Alex Carignan

Increasing Risk of Infectious Complications After Transrectal Ultrasound-Guided Prostate Biopsies: Time to Reassess Antimicrobial Prophylaxis?

BACKGROUND An increasing risk of infectious complications following transrectal ultrasound-guided prostate needle biopsy (PNB) has been observed recently in some centers. OBJECTIVE To delineate the risk factors associated with post-PNB bacteremia and/or urinary tract infection (UTI) and determine why this risk has risen over time. DESIGN, SETTING, AND PARTICIPANTS A case-control study in a Canadian tertiary-care center. Cases were all patients who developed bacteremia and/or UTIs after PNB between 2002 and 2011; controls were randomly selected among patients who underwent a PNB without such complications. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Crude and adjusted odds ratios and their 95% confidence intervals were calculated using logistic regression. RESULTS AND LIMITATIONS A total of 5798 PNBs were performed during the study period, following which there were 48 cases of urinary sepsis (42% with bacteremia). The incidence increased from 0.52 infections per 100 biopsies in 2002-2009 to 2.15 infections per 100 biopsies in 2010-2011 (p<0.001). Escherichia coli was the predominant pathogen (75% of cases). Among 42 patients whose post-PNB infection was caused by aerobic or facultative Gram-negative rods, 22 patients (52%) were infected by pathogens resistant to ciprofloxacin. Independent risk factors for post-PNB infection were diabetes, hospitalization during the preceding month, chronic obstructive pulmonary disease, and performance of the biopsy in 2010-2011. In 2010-2011, the minimal inhibitory concentrations for ciprofloxacin increased compared with 2002-2009 (p<0.03). The major limitation of the study was its retrospective hospital-based nature, which hampered data collection on outpatient antibiotic prescriptions. CONCLUSIONS In the past 2 yr, ciprofloxacin resistance contributed to the increasing incidence of post-PNB infections in our center. Novel antibacterial prophylaxis approaches need to be evaluated.

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.

Efficacy of Secondary Prophylaxis With Vancomycin for Preventing Recurrent Clostridium difficile Infections.

OBJECTIVES:Patients with Clostridium difficile infection (CDI) who are re-exposed to antibiotics have a high likelihood of recurrence. We aimed to determine whether oral vancomycin as secondary prophylaxis reduces the risk of recurrence in patients recently diagnosed with CDI who undergo subsequent antibiotic exposure (CDI-AE).METHODS:We conducted a retrospective cohort study of patients diagnosed with CDI (initial episode or recurrence) between 2003 and 2011 in two tertiary care centers in Quebec, Canada and who received antibiotics not targeted against CDI within 90 days after their CDI diagnosis. Risk factors for subsequent recurrence after this exposure to antibiotics were assessed through Cox regression analyses.RESULTS:We included 551 episodes of CDI-AE (379 initial episodes, 172 recurrences). Recurrence occurred after exposure to antibiotics in 181 episodes (32.9%). Recurrence was more likely in older patients (for each additional year of age: adjusted hazard ratio (AHR), 1.01; 95% confidence interval (CI), 1.00–1.03; P=0.02) and among cases where the CDI-AE episode was itself a first (AHR, 3.59; 95% CI, 2.52–5.13; P<0.0001) or a second recurrence (AHR, 4.88; 95% CI, 3.38–7.06; P<0.0001). Oral vancomycin prophylaxis decreased the risk of further recurrence in patients whose CDI-AE itself was a recurrence (AHR, 0.47; 95% CI, 0.32–0.69; P<0.0001) but not in those whose CDI-AE was an initial episode (AHR, 0.91; 95% CI, 0.57–1.45; P=0.68).CONCLUSIONS:Oral vancomycin appears as an effective strategy for decreasing the risk of further CDI recurrence in patients with a history of recurrent CDI who are re-exposed to antibiotics.

CCL18 from ascites promotes ovarian cancer cell migration through proline-rich tyrosine kinase 2 signaling

BackgroundOvarian cancer (OC) ascites consist in a proinflammatory tumor environment that is characterized by the presence of various cytokines, chemokines and growth factors. The presence of these inflammatory-related factors in ascites is associated with a more aggressive tumor phenotype. CCL18 is a member of CCL chemokines and its expression has been associated with poor prognosis in some cancers. However, its role in OC progression has not been established. Therefore, the aim of the current study was to elucidate the role of ascites CCL18 in OC progression.MethodsELISA and tissue microarrays were used to assess CCL18 in ascites and phospho-Pyk2 expression in cancer tissues respectively. Cell migration was assessed using Boyden chambers. CCL18 and ascites signaling was examined in ovarian cancer cells utilizing siRNA and exogenous gene expression.ResultsHere, we show that CCL18 levels are markedly increased in advanced serous OC ascites relative to peritoneal effusions from women with benign conditions. Ascites and CCL18 dose-dependently enhanced the migration of OC cell lines CaOV3 and OVCAR3. CCL18 levels in ascites positively correlated with the ability of ascites to promote cell migration. CCL18 blocking antibodies significantly attenuated ascites-induced cell migration. Ascites and CCL18 stimulated the phosphorylation of proline-rich tyrosine kinase 2 (Pyk2) in CaOV3 and OVCAR3 cells. Most importantly, the expression of phosphorylated Pyk2 in serous OC tumors was associated with shorter progression-free survival. Furthermore, enforced expression of Pyk2 promoted tumor cell migration while siRNA-mediated downregulation of Pyk2 attenuated cell migration. Downregulation of Pyk2 markedly inhibited ascites and CCL18-induced cell migration.ConclusionsTaken together, our findings establish an important role for CCL18, as a component of ascites, in the migration of tumor cells and identify Pyk2 as prognostic factor and a critical downstream signaling pathway for ascites-induced OC cell migration.

Ventilator associated pneumonia and endotracheal tube repositioning: An underrated risk factor

Aspiration of secretions toward lower airways potentially occurs during endotracheal tube (ETT) repositioning in mechanically ventilated patients in the intensive care unit and may be a risk factor for developing ventilator-associated pneumonia (VAP). This case-control study confirms that repositioning of the ETT is an independent risk factor for VAP.

Bezlotoxumab for the prevention of Clostridium difficile recurrence

ABSTRACT Introduction: Clostridium difficile infection is a major economic and clinical burden, due to its high frequency of recurrence. Currently recommended treatments are not efficient for prevention and may contribute to the risk of recurrent infection. In recent years, research has focused on strategies to lessen this risk. Bezlotoxumab is a monoclonal antibody that prevents recurrences of C. difficile infection through the antagonism of toxin B. Areas covered: In this review, the authors discuss the burden of C. difficile infection and its recurrences, the mechanisms underlying the recurrences, and current C. difficile treatments. They subsequently analyze the strategic therapeutic rationale for bezlotoxumab use, as well as the supporting clinical evidence. Expert opinion: Bezlotoxumab is an attractive solution for reducing the unacceptable level of recurrence that occurs with the currently recommended C. difficile treatments and other alternative therapies under consideration. Even though bezlotoxumab has not been tested in large-scale trials exclusively in cases of already established recurrent C.difficile infection (rCDI), it has an advantage over current treatments in that it does not interfere with the patient’s gut flora while directly neutralizing the key virulence factor. Although cost remains an important factor against its widespread use, simpler administration, fewer side-effects, and better social acceptability justify its consideration for treating rCDI.

Routine Surveillance Versus Independent Assessment by an Outcome Adjudication Committee in Assessing Patients for Sternal Surgical Site Infections After Cardiac Surgery

Based on a cohort of 966 patients, routine surveillance data were not sufficiently accurate for use in clinical trials investigating surgical site infections. Surveillance data can only be used if adequate 90-day follow-up is provided and if cases identified by surveillance are independently reviewed by a blinded outcome adjudication committee.

Secular trends in incidence of invasive beta-hemolytic streptococci and efficacy of adjunctive therapy in Quebec, Canada, 1996-2016

Objectives To examine secular changes in the incidence of invasive beta-hemolytic streptococcal infections, and to assess the efficacy of immunoglobulins and clindamycin as adjunctive therapies in the management of Streptococcus pyogenes infections. Methods Retrospective cohort study of all cases of invasive group A (GAS), B (GBS), C or G (GCGS) streptococcal infections managed in a Canadian tertiary center from 1996–2016. Population incidence was measured for diabetics and non-diabetics. Adjusted odds ratios (AOR) and their 95% confidence intervals (CI) were calculated by logistic regression. Results 741 cases were identified (GAS: 249; GBS: 304; GCGS: 188). While the incidence of invasive GAS infections fluctuated with no clear trend, incidence of invasive GBS and GCGS increased over time and were 8.4 and 6.3 times higher in diabetics. Mortality of invasive GAS infections decreased from 16% (6/37) in 1996–2001 to 4% (4/97) in 2011–15. Among patients with GAS infections, clindamycin administered concomitantly with a beta-lactam within 24 hours of admission decreased mortality (AOR: 0.04, 95%CI: 0.003–0.55, P = 0.02. Immunoglobulins had no such effect (AOR: 1.66, 95%CI: 0.16–17.36, P = 0.67). The protective effect of clindamycin was similar in patients with pneumonia/empyema compared to all others. Conclusion Incidence of GBS and GCGS infections increased due to an expansion of the high-risk population (elderly diabetics), but also rose in non-diabetics. No such secular change was seen for invasive GAS infections. The decrease in mortality in patients with invasive GAS infections presumably reflects better case-management. Adjunctive clindamycin reduced mortality in invasive GAS infections; immunoglobulins did not, but power was limited. The highest mortality was seen in patients with GAS pneumonia/empyema, for whom clindamycin was protective but underused.

A ten-year review of healthcare-associated bloodstream infections from forty hospitals in Québec, Canada

OBJECTIVE Healthcare-associated bloodstream infections (HABSI) are a significant cause of morbidity and mortality worldwide. In Québec, Canada, HABSI arising from acute-care hospitals have been monitored since April 2007 through the Surveillance des bactériémies nosocomiales panhospitalières (BACTOT) program, but this is the first detailed description of HABSI epidemiology. METHODS This retrospective, descriptive study was conducted using BACTOT surveillance data from hospitals that participated continuously between April 1, 2007, and March 31, 2017. HABSI cases and rates were stratified by hospital type and/or infection source. Temporal trends of rates were analyzed by fitting generalized estimating equation Poisson models, and they were stratified by infection source. RESULTS For 40 hospitals, 13,024 HABSI cases and 23,313,959 patient days were recorded, for an overall rate of 5.59 per 10,000 patient days (95% CI, 5.54-5.63). The most common infection sources were catheter-associated BSIs (23.0%), BSIs secondary to a urinary focus (21.5%), and non-catheter-associated primary BSIs (18.1%). Teaching hospitals and nonteaching hospitals with ICUs often had rates higher than nonteaching hospitals without ICUs. Annual HABSI rates did not exhibit statistically significant changes from year to year. Non-catheter-associated primary BSIs were the only HABSI type that exhibited a sustained change across the 10 years, increasing from 0.69 per 10,000 patient days (95% CI, 0.59-0.80) in 2007-2008 to 1.42 per 10,000 patient days (95% CI, 1.27-1.58) in 2016-2017. CONCLUSIONS Despite ongoing surveillance, overall HABSI rates have not decreased. The effect of BACTOT participation should be more closely investigated, and targeted interventions along alternative surveillance modalities should be considered, prioritizing high-burden and potentially preventable BSI types.

An Offer You Can’t Refuse: Clinical Impact of Accepting or Rejecting a Recommendation from an Antibiotic Stewardship Program

Abstract Background The outcomes associated with the acceptance or refusal of a recommendation from an antimicrobial stewardship program (ASP) on an individual level have not been studied yet. Our objective was to compare the clinical characteristics and mortality of patients for whom a recommendation from an ASP, based on prospective audit and feedback and triggered by a computerized decision support system, was accepted or refused. Methods We performed a retrospective cohort study of all hospitalized adult patients who received intravenous or oral antimicrobials in two tertiary care hospitals in Canada between 2014 and 2016, and for whom a recommendation was issued by an ASP. Results We identified 1,251 recommendations throughout the study period. Among the recommendations made by the pharmacist to prescribers, 1,144 (91.5%) were accepted. The most frequent interventions were immediate scheduling end of treatment (n = 364, 29%), dosing/frequency adjustments (n = 321, 26%), streamlining (n = 251, 20%), and switching from intravenous to oral therapy (n = 247, 20%). The antimicrobials most frequently targeted by recommendations were piperacillin/tazobactam (n = 273, 22%) and fluroquinolones (n = 267, 21). Overall, the length of the antimicrobial targeted by the recommendation was significantly shorter when a recommendation was accepted (0.37 days vs. 2.11 days; P < .001). In the multiple logistic regression analysis, the independent risk factors associated with in-hospital mortality were the Charlson score, issuance of a recommendation for a patient in the intensive care unit, the duration between admission and the recommendation, issuance of a recommendation in 2016 (compared with 2014), and age of the patient. A recommendation issued on a fluoroquinolone or oral penicillin/first generation cephalosporin was associated with lower odds of mortality. After adjustment, refusal of a recommendation by the attending physician was associated with a higher, albeit nonsignificant, risk of mortality (AOR, 1.81; 95% CI, 0.89–3.68; P = .10). Conclusion The duration of the antimicrobial treatment was significantly shorter when a recommendation triggered by an ASP program was accepted. This decrease in antimicrobial duration was not associated with increased mortality. Disclosures J. Perron, Lumed Inc., the company that commercializes APSS: Shareholder, Shareholder; V. Nault, Lumed Inc., the company that commercializes APSS: Shareholder, Shareholder; M. Beaudoin, Lumed Inc., the company that commercializes APSS: Shareholder, Shareholder; L. Valiquette, Lumed Inc., the company that commercializes APSS: Shareholder, Shareholder