Vincent Nault

Risk of Clostridium difficile Infection after Perioperative Antibacterial Prophylaxis before and during an Outbreak of Infection due to a Hypervirulent Strain

BACKGROUND Perioperative antibacterial prophylaxis (PAP) is an important component of surgical site infection prevention but may be associated with adverse effects, such as Clostridium difficile infection (CDI). Since the emergence of a hypervirulent strain of C. difficile, the risk of development of CDI after PAP has not been evaluated. The purpose of this study was to determine the risk of PAP-induced CDI after selected surgical procedures and to compare such risk before with such risk after the emergence of the hypervirulent strain of C. difficile. METHODS We performed a retrospective cohort study including all patients aged > or = 18 years who underwent either abdominal hysterectomy, hip arthroplasty, craniotomy, or colon, cardiac, or vascular surgery from August 1999 through May 2005 in a tertiary care hospital in Quebec, Canada. RESULTS A total of 8373 surgical procedures were performed, and PAP was used in 7600 of these interventions. Of 98 CDI episodes identified, 40 occurred after patients received PAP only. The risk of CDI was 14.9 cases per 1000 surgical procedures among patients who received PAP only during the period 2003-2005, compared with 0.7 cases per 1000 surgical procedures during the period 1999-2002 (P < .001). The independent risk factors associated with CDI in patients given PAP only were older age, administration of cefoxitin (rather than cefazolin) alone or in combination with another drug, and year of surgery. CONCLUSIONS In the context of a large epidemic of CDI associated with the emergence of a novel strain, 1.5% of patients who received PAP as their sole antibiotic treatment developed CDI. In situations in which the only purpose of PAP is to prevent infrequent and relatively benign infections, the risks may outweigh the benefits in some elderly patients.

Impact of guideline-consistent therapy on outcome of patients with healthcare-associated and community-acquired pneumonia

BACKGROUND A new category of healthcare-associated pneumonia (HCAP) has been added in the most recent American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines, since multidrug-resistant (MDR) pathogens are more common in patients with HCAP than in those with community-acquired pneumonia (CAP). The optimal empirical management of patients with HCAP remains controversial and adherence to guidelines is inconsistent. METHODS A retrospective cohort study of 3295 adults admitted for pneumonia in an academic centre of Canada, between 1997 and 2008. RESULTS MDR pathogens were more common among patients with HCAP than in those with CAP, but less so than in other studies. Compared with patients with CAP, those with HCAP had a higher all-cause 30 day mortality [68/563 (12%) versus 201/2732 (7%); P < 0.001] and more frequent need for mechanical ventilation [78/563 (14%) versus 276/2732 (10%); P = 0.01]. In patients with CAP, mortality was lower when treatment was concordant with guidelines [86/1557 (6%) versus 109/1097 (10%) if discordant; adjusted odds ratio 0.6 (0.4-0.8); P < 0.001]. In HCAP, mortality was similar whether or not empirical treatment was concordant with guidelines [6/35 (17%) versus 18/148 (12%) if discordant; P = 0.4]. However, 30 day mortality tended to be higher when the empirical treatment was microbiologically ineffective [4/22 (18%) versus 17/187 (9%) when effective; P = 0.3]. CONCLUSIONS HCAP is associated with worse outcomes than CAP. MDR pathogens were implicated in only a small fraction of HCAP cases. In our study, unlike CAP, non-respect of current HCAP guidelines had no adverse effect on the ultimate outcome. Strategies for the empirical management of HCAP should be tailored to the local epidemiological context.

Clinical and Healthcare Burden of Multiple Recurrences of Clostridium difficile Infection

BACKGROUND Clostridium difficile infection (CDI) is associated with a high risk of recurrence (rCDI). Few studies have focused on multiple recurrences. To evaluate the potential of novel treatments targeting recurrence, we assessed the burden and severity of rCDI. METHODS This was a retrospective cohort of adults diagnosed with CDI in a hospital in Sherbrooke, Canada (1998-2013). An rCDI episode was defined by the reappearance of diarrhea leading to a treatment, with or without a positive toxin assay, within 14-60 days after the previous episode. RESULTS We included 1527 patients. The probability of developing a first rCDI was 25% (354/1418); a second, 38% (128/334); a third, 29% (35/121); and a fourth or more, 27% (9/33). Two or more rCDIs were observed in 9% (128/1389) of patients. The risk of a first recurrence fluctuated over time, but there was no such variation for second or further recurrences. The proportion of severe cases decreased (47% for initial episodes, 31% for first recurrences, 25% for second, 17% for third), as did the risk of complicated CDI (5.8% to 2.8%). The severity and risk of complications of first recurrences decreased over time, while oral vancomycin was used more systemically. A hospital admission was needed for 34% (148/434) of recurrences. CONCLUSIONS This study documented the clinical and healthcare burden of rCDI: 34% of patients with rCDI needed admission, 28% developed severe CDI, and 4% developed a complication. Secular changes in the severity of recurrences could reflect variations in the predominant strain, or better management.

Evolution of the Global Burden of Viral Infections from Unsafe Medical Injections, 2000–2010

Background In 2000, the World Health Organization estimated that, in developing and transitional countries, unsafe injections accounted for respectively 5%, 32% and 40% of new infections with HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV). Safe injection campaigns were organized worldwide. The present study sought to measure the progress in reducing the transmission of these viruses through unsafe injections over the subsequent decade. Methods A mass action model was updated, to recalculate the number of injection-related HIV, HCV and HBV infections acquired in 2000 and provide estimates for 2010. Data about the annual number of unsafe injections were updated. HIV prevalence in various regions in 2000 and 2010 were calculated from UNAIDS data. The ratio of HIV prevalence in healthcare settings compared to the general population was estimated from a literature review. Improved regional estimates of the prevalence of HCV seropositivity, HBsAg and HBeAg antigenemia were used for 2000 and 2010. For HIV and HCV, revised estimates of the probability of transmission per episode of unsafe injection were used, with low and high values allowing sensitivity analyses. Results Despite a 13% population growth, there was a reduction of respectively 87% and 83% in the absolute numbers of HIV and HCV infections transmitted through injections. For HBV, the reduction was more marked (91%) due to the additional impact of vaccination. While injections-related cases had accounted for 4.6%–9.1% of newly acquired HIV infections in 2000, this proportion decreased to 0.7%–1.3% in 2010, when unsafe injections caused between 16,939 and 33,877 HIV infections, between 157,592 and 315,120 HCV infections, and 1,679,745 HBV infections. Conclusion From 2000 to 2010, substantial progress was made in reducing the burden of HIV, HCV and HBV infections transmitted through injections. In some regions, their elimination might become a reasonable public health goal.

Prediction of Complicated Clostridium difficile Infection by Pleural Effusion and Increased Wall Thickness on Computed Tomography

BACKGROUND Abdominal computed tomography (CT) is often used to evaluate complications in patients with Clostridium difficile infection (CDI), but no study has correlated CT findings with the risk of developing a complicated CDI. Furthermore, the value of CT has not been evaluated since the emergence of the BI/NAP1/027 hypervirulent strain of C. difficile. We sought to describe and correlate abdominal CT findings with complicated CDI and to compare them before and after the emergence of the epidemic strain. METHODS We conducted a retrospective cohort study of all hospitalized patients 18 years or older who, from 1 January 1998 through 31 December 2006, underwent abdominal CT within 72 h of their first positive stool sample. RESULTS Of 1189 patients with newly diagnosed CDI, 165 satisfied the inclusion criteria. Patients who underwent CT were younger, had higher peak white blood cell counts and serum creatinine levels, and were more likely to experience fever than those who did not undergo CT. No difference in CT findings was noted before and after the emergence of BI/NAP1/027 CDI. Pleural effusion (adjusted odds ratio [AOR], 2.6; 95% confidence interval [CI], 1.1-6.6), colonic wall thickness >15 mm (AOR, 6.0; 95% CI, 1.1-33.9), peak white blood cell count > or =30 x 10(9) cells/L (AOR, 4.8; 95% CI, 1.4-16.4), albumin level <20 g/L (AOR, 6.9; 95% CI, 2.4-20.1), and immunosuppression (AOR, 4.7; 95% CI, 1.5-15.3) were independently associated with complicated CDI. CONCLUSIONS In a selected sample of patients with CDI, CT provided prognostic information additional to what could be obtained from clinical and laboratory parameters. No change in CT characteristics was noted after the introduction of the BI/NAP1/027 strain in our center.

Antimicrobial stewardship in acute care centres: A survey of 68 hospitals in Quebec.

BACKGROUND Antimicrobial stewardship programs (ASPs) and quantitative monitoring of antimicrobial use are required to ensure that antimicrobials are used appropriately in the acute care setting, and have the potential to reduce costs and limit the spread of antimicrobial-resistant organisms and Clostridium difficile. Currently, it is not known what proportion of Quebec hospitals have an ASP and/or monitor antimicrobial use. OBJECTIVES To determine what proportion of Quebec hospitals have an ASP, and what is the nature of such a program. METHODS A detailed questionnaire was sent to the pharmacy directors of all acute care hospitals in the province of Quebec. Information was collected on antimicrobial surveillance; antimicrobial stewardship and resource allocation to these areas were assessed. RESULTS Questionnaires were completed for 68 of 81 (84%) hospitals contacted. ASPs were identified at 50 (74%) hospitals, but only 20 (29%) of hospitals had a quantitative antimicrobial surveillance program (QASP) in 2006. Academic centres (P=0.03) and hospitals with over 200 beds (P=0.02) were more likely to have a QASP. Even among hospitals with an ASP, 18% had less than one full-time pharmacist for a QASP. CONCLUSIONS Over one-quarter of Quebec hospitals do not have an ASP, and few hospitals in Quebec are currently evaluating their use of antimicrobials on a quantitative basis. In some cases, the lack of a QASP may be due to the allocation of insufficient pharmaceutical resources to antimicrobial stewardship (ie, less than one full-time pharmacist).

Evaluation of a machine learning capability for a clinical decision support system to enhance antimicrobial stewardship programs

OBJECTIVE Antimicrobial stewardship programs have been shown to limit the inappropriate use of antimicrobials. Hospitals are increasingly relying on clinical decision support systems to assist in the demanding prescription reviewing process. In previous work, we have reported on an emerging clinical decision support system for antimicrobial stewardship that can learn new rules supervised by user feedback. In this paper, we report on the evaluation of this system. METHODS The evaluated system uses a knowledge base coupled with a supervised learning module that extracts classification rules for inappropriate antimicrobial prescriptions using past recommendations for dose and dosing frequency adjustments, discontinuation of therapy, early switch from intravenous to oral therapy, and redundant antimicrobial spectrum. Over five weeks, the learning module was deployed alongside the baseline system to prospectively evaluate its ability to discover rules that complement the existing knowledge base for identifying inappropriate prescriptions of piperacillin-tazobactam, a frequently used antimicrobial. RESULTS The antimicrobial stewardship pharmacists reviewed 374 prescriptions, of which 209 (56% of 374) were identified as inappropriate leading to 43 recommendations to optimize prescriptions. The baseline system combined with the learning module triggered alerts in 270 prescriptions with a positive predictive value of identifying inappropriate prescriptions of 74%. Of these, 240 reviewed prescriptions were identified by the alerts of the baseline system with a positive predictive value of 82% and 105 reviewed prescriptions were identified by the alerts of the learning module with a positive predictive value of 62%. The combined system triggered alerts for all 43 recommendations, resulting in a rate of actionable alerts of 16% (43 recommendations of 270 reviewed alerts); the baseline system triggered alerts for 38 interventions, resulting in a rate of actionable alerts of 16% (38 of 240 reviewed alerts); and the learning module triggered alerts for 17 interventions, resulting in a rate of actionable alerts of 16% (17 of 105 reviewed alerts). The learning module triggered alerts for every inappropriate prescription missed by the knowledge base of the baseline system (n=5). CONCLUSIONS The learning module was able to extract clinically relevant rules for multiple types of antimicrobial alerts. The learned rules were shown to extend the knowledge base of the baseline system by identifying pharmacist interventions that were missed by the baseline system. The learned rules identified inappropriate prescribing practices that were not supported by local experts and were missing from its knowledge base. However, combining the baseline system and the learning module increased the number of false positives.

Evolution of the Global Use of Unsafe Medical Injections, 2000–2010

Objective Since 1999, substantial efforts have been made by the international community to reduce the risks associated with unsafe injections, through ministries of health, international donors, the World Health Organization and the Safe Injection Global Network. The present study attempted to measure the progress, or lack thereof, made over the 2000–2010 decade in reducing unsafe injections in ten regions of the world corresponding to developing and transitional economies. Methods Data about the number of injections per person per year and the proportion of re-use of syringes and needles were obtained for 2010, mainly from population surveys, and compared with previous estimates for 2000 which had used various sources of information including injection safety assessments, population surveys and published studies on injection practices. Results From 2000 to 2010, in developing countries and transitional economies, the average number of injections per person per year decreased from 3.40 to 2.88, while the proportion of re-use of injection devices dropped from 39.8% to 5.5%. Combining both factors the number of unsafe injections per person per year decreased from 1.35 to 0.16. Even if substantial progress has been made, the Eastern Mediterranean region remains problematic, with 0.57 unsafe injections per person per year. In sub-Saharan Africa and Latin America, people now receive on average only 0.04–0.05 unsafe injections per year. Conclusion Substantial progress has been made in reducing the number of unsafe injections in developing countries and transitional economies, essentially through a reduction in the re-use of injection devices. In some regions, elimination of unsafe injections might become a reasonable goal.

Burden of rotavirus disease: A population-based study in Eastern Townships, Quebec.

BACKGROUND Since July 2010, the National Advisory Committee on Immunization of Canada has recommended rotavirus vaccination for all healthy infants. However, before implementing this vaccine in routine health programs, Canadian provinces need to establish current epidemiological data on rotavirus-associated acute gastroenteritis (AGE). METHODS A retrospective cohort study of children <5 years of age with AGE from 2002 to 2008 was performed in Eastern Townships, Quebec (population in 2006: 298,780). Data were collected on visits to outpatient clinics, emergency department (ED) visits, hospitalizations (standard and short-stay units) and nosocomial AGE. The winter residual estimation and Brandt methods were used to estimate the proportion of AGE attributable to rotaviruses. RESULTS During the six-year study period, a total of 1435 hospitalizations, 3631 ED visits and 6220 ambulatory care visits were attributed to AGE. The specific rotavirus burden was estimated to be 449 to 666 for hospitalizations, 1050 to 1361 for ED visits and 1633 to 1687 for outpatient visits. The epidemic curve showed a periodicity with higher incidence in March and April. Short-stay unit hospitalizations represented 58% of all hospitalizations. The annual incidence rate of rotaviruses was estimated to be 50 to 74 per 10,000 children for hospitalizations, 117 to 152 per 10,000 children for ED visits and 182 to 188 per 10,000 children for outpatient visits. CONCLUSION Most available retrospective studies probably underestimate rotavirus-associated hospitalizations because they do not take into account short-stay unit hospitalizations. Furthermore, these data on emergency and outpatient visits provide an exhaustive appraisal of the rotavirus burden, which serves as crucial information for the evaluation of immunization programs.

Sustained impact of a computer-assisted antimicrobial stewardship intervention on antimicrobial use and length of stay

Objectives: Prospective audit and feedback interventions are the core components of an antimicrobial stewardship programme. Herein, we describe the sustained impact of an antimicrobial stewardship programme, based on a novel clinical decision-support system (Antimicrobial Prescription Surveillance System; APSS), on antimicrobial use and costs, hospital length of stay (LOS) in days and the proportion of inappropriate antimicrobial prescriptions. Methods: A quasi-experimental, retrospective study was conducted using interrupted time series between 2008 and 2013. Data on all hospitalized adults receiving antimicrobials were extracted from the data warehouse of a 677 bed academic centre. The intervention started in August 2010. Prospective audit and feedback interventions, led by a pharmacist, were triggered by APSS based on deviations from published and local guidelines. Changes in outcomes before and after the intervention were compared using segmented regression analysis. Results: APSS reviewed 40 605 hospitalizations for 35 778 patients who received antimicrobials. The intervention was associated with a decrease in the average LOS (level change −0.92, P < 0.01; trend −0.08, P < 0.01; intercept 11.4 days), antimicrobial consumption in DDDs/1000 inpatient days (level change −32.4, P < 0.01; trend −1.12, P < 0.02; intercept 243 DDDs per 1000 days of hospitalization), antimicrobial spending in Canadian dollars (level change −19 649, P = 0.01; trend −1881, P < 0.01; intercept