The incidence of infections caused by multi-drug resistant gram-negative bacteria is increasing worldwide. However, the currently available antibiotic options have been less effective in treating these infections.
As a result, physicians have resorted to using older generation antibiotics, such as colistin, which belongs to the polymyxin group of antibiotics and is effective against gram-negative bacteria. Although colistin had previously been the last resort antibiotic, it is being increasingly prescribed to deal with multi-drug resistant gram-negative bacteria. Although colistin dosing recommendations have been updated by the US Food and Drug Administration (FDA) as well as the European Union, there are serious concerns regarding the incidence of acute renal failure with colistin usage. A potential way to circumvent this issue of nephrotoxicity is to administer colistin in combination with a nephron-protective agent.
A new study
published in Antimicrobial Agents and Chemotherapy
, authored by lead investigator Thomas P. Lodise, PhD, PharmD, sought to determine if the combination of minocycline with colistin could decrease the incidence of acute renal failure in those treated. Minocycline belongs to the tetracycline class of antibiotics and has been shown to inhibit the synthesis of activators of the apoptotic pathway as well as activators of inflammation, which have been linked to causing nephrotoxicity in the polymyxin family. As a result, the authors hypothesized that combining minocycline with colistin may have a nephro-protective effect. To test this hypothesis, the authors utilized a large database to determine whether patients in the intensive care unit (ICU) who received a combination of colistin and minocycline were less likely to have acute renal failure compared with those receiving colistin alone.
The retrospective study consisted of 4,910 patients, 4817 of which belonged to the colistin-only group, while the remaining 93 patients received the combination therapy. The patients were part of the premier research database which contains data from over 600 hospitals in the United States, making up around 20% of the hospitalizations in the nation.
The authors found that in patients who received colistin alone, the occurrence of acute renal failure was 23.7% with rates increasing with prolonged colistin use. On the other hand, the overall occurrence of acute renal failure for those taking colistin and minocycline was 11.8%, with rates moderately increasing with prolonged usage. This demonstrates that the combination therapy results in a 50% reduction in rates of acute renal failure, supporting the authors’ hypothesis.
Although this study supports the idea that administering colistin with minocycline reduces colistin-induced acute renal failure, more work needs to be done to validate these results. Future prospective studies should incorporate laboratory, including creatinine levels, microbiologic, treatment, and outcomes data.
Moreover, the authors note that the patients who experienced acute renal failure were admitted to the hospital for three additional days, resulting in more than $10,000 in hospital costs. As a result, if the outcomes of this study are validated, there could be significant clinical implications that would improve the treatment of bacterial infections caused by multi-drug resistant gram-negative bacteria, particularly in critically ill patients.
Samar Mahmoud graduated from Drew University in 2011 with a BA in Biochemistry and Molecular Biology. After two years of working in the industry as a Quality Control Technician for a blood bank, she went back to school and graduated from Montclair State University in 2016 with an MS in Pharmaceutical Biochemistry. She is currently pursuing a PhD in Molecular and Cellular Biology at the University of Massachusetts at Amherst.
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