Most cited article - PubMed ID 11337221
Antibiotic selective pressure and development of bacterial resistance
The article describes activities of an antibiotic center at a university hospital in the Czech Republic and presents the results of antibiotic stewardship program implementation over a period of 10 years. It provides data on the development of resistance of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus to selected antibiotic agents as well as consumption data for various antibiotic classes. The genetic basis of resistance to beta-lactam antibiotics and its clonal spread were also assessed. The study showed significant correlations between aminoglycoside consumption and resistance of Escherichia coli and Klebsiella pneumoniae to gentamicin (r = 0.712, r = 0.869), fluoroquinolone consumption and resistance of Klebsiella pneumoniae to ciprofloxacin (r = 0.896), aminoglycoside consumption and resistance of Pseudomonas aeruginosa to amikacin (r = 0.716), as well as carbapenem consumption and resistance of Pseudomonas aeruginosa to meropenem (r = 0.855). Genotyping of ESBL- positive isolates of Klebsiella pneumoniae and Escherichia coli showed a predominance of CTX-M-type; in AmpC-positive strains, DHA, EBC and CIT enzymes prevailed. Of 19 meropenem-resistant strains of Klebsiella pneumoniae, two were identified as NDM-positive. Clonal spread of these strains was not detected. The results suggest that comprehensive antibiotic stewardship implementation in a healthcare facility may help to maintain the effectiveness of antibiotics against bacterial pathogens. Particularly beneficial is the work of clinical microbiologists who, among other things, approve administration of antibiotics to patients with bacterial infections and directly participate in their antibiotic therapy.
- Keywords
- antibiotic stewardship, clonal spread, consumption of antibiotics, resistance,
- Publication type
- Journal Article MeSH
BACKGROUND: Increasing bacterial resistance to antibiotics is one of the most serious problems in current medicine. An important factor contributing to the growing prevalence of multiresistant bacteria is application of antibiotics. This study aimed at analyzing the development of resistance of Enterobacteriaceae to selected beta-lactam, fluoroquinolone and aminoglycoside antibiotics in the University Hospital Olomouc and assessing the effect of selection pressure of these antibiotics. METHODS: For the period between 1 January 2000 and 31 December 2011, resistance of Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae and Proteus mirabilis to third- and fourth-generation cephalosporins, meropenem, piperacillin/tazobactam, fluoroquinolones and aminoglycosides was retrospectively studied. For the assessment of selection pressure of antibiotics, a parameter of defined daily dose in absolute annual consumption (DDDatb) based on the ATC/DDD classification and in relative annual consumption (RDDDatb) as the number of defined daily doses per 100 bed-days was used. The relationship between frequency of strains resistant to a particular antibiotic and antibiotic consumption was assessed by linear regression analysis using Spearman's correlation. The level of statistical significance was set at p < 0.05. RESULTS: A total of 113,027 isolates from the Enterobacteriaceae family were analyzed. There was a significant effect of selection pressure of the primary antibiotic in the following cases: piperacillin/tazobactam in Klebsiella pneumoniae, gentamicin in Klebsiella pneumoniae and Escherichia coli and amikacin in Escherichia coli and Enterobacter cloacae. Also, there was significant correlation between resistance to ceftazidime and consumption of piperacillin/tazobactam in Klebsiella pneumoniae and Escherichia coli. No relationship was found between consumption of third- and fourth-generation cephalosporins and resistance to ceftazidime or between fluoroquinolone consumption and resistance to ciprofloxacin. CONCLUSION: The study showed the effects of both direct and indirect selection pressure on increasing resistance to gentamicin, amikacin, piperacillin/tazobactam and ceftazidime. Given the fact that no correlation was found between resistance to fluoroquinolones and consumption of either primary or secondary antibiotics, we assume that the increasing resistance to fluoroquinolones is probably due to circulation of resistance genes in the bacterial population and that this resistance was not affected by reduced use of these antibiotics.
- MeSH
- Aminoglycosides therapeutic use MeSH
- Anti-Bacterial Agents therapeutic use MeSH
- beta-Lactams therapeutic use MeSH
- Enterobacter cloacae drug effects isolation & purification physiology MeSH
- Enterobacteriaceae Infections drug therapy microbiology MeSH
- Escherichia coli drug effects isolation & purification physiology MeSH
- Fluoroquinolones therapeutic use MeSH
- Klebsiella pneumoniae drug effects isolation & purification physiology MeSH
- Humans MeSH
- Linear Models MeSH
- Microbial Sensitivity Tests MeSH
- Drug Resistance, Multiple, Bacterial drug effects MeSH
- Proteus mirabilis drug effects isolation & purification physiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Aminoglycosides MeSH
- Anti-Bacterial Agents MeSH
- beta-Lactams MeSH
- Fluoroquinolones MeSH
OBJECTIVE: The study objective was to evaluate the impact of a restrictive antibiotic policy, efficacy of inpatient therapeutic and prophylactic antibiotic regimens and susceptibility patterns of infecting bacteria in 2000-2004. SETTING: A 500-bed general hospital in the Czech Republic. METHOD: A retrospective computerized survey of antibiotic prescribing practices over a five-year period 2000-2004, using medical records and laboratory data from the hospital information system (HIS). MAIN OUTCOME MEASURE: Consumption of antibiotics expressed in defined daily doses (DDDs) and Euros per 1,000 bed days. Resistance to antibiotics, average length of hospital stay, rate of inpatients treated with antibiotics, number of nosocomial infections per 1,000 bed days, median length of hospital stay and total mortality. RESULTS: Due to a restrictive antibiotic policy implemented in 2002, the use of several antibiotics in 2003 was significantly reduced but the consumption of several other antibiotics rose in 2003. In comparison with 2001 the cost of antibiotic agents (in Euro per 1,000 inpatient days) fell significantly by 31% in 2003 Euro 969.07 vs. Euro 671.34). The hospital saved about Euro 29,288 after the first year of implementation of the new antibiotic policy. The use of restricted antibiotics increased by 8%; however, the expenditure decreased by 26%. For non-restricted antibiotics, the use and expenditure decreased by 71% and 41%, respectively. Consequently, a net reduction of 55% Euro 804.36 vs. Euro 359.36) was achieved. CONCLUSION: The intervention was effective in reducing the use and cost of antibiotics. The HIS is a helpful tool for observing and evaluating the impacts of the measures taken and can be used for assessment of pharmacotherapy outcomes.
- MeSH
- Anti-Bacterial Agents economics therapeutic use MeSH
- Bacterial Infections drug therapy MeSH
- Drug Resistance, Bacterial * MeSH
- Length of Stay statistics & numerical data MeSH
- Cross Infection epidemiology MeSH
- Cost Control MeSH
- Humans MeSH
- Microbial Sensitivity Tests * MeSH
- Hospital Bed Capacity, 500 and over MeSH
- Hospitals, General MeSH
- Hospital Information Systems MeSH
- Retrospective Studies MeSH
- Practice Guidelines as Topic MeSH
- Drug Utilization statistics & numerical data MeSH
- Cost Savings MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Evaluation Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
- Names of Substances
- Anti-Bacterial Agents MeSH