Identification of antibiotic pairs with disjoint resistance: innovative progress made but questions remain
Authors: Dooshanveer C Nuckchady
Journal: The Lancet Microbe (2021)

I read with great interest the article by Andrew Beckley and Erik Wright,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 in which a score based on mutual information was used to look for antibiotic pairs that have concurrent resistance. Another study examined antibiotic pairs that could be used to cover Gram negative organisms.2Nuckchady DC, Colgrove R. Choice of antibiotics for initial double-coverage of suspected Gram-negative bacteremia. IDWeek 2013; October 2–6, 2013 (abstr 1336).Google Scholar This study used a Pearson's χ2 test to compare the expected versus the actual rate of dual resistance instead of analysing the component information since data on dual resistance are more easily interpretable. Of 527 possible antibiotic combinations, most antibiotic pairs did not confer significant additional benefits in terms of a reduction in resistance compared with the use of single antibiotics. Resistance to one class of antibiotics was predictive of resistance to a different class. Moreover, the antibiotic pair with the least disjoint resistance was the combination of a β-lactam with either an aminoglycoside or a fluoroquinolone, although the additional coverage obtained was small. Both findings are in line with the study by Beckley and Wright.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 It might be worth noting that, for patients allergic to penicillin, the most useful antibiotic pairs were an aminoglycoside combined with either aztreonam or a fluoroquinolone. Cross-resistance among gram negative organisms was less likely to be encountered in these instances. New approaches are needed to combat the rise of multidrug-resistant organisms. Both above studies suggest that antibiotic cycling and dual antibiotic combinations are not likely to have a major effect on the prevalence of antibiotic resistance. Future efforts should probably focus on rapid diagnostics, isolating patients colonised by resistant microorganisms, and shortening the antibiotic treatment duration.3Karam G Chastre J Wilcox MH Vincent J-L Antibiotic strategies in the era of multidrug resistance.Crit Care. 2016; 20: 136Crossref PubMed Scopus (135) Google Scholar I 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 remain – Authors' replyWe thank Huan Zhang and Yun Cai for their comments on our Article.1 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. 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