Off-label Use of Ceftazidime/Avibactam in Neonatal Intensive Care Unit: A Real-life Experience and Literature Review.

BACKGROUND: Multi/extensively drug-resistant bacterial infections have recently increased and new antimicrobial options are needed for difficult-to-treat infections. Ceftazidime/avibactam (CZA) has been approved for patients 3 months to 18 years of age, but real-life data on its off-label use in neonates and young infants are still scarce. MATERIALS: We report demographic, clinical and microbiologic data as well as outcome and safety of all cases of infants treated with CZA between January 1, 2021 and September 30, 2022 in a tertiary neonatal intensive care unit. We also review all neonatal cases previously reported. RESULTS: Twenty-one patients [17 males, with median gestational age 29 +2 (IQR 6 +6 ) weeks] received 31 CZA courses at a dose of 20-50 mg/kg/dose of ceftazidime q8h for suspected or proved multi/extensively drug-resistant infections. Median postnatal age at the onset of treatment was 44 days (IQR: 94 days). Twelve bacteremias, 2 urinary tract infections and 1 ventilator-acquired pneumonia were recorded. Twelve (39%) treatments were targeted, while 19 (61%) were empirically started due to known colonization with Klebsiella pneumoniae carbapenemase-producing Gram-negative bacteria. All patients had received multiple antibiotics prior and concomitantly with CZA. The most common pathogen identified at targeted administrations was carbapenem-resistant Klebsiella pneumoniae (83%). No serious adverse events attributed to the drug were detected. Twenty-one courses of CZA administration to 20 neonates with a median gestational age of 28.5 (IQR 3.5) weeks were previously reported without significant related adverse events. CONCLUSIONS: Favorable clinical and microbiologic responses in neonatal intensive care unit patients treated with CZA off-label were observed without significant and unexpected adverse events in critically ill neonates.

Circulating tumor necrosis factor-α levels in non-alcoholic fatty liver disease: A systematic review and a meta-analysis.

BACKGROUND AND AIM: To synthesize data on circulating tumor necrosis factor (TNF)-α levels between patients with histologically confirmed non-alcoholic fatty liver disease (NAFLD) (simple steatosis or non-alcoholic fatty liver [NAFL] and/or non-alcoholic steatohepatitis [NASH]) and controls. METHODS: We performed a systematic search in PubMed, Scopus, and Cochrane Library. Fifty-six studies, published between 2003 and 2019, were finally included, reporting data from 5848 individuals (1634 controls and 4214 NAFLD patients). RESULTS: Higher circulating TNF-α levels were observed in NAFLD patients than controls (standardized mean difference [SMD] 0.84; 95% confidence interval [95% CI] 0.59-1.09), NAFL patients than controls (SMD 0.56; 95% CI 0.27-0.85), NASH patients than controls (SMD 0.93; 95% CI 0.64-1.22), and NASH than NAFL patients (SMD 0.31; 95% CI 0.16-0.46). There were only minimal changes in the comparisons between groups after excluding studies with morbidly obese populations (n = 11), or pediatric/adolescent populations (n = 6), or other than enzyme-linked immunosorbent assay method of TNF-α measurement (n = 8). There was high heterogeneity among studies in all comparisons, which was not essentially affected after sensitivity analyses. The meta-regression analysis revealed that the male ratio was positively associated with TNF-α SMD in the comparison between patients with NASH and NAFL (beta = 0.809; 95% CI 0.052-1.566) and accounted for 36% (P = 0.037) of the heterogeneity in this pair of comparison. TNF-α SMD was not associated with age, body mass index, and alanine aminotransferase in any pair of comparisons. CONCLUSIONS: Circulating TNF-α levels were higher in patients with NAFLD compared with controls. Higher levels of circulating TNF-α were also associated with the severity of NAFLD.