Are Escherichia coli causing recurrent cystitis just ordinary Uropathogenic E. coli (UPEC) strains?

Specific determinants associated with Uropathogenic Escherichia coli (UPEC) causing recurrent cystitis are still poorly characterized. The aims of this study were (i) to describe genomic and phenotypic traits associated with recurrence using a large collection of recurrent and paired sporadic UPEC isolates, and (ii) to explore within-host genomic adaptation associated with recurrence using series of 2 to 5 sequential UPEC isolates. Whole genome comparative analyses between 24 recurrent cystitis isolates (RCIs) and 24 phylogenetically paired sporadic cystitis isolates (SCIs) suggested a lower prevalence of putative mobile genetic elements (MGE) in RCIs, such as plasmids and prophages. The intra-patient evolution of the 24 RCI series over time was characterized by SNP occurrence in genes involved in metabolism or membrane transport, and by plasmid loss in 5 out of the 24 RCI series. Genomic evolution occurred early in the course of recurrence, suggesting rapid adaptation to strong selection pressure in the urinary tract. However, RCIs did not exhibit specific virulence factor determinants and could not be distinguished from SCIs by their fitness, biofilm formation, or ability to invade HTB-9 bladder epithelial cells. Taken together, these results suggest a rapid but not convergent adaptation of RCIs that involves both strain- and host-specific characteristics.

Contribution of Antibiotic Susceptibility Testing and CH Typing Compared to Next-Generation Sequencing for the Diagnosis of Recurrent Urinary Tract Infections Due to Genetically Identical Escherichia coli Isolates: a Prospective Cohort Study of Cystitis in Women.

Recurrent cystitis is a common disease in women, mainly due to uropathogenic Escherichia coli (UPEC). For decades, typing methods now considered obsolete suggested that relapse by the same clone is dominant over reinfection, most UPEC strains being otherwise fully susceptible to antibiotics. We aimed to update these data. Thanks to a prospective study over 17 months, we recruited 323 women with cystitis. Of these, 251 of them had sporadic infection and 72 had recurrence, with 2 to 9 episodes per patient for a total of 131 UPEC isolates and 145 UPEC pairs at patient level. Phylogroups B2 (52.4%) and D (14.1%) were overall dominant, as expected due to their particular urovirulence. CH typing identified 119 distinct profiles with no CH type particularly associated with recurrence. Relapse was attested by CH typing for only 30.6% (22 out of 72), with very diverse situations ranging from all episodes due to the same clone to alternating reinfections and relapses. Next-generation sequencing confirmed the clonality for all but two of the 145 UPEC pairs. Antibiotic resistance was common for recurrent cystitis isolates (only 25 [17.2%] out of 145 UPEC pairs were fully susceptible), allowing us to predict UPEC clonality. Indeed, antibiotic susceptibility profile matched CH typing for 104 (71.7%) pairs. Finally, we demonstrated a large genetic diversity among UPEC isolates responsible for cystitis in women, even in cases of recurrence for which reinfection appeared dominant over relapse. Recurrent cystitis appears to be a heterogeneous disease requiring tailored treatment and prevention. IMPORTANCE More than half of women will experience cystitis during their lifetime. Among these women, 25% will experience a second episode within the following 6 months. It is epidemiologically important to discriminate relapses from reinfections. Relapse identification relies on long and laborious methods and might influence treatment. Therefore, the designation of time- and cost-effective strategies for this goal is of particular interest. Our work suggests using CH typing and antibiotic susceptibility profiles to type Escherichia coli, the main uropathogen.

General practitioners' clinical practice on the management of cystitis in Normandy, France: A clinical vignettes-based study.

RATIONALE, AIMS, AND OBJECTIVES: The objective was to measure the quality of clinical practice for the management of cystitis in adult women in general practice by collaborating with quality circles and the regional centre for antibiotic counsel. METHOD: This descriptive cross-sectional study was performed in 2018 in Normandy, France. A questionnaire composed of clinical vignettes was used to evaluate practices of general practitioners (GPs) with regard to cystitis classified into four categories: simple, at risk of complication, recurrent, and caused by multidrug-resistant bacteria. The 2017 French Infectious Diseases Society's guidelines were used as a reference. RESULTS: A total of 142 GPs participated in the study (45.5% of the solicited). Fosfomycin-trometamol and pivmecillinam were cited as first-line treatments for simple cystitis by 134 (94%) and 38 (27%) participants, respectively. For at risk of complication cystitis, the treatments cited were cefixime by 64 participants (45%), ofloxacin by 50 (35%), pivmecillinam by 49 (35%), fosfomycin-trometamol by 38 (27%), nitrofurantoin by 36 (25%), and amoxicillin-clavulanic acid by 28 (20%). Mean compliance rates were 85% for simple cystitis, 39% for at risk of complication cystitis, 60% for recurrent cystitis and 14% for cystitis caused by multidrug-resistant bacteria. Two criteria had less than 10% of the compliant answers: comprehensive knowledge of cystitis complication risk factors (9%) and positivity thresholds of urine cultures (10%). CONCLUSIONS: In this study, diagnostic means, follow-up testing, and simple cystitis treatment (with fosfomycin predominantly mentioned) were broadly compliant. The use of critical antibiotics was too frequent for at risk of complication cystitis. There may be a need to improve the knowledge of professionals on antibiotic resistance and appropriate antibiotic use.

Antibiotic treatment of acute uncomplicated cystitis based on rapid urine test and local epidemiology: lessons from a primary care series.

BACKGROUND: Acute uncomplicated cystitis (AUC) is an ideal target of optimization for antibiotic therapy in primary care. Because surveillance networks on urinary tract infections (UTI) mix complicated and uncomplicated UTI, reliable epidemiological data on AUC lack. Whether the antibiotic choice should be guided by a rapid urine test (RUT) for leukocytes and nitrites has not been extensively studied in daily practice. The aim of this primary care study was to investigate local epidemiology and RUT-daily use to determine the optimal strategy. METHODS: General practitioners included 18-65 years women with symptoms of AUC, performed a RUT and sent urines for analysis at a central laboratory. Different treatment strategies were simulated based on RUT and resistance results. RESULTS: Among 347 enrolled patients, 78% had a positive urine culture. Escherichia coli predominated (71%) with high rates of susceptibility to nitrofurantoin (100%), fosfomycin (99%), ofloxacin (97%), and even pivmecillinam (87%) and trimethoprim-sulfamethoxazole (87%). Modelization showed that the systematic use of RUT would reduce by 10% the number of patients treated. Fosfomycin for patients with positive RUT offered a 90% overall bacterial coverage, compared to 98% for nitrofurantoin. 95% for ofloxacin, 86% for trimethoprim-sulfamethoxazole and 78% for pivmecillinam. CONCLUSION: Local epidemiology surveillance data not biased by complicated UTI demonstrates that the worldwide increase in antibiotic resistance has not affected AUC yet. Fosfomycin first line in all patients with positive RUT seems the best treatment strategy for AUC, combining good bacterial coverage with expected low toxicity and limited effect on fecal flora. TRIAL REGISTRATION: The current study was registered at clinicaltrials.gov (NCT00958295).

Decreases in inflammatory and coagulation biomarkers levels in HIV-infected patients switching from enfuvirtide to raltegravir: ANRS 138 substudy.

Stored plasma specimens from 164 participants in the ANRS 138 trial were analyzed to determine interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and D-dimer levels at baseline and weeks 24 and 48. These virologically suppressed, treatment-experienced patients were randomly assigned to undergo an immediate switch (IS) or a deferred switch (DS; at week 24) from an enfuvirtide-based antiretroviral therapy (ART) regimen to a raltegravir-based regimen. At week 24, a significant decrease from baseline was observed in the IS arm, compared with the DS arm, for IL-6 level (-30% vs +10%; P < .002), hsCRP level (-46% vs +15%; P < .0001), and D-dimer level (-40% vs +6%; P < .0001). At week 48, there was a reproducible decrease in levels of all biomarkers in the DS arm.

[Diagnosis and treatment of community-acquired urinary tract infections in adults: what has changed. Comments on the 2008 guidelines of the French Health Products Safety Agency (AFSSAPS)]. / Prise en charge des infections urinaires communautaires de l'adulte : ce qui a changé. A propos des recommandations 2008 de l'Agence française de sécurité sanitaire des produits de santé (Afssaps).

This article comments on the new recommendations for the diagnosis and treatment of adult patients with community-acquired urinary tract infections (UTIs), issued in 2008 by the French Health Products Safety Agency (AFSSAPS). The terms uncomplicated and complicated UTIs have been retained ; complicated UTIs are those with risk factor for complication (rather than with established complications). In women, age (>or= 65 years) is no longer considered itself a risk factor for complications. In men, cystitis must be treated as prostatitis. The bacterial levels defining UTIs have been revised, but levels below the threshold cannot be used to rule out UTI in the presence of symptoms. For uncomplicated cystitis, only fosfomycin-trometamol is recommended as a first-line treatment, essentially because of its ecological advantages (resistance uncommon, no cross resistance with other antibiotic classes, specific class, sparing others). For recurrent cystitis, prophylactic antibiotic treatment must be limited to cases when other preventive measures are impossible. For complicated cystitis, the principle is to delay antibiotic therapy until the resistance profile results are available, when possible (because of the high risk of resistance). Delay must be avoided during pregnancy, however, because of maternal-fetal risks. The strategy for uncomplicated pyelonephritis has been simplified : no plain abdominal radiography, antibiotic therapy shortened to 10-14 days (even 7 days for regimen or relay including fluoroquinolone), and no routine verification by urine culture. For prostatitis, PSA testing is not recommended during the acute phase of prostatitis, and a 14-day antibiotic regimen is enough for the easiest-to-treat infections.

Acute bacterial prostatitis: heterogeneity in diagnostic criteria and management. Retrospective multicentric analysis of 371 patients diagnosed with acute prostatitis.

BACKGROUND: There is currently a lack of consensus for the diagnosis, investigations and treatments of acute bacterial prostatitis (AP). METHODS: The symptoms, investigations and treatments of 371 inpatients diagnosed with AP were analyzed through a retrospective study conducted in four departments - Urology (U), Infectious Diseases (ID), Internal Medicine (IM), Geriatrics (G) - of two French university hospitals. RESULTS: The cause of admission, symptoms, investigations and treatments depended markedly on the department of admission but not on the hospital. In U, patients commonly presented with a bladder outlet obstruction, they had a large imaging and functional check-up, and received alpha-blockers and anti-inflammatory drugs. In ID, patients were febrile and received longer and more appropriate antibiotic treatments. In G, patients presented with cognitive disorders and commonly had post-void urine volume measurements. In IM, patients presented with a wide range of symptoms, and had very diverse investigations and antibiotic regimen.Overall, a 3:1 ratio of community-acquired AP (CA-AP) to nosocomial AP (N-AP) was observed. Urine culture isolated mainly E. coli (58% of AP, 68% of CA-AP), with venereal agents constituting less than 1%. The probabilistic antibiotic treatments were similar for N-AP and CA-AP (58% bi-therapy; 63% fluoroquinolone-based regimen). For N-AP, these treatments were more likely to be inadequate (42% vs. 8%, p < 0.001) and had a higher rate of bacteriological failure (48% vs. 19%, p < 0.001). Clinical failure at follow-up was more common than bacteriological failure (75% versus 24%, p < 0.001). Patients older than 49 had more underlying urinary tract disorders and a higher rate of clinical failure (30% versus 10%, p < 0.0001). CONCLUSION: This study highlights the difficulties encountered on a daily basis by the physicians regarding the diagnosis and management of acute prostatitis.

[Management of fungal urinary tract infections]. / Prise en charge des mycoses urinaires.

Fungal urinary tract infections (funguria) are rare in community medicine, but common in hospitals where 10 to 30% of urine cultures isolate Candida species. Clinical features vary from asymptomatic urinary tract colonization (the most common situation) to cystitis, pyelonephritis, or even severe sepsis with fungemia. The pathologic nature of funguria is closely related to host factors, and management depends mainly on the patient's underlying health status. Microbiological diagnosis of funguria is usually based on a fungal concentration of more than 10(3)/mm(3) in urine. No cutoff point has been defined for leukocyte concentration in urine. Candida albicans is the most commonly isolated species, but previous antifungal treatment and previous hospitalization affect both species and susceptibility to antifungal agents. Treatment is recommended only when funguria is symptomatic or in cases of fungal colonization when host factors increase the risk of fungemia. The antifungal agents used for funguria are mainly fluconazole and amphotericin B deoxycholate, because other drugs have extremely low concentrations in urine. Primary and secondary preventions are essential. The reduction of risk factors requires removing urinary catheters, limiting antibiotic treatment, and optimizing diabetes mellitus treatment.

Developmentally regulated chromosome fragmentation linked to imprecise elimination of repeated sequences in paramecia.

The chromosomes of ciliates are fragmented at reproducible sites during the development of the polyploid somatic macronucleus, but the mechanisms involved appear to be quite diverse in different species. In Paramecium aurelia, the process is imprecise and results in de novo telomere addition at locally heterogeneous positions. To search for possible determinants of chromosome fragmentation, we have studied an approximately 21-kb fragmentation region from the germ line genome of P. primaurelia. The mapping and sequencing of alternative macronuclear versions of the region show that two distinct multicopy elements, a minisatellite and a degenerate transposon copy, are eliminated by an imprecise mechanism leading either to chromosome fragmentation and the formation of new telomeres or to the rejoining of flanking sequences. Heterogeneous internal deletions occur between short direct repeats containing TA dinucleotides. The complex rearrangement patterns produced vary slightly among genetically identical cell lines, show non-Mendelian inheritance during sexual reproduction, and can be experimentally modified by transformation of the maternal macronucleus with homologous sequences. These results suggest that chromosome fragmentation in Paramecium is the consequence of imprecise DNA elimination events that are distinct from the precise excision of single-copy internal eliminated sequences and that target multicopy germ line sequences by homology-dependent epigenetic mechanisms.

[Bacteriologic diagnosis and antibiotic therapy of urinary tract infections]. / Diagnostic bactériologique et antibiothérapie des infections urinaires.

The laboratory diagnosis and antibiotic treatment of urinary tract infections (UTIs) are very different depending on the clinical context. It is critical to distinguish between uncomplicated infections and infections complicated by abnormalities of the urinary tract or other host factors. Microscopic examination combined with urine culture remains the test of reference, excepted for uncomplicated cystitis. It requires rigorous method and analysis taking into account of clinical data. For empirical therapy, the choice is well codified in case of community acquired UTIs since the bacterial species involved are very stable over time and space, and since their antibiotic resistances are well known (with currently a high prevalence of resistance not only to aminopenicillins but also to amoxicillin-clavulanate and trimethoprim-sulfamethoxazole); in contrast, the treatment of nosocomial UTIs is difficult because of the diversity of causative organisms and of antibiotic resistance profiles.