ID Case Conference

Yvonne L. Ballard, MD30 January 2008

CC: Fatigue, Shortness of Breath49yo CM had a URI 2-3 weeks PTA. Sx included rhinorrhea, cough, malaise. Sx lasted one week, and resolved.4 days PTA, recurrent sx developed. 2 days PTA, pt presented to PCP, who performed a rapid flu test, which was positive. Pt treated with Tamiflu, which he started to take immediately.Sx progressed, and pt called EMS for severe fatigue and difficulty breathing

PMH: NonePSurgHx:

Appendectomy, age 23

All: NKDAMeds: Nicorette gumSocHx:

Lives with wife in CH4 healthy children

Ages 7, 9, 14, 17

Installs closetsChewed tobaccoOcc. BeerNo illicits

FamHx:Mom, dec, Pancreatic CADad, alive, healthyBrother, alive, healthyBrother, alive, Colon CA

Physical ExamT 36.0, P 130s, BP 157/73, RR 33WD, WN ill man; intubated, sedatedNCAT, Pupils dilated, minimally reactiveTachycardic, Reg rhythm, no m/g/rBS coarse bilaterally, diffuseAbd soft, NT, ND, NABSSkin: diffuse maculopapular rash on head, trunk, and extremitiesExt: no c/c/e. Cool extremities

Labs

D-dimer 3397Fibrinogen 857AT III activity 49%BNP 33,187CK 551, MB 24, Trop (–)PT 35, PTT 53, INR 2.6Lactate 7.3ABG 6.93/66/44/58%Etoh Screen Negative

117

4.4

91

13

60

6.857

4.375

192

5.434.1

24011.9

1.34.5

8.1

Micro DataUrine Culture - NegativeHIV ELISA - NegativeRPR - NRRMSF Serologies - NegativeCMV PCR - NegativeSkin Lesion HSV 1 and 2 PCR - NegativeEBV Serologies – Indicate previous exposure

Discussion…

Streptococcus pyogenes

Hospital CourseIntubated in the EDStarted on Vanc, Zosyn, LevaquinLevophed, Vasopressin, PhenylephrineBicarb gtt, IVF bolusesThree central lines placedMultiple modes of ventilation failedWorsening CXRPropofol gttPEA Arrest…Successful codeFamily consented for ECMO

Hospital Course, cont.Pt desats to 40s while en route to SICUPrep for ECMO beginsPt goes into AsystoleResuscitation unsuccessfulPronounced dead at 2:01 am, after 20 minute code

Micro DataBlood Culture, 4/4 bottles positive:

Streptococcus pyogenes (Group A Strep)

Induced sputum – Group A StrepRight Lung Biopsy – Group A StrepRight Lung Biopsy – Viral Cx NegativeRight Lung Biopsy – CMV PCR Negative

Micro DataGroup A Strep Sensitivity Testing

Penicillin G (MIC 0.032)Vancomycin (MIC 1)Levofloxacin (MIC 0.5)Erythromycin (sens)Clindamycin (sens)

Group A StreptococcusAerobic gram + coccus pairs and chainsCatalase negativeBeta-hemolytic on blood agarGrowth inhibited by bacitracin

GAS Disease Manifestations

Virulence FactorsM protein

Filamentous protein on cell membrane; has antiphagocytic propertiesTypes 1, 3, 12, and 28 most common in shockPts with decreased serum antibodies to M prot more susceptible to invasive infections

ExotoxinsPyrogenic exotoxins A, B, and C; SSA, MFCause cytotoxicity, pyrogenicity, and enhances lethal effects of endotoxins

Streptococcus pyogenesClinical presentations:

Pharyngitis, Sinusitis, Otitis MediaSkin and soft tissue infections

Impetigo, Erysipelas, Localized cellulitis

Invasive DiseaseBacteremiaNecrotizing Fasciitis, Gangrenous MyositisPneumoniaToxic Shock Syndrome

Diagnosis of STSSIsolation of GAS from normally sterile siteAND HypotensionPLUS evidence of organ failure (at least 2)

Renal failureCoagulopathyLiver involvementARDSSoft tissue necrosisErythematous macular rash

The Epidemiology of Invasive Group A Streptococcal Infection and Potential

Vaccine Implications: United States, 2000-2004

Data collection from CDC and ABCsPopulation of 29.7 million persons over 10 US citiesSan Francisco, Denver, Atlanta, Baltimore, Portland, Albany, Rochester, urban Tennessee, Minnesota, New Mexico, ConneticutJanuary 1, 2000 – December 31, 2004Invasive GAS = isolation of GAS from a normally sterile site or from a wound specimen obtained from a patient with nec fasc or STSS

CID 2007; 45: 853-62

5400 cases of invasive GASAvg annual incidence = 3.5 cases per 100,000 persons

CID 2007; 45: 853-62

Clinical PresentationCutaneous or soft tissue infection (36%)Primary Bacteremia (29%)Pneumonia (15%)GAS isolated from

Blood specimens (77%)Joint Fluid (8%)Surgical Specimens (6%)Peritoneal fluid (2%)Pleural fluid (2%)

CID 2007; 45: 853-62

CID 2007; 45: 853-62

CID 2007; 45: 853-62

Case Fatality RatesOverall, CFR was 13.7%Projections of US population estimate that 8950 – 11,500 invasive GAS infections occur annually, with 1050 – 1850 deathsPredictors of Death

Increasing AgeResidence in Nursing HomePresence of a Specific Disease SyndromeEmm type (1, 3, 12)Underlying condition

CID 2007; 45: 853-62

Morbidity and Mortality of Patients with Invasive Group A Streptococcal Infections

Admitted to the ICUChart review of all cases of invasive GAS admitted to ICUs in all Ontario, Toronto b/w Jan 1992 and June 200262 total patients

64% with skin/soft tissue infections20% with pneumonia68% had positive blood cultures50% with chronic disease

Overall mortality 40%Directly correlated with APACHE II scores and with the number of organ failures55% had STSS: Mortality rate = 68%

Chest 2006; 130; 1679-1686

TreatmentHemodynamic SupportSurgical TherapyEmpiric Antibiotics

Clindamycin PLUS:A carbapenem OR a PCN plus beta-lactamase inhibitor IVIG (1 gm/kg day one, then 0.5gm/kg days two and three)

Limitations in treatmentPCN/Beta-lactamase

Studies suggest PCN failure with large organsim burdenPBPs decrease in the stationary phase of bacterial growth in vitro

IVIGUsed as an adjunct to antibioticsAble to neutralize superantigens and facilitates opsonization of streptococciInadequate evidence to support its use

Post-Influenza PneumoniaMost common complication of influenzaMost frequent in patients with underlying chronic conditions

CV or Pulmonary DiseaseDM, Renal dz, HemoglobinopathyImmunosuppressedResidents of chronic care facilities

Primary Influenza Pneumonia vs. Secondary Bacterial Pneumonia

Secondary Bacterial Pneumonia

Accounts for ~25% of influenza-associated deathsInfluenza causes decrease in size of cells and loss of cilia in epithelium lining the trachea and bronchusS. pneumo most common organism (~48%)S. aureus second most common (19%)H. flu also implicatedTypically, a relapse of symptoms after some degree of improvement? Role of Oseltamivir

Curr Med Res Opin. 2007 Dec;23(12):2961-70

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