Estimating the impact of cefuroxime versus cefazolin and amoxicillin/clavulanate use on future collateral resistance: A retrospective comparison

Background: Quantitative estimates of collateral resistance induced by antibiotic use are scarce. Objectives: To estimate the effects of treatment with amoxicillin/clavulanate or cefazolin, compared with cefuroxime, on future resistance to ceftazidime among hospitalized patients. Methods: A retrospective analysis of patients with positive bacterial cultures hospitalized in an Israeli hospital during 2016-19 was conducted. Patients were restricted to those treated with amoxicillin/clavulanate, cefazolin or cefuroxime and re-hospitalized with a positive bacterial culture during the following year. Matching was performed using exact, Mahalanobis and propensity score matching. Each patient in the amoxicillin/clavulanate and cefazolin groups was matched to a single patient from the cefuroxime group, yielding 185:185 and 298:298 matched patients. Logistic regression and the g-formula (standardization) were used to estimate the OR, risk difference (RD) and number needed to harm (NNH). Results: Cefuroxime induced significantly higher resistance to ceftazidime than amoxicillin/clavulanate or cefazolin; the marginal OR was 1.76 (95% CI=1.16-2.83) compared with amoxicillin/clavulanate and 1.98 (95% CI=1.41-2.8) compared with cefazolin and the RD was 0.118 (95% CI=0.031-0.215) compared with amoxicillin/clavulanate and 0.131 (95% CI=0.058-0.197) compared with cefazolin. We also estimated the NNH; replacing amoxicillin/clavulanate or cefazolin with cefuroxime would yield ceftazidime resistance in 1 more patient for every 8.5 (95% CI=4.66-32.14) or 7.6 (95% CI=5.1-17.3) patients re-hospitalized in the following year, respectively. Conclusions: Our results indicate that treatment with amoxicillin/clavulanate or cefazolin is preferable to cefuroxime, in terms of future collateral resistance. The results presented here are a first step towards quantitative estimations of the ecological damage caused by different antibiotics.