Fluoroquinolone Usage Research Articles

Time Series Methods to Assess the Impact of Regulatory Action: A Study of UK Primary Care and Hospital Data on the Use of Fluoroquinolones.

To illustrate the interest in using interrupted time series (ITS) methods, this study evaluated the impact of the UK MHRA's March 2019 Risk Minimisation Measures (RMM) on fluoroquinolone usage. Monthly and quarterly fluoroquinolone use incidence rates from 2012 to 2022 were analysed across hospital care (Barts Health NHS Trust), primary care (Clinical Practice Research Datalink (CPRD) Aurum and CPRD GOLD), and linked records from both settings (East Scotland). Rates were stratified by age (19-59 and ≥ 60 years old). Seasonality-adjusted segmented regression and ARIMA models were employed to model quarterly and monthly rates, respectively. Post-RMM, with segmented regression, both age groups in Barts Health experienced nearly complete reductions (> 99%); CPRD Aurum saw 20.19% (19-59) and 19.29% ( 60) reductions; no significant changes in CPRD GOLD; East Scotland had 45.43% (19-59) and 41.47% ( 60) decreases. Slope analysis indicated increases for East Scotland (19-59) and both CPRD Aurum groups, but a decrease for CPRD GOLD's 60; ARIMA detected significant step changes in CPRD GOLD not identified by segmented regression and noted a significant slope increase in Barts Health's 19-59 group. Both models showed no post-modelling autocorrelations across databases, yet Barts Health's residuals were non-normally distributed with non-constant variance. Both segmented regression and ARIMA confirmed the reduction of fluoroquinolones use after RMM across four different UK primary care and hospital databases. Model diagnostics showed good performance in eliminating residual autocorrelation for both methods. However, diagnostics for hospital databases with low incident use revealed the presence of heteroscedasticity and non-normal white noise using both methods.

Comparative genomics of quinolone-resistant Escherichia coli from broilers and humans in Norway

BackgroundThe usage of fluoroquinolones in Norwegian livestock production is very low, including in broiler production. Historically, quinolone-resistant Escherichia coli (QREC) isolated from Norwegian production animals rarely occur. However, with the introduction of a selective screening method for QREC in the Norwegian monitoring programme for antimicrobial resistance in the veterinary sector in 2014; 89.5% of broiler caecal samples and 70.7% of broiler meat samples were positive. This triggered the concern if there could be possible links between broiler and human reservoirs of QREC. We are addressing this by characterizing genomes of QREC from humans (healthy carriers and patients) and broiler isolates (meat and caecum).ResultsThe most frequent mechanism for quinolone resistance in both broiler and human E. coli isolates were mutations in the chromosomally located gyrA and parC genes, although plasmid mediated quinolone resistance (PMQR) was also identified. There was some relatedness of the isolates within human and broiler groups, but little between these two groups. Further, some overlap was seen for isolates with the same sequence type isolated from broiler and humans, but overall, the SNP distance was high.ConclusionBased on data from this study, QREC from broiler makes a limited contribution to the incidence of QREC in humans in Norway.

Fluoroquinolones in Focus: Unraveling Prescription Trends among Clinician Specialties in Washington State

Background: An overall decrease of prescriptions for outpatient fluoroquinolones (FQs) following the FDA’s release of boxed warnings in 2016 was shown in a previous analysis1. An additional study found that this decline held true when further broken down by specialty 2. We sought to determine which different clinician specialties in Washington State (WA) continue to prescribe FQs and if these rates are congruent with previously conducted national analyses. Methods: We conducted a comprehensive analysis of Medicare Part D data from 2021. We identified specialty types contributing the highest proportions of FQ claims from the total volume of claims in 2021. Subsequently, we calculated the average FQ claims per 1,000 Medicare Part D beneficiaries for each specialty. The analysis excluded providers with missing beneficiary data. All dosage formulations were included (i.e. topical & oral). We repeated this process for each year from 2021 to 2013 to assess changes in the average FQ prescription rate for each specialty over time. Results: Our analysis encompassed 99,250 FQ prescriptions involving 976,209 Medicare Part D beneficiaries from January 1 to December 30, 2021. Among the specialties, urologists emerged as the highest prescribers of FQs to Medicare Part D beneficiaries, closely followed by ophthalmologists and family practitioners (Table 1). Notably, 72.4% of urologists prescribed FQs, while only 12.4% of family practitioners did so in 2021. Trend analysis indicated that the average FQ claims per 1,000 beneficiaries for urologists decreased from 251 claims per 1,000 beneficiaries (SD = 177.98) in 2013 to 130 claims per 1,000 beneficiaries (SD = 122.50) in 2021 (Figure 1A). In contrast, the only specialty types that had positive trends in average FQ claims per 1,000 beneficiaries from 2013 to 2021 included ophthalmologists, optometrists, and otolaryngologists (Figure 1A). Conclusion: Throughout the years leading up to 2021, most prescriber specialties contributing high volumes of FQ claims experienced a decline in FQ prescriptions. The positive trend noted amongst ophthalmologists, optometrists, and otolaryngologists could be due to the limited ability to differentiate between oral & topical FQ formulations within the dataset. These findings underscore the importance of understanding specialist prescribing behaviors and partnering with them to formulate tailored antibiotic stewardship guidance. By doing so, we can further promote patient safety and well-being in the context of FQ usage. Public health departments can promote more holistic antibiotic stewardship interventions and better patient safety outcomes with FQs. Ambulatory Fluoroquinolone Use in the United States 2015–2019 Outpatient Fluoroquinolone Prescription Fills.Disclosure: Erica Stohs: Contracted research - Merck; Contracted research – bioMerieux

Association Between Fluoroquinolones and Major Adverse Cardiovascular Events: A Systematic Review.

Fluoroquinolones (FQs) are routinely administered antibiotics that have demonstrated an increased propensity to cause major adverse cardiovascular events (MACE). We conducted a systematic review aimed to investigate the association between FQ usage and the risk of MACE. A comprehensive literature search was conducted using PubMed, Scopus, and the Cochrane Library from inception to September 2023 to retrieve studies comparing FQ administration with placebo and reporting the occurrence of MACE. Relevant studies that explored the occurrence of MACE, defined as "acute myocardial infarction, stroke, cardiovascular mortality, arrhythmia, or heart failure" with FQ usage were eligible for inclusion. Four studies with a total of 42,808 patients were included. Levofloxacin, moxifloxacin, and gatifloxacin were observed to have an increased propensity to cause MACE, particularly arrhythmias, whereas ciprofloxacin was associated with the lowest risk of causing MACE. Despite the methodological diversity in the included studies, this systematic review uncovered a consistent trend of heightened likelihood of MACE with FQ administration across studies, suggesting that elevated serum concentrations of some FQs may correlate with higher risks of MACE development. This systematic review emphasizes the need for cautious administration of FQs, particularly in patients with a preexisting cardiovascular condition. Routine cardiac monitoring using electrocardiograms is warranted for patients on high doses of FQs to preemptively detect the development of MACE, particularly arrhythmias.

The changing epidemiology of Clostridioides difficile infection and the NAP1/027 strain in two Québec hospitals: a 17-year time-series study.

To describe the epidemiology of healthcare-associated Clostridioides difficile infection (HA-CDI) in two Québec hospitals in Canada following the 2003 epidemic and to evaluate the impact of antibiotic stewardship on the incidence of HA-CDI and the NAP1/027 strain. Time-series analysis. Two Canadian tertiary care hospitals based in Montréal, Québec. Patients with a positive assay for toxigenic C. difficile were identified through infection control surveillance. All cases of HA-CDI, defined as symptoms occurring after 72 hours of hospital admission or within 4 weeks of hospitalization, were included. The incidence of HA-CDI and antibiotic utilization from 2003 to 2020 were analyzed with available C. difficile isolates. The impact of antibiotic utilization on HA-CDI incidence was estimated by a dynamic regression time-series model. Antibiotic utilization and the proportion of NAP1/027 strains were compared biannually for available isolates from 2010 to 2020. The incidence of HA-CDI decreased between 2003 and 2020 at both hospitals from 26.5 cases per 10,000 patient-days in 2003 to 4.9 cases per 10,000 patient-days in 2020 respectively. Over the study period, there were an increase in the utilization of third-generation cephalosporins and a decrease in usage of fluoroquinolones and clindamycin. A decrease in fluoroquinolone utilization was associated with a significant decrease in HA-CDI incidence as well as decrease in the NAP1/027 strain by approximately 80% in both hospitals. Decreased utilization of fluoroquinolones in two Québec hospitals was associated with a decrease in the incidence of HA-CDI and a genotype shift from NAP1/027 to non-NAP1/027 strains.

The epidemiology of Stenotrophomonas maltophilia and Achromobacter xylosoxidans infections.

Stenotrophomonas maltophilia and Achromobacter xylosoxidans are emerging nosocomial, non-glucose fermenting, Gram-negative pathogens. In this nested case-control trial, independent predictors for S. maltophilia infections were hemodialysis and recent antibiotic usage (overall), while recent usage of fluoroquinolones, was independently associated with A. xylosoxidans infections. Infections were independently associated with multiple worse outcomes.

Fluoroquinolones and the risk of aortic aneurysm or aortic dissection: an updated systematic review and meta-analysis including 53,651,283 patients.

The association between fluoroquinolone use and the risk of aortic aneurysm as well as the risk of aortic dissections remains uncertain, primarily due to conflicting findings from observational studies. We sought to conduct a double-systematic review and meta-analysis of all observational studies to assess the existence and extent of both these associations. The aim of our study is to assess the role of Fluoroquinolone on aortic aneurysm and aortic dissection in comparison to other antibiotics. MEDLINE and Cochrane CENTRAL were systematically searched up till June 2021 for observational studies studying the correlation between fluoroquinolone usage and aortic aneurysms and dissections. Random-effects pooling was used to calculate adjusted hazard ratios (HRs) with 95% confidence intervals (CI). To assess publication bias, propensity score matching was conducted, and heterogeneity was evaluated by using I2 statistics. Of 688 potentially relevant articles, 635 titles were screened. Ten studies were included in the systematic review, and 4 observational studies with 53,651,283 participants were eligible to be included in the meta-analysis. Pooled estimates showed that fluoroquinolone use was associated with a higher risk of aortic aneurysm when compared to other Antibiotics (HR 1.84, 95% CI 1.10-2.48; P<0.00001). However, fluoroquinolones had no significant effect on the risk of developing aortic dissection (HR 1.09, 95% CI 0.96-1.25; P=0.19). The present analysis suggests that fluoroquinolone usage is more strongly linked to aortic aneurysm than other antibiotics. However, there was no statistically significant link between fluoroquinolone and aortic dissection. As a result, clinicians should exercise caution when administering fluoroquinolone to patients who have a history of or are at risk of aortic disease.

Optical fiber SPR biosensor with frequency multiplexing compensated laser heterodyne feedback for ultrasensitive detection of fluoroquinolones

The widespread usage and discharge of fluoroquinolones (FQs) have caused negative environmental consequences that can threaten human health. The development of ultrasensitive and simple devices for detection of various FQs is an important requirement. Here, we proposed a novel optical fiber surface plasmon resonance biosensor to achieve the ultrasensitive detection of FQs, in which the frequency-shifted light returned to the laser resonator and stimulated laser heterodyne feedback interferometry to amplify the intensity changes caused by the refractive index (RI) variations. In addition, we further presented a quasi-common path frequency multiplexing compensation method to compensate for the noise of the developed biosensor, resulting in a RI resolution of 1.06 × 10−6 RIU. Besides, the gold nanorods were used to generate localized surface plasmon resonance to further amplify the signal to achieve the ultrasensitive detection. A variety of FQs were detected with ultra-low detection limits, including enrofloxacin (0.61 ng/L), ciprofloxacin (0.54 ng/L), norfloxacin (0.31 ng/L), pefloxacin (0.32 ng/L), and sarafloxacin hydrochloride (0.97 ng/L). With the advantages of high sensitivity, compact size, and remote operation capability, the developed biosensor holds the promise of detecting other antibiotics with universality in hard-to-reach spaces, thus having the potential to demonstrate a promising approach to environmental monitoring.

Quantifying patient- and hospital-level antimicrobial resistance dynamics in Staphylococcus aureus from routinely collected data.

Introduction. Antimicrobial resistance (AMR) to all antibiotic classes has been found in the pathogen Staphylococcus aureus. The reported prevalence of these resistances varies, driven by within-host AMR evolution at the patient level, and between-host transmission at the hospital level. Without dense longitudinal sampling, pragmatic analysis of AMR dynamics at multiple levels using routine surveillance data is essential to inform control measures.Gap Statement. The value and limitations of routinely collected hospital data to gain insight into AMR dynamics at the hospital and individual levels simultaneously are unclear.Methodology. We explored S. aureus AMR diversity in 70 000 isolates from a UK paediatric hospital between 2000-2021, using electronic datasets containing multiple routinely collected isolates per patient with phenotypic antibiograms and information on hospitalization and antibiotic consumption.Results. At the hospital level, the proportion of isolates that were meticillin-resistant (MRSA) increased between 2014-2020 from 25-50 %, before sharply decreasing to 30%, likely due to a change in inpatient demographics. Temporal trends in the proportion of isolates resistant to different antibiotics were often correlated in MRSA, but independent in meticillin-susceptible S. aureus. Ciprofloxacin resistance in MRSA decreased from 70-40 % of tested isolates between 2007-2020, likely linked to a national policy to reduce fluoroquinolone usage in 2007. At the patient level, we identified frequent AMR diversity, with 4 % of patients ever positive for S. aureus simultaneously carrying, at some point, multiple isolates with different resistances. We detected changes over time in AMR diversity in 3 % of patients ever positive for S. aureus. These changes equally represented gain and loss of resistance.Conclusion. Within this routinely collected dataset, we found that 65 % of changes in resistance within a patient's S. aureus population could not be explained by antibiotic exposure or between-patient transmission of bacteria, suggesting that within-host evolution via frequent gain and loss of AMR genes may be responsible for these changing AMR profiles. Our study highlights the value of exploring existing routine surveillance data to determine underlying mechanisms of AMR. These insights may substantially improve our understanding of the importance of antibiotic exposure variation, and the success of single S. aureus clones.

Bilateral Acute Iris Transillumination and Elevated Intraocular Pressure After COVID-19 Infection.

Bilateral acute iris transillumination (BAIT) is characterized by abundant pigment discharge into the anterior chamber. Atonic pupil and severe intraocular pressure (IOP) elevations may be observed. Generally, there is a viral upper respiratory tract infection or systemic fluoroquinolone usage before BAIT. Two cases with a recent history of coronavirus disease 2019 (COVID-19) presented with a complaint of decreased vision. Elevated IOP and iris transillumination defects were observed in both patients. Both patients were diagnosed with BAIT. Although elevated IOP was controlled with medical treatment in 1 patient, glaucoma surgery was performed in the other patient because it could not be controlled with medical treatment. As both patients received no systemic treatment for COVID-19, the pressure rise seems to be directly related to the viral infection alone through the inflammatory process. Atypical ocular presentations of COVID-19 should be kept in mind as it can have serious consequences.

New insight into adsorption and co-adsorption of chlortetracycline hydrochloride and ciprofloxacin hydrochloride by Ga-based metal-organic gel/sodium alginate composite beads

Due to the extensive usage of tetracyclines and fluoroquinolones for disease control, their residuals usually coexist in wastewater and seriously affect human health and the entire ecosystem. To mitigate this problem, developing efficient and recyclable absorbent has been urgently required to be put on the agenda. In this research, Ga-based MOGs (GMOGs) were synthesized to remove chlortetracycline hydrochloride (CTC) and ciprofloxacin hydrochloride (CIP) in aqueous solution, followed by incorporating GMOGs into low-cost sodium alginate (SA) matrix to gain GMOG/SA beads with enhanced adsorption property, fine recycling performance and stable reusability. In single system (S-system), the adsorption behaviors of CTC/CIP by GMOGs and GMOG/SA beads including key operating factors, kinetics, isotherms and practicability were investigated systematically, and the maximum adsorption capacities for CTC/CIP by GMOGs and GMOG/SA beads achieved 406.50/158.23 mg g−1 and 1085.19/862.07 mg g−1, respectively. Furthermore, the proposed adsorption mechanisms were discussed. In binary system (B-system), regardless of suppressed co-adsorption behaviors of CTC/CIP by GMOGs and GMOG/SA beads arising from the competitive effect between CTC and CIP, their adsorption capacities still reached 207.90/126.90 mg g−1 and 588.24/571.42 mg g−1, respectively. Moreover, the value of industrial application was evaluated by testing the adsorption performance of GMOG/SA beads in bead columns and real water. This work provides a potential practicable, effective and recycled exploration of GMOG/SA beads for remediating the CTC and CIP co-contaminated wastewater.

Prospective Assessment of Penicillin Allergy (PAPA): Evaluating the performance of penicillin allergy testing and post-delabelling outcomes among Hong Kong Chinese.

Incorrect penicillin 'allergy' labels predispose patients to adverse outcomes but are under-recognised in many Asian countries. Studies on performance and post-delabelling outcomes of penicillin allergy evaluation among Chinese remain scarce. To evaluate the diagnostic performance of allergy testing and post-delabelling outcomes among Chinese patients in a prospective penicillin allergy cohort - Prospective Assessment of Penicillin Allergy (PAPA). All adult patients (age ≥ 18 years) who underwent penicillin allergy evaluation between January 2020 to December 2021 were recruited and prospectively reviewed by both medical records and individual interviews at least 6 months after delabelling or allergy confirmation. Out of 372 patients who completed penicillin allergy evaluation, 335 (90%) patients were delabelled. The overall negative predictive value of penicillin skin testing was 95%, but lower for patients with non-immediate type reactions (88%). History of non-immediate symptom onset (OR = 4.501 [95%CI = 2.085-9.716], p < 0.001) and duration since index reaction (OR = 0.942 [95%CI = 0.899-0.987], p = 0.012) were associated with positive skin testing. After at least 6 months, 60 (18%) of de-labelled patients had received penicillins again without any adverse reactions. Fluoroquinolone-use was significantly lower among delabelled patients compared to those with penicillin allergy (38[11%] vs 11[30%], p = 0.004). After at least 6 months, one in six delabelled patients already received penicillins again safely, with significantly lower fluoroquinolone usage. None experienced adverse reactions. History of non-immediate onset and shorter duration since index reaction were associated with genuine allergy. In patients with severe non-immediate reactions, skin tests should be supplemented with thorough clinical history and adjunct diagnostic evaluations.

Influence of the Verordnung über Tierärztliche Hausapotheken on antimicrobial use in dogs and cats in Bavaria

Aim of the study was to collect data concerning the use of antibiotics (AB) in dogs and cats in veterinary practices and clinics in Bavaria, Germany. It was evaluated, whether changes in the use of AB since the amendment of the Verordnung über Tierärztliche Hausapotheken (TÄHAV, German Regulation on the Veterinary In-house Pharmacy) in March 2018 could be documented. Using 2 anonymous online surveys in 2017 and 2020, veterinarians treating dogs and cats in Bavaria were questioned about their usage of AB and their assessment of the current antimicrobial resistance situation. The results of both surveys were evaluated statistically and compared with each other. While in 2017 a total of 238 questionaries were evaluated, 160 could be included in 2020. The three most commonly used antibiotics for systemic therapy were Amoxicillin/Clavulanic acid (74.8 % of veterinarians), Enrofloxacin (56.7 %) and Amoxicillin (53.4 %) in 2017; and Amoxicillin/Clavulanic acid (88.8 %), Amoxicillin (67.5 %) and Metronidazole (33.8 %) in 2020, respectively. The participating veterinarians stated that their overall use of 3 rd and 4th generations cephalosporins (from 20.2 % of veterinarians in 2017 to 9.4 % in 2020, p = 0,005) as well as fluoroquinolones (from 80.3 % to 33.1 %, p < 0.001) had significantly declined. In 2020, the choice of AB in veterinarians was affected by legal requirements (83.8 %), tolerability (81.3 %), way of application (76.9 %), acceptance by the patient (70.0 %), and frequency of application (64.4 %), with the last parameter being significantly more important to veterinarians working in a practice (83.8 %, p = 0.004) than to veterinarians in a clinic. Veterinarians report a significantly reduced usage of fluoroquinolones and 3 rd and 4th generation cephalosporines in dogs and cats compared to 2017. These changes in prescribing practice could be a consequence of the amendment of the TÄHAV, which dictates a prohibition of rededication as well as an obligation for microbial sensitivity testing for these AB classes. Legal restrictions could have a positive influence on the amount and type of antibiotics used and therefore help to prevent antimicrobial resistance.

Association between fluoroquinolone exposure and children's growth and development: A multisite biomonitoring-based study in northern China

BackgroundAlthough animal experiments found that antibiotic exposure during early life increased adiposity, limited human epidemiological evidence is available for the effects of veterinary antibiotic exposure on children's growth and development. ObjectiveThis study was conducted to examine the body burden of fluoroquinolones in northern Chinese children and assess its association with growth and development. MethodsAfter recruiting 233 children aged 0–15 years from 12 different sites in northern China in 2020, we measured urinary concentrations of 5 respective fluoroquinolones (fleroxacin, ofloxacin, norfloxacin, ciprofloxacin, and enrofloxacin) by high performance liquid chromatography. Categories of children's growth and development were identified based on the Z score of body mass index. The health risks of individual and combined antibiotic exposure were estimated by the hazard quotient (HQ) and hazard index (HI), respectively. The association between children's growth and development with antibiotic concentrations was evaluated via multiple logistic regression analysis. ResultsIn total, 4 antibiotics, fleroxacin, ofloxacin, ciprofloxacin, and enrofloxacin, were found in urine samples of northern Chinese children at an overall frequency of 57.08%. Due to diet and economic differences, antibiotic concentrations in urine samples differed by study area, and the highest concentrations were found in Tianjin, Henan, and Beijing. The percentage of the participants with HQ > 1 caused by ciprofloxacin exposure was 20.61%, and the HI values in 23.18% of samples exceeded 1, suggesting potential health risks. The odds ratio (95% confidence interval) of overweight or obesity risk of tertile 2 of enrofloxacin was 3.01 (1.12, 8.11), indicating an increase in overweight or obesity risk for children with middle-concentration enrofloxacin exposure. ConclusionThis is the first study to show a positive association of enrofloxacin internal exposure with overweight or obesity risk in children, demonstrating that more attention should be given to the usage and disposal of fluoroquinolones to safeguard children's health.

Out of sight, out of mind: Impact of an antimicrobial stewardship initiative to reduce fluoroquinolone utilization

AbstractIntroductionIn June 2017, the antimicrobial stewardship team at Wesley Healthcare implemented a combination of strategies aimed at reducing fluoroquinolone usage. The components included suppression of fluoroquinolone susceptibility in Enterobacterales isolates, removal of fluoroquinolones as first‐line options in order sets, and introduction of a respiratory‐specific antibiogram.ObjectivesThe objective was to evaluate the impact of combined stewardship strategies on fluoroquinolone utilization.MethodsThis was a quality improvement study evaluating fluoroquinolone use within a health‐care system. The primary outcome was ciprofloxacin and levofloxacin usage in days of therapy (DOT) per 1000 inpatient days collected at monthly intervals for 24 months before and after the intervention. Overall antibacterial usage in DOT served as a control variable. The secondary outcomes were Escherichia coli and Pseudomonas aeruginosa susceptibility to ciprofloxacin measured at the same time points. An interrupted time series analysis using segmented regression was performed for all variables.ResultsThe mean monthly levofloxacin usage was reduced from 14.1 (95% confidence interval [CI], 12.7‐15.4) to 8.4 (95% CI, 7.6‐9.3) DOT. The mean monthly ciprofloxacin usage was reduced from 26.9 (95% CI, 24.6‐29.4) to 15.8 (95% CI, 14.0‐17.5) DOT. The trend in levofloxacin usage was reduced (P = .035), while a pre‐existing downward trend in ciprofloxacin usage was unchanged (P = .430). Overall antibacterial usage increased (P = .001). There were no differences in Escherichia coli or Pseudomonas aeruginosa susceptibilities observed.ConclusionThe use of combined antimicrobial stewardship strategies may be a viable intervention method to reduce fluoroquinolone usage. The combined strategy was effective in reducing levofloxacin usage, as demonstrated by the reduction of use and the downward usage trend.

Perioperative Fluoroquinolone Treatment Deteriorates Prognosis Following Coronary Artery Bypass Grafting.

Background: Former studies have revealed that fluoroquinolone (FQ) can induce aortic expansion and rupture. While FQ is widely used in perioperative anti-infection therapy, its impact on graft patency and patient survival is unknown. Methods: Coronary artery bypass grafting (CABG) data were extracted from the MIMIC-III database. Chi-square tests, Fisher’s exact tests, t-tests, or ANOVAs were used to compare baseline data between groups determined by FQ therapy status, depending on the data type. Propensity score matching was used to establish a balanced cohort. Cox regression was used to investigate the impact of FQ on CABG patient survival, whereas paired t-tests were used to analyze secondary results. Results: Of the 5030 patients who underwent CABG, 937 (18.6%) received oral or intravenous FQ therapy. Using propensity score matching, these 819 patients were successfully matched with 819 controls in a 1:1 ratio. Cox regression showed that FQ significantly decreased survival among CABG patients (HR: 1.62, 95% CI: 1.21–2.15, p = 0.001). Furthermore, FQ usage was associated with longer hospitalization (<0.0001), ICU duration (<0.0001), ventilation period (<0.0001), and duration of vasopressor administration (<0.0001). Conclusions: Perioperative FQ therapy was associated with worse prognosis and a more difficult recovery among patients with CABG.

105. Fluoroquinolone Stewardship at a Community Health-System: A Decade in Review

BackgroundFluoroquinolone stewardship is a common target for antimicrobial stewardship programs seeking to maintain or improve fluoroquinolone susceptibility rates. Additional benefits include reducing C. difficile infection rates, drug toxicities, and resistance to other antimicrobials as fluoroquinolones can co-select for resistance. The Norton Healthcare antimicrobial stewardship program was founded in 2011 and provides services at 4 adult hospitals with ~1600 beds. Main fluoroquinolone stewardship activities have included provider education, prospective audit and feedback, and guideline and order-set development. The purpose of this study was to describe the resistance and usage rates of fluoroquinolones over time. MethodsThis was a descriptive study examining individual adult hospital antibiograms from 2010 to 2020. Levofloxacin susceptibility rates to E. coli and P. aeruginosa were collated from annual antibiograms between 2010 and 2020 for outpatients and each adult hospital. Adult hospital resistance rates were aggregated and weighted accordingly to number of isolates per hospital per year. Additionally, levofloxacin and ciprofloxacin inpatient days of therapy (DOT) was collected since 2016 when DOT was first readily retrievable and was normalized per 1000 patient days to compare between different time points.ResultsOutpatient levofloxacin likelihood of activity against P. aeruginosa improved from 81% to 91%. Outpatient levofloxacin likelihood of activity against E. coli remained stable between 84 – 86% (Figure 1). Adult inpatient fluoroquinolone usage decreased by approximately 75% from 83.5 to 21.37 DOT/1000 patient days since 2016 (Figure 2). Adult inpatient levofloxacin likelihood of activity against P. aeruginosa improved from 53% to 83%. Adult inpatient levofloxacin likelihood of activity against E. coli improved from 65% to 75% (Figure 3). ConclusionThe Norton Healthcare antimicrobial stewardship program has been effective in reducing unnecessary fluoroquinolone usage and improving inpatient fluoroquinolone susceptibility rates. Future studies should examine opportunities to translate successes to the outpatient phase of care. Disclosures Ashley Wilde, PharmD, BCPS-AQ ID, Nothing to disclose Paul S. Schulz, MD, Gilead (Consultant, Speaker’s Bureau)Merck (Consultant, Speaker’s Bureau)

RISE OF RIFAXIMIN IN PAEDIATRIC INFECTIOUS DIARRHOEA

The incidence and risk of morality is high under the age of five years is due to diarrhoea. In India twenty percentages of paediatric deaths is due to diarrhoeal disease. It is the second cause of leading mortality in children after acute respiratory infections. Following on from the GEMS study when we looked at the data in the management of bacterial diarrhoea the primary treatments included oral rehydration solution, oral zinc probiotics and antibiotics. Anecdotally we noted that a lot of children were treated with oral antibiotics and the majority of them were treated with fluoroquinolones like Ofloxacin and drugs like Metronidazole there are multiple side-effects associated with the usage of fluoroquinolones and a major side-effect of that is the risk to the growing cartilage. We also noticed that irrational combinations such as imidazole like metronidazole have shown more problems than solutions .usage of Ofloxacin in children should be discouraged for all the side-effects plus the infectivity in the management of bacterial diarrhoea. The duration of treatment have paved the way for usage of drugs such as new molecules in paediatric i.e. rifaximin comes under the group of oral non-absorbable GI antibiotics broad-spectrum agents with antibacterial activity against gram positive and gram negative aerobes and Anaerobes makes Rifaximin a bactericidal drug in nature. Rifaximin is particularly recommended in children above the age of two years in acute infectious diarrhoea the mechanism of action of rifaximin is by inhibition of bacterial protein synthesis by reversibly binding to bacterial DNA dependent RNA polymerase. In this review we discussed the “phrma” behind rifaximin, clinical experience of rifaximin in children and indications and dosage of rifaximin in paediatric.

Occurrence of Escherichia coli non-susceptible to quinolones in faecal samples from fluoroquinolone-treated, contact and control pigs of different ages from 24 Swiss pig farms

BackgroundDespite their indispensability in human medicine, fluoroquinolones (FQ) are used for the treatment of bacterial infections in farm animals which increases the risk of transferring FQ-resistant bacteria into the environment and via the food chain to humans. The objectives of this observational study were to follow-up of the presence of quinolone non-susceptible Escherichia coli (QNSE) qualitatively and quantitatively in faecal samples of pigs at four time points (2 weeks old, 4 weeks old, 2 weeks post weaning and during fattening period). Moreover differences between groups of FQ-treated pigs, pigs with contact to treated pigs and control pigs were investigated. Additionally, quinolone and FQ resistance of Escherichia coli isolates of the faecal samples were investigated by determining minimum inhibitory concentrations (MICs).Results40.9% of 621 fecal samples contained QNSE. Proportion of samples with detectable QNSE from treated and contact pigs did not differ significantly and were highest in piglets of 2 and 4 weeks of age. However, the proportions of samples with QNSE were significantly lowest in control pigs (7/90; 7.8%; CI = 3.5–14.7%) among all groups. Also, the number of colony-forming units was lowest in both weaners and fattening pigs of the control group compared to treated and contact groups. Following CLSI human breakpoints, in total, 50.4% out of 254 isolates in faecal samples were intermediate or resistant to ciprofloxacin.ConclusionsQNSE were present in faeces of pigs independent of age or FQ background but significantly less were found in pigs from farms without FQ usage. Due to the long half-life of FQ, it is likely that only a prolonged absence of fluoroquinolone treatments in pig farming will lead to a reduced frequency of QNSE in the farm environment. Solutions need to be found to minimise the emergence and transfer of quinolone and FQ-resistant bacteria from treated pigs to contact pigs and to farms without FQ usage.

77. Out of Sight, Out of Mind: Impact of an Antimicrobial Stewardship Bundle on Fluoroquinolone Utilization

BackgroundFluoroquinolones are broad spectrum antimicrobials associated with a growing list of adverse effects, such as Clostridioides difficile infection, arrhythmias, central nervous system effects, tendon rupture and aortic aneurysm. Due to increasing concerns regarding adverse events and growing resistance, the antimicrobial stewardship team at Wesley Healthcare implemented a bundle aimed at reducing fluoroquinolone usage beginning in June 2017. The components of this bundle included suppression of fluoroquinolone susceptibility in Enterobacteriaceae isolates, removal of fluoroquinolones as first line options on order sets, and introduction of a respiratory specific antibiogram.MethodsThe objective was to evaluate the impact of the stewardship bundle on fluoroquinolone utilization. The primary outcome was ciprofloxacin and levofloxacin usage in days of therapy per 1000 inpatient days (DOT) collected at monthly intervals for 24 months before and after intervention. Overall antimicrobial usage in DOT served as a control variable. The secondary outcomes were E. coli and P. aeruginosa susceptibility to ciprofloxacin measured at the same time points as the primary outcome. An interrupted time-series analysis using segmented regression was performed for all variables.ResultsThe mean monthly levofloxacin usage was reduced from 14.1 (95% CI, 12.7 - 15.4) to 8.4 (95% CI, 7.6 - 9.3) DOT. The mean monthly ciprofloxacin usage was reduced from 26.9 (95% CI, 24.6 - 29.4) to 15.8 (95% CI, 14.0 - 17.5) DOT. The trend in levofloxacin usage was reduced (p=0.035), while a pre-existing downward trend in ciprofloxacin usage was unchanged (p=NS). Overall antimicrobial usage increased, likely due to increasing hematology/oncology populations during the study period. There were no differences in E. coli or P. aeruginosa susceptibilities observed.ConclusionThis antimicrobial stewardship bundle may be a useful intervention to reduce fluoroquinolone usage. The bundle may be of particular utility in reducing levofloxacin usage, as our results demonstrated a change in both its usage and trend in usage.Disclosures All Authors: No reported disclosures