Garcia, Bismarck Bisono

ABSTRACT Introduction Cytomegalovirus (CMV) causes substantial morbidity after solid organ transplantation. Valganciclovir (VGCV) remains a first‐line prophylactic agent, but it has significant myelosuppressive effect. Letermovir is approved for CMV prophylaxis in high‐risk kidney transplant recipients, but data on its use outside of that population are limited. We describe characteristics and outcomes of letermovir prophylaxis in non‐kidney transplant recipients. Methods We performed a retrospective, multi‐center study of all adult non‐kidney solid organ transplant recipients (SOTr) who received letermovir (March 2018–June 2024) for CMV prophylaxis. Outcomes included breakthrough and post‐prophylaxis delayed‐onset CMV infections, adverse events, and survival. Results A total of 64 patients were included in the final analysis. Of those, letermovir was used for primary prophylaxis in 56.2% of patients, while the remainder received it for secondary prophylaxis. The main rationale behind selecting letermovir was myelosuppression related to VGCV. During the median follow‐up of 361 days (IQR, 190–536), 40.6% remained on letermovir (median, 387 days); 25.0% completed prophylaxis (median, 116 days); and 34.3% discontinued prematurely (median, 49 days), mainly for cost barriers or adverse effects. Breakthrough infections occurred in 9 patients (14.1%), but only three (4.7%) were clinically significant. After stopping letermovir, 39.5% (15/38 among those who discontinued letermovir) developed post‐prophylaxis delayed‐onset CMV infection. Overall survival was 81.2%; there was one death attributed to CMV. Conclusion In this cohort of non‐kidney solid organ recipients, letermovir was well tolerated with low rates of clinically significant breakthrough infections. Early discontinuation was commonly cost‐driven. Post‐prophylaxis delayed‐onset CMV infections remain common. Large‐scale registry studies are needed to provide evidence for use of letermovir in non‐kidney transplant recipients.

Abstract Background Catheter-associated urinary tract infection (CAUTI) is one of the most prevalent nosocomial infection reported and is associated with significant resource expenditure across health care facilities. Methods We conducted a retrospective review of newly catheterized patients at a tertiary hospital over 12-months period. Demographic, clinical, and diagnostic data were collected. Based on the National Health Safety Network (NHSN) criteria, patients were divided into two groups: health care associated infection (HAI) and criteria not met (CNM). Outcome measures included secondary bloodstream infections, hospital re-admission, death, and microbiological relapse at 30 days of hospital discharge. These outcomes were compared between groups. Results A total of 314 patients were identified, of whom 55 (17.5%) met the criteria for HAI. Demographic, clinical and microbiological data are summarized in Tables 1-3. In comparison to the CNM group, the HAI group showed higher rates of fever, urinary frequency, bladder pain or tenderness, costovertebral angle tenderness, positive blood cultures, growth of urinary microorganisms >100,000 colony forming units (CFU), and imaging evidence of infection (p< 0.01). Blood stream infections were observed in 20 (6.6%) patients, with 12 of these in the HAI group, and were attributed to a urinary source in 7 cases. Composite outcomes were affected by fever (p< 0.01), imaging evidence of infection (p< 0.01) and presence of renal abscess, whereas the age of catheter, dysuria, bladder tenderness, urinary frequency, urinary CFU threshold didn't achieve statistical significance. After adjusting for the Charlson Comorbidity Index, the HAI group showed higher rates of re-occurrence of blood stream infections, re-admission and mortality within 30 days (Table 4). Conclusion Fever, imaging evidence of infection, and renal abscess were significant predictors of adverse composite outcomes, whereas catheter age, dysuria, bladder tenderness, urinary frequency, and urinary CFU threshold were not. Refinement of the NHSN surveillance definition of CAUTI may enhance targeted resource allocation for prevention efforts. Disclosures All Authors: No reported disclosures

Abstract Background Cytomegalovirus (CMV) infection remains one of the most prevalent and important infections following solid organ transplant (SOT). Treatment is often challenging, especially when dealing with refractory and resistant CMV infections.Table 1:Univariable logistic regression analyses of associations with early refractory CMV infectionTable 2:Univariable logistic regression analyses of associations with resistant CMV infection Methods We performed a retrospective cohort study of SOT recipients with clinically significant CMV infection (csCMVi) at a tertiary transplant center in the US during 2010-2016. The primary outcome was early refractory CMV infection and secondary outcomes were drug resistance, CMV recurrence, and mortality. Kaplan-Meier estimation, univariable logistic regression analysis, and multivariable Cox regression were used for outcome analysis.Table 3:Multivariable Cox regression analysis of associations with recurrent CMV infection after primary treatment endedNote: Refractory CMV was not included in the model for recurrent CMV as no patients with refractory infection had recurrence. Results A total of 145 SOT recipients with csCMVi were included. Most patients were recipients of liver (49%), followed by kidney (22.1%), heart (6.9%), lung (5.5%), and pancreas (4.1%). Multiple organ transplants accounted for 12.4% of the cohort. Most common induction was an anti-IL-2 antibody (43.9%) followed by ATG (29.5%). 82 (56.5%) had CMV D+/R- mismatch. In total, 34 (23.4%) had CMV syndrome, 38 (26.2%) had tissue-invasive CMV disease, while the rest (50.3%) were asymptomatic. After the initial 3 weeks of antiviral therapy, 13 (8.9%) patients had probable refractory csCMVi; most of them (10 [76.9%]) were CMV D+/R- mismatch. Longer time after transplant had lower risk (OR 0.68; CI 0.48-0.95, p=0.029) while lower absolute lymphocyte count (ALC) was higher risk of early refractory csCMVi (OR 1.54; CI 1.01-2.44, p=0.048) (Table 1). Drug-resistant CMV occurred in 7 patients (4.8%); a high initial CMV DNA level was associated with resistant csCMVi (OR 2; CI 1.08-3.93, p=0.031) (Table 2). Of 144 patients with post-treatment follow-up, 25 (17.2%) experienced recurrent csCMVi within 6 months. Table 3 shows the associations with recurrence of csCMVi after initial treatment. 30 patients (20.7%) died during a median follow-up of 4 years, but refractory, resistant or recurrent CMV were not associated with mortality. Conclusion Refractory csCMVi is associated with low ALC and an earlier onset post-transplant. Resistant csCMVi is associated with high levels of initial CMV DNA. Recurrence of csCMVi is common and possibly associated with low ALC at the end of antiviral treatment. Disclosures All Authors: No reported disclosures

Abstract Background Left ventricular assist devices (LVAD) have an associated infection rate of 13%–80% postimplant. An optimal strategy for surgical infection prophylaxis (SIP) at the time of implantation has not been well defined. We aimed to evaluate the different LVAD implantation antibiotic prophylaxis regimens as well as the incidence of LVAD infection at our institution. Methods We performed a single-center, retrospective study of patients who underwent LVAD implantation between February 2007 and June 2019. The primary outcome was the incidence of LVAD infection (LVADI), within 3 months and 1 year of placement, between patients who received expanded or narrow-spectrum regimens for SIP. We assessed outcomes using Kaplan-Meier, time-to-first event. We used a noninferiority analysis, which was established if the narrow-spectrum event rate was no more than 5% greater than the expanded-spectrum event rate. Results We included 399 patients, 305 (76.4%) patients received narrow-spectrum SIP, whereas the remaining 94 (23.6%) patients received the expanded-spectrum regimen. Statistical noninferiority of the narrow spectrum to the multiple drug regimen was demonstrated at both time points, and statistical superiority of the narrow-spectrum group across 12-month follow up was further evident (P = .037). Conclusions We report evidence supporting noninferiority, or even superiority, of the narrow-spectrum over expanded-spectrum antimicrobial prophylaxis strategy with respect to LVADI. These findings support data-driven antimicrobial prophylaxis strategies.

Abstract Background Directly observed Therapy (DOT) has proven to be a valuable asset used in ascertaining adherence to tuberculosis (TB) medications, methadone, psychiatric medications and HIV medications. Both HIV and TB share the need of adherence to treatment to avoid resistance. However, unlike TB, HIV treatment must be taken for life. Argus Community (Argus DOT) provides Directly Observed Therapy to assist with medication adherence to HIV positive patients with medication adherence barriers who are not virally suppressed as long as the patient is from an affiliated medical provider network which includes St. Barnabas Designated AIDS Center (SBH DAC). Methods SBH DAC started referring patients who have not been virally suppressed to Argus DOT March 2021 to help reach our goal of 90% virally suppressed rate (viral load < 200 copies/ml) by the end of 2021. Those who agreed to DOT were referred, accepted and enrolled in Argus. Argus DOT calls patients daily Monday to Friday to remind them to take their medications. We performed a retrospective chart review of SBH DAC/Argus DOT patients to see if this intervention improved our suppression rate from March 2021 to December 2021 and if there were any barriers for our patients in regards to receiving these benefits. Results 18 patients were approached by the DAC team to enroll in Argus DOT; of those 15 originally agreed to the program. 3 patients declined the enrollment. Of the 15 patients who agreed to the program, 6 patients discontinued the program and none of these 6 patients achieved viral load suppression. Results of 9 patients who stayed with Argus DOT: 8 out of 9 patients achieved a viral load < 200 copies/ml and one achieved 230 copies/ml from 2200 copies/ml. 2 patients achieve a viral load < 20 copies/ml (undetectable). Conclusion This small study shows Argus DOT as valuable asset in achieving decrease HIV viral load in patients with medication adherence barriers. 50% accepting and staying with the program achieved 89% viral suppression; close to the 90% needed to End the Epidemic. 9 out of 18 who did not agree or discontinued Argus DOT due to uncontrolled psychiatric, substance use, nonworking phones and distrust did not achieve viral suppression. Co-located psychiatric, substance use as well as in-house SBH DOT personnel is needed to achieve viral load suppression. Disclosures All Authors: No reported disclosures.