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PubMedDate not supplied

[Nosocomial infections. Some aspects].

Nosocomial infection is not a recent problem. However, it presents nowadays as a serious issue, not only due to the associated morbidity and mortality but also due to the economic burden on hospitals. The increased susceptibility of patients and the increased resistance to antibiotics by bacterial agents are important factors in the present situation. Among the different nosocomial pathogens, methicillin-resistant Staphylococcus aureus and Clostridium difficile are two of the most distressing for hospitals worldwide. Knowledge of their epidemiology, pathological and clinical particularities and treatment are fundamental in the observation and control of these infections. As a result of my recent experience in two teaching hospitals in the United States of America, I have decided to write the present paper.

Bacterial Infections↗
PubMed1995

Usefulness of culture in the diagnosis of Clostridium difficile infection.

Between January and April 1993, culture for Clostridium difficile and a faecal cytotoxin assay were performed on 500 selected specimens. Isolates from culture-positive patients from whom faecal samples were cytotoxin negative were also examined in vitro for cytotoxin production. The significance of a positive culture result in the absence of faecal cytotoxin was assessed. Forty-one of the 500 specimens were toxin positive. In only 25 of these was Clostridium difficile examination specifically requested. Six of nine culture-positive cytotoxin-negative patients (11 specimens) had recently received antibiotics. In four of these, Clostridium difficile was considered to be of possible clinical significance. Culture and in vitro determination of toxin production of isolates may aid in the diagnosis of some additional cases, but cytotoxin detection remains the single optimal routine laboratory method for diagnosis.

Adult↗
PubMed2005

[Reactive arthritis induced by Clostridium difficile enteritis].

This article reports the case of an acute monoarthritis of the ankle occurring in a HLA-B27 positive female patient who presented with diarrhea and fever. We retained the hypothesis of a Clostridium difficile colitis, as she had previously received an antibiotic treatment. The culture of the synovial fluid remained sterile, which postulated that this arthritis was reactive. The diagnosis was confirmed by the presence of toxins A and B in the stool and positive culture. The outcome was satisfactory with metronidazole therapy.

Ankle Joint↗
PubMed1999

Suppression of toxin production in Clostridium difficile VPI 10463 by amino acids.

The impact of various growth conditions on the expression of toxins and other proteins by Clostridium difficile VPI 10463 was studied. During non-starved conditions, the rate of toxin synthesis paralleled that of total protein during both exponential growth and stationary phase, and in both defined and complex media. Biotin limitation reduced growth rate and bulk protein synthesis, whereas toxin expression continued, leading to a 50- to 200-fold increase in intracellular toxin levels. Concomitantly, several 22 kDa proteins were up-regulated as revealed by two-dimensional PAGE analysis. The toxin yield was 30-fold higher in peptone yeast extract (PY) than in PY containing glucose (PYG). By contrast, glucose limitation reduced toxin yields by 20- to 100-fold in defined media. By elevating the buffering capacity and bicarbonate concentration, toxin yields were increased by 10-fold in PY and PYG. The high toxin production by C. difficile during growth in PY was lowered 100-fold by adding a blend of nine amino acids and several 60-100 kDa proteins were concomitantly down-regulated. It was concluded that toxin expression in C. difficile VPI 10463 was not affected by growth rate, growth phase, catabolite repression or the stringent response. Instead the co-expression of toxins and a few specific additional proteins appeared to be influenced by metabolic pathways involving CO2 assimilation, carboxylation reactions and metabolism of certain amino acids.

Amino Acids↗
PubMed1992

Effects of antibiotics and other drugs on toxin production in Clostridium difficile in vitro and in vivo.

In an attempt to understand more completely why patients treated with phenothiazines (chlorpromazine and cyamemazine), methotrexate, and certain antibiotics such as clindamycin have an increased risk of developing pseudomembranous colitis, the production of toxins A and B by Clostridium difficile in the presence of these drugs was measured in vitro as well as in vivo by using axenic mice. None of the drugs tested increased the production of toxins either in vitro or in vivo.

Animals↗
PubMed1996

Effects of Clostridium difficile toxin A and toxin B on phospholipase D activation in human promyelocytic leukemic HL60 cells.

The possible involvement of Rho family GTP-binding proteins in the regulation of phospholipase D (PLD) activity has recently been demonstrated. In the present study, to further examine the role of Rho family proteins in PLD activation of human promyelocytic leukemic HL60 cells, we used toxin A and toxin B from the anaerobic bacterium Clostridium difficile, which was shown to glucosylate Rho family proteins and inhibit their interaction with effectors. Pretreatment of [3H]oleic acid-labeled HL60 cell lysates with either one of the toxins resulted in a remarkable inhibition of membrane PLD activity stimulated by guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS). The magnitude of inhibition of PLD activity was correlated well with the extent of toxin A- or B-induced glucosylation of 22-kDa RhoA in HL60 cells, toxin B being more effective than toxin A. GTPgammaS-stimulated PLD activation measured with the exogenous substrate containing phosphatidylinositol 4,5-bisphosphate was also inhibited by toxin B. Toxin B had no effect on GTP-gammaS-induced translocation of RhoA from cytosol to membranes. Furthermore, the toxin B pretreatment also suppressed PLD activation induced by 4beta-phorbol 12-myristate 13-acetate in HL60 cell lysates. Thus, it was indicated that Rho family proteins play a key role in GTPgammaS- and 40-phorbol 12-myristate 13-acetate-induced PLD activity in HL60 cells. In addition, the results obtained here indicate that C. difficile toxins are a useful tool for researching the regulation of the Rho family protein-mediated PLD activation and also provide a clue toward understanding the pathogenic background of pseudomembranous colitis from the viewpoint of signal transduction.

ADP-Ribosylation Factors↗
PubMed2005

[Relapsing infections with Clostridium difficile].

Two women, aged 78 and 85 years, presented with watery diarrhoea and fever after a course of antibiotic therapy. Pseudo-membranous colitis was diagnosed, which was adequately treated. In both patients the C. difficile colitis relapsed, which was successfully treated with a pulse and tapering scheme of vancomycin. C. difficile infection is a frequent cause of antibiotic-associated diarrhoea. Clinical presentation can vary in severity. Cytotoxin testing, immunoassay and endoscopy are important tools in diagnosing C. difficile colitis. Like the first infection, the first relapse must be treated with metronidazole or vancomycin. To treat a second relapse, a pulse and tapering dose of vancomycin has been recommended. Nevertheless, multiple recurrences may occur, which are difficult to treat.

Aged↗
PubMed1993

Clostridium difficile colitis and diarrhea.

Clostridium difficile is now regarded as the most prevalent nosocomial pathogen, infecting as many as a quarter of hospitalized patients. The pathophysiology of infection with this unusual enteric pathogen involves alteration of the normal enteric flora by antibiotics, ingestion of spores, and colonization by C. difficile. The organism then releases potent exotoxins that produce an inflammatory colitis and diarrhea. A spectrum of host responses occurs, ranging from the asymptomatic carrier state to life-threatening pseudomembranous colitis. Effective therapy with vancomycin or metronidazole is available, but relapses occur in 15% to 20% of patients and may necessitate multiple courses of therapy.

Clostridioides difficile↗
PubMed1996

A predictive model to identify Clostridium difficile toxin in hospitalized patients with diarrhea.

OBJECTIVES: Although Clostridium difficile is a common pathogen in hospitalized patients with diarrhea, no study has attempted to develop a predictive model to estimate the likelihood of C. difficile positivity. METHODS: We conducted a cross-sectional study at a single hospital of 271 patients with diarrhea for whom stool was tested for C. difficile toxin. The sample was randomly divided into a subset to derive the model (n = 180) and another to validate it (n =91), and independent predictors of toxin positivity were identified using logistical regression analysis. RESULTS: C. difficile toxin was present in 81 patients and absent in 190. In the derivation set, a positive toxin was independently predicted (p < 0.0005) by readmission within 2 wk of prior hospitalization, by a white blood cell count > or = 10,000/mm3, and by presence of fecal leukocytes. In the validation set, C. difficile toxin was present in 24, 29, and 77% of patients with 0, 1, and > or = 2 risk factors, respectively. CONCLUSION: If validated prospectively and/or other centers, the model could identify patients who should be considered for empirical management while awaiting results of toxin assays.

Aged↗
PubMed1999

Clostridium difficile-associated diarrhea after short term vaginal administration of clindamycin.

A 32-yr-old woman developed frequent watery diarrhea with occult blood after 3 days treatment with clindamycin vaginal cream. Clostridium difficile toxin was demonstrated in stool samples and was considered the cause of an antibiotic-associated diarrhea. No other antibiotic was used at least 3 months before the start of diarrhea. To our knowledge, antibiotic-associated diarrhea after vaginal application has previously been reported only once.

Administration, Intravaginal↗
PubMed2001

Fatal chemotherapy associated Clostridium difficile infection--a case report.

Clostridium difficile associated diarrhoea or Pseudomembranous colitis occasionally occurs without prior antibiotic usage. While the association of chemotherapy and Clostridium difficile infection has previously been well recorded, the true incidence is unknown. We report a case of Clostridium difficile associated diarrhoea after chemotherapy for lung cancer. The fatal outcome in this case and the increasing use of chemotherapy in this country highlights the need to have a high index of suspicion in any case of unexplained diarrhoea post chemotherapy. A review of the literature is presented.

Aged↗
PubMed2005

[Clostridium difficile toxin A and other enteropathogens in stool specimens of children hospitalized due to acute diarrhoea].

A total of 74 fresh stool specimens obtained from children with acute diarrhoea (43) and without diarrhoea (31) were examined simultaneously for bacteria pathogens (culture methods) and for Clostridium difficile toxin A (Oxoid Toxin A Kits) and enteric viruses (only diarrhoeal samples) (Slidex Rota-Adeno Kits; bioMçrieux). One (49%) or dual with C. difficile (23%) enteric pathogens associated with community-acquired diarrhoea (58% bacteria and 14% viruses) in 31 (72%) children were recognized. Clostridium difficile associated diarrhoea (CDAD) (18,6%) and Salmonella enterica subsp. enterica serovar Enteritidis (16,3%) the most commonly were observed. Children were considered to have CDAD if they met special criteria such as the positive test for C. difficile toxin A, the presence of diarrhoea for at least 2 days and no other documented enteric pathogens. It was be found that antibiotic usage in the previous 3 weeks as a main risk factor for CDAD not be frequent (only 2/8 CDAD). The frequency of C. difficile toxin A detection in the diarrhoeal stool specimens from children treated or not treated with antibiotics was comparable (p>0,05); this same observed when stool specimens from children without diarrhoea were tested. The frequency of toxin A detection in stool specimens from children with acute diarrhoea (41,9%) and without diarrhoea (54,8%) was comparable (p>0,05) also. In conclusion, we recommended detection of toxin A by C. difficile toxin A Test as the rapid screening in diarrhoeal stool specimens only because the high predictive value of a negative test and the high sensitivity for CDAD with special criteria were found.

Acute Disease↗
PubMed2005

Diagnostic role of stool culture & toxin detection in antibiotic associated diarrhoea due to Clostridium difficile in children.

BACKGROUND & OBJECTIVE: Mere diagnosis of Clostridium difficile by culture does not help in the diagnosis of antibiotic associated diarrhoeae (AAD) due to C. difficile. Detection of toxins A and B form the mainstay in the diagnosis of AAD due to C. difficile. This study was undertaken to find out the role of stool culture and toxin detection in the diagnosis of AAD due to C. difficile. As there are very few documented reports from India about AAD due to C. difficile in children in the age group of 5-12 yr, this age group was selected. METHODS: Faecal samples were collected from 250 hospitalized children in the age group of 5-12 yr who developed diarrhoea on receiving antibiotics for different medical problems for more than five days duration. Also faecal samples of 250 age and sex matched controls were collected. Culture for C. difficile was done on cycloserine cefoxitin fructose egg yolk agar (CCFA) and colonies were identified by standard laboratory techniques. ELISA for toxins A and B detection and tissue culture on HeLa cells for toxin B detection were also done. RESULTS: Overall positivity was 18 per cent in this study group compared to the controls (P<0.001). Maximum positive cases were in 5-8 yr age group (84.4%). Severe diarrhoea, liquid stool with mucus and blood, faecal leucocytes >5/high power field, altered flora and presence of Gram-positive bacilli with oval subterminal spores on Gram stain were sensitive predictors for diagnosis of AAD due to C. difficile. Amongst positive cases, 68.9 per cent responded to discontinuation of antibiotics and 31.1 per cent to metronidazole therapy. INTERPRETATION & CONCLUSION: C. difficile was an important pathogen responsible for antibiotic associated diarrhoea (AAD) in children of 5-12 yr age group. Conservative use of antibiotics would be beneficial to decrease the incidence of AAD.

Anti-Bacterial Agents↗
PubMed1997

Clostridium difficile: a microbial enigma.

Nearly 150 years ago, Louis Pasteur introduced the world to the science of microbiology and to the fact that our environment contains microbes capable of causing disease. Subsequent to these discoveries, a pandemic of health care-related staphylococcal infections nearly a century later led to the recognition of hospital-associated (nosocomial) infection. Clearly such infections (nosohusial) now also afflict nursing home residents and patients who receive home health care.

Clostridioides difficile↗
PubMed1996

Clostridium difficile infection as a cause of severe sepsis.

Although colitis is often seen in critically all patients who have received multiple broad-spectrum antibiotics, there are no reports describing severe sepsis as a result of Clostridium difficile infection. We describe three cases of severe sepsis with local intestinal Clostridium difficile infection as the only identifiable etiology. The mechanism of severe sepsis may be a derangement of the gastrointestinal barrier function. This could result in absorption of microbes or endotoxin or activation of inflammatory cascades in the submucosa of the intestine or liver.

Adult↗
PubMed1991

Clostridium difficile--a common and costly colitis.

Clostridium difficile infection manifests as a self-limiting diarrhea, protracted colitis, or toxic pseudomembranous colitis. The incidence of C. difficile in a 514-bed community hospital was studied retrospectively; 155 patients of a total 18,262 admitted during 1988 were identified with C. difficile as an admitting or subsequent diagnosis. The method of diagnosis, mode of therapy, and related costs were analyzed. We have determined that education, with an emphasis on pathogenesis and prevention, is necessary to reduce the incidence in the hospital and the cost to the patient.

Adult↗
PubMed2005

Reduction in nosocomial transmission of drug-resistant bacteria after introduction of an alcohol-based handrub.

OBJECTIVE: To assess quantitatively the clinical impact of using an alcohol-based handrub (ABHR) in the hospital environment, measuring impact as the incidence of new, nosocomial isolates of drug-resistant organisms. DESIGN: An observational survey from 1998 to 2003 comparing the first 3 years of no ABHR use with the 3 years following, when an ABHR was provided for hand hygiene. SETTING: An inner-city, tertiary-care medical center. INTERVENTION: At baseline, an antimicrobial soap with 0.3% triclosan was provided for staff hand hygiene. The intervention was placement in all inpatient and all outpatient clinic rooms of wall-mounted dispensers of an ABHR with 62.5% ethyl alcohol. Data were collected on change in the incidence of three drug-resistant bacteria. RESULTS: During the 6 years of the survey, all new, nosocomially acquired isolates of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and Clostridium difficile-associated diarrhea were recorded. On comparison of the first 3 years with the final 3 years, there was a 21% decrease in new, nosocomially acquired MRSA (90 to 71 isolates per year; P = .01) and a 41% decrease in VRE (41 to 24 isolates per year; P < .001). The incidence of new isolates of C. difficile was essentially unchanged. CONCLUSION: In the 3 years following implementation of an ABHR, this hospital experienced the value of reductions in the incidence of nosocomially acquired drug-resistant bacteria. These reductions provide clinical validation of the recent CDC recommendation that ABHRs be the primary choice for hand decontamination.

Alcohols↗
PubMed2004

Toxin binding of tolevamer, a polyanionic drug that protects against antibiotic-associated diarrhea.

Tolevamer, (GT160-246), is a sodium salt of styrene sulfonate polymer that is under development for the treatment of diarrhea caused by infection with Clostridium difficile. Pulsed ultrafiltration binding experiments in phosphate buffer containing 0.15 M Na(+) provide per polymer chain dissociation constants of 133 nM and 8.7 microM for the binding of tolevamer to C. difficile toxins A and B, respectively. At 0.05 M Na(+), the binding of toxin A to tolevamer is irreversible, whereas the dissociation constant to toxin B under these conditions is 120 nM. Binding constants obtained from fluorescence polarization data for toxin A binding to tolevamer at 0.15 M Na(+) agree substantially with those obtained by pulsed ultrafiltration. The binding activity of tolevamer reported here correlates well with previously reported results for the inhibition of the biological activity of C. difficile toxins A and B. From the fluorescence polarization data, it is estimated that one toxin A molecule interacts with between 600 to 1000 monomer units on tolevamer at 0.15 M Na(+). Thus, the data suggest a very large interaction surface between polymer and toxin A.

Bacterial Toxins↗