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Comparing continuous and intermittent antibiotic infusion methods for sepsis treatment

Beta-lactam Intermittent Versus Continuous Infusion and Combination Antibiotic Therapy in Sepsis

Phase 4 Interventional Assistance Publique - Hôpitaux de Paris · NCT05681442

This study is testing whether giving antibiotics continuously or in bursts works better for people with severe infections caused by hard-to-treat bacteria.

Quick facts

PhasePhase 4
Study typeInterventional
Enrollment600 (estimated)
Ages18 Years and up
SexAll
SponsorAssistance Publique - Hôpitaux de Paris Academic / other
Drugs / interventionschemotherapy
Locations28 sites (Amiens and 27 other locations)
Trial IDNCT05681442 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of continuous versus intermittent infusion of beta-lactam antibiotics in patients with hospital-acquired sepsis or septic shock caused by multidrug-resistant Gram-negative bacteria. It employs a prospective multicenter, randomized, open-label design with a 2x2 factorial approach, allowing for the comparison of different infusion strategies and the use of combination versus monotherapy. Patients will be randomized into four treatment groups to assess the impact on 30-day mortality rates. The study aims to provide insights into optimal antibiotic administration methods for critically ill patients.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older who have been diagnosed with hospital-acquired sepsis or septic shock within the last 24 hours.

Not a fit: Patients who do not have risk factors for multidrug-resistant Gram-negative pathogens or those with sepsis not caused by these pathogens may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved survival rates for patients suffering from sepsis.

How similar studies have performed: Other studies have explored similar antibiotic infusion strategies, but this specific approach is novel in its factorial design and focus on multidrug-resistant organisms.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Adults (≥ 18 years)
* Hospital-acquired sepsis (according to sepsis 3.0 definitions) :

  * Patient hospitalized for more than 48 hours OR Patient discharged less than 48 hours ago
  * AND sepsis diagnosed within the last 24 hours
* One of the following risk factors for gram negative multidrug resistant pathogens:

  * Prior intravenous antibiotic use within 7 days prior to sepsis onset with the exception of antibiotic effective only against Gram-positive bacteria, penicillin A and macrolides
  * Prolonged hospital stay (≥ 15 days of hospitalization) within 3 months prior to sepsis onset Prolonged mechanical ventilation (≥ 5 days on mechanical ventilation) within 3 months prior to sepsis onset
  * Patients with indwelling devices (dialysis access lines, intravascular lines, urinary catheter, endotracheal or tracheostomy tube, gastrostomy or jejunostomy feeding tube)
  * Patients known to be infected, colonized or carriers of MDR gram negative bacteria within 3 months prior to sepsis onset
  * Exposure to an antibiotic (amoxicillin-clavulanic acid, C2G, C3G, fluoroquinolones) within 3 months prior to sepsis onset
  * A trip abroad to known geographical areas at risk (in particular the Indian subcontinent, South-East Asia, the Middle East and North Africa, the Mediterranean Basin) within 3 months prior to sepsis onset
  * A functional or organic abnormality of the urinary tract in case of urinary tract infection.
* Appropriate bacteriological sampling performed before starting antimicrobial therapy
* Expected stay in ICU of more than 3 days

Exclusion Criteria:

* A priori known resistance to all the proposed beta-lactams or to amikacin
* Need for extrarenal treatment at inclusion according to the criteria of Gaudry et al.
* Known hypersensitivity to ceftazidime, piperacillin-tazobactam, cefepime, meropenem, ceftazidime-avibactam, ceftazolane-avibactam or to any of the excipients included in the corresponding pharmaceutical drugs,
* Known hypersensitivity to any cephalosporin antibacterial agent,
* Know hypersentitivity to any penem antibacterial agent,
* Severe known hypersensitivity (eg, anaphylactic reaction, severe skin reaction) to any other beta-lactam antibiotic (eg, penicillins or monobactam ) or to any of its excipients.
* Known contraindication to the aminoglycoside family including

  * Hypersensitivity to the active substance, to any aminoglycoside antibacterial agent or to any of the excipients included in the corresponding pharmaceutical drugs,
  * Cirrhosis of grades B and C according to the Child-Pugh classification.
  * Myasthenia gravis.
  * Simultaneous administration of another aminoglycoside
  * Association with ataluren
* Non-complicated urinary tract infection (corresponding to a positive ECBU not responsible for sepsis)
* Bone marrow transplant or chemotherapy-induced neutropenia
* Infections for which long-term antibiotic treatment \> 8 days is strongly recommended (i.e., infective endocarditis, osteoarticular infections, anterior mediastinitis after cardiac surgery, hepatic or cerebral abscesses, chronic prostatitis for instance
* Presence of antibiotic therapyfor the new sepsis before randomisation: (\> 2 doses of antibiotics or \> 16h for continuous infusion
* Limitation of life support (comfort care applied only) at the time of screening
* Enrolment to another interventional drug study
* Pregnancy or breastfeeding
* Subject deprived of freedom, subject under a legal protective measure
* Non affiliation to any health insurance system
* Refusal to participate to the study (patient or legal representative or family member or close relative if present)

Where this trial is running

Amiens and 27 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Sepsis
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.