Research Spotlight

Smith, E. R., A. M. Fry, L. A. Hicks, K. E. Fleming-Dutra, B. Flannery, J. Ferdinands, M. A. Rolfes, E. T. Martin, A. S. Monto, R. K. Zimmerman, M. P. Nowalk, M. L. Jackson, H. Q. McLean, S. C. Olson, M. Gaglani and M. M. Patel (2020). “Reducing Antibiotic Use in Ambulatory Care through Influenza Vaccination.” Clin Infect Dis Apr 23. pii: ciaa464. [Epub ahead of print].

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BACKGROUND: Improving appropriate antibiotic use is crucial for combating antibiotic resistance and unnecessary adverse drug reactions. Acute respiratory illness (ARI) commonly causes outpatient visits and accounts for ~41% of antibiotics used in the United States (U.S.). We examined the influence of influenza vaccination on reducing antibiotic prescriptions among outpatients with ARI. METHODS: We enrolled outpatients aged >/=6 months with ARI from 50-60 U.S. clinics during five winters (2013-2018) and tested for influenza with RT-PCR; results were unavailable for clinical decision-making and clinical influenza testing was infrequent. We collected antibiotic prescriptions and diagnosis codes for ARI syndromes. We calculated vaccine effectiveness (VE) by comparing vaccination odds among influenza-positive cases to test-negative controls. We estimated ARI visits and antibiotic prescriptions averted by influenza vaccination using estimates of VE, coverage, and prevalence of antibiotic prescriptions and influenza. RESULTS: Among 37,487 ARI outpatients, 9,659 (26%) were influenza-positive. Overall, 36% of ARI and 26% of influenza-positive patients were prescribed antibiotics. The top three prevalent ARI syndromes included: viral upper respiratory tract infection (47%), pharyngitis (18%), and allergy or asthma (11%). Among patients testing positive for influenza, 77% did not receive an ICD-CM diagnostic code for influenza. Overall, VE against influenza-associated ARI was 35% (95%CI 32-39). Vaccination prevented 5.6% of all ARI syndromes, ranging from 2.8% (sinusitis) to 11% (clinical influenza). Influenza vaccination averted 1 in 25 (3.8%; 95%CI 3.6%-4.1%) antibiotic prescriptions among ARI outpatients during influenza seasons. CONCLUSION: Vaccination and accurate influenza diagnosis may curb unnecessary antibiotic use and reduce the global threat of antibiotic resistance.

Simpson, E., R. Bissonnette, L. F. Eichenfield, E. Guttman, B. King, J. I. Silverberg, L. A. Beck, T. Bieber, K. Reich, K. Kabashima, M. Seyger, E. Siegfried, G. Stingl, S. R. Feldman, A. Menter, P. van de Kerkhof, G. Yosipovitch, C. Paul, P. Martel, A. Dubost-Brama, J. Armstrong, R. Chavda, S. Frey, Y. Joubert, M. Milutinovic, A. Parneix, H. D. Teixeira, C. Y. Lin, L. Sun, P. Klekotka, B. Nickoloff, Y. Dutronc, L. Mallbris, J. M. Janes, A. M. DeLozier, F. Nunes and A. S. Paller (2020). “The validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD): The development and reliability testing of a novel clinical outcome measurement instrument for the severity of atopic dermatitis.” J Am Acad Dermatol Apr 25. pii: S0190-9622(20)30720-9. [Epub ahead of print].

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BACKGROUND: An Investigator Global Assessment (IGA) is recommended by health agencies for drug registration in atopic dermatitis (AD). Current IGA scales lack standardization. OBJECTIVES: To develop an IGA scale, training module, and clinical certification exam for use in AD trials, and establish content validity and assess reliability. METHODS: Expert dermatologists participated in the development of the validated IGA for AD (vIGA-AD). Reliability (inter-rater and intra-rater) was assessed by 2 web-based surveys. Clinical certification for investigators consisted of a training module and exam. RESULTS: Expert consensus was achieved around a 5-point IGA scale including morphological descriptions, and content validity was established. Survey 1 showed strong inter-rater reliability (Kendall’s coefficient of concordance W [Kendall’s W] = 0.809, intra-class correlation [ICC] = 0.817) and excellent agreement (weighted Kappa = 0.857). Survey 2, completed 5 months after training of dermatologists, showed improvements in scale reliability (Kendall’s W = 0.819, ICC = 0.852, weighted Kappa = 0.889). In this study 627 investigators completed vIGA-AD training and certification. LIMITATIONS: Ratings were assessed on photographs. CONCLUSION: A validated IGA scale and training module were developed with the intent of harmonizing assessment of disease severity in AD trials. Strong reliability and excellent agreement between assessments were observed.

Shealy, S. C., M. M. Brigmon, J. A. Justo, P. B. Bookstaver, J. Kohn and M. N. Al-Hasan (2020). “Impact of Reappraisal of Fluoroquinolone Minimum Inhibitory Concentration Susceptibility Breakpoints in Gram-Negative Bloodstream Isolates.” Antibiotics (Basel) 9(4).

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The Clinical Laboratory Standards Institute lowered the fluoroquinolone minimum inhibitory concentration (MIC) susceptibility breakpoints for Enterobacteriaceae and glucose non-fermenting Gram-negative bacilli in January 2019. This retrospective cohort study describes the impact of this reappraisal on ciprofloxacin susceptibility overall and in patients with risk factors for antimicrobial resistance. Gram-negative bloodstream isolates collected from hospitalized adults at Prisma Health-Midlands hospitals in South Carolina, USA, from January 2010 to December 2014 were included. Matched pairs mean difference (MD) with 95% confidence intervals (CI) were calculated to examine the change in ciprofloxacin susceptibility after MIC breakpoint reappraisal. Susceptibility of Enterobacteriaceae to ciprofloxacin declined by 5.2% (95% CI: -6.6, -3.8; p < 0.001) after reappraisal. The largest impact was demonstrated among Pseudomonas aeruginosa bloodstream isolates (MD -7.8, 95% CI: -14.6, -1.1; p = 0.02) despite more conservative revision in ciprofloxacin MIC breakpoints. Among antimicrobial resistance risk factors, fluoroquinolone exposure within the previous 90 days was associated with the largest change in ciprofloxacin susceptibility (MD -9.3, 95% CI: -16.1, -2.6; p = 0.007). Reappraisal of fluoroquinolone MIC breakpoints has a variable impact on the susceptibility of bloodstream isolates by microbiology and patient population. Healthcare systems should be vigilant to systematically adopt this updated recommendation in order to optimize antimicrobial therapy in patients with bloodstream and other serious infections.

Shah, P. B., F. G. P. Welt, E. Mahmud, A. Phillips, N. S. Kleiman, M. N. Young, M. Sherwood, W. Batchelor, D. D. Wang, L. Davidson, J. Wyman, S. Kadavath, M. Szerlip, J. Hermiller, D. Fullerton and S. Anwaruddin (2020). “Triage Considerations for Patients Referred for Structural Heart Disease Intervention During the Coronavirus Disease 2019 (COVID-19) Pandemic: An ACC /SCAI Consensus Statement.” Catheter Cardiovasc Interv Apr 6. [Epub ahead of print].

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The COVID-19 pandemic has strained health care resources around the world causing many institutions to curtail or stop elective procedures. This has resulted in the inability to care for patients valvular and structural heart disease (SHD) in a timely fashion potentially placing these patients at increased risk for adverse cardiovascular complications including congestive heart failure and death. The effective triage of these patients has become challenging in the current environment as clinicians have had to weigh the risk of bringing susceptible patients into the hospital environment during the COVID-19 pandemic versus the risk of delaying a needed procedure. In this document, we suggest guidelines as to how to triage patients in need of SHD interventions and provide a framework of how to decide when it may be appropriate to proceed with intervention despite the ongoing pandemic. In particular, we address the triage of patients in need of trans-catheter aortic valve replacement and percutaneous mitral valve repair. We also address procedural issues and considerations for the function of structural heart disease teams during the COVID-19 pandemic.

Schinstock, C. A., R. B. Mannon, K. Budde, A. S. Chong, M. Haas, S. Knechtle, C. Lefaucheur, R. A. Montgomery, P. Nickerson, S. G. Tullius, C. Ahn, M. Askar, M. Crespo, S. J. Chadban, S. Feng, S. C. Jordan, K. Man, M. Mengel, R. E. Morris, I. O’Doherty, B. H. Ozdemir, D. Seron, A. R. Tambur, K. Tanabe, J. L. Taupin and P. J. O’Connell (2020). “Recommended Treatment for Antibody-mediated Rejection After Kidney Transplantation: The 2019 Expert Consensus From the Transplantion Society Working Group.” Transplantation 104(5): 911-922.

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With the development of modern solid-phase assays to detect anti-HLA antibodies and a more precise histological classification, the diagnosis of antibody-mediated rejection (AMR) has become more common and is a major cause of kidney graft loss. Currently, there are no approved therapies and treatment guidelines are based on low-level evidence. The number of prospective randomized trials for the treatment of AMR is small, and the lack of an accepted common standard for care has been an impediment to the development of new therapies. To help alleviate this, The Transplantation Society convened a meeting of international experts to develop a consensus as to what is appropriate treatment for active and chronic active AMR. The aim was to reach a consensus for standard of care treatment against which new therapies could be evaluated. At the meeting, the underlying biology of AMR, the criteria for diagnosis, the clinical phenotypes, and outcomes were discussed. The evidence for different treatments was reviewed, and a consensus for what is acceptable standard of care for the treatment of active and chronic active AMR was presented. While it was agreed that the aims of treatment are to preserve renal function, reduce histological injury, and reduce the titer of donor-specific antibody, there was no conclusive evidence to support any specific therapy. As a result, the treatment recommendations are largely based on expert opinion. It is acknowledged that properly conducted and powered clinical trials of biologically plausible agents are urgently needed to improve patient outcomes.