Exposure to Non-Antimicrobial Drugs and Risk of Infection with Antibiotic-Resistant Enterobacteriaceae.

Antimicrobial resistance (AMR) has consistently been linked to antibiotic use. However, the roles of commonly prescribed non-antimicrobial drugs as drivers of AMR may be under-appreciated. Here, we studied a cohort of patients with community-acquired pyelonephritis and assessed the association of exposure to non-antimicrobial drugs at the time of hospital admission with infection with drug-resistant organisms (DRO). Associations identified on bivariate analyses were tested using a treatment effects estimator that models both outcome and treatment probability. Exposure to proton-pump inhibitors, beta-blockers, and antimetabolites was significantly associated with multiple resistance phenotypes. Clopidogrel, selective serotonin reuptake inhibitors, and anti-Xa agents were associated with single-drug resistance phenotypes. Antibiotic exposure and indwelling urinary catheters were covariates associated with AMR. Exposure to non-antimicrobial drugs significantly increased the probability of AMR in patients with no other risk factors for resistance. Non-antimicrobial drugs may affect the risk of infection with DRO through multiple mechanisms. If corroborated using additional datasets, these findings offer novel directions for predicting and mitigating AMR.

The impact of early versus late levodopa administration.

Long-term levodopa therapy in patients with Parkinson's disease (PD) is associated with motor complications including motor fluctuations (MF) and levodopa-induced dyskinesias (LID). The time to appearance of MF and LID is apparently related to both the timing and the duration of levodopa therapy, but is highly variable. We performed a retrospective analysis of all levodopa-treated PD patients to explore the effect of time from PD onset to levodopa initiation on time to MF or LID. We used a Cox multivariate regression model after stratifying patients into four quartiles, according to the time to levodopa initiation. Data from 170 PD patients (117 males, age at onset: 65.1 ± 11.6 years, time to levodopa treatment: 23.8 ± 28.4 months) was included in the analysis. Early levodopa administration was associated with a shorter time from diagnosis to both MF (p < 0.001) and LID (p = 0.001). The hazard ratio to develop MF and LID from the time of PD diagnosis was 2.48 (p < 0.001) and 2.71 (p = 0.002), respectively. In our population, we found that delaying levodopa administration was associated with a longer time to the appearance of motor complications after diagnosis. While disease duration is the most important determinant of the onset of motor complications, delaying levodopa could prolong the 'complication-free' period.