Clostridium difficile-associated diarrhoea and length of hospital stay.
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In vitro activity of new quinoxaline compounds against Campylobacter species and Clostridium difficile.
SC-44914 and SC-44942-A are two new quinoxaline compounds with a spectrum of activity similar to that of metronidazole. We studied the activity of SC-44914 and SC-44942-A against 35 Campylobacter jejuni, 30 C. coli, and 20 Clostridium (Cl.) difficile and compared it with that of metronidazole by utilizing an agar dilution method. The quinoxalines had little activity against the C. jejuni and C. coli [minimum inhibitory concentration (MIC)90 > or = 64 micrograms/ml]. SC-44914 and SC-44942-A had excellent activity against Cl. difficile (MIC90 < or = 0.06 micrograms/ml for SC 44914, and 0.5 micrograms/ml for SC-44942A).
Anti-Bacterial Agents↗
Passive immunisation of hamsters against Clostridium difficile infection using antibodies to surface layer proteins.
Clostridium difficile is a major cause of antibiotic-associated diarrhoea and the primary cause of pseudomembraneous colitis in hospitalised patients. We assessed the protective effect of anti-surface layer protein (SLP) antibodies on C. difficile infection in a lethal hamster challenge model. Post-challenge survival was significantly prolonged in the anti-SLP treated group compared with control groups (P=0.0281 and P=0.0283). The potential mechanism of action of the antiserum was shown to be through enhancement of C. difficile phagocytosis. This report indicates that anti-SLP antibodies can modulate the course of C. difficile infection and may therefore merit closer investigation for use as constituents of multi-component vaccines against C. difficile associated diarrhoea.
Animals↗
Clostridium difficile and Clostridium perfringens species detected in infant faecal microbiota using 16S rRNA targeted probes.
Clostridium perfringens and Clostridium difficile are pathogenic clostridia potentially associated with gastrointestinal infections and allergy in infants. To enable the molecular detection and quantification of these species in the infant gut, two 16S rRNA oligonucleotide probes were developed: Cdif198 for C. difficile and Cperf191 for C. perfringens. We defined the probes in silico using the RDP sequence database. The probes were then validated using FISH combined with flow cytometry and a collection of target and non-target strains, and faecal samples inoculated with dilutions of C. difficile and C. perfringens strains. These new probes were used to assess the composition of the intestinal microbiota of 33 infants of 1.5 to 18.5 months of age, associated with a panel of 8 probes targeting the predominant faecal bacterial groups of humans. The probes designed allowed detection and quantification of the relative proportions of C. difficile (0.5+/-1.0%) and C. perfringens (2.1+/-2.3%) in the microbiota of infants.
Clostridioides difficile↗
Evaluation of an interdisciplinary re-isolation policy for patients with previous Clostridium difficile diarrhea.
BACKGROUND: Diarrhea caused by Clostridium difficile is increasingly recognized as a nosocomial problem. The effectiveness and cost of a new program to decrease nosocomial spread by identifying patients scheduled for readmission who were previously positive for toxin was evaluated. METHODS: The Memorial Sloan-Kettering Cancer Center is a 410-bed comprehensive cancer center in New York City. Many patients are readmitted during their course of cancer therapy. In 1995 as a result of concern about the nosocomial spread of C difficile, we implemented a policy that all patients who were positive for C difficile toxin in the previous 6 months with no subsequent toxin-negative stool as an outpatient would be placed into contact isolation on readmission pending evaluation of stool specimens. Patients who were previously positive for C difficile toxin were identified to infection control and admitting office databases via computer. Admitting personnel contacted infection control with all readmissions to determine whether a private room was required. RESULTS: Between July 1, 1995, and June 30, 1996, 47 patients who were previously positive for C difficile toxin were readmitted. Before their first scheduled readmission, the specimens for 15 (32%) of these patients were negative for C difficile toxin. They were subsequently cleared as outpatients and were readmitted without isolation. Workup of the remaining 32 patients revealed that the specimens for 7 patients were positive for C difficile toxin and 86 isolation days were used. An additional 25 patients used 107 isolation days and were either cleared after a negative specimen was obtained in-house or discharged without having an appropriate specimen sent. Four patients (9%) had reoccurring C difficile after having toxin-negative stools. We estimate (because outpatient specimens were not collected) the cost incurred at $48,500 annually, including the incremental cost of hospital isolation and equipment. CONCLUSION: Our policy to control the spread of nosocomial C difficile required interdisciplinary cooperation between infection control and the admitting department. By identifying patients who were positive for toxin through admitting, we were able to place all potentially infected patients into isolation. Our positivity rate of 15% on readmission demonstrates the importance of this policy. The cost of controlling C difficile can be significantly lowered by clearing patients who were previously positive for toxin before hospital readmission.
Cancer Care Facilities↗
Prospective evaluation of environmental contamination by Clostridium difficile in isolation side rooms.
We determined prospectively the frequency, persistence and molecular epidemiology of Clostridium difficile environmental contamination after detergent-based cleaning in side rooms used to isolate patients with C. difficile diarrhoea. Approximately one-quarter of all environmental sites in side rooms sampled over four-week periods were contaminated with C. difficile. The overall side room prevalence of environmental C. difficile declined from 35% initially, to 24% in week 2, 18% in week 3, and 16% in week 4. The bed frame was the most common site from which C. difficile was recovered, although the floor was the most contaminated site in terms of total numbers of colonies. C. difficile was recovered significantly more frequently from swabs plated directly on to C. difficile selective media containing lysozyme than from enrichment broth (P< 0.001), emphasizing the benefit of lysozyme supplementation. The great majority of C. difficile isolates (87% of all isolates, 84% of patient isolates) was indistinguishable from the UK epidemic strain (PCR ribotype 1). It thus could not be determined whether environmental contamination was a cause or a consequence of diarrhoea. Our findings highlight the need for improved approaches to hospital environmental hygiene, and call into question current UK guidelines that recommend detergent-based cleaning to remove environmental C. difficile. In particular, improved cleaning of frequently touched sites in the immediate bed space area is required.
Adult↗
Prevalence of the ermB gene in Clostridium difficile strains isolated at a university teaching hospital from 1987 through 1998.
We analyzed 226 strains of Clostridium difficile for the presence of erythromycin ribosomal methylase B (ermB) genes. Forty-four strains (19.4%) carried ermB genes and were resistant to erythromycin. Toxin A and toxin B gene sequences were identified in 81.9% of these 44 strains. Strains of C. difficile that carry ermB genes are common etiologic agents of C. difficile-associated diarrhea.
Anti-Bacterial Agents↗
In vitro activity of new quinolones against Clostridium difficile.
We evaluated the in vitro activities of ofloxacin, levofloxacin, grepafloxacin, trovafloxacin and ciprofloxacin against Clostridium difficile. The MIC(90) was 128 mg/L for ofloxacin and levofloxacin, 64 mg/L for ciprofloxacin, 16 mg/L for grepafloxacin and 8 mg/L for trovafloxacin. Thirty per cent of isolates were resistant to trovafloxacin, and rates of resistance to ofloxacin, levofloxacin, grepafloxacin and ciprofloxacin were considerably higher. None of the antimicrobials studied would be a reliable therapeutic option against C. difficile. Whether some of the new fluoroquinolones can induce C. difficile-associated diarrhoea remains to be answered.
4-Quinolones↗
Failure of dietary oligofructose to prevent antibiotic-associated diarrhoea.
BACKGROUND: Oligofructose is metabolized by bifidobacteria, increasing their numbers in the colon. High bifidobacteria concentrations are important in providing 'colonization resistance' against pathogenic bacteria. AIM: To reduce the incidence of antibiotic-associated diarrhoea in elderly patients. METHODS: Patients over the age of 65 taking broad-spectrum antibiotics received either oligofructose or placebo. A baseline stool sample was cultured for Clostridium difficile and tested for C. difficile toxin. A further stool sample was analysed for C. difficile if diarrhoea developed. RESULTS: No difference was seen in the baseline characteristics, incidence of diarrhoea, C. difficile infection or hospital stay between the two groups (n = 435). Oligofructose increased bifidobacterial concentrations (P < 0.001, 95% CI: 0.69-1.72). A total of 116 (27%) patients developed diarrhoea of which 49 (11%) were C. difficile-positive and were more likely to be taking a cephalosporin (P = 0.006), be female (P < 0.001), to have lost more weight (P < 0.001, 95% CI: 0.99-2.00) and stayed longer in hospital (P < 0.001, 95% CI: 0.10-1.40). Amoxicillin (amoxycillin) and clavulanic acid increased diarrhoea not caused by C. difficile (P = 0.006). CONCLUSION: Oligofructose does not protect elderly patients receiving broad-spectrum antibiotics from antibiotic-associated diarrhoea whether caused by C. difficile or not. Oligofructose was well-tolerated and increased faecal bifidobacterial concentrations.
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Serum antitoxin antibodies mediate systemic and mucosal protection from Clostridium difficile disease in hamsters.
Clostridium difficile is the bacterial pathogen identified as the cause of pseudomembranous colitis and is principally responsible for nosocomial antibiotic-associated diarrhea and colitis. The pathologic findings associated with this infection are believed to be caused by two large (approximately 300-kDa) exotoxins, toxins A and B. Because of the mucosal nature of this infection, vaccination strategies aimed at providing prophylactic or therapeutic immune protection have included immunization by mucosal routes. Using the hamster model of C. difficile infection, we examined the protective efficacy of inactivated toxin (toxoid) vaccine formulations prepared as either culture filtrate or partially purified toxoid. We compared combination parenteral and mucosal vaccination regimens involving intranasal, intragastric, or rectal routes of immunization and found that rectal immunization in conjunction with intramuscular (i.m.) vaccination provided full protection of hamsters from death and diarrhea while the other mucosal routes did not. Protection was associated with high levels of toxin-neutralizing antibodies in serum. The requirement for adjuvants for protection was assessed by using sequential i.m. and rectal or i.m. vaccination regimens. Unexpectedly, i.m. immunization without adjuvant conferred the highest protection from death and diarrhea; this regimen elicited the highest serum anti-toxin B titers as well as toxin B neutralizing titers. Passive transfer of mouse antitoxin antibodies protected hamsters in a dose-dependent manner, demonstrating the principal role of circulating antitoxin antibodies in immunity from this toxin-mediated mucosal disease. These results suggest that prophylactic parenteral vaccination or intravenous immunotherapy could provide protection from C. difficile disease in humans.
Animals↗
Diarrheal disease due to Clostridium difficile in general practice.
A total of 288 stool samples from patients attending their general practitioners was examined for the presence of Clostridium difficile. C. difficile or its cytotoxin was found in 16 patients (5.5%) and was the most common enteric pathogen detected. Most patients had only mild to moderate diarrhea but in the majority of patients the diarrhea was protracted. Eleven of the 16 patients had received antimicrobial agents in the 3 mths preceding onset of diarrhea and there was good circumstantial evidence that 2 other patients had also been exposed. None of the patients had a history of any inflammatory bowel disease or possible occupational exposure. The prescribing habits of general practitioners with regard to antimicrobial agents were monitored for a 1 yr period. Tetracyclines and amoxycillin accounted for approximately 25% each of all prescriptions dispensed. Ten of the 16 patients were treated with antimicrobials (mainly metronidazole) and in most cases the diarrhea resolved. We conclude that C. difficile may be a significant cause of community-acquired diarrhea.
Adult↗
"Collateral damage": antibiotics and the risk of Clostridium difficile infection.
Patients undergoing orthopedic surgery are at increased risk for infection, and antimicrobial use continues to be required. Antimicrobial selection, however, is an important consideration given the increasing incidence and severity of C. difficile infection described in the literature. When choosing antimicrobials for prophylaxis and treatment, evaluate patients for risk factors that may predispose them to C. difficile infection. Patients receiving multiple antibiotics or broad-spectrum antibiotics, women, patients with concurrent proton pump inhibitor use, and those with renal failure are at increased risk. Choice of antibiotics should be evaluated for their potential or likelihood to cause C. difficile infection. When a number of these risk factors are present, avoiding the use of high-risk antibiotics may be warranted.
Antibiotic Prophylaxis↗
Value of Clostridium difficile antigen test in immunocompromised hosts in the tropics.
39 fecal and body fluid specimens of immunocompromised patients who developed diarrhoea were tested for Clostridium difficile antigen test. The test was identified in only 11 and in one ascitic fluid. Endoscopy was performed in 5 patients and it showed pseudomembranous colitis in one. Numerous antibiotics were associated with C. difficile related diarrhea: ampicillin, 43%; cephalosporins, 43% and clindamycin, 14%. Three Salmonella sp., and one Entamoeba histolytica were detected among patients who later developed C. difficile associated diarrhea. The effect of oral vancomycin and fusidic acid was demonstrated in patients with C. difficile related diarrhea or colitis. The C. difficile antigen test is promising diagnostic tool in immunocompromised hosts in the tropics where both Salmonella and E. histolytica all are endemic.
Anti-Bacterial Agents↗
Clostridium difficile-associated diarrhea in patients with HIV positivity and AIDS: a prospective controlled study.
OBJECTIVE: To compare the clinical manifestations and therapeutic responses of Clostridium difficile infection in HIV-infected and noninfected individuals. METHODS: Patients were identified for this study if they had C. difficile toxin in the stool. The patients were then followed prospectively by the investigators. All patients were treated with a standard regimen, and clinical and laboratory findings were recorded. Persistence and resolution or recurrence of symptoms and complications were recorded. RESULTS: A total of 87 patients were studied, of which 12 were HIV positive, 20 had AIDS, and 55 had no known HIV infection. The AIDS group was younger and had a lower total leukocyte count than the controls. There were no statistically significant differences in temperature, leukocytosis, clinical symptoms, therapeutic response, or recurrence or persistent of symptoms. CONCLUSIONS: Despite the immunosuppression of HIV infection, C. difficile infection behaves no differently in HIV/AIDS patients than it does in controls.
AIDS-Related Opportunistic Infections↗
[In vitro activities of sulopenem, a new parenteral penem, against anaerobes].
In vitro activities of sulopenem, a novel parenteral penem, was compared with those of imipenem, flomoxef, cefuzonam, cefoperazone and sulbactam/ampicillin against 66 reference strains (19 genera, 61 species) and 392 recent clinical isolates of anaerobic bacteria and fastidious aerobic bacteria. Sulopenem had a very broad spectrum against anaerobic bacteria. In general, this compound was active against anaerobic reference strains with MICs of < or = 0.78 micrograms/ml, while being the least active against Bifidobacterium spp. and less active than imipenem against Lactobacillus spp. Sulopenem was more active against Bacteroides fragilis isolates than imipenem and had the highest activities against Bacteroides thetaiotaomicron, Prevotella intermedia, Porphyromonas gingivalis, Fusobacterium spp. and Peptostreptococcus spp. among the antibiotics tested. Sulopenem was not hydrolyzed by oxyiminocephalosporinase type 1 produced by B. fragilis GAI-0558, GAI-7955 and GAI-10150 and its stability was comparable to imipenem. Its susceptibilities to hydrolysis by a metallo-beta-lactamase from B. fragilis GAI-30144 was less than imipenem. Sulopenem (120 mg/kg, 3 times a day for 4 days) was as effective as imipenem/cilastatin against a mixed intraabdominal mice infection due to E. coli and B. fragilis. Sulopenem (20 mg/kg twice a day for 5 days) did not induce an overgrowth of Clostridium difficile in the caecum of mice.
Ampicillin↗
Clostridium difficile-associated diarrhea in rheumatoid arthritis patients who are receiving therapy with low-dose chlorambucil.
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Clostridium difficile PCR ribotype 027 outbreaks in the Netherlands: recent surveillance data indicate that outbreaks are not easily controlled but interhospital transmission is limited.
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Clostridioides difficile↗
Clostridium difficile-associated pouchitis.
Pouchitis is the most common long-term sequela of ileal pouch-anal anastomosis (IPAA) following total proctocolectomy. No single pathogen is identified as being solely responsible for the pathogenesis of the disease. Here we describe a case of Clostridium difficile-associated pouchitis that was successfully treated with ciprofloxacin and tinidazole. Diagnosis and management of a patient with medically refractory pouchitis associated with Clostridium difficile infection is described. A 63-year-old male with underlying ulcerative colitis and IPAA presented with increased stool frequency and seepage for 2 months, which partially responded to oral metronidazole. While on the antibiotic therapy, pouch endoscopy was performed and showed severe pouchitis. Assays for Clostridium difficile toxins in stool specimens were positive. He was treated with a 4-week course of ciprofloxacin 500 mg BID and tinidazole 500 mg TID. His symptoms resolved within several days from the initiation of therapy. A repeat pouch endoscopy at week 5 showed a complete resolution of mucosal inflammation of the pouch, while tests for Clostridium difficile toxins became negative. Clostridium difficile-associated pouchitis is rare. However, Clostridium difficile infection should be excluded in patients with chronic refractory pouchitis.
Anti-Infective Agents↗