Use of Ceftazidime-avibactam for the Treatment of Extensively drug-resistant or Pan drug-resistant Klebsiella pneumoniae in Neonates and Children <5 Years of Age.

BACKGROUND: Emergence of extensively drug-resistant (XDR) or pan drug-resistant (PDR) Enterobacteriaceae is a major public threat especially for young patients. Treatment options for these bacteria are extremely limited with no safety data existing for neonates and children. Ceftazidime-avibactam has activity against Gram-negative bacteria producing Klebsiella pneumoniae carbapenemase, but virtually no data exist on its use in neonatal and pediatric patients. METHODS: We present a single-center case series of neonates and children <5 years treated with ceftazidime-avibactam for XDR or PDR K. pneumoniae infections until August 2018. Medical records of patients who received ceftazidime-avibactam for at least 2 days (6 doses) were reviewed. Clinical, laboratory and microbiologic data were collected using a prestructured form. Adverse events and clinical/microbiologic responses and 15- and 30-day outcome were assessed. RESULTS: In our case series, 8 patients (median age 53 days, range from 13 days to 4.5 years) received 9 courses of ceftazidime-avibactam at a dose of 62.5 mg/kg q8h for suspected or proven XDR/PDR K. pneumoniae infections including bloodstream infections (8 courses), central nervous system infections (2 courses) and urinary tract infection (1 course). All patients were critically ill and received other antibiotics prior and concomitantly with the administration of ceftazidime-avibactam. There was no treatment discontinuation due to adverse events. Clinical and microbiologic responses occurred in all patients, and no patient died by day 30. CONCLUSIONS: Administration of ceftazidime-avibactam appears to be well tolerated and efficacious against in vitro susceptible XDR or PDR Enterobacteriaceae without being associated with significant adverse events.

Vancomycin-resistant Enterococcus outbreak in a neonatal intensive care unit: epidemiology, molecular analysis and risk factors.

BACKGROUND: Vancomycin-resistant Enterococcus faecium (VRE) may cause outbreaks in neonatal intensive care units (NICU). We describe a biphasic VRE outbreak and identify risk factors for VRE acquisition. METHODS: After the occurrence of 2 cases of VRE infections in a 44-bed NICU, a bundle of interventions was implemented that included active surveillance cultures for VRE, enhanced infection control measures, and audits on antimicrobial use, from June to December 2008. Analysis was performed using polymerase chain reaction and pulse-field gel electrophoresis techniques. A case-control study was conducted to identify risk factors. RESULTS: Among 253 neonates screened, 101 (39.9%) were found to be colonized with VRE. During the first 9 weeks of the study period, 59 new cases were detected. Molecular analysis showed 1 predominant clone. During weeks 10-12, no new cases of VRE colonization were detected; however, at week 13, just when the outbreak appeared to be over, a second wave occurred, with 42 new cases and multiple clones detected. Multivariate analysis identified administration of antimicrobial therapy for late-onset neonatal sepsis and hospitalization during the first month of this outbreak as significant risk factors for VRE colonization. CONCLUSION: Both a high prevalence of VRE colonization and antimicrobial use promoted the transmission of VRE during this biphasic outbreak. Adherence to infection control measures and antimicrobial stewardship policies are of utmost importance.

Colistin administration to pediatric and neonatal patients.

Emergence of multidrug-resistant Gram-negative nosocomial pathogens has led to resurgence of colistin use. Safety and efficacy data regarding colistin use in pediatric patients are sparse, while optimal dosage has not been defined. We present a case series of neonates and children without cystic fibrosis treated with various doses of colistin intravenously. The records of patients who received colistin in a tertiary-care hospital from January 2007 to March 2009 were reviewed. Thirteen patients (median age 5 years, range 22 days to 14 years) received 19 courses of colistin as treatment of pneumonia, central nervous system infection, bacteremia, or complicated soft tissue infection. The isolated pathogens were Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. Daily dose of colistin (colistimethate) ranged between 40,000 and 225,000 IU/kg. Duration of administration ranged from 1 to 133 days. Other antimicrobials were co-administered in 18/19 courses. Increase of serum creatinine in one patient was associated with co-administration of colistin and gentamicin. Sixteen of 19 courses had a favorable outcome, and only two of the three deaths were infection-related. Colistin intravenous administration appears well tolerated even at higher than previously recommended doses and of prolonged duration.

Daptomycin use in a neonate: serum level monitoring and outcome.

We present a case of successfully treated persistent bacteremia due to Gram-positive bacteria with daptomycin in a preterm neonate. Daptomycin was given at higher doses (6 mg/kg/dose) and shorter intervals (every 12 hours) than those recommended for adults with no adverse events. Peak and trough serum concentrations of daptomycin were 27.3 and 11.6 µg/mL [DOSAGE ERROR CORRECTED] at day 4 as well as 22.9 and 7.9 µg/mL [DOSAGE ERROR CORRECTED]at day 11 after initiation of treatment, respectively.