Open-Label Randomized Trial of Early Clinical Outcomes of Ceftaroline Fosamil Versus Vancomycin for the Treatment of Acute Bacterial Skin and Skin Structure Infections at Risk of Methicillin-Resistant Staphylococcus aureus.

INTRODUCTION: Acute bacterial skin and skin structure infections (ABSSSIs) remain among the most common infectious processes seen in the clinical setting. For patients with complicated ABSSSIs deemed to require intravenous antibiotics, vancomycin remains the mainstay therapy. Ceftaroline has been shown to be non-inferior to vancomycin and may result in faster resolution of signs of infection. METHODS: Multicenter, prospective, open-label, randomized trial of ceftaroline versus vancomycin for the treatment of adult patients admitted for management of ABSSSIs from April 2012 to May 2016; 166 patients in the clinically evaluable (CE) group were needed to determine a 20% difference in primary outcome of clinical response at day 2 or 3 of antibiotics. Clinical response was defined as cessation of spread of lesion and improvement in systemic signs/symptoms of infection. A secondary outcome was a ≥ 20% reduction in lesion size at day 2 or 3 of antibiotics. RESULTS: One hundred seventy-four patients were enrolled in the intention-to-treat (ITT) group and 108 were CE. Among CE patients, 54 were randomized to ceftaroline and 54 to vancomycin. Baseline characteristics were similar except patients in the ceftaroline arm were older and had a non-significantly higher degree of comorbidities (median Charlson score 2 vs. 4, respectively). Cellulitis was the most common type of ABSSSI (85.2% vs. 79.6%, respectively). Rapid diagnostic testing of available cultures (n = 55) demonstrated high agreement with clinical microbiology for identification of Staphylococcus aureus (100%) and MRSA (100%). There was no significant difference in primary outcome of day 2 or 3 clinical response (50.0% vs. 51.9%). CONCLUSION: Early clinical response between vancomycin- and ceftaroline-treated ABSSSIs was similar. Patients with ABSSSIs rarely remained hospitalized for > 2-3 days, thus limiting our ability to critically assess clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02582203. FUNDING: Allergan plc.

Effect of vancomycin initial dosing on time to systemic inflammatory response syndrome resolution in patients with methicillin-resistant Staphylococcus aureus bacteremia.

Current guidelines suggest using vancomycin-loading doses for complicated infections despite a lack of evidence to support this practice. To address this gap, we performed a single-centre cohort study of 124 patients with sepsis due to methicillin-resistant Staphylococcus aureus bacteremia. Patients were allocated into two groups based on initial dose of vancomycin, <20 mg/kg or ≥20 mg/kg, and evaluated for time to resolution of systemic inflammatory response syndrome (SIRS). Among a cohort of 124 patients, 87 received vancomycin initial doses <20 mg/kg and 37 received ≥20 mg/kg. The median time to SIRS resolution was 109 h in the <20 mg/kg group compared to 67 h in the ≥20 mg/kg group. Cox proportional hazard modelling showed a faster resolution of SIRS in the ≥20 mg/kg group (HR = 1.72[1.09-2.73]). Vancomycin initial doses of ≥20 mg/kg led to faster resolution of SIRS although further studies are needed to evaluate the safety and efficacy of this approach.

A case series detailing the successful reversal of the effects of mifepristone using progesterone.

BACKGROUND: Some women who take mifepristone, a progesterone receptor antagonist, in order to terminate their pregnancies, change their minds and desire to stop the medical abortion process. There are only two articles in the medical literature documenting the reversal of the effects of mifepristone. OBJECTIVE: We present and analyze a series of women who attempted to reverse the effects of mifepristone by taking supplemental progesterone to determine if the reversal of the effects mifepristone with progesterone is possible and safe. Additionally, we compare different progesterone regimens to determine relative efficacies. METHODS: This is an observational case series of 754 patients who decided to attempt to reverse the medical abortion process after taking mifepristone but before taking the second drug in the protocol, misoprostol. We followed the patients, who were given progesterone in an effort to reverse the effects of mifepristone, and conducted statistical analyses to determine the efficacies of different protocols compared to a control mifepristone embryo survival rate, derived from the literature. RESULTS: Intramuscular progesterone and high dose oral progesterone were the most effective with reversal rates of 64% (P < 0.001) and 68% (P < 0.001), respectively. There was no apparent increased risk of birth defects. Conclusions: The reversal of the effects of mifepristone using progesterone is safe and effective.

Impact of a phenytoin loading dose program in the emergency department.

PURPOSE: The use of a combined physician-and pharmacist-directed phenytoin loading dose program in an emergency department (ED) was evaluated. METHODS: This single-center, observational, preimplementation-postimplementation study evaluated adult patients who received a phenytoin loading dose in the ED. The primary outcome compared the proportion of optimal phenytoin loading doses in the preimplementation and postimplementation groups. The postimplementation group was further stratified into pharmacist- and prescriber-dosing groups. Other outcomes evaluated included the numbers of appropriate serum phenytoin concentrations measured, adverse drug reactions (ADRs), and recurrence of seizures within 24 hours of loading dose administration in the preimplementation and postimplementation groups. RESULTS: There was no difference in the proportion of optimal phenytoin loading doses between the preimplementation and postimplementation groups (50% versus 62%, respectively; p=0.19). When stratified by individual groups, the rate of optimal phenytoin loading doses increased by 64% in the postimplementation pharmacist group (50% versus 82%, p=0.007), while the rate in the prescriber-dosing group remained relatively unchanged (50% versus 49%, p=0.91). The number of appropriate serum phenytoin concentrations significantly improved in the postimplementation versus preimplementation group (65% versus 40%, p=0.025). Rates of ADRs and recurrence of seizures did not differ across the study groups. CONCLUSION: No change in the percentage of optimal phenytoin loading doses in the ED was observed after implementation of a combined pharmacist- and physician- dosing program. When stratified into pharmacist or prescriber dosing, the pharmacist-led dosing program significantly improved the proportion of patients who received optimal phenytoin loading doses.

A second opinion: response to 100 professors.

Induced abortion is a controversial topic among obstetricians. "100 Professors" extolled the benefits of elective abortion in a Clinical Opinion published in AJOG. However, scientific balance requires the consideration of a second opinion from practitioners who care for both patients, and who recognize the humanity of both. Alternative approaches to the management of a problem pregnancy, as well as short and long term risks to women as published in the peer reviewed medical literature are discussed. Maintaining a position of "pro-choice" requires that practitioners also be given a right to exercise Hippocratic principles in accordance with their conscience.

Progesterone use to reverse the effects of mifepristone.

OBJECTIVE: To present a series of cases demonstrating successful reversal of mifepristone effects in women who chose to reverse the medical abortion process. CASE REPORTS: Four of 6 women who took mifepristone were able to carry their pregnancies to term after receiving intramuscular progesterone 200 mg. DISCUSSION: Mifepristone has been available in the US since 2000. By 2008, approximately 25% of abortions prior to 9 weeks were accomplished with mifepristone. Some women who take mifepristone wish to reverse the medical abortion process. Progesterone competes with mifepristone for the progesterone receptor and may reverse the effects of mifepristone. A PubMed literature search from 1996 to May 2012 did not reveal any trials or case studies evaluating the efficacy of progesterone use to reverse the effects of mifepristone. CONCLUSIONS: Health care professionals should be aware of the possible use of progesterone to reverse mifepristone in women who have begun the medical abortion process by taking mifepristone and then change their minds.

Validation of the effectiveness of a vancomycin nomogram in achieving target trough concentrations of 15-20 mg/L suggested by the vancomycin consensus guidelines.

STUDY OBJECTIVE: To assess and validate the effectiveness of a newly constructed vancomycin dosing nomogram in achieving target trough serum concentrations of 15-20 mg/L. DESIGN: Prospective multicenter study. SETTING: Five tertiary care teaching hospitals. PATIENTS: A total of 200 adults who required vancomycin dosages targeted to attain recommended trough vancomycin serum concentrations of 15-20 mg/L. INTERVENTION: The new nomogram, which based dosing on weight and renal function, was used to calculate patients' initial vancomycin dosages. Serum trough concentrations were measured before the fourth or fifth dose, and dosages were adjusted as needed. MEASUREMENTS AND MAIN RESULTS: Median patient age was 56 years (interquartile range [IQR] 49-65 yrs), median weight was 71.2 kg (IQR 63-85 kg), and median creatinine clearance was 66.5 ml/minute (IQR 52-82 ml/min). The median initial vancomycin trough concentration achieved was 17.5 mg/L (IQR 15.0-20.0 mg/L), with 116 patients (58%) achieving the initial target trough of 15-20 mg/L. The median percent error was 13.6%, and the mean ± SD error for predicted versus actual serum trough concentrations was -0.50 ± 0.021 mg/L. One hundred fifty-four patients (77%) eventually achieved the trough target concentration within a median of 2 days. One hundred forty patients (70%) achieved initial troughs of 14-21 mg/L and 160 (80%) achieved troughs of 13-22 mg/L. Nine patients (4.5%) experienced nephrotoxicity while receiving vancomycin, which occurred after a median of 8 days of therapy. The median initial vancomycin trough concentration for these patients was 18.5 mg/L (IQR 15.3-19.3 mg/L), with eight of the nine patients having trough concentrations of 15 mg/L or greater. CONCLUSION: Fifty-eight percent of patients achieved the target trough of 15-20 mg/L (median 17.5 mg/L). The performance of the nomogram improved to 80% when the trough range was adjusted to 13-22 mg/L. Caution should be applied when using this nomogram. The nomogram should not replace clinical judgment, and dosage adjustments should be based on pharmacokinetic-pharmacodynamic targets and clinical response.

Daptomycin versus vancomycin for complicated skin and skin structure infections: clinical and economic outcomes.

STUDY OBJECTIVE: To assess the effect of daptomycin compared with vancomycin on the clinical and economic outcomes in patients with complicated skin and skin structure infections. DESIGN: Prospective, open-label study. SETTING: Level 1 trauma center in Detroit, Michigan. PATIENTS: Fifty-three adult patients with complicated skin and skin structure infections at risk for methicillin-resistant Staphylococcus aureus (MRSA) infection who were treated with daptomycin and a matched cohort of 212 patients treated with vancomycin. INTERVENTION: Patients in the prospective arm received intravenous daptomycin 4 mg/kg every 24 hours for at least 3 days but not more than 14 days. Historical controls received at least 3 days of vancomycin dosed to achieve trough concentrations of 5-20 microg/ml. MEASUREMENTS AND MAIN RESULTS: Outcomes evaluated included blinded assessments of clinical resolution, duration of therapy, and costs. The most common diagnoses were cellulitis (31%), abscess (22%), and both cellulitis with abscess (37%). Microbiology differed significantly between groups, with S. aureus found in 27 patients (51%) in the daptomycin group and 167 patients (79%) in the vancomycin group and MRSA in 22 (42%) and 159 (75%), respectively (p<0.001). The proportions of patients with clinical improvement or resolution of their infections on days 3 and 5 were 90% versus 70% and 98% versus 81% in the daptomycin versus vancomycin groups, respectively (p<0.01 for both comparisons), and 100% at the end of therapy in both groups. Among patients with complete resolution of their infections (41 patients [77%] with daptomycin vs 89 patients [42%] with vancomycin, p<0.05), median duration of intravenous therapy was 4 and 7 days, respectively, (p<0.001), and hospital costs were $5027 and $7552 (p<0.001). CONCLUSIONS: Patients receiving daptomycin achieved more rapid resolution of symptoms and clinical cure and had a decreased duration of inpatient therapy compared with those receiving vancomycin. This study suggests that daptomycin is a cost-effective alternative to vancomycin for complicated skin and skin structure infections.

Treatment of severe decompensated heart failure with high-dose intravenous nitroglycerin: a feasibility and outcome analysis.

STUDY OBJECTIVE: We perform a feasibility and outcome assessment of the treatment of severe decompensated heart failure with high-dose nitroglycerin. METHODS: This study was designed as a nonrandomized, open-label, single-arm study of high-dose nitroglycerin. Patients with hypertension (systolic blood pressure > or = 160 mm Hg or mean arterial pressure > or = 120 mm Hg) who were refractory to initial therapy were eligible for inclusion. Enrolled patients began receiving a titratable nitroglycerin infusion and were given a bolus of high-dose nitroglycerin (2 mg). Repeated administration of high-dose nitroglycerin was allowed every 3 minutes, up to a total of 10 doses. Predefined effectiveness and safety outcomes were tracked throughout hospital admission. To provide a frame of reference for these outcomes, data were retrospectively compiled for similar patients with severe decompensated heart failure who did not receive high-dose nitroglycerin. RESULTS: Twenty-nine patients received high-dose nitroglycerin. Endotracheal intubation was required in 13.8% of patients, bilevel positive airway pressure (BiPAP) ventilation in 6.9%, and ICU admission in 37.9%. Symptomatic hypotension developed in 1 patient (3.4%), and biomarker evidence of myocardial infarction was found in 17.2% of patients. The mean dose of high-dose nitroglycerin was 6.5 mg (+/-3.4). For patients who were treated without high-dose nitroglycerin (n=45), endotracheal intubation occurred in 26.7%, BiPAP in 20.0%, and ICU admission in 80.0%. None of these patients developed symptomatic hypotension, and biomarker evidence of myocardial infarction was observed in 28.9% of patients. CONCLUSION: In this nonrandomized, open-label trial, high-dose nitroglycerin was associated with endotracheal intubation, BiPAP, and ICU admission less frequently than expected to occur without high-dose nitroglycerin, and adverse events were uncommon. Treatment of hypertensive, severely decompensated heart failure patients with high-dose nitroglycerin seems promising, but a randomized, blinded study is needed to more completely define its clinical utility. According to this trial, such a study seems feasible.

Documentation of pharmacists' interventions in an emergency department and associated cost avoidance.

PURPOSE: An analysis was conducted of pharmacist interventions and resuscitation experiences, including pharmacist participation in a hospital emergency department (ED), and the potential cost avoidance associated with the interventions made by the pharmacists. METHODS: All pharmacists working in the ED prospectively documented the pharmacist interventions that were accepted by physicians and nursing staff and entered into a spreadsheet on a weekly basis, between September 1, 2003, and December 31, 2003. Intervention categories included the provision of drug information; recommendations for dosage adjustment, formulary interchange, initiation of medications, alternative drug therapy, discontinuation of drug therapy, changes in medication therapy due to allergy notification, drug therapy duplication prevention, or changes in the route of drug administration; questions from nursing staff; order clarifications; drug compatibility issues; patient information; toxicology; and drug interaction identification. Intervention data were analyzed and the likelihood of harm was scored; interventions were classified and analyzed by calculating average cost, probability of harm, and potential cost avoidance. RESULTS: During the study, 2150 pharmacist interventions were documented. Pharmacists participated in the care of 1042 patients triaged to the resuscitation area of the ED. Cost avoidance during the study was determined to be 1,029,776 dollars. CONCLUSION: The most commonly documented interventions made by pharmacists involved in the care of patients visiting the ED included provision of drug information, dosage adjustment recommendations, responses to questions from nursing staff, formulary interchanges, and suggestions regarding initiation of drug therapy. The potential cost avoidance attributable to the pharmacist interventions during the study period was over 1 million dollars.

Pharmacoeconomic considerations associated with the use of intravenous-to-oral moxifloxacin for community-acquired pneumonia.

BACKGROUND: Intravenous-to-oral (iv/po) conversion is one cost-effective approach to the management of community-acquired pneumonia (CAP). METHODS: Consecutive patients with CAP were enrolled during 3 study periods (January-March of 2001, 2002, and 2004) with different pharmacy intervention (PI) strategies: iv beta -lactam plus a macrolide (no PI), iv beta-lactam plus a macrolide with iv/po PI (PI switch), and iv moxifloxacin with pharmacist-initiated automatic po moxifloxacin conversion (PI sequential). Costs and outcomes were compared among groups. RESULTS: Two hundred fifty-one patients were enrolled. The average Fine score was 75, and the mean age of patients was 51 years. In the PI groups, the duration of treatment with iv antibiotics was decreased. Clinical success on day 3 of therapy was improved in the PI sequential group but was similar in all 3 groups on day 7 of therapy and at the end of therapy. The length of stay in the hospital was similar for patients in all 3 groups (mean, 4.39 days). Antibiotic costs were significantly reduced, by $110/patient, in the PI sequential group. CONCLUSIONS: Conversion from iv to po therapy was accomplished more quickly when converting to the same agent with pharmacist-initiated automatic iv/po conversion, thus reducing the associated cost without compromising efficacy.

Characteristics of prophylactic antibiotic strategies after penetrating abdominal trauma at a level I urban trauma center: a comparison with the East guidelines.

BACKGROUND: Antibiotic prophylaxis, along with surgical intervention, is a key component in reducing infection in patients after penetrating abdominal trauma (PAT). Recent guidelines from the Eastern Association for the Surgery of Trauma (EAST) recommend that prophylaxis for < or = 24 hours is adequate for most patients. We compared antibiotic prophylaxis practices after PAT at our institution with EAST guidelines, quantified the incidence of infection, and identified risk factors for infection. METHODS: This study was a retrospective review of patients with PAT requiring a therapeutic laparotomy between July 1998 and January 2001. RESULTS: Antibiotic prophylaxis met EAST guidelines criteria in 21 of 97 patients (22%). There was a trend toward higher infection rates (18 of 76 vs. 3 of 21; = 0.273) when prophylaxis exceeded EAST recommendations. Multivariate analysis revealed blood transfusions to be the only predictor of infection (odds ratio, 6.9; 95% confidence interval, 2.42-19.95). CONCLUSION: Despite prophylactic antibiotic use often exceeding EAST criteria, many patients still developed infection. Blood transfusion was the only significant risk factor for infection.