SARS-CoV-2 Continuous Genetic Divergence and Changes in Multiplex RT-PCR Detection Pattern on Positive Retesting Median 150 Days after Initial Infection.

Being in the epicenter of the COVID-19 pandemic, our lab tested 193,054 specimens for SARS-CoV-2 RNA by diagnostic multiplex reverse transcription polymerase chain reaction (mRT-PCR) starting in March 2020, of which 17,196 specimens resulted positive. To investigate the dynamics of virus molecular evolution and epidemiology, whole genome amplification (WGA) and Next Generation Sequencing (NGS) were performed on 9516 isolates. 7586 isolates with a high quality were further analyzed for the mutation frequency and spectrum. Lastly, we evaluated the utility of the mRT-PCR detection pattern among 26 reinfected patients with repeat positive testing three months after testing negative from the initial infection. Our results show a continuation of the genetic divergence in viral genomes. Furthermore, our results indicate that independent mutations in the primer and probe regions of the nucleocapsid gene amplicon and envelope gene amplicon accumulate over time. Some of these mutations correlate with the changes of detection pattern of viral targets of mRT-PCR. Our data highlight the significance of a continuous genetic divergence on a gene amplification-based assay, the value of the mRT-PCR detection pattern for complementing the clinical diagnosis of reinfection, and the potential for WGA and NGS to identify mutation hotspots throughout the entire viral genome to optimize the design of the PCR-based gene amplification assay.

Omadacycline for the treatment of Mycobacterium abscessus infections: Case series and review of the literature.

Treatment of Mycobacterium abscessus infections are problematic due to inherent multidrug resistance and lack of response to antibacterials commonly used as therapy for other mycobacterial infections. We report the clinical success of five patients who received definitive-treatment with an omadacycline-containing combination regimen for M. abscessus infection.

Omadacycline in the treatment of community-acquired bacterial pneumonia in patients with comorbidities: a post-hoc analysis of the phase 3 OPTIC trial.

Introduction: The 2019 American Thoracic Society/Infectious Disease Society of America guidelines recommend respiratory fluoroquinolones to treat community-acquired bacterial pneumonia (CABP) in adults with comorbidities. Fluoroquinolones are effective against both typical and atypical pathogens. However, fluoroquinolone treatment has a risk of adverse effects, and the Food and Drug Administration has issued black box safety warnings for their use. Inpatient use of fluoroquinolones has reduced as a result; however, most antibiotic courses are completed as outpatients and discharge prescriptions account for the majority of fluoroquinolone use. As such, a new treatment option is needed to replace fluoroquinolones. Omadacycline is an aminomethylcycline antibiotic with a broad spectrum of activity and is available as a once-daily intravenous or bioequivalent oral formulation. Methods: This study assessed the safety and clinical efficacy of omadacycline compared with moxifloxacin for the treatment of adult CABP patients with Pneumonia Severity Index (PSI) risk class II/III and ≥1 comorbidity through a post-hoc analysis of the phase 3 OPTIC study (NCT02531438). Results: In total, 239 omadacycline- and 222 moxifloxacin-treated patients were assessed. The median age was similar between groups (omadacycline: 57 years; moxifloxacin: 58 years), with 26.0% and 26.6%, respectively, ≥65 years of age. Early clinical response was 91.6% for patients with ≥1 comorbidity treated with omadacycline and 91.4% for those treated with moxifloxacin. Post-treatment evaluation results for overall response were 89.1% in the omadacycline group and 87.4% in the moxifloxacin group. Conclusion: Safety warnings have reduced inpatient use of fluoroquinolones; however, outpatient and discharge prescriptions account for the majority of fluoroquinolone use. Outpatients with comorbidities need an efficacious alternative to fluoroquinolones. Omadacycline maintains the similar efficacy and benefits of fluoroquinolones as a once-daily, monotherapy, bioequivalent oral option with potent in vitro activity against the most common CABP pathogens, including S. pneumoniae and atypical pathogens, but offers a materially different safety profile consistent with its tetracycline heritage. In conclusion, both omadacycline and moxifloxacin exhibited similar efficacy in patients with PSI risk class II/III and comorbidities. Omadacycline fulfills an unmet need as an oral monotherapy treatment option for adult patients with CABP, which will further reduce the use of fluoroquinolones. Clinical trial registration: https://www.clinicaltrials.gov/study/NCT02531438, identifer: NCT02531438; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-004071-13, identifier: EudraCT #2013-004071-13.

Combination antibiotic therapy for treatment of a patient with infected prosthesis and peri-prosthetic abscess due to Klebsiella pneumoniae harboring New Delhi Metallo (NDM) beta-lactamase.

Treatment options for patients infected with multi-drug resistant gram-negative bacteria harboring metallo-beta-lactamases (MBLs) requires precision therapy. We present the case of a 20 year-old male with a right distal femoral peri-prosthetic abscess with presumed infected hardware and osteomyelitis in whom four multi-drug resistant gram negative bacteria were isolated. The rapid identification of an MBL producing organism, novel combination of therapy, and prompt infection prevention enforcement and education led to appropriate treatment of our patient as well as prevention of spread of organisms during and after hospitalization. This case illustrated successful management of multiple challenges faced by patients infected and/or harboring extensively resistant bacteria.

Implementation of a Collaborated Antimicrobial Stewardship Program and Outpatient Parenteral Antimicrobial Therapy (OPAT) Unit-driven Monoclonal Antibody Therapy Program for COVID-19 at an NYC Hospital.

OBJECTIVES: This study aimed to assess the processes and clinical outcomes of a joint collaboration between Antimicrobial Stewardship Program (ASP) and the outpatient parenteral antimicrobial therapy (OPAT) unit for delivery of monoclonal antibody therapy for mild-to-moderate COVID-19. METHODS: We carried out a retrospective, interim analysis of our COVID-19 monoclonal antibody therapy program. Outcomes included clinical response, incidence of hospitalization, and adverse events. RESULTS: A total of 175 patients (casirivimab-imdevimab, n = 130; bamlanivimab, n = 45) were treated between December 2020 and March 1, 2021. The median time from symptom onset was 6 (IQR 4, 8) days at time of treatment. Of 135 patients available for follow-up, 71.9% and 85.9% of patients reported symptom improvement within 3 and 7 days of treatment, respectively. A total of 9 (6.7%) patients required COVID-19-related hospitalization for progression of symptoms, all within 14 days of treatment. A total of 7 (4%) patients experienced an infusion-related reaction. CONCLUSIONS: ASP-OPAT collaboration is a novel approach to implement an efficient and safe monoclonal antibody therapy program for the treatment of mild-to-moderate COVID-19.