Antibiotic therapy for pelvic inflammatory disease.

BACKGROUND: Pelvic inflammatory disease (PID) affects 4% to 12% of women of reproductive age. The main intervention for acute PID is broad-spectrum antibiotics administered intravenously, intramuscularly or orally. We assessed the optimal treatment regimen for PID.  OBJECTIVES: To assess the effectiveness and safety of antibiotic regimens to treat PID. SEARCH METHODS: In January 2020, we searched the Cochrane Sexually Transmitted Infections Review Group's Specialized Register, which included randomized controlled trials (RCTs) from 1944 to 2020, located through hand and electronic searching; CENTRAL; MEDLINE; Embase; four other databases; and abstracts in selected publications. SELECTION CRITERIA: We included RCTs comparing antibiotics with placebo or other antibiotics for the treatment of PID in women of reproductive age, either as inpatient or outpatient treatment. We limited our review to a comparison of drugs in current use that are recommended by the 2015 US Centers for Disease Control and Prevention guidelines for treatment of PID. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two authors independently extracted data, assessed risk of bias and conducted GRADE assessments of the quality of evidence. MAIN RESULTS: We included 39 RCTs (6894 women) in this review, adding two new RCTs at this update. The quality of the evidence ranged from very low to high, the main limitations being serious risk of bias (due to poor reporting of study methods and lack of blinding), serious inconsistency, and serious imprecision. None of the studies reported quinolones and cephalosporins, or the outcomes laparoscopic evidence of resolution of PID based on physician opinion or fertility outcomes. Length of stay results were insufficiently reported for analysis. Regimens containing azithromycin versus regimens containing doxycycline We are uncertain whether there was a clinically relevant difference between azithromycin and doxycycline in rates of cure for mild-moderate PID (RR 1.18, 95% CI 0.89 to 1.55; 2 RCTs, 243 women; I2 = 72%; very low-quality evidence). The analyses may result in little or no difference between azithromycin and doxycycline in rates of severe PID (RR 1.00, 95% CI 0.96 to 1.05; 1 RCT, 309 women; low-quality evidence), or adverse effects leading to discontinuation of treatment (RR 0.71, 95% CI 0.38 to 1.34; 3 RCTs, 552 women; I2 = 0%; low-quality evidence). In a sensitivity analysis limited to a single study at low risk of bias, azithromycin probably improves the rates of cure in mild-moderate PID (RR 1.35, 95% CI 1.10 to 1.67; 133 women; moderate-quality evidence), compared to doxycycline.  Regimens containing quinolone versus regimens containing cephalosporin The analysis shows there may be little or no clinically relevant difference between quinolones and cephalosporins in rates of cure for mild-moderate PID (RR 1.05, 95% CI 0.98 to 1.14; 4 RCTs, 772 women; I2 = 15%; low-quality evidence), or severe PID (RR 1.06, 95% CI 0.91 to 1.23; 2 RCTs, 313 women; I2 = 7%; low-quality evidence). We are uncertain whether there was a difference between quinolones and cephalosporins in adverse effects leading to discontinuation of treatment (RR 2.24, 95% CI 0.52 to 9.72; 6 RCTs, 1085 women; I2 =  0%; very low-quality evidence). Regimens with nitroimidazole versus regimens without nitroimidazole There was probably little or no difference between regimens with or without nitroimidazoles (metronidazole) in rates of cure for mild-moderate PID (RR 1.02, 95% CI 0.95 to 1.09; 6 RCTs, 2660 women; I2 = 50%; moderate-quality evidence), or severe PID (RR 0.96, 95% CI 0.92 to 1.01; 11 RCTs, 1383 women; I2 = 0%; moderate-quality evidence). The evidence suggests that there was little to no difference in in adverse effects leading to discontinuation of treatment (RR 1.05, 95% CI 0.69 to 1.61; 17 studies, 4021 women; I2 = 0%; low-quality evidence). . In a sensitivity analysis limited to studies at low risk of bias, there was little or no difference for rates of cure in mild-moderate PID (RR 1.05, 95% CI 1.00 to 1.12; 3 RCTs, 1434 women; I2 = 0%; high-quality evidence). Regimens containing clindamycin plus aminoglycoside versus quinolone We are uncertain whether quinolone have little to no effect in  rates of cure for mild-moderate PID compared to clindamycin plus aminoglycoside (RR 0.88, 95% CI 0.69 to 1.13; 1 RCT, 25 women; very low-quality evidence). The analysis may result in little or no difference between quinolone vs. clindamycin plus aminoglycoside in severe PID (RR 1.02, 95% CI 0.87 to 1.19; 2 studies, 151 women; I2 =  0%; low-quality evidence). We are uncertain whether quinolone reduces adverse effects leading to discontinuation of treatment (RR 0.21, 95% CI 0.02 to 1.72; 3 RCTs, 163 women; I2 =  0%; very low-quality evidence). Regimens containing clindamycin plus aminoglycoside versus regimens containing cephalosporin We are uncertain whether clindamycin plus aminoglycoside improves the rates of cure for mild-moderate PID compared to cephalosporin (RR 1.02, 95% CI 0.95 to 1.09; 2 RCTs, 150 women; I2 =  0%; low-quality evidence). There was probably little or no difference in rates of cure in severe PID with clindamycin plus aminoglycoside compared to cephalosporin (RR 1.00, 95% CI 0.95 to 1.06; 10 RCTs, 959 women; I2= 21%; moderate-quality evidence). We are uncertain whether clindamycin plus aminoglycoside reduces adverse effects leading to discontinuation of treatment compared to cephalosporin (RR 0.78, 95% CI 0.18 to 3.42; 10 RCTs, 1172 women; I2 =  0%; very low-quality evidence). AUTHORS' CONCLUSIONS: We are uncertain whether one treatment was safer or more effective than any other for the cure of mild-moderate or severe PID Based on a single study at a low risk of bias, a macrolide (azithromycin) probably improves the rates of cure of mild-moderate PID, compared to tetracycline (doxycycline).

Antibiotic therapy for pelvic inflammatory disease: an abridged version of a Cochrane systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To assess the effectiveness and safety of antibiotic regimens used to treat pelvic inflammatory disease (PID). DESIGN: This is a systematic review and meta-analysis of randomised controlled trials (RCTs). Risk of bias was assessed using the criteria outlined in the Cochrane guidelines. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation. DATA SOURCES: Eight electronic databases were searched from date of inception up to July 2016. Database searches were complemented by screening of reference lists of relevant studies, trial registers, conference proceeding abstracts and grey literature. ELIGIBILITY CRITERIA: RCTs comparing the use of antibiotics with placebo or other antibiotics for the treatment of PID in women of reproductive age, either as inpatient or outpatient treatment. RESULTS: We included 37 RCTs (6348 women). The quality of evidence ranged from very low to high, the main limitations being serious risk of bias (due to poor reporting of study methods and lack of blinding), serious inconsistency and serious imprecision. There was no clear evidence of a difference in the rates of cure for mild-moderate or for severe PID for the comparisons of azithromycin versus doxycycline, quinolone versus cephalosporin, nitroimidazole versus no use of nitroimidazole, clindamycin plus aminoglycoside versus quinolone, or clindamycin plus aminoglycoside versus cephalosporin. No clear evidence of a difference between regimens in antibiotic-related adverse events leading to discontinuation of therapy was observed. CONCLUSIONS: We found no conclusive evidence that one regimen of antibiotics was safer or more effective than any other for the treatment of PID, and there was no clear evidence for the use of nitroimidazoles (metronidazole) compared with the use of other drugs with activity against anaerobes. More evidence is needed to assess treatments for women with PID, particularly comparing regimens with or without the addition of nitroimidazoles and the efficacy of azithromycin compared with doxycycline.

Antibiotic therapy for pelvic inflammatory disease.

BACKGROUND: Pelvic inflammatory disease (PID) is an infection that affects 4% to 12% of young women, and is one of the most common causes of morbidity in this age group. The main intervention for acute PID is the use of broad-spectrum antibiotics which cover Chlamydia trachomatis, Neisseria gonorrhoeae, and anaerobic bacteria, administered intravenously, intramuscularly, or orally. In this review, we assessed the optimal treatment regimen for PID. OBJECTIVES: To assess the effectiveness and safety of antibiotic regimens used to treat pelvic inflammatory disease. SEARCH METHODS: We searched the Cochrane Sexually Transmitted Infections Review Group's Specialized Register, which included randomized controlled trials (RCTs) from 1944 to 2016, located through electronic searching and handsearching; the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid platform (1991 to July 2016); MEDLINE (1946 to July 2016); Embase (1947 to July 2016); LILACS, iAHx interface (1982 to July 2016); World Health Organization International Clinical Trials Registry Platform (July 2016); Web of Science (2001 to July 2016); OpenGrey (1990, 1992, 1995, 1996, and 1997); and abstracts in selected publications. SELECTION CRITERIA: We included RCTs comparing the use of antibiotics with placebo or other antibiotics for the treatment of PID in women of reproductive age, either as inpatient or outpatient treatment. We limited our review to comparison of drugs in current use that are recommended for consideration by the 2015 US Centers for Disease Control and Prevention (CDC) guidelines for treatment of PID. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected trials for inclusion, extracted data, and assessed risk of bias. We contacted investigators to obtain missing information. We resolved disagreements by consensus or by consulting a fourth review author if necessary. We assessed the quality of the evidence using GRADE criteria, classifying it as high, moderate, low, or very low. We calculated Mantel-Haenszel risk ratios (RR), using either random-effects or fixed-effect models and number needed to treat for an additional beneficial outcome or for an additional harmful outcome, with their 95% confidence interval (CI), to measure the effect of the treatments. We conducted sensitivity analyses limited to studies at low risk of bias, for comparisons where such studies were available. MAIN RESULTS: We included 37 RCTs (6348 women). The quality of the evidence ranged from very low to high, the main limitations being serious risk of bias (due to poor reporting of study methods and lack of blinding), serious inconsistency, and serious imprecision. Azithromycin versus doxycyclineThere was no clear evidence of a difference between the two drugs in rates of cure for mild-moderate PID (RR 1.18, 95% CI 0.89 to 1.55, I2 = 72%, 2 RCTs, 243 women, very low-quality evidence), severe PID (RR 1.00, 95% CI 0.96 to 1.05, 1 RCT, 309 women, low-quality evidence), or adverse effects leading to discontinuation of treatment (RR 0.71, 95% CI 0.38 to 1.34, 3 RCTs, 552 women, I2 = 0%, low-quality evidence). In a sensitivity analysis limited to a single study at low risk of bias, azithromycin was superior to doxycycline in achieving cure in mild-moderate PID (RR 1.35, 95% CI 1.10 to 1.67, 133 women, moderate-quality evidence). Quinolone versus cephalosporinThere was no clear evidence of a difference between the two drugs in rates of cure for mild-moderate PID (RR 1.04, 95% CI 0.98 to 1.10, 3 RCTs, 459 women, I2 = 5%, low-quality evidence), severe PID (RR 1.06, 95% CI 0.91 to 1.23, 2 RCTs, 313 women, I2 = 7%, low-quality evidence), or adverse effects leading to discontinuation of treatment (RR 2.24, 95% CI 0.52 to 9.72, 5 RCTs, 772 women, I2 = 0%, very low-quality evidence). Nitroimidazole versus no use of nitroimidazoleThere was no conclusive evidence of a difference between the nitroimidazoles (metronidazole) group and the group receiving other drugs with activity over anaerobes (e.g. amoxicillin-clavulanate) in rates of cure for mild-moderate PID (RR 1.01, 95% CI 0.93 to 1.10, 5 RCTs, 2427 women, I2 = 60%, moderate-quality evidence), severe PID (RR 0.96, 95% CI 0.92 to 1.01, 11 RCTs, 1383 women, I2 = 0%, moderate-quality evidence), or adverse effects leading to discontinuation of treatment (RR 1.00, 95% CI 0.63 to 1.59; participants = 3788; studies = 16; I2 = 0% , low-quality evidence). In a sensitivity analysis limited to studies at low risk of bias, findings did not differ substantially from the main analysis (RR 1.06, 95% CI 0.98 to 1.15, 2 RCTs, 1201 women, I2 = 32%, high-quality evidence). Clindamycin plus aminoglycoside versus quinoloneThere was no evidence of a difference between the two groups in rates of cure for mild-moderate PID (RR 0.88, 95% CI 0.69 to 1.13, 1 RCT, 25 women, very low-quality evidence), severe PID (RR 1.02, 95% CI 0.87 to 1.19, 2 studies, 151 women, I2 = 0%, low-quality evidence), or adverse effects leading to discontinuation of treatment (RR 0.21, 95% CI 0.02 to 1.72, 3 RCTs, 163 women, very low-quality evidence). Clindamycin plus aminoglycoside versus cephalosporinThere was no clear evidence of a difference between the two groups in rates of cure for mild-moderate PID (RR 1.02, 95% CI 0.95 to 1.09, 2 RCTs, 150 women, I2 = 0%, low-quality evidence), severe PID (RR 1.00, 95% CI 0.95 to 1.06, 10 RCTs, 959 women, I2 = 21%, moderate-quality evidence), or adverse effects leading to discontinuation of treatment (RR 0.78, 95% CI 0.18 to 3.42, 10 RCTs, 1172 women, I2 = 0%, very low-quality evidence). AUTHORS' CONCLUSIONS: We found no conclusive evidence that one regimen of antibiotics was safer or more effective than any other for the cure of PID, and there was no clear evidence for the use of nitroimidazoles (metronidazole) compared to use of other drugs with activity over anaerobes. Moderate-quality evidence from a single study at low risk of bias suggested that a macrolide (azithromycin) may be more effective than a tetracycline (doxycycline) for curing mild-moderate PID. Our review considered only the drugs that are currently used and mentioned by the CDC.

Expression of elafin in fallopian tubes of ectopic pregnancies is reduced.

Elafin is a natural antimicrobial molecule member of the antileukoproteinase (Trappin) family that is normally expressed in the mucosa of human fallopian tubes and neutrophils. Ectopic pregnancy is a condition in which neutrophil influx is present. Current data on elafin expression on fallopian tubes with ectopic pregnancy do not differentiate the expression of elafin in these 2 compartments. The objective of this study was to analyze the protein expression of elafin on epithelial mucosa of fallopian tubes with and without ectopic pregnancy using immunohistochemical analysis. Tissue sections of ectopic pregnancies (n=10) and normal tubes (n=10) were analyzed for the intensity of the staining with 3,3'-diaminobenzidine using ImageJ software. Statistical analysis was performed using unpaired t test and analysis of covariance. Elafin expression (mean ± SD) in the mucosa of fallopian tubes was 73.3 ± 19.7 (control) versus 48.9 ± 17.8 (ectopic pregnancy) (P=0.009). The immunoexpression of elafin is reduced in tubal epithelium of ectopic pregnancies, compared with nonectopic pregnancy tubes.

MUC1 expression in fallopian tubes of women with hydrosalpinx.

OBJECTIVE: To analyze the expression of MUC1 in Fallopian tubes with or without hydrosalpinx, using four different types of antibody. STUDY DESIGN: In a case-control study, immunohistochemical expression of MUC1 was examined in Fallopian tubes derived from women with hydrosalpinx (n=10) and normal controls (n=10). Four different antibodies were used for the detection of both extracellular (214D4, HMFG1, VPM654) and intracellular (EPR1023) MUC1 epitopes. Staining intensity was measured with ImageJ software. Expression of MUC1 mRNA was quantified by quantitative RT-PCR. Statistical analysis was performed with Student t-test (mean ± SD) and Mann-Whitney U-test (median [range]). RESULTS: The mean (±SD) and median [range] intensity of MUC1 in controls vs. hydrosalpinx were: 214D4-67.5 ± 11.3 vs. 74.8 ± 14.69 (P=0.22); HMFG1-95.3 [642-1079] vs. 97.0 [502-1550] (P=0.91); VPM654-41.1 [314-914] vs. 46.0 [390-1424] (P=0.1); EPR1023-24.7 ± 7.3 vs. 57.4 ± 31.3 (P=0.01). MUC1 mRNA was 0.16 [008-05] vs. 0.09 [005-019] (P=0.06). Ectodomains and mRNA of MUC1 are unchanged in tubes from hydrosalpinx patients. In contrast, immunodetection of the MUC1 cytoplasmic tail is enhanced in tubes from hydrosalpinx. CONCLUSION: Fallopian tubes with hydrosalpinx have a selective accumulation of MUC1 cytoplasmic tail, but not difference in the ectodomain.

Comparison of HSCORE assessment of endometrial beta3 integrin subunit expression with digital HSCORE using computerized image analysis (ImageJ).

OBJECTIVE: To compare intraobserver and interobserver variation between traditional histological score (HSCORE) and digital HSCORE (D-HSCORE) performed by expert and naive researchers. STUDY DESIGN: Immunohistochemical analysis of beta3 integrin subunit of 100 endometrial biopsies obtained from the midluteal phase of the menstrual cycle were reanalyzed using ImageJ software (D-HSCORE). Mean intensity of 3,3'-diaminobenzidine on endometrial glands was read by an expert (HSCORE) versus inexperienced observer using HSCORE and D-HSCORE. RESULTS: The mean correlation [r(s)(95% CI)] between both methods was 0.86 (0.79-0.90) and highly significant (p < 0.0001) for the experienced individual. The naive researcher overestimated immunostaining, resulting (HSCORE) in negative samples. No discrepancies were seen with D-HSCORE. Interobserver variation for the inexperienced reader was 50% using HSCORE (cutoff 0.7) but 0% with D-HSCORE. Intraobserver variation using ImageJ was 0%. CONCLUSION: The D-HSCORE performed by an inexperienced researcher has high correlation to traditional HSCORE performed by an expert.

Daily dose of clindamycin versus standard divided doses in obstetrical and gynecological infections: a retrospective cohort study.

To compare the rates of cure of septic abortion and pelvic inflammatory disease using a daily dose of clindamycin with gentamicin versus divided doses, we conducted a retrospective cohort study, where the electronic records of 661 patients who used clindamycin 1 × , 3 × or 4 ×/day (groups 1, 3 and 4, respectively) between September 2002 and August 2010 were analysed. Major outcomes included rates of cure and failure according to the clinical records. Secondary endpoints were percentage of adverse effects related to medication regimen and the prevalence of positive VDRL and HIV. Similar conditions were observed in all groups - septic abortion: 167/116/123; pelvic inflammatory disease: 73/95/87 (groups 1, 3 and 4, respectively). No significant difference was found among groups for age or for rate of cure. Rates of cure (cure/total [rate (95%CI)]) in groups 1, 3 and 4 were 236/240 [0.983 (0.957-0.993)], 205/211 [0.971 (0.939-0.986)], 203/210 [0.966 (0.932-0.983)], respectively. Days of use of clindamycin was significantly reduced in group 1, compared to groups 3 and 4 (2.6 ± 1.3 vs. 3.5 ± 2.5 vs. 3.3 ± 1.9-mean ± SD; p < 0.0001 - ANOVA), but this may be due to differences in how length of therapy was measured and not the effect on clinical cure.