Drug-resistant Urinary Tract Infections Research Articles

Fosfomycin for the treatment of drug-resistant urinary tract infections: potential of an old drug not explored fully.

Increased emergence of bacterial resistance and the limited options of novel antimicrobial agents have necessitated the reintroduction of some old antimicrobial agents. One such drug is fosfomycin, but its potential has not been explored fully, especially in India. To analyze the in vitro activity of fosfomycin, against the urinary isolates and to compare it with in vitro activity of other orally administered antimicrobial agents. This was a prospective observational study conducted between July 2014 and June 2016. All consecutive, non-duplicate and clinically significant urinary isolates obtained from patients of all ages and both genders, diagnosed to have UTI, were included. Patients already on antibiotic therapy were excluded. Urine culture was performed by semiquantitative method on cysteine lactose electrolyte-deficient medium and the isolates obtained in significant count were subjected to antimicrobial sensitivity testing by the Kirby Bauer disk diffusion method as per CLSI guidelines. A total of 3947 non-repeating urinary isolates were included in the study, of which 2684 (68%) isolates originated from adult outpatients and remaining 1236 (32%) isolates from pediatric patients. Of these 2783 isolates were from enterobacteriaceae family. Out of these 2730 (98.1%) were sensitive to fosfomycin. Most [375 of 385 (97.4%)] Pseudomonas spp were also susceptible to fosfomycin. A majority of ESBL- (96.5%) and MBL (91.9%)-producing isolates were also susceptible to fosfomycin and so were of Gram-positive isolates [698/707 (96%)] and MRSA [61/69 (88.4%)] were susceptible to fosfomycin. Fosfomycin showed an excellent in vitro activity against all urinary pathogens, including the Gram-positive or Gram-negative, ESBL and MBL producers. Fosfomycin should be considered as a highly effective alternative in treatment UTIs in both adults and pediatric patients.

Effectiveness and Safety of Colistin in Multi Drug Resistant Urinary Tract Infections

Effectiveness and Safety of Colistin in Multi Drug Resistant Urinary Tract Infections

The economic burden of urinary tract infections in women visiting general practices in France: a cross-sectional survey.

BackgroundUrinary tract infections (UTIs) are among the most common bacterial infections. Despite this burden, there are few studies of the costs of UTIs. The objective of this study was to determine the costs of UTIs in women over 18 years of age who visit general practitioners in France.MethodsThe direct and indirect costs of clinical UTIs were estimated from societal, French National Health Insurance and patient perspectives. The study population was derived from a national cross-sectional survey entitled the Drug-Resistant Urinary Tract Infection (Druti). The Druti included every woman over 18 years of age who presented with symptoms of UTI and was conducted in France in 2012 and 2013 to estimate the annual incidence of UTIs due to antibiotic-resistant Enterobacteriaceae in women visiting general practitioners (GPs) for suspected UTIs.ResultsOf the 538 women included in Druti, 460 were followed over 8 weeks and included in the cost analysis. The mean age of the women was 46 years old. The median cost of care for one episode of a suspected UTI was €38, and the mean cost was €70. The annual societal cost was €58 million, and €29 million of this was reimbursed by the French National Health Insurance system. In 25 % of the cases, the suspected UTIs were associated with negative urine cultures. The societal cost of these suspected UTIs with negative urine cultures was €13.5 million. No significant difference was found between the costs of the UTIs due to antibiotic-resistant E. coli and those due to wild E. coli (p = 0.63).ConclusionIn the current context in which the care costs are continually increasing, the results of this study suggests that it is possible to decrease the cost of UTIs by reducing the costs of suspected UTIs and unnecessary treatments, as well as limiting the use of non-recommended tests.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-016-1620-2) contains supplementary material, which is available to authorized users.

Previous Antimicrobial Exposure Is Associated With Drug-Resistant Urinary Tract Infections in Children

The aim of this study was to evaluate the impact of previous antimicrobial exposure on the development of antimicrobial resistance in children with their first urinary tract infection (UTI). We conducted a retrospective cohort study of children aged 6 months to 6 years and received their first diagnosis of UTI in a network of 27 outpatient pediatric practices between July 1, 2001, and May 31, 2006. We examined the relationship between antimicrobial resistance in UTI isolates and exposure to specific antimicrobial agents (amoxicillin, amoxicillin-clavulanate, cefdinir, trimethoprim-sulfamethoxazole, and azithromycin) in the previous 120 days. We developed multivariable logistic regression models for resistance to ampicillin, amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, and first-generation and third-generation cephalosporins, adjusting for potential confounders such as age, number of siblings, recent hospitalizations, and child care exposure. Of the 533 children who had a first UTI, 8%, 14%, and 21% were exposed to antimicrobial agents within 30, 60, and 120 days before the UTI, respectively. Amoxicillin exposure within 30 days (odds ratio [OR]: 3.6 [95% confidence interval (CI): 1.6-8.2]) and 31 to 60 days (OR: 2.8 [95% CI: 1.0-7.5]) before UTI both were associated with ampicillin resistance. Exposure to amoxicillin >60 days before the UTI was not associated with ampicillin resistance. Amoxicillin exposure within 30 days of UTI was also associated with amoxicillin-clavulanate resistance (OR: 3.9 [95% CI: 1.8-8.7]). No association between exposure to other antimicrobial agents and resistance to any of the antimicrobial agents was seen. Recent antimicrobial exposure is associated with antimicrobial-resistant UTIs among pediatric outpatients, and the magnitude of this association decreases with time since exposure. Judicious antimicrobial prescribers should consider this association when selecting empiric antimicrobial agents for a new UTI and should use strategies to reduce unnecessary antimicrobial use to avoid development of resistant bacteria.

Previous Antimicrobial Exposure Is Associated With Drug-Resistant Urinary Tract Infections in Children

Previous Antimicrobial Exposure Is Associated With Drug-Resistant Urinary Tract Infections in Children

Clonal Composition ofEscherichia coliCausing Community-Acquired Urinary Tract Infections in the State of Rio de Janeiro, Brazil

Recent studies from North America and Europe have demonstrated community-wide clonal spread of uropathogenic Escherichia coli (UPEC). To investigate if a similar pattern of spread occurs in Brazil, we characterized UPEC from women with community-acquired urinary tract infection (UTI) in Rio de Janeiro. E. coli isolates from women with UTI in one public outpatient clinic were evaluated for antibiotic susceptibility, E. coli phylogenetic grouping, enterobacterial repetitive intergenic consensus (ERIC) 2 PCR and pulsed-field gel electrophoresis fingerprinting, and multilocus sequence typing. From March 2005 to November 2006, 344 patients were studied. Of these, 186 (54%) had confirmed UTI, 118 (63.4%) of which were caused by E. coli. More than 50% of these isolates were resistant to ampicillin and trimethoprim/sulfamethoxazole. Of these, 96 (81%) belonged to 19 ERIC2 clonal groups. The largest group included 15 isolates, all belonging to multilocus sequence typing group ST69 and phylogenetic group D; they had pulsed-field gel electrophoresis patterns sharing at least 89% similarity compared with the CgA reference strain ATCC BAA-457. CgA strains have been found to be widespread in the United States in the early 2000s. Clonal group E. coli strains accounted for a large proportion (52%) of all UTIs and 82% of the trimethoprim/sulfamethoxazole-resistant E. coli UTIs. Thus, as in North America and Europe, UPECs that cause UTI in Rio de Janeiro also show clonal distribution, and a substantial proportion of drug-resistant UTI is caused by a small set of genetically related E. coli strains.

Temporal Changes in the Prevalence of Community-Acquired Antimicrobial-Resistant Urinary Tract Infection Affected by Escherichia coli Clonal Group Composition

The changing prevalence of drug-resistant community-acquired urinary tract infection (UTI) is often attributed to local antimicrobial drug use or prescribing practices. However, recent molecular epidemiologic studies of community-acquired UTI suggest that other factors may play a greater role. We conducted a multiyear, cross-sectional study to characterize temporal changes in the prevalence of drug-resistant community-acquired UTI at a university community in California. During four 3.5-month sampling periods, urine samples from patients consecutively presenting to the university health service with symptoms of UTI were cultured for Escherichia coli. Antimicrobial susceptibility and genotyping tests of the E. coli isolates were performed. We recovered 780 E. coli isolates from 1667 patients with UTI. The prevalence of trimethoprim-sulfamethoxazole, ciprofloxacin, and nitrofurantoin resistance showed no trend over the 4 periods. The prevalence of ampicillin resistance decreased significantly over the last 2 study periods. A single clonal group accounted for 75% of this decrease. Enterobacterial repetitive intergenic consensus 2 PCR-based genotyping revealed that only 4 large clonal groups accounted for 52% of the UTIs resistant to trimethoprim-sulfamethoxazole, ciprofloxacin, or nitrofurantoin. No initially pansusceptible clonal groups gained resistance over time. This study revealed no obvious trend in the prevalence of drug-resistant community-acquired UTI in a single community. Prevalence at any time was influenced by a small number of E. coli clonal groups. This observation suggests that the introduction of strains that are drug resistant into a community plays a greater role in changing the prevalence of drug-resistant UTI than does the drug use or prescribing habits in that community.

Occurrence of Antibiotic-Resistant Uropathogenic Escherichia coli Clonal Group A in Wastewater Effluents

Isolates of Escherichia coli belonging to clonal group A (CGA), a recently described disseminated cause of drug-resistant urinary tract infections in humans, were present in four of seven sewage effluents collected from geographically dispersed areas of the United States. All 15 CGA isolates (1% of the 1,484 isolates analyzed) exhibited resistance to trimethoprim-sulfamethoxazole (TMP-SMZ), accounting for 19.5% of the 77 TMP-SMZ-resistant isolates. Antimicrobial resistance patterns, virulence traits, O:H serotypes, and phylogenetic groupings were compared for CGA and selected non-CGA isolates. The CGA isolates exhibited a wider diversity of resistance profiles and somatic antigens than that found in most previous characterizations of this clonal group. This is the first report of recovery from outside a human host of E. coli CGA isolates with virulence factor and antibiotic resistance profiles typical of CGA isolates from a human source. The occurrence of "human-type" CGA in wastewater effluents demonstrates a potential mode for the dissemination of this clonal group in the environment, with possible secondary transmission to new human or animal hosts.

Possible Animal Origin of Human-Associated, Multidrug-Resistant, Uropathogenic Escherichia coli

The multistate occurrence of cases of urinary tract infection (UTI) caused by trimethoprim-sulfamethoxazole (TMP-SMZ)-resistant Escherichia coli strains belonging to a single clonal group (designated as clonal group A [CgA]) in the United States has raised an intriguing hypothesis that these infections may have been spread by contaminated food products. The present study attempted to determine if CgA strains could be traced to food animals. A total of 495 animal and environmental E. coli isolates, which belonged to serogroups O11, O17, O73, and O77 and were collected between 1965 and 2002 by the Gastroenteric Disease Center at Pennsylvania State University (University Park, PA), were further subtyped by antimicrobial drug susceptibility, enterobacterial repetitive intergenic consensus (ERIC2) PCR, random amplified polymorphic DNA analysis, pulsed-field gel electrophoresis (PFGE), and virulence profile pattern. Of 495 isolates, 128 (26%) had an ERIC2 PCR electrophoretic pattern indistinguishable from that of the human prototype CgA strain, and 14 CgA isolates were resistant to TMP-SMZ. Cluster analysis of PFGE patterns showed that 1 of these 14 isolates, obtained from a cow in 1988, was 94% similar to a CgA uropathogenic human-associated E. coli strain. The pattern for this isolate was included among a cluster of PFGE patterns for 5 human-associated UTI isolates that were >80% similar to each other. These observations suggest that drug-resistant, uropathogenic human-associated E. coli strains potentially have an animal origin. The possibility that human drug-resistant UTI could be a foodborne illness has serious public health implications.

Rapid and specific detection of Escherichia coli clonal group A by gene-specific PCR.

PCR primers specific for the recently described antimicrobial resistance-associated Escherichia coli clonal group A (CGA), a widespread cause of drug-resistant urinary tract infections in the United States, were devised on the basis of a novel single-nucleotide polymorphism identified within the housekeeping gene fumC, i.e., C288T. In comparison with two reference PCR-based fingerprinting methods, ERIC2 PCR and random amplified polymorphic DNA (RAPD) analysis, a PCR assay incorporating the new primers provided 100% sensitivity and 100% specificity for the detection of CGA among 138 diverse clinical and reference E. coli isolates. E. coli reference (ECOR) strain 47 was shown to be a member or a close relative of CGA (by ERIC2 PCR and RAPD analysis, respectively) and yielded a positive assay result. The new CGA-specific PCR assay, which exhibited interlaboratory reproducibility and stability under various experimental conditions, should allow the rapid and specific detection of CGA by any laboratory equipped for diagnostic PCR.