September 26, 2014

expert reaction to study on antibiotic treatment failure

Researchers publishing in The BMJ have reported an increase in failure rate of antibiotics in four common infections within the UK from 1991 to 2012. There is growing concern around antimicrobial resistance, and the chief medical officer and others have expressed worry in the scale of the issue.

Prof Christine Dodd, President of the Society for Applied Microbiology, said:

“We welcome this paper and the data clearly reinforces the need for better diagnostics and responsible use of antibiotics.

“Actually, the situation with respect to treatment failure may not be as bad as we thought. Although there has been an increase in failure rate over the period of study, the overall picture is better than the evidence from hospital settings – where infections are often more severe – might have suggested.

“The authors also make the point that antibiotics can fail the first time, not because of resistance, but for a complex set of reasons such as because the antibiotic prescribed is not the right one; without rapid diagnostics, doctors must decide on which antibiotic to use, based on symptoms alone. There does appear to have been a change in prescribing practices over the time period.

“Patients and doctors therefore have to work together to contain the rise in antibiotic treatment failure by using antibiotics appropriately and following treatment regimens rigorously. Doctors must stay up-to-date with prescribing guidelines – failure rates were high when antibiotic prescribing was not in accordance with recommendations for first-line treatment. And guidelines must be under constant review to ensure they remain appropriate under changing circumstances.

“Although there was an increased failure rate with certain antibiotics used, it is reassuring to see that a number of the important broad spectrum drugs tested have maintained efficacy during the period studied, with treatment failure rates either maintained or falling slightly.

“Any actions following the conclusions of the paper are largely consistent with recent reports from the UK Chief Medical Officer and others. The paper also calls for monitoring of the rates of antimicrobial resistance and treatment failure and further study into the relationship between the two – this would be a very useful exercise.”

Dr Simon Clarke, Associate Professor in Cellular Microbiology, University of Reading, said:

“Antibiotic resistance is one of the major global health concerns we face, now and in the future. While it is not surprising that the amount of resistant infections has increased – we already know that it is a persistent problem that is only getting worse – the sheer numbers are of great concern.”

“Inappropriate prescription of antibiotics is believed to drive the occurrence of resistance. The authors suggest that GPs could play a central role in managing patient demand for antibiotics.”

“Studies carefully monitoring antibiotic prescription and levels of resistance to these important drugs are crucial. Earlier this year the Prime Minister said antibiotic resistance threatened taking the world back into the ‘dark ages of medicine’. We need to take action now if we are to see a light at the end of this long and problematic tunnel.”

Prof Chris Thomas, Professor of Molecular Genetics, University of Birmingham, said:

“This paper and its conclusions highlight an important source of information that can inform us about the effective use of antibiotics.  The authors are clear about the limitations on how we can interpret the data: they identify cases of failure as incidents where prescription of an antibiotic was followed within 30 days with a second prescription but for a different antibiotic implying that the first antibiotic failed.”

“However they do not know whether this conclusion is correct since there could be a number of reasons for a second prescription, the most trivial being that the patient had failed to take the antibiotic or had not followed the guidance correctly.  Thus this is not a criticism of the study but of the information available and illustrates ways in which we can either gather more information to increase the value of currently available data or link such information with additional existing data.”

“In particular it would be really useful to be able to associate the information on failure with outcome of microbiological and resistance phenotype testing for bacteria from the patients involved.  Since cases of treatment failure are still only a minority of prescription events but represent the potentially more serious cases, practical actions following this study should be feasible.”

Dr Richard Stabler, Senior Lecturer in Molecular Bacteriology at the London School of Hygiene & Tropical Medicine, said:

“This study is important because it focusses the research on what infections are circulating within the general community, beyond the usual monitoring by hospital infection control teams.”

“Using patient prescription records seems to be a good indicator of antimicrobial resistance. However, the authors acknowledge that there are some limitations, including the necessary exclusion of temporary GP registrations. This may have excluded certain disadvantaged groups, for example homeless people who tend to have higher levels of antimicrobial tuberculosis.”

“An important point was that use of non-recommended first line treatments had a notable increase in failure, which underlines that misuse of antibiotics can be a factor in generating resistant organisms. But interestingly some of the most frequently prescribed first line antibiotics showed the smallest rise in failure rates, for example amoxicillin and clarithromycin.”

“The overall picture presented is bleak but not unexpected, with rises in drug resistance rising in most categories. The increase in resistance is possibly lower than expected, certainly in comparison to hospital based studies, but without action and a continual increase in resistance, antimicrobial resistance is still a real threat.”

“Treatable infections becoming untreatable is a real possibility with several important infections, for example Tuberculosis and gonorrhoea, having already been documented to be almost totally resistant to all known classes of antimicrobials in some cases.”

Prof Mark Woolhouse, Professor of Infectious Disease Epidemiology, University of Edinburgh, said:

“First and foremost, this is a very welcome attempt to inject some epidemiological rigour into ongoing discussions about the importance of antimicrobial resistance to public health. Though antimicrobial resistance is a huge concern both nationally and internationally there is a worrying paucity of hard data that could inform health policy.”

“The authors have access to a massive data set: over 10 million prescriptions. They are only able to make indirect estimates of treatment “failure” and the records are often imprecise with regard to the clinical diagnosis. Nonetheless, the study does suggest that large numbers of patients (roughly 10% falling within the study’s clinical definitions) require further medical attention within 30 days of being prescribed an antibiotic. That’s obviously a worry. Moreover, the study shows that this fraction is rising, albeit slowly, over the past 20 years. I note that prescribing patterns have also changed over that period and it is possible that some of these changes reflect experience of treatment failures.”

“This study confirms that that GPs are prescribing antibiotics as frequently if not more frequently than ever and that the problem of antimicrobial resistance continues to grow. The upshot is that we are increasingly reliant on a dwindling arsenal of drugs. That supports calls to develop new drugs but also, and probably even more importantly in the long term, to reduce usage and develop alternative therapies.”

Prof Mark Fielder, Professor in Medical Microbiology, Kingston University, said:

“This paper examines antibiotic treatment failure in four infections types in the UK between 1991-2012 and raises some interesting points. For instance it notes that both treatment failure (and the reasons) and antibiotic resistance should continue to be monitored going forward, to establish their association going forward. The authors also make the important point that this sort of study could be broadened internationally to give a global overview. The paper contains data that largely supports the reports from the UK CGMO and others stating that the use of antibiotics should be judicious and warranted – care must be taken in prescribing.”

“There is a continued need for education across the spectrum with both patients and medical professionals being aware of the importance of this issue. This is due to the fact that with good guidelines for treatment and rigorous adherence we can help maintain effective antimicrobial therapies for longer. So ensuring that an antimicrobial is required, clearly relaying that information to patients and then making sure the prescribing guidelines are followed, do this and it can help preserve drug efficacy for longer. The authors make the point that primary care physicians can play an important role in containing antibiotic treatment failures by careful management of patient expectation whilst also adhering to approved treatment guidelines.”

‘Antibiotic treatment failure in four common infections in UK primary care 1991-2012: longitudinal analysis’ by Currie et al. published in The BMJ on Friday 26^th September. 

All our previous output on this subject can be seen at this weblink: http://www.sciencemediacentre.org/?s=antibiotics&cat

Declared interests

Prof Chris Thomas: Is Treasurer of the Society for General Microbiology and is funded by BBSRC to study antibiotic biosynthesis and has an active collaboration with GSK

No other declared interests.