minocycline and Clostridium-Infections

Clostridium difficile infection (CDI) has become the most frequent cause of nosocomial infectious diarrhoea in developed countries, causing an increase in mortality, recurrences or treatment failure. In the search for new and more effective drugs, researchers recently turned their attention to tigecycline, a broad-spectrum antibiotic of the glycylglycine class available as an intravenous formulation for human use, which has also shown in vitro activity against C. difficile. We performed a literature review of articles addressing in vitro as well as in vivo studies and case reports on the effectiveness of tigecycline, whose use is promising especially in light of its high faecal excretion. The available evidence suggests that tigecycline could play a role as an alternative therapeutic option for critically ill patients or cases of refractory CDI.

Topics: Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Diarrhea; Humans; Minocycline; Tigecycline; Treatment Outcome

Clostridium difficile colitis infection is on the rise and is considerably increasing the duration of hospital stay, as well as healthcare costs. The management of C. difficile colitis has become more challenging with the increasing failure of therapeutic response to metronidazole and oral vancomycin. Tigecycline is a new glycylcycline that has shown in vitro activity against C. difficile. We report herein a case of C. difficile colitis that failed to improve on a combination of metronidazole and oral vancomycin. The patient subsequently developed a surgical abdomen secondary to refractory C. difficile colitis, but was successfully treated with a combination of rifaximin and tigecycline after she refused to undergo surgical treatment.

Topics: Aged; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Colitis; Drug Therapy, Combination; Female; Humans; Metronidazole; Minocycline; Recurrence; Rifamycins; Rifaximin; Tigecycline; Treatment Outcome; Vancomycin

Clostridium difficile infection (CDI) is a significant cause of morbidity and mortality in both the acute care setting and the wider healthcare system. The purpose of this study was to evaluate the in vitro activity of fidaxomicin against C. difficile isolates from a university teaching hospital in China.. One hundred and one C. difficile isolates were collected and analyzed for toxin genes by multiplex PCR. The toxin gene positive strains were also typed by multilocus sequence typing (MLST) and PCR-ribotyping. The MICs of the isolates were determined against fidaxomicin, metronidazole, vancomycin, tigecycline and moxifloxacin, by the agar dilution method.. All the 101 isolates exhibited low MICs to fidaxomicin (0.032-1 mg/L), metronidazole (0.125-1 mg/L), vancomycin (0.25-2 mg/L) and tigecycline (0.016-0.5 mg/L). Tigecycline showed the lowest geometric mean MIC value (0.041 mg/L), followed by fidaxomicin (0.227 mg/L), metronidazole (0.345 mg/L), and vancomycin (0.579 mg/L). About 35% of the strains (n = 35) were resistant to moxifloxacin, and the resistance rate to moxifloxacin for A-B+CDT- isolates (85.0%) was much higher than that of A+B+CDT- (15.7%) and A-B-CDT- (29.2%) isolates (P < 0.001). The MIC values of fidaxomicin, metronidazole, vancomycin and moxifloxacin against the 3 ST1 isolates were higher than for other STs. All the 28 moxifloxacin-resistant toxigenic isolates carried a mutation either in gyrA or/and gyrB.. Fidaxomicin exhibited high antimicrobial activity against all C. difficile isolates tested, which shows promise as a new drug for treating Chinese CDI patients.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Toxins; China; Clostridioides difficile; Clostridium Infections; DNA Gyrase; DNA, Bacterial; Drug Resistance, Bacterial; Fidaxomicin; Fluoroquinolones; Genes, Bacterial; Hospitals, Teaching; Hospitals, University; Humans; Metronidazole; Microbial Sensitivity Tests; Minocycline; Moxifloxacin; Multilocus Sequence Typing; Ribotyping; Tigecycline; Vancomycin

Tigecycline is a third-line therapy for severe Clostridium difficile infection (CDI) in Australasian guidelines. Differences in strain types make it difficult to extrapolate international tigecycline efficacy data with combination or monotherapy to Australian practice, where experience is limited.. To evaluate the efficacy and adverse effects associated with tigecycline combination therapy for severe and severe-complicated CDI in an Australian healthcare setting.. This was a retrospective observational study at a metropolitan university-affiliated hospital. All patients between February 2013 and October 2016 treated with adjunctive intravenous tigecycline for >48 h for severe or severe-complicated CDI were included. Tigecycline was given in addition to oral vancomycin ± intravenous metronidazole. The primary outcome was all-cause mortality at 30 days from start of tigecycline combination therapy. Secondary outcomes included clinical cure, colectomy, adverse events and recurrence rates.. Thirteen patients with median age of 61 years had severe (n = 9) or severe-complicated (n = 4) CDI at tigecycline commencement. In 92% of patients, tigecycline started within 48 h after in-hospital CDI treatment, for median duration of 9 days. All-cause mortality at 30 days was 8% with no mortality in severe CDI and 25% (1/4) in patients with severe-complicated fulminant CDI, comparing favourably with historical rates of 9-38% and 30-80% in similar respective groups. Clinical cure was achieved in 77% of cases. There were no colectomies and one attributable tigecycline adverse reaction.. Tigecycline appears safe and effective as a part of combination therapy in severe CDI, and may be given earlier and for shorter durations than in current guidelines.

Topics: Administration, Intravenous; Aged; Aged, 80 and over; Anti-Bacterial Agents; Australia; Clostridioides difficile; Clostridium Infections; Cross Infection; Drug Therapy, Combination; Female; Humans; Male; Metronidazole; Middle Aged; Minocycline; Retrospective Studies; Tigecycline; Treatment Outcome; Vancomycin

We hypothesised that treatment with a tigecycline-based antimicrobial regimen for intra-abdominal infection (IAI) could be associated with lower rates of subsequent carbapenem-resistant Enterobacteriaceae (CRE) colonisation or Clostridium difficile infection (CDI) compared with a meropenem-based regimen.. We performed a retrospective, single-centre, matched (1:1) cohort analysis of all patients who received at least 5 days of empirical or targeted tigecycline (TIG)- or meropenem (MER)-based treatment regimens for IAI over a 50-month period. Patients with previous CRE colonisation and CDI were excluded. Risk factors for CRE and CDI were assessed with a Cox regression model that included treatment duration as a time-dependent variable. Thirty-day mortality was assessed with Kaplan-Meier curves.. We identified 168 TIG-treated and 168 MER-treated patients. The cumulative incidence rate ratio of CDI was 10-fold lower in TIG-treated vs. MER-treated patients (incidence rate ratio [IRR] 0.10/1000 patient-days, 95%CI 0.002-0.72, P = 0.007), but similar incidence rates were found for CRE colonisation (IRR 1.39/1000 patient-days, 95%CI 0.68-2.78, P = 0.36). In a multivariate Cox regression model, the receipt of a TIG- vs. MER-based regimen was associated with significantly lower rates of CDI (HR 0.07, 95%CI 0.03-0.71, P = 0.02), but not CRE (HR 1.12, 95% CI 0.45-2.83, P = 0.80). All-cause 30-day mortality was similar in the two groups (P = 0.46).. TIG-based regimens for IAI were associated with a 10-fold lower incidence of CDI compared with MER-based regimens, but there was no difference in the incidence of CRE colonisation.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carrier State; Clostridioides difficile; Clostridium Infections; Enterobacteriaceae Infections; Female; Humans; Incidence; Intraabdominal Infections; Male; Meropenem; Middle Aged; Minocycline; Retrospective Studies; Risk Factors; Survival Analysis; Thienamycins; Tigecycline; Young Adult

Clostridium difficile infection (CDI) is the most frequent cause of nosocomial diarrhoea in adults. Cancer patients, in particular, are at a higher risk for CDI. Limited clinical data exist regarding the use of tigecycline for the treatment of CDI, especially in patients with oncologic and haematologic malignancies.. To characterize the use of tigecycline for treatment of CDI in oncology patients at an academic cancer centre.. This was a retrospective, single-centre, single-arm, chart review evaluating the use of tigecycline for the management of CDI in oncology patients at an academic cancer centre.. The median age of CDI diagnosis in this patient group (N=66) was 65 years (range: 16-84) and the majority of patients had solid tumour malignancies. Fifty-six percent of patients had severe CDI, 70.3% of which were classified as having severe complicated disease. The median time to initiation of tigecycline therapy was 2 days (mean: 3.83) and the median number of tigecycline doses was 13 (range: 1-50). Twelve non-CDI breakthrough infections were observed, and four patients developed CDI while receiving tigecycline for non-CDI indications. The rate of death was 18% and the recurrence rate was 15.2%.. Tigecycline did not lead to overt benefits in outcomes of oncology patients with CDI when compared to historical data. In addition, several breakthrough CDIs were observed in patients who received the drug for a non-CDI indication. Further prospective research is needed to validate the use of tigecycline for management of CDI.

Topics: Academic Medical Centers; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Colitis; Female; Humans; Male; Middle Aged; Minocycline; Neoplasms; Retrospective Studies; Tigecycline; Treatment Outcome; Young Adult

Topics: Aged, 80 and over; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Diarrhea; Female; Humans; Minocycline; Salvage Therapy; Tigecycline; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Drug Resistance, Bacterial; Fecal Microbiota Transplantation; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Metronidazole; Middle Aged; Minocycline; Retrospective Studies; Tigecycline; Treatment Outcome; Young Adult

No new acquisition of Clostridium difficile occurred among 12 hospitalised patients receiving tigecycline, and pre-existing colonisation was reduced to undetectable levels in 2 patients. Moreover, 91% of stool suspensions obtained during tigecycline therapy exhibited inhibitory activity against C. difficile. These results suggest that tigecycline achieves sufficient concentrations to inhibit intestinal colonisation by C. difficile.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Cohort Studies; Feces; Female; Gastrointestinal Tract; Humans; Male; Middle Aged; Minocycline; Prospective Studies; Tigecycline

Antibiotics can play dual roles in Clostridium difficile infection (CDI); antibiotic treatment increases the risk of CDI, and antibiotics are used to treat CDI. The glycylcycline antibiotic tigecycline has broad antimicrobial activity, yet it is rarely associated with the development of CDI, presumably due to its activity against C. difficile. In this study, we investigated how tigecycline treatment affects the structure of the gut microbiota and susceptibility to CDI by treating mice with tigecycline (n = 20) or saline (n = 8) for 10 days. A sequence analysis of the bacterial 16S rRNA gene amplicons was used to monitor changes in the fecal microbiota. A subset of the mice was followed for 5 weeks after the end of treatment. The remaining mice were challenged with C. difficile strain VPI 10463 spores 2 days after the tigecycline treatment ended. Tigecycline treatment resulted in major shifts in the gut microbiota, including large decreases in Bacteroidetes levels and large increases in Proteobacteria levels. Mice with tigecycline-altered microbial communities were susceptible to challenge with C. difficile spores and developed clinical signs of severe CDI. Five weeks after the cessation of tigecycline treatment, the recovery of the bacterial community was incomplete and diversity was lower than in the untreated controls. Antibiotics with intrinsic activity against C. difficile can still alter the microbiota in a way that leads to susceptibility to CDI after discontinuation of the drug. These results indicate that microbiotic dynamics are key in the development of CDI, and a better understanding of these dynamics may lead to better strategies to prevent and treat this disease.

Topics: Animals; Clostridioides difficile; Clostridium Infections; Female; Gastrointestinal Tract; Male; Mice; Mice, Inbred C57BL; Microbiota; Minocycline; Tigecycline

Limited data suggest that tigecycline may be of value in the treatment of Clostridiumdifficile infection. We reviewed our experience using tigecycline to treat severe c. difficile and compared outcomes to similarly ill patients who did not receive tigecycline. We found no difference between the groups. Further study is needed before tigecycline can be recommended for use in severe C. difficile infection.

Topics: Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Humans; Middle Aged; Minocycline; Tigecycline

We report the first case of anaphylaxis to oral vancomycin in a cystic fibrosis patient with severe and relapsing Clostridium difficile infection (CDI) refractory to metronidazole. The patient's colitis has been successfully treated with a combination of intravenous metronidazole and tigecycline.

Topics: Administration, Oral; Adult; Anaphylaxis; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Cystic Fibrosis; Diarrhea; Enterocolitis, Pseudomembranous; Humans; Male; Metronidazole; Minocycline; Severity of Illness Index; Tigecycline; Vancomycin

Topics: Anti-Bacterial Agents; Clostridium; Clostridium Infections; Drug Resistance, Multiple, Bacterial; Europe; Humans; Minocycline; Tigecycline