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ID Case Conference. Yvonne L. Ballard, MD 30 January 2008. CC: Fatigue, Shortness of Breath 49yo 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.
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ID Case Conference Yvonne L. Ballard, MD 30 January 2008
CC: Fatigue, Shortness of Breath • 49yo 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: None PSurgHx: Appendectomy, age 23 All: NKDA Meds: Nicorette gum SocHx: Lives with wife in CH 4 healthy children Ages 7, 9, 14, 17 Installs closets Chewed tobacco Occ. Beer No illicits FamHx: Mom, dec, Pancreatic CA Dad, alive, healthy Brother, alive, healthy Brother, alive, Colon CA
Physical Exam • T 36.0, P 130s, BP 157/73, RR 33 • WD, WN ill man; intubated, sedated • NCAT, Pupils dilated, minimally reactive • Tachycardic, Reg rhythm, no m/g/r • BS coarse bilaterally, diffuse • Abd soft, NT, ND, NABS • Skin: diffuse maculopapular rash on head, trunk, and extremities • Ext: no c/c/e. Cool extremities
117 91 60 57 4.4 13 6.8 11.9 192 5.4 240 75 4.3 34.1 Labs • D-dimer 3397 • Fibrinogen 857 • AT III activity 49% • BNP 33,187 • CK 551, MB 24, Trop (–) • PT 35, PTT 53, INR 2.6 • Lactate 7.3 • ABG 6.93/66/44/58% • Etoh Screen Negative 4.5 1.3 8.1
Micro Data • Urine Culture - Negative • HIV ELISA - Negative • RPR - NR • RMSF Serologies - Negative • CMV PCR - Negative • Skin Lesion HSV 1 and 2 PCR - Negative • EBV Serologies – Indicate previous exposure
Hospital Course • Intubated in the ED • Started on Vanc, Zosyn, Levaquin • Levophed, Vasopressin, Phenylephrine • Bicarb gtt, IVF boluses • Three central lines placed • Multiple modes of ventilation failed • Worsening CXR • Propofol gtt • PEA Arrest…Successful code • Family consented for ECMO
Hospital Course, cont. • Pt desats to 40s while en route to SICU • Prep for ECMO begins • Pt goes into Asystole • Resuscitation unsuccessful • Pronounced dead at 2:01 am, after 20 minute code
Micro Data • Blood Culture, 4/4 bottles positive: • Streptococcus pyogenes (Group A Strep) • Induced sputum – Group A Strep • Right Lung Biopsy – Group A Strep • Right Lung Biopsy – Viral Cx Negative • Right Lung Biopsy – CMV PCR Negative
Micro Data • Group A Strep Sensitivity Testing • Penicillin G (MIC 0.032) • Vancomycin (MIC 1) • Levofloxacin (MIC 0.5) • Erythromycin (sens) • Clindamycin (sens)
Group A Streptococcus • Aerobic gram + coccus pairs and chains • Catalase negative • Beta-hemolytic on blood agar • Growth inhibited by bacitracin
Virulence Factors • M protein • Filamentous protein on cell membrane; has antiphagocytic properties • Types 1, 3, 12, and 28 most common in shock • Pts with decreased serum antibodies to M prot more susceptible to invasive infections • Exotoxins • Pyrogenic exotoxins A, B, and C; SSA, MF • Cause cytotoxicity, pyrogenicity, and enhances lethal effects of endotoxins
Streptococcus pyogenes • Clinical presentations: • Pharyngitis, Sinusitis, Otitis Media • Skin and soft tissue infections • Impetigo, Erysipelas, Localized cellulitis • Invasive Disease • Bacteremia • Necrotizing Fasciitis, Gangrenous Myositis • Pneumonia • Toxic Shock Syndrome
Diagnosis of STSS • Isolation of GAS from normally sterile site • AND Hypotension • PLUS evidence of organ failure (at least 2) • Renal failure • Coagulopathy • Liver involvement • ARDS • Soft tissue necrosis • Erythematous macular rash
The Epidemiology of Invasive Group A Streptococcal Infection and Potential Vaccine Implications: United States, 2000-2004 • Data collection from CDC and ABCs • Population of 29.7 million persons over 10 US cities • San Francisco, Denver, Atlanta, Baltimore, Portland, Albany, Rochester, urban Tennessee, Minnesota, New Mexico, Conneticut • January 1, 2000 – December 31, 2004 • Invasive 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 GAS • Avg annual incidence = 3.5 cases per 100,000 persons CID 2007; 45: 853-62
Clinical Presentation • Cutaneous 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
Case Fatality Rates • Overall, CFR was 13.7% • Projections of US population estimate that 8950 – 11,500 invasive GAS infections occur annually, with 1050 – 1850 deaths • Predictors of Death • Increasing Age • Residence in Nursing Home • Presence of a Specific Disease Syndrome • Emm 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 ICU • Chart review of all cases of invasive GAS admitted to ICUs in all Ontario, Toronto b/w Jan 1992 and June 2002 • 62 total patients • 64% with skin/soft tissue infections • 20% with pneumonia • 68% had positive blood cultures • 50% with chronic disease • Overall mortality 40% • Directly correlated with APACHE II scores and with the number of organ failures • 55% had STSS: Mortality rate = 68% Chest 2006; 130; 1679-1686
Treatment • Hemodynamic Support • Surgical Therapy • Empiric 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 treatment • PCN/Beta-lactamase • Studies suggest PCN failure with large organsim burden • PBPs decrease in the stationary phase of bacterial growth in vitro • IVIG • Used as an adjunct to antibiotics • Able to neutralize superantigens and facilitates opsonization of streptococci • Inadequate evidence to support its use
Post-Influenza Pneumonia • Most common complication of influenza • Most frequent in patients with underlying chronic conditions • CV or Pulmonary Disease • DM, Renal dz, Hemoglobinopathy • Immunosuppressed • Residents of chronic care facilities • Primary Influenza Pneumonia vs. Secondary Bacterial Pneumonia
Secondary Bacterial Pneumonia • Accounts for ~25% of influenza-associated deaths • Influenza causes decrease in size of cells and loss of cilia in epithelium lining the trachea and bronchus • S. pneumo most common organism (~48%) • S. aureus second most common (19%) • H. flu also implicated • Typically, a relapse of symptoms after some degree of improvement • ? Role of Oseltamivir Curr Med Res Opin. 2007 Dec;23(12):2961-70