A study to minimise the risks of emergence of drug-resistant bacteria in patients with Intensive Care Unit pulmonary infection by determining the optimal approach to administer existing antimicrobial treatments

Minimising the risks of emergence of antibiotic resistance during therapy by precise regimen individualisation and use of combination therapy

Status

Active, not recruiting

Phases

Unknown

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN47673027

Enrollment

Registered

2022-04-26

Start date

2022-09-01

Completion date

Unknown

Last updated

2022-10-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pulmonary infection Infections and Infestations

Interventions

80 patients over two sites will be recruited onto study. Patients shall be randomised on a 1:1:1:1 basis throughout the study and allocated using pre-generated lists produced by a statistician at the

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Intubated patients with clinician suspected Gram-negative pulmonary infection requiring antibacterial therapy 2. Adults aged 18 years upwards 3. Patient admitted to ICU for at least 5 days 4. Patient ventilated for at least 48 hours Inclusion criteria for analysis: Infection with a piperacillin-tazobactam and gentamicin susceptible Gram-negative organism.

Exclusion criteria

Exclusion criteria: 1. Patients for whom informed consent cannot be obtained 2. Allergies or intolerance to piperacillin-tazobactam or gentamicin 3. Neutropaenic sepsis 4. Past medical history of cystic fibrosis 5. Other underlying infections pulmonary process unlikely to respond to piperacillin/tazobactam with or without gentamicin (i.e. tuberculosis, fungal pneumonia) 6. Subject unlikely to survive longer than 24 hours 7. Prisoners 8. Pregnant women 9. Non-NHS patients

Design outcomes

Primary

Measure	Time frame
1. Clinical cure measured using resolution of temperature, reduction of CRP, change of antibiotics from trial medications by 7 days 2. Emergence of resistance measured using culture of respiratory secretions and rectal swabs taken at day 0 and at 7 days 3. Ventilator free days measured using clinical recording of ventilation status at 28 days 4. Mortality measured using recorded death on relevant healthcare data bases at 28 days 5. Mortality measured using recorded death on NHS record at 3 months 6. Proportion of patients with gentamicin and/or piperacillin related toxicity measured monitoring of adverse reactions and events throughout the study with focus on adverse reactions listed on both drugs Summary of Product Characteristics(SmPC) at the end of the study 7. Duration of ICU stay measured using relevant hospital IT systems at ICU discharge 8. Duration of hospitalisation measured using ..relevant hospital IT systems. at hospital discharge 9. Proportion of patients achieving pre-determined pharmacodynamics targets for piperacillin-tazobactam and gentamicin measured using pathogen specific MIC values and drug determination on days 1 to 5. 10. Clinical efficacy, defined as the suppression of emergence of antimicrobial resistance after 7 days antimicrobial therapy, measured using pathogen isolation and susceptibility testing from respiratory secretions and rectal swabs taken on day 0 and at 7 days	—

Measure

Time frame

1. Clinical cure measured using resolution of temperature, reduction of CRP, change of antibiotics from trial medications by 7 days 2. Emergence of resistance measured using culture of respiratory secretions and rectal swabs taken at day 0 and at 7 days 3. Ventilator free days measured using clinical recording of ventilation status at 28 days 4. Mortality measured using recorded death on relevant healthcare data bases at 28 days 5. Mortality measured using recorded death on NHS record at 3 months 6. Proportion of patients with gentamicin and/or piperacillin related toxicity measured monitoring of adverse reactions and events throughout the study with focus on adverse reactions listed on both drugs Summary of Product Characteristics(SmPC) at the end of the study 7. Duration of ICU stay measured using relevant hospital IT systems at ICU discharge 8. Duration of hospitalisation measured using ..relevant hospital IT systems. at hospital discharge 9. Proportion of patients achieving pre-determined pharmacodynamics targets for piperacillin-tazobactam and gentamicin measured using pathogen specific MIC values and drug determination on days 1 to 5. 10. Clinical efficacy, defined as the suppression of emergence of antimicrobial resistance after 7 days antimicrobial therapy, measured using pathogen isolation and susceptibility testing from respiratory secretions and rectal swabs taken on day 0 and at 7 days

—

Secondary

Measure	Time frame
There are no secondary outcome measures	—

Countries

United Kingdom

Contacts

Public ContactTony Timlin

Tony.Timlin@nbt.nhs.uk+44 117 414 9330

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Feb 4, 2026