Daptomycin for the treatment of Staphylococcus aureus infections complicated by septic pulmonary emboli.

The management of Staphylococcus aureus bacteremia is limited by high rates of methicillin resistance and the paucity of antibiotic agents with proven efficacy in complicated infectious syndromes, such as endocarditis. Vancomycin is the mainstay of therapy; however, salvage therapy is frequently required due to persistence of infection or drug toxicity. Daptomycin is FDA-approved for S. aureus bacteremia and right-sided endocarditis, but controversy exists regarding the role of this agent in the setting of septic pulmonary emboli. Sequestration by pulmonary surfactant renders daptomycin ineffective in bronchoalveolar pneumonia; however, the impact of this drug property on efficacy in hematogenous pulmonary infections is unclear. Herein we review the available evidence in order to inform the rationale use of daptomycin in S. aureus infections complicated by septic pulmonary emboli.

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.

Treatment of Paecilomyces variotii pneumonia with posaconazole: case report and literature review.

The fungi Paecilomyces variotii is a potential pathogen in immunocompromised and immunocompetent patients. Their rare association with clinical disease results in scarce literature regarding susceptibility and treatment. Here, we discuss a case involving successful treatment of probable P. variotii pneumonia with posaconazole after treatment failure with voriconazole. The current literature related to antifungal susceptibility profiles, microbiological identification methods and clinical management of infections caused by this organism is also reviewed.

New developments in the treatment of acute bacterial skin and skin structure infections: considerations for the effective use of dalbavancin.

Dalbavancin, an intravenous glycopeptide, was approved by the US Food and Drug Administration in May 2014 for use in adult patients with acute bacterial skin and skin structure infections. The recommended dosing regimen for effective use of dalbavancin is 1,000 mg followed by a 500 mg dose after 1 week. Two multinational, identically designed, non-inferiority trials, DISCOVER 1 and 2, demonstrated similar early clinical success with dalbavancin compared to vancomycin with an option to switch to oral linezolid. In a recently published non-inferiority trial, a single-dose regimen of dalbavancin was compared to the traditional two-dose administration and was found to have a non-inferior clinical response. In the aforementioned trials, dalbavancin was well tolerated, with patients experiencing transient adverse events of mild to moderate severity. The prolonged half-life, excellent skin and soft tissue penetration, bactericidal activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus, and convenient dosing make dalbavancin a reasonable option for the treatment of acute bacterial skin and skin structure infections in adult patients who have tried and failed other therapies.

Examining the Clinical Effectiveness of Non-Carbapenem ß-Lactams for the Treatment of Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae.

Treatment options for extended-spectrum ß-lactamase-producing Enterobacteriaceae are limited. Piperacillin-tazobactam and cefepime represent potential alternative treatment options; however, large prospective studies are lacking. This review evaluates the current literature regarding use of piperacillin-tazobactam and cefepime for the treatment of extended-spectrum ß-lactamase-producing Enterobacteriaceae. Antimicrobial stewardship programs can play a key role in guiding the best practices for the management of these challenging infections.

Impact of antimicrobial stewardship intervention on coagulase-negative Staphylococcus blood cultures in conjunction with rapid diagnostic testing.

Rapid diagnostic testing with matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) decreases the time to organism identification by 24 to 36 h compared to the amount of time required by conventional methods. However, there are limited data evaluating the impact of MALDI-TOF with real-time antimicrobial stewardship team (AST) review and intervention on antimicrobial prescribing and outcomes for patients with bacteremia and blood cultures contaminated with coagulase-negative Staphylococcus (CoNS). A quasiexperimental study was conducted to analyze the impact of rapid diagnostic testing with MALDI-TOF plus AST review and intervention for adult hospitalized patients with blood cultures positive for CoNS. Antibiotic prescribing patterns and clinical outcomes were compared before and after implementation of MALDI-TOF with AST intervention for patients with CoNS bacteremia and CoNS contamination. A total of 324 patients with a positive CoNS blood culture were included; 246 were deemed to have contaminated cultures (117 in the preintervention group and 129 in AST the intervention group), and 78 patients had bacteremia (46 in the preintervention group and 32 in the AST intervention group). No differences in demographics were seen between the groups, and similar rates of contamination occurred between the preintervention and AST intervention groups (64.3% versus 72.6%, P = 0.173). Patients with bacteremia were initiated on optimal therapy sooner in the AST intervention group (58.7 versus 34.4 h, P = 0.030), which was associated with a similarly decreased mortality (21.7% versus 3.1%, P = 0.023). Patients with CoNS-contaminated cultures had similar rates of mortality, lengths of hospitalization, recurrent bloodstream infections, and 30-day hospital readmissions, but the AST intervention group had a decreased duration of unnecessary antibiotic therapy (1.31 versus 3.89 days, P = 0.032) and a decreased number of vancomycin trough assays performed (0.88 versus 1.95, P < 0.001). In patients with CoNS bacteremia, rapid pathogen identification integrated with real-time stewardship interventions improved timely organism identification and initiation of antibiotic therapy. Patients in the AST group with blood cultures contaminated with CoNS had decreased inappropriate antimicrobial prescribing and decreased unnecessary serum vancomycin trough assays.

Impact of rapid organism identification via matrix-assisted laser desorption/ionization time-of-flight combined with antimicrobial stewardship team intervention in adult patients with bacteremia and candidemia.

BACKGROUND: Integration of rapid diagnostic testing via matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) with antimicrobial stewardship team (AST) intervention has the potential for early organism identification, customization of antibiotic therapy, and improvement in patient outcomes. The objective of this study was to assess the impact of this combined approach on clinical and antimicrobial therapy-related outcomes in patients with bloodstream infections. METHODS: A pre-post quasi-experimental study was conducted to analyze the impact of MALDI-TOF with AST intervention in patients with bloodstream infections. The AST provided evidence-based antibiotic recommendations after receiving real-time notification following blood culture Gram stain, organism identification, and antimicrobial susceptibilities. Outcomes were compared to a historic control group. RESULTS: A total of 501 patients with bacteremia or candidemia were included in the final analysis: 245 patients in the intervention group and 256 patients in the preintervention group. MALDI-TOF with AST intervention decreased time to organism identification (84.0 vs 55.9 hours, P < .001), and improved time to effective antibiotic therapy (30.1 vs 20.4 hours, P = .021) and optimal antibiotic therapy (90.3 vs 47.3 hours, P < .001). Mortality (20.3% vs 14.5%), length of intensive care unit stay (14.9 vs 8.3 days) and recurrent bacteremia (5.9% vs 2.0%) were lower in the intervention group on univariate analysis, and acceptance of an AST intervention was associated with a trend toward reduced mortality on multivariable analysis (odds ratio, 0.55, P = .075). CONCLUSION: MALDI-TOF with AST intervention decreased time to organism identification and time to effective and optimal antibiotic therapy.