Routine antibiotic prophylaxis after normal vaginal birth for reducing maternal infectious morbidity.

BACKGROUND: Infectious morbidities contribute to considerable maternal and perinatal morbidity and mortality, including women at no apparent increased risk of infection. To reduce the incidence of infections, antibiotics are often administered to women after uncomplicated childbirth, particularly in settings where women are at higher risk of puerperal infectious morbidities. OBJECTIVES: To assess whether routine administration of prophylactic antibiotics to women after normal (uncomplicated) vaginal birth, compared with placebo or no antibiotic prophylaxis, reduces postpartum maternal infectious morbidities and improves outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2017), LILACS, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (22 August 2017) and reference lists of retrieved studies. SELECTION CRITERIA: We planned to include randomised or quasi-randomised trials evaluating the use of prophylactic antibiotics versus placebo or no antibiotic prophylaxis. Trials using a cluster-randomised design would have been eligible for inclusion, but we found none.In future updates of this review, we will include studies published in abstract form only, provided sufficient information is available to assess risks of bias. We will consider excluded abstracts for inclusion once the full publication is available, or the authors provide more information.Trials using a cross-over design are not eligible for inclusion in this review. DATA COLLECTION AND ANALYSIS: Two review authors conducted independent assessment of trials for inclusion and risks of bias. They independently extracted data and checked them for accuracy, resolving differences in assessments by discussion. They evaluated methodological quality using standard Cochrane criteria and the GRADE approach.We present the summaries as risk ratios (RRs) and mean difference (MDs) using fixed- or random-effect models. For one primary outcome we found considerable heterogeneity and interaction. We explored further using subgroup analysis to investigate the effects of the randomisation unit. All review authors discussed and interpreted the results. MAIN RESULTS: One randomised controlled trial (RCT) and two quasi-RCTs contributed data on 1779 women who had uncomplicated vaginal births, comparing different antibiotic regimens with placebo or no treatment. The included trials took place in the 1960s (one trial) and 1990s (two trials). The trials were conducted in France, the USA and Brazil. Antibiotics administered included: oral sulphamethoxypyridazine or chloramphenicol for three to five days, and intravenous amoxicillin and clavulanic acid in a single dose one hour after birth. We rated most of the domains for risk of bias as high risk, with the exception of reporting bias and other potential bias.The quality of evidence ranged from low to very low, based on the GRADE quality assessment, given very serious design limitations of the included studies, few events and wide confidence intervals (CIs) of effect estimates.We found a decrease in the risk of endometritis (RR 0.28, 95% CI 0.09 to 0.83, two trials, 1364 women,very low quality). However, one trial reported zero events for this outcome and we rate the evidence as very low quality. There was little or no difference between groups for the risk of urinary tract infection (RR 0.25, 95% CI 0.05 to 1.19, two trials, 1706 women,low quality), wound infection after episiotomy (reported as wound dehiscence in the included trials) (RR 0.78, 95% CI 0.31 to 1.96, two trials, 1364 women, very low quality) and length of maternal hospital stay in days (MD -0.15, 95% CI -0.31 to 0.01, one trial, 1291 women, very low quality). Cost of care in US dollar equivalent was 2½ times higher in the control group compared to the group receiving antibiotics prophylaxis (USD 3600: USD 9000, one trial, 1291 women). There were few or no differences between treated and control groups for adverse effects of antibiotics (skin rash) reported in one woman in each of the two trials (RR 3.03, 95% CI 0.32 to 28.95, two trials, 1706 women, very low quality). The incidence of severe maternal infectious morbidity, antimicrobial resistance or women's satisfaction with care were not addressed by any of the included studies. AUTHORS' CONCLUSIONS: Routine administration of antibiotics may reduce the risk of endometritis after uncomplicated vaginal birth. The small number and nature of the trials limit the interpretation of the evidence for application in practice, particularly in settings where women may be at higher risk of developing endometritis. The use of antibiotics did not reduce the incidence of urinary tract infections, wound infection or the length of maternal hospital stay. Antibiotics are not a substitute for infection prevention and control measures around the time of childbirth and the postpartum period. The decision to routinely administer prophylactic antibiotics after normal vaginal births needs to be balanced by patient features, childbirth setting and provider experience, including considerations of the contribution of indiscriminate use of antibiotics to raising antimicrobial resistance. Well-designed and high-powered randomised controlled trials would help to evaluate the added value of routine antibiotic administration as a measure to prevent maternal infections after normal vaginal delivery.

The effect of sulphamethoxypyridazine on liver and plasma levels of vitamin A in rats.

1 Long-acting sulphonamides are highly bound to plasma proteins; the present study deals with the effects of this binding property upon a vitamin A compound also transported by plasma proteins. 2 Sulphamethoxypyridazine was administered in rats either orally or by intraperitoneal injection. 3 A significant fall in plasma vitamin A level and an increase in hepatic vitamin A concentration were observed. 4 These results suggest an interference by sulphamethoxypyridazine with the transport of vitamin A, either through competition between the drug and vitamin A for binding sites of plasma proteins, or through altered secretion of the vitamin from the liver.

A comparative study of some combined treatment regimens in acute toxoplasmosis in mice.

The effectiveness of five treatment regimens was compared to mice during acute and late infection with Toxoplasma gondii. Parasitic cure rates, as judged by failure of brain tissue from surviving mice to produce infection when inoculated into clean mice, were as follows: pyrimethamine + sulfamethoxypyridazine, 92%; clindamycin + sulfamethoxypyridazine, 75%; spiramycin + sulfamethoxypyridazine, 16.7%; trimethoprim + sulfamethoxypryridazine alone, 0%. Pyrimethamine + sulfamethoxypyridazine was the most effective combination against acute toxoplasmosis in mice.

[Studies on the therapeutics of experimental toxoplasmosis. II. Effect of acetylspiramycin alone or in combination with an immunopotentiator (CSP-II) or sulfamethopyrazine on Toxoplasma multiplication in the heart of mice acutely and chronically infected with Toxoplasma gondii (author's transl)].

Normal mice acutely and chronically infected with the S-273 strain of T. gondii, were treated with acetylspiramycin (ASPM) alone, 8 mg/mouse/day, per os, or in combination with an immunopotentiator (CSP-II), 10 mg/mouse/day, intraperitoneally, or sulfamethopyrazine (SMPZ), 2 mg/mouse/day, per os, for a period of 4 weeks. In the acute cases, a 99.4% cyst reduction was obtained with ASPM alone and no cysts were seen in the brains of mice treated with ASPM in combination with CSP-II or SMPZ. The organisms were significantly eradicated in the brain and heart tissues of mice treated with ASPM alone or in combination with CSP-II or SMPZ as shown by subinoculation to normal mice and the negative latex hemagglutination titers of the recipient mice. In the chronic cases, a cyst reduction of 52.4% was obtained with mice treated with ASPM in combination with CSP-II. A cyst reduction of 34.6%, 32.9% and 20.8% was obtained in the ASPM alone, CSP-II alone and ASPM in combination with SMPZ treated groups, respectively. A comparative clearing of the organisms in the heart tissues of mice treated with ASPM in combination with CSP-II was obtained compared to the other treatment groups but not in the brains of all groups.

[Sodium sulfapyridazine in new delayed-action bases for the treatment of bacterial conjunctivitis]. / Sul'fapiridazin-natrii v novykh prolongiruiushchikh osnovakh dlia lecheniia bakterial'nykh kon''iunktivitov.

Possible preparation of 10 per cent sodium sulfapyridazine ophthalmic drops containing aubazidan, a microbial polysaccharide, providing prolongation of the drops action and stability on the storage was studied. The pharmacokinetic studies showed that aubazidan which is a natural polymer provided high prolongation of the sulfapyridazine effect in the tissues of the anterior part of the eye in rabbits. The prolonged effect was similar to the previously observed effect of the solutions containing synthetic polymers such as 1 per cent polyacrylamide and polyvinyl . Satisfactory tolerance by the rabbit eye tissues of 6-fold daily instillations of the 10 per cent sodium sulfapyridazine solution with aubazidan for the observation period of 1 month was stated. When stored in vials the 10 per cent sodium sulfapyridazine ophthalmic drops with 0.5 per cent of aubazidan preserved the stability for 24 months with respect to the colour, transparency, viscosity, pH and drug content. It was demonstrated with using the agar diffusion method and Staphylococcus aureus, Proteus vulgaris, Escherichia coli and Pseudomonas aeruginosa as the test cultures that sodium sulfapyridazine completely preserved its antimicrobial activity in the presence of aubazidan. The data suggested that clinical trials of the 10 per cent sodium sulfapyridazine solution with 0.2-0.5 per cent of aubazidan were promising in prevention and therapy of bacterial conjunctivitis.

Bioavailability of sulfamethoxypyridazine following intramuscular or subcutaneous administration in goats.

The pharmacokinetics of sulfamethoxypyridazine (SMP) was investigated in goats after a single intramuscular (im) or subcutaneous (sc) administration (100 mg/kg body weight). The biological half lives of SMP following im and sc administration were found to be 11.0 and 13.7 h, respectively. The systemic availabilities of the drug were calculated to be 68.6 and 58.7% following im and sc injections, respectively. The rapidity of absorption, almost similar availability, comparatively longer biological half-life and ease of administration suggest that the sc route of administration might be preferred over the im route. To achieve and maintain serum concentrations 25 micrograms/mL, a rational dosage regimen of SMP for goats would be 55 and 38 mg/kg body weight as the loading and maintenance doses, respectively, with a dosage interval of 24 h by the sc route.

Sulphonamide and dapsone residues in bovine milk following intramammary infusion.

The elimination into bovine milk of sulphonamides (sulphadimidine and sulphamethoxypyridazine) and dapsone following intramammary infusion was studied. Determination of sulphonamides and dapsone in milk was performed by a high performance liquid chromatographic method with UV detection. The limit of quantification was 0.01 microgram/ml. Withdrawal times were established considering the maximum residue limits fixed by the European Community (100 micrograms/kg for sulphonamides and 25 micrograms/kg for dapsone). The diffusion of residues into milk from a quarter infused by the intramammary route to the untreated quarters was also studied.

[Methodology of hygienic standardization of allergenic mixtures of stable composition (a model of combined veterinary preparations)]. / K metodologii gigienicheskogo normirovaniia allergennykh smesei postoiannogo sostava (na modeli kombinirovannykh veterinarnykh preparatov).

The article presents the experimental study results of a comparative assessment of the allergenic activity of three newly developed veterinary preparations (both their major components and complete combined forms)--rivicycline, sulphapen and geovet . No increase in sensibilization was traced, and some indicators showed a weakened sensitizing ++ action of the combined preparations in comparison with the respective doses of the constituent allergic components. The allergy inducing components were determined. The authors recommended hygienic norm of the combined veterinary preparations, as mixtures with permanent composition, by their major allergic components. The proposed technique of a comparative express-test of allergic mixtures and their components may be recommended as another approach to express hygienic norming of the allergens.