Estimating the cost of antibiotic use on future collateral resistance: a retrospective comparison of cefuroxime versus cefazolin and amoxicillin/clavulanate

BackgroundQuantitative estimates of collateral resistance induced by antibiotic use are scarce. This study compared the effects of treatment with amoxicillin/clavulanate or cefazolin, compared to cefuroxime, on future resistance to ceftazidime among hospitalized patients.MethodsA retrospective analysis of patients with positive bacterial cultures hospitalized in an Israeli hospital during 2016-2019 was conducted. Patients were restricted to those treated with either amoxicillin/clavulanate, cefazolin, or cefuroxime and re-hospitalized with a positive bacterial culture during the following year. A 1:1 matching was performed for each patient in the amoxicillin/clavulanate and cefazolin groups, to a single patient from the cefuroxime group, yielding 185:185 and 298:298 matched patients. Logistic regression and g-formula (standardization) were used to estimate the odds ratio (OR), risk difference (RD), and number needed to harm (NNH).ResultsCefuroxime induced significantly higher resistance to ceftazidime than amoxicillin/clavulanate or cefazolin: the marginal OR was 1.76)95%CI 1.16-2.83) compared to amoxicillin/clavulanate, and 1.98 (95%CI 1.41-2.8) compared to cefazolin; The RD was 0.118 (95%CI 0.031-0.215) compared to amoxicillin/clavulanate, and 0.131 (95%CI 0.058-0.197) compared to cefazolin. We also estimated the NNH: replacing amoxicillin/clavulanate or cefazolin with cefuroxime would yield ceftazidime-resistance in one 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.ConclusionsOur 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.Key pointsWe performed a retrospective study estimating collateral resistance of treatment with cefuroxime relative to amoxicillin/clavulanate or cefazolin. Application of novel analytical methods allowed us to estimate the number needed to harm and hence ecological damage of the different treatments.