Antibiotic resistance during and beyond COVID-19

Abstract

Antibiotics underpin the 'modern medicine' that has increased life expectancy, leading to societies with sizeable vulnerable elderly populations who have suffered disproportionately during the current COVID-19 pandemic. Governments have responded by shuttering economies, limiting social interactions and refocusing healthcare. There are implications for antibiotic resistance both during and after these events. During spring 2020, COVID-19-stressed ICUs relaxed stewardship, perhaps promoting resistance. Counterpoised to this, more citizens died at home and total hospital antibiotic use declined, reducing selection pressure. Restricted travel and social distancing potentially reduced community import and transmission of resistant bacteria, though hard data are lacking. The future depends on the vaccines now being deployed. Unequivocal vaccine success should allow a swift return to normality. Vaccine failure followed by extended and successful non-pharmaceutical suppression may lead to the same point, but only after some delay, and with indefinite travel restrictions; sustainability is doubtful. Alternatively, failure of vaccines and control measures may prompt acceptance that we must live with the virus, as in the prolonged 1889-94 'influenza' (or coronavirus OC43) pandemic. Vaccine failure scenarios, particularly those accepting 'learning to live with the virus', favour increased outpatient management of non-COVID-19 infections using oral and long t _½ antibiotics. Ultimately, all models-except those envisaging societal collapse-suggest that COVID-19 will be controlled and that hospitals will revert to pre-2020 patterns with a large backlog of non-COVID-19 patients awaiting treatment. Clearing this will increase workloads, stresses, nosocomial infections, antibiotic use and resistance. New antibiotics, including cefiderocol, are part of the answer.

Figure 1.

Three measures of changing lifespan for men in the UK. Data Source: Office for National Statistics. LE, life expectancy. Patterns for women are similar though life expectancy is slightly longer.

Figure 2.

Incidence of E. coli bacteraemia in England and Wales, by age. Data source: PHE.

Figure 3.

First wave deaths from COVID-19 in France (strict lockdown; 13.8% Q2 fall in GDP), UK (moderate lockdown; 20.4% Q2 fall in GDP) and Sweden (no lockdown; 8.6% Q2 fall in GDP).

Figure 4.

Activity of recently licensed (USA and EU/UK) agents against problem groups of Gram-negative bacteria. Green, widely active (>90%); orange, variably active (50%–90%); red, rarely (<50%) or never active. ^aTrial evidence of efficacy.^bIn-use evidence of clinical activity against P. aeruginosa likely, based on phenotypes, to have these mechanisms.^cTrial evidence of efficacy.^dIn-use evidence of efficacy and of better outcomes than colistin combinations.^,eTrial evidence of better outcomes than colistin combinations.^fTrial evidence of activity against imipenem-resistant P. aeruginosa, likely to have owed their phenotypes to combination of loss of porin OprD and expression of AmpC.^gLicensing application withdrawn in EU. ^hMany isolates with NDM carbapenemases co-produce ArmA or RmtB 16S rRNA methyltransferases, conferring broad aminoglycoside resistance including plazomicin.ⁱGood in vitro activity against carbapenemase-producing Enterobacterales, but trial failures in cUTI.^jTrial evidence of activity.^kMICs raised for isolates with NDM carbapenemase compared with those for isolates with other carbapenemases; the proportion of these that count as resistant will depend on the breakpoints used.^lIn vitro activity, but excess mortality in CREDIBLE-CR study compared with colistin combinations, associated with Acinetobacter baumannii, suggesting the need for caution.