KLİNİK STENOTROPHOMONAS MALTOPHILIA İZOLATLARINDA KOLİSTİN HETERODİRENCİNİN ARAŞTIRILMASI
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Liste U., Investigation of colistin heteroresistance in clinical Stenotrophomonas maltophilia isolates ,Hacettepe University Faculty of Medicine, Thesis In Medical Microbiology, Ankara, 2019. Stenotrophomonas maltophilia is a multidrug-resistant gram-negative bacillus that is an opportunistic pathogen, particularly among hospitalized patients. It is also an important nosocomial pathogen associated with substantial morbidity and mortality, particularly in debilitated or immunocompromised patients and patients requiring ventilatory support in intensive care units. The incidence of human infection appears to have increased in recent years. S. maltophilia is a infectious agent associated with health services that. were reported to be in the third place after Acinetobacter spp. and Enterobacter spp. between 2010-2016. A variety of clinical syndromes caused by S. maltophilia have been described, including bacteremia, pneumonia, urinary tract infection, ocular infection, endocarditis, meningitis, soft tissue and wound infection, mastoiditis, epididymitis, cholangitis, osteochondritis, bursitis, and peritonitis. Therefore, new studies are needed on the epidemiology, risk factors and treatment of this microorganism, whose incidence is increasing all over the world S. maltophilia is intrinsically resistant to most antibiotics used in the empirical treatment of other gram-negative bacteria. TMP-SMX is the first agent for the treatment of S. maltophilia. Although some other agents, such as minocycline, ticarcillin-clavulonate, colistin, and aztreonam may show in vitro activity, the potential efficacy of these agents is questionable as there is insufficient clinical experience with these agents and S. maltophilia can rapidly develop resistance. However, when TMP / SMX resistance is seen, combination therapies are essential, especially in invasive infections. High intrinsic and acquired resistance in S. maltophilia necessitates this condition. The proposed combinations include trimethoprim-sulfamethoxazole and any second group of agents, including ceftazidime, ticarcillylin-clavulanate, aztreonam, colistin or a fluoroquinolone, provided both agents are effective in in vitro tests. Colistin is one of the few antimicrobials that retains activity against multi drug resistant Gram-negative bacteria . The success of using colistin in combination therapies in multi-drug resistant gram negative non-fermenter bacteria has been shown to prevent both toxicity and increase the efficacy of treatment. Overall, various studies show that recommended susceptibility testing methods for colistin in S. maltophilia may lead to unreliable results, mainly due to a complex interaction between different resistance mechanisms in the bacterial cells, including both adaptive resistance and heteroresistance. For this reason, in our study, antibiotic susceptibility to colistin, a drug that we think may be an alternative in the treatment of stenotrophomonas maltophilia infections isolated from various samples, was investigated with different methods. The presence of heteroresistance leading to treatment failures was also investigated for colistin. A total of 212 Stenotrophomonas maltophilia strains, which sent to the Bacteriology Laboratory of Hacettepe University Hospital between December 2015 and April 2018 were included in the study. Gradient test and broth microdilution methods were used for antibiotic susceptibility of colistin. These methods were repeated at two times for each strain. With these repetitions, it was observed that the reproducibility of the methods used in colistin sensitivity was a problem. 55 isolates that, have incompatibility between gradient test and broth microdilution methods and colonies within inhibition zone by gradient test, were evaluated for heteroresistance. The gold standard method PAP test was used to determine heteroresistance. 54 isolates were found to have heteroresistance. The frequency of colistin heteroresistance was 54/212 (25.5%). In one isolate, heteroresistance was not detected by repeated PAP test.
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