scholarly journals Antibacterial data synthesis challenges: a systematic review of treatments for complicated gram-negative urinary tract infections

Author(s):  
Ryan Dillon ◽  
Jennifer Uyei ◽  
Rajpal Singh ◽  
Eilish McCann

Aim: To determine the suitability of network meta-analysis (NMA) using antibacterial treatment evidence in complicated urinary tract infection. Materials & methods: We conducted a systematic literature review to identify published clinical trial data for complicated urinary tract infection treatments. We performed a feasibility assessment to determine whether the available evidence would support the creation of a robust NMA, considering key assumptions of homogeneity, similarity and consistency. Results: Twenty-five trials met eligibility criteria. Risk of bias was low, and individual studies met their primary end point(s). Assumptions central to the conduct of a robust NMA were not met. Heterogeneity was ubiquitous, including baseline pathogen, treatment and patient characteristics. Conclusion: Limited and heterogeneous data identified make the use of NMA to compare novel antibacterial agents impractical and likely unreliable.

1981 ◽  
Vol 9 (4) ◽  
pp. 283-287 ◽  
Author(s):  
C Frimodt-Møller ◽  
R Vejlsgaard

Twenty-six surgical-urological patients with severe underlying diseases of the urinary tract and an acute urinary tract infection received a 10-day treatment with either pivmecillinam, 400 mg three tmes daily (twelve patients), or the fixed dose combination of pivmecillinam/pivampicillin (pivmecillinam 200 mg plus pivampicillin 250 mg) three times daily (fourteen patients). Eleven of the fourteen patients given combined therapy were cured bacteriologically, compared to only four out of twelve patients taking pivmecillinam alone. Clinical success was achieved in eleven out of fourteen patients who received combination therapy and in seven out of twelve subjects given pivmecillinam. Mild gastro-intestinal discomfort was recorded in a few patients in both treatment groups. The results suggest that the combination of pivmecillinam and pivampicillin is a promising alternative in patients with complicated urinary tract infections.


2013 ◽  
Vol 57 (11) ◽  
pp. 5284-5290 ◽  
Author(s):  
Krishan P. Singh ◽  
Gang Li ◽  
Fanny S. Mitrani-Gold ◽  
Milena Kurtinecz ◽  
Jeffrey Wetherington ◽  
...  

ABSTRACTNoninferiority trial design and analyses are commonly used to establish the effectiveness of a new antimicrobial drug for treatment of serious infections such as complicated urinary tract infection (cUTI). A systematic review and meta-analysis were conducted to estimate the treatment effects of three potential active comparator drugs for the design of a noninferiority trial. The systematic review identified no placebo trials of cUTI, four clinical trials of cUTI with uncomplicated urinary tract infection as a proxy for placebo, and nine trials with reports of treatment effect estimates for doripenem, levofloxacin, or imipenem-cilastatin. In the meta-analysis, the primary efficacy endpoint of interest was the microbiological eradication rate at the test-of-cure visit in the microbiological intent-to-treat population. The estimated eradication rates and corresponding 95% confidence intervals (CI) were 31.8% (26.5% to 37.2%) for placebo, 81% (77.7% to 84.2%) for doripenem, 79% (75.9% to 82.2%) for levofloxacin, and 80.5% (71.9% to 89.1%) for imipenem-cilastatin. The treatment effect estimates were 40.5% for doripenem, 38.7% for levofloxacin, 34.7% for imipenem-cilastatin, and 40.8% overall. These treatment effect estimates can be used to inform the design and analysis of future noninferiority trials in cUTI study populations.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S792-S793
Author(s):  
Jeffrey Thompson ◽  
Alen Marijam ◽  
Fanny S Mitrani-Gold ◽  
Jonathon Wright ◽  
Ashish V Joshi

Abstract Background Uncomplicated urinary tract infections (uUTI) are generally treated empirically with antibiotics. However, antibiotic (AB) allergies limit the available oral treatment options for some patients. We assessed the proportion of self-reported AB allergies among US females with uUTI. Methods We performed a cross-sectional survey of US females ≥ 18 years of age with a self-reported urinary tract infection (UTI) in the 60 days prior to participation and a prescription of oral AB. Participants were further screened for evidence of a complicated urinary tract infection and, after exclusions, participants with a uUTI completed an online questionnaire about their most recent episode. Participants were from the Northeast (20%), Midwest (44%), South (20%), and West (16%) US. Descriptive self-reported allergy data were stratified into subgroups by whether the participant had recurrent UTI (defined as ≥ 2 uUTIs in the past 6 months or ≥ 3 uUTIs in past 12 months including index UTI), the number of different ABs given for the index episode (1, 2, ≥ 3), and whether the treatment was clinically appropriate according to Infectious Diseases Society of America uUTI guidelines. Results Overall, 375 female participants completed the questionnaire. The most commonly prescribed ABs for participants’ most recent uUTI were trimethoprim-sulfamethoxazole (TMP-SMX; 38.7%), ciprofloxacin (22.7%), and nitrofurantoin (18.9%) (Table 1). Most participants received only 1 AB for their uUTI (62.7%) and the majority were classified as having a non-recurrent uUTI (56.5%). No AB allergies were reported for most participants (69.3%); overall, 24.0% reported 1 AB allergy and 6.7% reported ≥ 2. A higher proportion of participants reported ≥ 2 allergies in the recurrent uUTI, ≥ 3 AB, and multiple AB subgroups (Table 2). The most common allergy was to TMP-SMX (15.7%), followed by amoxicillin-clavulanate (8.3%) and ciprofloxacin (5.3%) (Table 2). Similar allergy trends were seen across subgroups, except higher rates of ciprofloxacin allergy were seen in participants given multiple ABs (Table 2). Table 1. Antibiotics used to treat most recent uUTI Table 2 . Frequency of antibiotic allergies across cohort subgroups Conclusion AB allergies were relatively frequent in this uUTI cohort and the most common allergy was to TMP-SMX, which was the most prescribed AB. Allergies to ABs reduce the available treatment options for uUTI in some patients. Disclosures Jeffrey Thompson, PhD, Kantar Health (Employee, Employee of Kantar Health, which received funding from GlaxoSmithKline plc. to conduct this study) Alen Marijam, MSc, GlaxoSmithKline plc. (Employee, Shareholder) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder) Jonathon Wright, BSc, Kantar Health (Employee, Employee of Kantar Health, which received funding from GlaxoSmithKline plc. to conduct this study) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder)


1975 ◽  
Vol 20 (5) ◽  
pp. 261-264
Author(s):  
J. G. Gow

Forty-three patients were treated with cephazolin sodium, a parenteral cephalosporin antibiotic for 45 episodes of urinary tract infection complicated by a variety of underlying conditions. In 42 episodes, there was a satisfactory clinical response, and in 37 episodes this was associated with elimination of the bacterial pathogen from the urine. In 21 out of 31 patients available for examination 3 months later, the urine was still free of bacteria. A relatively prolonged plasma half-life and high urinary concentrations of the drug permit successful treatment of urinary tract infections with injections given only twice daily.


Author(s):  
Ased Ali ◽  
Rob Pickard

‘Complicated’ urinary tract infection (UTI) indicates infection occurring in anatomically or functionally abnormal urinary tract. Infections are not only more likely in such circumstances, but they are more likely to lead to complications such as acute pyelonephritis, and are frequently more difficult to eradicate, requiring more prolonged antimicrobial therapy. Some causes may be associated with susceptibility to specific micro-organisms. There may occasionally be a limited place for prophylactic therapy.


2019 ◽  
Author(s):  
Alejandro G Gonzalez-Garay ◽  
Liliana Velasco-Hidalgo ◽  
Eric Ochoa-Hein ◽  
Roberto Rivera-Luna

Abstract Background Uncomplicated urinary tract infection is considered an infection that occurs in healthy individuals who have a normal urinary tract, representing 5% of all annual medical visits. Several quinolones are available as second-line agents for treatment; however, we do not know which is the best antibiotic scheme for urinary tract infection; therefore, we conducted a network meta-analysis to hierarchize each quinolone according to its efficacy and safety. Methods MEDLINE, EMBASE and other databases were subjected to non-language-restricted searches up to 2018 for trials that included women treated with quinolones for uncomplicated urinary tract infection. Bias in the trials was assessed by two reviewers; the Cochrane Collaboration tool was used to analyze clinical and bacteriological remission, relapse, resistance, and adverse events. For direct comparisons, we obtained risk ratios and 95% confidence intervals by applying a fixed events model using Tau2 and Q2 tests to calculate the heterogeneity using trimethoprim/sulfamethoxazole as the common comparator across studies. For the network meta-analysis, we analyzed the indirect comparisons by Bucher's method. The results were summarized in a correlation matrix. Results We included 18 trials with 8765 women. For pre-menopausal women and treatment duration <3 days, norfloxacin and ofloxacin had a 57% of probability for achieving remission but with an 83% frequency of adverse events. For post-menopausal women, ciprofloxacin and ofloxacin were 82% more effective for remission with an 49% frequency of adverse events compared with other types of quinolones. Conclusions Compared with other quinolones, ofloxacin (200 mg) was more effective for remission, although with a high probability of adverse events; however, norfloxacin (400 mg) could be an alternative in treatment, due to it low probability of adverse events; even though additional trials are needed to confirm our findings, especially in treatment duration exceeds 3 days. PROSPERO registration CRD42015025886


2021 ◽  
Vol 13 ◽  
Author(s):  
Suparna Chatterjee ◽  
Dwaipayan Sarathi Chakraborty ◽  
Shouvik Choudhury ◽  
Sandeep Lahiry

: The incidence of Carbapenem resistant gram negative (CRGNB) bacterial infections has increased globally. The wide diversity of strains, multiplicity of infections and rapid development and spread of resistance are a matter of great concern both in community and hospital settings. Cefiderocol is a novel injectable siderophore containing cephalosporin with potent microbicidal activity against most Carbapenem Resistant Enterobacteriaceae (CRE). It has recently been approved by USFDA for the treatment of complicated urinary tract infections (cUTI) caused by susceptible gram-negative microorganisms. This review focuses on the salientpharmacological profile of the drug and the clinical studies that were undertaken.


2020 ◽  
Author(s):  
Aliakbar Vaisi-Raygani ◽  
Nader Salari ◽  
Mohammad mahdi Karami ◽  
Shadi Bokaee ◽  
Masoud Mohammadi ◽  
...  

Abstract Background Urinary tract infection is the most common infection in type 2 diabetic patients. Various studies have reported different outbreaks of urinary tract infections in type 2 diabetic patients, Therefore, the present study aimed to determine the prevalence of urinary tract infections in type 2 diabetic patients during a systematic review and meta-analysis to open windows to more detailed programs to reduce the incidence of urinary tract infections in type 2 diabetic patients. Methods In this study, systematic review and Meta-Analysis of study data related to the prevalence of urinary tract infection in type 2 diabetic patients using keywords including: Type 2 diabetes, urinary tract infection, diabetes, prevalence, Meta-Analysis and their English equivalents in SID, MagIran, IranMedex, IranDoc, Google scholar, Cochrane, Embase, Science Direct, Scopus, PubMed and Web of Science (ISI) databases over the years It was mined from 1993 to 2020.In order to perform the analysis of qualified studies, the model of random effects was used and the inconsistency of studies with I2 index was investigated. Data analysis was performed with Comprehensive Meta-Analysis (version 2). Results In a study of 15 studies with a sample size of 827,948 in Meta-Analysis, the overall prevalence of urinary tract infection in patients with type 2 diabetes was 11.5% (95% confidence interval: 7.8–16.7%). Increasing the number of years of research, the prevalence of urinary tract infections in diabetic patients of the Iranian type increased (P = 0.000), and with increasing age of participants (P = 0.000) and also with increasing sample size (P = 0.000), this prevalence decreased. Conclusion The results of this study show that urinary tract infections are highly prevalent in patients with type 2 diabetes, so due to the growing prevalence of diabetes and its complications such as urinary tract infections, the need for appropriate screening programs and health care policies is becoming more apparent.


Author(s):  
Fahimeh Bagheri Amiri ◽  
Sanaz Tavasoli ◽  
Nasrin Borumandnia ◽  
Maryam Taheri

Background: The prevalence and risk factors of urinary tract infection (UTI) in neonates with unexplained hyperbilirubinemia are not studied thoroughly. Since the prevalence of UTI is highly variable in different areas and countries, this study aimed to review the existing data of Iranian neonates with UTI presented with unexplained hyperbilirubinemia. Methods: This study is a meta-analysis of Iranian newborns with unexplained hyperbilirubinemia. We identified all studies indexed in international (Web of Science, PubMed, Scopus, Google Scholar) and national (Science Information Database, Magiran) databases from 2000-2018. Search terms included: Urinary Tract Infections OR UTI AND urine OR culture OR microbio, jaundice OR icter OR hyperbili, AND Iran. Results: Overall, 4210 neonates from 17 studies were included. The pooled prevalence of UTI in neonates with unexplained hyperbilirubinemia was 6.81% (95% CI: 4.86-8.77). Considering the subgroups analyses; the prevalence of UTI was higher in the prolonged vs. not-prolonged state (8.34% vs. 4.00%), low birth weight vs. normal birth weight (7.81% vs. 4.51%), and exclusive vs. non-exclusive breastfeeding (8.84% vs. 4.72%). Male gender and low birth weight increased the risk of UTI about two times compared to the female gender and normal birth weight, respectively. The results of the analyses in neonates with unconjugated hyperbilirubinemia also showed the above-mentioned subgroup differences.  


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