A study comparing two antibiotic combinations to determine which is more effective and safer for treating drug-resistant bacterial infections in children

ISRCTN	ISRCTN47229952
DOI	https://doi.org/10.1186/ISRCTN47229952
Cairo University, Faculty of Medicine, Research Ethics Commitee	N-51-2026
Sponsor	Cairo University hospitals
Funder	Cairo University Hospitals

Submission date: 19/06/2026
Registration date: 27/06/2026
Last edited: 26/06/2026

Recruitment status: Recruiting
Overall study status: Ongoing
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Syed Hasan
Principal investigator, Scientific

Huddersfield University
Huddersfield
HD1 3DH
United Kingdom

Phone	‪+44 (0)1484 256941
Email	s.hasan@hud.ac.uk

Mrs Walaa Elmeniar
Scientific, Public

Huddersfield University
Huddersfield
HD1 3DH
United Kingdom

Phone	‪+44 (0)7438930854
Email	Walaa.Elmeniar@hud.ac.uk

Prof Hanaa Rady
Scientific, Principal investigator

Cairo University
Cairo
12613
Egypt

Phone	+20 (0)1001482444
Email	Hanaaarady@gmail.com

Study information

Primary study design	Interventional
Allocation	Randomized controlled trial
Masking	Open (masking not used)
Control	Active
Assignment	Parallel
Purpose	Treatment
Scientific title	Clinical efficacy and safety of ceftazidime/avibactam–aztreonam compared with colistin–meropenem in pediatric patients with carbapenem-resistant Enterobacterales infections
Study objectives
Ethics approval(s)	1. Approved 07/03/2026, Cairo University, Faculty of Medicine, Research Ethics Committee (Cairo University, Cairo, 12613, Egypt; +20 (0)235674835; kasralainyrec@kasralainy.edu.eg), ref: N-51-2026 2. Approved 05/06/2026, Huddersfield University, School of Applied Sciences Research Integrity and Ethics Committee (School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, United Kingdom; +44 (0)1484422288; sas_ethics@hud.ac.uk), ref: SAS-SRIEC-05.06.2026WE_1
Health condition(s) or problem(s) studied	Carbapenem-resistant Enterobacterales infections in hospitalized patients
Intervention	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-generated random sequence (1:1 ratio) and sealed, opaque envelopes will be used for randomisation and allocation. Stratification by infection type (bloodstream vs non-bloodstream) may be applied if there is sufficient sample size for subgroup analysis. The CONSORT study flow diagram will be used.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Meropenem, colistin, ceftazidime, avibactam, aztreonam
Primary outcome measure(s)	Clinical success rate measured using the resolution of symptoms and no need for antibiotic change at days 7-14 Microbiological eradication measured using follow-up cultures at days 7 and 14 Mortality measured using the total number of infection-related deaths in that arm divided by the total number of enrolled patients in that arm and multiplying by 100 at days 7, 14 and 28 Time to fever resolution measured using a thermometer at baseline and over 72 hours Length of ICU Stay (LOS) at hospital discharge and up to 90 days, defined as the median of the number of days in the ICU from admission until discharge, measured using data from records, collected at one timepoint at the end of the study Incidence of acute kidney injury (AKI) measured using the Kidney Disease Improving Global Outcomes (KDIGO) criteria at baseline and during the therapy duration Adverse events (nephrotoxicity, hepatotoxicity, hypersensitivity reactions, and other treatment-related adverse events) throughout the treatment period (7-14 days) and up to 72 hours after the follow-up period measured using routine clinical practice during hospitalisation (nephrotoxicity and hepatotoxicity) and data recording, collected at one timepoint at the end of the study Sepsis markers measured using WBC count, CRP, platelet count, and shift left count at baseline and every other day for 14 days
Key secondary outcome measure(s)
Completion date	08/03/2027

Eligibility

Participant type(s)
Age group	Child
Lower age limit	3 Months
Upper age limit	16 Years
Sex	All
Target sample size at registration	76
Key inclusion criteria	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)
Key exclusion criteria	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
Date of first enrolment	20/06/2026
Date of final enrolment	06/03/2027

Locations

Countries of recruitment

Egypt

Study participating centres

Results and Publications

Individual participant data (IPD) Intention to share	No

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol file			19/06/2026	No	No

Additional files

49751_PROTOCOL.pdf: Protocol file

Editorial Notes

19/06/2026: Study's existence confirmed by the Huddersfield University, School of Applied Sciences Research Integrity and Ethics Committee.