Double-dose tigecycline more effective than standard doses, but with potentially more side effects

Twice-daily 100-mg doses of tigecycline leads to better clinical response, bacterial clearance, and survival in intensive care unit patients with ventilator-associated pneumonia (VAP), reports a recent meta-analysis. However, such a double-dose regimen may also show higher treatment toxicities.

Drawing from the databases of the Cochrane Center for Clinical Controlled Trials, PubMed, Embase, CNKI, VIP, Wanfang, and the China Biology Medicine, researchers retrieved nine studies deemed eligible, with a total of 740 VAP patients. Double-dose tigecycline was administered to 353 patients, while the remaining 387 were treated with the standard regimen (100 mg for the first dose followed by 50-mg administrations, twice-daily).

Clinical response rate was significantly higher in patients treated with double-dose tigecycline (relative risk [RR], 1.882, 95 percent confidence interval [CC], 1.615–2.193; p<0.05). The same was true for bacterial clearance rate, which was significantly superior after the double-dose regimen (RR, 1.718, 95 percent CI, 1.422–2.076; p<0.05).

However, for both outcome measures, the funnel plot was found to be roughly symmetrical (p=0.044 and p=0.025, respectively), indicating the presence of publication bias, and necessitating further clinical analyses.

Twenty-eight-day survival rate was likewise significantly better in the double-dose-treated patients (RR, 1.401, 95 percent CI, 1.009–1.944; p<0.05), an effect that was not affected by potential publication bias, according to the funnel plot (p=0.201).

In terms of safety, researchers found that adverse events were higher in the double-dose vs standard-dose regimens, though this difference failed to reach statistical significance (RR, 1.314, 95 percent CI, 0.865–1.997; p=0.2). Potential publication bias was significant for this outcome (p=0.025).