Intravenous Ceftazidime-Avibactam in Extremely Premature Neonates With Carbapenem-Resistant Enterobacteriaceae: Two Case Reports.

The increasing use of carbapenems has contributed to a notable distribution of carbapenem-resistant Enterobacteriaceae (CRE). Recently, the incidence of CRE-associated infections is increasing significantly in NICUs, which pose a grave challenge to clinical treatment. We report 2 cases of IV ceftazidimeavibactam use to treat CRE infections in extremely premature neonates. The first case was diagnosed with bacteraemia and meningitis and the second one was diagnosed with bacteraemia only. Due to the lack of neonatal-specific information for IV ceftazidime-avibactam, the usual pediatric dose (62.5 mg/kg/dose every 8 hours) was used in these patients. Clinical cure occurred in these 2 patients. Although blood cultures became sterile after starting ceftazidime-avibactam in the second case, the patient died, presumably owing to sepsis or various causes, such as prematurity and chronic lung disease. Large and randomized studies are necessary to ensure the safety and efficacy of IV ceftazidime-avibactam for the treatment of neonates with sepsis caused by multidrug resistant organisms.

[1]  M. Al-Mouqdad,et al.  Early initiation of broad-spectrum antibiotics in premature infants , 2022, Minerva Pediatrics.

[2]  M. Al-Mouqdad,et al.  The Use of Daptomycin in the Treatment of Persistent Coagulase-Negative Staphylococcal Sepsis in Premature Infants: A Case Series. , 2021, The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG.

[3]  Serkan Atıcı,et al.  Successful Treatment of Pandrug-resistant Klebsiella pneumoniae Infection With Ceftazidime-avibactam in a Preterm Infant: A Case Report. , 2020, The Pediatric infectious disease journal.

[4]  M. Bassetti,et al.  Optimal Management of Complicated Infections in the Pediatric Patient: The Role and Utility of Ceftazidime/Avibactam , 2020, Infection and drug resistance.

[5]  M. Al-Mouqdad,et al.  Early initiation of broad-spectrum antibiotics in premature infants. , 2019, Minerva pediatrica.

[6]  M. Vargas,et al.  Successful treatment of KPC-MDR septic shock with ceftazidime-avibactam in a pediatric critically ill patient , 2019, IDCases.

[7]  J. Bradley,et al.  Safety and Efficacy of Ceftazidime-Avibactam Plus Metronidazole in the Treatment of Children ≥3 Months to <18 Years With Complicated Intra-Abdominal Infection: Results From a Phase 2, Randomized, Controlled Trial. , 2019, The Pediatric infectious disease journal.

[8]  E. Roilides,et al.  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. , 2019, The Pediatric infectious disease journal.

[9]  M. Bassetti,et al.  Treatment of Infections Due to MDR Gram-Negative Bacteria , 2019, Front. Med..

[10]  O. Tenaillon,et al.  Successful Treatment of Bacteremia Due to NDM-1-Producing Morganella morganii with Aztreonam and Ceftazidime-Avibactam Combination in a Pediatric Patient with Hematologic Malignancy , 2018, Antimicrobial Agents and Chemotherapy.

[11]  M. Al-Mouqdad,et al.  A retrospective cohort study patient chart review of neonatal sepsis investigating responsible microorganisms and their antimicrobial susceptibility , 2018 .

[12]  R. Saha,et al.  Predictors for gut colonization of carbapenem‐resistant Enterobacteriaceae in neonates in a neonatal intensive care unit , 2018, American journal of infection control.

[13]  M. Shirley Ceftazidime-Avibactam: A Review in the Treatment of Serious Gram-Negative Bacterial Infections , 2018, Drugs.

[14]  W. Timp,et al.  Successful Treatment of Persistent Burkholderia cepacia Complex Bacteremia with Ceftazidime-Avibactam , 2018, Antimicrobial Agents and Chemotherapy.

[15]  S. Richter,et al.  Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae , 2018, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[16]  I. Gur,et al.  Vital signs analysis algorithm detects inflammatory response in premature infants with late onset sepsis and necrotizing enterocolitis , 2017, bioRxiv.

[17]  K. Timberlake,et al.  Levofloxacin Use in the Neonate: A Case Series. , 2017, The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG.

[18]  Diansong Zhou,et al.  Phase I Study Assessing the Pharmacokinetic Profile, Safety, and Tolerability of a Single Dose of Ceftazidime-Avibactam in Hospitalized Pediatric Patients , 2016, Antimicrobial Agents and Chemotherapy.

[19]  C. MacDougall,et al.  Beyond Susceptible and Resistant, Part III: Treatment of Infections due to Gram-Negative Organisms Producing Carbapenemases. , 2016, The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG.

[20]  K. Fairchild,et al.  Predictive monitoring for sepsis and necrotizing enterocolitis to prevent shock. , 2015, Seminars in fetal & neonatal medicine.

[21]  G. Daikos,et al.  Treating infections caused by carbapenemase-producing Enterobacteriaceae. , 2014, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[22]  V. Miriagou,et al.  Carbapenemase-Producing Klebsiella pneumoniae Bloodstream Infections: Lowering Mortality by Antibiotic Combination Schemes and the Role of Carbapenems , 2014, Antimicrobial Agents and Chemotherapy.

[23]  Chiang-Wen Lee,et al.  Risk Factors and Outcomes for Multidrug-Resistant Gram-Negative Bacteremia in the NICU , 2014, Pediatrics.

[24]  R. Bonomo,et al.  Carbapenem-resistant Enterobacteriaceae: a review of treatment and outcomes. , 2013, Diagnostic microbiology and infectious disease.

[25]  M. Bassetti,et al.  Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[26]  D. Paterson,et al.  Treatment Outcome of Bacteremia Due to KPC-Producing Klebsiella pneumoniae: Superiority of Combination Antimicrobial Regimens , 2012, Antimicrobial Agents and Chemotherapy.

[27]  M. P. Griffin,et al.  Heart Rate Characteristics and Clinical Signs in Neonatal Sepsis , 2007, Pediatric Research.

[28]  W. Poole,et al.  Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. , 2002, Pediatrics.

[29]  B. Stoll,et al.  Neonatal sepsis: progress towards improved outcomes. , 2014, The Journal of infection.