Dataset Information

Evaluation of disability in patients exposed to fluoroquinolones.

ABSTRACT: BACKGROUND:Fluoroquinolones are used for conditions including sinusitis, bronchitis, and urinary tract infections. It has been suggested that exposure to fluoroquinolones for these conditions is associated with disability resulting from adverse events in 2 or more organ systems. The objectives were to: describe: 1) fluoroquinolone, azithromycin, and sulfamethoxazole / trimethoprim utilization for these infections; 2) the rate of disability associated with exposure to each of these antibiotic classes and adverse events in 2 or more system organ classes, and 3) compare outcome rates for each of the antibiotic classes. METHODS:This study was conducted using administrative data to mitigate the limitations of spontaneous reports. The sampling frame was a U.S. population with both medical and disability insurance, including patients with the above uncomplicated infections who were prescribed the antibiotics of interest. The primary outcome was an incident short-term disability claim associated with adverse events in 2 different organ systems within 120?days of exposure. A matched analysis was used to compare the outcome for patients receiving each of the drug classes. RESULTS:After propensity score matching, there were 119,653 individuals in each of the exposure groups. There were 264 fluoroquinolone associated disability events and 243 azithromycin/ sulfamethoxazole associated disability events (relative risk =1.09 (95% CI: 0.92-1.30; calibrated p?=?0.84)). The results were not significantly different from the null hypothesis of no difference between groups. CONCLUSION:Comparative assessments are difficult to conduct in spontaneous reports. This examination of disability associated with adverse events in different system organ classes showed no difference between fluoroquinolones and azithromycin or sulfamethoxazole in administrative data.

SUBMITTER: Wilcox MA

PROVIDER: S-EPMC7268406 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Evaluation of disability in patients exposed to fluoroquinolones.

Wilcox Marsha A MA Villasis-Keever Angelina A Sena Anthony G AG Knoll Christopher C Fife Daniel D

BMC pharmacology & toxicology 20200603 1

<h4>Background</h4>Fluoroquinolones are used for conditions including sinusitis, bronchitis, and urinary tract infections. It has been suggested that exposure to fluoroquinolones for these conditions is associated with disability resulting from adverse events in 2 or more organ systems. The objectives were to: describe: 1) fluoroquinolone, azithromycin, and sulfamethoxazole / trimethoprim utilization for these infections; 2) the rate of disability associated with exposure to each of these antibi ...[more]

PMID: 32493505

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Project description:Automated systems (MicroScan WalkAway 96 Plus, Phoenix 100, and Vitek 2 Compact) are widely used in clinical laboratories nowadays. The aim of this study is to evaluate the performance of these three systems for susceptibility testing of aminoglycosides and fluoroquinolones against Carbapenem-resistant Enterobacteriaceae (CRE).A total of 75 CRE isolates were used in this study. Quinolone resistance determinants (QRDs) (qnrA, qnrB, qnrC, qnrD, qnrS, aac(6')-Ib-cr, oqxAB and qepA) and aminoglycoside resistance determinants (ARDs) (aac(6')-Ib, armA, npmA, rmtA, rmtB, rmtC, rmtD and rmtE) of these CRE were screened by PCR. The MICs of aminoglycosides (gentamicin and amikacin) and fluoroquinolones (ciprofloxacin and levofloxacin) to CRE obtained with the automated systems were compared with the reference method (agar dilution method).Totally, 97.3% (73/75) of CRE harbored QRDs. The qnr gene was the most common QRD determinant identified in 68 (96.7%), followed by aac (6')-Ib-cr in 56 (74.7%), oqxAB in 23 (30.7%), and qepA in 2 (2.7%), respectively. 22.7% (17/75) of CRE harbored ARD determinants. rmtA, rmtB and npmA were identified among these isolates in 6 (8.0%), 6 (8.0%) and 5 (6.7%), respectively. A total of 900 results were obtained in this study. Overall, the total error rate was 9.89%. Twenty-eight very major errors (3.11%), 22 major errors (2.44%) and 39 minor errors (4.33%) were identified against agar dilution method. The very major errors were almost evenly distributed between results for fluoroquinolones (2.89%) and aminoglycosides (3.33%), while the major errors and minor errors were more commonly found in the results of fluoroquinolones (3.11% and 6.44%, respectively) than aminoglycosides (1.78% and 2.22%, respectively).Our study shows that testing difficulties in susceptibility testing do exist in automated systems. We suggest clinical laboratories using automated systems should consider using a second, independent antimicrobial susceptibility testing method to validate aminoglycosides and fluoroquinolones susceptibility.

Project description:Persisters are the fraction of antibiotic-exposed bacteria transiently refractory to killing and are recognized as a cause of antibiotic treatment failure. The putative de-N-acetylase DnpA increases persister levels in Pseudomonas aeruginosa upon exposure to fluoroquinolones in broth. In this study the wild-type PAO1 and its dnpA insertion mutant (dnpA::Tn) were used in parallel and compared for their capacity to generate persisters in broth (surviving fraction after exposure to high antibiotic concentrations) and their susceptibility to antibiotics in models of intracellular infection of THP-1 monocytes and of biofilms grown in microtiter plates. Multiplication in monocytes was evaluated by fluorescence dilution of GFP (expressed under the control of an inducible promoter) using flow cytometry. Gene expression was measured by quantitative RT-PCR. When exposed to fluoroquinolones (ciprofloxacin or levofloxacin) but not to meropenem or amikacin, the dnpA::Tn mutant showed a 3- to 10-fold lower persister fraction in broth. In infected monocytes, fluoroquinolones (but not the other antibiotics) were more effective (difference in Emax: 1.5 log cfu) against the dnpA::Tn mutant than against the wild-type PAO1. Dividing intracellular bacteria were more frequently seen (1.5 to 1.9-fold) with the fluoroquinolone-exposed dnpA::Tn mutant than with its parental strain. Fluoroquinolones (but not the other antibiotics) were also 3-fold more potent to prevent biofilm formation by the dnpA::Tn mutant than by PAO1 as well as to act upon biofilms (1-3 days of maturity) formed by the mutant than by the parental strain. Fluoroquinolones induced the expression of gyrA (4.5-7 fold) and mexX (3.6-5.4 fold) in the parental strain but to a lower extent (3-4-fold for gyrA and 1.8-2.8-fold for mexX, respectively) in the dnpA::Tn mutant. Thus, our data show that a dnpA insertion mutant of P. aeruginosa is more receptive to fluoroquinolone antibacterial effects than its parental strain in infected monocytes or in biofilms. The mechanism of this higher responsiveness could involve a reduced overexpression of the fluoroquinolone target.

Project description:PurposeMigraine can negatively impact patient functioning and quality of life. Here, we report the effects of galcanezumab (GMB), a humanized monoclonal antibody that binds to calcitonin gene-related peptide, on patient-reported outcome (PRO) measures in migraine.MethodsCGAJ was a Phase III, randomized, open-label study (12-month open-label and 4-month post-treatment follow-up) in patients with episodic or chronic migraine. Patients aged 18-65 years with diagnosis of migraine (??4 migraine headache days per month) as defined by International Classification of Headache Disorders (ICHD)-3 beta guidelines were included in the study. Patients were randomized 1:1 with subcutaneous GMB 120 mg (with a loading dose of 240 mg) or GMB 240 mg given once monthly for 12 months. Changes from baseline in PRO measures such as Migraine-Specific Quality of Life Questionnaire v2.1 (MSQ) and Migraine Disability Assessment (MIDAS) were assessed.ResultsA total of 135 patients were randomized to each galcanezumab dose group. Mean (SD) baseline MSQ total scores were 53.85 (20.34) [GMB 120 mg] and 53.69 (18.79) [GMB 240 mg]. For MIDAS, mean (SD) total scores were 45.77 (42.06) [GMB 120 mg] and 53.96 (61.24) [GMB 240 mg]. Within-group mean improvement from baseline on MSQ and MIDAS total scores and all individual item/domain scores were statistically significant for both GMB dose groups, at all-time points during the treatment phase (p?<?0.001). For MSQ domain scores, greatest improvement was observed in the Role function-restrictive (RF-R) domain (overall least squares (LS) mean change?±?SE: 31.55?±?1.20 [GMB 120 mg] and 33.40?±?1.16 [GMB 240 mg]). For MIDAS, the overall LS mean change?±?SE from baseline across the entire 12-month treatment phase in total scores were: -33.58?±?2.11 (GMB 120 mg) and -32.67?±?2.04 (GMB 240 mg).ConclusionGalcanezumab was associated with statistically significant changes from baseline in the PRO measures across the entire 12-month treatment period. These results indicate improved health-related quality of life and decreased disability among patients treated with galcanezumab.

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Evaluation of disability in patients exposed to fluoroquinolones.

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Evaluation of disability in patients exposed to fluoroquinolones.

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