Hacettepe Üniversitesi Erişkin ve Onkoloji Hastanelerinde Yatan Hastalarda Saptanan Metisiline Dirençli Staphylococcus Aureus (MRSA) Bakteremisi Risk Faktörleri (2004-2011): Yuvalandırılmış Vaka Kontrol Araştırması

Abstract

The aim of this study was to determine the risk factors, antibiotic use and antibotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia isolates from hospitalized patients who are followed by Internal Medicine and Infectious Diseases Departments at Hacettepe University Adult and Oncology Hospitals between January 2004-December 2011. Control group patients have been selected randomly. They didn?t have MRSA bacteremia and they were in the same wards at the same months with case group patients. Patient data including risk factors, demographic features, antibiotic usage and antibiotic susceptibility have been recorded from the patient files and online hospital data system (Neksus). The demographic features, underlying chronic diseases, possible risk factors for MRSA bacteraemia, antibiotic usage and antibotic using times were compared for 198 patients. Ninety nine case group MRSA isolates have been isolated from blood culture. The identification of the isolates was made by Phoenix automated system (Becton Dickinson, USA). The isolates were retested for methicillin resistance by oxacillin (1µg, Oxoid, UK) disc diffusion test according to Clicical Laboratory Standards Institude (CSLI) and for the presence of mec-A gene by polymerase chain reaction (PCR). The susceptibility testing was performed by Etest (AB Biodisk, Sweden) and to some other antibiotics by disk diffusion methods according to the CLSI reccomendations. Isolates were stored at -800C until studied. S. aureus ATCC29213, S. aureus ATCC25923, S. aureus 27R ve S. aureus 8328 were included as control strains. There was no significantly difference between case and control patients in age, gender, presence of diabetes, chronic diseases, hemodialysis, malignancy, immunosuppression, and burn. The parameters those are thought as other risk factors: presence of obesity, cerebrovascular diseases, hospitalization in hospital and intensive care unit (ICU) history, central venous and arterial catheterization, invasive or non-invasive mechanical ventilation appliance, tracheostomi, nasogastric tube, urinary catheterization, gastrostomy, acute organ failure, surgical operation, usage of proton pump inhibitors (ppi), hydrogen (H2) reseptor blockers, parenteral nutrition have been found statistically significant in univariate regression analysis. In multivariete regression analysis four risk factors have been found as independent risk factors: Presence of obesity (OR:7,98; %95 GA:1,54-41,47; p=0,013), central venous catheterization (OR:6,65; %95 GA:1,77?25,00; p=0,005), nasogastric tube (OR:16,58; %95 GA:4,33?63,42; p<0,001) hydrogen (H2) reseptor blockers (OR:4,41; %95 GA:1,42?13,75; p=0,010). Usage of at least one antibiotic was statsitically higher than control group patients (OR:14,86; %95 GA:5,39-40,99; p<0,001). There were no statistically significance between case and control group in usage of ampicillin-sulbactam (SAM), amoxicillin-clavulanate (CAM), ciprofloxacin, levofloxacin, moxifloxacine, rifampin, gentamicin, ampicillin, trimethoprim-sulfamethoxazole, ertapenem, linezolid, 1st generation cephalosporin, cefuroxim, 3rd generation cephalosporin, and colistin. After grouping the antibiotics we repeated the analysis. In univariete analysis usage of SAM + CAM, flouroquinolons, aminoglycoside, piperacillin-tazobactam, meropenem, imipenem, vancomycin, teicoplanin and cephalosporins have been found statistically significantly higher in case group. After performing multivariate logistic regression analysis piperacillin-tazobactam (OR:6,82; %95 GA:2,53?18,38; p<0,001), imipenem (OR:3,97; %95 GA:1,20?13,08; p=0,023), vancomycin (OR:8,46; %95 GA:2,53?28,27; p=0,001) have been found independent risk faktors. Despite this significance in antibiotic usage long term antibiotic usage didn?t have any statistically significance. After performing Mann Withney-U test only long term meropenem (p=0.037) and cephalosporin (p<0.001) usage were increasing risk of MRSA bacteraemia. All 99 MRSA isolates were positive for mec-A gene. The isolates were highly resistance to (>90%) ciprofloxacin, rifampin, gentamicin, , cefoxitin, tetracyclin, and resistance to erythromycin was 70.7%, clindamycin 36.4%. The susceptability to trimethoprim-sulfamethoxazole was 100%, clindamycin 26.3%, and erythromycin 26.3%,. All of the 99 isolates were susceptible (100%) to vancomycin, tigecycline, linezolid, damptomycin, and teicoplanin. All HA-MRSA bacteraemia isolates were multi-resistant in our hospital. Vancomycin MIC values of all isolates were lower than 4 µg/ml. Mortality ratio was 34.6% in MIC ?1.0 µg/ml patients (17 of 49) whereas 60% in MIC > 1.0 µg/ml patients (30 of 50). Mortality rate was higher in higher (MIC>1.0 µg/ml) MIC values (p=0,012). One can say that increasing in vancomycine MIC value elevates the risk of mortality in MRSA bacteraemia. As a result obesity, usage of central venous catheter, H2 reseptor blockers, nagastric tube have been found as independent risk factor in MRSA bacteraemia. Usage of piperacillin-tazobactam, imipenem, vancomycin are the other independent risk factor in MRSA bacteraemia. Increasing vancomycin MIC value is a risk on MRSA bacteraemia mortality.