Colistin and rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii: a multicenter, randomized clinical trial.
- Colistin and rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii: a multicenter, randomized clinical trial.
P : life-threatening infections due to XDR A. baumannii
E : colistin alone
at an initial dose of 2 million units (equal to 160 mg of colistimethate sodium) every 8 hours intravenously or accord- ing to renal function
C : colistin (as above), plus rifampicin 600 mg every 12 hours intravenously
Death within 30 days from randomization occurred in 90 (43%) subjects, without difference between treatment arms (P = .95).
This was confirmed by multivariable analysis (odds ratio, 0.88 [95% confidence interval, .46-1.69], P = .71).
T : multicenter, parallel, randomized, open-label clinical trial
“Extensively drug resistant” was defined as resistance to carba- penems (MIC ≥16 mg/L) and to all other antimicrobial drug classes, except colistin.
HAP/VAP was diagnosed as an evolving infiltrate on chest radiograph with either fever or leu- kocytosis/leukopenia or purulent respiratory secretions with positive quantitative culture from tracheal aspirate (at least 106 colony-forming units [CFU]/mL) or bronchoalveolar lavage (at least 104 CFU/mL).
BSI was defined as positive blood cultures for Acb in the presence of systemic inflammatory signs.
Complicated intra-abdominal infections were diagnosed as a positive Acb culture of purulent exudate from abdominal collections, associated with a systemic inflammation.
Infection-related death was defined as death occurring in the presence of persistent clinical signs and microbiologic evidence of Acb infection (persistent pneumonia, abdominal discharge, septic shock, persistently positive cultures, raised inflammatory markers). Microbiologic eradication was defined as disappear- ance of Acb in all follow-up cultures from the primary source of infection (ie, blood, bronchoalveolar lavage, or bronchial as- pirate, drainage fluids) during treatment.
Clinical cure was defined as disappearance of symptoms and signs of infection, irrespective of Acb eradication at the site of in- fection.
Therapeutic failure was defined as worsening at any time or no improvement of clinical conditions by day 21 of therapy in the presence of persistently positive Acb cultures.
Renal toxicity was defined according to the RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria in terms of changes of serum creatinine levels relative to baseline. Hepatic toxicity was defined as an increase of conjugated bilirubin >3 mg/dL.
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The observed mortality rate was lower than that considered when the trial was planned (43% rather than 60%). The expected mortality of 60% in the control arm was based on our previ- ous clinical data.
Nonetheless, if we assumed a control arm mortality rate of 47% (ie, the mean value reported by a recent review), 175 subjects would be needed to detect the same effect. A potential limitation of this trial was the lack of blinding. However, the pragmatic design and the hard primary outcome made blinding not essential.