What is the efficacy and safety of colistin for the treatment of ventilator-associated pneumonia? A systematic review and meta-regression.

BACKGROUND: Experience with intravenous and aerosolized forms of colistin for the treatment of ventilator-associated pneumonia (VAP) in patients without cystic fibrosis is limited. We aimed to assess the safety and efficacy of colistin for the treatment of VAP. METHODS: We searched MEDLINE and Cochrane Database of Systematic Reviews for studies comparing colistin vs other antibiotics for treatment of VAP in patients without cystic fibrosis. QUOROM guidelines were followed, the I(2) method was used for heterogeneity, and a random-effects model for odds ratio (OR) estimates. RESULTS: Six controlled studies met the inclusion criteria. Clinical response did not differ significantly between colistin and control groups (OR, 1.14; 95% confidence interval [CI], .74-1.77; P = .56; I(2) = 0%). The efficacy of colistin was independent of study design (prospective OR, 0.89 [95% CI, .48-1.66; P = .71; I(2) = 0%]; retrospective OR, 1.45 [95% CI, .79-2.68; P = .23; I(2) = 0%]); randomized trials OR, 0.86 [95% CI, .43-1.74; P = .68; I(2) = 0%]). There was no indication of a significant change in clinical response after controlling for concomitant antibiotic treatment (intercept, 0.121; slope, 0.0315; P = .95). Treatment with colistin vs controls did not affect hospital mortality (OR, 0.92; 95% CI, .50-1.67; P = .78; I(2) = 34.59%) or nephrotoxicity (OR, 1.14; 95% CI, .59-2.20; P = .69; I(2) = 0%). Fourteen single-arm studies have been analyzed, and the results were in concordance with the findings of the controlled studies. CONCLUSIONS: Our results suggest that colistin may be as safe and as efficacious as standard antibiotics for the treatment of VAP.

Risk of cytomegalovirus disease in high-risk liver transplant recipients on valganciclovir prophylaxis: a systematic review and meta-analysis.

Valganciclovir (VGC) was approved by the Food and Drug Administration in 2004 as cytomegalovirus (CMV) prophylaxis except for liver transplant recipients because of their high incidence of CMV disease with this drug. However, surveys have shown its common off-label use for CMV prophylaxis in liver transplant recipients. We aimed to evaluate the risk of CMV disease with VGC prophylaxis in liver transplant recipients. All studies that evaluated liver transplant recipients and used VGC (900 or 450 mg daily) for the prevention of CMV disease were included. Five controlled studies (n = 483) were pooled with a random effects model; five single-arm studies (n = 380) were pooled for the prevalence rate of CMV disease. The risk of CMV disease with VGC versus ganciclovir was 1.81 [95% confidence interval (CI) = 1.00-3.29, P = 0.05, I(2) = 0%]. For high-risk (donor-positive/recipient-negative) patients, the risk of CMV disease was 1.96 (95% CI = 1.05-3.67, P = 0.035, I(2) = 0%). The risk of CMV disease remained significant with 900 mg of VGC daily (P = 0.04) but not with 450 mg of VGC daily (P = 0.76). The risk of leukopenia with VGC was 1.87 (95% CI = 1.03-3.37, P = 0.04, I(2) = 0%). In single-arm trials, the overall CMV disease rate was 12% (95% CI = 9%-16%, P < 0.001), and the rate for high-risk patients was 20% (95% CI = 10%-38%, P = 0.002). In conclusion, 900 mg of VGC daily may not be safe as CMV prophylaxis in high-risk liver transplant recipients because of the significant 2-fold increase in the risk of CMV disease and the 1.9-fold increase in the risk of leukopenia. Alternative CMV prophylaxis should be used for liver transplant recipients.

Two cases of Norwalk virus enteritis following small bowel transplantation treated with oral human serum immunoglobulin.

Protracted diarrhea is a challenging problem after small bowel transplantation. We report two patients who developed Norwalk virus enteritis after small bowel transplantation. Both received oral HSIG with resolution of diarrhea within 48 h.

Drug-induced QTc-interval prolongation in the intensive care unit: incidence and predictors.

There is a paucity of information regarding QTc prolongation in critically ill patients. A prospective observational study was conducted to assess the incidence and predictors of QTc prolongation associated with medications in intensive care unit (ICU) patients. Consecutive adult patients prescribed prespecified QTc-prolonging medications were assessed for development of the combined incidence of QTc >500 ms at anytime and QTc increase >60 ms above baseline. Over 3 months, 200 consecutive patients (63 ± 18 years; 52% female; 73% Caucasian; baseline QTc 447.3 ± 51.5 ms) were evaluated. The primary end point occurred in 48% of the patients (QTc >500 ms 40%, QTc increase >60 ms 29%). The majority of patients experienced a QTc >470 or 450 ms (60.5%). Mean increase in QTc at 48 hours was 20 ± 35 ms. Upon multivariate analysis, length of stay [odds ratio 1.30, 95% confidence interval (1.15, 1.47)] and baseline QTc [1.01 (1.01, 1.02)] were associated with an increased risk for the primary end point, while beta-blockers [0.41 (0.20, 0.81)] were associated with a risk reduction. In conclusion, increased risk of proarrhythmia, as assessed by QTc prolongation, occurs in the majority of ICU patients when prescribed medications with electrophysiologic properties. Increased vigilance is warranted. The possible protective effect of beta-blockers requires confirmation.