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  • Increased Antibiotic Resistance in Children

    Rising antibiotic resistance is a concern for every health organization and healthcare system. Antibiotic-resistant infections often require costlier, extended treatments, longer hospital stays, additional doctor visits and healthcare use and typically result in greater disability and death compared with infections that are usually easily treatable with antibiotics. Moreover, antibiotic resistance poses a greater burden to pediatric patients since children are at increased risk for adverse outcomes related to multidrug-resistant gram-negative enteric Enterobacteriaceae (MDR-GNE) infection and only a limited number of broad-spectrum antibiotics have been approved for pediatric use.

    A recent study published by researchers at Case Western Reserve University School of Medicine looked at the incidence of MDR-GNE infections in children from 2007 to 2015. The authors concluded that infections with the MDR-GNE increased by more than 700% for pediatric patients admitted to children's hospitals. The Enterobacteriaceae comprise a large family of gram-negative enteric bacilli from which MDR-GNE arose, which are resistant to almost all β-lactam antibiotics. MDR-GNE infection is an increasingly global public health concern, involved in 11.4% of gram-negative bacilli pediatric intra-abdominal infections worldwide between 2008 and 2010.

    Since data describing MDR-GNE infections in children are limited, researchers sought to characterize the current epidemiology of infection with MDR-GNE in hospitalized children in the U.S. and to assess the relationships between infection and resulting length of stay and death. Data were retrospectively pulled from the Pediatric Health Information System, an administrative database that contains inpatient, emergency department, ambulatory surgery and observation encounter-level data from 48 U.S. children's hospitals. As a surrogate for overall nonspecific antimicrobial resistance in Enterobacteriaceae, MDR-GNE was defined as the subset of these Enterobacteriaceae discharges that also included the ICD-9 codes V09.81, "Infection with microorganisms with resistance to multiple drugs" or V09.91, "Infection with drug-resistant microorganisms, unspecified, with multiple drug resistance."

    Of a total of 107,610 hospital discharges, 724 (0.7%) were associated with MDR-GNE. Throughout the study period from 2007 to 2015, the number of discharges with Enterobacteriaceae-associated infection remained relatively stable; however, the proportion of those with MDR-GNE infection rose significantly from 0.2% in January 2007 to 1.5% by March 2015. Pediatric patients with MDR-GNE infections were increasingly more likely to be associated with hospitalizations including an ICU stay. Regarding death before discharge, patients with an MDR-GNE infection had a higher crude risk of death compared with those without (2.9% vs 1.7%).

    Although pulling retrospective data from a health information system has its drawbacks, the study appears to be the first to examine the epidemiology of MDR-GNE infection across U.S. children's hospitals. It gives a sobering glimpse into the increasing incidence of infection with MDR-GNE in a pediatric population and the association with longer hospital lengths of stay and a trend toward a higher mortality rate. In the face of globally escalating antibiotic resistance, it becomes ever more important to adhere to hospital surveillance cultures, strict cohorting, limited use of third-generation cephalosporins and restricted agricultural antibiotic use to reduce the colonization of resistant bacteria. In addition to judicious approaches with the use of current antibiotics, there is an increasing requirement of development of novel antimicrobials for gram-negative bacteria, with the impetus being the threat of pandrug resistance. To this end, the Infectious Disease Society of America is pursuing an initiative for development of 10 new antibiotics against gram-negative bacilli by the year 2020.

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    1) Centers for Disease Control and Prevention. (2013). Antibiotic Resistance Threats in the United States, 2013. Retrieved from https://www.cdc.gov/drugresistance/threat-report-2013/.

    2) Meropol SB, Haupt AA, Debanne SM. Incidence and Outcomes of Infections Caused by Multidrug-Resistant Enterobacteriaceae in Children, 2007-2015. J Pediatric Infect Dis Soc. 2017. doi: 10.1093/jpids/piw093.

    3) Taneja N, Kaur H. Insights into Newer Antimicrobial Agents Against Gram-negative Bacteria. Microbiology Insights. 2016; 9: 9–19.