Gram-negative gut colonization in children newly diagnosed with malignancy: microbiology, antimicrobial resistance pattern, and clinical implications.
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BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) pose significant treatment difficulties owing to their high levels of antibiotic resistance. This study investigated the gut colonization rates of carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) and extended-spectrum β-lactamase-producing (ESBL) gram-negative bacteria (GNB). Moreover, this study evaluated the antibiotic susceptibility profiles of CP-CRE and ESBL-producing Gram-negative bacteria. It also examines the potential infectious complications that may arise in pediatric patients recently diagnosed with cancer. METHODS: This prospective cohort study was conducted at a referral teaching oncology hospital in Shiraz, Iran. Fecal samples were collected at three time points: within 48-72 h of hospitalization, at the end of the first chemotherapy session, and during the next admission. The first sample identified cases of community-acquired colonization, whereas the second and third samples assessed hospital-acquired colonization by gram-negative bacteria. The infectious outcomes examined in this study included neutropenic enterocolitis (typhlitis), a life-threatening condition, and bloodstream infection.Antimicrobial susceptibility testing was performed for all gram-negative isolates using Clinical and Laboratory Standards Institute (CLSI)-standardized disk diffusion methods. Extended-spectrum β-lactamase (ESBL) production was screened and confirmed phenotypically, according to the CLSI criteria. In a subset of Escherichia coli (E. coli) isolates, polymerase chain reaction (PCR) was used to detect key β-lactamase and carbapenemase genes (blaCTX-M, blaTEM, blaSHV, blaOXA-48, blaNDM, and blaKPC). RESULTS: Eighty-one patients with a median age of 6.0 ± 0.49 years and a male: female ratio of 1.25 were included. 57 (70%) patients had community-acquired (CA) colonization with GNB, whereas eight (10%) had hospital-acquired (HA) colonization. E. coli and Klebsiella spp. were the most common pathogens in both colonization groups. In vitro susceptibility testing showed that colistin, amikacin, and carbapenems had the highest activity against the isolates. ESBL-producing GNB were detected in 91/157 (58%) fecal samples, and CP-CRE was detected in 23/157 (14.6%) samples. Twelve (21%) CA colonizers developed infectious outcomes. CONCLUSIONS: The high incidence of CP-CRE colonization underscores the urgent need to monitor and control the spread of these highly resistant bacteria among newly diagnosed pediatric cancer patients in oncology settings.