The frequency and severity of colistin-induced nephrotoxicity in critically ill patients was consistent with previous reports in non-critically ill patients. Most cases of nephrotoxicity demonstrated in this study were mild and reversible. Patients receiving colistin therapy who have hypertension or chronic kidney disease should be monitored closely, and administration of additional nephrotoxic agents should be avoided in all patients when possible. Large, prospective trials are warranted to confirm these results.

BackgroundThe incidence of multi-drug resistant (MDR) gram-negative (GN) organisms including Pseudomonas and Acinetobacter spp has increased in the last decade, prompting re-evaluation of colistin for the management of these infections. Aerosolized colistin as an adjunct to intravenous therapy is a current option for the management of MDR-GN pneumonia, although data supporting this practice is limited. This study evaluates the efficacy of adjunctive aerosolized colistin in combination with intravenous colistin in critically ill patients with MDR-GN pneumonia.MethodsA retrospective multi-center cohort analysis comparing critically ill patients with MDR-GN pneumonia who received intravenous colistin (IV) alone or in combination with adjunctive aerosolized colistin (IV/AER) with a primary endpoint of clinical cure at the end of colistin therapy. Secondary endpoints included microbiologic cure, duration of mechanical ventilation, length of stay, and hospital mortality. A post-hoc subgroup analysis was performed for patients with high quality cultures used for diagnosis of MDR-GN pneumonia. Dichotomous data were compared using Fisher’s exact test while the student’s t-test or Mann–Whitney U test were used for continuous variables.ResultsNinety-five patients met criteria for evaluation with 51 patients receiving IV and 44 receiving IV/AER. Baseline characteristics were similar between the two groups. Twenty patients (39.2%) receiving IV and 24 (54.5%) receiving IV/AER achieved clinical cure (p = 0.135). There was no difference in microbiologic cure rates between the IV and IV/AER colistin groups (40.7vs. 44.4%, p = 0.805). The IV group demonstrated a trend towards higher pneumonia attributable mortality (70.4 vs. 40%, p = 0.055). In the subgroup analysis of patients with high quality respiratory cultures, there was a significantly lower clinical cure rate for those in the IV group as compared to the IV/AER group (31.3 vs. 57.1%, p = 0.033).ConclusionsAddition of aerosolized colistin to IV colistin may improve clinical cure and mortality for patients with MDR-GN pneumonia. Larger, prospective trials are warranted to confirm the benefit of adjunctive aerosolized colistin in critically ill patients with MDR-GN pneumonia.

Argatroban is a parenteral direct thrombin inhibitor labeled for anticoagulation in patients with confirmed or suspected heparin-induced thrombocytopenia in the United States. Currently there are no studies evaluating bleeding risk factors in Intensive Care Unit patients.To determine bleeding risk factors associated with argatroban therapy in the critically ill. Critically ill patients admitted between July 2007-June 2008 who received argatroban were included in this retrospective cohort study. The primary endpoint was the incidence of bleeding complications associated with argatroban. Major bleeding was defined as a hemoglobin reduction ≥2 g/dL plus a transfusion of ≥2 units of blood in a 24 h period, or a retroperitoneal, intracranial, prosthetic joint, or other life-threatening bleed. Minor bleeding was any overt bleeding not fitting the major bleeding definition. Secondary outcomes included identifying risk factors for bleeding. Seventy-three patients were included with 16 (21.9%) total bleeding complications, 7 (9.6%) major and 9 (12.3%) minor bleeds. Four risk factors for bleeding were identified by univariate analysis: major surgery prior to or during argatroban therapy (OR = 8.4, 95% CI: 2.3-30.1, p = 0.001), dosing weight >90 kg (OR = 4.8, 95% CI: 1.4-15.8, p = 0.01), total bilirubin >3 mg/dL (OR = 8.1, 95% CI: 2.1-31.1, p = 0.002), and baseline platelets ≤70 K/μL (OR = 4.2, 95 % CI: 1.1-16.3, p = 0.039).Risks and benefits of argatroban should be weighed in patients with major surgery prior to or during argatroban, dosing weight ≥90 kg, total bilirubin ≥3 mg/dL, and baseline platelets ≤70 K/μL.