Increased rate of multidrug-resistant gram-negative bacterial infections in hospitalized immunocompromised pediatric patients

Abstract

Introduction: Multidrug resistant Gram-negative bacterial infections are considered a major public health threat. Immunocompromised pediatric patients are at a great risk of severe or overwhelming infections. The aim of this study was to describe the frequency of infections with multidrug resistant (MDR) Gram-negative bacteria (GNB) in immunocompromised pediatric patients and to determine the risk factors. In addition, we aimed to identify the antimicrobial resistance patterns of these isolates.

Materials and methods: This was a retrospective observational study conducted at the American University of Beirut Medical Center (AUBMC) from 2009 to 2017. The study included immunocompromised patients 18 years of age or younger with infections caused by Gram-negative bacteria isolated from a sterile site, or nonsterile site in the setting of clinical infection.

Results: A total of 381 episodes of infection with GNB in 242 immunocompromised pediatric patients were identified. The mean age was 7.7 years. The most common pathogens were Enterobacterales followed by Pseudomonas and Acinetobacter spp. MDR GNB infections predominated causing 72% of the episodes, with alarming MDR rates among Escherichia coli (95.7%) and Klebsiella pneumoniae (82.7%). The overall rate of MDR GNB isolated increased from 62.7% in 2015 to 90% in 2017. Thrombocytopenia, chemotherapy and previous colonization or infection with the same organism during the past 12 months were found to be independent risk factors for infection with MDR GNB.

Conclusion: This study provides data on the epidemiology of infections with MDR GNB in immunocompromised pediatric patients and illustrates the alarmingly high prevalence of these infections. This necessitates the frequent revisiting of treatment guidelines in these high-risk patients and the implementation of judicious antimicrobial stewardship programs and infection control policies to stabilize or decrease the prevalence of these infections.

Keywords: adolescent; antimicrobial resistance; cancer; children; gram-negative bacteria; immunocompromised; inborn errors of immunity; multidrug resistance.

Figure 1

Flow chart of the study design. *Duplicated cultures, from same or different dates, responsible for the same episode of infection were excluded and only the first culture from each episode was included unless it was collected from different sites. Different cultures taken from the same site, during the same episode of infection, that yielded different organisms were included.

Figure 2

The distribution of Gram-negative bacteria isolated from infected immunocompromised pediatric patients (N =431). Klebsiella spp.: Klebsiella oxytoca (3), Klebsiella pneumoniae (95). Pseudomonas spp.: Pseudomonas aeruginosa (64), Pseudomonas fluorescens (3), Pseudomonas putrefaciens (1), Pseudomonas stutzeri (6), Pseudomonas spp. (1). Salmonella spp.: Salmonella enteritidis (7), Salmonella group C (2), Salmonella paratyphi (1), Salmonella not typable (1). Enterobacter spp.: Enterobacter aerogenes (1), Enterobacter cloacae (11), Enterobacter agglomerans (1). Acinetobacter spp.: Acinetobacter anitratus (4), Acinetobacter baumanii (5), Acinetobacter lwoffi (1). *Other organisms: Aeromonas hydrophilia, Aeromonas sobria, Brevundimonas vesicularis, Campylobacter spp. (2), Chryseomonas indologens (2), Citrobacter freundii (3), Citrobacter koseri, Comamonas acidovorans, Haemophilus influenzae not type B, Moraxella catarrhalis (2), Morganella morganii (2), Myroides spp., Ochobactrum anthropi, Ralstonia piketti (2), Serratia liquefaciens (2), Serratia marcescens, Shigella flexneri (2), Shigella sonnei.

Figure 3

The rate of the multidrug resistant phenotype in Gram-negative bacteria isolated from infected immunocompromised pediatric patients (N=431). *Other organisms: Aeromonas hydrophilia, Aeromonas sobria, Brevundimonas vesicularis, Campylobacter spp. (2), Chryseomonas indologens (2), Citrobacter freundii (3), Citrobacter koseri, Comamonas acidovorans, Haemophilus influenzae not type B, Moraxella catarrhalis (2), Morganella morganii (2), Myroides spp., Ochobactrum anthropi, Ralstonia piketti (2), Serratia liquefaciens (2), Serratia marcescens, Shigella flexneri (2), Shigella sonnei.

Figure 4

Distribution of Gram-negative bacterial isolates and their resistance phenotype according to the immunocompromised state. *Aeromonas sobria, Citrobacter koseri, Moraxella catarrhalis, Shigella flexneri # Citrobacter freundii, Moraxella catarrhalis, Morganella morganii, Ralstonia piketti, Serratia liquefaciens, Serratia marcescens, Shigella sonnei ⁺Aeromonas hydrophilia, Brevundimonas vesicularis, Campylobacter spp., Chryseomonas indologens, Citrobacter freundii, Comamonas acidovorans, Haemophilus influenzae not type B, Myroides spp., Ochobactrum anthropic, Ralstonia piketti, Serratia liquefaciens.

Figure 5

Number of Gram-negative bacterial isolates, their resistance phenotype, and percentage of multidrug resistance over the 9-year study period (N=431). The x-axis represents the years from 2009 to 2017 (to note that the included cultures were from June 1^st to December 31^st for the year 2009 and from January 1^st to June 31^st for 2017), and the y-axis is the number of organisms per year. The line graph represents the percentage of MDR GNB.