NEW YORK (Reuters Health) – Cycling and mixing, two strategies for rotating antibiotics, do not differ significantly in their impact on the prevalence of antibiotic-resistant gram-negative bacteria in the ICU, new research from Europe shows.
In a multinational, cluster-randomized crossover study, Dr. Pleun Joppe van Duijn of the Julius Center for Health Sciences and Primary Care in Utrecht, the Netherlands, and colleagues randomly assigned ICUs to use one of three antibiotic groups (third- or fourth-generation cephalosporins, piperacillin-tazobactam, or carbapenems) for six-week periods (cycling) or to use an alternative antibiotic class for each consecutive patient they treated (mixing).
They monitored antibiotic-resistant, Gram-negative Enterobacteriaceae with extended-spectrum beta-lactamase production or piperacillin-tazobactam resistance; Pseudomonas aeruginosa with piperacillin-tazobactam or carbapenem resistance; and Acinetobacter species.
As reported in The Lancet Infectious Diseases, online January 24, the researchers randomly assigned eight ICUs in five European countries to use either cycling or mixing, and enrolled patients from 2011 to 2014. During the cycling periods, 4,069 patients were admitted, compared to 4,707 during the mixing periods.
Of these, 745 patients during cycling and 853 patients during mixing took part in monthly point-prevalence surveys and were included in the main analysis.
The authors conducted the cycling or mixing for nine months, completed a one-month washout period, and then switched strategies for the next nine months.
They collected data from all admissions during the study and used as a primary endpoint the average unit-wide monthly point prevalence of antibiotic-resistant Gram-negative bacteria in respiratory and perineal swabs, adjusted for potential confounders.
They found no difference in all-cause in-ICU mortality between the intervention periods. The mean prevalence of the primary endpoint was 23% during cycling and 22% during mixing (P=0.64).
“There also was not a significant reduction within these interventions over time,” Dr. van Duijn told Reuters Health by email. “Large changes in antibiotic prescription patterns proved to be possible, during the interventions, and no outbreaks with multidrug-resistant bacteria occurred during these interventions.”
Three experts not involved in the study commended the work.
Dr. Jakob I. McSparron, assistant professor of medicine in the Division of Pulmonary and Critical Care Medicine at the University of Michigan in Ann Arbor, told Reuters Health by email, “This is a very robust, prospective, multicenter trial. This is the largest prospective trial investigating these antibiotic-rotation strategies. The study controlled for key potential confounders, and protocol adherence was high.”
“Given the negative results,” Dr. McSparron added, “more research needs to focus on other unit-based strategies. Clinicians need to remain vigilant about appropriate antibiotic use and discontinuation of antibiotics when they are not indicated.”
Dr. Abhijit Duggal, a critical care physician in the Medical ICU at Cleveland Clinic in Ohio, said, “The authors were exhaustive in their methodology. Most previous studies were not very strong.”
“Basic patient-specific aspects that have been proven, such as de-escalation of antibiotics, making sure hand hygiene practices are followed, remain the most important things we can do to care for these patients,” he told Reuters Health by phone.
Dr. Dawn Nolt, associate professor of pediatrics in the Division of Infectious Diseases at the School of Medicine at Oregon Health & Science University in Portland, told Reuters Health by email, “Although the percentages of patient deaths did not change during the different time periods (baseline, cycling, mixing), these are ‘all-cause’ deaths.”
“It would have been quite helpful to know whether the number of infection-related deaths varied. In addition, advances in intensive care have reduced patient deaths from infections but not necessarily overall actual infections (in which patients survived). It would have been helpful for the authors to comment on whether the number of infections changed during the interventions,” she added.
SOURCE: http://bit.ly/2nOIp0R
Lancet Infect Dis 2018.
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