Biology and management of methicillin resistant Staphylococcus aureus in cystic fibrosis

Abstract

Staphylococcus aureus is one of the earliest bacteria isolated from the respiratory tract in people with cystic fibrosis (CF). Its methicillin resistant form, MRSA, has gained attention due to the rapid increase in the last decades and worse outcomes with chronic infection. In the United States, prevalence of MRSA in CF is around 27%, but is much lower (3-18%) in most other countries. Methicillin is typically genetically encoded by the mecA gene, which encodes for an alternative penicillin binding protein (PRBa). This PRBa has low affinity to β-lactams, thereby enabling growth of S. aureus in the presence of penicillinase resistant penicillins and most other β-lactams. Non-mecA positive strains of MRSA, so-called borderline resistant (BORSA) have also been described. In addition to production of toxins, the virulence of S. aureus is conferred by its adaptability allowing persistence in face of antibiotic therapies and host defense. These adaptive growth mechanisms include small colony variants, biofilms, and growth under anaerobic conditions. Several reports have described successful eradication of MRSA, yet only two randomized trials of eradication during early infection have been conducted. A list of MRSA specific antibiotics with dosing relevant to CF patients is presented here. Many of these require special dosing in people with CF. Novel antibiotics are in trials for skin and soft tissue infections and it is unclear if and when those might be available for lung infections. Thus the best strategies for MRSA would be primary prevention.

Keywords: BORSA; antimicrobial resistance; outcomes; treatment; virulence.