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Sixty-eight hospital-admitted patients with a first episode of Clostridium difficile infection (CDI) were included and followed up during 1 year. Faeces samples were collected at 1, 2, 6 and 12 months after inclusion and analyzed for the presence of C. difficile toxin B, genes for toxin A, toxin B, binary toxin and TcdC deletion by PCR. All strains were also PCR-ribotyped and the MICs of the isolates were determined against eight antimicrobial agents. In 68 patients initially included, antibiotics, clinical signs and co-morbidities were analyzed and 56 were evaluable for recurrences. The mean number of different antibiotics given during 3 months prior to inclusion was 2.6 (range 0-6). Six patients had not received any antibiotics and three of them had diagnosed inflammatory bowel disease. Thirty-two patients (57%) had either a microbiological or clinical recurrence, 16 of whom had clinical recurrences that were confirmed microbiologically (13, 23%) or unconfirmed by culture (3, 5%). Twenty-nine patients were positive in at least one of the follow-up tests, 16 had the same ribotype in follow-up tests, i.e. relapse, and 13 a different ribotype, i.e., reinfection. Most common ribotypes were 078/126, 020, 023, 026, 014/077, 001 and 005. No strain of ribotype 027 was found. Strains ribotype 078/126 and 023 were positive for binary toxin and were the strains most prone to cause recurrence. All strains were sensitive to vancomycin and metronidazole. Patients with recurrences were significantly older (p = 0.02) and all patients had a high burden of comorbidities, which could explain the high fatality rate, 26 (38%) patients died during the 1-year follow-up.

One hundred thirty-three Clostridium difficile strains were collected from 71 patients and analyzed for the presence of C. difficile toxin B by the cell cytotoxicity neutralization assay, genes for toxin A, toxin B, binary toxin and TcdC deletion by PCR. All strains were also PCR-ribotyped and analyzed for sporulation frequency. The MICs of the isolates were determined against cadazolid and seven other antimicrobial agents by the agar dilution method. All isolates were positive for toxin B by the cell cytotoxicity neutralization assay. One hundred fourteen isolates were positive for toxin A and B and 16 isolates were positive for toxin A, toxin B and binary toxin by PCR. Three isolates were negative for toxin A but positive for toxin B. Thirty-three different ribotypes were identified. No strain of ribotype 027 was found. No differences in sporulation were noticed between the primary and recurrent isolates. All 133 isolates were sensitive to cadazolid (0.064–0.5 mg/l), fidaxomicin (0.008–0.125 mg/l), metronidazole (0.125–2 mg/l), vancomycin (0.125–1 mg/l) and tigecycline (0.032–0.25 mg/l). Three isolates were resistant to linezolid (8 mg/l), 15 isolates were resistant to moxifloxacin (8–32 mg/l) and 103 isolates were resistant to clindamycin (8–256 mg/l). No association between toxins A, B and binary toxin, ribotypes or the sporulation and the sensitivity to cadazolid could be found. Cadazolid has a potent in vitro activity against C. difficile.

Solithromycin is a novel fluoroketolide with high activity against bacteria associated with community-acquired respiratory tract infections as well as gonorrhea. However, data on the activity of solithromycin against anaerobic bacteria from the normal intestinal microbiota are scarce. In this study, 1024 Gram-positive and Gram-negative anaerobic isolates from the normal intestinal microbiota were analyzed for in-vitro susceptibility against solithromycin and compared to azithromycin, amoxicillin/clavulanic acid, ceftriaxone, metronidazole and levofloxacin by determining the minimum inhibitory concentration (MIC). Solithromycin was active against Bifidobacteria (MIC50, 0.008 mg/L) and Lactobacilli (MIC50, 0.008 mg/L). The MIC50 for Clostridia, Bacteroides, Prevotella and Veillonella were 0.5, 0.5, 0.125 and 0.016 mg/L, respectively. Gram-positive anaerobes were more susceptible to solithromycin as compared to the other antimicrobials tested. The activity of solithromycin against Gram-negative anaerobes was equal or higher as compared to other tested agents.

The human normal microflora is relatively stable at each ecological habitat under normal circumstances and acts as a barrier against colonization by potentially pathogenic microorganisms and against overgrowth of already present opportunistic microorganisms. Administration of antimicrobial agents causes disturbances in the ecological balance between the host and the normal microflora. The risk of emergence and spread of resistant strains between patients and dissemination of resistant determinants between microorganisms is reduced if colonization resistance is not disturbed by antimicrobial agents. In this article, the potential ecological effects of administration of new antimicrobial agents on the intestinal and oropharyngeal microflora are summarized. The review is based on clinical studies published during the past 10 years.

Thirty healthy subjects (15 males and 15 females) were randomly assigned in three groups and clindamycin (150 mg qid) or ciprofloxacin (500 mg bid) or placebo was given for a 10-day period. Skin, nasal, saliva, faeces samples were collected at day – 1, day 11, 1 month, 2 months, 4 months and 12 months post administration for microbiological analysis. Ciprofloxacin or clindamycin had no impact on the anaerobic skin microbiota and the proportions of antibiotic resistant anaerobic bacteria were similar as in the placebo group. Ciprofloxacin had impact on the Propionibacterium acnes in the nasal microbiota that normalized after 1 month, however, ciprofloxacin-resistant P. acnes strains increased at month 2 and month 12. Clindamycin had no impact on the nasal microbiota. In the oropharyngeal microbiota, a higher proportion of ciprofloxacin resistant Veillonella was found, it lasting up to 12 months post dosing. In the clindamycin group, clindamycin-resistant Prevotella spp. were found in increased proportions compared to placebo at various time points except month 4 in the saliva samples. The relative proportion of ciprofloxacin-resistant Bifidobacteria increased in the faecal samples on day 11, 1 month, 4 months and 12 months post dosing compared to placebo. The proportion of clindamycin-resistant Bacteroides spp. increased at 1, 2, 4 and 12 months post dosing compared to placebo in the faecal samples. No Clostridium difficile was recovered from any of the samples from any of the volunteers at any visit. The concentrations of ciprofloxacin or clindamycin in the faeces were higher than the MICs for most of the organisms present in the normal microbiota. No obvious correlation between the groups in resistant patterns for anaerobic bacteria was observed. In conclusion, based on the microbiological data of the microbiota as well as the results of the bioassays for ciprofloxacin and clindamycin concentrations in the faecal samples, oral administration of ciprofloxacin and clindamycin has an impact on the anaerobic microbiota and may have a long-term effect on the development and persistence of antibiotic-resistant anaerobes in the normal microbiota.

One hundred fourteen Clostridium difficile strains were collected from 67 patients and analyzed for the presence of C. difficile toxin B by the cell cytotoxoicity neutralization assay, genes for toxin A, toxin B, binary toxin and Tcd C deletion by PCR. All strains were also PCR-ribotyped. The MICs of the isolates were determined against MCB3681 and nine other antimicrobial agents by the agar dilution method. All isolates were positive for toxin B as well as for toxin A and B genes. In addition, 13 isolates were positive for the binary toxin genes. Thirty-two different ribotypes were identified. No strain of ribotype 027 was found. All 114 isolates were sensitive to MCB3681 (0.008–0.5 mg/l), cadazolid (0.064–0.5 mg/l), fidaxomicin (0.008–0.125 mg/l), metronidazole (0.125–2 mg/l), vancomycin (0.125–1 mg/l) and tigecycline (0.032–0.25 mg/l). Three isolates were resistant to linezolid (8 mg/l), 12 isolates were resistant to moxifloxacin (8–32 mg/l), 87 isolates were resistant to clindamycin (8–256 mg/l) and 107 isolates were resistant to ciprofloxacin (8–256 mg/l). No association between toxins A, B and binary toxin, ribotypes and the sensitivity to MCB3681 could be found. MCB3681 has a potent in vitro activity against C. difficile .