EXPERT ANALYSIS FROM ICAAC 2015

SAN DIEGO (FRONTLINE MEDICAL NEWS) This has been a banner year for various expert panels to weigh in on the treatment of diabetic foot infections, with three major organizations each releasing systematic reviews. And all three in-depth reports reached the same conclusion regarding the antimicrobials of choice: it really doesn’t matter.

“In general, there are no significant differences in outcomes in studies comparing different groups of antibiotics,” Dr. Edgar J.G. Peters declared at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

“You all want to know what is the magic bullet – what should we give our patients? Unfortunately, I can’t tell you. It depends on your local situation. But that doesn’t mean we should be fatalistic about diabetic foot infections. We now have a lot of data to support that we can use a lot of different antibiotics successfully. And in our review, we noticed that the quality level of the more recent studies, especially those in the last 5 years, has improved a lot,” said Dr. Peters of VU University Medical Center, Amsterdam, who was lead author of the systematic review by the International Working Group on the Diabetic Foot (Diabetes Metab Res Rev. 2015 Sep 7. doi: 10.1002/dmrr.2706. [Epub ahead of print].

That review noted one potential exception to the all-antibiotics-are-similarly-effective principle: a randomized phase-III study that found tigecycline to be inferior to ertapenem with or without vancoymycin ( Diagn Microbiol Infect Dis. 2014 Apr;78(4):469-80 ). This study was also cited in the 2015 systematic reviews by the Cochrane Collaboration and the UK National Institute for Health and Care Excellence . The finding was particularly noteworthy because the maker of tigecycline sponsored the study.

The systematic reviews followed somewhat different methodologies in reaching the same conclusion: The relative efficacy of different antibiotics used in the treatment of diabetic foot infections is unclear, largely due to low-quality evidence, flawed study designs, and bias. However, the Cochrane group found the literature does permit some reliable conclusions to be drawn as to the relative safety of the various antimicrobials. The evidence indicates that carbapenems have fewer adverse effects than anti-pseudomonal penicillins, daptomycin causes fewer complications than do semisynthetic penicillins, broad spectrum penicillins have fewer side effects than does linezolid, and ertapenem with or without vancomycin has fewer adverse events than does tigecycline.

Most side effects involved relatively mild nausea and diarrhea. The exception was linezolid, which was associated with an increased risk of anemia.

The International Working Group led by Dr. Peters looked beyond antimicrobials at evidence for other types of therapy for diabetic foot infections. The reviewers concluded that hyperbaric oxygen therapy has no effect on infection as an outcome, and that granulocyte-colony stimulating factor therapy showed mixed and inconclusive results based upon five studies. Two cohort studies suggest that early surgical debridement leads to a reduction in major amputations. And in patients with diabetic skin and soft tissue infection plus osteomyelitis, outcomes are improved if a bone biopsy is performed and antibiotics are targeted to the findings.

Dr. Peters pointed out that the studies of antimicrobial therapy for combined diabetic skin and soft tissue infection and osteomyelitis featured 6-28 days of treatment. That’s a surprisingly short course.

“I think 28 days is a pretty odd number,” he commented. “I don’t know about you, but we usually give antibiotics to those patients for a lot longer than 28 days.”

The internist shared several personal opinions derived from his in-depth review of the field of diabetic foot infection treatment.

“If antimicrobial therapies are equally effective, why not choose a cheap and narrow-spectrum one?” he suggested.

He recommended two high-quality sources useful in choosing a specific regimen: the International Working Group’s supplementary guidance document ( Diabetes Metab Res Rev. 2015 Sep 19. doi: 10.1002/dmrr.2699 . [Epub ahead of print] that accompanies the systematic review, and the Infectious Diseases Society of America 2012 guidelines, which Dr. Peters coauthored.

“Are IV antibiotics always necessary? I would say, probably not. Consider oral small-spectrum antibiotics for milder infections. It’s probably best to go broader-spectrum if you have a more severe infection because the stakes are higher in that case,” Dr. Peters said.

His in-depth examination of the evidence has taught him several other things. For one, 20-year-old studies are probably not terribly relevant to contemporary management of diabetic foot infections, given the considerable changes that have occurred in antimicrobial susceptibility and the organization of health care systems. And pathogen eradication is probably not a valid study endpoint.

Moreover, the available evidence does not support the popular notion that empiric coverage for Pseudomonas improves outcomes, he added.

Dr. Peters reported having no financial conflicts regarding his presentation.

bjancin@frontlinemedcom.com

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