Review: Staphylococcus aureus and MRSA in cystic fibrosis

BACKGROUND: Staphylococcus aureus (S. aureus) is one of the earliest bacteria detected in infants and children with cystic fibrosis (CF). The rise of methicillin resistant S. aureus (MRSA) in the last 10 years has caused a lot of attention to this organism. RESULTS: The aim of this review is to provide a general overview of methicillin sensitive S. aureus (MSSA) and MRSA, discuss special aspects of S. aureus in cystic fibrosis, and to review treatment concepts. Microbiology of the organism will be reviewed along with data regarding the epidemiology of both MSSA and MRSA. Antibiotic treatments both in regards to acute management and eradication of MSSA and MRSA will be reviewed. Prophylaxis of MSSA in CF remains controversial. Treatment with anti-staphylococcal agents reduces the infection rate with MSSA but may lead to a higher rate of infection with P. aeruginosa. In regards to MRSA, there is a paucity of clinical data regarding approaches to eradication. CONCLUSIONS: To advance the care of CF patients, controlled clinical trials are urgently needed to find the optimal approach to treating CF patients who are infected with either MSSA or MRSA

Interventions for the eradication of methicillin-resistant Staphylococcus aureus (MRSA) in people with cystic fibrosis

BACKGROUND: Cystic fibrosis is an inherited recessive disorder of chloride transport that is characterised by recurrent and persistent pulmonary infections from resistant organisms that result in lung function deterioration and early mortality in sufferers. Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as, not only an important infection in long-term hospitalised patients, but also as a potentially harmful pathogen in cystic fibrosis, and has been increasing steadily in prevalence internationally. Chronic pulmonary infection with MRSA is thought to confer cystic fibrosis patients with a worse overall clinical outcome and, in particular, result in an increased rate of decline in lung function. Clear guidance for the eradication of MRSA in cystic fibrosis, supported by robust evidence from good quality trials, is urgently needed. OBJECTIVES: To evaluate the effectiveness of treatment regimens designed to eradicate MRSA and to determine whether the eradication of MRSA confers better clinical and microbiological outcomes for people with cystic fibrosis. SEARCH METHODS: Randomised and quasi-randomised controlled trials were identified by searching the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register, MEDLINE, EMBASE, handsearching article reference lists and through contact with local and international experts in the field. Date of the last search of the Group's Cystic Fibrosis Trials Register: 24 January 2013. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing any combinations of topical, inhaled, oral or intravenous antimicrobials with the primary aim of eradicating MRSA compared with placebo, standard treatment or no treatment. DATA COLLECTION AND ANALYSIS: The authors independently assessed all search results for eligibility. No eligible trials were identified. MAIN RESULTS: No current published eligible trials were identified, although two ongoing clinical trials are likely to be eligible for inclusion in future updates of this review. AUTHORS' CONCLUSIONS: We did not identify any randomised trials which would allow us to make any evidence-based recommendations. Although the results of several non-randomised studies would suggest that, once isolated, the eradication of MRSA is possible; whether this has a significant impact on clinical outcome is still unclear. Further research is required to guide clinical decision making in the management of MRSA infection in cystic fibrosis

Treatment intensity and characteristics of MRSA infection in CF

Background: Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and interchange of hospital-associated strains carrying the staphylococcal chromosomal cassette mec-II (SCCmec-II) with those in the community (SCCmec-IV) has increased. This study assesses the impact of MRSA and different MRSA types on clinical outcomes, medication use, and antibiotic sensitivities. Methods: MRSA isolates from CF patients at our center were typed by SCCmec- and pvl status. Patient characteristics, lung function and nutrition are compared between MRSA types and to age, gender and Pseudomonas aeruginosa matched patients with chronic methicillin sensitive S. aureus (MSSA) infection. Results: Seventy-two percent of patients carry pvl negative SCCmec-II isolates. Seventeen percent of all MRSA were SCCmec-IV pvl positive (USA300). These patients were younger and fewer had chronic P. aeruginosa infection, whereas pvl-negative SCCmec-IV isolates show highest antibiotic resistance. Nutritional outcomes and FEV1 percent predicted (75.1±2.7 versus 77.9±2.7) did not differ in patients with MRSA compared to those with MSSA but MRSA patients received more pulmonary maintenance but not oral antibiotic medications. Conclusion: Patients with chronic MRSA are treated more intensely than age, gender and Pseudomonas aeruginosa matched MSSA-positive patients but clinical characteristics within MRSA patients vary depending on MRSA types

Progression of Polysomnographic Abnormalities in Mucolipidosis II (I-Cell Disease)

Mucolipidosis II (Inclusion cell or I-cell disease) is an autosomal recessive lysosomal storage disorder clinically comparable to the mucopolysaccharidoses (MPS), characterized by progressive respiratory and neurologic deterioration. Sleep problems, especially obstructive sleep apnea (OSA) and disrupted sleep architecture, are observed in other lysosomal storage diseases but have not been described in mucolipidosis II. We report the progression of polysomnographic abnormalities in a child with mucolipidosis II, demonstrated by worsening sleep-related hypoventilation, OSA, and sleep state fragmentation despite advancing PAP therapy. Background slowing and reduction in spindle activity on limited EEG may reflect progressive CNS disease affecting thalamic neurons

Population Pharmacokinetics and Safety of Ceftolozane-Tazobactam in Adult Cystic Fibrosis Patients Admitted with Acute Pulmonary Exacerbation

ABSTRACT Ceftolozane-tazobactam has potent activity against Pseudomonas aeruginosa , a pathogen associated with cystic fibrosis (CF) acute pulmonary exacerbations (APE). Due to the rapid elimination of many antibiotics, CF patients frequently have altered pharmacokinetics. In this multicenter, open-label study, we described the population pharmacokinetics and safety of ceftolozane-tazobactam at 3 g every 8 h (q8h) in 20 adult CF patients admitted with APE. Population pharmacokinetics were determined using the nonparametric adaptive grid program in Pmetrics for R. A 5,000-patient Monte Carlo simulation was performed to determine the probability of target attainment (PTA) for the ceftolozane component at 1.5 g and 3 g of ceftolozane-tazobactam q8h across a range of MICs using a primary threshold exposure of 60% free time above the MIC ( fT >MIC). In these 20 adult CF patients, ceftolozane and tazobactam concentration data were best described by 2-compartment models, and ceftolozane clearance (CL) was significantly correlated with creatinine clearance ( r = 0.71, P MIC, ceftolozane-tazobactam regimens of 1.5 g and 3 g q8h should achieve PTAs of ≥90% at MICs up to 4 and 8 μg/ml, respectively. Ceftolozane-tazobactam at 3 g q8h was well tolerated. These observations support additional studies of ceftolozane-tazobactam for Pseudomonas aeruginosa APE in CF patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02421120.

Relationship of Sleep to Pulmonary Function in Mucopolysaccharidosis II

To study the sleep characteristics, pulmonary function, and their relationships in an enzyme naive population of patients with mucopolysaccharidosis (MPS) II (Hunter syndrome)

Metabolomic biomarkers predictive of early structural lung disease in cystic fibrosis

Neutrophilic airway inflammation plays a role in early structural lung disease in cystic fibrosis (CF), but the mechanisms underlying this pathway are incompletely understood

Attenuation of host defense function of lung phagocytes in young cystic fibrosis patients

Recent reports suggest that endotoxin exposure can blunt phagocyte functions. The aim of this study was to examine whether lung phagocytic cells have altered host defense function in young cystic fibrosis (CF) patients, and to explore the contribution of neutrophil elastase (NE) and surfactant proteins to these effects

Biomarkers for cystic fibrosis drug development

To provide a review of the status of biomarkers in cystic fibrosis drug development, including regulatory definitions and considerations, a summary of biomarkers in current use with supportive data, current gaps, and future needs

Production of extended-spectrum β -lactamases and the potential indirect pathogenic role of Prevotella isolates from the cystic fibrosis respiratory microbiota

Extended-spectrum β-lactamase (ESBL) production and the prevalence of the β-lactamase-encoding gene blaTEM were determined in Prevotella isolates (n = 50) cultured from the respiratory tract of adults and young people with cystic fibrosis (CF). Time–kill studies were used to investigate the concept of passive antibiotic resistance and to ascertain whether a β-lactamase-positive Prevotella isolate can protect a recognised CF pathogen from the action of ceftazidime in vitro. The results indicated that approximately three-quarters (38/50; 76%) of Prevotella isolates produced ESBLs. Isolates positive for ESBL production had higher minimum inhibitory concentrations (MICs) of β-lactam antibiotics compared with isolates negative for production of ESBLs (P < 0.001). The blaTEM gene was detected more frequently in CF Prevotella isolates from paediatric patients compared with isolates from adults (P = 0.002), with sequence analysis demonstrating that 21/22 (95%) partial blaTEM genes detected were identical to blaTEM-116. Furthermore, a β-lactamase-positive Prevotella isolate protected Pseudomonas aeruginosa from the antimicrobial effects of ceftazidime (P = 0.03). Prevotella isolated from the CF respiratory microbiota produce ESBLs and may influence the pathogenesis of chronic lung infection via indirect methods, including shielding recognised pathogens from the action of ceftazidime