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38 emner vises.
Emerging Infectious Diseases, 10.05.2021
Tilføjet 11.05.2021
Emerging Infectious Diseases, 10.05.2021
Tilføjet 11.05.2021
Cook, L. C.
Infection and Immunity, 10.05.2021
Tilføjet 11.05.2021
M-type 28 Streptococcus pyogenes (Group A Strep, GAS) strains are highly associated with life-threatening puerperal infections. Genome sequencing has revealed a large mobile genetic element, RD2, present in most M28 GAS isolates but not found widely in other serotypes. Previous studies have linked RD2 to the ability of M28 GAS to colonize the vaginal tract. A new study by Roshika and colleagues use gain-of-function mutants in three different GAS serotypes to help determine why RD2 appears to have a serotype preference and what that could mean for GAS mucosal colonization and pathogenesis.
Læs mere Tjek på PubMedDongari-Bagtzoglou, A.
Infection and Immunity, 10.05.2021
Tilføjet 11.05.2021
This work combines a clinical investigation with a mouse model of fungal infection to study the role of bacterial microbiota in fungal invasion. The investigators identified a dysbiosis in the oropharyngeal mucosa that was associated with a high risk for invasive infection in hematologic oncology patients. This study builds on our current understanding that the pathogenesis of fungal infections has to be studied in the context of a specific host background and a site-specific bacterial microbiota.
Læs mere Tjek på PubMedSonawane, V. V., Ruth, M. M., Pennings, L. J., Svensson, E. M., Wertheim, H. F. L., Hoefsloot, W., Van Ingen, J.
Antimicrobial Agents And Chemotherapy, 10.05.2021
Tilføjet 11.05.2021
Objective: For Mycobacterium avium complex pulmonary disease (MAC-PD), current treatment regimens yield low cure rates. To obtain an evidence based combination therapy we assessed the in vitro activity of six drugs - clarithromycin (CLR), rifampicin (RIF), ethambutol (EMB), amikacin (AMK), clofazimine (CFZ), and minocycline (MIN) alone and in combinations against Mycobacterium avium and studied the contributions of individual antibiotics to efficacy.
Methods: The MICs of all antibiotics against M. avium ATCC 700898 were determined by broth microdilution. We performed time-kill kinetic assays (TKA) of all single drugs and clinically relevant two, three, four and five drug combinations against M. avium. Pharmacodynamic interactions of these combinations were assessed using area under the time-kill curve-derived effect size and Bliss independence.
Results: Adding a second drug yielded an average increase of the effect size (E) of 18.7 ± 32.9% log10 cfu/mL*day, though antagonism was seen in some combinations. Adding a third drug showed a lower increase in effect size (+12.2 ± 11.5%). The rifampicin-clofazimine-clarithromycin (E=102 log10 cfu/mL*day), rifampicin-amikacin-clarithromycin (E=101 log10 cfu/mL*day) and amikacin-minocycline-ethambutol (E=97.8 log10 cfu/mL*day) regimens proved more active than the recommended rifampicin-ethambutol-clarithromycin regimen (E=89.1 log10 cfu/mL*day). The addition of a fourth drug had little impact on effect size (+4.54 ± 3.08%).
Conclusions: In vitro, several two- and three-drug regimens are as effective as the currently recommended regimen for MAC-PD. Adding a fourth drug to any regimen had little additional effect. In vitro, the most promising regimen would be rifampicin-amikacin-macrolide or rifampicin-clofazimine-macrolide.
Læs mere Tjek på PubMedNguyen, N. T. Q., Gras, E., Tran, N. D., Nguyen, N. N. Y., Lam, H. H., Weiss, W. J., Doan, T. N. M., Diep, B. A.
Antimicrobial Agents And Chemotherapy, 10.05.2021
Tilføjet 11.05.2021
Development and validation of large animal models of Pseudomonas aeruginosa ventilator-associated pneumonia is needed for testing new drug candidates in a manner mimicking how they will be used clinically. We have developed a new model in which rabbits were ventilated with low-tidal volume and challenged with P. aeruginosa to recapitulate hallmark clinical features of acute respiratory distress syndrome (ARDS): acute lung injury and inflammation, progressive decrease in arterial oxygen partial pressure to fractional inspired oxygen PaO2:FiO2, leukopenia, neutropenia, thrombocytopenia, hyperlactatemia, severe hypotension, bacterial dissemination from lung to other organs, multiorgan dysfunction, and ultimately death. We evaluated the predictive power of this rabbit model for antibiotic efficacy testing by determining whether a humanized dosing regimen of meropenem, a potent antipseudomonal β-lactam antibiotic, when administered with or without intensive care unit (ICU)-supportive care (fluid challenge and norepinephrine), could halt or reverse natural disease progression. Our humanized meropenem dosing regimen produced plasma concentration-time profile in the rabbit model similar to those reported in patients with ventilator-associated bacterial pneumonia. In this rabbit model, treatment with humanized meropenem and ICU-supportive care achieved the highest level of survival, halted the worsening of ARDS biomarkers and reversed lethal hypotension, although treatment with humanized meropenem alone also conferred some protection when compared to treatment with placebo (saline) alone or placebo plus ICU-supportive care. In conclusion, this rabbit model could help predict whether an antibiotic will be efficacious for the treatment of human ventilator-associated pneumonia.
Læs mere Tjek på PubMedMok, S., Roycroft, E., Flanagan, P. R., Montgomery, L., Borroni, E., Rogers, T. R., Fitzgibbon, M. M.
Antimicrobial Agents And Chemotherapy, 10.05.2021
Tilføjet 11.05.2021
Pyrazinamide (PZA) is one of the first-line agents used for the treatment of tuberculosis. However, current phenotypic PZA susceptibility testing in the BACTEC MGIT 960 system is unreliable and false resistance is well documented. Rapid identification of resistance-associated mutations can confirm the phenotypic result. This study aimed to investigate the use of genotypic methods in combination with phenotypic susceptibility testing for confirmation of PZA resistant M. tuberculosis isolates. Sanger sequencing and/or whole genome sequencing were performed to detect mutations in pncA, rpsA, panD and clpC1. Isolates were screened for heteroresistance, and PZA susceptibility testing was performed in the BACTEC MGIT 960 system using a reduced inoculum to investigate false resistance.
Overall, 40 phenotypically PZA resistant isolates were identified. Of these, PZA resistance was confirmed in 22/40 (55%) isolates by detecting mutations in pncA, rpsA and panD genes. 16/40 (40%) isolates were found to be susceptible using the reduced inoculum method (i.e. false resistance). No mutations were detected in two PZA resistant isolates. False resistance was observed in isolates with MICs close to the critical concentration. In particular, EAI strains (lineage 1) appeared to have an elevated MIC that is close to the critical concentration. While this study illustrates the complexity and challenges associated with PZA susceptibility testing of M. tuberculosis, we conclude that a combination of genotypic and phenotypic drug susceptibility testing methods is required for accurate detection of PZA resistance.
Læs mere Tjek på PubMedWelte, R., Oberacher, H., Gasperetti, T., Pfisterer, H., Griesmacher, A., Santner, T., Lass-Flörl, C., Hörtnagl, C., Leitner-Rupprich, S., Aigner, M., Lorenz, I., Schmid, S., Edlinger, M., Eller, P., Dankl, D., Joannidis, M., Bellmann, R.
Antimicrobial Agents And Chemotherapy, 10.05.2021
Tilføjet 11.05.2021
Pharmacokinetics and antifungal activity of the echinocandins anidulafungin (AFG), micafungin (MFG) and caspofungin (CAS) were assessed in ascites fluid and plasma of critically ill adults treated for suspected or proven invasive candidiasis. Ascites fluid was obtained from ascites drains or during paracentesis. The antifungal activity of the echinocandins in ascites fluid was assessed by incubation of Candida (C.) albicans and C. glabrata at concentrations of 0.03 to 16.00 μg/ml. In addition, ascites fluid samples obtained from our study patients were inoculated with the same isolates and evaluated for fungal growth. These patient samples had to be spiked with echinocandins to restore the original concentrations, because echinocandins had been lost during sterile filtration. In ascites fluid specimens of 29 patients, echinocandin concentrations were below the simultaneous plasma levels. Serial sampling in 20 patients revealed a slower rise and decline of echinocandin concentrations in ascites fluid than in plasma. Proliferation of C. albicans in ascites fluid was slower than in culture medium and growth of C. glabrata was lacking, even in the absence of antifungals. In CAS-spiked ascites fluid samples, fungal CFU counts moderately declined, whereas spiking with AFG or MFG, had no relevant effect. In ascites fluid of our study patients, echinocandin concentrations achieved by therapeutic doses did not result in a consistent eradication of C. albicans or C. glabrata. Thus, therapeutic doses of AFG, MFG, or CAS may result in ascites fluid concentrations preventing relevant proliferation of C. albicans and C. glabrata, but do not warrant reliable eradication.
Læs mere Tjek på PubMedFredericks, L. R., Lee, M. D., Eckert, H. R., Li, S., Shipley, M. A., Roslund, C. R., Boikov, D. A., Kizer, E. A., Sobel, J. D., Rowley, P. A.
Antimicrobial Agents And Chemotherapy, 10.05.2021
Tilføjet 11.05.2021
Compared to other species of Candida yeasts, the growth of Candida glabrata was inhibited by many different strains of Saccharomyces killer yeasts. The ionophoric K1 and K2 killer toxins were broadly inhibitory to all clinical isolates of C. glabrata from patients with recurrent vulvovaginal candidiasis, despite high levels of resistance to clinically relevant antifungal therapeutics.
Læs mere Tjek på PubMedCheung, C. H. P., Alorabi, M., Hamilton, F., Takebayashi, Y., Mounsey, O., Heesom, K. J., Williams, P. B., Williams, O. M., Albur, M., MacGowan, A. P., Avison, M. B.
Antimicrobial Agents And Chemotherapy, 10.05.2021
Tilføjet 11.05.2021
Meropenem is a clinically important antibacterial reserved for treatment of multi-resistant infections. In meropenem-resistant bacteria of the family Enterobacterales, NDM-1 is considerably more common than IMP-1, despite both metallo-β-lactamases (MBLs) hydrolysing meropenem with almost identical kinetics. We show that blaNDM-1 consistently confers meropenem resistance in wild-type Enterobacterales, but blaIMP-1 does not. The reason is higher blaNDM-1 expression because of its stronger promoter. However, the cost of meropenem resistance is reduced fitness of blaNDM-1 positive Enterobacterales. In parallel, from a clinical case, we identified multiple Enterobacter spp. isolates carrying a plasmid-encoded blaNDM-1 having a modified promoter region. This modification lowered MBL production to a level associated with zero fitness cost but, consequently, the isolates were not meropenem resistant. However, we identified aKlebsiella pneumoniae isolate from this same clinical case carrying the same blaNDM-1 plasmid. This isolate was meropenem resistant despite low-level NDM-1 production because of a ramR mutation, reducing envelope permeability. Overall, therefore, we show how the resistance/fitness trade-off for MBL carriage can be resolved. The result is sporadic emergence of meropenem resistance in a clinical setting.
Læs mere Tjek på PubMedKazmierczak, K. M., Karlowsky, J. A., de Jonge, B. L. M., Stone, G. G., Sahm, D. F.
Antimicrobial Agents And Chemotherapy, 10.05.2021
Tilføjet 11.05.2021
To estimate the incidence of carbapenem-resistant Enterobacterales (CRE), a global collection of 81,781 surveillance isolates of Enterobacterales collected from patients in 39 countries in five geographic regions from 2012 to 2017 was studied. Overall, 3.3% of isolates were meropenem-nonsusceptible (MIC ≥2 μg/ml), ranging from 1.4% (North America) to 5.3% (Latin America) of isolates by region. Klebsiella pneumoniae accounted for the largest number of meropenem-nonsusceptible isolates (76.7%). The majority of meropenem-nonsusceptible Enterobacterales carried KPC-type carbapenemases (47.4%), metallo-β-lactamases (MBLs; 20.6%) or OXA-48-like β-lactamases (19.0%). Forty-three carbapenemase sequence variants (8 KPC-type, 4 GES-type, 7 OXA-48-like, 5 NDM-type, 7 IMP-type, and 12 VIM-type) were detected, with KPC-2, KPC-3, OXA-48, NDM-1, IMP-4, and VIM-1 identified as the most common variants of each carbapenemase type. The resistance mechanisms responsible for meropenem-nonsusceptibility varied by region. A total of 67.3% of all carbapenemase-positive isolates identified carried at least one additional plasmid-mediated or intrinsic chromosomally encoded extended-spectrum β-lactamase, AmpC β-lactamase, or carbapenemase. The overall percentage of meropenem-nonsusceptible Enterobacterales increased from 2.7% in 2012-2014 to 3.8% in 2015-2017. This increase could be attributed to the increasing proportion of carbapenemase-positive isolates that was observed, most notably among isolates carrying NDM-type MBLs in Asia/South Pacific, Europe and Latin America, OXA-48-like carbapenemases in Europe, Middle East/Africa and Asia/South Pacific, VIM-type MBLs in Europe, and KPC-type carbapenemases in Latin America. Ongoing CRE surveillance combined with a global antimicrobial stewardship strategy, sensitive clinical laboratory detection methods, and adherence to infection control practices will be needed to interrupt the spread of CRE.
Læs mere Tjek på PubMedCameron, A., Mangat, R., Taffner, S., Wang, J., Dumyati, G., Stanton, R. A., Daniels, J. B., Campbell, D., Lutgring, J. D., Pecora, N. D.
Antimicrobial Agents And Chemotherapy, 10.05.2021
Tilføjet 11.05.2021
Infections caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are a significant cause of morbidity and healthcare costs. Globally, the prevailing clonal type is ST131 in association with the blaCTX-M-15 β-lactamase gene. However, other ESBLs such as blaCTX-M-14 and blaCTX-M-27 can also be prevalent in some regions. We identified ST38 ESBL-producing E. coli from different regions in the US which carry blaCTX-M-27 embedded on two distinct plasmid types, suggesting the potential emergence of new ESBL lineages.
Læs mere Tjek på PubMedHeidrich, D., Pagani, D. M., Koehler, A., de Oliveira Alves, K., Scroferneker, M. L.
Antimicrobial Agents And Chemotherapy, 10.05.2021
Tilføjet 11.05.2021
Chromoblastomycosis (CBM) is a chronic subcutaneous infection caused by genera of melanized fungi: Fonsecaea, Cladophialophora, Phialophora, Exophiala and Rhinocladiella. Melanin is a virulence factor known to influence antifungal susceptibility. A specific inhibitor of melanin biosynthesis is tricyclazole. The aim of this study was to evaluate the effect of melanin inhibition on antifungal susceptibility of chromoblastomycosis agents and describe the susceptibility profile of some unusual CBM agents. Seventy-six clinical isolates, representing 13 species of the five main CBM agents genera, were studied. The antifungal susceptibility was performed according to the M38-A2 protocol of CLSI. In the melanin inhibition test, 16 mg/L of tricyclazole was added to the medium used in the inoculum preparation and the susceptibility assay. CBM agents were less susceptible to amphotericin B in comparison with azoles and terbinafine. The unusual species showed similar susceptibilities profiles to those of other species of the same genera. With tricyclazole exposition, MICs of terbinafine, posaconazole and itraconazole for Fonsecaea spp. significantly decreased (p<0,05). For Phialophora spp., this reduction was significative for posaconazole and itraconazole. For the other genera, there was a reduction in MICs of terbinafine and itraconazole, however, the statistical tests were not significant. Melanin inhibition can increase the antifungal susceptibility of most CBM agents to itraconazole and terbinafine, the main used drugs in the disease treatment. This increased susceptibility may open up new possibilities for therapy in refractory cases of CBM and/or caused by resistant fungal strains. Further studies are needed to confirm the same results in vivo.
Læs mere Tjek på PubMedRuelens, P., de Visser, J. A. G. M.
Antimicrobial Agents And Chemotherapy, 10.05.2021
Tilføjet 11.05.2021
Antibiotic-resistance trajectories with different final resistance may critically depend on the first mutation due to epistatic interactions. Here, we study the effect of mutation bias and concentration-dependent fitness effects of two clinically important mutations in TEM-1 β-lactamase initiating alternative trajectories to cefotaxime resistance. We show that mutation R164S, conferring relatively low resistance, is competitively superior over larger-effect mutation G238S at low cefotaxime concentrations, highlighting a critical influence of antibiotic concentration on long-term resistance evolution.
Læs mere Tjek på PubMedWu, X., Li, N., Wang, G., Liu, W., Yu, J., Cao, G., Wang, J., Chen, Y., Ma, J., Wu, J., Yang, H., Mao, X., He, J., Yu, Y., Qiu, C., Li, N., Yao, S., Feng, H., Yan, J., Zhang, W., Zhang, J.
Antimicrobial Agents And Chemotherapy, 10.05.2021
Tilføjet 11.05.2021
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread rapidly worldwide. This study is the first to report the tolerability, safety, pharmacokinetics (PK), and immunogenicity of a recombinant human anti-SARS-CoV-2 monoclonal antibody, etesevimab (CB6, JS016, LY3832479 or LY-CoV016), in healthy adults. This paper involves a randomized, double-blind, placebo-controlled, phase 1 study. A total of 40 participants were enrolled to receive a single intravenous dose of either etesevimab or a placebo in one of four sequential ascending intravenous dose cohorts. All 40 participants completed the study. Seventeen (42.5%) participants experienced 22 treatment emergent adverse events (TEAEs) that were drug-related, and the rates of these TEAEs among different dose cohorts were numerically comparable. No difference was observed between the combined etesevimab group and the placebo group. The exposure after etesevimab infusion increased in an approximately proportional manner as the dose increased from 2.5 to 50 mg/kg. The elimination half-life (t1/2) value did not differ among different dose cohorts and was estimated to be around 4 weeks. Etesevimab was well tolerated after administration of a single dose at a range of 2.5 mg/kg to 50 mg/kg in healthy Chinese adults. The PK profiles of etesevimab in healthy volunteers showed typical monoclonal antibody distribution and elimination characteristics. (This study has been registered at ClinicalTrials.gov under identifier NCT04441918.)
Læs mere Tjek på PubMedSchencking, I., Schäfer, E. M., Scanlan, J. H. W., Wenzel, B. M., Emmerich, R. E., Steinmetzer, T., Diederich, W. E., Schlitzer, M., Hartmann, R. K.
Antimicrobial Agents And Chemotherapy, 10.05.2021
Tilføjet 11.05.2021
RNase P is an essential enzyme responsible for tRNA 5'-end maturation. In most bacteria, the enzyme is a ribonucleoprotein consisting of a catalytic RNA subunit and a small protein cofactor termed RnpA. Several studies reported small molecule inhibitors directed against bacterial RNase P that were identified by high-throughput screenings. Using the bacterial RNase P enzymes from Thermotoga maritima, Bacillus subtilis and Staphylococcus aureus as model systems, we found that such compounds, including RNPA2000 and derivatives, iriginol hexaacetate and purpurin, induce the formation of insoluble aggregates of RnpA rather than acting as specific inhibitors. In the case of RNPA2000, aggregation was induced by Mg2+ ions. These findings were deduced from solubility analyses by microscopy and HPLC, RnpA-inhibitor co-pulldown experiments, detergent addition and RnpA titrations in enzyme activity assays. Finally, we used a B. subtilis RNase P depletion strain, whose lethal phenotype could be rescued by a protein-only RNase P of plant origin, for inhibition zone analyses on agar plates. These cell-based experiments argued against RNase P-specific inhibition of bacterial growth by RNPA2000. We were also unable to confirm the previously reported non-specific RNase activity of S. aureus RnpA itself. Our results indicate that high-throughput screenings searching for bacterial RNase P inhibitors are prone to the identification of "false positives" that are also termed Pan-assay interference compound s (PAINS).
Læs mere Tjek på PubMedDarlow, C. A., Docobo-Perez, F., Farrington, N., Johnson, A., McEntee, L., Unsworth, J., Jimenez-Valverde, A., Gastine, S., Dona, R. K., de Costa, R. M. A., Ellis, S., Franceschi, F., Standing, J. F., Sharland, M., Neely, M., Piddock, L., Das, S., Hope, W.
Antimicrobial Agents And Chemotherapy, 10.05.2021
Tilføjet 11.05.2021
Antimicrobial resistance (particularly by extended spectrum β-lactamase and aminoglycoside modifying enzyme production) in neonatal sepsis is a global problem, particularly in low- and middle-income countries, causing significant mortality. High rates of resistance are reported for the current WHO-recommended first-line antibiotic regimen for neonatal sepsis; ampicillin and gentamicin. We assessed the utility of fosfomycin and amikacin as a potential alternative regimen to be used in settings of increasingly prevalent antimicrobial resistance.
The combination was studied in a 16 arm dose ranged hollow-fiber infection model (HFIM) experiment. The combination of amikacin and fosfomycin enhanced bactericidal activity and prevented emergence of resistance compared to monotherapy of either antibiotic. Modelling of the experimental quantitative outputs and data from checkerboard assays, indicated synergy.
We further assessed the combination regimen at clinically relevant doses in HFIM with nine Enterobacterales strains with high fosfomycin/amikacin MICs and demonstrated successful kill to sterilisation in 6/9 strains. From these data, we propose a novel combination breakpoint threshold for microbiological success for this antimicrobial combination against Enterobacterales - MICF * MICA < 256 (where MICF and MICA are MICs for fosfomycin and amikacin). Monte Carlo simulations predict that a standard fosfomycin/amikacin neonatal regimen will achieve a >99% probability of pharmacodynamic success for strains with MICs below this threshold.
We conclude that the combination of fosfomycin with amikacin is a viable regimen for the empiric treatment of neonatal sepsis and is suitable for further clinical assessment in a randomised controlled trial.
Læs mere Tjek på PubMedSingh, K. V., Murray, B. E.
Antimicrobial Agents And Chemotherapy, 10.05.2021
Tilføjet 11.05.2021
In a mouse urinary tract infection model, omadacycline (OMC) was comparable to gentamicin and better than ciprofloxacin (CIP) against a tetracycline (TET) susceptible, CIP-R Escherichia coli strain. Gentamicin showed better efficacy than OMC against a TET-R, CIP-R E. coli strain and OMC again showed better efficacy than CIP against this strain. OMC may warrant further study as a potential option for UTI treatment against CIP-R E. coli strains.
Læs mere Tjek på PubMedLebreton, F., Corey, B. W., McElheny, C. L., Iovleva, A., Preston, L., Margulieux, K. R., Cybulski, R. J., McGann, P., Doi, Y., Bennett, J. W.
Antimicrobial Agents And Chemotherapy, 10.05.2021
Tilføjet 11.05.2021
KPC-82 is a KPC-2 variant, identified in a carbapenem non-susceptible Citrobacter koseri that confers high-level resistance to ceftazidime-avibactam. Genomic analysis revealed that blaKPC-82 is carried by a chromosomally integrated Tn4401 transposon (disrupting porin gene phoE) and evolved by a 6-nucleotide tandem-repeat duplication causing a two-amino-acid insertion (Ser-Asp) within the Ala267-Ser275 loop. Similar to related KPC variants, KPC-82 showed decreased carbapenemase activity when expressed in a heterologous background and remained susceptible to carbapenem/β-lactamase inhibitor combinations.
Læs mere Tjek på PubMedWasserman, S., Davis, A., Stek, C., Chirehwa, M., Botha, S., Daroowala, R., Bremer, M., Maxebengula, M., Koekemoer, S., Goliath, R., Jackson, A., Crede, T., Naude, J., Szymanski, P., Vallie, Y., Moosa, M. S., Wiesner, L., Black, J., Meintjes, G., Maartens, G., Wilkinson, R. J.
Antimicrobial Agents And Chemotherapy, 10.05.2021
Tilføjet 11.05.2021
Background
Higher doses of intravenous rifampicin may improve outcomes in tuberculous meningitis but is impractical in high burden settings. We hypothesized that plasma rifampicin exposures would be similar between oral 35 mg/kg and intravenous 20 mg/kg, which has been proposed for efficacy trials in tuberculous meningitis.
Materials and methods
We performed a randomized parallel group pharmacokinetic study nested within a clinical trial of intensified antimicrobial therapy for tuberculous meningitis. HIV-positive participants with tuberculous meningitis were recruited from South African hospitals and randomized to one of three rifampicin dosing groups: standard (oral 10 mg/kg), high dose (oral 35 mg/kg), and intravenous (intravenous 20 mg/kg). Intensive pharmacokinetic sampling was done on day 3. Data were described using non-compartmental analysis and exposures compared by geometric mean ratio (GMR).
Results
Forty-six participants underwent pharmacokinetic sampling (standard dose, n = 17; high dose oral, n= 15; intravenous, n = 14). Median CD4 count was 130 cells/mm3 (IQR 66 - 253). Rifampicin geometric mean AUC0-24 was 42.9 μg·h/mL (95% CI, 24.5 – 75.0) for standard dose; 295.2 μg·h/mL (95% CI, 189.9 – 458.8) for high dose oral; and 206.5 μg·h/mL (95% CI, 154.6 – 275.8) for intravenous administration. Rifampicin AUC0-24 GMR was 1.44 (90% CI, 0.84 - 2.21) and Cmax GMR was 0.89 (90% CI, 0.63 – 1.23) for high dose oral with respect to intravenous dosing.
Conclusions
Plasma rifampicin AUC0-24 was higher after an oral 35 mg/kg dose compared with intravenous administration at 20 mg/kg dose over the first few days of TB treatment. Findings support oral rifampicin dosing in future tuberculous meningitis trials.
Læs mere Tjek på PubMedMcGuire, R. J., Yu, S. C., Payne, P. R. O., Lai, A. M., Vazquez-Guillamet, M. C., Kollef, M. H., Michelson, A. P.
Antimicrobial Agents And Chemotherapy, 10.05.2021
Tilføjet 11.05.2021
Infection caused by carbapenem resistant (CR) organisms is a rising problem in the United States. While the risk factors for antibiotic resistance are well known, there remains a large need for the early identification of antibiotic resistant infections. Using machine learning (ML), we sought to develop a prediction model for carbapenem resistance. All patients >18 years of age admitted to a tertiary-care academic medical center between Jan 1, 2012 and Oct 10, 2017 with ≥1 bacterial culture were eligible for inclusion. All demographic, medication, vital sign, procedure, laboratory, and culture/sensitivity data was extracted from the electronic health record. Organisms were considered CR if a single isolate was reported as intermediate or resistant. CR and non-CR patients were temporally matched to maintain positive/negative case ratio. Extreme gradient boosting was used for model development. In total, 68,472 patients met inclusion criteria with 1,088 CR patients identified. Sixty-seven features were used for predictive modeling. The most important features were number of prior antibiotic days, recent central venous catheter placement, and inpatient surgery. After model training, the area under the receiver operating characteristic curve was 0.846. The sensitivity of the model was 30%, with a positive predictive value (PPV) of 30% and a negative predictive value of 99%. Using readily available clinical data, we were able to create a ML model capable of predicting CR infections at the time of culture collection with a high PPV.
Læs mere Tjek på PubMedKong, X., Tang, C., Singh, A., Ahmed, S. A., Al-Hatmi, A. M. S., Chowdhary, A., Nenoff, P., Gräser, Y., Hainsworth, S., Zhan, P., Meis, J. F., Verweij, P. E., Liu, W., de Hoog, G. S.
Antimicrobial Agents And Chemotherapy, 10.05.2021
Tilføjet 11.05.2021
Background: During the past decade, a prolonged and serious outbreak of dermatophytosis due to a terbinafine-resistant novel species in the Trichophyton mentagrophytes/T. interdigitale complex is ongoing in India, and it spreads to several European countries.
Objective: To investigate the molecular background of the squalene epoxidase (SQLE) gene in order to understand the risk of emergence and spread of multi-resistance in dermatophytes.
Methods: Antifungal susceptibility for fluconazole, griseofulvin, itraconazole, ketoconazole, miconazole, naftifine, sertaconazole, and terbinafine was tested in 135 isolates from India, China, Australia, Germany and The Netherlands. Based on the latest taxonomic insights, strains were identified as three species: T. mentagrophytes s. str. (n=35), T. indotineae (n=64 representing the Indian clone) and T. interdigitale s. str. (n=36).
Results: High minimum inhibitory concentrations (MICs) of terbinafine (>16 mg/L) were found in 34 (53%) T. indotineae isolates. These isolates showed an amino acid substitution in the 397th position of the SQLE gene. Elevated MICs of terbinafine (0.5 mg/L) were noted in 2 (3%) T. indotineae isolates; these isolates lead to Phe415Val and Leu393Ser of the SQLE gene. Stability of the effect of the mutations was proven by serial transfer on drug-free medium. Substitutions of Lys276Asn and Leu419Phe were found in susceptible T. mentagrophytes strains. The double mutant Phe377Leu/Ala448Thr showed higher MIC values for triazoles.
Conclusions: High MICs of terbinafine are as yet limited to T. indotineae, and are unlikely to be distributed through the T. mentagrophytes species complex by genetic exchange.
Læs mere Tjek på PubMedAlbasanz-Puig, A., Gudiol, C., Puerta-Alcalde, P., Ayaz, C. M., Machado, M., Herrera, F., Martin-Davila, P., Laporte-Amargos, J., Cardozo, C., Akova, M., Alvarez-Uria, A., Torres, D., Fortun, J., Garcia-Vidal, C., Munoz, P., Bergas, A., Pomares, H., Mercadal, S., Dura-Miralles, X., Garcia-Lerma, E., Pallares, N., Carratala, J.
Antimicrobial Agents And Chemotherapy, 10.05.2021
Tilføjet 11.05.2021
Objective: To test the hypothesis that the addition of an aminoglycoside to a ß-lactam antibiotic could provide better outcomes than ß-lactam monotherapy for the initial empirical treatment of hematological neutropenic patients with subsequently documented Gram-negative bacilli (GNB) bloodstream infection (BSI).
Methods: Multinational, retrospective, cohort study of GNB BSI episodes in hematological neutropenic patients in six centers (2010–2017). Combination therapy (ß-lactam plus aminoglycoside) was compared to ß-lactam monotherapy. The primary endpoint was the case-fatality rate assessed at 7 and 30-days from BSI onset. Secondary endpoints were nephrotoxicity and persistent BSI. Propensity score (PS) matching was performed.
Results: Among 542 GNB BSI episodes, 304 (56%) were initially treated with combination therapy, with cefepime plus amikacin being most common (158/304, 52%). Overall, Escherichia coli (273/304, 50.4%) was the main etiological agent, followed by Pseudomonas aeruginosa, which predominated in the combination group [76/304 (25%) vs. 28/238 (11.8%); p<0.001]. Multidrug resistance rates were similar between groups [83/294 (28.2%) vs. 63/233 (27%); p=0.95]. In the multivariate analysis combination therapy was associated with lower 7-day case-fatality rate (OR 0.37, 95%CI 0.14-0.91;p=0.035) with a tendency towards lower mortality at 30 days (OR 0.56, 95%CI 0.29–1.08;p=0.084). After PS-matching, these differences remained for the 7-day case-fatality rate (OR 0.33, 95%CI 0.13–0.82;p=0.017). In addition, aminoglycoside use was not significantly associated with renal function impairment (OR 1.12, 95%CI 0.26–4.87;p=0.9).
Conclusions: The addition of an aminoglycoside to the initial empirical therapy regimen for febrile neutropenic hematological patients should be considered.
Læs mere Tjek på PubMedJohansen, M. D., Shalini, , Kumar, S., Raynaud, C., Quan, D. H., Britton, W. J., Hansbro, P. M., Kumar, V., Kremer, L.
Antimicrobial Agents And Chemotherapy, 10.05.2021
Tilføjet 11.05.2021
Tuberculosis remains a leading cause of mortality among infectious diseases worldwide, prompting the need to discover new drugs to fight this disease. We report herein, the design, synthesis and anti-mycobacterial activity of isatin-mono/bis-isoniazid hybrids. Most of the compounds exhibited very high activity against Mycobacterium tuberculosis with minimal inhibitory concentrations in the range of 0.195-0.39 μg/mL and exerted a more potent bactericidal effect than the standard anti-tubercular drug isoniazid (INH). Importantly, these compounds were found to be well tolerated at high doses (>200 μg/mL) on Vero kidney cells, leading to high selectivity indices. Two of the most promising hybrids were evaluated for activity in THP-1 macrophages infected with M. tuberculosis, among which 11e was found to be slightly more effective than INH. Overexpression of InhA along with cross-resistance determination of the most potent compounds, selection of resistant mutants and biochemical analysis allowed us to decipher their mode of action. These compounds effectively inhibited mycolic acid biosynthesis and required KatG to exert their biological effects. Collectively, this suggests that the synthesized isatin-INH hybrids are promising anti-tubercular molecules for further evaluation in pre-clinical settings.
Læs mere Tjek på PubMedThorey K. Jonsdottir, Mikha Gabriela, Brendan S. Crabb, Tania F. de Koning-Ward, Paul R. Gilson
Trends in Parasitology, 10.05.2021
Tilføjet 11.05.2021
To survive inside red blood cells (RBCs), malaria parasites export many proteins to alter their host cell™s physiological properties. Although most proteins of this exportome are involved in immune avoidance or in the trafficking of exported proteins to the host membrane, about 20% are essential for parasite survival in culture but little is known about their biological functions. Here, we have combined information from large-scale genetic screens and targeted gene-disruption studies to tabulate all currently known Plasmodium falciparum exported proteins according to their likelihood of being essential.
Læs mere Tjek på PubMedWilliam L Hamilton, Tom Fieldman, Aminu Jahun, Ben Warne, Christopher J R Illingworth, Chris Jackson, Beth Blane, Elinor Moore, Michael P Weekes, Sharon J Peacock, Daniela De Angelis, Ian Goodfellow, Theodore Gouliouris, M Estée Török, Cambridge COVID-19 group
Lancet Infectious Diseases, 11.05.2021
Tilføjet 11.05.2021
Here, we provide an update on our previous Article,1 which described the use of rapid SARS-CoV-2 genome sequencing to investigate hospital-acquired infections (HAIs) at Cambridge University Hospitals NHS Foundation Trust (CUH), Cambridge, UK. CUH experienced a substantial second wave of COVID-19 (figure). Between Nov 2, 2020, and Feb 7, 2021, 162 (14%) of 1178 patients with COVID-19 at CUH had a suspected or definite HAI (as previously defined1), and 465 infected health-care workers (HCWs) were identified via the staff screening programme.
Læs mere Tjek på PubMedLixue Huang, Bin Cao
Lancet Infectious Diseases, 11.05.2021
Tilføjet 11.05.2021
As of early April, 2021, more than 2·8 million individuals have died globally from COVID-19. However, tens of millions of patients have survived COVID-19 and returned to everyday life. Increasing evidence has shown that a considerable proportion of patients did not recover fully and had lasting sequelae, described by various terms without consensus, including long COVID, post-COVID condition or syndrome, postacute (or late) sequelae of COVID-19, and post-acute COVID syndrome.1,2 Studies have mainly focused on patients with COVID-19 after hospital admission.
Læs mere Tjek på PubMedLars Christian Lund, Jesper Hallas, Henrik Nielsen, Anders Koch, Stine Hasling Mogensen, Nikolai Constantin Brun, Christian Fynbo Christiansen, Reimar Wernich Thomsen, Anton Pottegård
Lancet Infectious Diseases, 11.05.2021
Tilføjet 11.05.2021
The absolute risk of severe post-acute complications after SARS-CoV-2 infection not requiring hospital admission is low. However, increases in visits to general practitioners and outpatient hospital visits could indicate COVID-19 sequelae.
Læs mere Tjek på PubMedJiabing Wu, Xiuzhi Chen, Lei Gong, Shaohu Huo, Xuehuan Gao, Shuang Nie, Fang Chen, Sai Hou, Dandan Song, Wanwan Ma, Xuqin Jiang, Zhirong Liu
International Journal of Infectious Diseases, 10.05.2021
Tilføjet 11.05.2021
Amir Nutman, Elizabeth Temkin, Jonathan Lellouche, Nadya Rakovitsky, Amichay Hameir, George Daikos, Emanuele Durante-Mangoni, Ioannis Pavleas, Yael Dishon, Neta Petersiel, Dafna Yahav, Noa Eliakim, Mariano Bernardo, Domenico Iossa, Lena E. Friberg, Ursula Theuretzbacher, Leonard Leibovici, Mical Paul, Yehuda Carmeli, AIDA Study Group
Clinical Microbiology and Infection, 10.05.2021
Tilføjet 11.05.2021
Mortality among patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections varies between studies. We examined whether in vivo fitness of CRAB strains is associated with clinical outcomes in patients with CRAB infections.
Læs mere Tjek på PubMedLucy D. Guarnieri, Sara E. McBride, Eleanor Groden, Allison M. Gardner
PLoS One Infectious Diseases, 10.05.2021
Tilføjet 10.05.2021
by Lucy D. Guarnieri, Sara E. McBride, Eleanor Groden, Allison M. Gardner
The blacklegged tick (Ixodes scapularis) and the invasive European fire ant (Myrmica rubra) are both expanding throughout their sympatric range in coastal New England. Ixodes scapularis is the primary vector of the bacterium Borrelia burgdorferi, which is the causative agent of Lyme disease, and Mount Desert Island, Maine, home to Acadia National Park, currently is affected by a high Lyme disease burden. Ticks have many natural predators, including ants, although no previous studies have investigated interactions between these two species. To test the hypothesis that the presence of M. rubra alters I. scapularis abundance, we collected ticks by drag-sampling at eight ant-infested sites and eight uninfested control sites in Acadia National Park. We found that nymph density was significantly higher at ant-infested sites, while larval density was significantly higher at control sites. In addition, we conducted a laboratory bioassay to measure M. rubra aggression against I. scapularis larvae, nymphs, and adults and Dermacentor variabilis adults, and found that ant aggression was significantly higher against D. variabilis adults than I. scapularis adults. Our findings support the hypothesis that M. rubra has divergent effects across I. scapularis life stages, and we discuss possible ecological mechanisms, including optimal microclimate and predation, that could promote density of nymphs while inhibiting density of larvae.
Læs mere Tjek på PubMedDaniel Sammartino, Farrukh Jafri, Brennan Cook, Lisa La, Hyemin Kim, John Cardasis, Joshua Raff
PLoS One Infectious Diseases, 10.05.2021
Tilføjet 10.05.2021
by Daniel Sammartino, Farrukh Jafri, Brennan Cook, Lisa La, Hyemin Kim, John Cardasis, Joshua Raff
Background The coronavirus disease 2019 (COVID-19) pandemic overwhelmed healthcare systems, highlighting the need to better understand predictors of mortality and the impact of medical interventions.
Methods This retrospective cohort study examined data from every patient who tested positive for COVID-19 and was admitted to White Plains Hospital between March 9, 2020, and June 3, 2020. We used binomial logistic regression to analyze data for all patients, and propensity score matching for those treated with hydroxychloroquine and convalescent plasma (CP). The primary outcome of interest was inpatient mortality.
Results 1,108 admitted patients with COVID-19 were available for analysis, of which 124 (11.2%) were excluded due to incomplete data. Of the 984 patients included, 225 (22.9%) died. Risk for death decreased for each day later a patient was admitted [OR 0.970, CI 0.955 to 0.985; p < 0.001]. Elevated initial C-reactive protein (CRP) value was associated with a higher risk for death at 96 hours [OR 1.007, 1.002 to 1.012; p = 0.006]. Hydroxychloroquine and CP administration were each associated with increased mortality [OR 3.4, CI 1.614 to 7.396; p = 0.002, OR 2.8560, CI 1.361 to 6.160; p = 0.006 respectively].
Conclusions Elevated CRP carried significant odds of early death. Hydroxychloroquine and CP were each associated with higher risk for death, although CP was without titers and was administered at a median of five days from admission. Randomized or controlled studies will better describe the impact of CP. Mortality decreased as the pandemic progressed, suggesting that institutional capacity for dynamic evaluation of process and outcome measures may benefit COVID-19 survival.
Læs mere Tjek på PubMedCornelius D. Jamison, Margaret Greenwood-Ericksen, Caroline R. Richardson, Hwajung Choi, Tammy Chang
PLoS One Infectious Diseases, 10.05.2021
Tilføjet 10.05.2021
by Cornelius D. Jamison, Margaret Greenwood-Ericksen, Caroline R. Richardson, Hwajung Choi, Tammy Chang
Background The United States is experiencing a surge in Chlamydia trachomatis (CT) infections representing a critical need to improve sexually transmitted infection (STI) screening and treatment programs. To understand where patients with STIs seek healthcare, we evaluated the relationship between CT infections and the place where individuals report usually receiving healthcare.
Methods Our study used a nationally representative sample from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2016. The study population is adult patients, aged 18 to 39 years in whom a urine CT screen was obtained. Logistic regression models were used to determine if location of usual healthcare was predictive of a positive urine CT screen result. Models were adjusted for known confounders including age, gender, race/ethnicity, education, and insurance status.
Results In this nationally representative sample (n = 19,275; weighted n = 85.8 million), 1.9% of individuals had a positive urine CT result. Participants reported usually going to the doctor™s office (70.3%), œno place (24.8%), Emergency Department (ED) (3.3%), or œother place (1.7%) for healthcare. In adjusted models, the predicted probability of having a positive urine CT result is higher (4.9% vs 3.2%, p = 0.022; OR = 1.58) among those that reported the ED as their usual place for healthcare compared to those that reported going to a doctor™s office or clinic.
Conclusions Individuals having a positive urine CT screen are associated with using the ED as a usual source for healthcare. Understanding this association has the potential to improve STI clinical and policy interventions as the ED may be a critical site in combatting the record high rates of STIs.
Læs mere Tjek på PubMedPeter Buggisch, Hans Heiken, Stefan Mauss, Bernd Weber, Maria-Christina Jung, Herbert Görne, Renate Heyne, Holger Hinrichsen, Dennis Hidde, Bettina König, Ana Gabriela Pires dos Santos, Claus Niederau, Thomas Berg
PLoS One Infectious Diseases, 10.05.2021
Tilføjet 10.05.2021
by Peter Buggisch, Hans Heiken, Stefan Mauss, Bernd Weber, Maria-Christina Jung, Herbert Görne, Renate Heyne, Holger Hinrichsen, Dennis Hidde, Bettina König, Ana Gabriela Pires dos Santos, Claus Niederau, Thomas Berg
Despite the availability of highly effective and well-tolerated direct-acting antivirals, not all patients with chronic hepatitis C virus infection receive treatment. This retrospective, multi-centre, noninterventional, case-control study identified patients with chronic hepatitis C virus infection initiating (control) or not initiating (case) treatment at 43 sites in Germany from September 2017 to June 2018. It aimed to compare characteristics of the two patient populations and to identify factors involved in patient/physician decision to initiate/not initiate chronic hepatitis C virus treatment, with a particular focus on historical barriers. Overall, 793 patients were identified: 573 (72%) who received treatment and 220 (28%) who did not. In 42% of patients, the reason for not initiating treatment was patient wish, particularly due to fear of treatment (17%) or adverse events (13%). Other frequently observed reasons for not initiating treatment were in accordance with known historical barriers for physicians to initiate therapy, including perceived or expected lack of compliance (14.5%), high patient age (10.9%), comorbidities (15.0%), alcohol abuse (9.1%), hard drug use (7.7%), and opioid substitution therapy (4.5%). Patient wish against therapy was also a frequently reported reason for not initiating treatment in the postponed (35.2%) and not planned (47.0%) subgroups; of note, known historical factors were also common reasons for postponing treatment. Real-world and clinical trial evidence is accumulating, which suggests that such historical barriers do not negatively impact treatment effectiveness. Improved education is key to facilitate progress towards the World Health Organization target of eliminating viral hepatitis as a major public health threat by 2030.
Læs mere Tjek på PubMedUlrich von Both, Philipp Gerlach, Nicole Ritz, Matthias Bogyi, Folke Brinkmann, Stephanie Thee
PLoS One Infectious Diseases, 10.05.2021
Tilføjet 10.05.2021
by Ulrich von Both, Philipp Gerlach, Nicole Ritz, Matthias Bogyi, Folke Brinkmann, Stephanie Thee
Background Majority of active tuberculosis (TB) cases in children in low-incidence countries are due to rapid progression of infection (latent TB infection (LTBI)) to disease. We aimed to assess common practice for managing paediatric LTBI in Austria, Germany and Switzerland prior to the publication of the first joint national guideline for paediatric TB in 2017.
Methods Online-based survey amongst pediatricians, practitioners and staff working in the public health sector between July and November 2017. Data analysis was conducted using IBM SPSS.
Results A total of 191 individuals participated in the survey with 173 questionnaires included for final analysis. Twelve percent of respondents were from Austria, 60% from Germany and 28% from Switzerland. Proportion of children with LTBI and migrant background was estimated by the respondents to be >50% by 58%. Tuberculin skin test (TST) and interferon-γ-release-assay (IGRA), particularly Quantiferon-gold-test, were reported to be used in 86% and 88%, respectively. In children > 5 years with a positive TST or IGRA a chest x-ray was commonly reported to be performed (28%). Fifty-three percent reported to take a different diagnostic approach in children ≤ 5 years, mainly combining TST, IGRA and chest x-ray for initial testing (31%). Sixty-eight percent reported to prescribe isoniazid-monotherapy: for 9 (62%), or 6 months (6%), 31% reported to prescribe combination therapy of isoniazid and rifampicin. Dosing of isoniazid and rifampicin below current recommendations was reported by up to 22% of respondents. Blood-sampling before/during LTBI treatment was reported in >90% of respondents, performing a chest-X-ray at the end of treatment by 51%.
Conclusion This survey showed reported heterogeneity in the management of paediatric LTBI. Thus, regular and easily accessible educational activities and national up-to-date guidelines are key to ensure awareness and quality of care for children and adolescents with LTBI in low-incidence countries.
Læs mere Tjek på PubMedDaniel Graeber, Christoph Schmidt-Petri, Carsten Schröder
PLoS One Infectious Diseases, 10.05.2021
Tilføjet 10.05.2021
by Daniel Graeber, Christoph Schmidt-Petri, Carsten Schröder
Several vaccines against COVID-19 have now been developed and are already being rolled out around the world. The decision whether or not to get vaccinated has so far been left to the individual citizens. However, there are good reasons, both in theory as well as in practice, to believe that the willingness to get vaccinated might not be sufficiently high to achieve herd immunity. A policy of mandatory vaccination could ensure high levels of vaccination coverage, but its legitimacy is doubtful. We investigate the willingness to get vaccinated and the reasons for an acceptance (or rejection) of a policy of mandatory vaccination against COVID-19 in June and July 2020 in Germany based on a representative real time survey, a random sub-sample (SOEP-CoV) of the German Socio-Economic Panel (SOEP). Our results show that about 70 percent of adults in Germany would voluntarily get vaccinated against the coronavirus if a vaccine without side effects was available. About half of residents of Germany are in favor, and half against, a policy of mandatory vaccination. The approval rate for mandatory vaccination is significantly higher among those who would get vaccinated voluntarily (around 60 percent) than among those who would not get vaccinated voluntarily (27 percent). The individual willingness to get vaccinated and acceptance of a policy of mandatory vaccination correlates systematically with socio-demographic and psychological characteristics of the respondents. We conclude that as far as people™s declared intentions are concerned, herd immunity could be reached without a policy of mandatory vaccination, but that such a policy might be found acceptable too, were it to become necessary.
Læs mere Tjek på PubMedBroom, J., Broom, A., Anstey, C., Kenny, K., Young, S., Grieve, D., Sowden, D., Jangam, A., Henderson, A., Melon, A., Tabone, R., Farquhar, D., Harding, H., Panahi, S. E., Chin, T., Abdullah, M., Waterhouse, L., Lo, C., Parker, R., Bui, T. L., Wallis, M. C.
BMJ Open, 10.05.2021
Tilføjet 10.05.2021
Objectives
To assess an intervention for surgical antibiotic prophylaxis (SAP) improvement within surgical teams focused on addressing barriers and fostering enablers and ownership of guideline compliance.
Design
The Queensland Surgical Antibiotic Prophylaxis (QSAP) study was a multicentre, mixed methods study designed to address barriers and enablers to SAP compliance and facilitate engagement in self-directed audit/feedback and assess the efficacy of the intervention in improving compliance with SAP guidelines. The implementation was assessed using a 24-month interrupted time series design coupled with a qualitative evaluation.
Setting
The study was undertaken at three hospitals (one regional, two metropolitan) in Australia.
Participants
SAP-prescribing decisions for 1757 patients undergoing general surgical procedures from three health services were included. Six bimonthly time points, pre-implementation and post implementation of the intervention, were measured. Qualitative interviews were performed with 29 clinical team members. SAP improvements varied across site and time periods.
Intervention
QSAP embedded ownership of quality improvement in SAP within surgical teams and used known social influences to address barriers to and enablers of optimal SAP prescribing.
Results
The site that reported senior surgeon engagement showed steady and consistent improvement in prescribing over 24 months (prestudy and poststudy). Multiple factors, including resource issues, influenced engagement and sites/time points where these were present had no improvement in guideline compliance.
Conclusions
The barriers-enablers-ownership model shows promise in its ability to facilitate prescribing improvements and could be expanded into other areas of antimicrobial stewardship. Senior ownership was a predictor of success (or failure) of the intervention across sites and time periods. The key role of senior leaders in change leadership indicates the critical need to engage other specialties in the stewardship agenda. The influence of contextual factors in limiting engagement clearly identifies issues of resource distributions/inequalities within health systems as limiting antimicrobial optimisation potential.
Læs mere Tjek på PubMedKhan, N., Palepu, A., Dodek, P., Salmon, A., Leitch, H., Ruzycki, S., Townson, A., Lacaille, D.
BMJ Open, 10.05.2021
Tilføjet 10.05.2021
Objective
To determine the prevalence of physician burnout during the pandemic and differences by gender, ethnicity or sexual orientation.
Design, setting and participants
We conducted a cross-sectional survey (August–October in 2020) of internal medicine physicians at two academic hospitals in Vancouver, Canada.
Primary and secondary outcomes
Physician burnout and its components, emotional exhaustion, depersonalisation and personal accomplishment were measured using the Maslach Burnout Inventory.
Results
The response rate was 38% (n=302/803 respondents, 49% women,). The prevalence of burnout was 68% (emotional exhaustion 63%, depersonalisation 39%) and feeling low personal accomplishment 22%. In addition, 21% reported that they were considering quitting the profession or had quit a position. Women were more likely to report emotional exhaustion (OR 2.00, 95% CI: 1.07 to 3.73, p=0.03) and feeling low personal accomplishment (OR 2.26, 95% CI: 1.09 to 4.70, p=0.03) than men. Visible ethnic minority physicians were more likely to report feeling lower personal accomplishment than white physicians (OR 1.81, 95% CI: 1.28 to 2.55, p=0.001). There was no difference in emotional exhaustion or depersonalisation by ethnicity or sexual orientation. Physicians who reported that COVID-19 affected their burnout were more likely to report any burnout (OR: 3.74, 95% CI: 1.99 to 7.01, p<0.001) and consideration of quitting or quit (OR: 3.20, 95% CI: 1.34 to 7.66, p=0.009).
Conclusion
Burnout affects 2 out of 3 internal medicine physicians during the pandemic. Women, ethnic minority physicians and those who feel that COVID-19 affects burnout were more likely to report components of burnout. Further understanding of factors driving feelings of low personal accomplishment in women and ethnic minority physicians is needed.
Læs mere Tjek på PubMed