Oral Fluoroquinolone Use Research Articles

Establishment of an Antimicrobial Stewardship Program to Spare the Use of Oral Fluoroquinolones for Acute Uncomplicated Cystitis in Outpatients.

The increase in fluoroquinolone (FQ)-resistant Escherichia coli (EC) is a serious global problem. In addition, much of acute uncomplicated cystitis (AUC) cases are caused by EC. FQs have been selected for the treatment of cystitis in outpatients, and there is concern about treatment failure. It is therefore necessary to select appropriate antimicrobials to spare FQs. However, there are few reported effective antimicrobial stewardship programs (ASPs) for outpatients. We aimed to establish the effective ASP for outpatients diagnosed with AUC caused by EC, to spare the use of FQs, and to explore optimal oral antimicrobials for AUC. The study subjects were outpatients treated for AUC caused by extended-spectrum β-lactamase-non-producing EC (non-ESBL-EC). Based on the antibiogram results, we recommended cefaclor (CCL) as the initial treatment for AUC, and educated clinical pharmacists who also worked together to advocate for CCL or cephalexin (CEX) prescriptions. FQ usages decreased, and cephalosporin (Ceph) prescriptions increased in all medical departments. The Ceph group (n = 114; CCL = 60, CEX = 54) in the non-FQ group had fewer treatment failures than the FQ group (n = 86) (12.3% vs. 31.4%). Cephs, including CCL and CEX, were effective treatments for AUC caused by non-ESBL-EC. Antimicrobial selection based on antibiogram results and the practice of an ASP in collaboration with clinical pharmacists were useful for optimizing antimicrobial therapy in outpatients.

Changes in intravenous and oral antimicrobial prescriptions during the coronavirus disease 2019 (COVID-19) pandemic: an experience at a tertiary-care center.

Antimicrobial use during the coronavirus disease 2019 (COVID-19) pandemic at a tertiary-care center was analyzed using interrupted time-series analysis. Among intravenous antimicrobials, the use of azithromycin and third-generation cephalosporins significantly decreased during the current pandemic. Similarly, the use of oral antimicrobials, including azithromycin and fluoroquinolones, also decreased.

121. Evaluation of Multifaceted Antimicrobial Stewardship in Optimizing Antimicrobial Usage in Intraabdominal Infection at a Community Hospital

BackgroundTreatment of intraabdominal infections (IAI) commonly involves broad spectrum antimicrobials based on the severity and etiology of infections as well as the underlying medical conditions. However, the overuse of broad-spectrum agents has driven selection for Gram-negative and -positive resistance, as well as collateral consequences such as Clostridioides difficile colitis. We sought to evaluate the utilization of a pharmacy-driven multifaceted antimicrobial stewardship (AMS) intervention to optimize empiric antimicrobial therapy by risk stratification among IAI patients and reduce the number of antibiotic treatment days.MethodsThis is a single-center case observation study in hospitalized adult IAI patients on antimicrobial therapy from Dec 2019-Feb 2020 compared to patients from Dec 2020-Feb 2021 after initiation of AMS with daily prospective audit and feedback. The composite primary outcome is reduction of antibiotic treatment days and de-escalation from broad spectrum antibiotics (fluoroquinolones, piperacillin/tazobactam, and carbapenems) to cephalosporins. ResultsWe identified 40 patients each in the baseline (pre-AMS group) and post-AMS group via electronic medical record. Baseline characteristics were well-matched between groups. The majority of patients were diagnosed with community-acquired IAIs such as appendicitis, diverticulitis, and cholecystitis. Fluoroquinolone use as empiric therapy was significantly lower in the post-AMS group vs. pre-AMS group (2.5% vs. 25%, p< 0.001), while non-Pseudomonas cephalosporin use was increased (25% post-AMS vs. 0% pre-AMS, p< 0.001). Oral fluoroquinolone use at discharge was significantly decreased in the post-AMS group (p< 0.001). Antibiotic treatment days remained unchanged. There was no statistical difference between the two groups in 30-day mortality, 30-day readmission, relapse, and C. difficile colitis.ConclusionA multifaceted antimicrobial therapy intervention successfully reduced the use of fluoroquinolones in patients with community-acquired IAI during hospitalization and discharge. No differences in mortality, readmission, or relapse rates were observed.Disclosures All Authors: No reported disclosures

Oral Fluoroquinolone Use and the Risk of Acute Liver Injury: A Nationwide Cohort Study.

BackgroundAntibiotics are considered to be among the most frequent causes of drug-related acute liver injury (ALI). Although many ALIs have mild and reversible clinical outcomes, there is substantial risk of severe reactions leading to acute liver failure, need for liver transplant, and death. Recent studies have raised concerns of hepatotoxic potential related to the use of fluoroquinolones.MethodsThis study examined the risk of ALI associated with oral fluoroquinolone treatment compared with amoxicillin (419 930 courses, propensity score matched 1:1). The information on drug use was collected from a national, registry-based cohort derived from all Swedish adults aged 40–85 years.ResultsDuring a follow-up period of 60 days, users of oral fluoroquinolones had a >2-fold risk of ALI compared to users of amoxicillin (hazard ratio, 2.32 [95% confidence interval {CI}, 1.01–5.35). The adjusted absolute risk difference for use of fluoroquinolones as compared to amoxicillin was 4.94 (95% CI, .04–16.3) per 1 million episodes.ConclusionsIn this propensity score–matched study, fluoroquinolone treatment was associated with an increased risk of ALI in the first 2 months after starting treatment.

Oral fluoroquinolones and risk of aortic or mitral regurgitation: a nationwide nested case-control study.

Reports have suggested an increased risk of aortic and mitral regurgitation associated with oral fluoroquinolones (FQs) resulting in a safety warning published by the European Medicines Agency (EMA). However, these findings have not yet been replicated. Using Danish administrative registers, we conducted a nested case-control study in a nationwide cohort of individuals between 2005 and 2018. Cases were defined as the first occurrence of aortic or mitral regurgitation. Exposure of interest was the use of oral FQs. Hazard ratios (HRs) with 95% confidence intervals (95% CI) were obtained by fitting time-dependent Cox regression models, with penicillin V as comparator, to assess the association between FQ use and incident valvular regurgitation. We identified 38 370 cases of valvular regurgitation with 1 115 100 matched controls. FQ exposure was not significantly associated with increased rates of aortic or mitral regurgitation (HR 1.02, 95% CI 0.95-1.09) compared with penicillin V users. Investigating the cumulative defined daily doses (cDDD) of FQs yielded similar results with no significant association between increasing FQ use and valvular regurgitation (e.g. HR 1.08, 95% CI 0.95-1.23 for cDDD >10 compared with cDDD 1-5). These results were consistent across several analyses including a cohort of patients with hypertension and using a case definition based on valvular surgical interventions. In a nationwide nested case-control study, FQs were not significantly associated with increased rates of valvular regurgitation. Our findings do not support a possible causal connection between FQ exposure and incident valvular regurgitation.

Quality Appraisal of Ambulatory Oral Cephalosporin and Fluoroquinolone Use in the 16 German Federal States from 2014-2019.

Background: Despite concerns about causing bacterial resistance and serious side effects, oral cephalosporins and fluoroquinolones are still frequently prescribed in Germany. We aimed to test a method for the detection of regional quality differences in the use of oral cephalosporins and fluoroquinolones and to apply this to the German federal states. Methods: Use of antibiotics from 2014–2019 was analyzed using dispensing data from community pharmacies claimed to the statutory health insurance (SHI) funds. Quality of regional antibiotic use in 2019 was assessed by calculating indicators based on defined daily doses per 1000 SHI-insured persons per day (DID). Oral cephalosporin and fluoroquinolone use was followed by linear regression analyses. Results: The method used was suitable to find meaningful quality differences in ambulatory oral cephalosporin and fluoroquinolone use between the German federal states. In 2019, DID varied from 1.62 in Brandenburg to 3.17 in Rhineland-Palatinate for cephalosporins and from 0.47 in Brandenburg to 0.89 in Saarland for fluoroquinolones. The city-states Hamburg, Bremen, and Berlin showed highest quality with the applied indicator set. From 2014–2019, a significant decrease in utilization of oral cephalosporins was found in all federal states. During 2017–2019, all states showed a significant decline of fluoroquinolone use.

Initiatives to Reduce the Use of Oral Third-generation Cephalosporins and Fluoroquinolones to Help Achieve the Goals of the National Action Plan for Antimicrobial Resistance Control and Their Outcomes

Initiatives to Reduce the Use of Oral Third-generation Cephalosporins and Fluoroquinolones to Help Achieve the Goals of the National Action Plan for Antimicrobial Resistance Control and Their Outcomes

Fluoroquinolone use and risk of aortic aneurysm and dissection: nationwide cohort study

ObjectiveTo investigate whether oral fluoroquinolone use is associated with an increased risk of aortic aneurysm or dissection.DesignNationwide historical cohort study using linked register data on patient characteristics, filled prescriptions, and...

Association between oral fluoroquinolone use and lateral canthal tendon rupture: case report

ABSTRACTIt is well established and documented that fluoroquinolone use is associated with the development of tendinopathy. However, little is known about the possible effects of this class of antibiotics on the orbit. We present a case of lateral canthal tendon rupture that presented with an acute right lower eyelid ectropion in a young, renal compromised patient in the setting of recent fluoroquinolone use for pneumonia. Eye care clinicians need to be aware of the possible effects of fluoroquinolones on the eyelids.

Evaluating the Effectiveness of an Antimicrobial Stewardship Program on Reducing the Incidence Rate of Healthcare-Associated Clostridium difficile Infection: A Non-Randomized, Stepped Wedge, Single-Site, Observational Study.

BackgroundThe incidence rate of healthcare-associated Clostridium difficile infection (HA-CDI) is estimated at 1 in 100 patients. Antibiotic exposure is the most consistently reported risk factor for HA-CDI. Strategies to reduce the risk of HA-CDI have focused on reducing antibiotic utilization. Prospective audit and feedback is a commonly used antimicrobial stewardship intervention (ASi). The impact of this ASi on risk of HA-CDI is equivocal. This study examines the effectiveness of a prospective audit and feedback ASi on reducing the risk of HA-CDI.MethodsSingle-site, 339 bed community-hospital in Barrie, Ontario, Canada. Primary outcome is HA-CDI incidence rate. Daily prospective and audit ASi is the exposure variable. ASi implemented across 6 wards in a non-randomized, stepped wedge design. Criteria for ASi; any intravenous antibiotic use for ≥ 48 hrs, any oral fluoroquinolone or oral second generation cephalosporin use for ≥ 48 hrs, or any antimicrobial use for ≥ 5 days. HA-CDI cases and model covariates were aggregated by ward, year and month starting September 2008 and ending February 2016. Multi-level mixed effect negative binomial regression analysis was used to model the primary outcome, with intercept and slope coefficients for ward-level random effects estimated. Other covariates tested for inclusion in the final model were derived from previously published risk factors. Deviance residuals were used to assess the model’s goodness-of-fit.FindingsThe dataset included 486 observation periods, of which 350 were control periods and 136 were intervention periods. After accounting for all other model covariates, the estimated overall ASi incidence rate ratio (IRR) was 0.48 (95% 0.30, 0.79). The ASi effect was independent of antimicrobial utilization. The ASi did not seem to reduce the risk of Clostridium difficile infection on the surgery wards (IRR 0.87, 95% CI 0.45, 1.69) compared to the medicine wards (IRR 0.42, 95% CI 0.28, 0.63). The ward-level burden of Clostridium difficile as measured by the ward’s previous month’s total CDI cases (CDI Lag) and the ward’s current month’s community-associated CDI cases (CA-CDI) was significantly associated with an increased risk of HA-CDI, with the estimated CDI Lag IRR of 1.21 (95% 1.15, 1.28) and the estimated CA-CDI IRR of 1.10 (95% CI 1.01, 1.20). The ward-level random intercept and slope coefficients were not significant. The final model demonstrated good fit.ConclusionsIn this study, a daily prospective audit and feedback ASi resulted in a significant reduction in the risk of HA-CDI on the medicine wards, however, this effect was independent of an overall reduction in antibiotic utilization. In addition, the ward-level burden of Clostridium difficile was shown to significantly increase the risk of HA-CDI, reinforcing the importance of the environment as a source of HA-CDI.

Association between oral fluoroquinolones and seizures: A self-controlled case series study.

The aim of this study was to investigate the association and to estimate the crude absolute risk of seizure among patients exposed to fluoroquinolones (FQs) in Hong Kong and the United Kingdom. A self-controlled case series study was conducted. Data were collected from the Hong Kong Clinical Data Analysis and Reporting System database and the Clinical Practice Research Datalink. Patients who were prescribed any oral FQ and had an incident seizure diagnosis from 2001 to 2013 were included. The risk windows were defined as pre-FQ start, FQ-exposed, and post-FQ completion. Incidence rate ratios were estimated in all risk windows and compared with baseline periods. A post hoc subgroup analysis was conducted to examine the effect of patients with a history of seizure. An increased incidence rate ratio was found in the pre-FQ start periods and no association was found in the post-FQ completion periods in both databases. The crude absolute risk of an incident seizure in 10,000 oral FQ prescriptions was 0.72 (95% confidence interval 0.47-1.10) in the Clinical Data Analysis and Reporting System and 0.40 (95% confidence interval 0.30-0.54) in the Clinical Practice Research Datalink. The rate ratio during treatment was not higher than pre-FQ start periods among patients with a history of seizure, therefore the results did not raise serious concerns. This study does not support a causal association between the use of oral FQs and the subsequent occurrence of seizure. An increased risk before the FQ exposure period suggests that the clinical indication for which FQ was prescribed may have contributed to the development of seizure rather than the drug itself.

Oral fluoroquinolone use and serious arrhythmia: bi-national cohort study

Objective To evaluate if oral fluoroquinolone use is associated with an increased risk of serious arrhythmia.Design Bi-national cohort study, linking register data on filled prescriptions, cases of serious arrhythmia, and...

Association between oral fluoroquinolone use and the development of retinal detachment: a systematic review and meta-analysis of observational studies.

Several observational studies have been published investigating the association between oral fluoroquinolone use and the development of retinal detachment; however, the findings are not concordant. This study is a meta-analysis of the existing literature and estimates the overall absolute risk of such an event. Electronic databases were searched for observational studies on the association between oral fluoroquinolone and retinal detachment up to August 2014. Studies that did not meet the criteria for meta-analysis were narratively reviewed. Cases of retinal detachment during current fluoroquinolone use were also extracted for absolute risk calculation. Seven observational studies were included. Three (case-control and self-controlled case series studies) were eligible for meta-analysis and four (cohort studies) were narratively reviewed. The rate ratio of the case-control studies was 1.82 (95% CI 0.67-4.93), I(2) =96% and the incidence rate ratio of the self-controlled case series was 1.03 (95% CI 0.84-1.27), I(2) =36%. Three of the four cohort studies found no significant association between oral fluoroquinolone use and the development of retinal detachment. The pooled absolute risk of retinal detachment whilst on current oral fluoroquinolone treatment is estimated to be 4.85 per 1000000 prescriptions (95% CI 0.78-8.91). The findings of this systematic review and meta-analysis do not support an association between oral fluoroquinolone use and the development of retinal detachment. Given the low absolute risk, such an event would be rare if there were an association. The current prescribing practice for fluoroquinolones should not be altered because of a previously suggested potential risk of retinal detachment.

Oral fluoroquinolone use and risk of peripheral neuropathy: a pharmacoepidemiologic study.

To quantify the risk of peripheral neuropathy (PN) with oral fluoroquinolone (FQ) use. We conducted a case-control study within a cohort of men aged 45 to 80 years in the United States followed from 2001 to 2011. Cases were defined as those with the first physician visit diagnosis of PN, polyneuropathy, or drug-induced polyneuropathy. Four controls were matched to each case by age, follow-up, and calendar time using density-based sampling. As a sensitivity analysis, we also quantified the risk of PN with finasteride use, a drug that is not expected to increase the risk of PN. Rate ratios (RRs) for current users of FQs were computed using conditional logistic regression, which was adjusted for chronic renal failure, chronic liver disease, hypothyroidism, postherpetic neuralgia, and the use of nitrofurantoin and metronidazole. We identified 6,226 cases and 24,904 controls. Current users of FQs were at a higher risk of developing PN (RR = 1.83, 95% confidence interval [CI] 1.49-2.27). Current new users had the highest risk (RR = 2.07, 95% CI 1.56-2.74). No risk was observed for current users of finasteride (RR = 1.21, 95% CI 0.97-1.51). Current users, especially new users of FQs, are at a higher risk of developing PN. Despite the increase in the use of FQs, clinicians should weigh the benefits against the risk of adverse events when prescribing these drugs to their patients.

Exposure to Oral Fluoroquinolones and the Risk of Retinal Detachment: Retrospective Analyses of Two Large Healthcare Databases

BackgroundA recent Canadian case–control study reported a 4.5-fold increased risk of retinal detachment (RD) during oral fluoroquinolone use. Of the fluoroquinolone-exposed cases, 83 % were exposed to ciprofloxacin. We sought to replicate this finding, and assess whether it applied to all fluoroquinolones.MethodsIn two large US healthcare databases, we performed three case–control analyses: one replicating the recent study; one addressing additional potential confounders; and one that increased sample size by dropping the Canadian study’s requirement for a prior ophthalmologist visit. We also performed a self-controlled case-series (SCCS) analysis in which each subject served as his or her own comparator.ResultsIn the replication case–control analyses, the adjusted odds ratios (ORs) for any exposure to fluoroquinolones or ciprofloxacin were approximately 1.2 in both databases, and were statistically significant, and the ORs for current exposure were modestly above 1 in one database, modestly below 1 in the other, and not statistically significant. In the other case–control analyses, the ORs were close to 1. In a post hoc age-stratified case–control analysis, we observed an association of RD with fluoroquinolone exposure among older subjects in one of the two databases. All estimates from the SCCS analyses were below 1.2 and none was statistically significant.ConclusionThe present study does not confirm the recent Canadian study’s finding of a strong relationship between RD and current exposure to fluoroquinolones. Instead, it found a modest association between RD and current or any exposure to fluoroquinolones in the case–control analyses, and no association in the SCCS analyses.

Oral Fluoroquinolones and the Incidence of Rhegmatogenous Retinal Detachment and Symptomatic Retinal Breaks: A Population-Based Study

To examine whether oral fluoroquinolone antibiotics are associated with an increase in subsequent rhegmatogenous retinal detachment and symptomatic retinal breaks in a large population-based cohort. Population-based cohort study. Adult residents of Olmsted County, Minnesota, who were prescribed oral fluoroquinolone medications from January 1, 2003, to June 30, 2011. Comparison cohorts consisted of patients prescribed oral macrolide and β-lactam antibiotics during the study period. Procedure codes were used to identify retinal detachment repair and prophylaxis procedures occurring within 1 year of prescription dates. Travel clinic, pro re nata, and self-treatment prescriptions were excluded. Patients with tractional retinal detachment, previous retinal detachment repair, endophthalmitis, and necrotizing retinitis were excluded, as were those with intraocular surgery or severe head/eye trauma ≤90 days before the procedure. Rates of retinal detachment repair and prophylaxis procedures within 7, 30, 90, and 365 days of the first prescription were calculated and compared between antibiotic prescription cohorts using chi-square tests. Retinal detachment repair rates also were compared with the expected Olmsted County, Minnesota, rates using the one-sample log-rank test. Oral fluoroquinolones were prescribed for 38,046 patients (macrolide n = 48,074, β-lactam n = 69,079) during the study period. Retinal detachment repair procedures were performed within 365 days of the first prescription in 0.03% (95% confidence interval [CI], 0.01-0.06) of the fluoroquinolone cohort, 0.02% (95% CI, 0.01-0.03) of the macrolide cohort, and 0.03% (95% CI, 0.02-0.05) of the β-lactam cohort (P > 0.05). Retinal detachment prophylaxis procedures for symptomatic retinal breaks were performed within 365 days of the first prescription in 0.01% (95% CI, 0.00-0.03) of the fluoroquinolone cohort, 0.02% (95% CI, 0.01-0.04) of the macrolide cohort, and 0.02% (95% CI, 0.01-0.04) of the β-lactam cohort (P > 0.05). Similar comparisons of treatment rates within 7, 30, and 90 days of the first prescription were all nonsignificant between cohorts. Post-fluoroquinolone retinal detachment repair rates were similar to expected rates (36.8 per 100,000/year vs. 28.8 per 100,000/year for age- and sex-matched historical rates, P = 0.35). Oral fluoroquinolone use was not associated with an increased risk of rhegmatogenous retinal detachment or symptomatic retinal breaks in this population-based study.

Association Between Oral Fluoroquinolone Use and Retinal Detachment

A recent study of ophthalmologic patients found a strong association between fluoroquinolone use and retinal detachment. Given the prevalent use of fluoroquinolones, this could, if confirmed in the general population, translate to many excess cases of retinal detachment that are potentially preventable. To investigate if oral fluoroquinolone use is associated with an increased risk of retinal detachment. A nationwide, register-based cohort study in Denmark from 1997 through 2011, using linked data on participant characteristics, filled prescriptions, and cases of retinal detachment with surgical treatment (scleral buckling, vitrectomy, or pneumatic retinopexy). The cohort included 748,792 episodes of fluoroquinolone use (660,572 [88%] ciprofloxacin) and 5,520,446 control episodes of nonuse. Poisson regression was used to estimate rate ratios (RRs) for incident retinal detachment, adjusting for a propensity score that included a total of 21 variables. The risk windows were classified as current use (days 1-10 from start of treatment), recent use (days 11-30), past use (days 31-60), and distant use (days 61-180). A total of 566 cases of retinal detachment occurred, of which 465 (82%) were rhegmatogenous detachments; 72 in fluoroquinolone users and 494 in control nonusers. The crude incidence rate was 25.3 cases per 100,000 person-years in current users, 18.9 in recent users, 26.8 in past users, and 24.8 in distant users compared with 19.0 in nonusers. Compared with nonuse, fluoroquinolone use was not associated with a significantly increased risk of retinal detachment: the adjusted RRs were 1.29 (95% CI, 0.53 to 3.13) for current use; 0.97 (95% CI, 0.46 to 2.05) for recent use; 1.37 (95% CI, 0.80 to 2.35) for past use; and 1.27 (95% CI, 0.93 to 1.75) for distant use. The absolute risk difference, estimated as the adjusted number of retinal detachment cases per 1,000,000 treatment episodes, was 1.5 (95% CI, -2.4 to 11.1) for current use. In this cohort study based on the general Danish population, oral fluoroquinolone use was not associated with increased risk of retinal detachment. Given its limited power, this study can only rule out more than a 3-fold increase in the relative risk associated with current fluoroquinolone use; however, any differences in absolute risk are likely to be of minor, if any, clinical significance.

Oral Fluoroquinolone Use and Retinal Detachment

Oral Fluoroquinolone Use and Retinal Detachment

Association Between Recent Use of Fluoroquinolones and Rhegmatogenous Retinal Detachment: A Population-Based Cohort Study

An association between use of oral fluoroquinolones (FQs) and retinal detachment remains controversial. This study was to determine the association of recent use of oral FQs and rhegmatogenous retinal detachment (RRD) after adjustment for confounding factors known to be associated with RRD. This retrospective population-based cohort study with parallel groups included adults treated with an oral FQ (FQ cohort = 178 179 prescriptions) and propensity score-matched adults treated with oral amoxicillin (amoxicillin cohort = 178 179 prescriptions). The data were extracted from the Taiwan National Health Insurance Research Database from 1998 to 2010. Interaction terms were used to identify populations at risk. RRD was defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification. During the 90-day follow-up period, 96 patients (0.054%) in the FQ cohort developed RRD compared to 46 (0.026%) among the matched amoxicillin cohort. The overall adjusted hazard ratio (HR) for FQ use and RRD was 2.07 (95% confidence interval [CI], 1.45-2.96). The interval between use of oral FQs and onset of RRD was 35.5 days (interquartile range, 14-57 days). Interaction terms were not significant for age, sex, diabetes, indications for antimicrobials, or underlying ophthalmic conditions. The adjusted HRs differed for specific FQs. These were 10.68 (95% CI, 3.28-34.82) for ciprofloxacin, 2.41 (95% CI, .76-7.68) for levofloxacin, 2.00 (95% CI, 1.06-3.79) for norfloxacin, and 1.17 (95% CI, .59-2.31) for ofloxacin. The use of oral FQs was associated with the subsequent occurrence of RRD. The FQ risk was independent of age, sex, diabetes, indications for antimicrobials, and underlying ophthalmic conditions. Certain FQs carried higher risk of RRD.

Oral fluoroquinolone use and acute kidney injury

Oral fluoroquinolone use and acute kidney injury