Can the use of azithromycin during labour reduce the incidence of infection among puerperae and newborns? A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis investigated whether the use of azithromycin during labour or caesarean section reduces the incidence of sepsis and infection among mothers and newborns. DATA SOURCES: We independently searched the PubMed, Web of Science, Cochrane Library and EMBASE databases for relevant studies published before February, 2024. METHODS: We included RCTs that evaluated the effect of prenatal oral or intravenous azithromycin or placebo on intrapartum or postpartum infection incidence. We included studies evaluating women who had vaginal births as well as caesarean sections. Studies reporting maternal and neonatal infections were included in the current analysis. Review Manager 5.4 was used to analyse 6 randomized clinical trials involving 44,448 mothers and 44,820 newborns. The risk of bias of each included study was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions.Primary outcomes included the incidence of maternal sepsis and all-cause mortality and neonatal sepsis and all-cause mortality; secondary outcomes included maternal (endometritis, wound and surgical site infections, chorioamnionitis, and urinary tract infections) and neonatal outcomes (infections of the eyes, ears and skin). A random-effects model was used to test for overall effects and heterogeneity. RESULTS: The pooled odds ratios (ORs) were as follows: 0.65 for maternal sepsis (95% CI, 0.55-0.77; I2, 0%; P < .00001); 0.62 for endometritis (95% CI, 0.52-0.74; I2, 2%; P < .00001); and 0.43 for maternal wound or surgical site infection (95% CI, 0.24-0.78; P < .005); however, there was great heterogeneity among the studies (I2, 75%). The pooled OR for pyelonephritis and urinary tract infections was 0.3 (95% CI, 0.17-0.52; I2, 0%; P < .0001), and that for neonatal skin infections was 0.48 (95% CI, 0.35-0.65; I2, 0%, P < .00001). There was no significant difference in maternal all-cause mortality or incidence of chorioamnionitis between the two groups. No significant differences were observed in the incidence of neonatal sepsis or suspected sepsis, all-cause mortality, or infections of the eyes or ears. CONCLUSION: In this meta-analysis, azithromycin use during labour reduced the incidence of maternal sepsis, endometritis, incisional infections and urinary tract infections but did not reduce the incidence of neonatal-associated infections, except for neonatal skin infections. These findings indicate that azithromycin may be potentially beneficial for maternal postpartum infections, but its effect on neonatal prognosis remains unclear. Azithromycin should be used antenatally only if the clinical indication is clear and the potential benefits outweigh the harms.

Association between interleukin-19 gene polymorphisms and maternal puerperal infection.

Any bacterial infection of the genital tract after childbirth is called maternal puerperal infection. This infection accounts for 13% of pregnancy-related deaths and is the fifth leading cause of maternal mortality. Endometritis (postpartum uterine infection) has been associated with preeclampsia and maternal lethal bleeding in recent decades. In some studies, the presence of meconium in the amniotic fluid has been implicated in the development of endometritis. The study aimed to evaluate the association between interleukin-19 gene polymorphisms and maternal puerperal infection. In this study, 300 pregnant women with a gestational age of at least 37 weeks were studied. Patients were divided into two groups of 150 controls and cases. In the case group, amniotic fluid was impregnated with meconium, and in the control group, it was clear fluid. Both groups underwent cesarean section, and all received prophylactic antibiotics before surgery. Patients were evaluated for purpura infection in the first 40 days after delivery. Five ml of venous blood was taken from each patient and transferred to a tube containing EDTA anticoagulant. Genomic DNA was isolated using a particular kit. Then, the polymerase chain reaction was performed by the ARMS method. Data were analyzed using the chi-square test and SPSS software version 19 in case and control groups. This study's results indicate no significant difference in the frequency of AG, GG, and AA genotypes at position rs2243191 and rs1028181 IL-19 gene polymorphism between patients with puerperal infection and the control group (P>0.05). Also, no significant difference was observed in the frequency of both G and A alleles in the mentioned situations between patients and the control group (P>0.05). Based on the results of this study, no significant relationship was observed between IL-19 gene polymorphism at rs2243191 and rs1028181 locus and puerperal infection.

Pre-Caesarean Section Vaginal Preparation with Chlorhexidine Solution in Preventing Puerperal Infectious Morbidities: A Randomized Controlled Trial.

BACKGROUND: Globally, peripartum or puerperal infections account for about one tenth of maternal mortality, most of which occur in low income countries. Therefore, vaginal preparation with an antiseptic prior to a caesarean delivery could be considered an additional measure to prevent subsequent infectious morbidities. OBJECTIVES: To evaluate vaginal preparation with 0.3% chlorhexidine solution in the prevention of endometritis, surgical site infection and post-operative fever following emergency caesarean section. METHODS: This prospective randomized controlled trial (RCT) was conducted among 240 participants planned for emergency caesarean sections (CS) at term in the University of Medical Sciences Teaching Hospital Complex, Ondo State, Nigeria. Participants were randomised into either group "A" (study) or "B" (control). The former had vaginal preparation with 0.3% chlorhexidine gluconate immediately after anaesthesia while the latter received normal saline. Participants were followed up post-operatively during which clinical features of puerperal infectious morbidities were observed for each during admission as well as 8th and 14th days after delivery. RESULTS: The rate and risk of endometritis were significantly lower in the study group compared to the control; 5.0% versus 13.3%, respectively (chi squared =5.004; p=0.042, RR = 0.38; 95% CI = 0.15-0.94; p = 0.042; RRR = 0.62). Post-operative fever and surgical site infection, were also lower in the study group compared to the controls, but the difference was not statistically significant. CONCLUSION: When compared to placebo, pre-caesarean section vaginal preparation with 0.3% chlorhexidine solution significantly reduced only the rate and risk of post-operative endometritis among infectious morbidities.

CONTEXTE: À l'échelle mondiale, infections péripartum ou puerpérales représentent environ un dixième de la mortalité maternelle, dont la plupart se produisent dans les pays à faible revenu. Par conséquent, la préparation vaginale avec un antiseptique avant un accouchement par césarienne pourrait être considéré comme un mesure supplémentaire pour prévenir les morbidités infectieuses subséquentes. OBJECTIFS: Évaluer la préparation vaginale avec 0.3%solution de chlorhexidine dans la prévention de l'endométrite, site chirurgical infection et fièvre postopératoire après une césarienne d'urgence section. MÉTHODES: Cet essai prospectif randomisé contrôlé (ECR)a été menée auprès de 240 participants prévus pour une urgence césariennes (CS) à terme à l'Université des sciences médicales Complexe hospitalier universitaire, État d'Ondo, Nigéria. Les participants étaient randomisé dans le groupe "A" (étude) ou "B" (témoin). Celui-là avait une préparation vaginale avec 0.3 % de gluconate de chlorhexidine immédiatement après l'anesthésie alors que ce dernier a reçu une solution saline normale. Les participants ont été suivis postopératoirement au cours desquels des caractéristiques de morbidité infectieuse puerpérale ont été observées pour chaquelors de l'admission ainsi que les 8ème et 14ème jours après la livraison. RÉSULTATS: Le taux et le risque d'endométrite étaient significativement plus faibles dans le groupe d'étude par rapport au groupe témoin; 5.0 % contre 13.3 %, respectivement (chi carré =5.004; p=0.042, RR = 0.38; 95% CI = 0.15­0.94; p = 0.042; RRR = 0.62). Fièvre postopératoire et infection du site chirurgical, étaient également plus faibles dans le groupe d'étude par rapport aux témoins, mais lela différence n'était pas statistiquement significative. CONCLUSION: Par rapport au placebo, pré-césarienne préparation vaginale avec une solution de chlorhexidine à 0.3% significativement réduit uniquement le taux et le risque d'endométrite postopératoire chez morbidités infectieuses. Mots-clés: Chlorhexidine, Préparation Vaginale, Infection Puerpéral emorbidité, Césarienne, Endométrite, Fièvre Postopératoire, Infection Du Site Chirurgical.

Preincision adjunctive prophylaxis for cesarean deliveries a systematic review and meta-analysis.

OBJECTIVE: This study aimed to systematically review the relative effectiveness of preincision cefazolin with or without adjunctive prophylaxis (macrolides or metronidazole) vs cefazolin alone in decreasing the incidence of postcesarean delivery surgical site infections. DATA SOURCES: We performed a systematic search on PubMed, Ovid EMBASE, Google Scholar, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials from October 25, 2020, to November 25, 2020, to identify studies comparing cefazolin with adjunctive macrolides or metronidazole with cefazolin alone. The reference lists were reviewed, and a manual search of articles published after the last database search was performed. STUDY ELIGIBILITY CRITERIA: Overall, 3 randomized controlled trials and 1 prospective observational study of reproductive-age women undergoing cesarean deliveries were included in the study. We excluded studies of women who were immunocompromised (eg, patients who were HIV positive) or women with a diagnosis of chorioamnionitis before cesarean delivery. All patients received first-line cefazolin (either cefazolin 1 g or 2 g). We compared preincision cefazolin alone with preincision cefazolin plus adjunctive therapy (500 mg, oral or intravenous formulations of azithromycin, metronidazole, or clarithromycin). METHODS: A total of 6 review authors independently assessed the risk of bias for each study, using the Cochrane Risk of Bias criteria. Synthesis and further appraisal were done using the Grading of Recommendations, Assessment, Development, and Evaluation levels and the American College of Obstetricians and Gynecologists appraisal guidelines. Disagreements were resolved by discussion. Treatment effects were evaluated using meta-analysis, and pooled relative risks and 95% confidence intervals were generated using random-effects models using the Review Manager 5 software (version 5.4.1). RESULTS: Overall, 3 randomized controlled trials and 1 prospective observational study representing 2613 women met the criteria for inclusion. Significant reductions in surgical site infections (relative risk, 0.46; 95% confidence interval, 0.34-0.63; 3 randomized controlled trials) and the duration of hospital stay (weighted mean difference, -1.46; 95% confidence interval, -2.21 to -0.71; 2 randomized controlled trials) were observed with preincision cefazolin and adjunctive prophylaxis compared with cefazolin alone. No significant difference was observed in maternal febrile morbidity (relative risk, 0.38; 95% confidence interval, 0.11-1.25; 2 randomized controlled trials). CONCLUSION: Our findings have provided evidence for the use of preincision adjunctive extended-spectrum prophylaxis with cefazolin over cefazolin alone. However, future investigations are required to establish the relative efficacies of different adjunctive antibiotic options.

Different classes of antibiotics given to women routinely for preventing infection at caesarean section.

BACKGROUND: Caesarean section increases the risk of postpartum infection for women and prophylactic antibiotics have been shown to reduce the incidence; however, there are adverse effects. It is important to identify the most effective class of antibiotics to use and those with the least adverse effects.  OBJECTIVES: To determine, from the best available evidence, the balance of benefits and harms between different classes of antibiotic given prophylactically to women undergoing caesarean section, considering their effectiveness in reducing infectious complications for women and adverse effects on both mother and infant. SEARCH METHODS: For this 2020 update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (2 December 2019), and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing different classes of prophylactic antibiotics given to women undergoing caesarean section.  RCTs published in abstract form were also included. We excluded trials that compared drugs with placebo or drugs within a specific class; these are assessed in other Cochrane Reviews. We excluded quasi-RCTs and cross-over trials. Cluster-RCTs were eligible for inclusion but none were identified. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 39 studies, with 33 providing data (8073 women). Thirty-two studies (7690 women) contributing data administered antibiotics systemically, while one study (383 women) used lavage and was analysed separately. We identified three main comparisons that addressed clinically important questions on antibiotics at caesarean section (all systemic administration), but we only found studies for one comparison, 'antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors'.   We found no studies for the following comparisons: 'antistaphylococcal cephalosporins (1st and 2nd generation) versus lincosamides' and 'antistaphylococcal cephalosporins (1st and 2nd generation) versus lincosamides plus aminoglycosides'. Twenty-seven studies (22 provided data) included comparisons of cephalosporins (only) versus penicillins (only). However for this update, we only pooled data relating to different sub-classes of penicillins and cephalosporins where they are known to have similar spectra of action against agents likely to cause infection at caesarean section. Eight trials, providing data on 1540 women, reported on our main comparison, 'antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors'. We found data on four other comparisons of cephalosporins (only) versus penicillins (only) using systemic administration: antistaphylococcal cephalosporins (1st and 2nd generation) versus non-antistaphylococcal penicillins (natural and broad spectrum) (9 studies, 3093 women); minimally antistaphylococcal cephalosporins (3rd generation) versus non-antistaphylococcal penicillins (natural and broad spectrum) (4 studies, 854 women); minimally antistaphylococcal cephalosporins (3rd generation) versus broad spectrum penicillins plus betalactamase inhibitors (2 studies, 865 women); and minimally antistaphylococcal cephalosporins (3rd generation) versus broad spectrum and antistaphylococcal penicillins (1 study, 200 women). For other comparisons of different classes of antibiotics, only a small number of trials provided data for each comparison, and in all but one case data were not pooled. For all comparisons, there was a lack of good quality data and important outcomes often included few women. Three of the studies that contributed data were undertaken with drug company funding, one was funded by the hospital, and for all other studies the funding source was not reported. Most of the studies were at unclear risk of selection bias, reporting bias and other biases, partly due to the inclusion of many older trials where trial reports did not provide sufficient methodological information. We undertook GRADE assessment on the only main comparison reported by the included studies, antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors, and the certainty ranged from low to very low, mostly due to concerns about risk of bias, wide confidence intervals (CI), and few events. In terms of the primary outcomes for our main comparison of 'antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors': only one small study reported sepsis, and there were too few events to identify clear differences between the drugs (risk ratio (RR) 2.37, 95% CI 0.10 to 56.41, 1 study, 75 women, very low-certainty evidence). There may be little or no difference between these antibiotics in preventing endometritis (RR 1.10; 95% CI 0.76 to 1.60, 7 studies, 1161 women; low-certainty evidence). None of the included studies reported on infant sepsis or infant oral thrush. For our secondary outcomes, we found there may be little or no difference between interventions for maternal fever (RR 1.07, 95% CI 0.65 to 1.75, 3 studies, 678 women; low-certainty evidence). We are uncertain of the effects on maternal: wound infection (RR 0.78, 95% CI 0.32 to 1.90, 4 studies, 543 women), urinary tract infection (average RR 0.64, 95% CI 0.11 to 3.73, 4 studies, 496 women), composite adverse effects (RR 0.96, 95% CI 0.09 to 10.50, 2 studies, 468 women), and skin rash (RR 1.08, 95% CI 0.28 to 4.1, 3 studies, 591 women) (all very low certainty evidence). Although maternal allergic reactions were reported by two studies, there were no events. There were no infant outcomes reported in the included studies. For the other comparisons, the results for most outcomes had wide CIs, few studies and few women included. None of the included trials reported on longer-term maternal outcomes, or on any infant outcomes. AUTHORS' CONCLUSIONS: Based on the best currently available evidence, 'antistaphylococcal cephalosporins' and 'broad spectrum penicillins plus betalactamase inhibitors' may have similar efficacy at caesarean section when considering immediate postoperative infection, although we did not have clear evidence for several important outcomes. Most trials administered antibiotics at or after cord clamping, or post-operatively, so results may have limited applicability to current practice which generally favours administration prior to skin incision. We have no data on any infant outcomes, nor on late infections (up to 30 days) in the mother; these are important gaps in the evidence that warrant further research. Antimicrobial resistance is very important but more appropriately investigated by other trial designs.

Gestational iron deficiency anemia is associated with preterm birth, fetal growth restriction, and postpartum infections.

OBJECTIVES: Gestational IDA has been linked to adverse maternal and neonatal outcomes, but the impact of iron supplementation on outcome measures remains unclear. Our objective was to assess the effects of gestational IDA on pregnancy outcomes and compare outcomes in pregnancies treated with either oral or intravenous iron supplementation. METHODS: We evaluated maternal and neonatal outcomes in 215 pregnancies complicated with gestational IDA (Hb<100 g/L) and delivered in our tertiary unit between January 2016 and October 2018. All pregnancies from the same period served as a reference group (n=11,545). 163 anemic mothers received oral iron supplementation, and 52 mothers received intravenous iron supplementation. RESULTS: Gestational IDA was associated with an increased risk of preterm birth (10.2% vs. 6.1%, p=0.009) and fetal growth restriction (FGR) (1.9% vs. 0.3%, p=0.006). The gestational IDA group that received intravenous iron supplementation had a greater increase in Hb levels compared to those who received oral medication (18.0 g/L vs. 10.0 g/L, p<0.001), but no statistically significant differences in maternal and neonatal outcomes were detected. CONCLUSIONS: Compared to the reference group, prematurity, FGR, postpartum infections, and extended hospital stays were more common among mothers with gestational IDA, causing an additional burden on the families and the healthcare system.

Postpartum endometritis after uterine cleaning versus no cleaning in cesarean sections: Randomized clinical trial.

AIM: The aim of the study was to compare the rates of postpartum endometritis due to uterine cleaning and no cleaning in patients delivered by elective cesarean section. METHODS: This was a randomized clinical trial conducted at the Obstetrics and Gynecology Department, Suez Canal University Hospital, Ismailia, from June 2019 to November 2019. We recruited patients undergoing cesarean delivery aged 18-45 years with singleton pregnancy, intact membranes, either first or repeated delivery, without labor pains. Patients were allocated into two groups, uterine cleaning (336 patients) and no cleaning (312 patients). The main outcome measure was the occurrence of postpartum endometritis. RESULTS: Both groups were matched in their demographic characters. Twelve patients (3.6%) developed endometritis in the cleaning group versus one patient (0.3%) in the other one. Estimated blood loss was 754.35 ± 247.13 and 730.36 ± 232.77 for the cleaning and no cleaning groups, respectively, with a P value of 0.201. Septic wound infection (21 patients, 6.3%) was predominant in the cleaning group. CONCLUSION: Uterine cleaning after delivery of the placenta during CS can be omitted as a surgical step during the operation. It was associated with increased rates of postpartum endometritis and blood loss.

Prophylactic antibiotics in the prevention of infection after operative vaginal delivery (ANODE): a multicentre randomised controlled trial.

BACKGROUND: Risk factors for maternal infection are clearly recognised, including caesarean section and operative vaginal birth. Antibiotic prophylaxis at caesarean section is widely recommended because there is clear systematic review evidence that it reduces incidence of maternal infection. Current WHO guidelines do not recommend routine antibiotic prophylaxis for women undergoing operative vaginal birth because of insufficient evidence of effectiveness. We aimed to investigate whether antibiotic prophylaxis prevented maternal infection after operative vaginal birth. METHODS: In a blinded, randomised controlled trial done at 27 UK obstetric units, women (aged ≥16 years) were allocated to receive a single dose of intravenous amoxicillin and clavulanic acid or placebo (saline) following operative vaginal birth at 36 weeks gestation or later. The primary outcome was confirmed or suspected maternal infection within 6 weeks of delivery defined by a new prescription of antibiotics for specific indications, confirmed systemic infection on culture, or endometritis. We did an intention-to-treat analysis. This trial is registered with ISRCTN, number 11166984, and is closed to accrual. FINDINGS: Between March 13, 2016, and June 13, 2018, 3427 women were randomly assigned to treatment: 1719 to amoxicillin and clavulanic acid, and 1708 to placebo. Seven women withdrew, leaving 1715 in the amoxicillin and clavulanic acid group and 1705 in the placebo groups. Primary outcome data were missing for 195 (6%) women. Significantly fewer women allocated to amoxicillin and clavulanic acid had a confirmed or suspected infection (180 [11%] of 1619) than women allocated to placebo (306 [19%] of 1606; risk ratio 0·58, 95% CI 0·49-0·69; p<0·0001). One woman in the placebo group reported a skin rash and two women in the amoxicillin and clavulanic acid reported other allergic reactions, one of which was reported as a serious adverse event. Two other serious adverse events were reported, neither was considered causally related to the treatment. INTERPRETATION: This trial shows benefit of a single dose of prophylactic antibiotic after operative vaginal birth and guidance from WHO and other national organisations should be changed to reflect this. FUNDING: NIHR Health Technology Assessment programme.

Management of clinical chorioamnionitis: an evidence-based approach.

This review aimed to examine the existing evidence about interventions proposed for the treatment of clinical chorioamnionitis, with the goal of developing an evidence-based contemporary approach for the management of this condition. Most trials that assessed the use of antibiotics in clinical chorioamnionitis included patients with a gestational age of ≥34 weeks and in labor. The first-line antimicrobial regimen for the treatment of clinical chorioamnionitis is ampicillin combined with gentamicin, which should be initiated during the intrapartum period. In the event of a cesarean delivery, patients should receive clindamycin at the time of umbilical cord clamping. The administration of additional antibiotic therapy does not appear to be necessary after vaginal or cesarean delivery. However, if postdelivery antibiotics are prescribed, there is support for the administration of an additional dose. Patients can receive antipyretic agents, mainly acetaminophen, even though there is no clear evidence of their benefits. Current evidence suggests that the administration of antenatal corticosteroids for fetal lung maturation and of magnesium sulfate for fetal neuroprotection to patients with clinical chorioamnionitis between 24 0/7 and 33 6/7 weeks of gestation, and possibly between 23 0/7 and 23 6/7 weeks of gestation, has an overall beneficial effect on the infant. However, delivery should not be delayed to complete the full course of corticosteroids and magnesium sulfate. Once the diagnosis of clinical chorioamnionitis has been established, delivery should be considered, regardless of the gestational age. Vaginal delivery is the safer option and cesarean delivery should be reserved for standard obstetrical indications. The time interval between the diagnosis of clinical chorioamnionitis and delivery is not related to most adverse maternal and neonatal outcomes. Patients may require a higher dose of oxytocin to achieve adequate uterine activity or greater uterine activity to effect a given change in cervical dilation. The benefit of using continuous electronic fetal heart rate monitoring in these patients is unclear. We identified the following promising interventions for the management of clinical chorioamnionitis: (1) an antibiotic regimen including ceftriaxone, clarithromycin, and metronidazole that provides coverage against the most commonly identified microorganisms in patients with clinical chorioamnionitis; (2) vaginal cleansing with antiseptic solutions before cesarean delivery with the aim of decreasing the risk of endometritis and, possibly, postoperative wound infection; and (3) antenatal administration of N-acetylcysteine, an antioxidant and antiinflammatory agent, to reduce neonatal morbidity and mortality. Well-powered randomized controlled trials are needed to assess these interventions in patients with clinical chorioamnionitis.

Antibiotic prophylaxis for operative vaginal delivery.

BACKGROUND: Vacuum and forceps assisted vaginal deliveries are reported to increase the incidence of postpartum infections and maternal readmission to hospital compared to spontaneous vaginal delivery. Prophylactic antibiotics may be prescribed to prevent these infections. However, the benefit of antibiotic prophylaxis for operative vaginal deliveries is still unclear. This is an update of a review last published in 2017. OBJECTIVES: To assess the effectiveness and safety of antibiotic prophylaxis in reducing infectious puerperal morbidities in women undergoing operative vaginal deliveries including vacuum or forceps delivery, or both. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (5 July 2019), and reference lists of retrieved studies. SELECTION CRITERIA: All randomised controlled trials comparing any prophylactic antibiotic regimens with placebo or no treatment in women undergoing vacuum or forceps deliveries were eligible. Participants were all pregnant women without evidence of infections or other indications for antibiotics of any gestational age. Interventions were any antibiotic prophylaxis (any dosage regimen, any route of administration or at any time during delivery or the puerperium). DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias. Two review authors extracted the data independently using prepared data extraction forms. Any discrepancies were resolved by discussion and a consensus reached through discussion with all review authors. We assessed methodological quality of the two included studies using the GRADE approach. MAIN RESULTS: Two studies, involving 3813 women undergoing either vacuum or forceps deliveries, were included. One study involving 393 women compared the antibiotic intravenous cefotetan after cord clamping compared with no treatment. The other study involving 3420 women compared a single dose of intravenous amoxicillin and clavulanic acid with placebo using 20 mL of intravenous sterile 0.9% saline. The evidence suggests that prophylactic antibiotics reduce superficial perineal wound infection (risk ratio (RR) 0.53, 95% confidence interval (CI) 0.40 to 0.69; women = 3420; 1 study; high-certainty evidence), deep perineal wound infection (RR 0.46, 95% CI 0.31 to 0.69; women = 3420; 1 study; high-certainty evidence) and probably reduce wound breakdown (RR 0.52, 95% CI 0.43 to 0.63; women = 2593; 1 study; moderate-certainty evidence). We are unclear about the effect on organ or space perineal wound infection (RR 0.11, 95% CI 0.01 to 2.05; women = 3420; 1 study) and endometritis (average RR 0.32, 95% CI 0.04 to 2.64; 15/1907 versus 30/1906; women = 3813; 2 studies) based on low-certainty evidence with wide CIs that include no effect. Prophylactic antibiotics probably lower serious infectious complications (RR 0.44, 95% CI 0.22 to 0.89; women = 3420; 1 study; high-certainty evidence). They also have an important effect on reduction of confirmed or suspected maternal infection. The two included studies did not report on fever or urinary tract infection. It is unclear, based on low-certainty evidence, whether prophylactic antibiotics have any impact on maternal adverse reactions (RR 2.00, 95% CI 0.18 to 22.05; women = 2593; 1 study) and maternal length of stay (MD 0.09 days, 95% CI -0.23 to 0.41; women = 393; 1 study) as the CIs were wide and included no effect. Prophylactic antibiotics slightly improve perineal pain and health consequences of perineal pain and probably reduce costs. Prophylactic antibiotics did not have an important effect on dyspareunia (difficult or painful sexual intercourse) or breastfeeding at six weeks. Antibiotic prophylaxis may slightly improve maternal hospital re-admission and maternal health-related quality of life. Neonatal adverse reactions were not reported in any included trials. AUTHORS' CONCLUSIONS: Prophylactic intravenous antibiotics are effective in reducing infectious puerperal morbidities in terms of superficial and deep perineal wound infection or serious infectious complications in women undergoing operative vaginal deliveries without clinical indications for antibiotic administration after delivery. Prophylactic antibiotics slightly improve perineal pain and health consequences of perineal pain, probably reduce the costs, and may slightly reduce the maternal hospital re-admission and health-related quality of life. However, the effect on reduction of endometritis, organ or space perineal wound infection, maternal adverse reactions and maternal length of stay is unclear due to low-certainty evidence. As the evidence was mainly derived from a single multi-centre study conducted in a high-income setting, future well-designed randomised trials in other settings, particularly in low- and middle-income settings, are required to confirm the effect of antibiotic prophylaxis for operative vaginal delivery.

Risk factors, changes in serum inflammatory factors, and clinical prevention and control measures for puerperal infection.

BACKGROUND: To investigate the risk factors and changes in serum inflammatory factors in puerperal infection, and propose clinical prevention measures. METHODS: A total of 240 subjects with suspected puerperal infection treated in our hospital from January 2017 to December 2017 were collected, among which puerperal infection was definitely diagnosed in 40 cases, and it was excluded in 40 cases. Levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) were compared between the two groups, and the change trends of IL-6 and hs-CRP were recorded. RESULTS: Levels of IL-6, hs-CRP, and TNF-α in puerperal infection group were higher than those in non-infection group (P < .05). Levels of IL-6 and hs-CRP at enrollment and 1-3 days after enrollment in infection group were higher than those in non-infection group (P < .05). The body mass index >25, placenta previa, placenta accreta, postpartum hemorrhage, premature rupture of membrane, gestational diabetes mellitus, and anemia during pregnancy were relevant and independent risk factors for puerperal infection. Puerperal infection occurred in uterine cavity, vagina, pelvic peritoneum, pelvic tissue, incision, urinary system, etc, and gram-negative (G+) bacteria were dominated in pathogens. CONCLUSION: The inflammatory response of patients with puerperal infection is significantly enhanced.

Adjunctive Azithromycin Prophylaxis for Cesarean Delivery.

BACKGROUND: The addition of azithromycin to standard regimens for antibiotic prophylaxis before cesarean delivery may further reduce the rate of postoperative infection. We evaluated the benefits and safety of azithromycin-based extended-spectrum prophylaxis in women undergoing nonelective cesarean section. METHODS: In this trial conducted at 14 centers in the United States, we studied 2013 women who had a singleton pregnancy with a gestation of 24 weeks or more and who were undergoing cesarean delivery during labor or after membrane rupture. We randomly assigned 1019 to receive 500 mg of intravenous azithromycin and 994 to receive placebo. All the women were also scheduled to receive standard antibiotic prophylaxis. The primary outcome was a composite of endometritis, wound infection, or other infection occurring within 6 weeks. RESULTS: The primary outcome occurred in 62 women (6.1%) who received azithromycin and in 119 (12.0%) who received placebo (relative risk, 0.51; 95% confidence interval [CI], 0.38 to 0.68; P<0.001). There were significant differences between the azithromycin group and the placebo group in rates of endometritis (3.8% vs. 6.1%, P=0.02), wound infection (2.4% vs. 6.6%, P<0.001), and serious maternal adverse events (1.5% vs. 2.9%, P=0.03). There was no significant between-group difference in a secondary neonatal composite outcome that included neonatal death and serious neonatal complications (14.3% vs. 13.6%, P=0.63). CONCLUSIONS: Among women undergoing nonelective cesarean delivery who were all receiving standard antibiotic prophylaxis, extended-spectrum prophylaxis with adjunctive azithromycin was more effective than placebo in reducing the risk of postoperative infection. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; C/SOAP ClinicalTrials.gov number, NCT01235546 .).

Rediscovering Ignaz Philipp Semmelweis (1818-1865).

Ignaz Philipp Semmelweis was a Hungarian obstetrician who discovered the cause of puerperal or childbed fever (CBF) in 1847 when he was a 29-year-old Chief Resident ("first assistant") in the first clinic of the lying-in division of the Vienna General Hospital. Childbed fever was then the leading cause of maternal mortality, and so ravaged lying-in hospitals that they often had to be closed. The maternal mortality rate (MMR) from CBF at the first clinic where Semmelweis worked, and where only medical students were taught, was 3 times greater than at the second clinic, where only midwives were taught, and Semmelweis was determined to find out why. Semmelweis concluded that none of the purported causes of CBF could explain the difference in MMR between the 2 clinics, as they all affected both clinics equally. The clue to the real cause came after Semmelweis' beloved professor, Jacob Kolletschka, died after a student accidentally pricked Kolletscka's finger during an autopsy. Semmelweis reviewed Kolletschka's autopsy report, and noted that the findings were identical to those in mothers dying of CBF. He then made 2 groundbreaking inferences: that Kolletschka must have died of the same disease as mothers dying of CBF, and that the cause of CBF must be the same as the cause of Kolletschka's death, because if the 2 diseases were the same, they must have the same cause. Semmelweis quickly realized why the MMR from CBF was higher on the first clinic: medical students, who assisted at autopsies, were transferring the causative agent from cadavers to the birth canal of mothers in labor with their hands, and he soon discovered that it could also be transferred from living persons with purulent infections. Bacteria had not yet been discovered to cause infections, and Semmelweis called the agent "decaying animal organic matter." He implemented chlorine hand disinfection to remove this organic matter from the hands of the attendants, as soap and water alone had been ineffective. Hand disinfection reduced the MMR from CBF 3- to 10-fold, yet most leading obstetricians rejected Semmelweis' doctrine because it conflicted with all extant theories of the cause of CBF. His work was also used in the fight raging over academic freedom in the University of Vienna Medical School, which turned Semmelweis chief against him, and forced Semmelweis to return to Budapest, where he was equally successful in reducing MMR from CBF. But Semmelweis never received the recognition that his groundbreaking work deserved, and died an ignominious death in 1865 at the age of 47 in an asylum, where he was beaten by his attendants and died of his injuries. Fifteen years later, his work was validated by the adoption of the germ theory, and honors were belatedly showered on Semmelweis from all over the world; but over the last 40 years, a myth has been created that has tarnished Semmelweis' reputation by blaming the rejection of his work on Semmelweis' character flaws. This myth is shown to be a genre of reality fiction that is inconsistent with historical facts.

Antibiotics during Intrauterine Balloon Tamponade Is Associated with a Reduction in Endometritis.

OBJECTIVE: To evaluate whether prophylactic antibiotics at the time of placement of an intrauterine balloon tamponade (IBT) is associated with a reduction in postpartum endometritis. STUDY DESIGN: Retrospective cohort study of patients who received an IBT from January 1, 2012, to December 12, 2016. Patients were included if the IBT remained in place at least 2 hours and excluded if chorioamnionitis was present. Patients who received prophylactic antibiotics at the time of IBT placement were compared with those who did not. RESULTS: A total of 149 subjects received an IBT; 36 were excluded due to early removal or chorioamnionitis. Of the remaining, 59 received prophylactic antibiotics and 54 did not. Baseline characteristics were similar between the groups except mode of delivery. The majority (65%) of those who did not receive prophylactic antibiotics had a cesarean delivery (p = 0.03). The overall incidence of endometritis was 15%. The incidence of endometritis was greater among those patients who did not receive prophylactic antibiotics compared with those who did (5 vs. 26%; p < 0.002; odds ratio [OR]: 6.53; 95% confidence interval [CI]: 1.76-24.25). This association remained after adjustment for mode of delivery and receiving group B Streptococcus antibiotics prior to delivery (adjusted OR: 5.9; 95% CI: 1.58-22.35). CONCLUSION: Prophylactic antibiotics were associated with a reduction in postpartum endometritis among patients receiving an IBT.

Chorioamnionitis and Infectious Complications after Vaginal Delivery.

OBJECTIVE: To estimate the incidence of and define risk factors for postpartum infectious complications after vaginal birth after cesarean (VBAC) complicated by chorioamnionitis. STUDY DESIGN: A secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Unit Cesarean Registry was performed. The primary outcome was a composite of postpartum infection: endometritis, sepsis, pelvic abscess, urinary tract infection, necrotizing fasciitis, and septic pelvic thrombophlebitis. Peripartum predictors were compared using parametric and nonparametric tests, as appropriate, and multivariate predictors assessed using logistic regression. RESULTS: A total of 559 subjects had chorioamnionitis in labor and a successful VBAC. Twenty-four (4.3%) subjects experienced the primary outcome, mainly due to endometritis (19/24). Significant factors included preterm delivery <32 weeks (odds ratio [OR]: 3.05, 95% confidence interval [CI]: 1.32-7.06) and body mass index (BMI) ≥40 (OR: 4.63, 95% CI: 1.25-17.14). Receipt of postpartum antibiotics was protective against postpartum infection (OR: 0.28, 95% CI: 0.12-0.65). In multivariate analysis, preterm delivery <32 weeks, BMI ≥40, and receipt of postpartum antibiotics remained associated with postpartum infection. CONCLUSION: Nearly 5% of women with chorioamnionitis had a postpartum infectious complication after vaginal delivery, with higher rates in those delivering at <32 weeks and with prepregnancy BMI ≥40. Receipt of postpartum antibiotics decreased the odds of postpartum infection markedly.

Azithromycin-based Extended-Spectrum Antibiotic Prophylaxis for Cesarean: Role of Placental Colonization with Genital Ureaplasmas and Mycoplasmas.

OBJECTIVE: To explore whether the effect of azithromycin (AZI) on postcesarean infections varied by the presence/absence of genital mycoplasmataceae placental colonization. STUDY DESIGN: This was a single-center substudy of multicenter double-blind C/SOAP (Cesarean Section Optimal Antibiotic Prophylaxis) trial of women randomized to AZI or placebo (+cefazolin) antibiotic prophylaxis at cesarean. Chorioamnion/placenta specimens were tested for genital mycoplasmataceae colonization by polymerase chain reaction. Primary outcome was a composite of endometritis, wound infection, or other infections up to 6 weeks postpartum. Analysis was intent-to-treat; logistic regression was used to evaluate interactions between treatment assignment (AZI/placebo) and the presence/absence of mycoplasmataceae and to quantify effects of AZI in analyses stratified by the presence/absence of these microorganisms. RESULTS: Specimens from 613 women (303 AZI and 310 placebo) were evaluated. Baseline characteristics were similar between groups, and approximately 1/3 (30.3%) had mycoplasmataceae placental/chorioamnion colonization. There was no evidence of effect modification (p interaction = 0.79) between treatment assignment and the presence/absence of organisms. Stratified analyses showed fewer events in the AZI group in the presence (odds ratio [OR]: 0.42; 95% confidence interval [CI]: 0.17-1.01) and absence (OR: 0.49; 95% CI: 0.24-1) of mycoplasmataceae. Results were similar with endometritis/wound infections and with ureaplasmas/mycoplasmas considered separately. CONCLUSION: The reduction in postcesarean infection with AZI does not vary based on the presence or absence of genital mycoplasmataceae placental colonization.

Incidence and Risk Factors for Hospital Readmission or Unexpected Visits in Women Undergoing Unscheduled Cesarean Delivery.

OBJECTIVE: Hospital readmissions are increasingly tracked and assessed for value-based compensation. Our objective was to determine the incidence and risk factors associated with post-cesarean delivery (CD) readmissions or unexpected visits, defined as unexpected office or emergency room visits. STUDY DESIGN: This is a secondary analysis of a multicenter randomized controlled trial of adjunctive azithromycin prophylaxis for CD performed in laboring patients with viable pregnancies. Patients were followed up to 6 weeks postpartum. Our primary outcome was a composite of hospital readmission or unexpected visit, defined as unscheduled clinic or emergency department visits. Data of hospital readmissions, unexpected visits, and their reasons were collected. Demographics, antepartum, intrapartum, and postpartum risk factors were evaluated in bivariate analyses and multivariable logistic regression modeling. RESULTS: A total of 1,019 women were randomized to azithromycin and 994 to placebo. The prevalence of readmission or unexpected visit was 10.2% (95% confidence interval [CI]: 8.9-11.6), with rates of 3.8% (95% CI: 3.0-4.7%) hospital readmissions, 6.9% (95% CI: 5.8-8.0%) emergency room visits, and 4.2% (95% CI: 3.4-5.2%) unexpected clinic visits. The most common causes were infectious disease and hypertensive disorder. Women with readmissions or unexpected visits were more likely to be obese and diabetic, as well as experience longer length of ruptured membranes, intrauterine pressure catheter placement, and postpartum fevers. On multivariable analysis, diabetes (adjusted odds ratio [aOR]: 1.6, 95% CI: 1.1-2.4), prolonged ruptured membranes (aOR: 1.9, 95% CI: 1.3-2.8), and postpartum fevers (aOR: 4.6, 95% CI: 3.0-7.0) were significantly positively associated with readmission or unscheduled visit, while azithromycin was a protective (aOR: 0.6, 95% CI: 0.5-0.9). CONCLUSION: Women who had postpartum fever were at especially high risk for readmission or unexpected visits. Diabetes, prolonged ruptured membranes, and postpartum fevers were significantly associated with the adverse outcome, and azithromycin was associated with lower rates of readmission and unexpected visits.

Prophylactic antibiotics before cord clamping in cesarean delivery: a systematic review.

INTRODUCTION: The number of clinical trials investigating the optimal timing of prophylactic antibiotics in cesarean section has increased rapidly over the last few years. We conducted a systematic review to inform up-to-date evidence-based guidelines to prevent postpartum infectious morbidity in the mother and rule out any safety issues related to antepartum antibiotic exposure in infants. MATERIAL AND METHODS: Four bibliographic databases were searched for published reports of trials. Ongoing or unpublished studies were searched in Clinicaltrials.gov and the World Health Organization registry platform. Randomized controlled trials comparing antibiotic prophylaxis before and after cord clamping in cesarean section were eligible. Maternal and neonatal outcomes were assessed, and certainty of evidence graded. RESULTS: In total, 18 randomized controlled trials met the inclusion criteria. Those women who received antibiotics preoperatively were 28% (relative risk 0.72, 95% confidence interval 0.56-0.92, nine studies, 4342 women, high quality of evidence) less likely to show infectious morbidity as compared with those who received antibiotics after cord clamping. The risk of endomyometritis and/or endometritis was reduced by 43% (relative risk 0.57, 95% confidence interval 0.40-0.82, 13 studies, 6250 women, high quality of evidence) and the risk of wound infection by 38% (relative risk 0.62, 95% confidence interval 0.47-0.81, 14 studies, 6450 women, high quality of evidence) in those who received antibiotics preoperatively as compared to those who received antibiotics after cord clamping. For other maternal infections no significant differences were identified. The risk for neonatal outcomes, such as deaths attributed to infection, sepsis, neonatal antibiotic treatment, intensive care unit admission or antibiotic-related adverse events, was not found to be different, either clinically or statistically, when antibiotics were given before or after cord clamping (moderate to low quality of evidence). CONCLUSIONS: The evidence in favor of prophylactic antibiotic administration before, in comparison with after, cord clamping for major maternal infections was of high quality, meaning that further research would be unlikely to change the confidence in these findings. However, we recommend additional research reflecting the precision of the effect estimates for neonatal outcomes.

[Recollection of the great predecessor by a late successor leader]. / Semmelweis Ignác kései tanszékvezetoi utódjának megemlékezése.

Between 1990 and 2007, being the eighth successor leader following Ignác Semmelweis at the university department of obstetrics in Baross Street, what interested me mainly were the following: the lucky coincidences needed for the great discovery, the doctor's hopeless struggles, the circumstances of his death, his five burials and fourfold exhumations, the Hungarianization of his name and the deliberate or unintentional mistakes related to him. In the recollection, my impressions and experiences related to the great predecessor will be reviewed. Orv Hetil. 2018; 159(26): 1071-1078.

[Semmelweis - a contemplating human. Scientific historical lessons]. / Semmelweis ­ egy gondolkodó ember. Tudománytörténeti tanulságok.

In this article we examine why Semmelweis's seemingly simple, logical and practical discovery was categorically dismissed by the majority of his contemporaries, and why even many years after his death it was accepted with such reservation. We invoke wherever possible Semmelweis's own words citing from the series of articles appearing in the 'Orvosi Hetilap' [Hungarian Medical Weekly Journal] published in 1858 in Hungary, and also from the German language summary of the Journal published in 1860. We came to the conclusion that although Semmelweis did everything in his power to show the causal relationship between the development of puerperal fever (childbed fever) and some infectious substance on the hands of examining doctors and medical students, this was not convincing enough. The predominant theory at the time held that infection was caused by miasma transmitted in the air and therefore stubbornly precluded any notion of infectious matter physically transmitted on unclean hands. We also concluded that the causal sequence observed by Semmelweis was missing an essential empirical element: visual proof of the infectious agent he correctly postulated as physically transmitted. Visually demonstrating the presence of the infectious agent by means of a microscope would have made his case. This finally did occur but only two years after Semmelweis's death. Had the renowned Hungarian obstetrician realized the significance of taking advantage of the opportunity afforded by Dávid Gruby who was conducting experiments in the same town, a more convincing argument could have been made for his theory. In the 1840s and 1850s, Dávid Gruby was experimenting with various microscopic techniques and their application with success in Vienna before continuing his work in France. Gruby's work, especially that of microscopic observations of tissues, received international acceptance. Therefore, the involvement of Gruby and his work with microscopes to support Semmelweis's observations would most probably have forestalled much of the criticism and rejection his theory was initially awarded (among which perhaps Virchow's rejection proved the most damaging). Had Semmelweis utilized microscopic techniques, he would have been celebrated among the first to discover bacterial pathogens, contributing to the development of the currently predominant germ theory. Failure to utilize the microscope was the root cause leading to the tragedy of Semmelweis's rejection by the medical establishment of the time. Despite the increasing numbers of scientists utilizing the microscope at the University of Pest, offered to corroborate his daims with microscopic observations. Efforts have been made have since been to rehabilitate him as the key figure who not only discovered the method of transmission of infectious disease, but also implemented measures of prevention. Elevating him among the ranks of the ten greatest doctors who ever lived is certainly recognition due, but sadly denied to him in his lifetime. Orv Hetil. 2018; 159(26): 1055-1064.