Emerging Strategies to Combat ESKAPE Pathogens in the Era of Antimicrobial Resistance: A Review

The spread of antibiotic-resistant bacteria poses a substantial threat to morbidity and mortality worldwide. Due to its large public health and societal implications, multidrug-resistant tuberculosis has been long regarded by WHO as a global priority for investment in new drugs. In 2016, WHO was requested by member states to create a priority list of other antibiotic-resistant bacteria to support research and development of effective drugs.

Several well-recognized puzzles in microbiology have remained unsolved for decades. These include latent bacterial infections, unculturable microorganisms, persister cells and biofilm multidrug tolerance. Accumulating evidence suggests that these seemingly disparate phenomena result from the ability of bacteria to enter into a dormant (non-dividing) state. The molecular mechanisms that underlie the formation of dormant persister cells are now being unravelled and are the focus of this Review.

Health-care-associated infection is the most frequent result of unsafe patient care worldwide, but few data are available from the developing world. We aimed to assess the epidemiology of endemic health-care-associated infection in developing countries. We searched electronic databases and reference lists of relevant papers for articles published 1995-2008. Studies containing full or partial data from developing countries related to infection prevalence or incidence-including overall health-care-associated infection and major infection sites, and their microbiological cause-were selected. We classified studies as low-quality or high-quality according to predefined criteria. Data were pooled for analysis. Of 271 selected articles, 220 were included in the final analysis. Limited data were retrieved from some regions and many countries were not represented. 118 (54%) studies were low quality. In general, infection frequencies reported in high-quality studies were greater than those from low-quality studies. Prevalence of health-care-associated infection (pooled prevalence in high-quality studies, 15·5 per 100 patients [95% CI 12·6-18·9]) was much higher than proportions reported from Europe and the USA. Pooled overall health-care-associated infection density in adult intensive-care units was 47·9 per 1000 patient-days (95% CI 36·7-59·1), at least three times as high as densities reported from the USA. Surgical-site infection was the leading infection in hospitals (pooled cumulative incidence 5·6 per 100 surgical procedures), strikingly higher than proportions recorded in developed countries. Gram-negative bacilli represented the most common nosocomial isolates. Apart from meticillin resistance, noted in 158 of 290 (54%) Staphylococcus aureus isolates (in eight studies), very few articles reported antimicrobial resistance. The burden of health-care-associated infection in developing countries is high. Our findings indicate a need to improve surveillance and infection-control practices. World Health Organization. Copyright © 2011 Elsevier Ltd. All rights reserved.