The use of first-generation cephalosporin antibiotics, cefalexin and cefradine, is not associated with induction of simulated Clostridioides difficile infection.

OBJECTIVES: The use of broad-spectrum cephalosporins is associated with induction of Clostridioides difficile infection (CDI). Recent knowledge on the importance of the healthy microbiota in preventing pathogen colonization/outgrowth highlights the caution needed when prescribing broad-spectrum antibiotics. The use of historical narrow-spectrum antibiotics, such as first-generation cephalosporins, is gaining increased attention once more as they have a reduced impact on the microbiota whilst treating infections. Here, the effects of two first-generation cephalosporins, compared with a third-generation cephalosporin, on the human microbiota were investigated and their propensity to induce simulated CDI. METHODS: Three in vitro chemostat models, which simulate the physiochemical conditions of the human colon, were seeded with a human faecal slurry and instilled with either narrow-spectrum cephalosporins, cefalexin and cefradine, or a broad-spectrum cephalosporin, ceftriaxone, at concentrations reflective of colonic levels. RESULTS: Instillation of cefalexin was associated with reduced recoveries of Bifidobacterium and Enterobacteriaceae; however, Clostridium spp. recoveries remained unaffected. Cefradine exposure was associated with decreased recoveries of Bifidobacterium spp., Bacteroides spp. and Enterobacteriaceae. These changes were not associated with induction of CDI, as we observed a lack of C. difficile spore germination/proliferation, thus no toxin was detected. This is in contrast to a model exposed to ceftriaxone, where CDI was observed. CONCLUSIONS: These model data suggest that the minimal impact of first-generation cephalosporins, namely cefalexin and cefradine, on the intestinal microbiota results in a low propensity to induce CDI.

Eravacycline, a novel tetracycline derivative, does not induce Clostridioides difficile infection in an in vitro human gut model.

OBJECTIVES: The approval of new antibiotics is essential to combat infections caused by antimicrobial-resistant pathogens; however, such agents should be tested to determine their effect on the resident microbiota and propensity to select for opportunistic pathogens, such as Clostridioides difficile. Eravacycline is a new antibiotic for the treatment of complicated intra-abdominal infections. Here, we determined the effects of eravacycline compared with moxifloxacin on the microbiota and if these were conducive to induction of C. difficile infection (CDI). METHODS: We seeded in vitro chemostat models, which simulate the physiological conditions of the human colon, with a human faecal slurry and instilled gut-reflective concentrations of either eravacycline or moxifloxacin. RESULTS: Eravacycline instillation was associated with decreased Bifidobacterium, Lactobacillus and Clostridium species, which recovered 1 week after exposure. However, Bacteroides spp. levels decreased to below the limit of detection and did not recover prior to the end of the experiment. Post-eravacycline, a bloom of aerobic bacterial species occurred, including Enterobacteriaceae, compared with pre-antibiotic, which remained high for the duration of the experiment. These changes in microbiota were not associated with induction of CDI, as we observed a lack of C. difficile spore germination and thus no toxin was detected. Moxifloxacin exposure sufficiently disrupted the microbiota to induce simulated CDI, where C. difficile spore germination, outgrowth and toxin production were seen. CONCLUSIONS: These model data suggest that, despite the initial impact of eravacycline on the intestinal microbiota, similar to clinical trial data, this novel tetracycline has a low propensity to induce CDI.

Saphenous vein harvest with SaphLITE system versus conventional technique: a prospective, randomized study.

BACKGROUND: Minimally invasive saphenous vein harvest (MIVH) techniques have been evaluated and reported with heterogeneous results. The aim of this study was to evaluate the efficacy of MIVH on the outcomes of postoperative leg wound healing and pain using the SaphLITE retractor system. METHODS: Two hundred twenty-five patients undergoing elective coronary artery bypass grafting surgery were randomized to receive either SaphLITE vein harvest (SVH) or conventional open vein harvest (OVH). RESULTS: There were no significant differences between the two groups in demographics, postoperative mortalities and major complications. For SVH group and OVH group, total leg wound length was 18.33 +/- 7.93 cm vs 46.10 +/- 15.63 cm (p < 0.001), and vein harvest time was 50.70 +/- 16.55 minutes vs 40.35 +/- 16.43 minutes (p < 0.001). In-hospital leg wound healing disturbance (LWHD) rate was 4.7% for SVH group and 1.7% for OVH group (p = 0.190). Delayed LWHD rate was 16.0% for SVH group and 39.5% for OVH group (p < 0.001). Combined, LWHD rate was 20.8% for SVH group and 41.2% for OVH group (p = 0.001). There was no significant difference in the worst postoperative leg wound pain or length of hospital stay between the 2 groups. Double-blinded histologic examinations revealed normal vascular structure in the harvested veins from both groups. CONCLUSIONS: Our study demonstrated that harvesting saphenous vein with SaphLITE retractor system is a good technique which is associated with reduced rate of delayed LWHD, preserved venous structural integrity, and acceptable harvest speed.