Faculty Bibliography

The Infectious Diseases Society of America has identified the use of SARS-CoV-2 genomic load for prognostication purposes as a key research question. We designed a retrospective cohort study that included adult patients with COVID-19 pneumonia who had at least 2 positive nasopharyngeal tests at least 24 hours apart to study the correlation between the change in the genomic load of SARS-CoV-2, as reflected by the Cycle threshold (Ct) value of the RT-PCR, with change in clinical status. The Sequential Organ Failure Assessment (SOFA) score was used as a surrogate for patients' clinical status. Among 457 patients with COVID-19 pneumonia between 3/31/2020-4/10/2020, we identified 42 patients who met the inclusion criteria. The median initial SOFA score was 2 (IQR 2-3). 20 out of 42 patients had a lower SOFA score on their subsequent tests. We identified a statistically significant inverse correlation between the change in SOFA score and change in the Ct value with a decrease in SOFA score by 0.05 (SE 0.02; p<0.05) for an increase in Ct values by 1. This correlation was independent of the duration of symptoms. Our findings suggest that an increasing Ct value in sequential tests may be of prognostic value for patients diagnosed with COVID-19 pneumonia.

Neurologic manifestations of the novel coronavirus SARS-CoV-2 infection have received wide attention, but the mechanisms remain uncertain. Here, we describe computational data from public domain RNA-seq datasets and cerebrospinal fluid data from adult patients with severe COVID-19 pneumonia that suggest that SARS-CoV-2 infection of the central nervous system is unlikely. We found that the mRNAs encoding the ACE2 receptor and the TMPRSS2 transmembrane serine protease, both of which are required for viral entry into host cells, are minimally expressed in the major cell types of the brain. In addition, CSF samples from 13 adult encephalopathic COVID-19 patients diagnosed with the viral infection via nasopharyngeal swab RT-PCR did not show evidence for the virus. This particular finding is robust for two reasons. First, the RT-PCR diagnostic was validated for CSF studies using stringent criteria; and second, 61% of these patients had CSF testing within 1 week of a positive nasopharyngeal diagnostic test. We propose that neurologic sequelae of COVID-19 are not due to SARS-CoV-2 meningoencephalitis and that other etiologies are more likely mechanisms.

Background. Although blood cultures are the clinical diagnostic standard for candidemia, their delay in results and low sensitivity has lead to increasing the use of alternate tests and diagnostic algorithms. The T2Candida magnetic resonance assay (T2C) results in a few hours, but concomitant cultures are also needed. We compared results from the T2C with beta-d-glucan (BDG), blood cultures (BCx) and the Candida Sepsis Score (CSc) in diagnosis and management of candidemia. Methods. This retrospective observational study included patients from July 2017 to December 2018 who had a T2C as well as BCx. Positive (+) and negative (-) results of BCx and BDG within 24 hours (24 h) of T2C were recorded, with clinical data to determine CSc at the time of T2C (recent surgery, severe sepsis, parenteral nutrition, multifocal candida colonization). Results. There were 648 T2Cs done over the study period. Only the first +T2C for patients with multiple T2Cs on admission was included. There were 41 patients with +T2, in which 31 had a 24hBCx. Two patients were of pediatric age. There were 7 neutropenic, 1 post-transplant, and 27 intensive care (ICU) patients. Reasons for ordering T2C included sepsis and persistent fevers. In 18 (44%) patients, antifungals were given prior to the T2C. Eight among 31 24hBCx were positive for concordant Candida spp. (26%). Six of these 8 patients were on antifungal therapy when T2C was sent. Seventeen patients had a 24hBDG, with 7 positive (41%). Overall mean CSc in 27 ICU patients with +T2C was 2.2 +/- 0.8, and 40% of adult non-neutropenic ICU patients had a CSc of 3 or above. A central line was present in 26 patients, and was removed in 16 after +T2. In 213 patients with -T2C who had 24hBCx, only 1 BCx was positive, from a PICC line in a 2-year-old patient. Seven of the 41 patients with +T2C were treated for deep-seated candidiasis with 6 weeks antifungal therapy or longer; others received 1 to 4 weeks. Thirteen patients died while on antifungal therapy. Conclusion. T2Candida was used for diagnosis and management of candidemia in patients who had concomitant blood culture positive in 26%, beta-d-glucan positive in 41%, and ICU Candida sepsis score 3 or above in 40% patients. It did not miss candidemia in adults, compared with blood culture within 24 hours. Positive T2Candida helped expedite source control e.g line removal

Background. Staphylococcus aureus infection confers high mortality. S. aureus-colonized hospitalized patients are more likely to develop invasive infection and can transmit S. aureus to other patients in the absence of symptoms. Our health system has a baseline S. aureus colonization rate of 21% (MSSA and MRSA combined). To reduce risk of invasive S. aureus infection in our patients, we implemented an inpatient S. aureus screening and decolonization program. Methods. Interventions include universal S. aureus screening and targeted decolonization for all patients on the Medicine and Pediatrics inpatient services. Adult patients are screened at admission and change in the level of care; pediatric patients are screened weekly. S. aureus screening began incrementally by unit between 2016 and 2017, and extended to transplant units in 2018. All cultures are processed in the hospital microbiology lab for identification of MRSA and MSSA. S. aureus decolonization (mupirocin ointment in nares twice daily, chlorhexidine 2% wipes below the chin daily for 5 days) began in 2017 for patients with a central venous catheter, in intensive care unit or multibedded room. Decolonization was extended to all S. aureus-colonized patients beginning in June 2018, with involvement of a dedicated clinical nurse specialist. We compared compliance with screening and decolonization and the secondary outcome of MRSA bacteremia in the 6 month period before and after the addition of the clinical nurse specialist. Results. 21.5% of screened patients were colonized with S. aureus (82.4% MSSA, 17.6% MRSA). Screening compliance improved from 39.4% of eligible patients (N = 1805) to 52.1% (N = 2024) and decolonization increased from 18.6% of colonized patients to 41.2% comparing January-June 2018 with July-December 2018. The MRSA bacteremia rate fell from 0.2/1,000 patient-days in the first half of 2018 to 0.1/1,000 patient-days in the second half of 2018. Conclusion. A system-wide program that includes S. aureus screening and decolonization of hospitalized patients found that 21% of patients had S. aureus colonization. Screening and decolonization compliance increased with the introduction of a dedicated clinical nurse specialist, and the MRSA bloodstream infection rate fell

We describe the rapid and ongoing emergence across multiple US cities of a new multidrug-resistant E. coli clone - ST1193, resistant to fluoroquinolones (100%), trimethoprim/sulfamethoxazole (55%) and tetracycline (53%). ST1193 is associated with younger adults (age < 40 years) and currently comprises a quarter of fluoroquinolone-resistant clinical E. coli urine isolates.