title: Toxin production of Clostridium difficile in sub-MIC of vancomycin and clindamycin alone and in combination with ceftazidime.
abstract: Toxin production in Clostridium difficile (C. difficile) is a key process for induction of diarrhea. Several factors such as sub-MIC of antibiotics impact on toxin production. The aim of this research is investigation of sub-minimum inhibitory concentration (sub-MIC) of vancomycin (VAN), clindamycin (CLI) separately and in combination with ceftazidime (CAZ) on toxin production in C. difficile. About ∼106colony forming units (CFU) from 18-h culture of C. difficile ATCC 9689 and clinical isolates A+/B+/CTD-, were cultured anaerobically in the pre-reduced medium with appropriate concentration of separated and in combination antibiotics. After 24 and 48 h, 1 mL of culture was removed, centrifuged and the supernatant stored at-70 °C for later use. The evaluation of toxin production was carried out by the ELISA technique. All antibiotics alone and in combination formats inhibited toxin production over a period of 24 h. This effect is also observed in presence of VAN and CLI during a period of 48 h. Over a 4 h period, CAZ increased toxin production alone and in combination, especially with CLI. The data showed VAN and CLI decrease the level of toxins. In contrast, the CAZ not only increases the level of produced toxin, but also can interfere with VAN and CLI. Based on the results, combination therapy which is performed for treatment or prevention of other infections may cause toxin production and probably the severity of C. difficile AAD to increase.
authors.affiliation: Department of Microbiology and Virology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Ebrahim Rezazadeh
authors.initials: ER
authors.lastname: Zarandi
authors.affiliation: Department of Microbiology and Virology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Shahla
authors.initials: S
authors.lastname: Mansouri
authors.affiliation: Department of Community Medicine, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Nouzar
authors.initials: N
authors.lastname: Nakhaee
authors.affiliation: Department of Infectious Diseases, Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Farhad
authors.initials: F
authors.lastname: Sarafzadeh
authors.affiliation: Department of Microbiology and Virology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran. Electronic address: m_moradie@yahoo.co.uk.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Moradi
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D001427:Bacterial Toxins / Q000096:biosynthesis* / Q000235:genetics; D002442:Ceftazidime / Q000494:pharmacology*; D002981:Clindamycin / Q000494:pharmacology*; D016360:Clostridioides difficile / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification / Q000378:metabolism*; D015169:Colony Count, Microbial; D003967:Diarrhea / Q000188:drug therapy*; D004338:Drug Combinations; D024881:Drug Resistance, Bacterial; D004768:Enterotoxins / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D013997:Time Factors; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004338:Drug Combinations; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; D002981:Clindamycin; D014640:Vancomycin; D002442:Ceftazidime
keywords: Antibiotics; Clostridium difficile; Combination; Toxin production