Pilot Study of Aerosolised Plus Intravenous Vancomycin in Mechanically Ventilated Patients with Methicillin-Resistant Staphylococcus Aureus Pneumonia

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).

Keywords: aerosolised vancomycin; intensive care unit; mechanical ventilation; methicillin-resistant staphylococcus aureus; pneumonia.

Conflict of interest statement

Y.J. Cho and J.-H. Lee received a Seoul National University Bundang Hospital grant (03-2011-009). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Other authors declare no conflict of interest.

Figures

Figure 1

Patient recruitment. MRSA, methicillin-resistant Staphylococcus aureus. a Reasons for exclusion were as follows: active primary or metastatic lung cancer (n = 5), severe congestive heart failure (n = 4), severe acute respiratory distress syndrome (n = 4), uncontrolled asthma (n = 1), diffuse bronchiectasis (n = 2), chronic obstructive pulmonary disease (n = 7), combined pulmonary fibrosis and emphysema (n = 1), co-infection with nontuberculosis mycobacteria (n = 1), pleural effusion required percutaneous drainage (n = 3), pneumothorax (n = 1), destroyed lung due to previous tuberculosis (n = 1), viral pneumonia (n = 2), refusal to consent (n = 19).

Figure 2

Rate of treatment success and microbiologic eradication; D3, day 3 of aerosolised vancomycin treatment; EOT, the end day of aerosolised vancomycin treatment; EFU, the end day of all types of antibiotic treatment. Treatment success includes clinical cure and clinical improvement. The ratio in the figure is defined as number of corresponded patient divided by total number of included patient.

Figure 3

Vancomycin concentration in epithelial lining fluid. The black line denotes the average values of vancomycin concentration in epithelial lining fluid, and the grey line denotes vancomycin concentration of each of three patients. Bronchial alveolar lavage fluid or endotracheal aspirates were obtained for analysing vancomycin concentration in epithelial lining fluid. Vancomycin concentrations (mean ± standard deviation, mcg/mL) were 1.13 ± 1.27 (pre-aerosolised vancomycin), 42.49 ± 12.86 (post 1–2 h), 98.75 ± 21.79 (post 4–5 h), and 8.61 ± 3.08 (post 11–12 h), respectively.