minocycline and Enterocolitis--Pseudomembranous

To evaluate the evidence for the use of tigecycline in the treatment of Clostridium difficile infection (CDI).. Searches were performed (2004 to June 2011), using the EMBASE and MEDLINE databases, with the terms tigecycline, Tygacil, Clostridium difficile, C. difficile, Clostridium difficile infection, and CDI.. Six case reports that described the use of tigecycline for treatment of CDI were included for review. No clinical trials were identified.. In all case reports except 1, tigecycline (alone or in combination with other CDI therapies) was used for the treatment of CDI that was refractory to metronidazole and/or vancomycin. In 6 of the cases, treatment success was reported following initiation of tigecycline therapy; 1 patient died following a complicated hospitalization. The treatment duration with tigecycline was 2-4 weeks. In the cases with successful outcomes, symptoms began to improve within 1 week. None of these patients experienced recurrence during follow-up of various lengths. In vitro studies demonstrated a 90% minimum inhibitory concentration range for tigecycline of 0.016-0.25 mg/L for all C. difficile isolates. Tigecycline exhibited good fecal penetration because of primary biliary excretion of unchanged drug. Up to 59% of the dose is recovered in feces following administration over 4 days in healthy volunteers.. Case reports have suggested that tigecycline may be successful for treatment of severe or severe complicated CDI, when prior therapy has failed. Data demonstrating tigecycline use as initial therapy for CDI are limited; therefore, this option should be reserved for patients in whom other therapeutic options, including metronidazole and vancomycin, have failed. A randomized controlled trial is needed to assess the safety and efficacy of tigecycline in this patient population and better define the drug's role in the treatment of CDI.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Clostridioides difficile; Drug Resistance, Bacterial; Enterocolitis, Pseudomembranous; Feces; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Severity of Illness Index; Tigecycline

We aimed to compare the outcomes of patients with C.difficile infection (CDI) treated either with tigecycline associated with vancomycin, or with vancomycin alone.. This single-centre retrospective cohort study included all adults hospitalized from September 2014 through August 2015 for symptomatic, incident CDI confirmed by polymerase chain reaction for C. difficile toxin in stools. The primary outcome was the rate of favourable outcome, defined as a composite of clinical response (resolution of symptoms without need for additional CDI therapy) and achieving discharge without CDI-related surgery or intensive care; a secondary outcome was CDI recurrence. We constructed a non-parsimonious logistic regression model to calculate a propensity score (PS) for those receiving tigecycline.. In all, 266 patients were included: 62 patients received both vancomycin and tigecycline, and 204 patients received vancomycin alone. The patients from the two groups were similar regarding demographics and comorbidities but patients in the tigecycline group had a more severe CDI. A favourable outcome in the tigecycline group versus the vancomycin group was found in 50/62 (81%) versus 193/204 (95%). We matched patients receiving tigecycline or not according to the PS and 86 patients (43 pairs) could be matched. The OR for favourable outcome with tigecycline in the matched analysis was 0.92 (95% CI 0.60-1.44; p 0.74). The rate of CDI recurrences was 8/62 (13%) in the tigecycline group versus 39/204 (19%) in the vancomycin group (p 0.2).. Adding tigecycline to CDI standard therapy did not increase the clinical cure nor reduce the rate of CDI recurrences.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Clostridioides difficile; Enterocolitis, Pseudomembranous; Female; Humans; Male; Middle Aged; Minocycline; Polymerase Chain Reaction; Retrognathia; Tigecycline; Vancomycin

There are only a limited number of antimicrobials for treating severe Clostridium difficile infection (sCDI). Tigecycline shows significant in vitro effect against C. difficile and is approved for management of complicated intra-abdominal infections. Our aim was to analyse the efficacy of tigecycline compared with standard therapy (oral vancomycin plus intravenous metronidazole) in adults treated for sCDI. A retrospective cohort study of such patients hospitalized at our department from January 2014 to December 2015 was performed. Patients receiving tigecycline monotherapy were compared with patients treated with standard therapy alone. Diagnosis and severity of CDI were determined according to guidelines of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Primary outcome was clinical recovery, secondary outcomes were in-hospital and 90-day all-cause mortality and relapse, colectomy, and complication rates. Of the 359 patients hospitalized for sCDI, 90 (25.0%) were included, 45 in each group. Patients treated with tigecycline had significantly better outcomes of clinical cure (34/45, 75.6% vs. 24/45, 53.3%; p 0.02), less complicated disease course (13/45, 28.9% vs. 24/45, 53.3%; p 0.02), and less CDI sepsis (7/45, 15.6% vs. 18/45, 40.0%; p 0.009) compared with patients receiving standard therapy. Tigecycline usage was not associated with adverse drug reactions or need for colectomy. Rates of ileus, toxic megacolon, mortality, and relapse were similar between the two groups. Favourable outcomes suggest that tigecycline might be considered as a potential candidate for therapeutic use in cases of sCDI refractory to standard treatment.

Topics: Administration, Intravenous; Administration, Oral; Aged; Aged, 80 and over; Anti-Bacterial Agents; Clostridioides difficile; Colectomy; Enterocolitis, Pseudomembranous; Female; Humans; Intraabdominal Infections; Male; Metronidazole; Middle Aged; Minocycline; Recurrence; Retrospective Studies; Sepsis; Tigecycline; Treatment Outcome; Vancomycin

For surgeons the early identification of patients with clostridium difficile infections (CDI) is important, because the incidence and virulence of this potentially life-threatening disease are increasing.. The aim of this study was to describe the frequency of CDI among surgical patients, to analyze which treatment was successful and to define which factors were associated with mortality.. A retrospective analysis of patients with CDI was performed.. From January 2004 to June 2012 the overall incidence of CDI among all departments at the St. Josef Hospital, Ruhr University Bochum was 0.6 % (1669 out of 301,919 patients). In 2004 the number of surgical patients with CDI was 1 which increased to 41 in 2011. Before the diagnosis of CDI was made 84 % (151 out of 179) of patients had received an antibiotic treatment. Conservative management of CDI was performed with metronidazole in 75 % (134 out of 179), 60 % (107 out of 179) received vancomycin, while 44 % (79 out of 179) received a combination of metronidazole and vancomycin, tygecycline or fidaxomidin. The overall mortality was 7 % (12 out of 179). There was a significant association with mortality for patients with sepsis, readmission to the intensive care unit (ICU), requirement for vasopressor therapy and intubation with mechanical ventilation. In 4 % of patients (7 out of 179) colectomy was carried out. Despite maximum intensive care management, 86 % (6 out of 7) of patients who underwent colectomy ultimately died.. Although conservative management is successful for most patients with CDI, the mortality is high for patients who require intensive care management secondary to CDI. Mortality after colectomy for CDI is almost 100 %, mostly because the operation is usually only performed as a last resort in patients with sepsis. The most important risk factor for CDI is a prior antibiotic therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Clostridioides difficile; Cohort Studies; Cross Infection; Cross-Sectional Studies; Drug Therapy, Combination; Enterocolitis, Pseudomembranous; Female; Fidaxomicin; Germany; Hospital Mortality; Humans; Incidence; Intensive Care Units; Male; Metronidazole; Middle Aged; Minocycline; Patient Readmission; Retrospective Studies; Survival Rate; Tigecycline; Vancomycin; Young Adult

The glycylcycline antibiotic tigecycline was approved in 2005 for the treatment of complicated skin and soft tissue infections and complicated intra-abdominal infections. Tigecycline is broadly active against both Gram-negative and Gram-positive microorganisms, including Clostridium difficile. Tigecycline has a low MIC against C. difficile in vitro and thus may represent an alternate treatment for C. difficile infection (CDI). To assess the use of tigecycline for treatment of established CDI, 5- to 8-week-old C57BL/6 mice were colonized with C. difficile strain 630. After C. difficile colonization was established, mice (n = 10 per group) were treated with either a 5-day course of tigecycline (6.25 mg/kg every 12 h subcutaneously) or a 5-day course of vancomycin (0.4 mg/ml in drinking water) and compared to infected, untreated control mice. Mice were evaluated for clinical signs of CDI throughout treatment and at 1 week posttreatment to assess potential for disease development. Immediately following a treatment course, C. difficile was not detectable in the feces of vancomycin-treated mice but remained detectable in feces from tigecycline-treated and untreated control mice. Toxin activity and histopathological inflammation and edema were observed in the ceca and colons of untreated mice; tigecycline- and vancomycin-treated mice did not show such changes directly after treatment. One week after the conclusion of either antibiotic treatment, C. difficile load, toxin activity, and histopathology scores increased in the cecum and colon, indicating that C. difficile-associated disease occurred. In vitro growth studies confirmed that subinhibitory concentrations of tigecycline were able to suppress toxin activity and spore formation of C. difficile, whereas vancomycin did not. Taken together, these data show how tigecycline is able to alter C. difficile pathogenesis in a mouse model of CDI.

Topics: Animals; Anti-Bacterial Agents; Cecum; Clostridioides difficile; Colon; Enterocolitis, Pseudomembranous; Feces; Female; Male; Mice; Mice, Inbred C57BL; Minocycline; Tigecycline; Vancomycin

Topics: Aged, 80 and over; Anti-Bacterial Agents; Critical Illness; Enterocolitis, Pseudomembranous; Humans; Male; Minocycline; Tigecycline

The efficacy of oral tigecycline treatment (2 mg/kg of body weight for 7 days) of Clostridium difficile infection (CDI) was evaluated in the gnotobiotic pig model, and its effect on human gut microflora transplanted into the gnotobiotic pig was determined. Tigecycline oral treatment improved survival, clinical signs, and lesion severity and markedly decreased concentrations of Firmicutes but did not promote CDI. Our data showed that oral tigecycline treatment has a potential beneficial effect on the treatment of CDI.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Clostridioides difficile; Drug Administration Schedule; Enterocolitis, Pseudomembranous; Fluoroquinolones; Germ-Free Life; Humans; Interleukin-8; Microbiota; Minocycline; Pyrimidinones; Swine; Tigecycline; Vancomycin

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

Tigecycline is a broad-spectrum glycylcycline antibiotic with potent in vitro activity against Clostridium difficile. We used a mouse model to test the hypothesis that tigecycline has a low propensity to promote colonization and toxin production by C. difficile due to inhibitory activity in the colon. Mice (5 to 8 per group) received subcutaneous injections of tigecycline (low and high doses) alone or in combination with clindamycin for 6 days. Growth of and toxin production by 3 strains of C. difficile (tigecycline MICs ≤ 0.012 μg/ml) were measured in cecal contents collected 6 h or 3 days after the final antibiotic dose. Antibiotic concentrations were measured using a bioassay, and concentrations of total anaerobes and Bacteroides spp. were measured. The effects of tigecycline on rendering mice susceptible to colonization with and reducing the burden of C. difficile were also examined. In comparison to saline controls, clindamycin promoted the growth of C. difficile (P < 0.001) in cecal contents, whereas tigecycline did not. Tigecycline did not suppress total anaerobes or Bacteroides spp. in comparison to saline controls. Concurrent administration of tigecycline prevented clindamycin-induced promotion of C. difficile in cecal contents collected 6 h or 3 days (high dose only) after the final antibiotic dose. Tigecycline did not promote the establishment of colonization in mice, yet it did not reduce concentrations of C. difficile in animals with established colonization. In summary, tigecycline did not promote the growth of or toxin production by C. difficile, probably due to inhibitory activity against C. difficile and relative sparing of indigenous anaerobic microflora.

Topics: Animals; Anti-Bacterial Agents; Bacterial Toxins; Clindamycin; Clostridioides difficile; Colon; Disease Models, Animal; Enterocolitis, Pseudomembranous; Female; Humans; Mice; Minocycline; Tigecycline; Treatment Outcome

Topics: Aged, 80 and over; Anti-Bacterial Agents; Clostridioides difficile; Enterocolitis, Pseudomembranous; Female; Humans; Infusions, Intravenous; Minocycline; Recurrence; Tigecycline

Topics: Anti-Bacterial Agents; Clostridioides difficile; Enterocolitis, Pseudomembranous; Europe; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Topics: Anti-Bacterial Agents; Clostridioides difficile; Diarrhea; Enterocolitis, Pseudomembranous; Female; Humans; Metronidazole; Microbial Sensitivity Tests; Middle Aged; Minocycline; Tigecycline

Clostridium difficile infection is an emerging and often difficult-to-treat iatrogenic complication. Recent data suggest that tigecycline, a novel antibiotic with broad-spectrum antibacterial activity, can be used successfully to treat patients with severe Clostridium difficile infection. We report a 70-year-old man who developed severe Clostridium difficile infection, was admitted to the intensive care unit and eventually succumbed to complications of his illness despite receiving tigecycline for approximately three weeks in combination with vancomycin, metronidazole and intravenous immunoglobulin. Additionally, we discuss the unique challenges that emerged during tigecycline treatment, such as the development of Proteus mirabilis bacteraemia and of colonisation with Acinetobacter baumannii resistant to tigecycline. Finally, we review data on other cases reported in the medical literature. Even though tigecycline looks promising for the treatment of Clostridium difficile infection, we urge caution against its indiscriminate use for off label indications.

Topics: Aged; Anti-Bacterial Agents; Critical Care; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterocolitis, Pseudomembranous; Humans; Immunoglobulins, Intravenous; Male; Metronidazole; Minocycline; Severity of Illness Index; Tigecycline; Treatment Failure; Vancomycin

Clostridium difficile infection (CDI) has become more refractory to standard therapy. We describe 4 patients with severe refractory CDI who were successfully treated with tigecycline. Symptoms improved within 1 week. No relapses were observed. This favorable outcome suggests that tigecycline might be a useful alternative for treating severe refractory CDI.

Topics: Adult; Aged, 80 and over; Anti-Bacterial Agents; Clostridioides difficile; Complementary Therapies; Enterocolitis, Pseudomembranous; Female; Humans; Male; Middle Aged; Minocycline; Tigecycline; Treatment Outcome

Broad-spectrum antibiotics are often associated with a relatively high risk of Clostridium difficile infection (CDI). However, exceptions to this rule, e.g., piperacillin-tazobactam, show that marked inhibition of gut flora is not synonymous with CDI risk. Tigecycline has marked broad-spectrum activity that includes Gram-positive and Gram-negative facultative and obligate anaerobes. Antibiotic susceptibility, gut model and clinical trial data suggest that tigecycline is associated with a relatively low risk of CDI. Further clinical data should be obtained to confirm the results of these initial studies.

Topics: Adult; Aged; Anti-Bacterial Agents; Clostridioides difficile; Enterocolitis, Pseudomembranous; Female; Humans; Intestines; Male; Microbial Sensitivity Tests; Minocycline; Risk Factors; Tigecycline

Data on the risk of Clostridium difficile infection (CDI) associated with specific antibiotics are difficult to obtain because of confounding clinical factors. It is particularly important to evaluate the propensity of new antibiotics to induce CDI. We have examined the propensity of tigecycline to induce CDI using a human gut model.. We used a three-stage chemostat human gut model to study the effects of tigecycline on indigenous gut microflora and C. difficile. Two epidemic C. difficile were studied in separate experiments: PCR ribotype 001 (UK, CD001) and PCR ribotype 027 (North America, CD027). Tigecycline MICs for 39 C. difficile representing 19 distinct PCR ribotypes were also determined.. Tigecycline MICs were 0.06 mg/L for all the C. difficile strains. Peak tigecycline concentrations in the gut model were 10.9 and 11.7 mg/L in CD027 and CD001 experiments, respectively. Tigecycline instillation invoked marked decreases in numbers of bacteroides and bifidobacteria (10(7)-10(8) cfu/mL) and lesser reductions in facultative anaerobes. Despite markedly altered gut microflora, CD001 and CD027 remained as spores for the duration of the experiment, with no evidence of proliferation or cytotoxin production.. Tigecycline exposure did not induce C. difficile proliferation or cytotoxin production despite reduced competing microflora. The potency of tigecycline against C. difficile may contribute to the low risk of CDI induction. Factors other than gut microflora colonization resistance may be important in preventing C. difficile spore germination, proliferation and cytotoxin production.

Topics: Anti-Bacterial Agents; Cell Proliferation; Clostridioides difficile; Cytotoxins; Enterocolitis, Pseudomembranous; Humans; Intestines; Microbial Sensitivity Tests; Minocycline; Ribotyping; Tigecycline