Antibiotic cross-resistance in the lab and resistance co-occurrence in the clinic: Discrepancies and implications in E. coli

Introduction: Antibiotic resistance is an important public health issue, and vast resources are invested in researching new ways to fight it. Recent experimental works have shown that resistance to some antibiotics can result in increased susceptibility to others, namely induce cross-sensitivity. This phenomenon could be utilized to increase efficiency of antibiotic treatment strategies that minimize resistance. However, as conditions in experimental settings and in the clinic may differ substantially, the implications of cross-sensitivity for clinical settings are not guaranteed and should be examined. Methods: In this work we analyzed data of Escherichia coli isolates from patients' blood, sampled in Rabin Medical Center, Israel, to examine co-occurrence of resistance to antibiotics in the clinic. We compared the co-occurrence patterns with cross-sensitivity patterns observed in the lab. Results: Our data showed only positively associated occurrence of resistance, even with antibiotics that were shown to induce cross-sensitivity in laboratory conditions. We used a mathematical model to examine the potential effects of cross-sensitivity versus co-occurrence on the spread of drug resistance. Conclusions: We conclude that resistance frequencies in the clinic can have a substantial effect on the success of treatment strategies, and should be considered alongside experimental evidence of cross-sensitivity.