A Recurrence of Group A Streptococcal Toxic Shock Syndrome at ...

1,612 views

Published on

Published in: Health & Medicine
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
1,612
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
12
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide
  • Pt who received IVIG
  • End with conversation with brother (single mother caring for 8 yo Autistic son). Ethical issues of multiple limb amputees. Brother expressed that pt would be happiest being alive, pursue aggressive therapy.
  • A Recurrence of Group A Streptococcal Toxic Shock Syndrome at ...

    1. 1. A Recurrence of Group A StreptococcalA Recurrence of Group A Streptococcal Toxic Shock Syndrome at GUH:Toxic Shock Syndrome at GUH: Is thereIs there ever a good outcome?ever a good outcome? Jennifer Vittorio, MDJennifer Vittorio, MD Internal Medicine-PediatricsInternal Medicine-Pediatrics Georgetown University HospitalGeorgetown University Hospital
    2. 2. HistoryHistory  CC:CC: Transfer from OSH with Septic ShockTransfer from OSH with Septic Shock  HPI:HPI:  TC is 47 yo Caucasian female who was in her usual state of health until 1TC is 47 yo Caucasian female who was in her usual state of health until 1 week prior to admission at which time she reportedly had a brief 24-hourweek prior to admission at which time she reportedly had a brief 24-hour “viral-illness”“viral-illness”  Subsequently developed 2-3 days of watery diarrhea and abdominal painSubsequently developed 2-3 days of watery diarrhea and abdominal pain  She presented to OSH on 4/8/09 at 5PM with evidence of respiratoryShe presented to OSH on 4/8/09 at 5PM with evidence of respiratory and circulatory failure, was intubated and admitted to MICU for furtherand circulatory failure, was intubated and admitted to MICU for further monitoringmonitoring  She was started on vasopressors and broad-spectrum abx includingShe was started on vasopressors and broad-spectrum abx including vancomycin, clindamycin and zosynvancomycin, clindamycin and zosyn  Her LUE was noted to be mottled and cyanotic with delayed CRT.Her LUE was noted to be mottled and cyanotic with delayed CRT. Venous dopplers were negative for DVTVenous dopplers were negative for DVT  Clinical condition continued to decline over the course of the evening.Clinical condition continued to decline over the course of the evening. She developed rhabdomyolysis, renal failure and refractory hypotensionShe developed rhabdomyolysis, renal failure and refractory hypotension  She was transferred to GUH MICU on 4/9/09 at 3PM for furtherShe was transferred to GUH MICU on 4/9/09 at 3PM for further evaluation and treatmentevaluation and treatment
    3. 3. History cont.History cont.  PMH:PMH: Breast Cancer dx 2005 s/p CTX, XRT – inBreast Cancer dx 2005 s/p CTX, XRT – in remissionremission  PSH:PSH: Breast lumpectomyBreast lumpectomy  MEDS:MEDS: No home medsNo home meds  MEDS on Transfer:MEDS on Transfer: Levophed gtt, Neosynephrine gtt,Levophed gtt, Neosynephrine gtt, Vancomycin, Zosyn, Clindamycin, Heparin 5000 unitsVancomycin, Zosyn, Clindamycin, Heparin 5000 units subq tid, Dilaudid, Fentanyl, Protonixsubq tid, Dilaudid, Fentanyl, Protonix  ALL:ALL: NKDANKDA  Fam Hx:Fam Hx: DM, CADDM, CAD  Soc Hx:Soc Hx: Works for EPA. No tobacco, alcohol or illicitWorks for EPA. No tobacco, alcohol or illicit drug use. No recent travel. 8 year old healthy son.drug use. No recent travel. 8 year old healthy son. Brother is next of kin & provides much of the historyBrother is next of kin & provides much of the history
    4. 4. Physical ExamPhysical Exam  Vitals:Vitals: T – 37.0 BP – 110/86 P – 84 RR – 14 PaO2T – 37.0 BP – 110/86 P – 84 RR – 14 PaO2 – 100% AC 500/24/10 FiO2 100%– 100% AC 500/24/10 FiO2 100%  GEN:GEN: Intubated, sedated on ventIntubated, sedated on vent  HEENT:HEENT: NCAT; PERRL; anicteric sclera;NCAT; PERRL; anicteric sclera; mottled/cyanotic MMmottled/cyanotic MM  NECK:NECK: Supple, no thyromegaly, no LADSupple, no thyromegaly, no LAD  CV:CV: S1, S2, distant heart sounds, no m/r/gS1, S2, distant heart sounds, no m/r/g  PULM:PULM: CTAB antCTAB ant  ABD:ABD: NABS, soft, NT/ND, no hsmNABS, soft, NT/ND, no hsm  EXT:EXT: Mottled, cool, ecchymosis noted. DopplerableMottled, cool, ecchymosis noted. Dopplerable pulses LUEpulses LUE  SKIN:SKIN: Bullous lesion noted LUEBullous lesion noted LUE  VAGINAL:VAGINAL: No foreign objects in vaginal vaultNo foreign objects in vaginal vault
    5. 5. Bullous LesionBullous Lesion
    6. 6. Necrosis of FingertipsNecrosis of Fingertips
    7. 7. Laboratory StudiesLaboratory Studies  CBC:CBC:  BMP:BMP:  LFTS:LFTS: 2.72.7 1.21.2 1.01.0 433433 121121 12.7 35.8 52 N45 B21 L4 M27 E1 138 3.7 117 9 46 3.1 94 58 12.112.1 5.3 1.5 6.5
    8. 8. Laboratory Studies cont.Laboratory Studies cont.  Lactic Acid:Lactic Acid: 13.013.0  Lipase: 16Lipase: 16  Troponin I: 0.470Troponin I: 0.470  CPK:CPK: 24,68324,683  PT/INR: 30.7/PT/INR: 30.7/2.902.90  D dimer: >200D dimer: >200  Fibrinogen: 179Fibrinogen: 179  Blood Cx:Blood Cx: Gram + Cocci chainsGram + Cocci chains
    9. 9. Hospital CourseHospital Course  Admitted to MICU and continued on early goalAdmitted to MICU and continued on early goal directed therapy for septic shockdirected therapy for septic shock  Infectious disease, orthopedic, limb service consultationInfectious disease, orthopedic, limb service consultation were obtained at the time of admissionwere obtained at the time of admission  Diagnosed with Group A strep toxic shock syndromeDiagnosed with Group A strep toxic shock syndrome & LUE necrotizing fasciitis& LUE necrotizing fasciitis  Pt was started on abx therapy with meropenem,Pt was started on abx therapy with meropenem, clindamycin, vancomycinclindamycin, vancomycin  Received a course of IVIGReceived a course of IVIG  Taken to OR around 8 PM evening of admission andTaken to OR around 8 PM evening of admission and underwent LUE amputation. Diagnosis of necrotizingunderwent LUE amputation. Diagnosis of necrotizing fasciitis confirmedfasciitis confirmed
    10. 10. Hospital Course cont.Hospital Course cont.  Myonecrosis disseminated to remaining 3 limbsMyonecrosis disseminated to remaining 3 limbs & thoracic cavity& thoracic cavity  4/15/09: Patient underwent bilateral knee4/15/09: Patient underwent bilateral knee disarticulation & right lateral thigh fasciotomydisarticulation & right lateral thigh fasciotomy  4/17/09: Patient again hypotensive requiring4/17/09: Patient again hypotensive requiring vasopressor supportvasopressor support  Develops further necrosis of RUE, LE stumps,Develops further necrosis of RUE, LE stumps, & perineum& perineum  Pt continued to deteriorate. Code statusPt continued to deteriorate. Code status changed to DNR. Patient died on 4/19/09changed to DNR. Patient died on 4/19/09
    11. 11. GAS Toxic Shock SyndromeGAS Toxic Shock Syndrome  GAS is a common pathogen of the throat andGAS is a common pathogen of the throat and skin that causes pharyngitis and a spectrum ofskin that causes pharyngitis and a spectrum of skin and soft tissue infectionsskin and soft tissue infections  The incidence of invasive GAS infection in NorthThe incidence of invasive GAS infection in North America and Europe is an estimated 3.5 cases perAmerica and Europe is an estimated 3.5 cases per 100,000 persons annually100,000 persons annually11  8-14% of patients who develop invasive GAS8-14% of patients who develop invasive GAS infection will also develop GAS TSSinfection will also develop GAS TSS11  It is important to recognize GAS infections early and toIt is important to recognize GAS infections early and to treat appropriately in order to limit toxin production andtreat appropriately in order to limit toxin production and decrease morbidity and mortalitydecrease morbidity and mortality
    12. 12. Streptococcus pyogenesStreptococcus pyogenes
    13. 13. PathogenesisPathogenesis  GAS TSS is mediated by toxins that act as superantigensGAS TSS is mediated by toxins that act as superantigens which bypass the usual antigen-mediated immune responsewhich bypass the usual antigen-mediated immune response resulting in release of large quantities of inflammatoryresulting in release of large quantities of inflammatory cytokinescytokines  The major virulence factor of GAS isThe major virulence factor of GAS is M proteinM protein  M1 and M3 are the most virulentM1 and M3 are the most virulent  M protein makes the organism resistant to phagocytosis byM protein makes the organism resistant to phagocytosis by inhibiting activation of alternate complement pathways on theinhibiting activation of alternate complement pathways on the cell surfacecell surface  Streptococcal exotoxinsStreptococcal exotoxins are also elaborated by GASare also elaborated by GAS  Pyrogenic exotoxin A (SPEA) and B (SPEB) are found inPyrogenic exotoxin A (SPEA) and B (SPEB) are found in majority of casesmajority of cases  Trigger massive T cell proliferation and cytokine release resultingTrigger massive T cell proliferation and cytokine release resulting in capillary leak and tissue damagein capillary leak and tissue damage
    14. 14. Why are certain individuals more susceptibleWhy are certain individuals more susceptible to severe GAS infections?to severe GAS infections?  Studies have suggested that the presence of specific anti-MStudies have suggested that the presence of specific anti-M Ab confers some degree of host protection from that strainAb confers some degree of host protection from that strain of GAS. Once infected however, these Ab do not appear toof GAS. Once infected however, these Ab do not appear to offer protection from STSS.offer protection from STSS.  It has been proposed thatIt has been proposed that HLA Class IIHLA Class II allelic variationallelic variation contributes to differences in severity of invasive GAScontributes to differences in severity of invasive GAS infections through their ability to regulate cytokine responseinfections through their ability to regulate cytokine response triggered by streptococcal superantigenstriggered by streptococcal superantigens22  The complex immune cascade is initiated by the GASThe complex immune cascade is initiated by the GAS superantigen and the interplay with one’s immune systemsuperantigen and the interplay with one’s immune system determines the severity of illnessdetermines the severity of illness
    15. 15. Risk FactorsRisk Factors  Age <9 yr or >60 yrAge <9 yr or >60 yr  VaricellaVaricella  HIV/AIDSHIV/AIDS  CancerCancer  DiabetesDiabetes  Heart DiseaseHeart Disease  Lung DiseaseLung Disease  ?NSAIDS?NSAIDS  Alcohol AbuseAlcohol Abuse  Nursing HomeNursing Home ResidentResident  Minor TraumaMinor Trauma  Injury resulting inInjury resulting in hematoma, bruising,hematoma, bruising, muscle strainmuscle strain  Surgical ProceduresSurgical Procedures
    16. 16. DiagnosisDiagnosis The Working Group on Severe Streptoccocal Infections estThe Working Group on Severe Streptoccocal Infections est the following clinical guideline for diagnosis of GAS TSS:the following clinical guideline for diagnosis of GAS TSS:33  1. Isolation of GAS from sterile site1. Isolation of GAS from sterile site  2. Hypotension2. Hypotension  Adult SBP < 90 mmHgAdult SBP < 90 mmHg  Child SBP < 5Child SBP < 5thth % for age% for age  ANDAND two or more of the following:two or more of the following:  Renal impairmentRenal impairment  CoagulopathyCoagulopathy  Liver involvementLiver involvement  ARDSARDS  Erythematous macular rash, may desquamateErythematous macular rash, may desquamate  Soft tissue necrosisSoft tissue necrosis
    17. 17. TreatmentTreatment  AntibioticsAntibiotics  Beta-lactam antibiotics such as penicillin GBeta-lactam antibiotics such as penicillin G  Reduction in efficacy of PCN has been demonstrated when a highReduction in efficacy of PCN has been demonstrated when a high density of organisms is present (“Eagle Effect”)density of organisms is present (“Eagle Effect”)  Clindamycin (inhibits protein synthesis)Clindamycin (inhibits protein synthesis)  IVIGIVIG  Contains neutralizing antibody to streptococcal exotoxinContains neutralizing antibody to streptococcal exotoxin  Efficacy has yet to be proved in RCTEfficacy has yet to be proved in RCT  SurgerySurgery  Should be considered in pt who initially have fever, excruciatingShould be considered in pt who initially have fever, excruciating pain followed by progression to soft tissue swelling and formationpain followed by progression to soft tissue swelling and formation of violaceous vesicles and bullaeof violaceous vesicles and bullae  Debridement of all infected tissue should be carried out at firstDebridement of all infected tissue should be carried out at first operative procedureoperative procedure
    18. 18. Eagle EffectEagle Effect  First described by Eagle in 1952First described by Eagle in 195244  High inoculum of organisms encounteredHigh inoculum of organisms encountered in overwhelming infections leads to rapidin overwhelming infections leads to rapid attainment of the stationary growth phaseattainment of the stationary growth phase  Subsequent decrease in expression of cell wall penicillinSubsequent decrease in expression of cell wall penicillin binding proteins (PBPs), the molecular targets ofbinding proteins (PBPs), the molecular targets of penicillin, renders penicillin less effectivepenicillin, renders penicillin less effective  Clindamycin retains efficacy by inhibiting proteinClindamycin retains efficacy by inhibiting protein synthesissynthesis  Clindamycin is also a potent suppressor of toxinClindamycin is also a potent suppressor of toxin formation and facilitates phagocytosis by inhibition offormation and facilitates phagocytosis by inhibition of M-protein synthesisM-protein synthesis
    19. 19. Evidence for IVIGEvidence for IVIG  Several case reports have described the use of IVIG inSeveral case reports have described the use of IVIG in pt with STSSpt with STSS  Case control study of IVIG therapy in STSSCase control study of IVIG therapy in STSS demonstrated survival benefit in pt who received IVIGdemonstrated survival benefit in pt who received IVIG  A double blind, randomized, placebo-controlledA double blind, randomized, placebo-controlled European trial compared IVIG to placebo as adjunctiveEuropean trial compared IVIG to placebo as adjunctive therapy in adults with GAS TSS with or withouttherapy in adults with GAS TSS with or without necrotizing fasciitis. Trial was terminated because ofnecrotizing fasciitis. Trial was terminated because of slow pt recruitment. Results were obtained from 21 pt.slow pt recruitment. Results were obtained from 21 pt. The mortality rate was 36% in placebo group comparedThe mortality rate was 36% in placebo group compared to 10% in IVIG but statistical significance was notto 10% in IVIG but statistical significance was not reached (presumably because of small sample size)reached (presumably because of small sample size)55
    20. 20. A Recurrence of Group AA Recurrence of Group A Streptococcal Toxic Shock SyndromeStreptococcal Toxic Shock Syndrome at GUH:at GUH: Is there ever a goodIs there ever a good outcome?outcome?
    21. 21. Patient 2Patient 2  Pt is 62 year old previously healthy CaucasianPt is 62 year old previously healthy Caucasian female who presented to an OSH with 2 day hxfemale who presented to an OSH with 2 day hx of abdominal pain, nausea, non-bloody emesis,of abdominal pain, nausea, non-bloody emesis, and worsening mental statusand worsening mental status  At OSH the pt was noted to beAt OSH the pt was noted to be thrombocytopenic and was presumptivelythrombocytopenic and was presumptively diagnosed with TTP and transferred to GUHdiagnosed with TTP and transferred to GUH for further managementfor further management
    22. 22. Patient 2 cont.Patient 2 cont.  Upon transfer to GUH the pt was diagnosed with meningitis, septic shock and respiratory failure and was subsequently intubated  Skin examination was significant for petechial rash, purpura fulminans, and right thigh eschar  Her admission labs were notable for leukopenia, thrombocytopenia, acute renal failure
    23. 23. Purpura FulminansPurpura Fulminans
    24. 24. Patient 2 cont.Patient 2 cont.  Streptococcus pyogenesStreptococcus pyogenes grew from 4/4 blood culturegrew from 4/4 blood culture bottles within 8 hoursbottles within 8 hours  The patient was treated with penicillin G,The patient was treated with penicillin G, clindamycin, and IVIG x 3 dosesclindamycin, and IVIG x 3 doses  Microthrombosis of limbs became lifeMicrothrombosis of limbs became life threatening andthreatening and all 4 extremities wereall 4 extremities were amputatedamputated  The patient had a prolonged, complicated ICUThe patient had a prolonged, complicated ICU course but was ultimately discharged 2 monthscourse but was ultimately discharged 2 months later tolater to acute rehabacute rehab with plans for prosthesiswith plans for prosthesis fittingsfittings
    25. 25. PrognosisPrognosis  Mortality associated with GAS TSS ranged fromMortality associated with GAS TSS ranged from 33 to 81% in several population based studies33 to 81% in several population based studies66  A retrospective study of 66 pt with GAS TSS inA retrospective study of 66 pt with GAS TSS in Japan, noted the following statistically significantJapan, noted the following statistically significant finding amongst survivors and those who died:finding amongst survivors and those who died:77  Lower WBCLower WBC  Lower platelet countsLower platelet counts  Higher serum creatinineHigher serum creatinine  Lower body temperatureLower body temperature  Lower systolic blood pressureLower systolic blood pressure
    26. 26. Prognosis cont.Prognosis cont.  Prospective, population-based surveillance study conducted inProspective, population-based surveillance study conducted in Ontario, Canada from 1991 to 1995 uncovered the followingOntario, Canada from 1991 to 1995 uncovered the following findings:findings:88  77 clinical cases of Group A Strep NF uncovered during this time77 clinical cases of Group A Strep NF uncovered during this time period; 47 % of cases associated with GAS TSSperiod; 47 % of cases associated with GAS TSS  Overall case fatality rate was 34%Overall case fatality rate was 34%  Mortality was correlated with increasingMortality was correlated with increasing ageage, presence of, presence of hypotensionhypotension,, andand bacteremiabacteremia  Outcome was not correlated with M-type or the presence of spe geneOutcome was not correlated with M-type or the presence of spe gene  Surgical Role:Surgical Role:  16 pt did not have surgery (100% Mortality) – all of these pt died16 pt did not have surgery (100% Mortality) – all of these pt died  10/61 pt died despite surgery (16% Mortality): 6 had amputations, 410/61 pt died despite surgery (16% Mortality): 6 had amputations, 4 had debridement alonehad debridement alone  51 survivors had a median of 2 surgical procedures51 survivors had a median of 2 surgical procedures  12/51 (24%) of those who survived required amputation12/51 (24%) of those who survived required amputation  There was no difference in time to first surgical procedure in thoseThere was no difference in time to first surgical procedure in those who died compared with those who survivedwho died compared with those who survived  Pt who died were more likely to have had amputation as their initialPt who died were more likely to have had amputation as their initial procedureprocedure
    27. 27. Prognosis cont.Prognosis cont.  Mehta S, McGeer A, Low D, et al. Morbidity and mortalityMehta S, McGeer A, Low D, et al. Morbidity and mortality of patients with invasive Group A Streptococcal infectionsof patients with invasive Group A Streptococcal infections admitted to the ICU.admitted to the ICU. CHESTCHEST 2006; 130:1679-1686.2006; 130:1679-1686.  Prospective, population-based surveillance studyProspective, population-based surveillance study conducted in Ontario, Canadaconducted in Ontario, Canada  Overall mortality rate was 40%. Mortality rates inOverall mortality rate was 40%. Mortality rates in patients with and without GAS TSS were 68% and 8%patients with and without GAS TSS were 68% and 8% respectivelyrespectively  CoagulopathyCoagulopathy andand liver failureliver failure were associated withwere associated with increased mortalityincreased mortality  Use of IVIG, surgical intervention and clindamycin useUse of IVIG, surgical intervention and clindamycin use were not significantly associated with survivalwere not significantly associated with survival
    28. 28. SummarySummary  Group A Streptococcal TSS associated withGroup A Streptococcal TSS associated with necrotizing fasciitis continues to carry a highnecrotizing fasciitis continues to carry a high mortality ratemortality rate  In the ICU setting the mortality rate is as high asIn the ICU setting the mortality rate is as high as 68%68%  Survivors of GAS TSS can anticipate limb-Survivors of GAS TSS can anticipate limb- threatening morbidity with amputation rates asthreatening morbidity with amputation rates as high as 24%high as 24%  Without surgical intervention mortality ratesWithout surgical intervention mortality rates have approached 100%have approached 100%
    29. 29. Summary cont.Summary cont.  Although optimal management includes surgicalAlthough optimal management includes surgical intervention, the addition of clindamycin and theintervention, the addition of clindamycin and the administration of IVIG, data from the literatureadministration of IVIG, data from the literature using these modalities has not always resulted inusing these modalities has not always resulted in a favorable outcomea favorable outcome  The literature fails to address quality of lifeThe literature fails to address quality of life issues associated with this devastating illnessissues associated with this devastating illness
    30. 30. ReferencesReferences 1.1. Baxter F, McChesney J. Severe group A streptococcal infection andBaxter F, McChesney J. Severe group A streptococcal infection and streptococcal toxic shock syndrome.streptococcal toxic shock syndrome. Can J AnesthCan J Anesth 2000;47:1129-1140.2000;47:1129-1140. 2.2. Kotb M, Norrby-Teglund A, McGeer A, et al. An immunogenetic andKotb M, Norrby-Teglund A, McGeer A, et al. An immunogenetic and molecular basis for differences in outcomes of invasive group A streptococcalmolecular basis for differences in outcomes of invasive group A streptococcal infections.infections. Nat MedNat Med Published 2002; 8:1398-1404.Published 2002; 8:1398-1404. 3.3. Defining the group A streptococcal toxic shock syndrome: rationale andDefining the group A streptococcal toxic shock syndrome: rationale and consensus definition. The working group on severe streptococcal infections.consensus definition. The working group on severe streptococcal infections. JAMAJAMA 1993; 269:390.1993; 269:390. 4.4. Eagle H. Experimental approach to the problem of treatment failure withEagle H. Experimental approach to the problem of treatment failure with penicillin. I. Group A streptococcal infection in mice.penicillin. I. Group A streptococcal infection in mice. Am J MedAm J Med 1952: 13;389.1952: 13;389. 5.5. Darenberg J, Ihendyane N, Sjolin J, et al. Intravenous immunoglobulin GDarenberg J, Ihendyane N, Sjolin J, et al. Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: A European randomized,therapy in streptococcal toxic shock syndrome: A European randomized, double-blind, placebo-controlled trial.double-blind, placebo-controlled trial. Clin Infect DisClin Infect Dis 2003; 37:333.2003; 37:333. 6.6. Mehta S, McGeer A, Low D, et al. Morbidity and mortality of patients withMehta S, McGeer A, Low D, et al. Morbidity and mortality of patients with invasive Group A Streptococcal infections admitted to the ICU.invasive Group A Streptococcal infections admitted to the ICU. CHESTCHEST 2006;2006; 130:1679-1686.130:1679-1686. 7. Hasegawa T, Hashikawa SN, Nakamura T, et al. Factors determining prognosis in streptococcal toxic shock-like syndrome: results of a nationwide investigation in Japan. Microbes Infect 2004; 6:1073. 8.8. Kaul R, McGeer A, Low D, et al. Population-based surveillance for Group AKaul R, McGeer A, Low D, et al. Population-based surveillance for Group A Streptococcal necrotizing fasciitis: clinical features, prognostic indicators, andStreptococcal necrotizing fasciitis: clinical features, prognostic indicators, and microbiologic analysis of seventy-seven Cases.microbiologic analysis of seventy-seven Cases. Am J MedAm J Med 1997; 103:18-24.1997; 103:18-24.

    ×