Life threatening infections, or sepsis, are one of the most common reasons people end up in the intensive care unit or stay longer in the hospital than originally expected. To combat these infections, physicians can choose from several antibiotics, and often will use a combination of drugs until they are certain of what is causing the infection. However, as with every drug, there are risks. Antibiotics are no exception to this rule, making the choice a difficult one. On one hand, physicians need to treat the serious infection, but on the other hand, risks such as life-threatening kidney damage can occur with some of these drugs.
Recently, Mayo Clinic pharmacy resident Diana Schreier, Pharm.D., R.Ph.; led a research study to determine the safety of one particular combination of antibiotics for short-term use in the ICU. Published in Clinical Infectious Diseases, the team’s research shows that short-term use of the combination of piperacillin/tazobactam and vancomycin (PTZ/VAN) is no more toxic to the kidneys than other combinations.
This is an important finding, because prior to this research, small studies, mostly in non-ICU patients, indicated that PTZ/VAN can injure kidneys when used over a long period. Learning this, some ICU physicians stopped using this combination, and instead substituted other combinations that have their own risks, including toxicity to the brain or high potential to promote the development of resistant superbugs.
It was after noticing these shifts in practice that Dr. Schreier worried that misapplying these previous studies to broad use in the ICU could lead to loss of this important medication combination in the arsenal for clinicians.
“No one had previously looked at the kidney risk of these short-term treatments with combination PTZ/VAN in a rigorous way,” says Dr. Schreier. “We were seeing this practice shift, but without good evidence of how it applied to our sick ICU patients. We wanted to preserve these essential antibiotic combinations and give clinicians more confidence about the risks and benefits of the choices available to them.”
Over the years, because of widespread antibiotic use and even overuse, organisms have developed resistance to various antibiotics. Both the source of infection and level of resistance can vary between individuals and hospitals, so choosing the right combination of antibiotics becomes something of an art form for physicians.
Dr. Schreier and her colleagues hoped to ease concerns about the PTZ/VAN combination, allowing for continued use of this set of tools in critically ill patients.
“Usually combination therapy is started because we are unsure what organism is causing the patient’s infection,” she says. “In these cases, we are providing two or more antibiotics that cover a wide range of bugs that could be causing the infection. This allows us to treat the patient broadly while we wait for cultures to return and give us the definite cause.”
“The more tools we have in the toolbox in these situations, the better off our patients will be,” she says, “and with antibiotics, this is especially true. PTZ is very effective and covers many types of infections. Loss of it as a treatment would leave a huge hole that new drugs have yet to fill.”
During their research, the team looked at medical records for 3,299 ICU patients who received 24- to 72-hours of different commonly-used antibiotic combinations including vancomycin (VAN treats resistant staph infections) with piperacillin/tazobactam (PTZ/VAN), cefepime (CEF/VAN), or meropenem (MER/VAN). Overall, about 9 percent of the patients suffered moderate to severe kidney damage which did not differ between the antibiotics selected even after accounting for the many contributors to kidney damage in sick ICU patients. Further, the antibiotic combination chosen did not affect long-term kidney damage.
Because of this research, doctors can continue to rely on this long-used tool as one of the antibiotic options for patients, says Dr. Schreier.
“We are pleased to have been able to show that PTZ/VAN can remain viable for ICU care,” she says. “These new data are reassuring and highlight how important it is to perform large studies in specific high-risk groups before broadly applying information to everyone.”
She and her colleagues plan to continue to look for ways to expand understanding of which drugs work for what conditions, how they work, and ways to make them work better.
Editor’s note: Dr. Schreier is a second-year pharmacy resident in the Mayo Clinic School of Health Sciences. This research is part of the mentored training and development program within the residency program. It also is an example of the team science and collaborative spirit that abounds at Mayo Clinic. The Anesthesia Clinical Research Unit assisted with data extraction. Funding was provided by Mayo’s Midwest Pharmacy Research Committee and Mayo Clinic Center for Clinical and Translational Science (NIH grant UL1TR002377). In addition, Dr. Schreier’s mentor and the study senior author was Erin Barreto, Pharm.D., R.Ph.; director of the second-year Critical Care Pharmacy residency program, and a concurrent scholar in the Kern Health Care Delivery Scholars Program.