Impact of a bloodstream infection stewardship program in hospitalized patients.

BACKGROUND: Bloodstream infections (BSIs) in hospitalized patients represent sentinel events requiring timely and responsive antimicrobial prescribing. These infections represent an attractive but seldom-evaluated stewardship opportunity. METHODS: Retrospective pre-post study design, with review of patient charts 18 months before and after initiation of a hospital Bloodstream Infection Stewardship Program (BSISP). Pre-intervention, the ward and attending physician were notified of all positive blood cultures. Post-intervention, an infectious disease (ID) pharmacist collaborating with an ID consultant was also notified. RESULTS: Two hundred twenty-six eligible BSIs were identified pre-intervention and 195 post-intervention. The urinary tract was the most common source of infection; most common bloodstream isolates were Escherichia coli, Staphylococcus aureus, beta-hemolytic streptococci, and Klebsiella pneumoniae; 71.7% of infections were community acquired. Empiric therapy was not given in 17.3% of cases and inadequate in 16.4% of patients. Therapy was altered on the basis of Gram stain results ('directed therapy') in 54.6% of episodes and was inadequate in 3.5%. Compared to pre-intervention, the post-intervention cohort received directed therapy on average 4.36 hours earlier (p = 0.003), was more likely to receive appropriate definitive therapy (99.0% post versus 79.1% pre, p <0.001), stepped down to oral therapy earlier (6.0 versus 8.0 days, p = 0.031), and received fewer directed prescriptions (214 per 100 cases post versus 260 per 100 cases pre; p = 0.001), including fewer prescriptions of quinolones and clindamycin. CONCLUSIONS: A BSISP could be an effective strategy for improving antimicrobial prescribing in hospitalized patients with a BSI.

HISTORIQUE: Chez les patients hospitalisés, les infections sanguines sont des événements sentinelles qui exigent des prescriptions antimicrobiennes opportunes et adaptées. Ces infections représentent une possibilité de gestion attrayante, mais rarement évaluée. MÉTHODOLOGIE: Les chercheurs ont utilisé une méthodologie d'étude avant-après comportant l'analyse des dossiers des patients 18 mois avant et après un programme de gestion des infections sanguines (PGIS) en milieu hospitalier. Avant l'intervention, le médecin du service a été avisé de toutes les cultures sanguines positives. Après l'intervention, un pharmacien infectiologue qui collaborait avec un consultant en infectiologie a également été avisé. RÉSULTATS: Au total, les chercheurs ont relevé 226 infections sanguines admissibles avant l'intervention et 195 après l'intervention. Les voies urinaires étaient la principale source d'infection et les principaux isolats sanguins, l'Escherichia coli, le Staphylococcus aureus, les streptocoques bêta-hémolytiques et le Klebsiella pneumoniae; 71,7 % des infections étaient d'origine communautaire. Dans 17,3 % des cas, les patients n'ont pas reçu de traitement empirique et chez 16,4 % des patients, le traitement n'était pas approprié. Il était modifié en fonction des résultats de la coloration de Gram de base (« thérapie dirigée ¼) dans 54,6 % des épisodes et n'était pas approprié dans 3,5 % des cas. Par rapport à celle d'avant l'intervention, la cohorte d'après l'intervention a reçu une thérapie dirigée en moyenne 4,36 heures plus tôt (p = 0,003) et était plus susceptible de recevoir un traitement définitif approprié (99,0 % après par rapport à 79,1 % avant, p <0,001), de passer à un traitement par voie orale plus rapidement (6,0 jours plutôt que 8,0, p = 0,031) et de recevoir moins d'ordonnances dirigées (214 sur 100 cas après, par rapport à 260 sur 100 cas avant; p = 0,001), y compris moins d'ordonnances de quinolones et de clindamycine. CONCLUSIONS: Un PGIS pourrait être une stratégie efficace pour améliorer les prescriptions d'antimicrobiens chez des patients hospitalisés atteints d'une infection sanguine.

Real-life experience with ceftolozane/tazobactam in Canada: results from the CLEAR (Canadian LEadership on Antimicrobial Real-life usage) registry.

OBJECTIVES: Ceftolozane/tazobactam is a cephalosporin/ß-lactamase inhibitor combination with activity against Gram-negative bacilli. Here we report the use of ceftolozane/tazobactam in Canada using a national registry. METHODS: The CLEAR registry uses a REDCapTM online survey to capture details associated with clinical use of ceftolozane/tazobactam. RESULTS: Data from 51 patients treated in 2020 with ceftolozane/tazobactam are available. Infections treated included hospital-acquired bacterial pneumonia (37.3% of patients), ventilator-associated bacterial pneumonia (15.7%), bone and joint infection (11.8%), complicated intra-abdominal infection (7.8%) and complicated skin and skin-structure infection (7.8%). Moreover, 17.6% of patients had bacteraemia and 47.1% were in intensive care. Ceftolozane/tazobactam was primarily used as directed therapy for Pseudomonas aeruginosa infections (92.2% of patients). Ceftolozane/tazobactam was used because of resistance to (86.3%), failure of (11.8%) or adverse effects from (2.0%) previously prescribed antimicrobials. Ceftolozane/tazobactam susceptibility testing was performed on isolates from 88.2% of patients. Ceftolozane/tazobactam was used in combination with another antimicrobial active against Gram-negative bacilli in 39.2% of patients [aminoglycosides (15.7%), fluoroquinolones (9.8%) and colistin/polymyxin B (7.8%)]. The dosage regimen was customised in all patients based on creatinine clearance. The treatment duration was primarily >10 days (60.8% of patients), with microbiological success in 60.5% and clinical success in 64.4% of patients. Moreover, 7.8% of patients had adverse effects not requiring drug discontinuation. CONCLUSION: In Canada, ceftolozane/tazobactam is used as directed therapy to treat a variety of severe infections caused by multidrug-resistant P. aeruginosa. It is commonly used in combination with other antimicrobials with relatively high microbiological/clinical cure rates and an excellent safety profile.

Real-life experience with ceftobiprole in Canada: Results from the CLEAR (CanadianLEadership onAntimicrobialReal-life usage) registry.

OBJECTIVES: Ceftobiprole is an advanced-generation cephalosporin with a favourable safety profile. Published data on the clinical use of ceftobiprole are limited. We report use of ceftobiprole in Canadian patients using data captured by the CLEAR registry. METHODS: The CLEAR registry uses the web-based research data management program REDCap™ (online survey) to facilitate clinicians entering details associated with their clinical experiences using ceftobiprole. RESULTS: Data were available for 38 patients treated with ceftobiprole. The most common infections treated were endocarditis (42.1% of patients), bone and joint infection (23.7%) and hospital-associated bacterial pneumonia (15.8%). 92.1% of patients had bacteraemia and 21.1% were in intensive care. Ceftobiprole was used because of failure of (71.1%), resistance to (18.4%) or adverse effects from (10.5%) previously prescribed antimicrobial agents. Ceftobiprole was primarily used as directed therapy for methicillin-resistant Staphylococcus aureus (MRSA) infections (94.7% of patients). Ceftobiprole susceptibility testing was performed on isolates from 47.4% of patients. It was used concomitantly with daptomycin in 55.3% of patients and with vancomycin in 18.4% of patients. Treatment duration was primarily >10 days (65.8% of patients) with microbiological success in 97.0% and clinical success in 84.8% of patients. 2.6% of patients had gastrointestinal adverse effects. CONCLUSION: In Canada to date, ceftobiprole is used as directed therapy to treat a variety of severe infections caused by MRSA. It is primarily used in patients failing previous antimicrobials, is frequently added to, and thus used in combination with daptomycin or vancomycin with high microbiological and clinical cure rates and an excellent safety profile.

Optimizing Glycemic Control in Adults With Type 1 or Type 2 Diabetes Attending a Multidisciplinary Foot Clinic.

OBJECTIVES: To determine the impact of a diabetes nurse educator (DNE) on glycemic control in a multidisciplinary diabetes foot (MDF) clinic. METHODS: A prospective cohort trial to measure the impact of a DNE on glycemic control was conducted in an MDF clinic. Change in glycated hemoglobin (A1C) levels over time was measured against the percentage of patient visits (PPVs) accompanied by a glucose meter and/or diary. RESULTS: Increasing PPVs were significantly associated with decline in A1C levels in females. Every 10% increase in PPVs resulted in a 0.18% decrease in A1C levels (p<0.0001). To achieve a clinically important decrease of 1% in A1C levels, a 56% increase in PPVs was required. Increased A1C levels were significantly associated with higher baseline A1C levels (p<0.001) and increased hospital days for foot complications (p<0.0052). CONCLUSIONS: Regular, face-to-face contact with a DNE in an MDF clinic has a positive impact on glycemic control in females.

Patterns and correlates of cannabis use among individuals with HIV/AIDS in Maritime Canada.

BACKGROUND: The prevalence of cannabis use in HIV-infected individuals is high and its long-term effects are unclear. METHODS: The prevalence, perceived benefits and consequences, and predictors of cannabis use were studied using a cross-sectional survey in two immunodeficiency clinics in Maritime Canada. RESULTS: Current cannabis use was identified in 38.5% (87 of 226) of participants. Almost all cannabis users (85 of 87 [97.7%]) acknowledged its use for recreational purposes, with 21.8% (19 of 87) reporting medicinal cannabis use. The majority of patients enrolled in the present study reported mild or no symptoms related to HIV (n=179). Overall, 80.5% (70 of 87) of the cannabis-using participants reported a symptom-relieving benefit, mostly for relief of stress, anorexia or pain. Participants consumed a mean (± SD) of 18.3±21.1 g of cannabis per month and spent an average of $105.15±109.87 on cannabis per month. Cannabis use was associated with rural residence, lower income level, driving under the influence of a substance, and consumption of ecstasy and tobacco. Income level, ecstasy use and tobacco use were retained as significant predictors in regression modelling. Cannabis use was not associated with adverse psychological outcomes. DISCUSSION: Prolonged previous cannabis consumption and the substantial overlap between recreational and medicinal cannabis use highlight the challenges in obtaining a tenable definition of medicinal cannabis therapy.

HISTORIQUE: La prévalence de consommation de cannabis est élevée chez les personnes infectées par le VIH, mais on n'en connaît pas les effets à long terme. MÉTHODOLOGIE: Les chercheurs ont étudié la prévalence, les avantages perçus et les conséquences et prédicteurs de consommation de cannabis au moyen d'un sondage transversal mené dans deux cliniques d'immunodéficience des Maritimes, au Canada. RÉSULTATS: Les chercheurs ont constaté une consommation courante de cannabis chez 38,5 % des participants (87 sur 226). Presque tous les consommateurs de cannabis (85 sur 87 [97,7 %]) admettaient en prendre pour des fins récréatives, et 21,8 % (19 sur 87) indiquaient en prendre pour des fins médicinales. La majorité des patients qui participaient à la présente étude a déclaré des symptômes du VIH légers, sinon inexistants (n=179). Dans l'ensemble, 80,5 % des participants consommateurs de cannabis (70 sur 87) ont affirmé remarquer un soulagement des symptômes, particulièrement le stress, l'anorexie ou la douleur. Les participants consommaient en moyenne 18,3±21,1 g de cannabis par mois et dépensaient en moyenne 105,15±109,87 $ par mois pour se le procurer. La consommation de cannabis était liée à un logement en milieu rural, à un niveau de revenu plus bas, à la conduite sous l'influence d'une substance et à la consommation d'ecstasy et de tabac. Le niveau de revenu, la consommation d'ecstasy et la consommation de tabac étaient considérés comme des prédicteurs importants selon le modèle de régression. La consommation de cannabis ne s'associait pas à des résultats psychologiques indésirables. EXPOSÉ: Une consommation antérieure prolongée de cannabis et le chevauchement important entre la consommation de cannabis à des fins récréatives et médicinales font ressortir la difficulté d'obtenir une définition viable du traitement médicinal par le cannabis.

Decolonization of methicillin-resistant Staphylococcus aureus during routine hospital care: Efficacy and long-term follow-up.

BACKGROUND/OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) colonization is associated with a significant risk of subsequent MRSA infection in the hospital setting. The use of decolonization as an infection control strategy remains highly controversial despite publications evaluating more than 40 different decolonization regimens over the past 60 years. The present study describes the benefits and potential drawbacks of such an approach in the patient population. METHODS: A retrospective cohort study was performed to assess the efficacy and subsequent outcome for patients with newly identified MRSA colonization at the Horizon Health Network in Moncton, New Brunswick. RESULTS: A total of 241 patients with MRSA colonization or infection during the study period (2000 to 2005 inclusive) were identified. Eighty-nine MRSA-positive patients were decolonized according to a standardized regimen (hospital protocol group), and 98 received an alternative decolonization regimen (other treatment group). No attempt at decolonization was made for 54 patients (no treatment group). The hospital protocol group demonstrated superior overall successful decolonization compared with the other treatment group (67 of 84 [80%] versus 48 of 89 [54%]; OR 3.3; 95% CI 1.6 to 7.1; P=0.0004) and the no treatment group (four of 43 [9%]; OR 36.9; 95% CI 11.2 to 161.7; P<0.000001). The mean observed duration of culture negativity for the subgroup who remained MRSA culture negative over the long term was 419±398 days (range one to 1817 days). Successful decolonization occurred in 115 patients and permitted subsequent release from contact isolation for 4530 patient-days. The rate of clinical infection with MRSA was significantly lower in the hospital protocol group versus the other treatment group (16 of 89 [18%] versus 37 of 98 [38%]; OR 0.38; 95% CI 0.18 to 0.78; P=0.003). CONCLUSION: The present study supports recent reports indicating that MRSA decolonization can be successful using a multifactorial approach (chlorhexidine soap, enhanced hygiene/housekeeping and combination oral/topical antimicrobial therapy) in hospitalized patients, both over the short and long term. Unlike previous studies, decolonization appeared to be effective in a relatively unselected population, including patients with lines and catheters. Inability to decolonize was most closely associated with failure to use a standardized decolonization protocol.

Nocardia farcinica lung abscess presenting in the context of advanced HIV infection: Spontaneous resolution in response to highly active antiretroviral therapy alone.

A 43-year-old man, known to be HIV-positive, presented with a six-week history of symptoms including cough, hemoptysis, anterior chest pain, fever and wasting. His CD4 cell count was 46 cells/muL, and his chest x-ray showed a cavitating lesion in the left upper lobe. Sputum culture was positive for Nocardia farcinica. His infection resolved following initiation of antiretroviral therapy. Nocardia is an uncommon opportunistic pathogen in patients with HIV infection and is usually associated with advanced CD4 depletion, cavitary pneumonia, metastatic infection and high mortality. The impact of antiretroviral therapy on Nocardia infection in the setting of HIV has not been clearly elucidated. The current report is the first to present a case in which a complete clinical cure of Nocardia pneumonia has been documented, primarily in response to highly active antiretroviral therapy alone.

Tolevamer, a novel nonantibiotic polymer, compared with vancomycin in the treatment of mild to moderately severe Clostridium difficile-associated diarrhea.

BACKGROUND: Current antibiotic therapies for Clostridium difficile-associated diarrhea have limitations, including progression to severe disease, recurrent C. difficile-associated diarrhea, and selection for nosocomial pathogens. Tolevamer, a soluble, high-molecular weight, anionic polymer that binds C. difficile toxins A and B is a unique nonantibiotic treatment option. METHODS: In this 3-arm, multicenter, randomized, double-blind, active-controlled, parallel-design phase II study, patients with mild to moderately severe C. difficile-associated diarrhea were randomized to receive 3 g of tolevamer per day (n = 97), 6 g of tolevamer per day (n = 95), or 500 mg of vancomycin per day (n = 97). The primary efficacy parameter was time to resolution of diarrhea, defined as the first day of 2 consecutive days when the patient had hard or formed stools (any number) or < or = 2 stools of loose or watery consistency. RESULTS: In the per-protocol study population, resolution of diarrhea was achieved in 48 (67%) of 72 patients receiving 3 g of tolevamer per day (median time to resolution of diarrhea, 4.0 days; 95% confidence interval, 2.0-6.0 days), in 58 (83%) of 70 patients receiving 6 g of tolevamer per day (median time to resolution of diarrhea, 2.5 days; 95% confidence interval, 2.0-3.0 days), and in 73 (91%) of 80 patients receiving vancomycin (median time to resolution of diarrhea, 2.0 days; 95% confidence interval, 1.0-3.0 days). Tolevamer administered at a dosage of 6 g per day was found to be noninferior to vancomycin administered at a dosage of 500 mg per day with regard to time to resolution of diarrhea (P = .02) and was associated with a trend toward a lower recurrence rate. Tolevamer was well tolerated but was associated with an increased risk of hypokalemia. CONCLUSIONS: Tolevamer, a novel polystyrene binder of C. difficile toxins A and B, effectively treats mild to moderate C. difficile diarrhea and merits further clinical development.

A novel aqueous metronidazole 1% gel with hydrosolubilizing agents (HSA-3).

Rosacea is a common chronic dermatosis that often is characterized by the presence of facial erythema, visible blood vessels, papules, and pustules. Because the face is the predominant site of involvement, rosacea may cause serious psychologic trauma and can significantly affect the quality of life of individuals with the condition. The first topical therapy approved for rosacea by the US Food and Drug Administration was metronidazole for the treatment of inflammatory lesions and erythema. A stable aqueous gel formulation of 1% metronidazole has been developed with the novel combination of hydrosolubilizing agents. Metronidazole 1% gel is a clear gel that exhibits advantageous qualities. Some features of the new product include being highly spreadable, easy to use, cosmetically friendly, ultramild, nondrying, and moisturizing. Data are presented from a 21-day cumulative irritation study, an assessment of skin barrier function, an in vitro skin penetration study, an absorption following maximal topical exposure study, and a skin hydration study.

Immunomodulation with interferon-gamma and colony-stimulating factors for refractory fungal infections in patients with leukemia.

BACKGROUND: Invasive fungal infections (IFI) in immunocompromised patients are associated with significant morbidity and mortality, despite appropriate antifungal treatment and recovery from neutropenia. The outcome of these infections depends significantly on the overall state of immunosuppression, including mainly the phagocytic system (neutrophils and macrophages). Interferon-gamma (IFN-gamma), granulocyte-colony--stimulating factor (G-CSF) and granulocyte-macrophage-colony--stimulating factor (GM-CSF) are cytokines that enhance the activity of neutrophils and macrophages. METHODS: The authors reported 4 patients with leukemia and refractory invasive candidiasis or trichosporonosis despite 1-13 months of appropriate antifungal treatment. RESULTS: Cytokines were administered for 1.5-5 months without significant toxicity. For each patient, initiation of interferon-gamma plus a colony-stimulating factor resulted in a clinical response. The contribution of cytokines to control the fungal infection in these 4 patients was suggested by the strong inflammatory reaction observed in the 2 patients who had an immediate response (within 7 days of initiation of cytokine therapy) and by the good outcome in the 2 other patients in whom antifungal agents were discontinued at the start of cytokine therapy. CONCLUSIONS: These data suggested a potential role for immunomodulation in patients with leukemia with refractory invasive fungal infections.

A prospective, randomized trial of 3 or 14 days of ciprofloxacin treatment for acute urinary tract infection in patients with spinal cord injury.

BACKGROUND: Urinary tract infection (UTI) is common among patients with spinal cord injury. The optimal duration of treatment for symptomatic UTI has not been determined. METHODS: A randomized, double-blind, placebo-controlled trial compared 3-day and 14-day regimens of ciprofloxacin, 250 mg twice daily, for the treatment of acute UTI in patients with spinal cord injury. Patients with pyelonephritis, struvite stones, hydronephrosis, or long-term indwelling catheters were excluded from the trial. RESULTS: Sixty patients with spinal cord injury were enrolled in the trial, with 30 patients assigned to each study arm. The most common infecting organisms were Klebsiella species (30%), Enterococcus species (22%), and Escherichia coli (22%); 33% of the infections were polymicrobial. Microbiological cure at long-term follow-up was significantly better among patients who received therapy for 14 days than among patients who received therapy for 3 days. By 6 weeks of follow-up, microbiological relapse (in 11 [37%] of 30 patients vs. 2 [7%] of 30 patients; 95% confidence interval [CI], 1.38-3.18; P=.01) and symptomatic relapse (in 7 [23%] 30 patients vs. 0 of 30 patients; 95% CI, 1.69-3.13; P=.01) both occurred more frequently in patients treated for 3 days. Reinfection occurred with similar frequency in patients in the 2 study arms. Six of 7 evaluable patients with treatment failure had a fluoroquinolone-resistant organism isolated at enrollment. CONCLUSIONS: For patients with spinal cord injury, treatment of acute symptomatic UTI for 14 days leads to improved clinical and microbiological outcomes, compared with short-course therapy.