Characteristics of the antibiotic regimen that affect antimicrobial resistance in urinary pathogens.

Background: Treatment duration, treatment interval, formulation and type of antimicrobial (antibiotic) are modifiable factors that will influence antimicrobial selection pressure. Currently, the impact of the route of administration on the occurrence of resistance in humans is unclear. Methods: In this retrospective multi-center cohort study, we assessed the impact of different variables on antimicrobial resistance (AMR) in pathogens isolated from the urinary tract in older adults. A generalized estimating equations (GEE) model was constructed using 7397 Escherichia coli (E. coli) isolates. Results: Resistance in E. coli was higher when more antibiotics had been prescribed before isolation of the sample, especially in women (significant interaction p = 0.0016) and up to nine preceding prescriptions it was lower for higher proportions of preceding parenteral prescriptions (significant interactions p = 0.0067). The laboratory identity, dying, and the time between prescription and sampling were important confounders (p < 0.001). Conclusions: Our model describing shows a dose-response relation between antibiotic use and AMR in E. coli isolated from urine samples of older adults, and, for the first time, that higher proportions of preceding parenteral prescriptions are significantly associated with lower probabilities of AMR, provided that the number of preceding prescriptions is not extremely high (≥10 during the 1.5 year observation period; 93% of 5650 included patients). Trial registration: Retrospectively registered.

Persistence of antimicrobial resistance in respiratory streptococci.

OBJECTIVES: To assess whether persistence of antimicrobial resistance (i.e. non-susceptible resistance status) after treatment with penicillins or cephalosporins versus macrolides or tetracyclines differs and to compare the results obtained using routinely collected data with findings reported in prospective studies. METHODS: Routinely collected microbiological data from 14 voluntary participating laboratories (2005) containing information on resistance status and individual antimicrobial consumption patterns (mid 2004-2005) were analysed using a generalised estimating equation (GEE) approach. The link function was adjusted to acknowledge that the proportion of resistant isolates in the population not treated with antibiotics [baseline resistance (BR)] is not necessarily zero. To optimise the comparability of this study with prospective studies, the analysis was repeated after removal of 14 isolates from patients who did not survive 2005. RESULTS: BR estimates were unstable and their confidence intervals were wide, which called for a sensitivity analysis using an adjusted GEE model with three different BR estimates. All models indicated that the proportion of susceptible isolates differed by treatment group and increased significantly over time, with this increase being independent of treatment group. Persistence of resistance after exposure to macrolides or tetracyclines was approximately three times as long as after exposure to penicillins or cephalosporins. CONCLUSIONS: Resistance following treatment with macrolides or tetracyclines persists longer than following treatment with penicillins or cephalosporins, which confirms the findings from prospective studies and suggests the use of routinely collected data as a valuable alternative to determine such differences in persistence of resistance.