Penicillin de-labelling in vancouver, British Columbia, Canada: comparison of approaches, outcomes and future directions.

BACKGROUND: Inaccurate penicillin allergy labels lead to inappropriate antibiotic prescriptions and harmful patient consequences. System-wide efforts are needed to remove incorrect penicillin allergy labels, but more health services research is required on how to best deliver these services. METHODS: Data was extracted from five hospitals in Vancouver, British Columbia, Canada from October 2018-May 2022. The primary outcomes of this study were to outline de-labelling protocol designs, identify the roles of various healthcare professionals in de-labelling protocols and identify rates of de-labelling penicillin allergies and associated adverse events at various institutions. Our secondary outcome was to describe de-labelling rates for special populations, including pediatric, obstetric and immunocompromised subpopulations. To achieve these outcomes, participating institutions provided their de-labelling protocol designs and data on program participants. Protocols were then compared to find common themes and differences. Furthermore, adverse events were reviewed and percentages of patients de-labelled at each institution and in total were calculated. RESULTS: Protocols demonstrated a high level of variability, including different methods of participant identification, risk-stratification and roles of providers. All protocols used oral and direct oral challenges, heavily involved pharmacists and had physician oversight. Despite the differences, of the 711 patients enrolled in all programs, 697 (98.0%) were de-labelled. There were 9 adverse events (1.3%) with oral challenges with mainly minor symptoms. CONCLUSIONS: Our data demonstrates that de-labelling programs effectively and safely remove penicillin allergy labels, including pediatric, obstetric and immunocompromised patients. Consistent with current literature, most patients with a penicillin allergy label are not allergic. De-labelling programs could benefit from increasing clinician engagement by increasing accessibility of resources to providers, including guidance for de-labelling of special populations.

Reduced fixed dose tocilizumab 400 mg IV compared to weight-based dosing in critically ill patients with COVID-19: A before-after cohort study.

Background: Interleukin-6 inhibitors reduce mortality in severe COVID-19. British Columbia began using tocilizumab 8 mg/kg (maximum 800 mg) in January 2021 in critically ill patients with COVID-19, but due to drug shortages, decreased dosing to 400 mg IV fixed dose in April 2021. The aims of this study were twofold: to compare physiological responses and clinical outcomes of these two strategies, and examine the cost-effectiveness of treating all patients with 400 mg versus half the patients with 8 mg/kg and the other half without tocilizumab. Methods: This was a single-centre, before-after cohort study of critically ill COVID-19 patients treated with tocilizumab, and a control cohort treated with dexamethasone only. Physiological responses and clinical outcomes were compared between patients receiving both doses of tocilizumab and those receiving dexamethasone only. We built a decision tree model to examine cost-effectiveness. Findings: 152 patients were included; 40 received tocilizumab 8 mg/kg, 59 received 400 mg and 53 received dexamethasone only. Median CRP fell from 103 mg/L to 5.2 mg/L, 96 mg/L to 6.8 mg/L and from 81.3 mg/L to 48 mg/L in the 8 mg/kg, 400 mg tocilizumab, and dexamethasone only groups, respectively. 28-day mortality was 5% (n=2) vs 8% (n=5) vs 13% (n=7), with no significant difference in all pair-wise comparison. At an assumed willingness-to-pay threshold of $50,000 Canadian per life-year, utilizing 400 mg for all patients rather than 8 mg/kg for half the patients is cost-effective in 51.6% of 10,000 Monte Carlo simulations. Interpretation: Both doses of tocilizumab demonstrated comparable reduction of inflammation with similar 28-day mortality. Without consideration of equity, the net monetary benefits of providing 400 mg tocilizumab to all patients are comparable to 8 mg/kg to half the patients. In the context of ongoing drug shortages, fixed-dose 400 mg tocilizumab may be a practical, feasible and economical option. Funding: This work was supported by a gift donation from Hsu & Taylor Family to the VGH Foundation, and the Yale Bernard G. Forget Scholarship.

Safety of administering cefazolin versus other antibiotics in penicillin-allergic patients for surgical prophylaxis at a major Canadian teaching hospital.

BACKGROUND: Cefazolin surgical prophylaxis is associated with better patient outcomes; however, its use in penicillin-allergic patients is controversial. We evaluated the safety of cefazolin as surgical prophylaxis in penicillin-allergic patients, including those with anaphylaxis histories. METHODS: We conducted a pre and postintervention quality improvement evaluation of an institution-wide policy change at a tertiary-care hospital, before (October 2017-January 2018), during (February 2018-September 2018), and after (October 2018-October 2019) transition to routine cefazolin prophylaxis for penicillin-allergic patients, including those with anaphylaxis histories but excluding severe delayed reactions (eg, Stevens-Johnson syndrome). Retrospective data was collected on all surgical prophylaxis patients with penicillin-anaphylactic histories between October 2017 and September 2018. From October 2018, we prospectively reviewed adverse events with cefazolin. Primary outcome was adverse events in penicillin-allergic patients receiving cefazolin perioperatively. RESULTS: From October 2017 to October 2019, 27,467 operations were performed. Of 220 patients with penicillin-anaphylactic histories reviewed prior to the full policy change, no statistically significant differences were reported in allergic reactions (P = .70), surgical site infections (P = 1.00), or adverse events (P = .32) with cefazolin compared to other antibiotics. Postpolicy implementation, cefazolin usage increased 18.2%, while vancomycin and clindamycin decreased by 11.4% and 62.0%, respectively. No anaphylaxis was documented in penicillin-allergic patients receiving cefazolin in either the review or quality assurance follow-up after the change. Of 3 patients developing reactions to cefazolin, none had histories of penicillin allergy. Surgical site infection rates were similar between pre and postpolicy time periods (P = .842). CONCLUSION: Administration of cefazolin in penicillin-anaphylactic patients for surgical prophylaxis appears to be safe.

What Is the Evidence for Co-trimoxazole, Clindamycin, Doxycycline, and Minocycline in the Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) Pneumonia?

Objective: To review the evidence for trimethoprim-sulfamethoxazole (TMP-SMX), clindamycin, doxycycline, and minocycline in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Data Source: MEDLINE, PubMed, EMBASE, Google, Google Scholar, Cochrane Central Register of Controlled Trials from 1946 to May 20, 2019. The search was performed with the keywords methicillin-resistant Staphylococcus aureus, MRSA, Staphylococcus aureus, pneumonia, trimethoprim, sulfamethoxazole drug combination, trimethoprim, sulfamethoxazole, TMP-SMX, co-trimoxazole, clindamycin, doxycycline, and minocycline. Data Extraction: Studies reporting the use of the above antibiotics for MRSA pneumonia treatment with clinical outcomes were included. Search parameters were limited to English language and human studies only. Data Synthesis: The search yielded 16 relevant articles: 6 TMP-SMX, 8 clindamycin, zero doxycycline, and 2 minocycline. For TMP-SMX, prospective randomized trials showed variable results; however, these studies were not specifically designed to assess MRSA pneumonia treatment. Retrospective studies with clindamycin suggested that it could be used as monotherapy or in combination with other anti-MRSA antibiotics. There was no evidence for doxycycline use, but 2 small retrospective reviews appeared to support minocycline as a treatment option. Relevance to Patient Care and Clinical Practice: These antibiotics are often used in clinical practice as potential treatment options for MRSA pneumonia. This article reviews the evidence for the clinical efficacy and safety of these agents. Conclusions: There are limited data to support use of TMP-SMX, clindamycin, doxycycline, or minocycline in MRSA pneumonia treatment. Randomized controlled trials are required to determine the effectiveness of these antibiotics. Clinicians should base their decision to use these agents on a case-by-case basis depending on clinical status and susceptibility results.

Non-standard treatment for uncomplicated Chlamydia trachomatis urogenital infections: a systematic review.

OBJECTIVES: To review the literature for non-standard treatment options for uncomplicated Chlamydia trachomatis (CT) infections in adolescents and adults. DESIGN: Systematic review. DATA SOURCES: Ovid MEDLINE/PubMed, Ovid EMBASE, Cochrane Trials & Systematic Review Databases, CINAHL Plus with Full Text, Web of Science Core Collection, Scopus, ProQuest Dissertations & Theses Global, ClinicalTrials.gov and Health Canada Trials Database were searched for studies in English or French from 1 January 2006 to 6 August 2017. Keywords included CT, anti-infective or anti-bacterial agents, therapy/pharmacotherapy/management. REVIEW METHODS: Included were primary research studies. Outcome measures included clinical or microbiological cure, treatment failure and adverse events. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were assessed for risk of bias using the Revised Cochrane Risk of Bias V.2.0 tool for randomised and the Newcastle-Ottawa Quality Assessment Scale for non-randomised studies. FUNDING SOURCE: Public Health Agency of Canada. RESULTS: Of the 6899 records identified through the database search, 11 studies were included. One randomised controlled trial reported that delayed release doxycycline was non-inferior to azithromycin. Two studies examined higher doses of azithromycin but reported no additional benefit. One study looked at a 5-day azithromycin treatment regimen and reported a high cure rate. Two studies reported efficacy of sitafloxacin, and a single study supports the use of levofloxacin. Two phase 2 studies reported efficacy of single-dose rifalazil in both men and women. Only one retrospective study was identified that examined treatment in pregnant women and reported that efficacy with single-dose azithromycin exceeded that of amoxicillin and erythromycin. A single study examining the efficacy of a beta-lactam antibiotic was stopped early due to high treatment failures. CONCLUSIONS: The paucity of existing data highlights the need for further adequately powered studies to evaluate rifalazil, delayed release doxycycline, levofloxacin and other agents for the treatment of uncomplicated CT infections. PROSPERO REGISTRATION NUMBER: CRD42017073096.

Treatment of Acute Epididymitis: A Systematic Review and Discussion of the Implications for Treatment Based on Etiology.

A systematic review of studies completed in the last 11 years for the treatment of acute epididymitis identified 1534 records, of which 29 were assessed for eligibility, and only 1 study met the criteria for inclusion. This highlights the need for more prospective studies evaluating treatment regimens for acute epididymitis.

Perceptions of Hospital Pharmacists Concerning Clinical Research: A Survey Study.

BACKGROUND: Few studies have attempted to determine the proportion of Canadian hospital pharmacists involved in clinical research, despite a general consensus that research should be an essential component of a pharmacist's professional role. OBJECTIVES: The primary objective was to characterize the involvement in clinical pharmacy research of hospital pharmacists in the 4 health authorities of the Lower Mainland of British Columbia (collectively known as the Lower Mainland Pharmacy Services). The secondary objective was to identify perceived barriers to conducting research. METHODS: Pharmacists employed within Lower Mainland Pharmacy Services were invited to participate in an online cross-sectional survey, for completion in August and September 2015. Descriptive statistics were used to analyze the results. Groups of survey participants were compared to examine differences in measured outcomes. RESULTS: A total of 534 pharmacists were surveyed, with a response rate of 16% (85/534). Overall, 77% (55/71) of the respondents reported having participated in research, and 87% (62/71) expressed interest in conducting future research. Chart reviews (78%, 36/46) and surveys (41%, 19/46) were the most common study designs used in prior research. Participants self-identified their research-related strengths as literature evaluation (46%, 27/59) and hypothesis generation (44%, 26/59). Conversely, 81% (48/59) of respondents self-identified statistical analysis as a weakness. Most respondents stated that personal satisfaction (82%, 49/60) and the opportunity to learn about disease states (78%, 47/60) were the driving factors for conducting research. The most commonly cited barrier to conducting research was lack of time (92%, 55/60). Opportunities to join existing teams (73%, 44/60) and mentorship programs (70%, 42/60) were identified as the most popular arrangements for encouraging future research. CONCLUSIONS: Most of the pharmacists who responded to this survey reported having participated in clinical pharmacy research, but a lack of dedicated time appears to be a major hurdle to greater research participation. A targeted program increasing exposure to existing research teams and mentorship opportunities is recommended for promoting future research.

CONTEXTE: Peu d'études ont cherché à déterminer la proportion de "pharmaciens d'hôpitaux canadiens qui contribuent à la recherche clinique, et ce, malgré un consensus voulant que la recherche doive être un élément essentiel du rôle professionnel des pharmaciens. OBJECTIFS: L'objectif principal était d'offrir un portrait de la contribution à la recherche sur la pharmacie clinique des pharmaciens d'hôpitaux des quatre régies régionales des basses-terres continentales de la Colombie- Britannique (appelées collectivement Lower Mainland Pharmacy Services, c.-à-d. services de pharmacie des basses-terres continentales). L'objectif secondaire était de recenser les éléments perçus comme des obstacles à la réalisation de recherches. MÉTHODES: Les pharmaciens employés au sein des services de pharmacie des basses-terres continentales ont été invités à participer par voie électronique à une enquête transversale qui devait être complétée en août et en septembre 2015. Des statistiques descriptives ont été employées pour analyser les résultats. On a aussi comparé des groupes de participants à l'enquête afin d'examiner les différences entre les résultats mesurés. RÉSULTATS: Au total, 534 pharmaciens ont été sondés et le taux de réponse était de 16 % (85/534). Dans l'ensemble, 77 % (55/71) des répondants indiquaient avoir participé à des recherches et 87 % (62/71) souhaitaient faire de la recherche dans l'avenir. L'analyse de dossiers médicaux (78 %, 36/46) et les sondages (41 %, 19/46) représentaient les plans d'étude les plus utilisés par les répondants au cours de recherches antérieures. Les participants ont indiqué que leurs forces en lien avec la recherche étaient leur capacité d'évaluer la littérature (46 %, 27/59) et de formuler des hypothèses (44 %, 26/59). En revanche, 81 % (48/59) ont signalé l'analyse statistique comme leur point faible. La plupart des répondants croyaient que la satisfaction personnelle (82 %, 49/60) et la perspective d'acquérir des connaissances sur les maladies (78 %, 47/60) représentaient les principaux facteurs les motivant à faire de la recherche. Ce qui était évoqué le plus souvent comme un obstacle à la recherche était le manque de temps (92 %, 55/60). Les occasions de se joindre à des équipes en place (73 %, 44/60) et les programmes de mentorat (70 %, 42/60) ont été désignés comme les dispositions les plus attrayantes pour encourager à poursuivre de futures recherches. CONCLUSIONS: La plupart des pharmaciens ayant répondu au sondage ont indiqué avoir contribué à des recherches en pharmacie clinique, mais le manque de temps réservé pour la recherche semblait être un obstacle important à une plus grande participation aux activités de recherche. Un programme ciblé multipliant les possibilités de fréquenter des équipes de recherche déjà établies et offrant plus d'occasions de mentorat serait une façon de promouvoir de futures recherches.

Combination of Ceftriaxone and Ampicillin for the Treatment of Enterococcal Endocarditis: A Qualitative Systematic Review.

OBJECTIVE: The aim of this systematic review is to review all human trials assessing the efficacy and safety of ampicillin and ceftriaxone for enterococcal endocarditis and to discuss the clinical implications of the findings. DATA SOURCES: MEDLINE (1946-), EMBASE (1974-), CENTRAL, Google Scholar, and the World Health Organization Clinical Trials Registry Platform were searched through January 2017 using the search terms ampicillin, penicillin, ceftriaxone, cephalosporin, enterococ*, and endocarditis. Unpublished studies were eligible for inclusion. Additional references were identified from literature citations. STUDY SELECTION AND DATA EXTRACTION: Clinical trials in humans that reported on clinical efficacy or adverse outcomes with ceftriaxone and ampicillin therapy in patients with enterococcal endocarditis were included. Case reports, nonhuman, and non-English studies were excluded. DATA SYNTHESIS: Four observational clinical studies were identified. One examined the effects of ceftriaxone and ampicillin alone, and 3 compared the therapy to the current standard of care, ampicillin and gentamicin. The studies had small sample sizes and were not adequately designed or powered to establish noninferiority or equivalence to the current standard of care. Rates of clinical cure with ampicillin 2 g every 4 hours and ceftriaxone 2 g every 12 hours were similar to those of ampicillin and gentamicin. Ampicillin and ceftriaxone therapy was well tolerated with low rates of renal failure (0%-33%). CONCLUSION: The evidence to support the use of ampicillin and ceftriaxone for enterococcal endocarditis is not definitive. In the absence of compelling evidence, clinicians may consider ampicillin and ceftriaxone in patients with Enterococcus faecalis infection at high risk for nephrotoxicity or those with aminoglycoside-resistant pathogens.

A Review of Clinical Outcomes Associated with Two Meropenem Dosing Strategies.

Meropenem is a carbapenem antibiotic that exhibits time-dependent bactericidal activity, traditionally dosed intravenously at 1 g every 8 h. In order to maximize its pharmacodynamic activity and reduce costs, an alternative regimen employed by many institutions is 500 mg every 6 h. The objective of this review was to summarize and evaluate published literature comparing clinical outcomes associated with these two meropenem dosing regimens. The literature was searched up to October 2016 using the MEDLINE, EMBASE, and Google Scholar databases. Three retrospective cohort studies were identified that compared clinical outcomes in general infectious disease patients (two studies) and patients with febrile neutropenia (one study). All studies reported no difference in clinical outcomes (clinical success, time to defervescence, sign or symptom resolution, length of stay, mortality, need for other antibiotics, and seizure rates). One study reported reduced economic costs with the alternative dosing. Interpretation of findings was primarily limited by small sample sizes and generalizability. Based on the data reviewed, the alternative dosing regimen of meropenem 500 mg intravenously every 6 h could be considered a therapeutic option. Future studies are needed to confirm the findings of this review, especially in high-risk populations such as immunocompromised patients or those with severe infections.

Roles of Infectious Diseases Consultant Pharmacists and Antimicrobial Stewardship Pharmacists: A Survey of Canadian Tertiary Care Academic Hospitals.

BACKGROUND: Infectious diseases consultant (IDC) pharmacists work within an IDC service to care for inpatients with complex infections. With Accreditation Canada's new Required Organizational Practice promoting the establishment of antimicrobial stewardship (AMS) programs, AMS pharmacists are being employed in acute care hospitals. There is potential for overlap in responsibilities between IDC and AMS pharmacists, but there is no literature outlining the current duties for each group in Canada. OBJECTIVE: To describe the demographic characteristics and roles of IDC and AMS pharmacists in Canadian tertiary care academic hospitals. METHODS: A survey of IDC and AMS pharmacists at Canadian tertiary care academic hospitals was conducted between February and April 2015. The questionnaire included questions about the pharmacist's experience, education, and training; the institution where the pharmacist was practising; the IDC or AMS team characteristics; and the pharmacist's roles in clinical, educational, administrative, and research sectors. RESULTS: The survey response rate was 77% (68/88). The 68 respondents self-identified as IDC pharmacists (14 [21%]), AMS pharmacists (34 [50%]), or dual-role IDC and AMS pharmacists (20 [29%]). Compared with AMS pharmacists, IDC pharmacists reported more of the following unique clinical activities: directly communicating with patients, attending rounds, involving patients in decision-making, and providing patient education. The 3 groups of pharmacists described similar educational responsibilities. The AMS pharmacists performed more of the following administrative and research duties: development of antibiograms and preprinted orders, collection of antimicrobial metrics, and drug-use evaluations for antimicrobials. Dual-role IDC and AMS pharmacists were involved in fewer of the unique activities described by those who practised within a single subspecialty. CONCLUSIONS: Self-identified IDC and AMS pharmacists in Canadian tertiary care academic hospitals were performing many similar roles; however, distinct differences within the clinical, administrative, and research domains were identified among IDC pharmacists, AMS pharmacists, and those who identified as dual-role IDC and AMS pharmacists.

CONTEXTE: Les pharmaciens consultants en maladies infectieuses travaillent au sein d'un service de consultants en maladies infectieuses afin de prodiguer des soins aux patients hospitalisés atteints d'infections complexes. Or, en raison de la nouvelle Pratique organisationnelle requise d'Agrément Canada qui encourage la mise en œuvre de programmes de gérance des antimicrobiens, des pharmaciens sont affectés à cette fonction dans les hôpitaux de soins de courte durée. On distingue un possible chevauchement des responsabilités entre les pharmaciens consultants en maladies infectieuses et ceux chargés de la gérance des antimicrobiens, mais il n'y a aucun document qui définit les responsabilités actuelles pour chacun de ces groupes au Canada. OBJECTIF: Décrire les caractéristiques démographiques et les rôles des pharmaciens consultants en maladies infectieuses et de ceux chargés de la gérance des antimicrobiens dans les hôpitaux universitaires de soins tertiaires au Canada. MÉTHODES: Entre février et avril 2015, on a mené un sondage auprès des pharmaciens consultants en maladies infectieuses et de ceux chargés de la gérance des antimicrobiens travaillant dans les hôpitaux universitaires de soins tertiaires au Canada. Les questions portaient, entre autres, sur l'expérience du pharmacien, ses études et sa formation, l'établissement où il travaillait, les caractéristiques des équipes de consultants en maladies infectieuses et de gérance des antimicrobiens ainsi que sur ses rôles dans les secteurs cliniques et administratifs et dans les secteurs de la formation et de la recherche. RÉSULTATS: Le taux de réponse au sondage était de 77 % (68/88). Les 68 répondants s'identifiaient comme des pharmaciens consultants en maladies infectieuses (14 [21 %]), des pharmaciens chargés de la gérance des antimicrobiens (34 [50 %]) ou des pharmaciens occupant les deux rôles (20 [29 %]). Comparativement à leur collègues chargés de la gérance des antimicrobiens, les pharmaciens consultants en maladies infectieuses ont davantage indiqué accomplir les activités cliniques uniques suivantes : communiquer directement avec les patients, participer aux tournées médicales, amener les patients à participer aux prises de décisions et offrir des conseils aux patients. Les trois groupes de pharmaciens ont évoqué des responsabilités éducatives similaires. Les pharmaciens chargés de la gérance des antimicrobiens accomplissaient davantage les tâches administratives et de recherche suivantes : élaboration d'antibiogrammes et d'ordonnances préimprimées, cueillette de mesures sur les antimicrobiens et évaluation de l'utilisation des antimicrobiens. Les pharmaciens qui cumulaient les deux rôles participaient à un moins grand nombre des activités uniques décrites par ceux qui exerçaient une seule sous-spécialité. CONCLUSIONS: Les pharmaciens des hôpitaux universitaires de soins tertiaires au Canada qui s'identifiaient eux-mêmes comme des pharmaciens consultants en maladies infectieuses ou des pharmaciens chargés de la gérance des antimicrobiens exécutaient bon nombre de tâches similaires. Cependant, des différences marquées en ce qui touche aux domaines clinique et administratif et à celui de la recherche ont été repérées entre les pharmaciens consultants en maladies infectieuses, ceux chargés de la gérance des antimicrobiens et ceux occupant les deux rôles.

Acute Kidney Injury With Tobramycin-Impregnated Bone Cement Spacers in Prosthetic Joint Infections.

BACKGROUND: Antibiotic-impregnated bone cement spacer (ACS) with tobramycin ± vancomycin is commonly used in a 2-stage replacement of infected prosthetic joints. This procedure has been associated with development of acute kidney injury (AKI). OBJECTIVE: To determine the incidence and risk factors for AKI after implantation of tobramycin-impregnated ACS. METHODS: This prospective, observational study evaluated 50 consecutive patients who received tobramycin ACS for first-stage revision of an infected hip or knee arthroplasty from August 2011 to February 2013. AKI was defined as 50% or greater rise in serum creatinine (SCr) from baseline within the first 7 postoperative days (PODs). RESULTS: The incidence of AKI was 20%, with median onset occurring at POD 2 (interquartile range [IQR] = 1-3); patients with AKI had a longer median duration of hospital stay (16 days, IQR = 12-17, vs 10 days, IQR = 8-10; P = 0.03). Serum tobramycin concentrations were significantly higher in the AKI group, peaking on POD 1 (median 1.9 vs 0.9 µg/mL, P = 0.01). Risk factors for nephrotoxicity identified by multivariate analysis were use of bone cement premanufactured with gentamicin (OR = 8.2; 95% CI = 1.1-60; P = 0.04), administration of blood transfusions intraoperatively (OR = 32.5; 95% CI = 2.3-454.3; P = 0.01) and nonsteroidal anti-inflammatory drugs postoperatively (OR = 23.0; 95% CI = 1.3-397.7; P = 0.03). CONCLUSIONS: Tobramycin ACS is associated with a high risk of AKI. Measures to minimize AKI risk in the perioperative period include early detection through close monitoring of SCr, avoiding use of premanufactured bone cement containing gentamicin, and avoiding potential nephrotoxins within the first 72 hours postoperatively.

Horizontal infection prevention measures and a risk-managed approach to vancomycin-resistant enterococci: An evaluation.

BACKGROUND: The use of infection control measures in the management of vancomycin-resistant enterococci (VRE) is hotly debated. A risk-managed approach to VRE control after the introduction of 2 horizontal infection prevention measures-an environmental cleaning (EC) and an antimicrobial stewardship (AMS) program-was assessed. METHODS: Routine screening for VRE was discontinued 6 and 4 months after introduction of the EC and AMS programs, respectively. Only 4 units (intensive care, burns-trauma, solid organ transplant, and bone marrow transplant units) where patients were deemed to be at increased risk for VRE infection continued screening and contact precautions. Cost avoidance and value-added benefits were monitored by the hospital finance department. VRE monitoring on these high-risk units and facility-wide comprehensive bacteremia surveillance continued as per established protocols. Surveillance for methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile infection (CDI) remained unchanged. RESULTS: VRE bacteremia rates did not increase with the change to the VRE risk-managed approach. The number of patients requiring VRE isolation in all areas of the hospital decreased from an average of 32 to 6 beds per day. Statistically significant reductions in CDI and MRSA rates were observed possibly related to the aggressive decluttering, equipment cleaning, and AMS program elements. CONCLUSION: A risk-managed approach to VRE can be implemented without adverse consequences and potentially with significant benefits to a facility.

Critical appraisal of clinical practice guidelines in pediatric infectious diseases.

BACKGROUND: There is a need to critically appraise clinical practice guidelines in order to ensure safe and effective practices are being implemented to optimize patient care. Appraising guidelines within one therapeutic area enable recommendations for improvement during guideline creation and dissemination. OBJECTIVES: Study objectives were to systematically appraise selected published guidelines used in the treatment of pediatric infectious diseases and to make recommendations for improvement throughout the development and dissemination processes. SETTING: The study occurred between collaborative academic and practice-based institutions located in Canada and Qatar. METHODS: A literature search identified guidelines for management of pediatric infectious diseases from 1997 to 2013. Each guideline was appraised by four independent assessors, according to the appraisal of guidelines for research and evaluation II (AGREE II) instrument. Standardized domain scores were calculated for each guideline and pooled. Final endorsements for use in clinical practice were also determined. Inter-rater reliability was assessed using intraclass correlation coefficients. MAIN OUTCOME MEASURE: Standardized domain scores according to the AGREE II instrument. RESULTS: Twenty guidelines met inclusion criteria and were appraised. Pooled domain scores were: scope and purpose (69.9), stakeholder involvement (40.1), rigour of development (47.1), clarity of presentation (73.4), applicability (23.7), editorial independence (46.7), and overall assessment (55.8). Two (10%) guidelines were recommended for use without revision, 13 (65%) guidelines were recommended with modifications, and 5 (25%) guidelines were not recommended for implementation into practice. Inter-rater reliability was moderate to good with intra-class correlations of 0.65-0.93 per guideline. CONCLUSION: The majority of appraised guidelines were moderately rated, with a 25% of guidelines not recommended for use. Strategies for improvement require the involvement of all key stakeholders (caregivers, patients, and allied health professionals), and consideration of facilitators, barriers and resource implications during implementation. Additionally, critical appraisal of guidelines should become standard practice prior to adoption into clinical settings.

Vancomycin loading doses: a systematic review.

OBJECTIVE: To systematically assess the literature to ascertain the pharmacokinetics, pharmacodynamics, and clinical efficacy and safety associated with administration of a vancomycin loading dose (LD). DATA SOURCES: MEDLINE (1948-December 31, 2014), EMBASE (1980-December 31, 2014), Cochrane Central Register of Controlled Trials, International Pharmaceutical Abstracts (1970-December 31, 2014), Google and Google Scholar, and International Clinical Trials Registry Platform were searched using the following terms: vancomycin, glycopeptides, loading dose, dose-response relationship. STUDY SELECTION AND DATA EXTRACTION: Pharmacokinetic, pharmacodynamic, and clinical efficacy studies using vancomycin LDs to achieve trough concentrations of 15 to 20 mg/L were included. Nonhuman, non-English, oral vancomycin, and dialysis patient studies were excluded. Abstracts were included. Study quality was ranked using US Preventative Services Task Force 1996 classification system. Data on study design, baseline characteristics, exclusion criteria, dosing, study outcomes, and conclusions were extracted. DATA SYNTHESIS: A total of 8 studies (5 manuscripts [2 level I, 3 level II-3] and 3 abstracts) were cited. Of 6 adult studies, 4 concluded that administration of vancomycin LDs resulted in significantly more patients achieving troughs of 15 to 20 mg/L. Studies in children found that LDs did not lead to rapid attainment of vancomycin levels ≥15 mg/L. No studies assessed clinical or microbiological outcomes. Limitations included heterogeneity and inconsistent timing of concentration measurements. CONCLUSIONS: High-quality data to guide the use of vancomycin LDs are lacking. LDs may more rapidly attain vancomycin troughs of 15 to 20 mg/L in adults, but information in pediatrics, obesity, and renal impairment is limited. Further studies are required to determine benefit of LDs on clinical and microbiological outcomes.

Antimicrobial co-resistance patterns of gram-negative bacilli isolated from bloodstream infections: a longitudinal epidemiological study from 2002-2011.

BACKGROUND: Increasing multidrug resistance in gram-negative bacilli (GNB) infections poses a serious threat to public health. Few studies have analyzed co-resistance rates, defined as an antimicrobial susceptibility profile in a subset already resistant to one specific antibiotic. The epidemiologic and clinical utility of determining co-resistance rates are analyzed and discussed. METHODS: A 10-year retrospective study from 2002-2011 of bloodstream infections with GNB were analyzed from three hospitals in Greater Vancouver, BC, Canada. Descriptive statistics were calculated for antimicrobial resistance and co-resistance. Statistical analysis further described temporal trends of antimicrobial resistance, correlations of resistance between combinations of antimicrobials, and temporal trends in co-resistance patterns. RESULTS: The total number of unique blood stream isolates of GNB was 3280. Increasing resistance to individual antimicrobials was observed for E. coli, K. pneumoniae, K. oxytoca, E. cloacae, and P. aeruginosa. Ciprofloxacin resistance in E. coli peaked in 2006 at 40% and subsequently stabilized at 29% in 2011, corresponding to decreasing ciprofloxacin usage after 2007, as assessed by defined daily dose utilization data. High co-resistance rates were observed for ceftriaxone-resistant E. coli with ciprofloxacin (73%), ceftriaxone-resistant K. pneumoniae with trimethoprim-sulfamethoxazole (83%), ciprofloxacin-resistant E. cloacae with ticarcillin-clavulanate (91%), and piperacillin-tazobactam-resistant P. aeruginosa with ceftazidime (83%). CONCLUSIONS: Increasing antimicrobial resistance was demonstrated over the study period, which may partially be associated with antimicrobial consumption. The study of co-resistance rates in multidrug resistant GNB provides insight into the epidemiology of resistance acquisition, and may be used as a clinical tool to aid prescribing empiric antimicrobial therapy.

Evaluation of a Once-Daily Vancomycin Regimen in an Outpatient Leukemia/Bone Marrow Transplant Clinic (OD-VANCO Study).

BACKGROUND: The Leukemia/Bone Marrow Transplant Program of British Columbia manages patients with high-risk febrile neutropenia and those with non-neutropenic immunocompromised states in an outpatient clinic setting. Because the program treats outpatients only, once-daily administration of IV antibiotics is desirable. A high-dose, once-daily vancomycin nomogram was developed and implemented as part of the antibiotic treatment regimen. OBJECTIVE: To determine if therapeutic vancomycin trough levels could be achieved with a high-dose, once-daily regimen in this outpatient setting. METHODS: A prospective, single-centre, observational cohort study was conducted over a 7-month period. Outpatients in the Leukemia/Bone Marrow Transplant Program were started on IV vancomycin with the high-dose, once-daily vancomycin nomogram, and outcomes were assessed. RESULTS: Of 48 outpatients treated over the 7-month period, 10 (21%) had therapeutic vancomycin trough concentrations (i.e., greater than 10 mg/L). Thirty-five (90%) of the 39 patients with suspected clinical infection experienced clinical cure, and 6 (67%) of the 9 patients with documented microbiological infection experienced microbiological cure. Thirty (62%) of the 48 patients experienced symptoms of "red man syndrome", and 7 (15%) experienced some degree of nephrotoxicity. Two of 3 patients with laboratory-reported minimum inhibitory concentration (MIC) for identified pathogens had a calculated area under the curve to MIC ratio greater than or equal to 400. CONCLUSION: The high-dose, once-daily vancomycin nomogram was effective in attaining trough levels greater than 10 mg/L in only 21% of patients in this study. A substantial number of adverse drug reactions were observed. Given these results, high-dose, once-daily vancomycin is no longer recommended for outpatient therapy.

CONTEXTE: Le programme sur la leucémie et la greffe de moelle osseuse de la Colombie-Britannique (Leukemia/Bone Marrow Transplant Program of British Columbia) traite en consultation externe des patients avec une neutropénie fébrile à risque élevé et d'autres en états non neutropéniques d'immunovulnérabilité. Comme le programme s'adresse uniquement à des patients externes, une administration intraveineuse (IV) uniquotidienne d'antibiotiques est souhaitée. Pour cette raison, un nomogramme posologique pour la vancomycine à dose uniquotidienne élevée a été élaboré et mis en place dans le cadre du schéma d'antibiothérapie. OBJECTIF: Déterminer s'il est possible d'atteindre des concentrations minimales thérapeutiques de vancomycine à l'aide d'un schéma thérapeutique à dose uniquotidienne élevée dans ce service de consultation externe. MÉTHODES: Une étude de cohorte prospective observationnelle a été menée dans un seul centre sur une période de sept mois. Le nomogramme posologique a servi à commencer le traitement IV par la vancomycine à dose uniquotidienne élevée de patients externes participant au programme sur la leucémie et la greffe de moelle osseuse, et les résultats ont été évalués. RÉSULTATS: Parmi les quarante-huit patients externes traités pendant une période de sept mois, des concentrations minimales thérapeutiques de vancomycine (c.-à-d. plus de 10 mg/L) ont été atteintes chez dix (21 %) d'entre eux. Trente-cinq (90 %) des trente-neuf patients chez qui l'on soupçonnait une infection clinique ont obtenu une guérison clinique et une éradication microbiologique a été notée chez six (67 %) des neuf patients présentant une infection microbiologique attestée. Trente (62 %) des 48 patients ont présenté un syndrome de l'homme rouge et sept patients (15 %) ont manifesté un certain degré de néphrotoxicité. Deux des trois patients pour qui le laboratoire avait déterminé une concentration minimale inhibitrice (CMI) contre les agents pathogènes en cause avaient un rapport aire sous la courbe sur CMI égal ou supérieur à 400. CONCLUSION: Le nomogramme posologique pour la vancomycine à dose uniquotidienne élevée a permis d'atteindre des concentrations minimales de plus de 10 mg/L chez seulement 21 % des patients de cette étude. Un nombre considérable d'effets indésirables liés au médicament a été observé. Compte tenu de ces résultats, il n'est plus recommandé de donner des doses uniquotidiennes élevées de vancomycine à titre de traitement aux patients externes. [Traduction par l'éditeur].

Identification of risk factors for nephrotoxicity in patients receiving extended-duration, high-trough vancomycin therapy.

BACKGROUND: In the past, impurities in vancomycin formulations were thought to contribute to nephrotoxicity. In contrast, when current, purer formulations are dosed at conventional trough levels (i.e., 5-15 mg/L), the incidence of nephrotoxicity is relatively low. Recent guidelines have recommended targeting higher vancomycin trough levels in treatment of complicated methicillin-resistant Staphylococcus aureus infections. Dosing based on these higher trough levels may be associated with nephrotoxicity, so the potential risk factors for vancomycin-associated nephrotoxicity require clearer definition. OBJECTIVES: To determine the occurrence of nephrotoxicity in patients receiving more than 7 days of vancomycin therapy with high trough levels (15-20 mg/L) and to identify and evaluate specific risk factors related to development of vancomycin-associated nephrotoxicity (i.e., serum creatinine ≥ 44.2 µmol/L or increase ≥ 50% [i.e., ≥ 26.2 µmol/L] from baseline on 2 consecutive days). METHODS: Health care records were reviewed for patients seen at 2 major teaching hospitals between January 2008 and March 2011. Patients who had attained high trough levels of vancomycin were screened for eligibility. Patients with unstable renal function, those undergoing hemodialysis, and those for whom dosage and/or sampling times were unclear were excluded. Univariate and multivariate analyses were performed to identify risk factors associated with nephrotoxicity. Univariate variables with p < 0.1 were included in the logistic regression model. RESULTS: Of the 176 patients with high trough levels included in the analysis, 24 (14%) experienced nephrotoxicity. In univariate analysis, admission to a general medicine unit (the setting of care for 16 [67%] of the 24 patients with nephrotoxicity) and extended duration of vancomycin treatment were identified as risk factors for nephrotoxicity (p < 0.1). Other risk factors included gastrointestinal comorbidity (p = 0.056), malignancy (p = 0.044), and febrile neutropenia (p = 0.032). Multivariate analysis identified treatment on general medicine units and treatment courses longer than 7 days as independent predictors of vancomycin-associated nephrotoxicity. CONCLUSION: Patients being treated on general medicine units and those receiving vancomycin for more than 7 days had an increased likelihood of experiencing nephrotoxicity. The increased risk for patients on general medicine units is likely multifactorial. The relationship between treatment duration and risk of nephrotoxicity appeared to be linear. When using extended-duration, high-trough vancomycin therapy, clinicians should be vigilant in monitoring for nephrotoxicity.

CONTEXTE: On croyait autrefois que les impuretés contenues dans les préparations de vancomycine pouvaient contribuer à causer une néphrotoxicité. D'un autre côté, lorsque les préparations actuelles plus pures sont dosées selon les concentrations minimales classiques (c.-à-d., 5­15 mg/L), les cas de néphrotoxicité sont relativement peu nombreux. Des lignes directrices récentes recommandaient de viser des concentrations minimales plus élevées de vancomycine pour traiter les infections compliquées à Staphylococcus aureus résistant à la méthicilline. Comme ces concentrations minimales plus élevées peuvent être associées à la néphrotoxicité, il est nécessaire de mieux définir les facteurs de risque potentiels de néphrotoxicité associée à l'administration de vancomycine. OBJECTIFS: Déterminer le nombre de cas de néphrotoxicité chez les patients recevant un traitement de vancomycine de plus de sept jours avec des concentrations minimales élevées (15­20 mg/L), ainsi que cerner et évaluer les facteurs de risque précis associés à une néphrotoxicité causée par la vancomycine (c.-à-d., une créatinine sérique de ≥ 44,2 µmol/L ou une augmentation de ≥ 50 % [c.-à-d., ≥ 26,2 µmol/L] par rapport aux valeurs de base pendant deux jours consécutifs). MÉTHODES: Les dossiers médicaux des patients rencontrés entre janvier 2008 et mars 2011 dans deux importants hôpitaux universitaires ont été examinés. Les patients chez qui les concentrations minimales de vancomycine avaient atteint des valeurs élevées ont été évalués afin de juger s'ils étaient admissibles. Les patients dont la fonction rénale était instable, ceux qui subissaient une hémodialyse et ceux pour qui la posologie ou le temps d'échantillonnage n'étaient pas clairs ont été exclus. Des analyses univariée et multivariée ont été effectuées pour cerner les facteurs de risque associés à une néphrotoxicité. Les variables univariées dont le p était inférieur à 0,1 ont été incorporées dans le modèle de régression logistique. RÉSULTATS: Parmi les 176 patients avec des concentrations minimales élevées, 24 (14 %) ont souffert de néphrotoxicité. Lors de l'analyse univariée, l'hospitalisation dans un service de médecine générale (unité où les soins étaient prodigués pour 16 [67 %] des 24 patients souffrant de néphrotoxicité) ainsi que la prolongation du traitement avec la vancomycine ont été reconnues comme des facteurs de risque de néphrotoxicité (p < 0,1). La comorbidité gastro-intestinale (p = 0,056), le cancer (p = 0,044) et la neutropénie fébrile (p = 0,032) représentaient aussi des facteurs de risque. L'analyse multivariée a déterminé que le traitement dans un service de médecine générale et les traitements de plus de sept jours étaient des indicateurs indépendants de risque de néphrotoxicité associée à la prise de vancomycine. CONCLUSION: Les patients ayant été traités dans un service de médecine générale et ceux ayant reçu un traitement de vancomycine de plus de sept jours présentaient un plus grand risque de néphrotoxicité. Le risque accru pour les patients séjournant dans un service de médecine générale est probablement multifactoriel. Le lien entre la durée du traitement et le risque de néphrotoxicité semble linéaire. Lorsqu'ils font appel à un traitement de vancomycine à concentration minimale élevée, les cliniciens doivent procéder à un suivi attentif pour déceler tout signe de néphrotoxicité. [Traduction par l'éditeur].

Addition of rifampin to vancomycin for methicillin-resistant Staphylococcus aureus infections: what is the evidence?

OBJECTIVE: To evaluate evidence supporting efficacy and safety of the combination of vancomycin and rifampin for treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. DATA SOURCES: MEDLINE (1946-February 2013), EMBASE (1974-February 2013) and Cochrane Database of Systematic Reviews were searched. STUDY SELECTION: All human prospective trials and retrospective studies evaluating clinical outcomes of vancomycin-rifampin combinations were included. Case reports, case series, and in vitro or animal data were excluded. DATA EXTRACTION: Full-text articles were included and abstracts excluded; 43 of 421 references were reviewed. Five articles met inclusion and were evaluated. DATA SYNTHESIS: A nonrandomized prospective trial reported complete clearance of MRSA bacteremia at 24 hours in all 14 burn patients receiving vancomycin-rifampin therapy. In a case-control study of 42 patients with MRSA endocarditis, adding rifampin prolonged bacteremia (5.2 vs 2.1 days, p < 0.001), decreased survival rates (79% vs 95%, p = 0.048), resulted in drug interactions (52% of cases), and increased hepatic transaminases (21% vs 2%, p = 0.014). In a retrospective analysis of 28 patients with persistent MRSA bacteremia requiring salvage therapy, switching from vancomycin-based to linezolid-based treatment was associated with better salvage success than adding rifampin (88% vs 0%, p < 0.001). In a randomized open-label trial of 42 patients with MRSA endocarditis, addition of rifampin to vancomycin did not affect cure rates (90% combination vs 82% monotherapy, p > 0.20), but increased duration of bacteremia (9 vs 7 days, p > 0.20) compared with vancomycin monotherapy. Another randomized open-label trial of combination versus monotherapy for MRSA pneumonia in 93 intensive care unit patients reported higher clinical successes (53.7% vs 31.0%, p = 0.047), similar 30-day mortality rates, and more adverse events with combination therapy (11 vs 6). CONCLUSIONS: Limited evidence exists to support the adjunctive use of rifampin to treat MRSA infections. The combination may increase drug interactions, adverse effects, and rifampin resistance. Further studies are needed to define the role of rifampin adjunct therapy.

Drug use evaluation of moxifloxacin (avelox) using a hand-held electronic device at a canadian teaching hospital.

BACKGROUND: The use of moxifloxacin (Avelox) has increased at Vancouver General Hospital since its introduction onto the formulary in 2002. It is unclear, however, whether the use of the drug is optimal according to its indication. Hand-held electronic devices, such as personal digital assistants (PDAs), are novel tools that can be used during routine patient care to collect data for drug use evaluation (DUE) reviews. OBJECTIVE: We hypothesized that moxifloxacin was over-utilized and that opportunities existed to optimize its use. This study was designed to characterize moxifloxacin use in concordance with evidence-based assessment criteria. The feasibility of using a PDA device as a data-collection tool was also evaluated. DESIGN: An observational DUE was conducted over a 4-week period (from February 17 to March 16, 2007) at Vancouver General Hospital, a 955-bed tertiary care hospital. Inpatients who received at least one dose of moxifloxacin were enrolled. Evidence-based assessment criteria were developed to evaluate the appropriateness of moxifloxacin use, and a PDA database was developed for data collection. The primary endpoint was the proportion of moxifloxacin use for approved first-line indications. RESULTS: A total of 132 patients were included. Eighty-nine patients (67%) received moxifloxacin for first-line indications, including community-acquired pneumonia (57%) and acute exacerbation of chronic bronchitis (10%). Forty-three patients (33%) had alternative indications, primarily hospital-acquired pneumonia (25%). In 129 evaluable patients, approximately half (51%) of the clinical outcomes were successful; 37% were indeterminate; and 12% were failures. General medicine and respiratory service clinicians prescribed moxifloxacin more appropriately compared with surgical service personnel. Most of the pharmacists supported the use of PDAs as DUE data-collection tools. CONCLUSION: Overall, moxifloxacin utilization at Vancouver General Hospital was appropriate according to evidence-based assessment criteria. Additional opportunities to improve its use exist through health care staff education. PDAs are ideal data-collection tools for DUEs, as they can be conveniently used during routine patient care.