Predictors of asymptomatic Clostridium difficile colonization on hospital admission.

BACKGROUND: Clostridium difficile (CD) is the leading cause of health care-associated diarrhea and can result in asymptomatic carriage. Rates of asymptomatic CD colonization on hospital admission range from 1.4%-21%. The objective of this study was to evaluate host and bacterial factors associated with colonization on admission. METHODS: The Consortium de recherche québécois sur le Clostridium difficile study provided data for analysis, including demographic information, known risk factors, and potential confounding factors, prospectively collected for 5,232 patients from 6 hospitals in Quebec and Ontario over 15 months from 2006-2007. Stool or rectal swabs were obtained for culture on admission. Pulsed-field gel electrophoresis was performed on the isolates. The presence of antibody against CD toxins A and B was measured. RESULTS: There were 212 (4.05%) patients colonized with CD on admission, and 5,020 patients were not colonized with CD. Multivariate logistic regression analysis showed that hospitalization within the last 12 months, use of corticosteroids, prior CD infection, and presence of antibody against toxin B were associated with colonization on admission. Of patients colonized on admission, 79.4% had non-NAP1, non-NAP2 strains. CONCLUSION: There are identifiable risk factors among asymptomatic CD carriers that could serve in their detection and provide a basis for targeted screening.

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.).

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.

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

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.

A prognostic model for HIV seroconversion among injection drug users as a tool for stratification in clinical trials.

OBJECTIVE: The main goal of this study was to construct a prognostic model for HIV seroconversion among injection drug users (IDUs) using easy-to-measure risk indicators. DESIGN: Cox proportional hazards regression modeling was used for risk stratification in a heterogeneous population of IDUs with regards to HIV risk-taking behaviors. METHODS: Subjects were recruited in a prospective cohort of IDUs followed between September 1992 and October 2001. A total of 1602 men, seronegative at enrollment with at least 1 follow-up visit, were included in the analyses. Only variables that consistently predict HIV seroconversion in several settings were considered. The final model was used to assign a risk score for each participant. RESULTS: Three risk indicators were included in the risk score to predict HIV seroconversion: unstable housing, average cocaine injections per day, and having shared a syringe with a known HIV-positive partner. Kaplan-Meier survival functions were generated and risk score values stratified in 3 groups. HIV incidence rates per 100 person-years were as follows: 0.91 (95% CI, 0.55-1.52) for the low-risk group, 3.10 (95% CI, 2.49-3.84) for the moderate-risk group, and 7.82 (95% CI, 6.30-9.73) for the high-risk group (log-rank P value < 0.0001). CONCLUSION: If validated in other settings, this risk score may improve the prediction of outcome and allow more accurate stratification in clinical trials.

Comparison of HIV-specific CD8 T-cell responses among uninfected individuals exposed to HIV parenterally and mucosally.

OBJECTIVE: To assess the influence of route of HIV exposure on the development of HIV-specific CD8 T-cell responses in exposed, uninfected (EU) individuals. DESIGN: Two groups of EU exposed to virus through either sexual or intravenous contact were studied. Group I included subjects (n = 20) who had unprotected sexual contact with known HIV-infected partners and no intravenous HIV exposure; Group II included individuals (n = 27) who had shared needles with HIV-infected partners and had no sexual exposure to this virus. Between-group comparisons were made for the proportion of responders, breadth, magnitude, and specificity of HIV-specific responses. METHODS: : The interferon-gamma ELISPOT assay was used to detect HIV-specific effector activity. Peripheral blood mononuclear cells (PBMC) from each subject were stimulated with a panel of HIV peptides restricted to the MHC class I alleles expressed by the individual. RESULTS: A similar proportion of EU tested from each group (35.0% Group I versus 22.2% Group II) recognized at least one HIV peptide. Group I and II subjects recognized HIV peptides with a similar cumulative intensity of 130 +/- 67.5 and 182.9 +/- 184.2 spot forming cells/1 x 10 PBMC, respectively, and similar magnitude per stimulatory peptide of 82.7 and 78.4 SFC/1 x 10 PBMC, respectively. The proportion of stimulatory peptides derived from HIV Gag, reverse transcriptase, Env, and Nef was not significantly different between the two EU groups. HLA-A*0201 restricted HIV epitopes immunodominant in infected individuals are rarely stimulatory in EU subjects. CONCLUSIONS: Both mucosal and parenteral exposure to HIV can elicit HIV-specific CD8 T-cell responses with similar characteristics.

Intensity of drug injection as a determinant of sustained injection cessation among chronic drug users: the interface with social factors and service utilization.

AIMS: The objective of this study was to identify factors associated with sustained injection cessation and to examine further the relationship between the occurrence of sustained injection cessation of injection drug users (IDUs) and prior injection frequency. DESIGN AND SETTING: IDUs in the Montreal St Luc Cohort who had at least three consecutive interviews between 1995 and 1999 were included. Sustained injection cessation was defined as a period of at least 7 consecutive months without injection. All IDUs completed interview-administered questionnaires on socio-demographic characteristics, drug and sexual behaviours and health-related issues. Logistic regression was used for analyses. FINDINGS: A total of 186/1004 (18.5%) IDUs reported a period of sustained injection cessation during the study period. In multivariate analysis, HIV-positive status, 'booting' and cumulative time spent in prison were negatively associated with injection cessation, while injection initiation after 35 years of age and frequent crack use were positively associated with injection cessation. We found a negative association between the occurrence of injection cessation and the frequency of injection; the odds ratios (OR) for cessation were 0.49 [95% confidence interval (CI): 0.03, 0.78] for IDUs who injected 30-100 times and 0.21 (95% CI: 0.10, 0.46) for IDUs who injected more than 100 times in the previous month. Attending needle exchange programmes (NEPs) or pharmacies appeared to be a modifier of the relation between cessation and prior injection frequency. The OR was 0.68 (95% CI: 0.42, 1.12) for IDUs who injected 30-100 times prior to injection and attended NEPs or pharmacies and was 0.07 (0.01, 0.30) for IDUs who did not use these services. CONCLUSIONS: Overall, a fifth of IDUs experienced at least one episode of injection cessation of 7 months or more during a period of 4.5 years. Our data suggest that NEPs and pharmacies may have played a role in inducing injection cessation episodes in a subgroup of IDUs. Research is needed to better identify the characteristics of IDUs who could benefit from an injection cessation intervention strategy. This information is important for social and health policy planning.

HIV-specific CD8 T-cell activity in uninfected injection drug users is associated with maintenance of seronegativity.

OBJECTIVES: To 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. DESIGN: Twenty-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. METHODS: The enzyme-linked immunospot (ELIspot; Mabtech AB, Nacka, Sweden) assay was used to measure the frequency of HIV-specific interferon-gamma 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. RESULTS: Twelve 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; Fisher's exact test). This represents an odds ratio of 40.38 (95% confidence intervals 2.95 to > 3000). CONCLUSION: EUs 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.

HIV-positive notification and behavior changes in Montreal injection drug users.

This study examined the effect of an HIV-positive notification on the sexual and injection behaviors, living conditions, and medical demands of injection drug users (IDUs) in Montreal. The behavior changes of 73 IDUs who received an HIV-positive test result, and 219 IDUs who tested negative were compared, and the net difference (ND) in the proportion of IDUs adopting the particular change was determined. No significant changes were found in drug use or needle sharing practices. A higher proportion of IDUs who received an HIV-positive notification acquired unstable living conditions, ND = 20.7% (95% CI = 3.3, 38.1), began medical follow up, ND = 34.4% (95% CI = 20.8, 48.7), and increased needle exchange program (NEP) utilization, ND = 20.5% (95% CI = 8.3, 32.8). Compared with HIV-negative males, more HIV-positive male IDUs stopped sexual relations, ND = 24.6% (95% CI = 0.4, 48.9), and sex work, ND = 31.8% (95% CI = 12.4, 51.3), and fewer began new relations, ND = -38.2% (95% CI = -52.6, -23.9). The medical community and NEPs have an important role in providing support for newly diagnosed IDUs.

Should all stool specimens be routinely tested for Clostridium difficile?

OBJECTIVE: To determine the frequency with which Clostridium difficile was detected in stool specimens from outpatients and patients hospitalized for less than 4 days to assess the usefulness of routine laboratory screening for detecting this enteric pathogen. METHODS: Seven hundred and forty-one specimens from 398 patients were cultured over a 6-month period for Salmonella, Shigella, Yersinia, Escherichia coli O157:H7, Campylobacter and Clostridium difficile. Clostridium difficile culture-positive samples were further tested for cytotoxin production. RESULTS: Campylobacter, Salmonella, Shigella and E. coli O157:H7 were isolated in 50 (6.7%) specimens from 35 (8.8%) patients. Clostridium difficile was cultured from 88 (11.9%) specimens from 35 (8.8%) patients and its cytotoxin detected in 35 (4.7%) specimens of 12 (3%) patients. Clostridium difficile was the second most frequent enteric pathogen after Campylobacter. Of 178 (24%) specimens submitted with a specific request for Clostridium difficile testing, 13 (7.3%) were cytotoxin positive (three patients); of 563 specimens for which Clostridium difficile was not requested, 22 (3.9%) were cytotoxin positive (nine patients). CONCLUSIONS: Nine of 12 patients with cytotoxin-positive specimens would have gone undiagnosed in the laboratory had all stool samples submitted not been tested. These results suggest that Clostridium difficile disease is under-recognized and that testing all stool samples for Clostridium difficile may be warranted in our community of patients.