Dayna McManus

Combination liposomal amphotericin B, posaconazole and oral amphotericin B for treatment of gastrointestinal Mucorales in an immunocompromised patient

Mucormycosis is a life threatening infection caused by fungi in the order Mucorales. Mucormycosis can affect any organ system with rhino-orbital-cerebral and pulmonary infections being the most predominant infection types. Gastrointestinal mucormycosis is rare and accounts for only 4–7% of all cases. Here, we present a case of invasive gastrointestinal mucormycosis in an immunocompromised host treated with systemic and topical anti-mold therapy.

Telavancin for refractory MRSA bacteraemia in intermittent haemodialysis recipients

Background Patients with end-stage renal disease (ESRD) requiring intermittent haemodialysis (IHD) are at high risk of MRSA bacteraemia (MRSA-B) and often fail first-line therapy. The safety, effectiveness and optimal dosing of telavancin for MRSA-B in this patient population are unclear. Objectives We aimed to describe clinical outcomes of telavancin in the treatment of refractory MRSA-B in patients with ESRD requiring IHD. Patients and methods This was a retrospective study of hospitalized patients at two tertiary care academic medical centres with recurrent or persistent (≥3 days) MRSA-B treated with telavancin monotherapy. Outcomes included duration of MRSA-B (pre-telavancin versus post-telavancin) and microbiological failure (duration of MRSA-B ≥3 days after initiation of telavancin). Results Telavancin dosed 10 mg/kg three times weekly post-IHD or 10 mg/kg every 48 h resulted in microbiological cure in 7/8 (87.5%) refractory MRSA-B cases. Telavancin monotherapy was associated with a significant reduction in median duration of bacteraemia [16 days pre-telavancin (IQR 8-19 days) versus 1 day post-telavancin (IQR 0-2 days); P = 0.018]. Telavancin was well tolerated by all patients and no adverse events were reported. Conclusions Telavancin was very safe and highly effective in the treatment of refractory MRSA-B in a cohort of patients with ESRD requiring IHD. These data support the utility of telavancin in the armamentarium against refractory MRSA-B, particularly in the high-risk IHD-dependent population.

Utility of fosfomycin as antibacterial prophylaxis in patients with hematologic malignancies

PurposeProlonged and profound neutropenia is common among hematology and hematopoietic stem cell transplant (HSCT) patients as a result of chemotherapy. The National Comprehensive Cancer Network (NCCN) and Infectious Diseases Society of America (IDSA) currently recommend antibacterial prophylaxis in patients who are deemed at intermediate or high risk for infection. Specifically, fluoroquinolone prophylaxis should be considered for high-risk neutropenic patients. However, with prolonged and frequent exposure to fluoroquinolones, these high-risk patients may develop resistance to these agents. Patients may also have allergies or other contraindications which prohibit the use of fluoroquinolones for antibacterial prophylaxis. Unfortunately, there is no standard recommendation for alternative antimicrobial therapy in this patient population, as well as there is a lack of data to support the use of potential alternative agents.MethodsCurrently, Yale-New Haven Hospital utilizes fosfomycin for antibacterial prophylaxis in patients who are not eligible for fluoroquinolone therapy. The primary objective of this study was to assess the incidence of breakthrough infections in this population receiving fosfomycin. Secondary objectives included organisms identified, types of breakthrough infections, resistance patterns, and time from initiation to onset of fever.ResultsOf the 42 patients who received fosfomycin, 25 patients with 42 admissions met inclusion criteria. A total of 8 (19%) breakthrough infections occurred during the 42 admissions. Organisms included Klebsiella spp. (5), Streptococcus mitis/viridans (2), Pseudomonas aeruginosa (1), and coagulase-negative staphylococcus (1). Infections included the following: bacteremia (7), cellulitis (1), and urine (1).ConclusionGiven the low rate of breakthrough infections, fosfomycin may be a potential alternative option for antibacterial prophylaxis.

Long-Acting Lipoglycopeptides for Gram-Positive Bacteremia at the End of Life to Facilitate Hospice Care: A Report of 3 Cases

Abstract Administering and monitoring intravenous antimicrobials may cause discomfort in patients at the end of life and delay transition to hospice. We describe 3 patients with terminal cancer with methicillin-resistant Staphylococcus aureus, Streptococcus gallolyticus, and Granulicatella adiacens bacteremia who were managed with the long-acting lipoglycopeptide oritavancin to facilitate discharge to hospice.

Evaluating a voriconazole dose modification guideline to optimize dosing in patients with hematologic malignancies

Background Voriconazole is an azole antifungal utilized for prophylaxis and treatment of invasive fungal infections in hematologic patients. Previous studies have revealed decreased efficacy and increased toxicity with subtherapeutic <1 mcg/mL and supratherapeutic > 4 mcg/mL levels. A voriconazole dose modification guideline was introduced in July 2014 based on a retrospective analysis. Objective The primary objective was to evaluate the voriconazole dose modification guideline. Secondary objectives were to identify patient-specific characteristics that contribute to inadequate levels, adverse effects, and breakthrough invasive fungal infections. Methods This prospective study included 128 patients with 250 admissions who received voriconazole from July 2014 to February 2016. Eligible adult patients receiving voriconazole for prophylaxis or treatment with at least one trough level, drawn appropriately, were included. Demographics, adverse effects, and breakthrough invasive fungal infections were documented. Results Voriconazole use was categorized as: new start, new start with loading dose, or continuation of home therapy. The median initial levels were 1.5, 3.5, and 1.7 mcg/mL with 62% (73/119), 55% (6/11), and 60% (72/120) within the therapeutic range, respectively. Using the voriconazole dose modification guideline, 80% were within goal by the second dose adjustment. Age ≤ 30 and BMI ≤ 25 kg/m2 had higher rates of subtherapeutic levels in the new start cohorts (p = 0.024 and p = 0.009). Approximately 7.6% of patients experienced an adverse effect with neurologic/psychological being the most common. A total of 8.5% of patients had a possible, probable or proven breakthrough invasive fungal infections while on voriconazole. Conclusion Using the voriconazole dose modification guideline, the number of patients that reached therapeutic range improved from 36% to 80% by the second dose adjustment (p = 0.007). This voriconazole dose modification guideline can be utilized to help dose and adjust voriconazole in order to achieve therapeutic levels.

The Value of Antimicrobial Stewardship Team (AST) in Conjunction with Infectious Diseases Consult in Reducing the 30-day Mortality of Patients with Staphylococcus aureus Bacteremia in a Single Academic Medical Center.

Abstract Background Staphylococcus aureus bacteremia (SAB) is a common bloodstream infection with significant mortality. Infectious Disease consultation (IDC) has been shown to improve outcomes and adherence to standards of care (SOC). In our institution, IDC for SAB is not mandatory. Our study was a quality improvement initiative to measure the impact of IDC on patient outcomes and adherence to SOC. Methods A retrospective, observational study of all SAB cases in adults ≥18 years old at a 1541-bed academic medical center from January 1 to December 31, 2015 was performed. Those meeting inclusion criteria underwent chart review for demographics, co-morbidities, presence of IDC or antimicrobial stewardship team (AST) input, management including follow-up blood culture, echocardiography, antibiotic choice and duration, and outcomes including relapse and 30-day mortality. Results 236 patients met inclusion criteria and 174 (74%) had IDC. Patient characterestics were balanced in IDC and no IDC (NIDC) groups including age, sex, co-morbidities, methicillin-resistant SAB rates except for more immunosuppressed hosts, bone and joint infections,and endocarditis (P < 0.05) in the IDC group. SOC including performance of echocardiogram, appropriate antibiotic choice and treatment duration were adhered to more frequently in the IDC group (P < .005). Relapse rates were similar in IDC and NIDC groups (3% vs. 5%, P = 0.44,respectively). Lower 30-day mortality was observed with IDC but did not reach statistical significance (11% vs. 21%, P = .07). Patients with malignancy who had IDC had lower 30-day mortality compared with their counterpart in the NIDC group (6% vs. 35%, P = .01). In the NIDC group, 9/62 (15%) had an AST input that provided recommendations on antibiotic management. When these cases were combined with those with IDC, mortality was significantly improved compared with those without either IDC or AST input (11% vs. 23%, P = 0.04). Multivariate analysis revealed bacteremia clearance within 3 days and presence of AST input or IDC were predictors of survival while age>60 and ICU stay were predictors of mortality (P <.005). Conclusion Similar to prior studies, IDC was associated with increased adherence to standard management practices. Our study suggests that a pharmacy-driven AST can be an adjunct to IDC in improving outcomes of SAB. Disclosures All authors: No reported disclosures.