Antibiotics for early-onset neonatal infection Randomised controlled trials, including systematic

196 Pages·2012·1.4 MB·English

by  Cristina Visintin

Antibiotics for early-onset neonatal infection
Randomised controlled trials, including systematic reviews of randomised controlled trials for antibiotic treatment (covers review questions 5 to 8)
Study details Participants Interventions Methods Outcomes and results Comments
Full citation Sample size Intervention Details Results Limitations
Adair,C.D., N=120 N=60 women received Randomization was Neonatal sepsis: Neonatal sepsis is not
Ernest,J.M., ampicillin-sulbactam performed by a computer- Ampicillin/sulbactam defined
Sanchez-Ramos,L., 3.0 gm IV infusion in generated list of random group: 3/60 (5%)
Burrus,D.R., 100 ml fluid at the numbers that was Placebo group: 3/60 (5%)
Boles,M.L., diagnosis and repeated unavailble to caregivers Reported p value: NS
Veille,J.C., Characteristics every 6 hours untill birth
Meconium-stained Maternal age in years During labour if clinical NICU admissions: Other information
amniotic fluid- (SD): intra-amniotic infection Ampicillin/sulbactam Q 5-MSAF
associated infectious Ampicillin/sulbactam occured, the managing group: 10/60 (16.7%)
morbidity: a group: 24.5 (6.3) physician was allowed to Placebo group: 12/60 Intra amniotic infection
randomized, double- Placebo group: 25.9 Comparator choose antibiotic coverage (20%) defined as " a
blind trial of (6.3) N=60 women in control at their discretion. All Reported p value: NS temperature greater
ampicillin-sulbactam P value: NS group received identical caregivers were blinded to than 100.5F with the
prophylaxis, looking normal saline randomization status. If Neonatal hospital stay in presence of one or
Obstetrics and Gravidity (SD): CS was done cefazolin 2.0 days (SD): more of the following:
Gynecology, 88, 216- Ampicillin/sulbactam gm was adminstered at Ampicillin/sulbactam fetal and/or maternal
220, 1996 group: 2.0 (1.4) cord clamping group: 3.1 (6.1) n=60 tachycardia, uterine
Placebo group: 2.4 Placebo group: 3.0 (4.3) tendernedd, foul-
(1.7) Medical records were n=60 smelling AF, or
P value: NS reviewed after discharge. Reported p value: NS leukocytosis (white
Statistical analysis was blood cell count
Ref ID Parity (SD): performed with the Gestational age at birth in 20x109/L or greater).
85116 Ampicillin/sulbactam assistence of Stateview 4.0 weeks (SD):
group: 0.6 (0.9) software. Statistic analysis Ampicillin/sulbactam Postpartum
Placebo group: 0.8 included two-tailed group: 39.8 (1.0) endometritis was
(1.0) unpaired Student t test for Placebo group: 39.9 (1.2) defined as "a
P value: NS comparison between Reported p value: NS temperature greater
Country/ies where means and chi square test than 100.5F on two
the study was for evaluation of Birth weight in gm (SD): occastions after delivery
carried out categorical variables Ampicillin/sulbactam with the presence of
USA Ethnicity group: 3397.9 (509) uterine tenderness,
Placebo group: 3420 (394) foul-smelling lochia,
BAlmacpkic: illin/sulbactam Reported p value: NS a nd/or leukocytosis."
group: 25/60 (41.6%) Sample size calculation
Study type Placebo group: 26/60 : Assuming an alpha
Randomized (43.3%) Maternal outcomes level of 0.05 and beta
cotrolled trial P value: NS 0.20 (power 80%), 150
Intramniotic infection: patients would be
Antibiotics for early-onset neonatal infection - Randomised controlled trials, including systematic reviews of randomised controlled trials for antibiotic treatment (covers review
questions 5 to 8)

White: Ampicillin/sulbactam required todemonstrate
Ampicillin/sulbactam group: 4/60 (23.3%) a 70% reduction in the
Aim of the study group: 33/60 (55%) Placebo group: 14/60 intra amniotic infection
To evaluate the Placebo group: 31/60 (6.7%) rate from 25% in the
efficacy of (51.7%) Reported p value: 0.02 control group to a 7.5%
intrapartum P value: NS Reported Relative risk rate in the antibiotic
antibiotic prophylaxis (95% CI): 0.48 (0.22 to prophylaxis group.
in women with Other: 0.98)
meconium-stained Ampicillin/sulbactam
amniotic fluid (MSAF) group: 2/60 (3.3%) Endometritis:
Placebo group: 3/60 Ampicillin/sulbactam
(5%) group: 5/60 (16.7)
P value: NS Placebo group: 10/60
(8.3%)
Labour Reported p value: 0.16
charecteristics: Reported Relative risk

(95% CI): 0.64 (0.30 to

Induction of labor: 1.33)
Study dates
Ampicillin/sulbactam
September 1994-
group: 7/60 (11.6%)
March 1995
Placebo group: 11/60
(18.3%)
P value: NS

Source of funding Vaginal examination
Partially funded by (SD):
Roerig, a division of Ampicillin/sulbactam
Pfizer group: 6.5 (2.8)
Phramaceuticals® Placebo group: 6.0
(2.3)
P value: NS

Epidural:
Ampicillin/sulbactam
group: 54/60 (90%)
Placebo group:
52/60 (86.7%)
P value: NS

Oxytocin use:
Ampicillin/sulbactam
group: 12/60 (20%)
Placebo group:
10/60 (16.7%)
Antibiotics for early-onset neonatal infection - Randomised controlled trials, including systematic reviews of randomised controlled trials for antibiotic treatment (covers review
questions 5 to 8)

P value: NS

Duration of ROM in min
(SD):
Ampicillin/sulbactam
group: 539.6 (345.9)
Placebo group: 542.9
(374.5)
P value: NS

Duration of labour in
min (SD):
Ampicillin/sulbactam
group: 802.6 (327.7)
Placebo group: 754.6
(405.9)
P value: NS

Internal monitor

Intrauterine pressure
catheter:
Ampicillin/sulbactam
group: 17/60 (28.3)
Placebo group: 12/60
(20%)
P value: NS

Fetal scalp electrode:
Ampicillin/sulbactam
group: 29/60 (48.3)
Placebo group: 21/60
(42%)
P value: NS

Inclusion criteria
All women with
meconium-stained
Antibiotics for early-onset neonatal infection - Randomised controlled trials, including systematic reviews of randomised controlled trials for antibiotic treatment (covers review
questions 5 to 8)

amniotic fluid
complicating birth
attending the study
centre during the study
period

Exclusion criteria
Women with pencillin
and/or cephalosporin
allergy, evidence of
active infection,
presence of intrauterine
death, < 24 weeks'
gestation and h/o
antibiotic in the
previous 7 days were
excluded
Antibiotics for early-onset neonatal infection - Randomised controlled trials, including systematic reviews of randomised controlled trials for antibiotic treatment (covers review
questions 5 to 8)

Study details Participants Interventions Methods Outcomes and results Comments
Full citation Sample size Intervention Details Results Limitations
Gibbs,R.S., N=48 women with intra- N=26, intrapartum Specimens for a vaginal Neonatal sepsis defined as No blinding of women
Dinsmoor,M.J., amniotic infection treatment group: culture for aerobes and either bacteremia or death or healthcare providers
Newton,E.R., Ampicillin 2g IV every 6 mycoplaasma and with a clinical diagnosis of is reported.
Ramamurthy,R.S., A hour plus gentamicin peripheral blood culture for sepsis and positive
randomized trial of 1.5 mg/kg every 8 hour aerobes and anerobes peripheral cultures No adherence to
intrapartum versus (ampicillin was were obtained in all intention to treat
immediate Characteristics adminstered first). women. A complete blood Early neonatal sepsis: analysis as 3 women in
postpartum treatment Maternal age in years Treatment started count also performed . If Intrapartum group: 0/26 immediate postpartum
of women with intra- (SD): immediately after available, amniotic fluid (0%) group were excluded
amniotic infection, specimens for culture was also collected for Immediate postpartum from the analysis where
Obstetrics and Intrapartum group: 23.7 were collected and culture through an group: 4/19 (21%) protocol was violated.
Gynecology, 72, 823- (7.0) lasted untill women intrauterine pressure P value: 0.03
828, 1988 Immediate postpartum were afebrile for catheter. Group B Streptococcus Underpowered study as
group: 20.1 (3.5) approximately 48 hours (n=1), Staphylococcus optimal information size
P value: 0.03 Randomisation aureus (n=1), was calculated as 46
Duration of intrapartum was acheived by flipping a Streptococcus pneumoniae women in each arm but
Nulliparous: antibiotic treatment in coin. Allocation to (n=1) and E.coli (n=1) study had to be
Ref ID Intrapartum group: days (SD): 2.63 (2.39) treatment was by selection terminated by a joint
86038 21/26 (81%) of sealed envelopes Neonatal pneumonia: decision of Safety
Immediate postpartum Women undergoing Intrapartum group: 0/26 Commitee and
group: 16/19 (84%) Cesarean section Timing and mode of birth Immediate postpartum investigators due to
P value: NS received clindamycin was determined according group: 2/19 significant difference in
900 mg IV every 8- to usual obstetric piractice, No bacteria isolated from maternal and neonatal
Country/ies where Duration of labour hours, beginning after no specific time limit was peripheral culture outcomes.
the study was (hours): cord clamping set for birth after diagnosis diagnosis was made on X-
carried out Intrapartum group: 14.5 of intra-amniotic infection. ray findings.
USA (7.3) Maternal vaginal culture
Immediate postpartum All babies had peripheral revailed both E. coli and
group: 13.6 (5.6) blood culture and chest X- Klebsiella pneumoniae in Other information
P value: NS Comparator ray. X-rays were one case and no aerobic Q-5 Intrapartum
Study type N=22, immediate interpreted by staff organism in the second antiobiotics in CA
Randomized Duration of ROM postpartum treatment radiologist who was case where amniotic fluid
comparative trial (Inhtoraurpsa)r: tum group: 19.2 gNroo uinpt rapartum uclninaiwcaalr eco oufr sthee. neonate's cuureltaulryeti cguremw Ureaplasma
(19.2) prophylaxis,
Immediate postpartum antibiotics started CSF examination was Neonatal pneumonia or
group: 19.17 (15.0) immediately after performed only in babies sepsis:
Aim of the study P value: NS umbilical cord with referable signs. Intrapartum group: 0/26
To compare the clamping. Dosage, (81%)
neonatal outcomes in Interval between duration and addition of All babies received same Immediate postpartum
women with intra- diagnosis of intra- clindamycin for antibiotic regimen group: 6/19 (32%)
amniotic infection and Cesarean section as for
Antibiotics for early-onset neonatal infection - Randomised controlled trials, including systematic reviews of randomised controlled trials for antibiotic treatment (covers review
questions 5 to 8)

amniotic infection birth (hours): intrapartum (ampcillin 75mg/kg every P value: 0.03
treated with Intrapartum group: 3.4 group. There were 12 hour plus gentamicin
intrapartum versus (2.6) protocol violations for 2.5 mg/kg every 12 hour) Neonatal hospital stay
immediate Immediate postpartum three women who were which begun after the initial (days):
postpartum group: 4.1 (2.3) excluded from the neonatal evaluations ( Intrapartum group: 3.8
antibiotics P value: NS analysis. generally within 2 hours of (1.1) n=26
birth). If the culture and X- Immediate postpartum
Vaginal examinations ray were negative and group: 5.7 (3.0) n=19
(n): clinical course were P value: 0.02
Intrapartum group: 7.5 uncomplicated, antibiotic
Study dates (2.2) were discontinued after 72 Maternal outcomes:
May 5, 1987 - Immediate postpartum hours. If sepsis or
November 8, 1987 group: 7.9 (1.6) pneumonia were
P value: NS diagnosed treatment
continued for a minimum of Maximum maternal
Duration of internal 10 days. temprature postapartum
fetal monitoring (hours): (F):
Source of funding Intrapartum group: 11.6 Mother was contacted by Intrapartum group: 99.8
Not reported (6.5) telephne after four weeks (0.8) n=26
Immediate postpartum of discharge, if Immediate postpartum
group: 10.2 (4.8) unsuccessful follow-up was group: 10.3 (1.1) n=19
P value: NS attempted by letter and P value: 0.05
then by assessing hospital
Maximum temprature in records. Maternal febrile days:
labour (F): Intrapartum group: 0.44
Intrapartum group: Statistical analysis was (0.7) n=26
101.0 (0.7) done by either Fisher's Immediate postpartum
Immediate postpartum exact test or a chi-square group: 1.5/19 (2.1) n=19
group: 100.8 (0.6) test for discrete data, and P value: 0.05
P value: NS by t test for continous data
Maternal bacteremia:
Cesarean section: Intrapartum group: 3/26
Intrapartum group: 8/26 (12%)
(31%) Immediate postpartum
Immediate postpartum group: 1/19 (5%)
group: 7/19 (37%) P value: NS
P value: NS
Maternal postpartum
Amniotic fluid avialable hospital stay (days):
for culture: Intrapartum group: 4.0
Intrapartum group: (1.0) n=26
19/26 (73%) Immediate postpartum
Immediate postpartum group: 5.0 (1.9) n=19
group: 12/19 (63%)
Antibiotics for early-onset neonatal infection - Randomised controlled trials, including systematic reviews of randomised controlled trials for antibiotic treatment (covers review
questions 5 to 8)

P value: NS P value: 0.05

Inclusion criteria
Intra-amniotic infection
was diagnosed on the
basis of maternal fever
(≥ 100F) and ROM plus
2 or more of the
following signs:
maternal tachycardia (>
100/min), uteerine
tenderness, purulent or
foul amniotic fluid, fetal
tachycardia (>
160/min), or maternal
leukocytosis

Exclusion criteria
Women with < 34
weeks' gestation or
cervical dilatation < 4
cm at the time of
diagnosis
Antibiotics for early-onset neonatal infection - Randomised controlled trials, including systematic reviews of randomised controlled trials for antibiotic treatment (covers review
questions 5 to 8)

Study details Participants Interventions Methods Outcomes and results Comments
Full citation Sample size Intervention Details Results Limitations
Maberry,M.C., N=133 Triple agent After obtaining consent, Neonatal sepsis: Women and health
Gilstrap,L.C.,III, therapy;intervenous women were randomized Triple agent therapy group: carers were not blinded
Bawdon,R., Characteristics ampicillin, gentamicin via a table of random 2/64 (1.6%) to treatment allocation
Little,B.B., Dax,J., Estimated gestational and clindamycin numbers to receive either (1 Staphylococcus aureus
Anaerobic coverage age ≥ 36wks dosage and duration triple agent therapy or dual positive blood culture, 1 No adherence to
for intra-amnionic Triple agent therapy not reported agent therapy. Before Group B Streptococcus intention to treat
infection: maternal group: 56/64 starting antibiotic therapy, positive urine latex test) analysis as women who
and perinatal impact, Dual agent therapy maternal blood and urine Dual agent therapy group: did not receive all of
American Journal of group: 61/69 culture were sent for 1/69 (2.8%) their antibiotics were
Perinatology, 8, 338- aerobic and anerobic (1 excluded from the
341, 1991 Spontaneous labour: Comparator culture. Attempts were Staphylococcus epidermidi analysis
Triple agent therapy Dual agent made to obtain amniotic s positive blood culture)
group: 16/64 (25%) therapy;intervenous fluid sample via a Authors reported rigid
Dual agent therapy ampicillin and transcervical intrauterine Relative risk (95% CI): 2.16 inclusion criteria which
group: 16/69 (23%) gentamicin pressure catheter in all (0.20, 23.21)* resulted in a high
Ref ID P value: NS women and sent for culture proportion of exclusions
103106 Necrotising enterocolitis: (75%) from eligible

Induced labour: Maternal and neonatal Triple agent therapy group: population of women
Triple agent therapy records were reviewed . 0/64 (0%) diagnosed with

group: 13/64 (20%) Neonatal sepsis was Dual agent therapy group: chorioamnionitis

Dual agent therapy defined as a positive blood 0/69 (0%) (n=532) which might
Country/ies where
group: 18/69 (26%) or CSF culture or a positive lead to selection bias
the study was
P value: NS urine latex test for GBS. Relative risk (95% CI): NC*
carried out
Postpartum endometritis
USA Augmented labour: was defined as the Neonatal deaths:
Triple agent therapy presence of a temperature Triple agent therapy group:
group: 35/64 (55%) of 38C or higher on at least 2/64 (3.1%)
Dual agent therapy two occastions, excluding Dual agent therapy group:
Study type group: 35/69 (55%) the first postpartum day or 3/69 (4.3%)
Single centre RCT P value: NS by the persistence of a Other information
temperature of 38C or Relative risk (95% CI): 0.72
Q-5, Intrapartum
Spontaneous ROM: higher 48 hours (0.12, 4.16)* p=0.71
antibiotics
Triple agent therapy postdelivery
group: 11/64 (55%) Neonatal hospital stay
Aim of the study Dual agent therapy The majority of infants (days):
To assess the impact group: 8/69 (12%) received ampicillin and Triple agent therapy group:
of adding an P value: NS gentamicin for at least 48 8.0 (n=64)
antibiotic to provide hours pending culture Dual agent therapy group:
anerobic coverage Artificial ROM: results 7.0 (n=69)
for the treatment of Triple agent therapy
intra-amniotic group: 30/64 (47%) Statistical analysis was Postpartum Endometritis:
Antibiotics for early-onset neonatal infection - Randomised controlled trials, including systematic reviews of randomised controlled trials for antibiotic treatment (covers review
questions 5 to 8)

infection Dual agent therapy done using chi-square Triple agent therapy group:
group: 31/69 (45%) contingency table analysis 5/64
P value: NS or Fisher's exact probablity Vaginal delivery 0/34,
test Cesarean section 5/30
ROM before admission: Dual agent therapy group:
Study dates Triple agent therapy 10/69
December 1987 to group: 23/64 (36%) Vaginal delivery 5/39,
January 1989 Dual agent therapy Cesarean section 5/30
group: 30/69 (43%)
P value: NS Relative risk (95% CI): 0.54

(0.19, 1.49)*

Internal electronic
Source of funding
monitioring: *Calculated by the NCC-
Not reported
Triple agent therapy WCH technical team from
group: 61/64 (95%) data reported in the article
Dual agent therapy
group: 64/69 (93%)
P value: NS

External electronic
monitioring:
Triple agent therapy
group: 2/64 (3%)
Dual agent therapy
group: 4/69 (5%)
P value: NS

No electronic
monitoring:
Triple agent therapy
group: 1/64 (2%)
Dual agent therapy
group: 1/69 (2%)
P value: NS

Spotaneous vaginal
birth:
Triple agent therapy
group: 22/64 (34%)
Dual agent therapy
group: 29/69 (42%)
P value: NS

Assisted vaginal birth
Antibiotics for early-onset neonatal infection - Randomised controlled trials, including systematic reviews of randomised controlled trials for antibiotic treatment (covers review
questions 5 to 8)

(forceps):
Triple agent therapy
group: 12/64 (19%)
Dual agent therapy
group: 10/69 (14%)
P value: NS

Cesarean section:
Triple agent therapy
group: 30/64 (47%)
Dual agent therapy
group: 30/69 (43%)
P value: NS

Indication for Cesarean
section:
Dystocia:
Triple agent therapy
group: 26/30
Dual agent therapy
group: 20/30

Fetal distress:
Triple agent therapy
group: 3/30
Dual agent therapy
group: 7/30

Breech:
Triple agent therapy
group: 0/30
Dual agent therapy
group: 2/30

Other:
Triple agent therapy
group: 1/30
Dual agent therapy
group: 1/30

Inclusion criteria
Pregnant women of >
24 weeks'