[Susceptibility of Clostridium difficile to metronidazole using the E-test: effect of the culture medium]. / Sensibilité de Clostridium difficile au métronidazole par le E-test: influence du milieu de culture.

The treatment of intestinal Clostridium difficile infections rests on administration of either a glycopeptide or metronidazole. Given the current shifts in resistance patterns of anaerobes to antimicrobials, a study of the susceptibility of C. difficile to metronidazole was timely. The objective of this study was to evaluate the influence of the culture medium on the Minimal Inhibitory Concentration (MIC) of metronidazole as determined using the E-test. Thirty-one strains were grown on three different media supplemented with 5% horse blood, namely Columbia agar, Wilkens Chalgren agar, and Brucella agar. Results were compared to those obtained using the reference agar dilution method (ADM). As recommended by the French Society for Microbiology, susceptibility was defined as an MIC < or = 4 mg/L. When used on strains susceptible by the ADM, the E-test yielded lower values than the ADM with all three media. Furthermore, findings suggest that E-test results obtained with strains whose MIC is in the 4 to 8 mg/L range by the ADM should be interpreted with caution and, in some cases, tested using the ADM.

Effect of a single oral dose of two erythromycin ethylsuccinate formulations on gastric emptying in healthy volunteers: a scintigraphic study.

Macrolides are potential gastrokinetic agents. The purpose of this study was to assess the effect of a single oral dose of two erythromycin formulations on gastric emptying of the solid and liquid phases in twelve healthy volunteers and to seek a correlation between pharmacokinetic parameters and changes in gastric emptying. The gastric emptying times of liquids and solids were measured simultaneously by means of a scintigraphic technique after a single oral administration of amorphous erythromycin ethylsuccinate (500 mg), crystalline erythromycin ethylsuccinate (1000 mg) or a placebo, in a double-blind crossover study in three separate weeks. Blood samples were obtained for erythromycin assay. The two oral formulations induced a similar acceleration of gastric emptying. When compared to the placebo, both erythromycin preparations significantly shortened the gastric transit time of solids and liquids (respectively 30% and 20% on average, p < 0.01). The incidence of gastrointestinal side-effects was similar with the two erythromycin forms and the placebo. No correlation was found between the peak serum erythromycin concentrations and the solid or liquid gastric half-lives. With the amorphous formulation, the area under the plasma time-concentration curves was small and solid and liquid gastric emptying were strongly accelerated, pointing to a direct effect on the gastrointestinal smooth muscle.

Effects of two oral erythromycin ethylsuccinate formulations on the motility of the small intestine in human beings.

Fourteen-membered macrolides are known to produce alterations in digestive tract motor activity; these include the induction of strong gastric contractions and a decrease in the motility of the small intestine. The aim of the study was to compare the effects of two different formulations of erythromycin ethylsuccinate (EE) on duodenojejunal motility. Compared with the more commonly used crystalline formulation of EE (CEE), the amorphous formulation (AEE) has previously been described to have greater bioavailability and to induce significantly fewer gastrointestinal side effects when given at therapeutic and what have been considered to be equivalent oral doses (i.e., CEE, 1,000 mg every 12 h; AEE, 500 mg every 12 h). In a crossover double-blind study, duodenojejunal manometric recordings were performed for 10 volunteers treated with placebo, CEE at 1,000 mg, or AEE at 500 mg. Recordings for each volunteer were obtained for a fed period after a standard dinner and then for a nocturnal fasting period. When compared with the placebo, CEE significantly decreased the motility index of the duodenum during the 30 min after the peak serum erythromycin concentrations, shortened the duration of the fed state, and had no effect during the fasting state. In contrast, AEE did not significantly modify any motility parameter. Because AEE produced significantly lower concentrations in serum than CEE, these results do not necessarily imply that the two formulations of EE act differently on the motility of the small intestine.

Evaluation of a rapid agglutination test for detection of group B streptococci in the gastric aspirates of neonates.

A rapid commercial agglutination test (Bactigen Strepto B) for detection of group B streptococci in gastric aspirates of neonates was evaluated. One hundred and sixty-one gastric samples were analyzed with conventional bacteriological techniques and with the commercial test after modification of the extraction technique. The sensitivity of the test relative to the culture technique was 90.4%, the specificity 94.2%, the positive predictive value 70.3% and the negative predictive value 98.5%. The commercial test could be performed in one hour and showed good sensitivity and specificity. If a test result was negative colonization could be excluded, obviating the need for empirical antibiotic therapy, whereas a positive result suggested colonization or neonatal infection with group B streptococci.

Enterobacter cloacae cross-colonization in neonates demonstrated by ribotyping.

The intestinal colonization by Enterobacter cloacae strains with a derepressed cephalosporinase was studied in a paediatric ward between February 1990 and January 1991. Environmental sampling was performed simultaneously. Fifty-two isolates were recovered from 200 neonates (stool, blood) and 14 strains were isolated from the neonatal environment. An epidemiological study based on the typing of 36 Enterobacter cloacae isolates was carried out using antibiotyping, biotyping and ribotyping methods. The isolates selected were from 21 neonates (24 isolates), the neonatal ward environment (8 isolates) and from other wards (4 isolates). Thirty-two isolates had the same antibiotic resistance pattern, corresponding to a derepressed cephalosporinase and resistance to the following aminoglycosides: kanamycin, gentamicin, tobramycin and netilmicin. No predominant biotyping pattern could be established. Ribotyping done with two endonucleases (EcoRI and BamHI) showed 28 Enterobacter cloacae isolates to have a single pattern. Ribotyping was the most discriminating method used in this study, permitting identification of cross-contamination with Enterobacter cloacae in the paediatric ward.

[Prevalence of Clostridium difficile and toxin A in feces of HIV infected patients]. / Prévalence de Clostridium difficile et de la toxine A dans les selles de patients VIH positifs.

Patients with AIDS are immunodeficient, receive multiple antibiotic treatments, occasionally anti-cancer chemotherapy and are often hospitalised; thus they are susceptible to develop a Clostridium difficile infection. The aim of this study was to evaluate the role of C. difficile in diarrhoea in this patient population. Therefore, C. difficile and toxin A which plays a major role in pathogenicity were examined in faecal samples of HIV infected patients. Between January 1991 and June 1992, 102 stool samples from 67 patients were studied. Ninety p. cent of these patients were hospitalised (length > 3 days), 80% had a diagnosis of AIDS stage IV, and 66% had diarrhoea. Nineteen point four p. cent of the patients were carriers of C. difficile. Different associations were found: 1) presence of non toxigenic strains and absence of toxin A in stool samples (6 patients), 2) presence of toxigenic strains and absence of toxin A in stool samples (6 patients), 3) presence of toxigenic strains and toxin A in stool samples (2 patients). None of the patients developed a colitis or pseudomembranous colitis. The carrier rate was identical to those found in other hospitalised populations without AIDS. The prevalence of C. difficile diarrhoea or colitis is low. In this study, AIDS patients do not seem to constitute a risk group for C. difficile intestinal pathology. However, carriers of C. difficile were subjected to strict hygiene rules to prevent nosocomial spread.

[Yersinia enterocolitica infections and thalassemia major in children]. / Infections à Yersinia enterocolitica et thalassémie majeure chez l'enfant.

We report two cases of severe Yersinia enterocolitica infection in children with homozygous thalassemia. One patient had septicemia and the other had mesenteric adenitis. Two factors can enhance the infectivity of Yersinia enterocolitica in children with thalassemia: iron overload and deferoxamine therapy. Laparotomy and cefotaxime-netilmicin therapy were successful in the patient with mesenteric adenitis. In the patient with septicemia, cefotaxime-netilmicin, then doxycycline-netilmicin failed, and recovery was finally achieved under rifampicin-netilmicin. Because of the possibility of septicemic dissemination secondary to digestive Yersinia enterocolitica infection in children with thalassemia, we advocate immediate discontinuation of deferoxamine and prescription of oral antimicrobial therapy (trimethoprim-sulfamethoxazole for instance) in every thalassemic patient with febrile diarrhea.

[Implantation of Clostridium difficile in infants during antibiotherapy]. / Implantation de Clostridium difficile chez les nourrissons en cours d'antibiothérapie.

In the adults, it is known that antibiotics allow colonization by C. difficile and its multiplication, in infants this facts is discussed. To study the influence of antibiotic treatment on the colonization of infants' intestinal tract by C. difficile, we searched this bacteria twice a week in hospitalized newborns since their birth. The population was divided in 2 groups: one never received any antibiotic, the other was treated with beta-lactams. C. difficile was isolated on appropriated selective media, and identified by biochemical and enzymatic characters. The antimicrobial susceptibility of the isolated strains was determined by broth dilution method and by broth disk-elution method. In the 2 groups the results did not significantly differ: the colonization rates are 41% in the treated group and 46% in the untreated one. The susceptibility of the strains to the tested antibiotics was similar in the 2 groups. In the environmental and dietetic conditions of our study, the infants' colonization by C. difficile seems to be independent of the antibiotic treatment.

Changes in erythromycin pharmacokinetics induced by renal failure.

As erythromycin ototoxicity appears to be favored by renal insufficiency, its pharmacokinetics were assessed in chronic uremic patients treated by maintenance hemodialysis in comparison with normal subjects. Two groups of 8 patients each were studied, the first one on an interdialytic day, the second immediately after the end of an hemodialysis session. All subjects ingested a single dose of 1 gram of erythromycin ethylsuccinate. Times of peak serum concentration and biological half-lifes were similar in patients and in controls. Maximum serum concentrations and areas under the serum concentration time-curve were higher in patients than in controls whereas apparent oral clearances were lower in the former. The differences between the two groups of patients were not significant. These pharmacokinetic changes are suggestive of an enhanced bioavailability of erythromycin in chronic renal failure which might predispose uremics to the ototoxicity of the drug.

[Clostridium difficile and its cytotoxin in the stools of young hospitalized children. Influence of antibiotic treatment]. / Clostridium difficile et sa cytotoxine dans les selles de jeunes enfants hospitalisés. Influence du traitement antibiotique.

Clostridium difficile has been searched in 153 stool samples from 138 children aged 0 to 12 months. We divided the population in two groups depending on the antibiotic treatment. We have found C difficile in 39 samples (25%). The colonization rate increases with age ranging from 5% before 1 month, to 36% between 1 and 6 months and 54% between 6 and 13 months. An environmental sampling yielded once C difficile. Contamination may be related to the environment. 29% of the isolates produced a cytopathic toxin. Toxin titers in infants' stools range from 1/160 to 1/10240. One only of these children had diarrhea. C difficile and its toxin does not seem to infer any signs of enteric illness with infants. The results obtained with the group of non treated infants are not significantly different from the ones of the other group: the colonization rates are 21% in the non treated group and 29% in the other group. The rate of strains yielding a cytophatic toxin is similar in the 2 groups. It seems reasonable to agree that antibiotics do not influence the settlement of C difficile in infants' intestine.