Early initiation of three-drug combinations for the treatment of carbapenem-resistant A. baumannii among COVID-19 patients.

OBJECTIVES: We evaluated the clinical characteristics and outcomes of patients with COVID-19 who received three-drug combination regimens for treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections during a single-centre outbreak. Our objective was to describe the clinical outcomes and molecular characteristics and in vitro synergy of antibiotics against CRAB isolates. MATERIALS AND METHODS: Patients with severe COVID-19 admitted between April and July 2020 with CRAB infections were retrospectively evaluated. Clinical success was defined as resolution of signs/symptoms of infection without need for additional antibiotics. Representative isolates underwent whole-genome sequencing (WGS) and in vitro synergy of two- or three-drug combinations was assessed by checkerboard and time-kill assays, respectively. RESULTS: Eighteen patients with CRAB pneumonia or bacteraemia were included. Treatment regimens included high-dose ampicillin-sulbactam, meropenem, plus polymyxin B (SUL/MEM/PMB; 72%), SUL/PMB plus minocycline (MIN; 17%) or other combinations (12%). Clinical resolution was achieved in 50% of patients and 30-day mortality was 22% (4/18). Seven patients had recurrent infections, during which further antimicrobial resistance to SUL or PMB was not evident. PMB/SUL was the most active two-drug combination by checkerboard. Paired isolates collected before and after treatment with SUL/MEM/PMB did not demonstrate new gene mutations or differences in the activity of two- or three-drug combinations. CONCLUSIONS: Use of three-drug regimens for severe CRAB infections among COVID-19 resulted in high rates of clinical response and low mortality relative to previous studies. The emergence of further antibiotic resistance was not detected phenotypically or through WGS analysis. Additional studies are needed to elucidate preferred antibiotic combinations linked to the molecular characteristics of infecting strains.

Evaluation of Inappropriate COVID-19 RT-PCR Test Utilization at an Academic Medical Center.

BACKGROUND: An evolving COVID-19 testing landscape and issues with test supply allocation, especially in the current pandemic, has made it challenging for ordering providers. We audited orders of the Xpert® Xpress SARS-CoV-2 PCR with reverse transcription (RT-PCR) platform-the fastest of several other testing modalities available-to illuminate these challenges utilizing a multidisciplinary laboratory professional team consisting of a pathology resident and microbiology laboratory director. METHODS: Retrospective review of the first 5 hundred Xpert Xpress SARS-CoV-2 RT-PCR test orders from a 2-week period to determine test appropriateness based on the following indications: emergency surgery, emergent obstetric procedures, initial behavioral health admission, and later including discharge to skilled care facilities and pediatric admissions. Our hypothesis was that a significant proportion of orders for this testing platform were inappropriate. RESULTS: On review, a significant proportion of orders were incorrect, with 69.8% (n = 349, P < 0.0001) not meeting indications for rapid testing. Of all orders, 249 designated as emergency surgery were inappropriate, with 49.0% of those orders never proceeding with any surgical intervention; most of these were trauma related (64.6% were orders associated with a trauma unit). CONCLUSIONS: Significant, pervasive inappropriate ordering practices were identified at this center. A laboratory professional team can be key to identifying problems in testing and play a significant role in combating inappropriate test utilization.

Comparison of Three Sample-to-Answer RT-PCR Testing Platforms for the Detection of SARS-CoV-2 RNA in Positive Nasopharyngeal and Nasal Swabs.

BACKGROUND: The COVID-19 pandemic has strained clinical microbiology laboratories due to testing supply allocations. As a result, laboratories have had to invest in multiple COVID-19 assays performed on different testing instruments. Comparing the results achieved by testing positive samples between in-use assays can provide insights into which platforms may be interchangeable for testing in times of supply chain emergencies. METHODS: Nasopharyngeal and nasal swab specimens collected in viral transport media that tested positive on the Xpert® Xpress SARS-CoV-2 assay were tested on the ePlex® SARS-CoV-2 and BD SARS-CoV-2 Reagents for BD Max™ assays. Positive percent agreement was calculated using the Xpert Xpress SARS-CoV-2 assay as the reference method. RESULTS: We tested 78 positive swabs, resulting in a positive percentage agreement (PPA) of 92% (CI 84-97%) for the BD SARS-CoV-2 assay and 58% (CI 47-70%) for the ePlex assay. Following development of a new workflow for the ePlex, we detected SARS-CoV-2 in 7 additional samples, resulting in a new PPA of 68% (CI 56-78). CONCLUSIONS: During times of supply allocation and shortage of the Xpert Xpress SARS-CoV-2 assay, the BD SARS-CoV-2 assay is well suited to test substitutions due to its high PPA.