Quantitation of propofol metabolites by LC-MS/MS demonstrating long detection window for urine drug monitoring.

Introduction: Chromatographic methods for analysis of propofol and its metabolites have been widely used in pharmacokinetic studies of propofol distribution, metabolism, and clearance. Application of chromatographic methods is also needed in clinical and forensic laboratories for detecting and monitoring propofol misuse. Objective: We report a method for sensitive analysis of propofol, propofol 1-glucuronide (PG), 4-hydroxypropofol 1-glucuronide (1-QG), 4-hydroxypropofol 4-glucuronide (4-QG) and 4-hydroxypropofol 4-sulfate (4-QS) in urine by LC-MS/MS analysis. The method employs a simple dilute-and-analyze sample preparation with stable isotope internal standardization. Results: Validation studies demonstrate a linear calibration model (100-10,000 ng/mL), with dilution integrity verified for the extended range of concentrations experienced in propofol use. Criteria-based validation was achieved, including an average coefficient of variation of 6.5 % and a percent bias of -4.2 ng/mL. The method was evaluated in 12 surgical patients, with monitoring periods lasting up to 30 days following intravenous propofol administrations of 100-3000 mg on the day of surgery. While the concentration ratio of PG to 4-hydroxy propofol metabolite decreased significantly in the days following surgery, PG maintained the highest concentration in all specimens. Both PG and 1-QG were detectable throughout the monitoring periods, including in a patient monitored for 30 days. Lower concentrations were determined for 4-QG and 4-QS, with evidence of detection up to 20 days. Propofol was not detectable in any urine specimens, thereby proving ineffective for identifying drug use. Conclusion: The validated method for quantifying propofol metabolites demonstrates its applicability for the sensitive detection of propofol misuse over a long window of drug-use detection.

Impact of CFTR Modulation on Pseudomonas aeruginosa Infection in People With Cystic Fibrosis.

BACKGROUND: Pseudomonas aeruginosa is a multidrug-resistant pathogen causing recalcitrant pulmonary infections in people with cystic fibrosis (pwCF). Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have been developed that partially correct the defective chloride channel driving disease. Despite the many clinical benefits, studies in adults have demonstrated that while P. aeruginosa sputum load decreases, chronic infection persists. Here, we investigate how P. aeruginosa in pwCF may change in the altered lung environment after CFTR modulation. METHODS: P. aeruginosa strains (n = 105) were isolated from the sputum of 11 chronically colonized pwCF at baseline and up to 21 months posttreatment with elexacaftor-tezacaftor-ivacaftor or tezacaftor-ivacaftor. Phenotypic characterization and comparative genomics were performed. RESULTS: Clonal lineages of P. aeruginosa persisted after therapy, with no evidence of displacement by alternative strains. We identified commonly mutated genes among patient isolates that may be positively selected for in the CFTR-modulated lung. However, classic chronic P. aeruginosa phenotypes such as mucoid morphology were sustained, and isolates remained just as resistant to clinically relevant antibiotics. CONCLUSIONS: Despite the clinical benefits of CFTR modulators, clonal lineages of P. aeruginosa persist that may prove just as difficult to manage in the future, especially in pwCF with advanced lung disease.

Anti-Migratory and Cytotoxic Activities of [Ga(8-hydroxyquinolinato)3 ]: Roles of Endogenous Cu(II) and Drug-Induced Phenotypic Changes.

As shown by IncuCyte Zoom imaging proliferation assays, invasive triple-negative human breast MDA-MB-231 cancer cells treated with sub-toxic doses (5.0-20 µM, 72 h) of [GaQ3 ] (Q=8-hydroxyquinolinato) caused profound morphological changes and inhibition of cell migration, which were likely due to terminal cell differentiation or similar phenotypical change. This is the first demonstration of potential use of a metal complex in differentiation anti-cancer therapy. Additionally, a trace amount of Cu(II) (0.20 µM) added to the medium dramatically increased [GaQ3 ] cytotoxicity (IC50 ~2 µM, 72 h) due to its partial dissociation and the action of the HQ ligand as a Cu(II) ionophore, as shown with electrospray mass spectrometry and fluorescence spectroscopy assays in the medium. Hence, cytotoxicity of [GaQ3 ] is strongly linked to ligand binding of essential metal ions in the medium, for example, Cu(II). Appropriate delivery mechanisms of such complexes and their ligands could enable a powerful new triple therapeutic approach for cancer chemotherapy, including cytotoxicity against primary tumour, arrest of metastases, and activation of innate and adaptive immune responses.

A case review to describe variation in care following diagnosis of Perthes' disease.

AIMS: Perthes' disease is a condition which leads to necrosis of the femoral head. It is most commonly reported in children aged four to nine years, with recent statistics suggesting it affects around five per 100,000 children in the UK. Current treatment for the condition aims to maintain the best possible environment for the disease process to run its natural course. Management typically includes physiotherapy with or without surgical intervention. Physiotherapy intervention often will include strengthening/stretching programmes, exercise/activity advice, and, in some centres, will include intervention, such as hydrotherapy. There is significant variation in care with no consensus on which treatment option is best. The importance of work in this area has been demonstrated by the British Society for Children's Orthopaedic Surgery through the James Lind Alliance's prioritization of work to determine/identify surgical versus non-surgical management of Perthes' disease. It was identified as the fourth-highest priority for paediatric lower limb surgery research in 2018. METHODS: Five UK NHS centres, including those from the NEWS (North, East, West and South Yorkshire) orthopaedic group, contributed to this case review, with each entre providing clinical data from a minimum of five children. Information regarding both orthopaedic and physiotherapeutic management over a two-year post-diagnosis period was reviewed. RESULTS: Data were extracted from the clinical records of 32 children diagnosed with Perthes' disease; seven boys and 25 girls. The mean age of the children at diagnosis was 6.16 years (standard deviation (SD) 3.001). In all, 26 children were referred for physiotherapy. In the two-year period following diagnosis, children were seen a median of 7.5 times (interquartile range (IQR) 4.25 to 11) by an orthopaedic surgeon, and a median of 9.5 times (IQR 8 to 18.25) by a physiotherapist. One centre had operated on all of their children, while another had operated on none. Overall, 17 (53%) of the children were managed conservatively in the two-year follow-up period, and 15 (47%) of the children underwent surgery in the two-year follow-up period. CONCLUSION: The results of this case review demonstrate a variation of care provided to children in the UK with Perthes' disease. Further national and international understanding of current care is required to underpin the rationale for different treatment options in children with Perthes' disease.Cite this article: Bone Joint Open 2020;1-11:691-695.

Current infection control practices used in Australian and New Zealand cystic fibrosis centers.

BACKGROUND: The 2013 update of the Infection Prevention and Control (IP&C) Guideline outlined recommendations to prevent the spread of CF respiratory pathogens. We aimed to investigate the current infection control practices used in Australian and New Zealand (NZ) CF centers. METHODS: Two online surveys were distributed to Australian and NZ CF centers regarding the uptake of selected IP&C recommendations. One survey was distributed to all the Medical Directors and Lead CF Nurses and the second survey was distributed to all the Lead CF Physiotherapists. RESULTS: The response rate was 60% (60/100) for medical/nursing and 58% (14/24) for physiotherapy. Over 90% (55/60) of CF centers followed CF-specific infection control guidelines and consistent infection control practices were seen in most CF centers; 76% (41/54) had implemented segregation strategies for ambulatory care and no CF centers housed people with CF in shared inpatient accommodation. However, the application of contact precautions (wearing gloves and apron/gown) by healthcare professionals when reviewing a CF person was variable between CF center respondents but was most often used when seeing CF persons with MRSA infection in both ambulatory care and hospital admission (20/50, 40% and 42/45, 93% of CF centers, respectively). Mask wearing by people with CF was implemented into 61% (36/59) of centers. Hospital rooms were cleaned daily in 79% (37/47) of CF centers and the ambulatory care consult rooms were always cleaned between consults (49/49, 100%) and at the end of the clinic session (51/51, 100%); however the staff member tasked with cleaning changed with 37% (18/49) of CF centers responding that CF multidisciplinary team (MDT) members cleaned between patients whereas at the end of the clinic session, only 12% (6/51) of the CF MDT cleaned the consult room. CONCLUSIONS: Overall, Australian and NZ CF centers have adopted many recommendations from the IP&C. Although, the application of contact precautions was inconsistent and had overall a low level of adoption in CF centers. In ~ 25% of centers, mixed waiting areas occurred in the ambulatory care. Given the variability of responses, additional work is required to achieve greater consistency between centers.

The Impact of Hysteroscopic Tissue Removal Systems on Histopathologic Analysis for Benign and Cancerous Endometrial Pathology: An Ex Vivo Study.

OBJECTIVE: To assess the impact of hysteroscopic tissue removal systems (TRS) on histopathology tissue diagnosis. MEASUREMENTS AND METHODS: This is a paired-comparison ex vivo study in which 23 endometrial sections from hysterectomized uteri (13 benign and 10 hyperplasia/cancer) were analyzed in a simulation laboratory center at a university teaching hospital. After routine tissue processing, a section of endometrium was provided for ex vivo TRS with suture mounting to a uterine model (Polly, Remedy). Morcellated specimens using the Hologic® MyoSure hysteroscopic device were processed for histopathologic analysis by two blinded pathologists (Pa and Pb) and compared to the original specimens' tissue diagnoses. RESULTS: Sufficient tissue for evaluation was found in 100% (23/23) of TRS specimens by Pa and 91.3% by Pb. TRS specimen diagnoses were concordant with routine histologic diagnosis 86.9% (20/23, k = 0.76) for Pa and 80.9% (17/21, k = 0.68) for Pb. Sensitivity and specificity were 70%/100% for Pa and 80%/91% for Pb, respectively. The false-positive (overdiagnosed) and false-negative rates (underdiagnosed) were 0%/30% and 9%/20% for Pa and Pb. Both Pa and Pb underdiagnosed most specimens confirmed by routine tissue diagnosis. TRS specimen diagnoses between Pa and Pb were concordant in 76.2% (16/21, k = 0.60). CONCLUSION: TRS may adversely impact the ability to provide a histologic tissue analysis. Up to 30% of samples were overdiagnosed and 20% underdiagnosed. If confirmed, pathologists may need to reassess workflows to better offset potential underdiagnosis of malignant specimens as findings may be obscured through TRS. Additionally, surgeons may need to reconsider specimen handling, so highest yield specimens are provided to pathology.

Transmission of bacteria in bronchiectasis and chronic obstructive pulmonary disease: Low burden of cough aerosols.

BACKGROUND AND OBJECTIVE: Aerosol transmission of Pseudomonas aeruginosa has been suggested as a possible mode of respiratory infection spread in patients with cystic fibrosis (CF); however, whether this occurs in other suppurative lung diseases is unknown. Therefore, we aimed to determine if (i) patients with bronchiectasis (unrelated to CF) or chronic obstructive pulmonary disease (COPD) can aerosolize P. aeruginosa during coughing and (ii) if genetically indistinguishable (shared) P. aeruginosa strains are present in these disease cohorts. METHODS: People with bronchiectasis or COPD and P. aeruginosa respiratory infection were recruited for two studies. Aerosol study: Participants (n = 20) underwent cough testing using validated cough rigs to determine the survival of P. aeruginosa aerosols in the air over distance and duration. Genotyping study: P. aeruginosa sputum isolates (n = 95) were genotyped using the iPLEX20SNP platform, with a subset subjected to the enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) assay to ascertain their genetic relatedness. RESULTS: Aerosol study: Overall, 7 of 20 (35%) participants released P. aeruginosa cough aerosols during at least one of the cough aerosol tests. These cough aerosols remained viable for 4 m from the source and for 15 min after coughing. The mean total aerosol count of P. aeruginosa at 2 m was two colony-forming units. Typing study: No shared P. aeruginosa strains were identified. CONCLUSION: Low viable count of P. aeruginosa cough aerosols and a lack of shared P. aeruginosa strains observed suggest that aerosol transmission of P. aeruginosa is an unlikely mode of respiratory infection spread in patients with bronchiectasis and COPD.

Cystic fibrosis pathogens survive for extended periods within cough-generated droplet nuclei.

The airborne route is a potential pathway in the person-to-person transmission of bacterial strains among cystic fibrosis (CF) populations. In this cross-sectional study, we investigate the physical properties and survival of common non-Pseudomonas aeruginosa CF pathogens generated during coughing. We conclude that Gram-negative bacteria and Staphylococcus aureus are aerosolised during coughing, can travel up to 4 m and remain viable within droplet nuclei for up to 45 min. These results suggest that airborne person-to-person transmission is plausible for the CF pathogens we measured.

Overcoming the Challenging Cervix: Identification and Techniques to Access the Uterine Cavity.

IMPORTANCE: Cervical stenosis is a challenging clinical entity that requires prompt identification and management in order to avoid iatrogenic injury at the time of endocervical canal cannulation. OBJECTIVE: The aim of this study was to identify cervical stenosis and discuss associated etiologies, risk factors, and review medical and surgical approaches for overcoming cervical stenosis. EVIDENCE ACQUISITION: Computerized searches of MEDLINE and PubMed were conducted using the key words "cervix", "cervical stenosis," "embryo transfer," "hysteroscopy complications," "misoprostol," and "ultrasound." References from identified sources were manually searched to allow for a thorough review. Data from relevant sources were compiled to create this review. RESULTS: Transcervical access to the uterine cavity is frequently required for procedures such as hysteroscopy, dilation and curettage, endometrial biopsy, sonohysterogram, hysterosalpingogram, intrauterine insemination, embryo transfer in those undergoing in vitro fertilization, and insertion of intrauterine devices. These procedures can become complicated when difficult cannulation of the endocervical canal is encountered. Management strategies include preprocedural use of cervical-ripening agents or osmotic dilators, ultrasound guidance, no-touch vaginoscopy, manual dilatation, and hysteroscopic resection of the obstructed endocervical canal. CONCLUSIONS AND RELEVANCE: Cervical stenosis is associated with iatrogenic complications that can result in significant patient morbidity. In patients undergoing in vitro fertilization, difficult embryo transfer is associated with lower pregnancy rates. The clinician should carefully consider the patient's menopausal status, risk factors, and symptoms in order to anticipate difficult navigation of the endocervical canal. Various medical and surgical management strategies, including hysteroscopic resection, can be used to overcome the stenotic cervix.

Work environment risks for health care workers with cystic fibrosis.

In Australia and New Zealand, >50% of people with cystic fibrosis (CF) are adults and many of these people are pursuing vocational training and undertaking paid employment. More than 6% of adults with CF are working in health care. There is limited guidance in literature to support health care workers with CF (HCWcf) in training and in employment to support safe practice and to provide protection for themselves and their patients from the acquisition of health care associated infection. A multidisciplinary team of CF and Infectious Disease Clinicians, Infection Prevention and Control Practitioners, HCWcf, academic experts in medical ethics and representatives from universities, appraised the available evidence on the risk posed to and by HCWcf. Specific recommendations were made for HCWcf, CF health care teams, hospitals and universities to support the safe practice and appropriate support for HCWcf.

Face Masks and Cough Etiquette Reduce the Cough Aerosol Concentration of Pseudomonas aeruginosa in People with Cystic Fibrosis.

RATIONALE: People with cystic fibrosis (CF) generate Pseudomonas aeruginosa in droplet nuclei during coughing. The use of surgical masks has been recommended in healthcare settings to minimize pathogen transmission between patients with CF. OBJECTIVES: To determine if face masks and cough etiquette reduce viable P. aeruginosa aerosolized during coughing. METHODS: Twenty-five adults with CF and chronic P. aeruginosa infection were recruited. Participants performed six talking and coughing maneuvers, with or without face masks (surgical and N95) and hand covering the mouth when coughing (cough etiquette) in an aerosol-sampling device. An Andersen Cascade Impactor was used to sample the aerosol at 2 meters from each participant. Quantitative sputum and aerosol bacterial cultures were performed, and participants rated the mask comfort levels during the cough maneuvers. MEASUREMENTS AND MAIN RESULTS: During uncovered coughing (reference maneuver), 19 of 25 (76%) participants produced aerosols containing P. aeruginosa, with a positive correlation found between sputum P. aeruginosa concentration (measured as cfu/ml) and aerosol P. aeruginosa colony-forming units. There was a reduction in aerosol P. aeruginosa load during coughing with a surgical mask, coughing with an N95 mask, and cough etiquette compared with uncovered coughing (P < 0.001). A similar reduction in total colony-forming units was observed for both masks during coughing; yet, participants rated the surgical masks as more comfortable (P = 0.013). Cough etiquette provided approximately half the reduction of viable aerosols of the mask interventions during voluntary coughing. Talking was a low viable aerosol-producing activity. CONCLUSIONS: Face masks reduce cough-generated P. aeruginosa aerosols, with the surgical mask providing enhanced comfort. Cough etiquette was less effective at reducing viable aerosols.

Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium.

Lung infections with Mycobacterium abscessus, a species of multidrug-resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF), in whom M. abscessus accelerates inflammatory lung damage, leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole-genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.

A Novel Method and Its Application to Measuring Pathogen Decay in Bioaerosols from Patients with Respiratory Disease.

This work aimed to develop an in vivo approach for measuring the duration of human bioaerosol infectivity. To achieve this, techniques designed to target short-term and long-term bioaerosol aging, were combined in a tandem system and optimized for the collection of human respiratory bioaerosols, without contamination. To demonstrate the technique, cough aerosols were sampled from two persons with cystic fibrosis and chronic Pseudomonas aeruginosa infection. Measurements and cultures from aerosol ages of 10, 20, 40, 900 and 2700 seconds were used to determine the optimum droplet nucleus size for pathogen transport and the airborne bacterial biological decay. The droplet nuclei containing the greatest number of colony forming bacteria per unit volume of airborne sputum were between 1.5 and 2.6 µm. Larger nuclei of 3.9 µm, were more likely to produce a colony when impacted onto growth media, because the greater volume of sputum comprising the larger droplet nuclei, compensated for lower concentrations of bacteria within the sputum of larger nuclei. Although more likely to produce a colony, the larger droplet nuclei were small in number, and the greatest numbers of colonies were instead produced by nuclei from 1.5 to 5.7 µm. Very few colonies were produced by smaller droplet nuclei, despite their very large numbers. The concentration of viable bacteria within the dried sputum comprising the droplet nuclei exhibited an orderly dual decay over time with two distinct half-lives. Nuclei exhibiting a rapid biological decay process with a 10 second half-life were quickly exhausted, leaving only a subset characterized by a half-life of greater than 10 minutes. This finding implied that a subset of bacteria present in the aerosol was resistant to rapid biological decay and remained viable in room air long enough to represent an airborne infection risk.

Pulmonary artery enlargement and cystic fibrosis pulmonary exacerbations: a cohort study.

BACKGROUND: Acute pulmonary exacerbations are associated with progressive lung function decline and increased mortality in cystic fibrosis. The role of pulmonary vascular disease in pulmonary exacerbations is unknown. We aimed to assess the association between pulmonary artery enlargement (defined as pulmonary artery diameter to ascending aorta diameter [PA:A] ratio >1), a marker of pulmonary vascular disease, and exacerbations. METHODS: In this cohort study, we used clinical, CT imaging, and prospective exacerbation data from a previous prospective clinical trial (derivation cohort) and from The Prince Charles Hospital (TPCH; Brisbane, QLD, Australia) cystic fibrosis registry (validation cohort). In our derivation cohort, we included adults aged 18 years or older with cystic fibrosis and at least one CFTR nonsense mutation, who were enrolled in the trial between Sept 8, 2009, and Nov 30, 2010, randomly assigned to receive placebo, and had baseline CT imaging. Our validation cohort included adult patients with cystic fibrosis who had CT imaging performed between Jan 1, 2002, and Dec 31, 2014. We measured the PA:A ratio at the level of the pulmonary artery bifurcation on CT scans. Patients in each cohort were separated into two groups on the basis of PA:A ratio (>1 or ≤1) and were followed up for 1 year in the derivation cohort and 2 years in the validation cohort. The primary endpoint was the development of one or more acute pulmonary exacerbations during follow-up. We used linear and logistic regression models to determine associations between clinical factors, the PA:A ratio, and pulmonary exacerbations. We used Cox regression to determine the time to first exacerbation in the validation cohort. FINDINGS: 37 (50%) of 74 patients in the derivation cohort and 89 (47%) of 190 patients in the validation cohort had enlarged pulmonary arteries (PA:A>1). 50 (68%) patients in the derivation cohort had one or more exacerbations at 1 year and 133 (70%) patients in the validation cohort had one or more exacerbations at 2 years. At baseline, patients with pulmonary artery enlargement were younger than those without enlargement in both cohorts and had elevated sweat chloride concentrations in the derivation cohort (100·5 mmol/L [SD 10·9] vs 90·4 mmol/L [19·9]; difference 10·1 mmol/L [95% CI 2·5-17·7], p=0·017). Pulmonary artery enlargement was associated with exacerbations in the derivation cohort (odds ratio 3·49 [95% CI 1·18-10·3], p=0·023) when adjusted for sex, body-mass index (BMI), forced expiratory volume in 1 s (FEV1), and PA:A greater than 1, and in the validation cohort (2·41 [1·06-5·52], p=0·037) when adjusted for sex, BMI, chronic Pseudomonas aeruginosa infection, FEV1/FVC (forced vital capacity), PA:A greater than 1, and previous exacerbation. The time to first exacerbation was shorter in patients with enlarged pulmonary arteries than in those with normal-sized pulmonary arteries in the validation cohort (hazard ratio 1·66 [95% CI 1·18-2·34], p=0·0038) in unadjusted analysis, but not when adjusted for sex, BMI, exacerbations within 1 year before index CT scan, FEV1/FVC, and chronic P aeruginosa infection (1·14 [0·80-1·62], p=0·82). INTERPRETATION: Pulmonary artery enlargement is prevalent in adult patients with cystic fibrosis and was associated with acute pulmonary exacerbation risk in two well characterised cohorts. The PA:A ratio could be a predictive marker in cystic fibrosis. FUNDING: US National Heart, Lung, and Blood Institute/National Institutes of Health, Cystic Fibrosis Foundation, the University of Alabama at Birmingham, and the Queensland Health Fellowship.

Erythropoietin increases macrophage-mediated T cell suppression.

Erythropoietin (EPO), used to treat anemia in cancer patients, has been reported to accelerate tumor progression and increase mortality. Research of the mechanism for this effect has focused upon EPOR expression by tumor cells. We model the high macrophage to lymphocyte ratio found in tumor microenvironments (TMEs) by culturing peritoneal cavity (PerC) cells that naturally have a high macrophage to T cell ratio. Following TCR ligation, C57BL/6J PerC T cell proliferation is suppressed due to IFNγ-triggered inducible nitric oxide synthase (iNOS) expression. EPO was tested in the PerC culture model and found to increase T cell suppression. This effect could be abrogated by inhibiting iNOS by enzyme inhibition, genetic ablation, or blocking IFNγ signaling. Flow cytometry revealed the EPOR on CD11b(+)F4/80(+) macrophages. These results suggest that EPO could increase T cell suppression in the TME by acting directly on macrophages.

Methicillin-resistant Staphylococcus aureus acquisition in healthcare workers with cystic fibrosis: a retrospective cross-sectional study.

BACKGROUND: People with cystic fibrosis (CF) may work in healthcare settings risking nosocomial pathogen acquisition. The aim of this study was to determine the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection in adult healthcare workers with CF (HCWcf). METHODS: Data was collected in this observational study on MRSA acquisition from 405 CF patients attending an adult CF centre in Australia between 2001-2012. Demographic and clinical characteristics were compared between HCWcf and non-HCWcf. A sub-analysis was subsequently performed to compare demographic and clinical characteristics between those patients (HCWcf versus non-HCWcf) that acquired MRSA. We also investigated rates of chronic MRSA infection and the outcome of eradication treatment in HCWcf. RESULTS: A higher proportion of HCWcf acquired MRSA [n = 10/21] compared to non-HCWcf [n = 40/255] (P <0.001). The odds of MRSA acquisition were 8.4 (95 % CI, 3.0 - 23.4) times greater in HCWcf than non-HCWcf. HCWcf with MRSA were older (P = 0.02) and had better lung function (P = 0.009), yet hospitalisation rates were similar compared to non-HCWcf with MRSA. Chronic MRSA infection developed in 36/50 CF patients (HCWcf, n = 6; non-HCWcf, n = 30), with eradication therapy achieved in 5/6 (83 %) HCWcf. CONCLUSIONS: The rate of MRSA incidence was highest in HCWcf and the workplace is a possible source of acquisition. Vocational guidance should include the potential for MRSA acquisition for CF patients considering healthcare professions.