Christopher Giuliano

Are proton pump inhibitors associated with the development of community-acquired pneumonia? A meta-analysis

This study was presented at the American College of Chest Physicians meeting in Pittsburgh (PA, USA) in October 2011. The study objective was to evaluate the association of proton pump inhibitors (PPIs) and community-acquired pneumonia (CAP). The design was a meta-analysis of nine case–controlled and cohort studies. 120,863 pneumonia cases from 1987 to 2006 were included in the meta-analysis. PubMed and Ovid Medline were searched from inception through May 2011 by two investigators independently using keywords: PPI, pneumonia, CAP, anti-ulcer, antacid, omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole. This meta-analysis only included case–controlled and cohort studies that were published in full in English and evaluated PPI use and CAP incidence. Studies were excluded if they included the following patients: pediatric, Helicobacter pylori treatment and critically ill. Bibliographies of recent review articles and systematic reviews were hand-searched. Quality of studies was assessed using the Newcastle–Ottawa Quality Assessment Scale. Two investigators independently extracted data into standardized data collection forms that were confirmed by a third investigator. Data were analyzed based on current use of PPIs, duration of PPI use (<30 days or >180 days) and PPI dose (high vs low). Overall association of PPI and CAP was analyzed using the random effects model (Comprehensive Meta analysis® Version 2.0). Nine studies met all criteria for the primary outcome. Newcastle–Ottawa Quality Assessment Scale scores ranged from 4 to 8 out of 9. Current use of PPIs (odds ratio [OR]: 1.39; 95% CI: 1.09–1.76), PPI use <30 days (OR: 1.65; 95% CI: 1.25–2.19), PPI high dose (OR: 1.50; 95% CI: 1.33–1.68) and PPI low dose (OR: 1.17; 95% CI: 1.11–1.24) were significantly associated with CAP. There was no association between CAP and PPI use >180 days (OR: 1.10; 95% CI: 1.00–1.21). In conclusion, patients currently receiving PPIs, particularly <30 days or high dose, showed an association with CAP. Practitioners need to be vigilant about adverse effects of PPIs and consider alternative therapies.

Is the Combination of Piperacillin‐Tazobactam and Vancomycin Associated with Development of Acute Kidney Injury? A Meta‐analysis

To evaluate the association of the development of acute kidney injury (AKI) when piperacillin‐tazobactam is used in combination with vancomycin compared with vancomycin with or without a β‐lactam.

Empiric guideline-recommended weight-based vancomycin dosing and nephrotoxicity rates in patients with methicillin-resistant Staphylococcus aureus bacteremia: a retrospective cohort study

BackgroundPrevious studies have established a correlation between vancomycin troughs and nephrotoxicity. However, data are currently lacking regarding the effect of guideline-recommended weight-based dosing on nephrotoxicity in methicillin-resistant Staphylococcus aureus bacteremia (MRSAB).MethodsAdults who were at least 18 years of age with methicillin-resistant Staphylococcus aureus bacteremia and received of empiric vancomycin therapy for at least 48 hours (01/07/2002 and 30/06/2008) were included in this multicenter, retrospective cohort study. The association between guideline-recommended, weight-based vancomycin dosing (at least 15 mg/kg/dose) and nephrotoxicity (increase in serum creatinine (SCr) by more than 0.5 mg/dl or at least a 50% increase from baseline on at least two consecutive laboratory tests) was evaluated. Potential independent associations were evaluated using a multivariable general linear mixed-effect model.ResultsOverall, 23% of patients developed nephrotoxicity. Thirty-four percent of the 337 patients who met study criteria received weight-based dosing. The cohort was composed of 69% males with a median age of 55 years. The most common sources of MRSAB included skin/soft tissue (32%), catheter-related bloodstream bacteremia (20%), pulmonary (18%). Eighty-six percent of patients received twice daily dosing. Similar rates of nephrotoxicity were observed regardless of the receipt of guideline-recommended dosing (22% vs. 24%, OR 0.91 [95% CI 0.53-1.56]). This finding was confirmed in the multivariable analysis (OR 1.52 [95% CI 0.75-3.08]). Independent predictors of nephrotoxicity were (OR, 95% CI) vancomycin duration of greater than 15 days (3.36, 1.79-6.34), weight over 100 kg (2.74, 1.27-5.91), Pitt bacteremia score of 4 or greater (2.73, 1.29-5.79), vancomycin trough higher than 20 mcg/ml (2.36, 1.07-5.20), and age over 52 years (2.10, 1.08-4.08).ConclusionsOver one out of five patients in this study developed nephrotoxicity while receiving vancomycin for MRSAB. The receipt of guideline-recommended, weight-based vancomycin was not an independent risk factor for the development of nephrotoxicity.

Empiric guideline-recommended weight-based vancomycin dosing and mortality in methicillin-resistant Staphylococcus aureus bacteremia: A retrospective cohort study

BackgroundNo studies have evaluated the effect of guideline-recommended weight-based dosing on in-hospital mortality of patients with methicillin-resistant Staphylococcus aureus bacteremia.MethodsThis was a multicenter, retrospective, cohort study of patients with methicillin-resistant Staphylococcus aureus bacteremia receiving at least 48 hours of empiric vancomycin therapy between 01/07/2002 and 30/06/2008. We compared in-hospital mortality for patients treated empirically with weight-based, guideline-recommended vancomycin doses (at least 15 mg/kg/dose) to those treated with less than 15 mg/kg/dose. We used a general linear mixed multivariable model analysis with variables identified a priori through a conceptual framework based on the literature.ResultsA total of 337 patients who were admitted to the three hospitals were included in the cohort. One-third of patients received vancomycin empirically at the guideline-recommended dose. Guideline-recommended dosing was not associated with in-hospital mortality in the univariable (16% vs. 13%, OR 1.26 [95%CI 0.67-2.39]) or multivariable (OR 0.71, 95%CI 0.33-1.55) analysis. Independent predictors of in-hospital mortality were ICU admission, Pitt bacteremia score of 4 or greater, age 53 years or greater, and nephrotoxicity.ConclusionsEmpiric use of weight-based, guideline-recommended empiric vancomycin dosing was not associated with reduced mortality in this multicenter study.

Role of Dexamethasone in the Prevention of Migraine Recurrence in the Acute Care Setting: A Review

Abstract Patients with migraine headaches are commonly encountered by clinicians both in the clinic and in the emergency department. Migraines impose a significant financial burden on patients, caregivers, and society. Up to 49% of patients treated acutely for migraine headache will have a recurrence within 72 hours. Recurrence of migraines is dependent on a number of factors, including the choice of abortive agent, age, sex, and initial severity of the migraine. Dexamethasone has been proposed and studied as a medication that may decrease the frequency of such recurrences of migraine headaches in affected patients. Dexamethasone is a corticosteroid that has been proposed to prevent recurrence of migraines through its prevention of neurogenic inflammation. Initial trials, with less–than–ideal methodology, showed large decreases in the number of patients experiencing recurrent migraines. Later randomized controlled trials revealed mixed results, with subsequent meta–analyses showing an overall benefit in the prevention of recurrence of migraines. These meta–analyses suggest that dexamethasone will prevent recurrence in about 10% of patients, although trials that used higher doses of dexamethasone and followed patients for ≥ 72 hours showed a larger benefit. Very few adverse events were reported in the randomized controlled trials following a single dose of dexamethasone. Given the benign side effect profile and wide tolerability to a single high dose of dexamethasone, it appears to be a safe and modestly effective addition to standard migraine abortive therapy for the prevention of migraine recurrence. Dexamethasone should not be used in patients with non–migraine headaches or contraindications to steroids. Further studies should help delineate if dexamethasone can be tailored to specific patient populations and hence enhance its therapeutic effectiveness.

Empiric weight-based vancomycin in intensive care unit patients with methicillin-resistant Staphylococcus aureus bacteremia

Background:Previous studies were conducted in all hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia to determine safety and effectiveness of guideline-recommended, weight-based dosing of vancomycin. In these studies, it was observed that severely ill patients (Pitt bacteremia score ≥4 or intensive care unit [ICU] patients) were at an increased risk of mortality and/or nephrotoxicity. Therefore, a subanalysis of the effect of guideline-recommended vancomycin dosing on in-hospital mortality and nephrotoxicity in ICU patients with MRSA bacteremia was conducted. Methods:This multicenter, retrospective, cohort study was conducted in a subset of ICU patients from a previous MRSA bacteremia study. Patients were ≥18 years old and received ≥48 hours of empiric vancomycin from July 1, 2002, to June 30, 2008. The incidence of nephrotoxicity and in-hospital mortality was compared in patients who received guideline-recommended dosing (at least 15 mg/kg per dose) to patients who received non–guideline-recommended dosing of vancomycin. Multivariable generalized linear mixed-effects models were constructed to determine independent risk factors for in-hospital mortality and nephrotoxicity. Results:Guideline-recommended dosing was received by 34% of patients (n = 137). Nephrotoxicity occurred in 35% of patients receiving guideline-recommended dosing and 39% receiving non–guideline-recommended dosing (P = 0.67). In-hospital mortality rate was 24% among patients who received guideline-recommended dosing compared with 31% for non–guideline-recommended dosing (P = 0.40). Guideline-recommended dosing was not associated with nephrotoxicity (odds ratio: 1.10; 95% confidence interval: 0.43–2.79) or in-hospital mortality (odds ratio: 0.54; 95% confidence interval: 0.22–1.36) in the multivariable analysis. Conclusions:Guideline-recommended dosing of vancomycin in ICU patients with MRSA bacteremia is not significantly associated with nephrotoxicity or in-hospital mortality. However, the 7% absolute difference for in-hospital mortality suggests that larger studies are needed.

Early response of ceftaroline fosamic in the treatment of soft-tissue infections.

Evaluation of: Friedland DH, O’Neal T, Biek D et al. CANVAS 1 and 2: analysis of clinical response at day 3 in two Phase 3 trials of ceftaroline fosamil versus vancomycin plus aztreonam in treatment of acute bacterial skin and skin structure infections. Antimicrob. Agents Chemother. 56, 2231–2236 (2012). The US FDA recently approved ceftaroline fosamil (ceftaroline) for the treatment of acute bacterial skin and soft structure infections (ABSSSIs) and community-acquired pneumonia. In 2010, the FDA specified a new primary end point for ABSSSI of 3 days instead of the traditional test of cure. Friedland et al. used the new FDA end point in evaluating the CANVAS 1 and 2 trials. In the exploratory modified, intention-to-treat analysis, ceftaroline showed a superior clinical response at day 3 (74 vs 66.2%; difference 7.7%; 95% CI: 1.3–14%). The superior response of ceftaroline has biologic plausibility based on the in vitro activity of the antibiotic, suggesting that a true early clinical benefit may exist. However, owing to the potential for selection bias and lack of logistic regression analysis, caution should be used when extrapolating these results to clinical practice. Future trials utilizing this new end point in prospective ABSSSI trials will show over time the true value of such an end point.

Impact of empiric weight-based vancomycin dosing on nephrotoxicity and mortality in geriatric patients with methicillin-resistant Staphylococcus aureus bacteraemia

Few studies have evaluated the effect of vancomycin dosing on the health outcomes in geriatric patients. Data are needed to determine whether higher vancomycin dosing strategies are more effective in geriatric patients and/or lead to excessive rates of adverse events.

Eptifibatide-induced thrombocytopenia and subsequent thrombosis

Objective: To report a case of thrombocytopenia and thrombosis associated with the administration of eptifibatide. Case Summary: We describe the case of a 63-year-old male who developed thrombocytopenia and thrombosis associated with eptifibatide administration. Eptifibatide (2 μg/kg/min, following a 180-μg/kg bolus) was administered on hospital day 5, with a baseline platelet count of 302 × 103/μL. Ten hours after eptifibatide initiation in the catheterization laboratory, the patient experienced new-onset hypotension, shortness of breath, and tachycardia. Computed tomography angiography revealed bilateral, multilobar, pulmonary emboli. Platelet count decreased to 94 × 103/μL. Eptifibatide was discontinued and lepirudin 16.5 mg/h was administered because of high suspicion of heparin-induced thrombocytopenia (HIT). The platelet count returned to 127 × 103/μL on day 7. Heparin-induced platelet aggregation assay and antiplatelet factor 4 antibodies were negative. Eptifibatide-dependent platelet-reactive antibodies were detected in the patients serum. The patients platelet count continued to rise until day 16, when the patient was discharged on enoxaparin and warfarin. Discussion: Eptifibatide-associated thrombocytopenia has been described in several case reports, but concomitant thrombosis has been reported in only 2 cases. The Naranjo probability scale suggested a probable association between eptifibatide administration and the development of thrombosis and thrombocytopenia. Our patient also developed positive eptifibatide antibodies and had a negative HIT workup. These factors, in addition to the patients clinical presentation, suggested that eptifibatide was the most likely cause of thrombocytopenia and thrombosis. Conclusions: Despite the low incidence of thrombocytopenia and subsequent thrombosis with eptifibatide administration, it is imperative that patients receiving this drug have careful monitoring of their platelet count. If patients develop a profound thrombocytopenia in the setting of eptifibatide administration, we recommend evaluation for venous thromboembolism until further information is available about this adverse drug reaction.

“I Never Would Have Caught That Before”: Pharmacist Perceptions of Using Clinical Decision Support for Antimicrobial Stewardship in the United States

To systematically improve the appropriateness of antibiotic prescribing, antimicrobial stewardship programs have been developed. There is a paucity of literature examining how pharmacists perform antimicrobial stewardship using a clinical decision support system in a hospital setting. The purpose of this qualitative study was to develop a model exploring how pharmacists perform antimicrobial stewardship to identify areas for programmatic improvement. Semistructured interviews were conducted across a health care system until saturation of themes was reached. Pharmacists identified that self-efficacy and time were vital for antimicrobial stewardship to be performed, while culture of the hospital and attitude facilitated the process of stewardship. Antimicrobial stewardship programs using clinical decision support tools should ensure pharmacists have adequate time to address rules, provide easy-to-use resources and training to support self-efficacy, and engage influential physicians to support a culture of collaboration.