Decreased duration of intravenous cephalosporins in intensive care unit patients with selective digestive decontamination: a retrospective before-and-after study

European Journal of Clinical Microbiology & Infectious Diseases https://doi.org/10.1007/s10096-020-03966-w ORIGINAL ARTICLE Decreased duration of intravenous cephalosporins in intensive care unit patients with selective digestive decontamination: a retrospective before-and-after study Calypso Mathieu 1 & Roberta Abbate 1,2 & Zoe Meresse 1 & Emmanuelle Hammad 1 & Gary Duclos 1 & François Antonini 1 & Nadim Cassir 3 & Jeroen Schouten 4 & Laurent Zieleskiewicz 1 & Marc Leone 1,3,5 Received: 11 February 2020 / Accepted: 25 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020 Abstract Selective digestive decontamination (SDD) reduces the rate of infection and improves the outcomes of patients admitted to an intensive care unit (ICU). A risk associated with its use is the development of multi-drug-resistant organisms. We hypothesized that a 1-day reduction in systemic antimicrobial exposure in the SDD regimen would not affect the outcomes of our patients. In this before-and-after study design, 199 patients and 248 patients were included in a 3-day SDD group and a 2-day SDD group, respectively. The rates of hospital-acquired pneumonia and ICU infections were similar in both groups. The rates of bloodstream infection and bacteriuria were significantly lower in the 2-day SDD group than in the 3-day SDD group. Compared with the patients in the 3-day group, the patients in the 2-day SDD group received fewer antibiotics and less exposure to mechanical ventilation, and they used fewer ICU resources. The rates of ICU mortality and 28-day mortality were similar in both groups. The incidence of multi-drug-resistant organisms was similar in both groups. Within the limitations inherent to our study design, reducing the exposure of prophylactic systemic antibiotics in the SDD setting from 3 days to 2 days was not associated with impaired outcomes. Future randomized controlled trials should be conducted to test this hypothesis and investigate the effects on the development of multi-drug resistant organisms. Keywords Infection . Selective . Decontamination . Prophylaxis . Antibiotic Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10096-020-03966-w) contains supplementary material, which is available to authorized users. * Marc Leone 1 Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Hôpital Nord, Service d’anesthésie et de réanimation, Marseille, France 2 Department of Anesthesiology, University of Naples Federico II, Naples, Italy 3 MEPHI, IHU Méditerranée Infection, Aix-Marseille Université, Marseille, France 4 Department of Intensive Care, Radboudumc, Netherlands 5 Chemin des Bourrely, Service d’anesthésie et de réanimation, 13015 Marseille, France Infection is a major cause of morbidity and mortality in intensive care units (ICU) [1]. The most common ICU-acquired infections are due to hospital-associated pneumonia (HAP), which were reported to be 15 to 18 episodes per 1000 ventilator days in Europe and 12% in French healthcare Networks [2, 3]. In selective digestive decontamination (SDD), an enteral and oropharyngeal paste containing antimicrobials is combined with short-term systemic prophylactic antibiotics. In ICU patients, SDD has been associated with reductions in hospital mortality, HAP, and the duration of mechanical ventilation [4–8]. The French guidelines for HAP suggest the routine use of SDD to prevent HAP in units with low levels of antibiotic resistance [9]. Historically, the duration of systemic prophylactic antibiotic administration has been 4 days, but this duration has ranged from 2 to 5 days in previous studies [10]. Prolonged antibiotic therapy may lead to the emergence of multi-drug-resistant (MDR) organisms [11, 12]. Because the Eur J Clin Microbiol Infect Dis major fear associated with SDD use is the development of MDR organisms, reduction in the exposure to systemic antibiotics could decrease this risk, but it could be associated with the decreased efficiency of the procedure. We hypothesized that the reduction in the duration of the systemic prophylactic antibiotic would not affect the patient outcomes. In this before-and-after study, we aimed to evaluate the effects on the occurrence of HAP of the decrease in the duration of a systemic prophylactic antibiotic in the SDD setting from 3 to 2 days. The secondary goals were to assess the rates of ICU-acquired infections, the number of antibiotic-free days, ventilator-free days, vasopressor-free days, and ICUfree days, in addition to the septic shock and ICU- and 28day mortality rates in the 2-day and 3-day study periods. Materials and methods Study design and patients From February 2014 to March 2018, we conducted a retrospective before-and-after study in the 15-bed ICU of a 625bed university hospital (Hôpital Nord, Marseille, France). All patients admitted to the ICU for trauma, coma, or cardiac arrest with a length of stay of at least 3 days and requiring tracheal intubation at admission were included. Patients admitted for infection and receiving curative antibiotics or patients with inappropriate treatment (incomplete, duration error) were not included. The SDD regimen was started on the day of tracheal intubation. The oropharyngeal paste contained polymyxin E (2%), tobramycin (2%), and amphotericin B (2%). Enteral mixture was administered through a nasogastric tube in 10 ml of a suspension containing 100-mg polymyxin E, 80-mg tobramycin, and 500-mg amphotericin B. The application was performed three times daily until tracheal extubation in all patients. The systemic prophylactic antibiotic was cefazolin, which was administered intravenously at 1 g every 8 h, except in patients reporting an allergy (no systematic antibiotic in these patients). The patients were managed according to international guidelines [9]. In our ICU, antimicrobial stewardship is based on the protocols described elsewhere [13, 14]. In February 2016, the duration of systemic prophylactic antibiotic administration was reduced from 3 to 2 days to decrease the patients’ exposure to the antibiotic. The patients admitted from February 1, 2014, to February 1, 2016, were included in the 3-day SDD group, and those admitted from March 1, 2016, to March 1, 2018, were included in the 2-day SDD group. admission were collected from our electronic database. We recorded HAP and other ICU-acquired infections, including catheter-associated urinary tract infection (CAUTI), bloodstream infection, and others (e.g., meningitis and intraabdominal infection) between the day of admission and day 28. Once a week, all diagnosis of infection are discussed and reviewed by the same group of senior intensivists and an infectious diseases physician, and decisions are based according to international definitions (Supplemental data 1). The same definition was used during the pre- and post-intervention periods. We also recorded bacterial and Candida spp. co (...truncated)