Aztreonam for Neisseria gonorrhoeae: a systematic review and meta-analysis.
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ABSTRACT: Background
Ceftriaxone is the only consistently active antimicrobial agent recommended for the treatment of Neisseria gonorrhoeae. Although some new antimicrobials are in development, the necessity to expand treatment options in the near term may require using older drugs that have not been widely used to treat gonorrhoea.Methods
We conducted a literature review of clinical trials and case series, published from 1983 to 2017, reporting treatment efficacy results following administration of 1 g aztreonam intramuscularly or IV for uncomplicated gonococcal infections. We summed trial data, stratified by anatomical site of infection, and calculated summary efficacy estimates and 95% CI for each site of infection.Results
The 10 identified clinical trials enrolled 678, 38 and 16 individuals with urogenital, rectal and pharyngeal gonorrhoea, respectively. Aztreonam had an efficacy of 98.6% (95% CI: 97.5%-99.4%) for urogenital, 94.7% (95% CI: 82.3%-99.4%) for rectal and 81.3% (95% CI: 54.4%-96.0%) for pharyngeal gonococcal infections.Conclusions
Although most clinical trials included in this meta-analysis were conducted >30 years ago, aztreonam appears to have excellent efficacy for urogenital gonorrhoea; its efficacy at extragenital sites remains uncertain.
SUBMITTER: Barbee LA
PROVIDER: S-EPMC7303817 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundNeisseria gonorrhoeae (NG) infection is a serious public health problem. The third-generation extended-spectrum cephalosporins (ESCs) have been used as the first-line treatment for NG infection for almost three decades. However, in recent years, treatment failures with the oral third-generation ESCs have been reported worldwide. This study aimed to estimate worldwide susceptibility rates of NG to cefixime and cefpodoxime by analyzing data from all relevant published studies.Methodology/principal findingsTwo researchers independently searched five databases to identify studies on susceptibilities of NG to cefixime and cefpodoxime published between January 1, 1984 and October 15, 2012. A fixed-effect model was used to perform group analysis, and a ?2 test was employed to make subgroup comparison. Publication bias was assessed with the Begg rank correlation test. The pooled susceptibility rate of NG isolates to cefixime was 99.8% (95% CI: 99.7%-99.8%). The cefixime susceptibility rate of NG isolates from men was significantly lower than that from patients without information of gender or from men and women; the susceptibility rate of NG isolates from Asia was significantly lower than that from other continents; and the susceptibility rate of NG isolates collected before or during 2003 was significantly higher than that after 2003. The pooled susceptibility rate of NG isolates to cefpodoxime was 92.8% (95% CI: 89.0%-95.3%), which was lower than that to cefixime (92.8% vs. 99.8%, ?2 = 951.809, P<0.01).ConclusionsThe susceptibility rate of NG isolates to cefixime varied with the gender of patients and geographical location from which NG isolates were collected, and declined with time. The reported lower susceptibility rate of NG isolates to cefixime and associated treatment failures, as well as the emergence of NG strains with cephalosporin resistance call for the more effective control of NG infection and the development of new antibiotics.
| S-EPMC3909252 | biostudies-literature
Project description:(1) Background: The widespread development of resistance among Neisseria gonorrhoeae (NG) clinical isolates has been reported by surveillance systems around the world. This meta-analysis estimated the changes in susceptibility patterns among antibiotics under surveillance in Australia and New Zealand. (2) Methods: Articles published in English from 1980-2018, from Australia or New Zealand, that met the selection criteria were included. The meta-analysis was carried out using the R statistical software. (3) Results: In Australia, there has been decreasing susceptibility of gonococcal isolates to selected antimicrobials over time. Azithromycin (Odds Ratio (OR): 0.73; 95% Confidence Interval (CI) 0.64-0.82) and ceftriaxone (OR: 0.69; 95% CI 0.59-0.80) showed decreasing levels of susceptibility each year. Western Australia (OR: 0.76; 95% CI 0.60-0.96) and Victoria (OR: 0.74; 95% CI 0.60-0.90) also had decreasing levels of susceptibility to ceftriaxone over time compared with other states and territories. (4) Conclusions: The results highlight the need for the development of new approaches for managing cases of gonorrhoea. Improved antimicrobial stewardship, enhanced surveillance and contact tracing are needed to identify and respond to changes in antibiotic resistance in a timely manner. Increasing awareness and public health follow-up of cases can help to interrupt the cycle of infection and limit transmission.
| S-EPMC6963718 | biostudies-literature
Project description:Multidrug-resistant Neisseria gonorrhoeae infections have been declared 1 of the top 3 urgent threats to public health. Approaches to combat resistance include targeted therapy with antibiotics previously thought to be ineffective, made possible by rapid molecular assays to predict susceptibility. Previous studies have associated the gyrase A (gyrA) gene of N. gonorrhoeae with in vitro resistance to ciprofloxacin. We conducted a systematic review of studies comparing N. gonorrhoeae gyrA genotype results with conventional antimicrobial susceptibility testing results. We identified 31 studies meeting inclusion criteria, among which 7 different loci for mutations in the gyrA gene were identified, from 16 countries between the years of 1996 and 2016. We then performed a meta-analysis among those studies stratifying by use of real-time polymerase chain reaction (PCR) or non-real-time PCR technique, and compared the summary receiver operating characteristic curves between the 2 PCR methods. Among studies using real-time PCR, the pooled estimate of sensitivity and specificity of gyrA genotype results for the prediction of N. gonorrhoeae susceptibility to ciprofloxacin were 98.2% (95% confidence interval [CI], 96.5-99.1%) and 98.6% (95% CI, 97.0-99.3%), respectively. The summary operating characteristic curves for studies using real-time PCR techniques were well separated from those using non-real-time PCR techniques, with only slight overlap in the CIs, suggesting that real-time PCR techniques were a more accurate approach. GyrA genotype testing is a novel approach to combating the emergence of multidrug-resistant N. gonorrhoeae and is a sensitive and specific method to predict in vitro ciprofloxacin susceptibility.
| S-EPMC5407314 | biostudies-other
Project description:ObjectiveNeisseria gonorrhoeae (Ng) is the second most common sexually transmitted bacterial infection (STI), leading to serious health problems in men, women and newborns. While early antibiotic treatment is effective, infections are increasingly antibiotic-resistant. No systematic reviews present health problems associated with Ng infections or their likelihood of occurrence. The objective, therefore, was to conduct a systematic literature review to address these gaps.MethodsA systematic literature review was conducted of all studies with an English abstract published since 1950 (Pubmed)/1966 (Embase). The search included patients with a history of/current sexually transmitted Ng infection. Expected outcomes were defined from published reviews of gonorrhoea health problems. Observational studies with a control group were included. A decision tree determined the best quality studies for each outcome, prioritising generalisable populations, laboratory-confirmed diagnosis, clearly defined outcomes, no STI co-infections, adjusted analyses and risk estimates. Where feasible, a meta-analysis was performed; otherwise, the best quality study estimates were identified.FindingsIn total, 46 studies were included, and 22 health problems were identified. Of these problems, Ng infection was statistically significantly associated with preterm premature ruptures of membranes, preterm birth, low birth weight, stillbirth, infant death, neonatal ophthalmia, schizophrenia in offspring, pelvic inflammatory disease and subsequent tubal infertility, human immunodeficiency virus and prostate cancer/problems. High-quality evidence was generally lacking, with high heterogeneity across studies, and limited or inconclusive data on other health problems.ConclusionNg infection is associated with severe health problems in women, men and newborns. More high-quality comparative studies are needed to address the limitations in current knowledge.
| S-EPMC8572915 | biostudies-literature
Project description:Primary outcome(s): Colorectal cancer incidence, Colorectal tumor incidence
| 79216 | ecrin-mdr-crc
Project description:BACKGROUND:The vaginal microbiota may modulate susceptibility to human papillomavirus (HPV), Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasma genitalium infections. Persistent infection with a carcinogenic HPV is a prerequisite for cervical cancer, and C. trachomatis, N. gonorrheae and M. genitalium genital infections are all associated with pelvic inflammatory disease and subsequent infertility issues. OBJECTIVES:To evaluate the association between these infections and the vaginal microbiota. DATA SOURCES:The search was conducted on Medline and the Web of Science for articles published between 2000 and 2016. STUDY ELIGIBILITY CRITERIA:Inclusion criteria included a measure of association for vaginal microbiota and one of the considered STIs, female population, cohort, cross-sectional and interventional designs, and the use of PCR methods for pathogen detection. METHODS:The vaginal microbiota was dichotomized into high-Lactobacillus vaginal microbiota (HL-VMB) and low-Lactobacillus vaginal microbiota (LL-VMB), using either Nugent score, Amsel's criteria, presence of clue cells or gene sequencing. A random effects model assuming heterogeneity among the studies was used for each STI considered. RESULTS:The search yielded 1054 articles, of which 39 met the inclusion criteria. Measures of association with LL-VMB ranged from 0.6 (95% CI 0.3-1.2) to 2.8 (95% CI 0.3-28.0), 0.7 (95% CI 0.4-1.2) to 5.2 (95% CI 1.9-14.8), 0.8 (95% CI 0.5-1.4) to 3.8 (95% CI 0.4-36.2) and 0.4 (95% CI 0.1-1.5) to 6.1 (95% CI 2.0-18.5) for HPV, C. trachomatis, N. gonorrhoeae and M. genitalium infections, respectively. CONCLUSIONS:Although no clear trend for N. gonorrhoeae and M. genitalium infections could be detected, our results support a protective role of HL-VMB for HPV and C. trachomatis. Overall, these findings advocate for the use of high-resolution characterization methods for the vaginal microbiota and the need for longitudinal studies to lay the foundation for its integration in prevention and treatment strategies.
| S-EPMC7362580 | biostudies-literature
Project description:INTRODUCTION:Several bacterial sexually transmitted and genital mycoplasma infections during pregnancy have been associated with poor pregnancy and perinatal outcomes. Comprehensive and systematic information about associations between sexually transmitted infections (STI) and genital infections in pregnancy and adverse perinatal outcomes is needed to improve understanding about the evidence for causal associations between these infections and adverse pregnancy and neonatal outcomes. Our primary objective is to systematically review the literature about associations between: (1) Neisseria gonorrhoeae in pregnancy and preterm birth; (2) Mycoplasma genitalium in pregnancy and preterm birth; (3) M. hominis, Ureaplasma urealyticum and/or U. parvum in pregnancy and preterm birth. METHODS AND ANALYSIS:We will undertake a systematic search of Medline, Excerpta Medica database and the Cochrane Library and Cumulative Index to Nursing and Allied Health Literature. Following an initial screening of titles by one reviewer, abstracts will be independently assessed by two reviewers before screening of full-text articles. To exclude a manuscript, both reviewers need to agree on the decision. Any discrepancies will be resolved by discussion, or the adjudication of a third reviewer. Studies will be included if they report testing for one or more of N. gonorrhoeae, M. genitalium, M. hominis, U. urealyticum and/or U. parvum during pregnancy and report pregnancy and/or birth outcomes. In this review, the primary outcome is preterm birth. Secondary outcomes are premature rupture of membranes, low birth weight, spontaneous abortion, stillbirth, neonatal mortality and ophthalmia neonatorum. We will use standard definitions, or definitions reported by study authors. We will examine associations between exposure and outcome in forest plots, using the I2 statistic to examine between study heterogeneity. Where appropriate, we will use meta-analysis to combine results of individual studies. ETHICS AND DISSEMINATION:This systematic review of published literature does not require ethical committee approval. Results of this review will be published in a peer reviewed, open access journal. PROSPERO REGISTRATION NUMBER:CRD42016050962.
| S-EPMC6278811 | biostudies-other
Project description:The threat of ceftriaxone-resistant Neisseria gonorrhoeae necessitates new gonorrhea treatment regimens. Repurposing older antibiotics not routinely used for N. gonorrhoeae may expeditiously identify new therapies. Ideally, all recommended therapies should eradicate gonorrhea at the pharynx. Between April and September 2019, we enrolled men in an open-label, one-arm clinical trial of single-dose intramuscular aztreonam (2 g). Enrollment criterion included (i) nucleic acid amplification test (NAAT)-positive pharyngeal gonorrhea for ≤14 days or (ii) Gram stain-positive gonococcal urethritis plus report of performing oral sex in ≤2 months. At enrollment, we collected cultures from NAAT-positive or screening sites, and men returned 3 to 8 days following treatment for a test of cure (TOC) by culture. The per-protocol analysis required men to be culture positive at enrollment and to return for TOC. We calculated efficacy as the number of subjects with negative culture at TOC divided by the number culture positive at enrollment by anatomic site. Thirty-two men enrolled in the study; 21 were pharyngeal NAAT positive, and 11 had gonococcal urethritis. The per-protocol analysis included 17 men, 6 with pharyngeal, 9 with urethral, and 4 with rectal gonococcal infections. Aztreonam cured 2 of 6 pharyngeal infections (33%; 95% confidence interval [CI], 4.3% to 78%) and 3 of 4 rectal infections (75%; 95% CI, 19% to 99%). All 11 men with urethritis were cured (100%; 95% CI, 66% to 100%). The aztreonam MIC90 was 0.5 μg/ml (range, 0.06 to 2.0 μg/ml). All treatment failures occurred at a MIC of ≥0.25 μg/ml. Single-dose aztreonam is not a reliable treatment for gonorrhea at the pharynx but may be useful for men with gonococcal urethritis and beta-lactam allergy. (This study has been registered at ClinicalTrials.gov under identifier NCT03867734.).
| S-EPMC7927842 | biostudies-literature
Project description:BackgroundA high level of resistance in Neisseria gonorrhoeae has developed against penicillins, sulphonamides, tetracyclines and quinolones, and recent surveillance data have shown a gradual reduction in sensitivity to current first-line agents with an upward drift in the minimum inhibitory concentration of ceftriaxone. Laboratory sensitivity testing suggests that gentamicin, an aminoglycoside, may be an effective treatment option for gonorrhoea infection when used as a single intramuscular dose.MethodsA search of electronic reference databases and grey literature was used to identify randomised trials and well-conducted prospective studies with concurrent controls evaluating single-dose gentamicin against placebo or a comparator regimen in the treatment of uncomplicated gonorrhoea infection in men and women aged 16 years and over. The primary outcome was microbiological cure of N. gonorrhoeae.ResultsEight hundred and thirty-nine studies were identified, of which five (1,063 total participants) were included. All five studies administered single-dose gentamicin via intramuscular injection to men with uncomplicated gonococcal urethritis. Three studies were randomised trials, one was quasi-randomised and one was non-randomised but included a comparator arm. Comparator antibiotics included an alternative aminoglycoside or antibiotic used in the syndromic management of male urethritis. Methodology was poorly described in all five included studies. The high risk of bias within studies and clinical heterogeneity between studies meant that it was inappropriate to pool data for meta-analysis. Cure rates of 62% to 98% were reported with gentamicin treatment. The relative risk of cure was comparable between gentamicin and comparator antibiotics.ConclusionsThe studies identified provide insufficient data to support or refute the efficacy and safety of single-dose intramuscular gentamicin in the treatment of uncomplicated gonorrhoea infection. Additional randomised trials to evaluate gentamicin for this indication are therefore required.Systematic review registrationPROSPERO CRD42012002490.
| S-EPMC4188483 | biostudies-literature
Project description:Neisseria gonorrhoeae (N. gonorrhoeae) is now recognized as a commonly reported sexually transmitted pathogen, and the increasing drug resistance of N. gonorrhoeae has become a serious public health problem. The accuracy of molecular detection for detecting moderate-level azithromycin resistance is not well-established. We summarized the data from studies of the N. gonorrhoeae 23S rRNA mutation at position 2611 with azithromycin resistance to determine the relationship between the mutation and resistance. In this systematic review and meta-analysis, two researchers independently searched six databases for studies with data for the azithromycin minimum inhibitory concentrations (MICs) and the 23S rRNA mutation C2611T of each N. gonorrhoeae isolate. Since the breakpoint of moderate-level resistance to azithromycin (ML-AzmR) was not determined, we divided the moderate level into two groups according to the range of MICs (moderate resistance limited to 2-128 mg/L or 4-128 mg/L) for data extraction. A random-effects model was used to calculate the pooled sensitivity rate, the specificity rate, the pooled positive likelihood ratio (PLR), the negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR). Meta-regression analyses by detection method, isolates sampling (a random sample or not), location, and sample size were performed to explore the possible causes of heterogeneity. The potential publication bias of the included studies was conducted by the Deeks' test. We included 20 studies in our study: 20 studies have data of N. gonorrhoeae with MICs between 2 and 128 mg/L with mutation or without mutation at position 2611(4759 samples), and 14 studies have data of N. gonorrhoeae with MICs between 4 and 128 mg/L (3367 samples). In the group with the moderate level of 2-128 mg/L, the pooled sensitivity rate of the molecular assays was determined to be 71.9% (95% CI, 67.6-74%), the pooled specificity rate was 98.7% (95% CI, 98.2-99.0%), and the DOR ranged from 55.0 to 351.3 (mean, 139.1). In the 4-128 mg/L group, the pooled sensitivity rate was 91.9% (95% CI, 88.9-94.2%), the pooled specificity rate was 95.9% (95% CI, 95.1-96.6%), and the DOR ranged from 41.9 to 364.1 (mean, 123.6). Through this meta-analysis, we found that the C2611T mutation of 23S rRNA is valuable for the molecular diagnostic of moderate-level azithromycin resistance (ML-AzmR) in N. gonorrhoeae, especially when the moderate level is set at 4-128 mg/L. This rapid molecular detection method can be used for the rapid identification of ML-AzmR isolates in the clinic.
| S-EPMC8471969 | biostudies-literature