Annie-Claude Labbé

Impact of Emergency Colectomy on Survival of Patients With Fulminant Clostridium difficile Colitis During an Epidemic Caused by a Hypervirulent Strain

Objectives:To determine whether emergency colectomy reduces mortality in patients with fulminant Clostridium difficile-associated disease (CDAD), and to identify subgroups of patients more likely to benefit from the procedure. Summary Background Data:Many hospitals in Quebec, Canada, have noted since 2003 a dramatic increase in CDAD incidence and in the proportion of cases severe enough to require intensive care unit (ICU) admission. The decision to perform an emergency colectomy remains largely empirical. Methods:Retrospective observational cohort study of 165 cases of CDAD that required ICU admission or prolongation of ICU stay between January 2003 and June 2005 in 2 tertiary care hospitals of Quebec. Multivariate analysis was performed through logistic regression; adjusted odds ratios (AOR) and their 95% confidence intervals (CI) were calculated. The primary outcome was mortality within 30 days of ICU admission. Results:Eighty-seven (53%) cases resulted in death within 30 days of ICU admission, almost half (38 of 87, 44%) within 48 hours of ICU admission. The independent predictors of 30-day mortality were: leukocytosis ≥50 × 109/L (AOR, 18.6; 95% CI, 3.7–94.7), lactate ≥5 mmol/L (AOR, 12.4; 95% CI, 2.4–63.7), age ≥75 years (AOR, 6.5; 95% CI, 1.7–24.3), immunosuppression (AOR, 7.9; 95% CI, 2.3–27.2) and shock requiring vasopressors (AOR, 3.4; 95% CI, 1.3–8.7). After adjustment for these confounders, patients who had an emergency colectomy were less likely to die (AOR, 0.22; 95% CI, 0.07–0.67, P = 0.008) than those treated medically. Colectomy seemed more beneficial in patients aged 65 years or more, in those immunocompetent, those with a leukocytosis ≥20 × 109/L or lactate between 2.2 and 4.9 mmol/L. Conclusion:Emergency colectomy reduces mortality in some patients with fulminant CDAD.

Molecular Analysis of Clostridium difficile PCR Ribotype 027 Isolates from Eastern and Western Canada

ABSTRACT The prevalence and characteristics of PCR ribotype 027 strains of Clostridium difficile have come into question following recent outbreaks in Eastern Canada and elsewhere. In order to determine the distribution of this strain in other regions in Canada, we screened a bank of 1,419 isolates recovered from three different Canadian health regions between 2000 and 2004. Among isolates from a Montreal area hospital, PCR ribotype 027 strains represented 115/153 strains (75.2%) from 2003 to 2004, but ribotype 027 strains were absent in 2000 and 2001. In Calgary, by contrast, ribotype 027 rates have remained relatively stable over 4 years of surveillance, representing 51/685 (7.4%) hospital isolates and 62/373 (16.6%) strains from the community (P < 0.001). PCR ribotype 027 accounted for 8/135 (5.9%) hospital isolates in the Fraser Health Region in 2004. repetitive extragenic palindromic PCR was used to subtype a random selection of 027 isolates from each region. All 10 of the isolates from Quebec were of a single subtype, which was also dominant among isolates from Alberta (8/10 isolates) and British Columbia (6/8 isolates). Comparative sequencing of the tcdC repressor gene confirmed the documented 18-bp deletion and identified a second, single-base-pair deletion at position 117. Both deletions were conserved across all three provinces and were identified in a United Kingdom reference strain. The presence of a frameshift in the early portion of the tcdC gene implies serious functional disruption and may contribute to the hypervirulence of the 027 phenotype. PCR ribotype 027 strains appear to be widely distributed, to predate the Montreal outbreak, and to have measurable community presence in Western Canada.

Clostridium difficile Infections in a Canadian Tertiary Care Hospital before and during a Regional Epidemic Associated with the BI/NAP1/027 Strain

ABSTRACT Since 2002, an epidemic of Clostridium difficile infections has occurred in southern Quebec, Canada. At Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada, the incidence of C. difficile infections increased from 11/1,000 admissions (1999 to 2002) to 27/1,000 admissions (2003 to 2005). We compared the exposures and outcomes for patients infected with strains with different ribopatterns isolated before (n = 55) and during (n = 175) the epidemic, as well as the in vitro activities of antibiotics against those isolates. During the preepidemic period, 46 isolates (84%) were of ribotype 001, 1 was of ribotype 027, and 8 were of other ribopattern types. During the epidemic period, ribotype 027 strains accounted for 140 (80%) isolates; 26 (15%) were of ribotype 001, and 7 were of other ribopattern types. Ribotype 027 strains were highly resistant to fluoroquinolones (FQs) but were susceptible to clindamycin. A pattern of prior specific antibiotic exposure that selected for antibiotic-resistant ribotype C. difficile infections was observed for FQs (ribotype 027) and clindamycin (ribotype 001). The rate of mortality was higher among older patients, those with a high Charlson comorbidity index, and those with longer previous hospitalizations. By multivariate analysis, patients infected with ribotype 027 were twice as likely to die within 30 days of diagnosis than patients infected with other ribotypes (adjusted odds ratio, 2.06; 95% confidence interval, 1.00 to 4.22). The observations from this study support the notion that continued selective antibiotic pressure resulted in the superimposition of the hypertoxigenic ribotype 027 clone on top of the prior dominant ribotype 001 clone in a setting of preexisting high endemicity, thus leading to the high rates of morbidity and mortality seen in the Quebec outbreak. Stringent antibiotic stewardship measures, combined with aggressive infection control, are required to curtail the epidemic of C. difficile infections.

Mycoplasma genitalium: an organism commonly associated with cervicitis among west African sex workers

Objectives: To identify the contribution of Mycoplasma genitalium to the aetiology of cervicitis in sub-Saharan Africa and its relative importance in the overall burden of sexually transmitted infections among female sex workers (FSW). Methods: The study population consisted of FSW recruited in Ghana and Bénin during the initial visit of a randomised controlled trial. A questionnaire was administered, a pelvic examination carried out, and cervical samples obtained for detection of M genitalium, Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis. Clinical signs potentially indicating cervicitis were cervical discharge, pus on the cervical swab, bleeding after sampling, and inflammatory cervix. Results: Among 826 FSW, 26.3% were infected with M genitalium. N gonorrhoeae was strongly and independently associated with each of the four signs of cervicitis (adjusted odds ratios (AOR): 4.1 to 6.0). The AOR for C trachomatis were intermediate (1.3–4.1) and the AOR for M genitalium were lower (between 1.6 and 1.8) but statistically significant (p⩽0.05) for each sign. Conclusions:M genitalium is weakly associated with signs of cervicitis in west African FSW but is highly prevalent.

Interventions among male clients of female sex workers in Benin, West Africa: an essential component of targeted HIV preventive interventions

Objectives: To assess the impact of interventions targeted towards female sex workers (FSWs) and their male clients on client HIV/STI prevalence and sexual behaviour. Methods: From 1993 to 2006, an HIV/STI preventive intervention focusing on condom promotion and STI care was implemented among FSWs in Cotonou, Benin, and then expanded to cover their male sexual partners in 2000. The interventions were scaled up to five other cities of Benin in 2001–2002. Serial cross-sectional surveys of HIV/STI prevalence and sexual behaviour were carried out among clients in Cotonou in 1998, 2002 and 2005; and in the five other cities (O/Cotonou) in 2002 and 2005. Results: Significant declines in gonorrhoea prevalence among clients of FSWs: Cotonou, from 5.4% in 1998 to 1.6% in 2005; O/Cotonou: from 3.5% in 2002 to 0.59% in 2005. Chlamydia prevalence also declined O/Cotonou, from 4.8% to 1.8%, while HIV prevalence remained stable. Reported condom use by clients with both FSWs and casual non-FSW partners, but not regular partners, increased significantly. While condom use at last sex with an FSW was similar in Cotonou to O/Cotonou around the time of implementation of the interventions (56% in 1998 vs 49% in 2002, respectively), it had risen to similar levels by 2005 (95% and 96%, respectively). Conclusions: These results demonstrate that it is possible to implement preventive and clinical services for clients of FSWs, and suggest that such interventions, integrated with those targeted towards FSWs, can have a significant effect on sexual behaviour and STI prevalence (particularly gonorrhoea) among this population.

Risk factors for mortality following emergency colectomy for fulminant Clostridium difficile infection.

PURPOSE: This study evaluated risk factors for mortality after emergency colectomy for fulminant Clostridium difficile infection. METHODS: Retrospective study of 130 cases of Clostridium difficile infection that required a colectomy between 1994 and 2007 in four hospitals of Quebec, Canada. Primary outcome was 30-day mortality. RESULTS: Twenty-five cases underwent colectomy in 1994 to 2002, 41 in 2003, 40 in 2004, and 24 in 2005 to 2007. Common indications were septic shock (41 percent) and nonresponse to medical treatment (39 percent). Overall, 30-day mortality was 37 percent. Mortality increased with age but was not influenced by comorbidities burden. Mortality correlated with preoperative lactate (≤2.1 mmol/L: 26 percent; 2.2-4.9 mmol/L: 52 percent; ≥5.0 mmol/L: 75 percent, P < 0.001), leukocytosis (<20.0 × 109/L: 32 percent; 20.0-49.9 × 109/L: 33 percent; ≥50.0 × 109/L: 73 percent, P = 0.008), albumin (≥25 g/L: 19 percent; 15-24 g/L: 38 percent; <15 g/L: 52 percent, P = 0.04) and renal failure. In multivariate analysis, risk factors for mortality were age (per year, adjusted odds ratio: 1.03, 95 percent confidence interval: 1.00-1.06), preoperative lactate greater than or equal to 5.0 mmol/L (adjusted odds ratio: 10.32, 95 percent confidence interval: 2.59-41.1), leukocytosis greater than or equal to 50.0 ×109/L (adjusted odds ratio: 3.68, 95 percent confidence interval: 0.92-14.8) and albumin less than 15 g/L (adjusted odds ratio, 6.57, 95 percent confidence interval: 1.31-33.1). CONCLUSIONS: Incidence of Clostridium difficile infection-related emergency colectomies increased 20-fold during the epidemic. Postoperative mortality can be predicted by simple laboratory parameters. Three-fourths of patients with leukocytosis greater or equal to 50.0 ×109/L or lactate greater or equal to 5.0 mmol/L died. When possible, emergency colectomy should be performed earlier.

Surgical-site infection following spinal fusion: a case-control study in a children's hospital.

OBJECTIVES To determine the rates of surgical-site infections (SSIs) after spinal surgery and to identify the risk factors associated with infection. DESIGN SSIs had been identified by active prospective surveillance. A case-control study to identify risk factors was performed retrospectively. SETTING University-associated, tertiary-care pediatric hospital. PATIENTS All patients who underwent spinal surgery between 1994 and 1998. Cases were all patients who developed an SSI after spinal surgery. Controls were patients who did not develop an SSI, matched with the cases for the presence or absence of myelodysplasia and for the surgery date closest to that of the case. RESULTS There were 10 infections following 125 posterior spinal fusions, 4 infections after 50 combined anterior-posterior fusions, and none after 95 other operations. The infection rate was higher in patients with myelodysplasia (32 per 100 operations) than in other patients (3.4 per 100 operations; relative risk = 9.45; P < .001). Gram-negative organisms were more common in early infections and Staphylococcus aureus in later infections. Most infections occurred in fusion involving sacral vertebrae (odds ratio [OR] = 12.0; P = .019). Antibiotic prophylaxis was more frequently suboptimal in cases than in controls (OR = 5.5; P = .034). Five patients required removal of instrumentation and 4 others required surgical debridement. CONCLUSIONS Patients with myelodysplasia are at a higher risk for SSIs after spinal fusion. Optimal antibiotic prophylaxis may reduce the risk of infection, especially in high-risk patients such as those with myelodysplasia or those undergoing fusion involving the sacral area.

Risk Factors for Hepatitis C Virus Transmission in Colonial Cameroon

BACKGROUND In southern Cameroon, where SIV(cpz), the source of human immunodeficiency virus 1 (HIV-1) group M, is prevalent among wild chimpanzees, approximately 50% of some human birth cohorts have been infected with hepatitis C virus (HCV) through unclear mechanisms. METHODS To evaluate indirectly the hypothesis that medical interventions contributed to the early emergence of HIV-1, we conducted a cross-sectional study of 451 inhabitants of Ebolowa in southern Cameroon aged 60 years, using HCV as a marker of parenteral transmission of blood-borne viruses. We administered a questionnaire and tested serum for antibodies against HCV. Viral gene sequences were obtained from HCV-positive sera. Molecular clock analyses provided an independent source of information on epidemic history. RESULTS A total of 252 participants (56%) were HCV seropositive. HCV sequences were amplified and genotyped from 171 individuals. Independent risk factors for HCV seropositivity were older age, having received intravenous treatment against malaria, and having attended an ethnic school (women only), whereas having been circumcised by a traditional practitioner (men only) tended to be associated with HCV. In addition, transfusions were associated with HCV genotype 1 transmission. Molecular clock analyses of HCV genotypes 1, 2, and 4 revealed that each independently underwent exponential growth during the first half of the 20th century. CONCLUSIONS Medical interventions (intravenous antimalarial drugs, transfusions) and to a lesser extent traditional practices (circumcision) were associated with the massive transmission of HCV among this population decades ago. This finding supports the hypothesis that medical interventions contributed to the transmission of blood-borne viruses, perhaps including SIV(cpz) and HIV-1, in the same region during the early 20th century.

Evaluating large-scale HIV prevention interventions: study design for an integrated mathematical modelling approach

Background: There is an urgent need to evaluate HIV prevention interventions, thereby improving our understanding of what works, under what circumstances and what is cost effective. Objectives: To describe an integrated mathematical evaluation framework designed to assess the population-level impact of large-scale HIV interventions and applied in the context of Avahan, the Indian AIDS Initiative, in southern India. The Avahan Initiative is a large-scale HIV prevention intervention, funded by the Bill & Melinda Gates Foundation, which targets high-risk groups in selected districts of the six states most affected by the HIV/AIDS epidemic (Maharashtra, Karnataka, Tamil Nadu, Andhra Pradesh, Nagaland and Manipur) and along the national highways. Methods: One important component of the monitoring and evaluation of Avahan relies on an integrated mathematical framework that combines empirical biological and behavioural data from different subpopulations in the intervention areas, with the use of tailor-made transmission dynamics models embedded within a Bayesian framework. Results: An overview of the Avahan Initiative and the objectives of the monitoring and evaluation of the intervention is given. The rationale for choosing this evaluation design compared with other possible designs is presented, and the different components of the evaluation framework are described and its advantages and challenges are discussed, with illustrated examples. Conclusions: This is the first time such an approach has been applied on such a large scale. Lessons learnt from the CHARME project could help in the design of future evaluations of large-scale interventions in other settings, whereas the results of the evaluation will be of programmatic and public health relevance.

Development and Evaluation of a PCR Method for Detection of the Clostridium difficile Toxin B Gene in Stool Specimens

ABSTRACT A PCR assay detecting Clostridium difficile toxin B gene in stool specimens was compared to the cytotoxicity assay as the reference standard for the diagnosis of C. difficile antibiotic-associated diarrhea (CDAD). Overall, 118 stool samples were tested. All of the specimens that were negative by the cytotoxicity assay (59 out of 118) were also negative by the PCR method (specificity of 100%). Of the 59 cytotoxin-positive samples, 54 were PCR positive (sensitivity of 91.5%). This PCR method is promising for rapid diagnosis of CDAD.