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Women’s Health Conference 2014 Chicago Dr. Lovina Machado.

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1 Women’s Health Conference 2014 Chicago Dr. Lovina Machado

2 FULMINANT PUERPERAL SEPSIS DUE TO GROUP A STREPTOCOCCUS – KEY MANAGEMENT ISSUES DR. LOVINA MACHADO MBBS,DGO,MD,FRCOG,FRCPI Senior Consultant, Dept. of Obs & Gyn Sultan Qaboos University Hospital, Muscat, Oman Associate Program Director, OBGYN Residency Program, Oman Medical Specialty Board Dr. Lovina Machado

3 Outline  Historically …..  UN Millenium goals – sepsis related MMR  The client  About GAS, Why is it so virulent?  Typical features  Key Management Issues  Take home messages Dr. Lovina Machado

4 Historically speaking……  1500 BC – ancient Hindus ---childbed fever – hygiene- cut nails  500 BC – Hippocrates – postpartum fever due to suppression of lochia resulting from accumulation of humors  – Hieronymous Mercurialis –failure of lactation among affected women –milk instead of flowing to the breast, localised in the uterus → purulent discharge “milk fever’  UK, Scotland 1800’s..J. Bundell, T. Watson, R. Collins –cleanliness, hand hygiene, chlorination  Ignaz Semmelweis – Vienna – transmission route & hand hygiene. Reduced MMR from18% to 2.4% Dr. Lovina Machado

5 Global, regional, and national levels and causes of maternal mortality during 1990—2013: a systematic analysis for the Global Burden of Disease Study 2013 No. of maternal deaths from all causes in 188 countries between 1990 & The Lancet, Online, 2 May doi: /S (14) Dr. Lovina Machado

6 Global Causes of maternal death: a WHO systematic analysis  Estimated 287,000 maternal deaths worldwide in 2010 – most in lower & middle income countries- most avoidable  Reduction of maternal mortality – global health priority & is a target in the UN Millenium Devpt. Goals launched in Sept 2010  To achieve this, a 75% decrease in MMR between 1990 & 2015 is needed  Key is to understand the causes & report data accurately The Lancet, May Dr. Lovina Machado

7 Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015 Dr. Lovina Machado

8 Distribution of causes of death by Millenium Devpt. Goal regions Global Causes of Maternal Death: A WHO systematic analysis. Lancet May 2014 Sepsis 10.7% Dr. Lovina Machado

9 Causes of Maternal deaths in (A) Mean proportion (left) and total number (right) of maternal deaths due to different causes in 1990 and Error bars show 95% uncertainty intervals. Dr. Lovina Machado

10 WHO Estimated causes of maternal deaths worldwide. Dr. Lovina Machado

11 Sepsis related maternal deaths  Point estimates shown by bars & 95% CI by horizontal lines Dr. Lovina Machado

12 Risk factors for maternal sepsis in pregnancy Confidential Enquiries into Maternal Deaths : UK Obesity Diabetes Immuno-compromised Anemia Vaginal discharge H/o pevic infection H/o GBS infection Amniocentesis/ inv. procedures Cervical cerclage Prolonged SROM GAS inf. in close contacts/ family Dr. Lovina Machado

13 The client….  27 year old Omani lady, Para3  Presented to ER 36 hrs after a normal vaginal delivery with intact perineum  c/o generalized pain abdomen, colicky, giddiness, shortness of breath.  No associated nausea, vomiting, diarrhea or chest pain.  History of one spike of temp 38 degrees c. 18 hrs after delivery. Intermittent lower abd.pain – after pains. Uterus well contracted, lochia normal, Hb 12.9 gm/dl Dr. Lovina Machado

14 Examination Findings  Conscious, anxious, in pain, sweating  Temp 36.5, Pulse- 170/mt, BP: 101/59 mm Hg, RR 22/mt, Maintaining 100% saturation on room air.  BP dropped to 80/40, resuscitated with 2 L fluids, BP settled to 97/ /65mmhg.  Chest - clear, normal breath sounds.  Abdominal examination - generalized distension, diffuse tenderness all over abdomen.  Uterus 18 weeks size, well contracted.  Lochia normal. Dr. Lovina Machado

15 Initial investigations  CBC: HB 13.8 g/dl ( postdelivery - d/c Hb 12.9 g/dl),WBC,PLT normal, VPG: normal, pH 7.3  Troponin: -ve  RFT: raised urea 13,Cr normal,  ECG: sinus tachycardia  Chest Xray  USG pelvis and abdomen  CT pelvis and abdomen Dr. Lovina Machado

16  Distressed, dehydrated despite aggressive fluid resuscitation  BP 90/50 to 110/60 mmHg  Plt 130, coag deranged-APTT 55, INR 1.4, K+ 3.1  ABG- compensated metabolic acidosis  Morphine, cross match PRBC & FFP, NPO, Tazocin IV  Imaging, HDU, CVP line Dr. Lovina Machado

17 Imaging Studies  XR chest: normal.  XR abdomen :  Normal gaseous distribution of bowels in abdomen.  Gasless lower abdomen and ? pelvic mass/fluid.  Colon loaded with fecal matter. Air is seen in rectum.  No evidence of dilated bowel loops.  No evidence of pneumoperitoneum. Dr. Lovina Machado

18 USG Pelvis 21/03/2014 Fluid streaks in myometrium Grossly enlarged uterus, showing diffuse hypo and hyper echoic non vascular areas, more pronounced in lower uterine segment associated with scattered areas of fluid streaks within. No endometrial mass or fluid. Uterus integrity intact, no signs of rupture Dr. Lovina Machado

19 USG Pelvis 21/03/2014 Diffuse hypoechoic area Diffusely enlarged uterus with altered echoes No fluid in POD, haematoma 8x8 cms, appeared to be in the lower part of the uterus.organised Dr. Lovina Machado

20  HB not dropping, one spike of fever, no heavy vaginal bleeding, coagulation impaired ??? Infected haematoma ?Perforation Plan: Conservative manangement at this stage,  Tazocin IV, urinary catheter  involve haematologist re imapired coagulation  NPO for the next 24 hrs until her condition is stable  Follow up imaging  HDU check HB and Coag screen at 4 pm Dr. Lovina Machado

21 CE CT Abdomen 21/03/2014 Distorted ovaries & adnexa Hypo-attenuated enlarged uterus Dr. Lovina Machado

22 CE CT Abdomen 21/03/ Axial Moderate free fluid abdomen and pelvis. Grossly enlarged uterus with complete loss of its normal attenuation, being replaced by non enhancing hypo/low attenuation areas, more in lower uterine segment involving cervix too Bilateral ill defined / distorted ovaries and parametria. Dr. Lovina Machado

23 CT Abdomen + pelvis with IV contrast:  Impression:- Findings are suggestive of post partum status uterus with likely lower segment uterine hematoma with moderate free fluid in abdomen and pelvis.  No evidence of bowel perforation. Dr. Lovina Machado

24 Investig18/321/ / Hb WBC Neutro PLT Coag PT INR APTT Fibrinogen Creatinin Urea Bilirubin 5444 AST 6544 ALT 1112 Albumin Lactate 2.5 CRP Meropenem + Clindamyciin + Vancomycin added Dr. Lovina Machado

25 Meropenem + Clindamyciin + Vancomycin added Prothrombin complex concentrate 3 vials over 5 min each PT improved Taken for surgery with very high risk consent- hysterectomy, massive haemorrhage, death Surgeons also to scrub in NGT, Norepinephrine infusion, pneumatic compression device Dr. Lovina Machado

26 Operative findings Midline incision 1.8 L pus in peritoneal cavity. White flabby uterus Necrotic ovaries Dr. Lovina Machado

27 Uterus 17 x 11.5 x 11 cms, Myometrial wall thickness 4 cms, serosal surface greenish, haemorrhagic Dr. Lovina Machado

28 Postoperative course  ICU – intubated -mechanical ventilation  Ionotropic support – Noradrenaline – BP 88/54, pulse 130/mt  Plt – , TC 4.1, PT 11.9, Hb 12.1, CRP 296  Continued to spike temperature, multiorgan failure Vanco/Mero/Clinda/Anidulofungin  Hypocalcemic, hypokalemia, generalised edema  Atrial fibrillation x 2 – Amidiarone bolus & infusion  Coagulation deranged – 4 u PRBC, 4 U platelets  Paralytic ileus, abdominal distension Dr. Lovina Machado

29 Investig23/ / Hb WBC Neutro PLT 5434 Coag PT INR APTT Fib Creatinine 7955 Urea Bilirubin 4213 AST 3439 ALT 13 Albumin 2218 Lactate CRP 296 HR – /mt Spiking temp BP maintained 100/70 off ionotropes Platelets low, coag deranged – 4u Plt Weaned off ventilator D3 Micro result preliminary Dr. Lovina Machado

30 Colonies on Blood Agar Dr. Lovina Machado

31 Day 2 postop - Group A Streptococcus  IV Clindamycin + IV Penicillin G  IVIG 1 gm/kg that day, then 0.5 mg/kg x 2 days after  Further platelet transfusions  Still spiking fever but less  Histopathology results Dr. Lovina Machado

32 Necrosis and inflammation of myometrium Dr. Lovina Machado

33 Widespread microthrombi & microabscesses Dr. Lovina Machado

34  All resected tissues – bacteriology- heavy growth of strep. pyogenes  Day 6 – Diarrhoea, abdominal cramps, nausea, abd tenderness. ?pseudomembranous colitis  C. difficile sent,  Clindamycin stopped, Metro + oral vanco added  CT imaging  Hypertension- oral Labetalol  Still febrile intermittently, c/o flank pain Dr. Lovina Machado

35 Investi g 25/ /3 D4 27/328/329/3 D7 7/4 D16 Hb WBC Neutro PLT Coag PT INR APTT Fib Creatinine Urea Bilirubin 13 AST 39 ALT 13 Albumin 18 CRP Afebrile since D8 Perioral ulcers Tinnitus Peeling of skin Dr. Lovina Machado

36 Postop CE CT ABDOMEN D16- 08/04/2014 PE Pericardial effusion Moderate right pleural effusion and minimal pericardial effusion Dr. Lovina Machado

37 Postop CE CT ABDOMEN 08/04/2014 Scattered mildly distended small bowel loops with surrounding fat stranding, min. free fluid Small focal areas of fluid collections with enhancing wall in pelvis Loculated fluid collection Dr. Lovina Machado

38 Discharged  Discharged on 10/4…. 19 days post surgery Dr. Lovina Machado

39 Readmitted 14/5/2014  Acute abdominal pain  Severe vomiting – bilious  Constipation  Low grade fever Dr. Lovina Machado

40 CE CT Abdomen Coronal14/05/2014 Dilated prox. small bowel loops With thickened walls & fat stranding Obstruction site Transition narrowing distal jejunum (sub acute bowel obstruction-Closed loop pattern) Dr. Lovina Machado

41 At surgery  Imp: Small bowel vovlulus with ? Ac. Bowel ischemia  Emergency Laparotomy – Volvulus, release of adhesive band  Findings: Hemorrhagic fluid within the peritoneal cavity  - 20cm segment of proximal Ileum incarcerated by an adhesive band at approx. 200cm from the DJ flexure  - the knotted small bowel loop was congested with small dusky patch, but was viable with good peristalsis and good colour.  Pelvic findings: cervical stump neither felt nor seen, round ligaments and infundibulopelvic ligaments identified and ovaries -very small and nodular about 1 cm Dr. Lovina Machado

42  The fulminant nature of GAS poses impressive challenges from diagnostic & therapeutic perspectives.  Most present early with mild symptoms- sent home-return to ER with full blown sepsis in hrs  Shock occurs early in severe GAS infection - STSS  Early diagnosis imperative – requires a high index of suspicion  Diagnosis often established only after aggressive interventional management has begun. Dr. Lovina Machado

43 Incidence of invasive GAS  Incidence of invasive GAS infections is 1 to 5 cases per 100,000 population per year.  Approx. 20% of these are STSS  Most cases- primary & sporadic in nature  Epidemics of invasive GAS have been reported – health care workers, family contacts Dr. Lovina Machado

44 Group A Streptococcus Streptococcus pyogenes  Gram-positive, nonmotile, non-spore forming coccus  Occurs in chains or in pairs of cells.  Individual cells - round-to-ovoid cocci, µm in diameter Dr. Lovina Machado

45 Group A Streptococcus  Catalase-negative facultative anaerobe, requires blood enriched medium to grow.  GAS typically have a capsule composed of hyaluronic acid & exhibit beta (clear) hemolysis on blood agar. Dr. Lovina Machado

46 Cell surface structure of strep pyogenes & virulence factors Dr. Lovina Machado

47 Pathophysiology  Pyrogenic exotoxins SPE A,B and C - Superantigens  A & B induce human mononuclear cells to synthesize TNF- ᾳ, IL-1ß and IL-6 → fever, shock, tissue injury, TSS.  C - mild, scarlet fever  SSA and MF  Proteins  M protein responsible for invasiveness by impeding phagocytosis of streptococcus by human PMN Leucocytes + Pro-inflammatory  M type 1 and 3 strains common isolates  Others  DNAse Sda1, cysteine protease SpeB, hyaluronic acid capsule, serum opacity factor, IL-8 peptidase, & the cell wall group A carbohydrate Dr. Lovina Machado

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49 Net effect- T cell stimulation  Cytokine production contributes to the genesis of shock & organ failure  Peptidoglycan, lipoteichoic acid, killed organisms induce TNF- production by mononuclear cells  Exotoxin - Streptolysin O - potent inducer of TNF- & IL- 1ß.  Exotoxin A, B, SLO - additive effects inducing cytokines Dr. Lovina Machado

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51  SpeB and Ska/ Plasmin directly damage the host tissues, degrade the extracellular matrix proteins, and induce vascular dissemination via their enzymatic pathway  Exotoxins Streptococci elaborate surface proteins M-1 and M-3, exotoxins A, B, C, streptolysin O, and superantigen. The M proteins increase the microbes' ability to adhere to tissue and escape phagocytosis. Toxins A and B, damage endothelium, cause loss of microvascular integrity, and escape of plasma, that results in tissue oedema and impaired blood flow.  In addition, these toxins, together with streptolysin O, stimulate CD4 cells and macrophages to produce large amounts of TNF, interleukin-1 and 6. Systemic release of cytokines produces the systemic inflammatory response then progress to septic shock, multi-organ failure and death. TNF also induces additional injury to the vascular endothelium by stimulating neutrophil degranulation. These in turn activate the complement system, and the coagulation cascade, and worsening small vessel thrombosis and tissue ischaemia. The tissue ischaemia impedes the oxidative destruction of bacteria by PMNs and prevents adequate delivery of antibiotics. Thus, surgical debridement is the mainstay therapy of NF and antibiotics alone are not useful Dr. Lovina Machado

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53 Clinical isolates  M types 1,2,12 & 28 – most common isolates in pts. With shock & multiorgan failure  Sweden-80% of strains- M type 1 with pyrogenic exotoxin B mainly  USA- pyrogenic exotoxin A  Streptococcal superantigen (SSA) – a novel pyrogenic exotoxin from an M3 strain  Mitogenic factor in many M types Dr. Lovina Machado

54 Portal of entry of GAS Insect bites, burns, lacerations, abrasions, splinters Surgical procedures- lipectomy, Viral infections- influenza, varicella Symptomatic pharyngitis- rare “Outside-in” diagnosis Defined portal of entry 50% of pts with sepsis Life threatening GAS begins at exact site of minor non-penetrating trauma→ muscle tear, haematoma or deep bruise Severe pain, fever may be the only early manifestations Diagnosing STSS exceedingly difficult Shock & organ failure hours later “ Inside-out presentation Portal of entry not defined 50% of pts. With sepsis Dr. Lovina Machado

55 Routes of maternal infection 1.Colonization in vagina/rectum – Rare 0.03% 2.Asymptomatic carriers-throat, skin – 5-30% of population 3.Recent h/o sore throat in mum 4.Children at home/work who are carriers 5.Nosocomial infections- health care workers 6.Cesarean sections – invasive surgery. 7.Can follow normal deliveries Regardless of the type of delivery, postpartum patients have a 20 fold increased incidence of GAS as compared to nonb-pregnant women. Dr. Lovina Machado

56 Risk determinants for GAS to cause puerperal sepsis  1. Disrupted mucosal barriers  2. Altered immune status  3. Delayed diagnosis  4. Specific virulence of the GAS strain  5. Environmental exposure Dr. Lovina Machado

57 D/D of GAS puerperal sepsis  Sepsis due to other pathogens  Postpartum endometritis  Retained infected POC’s  Pelvic abscess  Hypotensive shock secondary to PPH  Endocarditis  Pulmonary embolism  Urosepsis/ pneumonia Dr. Lovina Machado

58 Other sepsis causing microbes  GBS- less severe disease  Staphylococcus  Mycoplasma  Chlamydia  Clostridium  Coliforms  Bacterial vaginosis organisms Dr. Lovina Machado

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60 Case definition of STSS 1. Isolation of GAS ( strep. Pyogenes) from a A. Normally sterile site – blood, CSF, tissuebiopsy, surgical wound B. Non-sterile site – throat, vagina, sputum 11. Clinical signs of severity A. Hypotension: Systolic ≤90 mm Hg in adults AND B. ≥ 2 of the following signs 1. Renal impairment : Cr ≥ 177µmol/L (≥ 2 mg/dl) or ≥2 fold elevation 2. Coagulopathy : Plt ≤100 x 10 9 /L or DIC (prolonged APTT,↓fibrinogen,↑FDP 3. Liver impairment : ASAT, ALAT, Bili ≥2 fold ↑ from baseline or ≥2”ce normal values 4. ARDS, hypoxemia in absence of cardiac failure, diffuse cap. Leak manifested by acute onset generalised edema, pleural effusion, peritoneal fluid, hypoalbuminemia 5. Generalised erythematous macular rash – may desquamate 6. Soft tissue necrosis, necrotising fasciitis, myositis, gangrene Probable case- meets clinical case definition + isolation from non-sterile site Definite case - meets clinical case definition + isolation from normally sterile site RCOG JAMA 1993 Dr. Lovina Machado

61 Defining STSS Dr. Lovina Machado

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63 Clinical course of strep. sepsis  Fulminant process that can progress to shock & organ failure within hours after acquisition of virulent strains of GAS  Initial signs & symptoms are mild & non-specific.  20% have flu like symptoms- fever, chills, myalgia, nausea, vomiting, diarrhoea  Pain- most common feature Dr. Lovina Machado

64 STSS  PAIN – most common initial symptom of STSS – abrupt in onset, severe – involving extremity, mimic peritonitis, PID, pulm embolism, acute MI  FEVER- common sign early in course of disease  STSS frequently misdiagnosed at this stage -food poisoning, viral gastroenteritis, DVT, cellulitis, muscle spasm  Confusion in 55% of pts. Coma Dr. Lovina Machado

65 STSS  80% devp. signs of soft tissue infection – swelling, erythema – Necrotising fasciitis, myositis requiring surgical intervention  20% - variety of presentations- endophthalmitis, perihepatitis, peritonitis, overwhelming sepsis  10% - diffuse scarlatina-like erythema  Later – hypotension, profound shock Dr. Lovina Machado

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67 Systematic Review 55 cases with symptomatic GAS in pregnancy  English 20 cases, French 2, Japanese 33 cases Yamada T et al. Invasive GAS infection in pregnancy. J of Infection 2010, 60, SymptomPercentage Concurrent/ preceding fever >3894 % Respiratory – sore throat40% GIT – diarrhoea, nausea, vomiting49% Early onset of shock/ hypotension91% Unusually strong uterine contractions (purulent uterine myometritis) 75% Non-reassuring CTG – fetal demise/NND66% Decreased consciousness31% Skin rash15% Maternal survival 42% ( 23/55) Neonatal survival 34% ( 20/59) Dr. Lovina Machado

68 Complications of GAS soft tissue infection Complication% of patients Shock95 ARDS55 Renal impairment Irreversible Reversible Bacteremia60 Death30 Dr. Lovina Machado

69 Lab evaluation - STSS  Serum CPK level –Elevated or rising – correlates with necrotising fasciitis or myositis  Initially- only mild leucocytosis  Striking-40-50% of immature neutrophils (band forms, metamyelocytes, myelocytes)  Blood culture +ve in 60%  Haemoglobinuria & elevated CPK – renal involvement  Renal impairment precedes hypotension in %  Hypoalbuminemia & hypocalcemia occur early & become profound hours after admission Dr. Lovina Machado

70 LRINEC (Lab Risk Factor Indicator for NF) Score D eveloped by Wong et al in scoring system using CRP, total WBC, Hb, serum sodium, creatinine & glucose levels ValueScore CRP (mg/L) ‧ WBC ‧ 25, Hg (g/dL) ‧ >13.5 ‧ ‧ < Na (mmol/L) ‧ >135 ‧ < Cr (mg/dL) ‧ Glucose (mg/dL) ‧ Score validated in a number of studies. Standard of investigation to diagnose NF in early clinical settings Score 6 -7 – probability of NF 50-75% Score ≥ 8 - probability of NF > 75% Positive predictive value 92% Negative predictive value 96% Dr. Lovina Machado

71 Management of streptococcal sepsis  Aggressive fluid resuscitation  Appropriate IV antibiotics within 1 hour of suspicion of sepsis  Source Control Dr. Lovina Machado

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73 Source control  Identify site of infection  Surgical intervention to remove necrotic infected foci – paramount importance  Multidisciplinary team – ICU, ID, haemat  CT/MRI- helpful but GAS does not form gas or frank abscess, so radiologist interpretation often not definitive  Swelling/edema in deep tissues may indicate deep-seated infection Dr. Lovina Machado

74 Surgical intervention  If labs – marked left shift, elevated creatinine, high CPK – further impetus to prompt surgery  Stakes higher & surgery more difficult when GAS involves abdomen, thorax, head or neck  Clost. Perfringens causes extensive gas in uterus- easy diagnosis & surgery  With GAS, uterus only modestly enlarged & edematous- mistaken for postpartum uterus  Shock or anatomic location of infection may make surgical intervention risky/ not possible Dr. Lovina Machado

75 Antibiotic choice Initial antibiotic management for necrotizing fascitis. Gram Stain Result Initial Empiric Therapy Gram-positive Cocci in Clusters Gram-positive Cocci in Pairs or Chains Polymicrobial- Gram+ve cocci + Gram-ve Bacilli Clindamycin plus any of following: imipenem, meropenem, amplicillin/sulbact am, piperacillin/tazob actam Clindamycin plus vancomycin, or monotherapy with linezolid Clindamycin plus any of following: piperacillin/tazoba ctam, amplicillin/ sulbactam, or high-dose penicillin Clindamycin plus any of the following: imipenem, meropenem, amplicillin/ sulbactam, piperacillin/tazoba ctam Dr. Lovina Machado

76 Antibiotic therapy  Strep. Pyogenes exquisitely susceptible to ß- lactam antibiotics.  Penicillin has excellent efficacy but if started late mortality may be high despite treatment – high colony count of GAS and loss of Penicillin binding protein(PBP) in stationary growth phase Dr. Lovina Machado

77 Clindamycin Better efficacy- modulates immune response to GAS infection  Efficacy unaffected by inoculum size/stage of growth  Suppresses bacterial toxin synthesis  Facilitates phagocytosis of S. pyogenes by inhibiting M protein synthesis  Suppresses synthesis of PBP’s which are also involved in cell wall synthesis & degradation  Longer postantibiotic effect  Suppresses lipopolysaccharide-induced monocyte synthesis of TNF- Dr. Lovina Machado

78 How to choose the antibiotics Dr. Lovina Machado

79 RCOG GTG 64a Bacterial sepsis in pregnancy Dr. Lovina Machado

80 Fluid resuscitation  Aggressive IV fluid replacement with crystalloids to achieve MAP > 60 mm Hg & tissue perfusion  Invasive monitoring – Maintain pulm artery occlusion pressure of mm Hg.  If hypotension persists,S. albumin conc & Hct checked. Profoundly low levels of albumin are common, haemolysins produced by GAS cause dramatic drops in circulating red cell mass.  PRBC ± Albumin may be useful. Dr. Lovina Machado

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82 Indications for transfer to ICU Surviving Sepsis Campaign Resuscitation Bundle SystemIndication CardiovascularHypotension or raised serum lactate persisting despite fluid resuscitation, need for ionotropic support RespiratoryPulmonary edema, mechanical ventilation, airway protection RenalRenal dialysis NeurologicalSignificantly decreased consciousness level MiscellaneousMultiorgan failure, uncorrected acidosis, hypothermia RCOG Adapted from Plaat and Wray Dr. Lovina Machado

83 Management in ICU  Monitoring Cardiac output mandatory in pts. With persistent hypotension  Mechanical ventilation generally needed- high incidence of ARDS  Intractable hypotension + diffuse capillary leak→ massive amounts of IV fluids (10-20L/day) may be needed. 10% rapidly improve  Pressors – Dopamine Dr. Lovina Machado

84 Strategies to neutralise toxins  IVIG – has antibodies against some toxins such as SpeA, SpeB & opsonic antibody against some M types of gas  Dialysis & haemoperfusion – reduce toxins + renal failure common in 50% of STSS pts.  Sweden- Stegmayr et al – Hemofiltration assoc with lowest recorded mortality rates- 14% Dr. Lovina Machado

85 Do we have any prophylaxis?  Cluster infections- nursing homes, health care workers times greater risk….Strict infection control practices  Vaccines – centred on M protein as the immunogen – hypervariable regions are the primary immunologic determinant for the M type…….Optimal……not yet available  Screening for vaginal carriage of GAS…. Rare inf, not cost effective  Latest technology to develop high titre humanized monoclonal antibodies that neutralise a variety of streptococcal virulence factors is ready but awaits production.  CDC –single case……..enhanced surveillance of contacts ≥ 2 postpartum/postsurgical cases…..demands full epidemiologic investig & cultures of involved health care team Dr. Lovina Machado

86 In conclusion ……….  Virulent strains of GAS causing life threatening sepsis have re- emerged in the last 25 years -  Must be recognized & treated early & aggressively to prevent severe morbidity & mortality  Be alert when postpartum women present with unstable vital signs, high fever or an “unexpected toxic” appearance  Most report an onset within the first few days postpartum in previously healthy women with rapid progress from fever & abdominal/ pelvic pain to ICU care for refractory vasopressor dependant shock & mulitorgan failure Dr. Lovina Machado

87 In conclusion ……….  Key management issues  Early recognition  Send labs, cultures, start broad spectrum IV antibiotics  Aggressive fluid resuscitation  Early source control- surgical intervention  Multidisciplinary team from the start  ICU care Dr. Lovina Machado

88 Tasks to be performed within the first 6 hours of identification of severe sepsis. Surviving Sepsis campaign Resuscitation Bundle  Obtain blood cultures prior to antibiotic administration  Adminster broad spectrum antibiotic within 1 hour of severe sepsis  Measure serum lactate within 6 hrs. ≥4 – tissue hypoperfusion  In the event of hypotension &/or serum lactate > 4 mmol/L, deliver an initial minimum 20 ml/kg crystalloid. Start vasopressors for hypotension not responding to initial fluid resuscitation to maintain MAP > 65 mm Hg  If persisting hypotension (septic shock) &/or lacate > 4 mmol/L - Achieve CVP of ≥ 8 mm Hg - Achieve central venous O2 sat.≥ 70% or mixed venous O2 sat ≥ 65% Dr. Lovina Machado

89 “Red flag” signs/symptoms for tertiary care referral  Pyrexia > 38 o C  Sustained tachycardia > 90 b/minute  Breathlessness – RR > 20/min – serious  Abdominal or chest pain  Diarrhoea/ vomiting  Uterine or renal angle pain and tenderness  Generally unwell, unduly anxious or distressed Dr. Lovina Machado

90 Infection Control issues  Isolate single room  Contact precautions  Waterproof dressing for breaks in skin of woman/care giver  Fluid repellant surgical masks with visors during surgery/ dressing change  Neonate to be given antibiotics Dr. Lovina Machado

91 References  Stevens Dennis L. Group A Streptococcal sepsis. Current Infectious Disease Reports 2003,5:  Busowski MT et al. Puerperal Group A Streptococcal infections: Case series & discussion. Case Reports in Medicine. Vol 2013/Article ID Hindawi  RCOG Green top guidelines No.64A, April 2012  RCOG Green top guidelines No.64B, April 2012  Global, regional, and national levels and causes of maternal mortality during 1990—2013: a systematic analysis for the Global Burden of Disease Study The Lancet, Online, 2 May doi: /S (14)  Yamada T. et al. Invasive GAS infections in pregnancy. J of Inf 2010; 60: Dr. Lovina Machado

92 RCOG Dr. Lovina Machado

93 RCOG Dr. Lovina Machado

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