Short-term decline in all-cause acquired infections with the routine use of a decontamination regimen combining topical polymyxin, tobramycin, and amphotericin B with mupirocin and chlorhexidine in the ICU: a single-center experience.

OBJECTIVES: In a multicenter, placebo-controlled, randomized, double-blind trial, we showed that acquired infections in intubated patients were reduced by the combination of topical polymyxin plus tobramycin and nasal mupirocin plus chlorhexidine body wash. Because intubated patients are particularly at risk for acquired infections, we reassessed the impact of this protocol as a routine procedure to control acquired infections in the ICU. DESIGN: Nonrandomized study comparing acquired infections in ICU patients during two 1-year periods: the last year before (group A, n = 925) and the first year after the implementation of the protocol (group B, n = 1,022). Acquired infections were prospectively recorded. SETTING: Polyvalent medical ICU at a university-affiliated hospital. PATIENTS: All patients admitted to the ICU. INTERVENTIONS: Administration of polymyxin/tobramycin/amphotericin B in the oropharynx and the gastric tube plus a mupirocin/chlorhexidine regimen in intubated patients and standard care in the other patients. MEASUREMENTS AND MAIN RESULTS: The comparison of acquired infection rates between groups was adjusted for differences at baseline. Infection rates were lower in group B compared with group A (5.3% vs 11.0%; p < 0.001), as were the incidence rates of total acquired infections (9.4 vs 23.6 per 1,000 patient-days; p < 0.001), intubation-related pneumonia (5.1 vs 17.1 per 1,000 ventilator-days; p < 0.001), and catheter-related bloodstream infections (1.0 vs 3.5 per 1,000 catheter-days; p = 0.03). There were fewer acquired infections caused by ceftazidime-resistant Enterobacteriaceae (0.8‰ vs 3.6‰; p < 0.001), ciprofloxacin-resistant Enterobacteriaceae (0.8‰ vs 2.5‰; p = 0.02), ciprofloxacin-resistant Pseudomonas aeruginosa (0.5‰ vs 1.6‰; p = 0.05), and colistin-resistant Gram-negative bacilli (0.7‰ vs 1.9‰; p = 0.04). Fewer patients got acquired infections due to multidrug-resistant aerobic Gram-negative bacilli (p = 0.008). CONCLUSIONS: In intubated patients, the use of topical polymyxin/tobramycin/amphotericin B plus mupirocin/chlorhexidine was associated with the reduction of all-cause ICU-acquired infections. Long-term emergence of multidrug-resistant organisms deserves further investigation.

3,4-diaminopyridine safety in clinical practice: an observational, retrospective cohort study.

Fatigue is one of the most common and disabling symptoms of multiple sclerosis (MS) and has a significant, often underestimated, impact on patients' quality of life. Current management is mainly symptomatic. 3,4-diaminopyridine (3,4-DAP) is a voltage-dependent potassium channel blocker that has been used on a named patient basis in Europe for many years to improve motor function and fatigue in patients with MS and other neuromuscular disorders, and it is undergoing the European approval process for Lambert-Eaton myasthenic syndrome (LEMS). The efficacy and safety of 3,4-DAP as symptomatic therapy in MS have not been widely evaluated. This study aimed to assess the safety profile of 3,4-DAP in routine clinical practice in an observational, retrospective study. The study involved 669 patients of the Rennes Multiple Sclerosis Clinic, France, who were treated with 3,4-DAP for the relief of fatigue during the period 1998-2003. Overall, 18.2% of patients presented adverse drug reactions (ADRs) while using moderate doses of 3,4-DAP (20-30 mg daily or up to 80 mg daily for patients with LEMS) for periods of up to 51 months. The majority of ADRs were mild to moderate and transient or reversible at the end of treatment (mean treatment duration = two months) or after dose adjustment. Most did not require discontinuation. The most commonly observed ADRs were paraesthesias. There was one case of epileptic seizure, one of hepatotoxicity and one of heart palpitations thought 'possibly' to be linked to 3,4-DAP. These underline the need for continued monitoring during treatment with 3,4-DAP.