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

Abstract

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 &lt;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.

<p>Clinical and Molecular Epidemiologic Characteristics of Ceftazidime/Avibactam-Resistant Carbapenem-Resistant <em>Klebsiella pneumoniae</em> in a Neonatal Intensive Care Unit in China</p>

“…17,23 CZA has been viewed as a valuable antibiotic against CRKP in American and European countries, 18,24 and the administration of CZA appears to be well tolerated and efficacious in pediatric patients. 12,13 In this study, the vitro activity of CZA against CRKP isolated from neonates was 77.7%. Two recent multicenter studies also showed that the vitro activity of CZA against CRKP in adults is high.…”

“…While resistance to CZA did not emerge, CZA sensitivity was somewhat lower in a case series of neonates and children <5 years of age patients with CRKP treated with CZA. 13 Resistance emerged in 14% of adult patients with CRKP treated with CZA, 11 and the predominant carbapenemase was KPC. As intestinal carriage of carbapenemase is an important source of transmission, 34 patient-to-patient transmission may be a significant factor in other CZAresistant CRKP isolates in this study.…”

“…Although CZA has not been recommended for use in pediatric patients, studies have shown that it is well tolerated and efficacious in pediatric patients. 12,13 Unfortunately, with the introduction of CZA therapy in clinic, CZA-resistant CRKP infections have emerged in adult patients. [14][15][16] Resistance to CZA in CRKP has been linked to mutations within the Ω-loop in bla KPC 17,18 or bla CTX-M.…”

Carbapenem-Resistant Gram-Negative Bacterial Infections in Children

“…Based on the results from these trials, the Food and Drug Administration (FDA) has recently approved its use in pediatric patients Ͼ3 months of age with complicated intra-abdominal infections (cIAIs), in conjunction with an agent active against anaerobic organisms, and also those with urinary tract infections (UTIs). Currently, clinical data on the treatment of CRE infections with ceftazidime-avibactam in the pediatric population are limited to a few case reports (32,(75)(76)(77)(78).…”

Ceftazidime-Avibactam for Hospital Acquired Pneumonia Due to Extended Drug-Resistant Klebsiella pneumoniae

“…Ceftazidime-avibactam has excellent activity against many extended spectrum β-lactamase, Amp-C, KP-carbapenemase and OXA-48 producing enterobacteriaceae; however it is not active against NDM strains [ 2 ]. Aztreonam is effective against NDM strains as NDM cannot hydrolyse aztreonam.…”