Clinical characteristics and outcomes of Pseudomonas aeruginosa bacteremia in febrile neutropenic children and adolescents with the impact of antibiotic resistance: a retrospective study

Abstract

BackgroundAlthough the proportion of Pseudomonas aeruginosa infections has reduced after the introduction of antibiotics with anti-pseudomonal effects, P. aeruginosa bacteremia still causes high mortality in immunocompromised patients. This study determined the clinical characteristics and outcomes of P. aeruginosa bacteremia and the antibiotic susceptibilities of strains isolated from febrile neutropenic patients.MethodsThirty-one febrile neutropenic children and adolescents with underlying hematologic/oncologic disorders diagnosed with P. aeruginosa bacteremia between 2011 and 2016 were enrolled in the study. Their medical records were retrospectively reviewed to evaluate the demographic and clinical characteristics. Antibiotic susceptibility rates of the isolated P. aeruginosa to eight antibiotic categories (anti-pseudomonal penicillin, anti-pseudomonal penicillin and β-lactamase inhibitor combination, anti-pseudomonal cephalosporin, monobactam, carbapenem, aminoglycoside, fluoroquinolone, and colistin) were also determined. Among the investigated factors, risk factors for mortality and infections by a multidrug-resistance (MDR) strain were determined.ResultsThirty-six episodes of P. aeruginosa bacteremia were identified. The mean age of the enrolled patients was 9.5 ± 5.4 years, and 26 (72.2%) episodes occurred in boys. Acute myeloid leukemia (41.7%) and acute lymphoblastic leukemia (33.3%) were the most common underlying disorders. The 30-day mortality was 38.9%, and 36.1% of the episodes were caused by MDR strains. The deceased patients were more likely to experience breakthrough infection (P = 0.036) and bacteremia (P = 0.005) due to MDR strains when compared with the patients who survived. The survived patients more likely received appropriate empirical antibiotic therapy (P = 0.024) and anti-pseudomonal β-lactam and aminoglycoside combination therapy (P = 0.039) compared with the deceased patients. The antibiotic susceptibility rates of the isolated P. aeruginosa strains were as follows: piperacillin/tazobactam, 67.6%; meropenem, 72.2%; and amikacin, 100%.ConclusionsMortality due to P. aeruginosa bacteremia remained at 38.9% in this study, and more than one-third of the isolated strains were MDR. In this context, empirical antibiotic combination therapy to expand the antibiotic spectrum may be a strategy to reduce mortality due to P. aeruginosa bacteremia in febrile neutropenic patients.

Piperacillin pharmacokinetics and target attainment in children with cancer and fever: Can we optimize our dosing strategy?

“…To evaluate the PTA of the predefined PK/PD targets, we used an intrainstitutional MIC range and the breakpoint for P. aeruginosa (16.0 mg/L), the latter representing worst‐case scenario MIC, due to various resistance mechanisms . Accordingly, current guidelines concerning empiric antimicrobial therapy in pediatric oncology patients recommend coverage for P. aeruginosa .…”

“…To evaluate the PTA of the predefined PK/PD targets, we used an intrainstitutional MIC range and the breakpoint for P. aeruginosa to various resistance mechanisms. 36,37 Accordingly, current guidelines concerning empiric antimicrobial therapy in pediatric oncology patients recommend coverage for P. aeruginosa. 5 We did not detect We believe that implementation of an optimized, prospective sampling approach with a total of 482 piperacillin concentrations improved the capability of our PK model to fully characterize the piperacillin concentration-time course in children with chemotherapy-induced fever.…”

Epidemiological features and risk factors for mortality in Pseudomonas aeruginosa bacteremia in children

“…High gross mortality rates were associated with patients that required admission to the ICU in some series. [11][12][13] In other series, the presence of respiratory distress and MV requirement was an independent risk factor related to mortality. 1,13 Consistent with other authors, 1,10,13 the clinical presentation of sepsis was also a predictor of mortality.…”

Dosage Regimens for Meropenem in Children with Pseudomonas Infections Do Not Meet Serum Concentration Targets

“…The FDA recommendations for treatment of serious, deep tissue infections with meropenem have been based on carefully performed PK analyses . Nevertheless, these infections are still associated with significant morbidity and further improvements in treatment are needed …”

“…[1][2][3]5 Nevertheless, these infections are still associated with significant morbidity and further improvements in treatment are needed. [31][32][33] Recent studies in adults suggest that treatment with beta-lactams in critically ill subjects may be associated with shorter T > MIC 90 than recommended and possibly inadequate clinical responses. [12][13][14][15][16][17] The report of Ohata et al 8 originally suggested that this may be the case for many children and, since the completion of our studies, two new reports have been published also suggesting an unacceptable risk for undertreatment in this population.…”