Study on Antibiotic Cycling and Mixing in Intensive Care Units

Introduction to Antibiotic Resistance

A recent study assessed the effectiveness of antibiotic cycling and mixing in reducing antibiotic resistance among Gram-negative bacteria in intensive care units (ICUs) across Europe. Antibiotic resistance poses a significant challenge in healthcare, particularly in hospital environments where patients with weakened immune systems are more susceptible to resistant infections.

Limitations of Existing Preventive Measures

Previous research indicates that established preventive measures, such as enhanced hand hygiene and universal chlorhexidine bathing, effectively reduce antibiotic resistance in Gram-positive bacteria, like methicillin-resistant Staphylococcus aureus. However, these interventions do not appear to curb the emergence of antibiotic-resistant Gram-negative bacteria, such as Enterobacteriaceae.

Understanding Antibiotic Cycling and Mixing

Definitions and Strategies

Antibiotic cycling and mixing are two strategies designed to mitigate antibiotic resistance by altering selective pressure in hospital settings.

– **Antibiotic Cycling**: This approach involves administering a specific antibiotic as the first-line treatment for all patients for a predetermined period, after which a different antibiotic is utilized. This cyclical use of various antibiotics aims to reduce resistance.

– **Antibiotic Mixing**: In this method, antibiotics are alternated after each patient begins treatment, maintaining the use of antibiotics from the same class.

Research Methodology

Study Design

A recent study published in *The Lancet* compared the effectiveness of antibiotic cycling and mixing on the prevalence of antibiotic resistance in Gram-negative bacteria across ICUs in Belgium, France, Germany, Portugal, and Slovenia.

The research consisted of a four-month baseline period utilizing standard antibiotic regimens, followed by a nine-month intervention period implementing either cycling or mixing. This was succeeded by a one-month washout period and another nine-month intervention phase.

Selection of Antibiotics

During the intervention periods, the researchers focused on third-generation and fourth-generation cephalosporins (e.g., cefotaxime, ceftriaxone, ceftazidime, and cefepime), piperacillin-tazobactam, and carbapenems (e.g., imipenem and meropenem). The order of antibiotic strategies was randomly assigned to each ICU.

Data Collection

Data regarding age, sex, admission diagnosis, length of stay, and validated illness severity scores were collected from all patients admitted to the ICUs.

Findings on Antibiotic Resistance

Study Results

Among the 38 assessed ICUs, only eight met the eligibility criteria—one from Belgium, two from France, two from Germany, one from Portugal, and two from Slovenia. A total of 10,980 patients were admitted throughout the study, with 2,204 during the baseline, 4,069 during the cycling period, and 4,707 during the mixing period. The results indicated that carbapenems were the most frequently used antibiotics, followed by third-generation and fourth-generation cephalosporins, and piperacillin-tazobactam.

The prevalence of antibiotic-resistant Gram-negative bacteria was 23% during the cycling period and 22% during the mixing period, showing no significant difference between the two strategies. ICU mortality rates were 11% during baseline and cycling periods, and 12% during the mixing period, which were also statistically similar.

Conclusions and Implications

The study concluded that the nine-month periods of antibiotic cycling and mixing did not significantly alter the prevalence of antibiotic-resistant Gram-negative bacteria in ICUs. Consequently, these strategies may not be effective for reducing antibiotic resistance in hospital settings. Existing hygiene measures, while effective against Gram-positive bacteria, have not proven successful against Gram-negative pathogens.

The authors noted that the study’s limitations include the small sample size and the limited number of ICUs analyzed, which may not represent the broader European hospital landscape. However, it is suggested that reducing the overall volume of antibiotics may help manage the emergence of antibiotic-resistant Gram-negative bacteria by decreasing selective pressure.

Reference

van Duijn P J, Verbrugghe W, Jorens P G, Spöhr F, Schedler D, Deja M, Rothbart A, Annane D, Lawrence C, Van J C-N, Misset B, Jereb M, Seme K, Šifrer F, Tomiç V, Estevez F, Carneiro J, Harbarth S, Eijkemans M J C, Bonten M. The effects of antibiotic cycling and mixing on antibiotic resistance in intensive care units: a cluster-randomised crossover trial. *The Lancet*. 2018; v.18: 401 – 409.