Background
Asymptomatic bacteriuria is a bacterial infection of the urine without any of the typical symptoms that are associated with a urinary infection, and occurs in 2% to 15% of pregnancies. If ...left untreated, up to 30% of mothers will develop acute pyelonephritis. Asymptomatic bacteriuria has been associated with low birthweight and preterm birth. This is an update of a review last published in 2015.
Objectives
To assess the effect of antibiotic treatment for asymptomatic bacteriuria on the development of pyelonephritis and the risk of low birthweight and preterm birth.
Search methods
For this update, we searched the Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) on 4 November 2018, and reference lists of retrieved studies.
Selection criteria
Randomised controlled trials (RCT) comparing antibiotic treatment with placebo or no treatment in pregnant women with asymptomatic bacteriuria found on antenatal screening. Trials using a cluster‐RCT design and quasi‐RCTs were eligible for inclusion, as were trials published in or letter form, but cross‐over studies were not.
Data collection and analysis
Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked for accuracy. We assessed the quality of the evidence using the GRADE approach.
Main results
We included 15 studies, involving over 2000 women. Antibiotic treatment compared with placebo or no treatment may reduce the incidence of pyelonephritis (average risk ratio (RR) 0.24, 95% confidence interval (CI) 0.13 to 0.41; 12 studies, 2017 women; low‐certainty evidence). Antibiotic treatment may be associated with a reduction in the incidence of preterm birth (RR 0.34, 95% CI 0.13 to 0.88; 3 studies, 327 women; low‐certainty evidence), and low birthweight babies (average RR 0.64, 95% CI 0.45 to 0.93; 6 studies, 1437 babies; low‐certainty evidence). There may be a reduction in persistent bacteriuria at the time of delivery (average RR 0.30, 95% CI 0.18 to 0.53; 4 studies; 596 women), but the results were inconclusive for serious adverse neonatal outcomes (average RR 0.64, 95% CI 0.23 to 1.79, 3 studies; 549 babies). There were very limited data on which to estimate the effect of antibiotics on other infant outcomes, and maternal adverse effects were rarely described.
Overall, we judged only one trial at low risk of bias across all domains; the other 14 studies were assessed as high or unclear risk of bias. Many studies lacked an adequate description of methods, and we could only judge the risk of bias as unclear, but in most studies, we assessed at least one domain at high risk of bias. We assessed the quality of the evidence for the three primary outcomes with GRADE software, and found low‐certainty evidence for pyelonephritis, preterm birth, and birthweight less than 2500 g.
Authors' conclusions
Antibiotic treatment may be effective in reducing the risk of pyelonephritis in pregnancy, but our confidence in the effect estimate is limited given the low certainty of the evidence. There may be a reduction in preterm birth and low birthweight with antibiotic treatment, consistent with theories about the role of infection in adverse pregnancy outcomes, but again, the confidence in the effect is limited given the low certainty of the evidence.
Research implications identified in this review include the need for an up‐to‐date cost‐effectiveness evaluation of diagnostic algorithms, and more evidence to learn whether there is a low‐risk group of women who are unlikely to benefit from treatment of asymptomatic bacteriuria.
Background
The single most important risk factor for postpartum maternal infection is cesarean section. Although guidelines endorse the use of prophylactic antibiotics for women undergoing cesarean ...section, there is not uniform implementation of this recommendation. This is an update of a Cochrane review first published in 1995 and last updated in 2010.
Objectives
To assess the effects of prophylactic antibiotics compared with no prophylactic antibiotics on infectious complications in women undergoing cesarean section.
Search methods
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2014) and reference lists of retrieved papers.
Selection criteria
Randomized controlled trials (RCTs) and quasi‐RCTs comparing the effects of prophylactic antibiotics versus no treatment in women undergoing cesarean section.
Data collection and analysis
Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. The clinically important primary outcomes were wound infection, endometritis, serious maternal infectious complications and adverse effects on the infant. We presented dichotomous data as risk ratios (RR), with 95% confidence intervals (CIs) and combined trials in meta‐analyses. We assessed the quality of evidence using the GRADE approach.
Main results
We identified 95 studies enrolling over 15,000 women. Compared with placebo or no treatment, the use of prophylactic antibiotics in women undergoing cesarean section reduced the incidence of wound infection (RR 0.40, 95% CI 0.35 to 0.46, 82 studies, 14,407 women), endometritis (RR 0.38, 95% CI 0.34 to 0.42, 83 studies, 13,548 women) and maternal serious infectious complications (RR 0.31, 95% CI 0.20 to 0.49, 32 studies, 6159 women). When only studies that included women undergoing an elective cesarean section were analyzed, there was also a reduction in the incidence of wound infections (RR 0.62, 95% CI 0.47 to 0.82, 17 studies, 3537 women) and endometritis (RR 0.38, 95% CI 0.24 to 0.61, 15 studies, 2502 women) with prophylactic antibiotics. Similar estimates of effect were seen whether the antibiotics were administered before the cord was clamped or after. The effect of different antibiotic regimens was studied and similar reductions in the incidence of infections were seen for most of the antibiotics and combinations.
There were no data on which to estimate the effect of maternal administration of antibiotics on infant outcomes. No studies systematically collected and reported on adverse infant outcomes nor the effect of antibiotics on the developing infant immune system. No studies reported on the incidence of oral candidiasis (thrush) in babies. Maternal adverse effects were also rarely described.
We judged the evidence for antibiotic treatment compared with no treatment to be of moderate quality; most studies lacked an adequate description of methods and were assessed as being at unclear risk of bias.
Authors' conclusions
The conclusions of this review support the recommendation that prophylactic antibiotics should be routinely administered to all women undergoing cesarean section to prevent infection. Compared with placebo or no treatment, the use of prophylactic antibiotics in women undergoing cesarean section reduced the incidence of wound infection, endometritis and serious infectious complications by 60% to 70%. There were few data on adverse effects and no information on the effect of antibiotics on the baby, making the assessment of overall benefits and harms difficult. Prophylactic antibiotics given to all women undergoing elective or non‐elective cesarean section is beneficial for women but there is uncertainty about the consequences for the baby.
Asymptomatic bacteriuria occurs in 2% to 10% of pregnancies and, if not treated, up to 30% of mothers will develop acute pyelonephritis. Asymptomatic bacteriuria has been associated with low ...birthweight and preterm birth.
To assess the effect of antibiotic treatment for asymptomatic bacteriuria on the development of pyelonephritis and the risk of low birthweight and preterm birth.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (19 March 2015) and reference lists of retrieved studies.
Randomized trials comparing antibiotic treatment with placebo or no treatment in pregnant women with asymptomatic bacteriuria found on antenatal screening.
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.
Fourteen studies, involving almost 2000 women, were included. Antibiotic treatment compared with placebo or no treatment reduced the incidence of pyelonephritis (average risk ratio (RR) 0.23, 95% confidence interval (CI) 0.13 to 0.41; 11 studies, 1932 women; very low quality evidence). Antibiotic treatment was also associated with a reduction in the incidence of low birthweight babies (average RR 0.64, 95% CI 0.45 to 0.93; six studies, 1437 babies; low quality evidence) and preterm birth (RR 0.27, 95% CI 0.11 to 0.62; two studies, 242 women; low quality evidence). A reduction in persistent bacteriuria at the time of delivery was seen (average RR 0.30, 95% CI 0.18 to 0.53; four studies; 596 women). There were very limited data on which to estimate the effect of antibiotics on other infant outcomes and maternal adverse effects were rarely described.Overall, all 14 studies were assessed as being at high or unclear risk of bias. While many studies lacked an adequate description of methods and the risk of bias could only be assessed as unclear, in almost all studies there was at least one domain where the risk of bias was judged as high. The three primary outcomes were assessed with GRADE software and given a quality rating. Evidence for pyelonephritis, preterm birth and birthweight less than 2500 g was assessed as of low or very low quality.
While antibiotic treatment is effective in reducing the risk of pyelonephritis in pregnancy, the estimate of the effect is very uncertain because of the very low quality of the evidence. The reduction in low birthweight and preterm birth with antibiotic treatment is consistent with theories about the role of infection in adverse pregnancy outcomes, but this association should be interpreted with caution given the very poor quality of the included studies.
The emerging SARS-CoV-2 variants of concern (VOCs) threaten the effectiveness of current COVID-19 vaccines administered intramuscularly and designed to only target the spike protein. There is a ...pressing need to develop next-generation vaccine strategies for broader and long-lasting protection. Using adenoviral vectors (Ad) of human and chimpanzee origin, we evaluated Ad-vectored trivalent COVID-19 vaccines expressing spike-1, nucleocapsid, and RdRp antigens in murine models. We show that single-dose intranasal immunization, particularly with chimpanzee Ad-vectored vaccine, is superior to intramuscular immunization in induction of the tripartite protective immunity consisting of local and systemic antibody responses, mucosal tissue-resident memory T cells and mucosal trained innate immunity. We further show that intranasal immunization provides protection against both the ancestral SARS-CoV-2 and two VOC, B.1.1.7 and B.1.351. Our findings indicate that respiratory mucosal delivery of Ad-vectored multivalent vaccine represents an effective next-generation COVID-19 vaccine strategy to induce all-around mucosal immunity against current and future VOC.
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•Two trivalent adenoviral-vectored COVID-19 vaccines were developed and evaluated•Intranasal, but not intramuscular, immunization induces tripartite mucosal immunity•Intranasal immunization protects against ancestral and variant strains of SARS-CoV-2•Optimal protection requires B and T cell immunity and trained innate immunity
Respiratory mucosal immunization with a next-generation adenoviral-vectored trivalent COVID-19 vaccine expressing spike, nucleocapsid, and RdRp antigens, induces all-around protective mucosal immunity against SARS-CoV-2 via induction of systemic and local antibodies, lung-tissue-resident memory T cells, and trained alveolar macrophages.
The single most important risk factor for postpartum maternal infection is cesarean section. Routine prophylaxis with antibiotics may reduce this risk and should be assessed in terms of benefits and ...harms.
To assess the effects of prophylactic antibiotics compared with no prophylactic antibiotics on infectious complications in women undergoing cesarean section.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (May 2009).
Randomized controlled trials (RCTs) and quasi-RCTs comparing the effects of prophylactic antibiotics versus no treatment in women undergoing cesarean section.
Two authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction.
We identified 86 studies involving over 13,000 women. Prophylactic antibiotics in women undergoing cesarean section substantially reduced the incidence of febrile morbidity (average risk ratio (RR) 0.45; 95% confidence interval (CI) 0.39 to 0.51, 50 studies, 8141 women), wound infection (average RR 0.39; 95% CI 0.32 to 0.48, 77 studies, 11,961 women), endometritis (RR 0.38; 95% CI 0.34 to 0.42, 79 studies, 12,142 women) and serious maternal infectious complications (RR 0.31; 95% CI 0.19 to 0.48, 31 studies, 5047 women). No conclusions can be made about other maternal adverse effects from these studies (RR 2.43; 95% CI 1.00 to 5.90, 13 studies, 2131 women). None of the 86 studies reported infant adverse outcomes and in particular there was no assessment of infant oral thrush. There was no systematic collection of data on bacterial drug resistance. The findings were similar whether the cesarean section was elective or non elective, and whether the antibiotic was given before or after umbilical cord clamping. Overall, the methodological quality of the trials was unclear and in only a few studies was it obvious that potential other sources of bias had been adequately addressed.
Endometritis was reduced by two thirds to three quarters and a decrease in wound infection was also identified. However, there was incomplete information collected about potential adverse effects, including the effect of antibiotics on the baby, making the assessment of overall benefits and harms complicated. Prophylactic antibiotics given to all women undergoing elective or non-elective cesarean section is clearly beneficial for women but there is uncertainty about the consequences for the baby.
Prophylactic antibiotics for cesarean section have been shown to reduce the incidence of maternal postoperative infectious morbidity. Many different antibiotic regimens have been reported to be ...effective.
The objective of this review was to determine which antibiotic regimen is most effective in reducing the incidence of infectious morbidity in women undergoing cesarean section.
We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register. The date of the most recent search was October 1998.
Randomized trials that included women undergoing cesarean section were included. Trials were required to compare at least two different antibiotic regimens. Trials that compared placebo with a single antibiotic regimen were not included as these are studies which have been analyzed in another Cochrane review.
Data were extracted from each publication independently by the reviewers. Reviewers were not blinded to the authors or sources of the articles. The primary outcome variable was endometritis but data on other infectious complications were collected where provided.
Fifty-one trials published between 1979 and 1994 were included in the review and four were excluded from the review. The following results refer to reductions in the incidence of endometritis. Both ampicillin and first generation cephalosporins have similar efficacy with an odds ratio (OR) of 1.27 (95% confidence interval (CI): 0.84-1.93). In comparing ampicillin with second or third generation cephalosporins the odds ratio was 0.83 (95% CI 0.54-1.26) and in comparing a first generation cephalosporin with a second or third generation agent the odds ratio was 1.21 (95% CI 0.97-1.51). A multiple dose regimen for prophylaxis appears to offer no added benefit over a single dose regimen; OR 0.92 (95% CI 0.70-1.23). Systemic and lavage routes of administration appear to have no difference in effect; OR 1.19 (95% CI 0.81-1.73). There was no significant heterogeneity between the trials contained in the various sub-group analyses, although confidence intervals were sometimes wide.
Both ampicillin and first generation cephalosporins have similar efficacy in reducing postoperative endometritis. There does not appear to be added benefit in utilizing a more broad spectrum agent or a multiple dose regimen. There is a need for an appropriately designed randomized trial to test the optimal timing of administration (immediately after the cord is clamped versus pre-operative).
Improvements in life expectancy and quality of life for HIV-positive women coupled with reduced vertical transmission will likely lead numerous HIV-positive women to consider becoming pregnant. In ...order to clarify the demand, and aid with appropriate health services planning for this population, our study aims to assess the fertility desires and intentions of HIV-positive women of reproductive age living in Ontario, Canada.
A cross-sectional study with recruitment stratified to match the geographic distribution of HIV-positive women of reproductive age (18-52) living in Ontario was carried out. Women were recruited from 38 sites between October 2007 and April 2009 and invited to complete a 189-item self-administered survey entitled "The HIV Pregnancy Planning Questionnaire" designed to assess fertility desires, intentions and actions. Logistic regression models were fit to calculate unadjusted and adjusted odds ratios of significant predictors of fertility intentions. The median age of the 490 participating HIV-positive women was 38 (IQR, 32-43) and 61%, 52%, 47% and 74% were born outside of Canada, living in Toronto, of African ethnicity and currently on antiretroviral therapy, respectively. Of total respondents, 69% (95% CI, 64%-73%) desired to give birth and 57% (95% CI, 53%-62%) intended to give birth in the future. In the multivariable model, the significant predictors of fertility intentions were: younger age (age<40) (p<0.0001), African ethnicity (p<0.0001), living in Toronto (p = 0.002), and a lower number of lifetime births (p = 0.02).
The proportions of HIV-positive women of reproductive age living in Ontario desiring and intending pregnancy were higher than reported in earlier North American studies. Proportions were more similar to those reported from African populations. Healthcare providers and policy makers need to consider increasing services and support for pregnancy planning for HIV-positive women. This may be particularly significant in jurisdictions with high levels of African immigration.
Group B streptococcal infection is common in pregnant women without causing harm. However it is also a significant cause of neonatal morbidity and mortality.
The objective of this review was to ...assess the effects of intrapartum administration of antibiotics to women on infant colonization with group B streptococcus, early onset neonatal group B streptococcus sepsis and neonatal death from infection.
The Cochrane Pregnancy and Childbirth Group trials register was searched.
Controlled trials of pregnant women colonized with group B streptococcus comparing intrapartum antibiotic administration with no treatment, and providing data on infant colonization with group B streptococcus and/or neonatal infection.
Eligibility and trial quality assessment were done by one reviewer.
Five trials were included. Overall quality was poor, with potential selection bias in all the identified studies. Intrapartum antibiotic treatment reduced the rate of infant colonization (odds ratio 0.10, 95% confidence interval 0.07 to 0.14) and early onset neonatal infection with group B streptococcus (odds ratio 0.17, 95% confidence interval 0.07 to 0.39). A difference in neonatal mortality was not seen (odds ratio 0.12, 95% confidence interval 0.01 to 2.00).
Intrapartum antibiotic treatment of women colonized with group B streptococcus appears to reduce neonatal infection. Effective strategies to detect maternal colonization with group B streptococcus and better data on maternal risk factors for neonatal group B streptococcus infection in different populations are required.
Pulmonary TB remains a leading global health issue, but the current Bacille Calmette-Guérin (BCG) vaccine fails to control it effectively. Much effort has gone into developing safe and effective ...boost vaccine candidates for use after the BCG prime vaccination. To date, almost all the lead candidates are being evaluated clinically via a parenteral route. Abundant experimental evidence suggests that parenteral boosting with a virus-based vaccine is much less effective than respiratory mucosal boosting, because the former fails to activate a type of T cell capable of rapidly transmigrating into the airway luminal space in the early phase of the Mycobacterium tuberculosis infection. The next few years will determine whether parenteral boosting with some of the lead vaccine candidates, particularly the protein-based vaccines, improves protection in humans over that by BCG. Much effort is needed to develop respiratory mucosal boost vaccines and to identify the reliable immune protective correlates in humans.
Background. To date, no randomized trial to address the use of adjunctive rifampin in addition to metronidazole for the treatment of Clostridium difficile–associated diarrhea has been reported. ...Rifampin has excellent in vitro activity against C. difficile and penetrates into cellular materials where the organisms may persist. Methods. This was a prospective, randomized, single-blinded study of 39 patients that compared therapy with metronidazole alone versus therapy with metronidazole and rifampin for 10 days to treat laboratory-confirmed primary episode C. difficile–associated diarrhea. Twenty patients were randomly assigned to the metronidazole group, and 19 were randomly assigned to the metronidazole and rifampin group. Data were analyzed by intention-to-treat analysis using the 2-tailed Kaplan-Meier method and the log-rank test. Results. Adjunctive rifampin treatment for 10 days, compared with treatment with metronidazole alone for 10 days, was associated with a similar median time to symptom improvement (9.0 days vs. 6.5 days; P = .74), a similar median time to first relapse (26 days vs. 16 days; P = .23), a similar proportion of patients with relapse by study day 40 (42% vs. 38%; P = 1.0), and a similar proportion of patients experiencing nonfatal adverse events (37% vs. 40%; P = .55). There were a significantly higher number of deaths in the metronidazole and rifampin group, compared with the metronidazole group (6 of 19 patients vs. 1 of 20 patients; P = .04), but there were fewer laboratory-confirmed relapses by study day 40 (2 vs. 4; P = .66). Conclusions. We conclude that there is no role for routine rifampin as an adjunct to treatment with metronidazole for hospitalized patients with C. difficile–associated diarrhea. The cure rates for both treatment groups remain unacceptably low, and better treatments are urgently needed.
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