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: