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Clinical Microbiology and Infection :... Dec 2022Randomised controlled trials (RCTs) investigated analgesics, herbal formulations, delayed prescription of antibiotics, and placebo to prevent overprescription of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Randomised controlled trials (RCTs) investigated analgesics, herbal formulations, delayed prescription of antibiotics, and placebo to prevent overprescription of antibiotics in women with uncomplicated urinary tract infections (uUTI).
OBJECTIVES
To estimate the effect of these strategies and to identify symptoms, signs, or other factors that indicate a benefit from these strategies.
DATA SOURCES
MEDLINE, EMBASE, Web of Science, LILACS, Cochrane Database of Systematic Reviews and of Controlled Trials, and ClinicalTrials.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS
RCTs investigating any strategies to reduce antibiotics vs. immediate antibiotics in adult women with uUTI in primary care.
METHODS
We extracted individual participant data (IPD) if available, otherwise aggregate data (AD). Bayesian random-effects meta-analysis of the AD was used for pairwise comparisons. Candidate moderators and prognostic indicators of treatment effects were investigated using generalised linear mixed models based on IPD.
RESULTS
We analysed IPD of 3524 patients from eight RCTs and AD of 78 patients. Non-antibiotic strategies increased the rates of incomplete recovery (OR 3.0; 95% credible interval (CrI), 1.7-5.5; Bayesian p-value (p) = 0.0017; τ = 0.6), subsequent antibiotic treatment (OR 3.5; 95% CrI, 2.1-5.8; p = 0.0003) and pyelonephritis (OR 5.6; 95% CrI, 2.3-13.9; p = 0.0003). Conversely, they decreased overall antibiotic use by 63%. Patients positive for urinary erythrocytes and urine culture were at increased risk for incomplete recovery (OR 4.7; 95% CrI, 2.1-10.8; p = 0.0010), but no difference was apparent where both were negative (OR 0.8; 95% CrI, 0.3-2.0; p = 0.667). In patients treated using non-antibiotic strategies, urinary erythrocytes and positive urine culture were independent prognostic indicators for subsequent antibiotic treatment and pyelonephritis.
CONCLUSIONS
Compared to immediate antibiotics, non-antibiotic strategies reduce overall antibiotic use but result in poorer clinical outcomes. The presence of erythrocytes and tests to confirm bacteria in urine could be used to target antibiotic prescribing.
Topics: Female; Adult; Humans; Anti-Bacterial Agents; Urinary Tract Infections; Pyelonephritis
PubMed: 35788049
DOI: 10.1016/j.cmi.2022.06.017 -
Clinical Microbiology and Infection :... Sep 2014Human polyomaviruses (HPyVs) are a growing challenge in immunocompromised patients in view of the increasing number of now 12 HPyV species and their diverse disease... (Review)
Review
Human polyomaviruses (HPyVs) are a growing challenge in immunocompromised patients in view of the increasing number of now 12 HPyV species and their diverse disease potential. Currently, histological evidence of disease is available for BKPyV causing nephropathy and haemorrhagic cystitis, JCPyV causing progressive multifocal leukoencephalopathy and occasionally nephropathy, MCPyV causing Merkel cell carcinoma and TSPyV causing trichodysplasia spinulosa, the last two being proliferative skin diseases. Here, the current role of HPyV in solid organ transplantation (SOT) was reviewed and recommendations regarding screening, monitoring and intervention were made. Pre-transplant screening of SOT donor or recipient for serostatus or active replication is currently not recommended for any HPyV. Post-transplant, however, regular clinical search for skin lesions, including those associated with MCPyV or TSPyV, is recommended in all SOT recipients. Also, regular screening for BKPyV replication (e.g. by plasma viral load) is recommended in kidney transplant recipients. For SOT patients with probable or proven HPyV disease, reducing immunosuppression should be considered to permit regaining of immune control. Antivirals would be desirable for treating proven HPyV disease, but are solely considered as adjunct local treatment of trichodysplasia spinulosa, whereas surgical resection and chemotherapy are key in Merkel cell carcinoma. Overall, the quality of the clinical evidence and the strength of most recommendations are presently limited, but are expected to improve in the coming years.
Topics: Epidemiological Monitoring; Europe; Humans; Immunocompromised Host; Immunosuppressive Agents; Infection Control; Mass Screening; Organ Transplantation; Polyomavirus Infections; Transplant Recipients
PubMed: 24476010
DOI: 10.1111/1469-0691.12538 -
Family Practice Sep 2017To summarize the evidence comparing the effectiveness of short and long courses of oral antibiotics for infections treated in outpatient settings. (Review)
Review
PURPOSE
To summarize the evidence comparing the effectiveness of short and long courses of oral antibiotics for infections treated in outpatient settings.
METHODS
We identified systematic reviews of randomized controlled trials for children and adults with bacterial infections treated in outpatient settings from Medline, Embase, CINAHL, Cochrane Database of Systematic Reviews and The Database of Review of Effects. Data were extracted on the primary outcome of clinical resolution and secondary outcomes.
RESULTS
We identified 30 potential reviews, and included 9. There was no difference in the clinical cure for children treated with short or long course antibiotics for Group A streptococcal tonsillopharyngitis (OR 1.03, 95% CI:0.97, 1.11); community acquired pneumonia (RR 0.99, 95% CI:0.97, 1.01); acute otitis media [<2 years old OR: 1.09 (95% CI:0.76, 1.57); ≥2 years old OR: 0.85 (95% CI:0.60, 1.21)]; or urinary tract infection (RR 1.06, 95% CI:0.64, 1.76). There was no difference in the clinical cure for adults treated with short or long course antibiotics for acute bacterial sinusitis (RR 0.95, 95% CI:0.81, 1.21); uncomplicated cystitis in non-pregnant women (RR 1.10, 95% CI:0.96, 1.25), or elderly women (RR: 0.98, 95% CI:0.62, 1.54); acute pyelonephritis (RR 1.03, 95% CI:0.80, 1.32); or community acquired pneumonia (RR: 0.96, 95% CI:0.74, 1.26). We found inadequate evidence about the effect on antibiotic resistance.
CONCLUSIONS
This overview of systematic reviews has identified good quality evidence that short course antibiotics are as effective as longer courses for most common infections managed in ambulatory care. The impact on antibiotic resistance and associated treatment failure requires further study.
Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; Outpatients; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Time Factors
PubMed: 28486675
DOI: 10.1093/fampra/cmx037 -
Open Forum Infectious Diseases Dec 2019Adenovirus (ADV) infection after kidney transplantation (KT) causes significant morbidity. Patient characteristics and outcomes of ADV infection in KT recipients were...
OBJECTIVE
Adenovirus (ADV) infection after kidney transplantation (KT) causes significant morbidity. Patient characteristics and outcomes of ADV infection in KT recipients were investigated.
METHOD
All adult KT recipients with ADV infection between January 2015 and June 2019 were included. ADV infection/disease was defined as detection of ADV DNA in clinical specimens/plus symptoms. Clinical and laboratory findings, treatments, and outcomes were assessed.
RESULTS
Adenovirus infection was diagnosed in 24 of 751 (3.2%) KT recipients. Twenty (83%) were male with a median age of 47 years (interquartile range [IQR], 36-58). Fifteen (63%) underwent deceased donor KT, and 13 (54%) received induction therapy. Twenty-one (88%) and 4 (17%) patients developed hemorrhagic cystitis and disseminated disease, respectively. There were equal distributions of early-onset (EOI) (≤3 months) and late-onset (LOI) (>3 months) infections. Patients who were diagnosed with EOI had lower median absolute lymphocyte counts compared with those with LOI (735/mm [IQR, 543-1123] vs 1122/mm [IQR, 784-1344], = .04). All achieved resolution after reduction of their immunosuppression regimen and 13 (54%) received cidofovir therapy. Eighteen (75%) developed allograft dysfunction, of which 67% were transient. One (4%) underwent nephrectomy for allograft failure and 1 (4%) died (non-ADV-related). Patients with EOI were more likely to receive cidofovir therapy (75% vs 33%, = .04) and develop other opportunistic infections (75% vs 8%, < .001).
CONCLUSIONS
Adenovirus infection after KT typically involves a genitourinary system and transiently impairs an allograft function. Those who developed early infection tend to have more lymphopenia, coinfection, and receive antiviral therapy.
PubMed: 32128332
DOI: 10.1093/ofid/ofz489 -
BMC Pregnancy and Childbirth Apr 2018Urinary tract infections (UTIs) are common in pregnancy and account for the highest proportion of primary care antibiotic prescriptions issued to pregnant women in the...
BACKGROUND
Urinary tract infections (UTIs) are common in pregnancy and account for the highest proportion of primary care antibiotic prescriptions issued to pregnant women in the UK. It is well known that antibiotic use is associated with increased antimicrobial resistance and therefore measures to minimise antibiotic use for UTI prevention have been studied. The efficacy and safety of these measures in pregnancy have not been addressed and therefore the aim of this study was to systematically review the literature to identify and evaluate potential measures to prevent UTIs in pregnant women.
METHODS
Ten databases (EMBASE, AMED, BNI, CINAHL, Medline, PubMed, PsycINFO, Cochrane Trials, Scopus and Science Direct) were systematically searched in July 2017 for studies reporting non-antibiotic measures to prevent UTIs in pregnancy. The terms ("urinary tract infection" or UTI or bacteriuria or cystitis) AND (prevention) AND (pregnan*) were used. The quality of the publications was appraised using the Critical Appraisal Skills Programme (CASP) checklists for cohort study, case-control study and randomised controlled trial. The results were synthesised using a textual narrative approach.
RESULTS
Search results yielded 3276 publications and after reviewing titles and removing duplicates, 57 full text articles were assessed for eligibility and eight were included in the review. Five different approaches (hygiene measures, cranberry juice, immunisation, ascorbic acid and Canephron® N) have been identified, all of which are reported to be safe in pregnancy.
CONCLUSION
The quality of the evidence varied considerably and only hygiene measures were supported by evidence to be recommended in practice. Future work needs to concentrate on strengthening the evidence base through improved design and reporting of studies with a focus on immunisation, ascorbic acid and Canephron® N.
Topics: Ascorbic Acid; Dietary Supplements; Female; Fruit and Vegetable Juices; Humans; Hygiene; Immunization; Phytotherapy; Plant Extracts; Pregnancy; Pregnancy Complications, Infectious; Prenatal Care; Urinary Tract Infections; Vaccinium macrocarpon
PubMed: 29653573
DOI: 10.1186/s12884-018-1732-2 -
Journal of Environmental and Public... 2020Antimicrobial resistance among community-acquired uropathogens is an emerging concern over the past decades that warrants a continuing reevaluation of the...
BACKGROUND
Antimicrobial resistance among community-acquired uropathogens is an emerging concern over the past decades that warrants a continuing reevaluation of the appropriateness of recommended empiric antimicrobial regimens for treatment of urinary tract infections (UTIs).
AIMS
To describe the microbial spectrum and resistance profile of community-acquired uropathogens and predictors of isolation of resistant strains.
METHODS
Between October 2017 and June 2019, individuals who visited the outpatient clinics for diagnosis of UTIs or screening of asymptomatic bacteriuria were included in the study if they were tested for urine culture in one of the three main medical diagnostic laboratories of Mashhad, Iran. The standard disk diffusion antimicrobial susceptibility testing was used, with the Clinical and Laboratory Standards Institute (CLSI) threshold cutoffs for susceptibility of isolated uropathogens.
RESULTS
Three hundred thirty cases were included with a median age of 47 years. Two hundred seventy-six (83.6%) were female. The most common isolated uropathogens were in 201 (60.9%) cases and species in 46 (13.9%) cases. isolates showed the highest rates of susceptibility to nitrofurantoin (89.3%), cefixime (75%), and gentamicin (72.4%). Exposure to antibiotics in the past 3 months was a predictor of resistance to ciprofloxacin (OR: 2.8, 95% CI: 1.33-6.28), and older age was a predictor of resistance to TMP-SMX (OR: 2.1, 95% CI: 1.07-3.97) among isolates. and species accounted for about two-thirds of community-acquired uropathogens. In regard to the high susceptibility rates, nitrofurantoin was identified as the first-choice agent for empiric treatment of community-acquired cystitis, while cefixime and gentamicin might be the second-choice alternatives. Ciprofloxacin and TMP-SMX, on the other hand, cannot be considered appropriate agents for empiric therapy of community-acquired UTIs, particularly in those who had exposure to antibiotics in the past 3 months and the elderly.
Topics: Adult; Anti-Bacterial Agents; Bacteria; Community-Acquired Infections; Drug Resistance, Bacterial; Female; Humans; Iran; Microbial Sensitivity Tests; Middle Aged; Risk Factors; Urinary Tract Infections
PubMed: 33082791
DOI: 10.1155/2020/3439497 -
Viruses Jul 2020Human BK polyomavirus (BKPyV) prevalence has been increasing due to the introduction of more potent immunosuppressive agents in transplant recipients, and its clinical...
Human BK polyomavirus (BKPyV) prevalence has been increasing due to the introduction of more potent immunosuppressive agents in transplant recipients, and its clinical interest. BKPyV has been linked mostly to polyomavirus-associated hemorrhagic cystitis, in allogenic hematopoietic stem cell transplant, and polyomavirus-associated nephropathy in kidney transplant patients. BKPyV is a circular double-stranded DNA virus that encodes for seven proteins, of which Viral Protein 1 (VP1), the major structural protein, has been extensively used for genotyping. BKPyV also contains the noncoding control region (NCCR), configured by five repeat blocks (OPQRS) known to be highly repetitive and diverse, and linked to viral infectivity and replication. BKPyV genetic diversity has been mainly studied based on the NCCR and , due to the high occurrence of BKPyV-associated diseases in transplant patients and their clinical implications. Here BKTyper is presented, a free online genotyper for BKPyV, based on a genotyping and a novel algorithm for NCCR block identification. genotyping is based on a modified implementation of the (BKTGR) algorithm, providing a maximum-likelihood phylogenetic tree using a custom internal BKPyV database. Novel NCCR block identification relies on a minimum of 12-bp motif recognition and a novel sorting algorithm. A graphical representation of the OPQRS block organization is provided.
Topics: Algorithms; BK Virus; Capsid Proteins; Genetic Variation; Genotyping Techniques; Phylogeny; RNA, Untranslated; Software; Virus Replication
PubMed: 32751885
DOI: 10.3390/v12080837 -
MBio Feb 2022Many antibiotic resistant uropathogenic Escherichia coli (UPEC) strains belong to clones defined by their multilocus sequence type (ST), with ST131 being the most...
Many antibiotic resistant uropathogenic Escherichia coli (UPEC) strains belong to clones defined by their multilocus sequence type (ST), with ST131 being the most dominant. Although we have a good understanding of resistance development to fluoroquinolones and third-generation cephalosporins by ST131, our understanding of the virulence repertoire that has contributed to its global dissemination is limited. Here we show that the genes encoding Afa/Dr fimbriae, a group of adhesins strongly associated with UPEC that cause gestational pyelonephritis and recurrent cystitis, are found in approximately one third of all ST131 strains. Sequence comparison of the AfaE adhesin protein revealed a unique allelic variant carried by 82.9% of -positive ST131 strains. We identify the regulatory region as a hotspot for the integration of insertion sequence (IS) elements, all but one of which alter transcription. Close investigation demonstrated that the integration of an IS element in the regulatory region leads to increased expression of Afa/Dr fimbriae, promoting enhanced adhesion to kidney epithelial cells and suggesting a mechanism for altered virulence. Finally, we provide evidence for a more widespread impact of IS on ST131 genome evolution, suggesting that IS dynamics contribute to strain level microevolution that impacts ST131 fitness. E. coli ST131 is the most common antibiotic resistant UPEC clone associated with human urinary tract and bloodstream infections. Understanding the features of ST131 that have driven its global dissemination remains a critical priority if we are to counter its increasing antibiotic resistance. Here, we utilized a large collection of ST131 isolates to investigate the prevalence, regulation, and function of Afa/Dr fimbriae, a well-characterized UPEC colonization and virulence factor. We show that the genes are found frequently in ST131 and demonstrate how the integration of IS elements in the regulatory region modulates Afa expression, presenting an example of altered virulence capacity. We also exploit a curated set of ST131 genomes to map the integration of the antibiotic resistance-associated IS element in the ST131 pangenome, providing evidence for its widespread impact on ST131 genome evolution.
Topics: Humans; Adhesins, Bacterial; Anti-Bacterial Agents; Clone Cells; DNA Transposable Elements; Drug Resistance, Multiple, Bacterial; Escherichia coli Infections; Urinary Tract Infections; Uropathogenic Escherichia coli; Virulence
PubMed: 35038925
DOI: 10.1128/mbio.03519-21 -
BMC Urology Apr 2005Interstitial cystitis (IC) is a chronic bladder disorder, with symptoms including pelvic and or perineal pain, urinary frequency, and urgency. The etiology of IC is... (Comparative Study)
Comparative Study
BACKGROUND
Interstitial cystitis (IC) is a chronic bladder disorder, with symptoms including pelvic and or perineal pain, urinary frequency, and urgency. The etiology of IC is unknown, but sensitive and specific biomarkers have been described, including antiproliferative factor (APF), heparin-binding epidermal growth factor-like growth factor (HB-EGF), and epidermal growth factor (EGF). However, the relative sensitivity of these biomarkers in ulcerative vs. nonulcerative IC is unknown, and these markers have yet to be validated in another laboratory. We therefore measured these markers in urine from patients with or without Hunner's ulcer, as well as normal controls, patients with bladder cancer, and patients with bacterial cystitis, at the First Hospital of China Medical University.
METHODS
Urine specimens were collected from two groups of Chinese IC patients (38 IC patients with Hunner's ulcers, 26 IC patients without Hunner's ulcers), 30 normal controls, 10 bacterial cystitis patients and 10 bladder cancer patients. APF activity was determined by measuring 3H-thymidine incorporation in vitro, and HB-EGF and EGF levels were determined by ELISA.
RESULTS
APF activity (inhibition of thymidine incorporation) was significantly greater in all IC patient urine specimens than in normal control specimens or in specimens from patients with bacterial cystitis or bladder cancer (p < 0.0001 for each comparison). Urine HB-EGF levels were also significantly lower and EGF levels significantly higher in both groups of IC patients than in the three control groups (p < 0.0001 for each comparison). Although APF and HB-EGF levels were similar in ulcerative and nonulcerative IC patients, EGF levels were significantly higher in IC patients with vs. without ulcers (p < 0.004).
CONCLUSION
These findings indicate that APF, HB-EGF and EGF are good biomarkers for both ulcerative and nonulcerative IC and validate their measurement as biomarkers for IC in Chinese patients.
Topics: Adult; Biomarkers; China; Cystitis, Interstitial; Epidermal Growth Factor; Female; Glycoproteins; Heparin-binding EGF-like Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Ulcer; Urinary Bladder Diseases
PubMed: 15862132
DOI: 10.1186/1471-2490-5-7 -
Nature Communications Sep 2021Uropathogenic Escherichia coli assemble surface structures termed pili or fimbriae to initiate infection of the urinary tract. P pili facilitate bacterial colonization...
Uropathogenic Escherichia coli assemble surface structures termed pili or fimbriae to initiate infection of the urinary tract. P pili facilitate bacterial colonization of the kidney and pyelonephritis. P pili are assembled through the conserved chaperone-usher pathway. Much of the structural and functional understanding of the chaperone-usher pathway has been gained through investigations of type 1 pili, which promote binding to the bladder and cystitis. In contrast, the structural basis for P pilus biogenesis at the usher has remained elusive. This is in part due to the flexible and variable-length P pilus tip fiber, creating structural heterogeneity, and difficulties isolating stable P pilus assembly intermediates. Here, we circumvent these hindrances and determine cryo-electron microscopy structures of the activated PapC usher in the process of secreting two- and three-subunit P pilus assembly intermediates, revealing processive steps in P pilus biogenesis and capturing new conformational dynamics of the usher assembly machine.
Topics: Cryoelectron Microscopy; Escherichia coli Proteins; Fimbriae Proteins; Fimbriae, Bacterial; Models, Molecular; Molecular Chaperones; Protein Binding; Protein Conformation; Uropathogenic Escherichia coli
PubMed: 34471127
DOI: 10.1038/s41467-021-25522-6