Levofloxacin Versus Ciprofloxacin in the Treatment of Urinary Tract Infections: Evidence-Based Analysis.
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ABSTRACT:
SUBMITTER: Cao D
PROVIDER: S-EPMC8060646 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The broad-spectrum C-8-cyano-fluoroquinolone finafloxacin displays enhanced activity under acidic conditions. This phase II clinical study compared the efficacies and safeties of finafloxacin and ciprofloxacin in patients with complicated urinary tract infection and/or pyelonephritis. A 5-day regimen with 800 mg finafloxacin once a day (q.d.) (FINA05) had results similar to those of a 10-day regimen with 800 mg finafloxacin q.d. (FINA10). Combined microbiological and clinical responses at the test-of-cure (TOC) visit were 70% for FINA05, 68% for FINA10, and 57% for a 10-day ciprofloxacin regimen (CIPRO10) in 193 patients (64 for FINA05, 68 for FINA10, and 61 for CIPRO10) of the microbiological intent-to-treat (mITT) population. Additionally, the clinical effects of ciprofloxacin on patients with an acidic urine pH (80% of patients) were reduced, whereas the effects of finafloxacin were unchanged. Finafloxacin was safe and well tolerated. Overall, 43.4% of the patients in the FINA05 group, 42.7% in the FINA10 group, and 54.2% in the CIPRO10 group experienced mostly mild and treatment-emergent but unrelated adverse events. A short-course regimen of 5 days of finafloxacin resulted in high eradication and improved clinical outcome rates compared to those for treatment with ciprofloxacin for 10 days. In contrast to those of ciprofloxacin, the clinical effects of finafloxacin were not reduced by acidic urine pH. Hospitalized adults were randomized 1:1:1 to finafloxacin treatment (800 mg q.d.) for either 5 or 10 days or to ciprofloxacin treatment (400 mg/500 mg b.i.d.) for 10 days with an optional switch from intravenous (i.v.) to oral administration at day 3. The primary endpoint was the combined microbiological and clinical response at the TOC visit in the microbiological intent-to-treat population. (This study has been registered at ClinicalTrials.gov under identifier NCT01928433.).
| S-EPMC5913919 | biostudies-literature
Project description:Fluoroquinolones are a guideline-recommended therapy for complicated urinary tract infections, including pyelonephritis. Elevated drug concentrations of fluoroquinolones in the urine and therapy with high-dose levofloxacin are believed to overcome resistance and effectively treat infections caused by resistant bacteria. The ASPECT-cUTI phase 3 clinical trial (ClinicalTrials.gov, NCT01345929 and NCT01345955 , both registered April 28, 2011) provided an opportunity to test this hypothesis by examining the clinical and microbiological outcomes of high-dose levofloxacin treatment by levofloxacin minimum inhibitory concentration.Patients were randomly assigned 1:1 to ceftolozane/tazobactam (1.5 g intravenous every 8 h) or levofloxacin (750 mg intravenous once daily) for 7 days of therapy. The ASPECT-cUTI study provided data on 370 patients with at least one isolate of Enterobacteriaceae at baseline who were treated with levofloxacin. Outcomes were assessed at the test-of-cure (5-9 days after treatment) and late follow-up (21-42 days after treatment) visits in the microbiologically evaluable population (N?=?327).Test-of-cure clinical cure rates above 90% were observed at minimum inhibitory concentrations ?4 ?g/mL. Microbiological eradication rates were consistently >90% at levofloxacin minimum inhibitory concentrations ?0.06 ?g/mL. Lack of eradication of causative pathogens at the test-of-cure visit increased the likelihood of relapse by the late follow-up visit.Results from this study do not support levofloxacin therapy for complicated urinary tract infections caused by organisms with levofloxacin minimum inhibitory concentrations ?4 ?g/mL.ClinicalTrials.gov, NCT01345929 and NCT01345955.
| S-EPMC5124239 | biostudies-literature
Project description:In 2018, the Clinical and Laboratory Standards Institute (CLSI) revised ciprofloxacin (CIP)-susceptible breakpoint for Enterobacteriaceae from ≤1 μg/mL to ≤0.25 μg/mL, based on pharmacokinetic-pharmacodynamic (PK-PD) analysis. However, clinical data supporting the lowered CIP breakpoint are insufficient. This retrospective cohort study evaluated the clinical outcomes of patients with bacteremic urinary tract infections (UTIs) caused by Enterobacteriaceae, which were previously CIP-susceptible and changed to non-susceptible. Bacteremic UTIs caused by Enterobacteriaceae with CIP minimal inhibitory concentration (MIC) ≤ 1 μg/mL were screened, and then patients treated with CIP as a definitive treatment were finally included. Patients in CIP-non-susceptible group (MIC = 0.5 or 1 μg/mL) were compared with patients in CIP-susceptible group (MIC ≤ 0.25 μg/mL). Primary endpoints were recurrence of UTIs within 4 weeks and 90 days. A total of 334 patients were evaluated, including 282 of CIP-susceptible and 52 of CIP-non-susceptible. There were no significant differences in clinical outcomes between two groups. In multivariate analysis, CIP non-susceptibility was not associated with recurrence of UTIs. CIP non-susceptibility based on a revised CIP breakpoint, which was formerly susceptible, was not associated with poor clinical outcomes in bacteremic UTI patients were treated with CIP, similar to those of the susceptible group. Further evaluation is needed to guide the selection of definitive antibiotics for UTIs.
| S-EPMC8074352 | biostudies-literature
Project description:Uncomplicated urinary tract infections (UTI) are common in general practice, and are usually treated with antibiotics. Recurrent UTI often pose a serious problem for affected women. Little is known about recurrent UTI and complications when uncomplicated UTI are treated without antibiotics. With ICUTI (Immediate vs. conditional antibiotic use in uncomplicated UTI, funded by BMBF No. 01KG1105) we assessed whether initial symptomatic treatment with ibuprofen could be a treatment alternative for uncomplicated UTI. The presented analysis aims to assess the influence of initial (non-)antibiotic treatment on recurrent UTI rates and pyelonephritis after day 28 up to 6 months after trial participation.This study is a retrospective long-term follow-up analysis of ICUTI patients, surveyed telephonically six months after inclusion in the trial. Recurrent UTI, pyelonephritis or hospitalizations were documented. Statistical evaluation was performed by descriptive and multivariate analyses with SPSS 21.For the six months follow-up survey, 386 trial participants could be contacted (494 had been included in ICUTI initially, 446 had completed the trial). From day 28 until 6 months after inclusion in ICUTI, 84 recurrent UTI were reported by 80 patients. Univariate and multivariate analyses showed no effect of initial treatment group or antibiotic treatment on number of patients with recurrent UTI. Yet, both analyses showed that patients with a history of previous UTI had significantly more often recurrent UTI. Pyelonephritis occurred in two patients of the antibiotic group and in one patient in the non-antibiotic group.This follow-up analysis of a trial comparing antibiotic vs. symptomatic treatment for uncomplicated UTI showed that non-antibiotic treatment has no negative impact on recurrent UTI rates or pyelonephritis after day 28 and up to six months after initial treatment. Thus, a four week follow-up in UTI trials seems adequate.
| S-EPMC4749724 | biostudies-other
Project description:The present study investigated the incidence of hyperammonemia in urinary tract infections and explored the utility of urinary obstruction relief and antimicrobial administration to improve hyperammonemia.This was an observational study. Subjects were patients who were diagnosed with urinary tract infection and hospitalized between June 2008 and June 2009. We measured plasma ammonia levels on admission in patients who were clinically diagnosed with urinary tract infection and hospitalized. We assessed each patient's level of consciousness on admission using the Glasgow Coma Scale (GCS) and performed urine and blood cultures. We also assessed hearing prior to hospitalization using the Eastern Cooperative Oncology Group performance status (ECOG-PS). In cases with high ammonia levels on admission, plasma ammonia and GCS were measured 24 hours and 5-7 days later.Sixty-seven candidates were enrolled; of these, 60 cases (89.6%) with bacterial cell counts ≥10(4) CFU/mL were studied. Five cases (8.3%) presented with high plasma ammonia levels. Cases with hyperammonemia were significantly more likely to present with low GCS scores and urinary retention rate. All five cases received antimicrobial therapy with an indwelling bladder catheter to relieve urinary retention. The case 5 patient died shortly after admission due to complicated aspiration pneumonia; in the remaining cases, plasma ammonia levels were rapidly normalized and the level of consciousness improved.The occurrence of hyperammonemia in urinary tract infections is not rare. The cause of hyperammonemia is urinary retention obstruction. Therefore, along with antimicrobial administration, relief of obstruction is important for the treatment of hyperammonemia caused by this mechanism.
| S-EPMC4546155 | biostudies-other
Project description:Urinary tract infections (UTIs) are a severe public health problem and are caused by a range of pathogens, but most commonly by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis and Staphylococcus saprophyticus. High recurrence rates and increasing antimicrobial resistance among uropathogens threaten to greatly increase the economic burden of these infections. In this Review, we discuss how basic science studies are elucidating the molecular details of the crosstalk that occurs at the host-pathogen interface, as well as the consequences of these interactions for the pathophysiology of UTIs. We also describe current efforts to translate this knowledge into new clinical treatments for UTIs.
| S-EPMC4457377 | biostudies-literature
Project description:The urinary tract is constantly exposed to different microorganisms that colonize the gastrointestinal tract and the urinary tract is normally well prepared to resist infections by these microorganisms. This resistance to infection is mainly accomplished by the versatility of the immune system in the urinary tract, with both innate and adaptive immune responses. With the increasing knowledge of how the immune system works in the urinary tract and also the recognition of the virulence attributes of uropathogens, several potentially effective and tailored strategies to contain or prevent urinary tract infections have emerged.
| S-EPMC7418169 | biostudies-literature
Project description:A urinary tract infection (UTI) is a collective term for infections that involve any part of the urinary tract. It is one of the most common infections in local primary care. The incidence of UTIs in adult males aged under 50 years is low, with adult women being 30 times more likely than men to develop a UTI. Appropriate classification of UTI into simple or complicated forms guides its management and the ORENUC classification can be used. Diagnosis of a UTI is based on a focused history, with appropriate investigations depending on individual risk factors. Simple uncomplicated cystitis responds very well to oral antibiotics, but complicated UTIs may require early imaging, and referral to the emergency department or hospitalisation to prevent urosepsis may be warranted. Escherichia coli remains the predominant uropathogen in acute community-acquired uncomplicated UTIs and amoxicillin-clavulanate is useful as a first-line antibiotic. Family physicians are capable of managing most UTIs if guided by appropriate history, investigations and appropriate antibiotics to achieve good outcomes and minimise antibiotic resistance.
| S-EPMC5027397 | biostudies-literature
Project description:Gram-positive bacteria in the genus Enterococcus are a frequent cause of catheter-associated urinary tract infection (CAUTI), a disease whose treatment is increasingly challenged by multiantibiotic-resistant strains. We have recently shown that E. faecalis uses the Ebp pilus, a heteropolymeric surface fiber, to bind the host protein fibrinogen as a critical step in CAUTI pathogenesis. Fibrinogen is deposited on catheters due to catheter-induced inflammation and is recognized by the N-terminal domain of EbpA (EbpANTD), the Ebp pilus's adhesin. In a murine model, vaccination with EbpANTD confers significant protection against CAUTI. Here, we explored the mechanism of protection using passive transfer of immune sera to show that antisera blocking EbpANTD-fibrinogen interactions not only is prophylactic but also can act therapeutically to reduce bacterial titers of an existing infection. Analysis of 55 clinical CAUTI, bloodstream, and gastrointestinal isolates, including E. faecalis, E. faecium, and vancomycin-resistant enterococci (VRE), revealed a diversity of levels of EbpA expression and fibrinogen-binding efficiency in vitro Strikingly, analysis of 10 strains representative of fibrinogen-binding diversity demonstrated that, irrespective of EbpA levels, EbpANTD antibodies were universally protective. The results indicate that, despite diversity in levels of fibrinogen binding, strategies that target the disruption of EbpANTD-fibrinogen interactions have considerable promise for treatment of CAUTI.ImportanceUrinary catheterization is a routine medical procedure, and it has been estimated that 30 million Foley catheters are used annually in the United States. Importantly, placement of a urinary catheter renders the patient susceptible to developing a catheter-associated urinary tract infection, accounting for 1 million cases per year. Additionally, these infections can lead to serious complications, including bloodstream infection and death. Enterococcus strains are a common cause of these infections, and management of enterococcal infections has been more difficult in recent years due to the development of antibiotic resistance and the ability of strains to disseminate, resulting in a major threat in hospital settings. In this study, we developed an antibiotic-sparing treatment that is effective against diverse enterococcal isolates, including vancomycin-resistant enterococci, during catheter-associated urinary tract infections.
| S-EPMC5080383 | biostudies-literature
Project description:BackgroundOveruse of fluoroquinolone antibiotics is associated with outbreaks of methicillin-resistant Staphylococcus aureus and of Clostridium difficile-associated diarrhea and increasing resistance in gram-negative organisms. Over the past decade, resistance of Escherichia coli to ciprofloxacin has increased in the Regina Qu'Appelle Health Region. In August 2011, an exploratory audit of the Regina General Hospital (RGH) emergency department showed that 20% of new antibiotic orders were for fluoroquinolones, and 60% of these new fluoroquinolone orders were for ciprofloxacin. It was postulated that ciprofloxacin was predominantly prescribed for outpatients with urinary tract infection.ObjectiveTo develop, implement, and evaluate a best-practice algorithm for the empiric treatment of uncomplicated urinary tract infection in the RGH emergency department, as part of an educational initiative for emergency physicians.MethodsA literature review was conducted and local antibiogram data were analyzed to establish a best-practice algorithm for treatment of uncomplicated urinary tract infection in outpatients seen in the emergency department. A chart review was conducted from January to March 2011 to establish a baseline of empiric antibiotic use. An educational strategy targeting emergency physicians described changes in antibiotic resistance patterns in the health region, principles of antimicrobial stewardship, drivers of resistance, and the results of a literature review of best practice for urinary tract infection in outpatients. A post-intervention audit was conducted from January to March 2012 to determine changes in practice.ResultsComparison of results from the post-intervention audit with baseline data showed that adherence to best practice increased significantly, from 41% (39/96) before the intervention to 66% (50/76) after the intervention (odds ratio [OR] 2.81, 95% confidence interval [CI] 1.51-5.25; p < 0.001). There was also a significant change in overall antibiotic selection (OR 0.25, 95% CI 0.11-0.58; p < 0.001). Further analysis suggested that this significant change was driven by a decrease in use of ciprofloxacin, from 32% (31/96) to 11% (8/76).ConclusionCreation of a best-practice algorithm and education focused on emergency physicians significantly increased adherence to best practice and optimized antibiotic prescribing for outpatients with uncomplicated urinary tract infection by limiting overuse of fluoroquinolones, primarily ciprofloxacin.
| S-EPMC4006756 | biostudies-literature