Biology and management of methicillin resistantStaphylococcus aureusin 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.

Prevalence of Staphylococcus aureus and Use of Antistaphylococcal Therapy in Children Hospitalized with Pneumonia

“…Although Staphylococcus aureus pneumonia is common in children with cystic fibrosis and those with healthcare-associated infections (eg, ventilator-associated pneumonia), 1,2 S. aureus is an uncommon cause of community-acquired pneumonia in children. In recent years, concerns have arisen about the increasing frequency and severity of staphylococcal pneumonia, largely fueled by the emergence of community-associated methicillin-resistant S. aureus (MRSA).…”

Antimicrobial Treatment of Staphylococcus aureus in Patients With Cystic Fibrosis

“…Due to the production of several virulence factors (Akil and Muhlebach, 2018), the presence of S. aureus in the respiratory tract is associated with significant lung alterations. The development of a relevant inflammatory response, which is more severe than the inflammatory response to other common respiratory bacteria and less severe than only the response to P. aeruginosa (Gangell et al, 2011), further increases damage to the lung structure and functions.…”

“…Several risk factors for persistent S. aureus infection in people with CF have been identified. The persistence of MRSA has been associated with receiving care at a CF center with increased MRSA prevalence, the presence of pancreatic insufficiency, CF-related diabetes, and the number of hospitalizations per year (Akil and Muhlebach, 2018). However, the most important reason seems to be the ability of the pathogen to develop adaptive mechanisms that allow it to resist antibiotic pressure and host defenses.…”

“…Contrary to what has been demonstrated for Pseudomonas aeruginosa (Lund-Palau et al, 2016), it is not definitively known whether prevention of S. aureus colonization is an effective and safe measure to reduce the risk of early lung infections (Smyth and Rosenfeld, 2017). Moreover, although there is general agreement that antibiotics must be administered to treat acute S. aureus infections (Akil and Muhlebach, 2018), it is not known which kind of therapy is the most effective to reduce the risk of chronic S. aureus disease, particularly when methicillin-resistant S. aureus (MRSA) strains are the causative agents (Muhlebach, 2017). Finally, when persistence of S. aureus in the respiratory tract occurs, there is no agreement on how best to eradicate S. aureus from the lung (Ahmed and Mukherjee, 2018).…”

<p>Recent advances in <em>Staphylococcus aureus</em> infection: focus on vaccine development</p>

“…Despite causing infections in seriously ill patients, S. aureus has also been reported as the most predominant bacterial causative agent of community-acquired pneumonia 21. Cystic fibrosis, a predominantly P. aeruginosa- associated disease, has also been found to be caused by S. aureus 22…”