Infectious Disease

Chatterjee, P., Choi, H., Ochoa, B., Garmon, G., Coppin, J.D., Allton, Y., Lukey, J., Williams, M.D., Navarathna, D. and Jinadatha, C. (2020). “Clade-specific variation in susceptibility of Candida auris to broad-spectrum ultraviolet C light (UV-C).” Infect Control Hosp Epidemiol Oct 13;1-4. [Epub ahead of print].

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BACKGROUND: Candida auris is an emerging and often multidrug-resistant fungal pathogen with an exceptional ability to persist on hospital surfaces. These surfaces can act as a potential source of transmission. Therefore, effective disinfection strategies are urgently needed. We investigated the efficacy of ultraviolet C light (UV-C) disinfection for C. auris isolates belonging to 4 different clades. METHODS: In vitro testing of C. auris isolates was conducted using 106 colony-forming units (CFU) spread on 20-mm diameter steel carriers and exposed to a broad-spectrum UV-C light source for 10, 20, and 30 minutes at a 1.5 m (5 feet) distance. Post-UV survivors on the coupons were subsequently plated. Colony counts and log reductions were recorded, calculated, and compared to untreated control carriers. Identification of all isolates were confirmed by MALDI-TOF and morphology was visualized by microscopy. RESULTS: We observed an increased susceptibility of C. auris to UV-C in 8 isolates belonging to clades I, II and IV with increasing UV exposure time. The range of log kill (0.8-1.19) was highest for these isolates at 30 minutes. But relatively no change in log kill (0.04-0.35) with increasing time in isolates belonging to clade III were noted. Interestingly, C. auris isolates susceptible to UV-C were mostly nonaggregating, but the isolates that were more resistant to UV exposure formed aggregates. CONCLUSIONS: Our study suggests variability in susceptibility to UV-C of C. auris isolates belonging to different clades. More studies are needed to assess whether a cumulative impact of prolonged UV-C exposure provides additional benefit.

Martin, E.T., Cheng, C., Petrie, J.G., Alyanak, E., Gaglani, M., Middleton, D.B., Ghamande, S., Silveira, F.P., Murthy, K., Zimmerman, R.K., Monto, A.S., Trabue, C., Talbot, H.K. and Ferdinands, J.M. (2020). “Low influenza vaccine effectiveness against A(H3N2) associated hospitalizations in the 2016-2017 and 2017-2018 seasons of the Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN).” J Infect Dis Nov 3;jiaa685. [Epub ahead of print].

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INTRODUCTION: The 2016-2017 and 2017-2018 influenza seasons were notable for high number of hospitalizations for influenza A(H3N2) despite vaccine and circulating strain match. METHODS: We evaluated vaccine effectiveness (VE) against hospitalization in the test-negative HAIVEN study. Nasal-throat swabs were tested by RT-PCR for influenza and VE was determined based on odds of vaccination by generalized estimating equations. Vaccine-specific antibody was measured in a subset of enrollees. RESULTS: A total of 6,129 adults were enrolled from ten hospitals. Adjusted VE against A(H3N2) was 22.8% (95% C.I. 8.3%, 35.0%), pooled across both years and 49.4% (95% C.I. 34.3%, 61.1%) against B/Yamagata. In 2017-2018, the A(H3N2) VE point estimate for the cell-based vaccine was 43.0% (95% C.I. -36.3%, 76.1%; 56 vaccine recipients) compared to 24.0% (95% C.I. 3.9%, 39.9%) for egg based vaccines. Among 643 with serology data, hemagglutinin antibodies against the egg-based A(H3N2) vaccine strain were increased in influenza-negative individuals. CONCLUSIONS: Low VE for the A/Hong Kong/4801/2014 vaccine virus in both A(H3N2) seasons emphasizes concerns for continued changes in H3N2 antigenic epitopes, including changes that may impact glycosylation and ultimately reduce VE.

Palazzuoli, A., Ruberto, F., De Ferrari, G.M., Forleo, G., Secco, G.G., Ruocco, G.M., D’Ascenzo, F., Mojoli, F., Monticone, S., Paggi, A., Vicenzi, M., Corcione, S., Palazzo, A.G., Landolina, M., Taravelli, E., Tavazzi, G., Blasi, F., Mancone, M., Birtolo, L.I., Alessandri, F., Infusino, F., Pugliese, F., Fedele, F., De Rosa, F.G., Emmett, M., Schussler, J.M., McCullough, P.A. and Tecson, K.M. (2020). “Inpatient Mortality According to Level of Respiratory Support Received for Severe Acute Respiratory Syndrome Coronavirus 2 (Coronavirus Disease 2019) Infection: A Prospective Multicenter Study.” Crit Care Explor 2(9): e0220.

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OBJECTIVES: To describe patients according to the maximum degree of respiratory support received and report their inpatient mortality due to coronavirus disease 2019. DESIGN: Analysis of patients in the Coracle registry from February 22, 2020, to April 1, 2020. SETTING: Hospitals in the Piedmont, Lombardy, Tuscany, and Lazio regions of Italy. PATIENTS: Nine-hundred forty-eight patients hospitalized for coronavirus disease 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 948 patients, 122 (12.87%) received invasive ventilation, 637 (67.19%) received supplemental oxygen only, and 189 (19.94%) received no respiratory support. The median (quartile 1-quartile 3) age was 65 years (54-76.59 yr), and there was evidence of differential respiratory treatment by decade of life (p = 0.0046); patients greater than 80 years old were generally not intubated. There were 606 men (63.9%) in this study, and they were more likely to receive respiratory support than women (p < 0.0001). The rate of in-hospital death for invasive ventilation recipients was 22.95%, 12.87% for supplemental oxygen recipients, and 7.41% for those who received neither (p = 0.0004). A sensitivity analysis of the 770 patients less than 80 years old revealed a lower, but similar mortality trend (18.02%, 8.10%, 5.23%; p = 0.0008) among the 14.42%, 65.71%, and 19.87% of patients treated with mechanical ventilation, supplemental oxygen only, or neither. Overall, invasive ventilation recipients who died were significantly older than those who survived (median age: 68.5 yr [60-81.36 yr] vs 62.5 yr [55.52-71 yr]; p = 0.0145). CONCLUSIONS: Among patients hospitalized for coronavirus disease 2019, 13% received mechanical ventilation, which was associated with a mortality rate of 23%.

Chapagain, M., Gumbo, T., Heysell, S.K. and Srivastava, S. (2020). “Comparison of a Novel Regimen of Rifapentine, Tedizolid, and Minocycline with Standard Regimens for Treatment of Pulmonary Mycobacterium kansasii.” Antimicrob Agents Chemother 64(10).

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The combination of isoniazid, rifampin, and ethambutol is recommended by the American Thoracic Society (ATS) for treatment of pulmonary Mycobacterium kansasii, while the British Thoracic Society (BTS) recommends clarithromycin, rifampin and ethambutol. Unfortunately, therapy duration for both regimens lasts for years. In this study, we administered tedizolid, minocycline, clarithromycin, and rifapentine as monotherapy as well as novel combinations in the intracellular hollow-fiber model system of M. kansasii (HFS-Mkn) in a 28-day study. The ATS and BTS regimens were used as comparators. Repetitive sampling was used to validate the intended intrapulmonary pharmacokinetics of each drug and to monitor changes in M. kansasii burden. As monotherapy, tedizolid at an observed area under the concentration-time curve from 0 to 24 h (AUC(0-24))/MIC of 5.85 and minocycline at an AUC(0-24)/MIC of 5.77 failed to kill the bacteria below day 0 (stasis), clarithromycin at an AUC(0-24)/MIC of 2.4 held the bacterial burden at stasis, but rifapentine at an AUC(0-24)/MIC of 140 killed 2 log(10) CFU/ml below stasis. The BTS regimen kill slope was -0.083 ± 0.035 CFU/ml/day, which was significantly superior to the ATS regimen slope of -0.038 ± 0.038 CFU/ml/day. The rifapentine-tedizolid-minocycline combination kill slope was -0.119 ± 0.031 CFU/ml/day, superior to that of the ATS regimen and comparable to that of the BTS regimen. In conclusion, the BTS regimen and the novel rifapentine-tedizolid-minocycline regimen showed better kill of intracellular bacteria in the HFS-Mkn However, the efficacy of the new combination regimen remains to be tested in clinical settings.

Lat, T.I., Patel, C.D., Ehrig, J.C., Moslander, C. and Sanchez, J.F. (2020). “Therapeutic Options in the Treatment of SARS-CoV-2 in the Pregnant Patient.” Am J Obstet Gynecol MFM Sep 12;100224. [Epub ahead of print.].

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The SARS-CoV-2 pandemic has resulted in the development of various therapeutics to treat and prevent major complications related to the virus; pregnant patients are vulnerable to acquiring SARS-CoV-2 due to frequent contact with the healthcare setting. Despite publication of a plethora of case series and randomized control trials of SARS- CoV-2 therapeutics, few have addressed treatment in the pregnant population. To date, there have been no published review of therapeutics in the pregnant patient infected with SARS-CoV-2. We provide the first review of available treatments for SARS-CoV-2, various trials with inclusion and exclusion of the pregnant patients, and potential side effects of each treatment in the pregnant patient.