Erica S. Shenoy

Comparative Evaluation of the Tolerability of Cefazolin and Nafcillin for Treatment of Methicillin-Susceptible Staphylococcus aureus Infections in the Outpatient Setting

BACKGROUND Nafcillin and cefazolin are considered first-line therapy for most infections with methicillin-susceptible Staphylococcus aureus (MSSA), and recent studies have suggested similar clinical efficacy. Limited data are available on the comparative tolerability of these agents. METHODS In this retrospective cohort analysis of patients treated with either nafcillin or cefazolin for MSSA infection in the outpatient parenteral antimicrobial therapy clinic at Massachusetts General Hospital from 2007 to 2011, the frequency of premature antimicrobial discontinuation (PAD) and drug-emergent events (DEEs) was calculated. RESULTS Three hundred sixty-six and 119 patients were treated with nafcillin or cefazolin, respectively. The median anticipated duration of therapy was comparable at 28 (interquartile range [IQR], 16-37) and 29 (IQR, 24-39) days, respectively, for those treated with nafcillin and cefazolin. Fewer patients completed the prespecified treatment course with nafcillin than with cefazolin (PAD rate, 33.8% vs 6.7%; P < .0001). The hazard ratio for PAD in the nafcillin vs cefazolin groups was 2.81 (95% confidence interval [CI], 1.26-3.68). More patients in the nafcillin group developed rash (13.9% vs 4.2%; P = .002), renal dysfunction (11.4% vs 3.3%; P = .006), and liver function abnormalities (8.1% vs 1.6%; P = .01). Overall rates of DEEs per 1000 patient-days were 16.9 (95% CI, 10.4-27.3) and 4.8 (95% CI, 1.1-10.2), respectively. In 9 cases of nafcillin discontinuation, treatment was changed to cefazolin; all 9 completed treatment with no further observed DEEs. CONCLUSIONS Nafcillin treatment was associated with higher rates of both PAD as well as DEEs compared with cefazolin treatment. This difference in tolerability, in addition to efficacy and cost, should be considered when decisions for outpatient parenteral MSSA treatment are made.

Discontinuation of Contact Precautions for Methicillin-Resistant Staphylococcus aureus: A Randomized Controlled Trial Comparing Passive and Active Screening With Culture and Polymerase Chain Reaction

BACKGROUND There have been no randomized controlled trials comparing active and passive screening for documenting clearance of colonization with methicillin-resistant Staphylococcus aureus (MRSA). We compared the efficacy of active and passive screening using both culture and commercial polymerase chain reaction (PCR) for documentation of MRSA clearance and discontinuation of MRSA contact precautions (CPs). METHODS Inpatients with a history of MRSA infection or colonization enrolled between December 2010 and September 2011 were randomized to either passive (nonintervention arm; n = 202; observation with local standard of care) or active screening (intervention arm; n = 405; study staff screened using culture and commercial PCR). The primary outcome was discontinuation of CPs by trial arm based on 3 negative cultures. In the intervention arm, sensitivity, specificity, and positive and negative predictive values of the first PCR were compared to cultures. RESULTS CPs were discontinued significantly more often (rate ratio [RR], 4.1; 95% confidence interval [CI], 2.3%-7.1%) in the intervention arm, including in an intent-to-screen analysis (RR, 2.6; 95% CI, 1.5%-4.7%). The first PCR, compared to 3 cultures, detected MRSA with a sensitivity of 93.9% (95% CI, 85.4%-97.6%), a specificity of 92.0% (95% CI, 85.9%-95.6%), a positive predictive value of 86.1% (95% CI, 75.9%-93.1%), and a negative predictive value of 96.6% (95% CI, 91.6%-99.1%). CONCLUSIONS Compared to passive screening using culture methods, active screening resulted in discontinuation of MRSA CPs at a significantly higher frequency. Active screening with a single PCR would significantly increase the completion of the screening process. Clinical Trials Registration. NCT01234831.

The effect of vaccination on children's physical and cognitive development in the Philippines

We use data from the Cebu Longitudinal Health and Nutrition Survey (CLHNS) in the Philippines to link vaccination in the first 2 years of life with later physical and cognitive development in children. We use propensity score matching to estimate the causal effect of vaccination on child development. We find no effect of vaccination on later height or weight, but full childhood vaccination for measles, polio, Tuberculosis (TB), Diphtheria, Pertussis and Tetanus (DPT) significantly increases cognitive test scores relative to matched children who received no vaccinations. The size of the effect is large, raising test scores, on average, by about half an SD.

Tackling inpatient penicillin allergies: Assessing tools for antimicrobial stewardship

Background Reported penicillin allergy rarely reflects penicillin intolerance. Failure to address inpatient penicillin allergies results in more broad‐spectrum antibiotic use, treatment failures, and adverse drug events. Objective We aimed to determine the optimal approach to penicillin allergies among medical inpatients. Methods We evaluated internal medicine inpatients reporting penicillin allergy in 3 periods: (1) standard of care (SOC), (2) penicillin skin testing (ST), and (3) computerized guideline application with decision support (APP). The primary outcome was use of a penicillin or cephalosporin, comparing interventions to SOC using multivariable logistic regression. Results There were 625 patients: SOC, 148; ST, 278; and APP, 199. Of 278 ST patients, 179 (64%) were skin test eligible; 43 (24%) received testing and none were allergic. In the APP period, there were 292 unique Web site views; 112 users (38%) completed clinical decision support. Although ST period patients did not have increased odds of penicillin or cephalosporin use overall (adjusted odds ratio [aOR] 1.3; 95% CI, 0.8‐2.0), we observed significant increased odds of penicillin or cephalosporin use overall in the APP period (aOR, 1.8; 95% CI, 1.1‐2.9) and in a per‐protocol analysis of the skin tested subset (aOR, 5.7; 95% CI, 2.6‐12.5). Conclusions Both APP and ST—when completed—increased the use of penicillin and cephalosporin antibiotics among inpatients reporting penicillin allergy. While the skin tested subset showed an almost 6‐fold impact, the computerized guideline significantly increased penicillin or cephalosporin use overall nearly 2‐fold and was readily implemented.

Natalizumab and HSV meningitis

Natalizumab (Tysabri, Biogen Idec and Elan Pharmaceuticals) is a monoclonal antibody approved for use in patients with relapsing multiple sclerosis (MS) as well as moderate to severe Crohn’s disease. We report the first case of a patient with a history of MS, on monthly natalizumab, who developed HSV-2 meningitis. We discuss the mechanism of action of natalizumab and review what is known about the reactivation of herpes infection in association with this medication. The question of herpes simplex virus (HSV) and varicella zoster virus (VZV) prophylaxis for patients is raised.

Resource burden associated with contact precautions for methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus: the patient access managers' perspective.

We surveyed patient access managers on the impact of contact precautions (CP) for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE) on time to bed assignment, and we investigated the factors influencing infection control policies allowing for discontinuation of CP. The majority of respondents reported an increase in time to bed assignment for patients with a history of MRSA and/or VRE infection or colonization.

National survey of infection preventionists: policies for discontinuation of contact precautions for methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus.

Precautions for Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococcus Author(s): Erica S. Shenoy, MD, PhD; Heather Hsu, MPH; Farzad Noubary, PhD; David C. Hooper, MD; Rochelle P. Walensky, MD, MPH Source: Infection Control and Hospital Epidemiology, Vol. 33, No. 12 (December 2012), pp. 1272-1275 Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiology of America Stable URL: http://www.jstor.org/stable/10.1086/668427 . Accessed: 13/05/2014 21:52

The Impact of Reporting a Prior Penicillin Allergy on the Treatment of Methicillin-Sensitive Staphylococcus aureus Bacteremia.

Background Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is a morbid infection with mortality benefit from receipt of parenteral β-lactam therapy. A substantial portion of MSSA bacteremia patients report penicillin allergy, but infrequently have true allergy. Objective To determine the frequency and predictors of optimal and adequate therapy in patients with MSSA bacteremia. Design Retrospective cohort. Participants Adult inpatients with MSSA bacteremia, January 2009 through October 2013. Main Measures The primary measure was a trial of optimal therapy (OT), defined as ≥3 inpatient days or discharge on any first-line agents (nafcillin, oxacillin, cefazolin, or penicillin G, if susceptible). The secondary measure was completion of adequate therapy (AT), defined as ≥10 inpatient days or discharge on an agent appropriate for MSSA bacteremia. Data were electronically gathered with key variables manually validated through chart review. Log-binomial regression models were used to determine the frequency and predictors of outcomes. Key Results Of 456 patients, 346 (76%) received a trial of OT. Patients reporting penicillin allergy (13%) were less likely to receive OT trial than those without penicillin allergy (47% vs. 80%, p <0.001). Adjusting for other factors, penicillin allergy was the largest negative predictor of OT trial (RR 0.64 [0.49, 0.83]). Infectious Disease (ID) consultation was the largest positive predictor of OT trial across all patients (RR 1.34 [1.14, 1.57]). Allergy/Immunology consultation was the single most important predictor of OT trial among patients reporting penicillin allergy (RR 2.33 [1.44, 3.77]). Of 440 patients, 391 (89%) completed AT, with ID consultation the largest positive predictor of the outcome (RR 1.28 [1.15, 1.43]). Conclusions Nearly 25% of patients with MSSA bacteremia did not receive OT trial and about 10% did not receive AT completion. Reported penicillin allergy reduced, and ID consult increased, the likelihood of OT. Allergy evaluation, coupled with ID consultation, may improve outcomes in MSSA bacteremic patients.

Addressing Inpatient Beta-Lactam Allergies: A Multihospital Implementation

Addressing inaccurate penicillin allergies is encouraged as part of antibiotic stewardship in the inpatient setting. However, implementing interventions targeted at the 10% to 15% of inpatients reporting a previous penicillin allergy can pose substantial logistic challenges. We implemented a computerized guideline for patients with reported beta-lactam allergy at 5 hospitals within a single health care system in the Boston area. In this article, we describe our implementation roadmap, including both successes achieved and challenges faced. We explain key implementation steps, including assembling a team, stakeholder engagement, developing or selecting an approach, spreading the change, establishing measures, and measuring impact. The objective was to detail the lessons learned while empowering others to be part of this important, multidisciplinary work to improve the care of patients with reported beta-lactam allergies.

Tolerability of Cefazolin after Immune-Mediated Hypersensitivity Reactions to Nafcillin in the Outpatient Setting

ABSTRACT The objective of the present study was to assess the safety and tolerability of cefazolin therapy among patients with methicillin-sensitive Gram-positive bacterial infections who develop non-IgE-mediated hypersensitivity reactions (HSRs) to nafcillin. In this retrospective cohort analysis of the Outpatient Parenteral Antimicrobial Therapy program at the Massachusetts General Hospital from 2007 through 2013, we identified patients switched from nafcillin to cefazolin after an immune-mediated HSR. We reviewed patient demographics, details about the original HSR, and outcomes after the switch to cefazolin therapy. HSRs were classified by reaction type and likely mechanism. There were 467 patients treated with nafcillin, of which 60 (12.8%) were switched to cefazolin during their prescribed course. Of the 60 patients who transitioned to cefazolin, 17 (28.3%) were switched because of non-IgE-mediated HSRs. HSRs included maculopapular rash (n = 10), immune-mediated nephritis (n = 3), isolated eosinophilia (n = 2), immune-mediated hepatitis (n = 1), and a serum sickness-like reaction (n = 1). All but one patient (94.1%) who switched to cefazolin tolerated the drug with resolution of the HSR and completed their therapy with cefazolin. No patient experienced worsening of their rash or progressive organ dysfunction. With appropriate monitoring, therapy with cefazolin after non-IgE-mediated HSRs to nafcillin appears to be safe.