Gordon Dow

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.

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.

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

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

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.

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

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.

Diabetic Foot Care Plan

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.

Legionella-Associated Lung Abscess: Critical Pathogen or Minor Isolate?

Diabetes mellitus is the number one cause of limb loss in North America, and is associated with growing, unacceptable rates of morbidity, mortality and economic loss. Approximately 80% of these amputations are preceded by the development of foot ulceration. Various disciplines have studied the prevention and management of foot ulceration in those with diabetes. The present care plan was constructed to incorporate the important contributions from these disciplines into practical therapeutic guidelines. The care plan has been divided into three basic sections: assessment, general management and antibiotic therapy. Each of these sections is described in detail and borrows heavily from previous Canadian position papers. Application of the care plan is illustrated by multiple diabetic foot clinical scenarios, which have been categorized according to the Wagner classification.

Impact of an Antimicrobial Stewardship Bloodstream Surveillance Program (BSP) in Hospitalized Patients

Two cases of lung abscess, in which Legionella species were identified in association with other bacterial isolates, are presented. In the first case, Legionella pneumophila and Klebsiella pneumoniae were identified in a 24-year-old post renal transplant patient with a right upper lobe pulmonary abscess. Healing did not occur until the institution of specific therapy directed against legionella. In the second case, Legionella micdadei and several other respiratory bacterial pathogens were identified in a 74-year-old woman with a lung abscess. The patient later died with multisystem failure despite adequate antimicrobial therapy. Prior cases of legionella-associated lung abscess have occurred predominantly in corticosteroid-treated patients. The role of coexisting bacterial isolates remains obscure.