In this cohort of patients receiving ceftriaxone, doxycycline was associated with lower risk of CDI. Guidelines recommend this combination as a second-line regimen for some patients with community-acquired pneumonia (CAP). Further clinical studies would help define whether doxycycline-containing regimens should be a preferred therapy for CAP.
Staphylococcus aureus is a leading cause of bacteremia (1, 2). Even when an individual is appropriately treated, the risk of mortality from S. aureus bacteremia (SAB) is 20 to 40% per episode (3-8). Furthermore, the morbidity from SAB is striking, with 10 to 15% of episodes being complicated by endocarditis or a risk of metastatic disease elsewhere in the body (9, 10). The financial consequences of SAB are also significant, with health care costs ranging from $12,078 to $25,573 per episode of SAB (11-13). Typically, SAB is treated with narrow-spectrum beta-lactam antibiotics for methicillin-susceptible S. aureus (MSSA) isolates and the glycopeptide antibiotic vancomycin for methicillin-resistant S. aureus (MRSA) isolates (14-17). Isolates with vancomycin MICs of Յ2 g/ml are considered susceptible, those with MICs of 4 to 8 g/ml are considered intermediately resistant, and those with MICs of Ͼ8 g/ml are designated resistant (18). The question of whether infection by S. aureus strains with vancomycin MICs of 2 g/ml is associated with worse outcomes has been a topic of much research, although a consensus has not been reached. Compared with research methods such as Epsilometer testing (Etest) or broth microdilution (BMD), automated MIC measurements can be off by 1 dilution in either direction (e.g., a value of 2 g/ml could mean 1 or 4 g/ml if repeated) (19,20), which adds to the deliberation over interpreting study results, although consistency between BMD and Etest results can also vary. In addition, most studies have focused on MRSA, but the role of vancomycin MIC in MSSA infection has not been fully evaluated. A number of studies, including systematic reviews and meta-analyses, have demonstrated increased mortality in the setting of SAB with vancomycin MICs of Ն2.0 g/ml (21-28). Conversely, others have shown an increased risk of mortality in individuals with MICs of Ͻ2.0 g/ml (29-32). In spite of these data, the majority of studies have failed to show any significant increase in the risk of mortality attributable to vancomycin MIC (5,26,. A recent rigorous meta-analysis failed to demonstrate increased 30-day or in-hospital mortality attributable to vancomycin MIC, irrespective of the MIC cutoff that was chosen (1.5, 2.0, 4.0, or 8.0 g/ml) (5). Although valuable, meta-analyses are lim-
IntroductionIntroduction of new antibiotics enabling single-dose administration, such as oritavancin may significantly impact site of care decisions for patients with acute bacterial skin and skin structure infections (ABSSSI). This analysis compared the efficacy of single-dose oritavancin with multiple-dose vancomycin in patients categorized according to disease severity via modified Eron classification and management setting.MethodsSOLO I and II were phase 3 studies evaluating single-dose oritavancin versus 7–10 days of vancomycin for treatment of ABSSSI. Patient characteristics were collected at baseline and retrospectively analyzed. Study protocols were amended, allowing outpatient management at the discretion of investigators. In this post hoc analysis, patients were categorized according to a modified Eron severity classification and management setting (outpatient vs. inpatient) and the efficacy compared.ResultsOverall, 1910 patients in the SOLO trials were categorized into Class I (520, 26.5%), II (790, 40.3%), and III (600, 30.6%). Of the 767 patients (40%) in the SOLO trials who were managed entirely in the outpatient setting 40.3% were categorized as Class II and 30.6% were Class III. Clinical efficacy was similar between oritavancin and vancomycin treatment groups, regardless of severity classification and across inpatient and outpatient settings. Class III patients had lower response rates (oritavancin 73.3%, vancomycin 76.6%) at early clinical evaluation when compared to patients in Class I (82.6%) or II (86.1%); however, clinical cure rates at the post-therapy evaluation were similar for Class III patients (oritavancin 79.8%, vancomycin 79.9%) when compared to Class I and II patients (79.1–85.7%).ConclusionSingle-dose oritavancin therapy results in efficacy comparable to multiple-dose vancomycin in patients categorized according to modified Eron disease severity classification regardless of whether management occurred in the inpatient or outpatient setting.FundingThe Medicines Company, Parsippany, NJ, USA.Trial registrationClinicalTrials.gov identifiers, NCT01252719 (SOLO I) and NCT01252732 (SOLO II).
Invasive candidiasis is a common nosocomial infection, especially among the critically ill and immunocompromised patient populations. The recent standardization and increasing availability of antifungal susceptibility testing has the potential to optimize the selection of antifungal therapy. Treatment has been revolutionized in recent years with the marketing of several antifungal agents with excellent activity against Candida spp. These agents include the triazoles, fluconazole and voriconazole, and the echinocandin antifungals. While more expensive by acquisition cost, these newer agents are less toxic than the previously used drugs, and the triazoles offer the additional benefit of oral administration. The availability of new agents, future adoption of diagnostic tests for candidiasis, and susceptibility testing will have a major impact in the management of invasive candidiasis.
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