Tedavide Kullanılan Antibiyotiklerin Submik Konsantrasyonlarının Tekrarlayan Clostrıdıum Diffıcile Enfeksiyonlarında Biyofilm Oluşumuna ve Toksin Üretimine Etkisi

Abstract

Despite specific antibiotic treatments in C. difficile infections, high rate of recurrence is observed in 20%‐30% of the cases. We have hospitalized fifteen patients (30 isolates) at Marmara University Pendik Training and Research Hospital between 2012‐2015.These patients, forming the study group for this thesis, developed C. difficile infections due to antibiotic treatment at least twice. All patients’stool samples for toxin A + B test was found to be positive and C. difficile have been isolated from all the stool cultures. According to the gene sequences revealed by Rep‐PCR , these strains were investigated whether they are closely related. 22 origin (73%) was closely related, 8 origin (27%) was different from each other. By using Agar Dilution method in the two strains that were isolated twice, a two fold increase in MIC values for ceftriaxone was detected in the second isolations was observed,but not in the other isolates. Biofilm producing bacterial pathogens have been associated with increase in antibiotic resistance and chronical, recurrent infections. Without antibiotic effect 9(30%) strains were detected to be biofilm positive while in the presence of 1/2‐1/64 subMIC values of the antibiotics, in the medium with vancomycin a statistically significant increase was seen expect for 1/2 subMIC, a similar increase was observed in all the subMIC values of metronidazole (p< 0.05). When toxin A + B values were compared with the medium without antibiotics and with the medium with 1/2‐1/64 subMIC values of the antibiotics, a 25% and more increase in toxin A + B values was detected in a maximum of 20% of the strains. In the repeated isolates toxin A and toxin B genes have been shown by PCR, but variant (tcd A‐/tcd B+) or “binary toxin” gene was not detected. As a result, increase in biofilm and toxin levels in the subMIC concentrations of the frequently used antibiotics in the treatment of C. difficile is considered to predispose resistance against host defence and repeated infections.