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1. Randomized Trial Evaluating Clinical Impact of RAPid IDentification and Susceptibility Testing for Gram-negative Bacteremia: RAPIDS-GN

   Banerjee R.; Komarow L.; Virk A.; Rajapakse N.; Schuetz A.; Dylla B.; Earley M.; Lok J.J.; Kohner P.; Ihde S.; et al (July 2021, Clinical infectious diseases)

   Background. Rapid blood culture diagnostics are of unclear benefit for patients with gram-negative bacilli (GNB) bloodstream infections (BSIs). We conducted a multicenter, randomized, controlled trial comparing outcomes of patients with GNB BSIs who had blood culture testing with standard-of-care (SOC) culture and antimicrobial susceptibility testing (AST) vs rapid organism identification (ID) and phenotypic AST using the Accelerate Pheno System (RAPID). Methods. Patients with positive blood cultures with Gram stains showing GNB were randomized to SOC testing with antimicrobial stewardship (AS) review or RAPID with AS. The primary outcome was time to first antibiotic modification within 72 hours of randomization. Results. Of 500 randomized patients, 448 were included (226 SOC, 222 RAPID). Mean (standard deviation) time to results was faster for RAPID than SOC for organism ID (2.7 [1.2] vs 11.7 [10.5] hours; P < .001) and AST (13.5 [56] vs 44.9 [12.1] hours; P < .001). Median (interquartile range [IQR]) time to first antibiotic modification was faster in the RAPID arm vs the SOC arm for overall antibiotics (8.6 [2.6–27.6] vs 14.9 [3.3–41.1] hours; P = .02) and gram-negative antibiotics (17.3 [4.9–72] vs 42.1 [10.1–72] hours; P < .001). Median (IQR) time to antibiotic escalation was faster in the RAPID arm vs the SOC arm for antimicrobial-resistant BSIs (18.4 [5.8–72] vs 61.7 [30.4–72] hours; P = .01). There were no differences between the arms in patient outcomes. Conclusions. Rapid organism ID and phenotypic AST led to faster changes in antibiotic therapy for gram-negative BSIs. 

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2. Hospital antimicrobial stewardship: profiling the oral microbiome after exposure to COVID-19 and antibiotics

   https://doi.org/10.3389/fmicb.2024.1346762  

   Buendia, Patricia; Fernandez, Krystal; Raley, Castle; Rahnavard, Ali; Crandall, Keith A; Castro, Jose Guillermo (February 2024, Frontiers in Microbiology)

   IntroductionDuring the COVID-19 Delta variant surge, the CLAIRE cross-sectional study sampled saliva from 120 hospitalized patients, 116 of whom had a positive COVID-19 PCR test. Patients received antibiotics upon admission due to possible secondary bacterial infections, with patients at risk of sepsis receiving broad-spectrum antibiotics (BSA). MethodsThe saliva samples were analyzed with shotgun DNA metagenomics and respiratory RNA virome sequencing. Medical records for the period of hospitalization were obtained for all patients. Once hospitalization outcomes were known, patients were classified based on their COVID-19 disease severity and the antibiotics they received. ResultsOur study reveals that BSA regimens differentially impacted the human salivary microbiome and disease progression. 12 patients died and all of them received BSA. Significant associations were found between the composition of the COVID-19 saliva microbiome and BSA use, between SARS-CoV-2 genome coverage and severity of disease. We also found significant associations between the non-bacterial microbiome and severity of disease, withCandida albicansdetected most frequently in critical patients. For patients who did not receive BSA before saliva sampling, our study suggestsStaphylococcus aureusas a potential risk factor for sepsis. DiscussionOur results indicate that the course of the infection may be explained by both monitoring antibiotic treatment and profiling a patient’s salivary microbiome, establishing a compelling link between microbiome and the specific antibiotic type and timing of treatment. This approach can aid with emergency room triage and inpatient management but also requires a better understanding of and access to narrow-spectrum agents that target pathogenic bacteria. 

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3. Gender, Soft Skills, and Patient Experience in Online Physician Reviews: A Large-Scale Text Analysis

   https://doi.org/10.2196/14455  

   Dunivin, Zackary; Zadunayski, Lindsay; Baskota, Ujjwal; Siek, Katie; Mankoff, Jennifer (January 2020, Journal of Medical Internet Research)

   Background Online physician reviews are an important source of information for prospective patients. In addition, they represent an untapped resource for studying the effects of gender on the doctor-patient relationship. Understanding gender differences in online reviews is important because it may impact the value of those reviews to patients. Documenting gender differences in patient experience may also help to improve the doctor-patient relationship. This is the first large-scale study of physician reviews to extensively investigate gender bias in online reviews or offer recommendations for improvements to online review systems to correct for gender bias and aid patients in selecting a physician. Objective This study examines 154,305 reviews from across the United States for all medical specialties. Our analysis includes a qualitative and quantitative examination of review content and physician rating with regard to doctor and reviewer gender. Methods A total of 154,305 reviews were sampled from Google Place reviews. Reviewer and doctor gender were inferred from names. Reviews were coded for overall patient experience (negative or positive) by collapsing a 5-star scale and coded for general categories (process, positive/negative soft skills), which were further subdivided into themes. Computational text processing methods were employed to apply this codebook to the entire data set, rendering it tractable to quantitative methods. Specifically, we estimated binary regression models to examine relationships between physician rating, patient experience themes, physician gender, and reviewer gender). Results Female reviewers wrote 60% more reviews than men. Male reviewers were more likely to give negative reviews (odds ratio [OR] 1.15, 95% CI 1.10-1.19; P<.001). Reviews of female physicians were considerably more negative than those of male physicians (OR 1.99, 95% CI 1.94-2.14; P<.001). Soft skills were more likely to be mentioned in the reviews written by female reviewers and about female physicians. Negative reviews of female doctors were more likely to mention candor (OR 1.61, 95% CI 1.42-1.82; P<.001) and amicability (OR 1.63, 95% CI 1.47-1.90; P<.001). Disrespect was associated with both female physicians (OR 1.42, 95% CI 1.35-1.51; P<.001) and female reviewers (OR 1.27, 95% CI 1.19-1.35; P<.001). Female patients were less likely to report disrespect from female doctors than expected from the base ORs (OR 1.19, 95% CI 1.04-1.32; P=.008), but this effect overrode only the effect for female reviewers. Conclusions This work reinforces findings in the extensive literature on gender differences and gender bias in patient-physician interaction. Its novel contribution lies in highlighting gender differences in online reviews. These reviews inform patients’ choice of doctor and thus affect both patients and physicians. The evidence of gender bias documented here suggests review sites may be improved by providing information about gender differences, controlling for gender when presenting composite ratings for physicians, and helping users write less biased reviews. 

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4. Role of internal loop dynamics in antibiotic permeability of outer membrane porins

   https://doi.org/10.1073/pnas.2117009119  

   Vasan, Archit Kumar; Haloi, Nandan; Ulrich, Rebecca Joy; Metcalf, Mary Elizabeth; Wen, Po-Chao; Metcalf, William W.; Hergenrother, Paul J.; Shukla, Diwakar; Tajkhorshid, Emad (February 2022, Proceedings of the National Academy of Sciences)

   Andrej Sali, Bioengineering & (Ed.)

   Significance Antibiotic resistance in Gram-negative pathogens has been identified as an urgent threat to human health by the World Health Organization. The major challenge with treating infections by these pathogens is developing antibiotics that can traverse the dense bacterial outer membrane (OM) formed by a mesh of lipopolysaccharides. Effective antibiotics permeate through OM porins, which have evolved for nutrient diffusion; however, the conformational states of these porins regulating permeation are still unclear. Here, we used molecular dynamics simulations, free energy calculations, Markov-state modeling, and whole-cell accumulation assays to provide mechanistic insight on how a porin shifts between open and closed states. We provide a mechanism of how Gram-negative bacteria confer resistance to antibiotics. 

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5. Global trends in inappropriate use of antibiotics, 2000–2021: scoping review and prevalence estimates

   https://doi.org/10.1136/bmjph-2024-002411  

   Mulchandani, Ranya; Tiseo, Katie; Nandi, Arindam; Klein, Eili; Gandra, Sumanth; Laxminarayan, Ramanan; Van_Boeckel, Thomas (January 2025, BMJ Public Health)

   IntroductionInappropriate antibiotic use is a major driver of antimicrobial resistance. However, the scope of literature and its prevalence across world regions remain largely unknown, as do the most common indicators and study designs used. In this study, we summarised the current literature on inappropriate use of antibiotics by world regions. We also provided the first global estimates of the overall amount of antibiotics that are potentially used inappropriately each year. MethodsWe considered both patient and provider-mediated inappropriate antibiotic use. We reviewed 412 studies published between 2000 and 2021 and used beta regression and marginal contrasts to compare prevalence of inappropriate use by study design, indicator, world region, and national income level. Country-level sales of antibiotics from 2022 were combined with inappropriate antibiotic use estimates derived from two study designs (clinical audits and patient interviews) and one indicator (lack of indication) to estimate the amount of antibiotics inappropriately used globally. ResultsClinical audits (50.1%, 208/412) and ‘non-prescription’ use (37.1%, 153/412) were the most common study design and indicator, respectively, used to estimate inappropriate antibiotic use. Inappropriate antibiotic use prevalence was ~6% higher in low-income and middle-income than in high-income countries. However, this difference disappeared after accounting for a proxy of access to care: physicians per capita. Globally, based on clinical audits, patient interviews and lack of indication, the estimated proportion of inappropriate antibiotic use was 29.5%, 36.5% and 30.8%, respectively, with an average of ~30% (~13 000 000 kg) the equivalent of the annual antibiotic consumption in China. ConclusionsInappropriate antibiotic use is highly prevalent across all countries regardless of national income level, with a third of global antibiotic consumption potentially due to unnecessary prescription (‘lack of indication’). Antibiotic stewardship efforts and defining internationally standardised indicators are needed to track progress in reducing the occurrence of inappropriate antibiotic use where necessary, as well as identifying gaps in access to care. 

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