In low- and middle-income countries, carbapenem resistance may be associated with increased mortality and length of hospital stay in patients with bloodstream infections, according to a study published in Lancet Infectious Diseases.

Antimicrobial resistance is a significant economic and global health threat. Strategies such as infection control measures, new antimicrobial development, and antimicrobial stewardship are helping to ameliorate the threat of antimicrobial resistance, but there continues to be a need for accurate estimations of this burden to make informed decisions about the allocation of resources.

One of the paramount concerns is the progressively developing resistance to “last-line” antibiotics such as carbapenems. Few studies have assessed the effects of carbapenem resistance on health outcomes, and most of the studies performed have been in high-income settings when the greatest burden is among low- and middle-income countries. Further, there is a near complete absence of data regarding antimicrobial resistance in these low- and middle-income countries, creating a significant gap in knowledge. Therefore, this multinational prospective cohort study quantified the clinical effect of carbapenem resistance on mortality and length of hospital stay among inpatients with a bloodstream infection caused by Enterobacteriaceae in low- and middle-income countries.

Patients were recruited from 16 sites in 10 countries: Pakistan, Bangladesh, Colombia, Egypt, Ghana, Lebanon, Nepal, Nigeria, Vietnam, and India. While recruiting, hospitals diagnosed patients with either carbapenem-susceptible Enterobacteriaceae (CSE) or carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infections. In total, 297 patients were included in the study; 174 patients had a CSE bloodstream infection and 123 had a CRE bloodstream infection. Patients were excluded if they had previously been enrolled in the study or were not treated with curative intent at the time of onset of the bloodstream infection. Central laboratories performed confirmatory testing and molecular characterization, which included strain typing. Proportional sub-distribution hazard models with inverse probability weighting to estimate the effect of carbapenem resistance on probability of discharge alive and in-hospital death were applied; multistate modelling was applied for excess length of hospital stay.

In-hospital mortality occurred in 35 (20%) patients with CSE bloodstream infections and 43 (35%) patients with CRE bloodstream infections. The most commonly prescribed antibiotics for patients with CRE bloodstream infection from day 3 onward were carbapenems (55 [59%] patients), polymyxins (48 [52%] patients), and antibiotics from both classes (35 [38%] patients). The most commonly prescribed antibiotic for patients with CSE bloodstream infection was carbapenems, 65 (39%) during the first 3 days and 63 (47%) on subsequent days. In addition, carbapenem resistance was associated with an increased length of hospital stay (3.7 days; 95% CI, 0.3-6.9), increased probability of in-hospital mortality (adjusted sub-distribution hazard ratio, 1.75), and decreased probability of discharge alive (0.61).

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Researchers also noted that although the incidence of septic shock was similar between patients with CSE and CRE bloodstream infection (26% and 27%, respectively), patients with CRE infection more commonly had persistent bacteremia compared with those with CSE infection (17% vs 8%).

Overall, the study authors concluded that, “These data will inform global estimates of the burden of antimicrobial resistance and reinforce the need for better strategies to prevent, diagnose, and treat CRE infections in [low-income and middle-income countries].

Reference

Stewardson AJ, Marimuthu K, Sengupta S, et al. Effect of carbapenem resistance on outcomes of bloodstream infection caused by Enterobacteriaceae in low-income and middle -income countries (PANORAMA): a multinational prospective cohort study. Lancet Infect Dis. 2019;19:601-610.