Colistin versus Colistin Combined with Ampicillin-Sulbactam for Multiresistant Ventilator-associated Pneumonia Treatment: An Open-label Prospective Study.

BACKGROUND

Retrospective studies have reported good clinical success rates using colistin as monotherapy to treat ventilator-associated pneumonia (VAP), comparable to that obtained with colistin combined with other antibiotics. However, inadequate penetration into the pulmonary parenchyma for colistin has been shown in animal models.

AIM

The aim of the study was to study prospectively the outcome, measured as clinical response and survival, of intravenously administered colistin versus colistin combined with high-dose ampicillin-sulbactam in Intensive Care Unit (ICU) patients with multiresistant VAP.

METHODS AND SUBJECTS

This prospective, open-label, randomized study included consecutive patients who developed microbiologically documented VAP due to with carbapenem-resistant strains but susceptible to colistin and ampicillin-sulbactam. Seventy-four patients were screened, but finally, 39 participants were enrolled and finished the study Patients received colistin (Group A - 19 patients) or colistin and ampicillin/sulbactam (Group B - 20 patients). The clinical response of VAP was assessed on day 4 to 5 of treatment (early response). If therapy was considered unsuccessful after this period, ampicillin/sulbactam was added in Group A or changed therapy in B.

RESULTS

Early cure rates in Group A and B were 15.8% and 70%, respectively ( = 0.001). Multiple regression analysis revealed that combination treatment (odds ratio [OR]: 43.6, 95% confidence interval [CI]: 3.594-530.9) and Sequential Organ Failure Assessment score <8 (OR: 0.022, 95% CI: 0.001-0.43) were independently associated with favorable clinical response. APACHE II score ≤15 (OR: 0.049, 95% CI: 0.003-0.0942) and an early favorable response to treatment (OR: 244.4, 95% CI: 2.151-27850.9) were associated with survival and discharge from ICU.

CONCLUSION

Combination therapy with colistin and a high dose of ampicillin/sulbactam was associated with a more favorable clinical response to VAP due to carbapenem-resistant than colistin monotherapy.