Rifampicin and sodium fusidate reduces the frequency of methicillin-resistant Staphylococcus aureus (MRSA) isolation in adults with cystic fibrosis and chronic MRSA infection

Abstract

Nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) to patients with cystic fibrosis (CF) frequently results in chronic respiratory tract carriage. This is an increasing problem, adds to the burden of glycopeptide antibiotic use in hospitals, and represents a relative contraindication to lung transplantation. The aim of this study was to determine whether it is possible to eradicate MRSA with prolonged oral combination antibiotics, and whether this treatment is associated with improved clinical status. Adult CF patients (six male, one female) with chronic MRSA infection were treated for six months with rifampicin and sodium fusidate. Outcome data were examined for six months before treatment, on treatment and after treatment. The patients had a mean age of 29.3 (standard deviation=6.3) years and FEV₁ of 36.1% (standard deviation=12.7) predicted. The mean duration of MRSA isolation was 31 months. MRSA isolates identified in these patients was of the same lineage as the known endemic strain at the hospital when assessed by pulsed-field gel electrophoresis. Five of the seven had no evidence of MRSA during and for at least six months after rifampicin and sodium fusidate. The proportion of sputum samples positive for MRSA was lower during the six months of treatment (0.13) and after treatment (0.19) compared with before treatment (0.85) (P<0.0001). There was a reduction in the number of days of intravenous antibiotics per six months with 20.3±17.6 on treatment compared with 50.7 before treatment and 33.0 after treatment (P=0.02). There was no change in lung function. Gastrointestinal side effects occurred in three, but led to therapy cessation in only one patient. Despite the use of antibiotics with anti-staphylococcal activity for treatment of respiratory exacerbation, MRSA infection persists. MRSA can be eradicated from the sputum of patients with CF and chronic MRSA carriage by using rifampicin and sodium fusidate for six months. This finding was associated with a significant reduction in the duration of intravenous antibiotic treatment during therapy.

Introduction

Chronic isolation of methicillin-resistant Staphylococcus aureus (MRSA) from sputum in patients with cystic fibrosis (CF) is an increasing clinical problem for which treatment options are limited. The recent North American Cystic Fibrosis Data Registry has reported that 6% of children and adults with CF had MRSA isolated from respiratory secretions.¹ The prevalence of infection ranges widely between CF centres in the USA, from no MRSA to 19.3% of a clinic population.¹

Established risk factors for MRSA colonization in hospitalized patients include prolonged hospital admission, undergoing a surgical procedure, management in an intensive care unit and exposure to broad-spectrum parenteral antibiotic therapy.² Increasing survival in patients with CF is associated with frequent hospital contact and antibiotic exposure, factors that are likely to be associated with higher rates of chronic infection from a number of multi-resistant bacteria including Stenotrophomonas maltophilia, Achromobacter xylosoxidans and MRSA.³ As a result of limited therapeutic options and the potential for causing postoperative morbidity, MRSA infection remains a relative contraindication for lung transplantation.⁴

There is some evidence that the acquisition of MRSA is associated with increased requirement for intravenous antibiotics, but currently there is no evidence that MRSA infection increases mortality or alters the rate of lung function decline in patients with CF.⁵ While there is reasonable evidence that sensitive S. aureus can at least temporarily be cleared from sputum with antibiotic therapy,⁶ there is no evidence that the treatment of MRSA leads to either eradication of the organism or improved health. Previous experience at our institution has suggested that the isolation of MRSA persists despite parenteral therapy with glycopeptide antibiotics.

At our institution, MRSA infection of acute-care patients is an acknowledged problem. Relatively high rates of MRSA acquisition by non-CF patients, especially in cardiac surgery in the late 1990s, was reflected in a corresponding increased rate of acquisition by CF patients, supporting the likelihood of nosocomial spread. Although postoperative cardiac surgical wound infection with MRSA is associated with significant morbidity and at times, mortality, the direct consequences are seldom long-term. However, acquisition of respiratory MRSA in CF patients presents long-term challenges to management. We report the results of an observational study to determine whether it is possible to eradicate MRSA with prolonged oral combination antibiotics directed specifically at MRSA, and whether such therapy results in improved clinical outcome.