Advancing Digital Health Equity: A Policy Paper of the Infectious Diseases Society of America and the HIV Medicine Association.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has revolutionized the practice of ambulatory medicine, triggering rapid dissemination of digital healthcare modalities, including synchronous video visits. However, social determinants of health, such as age, race, income, and others, predict readiness for telemedicine and individuals who are not able to connect virtually may become lost to care. This is particularly relevant to the practice of infectious diseases (ID) and human immunodeficiency virus (HIV) medicine, as we care for high proportions of individuals whose health outcomes are affected by such factors. Furthermore, delivering high-quality clinical care in ID and HIV practice necessitates discussion of sensitive topics, which is challenging over video without proper preparation. We describe the "digital divide," emphasize the relevance to ID and HIV practice, underscore the need to study the issue and develop interventions to mitigate its impact, and provide suggestions for optimizing telemedicine in ID and HIV clinics.

Homozygosity for the toll-like receptor 2 R753Q single-nucleotide polymorphism is a risk factor for cytomegalovirus disease after liver transplantation.

Immunity against cytomegalovirus (CMV) is initiated after its recognition by Toll-like receptor 2 (TLR2). We assessed the association between a single-nucleotide polymorphism (SNP) that impairs TLR2 function and CMV disease in a cohort of 737 liver recipients. Ninety-two of 737 patients (7.1%, 10.9%, 12.3%, and 12.5% by 3, 6, 12, and 24 months, respectively) developed CMV disease. Kaplan-Meier estimation demonstrated an association between TLR2 R753Q SNP homozygosity and CMV disease (P = .044), especially tissue-invasive CMV disease (P = .001). A multivariate Cox proportional hazard model that accounted for other significant predictors demonstrated a significant association between TLR2 R753Q SNP homozygosity and tissue-invasive CMV disease (hazard ratio, 3.407; 95% confidence interval, 1.518-7.644; P = .0029). In conclusion, homozygosity for TLR2 R753Q SNP is a marker for CMV disease risk, especially for tissue-invasive disease, after liver transplantation. This observation supports the critical role of TLR2 in the pathogenesis of CMV disease in humans.

Invasive aspergillosis among heart transplant recipients is rare but causes rapid death due to septic shock and multiple organ dysfunction syndrome.

Between 2000 and 2011, proven or probable invasive aspergillosis (IA) was diagnosed in 1.7% (8/455) of heart transplant (HTx) recipients at our center, in the absence of antifungal prophylaxis. All patients had invasive pulmonary infections and 75% (6/8) were diagnosed during 2 separate 3-month periods. Cases were notable for their association with septic shock and multiple organ dysfunction syndrome (MODS) (75%, 6/8 each), non-specific clinical and radiographic findings, and rapid mortality despite mould-active antifungal therapy (88%, 7/8; occuring at a median 11 days after diagnosis). All patients had predisposing conditions known to be risk factors for IA. For patients with early IA (within 90 days of HTx), conditions included hemodialysis, thoracic re-operation, and the presence of another case in the institution within the preceding 3 months. For late-onset IA, conditions included hemodialysis and receipt of augmented immunosuppression. Clinicians should suspect IA in HTx recipients with risk factors who present with non-specific and unexplained respiratory syndromes, including those in septic shock and MODS, and institute prompt antifungal therapy without waiting for the results of cultures or other diagnostic tests.

In-Person Versus Tele-Infectious Disease (Tele-ID) Care: Is One Better?

We compared outcomes at 3 community hospitals before and after switching from in-person to a Tele-ID group from an academic medical center. Compared to in-person, Tele-ID received significantly more consultations with similar outcomes for length of hospital stay, transfers, readmission, and mortality. Tele-ID is a suitable alternative for community settings.

Impact of Clinical Decision Support System Implementation at a Community Hospital With an Existing Tele-Antimicrobial Stewardship Program.

Background: Lack of on-site antimicrobial stewardship expertise is a barrier to establishing successful programs. Tele-antimicrobial stewardship programs (TASPs) utilizing a clinical decision support system (CDSS) can address these challenges. Methods: This interrupted time series study reports the impact of CDSS implementation (February 2020) within an existing TASP on antimicrobial usage in a community hospital. Segmented regression analysis was used to assess differences in antimicrobial usage from January 2018 through December 2021. Pre- and post-CDSS frequencies of intravenous vs oral antimicrobials, time to optimal therapy (TTOT), pharmacist efficiency (number of documented interventions per month), and percentage of hospitalized patients receiving antimicrobials were compared with descriptive statistics. Results: Implementation of a CDSS into an existing TASP was associated with an immediate 11% reduction in antimicrobial usage (level change, P < .0001). Antimicrobial usage was already trending down by 0.25% per month (pre-CDSS slope, P < .0001) and continued to trend down at a similar rate after implementation (post-CDSS slope, P = .0129). Frequency of use of select oral agents increased from 38% to 57%. Median TTOT was 1 day faster (2.9 days pre-CDSS vs 1.9 days post-CDSS). On average, pharmacists documented 2.2-fold more interventions per month (198 vs 90) and patients received 1.03 fewer days of antimicrobials per admission post-CDSS. Conclusions: Implementation of a CDSS within an established TASP at a community hospital resulted in decreased antimicrobial usage, higher rates of oral usage, faster TTOT, and improved pharmacist efficiency.

Spectrum of early-onset and late-onset bacteremias after liver transplantation: implications for management.

Bacteremia is a significant cause of morbidity and mortality after liver transplantation. The characterization of the microbiological spectrum of bacteremia after liver transplantation may help physicians in choosing the initial empirical antimicrobial therapy for patients presenting with sepsis. The clinical and microbiology records of patients who received liver transplantation from January 1997 to March 2006 were reviewed. One hundred twenty-three of the 737 liver recipients (16.7%) developed bacteremia during the median follow-up period of 5.8 years (interquartile range = 2.5-8.8 years); 92 patients (12.5%) had gram-positive bacteremia (GPB), whereas 47 (6.4%) had gram-negative bacteremia (GNB). Nosocomial bacteremia was significantly more frequent among patients with early-onset GPB or GNB versus patients with late-onset GPB (66.7% versus 23.7%, P < 0.001) or GNB (70.6% versus 20.0%, P = 0.001). Peritonitis (33.3% versus 7.9%, P = 0.004) and wound infections (13.0% versus 0%, P = 0.04) as sources were more common in patients with early-onset GPB versus patients with late-onset GPB. Likewise, peritonitis was a more common source of early-onset GNB than late-onset GNB (41.2% versus 6.7%, P = 0.007). Staphylococcus aureus and Enterococcus faecium were the most common pathogens in patients with early-onset GPB, whereas Enterococcus faecalis and Streptococcus species were most common in patients with late-onset GPB. Pseudomonas aeruginosa and anaerobes were the most common pathogens in patients with early-onset GNB, whereas Escherichia coli was most common in patients with late-onset GNB. In conclusion, the microbiological spectra of early-onset and late-onset bacteremias differ, and this should be considered by those determining the initial empirical treatment of liver transplant recipients suspected to have bacteremias.

Toll-like receptor 2 polymorphism and Gram-positive bacterial infections after liver transplantation.

Toll-like receptor 2 (TLR2) is an immune sensor for gram-positive bacterial cell wall components. Single-nucleotide polymorphisms (SNPs) in the TLR2 gene that impair its function may, therefore, influence the risk and outcomes of gram-positive bacterial infections. In a cohort of 694 liver transplant recipients, we assessed the TLR2 SNP that is translated into an amino acid substitution of arginine for glutamine at position 753 (R753Q), and we found that its presence was associated with the clinical characteristics and outcomes of gram-positive bacterial infections. The proportions of patients with the TLR2 R753Q SNP did not significantly differ between those with gram-positive bacterial infections and those without gram-positive bacterial infections (9.6% versus 9.6%, P = 0.999). However, in patients with the TLR2 R753Q SNP, higher rates of infection recurrence (27.8% versus 11.8%, P = 0.07) and initial septic shock (11.1% versus 1.2%, P = 0.047) were observed. Chronic hepatitis C [relative risk (RR) = 3.37, 95% confidence interval (CI) = 1.24-9.13, P = 0.02], initial septic shock (RR = 15.13, 95% CI = 2.84-80.54, P = 0.001), and central venous catheter-related bacteremia (RR = 7.22, 95% CI = 2.54-20.51, P < 0.001) were significantly associated with 90-day all-cause mortality after gram-positive bacterial infections. In contrast, the presence of the TLR2 R753Q SNP was not significantly associated with mortality.

Telemedicine and Infectious Diseases Practice: A Leap Forward or a Step Back?

Infectious Diseases (ID) specialists pride themselves on performing a thorough history and physical exam, and developing a comprehensive diagnosis and management plan. A timely question is whether this tradition is at risk from the coming wave of telemedicine in clinical practice? It would not be if ID specialists embrace the changes ahead and leverage new technologies to enhance the efficiency and reach of their clinical practices. In this report, we highlight the opportunities and challenges offered by telemedicine for ID practice (Table 1).

Staphylococcus aureus infections in the early period after lung transplantation: epidemiology, risk factors, and outcomes.

BACKGROUND: Staphylococcus aureus infections among lung transplant recipients are poorly studied. METHODS: We conducted a 5-year retrospective study of the epidemiology, clinical manifestations, risk factors, and outcomes of patients infected with S aureus within the first 90 days after lung transplantation. RESULTS: An S aureus infection developed in 109 of 596 lung transplant (18%) recipients. Methicillin-susceptible S aureus (MSSA; 62%) was more common than methicillin-resistant S aureus (MRSA; 38%); however, the proportion of infections caused by MRSA increased over time. Pneumonia (48%) was the most common infection, followed by tracheobronchitis (26%), bacteremia (12%), intrathoracic infections (7%), and skin/soft tissue infections (7%). Risk factors included mechanical ventilation for > 5 days and isolation of S aureus from recipients' sterility cultures. Patients with MRSA cultured from the nares or respiratory tract at the time of transplant were at an increased risk for MRSA infection (p < 0.0001 and p = 0.02, respectively). Infected patients required longer hospital and intensive care unit stays (p < 0.0001 for both), but the 30- and 90-day mortality rates from the onset of infection were only 7% and 12%, respectively. However, infected patients had higher rates of acute and chronic rejection at 1 (p = 0.048) and 3 years (p = 0.002), and higher rates of mortality at 1 (p = 0.058) and 3 years (p = 0.009). CONCLUSIONS: S aureus infections within the first 90 days of lung transplant were associated with low short-term mortality but increased long-term rates of mortality and acute and chronic rejection. Future studies are needed to explore the utility of S aureus eradication strategies in reducing disease burden and improving outcomes.

Toll-like receptor 4 polymorphisms and the risk of gram-negative bacterial infections after liver transplantation.

BACKGROUND: Toll-like receptor 4 (TLR4) is the main immune molecule that recognizes lipopolysaccharide from gram-negative bacteria. Single-nucleotide polymorphisms (SNPs) in the TLR4 gene that impair lipopolysaccharide recognition may influence gram-negative bacterial infections after liver transplantation. METHODS: TLR4 D299G and T399I SNPs were assessed in a cohort of 706 liver transplant recipients and were associated with the clinical characteristics and outcome of gram-negative bacterial infections. Cox proportional hazard model was performed to determine covariates associated with outcomes after gram-negative bacterial infections. RESULTS: Of 706 patients, there were 108 with microbiologically confirmed gram-negative bacterial infections, 135 with clinically suspected but not confirmed infections, and 463 patients without gram-negative bacterial infections. The proportions of TLR4 D299G (5/108 [4.6%] vs. 32/463 [6.9%]; P=0.39) and T399I SNPs (19/108 [17.6%] vs. 68/463 [14.7%]; P=0.45) did not differ between those with or without microbiologically confirmed gram-negative bacterial infections. Female gender (odds ratio 2.30, 95% confidence interval [CI]1.50-3.53; P<0.001) and ulcerative colitis (odds ratio 2.18, 95% CI 1.08-4.38; P=0.03) were associated with gram-negative bacterial infections. Among 108 patients with gram-negative bacterial infections, alcoholic liver disease (relative risk [RR] 4.87, 95% CI 1.54-15.44; P=0.007), initial septic shock (RR 10.19, 95% CI 2.70-38.37; P=0.001), and nosocomially-acquired infection (RR 4.61, 95% CI 1.51-14.14; P=0.007) were significantly associated with 90-day mortality after gram-negative bacterial infections. In contrast, TLR4 D299G and T399I SNPs were not significantly associated with mortality after gram-negative bacterial infections. CONCLUSION: In this cohort of liver transplant recipients with long-term follow-up, no significant association was observed between TLR4 D299G and T399I SNPs and the risk and outcome of gram-negative bacterial infections.