Efficacy of Eravacycline Versus Best Previously Available Therapy for Adults With Pneumonia Due to Difficult-to-Treat Resistant (DTR) Acinetobacter baumannii.

BACKGROUND: Multidrug-resistant Acinetobacter baumannii remains challenging to treat. Although eravacycline has in vitro activity against this pathogen, there are no studies evaluating outcomes. OBJECTIVE: To assess the efficacy of eravacycline compared with best previously available therapy in adults with difficult-to-treat resistant (DTR) A. baumannii pneumonia. METHODS: This was a retrospective study of adults hospitalized for pneumonia with DTR A. baumannii. Patients receiving eravacycline were compared with those receiving best previously available therapy. The primary outcome was 30-day in-hospital mortality. Secondary outcomes included clinical cure at Day 14, hospital and intensive care unit (ICU) length of stay, microbiologic cure, and readmission within 90 days with a positive A. baumannii respiratory culture. RESULTS: Ninety-three patients were included, with 27 receiving eravacycline. Eravacycline was associated with higher 30-day mortality (33% vs 15%; P = 0.048), lower microbiologic cure (17% vs 59%; P = 0.004), and longer durations of mechanical ventilation (10.5 vs 6.5 days; P = 0.016). At baseline, eravacycline patients had more A. baumannii bacteremia and coinfection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Among bacteremic patients, all 4 receiving eravacycline died by Day 30 and both patients receiving best previously available therapy survived. Upon exclusion of patients with bacteremia and SARS-CoV-2, there were no differences between the groups across any outcomes. CONCLUSIONS: Eravacycline-based combination therapy had similar outcomes to best previously available combination therapy for adults with DTR A. baumannii pneumonia. However, eravacycline should be used with caution in the setting of bacteremia as outcomes were poor in this population.

Continuous infusion versus intermittent infusion vancomycin in a burn center intensive care unit.

BACKGROUND: Vancomycin is a common and critical drug for empiric antimicrobial therapy in the infected burn patient. However, profound physiologic changes may impede the clinical effectiveness and amplify the potential nephrotoxicity of vancomycin. METHODS: This was a retrospective cohort study at a large academic medical center and regional burn center. Patients with ≥10% total body surface area burn that received intravenous vancomycin were considered for study inclusion. Patients were assigned to the intermittent infusion or continuous infusion cohort if they received vancomycin for ≥48 h with ≥1 documented vancomycin serum concentration. The target steady state drug level for continuous infusion was 17-22 mg/L. The target steady state trough drug level for intermittent infusion was 15-20 mg/L. The primary efficacy and safety outcomes were time to therapeutic drug level and nephrotoxicity respectively. RESULTS: Thirty continuous infusion subjects with 88 plasma drug levels and thirty intermittent infusion subjects with 80 plasma drug levels were analyzed within the study period. There was a significant difference in the number of subjects that achieved a plasma vancomycin level within the target range during the course of therapy (73.3% for continuous infusion vs. 26.7% for intermittent infusion, p = 0.0003). The time to therapeutic level was 3.90 days for continuous infusion and 5.22 days for intermittent infusion (p = 0.0393). Nephrotoxicity occurred less frequently in the continuous infusion cohort (23.3% vs. 53.8%). CONCLUSION: Continuous infusion vancomycin was associated with more rapid attainment of target levels and a lower rate of nephrotoxicity.

Modulation of saccade trajectories during sequential saccades.

The planning and execution of sequential saccades can overlap in time, and abrupt changes in neural activity in the oculomotor system can alter the normal trajectory of saccades. In this study, we analyzed saccade trajectories to assess the combined programming of sequential saccades. In two separate psychophysical experiments, subjects were instructed to make a sequence of two saccades. The results showed modulation of saccade curvature by the direction and amplitude of both the preceding and following saccade: saccade curvature is modulated in the direction of preceding saccades and away from the direction of following saccades. Moreover, larger preceding and following saccades have stronger effects on curvature. These results support the idea that sequential saccades are programmed concurrently. Finally, the amount of saccade curvature is correlated with the deviation of saccade start and end points, and the time of maximum deviation of saccade trajectories is highly consistent in both experiments. Based on this, we propose a novel benefit for the modulation of saccade trajectories by the oculomotor system: minimizing the saccadic error in sequential saccades.NEW & NOTEWORTHY We show that in saccade sequences, saccade trajectory is modulated in the direction of the preceding saccade and away from the following saccade. The magnitude of this effect is correlated with preceding and following saccade amplitude. This confirms that programming of sequential saccades overlaps. Curvature is also correlated with the deviation of saccade start and end points. Thus, we propose a novel benefit for the modulation of saccade trajectories: minimizing end point error in sequential saccades.

The Association Between Scholarly Impact and National Institutes of Health Funding in Orthopaedic Surgery.

The assessment of scholarly productivity assumes a strong role in evaluating faculty in academic orthopaedic surgery. The investigators examine the association between scholarly impact, as measured by the h-index, and National Institutes of Health (NIH) funding in orthopaedic surgery. Orthopaedic surgery faculty from 20 randomly chosen departments that received NIH-funding were compared to non-NIH funded faculty from the same departments. Faculty members in orthopaedic surgery departments who received NIH funding had higher scholarly impact as measured by h-index than their non-funded peers (h = 11.98 versus 4.45; p < 0.0001). This relationship holds across academic ranks, terminal degrees, and institutions. Investigators with higher academic rank had higher scholarly impact (h = assistant 3.29 versus associate 5.12 versus full professor 7.94; p < 1 x 10-7) as well as higher NIH-funding (assistant $16,580 versus associate $26,368 versus full professor $113,129; p < 1 x 10-7). Increasing individual NIH funding is correlated with elevated scholarly impact (ß = 4.64; p < 0.0001). Increasing total departmental NIH funding is correlated to increased departmental scholarly impact (ß = 1.04; p < 0.0001). The h-index is strongly associated with NIH funding, academic rank, and sole PhD holding faculty. Increasing scholarly impact is also correlated with higher NIH funding. The h-index is an objective and easily calculable measure of assessing individual research productivity.

Antimicrobial stewardship programs that target only high-cost, broad-spectrum antimicrobials miss opportunities to reduce Clostridium difficile infections.

Antimicrobial stewardship programs are promoted as a strategy to reduce Clostridium difficile infections. We implemented an antimicrobial stewardship program comprised of formulary restriction plus prospective audit with feedback for high-cost and broad-spectrum antimicrobials. Subsequently, we reviewed all heath care facility-onset, health care facility-associated C difficile infections. We found that most of these infections were associated with the antecedent receipt of nonaudited, and often unnecessary, antimicrobials.

Isavuconazole in the treatment of invasive aspergillosis and mucormycosis infections.

We have a limited arsenal with which to treat invasive fungal infections caused by Aspergillus and Mucorales. The morbidity and mortality for both pathogens remains high. A triazole antifungal, isavuconazole, was recently granted approval by the US Food and Drug Administration and the European Medicines Agency for the treatment of invasive aspergillosis and mucormycosis. A randomized double-blind comparison trial for the treatment of invasive aspergillosis found isavuconazole noninferior to voriconazole. A separate, open-label study evaluating the efficacy of isavuconazole in the treatment of mucormycosis found comparable response rates to amphotericin B and posaconazole treated historical controls. The prodrug isavuconazonium sulfate is commercially available in both an oral and intravenous formulation and is generally well tolerated. Isavuconazole's broad spectrum of activity, limited side effect profile, and favorable pharmacokinetics will likely solidify its place in therapy.

Amphotericin B-impregnated bone cement to treat refractory coccidioidal osteomyelitis.

Use of amphotericin B-impregnated bone cement in combination with systemic antifungals for the treatment of coccidioidal osteomyelitis offers the potential for sustained local concentrations of drug at the site of the infection. Amphotericin B levels in bone of up to 5.1 µg/g have been demonstrated 4 months after placement of bone cement.

Bioavailability of soil organic matter and microbial community dynamics upon permafrost thaw.

Amplified Arctic warming could thaw 25% of the permafrost area by 2100, exposing vast amounts of currently fixed organic carbon to microbially mediated decomposition and release of greenhouse gasses through soil organic matter (SOM) respiration. We performed time-series incubation experiments with Holocene permafrost soils at 4°C for up to 11 days to determine changes in exoenzyme activities (EEAs) (i.e. phosphatase, ß-glucosidase, aminopeptidase) as a measure for the bioavailability of SOM in response to permafrost thaw. We also profiled SSU rRNA transcripts to follow the qualitative and quantitative changes in viable prokaryotes and eukaryotes during incubation. EEA, amount of rRNA transcripts and microbial community structures differed substantially between the various soil intervals in response to thaw: after 11 days of incubation, the active layer became slightly depleted in C and P and harboured bacterial phyla indicative of more oligotrophic conditions (Acidobacteria). A fast response in phosphatase and ß-glucosidase upon thaw, and a predominance of active copiotrophic Bacteroidetes, showed that the upper permafrost plate serves as storage of easily degradable carbon derived from the overlying thawed active layer during summer. EEA profiles and microbial community dynamics furthermore suggest that the deeper and older permafrost intervals mainly contain recalcitrant SOM, and that extracellular soil-bound exoenzymes play a role in the initial cleavage of biopolymers, which could kick-start microbial growth upon thaw. Basidiomycetous fungi and Candidate Subdivision OP5 bacteria were the first to respond in freshly thawed deeper permafrost intervals, and might play an important role in the decomposition of recalcitrant SOM to release more labile substrates to support the major bacterial phyla (ß-Proteobacteria, Actinobacteria, Firmicutes), which predominated thereafter.