Efficacy of Colistin Monotherapy Versus Colistin Plus Minocycline for Carbapenem-Resistant A. Baumannii Infection

Efficacy of Colistin Monotherapy Versus Colistin Plus Minocycline for Carbapenem-Resistant A. Baumannii Infection

Efficacy of Colistin Monotherapy Versus Colistin Plus Minocycline for Therapy of Carbapenem-Resistant Acinetobacter Baumannii Infection

Acinetobacter baumannii causes severe infections (pneumonia, bacteremia, organ space) with high lethality in hospitalised critically ill patients. It can acquire resistance to all classes of antibiotics (multidrug resistance, MDR) except an 'old' drug, colistin, which may be the only therapeutic option. The addition of minocycline to colistin has been shown to be synergistic in vitro, and may be promising in vivo, but this combination has not been limited to case report or case series in comparison with colistin alone.

The purpose of this double-blind, randomized, parallel, placebo-controlled clinical trial is to assess whether the association of colistin and minocycline reduces significantly the mortality of patients with severe MDR A. baumannii infections compared with colistin alone. The trial will enroll 94 patients from internal medicine ward and intensive care units (ICU) of an university care hospitals where MDR A. baumannii infection is endemic with epidemic phases. Patients will be randomly allocated to either colistin plus placebo (control arm) or colistin plus minocycline (experimental arm). Primary end point is overall mortality, defined as death occurring within 28 days from randomisation.

Colistin, 150 mg every 8 hours intravenously or according to renal function, plus Minocycline, 200 mg every 12 hours orally

The study primary outcome is patient overall mortality, defined as death occurring during hospitalisation or within 28 days from randomization.

Microbiological eradication is defined as the disappearance of A. baumannii in cultures from blood, bronchial aspirate, urines and drainage fluids.

Renal toxicity is defined as decrease of creatinine clearance below 50 ml/min or >50% reduction in the creatinine clearance relative to the baseline.

Inclusion Criteria: Clinical and microbiological evidence of a severe infection due to multi-drug resistant A. baumannii during hospitalization Susceptibility of the A. baumannii isolate to colistin (MIC < or =2 mg/l). Exclusion Criteria: Treatment with one of the study drugs prior to the diagnosis of A. baumannii infection more than 48 hours Severe liver dysfunction History of prior hypersensitivity to the study drugs Pregnancy and lactation

Koomanachai P, Tiengrim S, Kiratisin P, Thamlikitkul V. Efficacy and safety of colistin (colistimethate sodium) for therapy of infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii in Siriraj Hospital, Bangkok, Thailand. Int J Infect Dis. 2007 Sep;11(5):402-6. doi: 10.1016/j.ijid.2006.09.011. Epub 2007 Feb 8.

Thamlikitkul V, Tiengrim S, Seenama C. Comparative in vitro activity of minocycline and selected antibiotics against carbapenem-resistant Acinetobacter baumannii from Thailand. Int J Antimicrob Agents. 2016 Jan;47(1):101-2. doi: 10.1016/j.ijantimicag.2015.11.006. Epub 2015 Dec 11. No abstract available.