According to a researched report in The Lancet Infectious Diseases, the addition of meropenem to colistin provides no additional therapeutic benefit to patients suffering with A. baumannii or other carbarpenem-resistant bacteria.
This question was the focus of a random trial covering three countries on an open-label, controlled basis. While studies conducted prior to the start of this one showed a boost to bactericidal activity when it came to polymyxin-carbapenem combinations, this further study contradicted those findings for those with gram-negative bacterial infections.
The study orchestrated by Mical Paul, MD, the director of infectious diseases at Rambam Health Care Campus and associate professor in Haifa, Israel, showed these results. His study included hundreds of people in hospital settings.
He and his colleagues also working on this research reported no observances that lead to stating that the combination therapy improved or changed survival rates, microbiological or clinical cure rates, or improved levels of resistance to the bacteria. Since the study primarily dealt with A. baumannii, they did note that other non-dominant bacterium such as Klebsiella pneumonia or Pseudomonas aeruginosa could have different results.
They also concluded that since carbapenem resistance increases with carbapenem use, the overall recommendation dissuades practitioners from using it to battle A baumannii and other infections known to become resistant. While other bacterial infections did not show the same levels of resistance, they stress the importance of increased randomized trials for various combination therapy regimens before they become commonly used in the industry.
Resistance rates for gram-negative bacteria strains grow all around the world. The CDC in the USA has coined the phrase "nightmare bacteria" for Enterobacteriaceae, one type that is highly resistant to carbapenem therapy. The remaining effective treatment combines colistin and polymyxin B, though there is some worry about building resistance in the face of few other treatment choices.
Paul and his colleagues echo this concern. They state that physicians in general are not confident about using polymyxin to counteract carbapenem-resistant, gram-negative bacterial infections. Mortality rates remain high, which drives more researchers to seek out the best possible antimicrobial combinations to combat these strains.
The 406 people involved in the afore-mentioned research study conducted by Mical Paul et al were from Italy, Greece, and Israel. Each had either bacteremia, urosepsis, or ventilator-associated or hospital-acquired pneumonia. Each illness had carbapenem-resistant, gram-negative bacteria at its source. In the majority of cases, that bacteria was A. baumannii.
The research gave a random selection of these patients either colistin monotherapy or colistin in conjunction with meropenem. Data was collected between October 1, 2013 and December 31, 2016. After 14 days after randomized treatment, the most common outcome was clinical failure.
This failure consisted of a 79% rate in the colistin monotherapy group and a 73% rate in the combination group. These close clinical failure rates indicate no sufficient benefit for the addition of meropenem to the therapy regimen. Combination medications did decrease how many patients experience mild renal failure but increased the chance of diarrhea as a side effect.
Similar findings were highlighted by Robert A. Bonomo, MD and Federico Perez, MD (both working at the Case VA Center for Antimicrobial Resistance and Epidemiology and Case Western Reserve University School of Medicine). They indicated two previous controlled studies of people similarly affected by carbapenem-resistant A. baumannii bacteria. Those patients received either colistin by itself or colistin with rifampicin. An additional small study was done with monotherapy or colistin combined with fosfomycin.
Although none of these randomized research trials shone a light on combination therapy that provided exceptional or considerable benefits, Bonomo and Perez feel it important to continue researching combinations. In the face of bacteria such as A. baumannii and others that are resistance to carbapenem, the medical community needs more data on how combination therapy affects different phenotypes or genotypes of bacterium.
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