Staphylococcus aureus bacteraemia

In the United Kingdom reporting of bacteraemia due to methicillin resistant Staphylococcus aureus (MRSA) infections is mandatory, and reduction in bacteraemia rates is a performance target for NHS trusts. Rates of S aureus bacteraemia remain high around the world, so we need forms of surveillance that will allow better understanding of its causes.

In a recent BMJ article Wyllie and colleagues describe the use of linked data to investigate secular trends in bacteraemia caused by S aureus. Using anonymised data on hospital admissions of patients and linking them to information on isolates of S aureus, they  found that about a third of patients with S aureus bacteraemia died within 30 days. The risk of death was similar for methicillin sensitive and methicillin resistant S aureus infections.

Between 1997 and 2003, rates of MRSA in these Oxfordshire hospitals increased while rates for methicillin sensitive S aureus (MSSA) strains remained constant. In other words, methicillin resistant strains did not displace methicillin susceptible strains: indeed they added considerably to the burden of disease. This paper serves as a reminder that health services must concentrate efforts on preventing all kinds of S aureus bacteraemia, to appreciate the importance of both methicillin resistant and methicillin sensitive strains, and to look critically at the successes and failures of control measures. Furthermore, these findings will reflect the experience of many readers and pose important questions.

A mathematical model published two years ago described how loss of infection control can occur by stealth: measures for screening and isolation may seem effective for years but, as increasing numbers of colonised patients are discharged and readmitted, infection rates reach a threshold where suddenly resources become overwhelmed. Loss of control at one hospital has knock-on effects at units that share the same pool of colonised patients. Such is the experience in the UK.

Around a third of humans are colonised with S aureus. Conservative estimates of the number of MRSA carriers worldwide range from 2 million to 53 million, and this pool is growing. The Netherlands is one of the few countries where this rising tide has been held back. A model developed using Dutch data suggests that one factor necessary for control is attempted eradication of carriage on discharge from hospital. Optimistically, this Dutch model suggests that, even when MRSA becomes endemic, it may be possible to reverse the situation by a coordinated reinstatement of search and destroy measures (including eradication on discharge). To do this properly would require a huge investment in facilities, however, and might take a decade or so to bear fruit.

For practical purposes we may be already past the point of no return. Given that the patients studied in the BMJ article were general medical and surgical patients and were not selected from high risk groups, it may be more pragmatic to concentrate on measures that prevent all forms of S aureus bacteraemia (such as better management of vascular devices) and to optimise treatment of bacteraemia.

For example, some doubt remains about the optimal duration of antibiotic treatment for S aureus bacteraemia and carefully planned multicentre prospective comparative trials in selected patient groups are needed to evaluate antibiotics, including several recently licensed agents, for the treatment of MRSA bacteraemia.

Eradication of MRSA alone will not solve the problem of invasive S aureus infection, not least because strains of S aureus that are sensitive to methicillin still account for many infections. Measures that focus on detecting carriage draw attention away from the real problem of invasive disease and shake the foundation of reasoned intellectual debate on staphylococcal infection.

Collecting patient centred data over long periods at representative centres would allow more detailed surveillance and could inform prospective intervention studies on the prevention and treatment of bacteraemia. Along with greater understanding of the evolutionary biology of these strains of bacteria, better management of community acquired MRSA, and more rational use of antibiotics (antibiotic stewardship), such surveillance could greatly improve the management of invasive staphylococcal infection and save lives.

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Relative risks and odds ratios in abstracts

A study was set up to compare the distribution of P values in abstracts of randomised controlled trials with that in observational studies, and to check the P values.

A cross sectional study was undertaken of all 260 abstracts in PubMed of articles published in 2003 that contained the phrases "relative risk" or "odds ratio" and reported results from a randomised trial, and random samples of 130 abstracts from cohort studies and 130 from case-control studies. P values were noted or calculated if unreported.

The first result in the abstract was statistically significant in 70% of the trials, 84% of cohort studies, and 84% of case-control studies.

Although many of these results were derived from subgroup or secondary analyses, or biased selection of results, they were presented without reservations in 98% of the trials.

Generally one cannot believe P values from abstracts

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Trastuzumab and breast cancer

The National Institute for Health and Clinical Excellence (NICE) has issued its final guidance to English and Welsh health service trusts for the use of trastuzumab (Herceptin) for the treatment of early stage breast cancer in women with HER2 positive disease and free of heart disease. It recommends that:

· Herceptin be provided at three weekly intervals for a year or until disease recurrence—whichever is sooner—after surgery, chemotherapy, and radiotherapy, if applicable

· Heart function be assessed before treatment starts and repeated quarterly in women whose left ventricular ejection fraction drops 10%

· Herceptin be avoided in women with a left ventricular ejection fraction of 55% or less, heart disease, including arrhythmias, or poorly controlled high blood pressure.

The move, which comes three months after the drug was licensed for use in Europe, follows rejection of an appeal against the institute's draft proposals, made by Newbury and Community Primary Care Trust at the end of July.

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