Risk factors for, and molecular epidemiology and clinical outcomes of, carbapenem- and polymyxin-resistant Gram-negative bacterial infections in pregnant women, infants, and toddlers: a systematic review and meta-analyses.

In the following systematic review and meta-analyses, we report several conclusions about resistance to carbapenem and polymyxin last-resort antibiotics for treating multidrug-resistant bacterial infections among pregnant women and infants. Resistance to carbapenems and polymyxins is increasing, even in otherwise vulnerable groups such as pregnant women, toddlers, and infants, for whom therapeutic options are limited. In almost all countries, carbapenem-/polymyxin-resistant Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii infect and/or colonize neonates and pregnant women, causing periodic outbreaks with very high infant mortalities. Downregulation of plasmid-borne blaNDM , blaKPC , blaOXA-48 , blaIMP, blaVIM , blaGES-5 , and ompK35/36 in clonal strains accelerates the horizontal and vertical transmissions of carbapenem resistance among these pathogens. New Delhi metallo-β-lactamase (NDM)-positive isolates in infants/neonates have been mainly detected in China and India, while OXA-48-positive isolates in infants/neonates have been mainly detected in Africa. NDM-positive isolates in pregnant women have been found only in Madagascar. Antibiotic therapy, prolonged hospitalization, invasive procedures, mechanical ventilation, low birth weight, and preterm delivery have been common risk factors associated with carbapenem/polymyxin resistance. The use of polymyxins to treat carbapenem-resistant infections may be selecting for resistance to both agents, restricting therapeutic options for infected infants and pregnant women. Currently, low- and middle-income countries have the highest burden of these pathogens. Antibiotic stewardship, periodic rectal and vaginal screening, and strict infection control practices in neonatal ICUs are necessary to forestall future outbreaks and deaths.