Study characteristics

Methods

RCT. Individual women. 2‐arm study.

Participants

Inclusion criteria

• Women having elective CS for various reasons.

• N = 200.

Exclusion criteria

• Women who had received antibiotics within previous 2 weeks; had visible signs of infection; elevated temperature; allergic to the antimicrobials used.

Interventions

Intervention: 3^rd generation cephalosporin (C3).

• Ceftriaxone (C3).

• 1 g single dose intravenously at induction of anaesthesia.

• N = 100.

Comparator: broad spectrum penicillin (P2) plus antistaphylococcal penicillin (P3).

• Ampicillin (P2) + cloxacillin (P3).

• 1 g intravenously at induction of anaesthesia then every 8 hours (3 doses).

• N = 100.

Subgroups

• Type of CS: elective

Comparison 13.1

Outcomes

Postoperative febrile morbidity; postoperative infection; endometritis; wound infection; pelvic abscess; peritonitis; other febrile morbidity.

Notes

Dates: January to June 2001

Setting: Wad Medani Teaching Hospital, Central Sudan.

Funding sources: the drugs were donated by Alhikma Company, Wad Medani, Sudan.

Declarations of interest: not reported.

Additional information

• Costs: the report also includes a comment on costs, however, no data are provided that could be included in this review: Quote: "Although the prices of these 2 drugs do not differ much, the single dose of ceftrixone is certainly easier to administer than the 3 doses of ampicillin/cloxacillin and can save a great deal of nursing time".

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote:“...were randomised...”

Allocation concealment (selection bias)

Unclear risk

Quote:“...were randomised...”

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Not blinded and the drug regimens were different, 1 a single dose, the other 3 doses.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No information.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No loss to follow‐up.

Selective reporting (reporting bias)

High risk

We did not assess trial protocol,but the publication reported more outcomes than their methods indicated e.g. low Apgar scores; death; maternal vomiting and maternal skin rash.

Other bias

Unclear risk

No statistical differences in admission variables between the 2 groups. Data and P values provided on temperature, weight, gestational age, pre‐operative Hb. However, other aspects of bias unclear. · Quote:"The drugs were donated by Alhikma Company, Wad Medani, Sudan." but it seems unclear whether this might give the company any influence or not.

Study characteristics

Methods

RCT. Individual women. 2‐arm study.

Participants

Inclusion criteria

• Women having elective CSs for various reasons, with no added risk factors for infection, and who were informed, counselled, and consented to participate in the study.

• N = 200.

Exclusion criteria

• Women who were excluded from the study were those who had received antibiotics within the 2 weeks prior to the operation, those who had any visible infection at any site or elevated temperature at the time of the operation, those who had rupture of the membranes prior to CS, and those who were allergic to any of the antimicrobials used. Also excluded were those who were anaemic (PCV < 33%), were human immunodeficiency virus‐positive, or who did not wish to participate in the study.

Interventions

Intervention: other antibiotic regimen (multiple classes)

• Ampiclox (ampicillin [P2] + cloxacillin [P3]) + gentamicin (A) + metronidazole (N), multiple doses.

• Ampiclox was administered at a dose of 1 g 6‐hourly, gentamicin at 80 mg 8‐hourly, and metronidazole at 500 mg 8‐hourly (all intravenous for first 48 hours), and converted after 48 hours to ampiclox capsules 500 mg 6‐hourly for 5 days, IM gentamicin 80 mg 8‐hourly for 3 days, and metronidazole tablets 400 mg 8‐hourly for 5 days.

• Unclear when first dose given, but methods describe this regimen where all drugs are given postoperatively as  quote: "commonly used" in Nigeria, implying postoperative commencement in this trial. 

• N = 100.

Comparator: 3^rd generation cephalosporin (C3)

• Ceftriaxone (C3) single dose.

• 1 g single dose, intravenously, after clamping of the cord.

• N = 100.

Subgroups

• Type of CS: elective

Comparison 18.1

Outcomes

Endometritis, UTIs, febrile morbidities, wound infections, duration of hospital stay, cost of antibiotic therapy.

Notes

Dates: not reported.

Setting: obstetric units of the Obafemi Awolowo University Teaching Hospital complex, Ile‐Ife, and the Seventh Day Adventist Hospital Ile‐Ife, Osun State, Nigeria.

Funding sources: not reported.

Declarations of interest: quote:“The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.”

Additional information

• Costs: data are reported relating to cost of antibiotic therapy under comparison 18.

• This trial reported cephalosporin C3 as the intervention and the mixed regimen as the comparator. For the purpose of presenting multiple analyses of mixed regimens compared with cephalosporins in a coherent fashion, we have inverted the intervention and comparator in this review.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Randomization was done using the method of block randomization with randomized numbers picked from a table of random numbers."

Allocation concealment (selection bias)

Low risk

Patients were allocated by quote: “...opening a sealed envelope; these were arranged serially”.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Different drug administration methods for the 2 groups.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No information provided.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No loss to follow‐up.

Selective reporting (reporting bias)

Unclear risk

Reported outcomes were as prespecified in the methods section, but we did not assess trial protocol.

Other bias

Unclear risk

No statistical differences in baseline variables between the 2 groups but it was unclear about other possible biases.

Study characteristics

Methods

RCT. Individual women. Multi‐centre (6 centres). 2‐arm study.

Participants

Inclusion criteria

• Women undergoing primary or repeat CS.

• N = 346 but analysed 283

Exclusion criteria

• Use of antimicrobial therapy within previous 7 days; sensitivity to cephalosporins or penicillin; abnormal renal or hepatic laboratory tests; intention to breastfeed within 24 hours of birth; infection at the time of enrolment.

Interventions

Intervention: 2^nd generation cephalosporin (C2).

• Cefoxitin (C2)

• 6 g total. 3 IV doses of 2 g each at 4‐hour intervals starting immediately after cord clamping.

• N = 177 but 147 analysed.

Comparator: broad spectrum penicillin (P2).

• Piperacillin (P2)

• 6 g total. 3 IV doses of 2 g each at 4‐hour intervals starting immediately after cord clamping.

• N = 169 but 136 analysed.

Subgroups

• Type of CS: mixed, elective and non‐elective

• Generation of cephalosporin and type of penicillin: 2^nd generation cephalosporin, C2; broad spectrum penicillin, P2

• No primary outcome data for subgroup analyses

Comparisons: 4

Outcomes

Satisfactory prophylactic response; febrile morbidity (temperature > 38 ºC x 2 occasions, 6 hours apart, not included first 24 hours post operation; wound infection).

Notes

Dates of study: not reported.

Setting: women from hospitals and universities of San Francisco, Atlanta, Memphis, Los Angeles, Phoenix, New York.

Additional information

• This study included some long‐term follow‐up. 'Unsatisfactory prophylaxis ‐ bacterial infection within 3‐10 weeks' was 11/147 with cephalosporin and 15/136 with penicillin (RR 0.68, 95% CI 0.23 to 1.43).

• Costs: this trial did not provide any information or comment on costs of treatment.

Funding sources: not reported.

Declarations of interest: not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

“...a computer‐generated randomization schedule...”

Allocation concealment (selection bias)

Low risk

“...a computer‐generated randomization schedule maintained by each hospital pharmacy...”

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

“The investigator and his (or her) staff were blinded as to antibiotic assignment. The code was not broken by the investigator until the last patient had been evaluated for prophylactic response.”

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

“The investigator and his (or her) staff were blinded as to antibiotic assignment. The code was not broken by the investigator until the last patient had been evaluated for prophylactic response.”

Incomplete outcome data (attrition bias)
All outcomes

High risk

Excluded after randomisation: cephalosporin group 30/177 (16.9%) and penicillin group 33/119 (19.5%). Also differential loss from 2 groups.

Selective reporting (reporting bias)

Unclear risk

Publication seemed to report on the outcomes listed in the methods section, but we did not assess trial protocol.

Other bias

Unclear risk

Study not stopped early; similar baseline characteristics for weight; height and race, but significant difference in mean age ‐ though not considered important. Other aspects of bias were unclear. No information on funding source of study.

Study characteristics

Methods

RCT. Individual women. 2‐arm study.

Participants

Inclusion criteria

• Women undergoing CS and at high risk of developing postoperative infection.

• Criteria for high risk: > 4 pre‐operative vaginal examinations; internal fetal monitoring; obesity; ruptured membranes for > 30 minutes; meconium‐stained amniotic fluid; labour of any duration before the operation.     

• 16 to 48 years.

• N = 196 but 26 excluded for protocol violations = 170 analysed.

Exclusion criteria

• Women with hypersensitivity to penicillins or cephalosporins; those with required concomitant antibiotic therapy; or had received antibiotics during 72 hours preceding enrolment; those in another drug study; women with immunological, renal or hepatic impairment or who had concomitant infections that might confuse the interpretation of the results.

Interventions

Intervention: 2^nd generation cephalosporin (C2).

• Cefotetan (C2)

• 1 g, single dose, IV, at time of cord clamping.

• N = 83.

Comparator: broad spectrum penicillin plus betalactamase inhibitor (P2+)

• Ampicillin + sulbactam (0.5 g) (P2+).

• 1 g, single dose, IV, at time of cord clamping.

• N = 87.

Subgroups

• Type of CS: unclear (subgroup 3)

• Generation of cephalosporin and type of penicillin: 2nd generation cephalosporin, C2 (subgroup 2)

Comparisons: 1, 2 (subgroup 3), 3 (subgroup 2)

Outcomes

Treatment success; incision site infection; endometritis; UTI; febrile morbidity; peak recorded temperature; days in hospital.

Notes

Dates of study: not reported.

Setting: Westchester County Medical Center, USA.

Funding sources: Quote: "This work was supported by a grant (89‐S‐0591, R‐0102) from The Reorig Division of Pfizer Inc."

Declarations of interest: not reported.

Additional information

• Costs: this trial did not provide any data or specific information on costs of treatment, however the authors observed in their discussion that cefotetan's lower cost was one reason among several that it had quote: "reportedly replaced cefoxitin" as the treatment of choice for pelvic infections such as endometritis.

• In the original trial report, the intervention group received ampicillin‐sulbactam and the control group received cefotetan.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

“A computer was used to generate a list of random numbers for two groups.”

Allocation concealment (selection bias)

Low risk

“Treatment assignments were placed in numbered, sealed and opaque envelopes."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

“Neither patient nor obstetrician was informed of the antibiotic assignment. The study drugs were administered by the anaesthesiologist in the operating room immediately after the umbilical cord was clamped”

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

“Neither patient nor obstetrician was informed of the antibiotic assignment", although it is unclear whether outcome assessors were blinded.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

26/196 (13%) women were excluded because of protocol violations.

Selective reporting (reporting bias)

Unclear risk

Publication seemed to report on the outcomes listed in the methods section, but wee did not assess the trial protocol.

Other bias

Unclear risk

"This work was supported by a grant (89‐S‐0591, R‐0102) from The Reorig Division of Pfizer Inc."

Not stopped early; no imbalance in baseline characteristics assessed on: on age; race; weight; height; BP; temperature and pulse but other aspects of bias were unclear.

Study characteristics

Methods

RCT. Individual women. 3‐arm study.

Participants

Inclusion criteria

• Women undergoing CS following labour for > 2 hours without evidence of infection.

• N = 114.

Exclusion criteria

• Inability to understand or give consent; oral temperature > 100⁰F; antibiotic treatment within 72 hours prior to birth; allergies to study antibiotics; intention to breastfeed.

• Requirement of additional antibiotics during or after CS ‐ this may contribute to high risk of bias through exclusion after randomisation.

Interventions

Intervention: 2^nd generation cephalosporin (C2).

• Cefotetan (C2)

• 1 g, single dose, IV after umbilical cord clamping.

• N = 42.

Comparator 1: broad spectrum penicillin plus betalactamase inhibitor (P2+)

• Ampicillin + sulbactam (P2+)

• 1.5 g, single dose, IV after umbilical cord clamping.

• N = 33.

Comparator 2: Fluroquinolone (F)

• Ciprofloxacin (F)

• 200 mg, single dose, IV after umbilical cord clamping.

• N = 39.

Subgroups

• Type of CS: mixed (subgroup 3). Although the inclusion criteria state that all women have been in labour for at least 2 hours (i.e. all CA=S non‐elective), the reasons reported for CS in the results include some antenatal reasons, therefore we have reported under mixed type of CS.

• Generation of cephalosporin and type of penicillin: 2^nd generation cephalosporin, C2 (subgroup 2)

Comparisons: 1; 2 (subgroup 3); 3 (subgroup 2); 14; 15

Outcomes

Endometritis; pneumonia; bacteraemia; UTI; would infection; postpartum stay > 6 days.

Notes

Dates of study: not reported

Setting: Tampa General Hospital, USA.

Funding sources: not reported.

Declarations of interest: not reported.

Additional information

• Costs: this trial reported on the costs of each drug at this hospital (see table 4), describing 3 different figures: the 'hospital cost' of the drug; the 'patient cost' of the drug; and the 'total cost to patient' of the drug (this last being by far the highest figure). The total cost per patient was: USD 72.00 for cefotetan 1g; USD 51.00 for ampicillin‐sulbactam 1.5g; and USD 78.00 for ciproflaxin 200mg. We have reported this narratively in our results.

• The data reported for bacteraemia have been reported under the outcome 'maternal sepsis' in this update.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: “... prospectively randomised...”

Allocation concealment (selection bias)

Unclear risk

Quote: “... prospectively randomised...”

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: “Investigators were blinded to treatment.”

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: “Investigators were blinded to treatment.”

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No loss to follow‐up.

Selective reporting (reporting bias)

Unclear risk

Publication reported on the outcomes listed in the methods section, but we‐e did not assess trial protocol.

Other bias

Unclear risk

Baseline characteristics similar for: primaparous; weight; gestation; race; repeat CS; Hb but there was a statistically significant difference in age considered not to be clinically important. Other aspects of bias were unclear. No information about funding source of study.

Study characteristics

Methods

RCT. Individual women. 2‐arm study.

Participants

Inclusion criteria

• Women undergoing CS. All considered at risk of infection.

• Rupture of membranes > 6 hours; labour ≥ 12 hours; cervical effacement and dilatation > 4 cm; > 4 vaginal examinations.

• N = 109 but analysed 106

Exclusion criteria

• History of allergies to penicillin or cephalosporin; not co‐operative; oral temperature > 38 ºC within period 24 hours prior to operation; received antibiotics within 7 days prior to CS.

Interventions

Intervention: 1^st generation cephalosporin (C1).

• Cefazolin.

• 3 g total; 1 g every 6 hours up to 3 doses; IV; just after cord clamping.

• N = 53 randomised. 1 woman could not be evaluated because she was febrile in the labour room and so was excluded, leaving N = 52.

Comparator: broad spectrum penicillin (P2).

• Ampicillin.

• 3 g total; 1 g every 6 hours up to 3 doses; IV; just after cord clamping.

• N = 56 randomised ‐ 2 women could not be evaluated because they were febrile in the labour room and so were excluded, leaving N = 54.

Subgroups

• Type of CS: non‐elective

• Generation of cephalosporin: 1st generation cephalosporin, C1 (subgroup 1)

• Type of penicillin: broad spectrum penicillin, P2 (subgroup 2)

Comparisons: 4; 5 (subgroup 2); 6 (subgroup 1); 7 (subgroup 2)

Outcomes

Febrile morbidity; endometritis; parametritis; UTI; wound infection.

Notes

Dates: 1st January 1990 to 31 December 1992.

Setting: Inburi Hospital, Thailand.

Funding sources: not reported.

Declarations of interest: not reported.

Additional information

• Costs: this trial did not provide any information or comment on costs of treatment.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: “... assigned randomly...”

Allocation concealment (selection bias)

Unclear risk

Quote: “... assigned randomly...”

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

No information provided.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No information provided.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Only 3 women excluded.

Selective reporting (reporting bias)

Unclear risk

Publication reported on the outcomes listed in the methods section, but wee did not assess the trial protocol.

Other bias

Unclear risk

Baseline characteristics similar between groups on: age; height; weight; gravidity; gestation; preoperative haematocrit. However, other aspects of bias unclear. No information about funding source of study.

Study characteristics

Methods

RCT. Individual women. 5‐arm study.

Participants

Inclusion criteria

• Women undergoing CS.

• N = 204 in this review (though 360 in study which included a placebo group).

Exclusion criteria

• Women with a history of penicillin or cephalosporin allergy, those taking antibiotics, those with known infectious process at the time of operation (e.g. chorioamnionitis or UTI).

Interventions

Intervention 1: 1^st generation cephalosporin (C1).

• Cephapirin.

• 2 g; lavage.

• N = 70 ‐ reported in Table 4 Post‐operative morbidity (but 70 reported in Table 2 Risk factors).

Intervention 2: 2^nd generation cephalosporin (C2).

• Cefamandole.

• 2 g; lavage.

• N = 64 ‐ reported in Table 4 Post‐operative morbidity (but 70 reported in Table 2 Risk factors).

Comparator: broad spectrum penicillin (P2).

• Ampicillin.

• 2 g; lavage.

• N = 70.

4th group ‐ moxalactam disodium (1‐oxa‐beta‐lactam antibiotic: N = 64 in Table 4 (but 79 in Table 2).

5th group ‐ placebo (N = 77).

Vitamin added to each solution for disguise.

Subgroups

• Type of CS: unclear

Comparison: this trial used lavage and therefore would have been analysed separately from IV trials, under comparison 21. However, we have not included data from this trial in the current update because there is inconsistency in the denominators detailed in the trial report.

Outcomes

Endometritis (temperature > 37.8 ºC, uterine tenderness, pelvic irritation without other localising signs); wound infection (breakdown, positive culture and/or cellulitis): febrile morbidity (temperature > 100.4 x 2. 6 hours apart, excluded first 24 hours); mean duration of hospital stay.

Notes

Dates: 1 December 1982 to 31 May 1984.

Setting: Madigan Army Medical Center, USA.

Funding sources: not reported.

Declarations of interest: not reported.

Additional information

• No usable data: the numbers of women reported in each group differed in the Tables. Unlike previous publications of this review, for this update we have chosen not to included any data in data and analysis section.

• Costs: this trial did not provide any information or comment on costs of treatment.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: “A computer‐generated table of pseudo‐random numbers using the mixed congruential method was used by the pharmacy to assign each patient to one of five groups.”

Allocation concealment (selection bias)

Low risk

Quote: “A computer‐generated table of pseudo‐random numbers using the mixed congruential method was used by the pharmacy to assign each patient to one of five groups.”

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: “Patients and physicians were unaware of the group assignment until after completion of the study...”

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: “Patients and physicians were unaware of the group assignment until after completion of the study...”

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

No explanation for differences between the numbers of the initially randomised groups and the groups included in the morbidity analysis (cephapirin 79 vs 70, cefamandole 70 vs 64, moxalactam 64 vs 79). The total of women included is the same (360); therefore we can assume that women originally assigned to 1 group received other treatment and they were not analysed by intention to treat. The uneven numbers may be due to lack of block‐randomisation.

Selective reporting (reporting bias)

Unclear risk

Publication reported on the outcomes listed in the methods section, but we did not assess trial protocol.

Other bias

Unclear risk

Baseline characteristics similar on: age; parity; gestation. Small difference on gravidity but not considered clinically important. However, other aspects of bias unclear. No information about funding source of study.

Study characteristics

Methods

RCT. Individual women. 2‐arm study.

Participants

Inclusion criteria

• Women undergoing CS.

• N = 300.

Exclusion criteria

• Not documented.

Interventions

Intervention: 2^nd generation cephalosporin (C2).

• Cefotetan.

• 2 g; IV; single dose when the cord is clamped.

• N = 106.

Comparator: broad spectrum penicillin (P2).

• Mezlocillin.

• 2 g; IV; single dose when the cord is clamped.

• N = 194.

Subgroups

• Type of CS: unclear

Comparisons: no usable data reported

Outcomes

Fever > 38 ºC; endometritis; wound infection; UTIs; asymptomatic bacteriuria.

Notes

Dates of study: not reported.

Setting: Obstetric and Gynecologic department of UCSC, Como, Italy.

Funding sources: not reported.

Declarations of interest: not reported.

Additional information

• No data for this review

• Conference abstract only.

• Costs: this trial did not provide any information or comment on costs of treatment.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No information provided.

Allocation concealment (selection bias)

Unclear risk

No information provided.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

No information provided.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No information provided.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

No information provided.

Selective reporting (reporting bias)

High risk

We did not assess the trial protocol, but the conference abstract did not report pre‐specified outcomes to be assessed in the methods section.

Other bias

Unclear risk

No information provided. Also no information about funding source of study.

Study characteristics

Methods

RCT. 2 parallel‐arm study. Women randomised individually.

Participants

Inclusion criteria

• Women undergoing elective CS

• Normal temperature and blood test results before the CS operation

• No infection symptoms

• No medical comorbidities (e.g. diabetes, heart failure, and TB)

• Hb >= 100 g/L

• No history of penicillin allergy

• N = 100

Exclusion criteria

• Not documented.

Interventions

Intervention: 1st generation cephalosporin (C1) + nitroimadazole (N)

• Cefazolin (C1) + metronidazole (N).

• IV cefazolin sodium 2 g (with 5% glucose 250 mL) and 0.5% metronidazole 200 mL gtt after clamp of the cord. After the CS operation, IV cefazolin sodium 2 g (with 5% glucose 250 mL) 12‐hourly and 0.5% metronidazole 200 mL 6‐hourly.

• Total number randomised: N = 48.

Comparator: natural penicillin (P1) plus broad spectrum penicillin (P2) plus nitroimadazole (N)

• Ampicillin (P2) + benzylpenicillin (P1) + metronidazole (N)

• IV ampicillin sodium 3 g (with 5% glucose 250 mL) and 0.5% metronidazole 200 mL, gtt, after clamp of the cord. After CS operation, IV 0.5% metronidazole 200 mL 6‐hourly for 1 day, ampicillin sodium 3 g (with 5% glucose 250 mL) 12‐hourly for 3 days, and benzyl penicillin sodium 4×10⁶ U (with 5% glucose 250 mL) 12‐hourly for 3 days.

• Total number randomised: N = 52.

Subgroups

• Type of CS: elective

Comparisons: 20.2

Outcomes

Infection, duration of medication, cost of antibacterial agents and total drug cost during hospitalisation, adverse drug reactions, temperature at day after CS operation

Notes

Dates: Oct 2005 to Oct 2006

Setting: Central Hospital of Changnin District of Shanghai, China.

Funding sources: not reported.

Declarations of interest: not reported.

Additional information

• Data extraction: only undertaken by 1 person for the full text due to restricted available help with translation from Chinese

• Total drug cost during hospitalisation also reported in rmb (314.69 [SD128.77] n = 48 vs 511.88 [SD263.78] n = 52)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Envelopes were prepared. The surgeon “randomly” draw envelope to decide which group the patient will go.

Allocation concealment (selection bias)

High risk

Envelopes were prepared. The surgeon “randomly” draw envelope to decide which group the patient will go. This is akin to a revealed list, and it would have been easy to subvert the allocation.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

No placebo was used and the drug administration routes were different.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No information provided.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No loss to follow‐up

Selective reporting (reporting bias)

High risk

Publication reported on the outcomes listed in the methods section with the addition of adverse drug reactions, but we did not assess the trial protocol.

Other bias

Unclear risk

Baseline indicators (e.g. maternal age, Hb) were comparable between the 2 groups but it was unclear about other possible biases.

Study characteristics

Methods

RCT. Individual women. 10‐arm study.

Participants

Inclusion criteria

• Women in labour giving birth by CS.

• Labour > 2 hours; afebrile.

• N = 1580.

Exclusion criteria

• Antibiotics within previous 7 days.

Interventions

Interventions: 1st, 2nd and 3rd generation cephalosporins (C1, C2, C3).

1. Cefazolin (C1), 1 g x 3 doses (N = 142).

2. Cefazolin (C1), 1 g (N = 217).

3. Cefazolin (C1), 2 g (N = 161).

4. Ceftizoxime (C3), 1 g (N = 145).

5. Cefonicid (C2), 1 g (N = 147).

6. Cefotetan (C2), 1 g (N = 148).

7. Cefoxitin (C2), 1 g (N = 155).

8. Cefoxitin (C2), 2 g (N = 162).

• All single dose IV immediately after cord clamping

• Total N = 1277.

Comparator: broad spectrum penicillins (P2).

1. Ampicillin (P2), 2 g (N = 148).

2. Piperacillin (P2), 4 g (N = 155).

• All single dose IV immediately after cord clamping

• Total N = 303.

Subgroups

• Type of CS: non‐elective (subgroup 2)

• Generation of cephalosporins and type of penicillin: various

Comparisons: 4; 5 (subgroup 2); 6 (subgroup 1); 7 (subgroup 2); 8; 10 (subgroup 2)

Outcomes

Endometritis (defined as temperature > 37.8 ºC x 2, 4 hours apart, excluding 24 hours after delivery plus tachycardia, white blood count > 14, uterine tenderness).

Notes

Dates: 7 December 1989 to 1 July 1989.

Setting: Harris County Hospital, USA. Mixed ethnic population.

Funding sources: not reported.

Declarations of interest: not reported.

Additional information

• Study reported as 'ongoing' and so randomisation was not complete and 1 group had a many more women than the others. This is likely to contribute to high risk of bias.

• For this update, all C1 and C2 antibiotics were analysed together, in comparison with all P2. C3 was also compared separately with P2.

• Costs: this trial did not provide any information or comment on costs of treatment.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: “...randomised...according to a computer‐generated schedule.”

Allocation concealment (selection bias)

Unclear risk

No information provided.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Prospective, open, randomised study.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Prospective, open, randomised study but assessors may have been blinded.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

No loss to follow‐up as yet but study still on‐going at time of publication.

Selective reporting (reporting bias)

Unclear risk

Publication reported no maternal adverse reactions as well as the 1 pre‐specified outcome of endometritis, however, we did not assess trial protocol.

Other bias

Unclear risk

The difference in the numbers allocated to groups (ranging from 142 to 217) is reported as likely to be due to the study being on‐going and the randomisation schedule not complete or to some statistical issue, this is unclear. No information on funding source of study.

Study characteristics

Methods

RCT. Individual women. 2‐arm study.

Participants

Inclusion criteria

• Women undergoing CS.

• N = 263.

Exclusion criteria

• Women with drug allergies, antibiotics within 7 days, infection at time of enrolment, renal or hepatic dysfunction.

Interventions

Intervention: cephalosporin (C2).

• Cefoxitin.

• 2 g; after cord clamped; plus 2 additional doses (2 g) at 4 hours apart (route not described).

• N = 131.

Comparator: penicillin (P2).

• Piperacillin.

• 2 g; after cord clamped; plus 2 additional doses (2 g) at 4 hours apart (route not described).

• N = 132.

Subgroups

• Type of CS: unclear

• No primary outcomes reported so no data in subgroup analyses

Comparison: 4

Outcomes

Febrile morbidity; duration of hospitalisation; administration of systematic antibiotics postoperatively; wound healing; infection at operation site.

Notes

Dates of study: not reported.

Setting: UCLA Medical Center, USA.

Funding sources: not reported.

Declarations of interest: not reported.

Additional information

• This study also reports the 'cost of prophylactic failure in caesarean section', with respect to 4 different antibiotic regimens (ampicillin, cephalothin, cefoxitin, pipperacillin.). The cost of treatment was not specified, and many other factors were included in the calculation of total minimum cost of failure. Data reported relating to cost of failure for 100 women (ampicillin USD 140 833; cephalothin USD 91 848; cefoxitin USD 79 074; piperacillin USD 26 358) were not meta‐analysed but are summarised narratively in the 'effects of interventions' in this review. The authors concluded that, "When a drug such as piperacillin is used consistently for prophylaxis in caesarean section, significant cost savings can be realised”.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: “...randomly assigned...”.

Allocation concealment (selection bias)

Unclear risk

Quote: “...randomly assigned...”.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not described.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not described.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

There appeared to be no loss to follow‐up.

Selective reporting (reporting bias)

Unclear risk

Publication reported on the pre‐specified outcomes in the methods section, but we did not assess trial protocol.

Other bias

Unclear risk

No baseline imbalances on: age; weight; duration of surgery. However, other aspects of possible bias were unclear. No information on funding source of study.

Study characteristics

Methods

RCT. 2‐arm parallel study. Women randomised individually.

Participants

Inclusion criteria

• Women undergoing CS, elective and emergency.

• N = 280 but analysed 232

Exclusion criteria

Women who declined to participate in the study; severe immunosuppression of any cause; stage 3 and 4 HIV infection; prolonged rupture of membranes more than 12 hours; surgery longer than 3 hours; chorioamnionitis diagnosed pre‐operatively and obvious concurrent infection that requires therapeutic antibiotics.

Interventions

Intervention: 3^rd generation cephalosporin (C3) plus metronidazole (N).

• Single dose of ceftriaxone 1 g IV plus metronidazole 500 mg IV pre‐operatively and no further antibiotics postoperatively, except for treatment of infection.

• Total number randomised: N = 136 randomised, analysis on 112.

Comparator: penicillin (P1) + amoxicillin (P2) + metronidazole(N) + chloramphenicol (Am)

• Antibiotics for 1 week as follows: pre‐operatively benzyl penicillin 5 MU IV and chloramphenicol 1g IV Postoperatively within 24 hours of the operation: IV benzyl penicillin 2.5 MU 6‐hourly for 3 doses and IV chloramphenicol 500 mg 6‐hourly for 3 doses. From day 1 postoperatively, amoxicillin 500 mg three times daily for 7 days, metronidazole 400 mg three times daily for 7 days.

• Total number randomised: N = 144, analysis on 120.

Subgroups

• Type of CS: both elective and non‐elective

Comparisons: 20.3

Outcomes

Pyrexia; admission with puerperal sepsis; wound sepsis; death; duration of hospital stay; laparotomy for pelvic abscess.

Notes

Dates: 2 February 2012 to 30 May 2012.

Setting: Parirenyatwa and Harare (tertiary) hospitals, Zimbabwe.

Funding sources: not reported.

Declarations of interest: authors report 'No conflict of interest' and they alone are responsible for the content and writing of the paper.

Additional information

• Costs: the authors provide some data relating to costs which have reported narratively in our results. They state that quote: “[o]ur study showed that the two arms are equivalent in preventing infective morbidity. A vial of 1 g of ceftriaxone costs US $ 1.50 and a vial of 500 mg of metronidazole costs US $ 1.50. The cost of antibiotics for a patient on Arm 1 [C3 plus N] would be US $ 3; in contrast a patient in Arm 2 [P1 plus P2 plus N plus Am] would need US $ 10 for antibiotics and would receive at least 13 doses of antibiotics during her hospital stay.”

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No information provided.

Allocation concealment (selection bias)

High risk

Randomisation was by taking a ticket from a box. There was an A4 envelope of tickets at each of the 2 maternity units. Each envelope contained 75 tickets marked Arm 1 and 75 marked Arm 2. The ticket for Arm 1 was identical to that of Arm 2 in size, shape and material. This process could have been open to manipulation (e.g. returning a ticket and taking a different one).

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Not really possible to blind as 1 group had a single dose and the other had a weeks prescription.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No information so most likely assessors were not blinded either.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Women lost to follow‐up were 24 in each group, 21% for intervention and 20% for comparator.

Selective reporting (reporting bias)

Unclear risk

Publication reported on all the outcomes pre‐specified in the methods section, but we did not assess the trial protocol.

Other bias

Unclear risk

Baseline data showed no imbalance on: age; marital status; education; occupation; booking status; HIV. Otherwise unclear. Authors report 'No conflict of interest' and they alone are responsible for the content and writing of the paper. So appears to have no drug company involvement.

Study characteristics

Methods

RCT. Individual women. Multi‐centre. 2‐arm study.

Participants

Inclusion criteria

• Women who were in labour or had ruptured membranes and were about to have an indicated CS (repeat procedure, malpresentation, arrest of the active phase of labour).

• N = 84.

Exclusion criteria

• Women who had received antibiotics within 7 days of the CS or who had a diagnosis of intra‐amniotic infection.

Interventions

Intervention: cephalosporin (C1).

• Cefazolin.

• 1 g; IV; after cord clamped.

• N = unclear.

Comparator: penicillin (P2).

• Ampicillin.

• 2 g; IV; after cord clamped.

• N = unclear.

Subgroups

• Type of CS: non‐elective

• Generation of cephalosporin and type of penicillin:

Comparison: no data were analysed in this review

Outcomes

Genital tract cultures.

Notes

Dates of study: July 1st 1989 to December 31st 1990.

Setting: University Medical Centre, Lubbock & LBJ General Hospital, Houston, Texas, USA.

Funding sources: not reported.

Declarations of interest: not reported.

Additional information

• No data for this review as the number of women in each group is unclear

• Costs: this trial did not provide any information or comment on costs of treatment.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "...computer‐generated number..."

Allocation concealment (selection bias)

Unclear risk

No information provided.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Antibiotic administration was not blinded.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Antibiotic administration was not blinded but outcome assessor could have been blinded.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No exclusions of women were reported.

Selective reporting (reporting bias)

Unclear risk

Publication reported on pre‐ and postoperative genital tract cultures as pre‐specified, but we did not asses trial protocol.

Other bias

Unclear risk

Baseline characteristics across groups not reported and other aspects of possible bias unclear. No information about funding source of study.

Study characteristics

Methods

RCT. Individual women. 2‐arm study.

Participants

Inclusion criteria

• Quote: “Women who were scheduled to undergo hysterectomy for benign disease and elective cesarean delivery were enrolled in this trial”. However, only women underwent CS will be included in the review.

• N = 122 women having elective CS (60 having hysterectomy)

Exclusion criteria

• Quote: “We excluded patients who gave history of hypersensitivity to penicillin or cephalosporin; or signs of pre‐existing infections and those who had received antibiotic therapy within the last seven days prior to surgery.”

Interventions

Intervention: 1^st generation cephalosporin (C1).

• Cefazolin 2 g, administered IV.

• Medication was administered as a single dose.

• Immediately after clamping the umbilical cord.

• Total number randomised: N = 67.

Comparator: broad spectrum penicillin plus betalactamase inhibitor (P2+).

• Amoxycillin‐clavulanic acid 2.4 g (co‐amoxyclav) ‐ administered IV.

• Medication was administered as a single dose.

• Immediately after clamping the umbilical cord.

• Total number randomised: N = 55

Subgroups

• Type of CS: elective

• Generation of cephalosporin and type of penicillin: 1^st generation cephalosporin, C1 (subgroup 1)

Comparisons: 1; 2 (subgroup 1); 3 (subgroup 1)

Outcomes

Outcomes: fever and infection, endometritis.

Reported outcomes: postoperative hospital stay, wound infection, asymptomatic bacteriuria, total infection, postoperative urinary infection.

Notes

Dates of study: April 2004 to September 2005.

Setting: Kasturba Hospital, Manipal, Karnataka, India.

Funding sources: not reported.

Declarations of interest: not reported.

Additional information

• Costs: this trial did not provide any data on costs of treatment, although the authors commented that "“If drug costs only are considered, the use of AMX/CL [co‐amoxyclav] was more expensive.”

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No information provided.

Allocation concealment (selection bias)

Unclear risk

No information provided.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

No information provided.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No information provided.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No loss of follow‐up was reported.

Selective reporting (reporting bias)

Unclear risk

Publication seemed to report on the outcomes listed in the methods section, but we did not assess the trial protocol.

Other bias

Unclear risk

Baseline characteristics were similar for: age; BMI; associated disease; type of surgery (primary CS or not). Other possible biases were unclear. No information about funding source for study.

Study characteristics

Methods

RCT 2 parallel treatment groups, women randomised individually.

Participants

Inclusion criteria

• Women undergoing CS, elective or emergency.

• N = 760 randomised with 746 analysed.

Exclusion criteria

• Women known to be hypersensitive to any of the trial drugs; any antibiotic treatment 2 weeks prior to surgery; presence of chorioamnionitis; diabetes; malnutrition; obesity, > 85 kg; immuno‐compromised state; > 3 times per vaginal examination for intrapartum cases; prolonged preoperative hospitalisation and duration of labour > 6 hours.

Interventions

Intervention: 3^rd generation cephalosporin (C3).

• Cefotaxime 1 g single dose IV.

• Just after clamping the umbilical cord.

• Total number randomised: N = 380 but 372 analysed.

Comparator: broad spectrum penicillin plus betalactamase inhibitor (P2+)

• Amoxicillin–clavulanic acid combination 1.2 g single dose IV.

• Just after clamping the umbilical cord.

• Total number randomised: N = 380 but 374 analysed.

Subgroups

• Type of CS: mixed, elective and non‐elective (subgroup 3)

Comparisons: 11; 12 (subgroup 3)

Outcomes

Febrile morbidity, wound healing, endometritis, side effects of antibiotics.

Reported outcomes: quote: “fever, mild or moderate wound infection, endometritis, UTI or any serious infection, fever in the 5th postoperative period, adverse reactions, duration of hospital stay.”

Notes

Dates of study: not reported.

Setting: tertiary care teaching hospital in Kolkata, India.

Funding sources: not reported.

Declarations of interest: not reported.

Additional information

• 2020 update: we corrected data entry for would infection and urinary tract infection.

• Costs: this trial did not provide any information on costs of treatment, however the authors state that, quote: “[l]ess costly cefotaxime should be preferred compared to more costly amoxicillin–clavulanic acid combination for prophylaxis at cesarean section.”

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: “Randomization was done a priori by computer in blocks of 40.”

Allocation concealment (selection bias)

Unclear risk

Quote: "The randomization list remained in the custody of the principal investigator."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: “Being a double blind study, the nature or medication being received by individual trial subjects was not known to the subject or the project clinician”.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: “Being a double blind study, the nature or medication being received by individual trial subjects was not known to the subject or the project clinician”. It seemed most likely considering the outcomes assessed that assessors were blinded as well.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote: “A total of 760 patients were recruited for the study. Eight patients in the cefotaxime group and six patients in the amoxicillin–clavulanic acid group had to be excluded from final analysis for various reasons”.

Selective reporting (reporting bias)

Unclear risk

Reported outcomes were as pre‐specified in the methods section, but we did not assess the trial protocol.

Other bias

Unclear risk

Baseline characteristics were similar for: age; parity; gestation. Other possible biases were unclear.

No information about funding source of trial.

Study characteristics

Methods

RCT. Individual women. 2‐arm study.

Participants

Inclusion criteria

• Women having an emergency CS.

• N = 288 but data on 241.

Exclusion criteria

• Women with allergies to antibiotics; use of antibiotics within previous 24 hours; pathology that should be treated with antibiotics; chorioamnionitis; fever on admission; need of transfusion before or during the CS; ruptured membranes > 24 hours; body weight > 132 kg; elective CS.

Interventions

Intervention: aminoglycoside (A) + nitroimidazole (N)

• 160 mg gentamicin (A) and metronidazole (N) IV.

• IV before operation starts, so before cord clamping.

• No more antibiotics given postoperatively.

• N = 143 randomised but 116 in analysis.

Comparator: natural penicillins (P1) + nitroimidazole (N) + macrolide (M)

• Penicillin (P1) 4,000,000 UI IV for 6 hours and metronidazole (N) 500 mg IV 8 hours during 1^st 24 hours. Then erythromycin (M) 500 mg 6‐hourly orally and metronidazole (N) 500 mg 8‐hourly orally during 6 days.

• IV for 1^st 24 hours then orally for 6 days. No antibiotics were given in theatre, all were postoperative. 

• No other antibiotics given.

• N = 145 randomised but 125 in analysis.

Subgroups

• Type of CS: non‐elective

Comparisons: 20.1

Outcomes

Maternal endometritis; would infection; UTI; peritonitis; evisceration; postoperative infection; stillbirth, maternal length of hospital stay, costs

Notes

Dates: January to June 2000.

Setting: Maternity Unit, Hospital Central de Maputo, Mozambique. Quaternary level care.

Funding sources: not reported.

Declarations of interest: not reported.

Additional information

• 2020 update: we corrected data entry for maternal endometritis and maternal sepsis.

• Costs: the authors provide some data relating to costs, which we have reported narratively in our results. They state that, quote: “as to the costs of antibiotics, the single dose of prophylactic antibiotics cost US$0.78 [A plus N] whereas the standard postoperative scheme [P1 plus N plus M] followed at Maputo Central Hospital costs US$8.37, the former regime thus being less than one‐tenth as expensive as the latter. The costs of the caesarean section, intravenous fluids, nursing and hospital stay are almost the same in both groups.”

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: “...randomly constituted...”.

Allocation concealment (selection bias)

Unclear risk

Quote: “The anaesthetist administered the antibiotics according to the code written in the exercise book in the sequential order of admission to the theatre...the code was then written on the patient’s file so that the surgeon could prescribe...the doctor on duty was not aware of the group to which the patient was allocated. The principle investigator was not allowed either to select cases to be enrolled in the study or to follow the patients in the ward.”

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Non‐blinded comparative study. Although the doctor on duty was reported as not aware of the group to which the woman was allocated, the anaesthetist and surgeon were aware and overall the study was described as not blinded.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Non‐blinded comparative study. Quote: “Medical doctors allowing the patients to leave the maternity ward knew the regimen followed by the patients in order to not modify the antibiotics given…”.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

288 women randomised and analysis on 241 so 47/288 (16.3%) loss.

Selective reporting (reporting bias)

Unclear risk

We did not assess trial protocol but the publication reported more outcomes that their methods indicated e.g. maternal and infant deaths, stillbirths, septicaemia with or without sepsis, however these outcomes are not reported in this Cochrane Review.

Other bias

Unclear risk

Baseline characteristics similar for:age; parity; gestation. However, other possible biases are unclear. No information about funding source of study.

Study characteristics

Methods

RCT. Individual women. 2‐arm study.

Participants

Inclusion criteria

• Women having a CS.

• N = 119.

Exclusion criteria

• Women were excluded if they were allergic to penicillin or cephalosporin, or if they had been given a pre‐operative antibiotic treatment within 2 weeks prior to CS.

Interventions

Intervention: 3^rd generation cephalosporin (C3)

• Cefotaxime (C3)

• 1 g IV with 20 mL NaCl, single dose, after cord clamping. 

• N = 59.

Comparator: broad spectrum penicillin plus betalactamase inhibitor (P2+)

• Amoxicillin plus clavulanic acid (P2+)

• 1.2 g IV with 20 mL NaCl, single dose, after cord clamping.

• N = 60.

Subgroups

• Type of CS: unclear (subgroup 3)

Comparisons: 11; 12 (subgroup 3)

Outcomes

Endometritis (temperature > 37.5 ºC, uterine tenderness); UTI; wound infection.

Notes

Dates: 17 October 1987 to 24 February 1989.

Setting: Kantonspital Hospital, Winterthur, Switzerland.

Translation: from German.

Funding sources: not reported.

Declarations of interest: not reported.

Additional information

• Costs: this trial did not provide any information or comment on costs of treatment.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

The translation reports: "A midwife not involved in the study pulled the names from a randomised list and provided the medications in neutral syringes in the operating room." It is unclear if a 'randomised list', is the same as a 'random table' and until we are able to check this we are reporting this as unclear.

Allocation concealment (selection bias)

Unclear risk

A midwife who was not part of the study divided the women into 2 treatment groups, cefotaxime and amoxicillin/clavulanic acid, according to a randomised list.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Double‐blind trial.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Double‐blind trial.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No loss to follow‐up.

Selective reporting (reporting bias)

Unclear risk

We did not assess trial protocol and there is no information in the translation which helps us assess if there is selective reporting.

Other bias

Unclear risk

Baseline characteristics similar for age. However, other possible biases unclear. No information about funding source of study.

Study characteristics

Methods

RCT. Individual women. 2‐arm study.

Participants

Inclusion criteria

• Women who underwent emergency CS.

• N = 233.

Exclusion criteria

• No information provided.

Interventions

Intervention: 3^rd generation cephalosporin (C3).

• Ceftriaxone (C3)

• 1 g, IV, followed by 4 × 6‐hourly doses of a placebo (physiological saline).

• Timing of first dose not reported.

• N = 108.

Comparator: broad spectrum penicillin (P2).

• Ampicillin (P2)

• 1 g, IV, plus 4 × 6‐hourly doses of 500 mg of ampicillin.

• Timing of first dose not reported.

• N = 125.

Subgroups

• Type of CS: non‐elective

• No primary outcome data for subgroup analyses.

Comparisons: 8

Outcomes

Abdominal and/or wound sepsis; febrile morbidity; hospital stay; antibiotic and consumable costs.

Notes

Dates of study: not reported.

Setting: Ga‐Rankuwa Hospital, South Africa.

Conference abstract only.

Funding sources: not reported.

Declarations of interest: not reported.

Additional information

• Costs: the trial authors provided a brief comment on costs that we have reported narratively in our results: quote: "Ceftriaxone was associated with lower management costs. This being attributable to its once daily dosage and less hospital stay for those who received this antibiotic. The net saving in cost by using ceftriaxone instead of ampicillin was [ZAR]883.54 per patient."

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No information provided.

Allocation concealment (selection bias)

Unclear risk

No information provided.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Double‐blind study.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Double‐blind study although it is unclear whether assessors might have known allocation or not.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

None reported, but there is no information on the denominators in either group for us to be sure there was no loss of participants.

Selective reporting (reporting bias)

Unclear risk

Reported outcomes in the conference abstract were as pre‐specified in the methods section, but we did not assess trial protocol.

Other bias

Unclear risk

2 groups reported as similar in baseline characteristics on: age; gestation; type of incision; length of surgery, but no data provided. Other aspects of potential bias were unclear. No information about funding source of study.

Study characteristics

Methods

RCT. Individual women. Study in 2 parts.

Study 1: compared a penicillin vs placebo (so not included in this review).

Study 2: compared a cephalosporin vs a penicillin.

Participants

Inclusion criteria

• Women having CS.

• N = 396, 9 charts not available and 4 women did not meet inclusion criteria, leaving 383 for analysis.

Exclusion criteria

• Women who had antibiotics within 2 weeks of CS and those allergic to penicillin.

Interventions

Intervention: 2^nd generation cephalosporin (C2).

• Cefoxitin (C2)

• 2 g in 1.5 L, by intraoperative irrigation.

• N = 186.

Comparator: broad spectrum penicillin (P2).

• Ticarcillin (P2)

• 5 g in 1.2 L, by intraoperative irrigation.

• N = 197.

Subgroups

• Type of CS: both elective and non‐elective

Comparisons: antibiotics were administered by lavage, and therefore for the 2020 update this trial was analysed separately from IV trials, under comparison 21.1

Outcomes

Endometritis; wound infection (criteria not specified): UTI (criteria not specified): sepsis.

Notes

Dates of study: June 1985 to April 1987. Quote: “The first part of the study encompassed seven months (Part 1) and the second part, 15 months, ending in April 1987 (Part 2).”

Setting: Louisiana State University Hospital, USA.

Funding sources: not reported.

Declarations of interest: not reported.

Additional information

• Costs: this trial did not provide any information or comment on costs of treatment.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: “...random double‐blind fashion...”.

Allocation concealment (selection bias)

Unclear risk

Quote: “...random double‐blind fashion...”.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Double‐blind study.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Although a double‐blind study, it is unclear whether the outcome assessors might have not know allocation.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

396 women were reported to be included with 383 providing data, 186 in cephalosporin group and 197 in penicillin group (loss of 13/396 = 3.3%). Data were not reported for women with elective CS for UTI, but they were reported for non‐elective CS.

Selective reporting (reporting bias)

High risk

We did not assess trial protocol, but fewer outcomes were reported for elective CS (septicaemia and UTI missing) than for non‐elective CS.

Other bias

Unclear risk

Baseline characteristics were similar for age; gestation; gravidity; parity; length of labour. However, other potential biases were unclear. No information about funding source of study.

Study characteristics

Methods

RCT. Individual women. 3‐arm study.

Participants

Inclusion criteria

• All women undergoing emergency CS.

• Women in active labour with membrane rupture prior to surgery; rectal temperature < 37.8 ºC; no history of penicillin or cephalosporin allergy; no antibiotic therapy in previous 2 weeks.

• N = 195 but data on 188.

Exclusion criteria

• None specified.

Interventions

Intervention 1: 1^st generation cephalosporin (C1).

• Cefazolin (C1)

• 3g total; 1 g IV after cord clamped and 2 further doses at 6 and 12 hours post‐operation.

• N = 67.

Intervention 2: 3^rd generation cephalosporin (C3).

• Cefotaxime (C3)

• 3g total; 1 g IV after cord clamped and 2 further doses at 6 and 12 hours post‐operation.

• N = 55.

Comparator: broad spectrum penicillin (P2).

• Ampicillin (P2)

• 3g total; 1 g IV after cord clamped and 2 further doses at 6 and 12 hours post‐operation.

• N = 59.

• For the purposes of this review we have pooled the data for cefazolin and cefotaxime. Any differences between these 2 cephalosporins will be assessed in the review on 'Different regimens of cephalosporin antibiotic prophylaxis at caesarean section for reducing maternal morbidity'.

Subgroups

• Type of CS: non‐elective

• Generation of cephalosporin and type of penicillin: various

Comparisons: 4; 5 (subgroup 2); 6 (subgroup 1); 7 (subgroup 2); 8; 9 (subgroup 2); 10 (subgroup 2)

Outcomes

Endometritis (temperature > 38 ºC, foul lochia, uterine tenderness); UTI; wound infection; febrile morbidity (temp > 38 ºC x 2, 6 hours apart, excluding first 24 hours), antibiotic and hospitalisation costs

Notes

Dates: December 1979 to December 1981.

Setting: Women's Centre at the Health Sciences Winnipeg, Canada.

Funding sources: not reported.

Declarations of interest: not reported.

Additional information

• Costs: this trial reports 3 figures relating to costs per patient: antibiotics costs; hospitalisation costs (calculated based on mean duration of hospitalisation of all successes and failures); total costs (sum of first 2 figures). Total costs per woman were: ampicillin CAD 2011.85; cefazolin CAD 1870.75; cefotaxime CAD 1764.50. We have reported these data narratively in our results. The authors conclude that, quote: "when antibiotic and hospitalisation costs were combined, cefotaxime was the least expensive regimen.”

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: “...randomised...”.

Allocation concealment (selection bias)

Unclear risk

Quote: “..unlabelled but number‐coded, previously randomised vials...”. Also, unclear because sequence generation is unclear.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Double‐blind trial.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: “Only pharmacist was aware of the drug code.”

Incomplete outcome data (attrition bias)
All outcomes

Low risk

7/195 (3.6%) lost to follow‐up. Similar across groups.

Selective reporting (reporting bias)

Unclear risk

We did not assess trial protocol, but the study did not report the Apgar scores, meconium staining and sepsis in the infant as pre‐specified in the methods section, however these are not priority outcomes in this Cochrane Review.

Other bias

Unclear risk

Baseline characteristics similar for age and race. However, other possible biases were unclear. No information about funding source of study.

Study characteristics

Methods

RCT. Individual women. 2‐arm study.

Participants

Inclusion criteria

• Women undergoing emergency CS.

• N = 400 but 379 analysed.

Exclusion criteria

• No information provided.

Interventions

Intervention: 1^st generation cephalosporin (C1).

• Cefazolin.

• 1 g single dose (route not described) after clamping the umbilical cord.

• N = 191.

Comparator: broad spectrum penicillin plus betalactamase inhibitors (P2+)

• Amoxicillin plus clavulanic acid.

• 1.2 g single dose (route not described) after clamping the umbilical cord.

• N = 188.

Subgroups

• Type of CS: non‐elective (ii)

• No primary outcome data for subgroup analyses

Comparisons: 1

Outcomes

Febrile and infectious morbidity.

Notes

Dates of study: not reported.

Setting: Department of Obstetric and Gynecology, Khon Kaen University, Thailand.

Funding sources: not reported.

Declarations of interest: not reported.

Additional information

• Conference abstract only

• Costs: this trial did not provide any information or comment on costs of treatment.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No information provided.

Allocation concealment (selection bias)

Unclear risk

Although the published abstract provided no information, the registration of the study with the Oxford Database of Perinatal Trials reported allocation was "by sealed, numbered envelopes" but it is unclear if these had to be used in sequential order.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

‘Partially blinded’.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

‘Partially blinded’.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No loss to follow‐up reported.

Selective reporting (reporting bias)

Unclear risk

Trial registration form only asks for principle outcomes (febrile morbidity & infectious morbidity) both of which are reported in the Conference abstract, but we did not assess the trial protocol.

Other bias

Unclear risk

No baseline data provided and other possible biases unclear. No information about funding source of study.

Study characteristics

Methods

RCT. Individual women. 2‐arm study.

Participants

Inclusion criteria

• Women undergoing non‐elective CS.

• N = 48.

Exclusion criteria

• Allergy to penicillin or cephalosporin; impaired renal and/or liver function; fever (> 38 ºC and/or clinical signs of infection); antibiotic therapy 48 hours prior to the surgical procedure.

Interventions

Intervention: 0ther betalactam: carbapenem (Ca).

• Imipenem (Ca)

• 500 mg IV after cord clamped.

• N = 22.

Comparator: 3^rd generation cephalosporin (C3).

• Cefotamine (C3)

• 1 g IV after cord clamped and 3 additional doses every 12 hours.

• N = 26.

Subgroups

• Type of CS: non‐elective (subgroup 2)

Comparisons: 16

Outcomes

Infective complications after the CS (endometritis, infection of the wound, peritonitis, urinary infections, other causes, fever morbidity).

Notes

Dates: 1 January 1988 to 30 September 1988.

Setting: Umberto I Hospital, Frosinone, Italy.

Funding sources: not reported.

Declarations of interest: unclear. The original paper was not in English.

Additional information

• Translated from Italian.

• Costs: this trial did not provide any information or comment on costs of treatment.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Women reported to be divided randomly into 2 groups.

Allocation concealment (selection bias)

Unclear risk

No information.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

No information.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No information.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No loss to follow‐up.

Selective reporting (reporting bias)

Unclear risk

We did not assess trial protocol and were unable to assess if there was selective reporting from the translation.

Other bias

Unclear risk

No differences in baseline characteristics for: age, parity, length of PROM and number of vaginal examination between 2 groups. Other possible biases were unclear. No information about funding source of study.

Study characteristics

Methods

A prospective, randomised, open‐label, single‐site study,with 2 parallel arms. Women randomised individually.

Participants

Inclusion criteria

• Women undergoing CS for any indication at a gestation of 37 weeks 0 days or more.

• N = 132.

Exclusion criteria

• Preoperative clinical diagnosis of chorioamnionitis, a fever of 38° or higher at any point during admission, prior antibiotic use within 2 weeks, known HIV‐positive status, known allergy to penicillin or cephalosporin, and insulin‐dependent diabetes.

Interventions

Intervention: 1^st generation cephalosporin (C1).

• Cefazolin (C1) 1 g.

• Administered intravenously no more than 60 minutes prior to skin incision.

• Single dose.

• Postoperative antibiotics were administered only if there was a diagnosis of infection, and were not given routinely.

• Total number randomised: N = 66.

Comparator: (usual care): broad spectrum penicillin (P2)

• Ampicillin (P2) 2 g (usual care group).

• Administered intravenously no more than 60 minutes prior to skin incision.

• Single dose.

• Postoperative antibiotics were administered only if there was a diagnosis of infection, and were not given routinely.

• Total number randomised: N = 66.

Subgroups

• Type of CS: both elective and non‐elective

• Generation of cephalosporin and type of penicillin:

Comparisons: 1; 2 (subgroup 3); 3 (subgroup 1); 4 (subgroup 2)

Outcomes

Outcomes: the primary outcome variable was postoperative febrile morbidity. Secondary outcomes were infection‐related complications defined as endometritis, wound infection, UTI, fever with unexplained source, need for therapeutic antibiotics, and length of postoperative days in hospital (starting the day after surgery and including the day of discharge).

Reported outcomes: febrile morbidity, endometritis, wound infection, UTI, unexplained fever(febrile morbidity), required therapeutic antibiotics, length of postoperative stay, allergic reactions.

Notes

Dates: March 1 to May 31, 2012.

Setting: The Centre Hospitalier Universitaire de Kigali/University Teaching Hospital of Kigali (CHUK), which is located in Kigali, the capital of Rwanda, is 1 of 3 tertiary care referral hospitals in the Rwandan healthcare system and, compared with district hospitals, receives a disproportionate number of women needing CS.

Funding sources: not reported.

Declarations of interest: reported that authors have no conflict of interest.

Additional information

• Costs: this trial did not provide any information or comment on costs of treatment.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "The cards inside the envelopes were randomized by the principle investigator using a random integer generator."

Allocation concealment (selection bias)

Low risk

Quote: “The women were preoperatively randomized to one of two study groups via numerically ordered cards in sealed envelopes...The allocated envelopes were opened by clinicians only after the decision for cesarean delivery was made."

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Quote: “...open‐label...”.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

As an open‐label RCT the investigators were not blinded but the assessors could have been blinded.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote: "No women were lost to follow‐up”.

Selective reporting (reporting bias)

Unclear risk

Reported outcomes were as pre‐specified in the methods section, but we did not assess the trial protocol.

Other bias

Unclear risk

Not known. Reported that authors have no conflict of interest. Funding source of study not reported.

Study characteristics

Methods

A randomised prospective study with 2 parallel arms. Women randomised individually.

Participants

Inclusion criteria

• Women undergoing CS ‐ elective, non‐elective in labour and emergency.

• N = 70.

Exclusion criteria

• Women who had signs of obvious infection, suspected renal impairment by history or lab evidence, who has known drug hypersensitivity to azithromycin or cephalosporin, who were recently administered with antibiotics, diabetic and anaemic pregnant women.

Interventions

Intervention: macrolide (M).

• 500 mg of azithromycin (M)

• Single dose (route not described), half an hour prior to the surgery.

• Total number randomised: N = 35.

Comparator: 1^st generation cephalosporin (C1).

• 1 g of cefazolin (C1)

• Single dose (route not described), half an hour prior to the surgery.

• Total number randomised: N = 35.

Subgroups

• Type of CS: both elective and non‐elective

Comparisons: 17

Outcomes

Reported outcomes: postoperative fever, wound healing duration (healing within 10 days, healing within 20 days), pain for 6 days, pain for 7‐9 days, infection, PV discharge.

Notes

Study dates: September 2011 to February 2012. Follow‐up of the cases were finished in March 2012.

Setting: Department of Obstetrics & Gynaecology, SRM Medical Research Centre and Hospital in Kattankulathur, Kancheepuram District, India.

Funding sources: not reported.

Declarations of interest: not reported.

Additional information

• The authors do report infection (M = 3/35 vs C1 = 0/35) but do not specify where the infection is, therefore these results are not included in the analyses.

• Costs: this trial did not provide any information or comment on costs of treatment.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: “The pregnant women were randomly given either Azithromycin or cefazolinas prophylactic antibiotics” and "(Antibiotics) were given ... in a random order ...”.

Allocation concealment (selection bias)

Unclear risk

Quote: "The pregnant women were randomly given either Azithromycin or Cefazolinas prophylactic antibiotics".

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

No information on this.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No information on this.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No losses of follow‐up were reported.

Selective reporting (reporting bias)

Unclear risk

Pre‐specified outcomes were fever or infection without specifying the type of infections which were reported on, and we did not assess the trial protocol

Other bias

Unclear risk

Not known. No information about funding source of study.

Study characteristics

Methods

RCT. Individual women. 3‐arm study.

Participants

Inclusion criteria

• Women undergoing emergency CS.

• N = 145 in the cephalosporin vs penicillin comparison (though 222 in the whole study which included 'No antibiotic' group).

Exclusion criteria

• Known hypersensitivity to either antibiotic, the presence of infection or fever before the operation, women already on antibiotics for any reason and women with multiple pregnancies.

Interventions

Intervention 1: cephalosporin (C3)

• Cefoperazone (C3)

• 3 doses of 1 g at 12‐hourly intervals (route not described).

• First dose given at induction of anaesthesia and the total number of doses of antibiotics given was calculated to give coverage for the first 24 hours after surgery.

• N = 71, then 1 excluded.

Intervention 2: penicillin (P2)

• Ampicillin (P2)

• 4 doses of 500 mg at 6‐hourly intervals (route not described).

• First dose given at induction of anaesthesia and the total number of doses of antibiotics given was calculated to give coverage for the first 24 hours after surgery.

• N = 74.

Comparator: ‐ data not used in this review

• No antibiotics.

• No data included in this review.

• N = 77, then 1 excluded.

Subgroups

• Type of CS: non‐elective

Comparisons: this trial would have been reported under comparison 8, however due to inconsistencies in the published report, data were not included in the analysis.

Outcomes

Febrile morbidity; wound infection.

Notes

Dates: March to August 1991.

Setting: Ipoh General Hospital, Ipoh, Perak Darul Ridzuan, Malasyia.

Funding sources: not reported.

Declarations of interest: not reported.

Additional information

• Inconsistency in data. There was inconsistency in the number of women reported in each group between the table and the text. The study took place too long ago to obtain clarification from trial authors, therefore for this update (2020) we have removed data from this trial from the analysis.

• Costs: this trial did not provide any data on costs of treatment, although the authors stated, "[i]t is not easy to itemise and determine hospital costs accurately but from a limited assessment of our results, we were able to find quite definitive cost savings from prescribing prophylactic cefoperazone to cases of emergency caesarean section.”

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

A randomised trial.

Allocation concealment (selection bias)

Unclear risk

No information provided.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

No information provided.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No information provided.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

2 women excluded ‐ 1 from each group.

Selective reporting (reporting bias)

Unclear risk

Pre‐specified outcomes were 'wound infection' without being specific on the measures to be reported and wee did not assess the trial protocol.

Other bias

Unclear risk

Baseline characteristics similar for: age; race; parity; gestation. Other possible biases were unclear. No information about funding source of study.

Study characteristics

Methods

RCT. Individual women. 3‐arm study.

Participants

Inclusion criteria

• Women undergoing CS.

• Gravid women in labour or having had rupture of membranes for 6 hours.

• N = 300, but analysis on 292.

Exclusion criteria

• < 18 years of age, known allergy to penicillin or cephalosporin antibiotics, antibiotic therapy within 72 hours prior to hospital admission, history of group B streptococcal infection, prophylactic antibiotic therapy for underlying medical illness or enhancement of fetal lung maturity, or clinical evidence of chorioamnionitis at the time of CS.

Interventions

Intervention 1: 1^st generation cephalosporin (C1).

• Cefazolin.

• 1 g, IV, single dose, after cord clamping.

• N = 98.

Intervention 2: 2^nd generation cephalosporin (C2).

• Cefotetan.

• 1 g, IV, single dose, after cord clamping.

• N = 99.

Comparator: broad spectrum penicillin plus betalactamase inhibitor (P2+)

• Ampicillin + sulbactam.

• 1.5 g, IV, single dose, after cord clamping.

• N = 95.

Subgroups

• Type of CS: non‐elective (subgroup 2)

• Generation of cephalosporin: 1^st generation, C1 (subgroup 1); 2^nd generation, C2 (subgroup 2)

Comparisons: 1; 2 (subgroup 2); 3 (subgroups 1 and 2)

Outcomes

Endometritis.

Notes

Dates: July 1988 to November 1990.

Setting: New York Hospital, University‐based, USA.

Funding sources: not reported.

Declarations of interest: not reported.

Additional information

• 2020 update: we corrected the data entry on endometritis and maternal skin rash.

• Costs: this trial did not provide any information or comment on costs of treatment.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: “Prospective randomized trial”.

Allocation concealment (selection bias)

Unclear risk

No information provided.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

No information provided.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No information provided.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

8 out of 300 women (2.7%) were excluded from the analysis.

Selective reporting (reporting bias)

High risk

We did not assess the trial protocol, but additional outcomes were reported which were not pre‐specified, e.g. complications, hospital stay, side effects.

Other bias

Unclear risk

There was insufficient information to assess other possible biases. No information about funding source of study.

Study characteristics

Methods

RCT. Individual women. 2‐arm study.

Participants

Inclusion

• Women undergoing CS.

• N = 200.

Exclusion

• Hypersensitivity to drugs being used; any antibiotic treatment 2 weeks prior to surgery; chorioamnionitis.

Interventions

Intervention: antistaphylococcal penicillin (P3) plus aminoglycoside (A)

• Cloxacillin (P3) (1 g, 8‐hourly for 48 hours) followed by oral cloxacillin (500 mg, 8‐hourly for 72 hours. Also gentamycin (A) (80 mg IV/IM 12‐hourly for 5 days); all given postoperatively. 

• N = 100.

Comparator: 3rd generation cephalosporin (C3).

• Cefotoxime (C3)

• 1 g IV, single dose after clamping the umbilical cord.

• N = 100.

Subgroups

• Type of CS: unclear

Comparisons: 18.2

Outcomes

Postpartum infection; wound infection; fever; duration in hospital.

Notes

Dates of study: July 1995 to July 1997.

Setting: Naval Hospital INHS Asvini Colaba, Mumbai, India.

Funding sources: not reported.

Declarations of interest: not reported.

Further information:

• Costs: this trial reported on the costs of the drugs studied, stating that, "[c]ost effectiveness of two regimens was also studied. The cost of 1 g of cefotoxime was Rs. 100 while the cost drugs in gentamycin and cloxacillin regimens worked out to be Rs. 210. The additional costs of syringes in the study and control group was Rs. 6 and Rs. 120 respectively. [...] The cost of single dose of cefotoxime was one‐third (Rs. 106) the cost of the conventional 5 days gentamycin cloxacillin combination (Rs. 320), therefore, the former was found to be more cost effective." The total cost of drugs and syringes per women in each group is reported narratively in our results.

• This trial reported cephalosporin C3 as the intervention and the mixed regimen as the comparator. For the purpose of presenting multiple analyses of mixed regimens compared with cephalosporins in a coherent fashion, we have inverted the intervention and comparator in this review.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "...randomly assigned...".

Allocation concealment (selection bias)

Unclear risk

No information provided.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

No information provided.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No information provided.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No loss to follow‐up was reported.

Selective reporting (reporting bias)

Unclear risk

Pre‐specified outcomes only were reported but we did not assess the trial protocol.

Other bias

Unclear risk

Insufficient information to assess other possible biases. No information about funding source of study.