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1.
Science ; 354(6313): 751-757, 2016 11 11.
Article in English | MEDLINE | ID: mdl-27846606

ABSTRACT

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.


Subject(s)
Communicable Diseases, Emerging/microbiology , Cystic Fibrosis/microbiology , Drug Resistance, Multiple, Bacterial , Mycobacterium Infections, Nontuberculous/microbiology , Nontuberculous Mycobacteria/classification , Animals , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/pathology , Communicable Diseases, Emerging/transmission , Cystic Fibrosis/epidemiology , Cystic Fibrosis/pathology , Genome, Bacterial , Genomics , Humans , Incidence , Lung/microbiology , Lung/pathology , Mice , Mice, SCID , Mycobacterium Infections, Nontuberculous/epidemiology , Mycobacterium Infections, Nontuberculous/pathology , Mycobacterium Infections, Nontuberculous/transmission , Nontuberculous Mycobacteria/genetics , Nontuberculous Mycobacteria/isolation & purification , Phylogeny , Pneumonia, Bacterial/epidemiology , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/pathology , Pneumonia, Bacterial/transmission , Polymorphism, Single Nucleotide , Sequence Analysis, DNA
3.
J Antimicrob Chemother ; 56(3): 566-8, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16076879

ABSTRACT

OBJECTIVES: Compliance with our local hospital policy for gentamicin administration and monitoring was found to be inadequate on audit. A gentamicin monitoring form was introduced with the aim of improving staff compliance with the policy thus minimizing the risks of toxicity while ensuring adequate dosing. PATIENTS AND METHODS: The initial audit examined the prescribing, administration and monitoring of intravenous gentamicin given to 20 patients. The introduction of a gentamicin monitoring form was prompted by unsatisfactory initial dosing and subsequent monitoring and adjustment of gentamicin doses. RESULTS: Following introduction of the monitoring form, the proportion of appropriate starting doses had increased from 13 out of 20 to 18 out of 20 prescriptions. The timing of initial serum levels was significantly better: 18 timed correctly, compared with 12 in initial audit. Subsequent administration and monitoring appeared more compliant with fewer doses inappropriately omitted and more levels checked appropriately. No improvement was seen in the quality of dose adjustment. CONCLUSIONS: In conjunction with the support and advice of the pharmacy and microbiology departments, the use of a gentamicin monitoring form can improve the quality of intravenous gentamicin use in the hospital setting.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Drug Monitoring/methods , Drug Prescriptions , Gentamicins/therapeutic use , Guideline Adherence , Anti-Bacterial Agents/adverse effects , Drug Utilization , Drug Utilization Review , Gentamicins/adverse effects , Guideline Adherence/organization & administration , Hospitals , Humans , Infections/drug therapy , Kidney/drug effects , Kidney Diseases/chemically induced , Kidney Diseases/physiopathology
4.
J Infect ; 50(2): 120-4, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15667912

ABSTRACT

OBJECTIVES: This study was carried out to determine local levels of compliance with guidelines from the British Infection Society (BIS) for the early management and investigation of adult patients presenting with possible bacterial meningitis [J Infect 39 (1999) 1; J Infect 46 (2003) 75]. METHODS: Patients investigated for possible bacterial meningitis at Wythenshawe Hospital, Manchester were identified retrospectively by a computer search of microbiology requests. The clinical presentation, laboratory investigations and early antibiotic management were reviewed. RESULTS: Only two of 26 patients who presented over a 9-month period were confirmed to have bacterial meningitis. Basic laboratory investigations were carried out on all patients. Samples for more specific investigations to determine the aetiological agent such as polymerase chain reaction, serology or throat swab culture, were frequently omitted by the clinicians. The choice of antibiotic therapy was generally appropriate for the treatment of bacterial meningitis with large variation in the dosage prescribed. Both patients with confirmed bacterial meningitis received appropriate doses. CONCLUSIONS: Compliance with BIS guidelines was incomplete in a group of patients presenting with possible bacterial meningitis. Access to a simplified outline of recommendations for early investigation and management of adult patients with possible bacterial meningitis may optimise guideline compliance and patient outcome. SUMMARY: Appropriate early investigation and management of bacterial meningitis in adults can optimise the outcome of this high mortality disease. Guidelines published by the BIS in 1999 detailed the recommended initial management of such patients [J Infect 39 (1999) 1]. In this study, the level of adherence to these guidelines was investigated for patients with possible bacterial meningitis who presented to a hospital in Manchester. The results showed that basic investigations such as peripheral blood count and blood cultures were almost invariably carried out, whereas, more specific investigations such as meningococcal PCR, serology and throat swab were frequently omitted. The choice of antibiotic was in agreement with the guidelines for the majority of cases but highlighted a considerable variability in dosage prescribed. The availability of a simple flow-chart outlining the early management of suspected bacterial meningitis and meningococcal septicaemia in adults produced by the BIS in 2003 may raise awareness of and compliance with their guidelines, thus optimising patient outcome.


Subject(s)
Medical Audit , Meningitis, Bacterial/diagnosis , Adolescent , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Bacteremia/diagnosis , Bacteremia/drug therapy , Bacteremia/microbiology , Female , Guideline Adherence , Humans , Male , Meningitis, Bacterial/drug therapy , Meningitis, Bacterial/microbiology , Meningitis, Meningococcal/diagnosis , Meningitis, Meningococcal/drug therapy , Meningitis, Meningococcal/microbiology , Meningitis, Pneumococcal/diagnosis , Meningitis, Pneumococcal/drug therapy , Meningitis, Pneumococcal/microbiology , Middle Aged , United Kingdom
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