Poxy models and rash decisions.
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Biomedical subjects
Publications and source records attributed to Ben Cooper.
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OBJECTIVES: Linezolid, the only commercially available oxazolidinone, is indicated for the treatment of Gram-positive infections, although little has been published specifically on its use in the critically ill. A randomized, prospective study was therefore performed to compare linezolid with the glycopeptide antibiotic, teicoplanin, for the treatment of suspected or proven Gram-positive infections in an intensive care population. METHODS: Using a double-blind, double-dummy, prospective design, patients were randomized to (i) intravenous linezolid (600 mg/12 h) plus teicoplanin dummy [one dose/12 h for three doses then every 24 h intravenously (iv)] or (ii) teicoplanin (400 mg/12 h for three doses then 400 mg/24 h iv) plus linezolid dummy (one dose/12 h iv). Other antibiotics were used in combination with the trial agents in empirical treatment. Clinical and microbiological assessments were made daily in the first week, and at 8 and 21 days after treatment. RESULTS: One hundred patients received linezolid plus placebo-teicoplanin, whereas 102 received teicoplanin plus placebo-linezolid. Population baseline characteristics were similar in both groups. At end of treatment, clinical success [71 (78.9%) linezolid versus 67 (72.8%) teicoplanin] and microbiological success [49 (70.0%) versus 45 (66.2%)] rates were similar, as were adverse effects, intensive care unit mortality, and success rates at short- and long-term follow-up. Linezolid was superior at initial clearance of methicillin-resistant Staphylococcus aureus (MRSA) colonization (end of treatment, 51.1% versus 18.6%, P = 0.002). Two MRSA isolates showed reduced susceptibility to teicoplanin. CONCLUSIONS: Linezolid has similar safety and efficacy to teicoplanin in treating Gram-positive infections in the critically ill. Short-term MRSA clearance achieved with linezolid suggests better skin and mucosal penetration.
Surveillance data for communicable nosocomial pathogens usually consist of short time series of low-numbered counts of infected patients. These often show overdispersion and autocorrelation. To date, almost all analyses of such data have ignored the communicable nature of the organisms and have used methods appropriate only for independent outcomes. Inferences that depend on such analyses cannot be considered reliable when patient-to-patient transmission is important. We propose a new method for analysing these data based on a mechanistic model of the epidemic process. Since important nosocomial pathogens are often carried asymptomatically with overt infection developing in only a proportion of patients, the epidemic process is usually only partially observed by routine surveillance data. We therefore develop a 'structured' hidden Markov model where the underlying Markov chain is generated by a simple transmission model. We apply both structured and standard (unstructured) hidden Markov models to time series for three important pathogens. We find that both methods can offer marked improvements over currently used approaches when nosocomial spread is important. Compared to the standard hidden Markov model, the new approach is more parsimonious, is more biologically plausible, and allows key epidemiological parameters to be estimated.
Severe acute respiratory syndrome (SARS) is a recently described illness of humans that has spread widely over the past 6 months. With the use of detailed epidemiologic data from Singapore and epidemic curves from other settings, we estimated the reproductive number for SARS in the absence of interventions and in the presence of control efforts. We estimate that a single infectious case of SARS will infect about three secondary cases in a population that has not yet instituted control measures. Public-health efforts to reduce transmission are expected to have a substantial impact on reducing the size of the epidemic.
BACKGROUND: Hospital-acquired infection due to meticillin-resistant Staphylococcus aureus (MRSA) is common within intensive-care units. Single room or cohort isolation of infected or colonised patients is used to reduce spread, but its benefit over and above other contact precautions is not known. We aimed to assess the effectiveness of moving versus not moving infected or colonised patients in intensive-care units to prevent transmission of MRSA. METHODS: We undertook a prospective 1-year study in the intensive-care units of two teaching hospitals. Admission and weekly screens were used to ascertain the incidence of MRSA colonisation. In the middle 6 months, MRSA-positive patients were not moved to a single room or cohort nursed unless they were carrying other multiresistant or notifiable pathogens. Standard precautions were practised throughout. Hand hygiene was encouraged and compliance audited. FINDINGS: Patients' characteristics and MRSA acquisition rates were similar in the periods when patients were moved and not moved. The crude (unadjusted) Cox proportional-hazards model showed no evidence of increased transmission during the non-move phase (0.73 [95% CI 0.49-1.10], p=0.94 one-sided). There were no changes in transmission of any particular strain of MRSA nor in handwashing frequency between management phases. INTERPRETATION: Moving MRSA-positive patients into single rooms or cohorted bays does not reduce crossinfection. Because transfer and isolation of critically ill patients in single rooms carries potential risks, our findings suggest that re-evaluation of isolation policies is required in intensive-care units where MRSA is endemic, and that more effective means of preventing spread of MRSA in such settings need to be found.