Can the Future of ID Escape the Inertial Dogma of Its Past? The Exemplars of Shorter Is Better and Oral Is the New IV.

Like all fields of medicine, Infectious Diseases is rife with dogma that underpins much clinical practice. In this study, we discuss 2 specific examples of historical practice that have been overturned recently by numerous prospective studies: traditional durations of antimicrobial therapy and the necessity of intravenous (IV)-only therapy for specific infectious syndromes. These dogmas are based on uncontrolled case series from >50 years ago, amplified by the opinions of eminent experts. In contrast, more than 120 modern, randomized controlled trials have established that shorter durations of therapy are equally effective for many infections. Furthermore, 21 concordant randomized controlled trials have demonstrated that oral antibiotic therapy is at least as effective as IV-only therapy for osteomyelitis, bacteremia, and endocarditis. Nevertheless, practitioners in many clinical settings remain refractory to adopting these changes. It is time for Infectious Diseases to move beyond its history of eminent opinion-based medicine and truly into the era of evidenced-based medicine

Use of Novel Strategies to Develop Guidelines for Management of Pyogenic Osteomyelitis in Adults: A WikiGuidelines Group Consensus Statement.

Importance Traditional approaches to practice guidelines frequently result in dissociation between strength of recommendation and quality of evidence. Objective To construct a clinical guideline for pyogenic osteomyelitis management, with a new standard of evidence to resolve the gap between strength of recommendation and quality of evidence, through the use of a novel open access approach utilizing social media tools. Evidence Review This consensus statement and systematic review study used a novel approach from the WikiGuidelines Group, an open access collaborative research project, to construct clinical guidelines for pyogenic osteomyelitis. In June 2021 and February 2022, authors recruited via social media conducted multiple PubMed literature searches, including all years and languages, regarding osteomyelitis management; criteria for article quality and inclusion were specified in the group's charter. The GRADE system for evaluating evidence was not used based on previously published concerns regarding the potential dissociation between strength of recommendation and quality of evidence. Instead, the charter required that clear recommendations be made only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were drafted to discuss pros and cons of care choices. Both clear recommendations and clinical reviews were planned with the intention to be regularly updated as new data become available. Findings Sixty-three participants with diverse expertise from 8 countries developed the group's charter and its first guideline on pyogenic osteomyelitis. These participants included both nonacademic and academic physicians and pharmacists specializing in general internal medicine or hospital medicine, infectious diseases, orthopedic surgery, pharmacology, and medical microbiology. Of the 7 questions addressed in the guideline, 2 clear recommendations were offered for the use of oral antibiotic therapy and the duration of therapy. In addition, 5 clinical reviews were authored addressing diagnosis, approaches to osteomyelitis underlying a pressure ulcer, timing for the administration of empirical therapy, specific antimicrobial options (including empirical regimens, use of antimicrobials targeting resistant pathogens, the role of bone penetration, and the use of rifampin as adjunctive therapy), and the role of biomarkers and imaging to assess responses to therapy. Conclusions and Relevance The WikiGuidelines approach offers a novel methodology for clinical guideline development that precludes recommendations based on low-quality data or opinion. The primary limitation is the need for more rigorous clinical investigations, enabling additional clear recommendations for clinical questions currently unresolved by high-quality data

Guidelines for Diagnosis and Management of Infective Endocarditis in Adults: A WikiGuidelines Group Consensus Statement.

IMPORTANCE Practice guidelines often provide recommendations in which the strength of the recommendation is dissociated from the quality of the evidence. OBJECTIVE To create a clinical guideline for the diagnosis and management of adult bacterial infective endocarditis (IE) that addresses the gap between the evidence and recommendation strength. EVIDENCE REVIEW This consensus statement and systematic review applied an approach previously established by the WikiGuidelines Group to construct collaborative clinical guidelines. In April 2022 a call to new and existing members was released electronically (social media and email) for the next WikiGuidelines topic, and subsequently, topics and questions related to the diagnosis and management of adult bacterial IE were crowdsourced and prioritized by vote. For each topic, PubMed literature searches were conducted including all years and languages. Evidence was reported according to the WikiGuidelines charter: clear recommendations were established only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were crafted discussing the risks and benefits of different approaches. FINDINGS A total of 51 members from 10 countries reviewed 587 articles and submitted information relevant to 4 sections: establishing the diagnosis of IE (9 questions); multidisciplinary IE teams (1 question); prophylaxis (2 questions); and treatment (5 questions). Of 17 unique questions, a clear recommendation could only be provided for 1 question: 3 randomized clinical trials have established that oral transitional therapy is at least as effective as intravenous (IV)-only therapy for the treatment of IE. Clinical reviews were generated for the remaining questions. CONCLUSIONS AND RELEVANCE In this consensus statement that applied the WikiGuideline method for clinical guideline development, oral transitional therapy was at least as effective as IV-only therapy for the treatment of IE. Several randomized clinical trials are underway to inform other areas of practice, and further research is needed

The PEST (Pathology, Epidemiology, Severity, Treatment) approach to optimizing antimicrobial therapy

Abstract Background Selecting an empiric antimicrobial regimen can be difficult for early learners and misuse of antibiotics can lead to adverse events and antimicrobial resistance. There have been few interventions that have focused on improving antibiotic decision making, as a form of therapeutic reasoning, for post-graduate trainees. We describe here an approach to aid internal medicine interns in their therapeutic reasoning, particularly when it comes to diagnosing and empirically treating infections. Methods The PEST (pathology, epidemiology, severity, treatment) model was created as a four-step approach to therapeutic reasoning and choosing an appropriate antimicrobial regimen for a given infectious disease syndrome. In February 2020, we conducted two independent teaching sessions for interns on the PEST approach. We assessed pre-and post-teaching responses to five clinical vignette-based questions. Results were presented as a percentage of interns who chose an appropriate antibiotic and provided sufficient therapeutic reasoning as defined by using at least three out of the four PEST criteria. Statistical analysis occurred via Fischer’s exact test to determine the level of statistical significance between responses. Results Twenty-seven interns participated in the activity. At baseline, several interns had incorporated aspects of the PEST approach in their pre-teaching responses. Ten interns commented on the usefulness of such a systematic approach. While there was no statistically significant difference in antibiotic selection, the teaching session demonstrated a trend towards significance in improving therapeutic reasoning as defined by the PEST strategy. Conclusion Our results suggested an improvement in using a structured cognitive tool such as the PEST approach to reinforce therapeutic reasoning, but the method did little to improve antibiotic selection. Some interns used select “PEST” concepts prior to the intervention suggesting that the PEST approach may enhance prior knowledge or clinical reasoning skills. Continued incorporation of the PEST approach using a case-based framework may solidify conceptual and practical knowledge of antimicrobial selection. Further studies are needed to assess the impact of such teaching interventions

The PEST (Pathology, Epidemiology, Severity, Treatment) approach to optimizing antimicrobial therapy

BackgroundSelecting an empiric antimicrobial regimen can be difficult for early learners and misuse of antibiotics can lead to adverse events and antimicrobial resistance. There have been few interventions that have focused on improving antibiotic decision making, as a form of therapeutic reasoning, for post-graduate trainees. We describe here an approach to aid internal medicine interns in their therapeutic reasoning, particularly when it comes to diagnosing and empirically treating infections.MethodsThe PEST (pathology, epidemiology, severity, treatment) model was created as a four-step approach to therapeutic reasoning and choosing an appropriate antimicrobial regimen for a given infectious disease syndrome. In February 2020, we conducted two independent teaching sessions for interns on the PEST approach. We assessed pre-and post-teaching responses to five clinical vignette-based questions. Results were presented as a percentage of interns who chose an appropriate antibiotic and provided sufficient therapeutic reasoning as defined by using at least three out of the four PEST criteria. Statistical analysis occurred via Fischer's exact test to determine the level of statistical significance between responses.ResultsTwenty-seven interns participated in the activity. At baseline, several interns had incorporated aspects of the PEST approach in their pre-teaching responses. Ten interns commented on the usefulness of such a systematic approach. While there was no statistically significant difference in antibiotic selection, the teaching session demonstrated a trend towards significance in improving therapeutic reasoning as defined by the PEST strategy.ConclusionOur results suggested an improvement in using a structured cognitive tool such as the PEST approach to reinforce therapeutic reasoning, but the method did little to improve antibiotic selection. Some interns used select "PEST" concepts prior to the intervention suggesting that the PEST approach may enhance prior knowledge or clinical reasoning skills. Continued incorporation of the PEST approach using a case-based framework may solidify conceptual and practical knowledge of antimicrobial selection. Further studies are needed to assess the impact of such teaching interventions

Case Report and Genomic Analysis of Cefiderocol-Resistant Escherichia coli Clinical Isolates

ObjectivesCefiderocol is a novel siderophore cephalosporin with in vitro activity against multidrug-resistant (MDR), gram-negative bacteria and intrinsic structural stability to all classes of carbapenemases. We sought to identify gene variants that could affect the mechanism of action (MOA) of cefiderocol.MethodsWe report a case of bacteremia in a liver transplant candidate with a strain of carbapenem-resistant Escherichia coli that was found to be resistant to cefiderocol despite no prior treatment with this antimicrobial agent. Using whole-genome sequencing, we characterized the genomic content of this E coli isolate and assessed for genetic variants between related strains that were found to be cefiderocol susceptible.ResultsWe identified several variants in genes with the potential to affect the mechanism of action of cefiderocol.ConclusionsThe cefiderocol resistance in the E coli isolate identified in this study is likely due to mutations in the cirA gene, an iron transporter gene

Universal and Serial Laboratory Testing for SARS-CoV-2 at a Long-Term Care Skilled Nursing Facility for Veterans - Los Angeles, California, 2020.

On March 28, 2020, two residents of a long-term care skilled nursing facility (SNF) at the Veterans Affairs Greater Los Angeles Healthcare System (VAGLAHS) had positive test results for SARS-CoV-2, the cause of coronavirus disease 2019 (COVID-19), by reverse transcription-polymerase chain reaction (RT-PCR) testing of nasopharyngeal specimens collected on March 26 and March 27. During March 29-April 23, all SNF residents, regardless of symptoms, underwent serial (approximately weekly) nasopharyngeal SARS-CoV-2 RT-PCR testing, and positive results were communicated to the county health department. All SNF clinical and nonclinical staff members were also screened for SARS-CoV-2 by RT-PCR during March 29-April 10. Nineteen of 99 (19%) residents and eight of 136 (6%) staff members had positive test results for SARS-CoV-2 during March 28-April 10; no further resident cases were identified on subsequent testing on April 13, April 22, and April 23. Fourteen of the 19 residents with COVID-19 were asymptomatic at the time of testing. Among these residents, eight developed symptoms 1-5 days after specimen collection and were later classified as presymptomatic; one of these patients died. This report describes an outbreak of COVID-19 in an SNF, with case identification accomplished by implementing several rounds of RT-PCR testing, permitting rapid isolation of both symptomatic and asymptomatic residents with COVID-19. The outbreak was successfully contained following implementation of this strategy

Universal and Serial Laboratory Testing for SARS-CoV-2 at a Long-Term Care Skilled Nursing Facility for Veterans - Los Angeles, California, 2020.

On March 28, 2020, two residents of a long-term care skilled nursing facility (SNF) at the Veterans Affairs Greater Los Angeles Healthcare System (VAGLAHS) had positive test results for SARS-CoV-2, the cause of coronavirus disease 2019 (COVID-19), by reverse transcription-polymerase chain reaction (RT-PCR) testing of nasopharyngeal specimens collected on March 26 and March 27. During March 29-April 23, all SNF residents, regardless of symptoms, underwent serial (approximately weekly) nasopharyngeal SARS-CoV-2 RT-PCR testing, and positive results were communicated to the county health department. All SNF clinical and nonclinical staff members were also screened for SARS-CoV-2 by RT-PCR during March 29-April 10. Nineteen of 99 (19%) residents and eight of 136 (6%) staff members had positive test results for SARS-CoV-2 during March 28-April 10; no further resident cases were identified on subsequent testing on April 13, April 22, and April 23. Fourteen of the 19 residents with COVID-19 were asymptomatic at the time of testing. Among these residents, eight developed symptoms 1-5 days after specimen collection and were later classified as presymptomatic; one of these patients died. This report describes an outbreak of COVID-19 in an SNF, with case identification accomplished by implementing several rounds of RT-PCR testing, permitting rapid isolation of both symptomatic and asymptomatic residents with COVID-19. The outbreak was successfully contained following implementation of this strategy