Clinical efficacy and safety of ceftazidime/avibactam–aztreonam compared with colistin–meropenem in pediatric patients with carbapenem-resistant Enterobacterales infections
Carbapenem-resistant Enterobacterales infections in hospitalized patients
Case group: Arm A (control group): Meropenem + colistin, the standard treatment for carbapenem-resistant enterobacterals (CRE) in Egypt. Dosage given and frequency of administration: Meropenem: standard paediatric dosing per weight 40 mg/kg/dose every 8 hours; maximum dose: 2,000 mg/dose Colistin: weight-based IV dosing per hospital protocol and renal function. Mild to moderate infections: 75,000 IU/kg every 12 hours in normal renal function. Severe or life-threatening infections: 75,000 IU/kg every 8 hours in normal renal function. Renal impairment: dose adjustment according to hospital protocol. Duration: 7–14 days, depending on the site of infection. Arm B (case group): Ceftazidime–avibactam and aztreonam as a combination treatment for CRE recommended by the Infectious Diseases Society of America guidelines. Dosage given and frequency of administration: Ceftazidime–avibactam: standard paediatric dosing per weight and age. Infants ≥3 months to <6 months: 40 mg ceftazidime/kg/dose every 8 hours. Infants ≥6 months, children, and adolescents <18 years: 50 mg ceftazidime/kg/dose every 8 hours, maximum dose 2000 mg ceftazidime/dose. Adolescents ≥18 years: 2000 mg ceftazidime every 8 hours. Aztreonam: standard paediatric dosing per weight. Mild to moderate infection: 30 mg/kg every 8 hours, maximum 3000 mg/day Severe infections: 40 mg/kg every 8 hours, maximum 8000 mg/day Duration: 7–14 days, depending on the site of infection. Follow-up for all treatment arms: baseline and daily follow-up of the following: 1. Hemodynamic stability markers such as heart rate, blood pressure, the need to use vasoactive agents, and the mode of oxygenation 2. Organ dysfunction markers in renal and liver failure, such as urine output, creatinine, ALT, AST, albumin and bilirubin 3. Sepsis markers such as fever, C-reactive protein (CRP), white blood cells (WBCs), platelet count, and shift left 4. Microbial clearance and eradication after 7-14 days Randomisation process: A computer-ge
1. Age more than 3 months for both sexes 2. Hospitalized patients with a proven infection 3. Culture or BioFire showed carbapenem-resistant Enterobacterales (CRE)
1. Co-infection with other microorganisms in conjunction with CRE 2. Empirical use 3. Duration of treatment combination is less than 48 hours 4. Expected survival is less than 48 hours 5. Known allergy to study drugs 6. Renal replacement therapy