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Background Vancomycin is the most commonly administered antibiotic in hospitalized patients, but optimal exposure targets remain controversial. To clarify the therapeutic exposure range, this study evaluated the association between vancomycin exposure and outcomes in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Methods This was a prospective, multicenter (n = 14), observational study of 265 hospitalized adults with MRSA bacteremia treated with vancomycin. The primary outcome was treatment failure (TF), defined as 30-day mortality or persistent bacteremia ≥7 days. Secondary outcomes included acute kidney injury (AKI). The study was powered to compare TF between patients who achieved or did not achieve day 2 area under the curve to minimum inhibitory concentration (AUC/MIC) thresholds previously found to be associated with lower incidences of TF. The thresholds, analyzed separately as co-primary endpoints, were AUC/MIC by broth microdilution ≥650 and AUC/MIC by Etest ≥320. Results Treatment failure and AKI occurred in 18% and 26% of patients, respectively. Achievement of the prespecified day 2 AUC/MIC thresholds was not associated with less TF. Alternative day 2 AUC/MIC thresholds associated with lower TF risks were not identified. A relationship between the day 2 AUC and AKI was observed. Patients with day 2 AUC ≤515 experienced the best global outcomes (no TF and no AKI). Conclusions Higher vancomycin exposures did not confer a lower TF risk but were associated with more AKI. The findings suggest that vancomycin dosing should be guided by the AUC and day 2 AUCs should be ≤515. As few patients had day 2 AUCs <400, further study is needed to define the lower bound of the therapeutic range. [ABSTRACT FROM AUTHOR]

Purulent pericarditis caused by Candida species is a rare and often undiagnosed disease. We recently treated a patient in whom purulent pericarditis due to Candida albicans developed following thoracic surgery. The patient survived after receiving a combination of surgical and medical therapy. A literature review revealed 24 additional cases of purulent pericarditis caused by Candida species. Twenty-one of the patients either had undergone thoracic surgery or had had disseminated candidiasis. None of the 12 patients described before 1980 survived, whereas six (46%) of the 13 patients described after 1980 survived. No patient survived without pericardiectomy (five of six survivors) or at least pericardiocentesis (one survivor). All survivors received full courses of amphotericin B therapy. An increased utilization of echocardiography, along with an increased recognition of the patient populations at risk, has been instrumental in early detection and improved outcome of purulent pericarditis. A combination of prolonged amphotericin B therapy and pericardiectomy appears to be the best approach for achieving a cure. [ABSTRACT FROM PUBLISHER]

We conducted a randomized, prospective, open comparison to evaluate the efficacy and safety of cefepime and ceftazidime in the treatment of hospitalized patients with suspected gram-negative bacteremia. Twenty-eight patients with signs and symptoms of sepsis were prospectively randomized to receive cefepime (13 patients) or ceftazidime (15 patients). Cultures of blood obtained at entry into the study were positive for 24 (85.7%) of 28 patients. Eight patients had two or more positive pretreatment blood cultures, and the remaining 16 had one positive pre-treatment blood culture. The most commonly isolated blood pathogen was Escherichia coli. Eleven of 13 patients treated with cefepime and 12 of 15 patients treated with ceftazidime were clinically cured. Adverse effects attributable to therapy with the study drugs were minimal in both groups of patients and included rash, headache, nausea, and diarrhea. Our results suggest that cefepime is as efficacious and well tolerated as is ceftazidime in the treatment of hospitalized patients with documented gram-negative bacteremia. [ABSTRACT FROM PUBLISHER]

Importance: The appropriate duration of antibiotics for staphylococcal bacteremia is unknown., Objective: To test whether an algorithm that defines treatment duration for staphylococcal bacteremia vs standard of care provides noninferior efficacy without increasing severe adverse events., Design, Setting, and Participants: A randomized trial involving adults with staphylococcal bacteremia was conducted at 16 academic medical centers in the United States (n = 15) and Spain (n = 1) from April 2011 to March 2017. Patients were followed up for 42 days beyond end of therapy for those with Staphylococcus aureus and 28 days for those with coagulase-negative staphylococcal bacteremia. Eligible patients were 18 years or older and had 1 or more blood cultures positive for S aureus or coagulase-negative staphylococci. Patients were excluded if they had known or suspected complicated infection at the time of randomization., Interventions: Patients were randomized to algorithm-based therapy (n = 255) or usual practice (n = 254). Diagnostic evaluation, antibiotic selection, and duration of therapy were predefined for the algorithm group, whereas clinicians caring for patients in the usual practice group had unrestricted choice of antibiotics, duration, and other aspects of clinical care., Main Outcomes and Measures: Coprimary outcomes were (1) clinical success, as determined by a blinded adjudication committee and tested for noninferiority within a 15% margin; and (2) serious adverse event rates in the intention-to-treat population, tested for superiority. The prespecified secondary outcome measure, tested for superiority, was antibiotic days among per-protocol patients with simple or uncomplicated bacteremia., Results: Among the 509 patients randomized (mean age, 56.6 [SD, 16.8] years; 226 [44.4%] women), 480 (94.3%) completed the trial. Clinical success was documented in 209 of 255 patients assigned to algorithm-based therapy and 207 of 254 randomized to usual practice (82.0% vs 81.5%; difference, 0.5% [1-sided 97.5% CI, -6.2% to ∞]). Serious adverse events were reported in 32.5% of algorithm-based therapy patients and 28.3% of usual practice patients (difference, 4.2% [95% CI, -3.8% to 12.2%]). Among per-protocol patients with simple or uncomplicated bacteremia, mean duration of therapy was 4.4 days for algorithm-based therapy vs 6.2 days for usual practice (difference, -1.8 days [95% CI, -3.1 to -0.6])., Conclusions and Relevance: Among patients with staphylococcal bacteremia, the use of an algorithm to guide testing and treatment compared with usual care resulted in a noninferior rate of clinical success. Rates of serious adverse events were not significantly different, but interpretation is limited by wide confidence intervals. Further research is needed to assess the utility of the algorithm., Trial Registration: ClinicalTrials.gov Identifier: NCT01191840.