A multicentre stewardship initiative to decrease excessive duration of antibiotic therapy for the treatment of community-acquired pneumonia.

Background: The increased emphasis on pneumonia-related performance measures and patient outcomes has led hospitals to implement multifaceted approaches to quickly identify patients with community-acquired pneumonia (CAP), start timely therapy and reduce readmission. However, there has been minimal focus on duration of therapy (DOT) and patients often receive prolonged antibiotic courses. The IDSA and American Thoracic Society (IDSA/ATS) CAP guidelines recommend 5 days of therapy for clinically stable patients that quickly defervesce and stewardship teams are well positioned to influence prescribing practices. Objectives: Determine the impact of a prospective stewardship intervention on total antibiotic DOT and associated clinical outcomes in hospitalized patients with CAP. Methods: This multicentre, quasi-experimental study evaluated three concurrent interventions over a 6 month period to promote appropriate DOT. All centres updated institutional CAP guidelines to promote IDSA/ATS-concordant DOT, provided education and conducted daily audit and feedback with intervention to provide patient-specific DOT recommendations. Results: A total of 600 patients with CAP were included (307 in the historical control group and 293 in the stewardship intervention group). The stewardship intervention increased compliance with DOT recommendations (42% versus 5.6%, P < 0.001) and reduced the median DOT per patient (6 versus 9 days, P < 0.001). Clinical outcomes, including mortality, readmission with pneumonia, presentation to the emergency centre/clinic with pneumonia and incidence of Clostridium difficile infection within 30 days of discharge, were not different between groups. Conclusions: This multicentre evaluation of a stewardship intervention in hospitalized CAP patients reduced the total antibiotic DOT and increased guideline-concordant DOT without adversely affecting patient outcomes.

Comparison of outcomes with vancomycin or metronidazole for mild-to-moderate Clostridium difficile associated diarrhea among solid organ transplant recipients: A retrospective cohort study.

BACKGROUND: Current guidelines recommend oral vancomycin or fidaxomicin for the treatment of mild-to-moderate Clostridium difficile associated diarrhea (CDAD), while metronidazole is recommended as an alternative when oral vancomycin and fidaxomicin are unavailable. However, data are lacking among the solid organ transplant (SOT) population. METHODS: This single center, retrospective cohort study evaluated adult SOT recipients with mild-to-moderate CDAD. Analysis 1 evaluated patients receiving initial therapy with metronidazole vs oral vancomycin for at least 72 hours. Analysis 2 evaluated patients receiving metronidazole vs oral vancomycin for at least 70% of the treatment duration. The primary outcome was treatment failure. Secondary outcomes included CDAD recurrence and all-cause mortality. RESULTS: Analysis 1 included 71 patients (metronidazole n = 50, oral vancomycin n = 21) and analysis 2 included 75 patients (metronidazole n = 42, oral vancomycin n = 33). No significant differences in C. difficile risk factors were observed between groups in either analysis. However, in both analyses, more patients in the oral vancomycin arm received antibiotics during the CDAD episode (analysis 1, 52% vs 26%, P = .03; analysis 2, 55% vs 32%, P < .01). Neither analysis demonstrated differences in treatment failure (analysis 1, metronidazole 16%, oral vancomycin 10%, P = .71; analysis 2, metronidazole 2%, oral vancomycin 6%, P = .58). CDAD recurrence and all-cause mortality were similar across groups in both analyses. CONCLUSIONS: Results suggest that both metronidazole and oral vancomycin are reasonable options for the treatment of mild-to-moderate CDAD in patients with SOT. No difference in treatment failure was observed; however, oral vancomycin may be preferred for higher risk patients, such as those receiving concurrent antibiotics.

Comparison of cefazolin versus oxacillin for treatment of complicated bacteremia caused by methicillin-susceptible Staphylococcus aureus.

Contrary to prior case reports that described occasional clinical failures with cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infections, recent studies have demonstrated no difference in outcomes between cefazolin and antistaphylococcal penicillins for the treatment of MSSA bacteremia. While promising, these studies described low frequencies of high-inoculum infections, such as endocarditis. This retrospective study compares clinical outcomes of cefazolin versus oxacillin for complicated MSSA bacteremia at two tertiary care hospitals between January 2008 and June 2012. Fifty-nine patients treated with cefazolin and 34 patients treated with oxacillin were included. Osteoarticular (41%) and endovascular (20%) sources were the predominant sites of infection. The rates of clinical cure at the end of therapy were similar between cefazolin and oxacillin (95% versus 88%; P=0.25), but overall failure at 90 days was higher in the oxacillin arm (47% versus 24%; P=0.04). Failures were more likely to have received surgical interventions (63% versus 40%; P=0.05) and to have an osteoarticular source (57% versus 33%; P=0.04). Failures also had a longer duration of bacteremia (7 versus 3 days; P=0.0002), which was the only predictor of failure. Antibiotic selection was not predictive of failure. Rates of adverse drug events were higher in the oxacillin arm (30% versus 3%; P=0.0006), and oxacillin was more frequently discontinued due to adverse drug events (21% versus 3%; P=0.01). Cefazolin appears similar to oxacillin for the treatment of complicated MSSA bacteremia but with significantly improved safety. The higher rates of failure with oxacillin may have been confounded by other patient factors and warrant further investigation.

Systemic preexposure prophylaxis for HIV: translating clinical data to clinical practice.

OBJECTIVE: To assess the real-world implications of oral tenofovir-emtricitabine (TDF-FTC) for HIV preexposure prophylaxis (PrEP) in clinical practice and highlight important considerations for its implementation. DATA SOURCES: A search of PubMed (January 1996 through June 2013) was conducted using the terms HIV preexposure prophylaxis, HIV prevention, tenofovir, and emtricitabine. Abstracts from 2012-2013 HIV/AIDS conferences were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All pertinent original studies and review articles published in English were evaluated for inclusion. Reference citations from identified articles were examined for additional content. DATA SYNTHESIS: Although antiretroviral therapy has been highly successful in reducing AIDS outcomes and death in HIV-infected patients worldwide, transmission of HIV remains a major global health problem. The recent approval of oral TDF-FTC for HIV PrEP represents the latest biomedical intervention to help control this epidemic. Four published randomized studies evaluated the efficacy and safety of this combination to prevent HIV transmission in several at-risk populations, including men who have sex with men, serodiscordant couples, and heterosexuals residing in endemic regions. Overall, these studies demonstrated significant risk reductions in the incidence of new HIV infections with good short-term tolerability. Despite promising results from clinical studies, several limitations may hinder the utility of PrEP in clinical practice. Most importantly, PrEP was studied in the context of a comprehensive prevention program, including intensive counseling on adherence, high-risk behaviors, and traditional preventative measures. If PrEP is implemented without these adjunct measures, concerns about failure and increased resistance may eventually be realized. CONCLUSION: The greatest impact of PrEP, both clinically and financially, will likely arise from judicious application in select high-risk populations. If used appropriately, PrEP has the potential to augment reductions in the current incidence of new HIV infections, and pharmacists will have an important role in the careful selection and counseling of these targeted populations.

Treatment of Helicobacter pylori in Special Patient Populations.

Helicobacter pylori infection can lead to gastritis, gastric and duodenal ulcers, and gastric cancer. Consequently, complete eradication is the goal of therapy. First-line therapy for H. pylori infection includes clarithromycin triple therapy (clarithromycin, proton pump inhibitor [PPI], and amoxicillin or metronidazole), bismuth quadruple therapy (bismuth salt, PPI, tetracycline, and metronidazole or amoxicillin), or concomitant therapy (clarithromycin, PPI, amoxicillin, and metronidazole). However, many patients have relative contraindications to the antibiotics included in these regimens, making therapy selection difficult. Furthermore, failure of initial therapy makes selection of second-line therapy challenging due to concerns for potential resistance to agents included in the initial regimen. This review discusses H. pylori microbiology, including antibiotic resistance, and summarizes the existing evidence for first- and second-line treatment regimens that may be considered for special populations such as patients with penicillin allergies, patients with or at risk for QTc-interval prolongation, and patients who are pregnant, breastfeeding, or elderly.

ß-Lactam Therapy for Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Comparative Review of Cefazolin versus Antistaphylococcal Penicillins.

Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia is associated with high morbidity and mortality. Traditionally, antistaphylococcal penicillins (ASPs) have been considered the agents of choice for the treatment of MSSA bacteremia. Vancomycin has been demonstrated to have poorer outcomes in several studies and is only recommended for patients with severe penicillin allergies. Although cefazolin is considered as an alternative to the ASPs for patients with nonsevere penicillin allergies, cefazolin offers several pharmacologic advantages over ASPs, such as more convenient dosing regimens, and antimicrobial stewardship programs are increasingly using cefazolin as the preferential agent for MSSA infections as part of cost-saving initiatives. Concerns about susceptibility to hydrolysis by type A ß-lactamases, particularly at high inocula seen in deep-seated infections such as endocarditis; selective pressures from unnecessary gram-negative coverage; and lack of comparative clinical data have precluded recommending cefazolin as a first-line therapy for MSSA bacteremia. Recent clinical studies, however, have suggested similar clinical efficacy but better tolerability, with lower rates of discontinuation due to adverse drug reactions, of cefazolin compared with ASPs. Other variables, such as adequate source control (e.g., intravascular catheter removal, debridement, or drainage) and enhanced pharmacodynamics through aggressive cefazolin dosing, may mitigate the role of cefazolin inoculum effect and factor into determining improved clinical outcomes. In this review, we highlight the utility of cefazolin versus ASPs in the treatment of MSSA bacteremia with a focus on clinical efficacy and safety.

Role of New Antifungal Agents in the Treatment of Invasive Fungal Infections in Transplant Recipients: Isavuconazole and New Posaconazole Formulations.

Invasive fungal infections are a major cause of morbidity and mortality among solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Transplant patients are at risk for such invasive fungal infections. The most common invasive fungal infections are invasive candidiasis in the SOT and invasive aspergillosis in the HSCT. In this article, we will discuss the epidemiology of invasive fungal infections in the transplant recipients and susceptibility patterns of the fungi associated with these infections. Additionally, the pharmacology and clinical efficacy of the new antifungal, isavuconazole, and the new posaconazole formulations will be reviewed. Isavuconazole is a new extended-spectrum triazole that was recently approved for the treatment of invasive aspergillosis and mucormycosis. Advantages of this triazole include the availability of a water-soluble intravenous formulation, excellent bioavailability of the oral formulation, and predictable pharmacokinetics in adults. Posaconazole, a broad-spectrum triazole antifungal agent, is approved for the prevention of invasive aspergillosis and candidiasis in addition to the treatment of oropharyngeal candidiasis. Posaconazole oral suspension solution has shown some limitations in the setting of fasting state absorption, elevated gastrointestinal pH, and increased motility. The newly approved delayed-release oral tablet and intravenous solution formulations provide additional treatment options by reducing interpatient variability and providing flexibility in these set of critically ill patients. This review will detail these most recent studies.

Clinical and economic impact of substituting dexmedetomidine for propofol due to a US drug shortage: examination of coronary artery bypass graft patients at an urban medical centre.

BACKGROUND: Propofol has reduced healthcare costs in coronary artery bypass graft (CABG) surgery patients by decreasing post-operative duration of mechanical ventilation. However, the US shortage of propofol necessitated the use of alternative agents. OBJECTIVE: This study sought to evaluate clinical and economic implications of substituting dexmedetomidine for propofol in patients undergoing CABG surgery. METHODS: This was a retrospective cohort study. Patients undergoing isolated, elective CABG surgery and sedated with either propofol or dexmedetomidine during the study period were included. The cohorts were matched 1:1 based on important characteristics. The primary outcome was the number of patients achieving a post-operative duration of mechanical ventilation ≤6 h. Secondary outcomes were post-operative intensive care unit (ICU) length of stay (LOS) ≤48 h, total post-operative LOS ≤5 days, the need for adjunctive opioid therapy and associated cost savings. Variables recorded included patient demographics, co-morbid medical conditions, health risks, sedation drug doses, post-operative medical complications and sedation-related adverse events. Univariate and multivariate analyses were completed to examine the relationship between these covariates and post-operative LOS. The cost analysis consisted of examination of the net financial benefit (or cost) of choosing dexmedetomidine versus propofol in the study population, with utilisation observed in the study converted to costs using institutional data from the Premier database. RESULTS: Eighty-four patients were included, with 42 patients per cohort. Mechanical ventilation duration ≤6 h was achieved in 24 (57.1 %) versus 7 (16.7 %) in the dexmedetomidine and propofol cohorts, respectively (p < 0.001). More patients treated with dexmedetomidine achieved ICU LOS ≤48 h (p < 0.05) and total hospital LOS ≤5 days (p < 0.05), as compared with the propofol group. Multivariate analysis revealed that having one or more post-operative medical complication was the most significant predictor of increased post-operative LOS, whereas choosing dexmedetomidine was also significant in terms of reduced post-operative LOS. The estimated net financial benefit of choosing dexmedetomidine versus propofol was US$2,613 per patient (year 2012 value). CONCLUSIONS: Findings suggest that use of dexmedetomidine as an alternative to propofol for sedation of CABG patients post-operatively contributes to reduced mechanical ventilation time, ICU LOS and post-operative LOS. Higher drug costs resulting from the propofol shortage were offset by savings in post-operative room and board costs. Additional savings may be possible by preventing medical complications to the extent possible.