ro13-9904 and Clostridium-Infections

Clostridium difficile infection (CDI) remains one of the most important healthcare-associated infections of the last two decades. The pathogen is a Gram-positive, toxin-producing, anaerobic, rod-shaped and sporeforming bacterium; it is ubiquitous in the human environment. Transmission occurs by the fecal-oral route. The consequence of the action of bacterial toxins is initially a local inflammatory reaction, which then goes into systemic inflammation. Clinical presentation is varied; some patients are asymptomatic, in symptomatic form the main symptom is diarrhea of varying severity, which is sometimes accompanied by acute abdominal pain, nausea, vomiting and high fever. Risk factors of CDI include prior antibiotic use, increasing age and recent hospitalisation. Extremely rarely does CDI occur in immunocompetent patients under 30 years of age, even if previously treated with an antibiotic. Here presented are two untypical cases of CDI development in the lower age group, in the presence of additional risk factors of comorbid gastrointestinal tract infections. Both developed infections are following recent infection - Salmonella enterididis in the first case and Salmonella typhi in the second case. Therefore, the article also contains basic principles for the diagnosis and treatment of Salmonella spp.

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Ceftriaxone; Clostridioides difficile; Clostridium Infections; Female; Humans; Metronidazole; Risk Factors; Salmonella enteritidis; Salmonella Infections; Salmonella typhi; Treatment Outcome; Vancomycin

Topics: Ceftriaxone; Clostridioides difficile; Clostridium Infections; Emergencies; Gases; Gastritis; Gastroscopy; Gentamicins; Humans; Laparotomy; Male; Middle Aged; Portal Vein; Risk Factors; Tomography, X-Ray Computed; Treatment Outcome

We determined the in vitro activity of SMT19969 and 11 comparators, including metronidazole, vancomycin, and fidaxomicin, against 107 C. difficile isolates of different antimicrobial resistance phenotypes. Fidaxomicin and SMT19969 were the most active. The fidaxomicin and SMT19969 geometric mean MICs were highest in ribotypes known to show multiple resistance. Coresistance to linezolid and moxifloxacin was evident in ribotypes 001, 017, 027, and 356. The high-level ceftriaxone resistance in ribotypes 356 and 018 was location linked.

Topics: Aminoglycosides; Anti-Bacterial Agents; Benzimidazoles; Ceftriaxone; Clostridioides difficile; Clostridium Infections; Drug Resistance, Multiple, Bacterial; Fidaxomicin; Fluoroquinolones; Humans; Linezolid; Metronidazole; Microbial Sensitivity Tests; Moxifloxacin; Phenotype; Pyridines; Ribotyping; Vancomycin

Clostridium difficile infection (CDI) is one of the most common gastrointestinal complication after antimicrobial treatment. It is estimated that CDI after pneumonia treatment is connected with a higher mortality than other causes of hospitalization. The aim of the study was to assess the relationship between the kind of antibiotic used for pneumonia treatment and mortality from post-pneumonia CDI. We addressed the issue by examining retrospectively the records of 217 patients who met the diagnostic criteria of CDI. Ninety four of those patients (43.3 %) came down with CDI infection after pneumonia treatment. Fifty of the 94 patients went through severe or severe and complicated CDI. The distribution of antecedent antibiotic treatment of pneumonia in these 50 patients was as follows: ceftriaxone in 14 (28 %) cases, amoxicillin with clavulanate in 9 (18 %), ciprofloxacin in 8 (16.0 %), clarithromycin in 7 (14 %), and cefuroxime and imipenem in 6 (12 %) each. The findings revealed a borderline enhancement in the proportion of deaths due to CDI in the ceftriaxone group compared with the ciprofloxacin, cefuroxime, and imipenem groups. The corollary is that ceftriaxone should be shunned in pneumonia treatment. The study demonstrates an association between the use of a specific antibiotic for pneumonia treatment and post-pneumonia mortality in patients who developed CDI.

Topics: Aged; Aged, 80 and over; Amoxicillin; Anti-Bacterial Agents; Ceftriaxone; Cefuroxime; Ciprofloxacin; Clarithromycin; Clavulanic Acid; Clostridioides difficile; Clostridium Infections; Cross Infection; Female; Hospitalization; Host-Pathogen Interactions; Humans; Imipenem; Male; Pneumonia; Retrospective Studies; Treatment Outcome

Since data about Clostridium difficile infection in sub-Saharan Africa are scarce, we determined its epidemiology and risk factors in a cross-sectional study in Eikwe, a rural community in Ghana. We tested stool samples from 176 hospitalized patients with diarrhoea and from 131 asymptomatic non-hospitalized individuals for C. difficile and some other enteric pathogens. The overall prevalence rate of C. difficile was 4.9% with ribotype 084 being predominant. With 75% of the isolates, a high rate of nontoxigenic strains was present in symptomatic patients, most of whom had no other identified enteric pathogens. All strains were susceptible against metronidazole and vancomycin, respectively. Data on lifestyle and medical history showed that age <5years (p=0.004), and use of ceftriaxone (p=0.023) were the most important risk factors for C. difficile carriage status. Although our data suggest that C. difficile is currently not a major cause of diarrhoea in this setting, the epidemiology of C. difficile in sub-Saharan Africa awaits further investigation.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Toxins; Carrier State; Ceftriaxone; Child; Child, Preschool; Clostridioides difficile; Clostridium Infections; Cross-Sectional Studies; Diarrhea; Feces; Female; Ghana; Hospitalization; Humans; Infant; Infant, Newborn; Male; Metronidazole; Microbial Sensitivity Tests; Middle Aged; Prevalence; Prospective Studies; Ribotyping; Risk Factors; Rural Population; Vancomycin; Young Adult

To examine the effects of exposure to ceftaroline or ceftriaxone on the epidemic Clostridium difficile strain PCR ribotype 027 and the indigenous gut microflora in an in vitro human gut model. Additionally, the MICs of ceftriaxone and ceftaroline for 60 C. difficile isolates were determined.. Two triple-stage chemostat gut models were primed with human faeces and exposed to ceftaroline (10 mg/L, twice daily, 7 days) or ceftriaxone (150 mg/L, once daily, 7 days). Populations of indigenous gut microorganisms, C. difficile total viable counts, spore counts, cytotoxin titres and antimicrobial concentrations were monitored throughout. MICs were determined by a standard agar incorporation method.. In the gut model, both ceftaroline and ceftriaxone induced C. difficile spore germination, proliferation and toxin production, although germination occurred 5 days later in the ceftaroline-exposed model. Toxin detection was sustained until the end of the experimental period in both models. No active antimicrobial was detected in vessel 3 of either model, although inhibitory effects on microflora populations were observed. Ceftaroline was ∼8-fold more active against C. difficile than ceftriaxone (geometric mean MICs, 3.38 versus 28.18 mg/L; MIC90s, 4 versus 64 mg/L; and MIC ranges, 0.125-16 versus 8-128 mg/L).. Ceftaroline, like ceftriaxone, can induce simulated C. difficile infection in a human gut model. However, low in vivo gut concentrations of ceftaroline and increased activity against C. difficile in comparison with ceftriaxone mean that the true propensity of this novel cephalosporin to induce C. difficile infection remains unclear.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Load; Bacterial Toxins; Ceftaroline; Ceftriaxone; Cephalosporins; Clostridioides difficile; Clostridium Infections; Gastrointestinal Tract; Healthy Volunteers; Human Activities; Humans; Microbial Sensitivity Tests; Models, Theoretical

Increased incidence and severity of Clostridium difficile infections (CDIs) is of major concern. However, by minimizing known risk factors, the incidence can be decreased. The aim of this investigation was to calculate the incidence and assess risk factors for CDI in our population. A 1-year prospective population-based nationwide study in Iceland of CDIs was carried out. For risk factor evaluation, each case was matched with two age- and sex-matched controls that tested negative for C. difficile toxin. A total of 128 CDIs were identified. The crude incidence was 54 cases annually per 100,000 population >18 years of age. Incidence increased exponentially with older age (319 per 100,000 population >86 years of age). Community-acquired origin was 27 %. Independent risk factors included: dicloxacillin (odds ratio [OR]: 7.55, 95 % confidence interval [CI]: 1.89-30.1), clindamycin (OR: 6.09, 95 % CI: 2.23-16.61), ceftriaxone (OR: 4.28, 95 % CI: 1.59-11.49), living in a retirement home (OR: 3.9, 95 % CI: 1.69-9.16), recent hospital stay (OR: 2.3, 95 % CI: 1.37-3.87). Proton pump inhibitors (PPIs) were used by 60/111 (54 %) versus 91/222 (41 %) (p = 0.026) and ciprofloxacin 19/111 (17 %) versus 19/222 (9 %) (p = 0.027) for cases and controls, respectively. In all, 75 % of primary CDIs treated with metronidazole recovered from one course of treatment. CDI was mostly found among elderly patients. The most commonly identified risk factors were broad-spectrum antibiotics and recent contact with health care institutions. PPI use was significantly more prevalent among CDI patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; Bacterial Toxins; Case-Control Studies; Ceftriaxone; Child; Child, Preschool; Clindamycin; Clostridioides difficile; Clostridium Infections; Community-Acquired Infections; Confidence Intervals; Diarrhea; Dicloxacillin; Enterotoxins; Female; Humans; Iceland; Incidence; Infant; Length of Stay; Male; Metronidazole; Middle Aged; Odds Ratio; Prospective Studies; Proton Pump Inhibitors; Risk Factors; Treatment Outcome; Young Adult

The impact of changes in antibiotic policy on Clostridium difficile-associated diarrhoea (CDAD), over a five-year period between 1995 and 2000, were studied in the Preston Acute Hospitals Trust. In 1996 the policy was changed in the Preston Acute Hospitals Trust from cefotaxime to ceftriaxone for initial treatment of severe sepsis or pneumonia in medical patients. Over the next nine months the average number of patients with C. difficile toxin-positive stools per quarter increased from 16 to 39. The predicted use of ceftriaxone exceeded by 65% an estimate based on prior use of cefotaxime. A policy of restricted duration of ceftriaxone was introduced, and although this reduced usage by over 50%, CDAD continued at an average of 9.2 cases per month, despite withdrawal of oral cephalosporins in December 1998. In August 1999 levofloxacin was substituted for ceftriaxone in the policy. The incidence of CDAD fell progressively to five cases per month by 2000. It would appear that a short (typically three dose) course of third-generation cephalosporin poses a similar risk for CDAD as a more prolonged course. The six-month delay in the decline of CDAD after virtual withdrawal of cephalosporins may reflect a slowly diminishing environmental reservoir.

Topics: Anti-Bacterial Agents; Ceftriaxone; Clostridioides difficile; Clostridium Infections; Cross Infection; Diarrhea; Drug Utilization Review; England; Feces; Hospitals, District; Hospitals, General; Humans; Incidence; Infection Control; Organizational Policy; Patient Selection; Practice Patterns, Physicians'; Risk Factors

Topics: Adult; Ceftriaxone; Cephalosporins; Clostridium Infections; Diagnosis, Differential; Echocardiography; Endocarditis; Enterobacteriaceae Infections; Escherichia; Heart Injuries; Humans; Male; Wounds, Gunshot

Convalescent outpatient parenteral antibiotic therapy with ceftriaxone was evaluated in an uncontrolled study of 101 children with documented serious bacterial infections, including meningitis. Criteria for outpatient therapy were established to assure that risks of complications from the illness were minimal at the time of discharge from the hospital. Daily physician visits and motivated, capable parents were considered essential in outpatient management. Ceftriaxone was given once daily to children with non-central nervous system infections and once or twice daily intravenously to children with meningitis. The mean durations of therapy for children with non-central nervous system infections and with meningitis were 2.4 and 4.6 days, respectively. No child enrolled in this study was readmitted to the hospital for medical or social reasons. Probable complications of treatment included diarrhea in 13% of children with meningitis and in 6% of children with non-central nervous system infections. One child with meningitis developed pseudomembranous colitis. For children who are infected with bacteria that are highly susceptible to ceftriaxone, single daily dose outpatient therapy is a reasonable option for management if a good clinical response to initial treatment is demonstrated and the risks of complications of the disease process are negligible.

Topics: Adolescent; Ambulatory Care; Bacterial Infections; Bacterial Toxins; Blood Bactericidal Activity; Ceftriaxone; Child; Child, Preschool; Clostridium Infections; Diarrhea; Feces; Female; Humans; Infant; Infant, Newborn; Male; Meningitis; Prognosis; Prospective Studies