UK groups unveil in-depth guidance for MDR gram-negative infections

With multidrug resistant (MDR) gram-negative bacterial (GNB) infections becoming an increasing serious health threat and few new drugs coming down the pipeline to treat them, doctors are faced with frequent complex decisions on how to best use current treatments, and yesterday a British working group published a detailed guide to help streamline the process.

The working group included members of three organizations: the British Society for Antimicrobial Chemotherapy (BSAC), the Healthcare Infection Society, and the British Infection Society. The expert panel also included three patients who had been treated for healthcare-associated infections. The team published its report yesterday in a supplement to the Journal of Antimicrobial Chemotherapy.

In a foreword to the report, Dilip Nathwani, OBE, honorary professor of infection at the University of Dundee and president of the BSAC, said synthesizing the information for the new guidance was complex and challenging. "The guidelines are comprehensive and the variable nature of the strength of recommendations reflects the current and evolving evidence base," he said, adding that the groups hope the document will help support the development and implementation of local guidance.

He said the working group acknowledges that the recommendations in the report mainly support UK practice, "but we believe they will prove valuable elsewhere too."

More than 100 treatment recommendations

The main part guidance focuses on more than 100 recommendations on appropriate treatment for MDR BNBs, all backed by an extensive literature review. One of the challenges the experts found was few good comparative randomized clinical trials that support licensed older drugs. The group graded each recommendation based on the strength of the scientific evidence.

Recommendations regarding treatment fall into four main areas:

  • Intravenous treatment options, weighing the clinical efficacy of certain drugs against specific types of MDR GNB infections and recommended antibiotics for secondary or tertiary care (treatment suggestions are summarized in an algorithm)
  • Oral agents for secondary or tertiary care treatment
  • Oral antibiotics preferred for treating uncomplicated urinary tract infections due to MDR GNB in the community, including diagnosis and treatment algorithms
  • Managing urinary tract infections in general

MDR definition, stewardship considerations

The working group also tackled other overarching topics related to the treatment of MDR GNB infections, including a new definition of MDR. They noted that the current international definition is complex and unsatisfactory and hampers establishing and monitoring improvement programs. They wrote that a more practical approach might be to consider oral and parenteral drugs separately when defining MDR.

"Furthermore, one should base definitions on susceptibility rather than resistance, as the former is more likely to be sought clinically by further testing with MDR strains," they wrote.

For oral drugs multiresistance can be defined as a bacterium susceptible to only one or no readily available oral agent active against systemic or upper urinary tract infections. For parenteral antibiotics, it may be practical to consider isolates multiresistant if only two or fewer unrelated antibiotics are active against the bacterium.

Another major topic the group explored was the impact of good antibiotic stewardship in secondary or tertiary care settings. In a nutshell, they found that decreased prescribing of specific antibiotics was associated with reductions in colonization and infections from carbapenem-, aminoglycoside-, or cephalosporin-resistant bacteria, but results weren't consistent across all initiatives.

Restrictive rather than persuasive prescribing can lead to significant short-term changes over a 1- to 2-year period and should be used, but there is less evidence that they contributed to reduced prevalence of resistant GNB, the experts note. More data on clinical outcome, prescribing, and resistance are needed to monitor outcomes and offer consistent standards between hospitals, they add, and audit and feedback should be used to reduce antimicrobial use in hospitals, based on local and national advice.

The team also spelled out key research priorities over the next 5 years, aside from the need for new antibiotic compounds and formulations. Examples include diagnostic tests and serum markers to help clinicians decide when to start and stop treatment, rapid tests for multiple resistant organisms in urine and blood, and randomized controlled trials of new and old agents for treating gram-negative infections in areas where multiresistance is likely, such as hospital admission areas, critical care units, and urology wards.

See also:

Mar 5 J Antimicrob Chemother report

Mar 5 J Antimicrob Chemother report foreword

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