Identification of antibiotic pairs with disjoint resistance: innovative progress made but questions remain – Authors' reply
Authors: Erik S Wright, Andrew Beckley
Journal: The Lancet Microbe (2021)

We thank Huan Zhang and Yun Cai for their comments on our Article.1Beckley AM Wright ES Identification of antibiotic pairs that evade concurrent resistance via a retrospective analysis of antimicrobial susceptibility test results.Lancet Microbe. 2021; 2: e545-e554Summary Full Text Full Text PDF PubMed Google Scholar Although conditioning on resistance to an antibiotic could result in a subpopulation that is more resistant to other antibiotics, this does not inherently bias the mutual information score (MIS) of the subpopulation. Zhang and Cai note that several of the antibiotic pairs with statistically significant disjoint resistance originated from the subpopulation of Escherichia coli resistant to tobramycin, which displayed concurrent resistance with one of the antibiotics in the identified pairs. However, the average MISs of the disjoint resistant antibiotics paired with their corresponding conditioning antibiotic (0·074) were lower than those of the other antibiotic pairs overall (0·087) for E coli. This observation is the opposite of what would be expected if there were a bias towards disjoint resistance. Second, the authors suggest using a multiplied change in minimum inhibitory concentration rather than susceptible or resistant designations. As reported in our Article, we would have preferred continuous rather than discrete data, but this was not part of our dataset. Third, Klebsiella pneumoniae had low rates of carbapenem resistance (ertapenem, 1·17%; imipenem, 1·89%; and meropenem, 2·39%), so this was not a clerical error. We thank Dooshanveer Nuckchady for his comments on our Article. We note that we only identified potential antibiotic pairs for treatment of infections with alternating antibiotics. We did not draw any conclusions about treatments with multiple antibiotics at the same time. We declare no competing interests Identification of antibiotic pairs that evade concurrent resistance via a retrospective analysis of antimicrobial susceptibility test resultsThe high frequency of concurrent resistance shows that bacteria have means of counteracting multiple antibiotics at a time. The almost complete absence of disjoint resistance at the species level implies that treatment strategies based on alternating between antibiotics might require subspecies level pathogen identification and be limited to a few antibiotic pairings. Full-Text PDF Open AccessIdentification of antibiotic pairs with disjoint resistance: innovative progress made but questions remainI read with great interest the article by Andrew Beckley and Erik Wright,1 in which a score based on mutual information was used to look for antibiotic pairs that have concurrent resistance. Full-Text PDF Open AccessIdentification of antibiotic pairs with disjoint resistance: innovative progress made but questions remainWe have read the study by Andrew Beckley and Erik Wright1 with great interest, which identified the antibiotic pairs with disjoint resistance in subpopulations of the six most frequently isolated bacterial species (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Enterococcus faecalis, Pseudomonas aeruginosa, and Proteus mirabilis). The results of this study are innovative and indicate progress in this field, but we have one serious concern about the classification criteria of the subpopulations and consequent high resistance rate of potential antibiotics in the subgroup. Full-Text PDF Open Access