Effect of Antimicrobial Stewardship Program on Carbapenems Consumption and Klebsiella Resistance in the Intensive Care Units
Abstract:
Introduction: The prevalence of carbapenem-resistant Klebsiella strains and their related mortality are increasing worldwide. These pandemics impose optimizing antibiotic consumption through the application of the antibiotic stewardship programs. We aimed to evaluate the impact of applying antibiotic stewardship programs on carbapenem consumption and the klebsiella resistance pattern in critically ill patients of a large Egyptian hospital.
Method: We retrospectively evaluated critically ill patients with isolated Klebsiella species from the ICU of Elaraby hospital, Egypt during the period from April 2017 to January 2019. We collected data related to carbapenem consumption (expressed as defined daily dose /1000 patient-days) and Klebsiella clinical isolates and their antimicrobial susceptibility pattern. Based on Klebsiella sensitivity, as sensitive to ceftriaxone and cefotaxime, resistant to ceftriaxone/cefotaxime, or resistance to meropenem/imipenem, Klebsiella isolates were classified as grades 1, 2, or 3, respectively. Our primary outcome was the change in carbapenem consumption after implementing the program, while the secondary outcomes were the change in the incidence of carbapenem-resistant Klebsiella.
Results: The study included 205 patients with isolated Klebsiella species during the study period. The antibiotic stewardship program started in March 2018. Out of the 205 patients, 61 patients (29.8%) represented the pre-intervention sample, and 144 patients (70.2%) represented the post-intervention sample. Applying the antibiotic stewardship program was associated with a significant decrease in the carbapenem consumption from 38.9 to 26.6 defined daily dose /1000 patient-days (P=0.02). The incidence of carbapenem-resistant Klebsiella was decreased from 85.25% of total Klebsiella isolates to 48.6% (P<0.001). Klebsiella species were more likely to be in a lower category of resistance after applying the program with an odds ratio (OR) = 6.3 (2.88-13.73) using ordinal logistic regression.
Conclusion: Applying the antibiotic stewardship program could reduce the unnecessary carbapenems use in the ICU with a subsequent decrease in the emergence of the Klebsiella resistant strains.
Keywords: carbapenems, Klebsiella, intensive care unit, resistance, defined daily dose.
INTRODUCTION
Emerging multidrug-resistant (MDR) and extensively-drug-resistant (XDR) gram-negative bacteria have become one of the major threats to human health worldwide (Sherry & Howden, 2018). A striking increase in the occurrence of antibiotic-resistant gram-negative organisms, including carbapenem-resistant Enterobacteriaceae (CRE) was reported during the last decades (S. L. Solomon & Oliver, 2014). Considering that only a few novel antibiotics are in the pipeline, antibiotic resistance should be considered as a global health problem(America, 2011; Bassetti, Merelli, Temperoni, & Astilean, 2013). Gram-negative bacteria were seen to be associated with higher rates of septic shock and mortality compared to other bacteria (Abe et al., 2010). Gram-negative MDR bacteria were found in 93.6% of 126 nonduplicate gram-negative isolates from hospitalized patients in Egypt (Khalifa et al., 2019).
The increased antibiotic consumption and inappropriate antibiotic use were reported by many authors to be associated with more antibiotic resistance (Bell, Schellevis, Stobberingh, Goossens, & Pringle, 2014; Costelloe, Metcalfe, Lovering, Mant, & Hay, 2010; McNulty, 2012; Van De Sande-Bruinsma et al., 2008). The inappropriate use of antibiotics was also found to be a significant mortality predictor (Maeda et al., 2016).
It was estimated in one study that about 70 % of intensive care units (ICU) patients had antibiotics prescribed to them during their hospitalization (Vincent et al., 2009). In addition to this high prevalence of antibiotic use, the poor outcomes of ICU patients from resistant gram-negative infections (Hidron et al., 2008; Shorr, Zilberberg, Micek, & Kollef, 2014) render them an important population target for rationalized antibiotic use.
A Chinese study reported a 20.8% incidence of carbapenem-resistant Klebsiella (CRK) in ICU patients (Shu et al., 2019). Similarly, a high incidence of extended-spectrum beta-lactamase (ESBL) andKlebsiella pneumoniae carbapenemase (KPC) producing Klebsiella was reported in middle east countries including Egypt (Abdallah et al., 2015; Al-Agamy, Shibl, & Tawfik, 2009; Amer, Khalil, & Abd EL Wahab, 2016; Metwally, Gomaa, Attallah, & Kamel, 2013). However, the interventional programs reduced the prescribed antibiotics to hospitalized patients, decreased cost and bacterial resistance, and improved clinical outcomes (Davey et al., 2013; Yong, Buising, Cheng, & Thursky, 2010).
A guideline released by the Infectious Diseases Society of America (IDSA) and supported by the American Academy of Pediatrics, American Society of Health-System Pharmacists, and other Societies recommended the establishment of a multidisciplinary antimicrobial stewardship team including a physician, clinical pharmacist, and other members. The core task of the team is a prospective audit with intervention, feedback, formulary restriction, and preauthorization (Dellit et al., 2007). The implementation of the antimicrobial stewardship program (ASP) decreased rates of Clostridium difficile , methicillin-resistantStaphylococcus aureus , and vancomycin-resistant enterococci nosocomial infection and reduced the antimicrobial expenditure (Nowak, Nelson, Breidenbach, Thompson, & Carson, 2012).
The resistance pattern of gram-negative bacteria Klebsiellaspecies in Egypt was not adequately studied especially in rural areas. This study was intended to evaluate the impact of an antibiotic stewardship program on the carbapenem consumption and Klebsiellaresistance pattern in critical care areas of an Egyptian rural hospital. Also, to study the relationship between carbapenems use and the development of Klebsiella resistance.
2. MATERIALS AND METHOD: