Complete genome sequence, phenotypic correlation and pangenome analysis of uropathogenic Klebsiella spp.

Urinary tract infections (UTI) by antibiotic resistant and virulent K. pneumoniae are a growing concern. Understanding the genome and validating the genomic profile along with pangenome analysis will facilitate surveillance of high-risk clones of K. pneumoniae to underpin management strategies toward early detection. The present study aims to correlate resistome with phenotypic antimicrobial resistance and virulome with pathogenicity in Klebsiella spp. The present study aimed to perform complete genome sequences of Klebsiella spp. and to analyse the correlation of resistome with phenotypic antimicrobial resistance and virulome with pathogenicity. To understand the resistome, pangenome and virulome in the Klebsiella spp, the ResFinder, CARD, IS Finder, PlasmidFinder, PHASTER, Roary, VFDB were used. The phenotypic susceptibility profiling identified the uropathogenic kp3 to exhibit multi drug resistance. The resistome and in vitro antimicrobial profiling showed concordance with all the tested antibiotics against the study strains. Hypermucoviscosity was not observed for any of the test isolates; this phenotypic character matches perfectly with the absence of rmpA and magA genes. To the best of our knowledge, this is the first report on the presence of ste, stf, stc and sti major fimbrial operons of Salmonella enterica serotype Typhimurium in K. pneumoniae genome. The study identifies the discordance of virulome and virulence in Klebsiella spp. The complete genome analysis and phenotypic correlation identify uropathogenic K. pneumoniae kp3 as a carbapenem-resistant and virulent pathogen. The Pangenome of K. pneumoniae was open suggesting high genetic diversity. Diverse K serotypes were observed. Sequence typing reveals the prevalence of K. pneumoniae high-risk clones in UTI catheterised patients. The study also highlights the concordance of resistome and in vitro susceptibility tests. Importantly, the study identifies the necessity of virulome and phenotypic virulence markers for timely diagnosis and immediate treatment for the management of high-risk K. pneumoniae clones.

Comparison of the penile microbiome in infant male circumcision: Mogen clamp versus Shangring.

BACKGROUND: This study aimed to characterise the infant penile (coronal sulcus) microbiome and the effects of early infant male circumcision (EIMC), following a standard surgical method (Mogen Clamp) and a non-surgical alternative (ShangRing). METHODS: We collected coronal sulcus swabs at baseline and on days 7 and 14 post-circumcision from infants assigned to receive EIMC by Mogen Clamp (n = 15) or ShangRing (n = 15), in a randomised trial in Rakai and Kakuuto, Uganda. We used 16S rRNA gene-based sequencing and broad-coverage qPCR to characterise the infant penile microbiome and assess the effects of EIMC in both study arms. FINDINGS: Prior to EIMC, the infant penile microbiome had a mixture of facultative and strict anaerobes. In both study arms, EIMC caused penile microbiome proportional abundance changes characterised by decreases in penile anaerobes [ShangRing Prevotella: -15.0%, (SD = 19.1); Mogen clamp Prevotella: -3.6% (11.2); ShangRing Veillonella: -11.3% (17.2); Mogen clamp Veillonella: -2.6% (11.8)] and increases in skin-associated facultative anaerobes [ShangRing Corynebacterium: 24.9%, (22.4); Mogen clamp Corynebacterium: 4.7% (21.3); ShangRing Staphylococcus: 21.1% (20.5); Mogen clamp Staphylococcus: 18.1% (20.1)]. Clostridium tetani was not detected during the study. INTERPRETATION: Mogen Clamp and ShangRing EIMC both changed the composition of the infant penile microbiome by reducing the proportional abundances of anaerobes and uropathogens, which is consistent with medical male circumcision findings in adults. C. tetani was not increased by either EIMC method. FUNDING: Bill and Melinda Gates Foundation.

Macrolide Resistance in the Aerococcus urinae Complex: Implications for Integrative and Conjugative Elements.

The recognition of the Aerococcus urinae complex (AUC) as an emerging uropathogen has led to growing concerns due to a limited understanding of its disease spectrum and antibiotic resistance profiles. Here, we investigated the prevalence of macrolide resistance within urinary AUC isolates, shedding light on potential genetic mechanisms. Phenotypic testing revealed a high rate of macrolide resistance: 45%, among a total of 189 urinary AUC isolates. Genomic analysis identified integrative and conjugative elements (ICEs) as carriers of the macrolide resistance gene ermA, suggesting horizontal gene transfer as a mechanism of resistance. Furthermore, comparison with publicly available genomes of related pathogens revealed high ICE sequence homogeneity, highlighting the potential for cross-species dissemination of resistance determinants. Understanding mechanisms of resistance is crucial for developing effective surveillance strategies and improving antibiotic use. Furthermore, the findings underscore the importance of considering the broader ecological context of resistance dissemination, emphasizing the need for community-level surveillance to combat the spread of antibiotic resistance within the urinary microbiome.

Prevalence, antibiotic resistance pattern for bacteriuria from patients with urinary tract infections.

Background and Aims: Antibiotic resistance presents a significant global public health challenge, particularly for urinary tract infections (UTIs), and is notably severe in developing countries. Surveillance of the antimicrobial susceptibility patterns of UTI-causing bacteria is crucial for effective treatment selection. This study aimed to analyze these patterns in bacteria isolated from the urine samples of patients at Mughda Medical College Hospital, Dhaka, Bangladesh. Methods: A retrospective study (January 2019 to December 2020) at Mugdha Medical College and Hospital, Dhaka, examined clinical and laboratory data from patients with positive urine cultures (≥105 CFU/mL). The study classified patients into four age groups: children (1-<18 years), young adults (18-<33 years), middle-aged adults (33-50 years), and old adults (>50 years). The standard Kirby-Bauer method was used to assess antibiotic sensitivity to 28 common antibiotics. Results: Among 243 positive urine cultures in both community- and hospital-acquired UTIs, Escherichia coli was the most common uropathogen (65.84%), followed by Klebsiella spp. (12.34%), Enterococcus spp. (8.23%), and other types of bacteria. Conclusion: Old adults are particularly vulnerable to UTIs, with E. coli being the predominant causative agent in the study region. The observed antimicrobial resistance patterns underscore the necessity of judicious antibiotic selection to effectively treat UTIs across different age groups.

Enhancing a multi-purpose artificial urine for culture and gene expression studies of uropathogenic Escherichia coli strains.

AIMS: The main objective of this study was to modify a recently reported multi-purpose artificial urine (MP-AU) for culture and gene expression studies of uropathogenic Escherichia coli (UPEC) strains. METHODS AND RESULTS: We used liquid chromatography mass spectrometry (LC-MS) to identify and adjust the metabolic profile of MP-AU closer to that of pooled human urine (PHU). Modification in this way facilitated growth of UPEC strains with growth rates similar to those obtained in PHU. Transcriptomic analysis of UPEC strains cultured in enhanced artificial urine (enhanced AU) and PHU showed that the gene expression profiles are similar, with <7% of genes differentially expressed between the two conditions. CONCLUSIONS: Enhancing an MP-AU with metabolites identified in PHU allows the enhanced AU to be used as a substitute for the culture and in vitro gene expression studies of UPEC strains.

Draft genomic sequence for uropathogenic Staphylococcus saprophyticus ATCC 49453.

Staphylococcus saprophyticus, a common contaminant of foods, causes urinary tract infections in humans. Here, we report the draft genomic sequence for S. saprophyticus ATCC 49453, which is currently being used in food safety research.

Uropathogens and their antimicrobial-resistant pattern among suspected urinary tract infections patients in eastern Nepal: A hospital inpatients-based study.

Background: Urinary tract infections are the primary factors that cause mortality and morbidity in patients with underlying comorbid conditions and are responsible for most hospital admissions worldwide. Objectives: The study aims to identify the common bacterial uropathogens and determine their antimicrobial susceptibility pattern, including multidrug-resistant/extensively drug-resistant bacteria. Methods: The descriptive cross-sectional study was conducted among inpatients provisionally suspected of urinary tract infections in the medical ward of Koshi Hospital, Biratnagar, Nepal. Samples were inoculated in a cystine lysine electrolyte-deficient medium, and pure growth of significant bacteria was further subjected Gram staining, biochemical identification, and antimicrobial susceptibility testing as per laboratory standard procedure and Clinical Laboratory Standards Institute guidelines, respectively. Descriptive and inferential statistical analysis was performed to analyze the outcomes and a p-value < 0.05 was considered statistically significant. Results: A total of 305 patients urine specimens were examined, of which 251 (82.29%) samples resulted in significant bacterial growth in the culture. Escherichia coli (62.94%) was the most predominantly isolated organism, followed by Klebsiella pneumoniae (12.35%), Staphylococcus aureus (9.16%), and Pseudomonas aeruginosa (8.76%). Among antimicrobials, colistin had shown absolute susceptibility (100%) toward gram-negative uropathogens followed by carbapenem and aminoglycosides in a majority of uropathogens. Escherichia coli was found to be the leading drug-resistant bacteria (70%) among uropathogens. The presence of multidrug-resistant/extensively drug-resistant bacteria uropathogens was found to be significantly associated with diabetes mellitus and those with combined antimicrobial therapies. Diabetic patients were twice (OR~2) more likely to colonize and develop uropathogens as compared to non-diabetics. Conclusion: Escherichia coli was the most common uropathogens followed by Klebsiella pneumoniae in urinary tract infection patients. The polymyxin group (colistin) of antimicrobials was found to be effective in all multidrug-resistant and extensively drug-resistant uropathogens. The study recommends the need of optimized antimicrobial stewardship program to develop effective strategies in the management of urinary tract infections in diverse healthcare settings.

The dataset on the draft whole-genome sequences of two Pseudomonas aeruginosa strains isolated from urine samples of patients with urinary tract diseases.

Pseudomonas aeruginosa is a widespread multidrug-resistant opportunistic human pathogen with an extremely high mortality rate that leads to urinary tract infection morbidities in particular. Variability and dynamics in genome features and ecological flexibility help these bacteria adapt to many environments and hosts and underlie their broad antibiotic resistance. Overall, studies aimed at obtaining a deeper understanding of the genome organization of UTI-associated P. aeruginosa strains are of high importance for sustainable health care worldwide. Herein, we report the draft assembly of entire genomes of two P. aeruginosa strains, PA18 and PA23, isolated from voided urine of patients with urinary tract diseases (hydronephrosis and urolithiasis, respectively) and determine the most important genetic features for pathogenesis and virulence. Whole-genome sequencing and annotation of genomes revealed high similarity between the two UTI strains along with differences in comparison with other uropathogenic P. aeruginosa and reference strains. The 6 981 635 bp and 6 948 153 bp draft genome sequences with GC contents of 65.9% and 65.8%, respectively, provide new insights into the virulence genetic factors and genes associated with antimicrobial resistance. The whole genome data of PA18 and PA23 have been deposited in the NCBI GenBank database (accession numbers JAQRBF000000000.1 and JAQRBG000000000.1, respectively).

Bacterial profile and extended spectrum beta lactamase screening of urinary tract infection among asymptomatic and symptomatic pregnant women attending antenatal care in ALERT Hospital, Addis Ababa, Ethiopia.

Introduction: The occurrence of extended spectrum beta lactamase-producing uropathogens, especially in pregnant women can result in life-threatening condition and morbidity for both the mother and the newborn due to very limited drug options for treatment of these pathogens. The aim of this study was to determine the bacterial profile, associated factors, and their antimicrobial susceptibility patterns and to identify extended spectrum beta lactamase-producing bacterial uropathogens. Methods: A hospital-based cross-sectional study was conducted from July to September 2018 on a total of 177 pregnant women with and without symptoms of urinary tract infection at ALERT Hospital, Addis Ababa, Ethiopia. From these study participants, 72 have symptoms, whereas 105 have no symptoms. All urine samples were inoculated onto cysteine lactose electrolyte deficient medium and MacConkey agar. Colonies were counted to check the presence of significant bacteriuria. Pure isolates of bacterial pathogen were characterized and identified at species level by colony morphology, gram stain, and standard biochemical procedures. All Gram-negative isolates were put into Muller-Hinton agar plates for antibiotic susceptibility test by Kirby-Bauer disc diffusion technique. Extended spectrum beta lactamase was detected using double-disk synergy methods on Muller-Hinton agar. The data were double entered into epidemiological Information system and analyzed using Statistical Package for Social Science version 26. Results: The overall proportion of urinary tract infection among pregnant women was 14.7% (n = 26/177). Klebsiella pneumoniae was the predominant bacterial etiologic agent of urinary tract infection 26.9% (n = 7/26). The proportion of extended spectrum beta lactamase among Gram-negative isolates was 50% (n = 6/12). Among extended spectrum beta lactamase-producing isolates (100%), all are resistance to amikacin and gentamicin while intermediate level resistance rate of 66.7% was observed among trimethoprim-sulphamethoxazole. They were susceptible for some limited drugs, and these were Nitrofurantoin (83.3%) and Chloramphenicol (83.3%). Conclusions: Majority of extended spectrum beta lactamase-producing isolates exhibited co-resistance to other commonly prescribed antibiotics. This indicates that the option of treatment for these pathogens rapidly decreased from time to time which results serious life-threatening conditions, especially in mother and newborn unless the appropriate measure is taken.

MODERN TRENDS OF CHANGES IN THE MICROBIOTA OF UROGENITAL SYSTEM IN PATIENTS WITH UROLITHIASIS.

OBJECTIVE: Aim: Analysis of trends in the microbial communities of the genitourinary system in patients with urolithiasis. PATIENTS AND METHODS: Materials and Methods: 165 urine samples from patients with urolithiasis was examined. The quantitative isolation of microflora was carried out using the bacteriological method. Microorganisms were identified using API biochemical test systems (bioMerieux, France). The percentage of the various types of microorganisms was determined. The reliability of differences in the frequency of various types of microorganisms isolation in a monoculture and the composition of microbial associations was determined by two-field tables with Fisher's Exact criterion. The GraphPad Prism 7 software was used. RESULTS: Results: 198 bacterial cultures of various types were isolated. In one case, a Candida culture was isolated. E. faecalis was the most frequently isolated culture (29.1% of the isolated strains number); E. coli (18.1% of the total number of isolated cultures; K. pneumoniae (11.1%). There were no significant differences in the rate of E. faecalis compared to E. coli. K. pneumonia was isolated significantly less frequently than E. faecalis. These types of microorganisms were also leaders in the formation of bacterial mixes. In addition, these species are involved in the urease activity of bacteria (directly or indirectly), which contributes to the formation of stones in the genitourinary system. CONCLUSION: Conclusions: E. faecalis is the species most often isolated from patients with purulent-inflammatory processes in patients with urolithiasis, both in the case of mono-infection and as part of mixed bacterial cultures.

Complete closed genome sequences of three multidrug-resistant uropathogenic Escherichia coli.

Infection by antibiotic-resistant extraintestinal pathogenic Escherichia coli may result in treatment failure and thus pose a serious public health threat. Here we report the complete closed genome sequence of three multidrug-resistant (MDR) human uropathogenic E. coli isolates using long-read sequencing technology and de novo assembly.

Nitrofurantoin: properties and potential in treatment of urinary tract infection: a narrative review.

Nitrofurantoin (NF), a wide-spectrum antibiotic accessible since 1953, is utilized widely to treat urinary tract infections as it usually stays active against drug-resistant uropathogen. The use of Nitrofurantoin has increased exponentially since new guidelines have repositioned it as first-line therapy for uncomplicated lower urinary tract infection (UTI). To, although fluoroquinolones are usually used to re-evaluate the first- and second-line therapies for treating uncomplicated UTI, their level of utilization is thought to be inappropriately excessive and will eventually have a detrimental impact; thus, we hypothesize that NF might be the best choice for this condition, because of its low frequency of utilization and its high susceptibility in common UTI pathogens. It can be concluded from this review that NF can be considered as the most effective drug in the treatment of acute urinary infection, but due to the long-term side effects of this drug, especially in elderly patients, it is essential to introduce some criteria for prescribing NF in cases of chronic UTI.

Advantage of precision metagenomics for urinary tract infection diagnostics.

Background: Urinary tract infections (UTIs) remain a diagnostic challenge and often promote antibiotic overuse. Despite urine culture being the gold standard for UTI diagnosis, some uropathogens may lead to false-negative or inconclusive results. Although PCR testing is fast and highly sensitive, its diagnostic yield is limited to targeted microorganisms. Metagenomic next-generation sequencing (mNGS) is a hypothesis-free approach with potential of deciphering the urobiome. However, clinically relevant information is often buried in the enormous amount of sequencing data. Methods: Precision metagenomics (PM) is a hybridization capture-based method with potential of enhanced discovery power and better diagnostic yield without diluting clinically relevant information. We collected 47 urine samples of clinically suspected UTI and in parallel tested each sample by microbial culture, PCR, and PM; then, we comparatively analyzed the results. Next, we phenotypically classified the cumulative microbial population using the Explify® data analysis platform for potential pathogenicity. Results: Results revealed 100% positive predictive agreement (PPA) with culture results, which identified only 13 different microorganisms, compared to 19 and 62 organisms identified by PCR and PM, respectively. All identified organisms were classified into phenotypic groups (0-3) with increasing pathogenic potential and clinical relevance. This PM can simultaneously quantify and phenotypically classify the organisms readily through bioinformatic platforms like Explify®, essentially providing dissected and quantitative results for timely and accurate empiric UTI treatment. Conclusion: PM offers potential for building effective diagnostic models beyond usual care testing in complex UTI diseases. Future studies should assess the impact of PM-guided UTI management on clinical outcomes.

Quantitative multiplex polymerase chain reaction in copies ml-1 linearly correlates with standard urine culture in colonies ml-1 for urinary tract infection (UTI) pathogens.

Standard urine culture (SUC) is the current standard method for confirmation of a urinary tract infection (UTI). SUC identifies microorganisms in urine samples and semi-quantifies these as colony-forming units (CFUs) ml-1. In contrast, quantitative multiplex polymerase chain reaction (q-MPCR) is a culture-independent assay in which the microbes are quantified by targeting genomic sequences and reported as cells ml-1, calculated from copies ml-1. Using serial dilutions within the 104-105 cells ml-1 range, the usual reporting range of SUC, this study compared the quantification results based on SUC and q-MPCR for four uropathogens with the control hemocytometer counts. The results revealed a linear relationship and a 1:1 correlation between the q-MPCR and SUC results. Additional q-MPCR quantification of 36 uropathogenic non-fastidious and fastidious bacteria and yeast indicated a reproducible linear correlation in a 1:1 manner with the control counts over a range of cell densities (103-106 cells ml-1). The results confirm that the quantifications by q-MPCR in cells ml-1 and by SUC in CFUs ml-1 are comparable and answer to the lingering question of how the results of these two methods correlate. Moreover, q-MPCR provided accurate quantification of various microorganisms over wider cell density ranges without the time required for microbial growth.

[Chronic cystitis: how to prolong the relapse-free period?]

INTRODUCTION: Chronic cystitis predominates in the structure of urinary tract infections (UTIs). International guidelines are mainly focused on the treatment of acute uncomplicated cystitis; the approaches for managing patients with chronic cystitis has not been sufficiently developed. MATERIAL AND METHODS: A total of 91 patients were included in prospective multicenter randomized comparative controlled study. They were divided into three groups. In the group 1, 32 women received only standard antibiotic therapy for 5 days. In the group 2, 28 patients (received standard therapy plus rectal suppositories Superlymph 25 IU 1 time per day for 10 days). In the main group, 31 women received standard therapy in combination with the use of rectal suppositories Superlymph at a dose of 10 IU 1 time per day for 20 days. Standard antibiotic therapy included fosfomycin trometamol 3.0 g once and furazidin 100 mg three times for 5 days. To assess the long-term results, patients were invited for a follow-up 6 months after the end of therapy. AIM: To determine the long-term results of combined etiologic and pathogenetic therapy, including Superlymph rectal suppositories at a dose of 10 U and 25 U, in patients with chronic cystitis. RESULTS: Six months later, 82/91 (90.1%) women were examined to assess the long-term results. At 6 months, in group 1 a relapse of the cystitis developed in 17 women (60.7%) after an average of 67.3+/-9.4 days. In group 2, recurrence was observed in 12 patients (44.4%), and the relapse-free period was longer, averaging of 84.3+/-9.2 days. The best results were demonstrated in the main group, in which the relapse-free period lasted an average of 123.5+/-8.7 days, and a relapse developed in only 8 cases (29.6%). In 19 patients (70.4%) there were no symptoms after six months. Differences between groups were highly significant (p<0.001). In all groups, none of the patients had more than one recurrence of the cystitis during the follow-up. CONCLUSION: Combined antibiotic therapy results in the absence of recurrence within six months in 39.3% of patients with chronic cystitis. Complex etiologic and pathogenetic therapy, including Superlymph rectal suppositories, allows to significantly reduce the number of recurrences and prolong the relapse-free period. Among the patients who received a course of local cytokine therapy at a dose of 25 units for 10 days, 55.6% did not have a recurrence of chronic cystitis within 6 months. In the group of patients who, along with etiologic therapy, received Superlymph rectal suppositories at a dose of 10 IU for 20 days, a relapse was absent in 70.4% of patients.

Prevalence of Bacterial Urinary Tract Infection, Associated Risk Factors, and Antimicrobial Resistance Pattern in Addis Ababa, Ethiopia: A Cross-Sectional Study.

Background: Urinary tract infections (UTIs) brought a significant and serious health-related problem that may lead to the subsequent development of serious indications with the challenge of the emergence of antibiotic resistance. Therefore, the choice of antibiotics depends on the accuracy of the diagnostic tool of UTIs to minimize false results that may subject patients to wrong treatments. This study aimed to determine the prevalence of bacteriuria, associated factors, and AMR pattern of UTI-suspected patients. Methods: A cross-sectional study was conducted from March to May 2022, at Arsho Advanced Medical Laboratory (AAML), Addis Ababa, Ethiopia. Species identification and isolation from bacterial colonies were characterized by gram stain and biochemical properties followed by antibiotic susceptibility testing using the Kirby-Bauer method on Muller-Hinton agar. Logistic regression analysis was carried out to determine the association between the independent variables and significant bacterial growth to identify factors that affect the prevalence of UTI. A test is considered statistically significant that has a P value less than 0.05. Results: Out of 141 (31.6%) which yielded significant bacteriuria, 16 different species of bacterial uropathogens were identified. A total of 105/446 (91 Gram-negative and 14 Gram-positive) of bacterial growth in the female gender and 36/446 (33 Gram-negative and 3 Gram positive) in male were observed with a P value of 0.03. The most predominant bacteria were E. coli followed by Klebsiella pneumoniae. Amoxicillin had shown the highest resistance rate (100%) followed by Ampicillin (98.9%). Females and participants with previous infections were shown to be associated with significant bacterial growth. Conclusion: Based on our study finding, the ordinarily used antibiotics seem to face emerging resistant strains, which needs considerable and due attention to the impact of UTI in developing countries including Ethiopia. History of previous UTIs and female gender were shown to be possible risk factors associated with UTIs.

Increased demand of urine cultures from Danish general practice: a five-year register-based study.

OBJECTIVE: To characterise and explore the development in the number and content of urine samples sent from general practice in the North Denmark Region to the Department of Clinical Microbiology (DCM) at Aalborg University Hospital during a five-year period. DESIGN: A register-based study. SETTING: General practice. SUBJECTS: Urine samples received at DCM, Aalborg University Hospital from general practice between 2017 and 2022. MAIN OUTCOME MEASURES: Number and content of urine samples. RESULTS: A total of 255,271 urine samples from general practice were received at DCM, with 76.1% being from female patients. Uropathogens were identified in 43.0% of the samples. During the five-year period, a 23.0% increase in the number of urine samples per person (incidence rate ratio (IRR) 1.23, 95% CI 1.21-1.25) was observed. A slight increase in the proportion of positive cultures (risk ratio (RR) 1.03, 95% CI 1.01-1.05) was seen. No notable change in the patient population (age, gender) was observed. Overall, Escherichia coli was the most identified uropathogen (60.4%) followed by Klebsiella spp. (8.7%) and Enterococcus spp. (7.7%). Distribution of the various uropathogens differed slightly depending on patient gender and age, importantly E. coli was less frequently observed in males aged >65 years. CONCLUSION: During the past five years an increasing amount of urine cultures have been requested at DCM from general practice. Importantly, the cause(s) of this increasing demand needs to be explored further in future studies.

Appropriate diagnostics of urinary tract infections can reduce the use of antibiotics in general practice.From 2017 to 2022 a 23% increase per person in requested urine cultures from general practice was observed.A slight increase in positive cultures was found, but no notable change in the patient population (age, gender) was seen.E. coli was the most identified uropathogen independent of gender and age, however, the proportion differed within the various groups.

Antibiotic management of urinary tract infections in the post-antibiotic era: a narrative review highlighting diagnostic and antimicrobial stewardship.

BACKGROUND: As one of the most common indications for antimicrobial prescription in the community, the management of urinary tract infections (UTIs) is both complicated by, and a driver of, antimicrobial resistance. OBJECTIVES: To highlight the key clinical decisions involved in the diagnosis and treatment of UTIs in adult women, focusing on clinical effectiveness and both diagnostic and antimicrobial stewardship as we approach the post-antimicrobial era. SOURCES: Literature reviewed via directed PubMed searches and manual searching of the reference list for included studies to identify key references to respond to the objectives. A strict time limit was not applied. We prioritised recent publications, randomised trials, and systematic reviews (with or without meta-analyses) where available. Searches were limited to English language articles. A formal quality assessment was not performed; however, the strengths and limitations of each paper were reviewed by the authors throughout the preparation of this manuscript. CONTENT: We discuss the management of UTIs in ambulatory adult women, with particular focus on uncomplicated infections. We address the diagnosis of UTIs, including the following: definition and categorisation; bedside assessments and point-of-care tests; and the indications for, and use of, laboratory tests. We then discuss the treatment of UTIs, including the following: indications for treatment, antimicrobial sparing approaches, key considerations when selecting a specific antimicrobial agent, specific treatment scenarios, and duration of treatment. We finally outline emerging areas of interest in this field. IMPLICATIONS: The steady increase in antimicrobial resistance among common uropathogens has had a substantial affect on the management of UTIs. Regarding both diagnosis and treatment, the clinician must consider both the patient (clinical effectiveness and adverse effects, including collateral damage) and the community more broadly (population-level antimicrobial selection pressure).

Antibiotic resistance of uropathogens among the community-dwelling pregnant and nonpregnant female: a step towards antibiotic stewardship.

BACKGROUND: Indiscriminate and widespread use of antibiotics has resulted in emergence of many antibiotic-resistant organisms. Antibiotic administration during pregnancy is mostly avoided, unless there is compelling medical condition. We hypothesized that the uropathogens isolated from pregnant women would be more susceptible to antibiotics compared to those isolated from nonpregnant women, thus will be helpful in formulating separate empiric guideline for pregnant women based on the resistance pattern. METHODS: This was a prospective cross-sectional study conducted over a period of 2 years in which females with the clinical diagnosis of either cystitis or asymptomatic bacteriuria during pregnancy were included from the community settings. Uropathogen species and their antimicrobial resistance pattern were compared between the pregnant and nonpregnant groups. After accounting for centre-to-centre variation and adjusting for age and socio-economic status, the adjusted odds ratio for antibiotic resistance was calculated and compared between pregnant and nonpregnant women using logistic regression analysis. RESULTS: A total of 1758 women (pregnant: 43.3%; nonpregnant: 56.6%) were screened in the study over a period of 2 years, out of which 9.3% (163/1758) were having significant bacteriuria. Escherichia coli and Klebsiella pneumoniae were the two commonest uropathogen in both the groups; their prevalence being 83.6% in pregnant women and 85.2% in nonpregnant women, respectively. Resistance against ampicillin, cefixime, cefoxitin, ceftazidime, ceftriaxone and amoxicillin-clavulanic acid were found significantly lower in the pregnant women compared to nonpregnant. After adjusting the age and socio-economic status accounting for centre-to-centre variation, the odds of resistance for cefixime, amoxicillin-clavulanic acid and co-trimoxazole were found lower and statistically significant among the pregnant women group. CONCLUSIONS: The antimicrobial resistance was significantly higher among the community-dwelling nonpregnant women compared to pregnant women in case of few antibiotics. The study highlighted the need of building local antibiogram that could help to initiate the empirical treatment and thus prevent emergence of antimicrobial resistance.

The Antimicrobial Resistance (AMR) Rates of Uropathogens in a Rural Western African Area-A Retrospective Single-Center Study from Kpando, Ghana.

Little is known about the antimicrobial resistance (AMR) status of uropathogens in Western Africa. We performed a retrospective evaluation of urine cultures collected from the rural Margret Marquart Catholic Hospital, Kpando, Ghana during the time period from October 2019−December 2021. Urine samples from 348 patients (median age 40 years, 52.6% male) were examined. Of these, 125 (35.9%) showed either fungal or bacterial growth, including Escherichia coli in 48 (38.4%), Candida species (spp.) in 29 (23.2%), Klebsiella spp. in 27 (21.6%), Proteus spp. in 12 (9.6%), Citrobacter spp. in 10 (8.0%), Salmonella spp. in 4 (3.2%), Staphylococcus spp. in 3 (2.4%), and Pseudomonas spp. in 2 (1.6%) cases. Two bacterial spp. were detected in 7 samples (5.6%). Antibiotic susceptibility testing showed resistance to a mean 8.6 out of 11 tested antibiotics per patient. Significant predictors (p < 0.05) of bacterial growth were age (OR 1.03), female sex (OR 3.84), and the number of pus cells (OR 1.05) and epithelial cells (OR 1.07) in urine microscopy. We observed an alarmingly high AMR rate among the uropathogens detected, even to reserve antibiotics. A similar resistance profile can be expected in West African patients living in high-income countries. These observations warrant the implementation of restrictive antibiotic protocols, together with the expansion of urine culture testing capacities, improvement of documentation and reporting of AMR rates, and continued research and development of new antibiotic therapies in order to stem the progression of AMR in this West African region.