Abstract
Treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in critically ill patients remains unsatisfactory. This pilot study aimed to evaluate the clinical outcomes of aerosolised vancomycin in addition to intravenous administration in this setting. This was a prospective, noncomparative, phase II trial. Patients receiving mechanical ventilation for >48 h in intensive care units (ICUs) were screened; those receiving intravenous vancomycin for MRSA pneumonia were enrolled. Patients received aerosolised vancomycin (250 mg every 12 h for five days) via a vibrating mesh nebuliser. The primary outcome was treatment success (clinical cure or improvement) at the conclusion of antibiotic treatment. Vancomycin concentrations were measured in bronchoalveolar lavage fluid according to administration time. Twenty patients were enrolled (median age 75 years and 13 (65%) men; 18 (90%) cases with nosocomial pneumonia). Thirteen patients (65%) showed clinical cure or improvement. Microbiological eradication of MRSA was confirmed in 14 patients (70%). ICU and hospital mortality rates were 30% and 35%, respectively. Maximum aerosolised vancomycin concentration was observed 4–5 h after nebulising (98.75 ± 21.79 mcg/mL). No additional systemic adverse effects occurred following aerosol vancomycin treatment. Aerosolised vancomycin combination therapy may be an alternative treatment for patients with severe MRSA pneumonia receiving mechanical ventilation (ClinicalTrials.gov number, NCT01925066).
Highlights
Ventilator-associated pneumonia is one of the most prevalent nosocomial infections in the intensive care unit (ICU), which leads to poor treatment outcomes and high socioeconomic burden [1]
methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia is generally treated with systemic vancomycin or linezolid, but therapeutic responses are unsatisfactory [3]
Vancomycin concentrations were 1.13 ± 1.27, 42.49 ± 12.86, 98.75 ± 21.79, and 8.61 ± 3.08, respectively. This is the first prospective study to evaluate the efficacy of additional Aerosolised vancomycin (AV) treatment in mechanically ventilated patients with MRSA pneumonia, this was a single-arm design
Summary
Ventilator-associated pneumonia is one of the most prevalent nosocomial infections in the intensive care unit (ICU), which leads to poor treatment outcomes and high socioeconomic burden [1]. Multidrug-resistant bacteria are a common problem, and methicillin-resistant Staphylococcus aureus (MRSA) is a major component of Gram-positive bacteria [2]. MRSA nosocomial pneumonia is generally treated with systemic vancomycin or linezolid, but therapeutic responses are unsatisfactory [3]. Prolonged courses of systemic vancomycin treatment are frequently associated with significant nephrotoxicity [4]. Lung penetration is poor and variable, in critically ill patients [5,6]. Linezolid produces significantly increased risk of thrombocytopenia and gastrointestinal events [7]
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