Impact of Combined Low-Level Mupirocin and Genotypic Chlorhexidine Resistance on Persistent Methicillin-Resistant Staphylococcus aureus Carriage After Decolonization Therapy: A Case-control Study

The clinical significance of low-level mupirocin and genotypic chlorhexidine resistance remains unclear. This case-control study demonstrates that combined low-level mupirocin and genotypic chlorhexidine resistance significantly increases the risk of persistent MRSA carriage after decolonization therapy (OR 3.4, 95% CI 1.5-7.8

Rheumatoid leptomeningitis presenting with an acute neuropsychiatric disorder

Leptomeningitis is a rare central nervous system manifestation of rheumatoid arthritis, generally in patients with established chronic rheumatoid disease. We report a 41-year-old man without previous rheumatoid arthritis or psychiatric disorder who presented with an acute neuropsychiatric disturbance and polyarthralgia. His MR scan of brain showed asymmetric bifrontal leptomeningitis, confirmed on (18F)-fluoro-D-glucose-positron emission tomography. Other investigations showed highly positive serum and cerebrospinal fluid anti-cyclic citrullinated peptide. A leptomeningeal biopsy showed necrotising leptomeningeal inflammation with ill-defined granulomas and lymphoplasmacytic infiltrate without organisms. Prolonged high-dose corticosteroids and then rituximab resulted in recovery. Chronic leptomeningitis can present with an acute neuropsychiatric disorder. We highlight that early rheumatoid disease can, rarely, cause a chronic leptomeningitis, reversible with immunotherapy

Comparison of strategies to reduce meticillin-resistant Staphylococcus aureus rates in surgical patients: a controlled multicentre intervention trial.

Objective: To compare the effect of two strategies (enhanced hand hygiene vs meticillin-resistant Staphylococcus aureus (MRSA) screening and decolonisation) alone and in combination on MRSA rates in surgical wards. Design: Prospective, controlled, interventional cohort study, with 6-month baseline, 12-month intervention and 6-month washout phases. Setting: 33 surgical wards of 10 hospitals in nine countries in Europe and Israel. Participants: All patients admitted to the enrolled wards for more than 24 h. Interventions: The two strategies compared were (1) enhanced hand hygiene promotion and (2) universal MRSA screening with contact precautions and decolonisation (intranasal mupirocin and chlorhexidine bathing) of MRSA carriers. Four hospitals were assigned to each intervention and two hospitals combined both strategies, using targeted MRSA screening. Outcome measures: Monthly rates of MRSA clinical cultures per 100 susceptible patients (primary outcome) and MRSA infections per 100 admissions (secondary outcome). Planned subgroup analysis for clean surgery wards was performed. Results: After adjusting for clustering and potential confounders, neither strategy when used alone was associated with significant changes in MRSA rates. Combining both strategies was associated with a reduction in the rate of MRSA clinical cultures of 12% per month (adjusted incidence rate ratios (aIRR) 0.88, 95% CI 0.79 to 0.98). In clean surgery wards, strategy 2 (MRSA screening, contact precautions and decolonisation) was associated with decreasing rates of MRSA clinical cultures (15% monthly decrease, aIRR 0.85, 95% CI 0.74 to 0.97) and MRSA infections (17% monthly decrease, aIRR 0.83, 95% CI 0.69 to 0.99). Conclusions: In surgical wards with relatively low MRSA prevalence, a combination of enhanced standard and MRSA-specific infection control approaches was required to reduce MRSA rates. Implementation of single interventions was not effective, except in clean surgery wards where MRSA screening coupled with contact precautions and decolonisation was associated with significant reductions in MRSA clinical culture and infection rates. Trial registration clinicaltrials.gov identifier: NCT0068586

Variable performance of models for predicting methicillin-resistant Staphylococcus aureus carriage in European surgical wards

BACKGROUND: Predictive models to identify unknown methicillin-resistant Staphylococcus aureus (MRSA) carriage on admission may optimise targeted MRSA screening and efficient use of resources. However, common approaches to model selection can result in overconfident estimates and poor predictive performance. We aimed to compare the performance of various models to predict previously unknown MRSA carriage on admission to surgical wards. METHODS: The study analysed data collected during a prospective cohort study which enrolled consecutive adult patients admitted to 13 surgical wards in 4 European hospitals. The participating hospitals were located in Athens (Greece), Barcelona (Spain), Cremona (Italy) and Paris (France). Universal admission MRSA screening was performed in the surgical wards. Data regarding demographic characteristics and potential risk factors for MRSA carriage were prospectively collected during the study period. Four logistic regression models were used to predict probabilities of unknown MRSA carriage using risk factor data: 'Stepwise' (variables selected by backward elimination); 'Best BMA' (model with highest posterior probability using Bayesian model averaging which accounts for uncertainty in model choice); 'BMA' (average of all models selected with BMA); and 'Simple' (model including variables selected >50% of the time by both Stepwise and BMA approaches applied to repeated random sub-samples of 50% of the data). To assess model performance, cross-validation against data not used for model fitting was conducted and net reclassification improvement (NRI) was calculated. RESULTS: Of 2,901 patients enrolled, 111 (3.8%) were newly identified MRSA carriers. Recent hospitalisation and presence of a wound/ulcer were significantly associated with MRSA carriage in all models. While all models demonstrated limited predictive ability (mean c-statistics <0.7) the Simple model consistently detected more MRSA-positive individuals despite screening fewer patients than the Stepwise model. Moreover, the Simple model improved reclassification of patients into appropriate risk strata compared with the Stepwise model (NRI 6.6%, P = .07). CONCLUSIONS: Though commonly used, models developed using stepwise variable selection can have relatively poor predictive value. When developing MRSA risk indices, simpler models, which account for uncertainty in model selection, may better stratify patients' risk of unknown MRSA carriage

Prevention and Control of Methicillin-Resistant Staphylococcus aureus in Acute Care Settings

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of health care-associated infections worldwide. Controversies with regard to the effectiveness of various MRSA control strategies have contributed to varying approaches to the control of this pathogen in different settings. However, new evidence from large-scale studies has emerged, particularly with regards to MRSA screening and decolonization strategies, which will inform future control practices. The implementation as well as outcomes of control measures in the real world is not only influenced by scientific evidence but also depends on economic, administrative, governmental, and political influences

Control of methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of nosocomial infections worldwide. Different approaches to the control of this pathogen have met with varying degrees of success in different health care settings. Controversies exist with regards to various MRSA control strategies. The implementation and outcomes of control measures depend on several factors, including scientific, economic, administrative, governmental, and political influences. It is clear that flexibility to adapt and institute these measures in the context of local epidemiology and resources is required

Methicillin-resistant Staphylococcus aureus: an update on prevention and control in acute care settings

Abstract Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of health-care-associated infections. Controversies regarding the effectiveness of various control strategies have contributed to varying approaches to MRSA control. However, new evidence from large-scale studies has emerged, particularly concerning screening and decolonization. Importantly, implementation and outcomes of control measures in practice are not only influenced by scientific evidence, but also economic, administrative, and political factors, as demonstrated by decreasing MRSA rates in a number of countries after concerted and coordinated efforts at a national level. Flexibility to adapt measures based on local epidemiology and resources is essential for successful MRSA control.</p

Mupirocin-induced mutations in ileS in various genetic backgrounds of methicillin-resistant Staphylococcus aureus

Topical mupirocin is widely used for the decolonization of methicillin-resistant Staphylococcus aureus (MRSA) carriers. We evaluated the capacity of various MRSA clonotypes to develop mutations in the ileS gene associated with low-level mupirocin resistance. Twenty-four mupirocin-sensitive MRSA isolates from a variety of genotypes (determined by multilocus variable number of tandem repeats assay) were selected. Mupirocin MICs were determined by Etest. The isolates were then incubated in sub-inhibitory concentrations of mupirocin for 7-14 days. Repeat MIC determination and sequencing of the ileS gene were then performed. Doubling times of isolates exposed and unexposed to mupirocin were compared. We found that exposure to mupirocin led to rapid induction of low-level resistance (MICs 8-24 μg/ml) in 11 of 24 (46%) MRSA isolates. This phenomenon was observed in strains with diverse genetic backgrounds. Various mutations were detected in 18 of 24 (75%) MRSA isolates. Acquisition of mutations appeared to be a stepwise process during prolonged incubation with the drug. Among five low-level resistant isolates with the highest MICs, four tested sensitive after incubation in the absence of mupirocin but there was no reversion to the susceptible wild-type primary sequence. Resistance was not associated with significant fitness cost, suggesting that low-level mupirocin-resistant MRSA strains may have a selective advantage in facilities where mupirocin is commonly used. Our findings emphasize the importance of the judicious use of this topical agent and the need to closely monitor for the emergence of resistance