Womens Health Conference 2014 Chicago Dr. Lovina Machado Slide 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 Slide 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 Slide 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
1530-1606 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 1800s..J.
Bundell, T. Watson, R. Collins cleanliness, hand hygiene,
chlorination 1844- Ignaz Semmelweis Vienna transmission route &
hand hygiene. Reduced MMR from18% to 2.4% Dr. Lovina Machado Slide
5 Global, regional, and national levels and causes of maternal
mortality during 19902013: a systematic analysis for the Global
Burden of Disease Study 2013 No. of maternal deaths from all causes
in 188 countries between 1990 & 2013. The Lancet, Online, 2 May
2014. doi:10.1016/S0140-6736(14)60696-6 Dr. Lovina Machado Slide 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
2014. http://dx.doi.org/10.1016/S2214-109X(14)70227-X Dr. Lovina
Machado Slide 7 Global rates of change suggest that only 16
countries will achieve the MDG 5 target by 2015 Dr. Lovina Machado
Slide 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 Slide 9 Causes of
Maternal deaths in 1990-2013 (A) Mean proportion (left) and total
number (right) of maternal deaths due to different causes in 1990
and 2013. Error bars show 95% uncertainty intervals. Dr. Lovina
Machado Slide 10 WHO Estimated causes of maternal deaths worldwide.
Dr. Lovina Machado Slide 11 Sepsis related maternal deaths Point
estimates shown by bars & 95% CI by horizontal lines Dr. Lovina
Machado Slide 12 Risk factors for maternal sepsis in
pregnancy2005-2008 - 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 Slide 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 Slide
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 97/66 - 110/65mmhg. 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 Slide 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 Slide 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 Slide 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 Slide 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 Slide 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 Slide 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
Slide 21 CE CT Abdomen 21/03/2014 Distorted ovaries & adnexa
Hypo-attenuated enlarged uterus Dr. Lovina Machado Slide 22 CE CT
Abdomen 21/03/2014 - 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
Slide 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
Slide 24 Investig18/321/3 05.0020.00 22/3 13.00 Hb 12.513.811.410.9
WBC 8.23.51.73.3 Neutro 2.93.21.12.6 PLT 2241539569 Coag PT
1015.714.815.7 INR 0.921.41.321.4 APTT 37.255.256.551.3 Fibrinogen
7.23.94.7 Creatinin 7510999 Urea 1316.515.7 Bilirubin 5444 AST 6544
ALT 1112 Albumin 302219 Lactate 2.5 CRP 281 296 Meropenem +
Clindamyciin + Vancomycin added Dr. Lovina Machado Slide 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 Slide 26 Operative
findings Midline incision 1.8 L pus in peritoneal cavity. White
flabby uterus Necrotic ovaries Dr. Lovina Machado Slide 27 Uterus
17 x 11.5 x 11 cms, Myometrial wall thickness 4 cms, serosal
surface greenish, haemorrhagic Dr. Lovina Machado Slide 28
Postoperative course ICU intubated -mechanical ventilation
Ionotropic support Noradrenaline BP 88/54, pulse 130/mt Plt 54- 34,
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 Slide 29
Investig23/3 05.00 24/3 05.00 Hb 11.711.8 WBC 8.313.4 Neutro
7.211.5 PLT 5434 Coag PT 11.611.4 INR 1.061.04 APTT 42.649.4 Fib
5.45.2 Creatinine 7955 Urea 13.110.2 Bilirubin 4213 AST 3439 ALT 13
Albumin 2218 Lactate CRP 296 HR 130-140/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 Slide 30 Colonies on Blood Agar Dr. Lovina Machado Slide 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 Slide 32 Necrosis and inflammation of
myometrium Dr. Lovina Machado Slide 33 Widespread microthrombi
& microabscesses Dr. Lovina Machado Slide 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
Slide 35 Investi g 25/3 0500 26/3 D4 27/328/329/3 D7 7/4 D16 Hb
10.7 1211.510.79.5 WBC 1210.113.216.315.48.9 Neutro
108.29.711.910.24.9 PLT 3455146299418719 Coag PT
11.416.1141313.413.5 INR 1.041.431.261.181.211.22 APTT
42.54641.945.845.937 Fib 4.43.73.94.24.14 Creatinine 493829302933
Urea 9.17.44.121.51.2 Bilirubin 13 AST 39 ALT 13 Albumin 18 CRP
1168647131139 24 Afebrile since D8 Perioral ulcers Tinnitus Peeling
of skin Dr. Lovina Machado Slide 36 Postop CE CT ABDOMEN D16-
08/04/2014 PE Pericardial effusion Moderate right pleural effusion
and minimal pericardial effusion Dr. Lovina Machado Slide 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 Slide 38 Discharged Discharged
on 10/4. 19 days post surgery Dr. Lovina Machado Slide 39
Readmitted 14/5/2014 Acute abdominal pain Severe vomiting bilious
Constipation Low grade fever Dr. Lovina Machado Slide 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 Slide 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 Slide 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 12-24 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 Slide 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 Slide 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,
0.6-1.0 m in diameter Dr. Lovina Machado Slide 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 Slide 46 Cell surface structure of
strep pyogenes & virulence factors Dr. Lovina Machado Slide 47
Pathophysiology Pyrogenic exotoxins SPE A,B and C - Superantigens A
& B induce human mononuclear cells to synthesize TNF- , IL-1
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 Slide 48 Slide 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- 1. Exotoxin A, B,
SLO - additive effects inducing cytokines Dr. Lovina Machado Slide
50 Slide 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 Slide 52 Slide 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 Slide 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 48-96 hours later Inside-out presentation Portal of
entry not defined 50% of pts. With sepsis Dr. Lovina Machado Slide
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 Slide 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 Slide 57 D/D of GAS
puerperal sepsis Sepsis due to other pathogens Postpartum
endometritis Retained infected POCs Pelvic abscess Hypotensive
shock secondary to PPH Endocarditis Pulmonary embolism Urosepsis/
pneumonia Dr. Lovina Machado Slide 58 Other sepsis causing microbes
GBS- less severe disease Staphylococcus Mycoplasma Chlamydia
Clostridium Coliforms Bacterial vaginosis organisms Dr. Lovina
Machado Slide 59 Slide 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 177mol/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 2ce 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 Slide 61 Defining
STSS Dr. Lovina Machado Slide 62 Slide 63 Clinical course of strep.
sepsis Fulminant process that can progress to shock & organ
failure within 48-96 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 Slide 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 Slide 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 Slide 66 Slide 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, 60,412-24 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 Slide 68
Complications of GAS soft tissue infection Complication% of
patients Shock95 ARDS55 Renal impairment Irreversible Reversible 80
10 70 Bacteremia60 Death30 Dr. Lovina Machado Slide 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 40 -50% Hypoalbuminemia &
hypocalcemia occur early & become profound 24-48 hours after
admission Dr. Lovina Machado Slide 70 LRINEC (Lab Risk Factor
Indicator for NF) Score D eveloped by Wong et al in 2004 - scoring
system using CRP, total WBC, Hb, serum sodium, creatinine &
glucose levels ValueScore CRP (mg/L) 150 0404 WBC 25,000 012012 Hg
(g/dL) >13.5 11-13.5 135 75% Positive predictive value 92%
Negative predictive value 96% Dr. Lovina Machado Slide 71
Management of streptococcal sepsis Aggressive fluid resuscitation
Appropriate IV antibiotics within 1 hour of suspicion of sepsis
Source Control Dr. Lovina Machado Slide 72 Slide 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 Slide 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 Slide 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 Slide 76 Antibiotic therapy Strep. Pyogenes
exquisitely susceptible to - 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
Slide 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
PBPs which are also involved in cell wall synthesis &
degradation Longer postantibiotic effect Suppresses
lipopolysaccharide-induced monocyte synthesis of TNF- Dr. Lovina
Machado Slide 78 How to choose the antibiotics Dr. Lovina Machado
Slide 79 RCOG GTG 64a Bacterial sepsis in pregnancy Dr. Lovina
Machado Slide 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 12-16 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 Slide 81
Slide 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 2008. Dr. Lovina Machado Slide 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 Slide 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 Slide 85 Do we have any prophylaxis? Cluster
infections- nursing homes, health care workers. 50-200 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.Optimalnot 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 Slide 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 Slide 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 Slide 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 Slide 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 Slide 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 Slide 91 References Stevens Dennis
L. Group A Streptococcal sepsis. Current Infectious Disease Reports
2003,5:379-386 Busowski MT et al. Puerperal Group A Streptococcal
infections: Case series & discussion. Case Reports in Medicine.
Vol 2013/Article ID 751329. 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 19902013: a systematic analysis for the Global
Burden of Disease Study 2013. The Lancet, Online, 2 May 2014.
doi:10.1016/S0140- 6736(14)60696-6 Yamada T. et al. Invasive GAS
infections in pregnancy. J of Inf 2010; 60: 417-424. Dr. Lovina
Machado Slide 92 RCOG Dr. Lovina Machado Slide 93 RCOG Dr. Lovina
Machado Slide 94
