Exploiting antibiotic combinations to overcome resistance

The global antimicrobial resistance crisis has resulted in widespread prescribing of clinically untested antibacterial regimens. The intervention of urgency to protect the antibiotics we have, is to ensure only those who absolutely need antibiotics (to prevent undue suffering or to treat sight, limb or life-threatening infections) receive them. The development of novel diagnostics, antimicrobials and approaches to infection management is also vital. To avoid repeating history however, understanding of how we can prescribe old and new antibiotics to treat infection and prevent the evolution, selection and spread of resistance in target and non-target bacteria is mandatory. Although there is expanding experience of treating extensively-drug-resistant (XDR) Gram-negative infections, our knowledge of how to optimally prescribe antibiotics to overcome resistance mechanisms and/or inhibit resistance, including in susceptible bacteria, is rudimentary.

One approach is to prescribe antibiotic combinations, which has become a standard-of-care for serious XDR-Gram-negative infections, using predominantly colistin-based regimens [1], but without high-quality clinical evidence. However, with few exceptions, both historic and recent evidence suggests that combinations result in more harm than good [2,3]. Emerging evidence also suggests that new agents for Gram-negative infections, whether combined or not, are better than colistin [4,5].

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