Nebulized Vancomycin for Eradication of Persistent MRSA in Patients with Cystic Fibrosis

By Elliott C. Dasenbrook, MD, MHS

Methicillin-resistant Staphylococcus aureus (MRSA) increases the risk of death for people with cystic fibrosis (CF). Studies reveal a dramatic increase in the number of individuals with CF living with MRSA infection, now comprising 25 percent of the CF population in the United States. Cleveland Clinic is leading research on MRSA in CF patients. Results of our recent study, the Persistent MRSA Eradication Protocol (PMEP), emphasize the difficulty of eradicating persistent MRSA infection, even with multimodal antibiotics.

This double-blind, randomized, placebo-controlled trial tested the use of nebulized vancomycin for treating CF patients with persistent MRSA. The results were published in the Journal of Cystic Fibrosis and showed that while inhaled vancomycin did suppress MRSA infection, chronic MRSA infection cannot be eradicated despite a comprehensive treatment protocol. This underscores the importance of infection prevention and control to prevent patients from acquiring MRSA infection in the first place.

Recruitment challenges and adverse events

We randomized 29 patients with persistent MRSA infection (two positive MRSA respiratory cultures in the past two years at least six months apart as well as two positive cultures during the screening period). Participants received either nebulized placebo or vancomycin (250 mg in 5 cc sterile water) twice per day, and all patients received oral trimethoprim/sulfamethoxazole or doxycycline, rifampin, mupirocin and Hibiclens liquid skin cleanser, as well as environmental decontamination.

Four patients from the intervention arm withdrew from the study due to bronchospasm. Though we hoped to recruit 40 patients to power the study adequately, we analyzed 25 participants due to challenges with recruitment and enrollment as well as withdrawals.

The primary endpoint was rate of infection at a one-month follow-up visit, at which time 20 percent of subjects in each group had a sputum culture negative for MRSA. At the three-month follow-up visit, the intervention group was unchanged, whereas only 13 percent of the placebo group was MRSA negative. We also did not observe a statistically significant difference in forced expiratory volume in one second (FEV1) between the groups at any time.

Our findings contrast with previous studies that suggest inhaled vancomycin may warrant inclusion in an aggressive eradication strategy. Our study was small, but our inclusion criteria were stringent as we did not want patients with intermittent MRSA to dilute the results. This study did not address the question of whether inhaled vancomyin may be beneficial as a suppressive treatment for chronic MRSA infection. This is also an important question as CF patients chronically infected with respiratory tract Pseudomonas aeruginosa benefit from repeated courses of inhaled antibiotics.

Our findings underscore the challenging nature of MRSA in CF established by our large registry study that tracked nearly 20,000 patients with CF in the U.S. Cystic Fibrosis Patient Registry and found no easily modifiable patient-level risk factors.

Advances in infection control and treatment at Cleveland Clinic

Persistent MRSA in patients with CF is not easy to prevent or treat, but stringent infection control practices can reduce transmission and optimize outcomes. When patients with CF present to Cleveland Clinic for ambulatory visits, we utilize robust infection control practices, including immediately placing the patient in a clinic room where vital signs and spirometry are obtained and the entire visit is conducted. When patients with CF present to our emergency department, radiology department or other hospital sites, an alert in the electronic medical record notifies the provider that special infection control precautions must be implemented.

Our expertise in treatment and infection control protocols for MRSA infections in CF patients continues to grow and evolve as we seek to address this dangerous risk.

Dr. Dasenbrook directs Cleveland Clinic’s Adult Cystic Fibrosis Program which is accredited by the U.S. Cystic Fibrosis Foundation.