Faculty Bibliography

Background: The Infectious Diseases Society of America has identified the potential use of SARS-CoV-2 genomic load for prognostication purposes as a key research question.
Method(s): 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 in nasopharyngeal samples, as reflected by the Cycle threshold (Ct) value of the real-time Polymerase Chain Reaction (PCR) assay, with change in clinical status. The Sequential Organ Failure Assessment (SOFA) score was used as a surrogate for patients' clinical status. A linear mixed-effects regression analysis was performed.
Result(s): Among 457 patients who presented to the emergency department 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.
Conclusion(s): Our findings suggest that an increasing Ct value in sequential tests may be of prognostic value for patients diagnosed with COVID-19 pneumonia. Before repeat testing can be recommended routinely in clinical practice as a predictor of disease outcomes, prospective studies with a standardized interval between repeat tests should confirm our findings. (Table Presented)

Background: SARS-CoV-2, the cause of COVID-19 pneumonia, is associated with heterogenous presentations ranging from asymptomatic infection to severe respiratory failure. We explored the association of SARS-CoV-2 genomic load as a risk factor for adverse patient outcomes.
Method(s): We included adult patients admitted to the hospital with clinical and radiographic findings of pneumonia and a confirmatory polymerase chain reaction (PCR) test of SARS-CoV-2 within 24 hours of admission. We segregated patients into 3 genomic load status groups: low (Cycle threshold (Ct) >=35) intermediate (25< Ct< 35) and high (Ct <=25) using real-time PCR. The primary outcome was a composite outcome of death, intubation and/or use of extracorporeal membrane oxygenation. Secondary outcomes included severity of pneumonia on admission, as measured by the Pneumonia Severity Index (PSI). Sensitivity analyses were performed to include Acute Respiratory Distress Syndrome (ARDS) in the composite outcome and varying Ct classification breakpoints.
Result(s): Of 457 patients positive for SARS-CoV-2 assay from March 31st to April 10th 2020, 316 met inclusion criteria and were included in the final analysis. Included patients were followed for a median of 25 days (IQR 21-28). High genomic load at presentation was associated with higher Charlson Comorbidity Index scores (p=0.005), transplant recipient status (p< 0.001) and duration of illness less than 7 days (p=0.005). Importantly, patients with high genomic load were more likely to reach the primary endpoint (p=0.001), and had higher PSI scores on admission (p=0.03). In multivariate analysis, high genomic load remained an independent predictor of primary outcome. Results remained significant in sensitivity analyses.
Conclusion(s): High genomic load of SARS-CoV-2 in nasopharyngeal samples at the time of admission is independently associated with mortality and intubation. This finding should prompt further research on the role of viral load as a clinical predictor and possible modifiable risk factor for adverse outcomes as treatment strategies evolve in this global pandemic. (Table Presented)

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.

Background. Pre-travel medical consultations attempt to reduce travel-associated risks by behavioral modification, vaccination, and medications. Provider understanding of quantitative risk of commonly discussed travel topics is poorly characterized. We investigated travel medicine provider understanding of quantitative risk of common travel-associated diseases, and explored how providers relay risk estimates to travelers. Methods. After institutional review board (IRB) approval, an online anonymous survey was sent to the International Society for Travel Medicine Listserv. Travel medicine experience, practice patterns and demographics were recorded. Respondents estimated quantitative risk of various destination-specific diseases. Descriptive statistics were completed. Results. Of 114 respondents, most were experienced travel medicine providers (79% saw >6 travel visits monthly). Overall risk estimates are in Table 1. Compared with published literature, providers gave accurate risk estimates for some diseases (yellow fever, traveler's diarrhea), but overestimated quantitative risk for others (Japanese encephalitis, hepatitis A, cholera). Interquartile range was greatest for Japanese encephalitis and cholera, reflecting a wider range of risk estimates. Most (81%) providers used general risk descriptions (high, low, none) and a minority (14%) discussed quantitative risk with travelers. Conclusion. Experienced travel medicine providers overestimated risk of several vaccine preventable illnesses, though risk estimates for others were close to published estimates. Most providers do not use quantitative risk in pre-travel consultations. Improved quantitative risk understanding may improve the quality of pre-travel consultations. (Table Presented)

A 78-year-old man developed right knee pain and swelling without other systemic symptoms. He had travelled frequently to the Central Valley of California. He was diagnosed with coccidioidomycosis based on joint fluid culture. Coccidioidal complement fixation antibody titres were extremely elevated. Arthroscopic debridement and fluconazole therapy did not lead to satisfactory improvement. Subsequent open debridement and change to itraconazole was followed by resolution of clinical signs of infection.

A 63-year-old man developed scrotal swelling that became bilateral over 2 months. His symptoms persisted after treatment for epididymitis, and he developed a scrotal fistula with drainage. Mycobacterium tuberculosis grew from the urine and fistula. His symptoms resolved and fistula closed with medical therapy. His case highlights the importance of early recognition, diagnosis and treatment of this form of extrapulmonary tuberculosis.

Coxiella burnetii is the causative pathogen of the zoonotic infection Q fever. Most patients with Q fever experience a non-specific febrile illness, hepatitis or pneumonia. Q fever has recently been described as a cause of prosthetic joint septic arthritis, but remains very uncommonly reported. We present a case of Q fever prosthetic joint septic arthritis that has responded to a combination of two-stage surgical exchange and prolonged medical treatment with doxycycline and hydroxychloroquine.

BACKGROUND To design better antimicrobial stewardship programs, detailed data on the primary drivers and patterns of antibiotic use are needed. OBJECTIVE To characterize the indications for antibiotic therapy, agents used, duration, combinations, and microbiological justification in 6 acute-care US facilities with varied location, size, and type of antimicrobial stewardship programs. DESIGN, PARTICIPANTS, AND SETTING Retrospective medical chart review was performed on a random cross-sectional sample of 1,200 adult inpatients, hospitalized (>24 hrs) in 6 hospitals, and receiving at least 1 antibiotic dose on 4 index dates chosen at equal intervals through a 1-year study period (October 1, 2009-September 30, 2010). METHODS Infectious disease specialists recorded patient demographic characteristics, comorbidities, microbiological and radiological testing, and agents used, dose, duration, and indication for antibiotic prescriptions. RESULTS On the index dates 4,119 (60.5%) of 6,812 inpatients were receiving antibiotics. The random sample of 1,200 case patients was receiving 2,527 antibiotics (average: 2.1 per patient); 540 (21.4%) were prophylactic and 1,987 (78.6%) were therapeutic, of which 372 (18.7%) were pathogen-directed at start. Of the 1,615 empirical starts, 382 (23.7%) were subsequently pathogen-directed and 1,231 (76.2%) remained empirical. Use was primarily for respiratory (27.6% of prescriptions) followed by gastrointestinal (13.1%) infections. Fluoroquinolones, vancomycin, and antipseudomonal penicillins together accounted for 47.1% of therapy-days. CONCLUSIONS Use of broad-spectrum empirical therapy was prevalent in 6 US acute care facilities and in most instances was not subsequently pathogen directed. Fluoroquinolones, vancomycin, and antipseudomonal penicillins were the most frequently used antibiotics, particularly for respiratory indications. Infect. Control Hosp. Epidemiol. 2015;37(1):70-79.

BACKGROUND: Modification of empirical antimicrobials when warranted by culture results or clinical signs is recommended to control antimicrobial overuse and resistance. We aimed to assess the frequency with which patients were started on empirical antimicrobials, characteristics of the empirical regimen and the clinical characteristics of patients at the time of starting antimicrobials, patterns of changes to empirical therapy at different timepoints, and modifiable factors associated with changes to the initial empirical regimen in the first 5 days of therapy. METHODS: We did a chart review of adult inpatients receiving one or more antimicrobials in six US hospitals on 4 days during 2009 and 2010. Our primary outcome was the modification of antimicrobial regimen on or before the 5th day of empirical therapy, analysed as a three-category variable. Bivariate analyses were used to establish demographic and clinical variables associated with the outcome. Variables with p values below 0.1 were included in a multivariable generalised linear latent and mixed model with multinomial logit link to adjust for clustering within hospitals and accommodate a non-binary outcome variable. FINDINGS: Across the six study sites, 4119 (60%) of 6812 inpatients received antimicrobials. Of 1200 randomly selected patients with active antimicrobials, 730 (61%) met inclusion criteria. At the start of therapy, 220 (30%) patients were afebrile and had normal white blood cell counts. Appropriate cultures were collected from 432 (59%) patients, and 250 (58%) were negative. By the 5th day of therapy, 12.5% of empirical antimicrobials were escalated, 21.5% were narrowed or discontinued, and 66.4% were unchanged. Narrowing or discontinuation was more likely when cultures were collected at the start of therapy (adjusted OR 1.68, 95% CI 1.05-2.70) and no infection was noted on an initial radiological study (1.76, 1.11-2.79). Escalation was associated with multiple infection sites (2.54, 1.34-4.83) and a positive culture (1.99, 1.20-3.29). INTERPRETATION: Broad-spectrum empirical therapy is common, even when clinical signs of infection are absent. Fewer than one in three inpatients have their regimens narrowed within 5 days of starting empirical antimicrobials. Improved diagnostic methods and continued education are needed to guide discontinuation of antimicrobials. FUNDING: US Centers for Disease Control and Prevention, Division of Healthcare Quality Promotion; Robert Wood Johnson Foundation; US Department of Veterans Administration; US Department of Homeland Security.