Bench-to-bedside review: Understanding the impact of resistance and virulence factors on methicillin-resistant Staphylococcus aureus infections in the intensive care unit

Methicillin-resistant Staphylococcus aureus (MRSA) displays a remarkable array of resistance and virulence factors, which have contributed to its prominent role in infections of the critically ill. We are beginning to understand the function and regulation of some of these factors and efforts are ongoing to better characterize the complex interplay between the microorganism and host response. It is important that clinicians recognize the changing resistance patterns and epidemiology of Staphylococcus spp., as these factors may impact patient outcomes. Community-associated MRSA clones have emerged as an increasingly important subset of Staphyloccocus aureus and MRSA can no longer be considered as solely a nosocomial pathogen. When initiating empiric antibiotics, it is of vital importance that this therapy be timely and appropriate, as delays in treatment are associated with adverse outcomes. Although vancomycin has long been considered a first-line therapy for serious MRSA infections, multiple concerns with this agent have opened the door for existing and investigational agents demonstrating efficacy in this role

Clinical effectiveness of a sedation protocol minimizing benzodiazepine infusions and favoring early dexmedetomidine: A before-after study

INTRODUCTION: Randomized controlled trials suggest clinical outcomes may be improved with dexmedetomidine as compared to benzodiazepines, however further study and validation is needed. The objective of this study was to determine the clinical effectiveness of a sedation protocol minimizing benzodiazepine use in favor of early dexmedetomidine. METHODS: This was a before-after study including adult surgical and medical ICU patients requiring mechanical ventilation and continuous sedation for at least 24 hours. The before phase included consecutive patients admitted between April 1 and August 31, 2011. Subsequently, the protocol was modified to minimize use of benzodiazepines in favor of early dexmedetomidine through a multidisciplinary approach and staff education was provided. The after phase included consecutive eligible patients between May 1 and October 31, 2012. RESULTS: 199 patients were included, with 97 patients in the before and 102 in the after phase. Baseline characteristics were well balanced between groups. Use of midazolam as initial sedation (58% vs. 27%, p \u3c 0.0001) or at any point during the ICU stay (76% vs. 48%, p \u3c 0.0001) was significantly reduced in the after phase. Dexmedetomidine use as initial sedation (2% vs. 39%, p \u3c 0.0001) or at any point during the ICU stay (39% vs. 82%, p \u3c 0.0001) significantly increased. Both the prevalence (81% vs. 93%, p =0.013) and median percent of days with delirium (55% (IQR 18-83) vs. 71% (IQR 45-100), p = 0.001) were increased in the after phase. The median duration of mechanical ventilation was significantly reduced in the after phase (110 (IQR 59-192) vs. 74.5 (IQR 42-148) hrs, p = 0.029) and significantly fewer patients required tracheostomy (20% vs. 9%, p = 0.040). The median ICU length of stay was 8 (IQR 4-12) days in the before phase and 6 (IQR 3-11) days in the after phase (p = 0.252). CONCLUSIONS: Implementing a sedation protocol that targeted light sedation and reduced benzodiazepine use led to significant improvements in the duration of mechanical ventilation and requirement for tracheostomy despite increases in the prevalence and duration of ICU delirium

Confronting the challenge of beta-lactam allergies: a quasi-experimental study assessing impact of pharmacy-led interventions

OBJECTIVE: To improve allergy history documentation and increase the use of beta-lactams when appropriate in patients with a reported beta-lactam allergy. METHODS: This pre-post study was conducted at a 167-bed tertiary care community hospital and evaluated multidisciplinary interventions on allergy documentation and antibiotic selection. Interventions included education, creation of local practice guidelines, and modified practices for pharmacists and pharmacy technicians. Inpatients with a reported beta-lactam allergy receiving at least 1 antibiotic for \u3e24 hours were included; first admissions were assessed. Primary outcomes were documentation of reaction type and percentage of patients receiving non-beta-lactam therapy. Secondary outcomes included documentation of previously tolerated beta-lactams, modification of non-beta-lactam therapy, discharge antibiotics, and adverse reactions. RESULTS: A total of 179 patients were included, 91 preintervention and 88 postintervention. No significant differences were observed between the before versus after groups in the percentage of patients with documentation of reaction type (90.1% vs 89.8%, P = .940) or the overall percentage of patients receiving non-beta-lactams (86.8% vs 84.1%, P = .605). However, significantly more patients in the after phase had documentation of previously tolerated beta-lactams (8.8% vs 28.4%, P = .001), and among patients receiving a non-beta-lactam, a greater percentage was subsequently switched to a beta-lactam (11.4% vs 25.7%, P = .022). One allergic reaction was documented during the study, which occurred in the before phase. CONCLUSION: Multidisciplinary education and local guideline implementation led by pharmacists may improve allergy documentation and antibiotic selection in patients with reported beta-lactam allergies

Examining the relationship between vancomycin area under the concentration time curve and serum trough levels in adults with presumed or documented staphylococcal infections

BACKGROUND: Investigations of the relationship between vancomycin trough concentrations and area under the concentration time curve (AUC) are growing but still limited. The authors sought to determine vancomycin exposure among hospitalized adults with presumed or confirmed invasive staphylococcal infections using two-level pharmacokinetic monitoring in order to inform changes to an institutional vancomycin dosing protocol. METHODS: This was a retrospective observational study performed in two acute care hospitals. Adults prescribed vancomycin (therapeutic trough 15-20mg/L) for a presumed or documented invasive staphylococcal infection were evaluated. Two steady-state serum vancomycin levels were used to determine each patient\u27s 24-hour AUC to MIC ratio (AUC/MIC) using a non-Bayesian, equation-based approach. Patient demographics and crude clinical outcomes were also collected. RESULTS: Thirty-four patients were included in the study, with two patients having vancomycin levels drawn twice (36 sets of levels). Most patients were located in an intensive care unit (91.2%) and 85.3% of patients were prescribed vancomycin for bacteremia, pneumonia, or endocarditis. The mean ± standard deviation vancomycin Cmin was 16.6 ± 6.1mg/L and the mean AUC/MIC was 588 ± 156mg/L*hr. The rate of 24-hour vancomycin AUC/MIC target attainment was 91.2% (n=31/34). Of the patients with a Cmin \u3e 9mg/L, 100%(n=33) achieved AUC /MICvalues \u3e400mg/L*hr and 93.9% were \u3e 500mg/L*hr. There was a strong correlation between vancomycin Cmin and AUC24hr (R=0.731; p\u3c0.001). CONCLUSIONS: Targeting a vancomycin trough between 15 and 20 mg/L frequently resulted in an AUC/MIC greater than thought to be necessary for efficacy optimization. Considering these findings alongside the practical challenges associated with wide-scale implementation of AUC monitoring, reducing the target trough as a means to prevent vancomycin overexposure warrants clinical consideration and further evaluation

Road map for research training in the residency learning experience

The American Society of Health-System Pharmacists residency accreditation standards require all postgraduate residency training programs to teach and evaluate a resident\u27s ability to advance practice through project development and presentation, underscoring the importance of conducting research in today\u27s professional climate. Although many residents express strong interest in research participation and contributing to the medical literature, many obstacles to publication have been identified. We aim to illustrate a deliberate approach to teaching this material and structuring the longitudinal experience in a way that maximizes resources to overcome these barriers. Such efforts should aid residents, advisors, and program directors in establishing curriculum which leads to successful completion and publication of pharmacy resident\u27s research projects