȸº¹µÈ ÀÌµé º¸´Ù Group A polysaccharide¿¡ ´ëÇÑ Ab°¡ prolonged persistenceÇÏ´Ù.

           cross relative antigenÀÌ cell membraneÀ̳ª cell wall¿¡¼­ originally described

           ---> cross-reactivity between Group A streptococci M proteins and human tissue.

           ---> abnormal immune response¾ß±â.

       6. genetic influence¿¡µµ ºÒ±¸Çϰí, Rheumatic individual ÀÇ 70-90%¿¡¼­

         non-T lymphocyte¿¡ specific allergen (+)À̰í control¿¡¼­´Â 30%¿¡¼­ (+)

       7. Group A Streptococci¿¡ ÀÇÇÑ URIÈÄ RFÀÇ pathogenetic mechanismÀº organismÀÇ specific charateristics¿Í           ¾ÆÁ÷ È®½ÇÇÏ°Ô ¹àÇôÁöÁö ¾ÊÀº human hostÀÇ genetic predispositionÀÇ combination¿¡ ÀÇÇÑ´Ù.

Clinical Manifestation & Diagnosis

¢ÞTable 175-2

Major Criteria

Carditis

    ; 40-80%

    ; pancarditis involving peri-, epi-, myo-, & endocardium

    ; *only residual symptom resulting in chronic change

    ; common manifestation

         - vavular insufficiency

                   / *present in acute stage

                   / *MV : ¡ãcommon

                   / MV with AV

           - scarring with typical fishmouth abnormality or calcified valve --> stenosis.

                   / later in chronic stage

    ; other manifestation

           - pericarditis, pericardial effusion, arrhythmia (usually 1st heart block but 3rd complete heart block may occur)

Polyarthritis

    ; ¡ãconfusing major criteria

    ; tender, migratory

    ; affect several different joint, elbow, knee, ankle, wrist

  ; *need not symmetric

    ; *not result in chronic joint disease

    ; following anti-inflammatory therapy, *disappear in 12-24hr.

Chorea

    ; 10%ÀÌÇÏ

    ; *occur much later than other manifestation

    ; ¡ãbest signs in school aged children

           - marked deterioration in handwritting

    ; disappear within weeks to months.

Erythma Marginatum

    ; onset early in disease

    ; nonspecific pink macule over trunk

           --> branching in the middle of the lesion

    --> serpiginous-looking lesion

    ; worse with application of heat

    ; *dose not itching

Subcutaneous Nodule

    ; *¡ãcommonly observed in pt with servere carditis

    ; pea sized nodule, firm, *not tender, no inflammation

  ; *extensor surface of joint (knee, elbow,spines)

Minor Criteria

# fever

    ; no higher than 101-102¢µ

    ; 103 or 104¢µ ÀÌ»ó½Ã reevaluation & consideration of other ds

Evidence Of Group A Streptococcal Infection

; positive throat culture, a hitory of scalet fever, elevated streptococcal Ab

; streptococcal Ab

    - antistreptolysin O (ASO)

    - antideoxyribonuclease B (anti-DNase B)

    - antihyalunidase (AH)

Differential Diagnosis

Complication

; rheumatic valvular heart disease

    - *¡ãmajor complication

Laboratory Findings

# Throat Culture

    ; *gold standard for confirmation of the presence of group A streptococcus

    ; *at least one throat culture before antibiotics therapy

# Streptococcal Ab Test

    ; ASO

           - *¡ãcommonly used

           - peak 3-6 wk after infection

    ; anti-DNase B test

           - peak 6-8 wk after infection

  ; AH test

# acute phase reactant

    ; ESR, CRP

    ; nonspecific

# reumatoid factor, ANA, complement, serum gammaglobuline elevation

    ; rare helpfull

# EKG

    ; 1st degree heart block, rarely 2nd, 3rd degree heart block

  ; 1st attack

           - EKG unremarkable

  ; chronic rheumatic heart disease

           - LAE

# Echocardiogram

# Chest PA

Treatment

# ¢¾3 Approaches

  1) treatment of the group A streptococcal infection that lead to the disease

    2) use of anti-inflammatory agents to control the clinical manifestation of the disease

    3) other supportive therapy, including CHF

# Treatment Of Streptococcal Infection

    ; *10 full days of oral agents

           or *single im injection of 1200000 units of benzathine penicillin G

    ; sulfadiazine

           - not an appropriate agent for acute streptococcal pharyngitis

# Control Of Clinical Manifestation

    ; *three systemic manifestatio given acute treatment

           - Arthritis, Carditis, Sydenham chorea

    ; Salicylates

       - prompt, dramatic relief of arthritis

                   / within 12-24 hr

                   / early salicylates --> interuption of diagnosis for arthritis

                           : *recommend small doses of codeine or similar durgs

           - mild carditis without CHF

                   / Salicylate alone

           - CHF or significant manifestation of carditis

                   / corticosteroid + salicylates

                   / *given during last week of corticosteroid therapy

                           and then *continued for 3-4wks after steroid discontinued

           - *90-120mg/kg/24hr #4

                   / blood levels 20-25 mg/dl

                   / carful monitoring of LFT

    ; Corticosteroid

           - congestive heart failure or other significant manifestation of carditis

    - *PRS 2.5 mg/kg/24 hr, # 2

       - short course : 2-3 wk

                   / if SE, alternate-day steroid Tx

    ; Treatment of Sydenham chorea ( controversal )

         - P-b, *CPZ(more papular)

         - diazepam

                   / recently used for mild chorea

           - *haloperidol

                   / severe chorea

# other supportive therapy

    ; CHF

           - diuretics or cardiac glycosides

           - bed rests

                   / not neccessary long-term priods

                   / *during therapy of patients with CHF

    ; Erythma marginatum & subcutaneous nodule

           - no specific therapy

Prevention

¢ÞTable 175-3 Primary and secondary prevention of rheumatic fever

Chapter176. Pneumococcal Infection

Etiology

    - Streptococcus pneumoniae

   1. G(+), lacet shaped, encapsulated diplococcus

   2. serotype

       : identified by type specific capsular polysaccharide

   3. cross-react of antisera

       ¨ç other pneumococcal types

       ¨è other bactetrial species ; E coli, group B streptococcus

                                   H. influenza type b

   4. virulence

       - related to the size of the capsule (°°Àº size¶óµµ ´Ù¸¦ ¼ö ÀÖÀ½)

       - human pathogen : smooth, encapsulated strains

       - capsular matrial ; phagocytosis ¹æÇØ

        # fully encapsulated strain (type 3) --> extraordinarily virulent

   5. quellung reaction

       : pneumococcalÀ» homologus type-specific antisera¿¡ exposure ÇßÀ»¶§

        antiserumÀº °¢°¢ÀÇ capsular polysaccharide¿Í combineÇÏ¿©

        capsuleÀÌ refractileÇØÁü

   6. incomplete (alpha) hemolysis on solid media

        --> unpigmented, umbilicated colony

   7. ±×¿Ü antigen

      ¨ç C-substance

             - cell wall Ag.

             - species¸¦ ³ªÅ¸³¿

             - teichoic acid-containing phosphocholine/and galactosamine 6-phosphate

             - precipitate with an acute beta-globulin

             - C-reactive protein

                   : activate complement and stimulation phagocytosis

      ¨è R antigen

             - species specific protein

      ¨é A type specific protein (M antigen)

             - dose not confer significant antiphagocytic properties

                 --> negligible immunity

   8. antibodies

      ¨ç antibodies to pneumococcal surface protein A (PspA)

          - protective against some pneumococcal strains

      ¨è antibodies to the capsular polysaccharide

   9. toxins - human ds.¿¡ ÀÖ¾î pathogenesis´Â ¹àÇôÁ® ÀÖÁö ¾ÊÀ½

      ¨ç hemolytic toxin (pneumolysin)

      ¨è toxic neuramidase

      ¨é purpura-producing factor : autolysis¶§ ºÐºñ

Epidemiology

   1. isolation peak age : first 2yr of life

# carriage rate

    ; *highest in Desember to April

  ; lowest in July to September

# ¡ÚPeak Incidence

    ; meningitis - 3-5mo

    ; otitis media - 6-12mo

  ; pneumonia - 13-18mo

# bacteremia, pneumonia, otitis media

    ; *¡ãcommon bacterial cause : S. pneumoniae

# meningitis     

    ; 3rd bacterial cause : S. pneumoniae

# 2¼¼ÀÌÇÏÀÇ children¿¡ À־  polysacharride capsule antigen¿¡ ´ëÇÑ

       antibody¸¦ »ý¼ºÇÏ´Â ´É·Â °¨¼Ò

      -->¨ç increased suseptibility to pneumococcal inf.

          ¨è decreased vaccine effectiveness

# male > female

# native American and black > white

# *occurs sporadically

    ; person to person spread by respiratory droplet

# diseaseÀÇ frequency¿Í severity°¡ Áõ°¡ÇÏ´Â °æ¿ì

        ¨ç sickle cell ds

        ¨è asplenia, splenosis

        ¨é deficiencies in humoral (B cell) immunity

        ¨ê AIDS

        ¨ë malignancy (leukemia, lymphoma)

        ¨ì complement deficiency

Pathogenesis & Pathology

# *produce disease by invasion

   1. host defence mechanism

        ¨ç presence of other bacteria in nasopharynx

            --> limit the multiplication of pneumococci

        ¨è epiglottic reflex, cilia of the respiratory epithelium

            --> move infected mucus upward toward the pharynx

        ¨é interaction of the bacteria with alveolar macrophages

            --> interaction of bacteria with alveolar macrophages

# *frequently follow viral respiratory infection

        ¨ç produce mucosal damage

        ¨è diminish the epithelial ciliary activity

        ¨é depress the function of alveolar macrophages

   3. phgocytosis may be impeded by respiratory secretion and the alveolar exudate

   4. spread

        ¨ç lymphatics

        ¨è blood stream (bacteremia)

        ¨é direct extension from a local site

   5. severity related to

        ¨ç virulence & number of organism

        ¨è integrity of specific host defenses

   6. poor prognosis

        ¨ç large numbers of pneumococci

        ¨è significant concentration of capsular polysaccharide in the circulation

   7. complement deficiency

        ¨ç terminal component (C©ý- C  )deficiency

            : recurrent pyogenic infection (S. pneumoniae)

        ¨è C©üdeficiency

            : S. pneumoniae infection

   8. asplenic patient

        ¨ç deficient opsonization

        ¨è abscence of filtering function of spleen

   9. Sickle cell disease and other hamoglobinopathies¿¡¼­ÀÇ pneumococcal infection

        ¨ç more prevalent

        ¨è 2¼¼ÀÌÇÏ -- high risk (Ab. productionÀÌ attenuated)

        ¨é deficit in Ab-independent properidin (alternate) pathway of complement activation

        ¨ê properidin deficiency and deficient Ab production

             --> defect in Ab-independent and Ab-dependent opsonophagocytosis

                    of pneumococcus

        ¨ë ³ªÀ̵é¸é anti-capsular Ab.¸¦ ¸¸µé¾î Ab-dependent opsonophagocytosis¸¦

              augmenting

  10. B and T cell immunodeficiency syndrome

      : phagocytosis efficacy °¨¼Ò

       - lack of opsonic anticapsular Ab. ¿Í failure to produce lysis and agglutination

           of bacteria

  11. Opsonization of pneumonia infection

     a) classic and properidin (or alterative) complement pathway¿¡ ´Þ·ÁÀÖ´Ù.

     b) diseaseÀÇ È¸º¹Àº opsoninÀ¸·Î ÀÛ¿ëÇÏ´Â anticapsular Ab ( enhancing phagocytosis and

          ultimately killing the pneumococcus)ÀÇ development¿¡ ´Þ·ÁÀÖ´Ù.

  12. Spread of infection

       : enhanced by the antiphagocytic properties of pneumococcal capsule

Clinical Manifestation

  1. related to the site of infection

        ¨ç pneumonia

        ¨è otitis media

        ¨é sinusitis & pharyngitis

        ¨ê abscess of the upper airway

        ¨ë laryngotracheobronchitis

        ¨ì peritonitis

        ¨í bacteremia

  2. local infection

        ¨ç empyema

        ¨è pericarditis

        ¨é mastiditis

        ¨ê epidural abscess

        ¨ë meningitis (rare)

  3. bacteremia

        ¨ç meningitis

        ¨è septic arthritis

        ¨é osteomyelitis

        ¨ê endocarditis

        ¨ë brain abscess

        ¨ì renal glomerular-caplillary and cortical arteriolar thrombosis

        ¨í localized gingival lesion

        ¨î gangrenous areas of skin on the face or extremities

        ¨ï immune complex glomerulonephritis

        ¨ð DIC

Dignosis

  1. recovery of pneumococci from th site of inf. or blood

     (but. nose or throat¿¡¼­ ¹ß°ßµÇ´Â ±ÕÁÖ´Â disease¿Í °ü°è¾ø´Ù.)

# blood culture

  ; *obtained for all children with pneumonia, meningitis, arthritis, osteomyelitis, peritonitis, pericarditis, gangrenous skin lesion

       ¨è localized sign of inf. ÀÌ ¾øÀ¸¸é¼­ high fever¿Í leukocytosis¸¦ °¡Áö´Â 1-24Mo child

  3. pneumococci

       ¨ç Gram(+) lancet-shaped diplococci

       ¨è pneumococcal meningitis Ãʱâ

           --> many bacteria in a relatively acellular CSF

  4. the latex particle agglutination test

       ¨ç rapid diagnosis

       ¨è Gram stain¿¡¼­ º¸ÀÌ´Â °æ¿ì´Â ÇÊ¿ä¾ø´Ù

       ¨é pneumococcal bacteremia¸¦ Dx.Çϴµ¥ sensitive

       ¨ê localized inf. --> negative

  5. leukocytosis

  6. ESR Áõ°¡

Prevention

# polyvalent pneumococcal vaccines

  ; *2¼¼ÀÌÇÏ childern¿¡¼­ resposiveness´Â unpredictable

    ; 23-valent pneumococcal vaccineÀÌ »ç¿ëµÈ´Ù.

         - purifed polysaccharide from 23 pneumococcal serotype

         - bacteremia, meningitis --> 95% response

           otitis media --> 85%

     3. vaccine¿¡ ´ëÇÑ clinical efficacy´Â controversial

     4. routine reimmunization is not recommanded

# ¡ÚRecommanded Immunization Indication After 2yr

          ¨ç sickle cell anemia

          ¨è functional or anatomic asplenia

          ¨é nephrotic syndrome

          ¨ê splenectomy following staging laparotomy for Hodgkin's ds.

          ¨ë CSF leakage

          ¨ì HIV infecton

       cf) recurrent otitis media or sinusitisÀÇ ¿¹¹æ¿¡´Â ±ÇÇÏÁö ¾ÊÀ½

     6. reimmunization

          : particular high risk patient

             optimal time interval --> unknown

# Penicillin prophylaxis

     1. pneumococcal sepsis risk°¡ ÀÖ´Â children

     2. Pc V potassium (125mg twice daily : 5¼¼ÀÌÇÏ, 250mg twice daily : 5¼¼ÀÌ»ó)

     3. Benzathine Pc IM monthly

         - overwhelming sepsis ¸¦ preventtionÇϴµ¥ È¿°ú

     4. Erythromycin

         - Pc¿¡ allergy°¡ ÀÖ´Â patient

Treatment

# ¡ÚPenicillin

    ; *Tx of choice

  Pc G : drug of choice for Pc-susceptable strains

    - 200.000-250.000U/kg/24hr, every 4-6hr

       : for bacteremia or pneumonia

    - 300.000U/kg/24hr, every 4-6hr

       : for meningitis

  oral Pc V

    - 50-100mg/kg/24hr, every 6-8hr

       : for minor infections

# Vancomycin (60mg/kg/24hr, every 6hr)

           : highly Pc resistent and for multipley resistent strains

    3. Cefotaxime and Cefotriaxone

           : ÃÖ±Ù resistant and Tx. failure°¡ º¸°íµÇ°í ÀÖ´Ù

    4. EM, cephalosporin, CM, bactrim

         --> effective for susceptible strain without meningitis

              alternate therapy for who are allergic to Pc.

Prognosis

     : depend on the

          ¨ç integrity of host defense

          ¨è virulence of the infecting organism

          ¨é age of the host

          ¨ê sithe of infection

          ¨ë adequacy of treat

Chapter 177. Haemophilus Influenza

(Àü¹ÝÀûÀ¸·Î Ãß°¡³»¿ë ¸¹À½ --> »õ·Î Á¤¸®)

Microbiology

# H. influenza

         - fastidious, G(-) pleomorphic coccobacilli

         - require factor ¥¹ (hematin, heat stable)

                         ¥´ (phosphophyridine nuclotide, heat stable)

                        for growth

# encapsulated strains

  ; surrounded by polysaccharide capsule

    ; *serotyed into six antigenitically & biochemically distinct type

           - designaged a-f

           - *type b : ¡ãvirulent

# classified into 8 biotypes

 indole & urea metabolism and ornithin decarboxylase

 important in epidemiology & pathogenesis

    ¨ç biotype ¥°

          : the most isolated form

            94% of serotype b

    ¨è biotype ¥± ¥² ¥³

          : genitourinary tract

    ¨é biotype ¥³ : neonatal inf.

    ¨ê biotype ¥´

          : otitis media or aSx. resp. inf.

Epidemiology

# serotype b

    ; major cause of invasive disease in children

    ; more than 95%

# ¡ÚNon-Encapsulated (Nontypable) H. Influenza

    ; *invasive ds. in the neonate, immunocompromised children, child in certain developing country

    ; *common etiologic agent for certain mucosal infection such as otitids media, sinusitis

    ; *asso. with chronic bronchitis in adults

    3. human is the only natural host for H. influenza

         - normal respiratory flora in 60-90% of healthy children

         - non-typable

              cf) serotype b --> infrequent (2-5%)

    4. H. influenza type b vaccine»ç¿ëÈÄ

         --> invasive ds. incidence°¡ ÀÌÀüº¸´Ù 90%ÀÌ»ó °¨¼Ò

    5. age distribution

         - 5¼¼ÀÌÇÏ-->90%, 2¼¼ÀÌÇÏ-->69-82%, 1¼¼ÀÌÇÏ-->50%

         - peak age : 6mo-12mo

         - male>female

    6. increased risk

          ¨ç sickle cell ds.

          ¨è asplenia

          ¨é cong. & acquired immunodeficiency

          ¨ê malignancy

    7. Socioeconomic risk factor

          ¨ç day care outside home

          ¨è the presence of sibling of elementary school age or younger

          ¨é short duration of breat feeding

          ¨ê parental smoking

          ¨ë prev. hospitalization for invasive H. influenza type b

          ¨ì history of otitis media

    8. mode of transmission

         : direct contact or inhalation of respiratory tract droplets

    9. attack rate for secondary H. influenza type b ds. in househol contact

          --> high in susceptible children less 24mo (3.2%)

Pathogenesis

    1. attach to non-ciliated colummnar epithelial cell

           --> within the cell or intercellular space

           --> entravascular compartment

         # type b PRP --> resistent intravascular clearance mechanism

    2. non-invasive H. influenza

        : direct invasion from the pharynx

            --> otitis media, sinusitis, bronchitis

Antibiotics Resistance  

    1. Ampicillin

       ¨ç 1988. USA : 29.5% of H. influenza type b

                     --> B-lactamase »ý¼º, ampicillin resistence

       ¨è a few isolates

             --> non produce B-lactamase but ampicillin resistance

 

    2. CM

       ¨ç chloramphenicol acetyl transferase (CAT) --> CM resistance

       ¨è both ampicillin and CM resistance --> 1%ÀÌÇÏ

    3. TMP-SMX, or amoxacillin calvulanate - 1%ÀÌÇÏ

Immunity  

    1. Anti PRP antibody

         ¨ç Age related fashion

         ¨è facilitates clearance of H. influenza type b from blood

    2. The mechanism of action of anti-PRP antibodies

         ¨ç opsonization

         ¨è classic & alternative complement pathway

         ¨é macrophage of the reticuloendothelial system

# concentration of circulating anti-PRP antibody

  ; 0.15-1.0ug/ml

       --> prtect against invasive infection

    ; infant

       - lower anti PRP Ab. conc.

    - ¢¾Why ?

                   / *maturation delay in the immunologic responses to thymus-independent type 2 (TI-2) antigens such as PRP

                   / PRP imunization depends on age

                           : 6moÀÌÇÏ --> anti-PRP antibody»ý¼ºÀÌ °ÅÀÇ ¾ø´Ù.

           : 18-24moÀÌ»ó -->geometric mean anti PRP respose (>1ug/ml)

           - *conjugate vaccineÀ¸·Î immunizationÇØ¾ß ÇÑ´Ù.

# conjugate vaccine

  ; *acts as thymus- dependent (TD) antigen

        - *exception) PRP-OMP : thymus independent type 1 (TI-1) properties

        - ¡ÚTable 177-1

  ; in child

           - *memory response occur rapidly on exposure to PRP

           --> *15°³¿ùÀÌÈÄ¿¡´Â 1ȸ¸¸ Á¢Á¾ °¡´É

# Immunity to non-typable H. influenza

    ; outer membrane protein(OMP)¿¡ ´ëÇÑ Ab.

          ¨ç P6 (major OMP)

          ¨è P2

Laboratory Diagnosis

    1. direct exam.

        a) Gram staining

        b) staining with methylene blue

    2. culture

        a) primary isolation

            - chocolate agar

            - Hemophilus isolation agar

            - blood agar plates using staphylococcus streak technique

        b) serotyping

            - slide agglutination with type specific antisera

        c) detection of PRP

       # rapid Dx. H. influenza type b by detect capsular polysaccharide

             ¨ç CIE

             ¨è latex particle agglutination --> most sensitive

             ¨é Co-A ( staphylococcal protein A coagglutination )

             ¨ê ELISA

Clinical menifestation & Treatment  

    1. initial empric antibiotic Tx.

        - should include agent against ampicilline resistent strain

        - normal sterile site¿¡¼­ ºÐ¸®µÈ H. type b  dml 20-40%¿¡¼­ ampicilline resistent

            --> cefotamie or cefotriaxoneÀÌ intial Tx.

    2. etiologic agent ºÐ¸®ÈÄ

        - ampicillin susceptable strain

            --> ampicillin

        - oral antibiotics

            : parenteral route·Î initialehls Tx.ÀÇ complete

            : amoxicilline, amoxicillin-clavulanate, cefixime, CM

Meningitis

# *Type b

    ; leading cause

    ; N. meningitidis or S. pneumoniaeµîÀÇ meninigitis¿Í ±¸º°ÀÌ ¾î·Æ´Ù.

  ; lung, joint, pericardium globe¿¡ complicationµ¿¹Ý

# antibiotics

           - 7-14day

           - cefotaxime, ceftriaxone, ampicillin, CM

      3. prognosis

          : depend on

              ¨ç age of presentation

              ¨è duration of illness before appropriate antimicrobial Tx.

              ¨é CSF state

              ¨ê rapidity of capsular polysaccharide conc. clearing from CSF, blood & urine

      4. complication

           ¨ç SIADH

           ¨è focal neurologic deficit

                # hearing impairment (6%)

                    : inflammation of cochlea and labyrinth

                # Dexamethasone (0.6mg/kg/24hr #4, #6)

                    - antimicrobial Tx.Á÷Àü¿¡ Åõ¿©

                    - bilat. hearing lossÀÇ incidence °¨¼Ò

           ¨é behavior problems, language disorders

           ¨ê impaired vision, mental retardation, motor abnormality, ataxia,

              seizure, hydrocephalus

Cellulitis

        - young children cellulitisÀÇ 5-14%, 2¼¼ÀÌÇÏÀÇ 85%

        - frequent associated with URI but no trauma history

        - most common infected site : cheek, preseptal region

        - lesion : indistinct margin, tender, indulated

                     violaceous or bluish purple color

        - complecated with meningitis or septic arthritis

        - antibiotics : Sx. & SgÀÌ »ç¶óÁøÈÄ 1ÁÖ ÈÄ ±îÁö Åõ¿©

       cf) celluitis¿¡¼­ prolonged fever --> concomitant inf ÀǽÉ

Orbit Or Preseptal Infection

        1. red swollen eye

            ¨ç with inf of superficial tissue layers ant. to the orbit

                  --> preseptal cellulitis

            ¨è with inf of orbit & it's content

                  --> orbital cellulitis or abscess

                        subperiosteal abscess

        2. Sx. & Sg.

             : fever, edema, tenderness, warmth of the lid & purple discoloration

        3. DDx.

           ¨ç S.pneumoniae

           ¨è S. aureus

           ¨é group A B-hemolytic streptococcus

            --> no fever , interruption of integument (insect bite)

        4. Inf. involving the orbit : rare

             - lid edema

             - proptosis, chemosis, impaired vision, limitation of extracellular movement

             - CT, USG --> inf. extent È®ÀÎ

         5. Tx.

             ¨ç preseptal cellulitis without meningitis

                  --> 5days parenteral Tx until no fever & eythema

             ¨è orbital inf. --> Àü Ä¡·á±â°£À» parenteral

            # total 10ÀÏ ÀÌ»ó

             ¨é abscess --> I & D and more prolonged Tx.

Suprglottitis Or Acue Epiglottitis

         : 2-7¼¼ , almost --> type b H. influenza

Uvulitis

        - rare

        - alone or aoncomitant of pharyngitis or epiglottitis

Pneumonia

        - 4¼¼ÀÌÇÏ

        - common associated with meningitis, epiglottitis

Septic Arthritis

        - most common affected site : knee, hip, elbow, .ankle

        - associated with meningitis

Osteomyelitis

Pericarditis

        - children¿¡¼­ pericaditisÀÇ 15% Â÷Áö

        - 2-4¼¼

        - meningitis¿¡ ÁØÇؼ­ Ä¡·á

Bacteremia Without Associated Focus

       ¨ç risk factor for occult bacteremia

           - fever (>39¡É)

           - leukocytosis (>15.000)

       ¨è H. influenza type b. bacteremiaÀÇ 26% --> meningitis

       ¨é initial parenteral antibiotic Tx (2-5ÀÏ).ÈÄ P.O·Î 7-10ÀÏ Ä¡·á

Invasive Ds. Of Neonate

       ¨ç nontypable H. influenza --> more common

       ¨è »ýÈÄ 24½Ã°£ À̳»¿¡ »ê¸ðÀÇ amnionitis³ª PROM°ú ¿¬°üµÇ¾î infectionÀÌ ³ªÅ¸³ª¸é

            organismÀÇ transmissionÀº maternal tractÀ» ÅëÇØ¼­ÀÌ´Ù.

Non-Invasive Ds.

Otitis Media

      a) most common bacterial pathogen

           ¨ç S pneumoniae

           ¨è H. influenza (nontypable)

           ¨é Moraxella catarrhalis

      b) first line antibiotics --> amoxicillin or ampicillin , ceftriaxine

      c) treatment failure or B-lactamase producing isolates

           ¨ç cefaclor

           ¨è amoxicillin-clavulanate

           ¨é SMX-TMP

           ¨ê EM-sulfisoxazole

Conjunctivitis

Sinusitis

      a) acute sinusitis

          cause --> otitis media¿Í µ¿ÀÏ

      b) chronic sinisitis

          : 1³âÀÌ»ó severe sinusitis

        - cause

             ¨ç S.aureus

             ¨è anaerobs

                  : peptococcus, peptostreptococcus, bacteroides

             ¨é non-typable H. influenza

             ¨ê streptococcus viridance

      c) Tx.

           ¨ç amoxicillin

           ¨è amoxicillin-clavuanate

           ¨é EM-sulfisoxazole

Prevention Of Serotype B Infection

Chemophylaxis

    1. Ix.

       ¨ç invasive H. influenza Pt.¿Í Á¢ÃËÇÑ 48moÀÌÇÏÀÇ unvaccinated close contact

       ¨è secondary ds.ÀÇ risk´Â age¿¡ ¹Ýºñ·Ê

       ¨é use of high efficacy conjugate vaccine --> chemoprophylaxisÀÇ ¿ä±¸ °¨¼Ò

    2. the goal of chemoprophylaxis

         : close contact³»ÀÇ colonization Á¦°Å

    3. Rifampin

          : 0-1mo. 10mg/kg/dose,  >1mo, 20mg/kg/dose,  max.600mg

             4days

    4. full immunization of H. influenza typ b conjugate vaccine

         ¨ç 15moÀÌ»ó --> 1 dose

         ¨è 12mo-14mo --> 2 dose

         ¨é 12moÀÌÀü 1dose & 12moÀÌÈÄ 1 booster dose

Immunoprophylaxis Vaccines

    1. 4 licenced H. influenza type b. conjugate vaccine (Table 177-1)

        : differ in the carrier protein, the saccharide molecular size,

                    and the method of conjugate the saccharide to protein

       ¨ç PRP-D (ProHIBit)

            : diphtheria toxoid as the carrer protein

       ¨è HbOC (HIBTITER)

            : an oligosaccharide linked to a non-toxic mutant diphtheria toxin (CRM197)

       ¨é PRP-OMP

            : outer membrane protein complex of N. menigitidis group B as the carrier

       ¨ê PRP-T (Act HIB/OmniHib)

            : tetanus toxoid carrier

    2. combine vaccines contain H.influenza thyp b

       ¨ç HbOC with DTP (TETRAMUNE)

       ¨è PRP-T ¿Í DTP¸¦ ÁÖ»çÁ÷Àü¿¡ È¥ÇÕ

Chapter 178. Meningococcal Infection

Etiology

# N. meningitidis

    ; *G(-) diplococcus (0.6 x 0.8um), biscuit shape

  ; common commensal organism of the human nasopharynx

  ; not isolated from animal or environmental source

      . 5-10% CO2ÀÇ atmosphere ¿¡¼­ 35-37µµÀÇ moist environment¿¡¼­ Àß ÀÚ¶÷

      . growth media

        : supplemental chocolate agar, Mueller-Hinton agar, blood agar base,

          trypticase soy agar

    ½Å . cell wall : cytochrome oxidase Æ÷ÇÔ

                -> positive oxidase test result

    ½Å . glucose or maltose¸¦ acid·Î  ferment ½Ãų ¼ö ÀÖ´ÂÁö ±×¸®°í sucrose or lactose

        ¸¦ ferment ½Ãų ¼ö ¾ø´Â Áö¿¡ µû¶ó N. meningitidis´Â identifyµÈ´Ù

    ½Å . indole & hydrogen sulfide : not formed

  2) serogroups

     : capsular polysaccharide¿¡¼­ antigenic difference¿¡ µû¶ó divideµÈ´Ù

       . Àû¾îµµ 13 serogroupsÀÌ identified

       . gr. A, B, C, W, Y : most meningococcal disease¾ß±â

Epidemiology

 ½Å1)meningococcal dissemination

      : ÁÖ·Î endemic disease·Î ¹ß»ý

       a. endemic disease

           - caused by heterogenous gr. of serotype

           - geographically clustered area¿¡¼­ Àß ¹ß»ý

       b. epidemics

           - developed countries¿¡¼­´Â rare, but developing countries¿¡¼­

               significant problem¾ß±â

           - caused by single serotype

           - multilocus enzyme genetic method

              : caused by strains derived from single clonotype

# highest attack rate

    ; winter & early spring

  ; male 55%

    ; younger than 1yr 29%

           - *younger than 4mo : 26/100,000 infants, peak incidence

    ; younger than 2yr 46%

    ; older than 30yr 25%

# incidence among serogroup

    ; ¡Úserogroup B disease 46%

  ;    "     C   "    45%(69% older than 2yr)

    ;    "     A   "   

           - major health problem in developing world

# meningitis : 48% of case

# isolation rate

  ; blood (66%), CSF(51%), joint fluid(1%)

Pathogenesis

   1) N. meningitidis : acquired by respiratory route

       a. colonization of nasopharynx

          -> lead to aSx carriage (dissemination : rare)

          -> persist for weaks to months

         ½Å # carriage rate

               nonepidemic period

                  - normal population : variable (2-30%)

                  - day-care center & crowding condition : higher

               epidemic period

                  - 100% in closed population

   2) colonization of nasopharynx

        -> evade mucosal IgA & adhere to epithelial cell by secretion of protease

            # protease : a. protein-rich ring & region of IgA¸¦ cleave½Ã۰í nonfunctional

                        b. meningococci & gonococci (+)

                           nonpathogenic Neisseria (-)

        -> nonciliated epithelial cell¿¡ selectively bind

            (by parasite-directed endocytotic process)

 

   3) dissemination in blood-stream

       . serum Ab

           : lead to complement-mediated bacterial lysis

              -> block the dissemination

           : directed against

               a. capsular polysaccharide

               b. subcapsular protein

               c. lipooligosaccharide Ag

 

  ½Å4) newborn infants

        . protective Ab (maternal origin IgG)

        . 3-24Mo°æ Ab°¨¼Ò -> highest incidence

          (most adulthood : natural immunity developed)

        . source of immunity

           # infants - high carriage rate of unencapsulated, nonpathogenic neisserial strain,

                       N. lactamiaca

                   -> development of bactericidal Ab against meningococcus

    5) meningococcal dis.ÀÇ risk Áõ°¡ ÇÏ´Â °æ¿ì

        . primary or

           acquired complement deficiency( SLE, nephrotic synd., multiple myeloma, hepatic failure)

        . properdin, factor D or terminal-component deficiency°¡ ÀÖ´Â individualÀÇ 50-60%

# ¡ÚGroup B Capsule

  ; *homopolymer of sialic acid

  ; *inhibit alternative complement pathway activation

    ; ¡Ú±×·¯¹Ç·Î serotype B meningococci°¡ young children¿¡ ÈçÇÏ´Ù.

Pathology

    1) intravascular coagulation with deposition of fibrin in small vessels

        -> hemorrhage & necrosis in any organ system

    2) meningococcemia½Ã involvedµÇ´Â major organ system

         . heart

         . CNS

         . skin

         . mucous & serous membrane

         . adrenals

   

        a. myocarditis

           : »ç¸Áȯ¾ÆÀÇ 50%ÀÌ»ó

        b. cutaneous hemorrhage (petechia to purpura)

           - occur in most fetal inf.

           - asso. with acute vasculitis with fibrin deposition in arterioles and capillaries

        c. diffuse adrenal hemmorrhage

           - occur in fulminant meningococcemia

            (Waterhouse-Friderichsen synd.)

        d. meningitis

           - acute inflammatory cells in the leptomeninges & perivascular spaces

           - focal cerebral involve : uncommon

  ½Å3) interaction of endotoxin & complement system

       : key in the pathogenesis of cl. manifestation

        a. C' activation

           : correlates with concentration of meningococcal lipooligosaccharide in the plasma

        b. concentration of circulating endotoxin

           : directly correlated with

              . activation of the fibrinolytic system

              . development of DIC

              . multiple organ system failure

              . septic shock

              . death

        c. level of endotoxemia

           : correlates with the concentration of circulating cytokines

             (endotoxin-stimulated monocyte & macrophages¿¡¼­ release)

        d. concentration of tumor necrosis factor-alpha and interleukins

           : directly asso. with fatal meningococcal diseases

Clinical Manifestation

    1) disease spectrum

       : vary widely from fever and occult bacteremia to sepsis, shock & death

        # recognized pattern

            a. bacteremia without sepsis

            b. meningococcemia sepsis without meningitis

            c. meningitis with or without meningococcemia

            d. meningoencephalitis

            e. inf. of specific organs

    2) . well-recognized entity : occult bacteremia in a febrile child

       . upper resp. or G-I Sx or maculopapular rash : (+)

       . spontaneous recovery without Abc °¡´ÉÇÏÁö¸¸ ÀϺδ meningitis developed

    3) acute meningococcemia

        : viral-like illness¿Í À¯»ç

           - pharyngitis, fever, myalgia, weakness, headache

        a. with widespread hematogenoous dissemination

           - rapidly progress to septic shock

               . hypotension

               . DIC

               . acidosis

               . adrenal hemorrhage

               . renal failure

               . myocardial failure

               . coma

           - meningitis : may or may not develope

           - pneumonia, myocarditis, purulent pericarditis, septic arthritis

        b. seizure & focal neurologic sg. in the meningitis

           - pneumococcus, or H. influenzaº¸´Ù less frequent

        c. meningoencephalitis

           - rarely, diffuse brain involve

  ½Å4) presenting sx & sg

          . fever(71%)

          . hypothermia(4%)

          . shock(42%)

          . petechia or purpura (71%), both(49%)

          . purpura fulminans(16%)

          . maculopapular, pustular, bullous lesion

          . irritability(21%), lethargy(30%), emesis(34%)

          . diarrhea, cough, rhinorrhea, seizure, arthritis : less frequent(6-10%)

 

   5) Lab

          . leukopenia(21%), low platelet count(14%)

          . WBC count range : 0.9-46/mm3 x 103

          . blood culture : 48% (+), meningitis¿¡¼­´Â 55%(+)

   ½Å6) a. CSF pleocytosis(-), hypoglycorrhachia(-) or G. stain»ó detectµÇ´Â organismÀÌ ¾ø´Â

         °æ¿ì¿¡ À־ 6%¿¡¼­ CSF»ó ±Õ isolated

       b. arthritis pt 8¸íÁß 5¸í : joint fluid -> isolated

       c. 8%¿¡¼­ x-ray »ó pneumonia (+)

           - primary meningococcal pn.Áß 15%¿¡¼­ pleural effusion or empyemaµ¿¹Ý

    7) chronic meningococcemia

          . rare, occur in children & adult

          . sx : fever, nontoxic apperance, arthralgia, headache, rash

               (rash - disseminated gonococcal inf.°ú À¯»ç)

          . blood culture : initially sterile

          . Cx : specific Tx ÇÏÁö ¾Ê´Â °æ¿ì -> meningitis

Diagnosis

# ¡ÚIsolation Of Organism

  ; blood, CSF, synovial fluid

           - usually used

    ; nasopharynx - not diagnostic

    ; petechial or purpuric lesion

           - variable successful

# Counterimmunoelectrophoresis & latex agglutination test

    ; detection of meningococcal capsular polysaccharide

    ; CSF, serum, joint fluid, urine

    ; false(-) occur

         . cross-reactive Ag(E.coli K1)

             -> gr.B meningococcus¿Í cross-react

             -> specificity°¨¼Ò

# antisera & monoclonal Ab

         . identify different serogroup

         . useful

            - early in inf.

            - received Abc

            - rendering cultures sterile

# ancillary data

         . ESR & CRP Áõ°¡

         . leukocytopenia or leukocytosis

         . proteinuria, hematuria

         . thrombocytopenia

         . pts with DIC

             - prothrombin & fibrinogen°¨¼Ò

         . complement deficiency

Differential Diagnosis

     a. acute bacterial or viral meningitis

     b. mycoplasma inf.

     c. leptospirosis    

     d. syphilis     

     e. acute hemorrhagic encephalitis

     f. encephalopathies 

     g. serum sickness    

     h. collagen-vascular disease

     i. H-S purpura   

     j. hemolytic uremic synd.  

     k. congestion of various poisons

 

   # the morbilliform rash : confused with any macular or maculopapular viral exanthem

      -  meningococcemia¶§ÀÇ rash¿Í °¨º°ÇØ¾ß ÇÒ Áúȯ

         a. septicemia due to many G(-) organism

         b. overwhelming septicemia with G(+) organisms

         c. bacterial endocarditis

         d. Rocky Mountain spotted fever

         e. epidemic typhus

         f. Ehrlichia canis inf.

         g. inf. with echoviruses(esp. types 6, 9, 16)

         h. coxsackievirus infecions(esp. type A2, A4, A9, A16)

         i. rubella

         j. rubeola & atypical rubella

         k. H-S purpura

         l. Kawasaki ds.

         m. idiopathic thrombocytopenia

         n. erythema multiforme or erythema nodosum

              due to drugs or infectious or non infectious ds. process

Complication

     1) acute Cx : related to

         +- . inflammatory change

         |  . vasculitis

         |  . DIC

         +- . hypotension of invasive meningococcal disease

         1. meningococcemia

              . adrenal hemorrhage

              . arthritis

              . myocarditis

              . pneumonia

              . lung abscess

              . peritonitis

              . renal infarcts

         2. vasculitis

              . skin loss with secondary inf.

              . tissue necrosis

              . gangrene

         3. bone involvement

              . growth disturbance

              . late skeletal deformities secondary to epiphyseal avascular necrosis

                 & epiphyseal-metaphyseal defects

         4. meningitis : rarely

              . subdural effusion

              . empyema

              . brain abscess

         5. deafness : mc neurologic sequale 0-38%

            ataxia, seizure, blindness, cranial n. palsies, hemiparesis or quadriparesis, 

            obstructive hydrocephalus

 

     2) late Cx

         . due to immune complex mediated

         . apparent 4-9day after the onset of illness

         . usual manifestation

            - arthritis & cutaneous vasculitis

         . arthritis

            - monoarticular or oligoarticular

            - effusion : sterile & respond to NSAID

            - permanent joint deformity : uncommon

         . Abc Tx 5ÀÏ ÈÄ¿¡µµ persistence of fever

            : immune complex-mediated Cx¿¡ ´ëÇØ evaluation

Prevention

# prophylaxis Ix

  ; house-hold, day-care, & nursery school contacts

  ; contact with pt's oral secretion

  ; intimate exposure

   - mouth to mouth resuscitation

   - intubation

   - suctioning before Abc Tx

# rifampin

   : *10mg/kg (max 600mg) po every 12hr for 2days (total 4 dose)

   : very young infant - 5mg/kg

# sulfonamide : sensitive ÇÑ °æ¿ì

# vaccination

    ; quadrivalent vaccine

        - composed of capsular polysaccharide of menigococcal group A, C, Y and W-135

    ; *immunogenic in adult, but unreliable in children under 2yr

    ; group B polysaccharides

           - *poor immunogenic in chidren & adults

    ; *not recommended as routine

Treatment

    ; ¡Úaqueous PC G

           - drug of choice

       - *250,000 to 300,000 u/kg/24hr IV in six divided dose

  ; CM sodium succinate

    - 75-100mg/kg/24hr IV 4 divided dose

       - pc¿¡ allergy ÀÖ´Â °æ¿ì

  ; cefotaxime (200mg/kg/24hr) & ceftriaxone (100mg/kg/24hr)

    - empirical Tx & pc¿¡ allergy ÀÖÀ»¶§

  ; duration

           - ¡Ú7days

Prognosis

# mortality rate

    ; 8-12%

# ¡ÚPoor Px Factor

  ; hypothermia

    ; hypotension

    ; purpura fulminance

    ; *seizure or shock on presentation

    ; leukopenia

    ; thrombocytopenia 

    ; high circulating level of endotoxin & tumor necrosis factor

    ; some studies, included

        - petechia within 12hr of admission

        - hyperpyrexia

        - *absence of meningitis

Chapter 179. Gonococcal Infections

Etiology

  1) N. gonorrhea

       . nonmotile, aerobic, non-spor-forming, G(-)intracellular diplococcus

       . optimal growth

          : 35-37µµ & PH 7.2-7.6 in an atmosphere of 3-5% CO2

       . Thayer-Martin or Transgrow media

       . other Neisseria¿Í °¨º°Á¡

           gonococci - fermentation of glucose but not maltose, sucrose, or lactose

  2) most widely used serotyping system

     : based on antigenic difference in protein I found in the outer membrane

        protein I : 1A

                   1B

  3) monoclonal Ab

         1A-1

         1B-12

Epidemiology

  1) occur only in humans

  2) highest incidence : male : 20-24¼¼ july-september > january-april

                       female :15-19¼¼

  3) risk factor

       . nonwhite race

       . homosexuallity

       . No. of sexual partnerÁõ°¡

       . prostitution

       . STD(+)

       . unmarried state

       . poverty

       . failure to use of condom

 ½Å4) gonococcal inf. of neonate

       . peripartum exposure to infected exudate from cervix

       . begin 2 to 5 days after birth

       . incidence

          : preg. woman ¿¡ À־ prenatal screening for gonorrhea

           & ophthalmic prophylaxis À¯¹«¿¡ Á¿ìµÊ

       . prevalance

          : < 1% in US prenatal populations

Pathology

1) mucosal invasion by gonococci

   -> local inflammatory responce

   -> purulent exudate (PMNL + desquamated epithelium)

2) lipooligosaccharide (endotoxin)

   . direct cytotoxicity -> ciliostasis & sloughing of ciliated epithelial cell

   . bind bactericidal IgM Ab & serum C'

     -> subepithelial space¿¡¼­ acute inflammatory response

   . tumor necrosis factor & other cytokines

     -> cytotoxicity

3) purulent discharge

     -> block ducts of paraurethral(Skene) or vaginal (Bartholin)glands

     -> cysts or abscess

4) gonococci

      -> ascend the urogenital tract

      -> endometritis, salpingitis, peritonitis : postpubertal females

      -> urethritis, epididymitis : postpubertal males

# ¢¾Fitz-Hugh-Curtis Syndrome

    ; perihepatitis

    ; dissemination through peritoneum from fallopian tube to liver capsules

Pathogenesis

   1. selective pressure from different mucosal environment

     -> change in the outer membrane of the organism

          . exposure of variants of pili

          . opacity or Opa protein(protein II)

          . lipooligosaccharide

     -> gonococcal attachment

         invasion of human cell

         replication

         evasion of the host's immune response

   2. gonococcal IgA protease

      . cleaving the molecule in the hinge region

        -> inactivate IgA1

      . colonization or invasion of host mucosal surface¿¡ °ü¿©

   3. gonococci

      : adhere to microvilli of nonciliated epithelial cell by hairlike protein structure(pili)

        # pili : . high frequency antigenic variation

               . protect the gonococcus from phagocytosis and complement-

                 mediated killing

 ½Å4. other phenotypic changes

       . iron-repressible protein for binding transferrin or lactoferrin

       . anaerobically expressed protein

       . synthesis of protein-mediated by contact with epithelial cells

   5. 24hr after attachment

      epithelial cell invaginate & surround the gonococcus in a phagocytic vacuole

       (by the gonococcal outer membrane protein I)

     -> alteration in membrane permeability

     -> phagocytic vacuole

          : exocytosis¿¡ ÀÇÇØ subepithelial space³»·Î gonococciÀ» release

     -> local disease(salpingitis)

          or disseminate (blood stream or lymphatics)

   6. host factor

      1) influence the incidence & manifestation of gonococcal inf.

      2) prepubertal female

          . vulvovaginitis

          . rarely salpingitis

      3) neonate & mature female

           : resist inf.

      4) postpubertal female

           : salpingitis esp. menses

   7. population at risk for DGI

      1) aSx carrier

      2) neonates

      3) menstruating, pregnant, & postpartum female

      4) homosexual

      5) immunocompromised hosts

   8. PC resistant gonococci Áõ°¡ ÀÌÀ¯

      1) plasmid-mediated B-lactamase (penicillinase) production

         : absolute resistance

      2) chromosomally mediated resistance

         : relative resistance

 ½Å 9. PPNG : all PC & 1st cepha ¿¡ resist

              but not to 2nd & 3rd cephalosporin

      # PC or TC¿¡ resist : 32%

         : PPNG - 11%

           TRNG - 5-7%

           PPNG & TRNG - 2%

         : chromosomally mediated resistance - 14%

Clinical Manifestation

Asymptomatic Gonorrhea

      a. isolated oropharynx of young (2-9yr of age)

          : abused sexually by male contacts

      b. oropharyngeal Sx : abscent

      c. 12-19yr females : 12%

                          most of girl - asymtomatic

      d. 68% of infected United States military men : asymtomatic

      e. 80% of sexually mature females with urogenital gonorrheal inf.

          : asymtomatic

      f. 20% of rectal inf. & 78% of pharyngeal gonococcal inf.

        : asymtomatic in homosexual men

Uncomplicated Gonorrhea

      a. genital gonorrhea

         : incubation period - 2-5 days in men

                              5-10 days in women

         : primary inf.  - urethra of the male

                        - vulva & vagina of the prepubertal females

                        - cervix of the postpubertal females

      b. urethritis

          : purulent discharge

          : burning on urination without urgency or frequency

      c. vulvovaginitis

          : prepubertal female

          : purulent vaginal discharge

          : dysuria

      d. cervicitis & urethritis

          : purulent discharge, suprapubic pain, dysuria, intermenstrual bleeding, dyspareunia

          : cervix - inflamed & tender

      e. gonococcal ophthalmitis

          : unilateral or bilateral

          : ophthamia neonatorum - 1-4days after birth

          : if treatment not promptly - corneal ulceration, rupture, blindness

Disseminated Gonoccal Infection

    ; hematogenous dissemination : 1-3% of all gonococcal inf.

 women : Sx. beginning 7-30 days after inf.

         and within 7 days of menstruation

 most common manifestation

 : arthritis, tenosynovitis, dermatitis

 : rarely carditis, meningitis, osteomyelitis

 most common initial sx

 : polyarthralgias with fever

 25% : complain of skin lesion

 80-90% of cervical culture : positive in women with DGI

 50-60% of urethral culture : positive in male

 pharyngeal culture : positive in 50-60%

 rectal culture : positive in 15%

 classification

 . tenosynovitis-dermatitis Sd.

    : more common

    : fever, chill, skin lesion, polyarthralgia

    : blood culture-positive(30-40%)

    : synovial fluid culture - negative

 . suppurative arthritis sd.

    : monoarticualar arthritis (knee)

    : synovial fluid culture-positive(45-55%)

    : blood culture-negative

 DGI in neonate : polyarticular septic arthritis

 dermatologic lesion

 . painful discrete

 . 1-20mm pink or red macules

   -> maculopapular, vesicular, bullous, pustule, petechial lesion

 . lesion number : 5-40

 . 20-30% of lesion : contain gonococci

 acute endocarditis

 : uncommon(1-2%)

 : fetal manifestation of DGI - rapid destruction of aortic valve

 meningitis

 : documented

Complication

    1) result from the spread of gonococci from a local site of invasion

    2) postpubertal females

       1. endometritis

       2. salpingitis, peritonitis(pelvic inflammatory disease)

       3. manifestation of PID

           . sign of lower genital tract inf.

              -- vaginal discharge, suprapubic pain, cervical tenderness

           . upper genital tract inf.

              -- fever, leukocytosis, elevated ESR, adnexal tenderness or mass

       4. DDX

           . gynecologic

              -- ovarian cyst, ovarian tumor, ectopic preg.

           . intraabdomial

              -- appendicitis, UTI, inflammatory bowel ds.

       5. Fitz-Hugh-Curtis Sd.

           : perihepatitis

           : RUQ pain, with or without signs of salpingitis

       6. perihepatitis due to Chlamydia trachomatis

       7. progression to PID

           . 20% of cases of gonococcal cervicitis

           . isolated in 40% of cases of PID

           . untreated

              : hydrosalpinx, pyosalpinx, tubo-ovarian abscess, sterility

           . treated

              : risk of sterility

                  - 20% after one episode of salpingitis

                  - 60% with three or more episodes

           . risk of ectopic preg.

              : 7-fold after one or more episodes of salpingitis

           . additional sequelae of PID

              : chronic pain, dyspareunia, inc. risk of recurrent PID

       8. high risk of septic abortion

           : urogenital gonococcal inf. acquired during the 1st trimester

       9. after 16weeks

           : inf. --> chorioamnionitis, PROM, premature delivery

Diagnosis & Differential Diagnosis

# definitive Dx

  ; isolation of N. gonorrhea

    2) DDx of gonococcal urethritis & vulvovaginitis

        : beta-hemolytic streptococci, C. trachomatis, Mycoplasma hominis,

          Trichomonas vaginalis, Candida albicans

        : rare - Herpesvirus hominis type 2

# identification of G(-) intracellular diplococci(within leukocytes) in urthral discharge

    ; male - presumptive Dx

  ; female

           - *not sufficient

       - *due to Mima polymorpha & Moraxella (normal vaginal flora) : similar appearance

# bacteriologic culture

  ; gold standard for the Dx of N. gonorrhea

  ; *specimen from cervix, rectum, pharynx

           - *use Tayer-Martin medium (selective culture media)

    ; specimen from synovial fluic, blood, CSF

           - use chocolate agar medium

    ; DGI suspect

           - blood, pharynx, rectum, urethra, cervix, synovial fluid¿¡¼­ culture

        : colonies of N. gonorrhoeae -- oxidase positive

           DDx of M. polymorpha & N. lactamica : carbohydrate utilization test

        : gonococci -- fermentation glucose

                       but not maltose, lactose, sucrose

                   -- tested for beta-lactamase production

    5) rapid slide coagglutination test (Phadebact)

        : sensitivity of 96-98%

        : cross reacts with commensial N. species

    6) enzyme immunoassay test(Gonozyme)

        : more sensitive than G stain(80-92%)

        : cannot be used for rectal or pharyngeal infections

    7) DDx of gonococcal arthritis

        : other forms of septic arthritis

           -- rhematic fever, rheumatoid arthritis, Reitier Sd., inflammatory bowel ds.,

              arthritis secondary to rubella or rubella immunization

    8) DDx of gonococcal conjunctivitis in the newborn

        : chemical conjuctivitis by silver nitrate drop

        : by C. trachomatis, S. aureus, group A or B streptococcus, P. aeruginosa,

           herpesvirus type 2

Prevention

# gonococcal opthalmia neonatum

  ; *conjunctival sac¿¡ 1% silver nitrate solution

  ; EM(0.5%) or TC(1%) ophthalmic ointment

    2) Gono(+) mother --> infant (high risk for gonococcal ophthalmitis)

       - ceftriaxone : 125mg IM single

                    : 25-50mg IM single IM LBWI

Treatment

# general principles

    ; ¡Úceftriaxone recommended as initial Tx for all ages

# uncomplicated gonorrhea in penicillin-allergic individuals

    ; spectinomycin 40mg/kg single im

    ; ciprofloxacin 500mg orally for 1 dose

    ; EM

       - during preg. added to spectinomycin or ceftriaxone

# DGI

    ; ¡Úceftriaxone

           - initial Tx

    - *50mg/kg/24hr(max. 1g/24hr) iv or im for 7day

    ; endocarditis or meningitis

         - ceftriaxone 50mg/kg(max, 2g) iv

           - endocarditis : 4wks

         - meningitis : 10-14days

    ; penicillin sensitive DGI

         - aqueous PCG 100,000-200,000 U/kg/24hr six divided dose iv for 7-10 days

    - meningitis & endocarditis

           / 250,000 U/kg/24hr for same duration

4. concurrent Tx with doxycyclin

          : Tx of genital chlamydia inf.

    6) infants born to mothers with known gonococcal inf.

      1. evaluated for sepsis with blood & CSF cultures

      2. ceftriaxone : drug of choice,  50ug/kg IM or IV once, max 125mg

                   : topical prophylaxis - not adequate

    7) neonates with gonococcal ophthalmitis

      1. evaluated for DGI

      2. ceftriaxone 25-50mg/kg/D IV or IM every day for 7 days

      3. concomittant saline irrigation of eye

    8) PID

      1. due to N. gonorrhoeae, C. trachomatis,

            endogenous flora(streptococci, anaerobes, G(-)bacilli)

      2. cefoxitin 2g IV every 6hr + doxycycline 100mg oral or IV every 12hr or

        cefotetan 2g IV every 12hr +            "

      3. at least 48hr after the pt. shows improvement

      4. oral doxycycline : total of 10-14 days

      5. alternative

         : clindamycin, 900mg IV every 8hr + loading dose of gentamicin

                                            (2mg/kg IM or IV)

                                           maintenance dose 1.5mg/kg every 8hr

Chapter 180. Diphtheria

Etiology

# Corynebacterium species

  ; aerobic, nonencapsulated, non-spore-forming, nonmotile, pleomorphic, G(+) bacilli

  ; cystinetellurite blood agar

# 3 biotypes

  ; mitis

    ; gravis

  ; intermedius

      -> capable of causing diphtheria

# demonstration of diphtheritic toxin

  ; in vitro

           - *agar immunoprecipitin technique(Elek test)

    - PCR

    ; in vivo

           - toxin neutralization test (lethality test)

# *toxigenic strains ´Â colony type, microscopy, biochemical test·Î ±¸ºÐÇÒ ¼ö ¾ø´Ù.

Epidermiology

   1) C. diphtheria

      : exclusive inhabitant of human mucous membrane & skin

   2) spread

        . airborne resp. droplets

        . symptomatic individuals ÀÇ resp. secretion or infected skin lesionÀÇ exudate¿Í direct contact

        . asymptomatic resp. carrier

            : important in transmission

# incidence

    ; begin to fall

    ; primarily affected children younger than 15yr

           --> *ÃÖ±Ù¿¡´Â vaccinationÀ» ÇÏÁö ¾ÊÀº adult·Î shift endemic onset

# survery of antitoxin level in Sweden

    ; childhood - 95% protective rate

    ; younger than 20yr - 81%

    ; older than 60yr

           - female 19%, male 44%

# cutaneous infection

    ; infrequently complication

    ; ¡Úcompared with mucosal infection

           - more prolonged bacterial shedding

    - increased contamination of environment

    - increased transmission to pharynx & skin of close contacts

# ¡ÚOutbreaks Associated Factors

    ; homelessness

  ; crowding

  ; poverty

  ; alcoholism

  ; poor hygiene

  ; contaminated fomites

  ; underlying dermatosis

    ; introduction of new strain from exogenous sources

Pathogenesis

# toxigenic and nontoxigenic C. diphtheria organisms

    ; skin & mucosal infection or distant infection after bacteremia

           --> superficial layer of skin lesion or resp. mucosa

           --> *produce 62-KD polypeptide exotoxin

       --> inhibit protein synthesis

    --> cause local tissue necrosis

# resp. tract infection

    ; dense necrotic coagulation of organism, epithelial cell, fibrin, leukocyte & erythrocyte within first few days

           --> become gray-brown adherent pseudomembrane

       --> removal - difficult

    - reveals a bleeding edematous submucosa

   5) early local effect of toxin

      : paralysis of palate & hypopharynx

   6) toxin absorption ½Ã Cx

      . necrosis of kidney tubules

      . thrombocytopenia

      . myocardiopathy         -+

      . demyelination of nerves -+  --> occur 2-10wks after mucocutaneous inf.

Clinical Manifestation

Resp. Tract Diphtheria

# primary focus

    ; tonsil or pharynx (94%)

  ; nose & larynx (2nd common sites)

# *IP for 2-4 days

# fever : 39µµ ÀÌ»óÀº rare

# ¡ÚInfection Of The Ant. Nares

  ; *more common in infants

  ; *serosanguinous, purulent, erosive rhinitis with memb. formation

  ; *shallow ulceration of the external nares & upper lip

# tonsilar & pharyngeal diphtheria

          . sore throat : universal early sx

          . fever : 50%¿¡¼­

          . dysphagia, hoarseness, malaise or headache : fewer

      7. mild pharyngeal injection

          -> unilat. or bilat. tonsilar memb. formation

          -> extend to uvula, soft palate, post. oropharynx, hypopharnx, and glottic areas

      8. underlying soft tissue edema & enlarged lymph nodes

          -> bull-neck appearance

      9. degree of local extension¿¡ µû¶ó¼­

          . profound prostration

          . bull-neck appearance

          . fatality from airway compromise or toxin-mediated Cx

 

       10. DDx

           a. exudative phayngitis due to strep. pyogenes & E-B virus

              : leather-like adherent memb., extension beyond the facial area,

                relative lack of fever, dysphagia

                 -> diphtheria

           b. vincent angina, infective phlebitis & thrombosis of the jugular vein.

              & mucositis in pts undergoing cancer chemoTx

              : clinical setting¿¡ ÀÇÇØ

           c. inf. of the larynx, trachea & bronchi

              : pharyngeal inf.¿¡ ÀÇÇÑ primary or secondary extension

              : hoarseness, stridor, dyspnea, & croupy cough

           d. bacterial epiglottitis, severe viral laryngotracheobronchitis,

              & staphylococcal or strep. tracheitis

              : diphtheria pt¿¡¼­ÀÇ Sx & SgÀº ºñ±³Àû Àû°í

                laryngobronchoscopy & intubation¶§ adherent pseudomemb.À» Á÷Á¢ °üÂûÇÏ¿© °¨º°

# laryngeal diphtheria

  ; *highly prone to suffocation

    ; edema of soft tissue, obstructing dense cast of resp. epithelium & necrotic coagulation

Cutaneous Diphtheria

     1. classic cutaneous diphtheria

         . indolent, nonprogressive inf.

         . superficial, ecthymic, nonhealing ulcer with gray-brown memb.

     2. diphtheric skin inf.

         . strep. or sta. impetigo¿Í DDx Èûµé´Ù

         . frequently coexist

     3. underlying dermatoses, laceration, burn, bites or impetigo

        : secondarily contaminated

     4. site : extrimity (more common), trunk, head

     5. sx  a. pain, tenderness, erythema, & exudate : typical

            b. local hyperesthesia or hypesthesia : unusual

     6. resp. tr. colonization or symptomatic inf. & toxic Cx

         : ¼Ò¼öÀÇ È¯¾Æ¿¡¼­ (+)

Infection At Other Sites

      - ear (otitis externa)

      - eye(purulent and ulcerative conjunctivitis)

      - genital tract (purulent & ulcerative vulvovaginitis)

Toxic Myocardiopathy

      1. ptÁß 10-25%, »ç¸Á¿øÀÎ Áß 50-60%

      2. risk for significant Cx

          . extent & severity of exudative local oropharyngeal ds.

          . delay in adminstration of antitoxin

      3. first evidence of cardiac toxicity

          : 2nd to 3rd wk. of illness as pharyngeal ds. improve

            (but 1wk or 6wks °æ¿¡µµ ³ªÅ¸³¯ ¼ö ÀÖ´Ù.)

      4. tachycardia

         . fever¿Í ºñ·ÊÇÏÁö ¾ÊÀ½

         . may be evidence of cardiac toxicity or autonomic n. system dysfunction

      5. EKG

         . prolonged P-R interval

         . changes in the ST-T wave

         . single or progressive dysrhythmia

             - 1st, 2nd, 3rd degree heart block

             - atrioventricular dissociation

             - ventricular tachycardia

      6. echocardiogram

          : dilated & hypertrophic cardiomyopathy

      7. CHF : incidious or acute onset

      8. elevation of serum aspartate aminotransferase conc.

          : parallels the severity of myonecrosis

Toxic Neuropathy

     1. neurologic Cx

        . parallel the extent of primary inf.

        . multiphasic in onset

     2. acutely or 2-3wk after onset of oropharyngeal inflammation

        -> hypesthesia, & local paralysis of soft palate

     3. weakness of the post. pharyngeal, laryngeal & facial n.

        -> nasal quality in the voice, difficulty in swallowing

            & risk of death from aspiration

     4. cranial neuropathy

         . occure in the 5wks

         . oculomotor & ciliary paralysis

            - strabismus, blurred vision, difficulty with accommodation

     5. symmetric polyneuropathy

         . 10days to 3 Mo after oropharyngeal inf.

         . motor deficit with diminished deep tendon reflex

     6. prox. muscle weakness of the extrimity

        -> progressing distally

       distal weakness (more common)

        -> progressing proximally

        -> clinical & CSF finding

             : G-B synd.°ú °¨º° Èûµê

     7. paralysis of the diaphragm

     8. complete recovery is likely

     9. rarely, 2 or 3 wk after onset of illness

        -> dysfunction of the vasomotor centers

        -> hypotension or cardiac failure

Management

The Patient

Diagnostic Test

      . specimen for culture

          : nose, throat & other mucocutaneous lesion

Antitoxin

    ; *mainstay of therapy

    ; *adminstered on the basis of clinical diagnosis

        - ¡ÚWhy ?

                   / *neutralizes only free toxin

             / *diminished effect after onset of mucocutaneous Sx

    ; degree of toxicity, site & size of the memb. & duration of illness¿¡ µû¶ó Åõ¿©

      ¡ÚTable 180-1

        - once at empiric dosage

        - ÁÖ·Î IV route

        - infusion over 30-60min

    4) local manifestation of cutaneous diphtheric ¿¡´Â no valuable

       but toxic sequalae ³ªÅ¸³¯¼ö Àֱ⠶§¹®¿¡ »ç¿ëÇÏ´Â °ÍÀÌ ÁÁ´Ù

    5) 8% of Pt. given equine antitoxin

       -> serum sickness develope

 

    6) 10% of individuals

       : pre-existing hypersensitivity to horse protein

       -> infusionÀü¿¡ test½ÃÇàÇØ¾ß ÇÔ

       -> negative control(saline) & positive control (histamine)with

           epinephrine & available resuscitative equipment

 

    7) intradermal test

       a. 0.02 ml of 1:100 saline-diluted antitoxin

       b. if animal allergy Hx(+), or prior exposure to animal serum,

        -> 1:1000 saline-diluted antitoxin

       c. immediate reaction

          : wheal with surrounding erythema at least 3mm larger than the negative control test result,

             lead at 15 to 20min

    8) desensitization

        (table 180-2)

       - immediate reactionÀ» º¸ÀÌ´Â °æ¿ì protocol¿¡ µû¶ó¼­

       - with successive dose every 15min

       - negative test results

        : physiologic saline or 5% glucose solution 10ml·Î dilutionµÈ prelimimary dose of 0.5ml of antitoxin

             -> 30min observationÇϸ鼭 °¡´ÉÇÑ slowly given

             -> remainder : diluted 1:20 & 1ml/minÃʰúÇÏÁö ¾Ê°Ô Åõ¿©

    9) IV immunoglobulin

        : contain Ab to diphtheria toxin

    10) antitoxin

       : asymptomatic carrier¿¡´Â not recommend

Antimicrobial Therapy

    ; halt toxin production, treat localized inf., prevent transmission of the organism to contacts

    ; EM

           - *nasopharyngeal carrier½Ã PCº¸´Ù superior

    - 40-50mg/24hr max. 2g/24hr, oral or parenteral for 14days

    ; PC

        - *aqueous crystalline PC 100,000-150,000 u/kg/24hr #4 IM or IV for 14days

           - procaine PC 25,000-50,000u/kg/24hr #2 IM for 14days

    ; cutaneous diphtheria

       : 7-10ÀÏ Ä¡·á

    ; Tx Á¾°á ÈÄ 24hr °£°ÝÀ¸·Î nose & throat (or skin) culture¿¡¼­ negative³ª¿Í¾ß ÇÔ

        if culture (+) -> EM therapy repeat

Other Measures

    1) pharyngeal diphtheria

          - strict isolation

       cutaneous diphtheria

          - Tx Á¾°á ÈÄ negative culture  ³ª¿Ã ¶§±îÁö contact isolation

    2) cutaneous wound

        - soap & water·Î cleaning

    3) bed rest

        - acute phaseµ¿¾È

        - return of physical activity guided by the degree of toxicity

           & cardiac involvement

    4) orophayngeal & laryngeal diphtheria

        - artificial airway·Î airway obstruction & aspirationÀ» avoid

    5) steroid Tx : not recommend

    6) myocarditis ½Ã digitalis therapy

         : dysrrhythmia ÁÖÀÇ ¿äÇÔ

    7) Px: depend on

        . virulence of organism

            : subspecies gravis°¡ highest fatality

        . age

        . immunization status

        . site of inf.

        . speed of administration of the toxin

    8) Cx of most diphtheria-related death

        . mechanical obstruction from laryngeal or bull-neck diphtheria

        . myocarditis

    9) case fatality rate

        : 10% for resp. tract diphtheria

    ; *administration of diphtheria toxoid

           - at recovery

           - *not all patients develop antibodies after infection

Esposed Persons

Asymptomatic Case Contacts

  ½Å1) several steps

      a. 7day ÀÇ IPµ¿¾È closely monitored

      b. nose, throat, & cutaneous lesion culture

      c. immunization status¿Í »ó°ü¾øÀÌ antimicrobial prophylaxis

          - oral EM(40-50mg/kg/24hr for 7-10day, max 2g/24hr)

          - if intolerant of EM, or if complete compliance is not assured

               : benzathine PC IM

                 < 30kg : 60¸¸ u

                 > 30kg : 120¸¸ u

          - presumed but not proved

      d. diphtheria toxoid vaccine, in age-appropriate conc.

          - 5³â À̳»¿¡ booster doseÀ» ¹ÞÁö ¾ÊÀº immunized individual

          - 4th dose ¹ÞÁö ¾ÊÀº children

               : should be vaccinated

          - 3 dose of diphtheria toxoid ÀÌÇÏ       -+

            immunization status À» Àß ¸ð¸£´Â °æ¿ì -+ --> primary schedule¿¡ µû¶ó

                                                          immunized ½ÃÅ´

Asymptomatic Carrier

   ½Å1) several steps

        a. antimicrobial prophylaxis : 7-10 day

        b. age-appropriate preparation of diphtheria toxoid

            : 1³â À̳» booster dose ¹ÞÁö ¾ÊÀº °æ¿ì Áï½Ã Åõ¿©

        c. TxÁ¾°áÈÄ 24hr °£°ÝÀ¸·Î culture ½ÃÇà - 2ȸ ÀÌ»ó negative³ª¿Ã ¶§±îÁö isolation

              strict isolation : resp. tr. colonization

              contact isolation : cutaneous colonization only

        d. case & carrierÀÇ Tx Á¾°áÈÄ 2ÁÖ°æ repeat culture

            if positive - oral EM for 10days & follow up culture

    2) antitoxin

        : inadequately immunized ÀÏÁö¶óµµ asymptomatic close contacts or

          carrier ¿¡´Â not recommend

Prevention

    * serum antitoxin conc.

         0.01 IU/ml : minimum protective level

         0.1 IU/ml  : certain protective level

Preparation

     1) diphtheric toxoid

          prepared by  . formaldehyde treatment of toxin

                       . standardized for potency

                       . absorbed to aluminum salts

              -> enhanced immunogenecity

     2) pediatric preparation

           - DTP, DT, DTaP

           - contain 6.7-12.5 Lf units of diphtheria toxoid per 0.5 ml dose

        adult preparation

           - Td

           - contain no more than 2 Lf unit of toxoid per 0.5ml dose

     3) 6¼¼±îÁö

           higher-potency(i.e. D) formulation of toxoid

              : primary series and booster doses

                -> superior immunogenicity & minimal reactogenicity

        7¼¼ ÀÌ»ó

           Td : primary series & booster doses

                ¡ñ lower conc. of diphtheria toxoid

                      . adequately immunogenic

                      . increasing content of toxoid

                           -> age Áõ°¡ÇÒ¼ö·Î reactogenicity Áõ°¡

Schedules

     1) 6wk-7¼¼ ±îÁö

         : 5ȸ 0.5ml dose of diphtheria containing(D) vaccine

         a. primary series

            : 2, 4, 6 Mo

         b. 4th dose

            : 3dose ÈÄ 6-12Mo

         c. booster : 4-6¼¼

     2) 7¼¼ ÀÌ»ó

         : 3ȸ 0.5ml dose of diphtheria containing vaccine

          . primary series

              : 4-8ÁÖ °£°ÝÀ¸·Î 2dose

                3rd dose´Â 2nd dose ÈÄ 6-12Mo

     3) 1¼¼ Àü¿¡ DTP or DT Á¢Á¾½Ã

           - 6¼¼±îÁö total 5ȸ 0.5ml dose of diphtheria containing vaccine

        1¼¼ ÀÌÈÄ

            primary series : 3ȸ 0.5ml dose

            booster : 4-6¼¼