Antibiotic-Resistant Gram-Negative Bacteremia in Febrile Neutropenic Children

Children with malignancy receiving chemotherapy are prone to suffer from bacteremia and sepsis, which may consequently lead to significant neutropenia, loss of mucosal integrity, and the need for an indwelling central venous catheter. Bacteremia reportedly occurs more often in neutropenic than non-neutropenic episodes (20% vs. 3%) [1], and the presence of sepsis or bacteremia confers a 10-fold increase in the risk of death [2]. Further, febrile episodes are observed in 34% of neutropenic periods in pediatric cancer patients, with bacteremia identified in 10-20% of cases; however, up to 79% of episodes of febrile neutropenia are not associated with serious infection [3]. Pathogens associated with bacteremia and the rates of resistance in febrile neutropenic children vary depending on the time and location. Lee et al. [4] conducted a single-center pediatric retrospective study in Seoul, Korea, including 336 bacteremia episodes occurring in 186 febrile neutropenic children over 4 consecutive years, to describe the distribution of the causative bacteria and clinical impact of antibiotic-resistant organisms. Even though there is substantial evidence of a significant shift towards more Gram-positive isolates from blood-cultures in febrile neutropenic children [5], more than 50% of bacteremia cases were caused by Gram-negative bacteria in Lee’s study [4]. Moreover, the portion of Gram-positive bacteremia in febrile neutropenic children might be overestimated because the normal skin florae, including coagulase-negative staphylococci, were considered true pathogens in cases with indwelling vascular catheters and use of antibiotics [4]. However, coagulase-negative staphylococci, which are generally low-virulent, can cause serious infection in febrile neutropenic children, and may thus need to be regarded as an actual pathogen in these situations if an alternative source of infection is not identified [6]. Multi-drug resistance (MDR), defined as diminished sensitivity to ≥3 of the broad-spectrum antibiotic classes, is known to be associated with increased morbidity and mortality in febrile neutropenia [7]. Lee et al. [4] concluded that antibiotic-resistant organisms were significantly associated with increased overall mortality in febrile neutropenic bacteremia, although antibiotic-resistant Gram-positive bacteria such as methicillin-resistant Staphylococcus spp. and vancomycin-resistant Enterococcus spp. were not associated with higher morbidity and mortality compared to nonantibiotic-resistant Gram-positive bacteria. However, antibiotic-resistant