Impact on Duration of Antibiotic Therapy of Rapid Molecular Diagnostic Method for Rapid Analysis of Susceptibility of Peritoneal Samples in Postoperative Peritonitis in ICU Patients
Trial Snapshot
- Phase
- Not Applicable
- Status
- Terminated
- Enrollment
- 16
- Locations
- 7
- Primary Endpoint
- The proportion of patients with adequate anti-infective treatment on D1
Study Overview
Brief Summary
Hospitals, and more specifically Intensive Care Units (ICU), face the challenging issue of emergence and rapid spread of multi-drug resistant bacteria (MDR). In some cases, the therapeutic choice is extremely limited. Prevention and adequacy of antibiotic therapy (AB) are the key responses applied toward these threats. A delayed adequate AB is a known factor of poor prognosis. Intra-abdominal infections (IAI) are frequent, polymicrobial and life threatening diseases. Source control and adequate AB are instrumental issues in this setting. Despite technical advances, susceptibility testing of the microorganisms collected from peritoneal samples is not usually available before day two or three after surgery. In this time lapse, empiric AB might be inadequate (not targeting all the pathogens, which leads to a prolonged duration of AB and potential increased morbidity/mortality risk) or too broad (with the two issues of ecology with an increased risk of selection of MDR bacteria and additional costs). In a pilot study evaluating the potential benefit of a direct culture of peritoneal samples from resuscitation patients treated for peritonitis, we observed that conventional treatment made it possible to obtain microbiological results within a median of 3 [extremes 2-7] days whereas a direct microbiological technique by E-test gave results in 1 [1-2] days (p <0.0001). With this technique close to conventional microbiological, a change in antibiotic therapy could have been achieved within an average of 1 [1-2] days versus 4 [1-11] days with conventional management (p = 0, 0006).
The development of modern molecular techniques suggests that a large margin of improvement for the rendering and the precision of the results is possible.
Detailed Description
BACKGROUND
Antiinfective agents are aimed at eradicating microorganisms, or at least significantly reducing the size of inoculum to facilitate the natural activity of host defence mechanisms. One of the most challenging issues faced by prescribers is the emergence of multidrug resistant bacteria (MDR) and fungi, especially in the ICU setting. In some instances, the therapeutic options are extremely limited or even totally inadequate.
The responses to this threat are improvements in prevention of nosocomial infection, antiinfective stewardship policy, and a better use of available resources including optimization of antibiotic therapy from the empiric phase of treatment. The optimization of antibiotic and antifungal therapy is a key issue. In a recent paper analysing the antibiotic prescription in a tertiary care hospital over a 9 to 10 weeks period, the authors reported an inappropriateness in 37% of the cases involving indication of therapy (17.5%), choice of the spectrum (7.6%) and application of the treatment (dosage, timing, duration…)(9.3%).
Delayed adequacy for antibiotic therapy is a known factor of prolonged duration of anti-infective therapy and consequently of selection pressure. Adequacy is defined as the microbiologically effective antimicrobial treatment against the causative pathogens. A decreased duration of antibiotic therapy is an easy to implement strategy to decrease the emergence of resistance both at individual and community levels. This strategy of a reduced duration of therapy has additional potential advantages such decreased incidence of adverse effects and reduced costs.
The selection of an empiric antibiotic (AB) therapy is often a difficult challenge. Despite advances in conventional microbiologic techniques, identification and susceptibility testing of the microorganisms collected from a suspected infectious site are not usually available before day two or three after sampling. In this time lapse, empiric AB therapy might not target all the pathogens, which leads to a prolonged duration of AB and potential increased morbidity/mortality rates. To overcome this uncertainty, physicians frequently prescribe very broad-spectrum empiric regimens to target a maximum number of potential pathogens. This is specifically the case in ICUs where life-threatening infections justify this policy. However, as mentioned above, the consequences in terms of selection pressure, cost and adverse effects are of major importance.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients will be eligible providing that they meet all the following criteria:
- •having a surgery for a suspicion of post-operative peritonitis;
- •free, informed and written consent of the patient, or his relatives or the trusted person previously designated or failing that, inclusion in an emergency situation
Exclusion Criteria
- •Patients will not be eligible if they meet at least one of the following criteria
- •age under 18 years;
- •current pregnancy;
- •poor chance of survival (SAPS II > 65 points within 12 hours before inclusion);
- •patient for whom a limitation of care has been decided
- •patient included in another therapeutic trial involving antibiotics agents
- •patient who has already participated in this study
- •patients unable to give consent (under guardianship or curatorship)
- •patient not affiliated to social security
- •Randomization criteria:
- •surgical samples collected during reoperation for microbiological purpose;
- •the two surgical samples can be processed by the microbiology laboratory within a maximum period of 8 hours between the start of the two techniques
Arms & Interventions
multiplex PCR
peritoneal samples will be analysed using Unyvero IAI test and using conventional method
Intervention: rapid molecular diagnosis (Other)
multiplex PCR
peritoneal samples will be analysed using Unyvero IAI test and using conventional method
Intervention: conventional method analysis (Other)
conventional method
peritoneal samples will be analysed using only conventional method
Intervention: conventional method analysis (Other)
Outcomes
Primary Outcomes
The proportion of patients with adequate anti-infective treatment on D1
Time Frame: day 1
An anti-infective treatment is adequate if the anti-infective agents administered correspond to the simplest effective anti-infective treatment as determined by conventional microbiology
Secondary Outcomes
- Death at D28(day 28)
- The proportion of patients with de-escalation on D1(day 1)
- The proportion of patients with resumption or prolongation of the antibiotic until discharge from hospital or until D28.(day 28)
- Length of hospital stay in days.(day 28)
- The proportion of patients with adequate antifungal treatment on D1(day 1)
- The time in hours between randomization and adequate anti-infective treatment (antibiotic and antifungal)(day 28)
- The time in hours between randomization and adequate antibiotic treatment(day 28)
- Length of stay in intensive care in days.(day 28)
- The proportion of patients with emergence of at least one multidrug-resistant bacteria on clinical or hygiene samples (rectal and oropharyngeal swabs).(day 28)
- Evaluate the diagnostic performance of the Unyvero IAI test in the intervention group compared to the conventional technique(day 28)
- The proportion of patients with adequate antibiotic treatment on D1(day 1)
- The time in hours between randomization and adequate antifungal treatment(day 28)
- The proportion of patients with clinical failure until D28(day 28)
- The proportion of patients with microbiological failure until D28(day 28)
- Occurrence of organ failure in intensive care(day 28)