Transcript Infections & obstetrics

Dr Mona Shroff
www.obgyntoday.info
Case 1 : Mrs. A. G1P0,
27 wks pregnancy,
comes to LxR with preterm labour pains.
No h/o leaking p/v
No fever(>100.4),
No maternal /fetal tachycardia,
No uterine tenderness
O/E : mild contractions
Cx :2 cms dilated ,membranes intact
Dr Mona Shroff
www.obgyntoday.info
What is the probability of
this patient in preterm
labour with intact
membranes having
intrauterine infection?
Dr Mona Shroff
www.obgyntoday.info
Intraamniotic infection - 10 %
using PCR - 30-55%
Histological chorioamnionitis 5% overall
94%(21-24wks)
most subclinical, only 13% had fever
V. high probability of infection if:
Clinical S/S of chorioamnionitis
Early gestational age (<28 wks)
Failure of tocolysis (before 2nd agent started)
Russel P.Am.J.Diagn Gynaecol Obstet 1989;1:127-37
Hitti J,Riley D,Krohn M.Clin Infect Dis 1997;24:1228-32
Oyarzun E,Kato S,etal.Am J Obstet Gynaecol 1998;179:1115-9
Markenson G,Martin R,et al. S,etal.Am J Obstet Gynaecol 1997;177:1471-7
Dr Mona Shroff
www.obgyntoday.info
Considering that most
of us would want to
prolong this pregnancy ,
what are the maternal
& fetal risks associated with
presumed intrauterine
infection…?
Dr Mona Shroff
www.obgyntoday.info
Maternal consequencies
Initiation of labor, postpartum endometritis
septic shock, ARDS, DIC, and acute renal failure
Fetal consequencies
Infected fetuses can rapidly decompensate
during labor.
Fulminant sepsis, neonatal death, developmental
delay & Infants exposed to intrauterine infection
can present with
- neonatal encephalopathy ,
- periventricular leucomalacia and
- an increased risk of cerebral palsy (Hagberg
2002).
Dr Mona Shroff
www.obgyntoday.info
• Considering the chance of subclinical
infection,being the cause of PTL…
…would you start antibiotics
routinely in all cases of preterm labour
being managed conservatively as an
adjunct to tocolysis…..?
If no ; ; why not?
If yes ; which antibiotic & what dose…?
Dr Mona Shroff
www.obgyntoday.info
Meta-analysis of the 11 trials
(7428 women enrolled; ’ORACLE II 2001’ trial largest)
shows a reduction in maternal infection with the use of
prophylactic antibiotics (relative risk 0.74) but fails to
demonstrate a benefit or harm for any of the prespecified
neonatal outcomes.
In fact it raises concerns about increased neonatal mortality for
those who received antibiotics !!!
Antibiotics should not be given routinely to patients
with preterm labour with intact membranes for the purpose
of prolonging pregnancy.
King J, Flenady V. Prophylactic antibiotics for inhibiting preterm labour with intact membranes.
Cochrane Database of SystematicReviews 2002, Issue 4
Dr Mona Shroff
www.obgyntoday.info
The finding of a reduction in maternal
infection in women receiving prophylactic
antibiotics, needs to be seen in the light of an
incidence in the control group of 11.2%.
Given that maternal infection is clinically
relatively easy to diagnose and treat, this
would argue against prophylactic antibiotics
to prevent it, as 88.9% of women would be
receiving antibiotics unnecessarily.
Dr Mona Shroff
www.obgyntoday.info
Would you like to confirm the
intrauterine infection in all cases of
established preterm labour, by
amniocentesis & C/S of amniotic
fluid while trying to arrest the
preterm labour , keeping in mind
the adverse consequencies of fetal
infection?
Dr Mona Shroff
www.obgyntoday.info
amniocentesis…..
Not advisable for all pts in preterm labour
(itself may predispose to infection)
But strongly recommended for patients
with v. high probability of infection :
Clinical S/S of chorioamnionitis
Early gestational age (<28 wks)
Failure of tocolysis (before 2nd agent
started)
Dr Mona Shroff
www.obgyntoday.info
• Amniotic Fluid
Glucose < 16-20 mg/dl
Grams stain positive
leucocyte esterase
Culture :
Gold Standard
Dr Mona Shroff
www.obgyntoday.info
•
If infection is confirmed
clinically or amniocentesis , what
would be your line of
management…?
Conservative Vs Delivery !!!
Antibiotics before vs after baby delivery !!!
Choice of antibiotic & why !!!
Dr Mona Shroff
www.obgyntoday.info
Conservative Vs Delivery !!!
Delivery is indicated once a diagnosis
of intraamniotic infection is established.
From the available evidence, a
diagnosis to delivery interval of upto
twelve hours is not associated with
increased neonatal morbidity.
(Gibbs 1980; Hauth 1985)
Dr Mona Shroff
www.obgyntoday.info
Immediate Vs Postpartum Ab
Whether to begin parenteral antibiotic
administration immediately after making the
diagnosis or after delivery has been
controversial.
While immediate administration of antibiotics
may limit maternal sepsis, intrapartum
antibiotic therapy could obscure the
diagnosis of neonatal sepsis and affect the
management of the infant.
Dr Mona Shroff
www.obgyntoday.info
Intrapartum treatment with antibiotics
for intraamniotic infection was
associated with a reduction in
neonatal sepsis (relative risk 0.08)
pneumonia (RR 0.15)
compared with treatment given
immediately postpartum, although these
results did not reach statistical significance
(number of women studied = 45).
Hopkins L, Smaill F.
Antibiotic regimens for management of intraamniotic infection.
Cochrane Database of Systematic Reviews 2002,
Dr Mona Shroff
www.obgyntoday.info
Choice of Antibiotic
There was no evidence to support the use
of a more broad-spectrum regimen than
ampicillin (2 gms IV 6hrly) and gentamicin
for the treatment of intraamniotic infection.
(both cross placenta well)
There was no difference in the outcomes of
neonatal sepsis (RR 2.16) or neonatal death
(RR 0.72) between a regimen with and without
anaerobic activity
Hopkins L, Smaill F. Antibiotic regimens for management of
intraamniotic infection. Cochrane Database of Systematic
Reviews 2002,
Dr Mona Shroff
www.obgyntoday.info
Those ’macrolide’ antibiotics
(such as clindamycin and erythromycin)
which shut down bacterial virulence
have theoretical advantages over the
beta-lactam antibiotics (penicillins,
cephalosporins), which by destroying
bacteria release endotoxins which
may worsen the outcomes for infants
born preterm (McGregor 1997).
Dr Mona Shroff
www.obgyntoday.info
Implications for practice
 Antibiotics should not be given routinely to patients
with preterm labour with intact membranes for the
purpose of prolonging pregnancy.
 Amniocentesis for culture & antibiotics should be
strongly considered if:
Clinical S/S of chorioamnionitis
Early gestational age (<28 wks)
Failure of tocolysis (before 2nd agent started)
 Delivery & antibiotcs indicated once a diagnosis of
intraamniotic infection is established (clinical/culture)..
Antibiotic preferable are macrolide group
(erythromycin/clindamycin)
 Current evidence favours immediate intrapartum Ab.
Dr Mona Shroff
www.obgyntoday.info
Implications for research
Further research may be justified
(when sensitive serological/biochemical
markers for subclinical infection become
available)…In order to determine..if there is
a subgroup of women who could
experience benefit from antibiotic
treatment for preterm labour prior to
membrane rupture, and to identify which
antibiotic or combination of antibiotics is
most effective.
Oral Erythromycin + Amoxicillin currently
studied
Dr Mona Shroff
www.obgyntoday.info
Implications for research
Although the trend was towards improved
neonatal outcomes when antibiotics were
administered intrapartum, adverse neonatal
events associated with antibiotic administration
were not specically sought.
Further trials should be designed to look at
longer
term
outcomes,
including
the
consequences of neonatal cerebral damage,
provide a thorough understanding of the
pharmcokinetic
profile
of
the
drugs
administered intrapartum and evaluate more
comprehensively the effectiveness of different
regimens.
Dr Mona Shroff
www.obgyntoday.info
Winston Churchill
Charles Darwin
Mark Twain
Napoleon
Dr Mona Shroff
Bonaparte
www.obgyntoday.info
Albert Einstein
Issac Newton
If Mrs.A. had come to you for ANC at 8
wks pregnancy, would you screen her for...
-
Bacterial vaginosis
Asymptomatic bacteriuria
Trichomonas vaginitis
Chlamydia trachomatis,
N. gonorrhoea
- GBS carriage
Infections during pregnancy for which there
is good evidence of an increased risk of preterm
birth and preterm prelabour rupture of the
membranes
Dr Mona Shroff
www.obgyntoday.info
Some facts
B.V.
Bacterial vaginosis is present in up to
20% of women during pregnancy
(Lamont 1993).
The majority of these cases will be
asymptomatic.
BV ass. with 2 fold increase risk of PTB;
Greatest risk being when BV before 16
wks.
Dr Mona Shroff
www.obgyntoday.info
Bacterial vaginosis
 The results of trials that treat bacterial vaginosis in
pregnancy, however, are not encouraging.
 Treatment before 20 weeks‘ gestation may reduce the
risk of preterm birth less than 37 weeks (Peto OR 0.63)
 In women with a previous preterm birth, the use of
antibiotics was associated with a statistically
significant decreased risk of preterm PROM (Peto OR
0.14),and low birthweight , without significant
reduction in PTB.
 Vaginal antibiotics appear to have no effect on any
measure of preterm birth (Peto OR 0.88)
 No evidence of a reduction in neonatal sepsis with Rx.
McDonald HM, Brocklehurst P, Gordon A.
Antibiotics for treating bacterial vaginosis in pregnancy. Cochrane Database of
Systematic Reviews 2007, Issue 1.
Dr Mona Shroff
(fifteen trials of good quality, involving 5888 women.)
www.obgyntoday.info
Implications for practice
 The evidence to date does not suggest any
benefit in screening and treating all
pregnant women for asymptomatic
bacterial vaginosis to prevent preterm birth.
 Symptomatic/ previous preterm birth, screening & treatment before 20 weeks
 Oral metronidazole/clindamycin x 7 days
Dr Mona Shroff
www.obgyntoday.info
Some facts
Asymptomatic Bacteriuria
 Asymptomatic bacteriuria (detection of more than 100,000
bacterial/ml in a single voided midstream urine) occurs in
2%to10% of pregnancies and, if not treated, upto 30%of
them will develop acute pyelonephritis.
 Asymptomatic bacteriuria has been associated with low
birthweight and preterm delivery.
 Because the performance of rapid urine screening tests in
pregnancy is poor, quantitative culture remains the gold
standard for diagnosis...
 E. coli is the most common pathogen associated with
asymptomatic bacteriuria, representing at least 80% of
isolates. Other organisms include other gram negative
Dr Mona Shroff
bacteria and group B streptococci.
www.obgyntoday.info
Asymptomatic Bacteriuria
Screening & Rx
– Standard
recommendation in most ANC guidelines.
Antibiotic treatment
was effective in
reducing the incidence of pyelonephritis in
women with asymptomatic bacteriuria (RR
0.23) & reduction in the incidence of LBW (RR
0.66).
There was no evidence of a reduction in
preterm delivery
Smaill F, Vazquez JC.
Antibiotics for asymptomatic bacteriuria in pregnancy.
Dr Mona Shroff
www.obgyntoday.info
Cochrane Database of Systematic Reviews 2007, Issue 2.
The choice Rx:

Sulfonamide /a penicillin/
cephalosporin / nitrofurantoin, based on
the results of susceptibility testing.
 The optimal duration of treatment is unknown and
standard treatment regimens are currently
recommended
 Sulfonamides : avoided during the late stage of
pregnancy ,and breast feeding should be
discontinued if sulfonamides are taken because of
potential kernicterus or hemolysis ,due to G6PD
deficiency in the infant
Dr Mona Shroff
www.obgyntoday.info
Implications for practice

Routine screening & Rx of
asymptomatic bacteriuria at first
prenatal visit is recommended (if local
incidence > 2% -cost effective)
Antibiotic dep. on sensitivity testing &
fetomaternal S/E. : Standard dose :
optimal duration unknown(3-10d)
Dr Mona Shroff
www.obgyntoday.info
Implications for research
None of these studies adequately addressed
 the most appropriate time is to perform the
initial screening culture,
 how often to repeat a negative culture and
 how best to monitor women initially treated for
asymptomatic bacteriuria.
There is a need to define the appropriate frequency of
follow-up cultures and re-treatment strategies.
Dr Mona Shroff
www.obgyntoday.info
Trichomonas vaginitis
 Ass. with small but significant increased risk of PTB (OR
1.3).
 A couple of large RCTs of screening & Rx of
asymptomatic TV in preg ,found no benefit ,but
actually increased risk of PTB(RR 1.8),LBW(RR 2.49) &
childhood mortality within 2yrs.
 Mech. Unclear but possibly dying trichomonads
release inflammatory mediators & viruses that trigger
PTL.
 Treatment of symptomatic TV however is
recommended.
 Oral metronidazole safe even in first trimester.
Dr Mona Shroff
www.obgyntoday.info
Klebanoff M,Carey J,et al.N Engl J Med 2001;345:487-93
Kigozi G,Brahmbhatt H,et al.Am J Obstet Gynecol 2003;189:1398-400
Chlamydia : Screen with cervical swab
& treat not to reduce PTB but to
reduce vertical transmission & STD.
N.Gonorrhoea : Screen only high risk
women & Rx to reduce vertical
transmission & STD.
Dr Mona Shroff
www.obgyntoday.info
GBS carrier
• Not ass. with PTB ,but intrapartum fetal exposure
leads to early/late neonatal sepsis.
• CDC guidelines recommend screening of all pts at
35-37 wks pregnancy (vaginal & anorectal swab) &
intrapartum Px to carriers.(Ampi 2gms IV 6hrly)
• Indian data (10 yr study CMC Vellore)
carrier rate : 10-15% (special broth used)
neonatal GBS sepsis rate : 0.17/1000
 Screening may not be cost effective in our setup
Dr Mona Shroff
www.obgyntoday.info
•
If same Mrs.A ,28 wks G1P0, has come
with PPROM, & you have decided for
conservative Mx ,(if not long at least till
steroid cover),obviously you would want to
start antibotics….
 Which antibiotics are recommended based
on evidence & why?
 What other precautions would you take?
Dr Mona Shroff
www.obgyntoday.info
Preterm rupture of membranes
PTB: substantial neonatal morbidity and mortality.
One cause, associated with pROM, is often
subclinical infection & pROM can in turn predispose
to infection.
 Maternal antibiotic therapy might lessen infectious
morbidity and delay labour, but could suppress labour
without treating underlying infection. Such prolongation of
intrauterine infection may have adverse consequences for
the health of the baby.
Two observational studies (Murphy 1995; Spinillo 1995)
showed a positive correlation between the duration of
rupture of membranes and the risk of cerebral palsy or
other neurodevelopmental impairment.
Dr Mona Shroff
www.obgyntoday.info
• Routine antibiotic administration to women with pROM
reduces maternal and neonatal morbidity.
• Statistically significant reduction in
- chorioamnionitis ,
- numbers of babies born within 48 hours
- neonatal infection (RR 0.68),
- use of surfactant (RR 0.83) & oxygen therapy (RR0.88)
- abnormal cerebral ultrasound scan prior to
discharge from hospital (RR 0.82).
 Co-amoxiclav was associated with an increased risk of neonatal
necrotising enterocolitis (RR 4.60).
 From the available evidence, erythromycin would seem a better
choice.
Kenyon S, Boulvain M, Neilson J.
Antibiotics for preterm rupture of membranes. Cochrane Database of Systematic
Reviews 2003, Issue2. (Twenty-two trials - over 6000 women and their babies)
Dr Mona Shroff
www.obgyntoday.info
Other precautions
No vaginal examination , unless cervix appears
grossly dilated on P/S or patient appears in advanced
labour or clear signs of infection precluding
conservative management.
 Close W/F S/O infection.
 Consider amniocentesis for culture.
Dr Mona Shroff
www.obgyntoday.info
• Would you like to get done a routine WBC
count?
• How helpful is count in Mx decision?
Dr Mona Shroff
www.obgyntoday.info
• Elevated WBC count may support
suspicious clinical findings but may be
artificially elevated by recent
STEROID administration.(within 5-7
days, as early as two hours after the
first injection),( 35-65% rise)
• But total count remain less than 20000
cells/cc in steroid induced leucocytosis
J Perinat Med. 2002;30(4):287-91
Aust N Z J Obstet Gynaecol. 1998 Nov;38(4):396-8.
Med Wieku Rozwoj. 2003 Jul-Sep;7(3 Suppl 1):261-70
Deibel N,Parsons M,et al,J Perinat Med. 1998;26(3):204-7
Dr Mona Shroff
Denison F,et al,Br J Obstet
Gynaecol. 1997 Jul;104(7):851-3.
www.obgyntoday.info
Implications for practice
 Antibiotic treatment following pPROM is
associated with a statistically signicant delay
in women giving birth and reductions in
major markers of neonatal morbidity allow
sufficient time for prophylactic prenatal
corticosteroids to take effect .
 On the basis of the available evidence
erythromycin appears the antibiotic of choice.
 Co-amoxiclav avoided
Dr Mona Shroff
www.obgyntoday.info
Further evaluation of the long-term
outcome on health and development of
children following this intervention is
important.
Near term PROM
• If Mrs.A comes at 36 weeks with PROM of 2
hrs, what would be your line of management
based on evidence?
- Immediate induction of labour – Y/N?
- Antibiotics – Y/N?
- Why?
- When antibiotics?
Dr Mona Shroff
www.obgyntoday.info
PROM at or near term

The use of antibiotics resulted in a statistically signicant
reduction in maternal infectious morbidity
(chorioamnionitis or endometritis): RR 0.43 (3% vs 7%)

No statistically significant differences were shown for
outcomes of neonatal morbidity.
Given the low rate of maternal infection in the control population
(7%), increasing bacterial resistance and S/E with antibiotic use, it
does not seem justiable to expose all women with term PROM to
antibiotics when treatment can be restricted to those who develop
clinical indications for antibiotic treatment.(fever,maternal/fetal
tachycardia, leaking > 12 hrs ,foul smelling liquor,,ut tenderness)
Flenady V, King J. Antibiotics for prelabour rupture of membranes at or near term.
Cochrane Database of Systematic Reviews 2002, Issue3.
Dr Mona Shroff
(two trials, involving a total of 838 women)
www.obgyntoday.info
Implications for practice

Until more reliable evidence is
available indicating overall benefit from
prelabour prophylactic antibiotics for
term PROM it would seem prudent that
their routine use in PROM <12 hrs be
avoided.
 Immediate induction of labour
recommended.
Dr Mona Shroff
www.obgyntoday.info
Implications for research
Further well designed
randomised controlled trials
(adequately sized to address
clinically important maternal
and neonatal outcomes and
include a cost analysis) are
needed.
Dr Mona Shroff
www.obgyntoday.info
Dr Mona Shroff
www.obgyntoday.info