ro13-9904 and Enterocolitis--Pseudomembranous

A 16-year-old Hispanic man was transferred to our level I paediatric trauma centre with pancreatitis. Ten days prior, he had sustained a gunshot wound to the abdomen requiring an exploratory laparotomy for repair of a traumatic left diaphragmatic injury. Additional injuries included gastric, renal, liver and pancreatic lacerations as well as a T12 burst fracture that resulted in paraplegia. Conservative management of pancreatitis was unsuccessful over the next 10 days, resulting in progressive symptoms of severe unresolved pain, nausea, emesis and rising lipase. Workup for post-traumatic, biliary and drug-associated causes of pancreatitis was negative, and no anatomical abnormalities were found on imaging. A fever workup on hospital day 10 revealed a urinary tract infection with non-typhoid

Topics: Abdomen; Adolescent; Anti-Bacterial Agents; Ceftriaxone; Clostridioides difficile; Enterocolitis, Pseudomembranous; Humans; Male; Metronidazole; Pancreatitis; Salmonella; Salmonella Infections; Sulfamethoxazole; Trimethoprim; Wounds, Gunshot

Incidence of antibiotic- associated diarrhoea is a common (10-30%) but pseudomembranous colitis (PMC) is less frequent (1-5%). Fluoroquinolones, clindamycin, penicillins, cephalosporins (mostly third generation) are commonly associated with PMC. The association between cephalosporins and PMC is now well established.. A 78 year old male patient developed pseudomembraneous colitis after administration of Ceftriaxone and Cefazoline for the treatment of pleural effusion. The reaction was confirmed by ultrasonography and CT scan. Causative agents were stopped and patient was managed by systemic therapy. Patient was expired due to respiratory complications as there was complexity in management of disease due to development of pseudomembraneous colitis.. Increase awareness of prescribers for high-risk drugs, close monitoring, with immediate withdrawal of the culprit drug can reduce the complexity of management that occur due to development of such adverse drug reaction.

Topics: Aged; Anti-Bacterial Agents; Cefazolin; Ceftriaxone; Cephalosporins; Drug Therapy, Combination; Enterocolitis, Pseudomembranous; Fatal Outcome; Humans; Male

The host response to Clostridium difficile infection in antibiotic-treated mice is characterized by robust recruitment of Gr-1(+) cells, increased expression of inflammatory cytokines including tumour necrosis factor-α (TNF-α), and the development of severe epithelial damage. To investigate the role of Gr-1(+) cells and TNF-α during C. difficile colitis, we treated infected mice with monoclonal antibodies against Gr-1 or TNF-α. Mice were challenged with vegetative cells of C. difficile strain VPI 10463 following treatment with the third-generation cephalosporin ceftriaxone. Ceftriaxone treatment alone was associated with significant changes in cytokine expression within the colonic mucosa but not overt inflammatory histopathological changes. In comparison, C. difficile infection following ceftriaxone treatment was associated with increased expression of inflammatory cytokines and chemokines including Cxcl1, Cxcl2, Il1b, Il17f and Tnfa, as well as robust recruitment of Ly6C(Mid)  Gr-1(High) neutrophils and Ly6C(High) Gr-1(Mid) monocytes and the development of severe colonic histopathology. Anti-Gr-1 antibody treatment resulted in effective depletion of both Ly6C(Mid) Gr-1(High) neutrophils and Ly6C(High) Gr-1(Mid) monocytes: however, we observed no protection from the development of severe pathology or reduction in expression of the pro-inflammatory cytokines Il1b, Il6, Il33 and Tnfa following anti-Gr-1 treatment. By contrast, anti-TNF-α treatment did not affect Gr-1(+) cell recruitment, but was associated with increased expression of Il6 and Il1b. Additionally, Ffar2, Ffar3, Tslp, Tff and Ang4 expression was significantly reduced in anti-TNF-α-treated animals, in association with marked intestinal histopathology. These studies raise the possibility that TNF-α may play a role in restraining inflammation and protecting the epithelium during C. difficile infection.

Topics: Animals; Anti-Inflammatory Agents; Antibodies, Monoclonal; Ceftriaxone; Clostridioides difficile; Colon; Disease Models, Animal; Enterocolitis, Pseudomembranous; Gene Expression Regulation; Host-Pathogen Interactions; Inflammation Mediators; Intestinal Mucosa; Male; Mice, Inbred C57BL; Microbiota; Monocytes; Neutrophils; Receptors, Cell Surface; Signal Transduction; Time Factors; Tumor Necrosis Factor-alpha

Receipt of antibiotics is a major risk factor for Clostridium difficile infection (CDI). Doxycycline has been associated with a lower risk for CDI than other antibiotics. We investigated whether doxycycline protected against development of CDI in hospitalized patients receiving ceftriaxone, a high-risk antibiotic for CDI.. We studied adults admitted to an academic county hospital between 1 June 2005 and 31 December 2010 who received ceftriaxone to determine whether the additional receipt of doxycycline decreased the risk of CDI. Patients were followed from first administration of ceftriaxone to occurrence of CDI or administrative closure 30 days later.. Two thousand three hundred five unique patients comprising 2734 hospitalizations were studied. Overall, 43 patients developed CDI within 30 days of ceftriaxone receipt, an incidence of 5.60 cases per 10 000 patient-days. The incidence of CDI was 1.67 cases per 10 000 patient-days in those receiving doxycycline, compared to 8.11 per 10 000 patient-days in those who did not receive doxycycline. In a multivariable model adjusted for age, gender, race, comorbidities, hospital duration, pneumonia diagnosis, surgical admission, and duration of ceftriaxone and other antibiotics, for each day of doxycycline receipt the rate of CDI was 27% lower than a patient who did not receive doxycycline (hazard ratio, 0.73; 95% confidence interval, .56-.96).. In this cohort of patients receiving ceftriaxone, doxycycline was associated with lower risk of CDI. Guidelines recommend this combination as a second-line regimen for some patients with community-acquired pneumonia (CAP). Further clinical studies would help define whether doxycycline-containing regimens should be a preferred therapy for CAP.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Ceftriaxone; Clostridioides difficile; Cohort Studies; Doxycycline; Enterocolitis, Pseudomembranous; Female; Humans; Male; Middle Aged; Proportional Hazards Models

Non-toxigenic strains of Clostridium difficile are highly effective in preventing toxigenic C. difficile infection in hamsters when given following a single dose of an antimicrobial agent. The goal of this study was to determine the ability of non-toxigenic C. difficile to colonise hamsters during administration of an antibiotic to which the organisms are resistant - ceftriaxone - and an antibiotic to which they are susceptible - ampicillin - and to determine if non-toxigenic colonisation is protective against toxigenic strain challenge. Groups of four or five hamsters were administered daily ceftriaxone 60 mg/kg/d intraperitoneally or ampicillin 60 mg/kg/d orally for 5 days. Three non-toxigenic strains of C. difficile, M3, M23, and T7 (MICs 96-128 mg/L) were each given orally at a dose of 1 x 10(6) spores to groups of five animals 3h after the first dose of ceftriaxone. All animals were colonised successfully by day 3 of the study and when challenged with 1 x 10(6) spores of toxigenic strain J9 (MIC >256 mg/L) on day 3 all animals survived, whereas the control animal given ceftriaxone, but not non-toxigenic C. difficile, died within 48h of challenge. When groups of four hamsters were given ampicillin, administration of non-toxigenic strain M3 (MIC 2 mg/L) or toxigenic strain J9 (MIC 0.75 mg/L) at 1 x 10(6) spores did not result in any colonisation or infection of the animals until day 8, 3 days after the last ampicillin dose. A protection study was designed by giving M3 spores to groups of five animals daily for 5 days beginning on day 1, 3, or 5 of ampicillin. Toxigenic challenge was given with J9 spores on day 3 of each M3 regimen. M3 colonised all animals by day 8 and none became infected with J9. Colonisation by non-toxigenic C. difficile is an effective prevention strategy during antibiotic administration of ceftriaxone or ampicillin, but multiple-day administration is required for ampicillin and colonisation does not occur until several days after the drug is discontinued.

Topics: Ampicillin; Animals; Anti-Bacterial Agents; Antibiosis; Ceftriaxone; Clostridioides difficile; Cricetinae; Drug Resistance, Bacterial; Enterocolitis, Pseudomembranous; Microbial Sensitivity Tests; Probiotics; Survival Analysis

Clostridium difficile-associated diarrhea (CDAD) is a leading cause of nosocomial diarrhea in the United States, and may be associated with significant morbidity and occasional mortality. Diarrhea is also very common among hospitalized patients and is often related to a variety of factors not related to C difficile infection.. We performed a retrospective case-control study at a tertiary care community medical center to delineate factors that are predictive of CDAD among hospitalized patients with new-onset diarrhea (ie, not present at the time of admission). Controls were selected based on negative C difficile toxin test(s) (CDTTs) (> 95% by cytotoxic assay), presence on the same ward as the patients with first positive CDTT, and hospitalization around the same period as the positive cases.. The study involved 352 patients (88 cases and 264 controls). In univariate analysis, age 75 years or greater, exposure to cefazolin or levofloxacin during the 4-week period preceding CDTT, and hospitalization for 7 days or greater before CDTT were significantly associated with a positive test; male gender and prior ceftriaxone exposure nearly reached statistical significance. Multivariate logistic regression analysis revealed age 75 years or greater (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.3-3.7), hospitalization for 7 days or more (OR 2.3, 95% CI 1.3-3.8], and prior exposure to cefazolin (OR 3.5, 95% CI 1.6-7.5) or levofloxacin (OR 2.1, 95% CI 1.2-3.7) as independent predictors of a positive CDTT; male gender nearly achieved statistical significance (OR 1.6, 95% CI 0.9-2.7).. Among hospitalized patients with diarrhea who underwent testing for C difficile toxin, age 75 years or older, hospitalization for 7 days or greater, and recent exposure to cefazolin or levofloxacin were important predictors of a positive CDTT. These findings may help in the initiation of early presumptive treatment for CDAD, and appropriate isolation of higher risk patients before results become available. In addition, consideration of these risk factors may help in deciding whether a CDTT should be repeated when the first test is negative. Our study also supports more judicious use of antibiotics, particularly cefazolin and levofloxacin, in reducing the risk of CDAD in hospitalized patients.

Topics: Aged; Analysis of Variance; Case-Control Studies; Cefazolin; Ceftriaxone; Clostridioides difficile; Confidence Intervals; Cross Infection; Diarrhea; Drug Therapy, Combination; Enterocolitis, Pseudomembranous; Female; Hospitalization; Humans; Incidence; Levofloxacin; Male; Missouri; Multivariate Analysis; Odds Ratio; Ofloxacin; Regression Analysis; Retrospective Studies; Risk Factors

Topics: Aged; Anti-Bacterial Agents; Bacterial Typing Techniques; Ceftriaxone; Colonoscopy; Diagnosis, Differential; Enterocolitis, Pseudomembranous; Female; Humans; Salmonella enterica

Topics: Anti-Bacterial Agents; Ceftriaxone; Child, Preschool; Clostridioides difficile; Diagnosis, Differential; Diarrhea; Edema; Enterocolitis, Pseudomembranous; Esophagus; Female; Fever; Foreign Bodies; Gastritis, Hypertrophic; Humans; Infant; Male; Radiography; Respiratory Sounds; Vomiting

The influence of long-term ceftriaxone administration on the emergence of Clostridium difficile was studied with 80 patients receiving ceftriaxone for 14 days. In five patients (6.3%) C. difficile was cultured. The appearance of gastrointestinal disturbances during treatment with ceftriaxone was common, but the rate of emergence of C. difficile in immunocompetent patients was not high.

Topics: Adolescent; Adult; Aged; Ceftriaxone; Child; Child, Preschool; Clostridioides difficile; Diarrhea; Drug Resistance, Microbial; Enterocolitis, Pseudomembranous; Feces; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged

Lyme disease, now the most common tick-borne illness in the United States, has recently received much media attention, due in part to its potentially serious sequelae in untreated patients. Because a rare patient with late illness may lack antibodies to the etiologic agent, Borrelia burgdorferi, physicians may be tempted to give empiric antibiotics for illnesses that may not be Lyme disease. We have described a patient who, despite negative laboratory evidence for late Lyme disease, was treated for 3 weeks with intravenous ceftriaxone and sustained serious complications, including granulocytopenia, fever, hepatitis, and Clostridium difficile-associated diarrhea. We caution physicians to weight carefully the risks of empiric treatment for ill-defined medical problems, and to recognize the hazards of even "safe" medications.

Topics: Adult; Agranulocytosis; Ceftriaxone; Enterocolitis, Pseudomembranous; Humans; Injections, Intravenous; Lyme Disease; Male; Serologic Tests

Topics: Aged; Ceftriaxone; Ciprofloxacin; Diarrhea; Enterocolitis, Pseudomembranous; Female; Humans; Male