François Lamothe

Host and Pathogen Factors for Clostridium difficile Infection and Colonization

BACKGROUND Clostridium difficile infection is the leading cause of health care-associated diarrhea, and the bacterium can also be carried asymptomatically. The objective of this study was to identify host and bacterial factors associated with health care-associated acquisition of C. difficile infection and colonization. METHODS We conducted a 15-month prospective study in six Canadian hospitals in Quebec and Ontario. Demographic information, known risk factors, potential confounding factors, and weekly stool samples or rectal swabs were collected. Pulsed-field gel electrophoresis (PFGE) was performed on C. difficile isolates to determine the genotype. Levels of serum antibodies against C. difficile toxins A and B were measured. RESULTS A total of 4143 patients were included in the study; 117 (2.8%) and 123 (3.0%) had health care-associated C. difficile infection and colonization, respectively. Older age and use of antibiotics and proton-pump inhibitors were significantly associated with health care-associated C. difficile infection. Hospitalization in the previous 2 months; use of chemotherapy, proton-pump inhibitors, and H(2) blockers; and antibodies against toxin B were associated with health care-associated C. difficile colonization. Among patients with health care-associated C. difficile infection and those with colonization, 62.7% and 36.1%, respectively, had the North American PFGE type 1 (NAP1) strain. CONCLUSIONS In this study, health care-associated C. difficile infection and colonization were differentially associated with defined host and pathogen variables. The NAP1 strain was predominant among patients with C. difficile infection, whereas asymptomatic patients were more likely to be colonized with other strains. (Funded by the Consortium de Recherche sur le Clostridium difficile.).

In vitro susceptibility of Clostridium difficile clinical isolates from a multi-institutional outbreak in Southern Québec, Canada.

ABSTRACT Clostridium difficile isolates from a 2004 outbreak in Québec, Canada, were all found to be susceptible to metronidazole, vancomycin, rifampin, and meropenem but resistant to bacitracin, cefotaxime, ciprofloxacin, and levofloxacin, and most (>80%) were resistant to ceftriaxone, clarithromycin, gatifloxacin, and moxifloxacin. The predominant NAP1 isolates were susceptible to clindamycin, while the NAP2 isolates were resistant.

Thiamine deficiency and wernicke's encephalopathy in AIDS

Several neuropathological reports in the last 5 years have described brain lesions characteristic of Wernickes Encephalopathy in patients with AIDS. Using the erythrocyte transketolase activation assay, we now report biochemical evidence of thiamine deficiency in 9/39 (23%) of patients with AIDS or AIDS-related complex. In no cases was there history of alcohol abuse nor were there clinical signs of Wernickes Encephalopathy. Thiamine deficiency in these patients most likely results from the cachexia and catabolic state characteristic of AIDS. In view of (i) the confirmed neuropathological evidence of Wernickes Encephalopathy in AIDS patients, (ii) the significant thiamine deficiency in these patients and (iii) the difficulties of clinical diagnosis of Wernickes Encephalopathy, it is recommended that dietary thiamine supplementation be initiated in all newly diagnosed cases of AIDS or AIDS-related complex.

Role of the beta-lactamase of Campylobacter jejuni in resistance to beta-lactam agents.

We studied the role of the beta-lactamase of Campylobacter jejuni in resistance to beta-lactam agents. beta-Lactamase-positive strains were more resistant than beta-lactamase-negative strains to amoxicillin, ampicillin, and ticarcillin (P less than 0.05). With penicillin G, piperacillin, imipenem, and six cephalosporins, the susceptibility levels were similar for both beta-lactamase-positive and -negative strains. By using spectrophotometric and microbiological assays, the beta-lactamase from three strains hydrolyzed ampicillin, amoxicillin, penicillin G, cloxacillin, and, partially, cephalothin. Ticarcillin and piperacillin were partially hydrolyzed in the microbiological assay. There was no activity against five other cephalosporins or imipenem. Isoelectric focusing of the enzyme showed a pI of 8.8. Tazobactam was the best inhibitor of the enzyme, followed by clavulanic acid, sulbactam, and cefoxitin, while EDTA and p-chloromercuribenzoate had no activity. All beta-lactamase-positive strains became susceptible to amoxicillin and ampicillin with 1 micrograms of clavulanic acid per ml. With the same inhibitor, there was a reduced but significant effect for ticarcillin but no effect for penicillin G or piperacillin. Sulbactam had no effect and tazobactam was effective only at 2 micrograms/ml on amoxicillin and ampicillin. The beta-lactamase of C. jejuni seems to be a penicillinase with a role in resistance for only amoxicillin, ampicillin, and ticarcillin.

Trends in Human Immunodeficiency Virus Incidence and Risk Behavior Among Injection Drug Users in Montreal, Canada: A 16-Year Longitudinal Study

The authors sought to investigate trends in the incidence of human immunodeficiency virus (HIV) infection, evaluate changes in risk behavior, and assess associations between syringe access programs and HIV seroconversion among injection drug users (IDUs) in Montreal, Canada, who were recruited and followed for a prospective cohort study between 1992 and 2008. Methods included Kaplan-Meier survival analysis and time-varying Cox regression models. Of 2,137 HIV-seronegative IDUs at enrollment, 148 became HIV-positive within 4 years (incidence: 3.3 cases/100 person-years; 95% confidence interval: 2.8, 3.9). An annual HIV incidence decline of 0.06 cases/100 person-years prior to 2000 was followed by a more rapid annual decline of 0.24 cases/100 person-years during and after 2000. Behavioral trends included increasing cocaine and heroin use and decreasing proportions of IDUs reporting any syringe-sharing or sharing a syringe with an HIV-positive person. In multivariate analyses, HIV seroconversion was associated with male gender, unstable housing, intravenous cocaine use, and sharing syringes or having sex with an HIV-positive partner. Always acquiring syringes from safe sources conferred a reduced risk of HIV acquisition among participants recruited after 2004, but this association was not statistically significant for participants recruited earlier. In conclusion, HIV incidence has declined in this cohort, with an acceleration of the reduction in HIV transmission after 2000.

Hiv-specific Cd8 T-cell activity in uninfected injection drug users is associated with maintenance of seronegativity

ObjectivesTo determine whether HIV-exposed, uninfected subjects (EUs) having HIV-specific effector activity are at a reduced risk for seroconverting compared with EUs with no HIV-specific effector responses. DesignTwenty-eight intravenous drug users (IVDU) with documented risk for HIV infection over a 1-year period were screened for the presence of HIV-specific CD8+ effector cell activity. Group I included 18 IVDUs who remained seronegative despite exposure to HIV through needle sharing with partner(s) known to be HIV infected. Group II included 10 IVDUs who seroconverted after similar HIV exposure. MethodsThe enzyme-linked immunospot (ELIspot; Mabtech AB, Nacka, Sweden) assay was used to measure the frequency of HIV-specific interferon-γ secreting cells. Peripheral blood mononuclear cells (PBMC) were stimulated with a panel of synthetic HIV peptides in a major histocompatibility complex class I antigen-restricted fashion. PBMC from group II were obtained from timepoints 7 months or less before seroconversion. ResultsTwelve of 18 (66.7%) persistently seronegative subjects versus none of 10 seroconverters exhibited detectable HIV-specific effector responses at the sampling date (P < 0.001; Fishers exact test). This represents an odds ratio of 40.38 (95% confidence intervals 2.95 to > 3000). ConclusionEUs who have developed HIV-specific effector responses are at a reduced risk for seroconversion compared with EUs who do not develop this type of immunity. This observation supports the hypothesis that HIV-specific effector responses are a correlate of immune protection from HIV infection.

Illicit Use of Methadone Among IV Drug Users in Montreal

Few studies have been done on the prevalence of illicit methadone use. Five hundred fifty-nine IV drug users recruited in various ways in Montreal were interviewed concerning their drug use as part of a longitudinal study on HIV infection. Of this number, 133 had heroin as their drug of preference and 426 cocaine. Among the cocaine group, 202 also used heroin. The lifetime prevalence of any illicit methadone use was 59.4% in the heroin group, 26.7% in the cocaine/heroin group, and 3.6% in the cocaine-only group. The 6-month (preceding the interview) prevalence of any illicit use was 42.1%, 6.9%, and 1.3%, respectively, and the prevalence of at least weekly illicit use during that period was 6.3%, 2.0%, and 0%, respectively. The prevalence of illicit methadone use is significant in the population studied. Whether this level of use will be affected by more stringent control on methadone prescription and dispensation remains to be demonstrated.

Susceptibilities of beta-lactamase-positive and -negative strains of Campylobacter coli to beta-lactam agents.

The percentages of susceptibility of 28 strains of Campylobacter coli to beta-lactam agents were 96% for amoxicillin and ampicillin, 57% for ticarcillin, 4% for cefoxitin and cefuroxime, 61% for cefotaxime, and 11% for ceftazidime. None of the strains were susceptible to penicillin G, piperacillin, cefazolin, cephalothin, cefamandole, and cefoperazone. All strains were susceptible to imipenem and ciprofloxacin, and 21% were susceptible to erythromycin. A beta-lactamase was detected in 68% of the strains by cefinase disks and by the nitrocefin method. The beta-lactamase-positive strains were significantly less susceptible to amoxicillin, ampicillin, and ticarcillin than the beta-lactamase-negative strains (P < or = 0.003). Clavulanic acid (0.25 microgram/ml) but not sulbactam and tazobactam (2 micrograms/ml) lowered to susceptible levels the amoxicillin and ampicillin MICs of the only strain of C. coli resistant to amoxicillin, ampicillin, and ticarcillin.

Risk behaviour change and HIV infection among injection drug users in Montreal.

ObjectiveTo investigate the independent association between changes in risk behaviour and HIV seroconversion risk among Montreal injection drug users (IDU). DesignA longitudinal study of risk behaviour change and the maintenance of low-risk practices. At baseline and semi-annually, subjects were tested for HIV, and questionnaires on risk behaviour were completed. ResultsA total of 833 IDU were recruited from January 1992 to June 1998, and completed a minimum of three visits. Large fluctuations in risk behaviour were observed, and the risk of HIV infection appeared to be dependent upon the consistency of risk behaviour practised. IDU who consistently engaged in risky behaviour were at high risk of HIV infection. IDU who attempted to practise low-risk behaviour but experienced relapses to risky behaviour were also at considerable risk of infection. IDU who managed to maintain low-risk practices were at minimal risk. Using Cox regression analysis, the hazard ratio (HR) of HIV seroconversion among IDU who consistently and inconsistently shared needles with an HIV-positive partner was 8.17 (95% CI 3.59–18.59) and 2.63 (95% CI 1.33–5.17), respectively, relative to non-needle sharers. Corresponding HIV incidence rates were 30.42 per 100 person-years (py) among consistent sharers, 13.78 per 100 py among inconsistent sharers and 2.51 per 100 py among non-sharers. ConclusionAlthough some HIV risk reduction was evident, behaviour change seems to be effective only in IDU who adopt and maintain low-risk practices. Additional strategies may be needed to assist IDU in the maintenance of low-risk practices.

Update on Pan-American Activities in the Field of Anaerobes: Canada

During the past 15 years, important contributions have been made to the field of anaerobes in Canada. Studies on the importance of the intestinal flora as a source of vitamin K for humans, investigations of the mechanisms of synergy in polymicrobial infections, and extensive research on the field of immunocompetence of surgical patients have provided interesting and valuable information. Several clinical and epidemiological studies of anaerobic infections have been carried out. Rapid methods have been developed for the identification and susceptibility testing of clinical isolates. National and regional surveys have been conducted on the susceptibility patterns of the Bacteroides fragilis group. Studies on the mechanism of action of metronidazole and on the mechanisms of resistance of Bacteroides species have also been carried out. The Canadian Infectious. Disease Society has published position papers on therapy with cefotetan, ceftizoxime, and imipenem and on antimicrobial prophylaxis in surgical patients.