Absolute Lymphocyte Count: A Predictor of Recurrent Cytomegalovirus Disease in Solid Organ Transplant Recipients.

Background: Recurrent cytomegalovirus (CMV) disease in solid organ transplant recipients frequently occurs despite effective antiviral therapy. We previously demonstrated that patients with lymphopenia before liver transplantation are more likely to develop posttransplant infectious complications including CMV. The aim of this study was to explore absolute lymphocyte count (ALC) as a predictor of relapse following treatment for CMV disease. Methods: We performed a retrospective cohort study of heart, liver, and kidney transplant recipients treated for an episode of CMV disease. Our primary outcome was time to relapse of CMV within 6 months. Data on potential predictors of relapse including ALC were collected at the time of CMV treatment completion. Univariate and multivariate hazard ratios (HRs) were calculated with a Cox model. Multiple imputation was used to complete the data. Results: Relapse occurred in 33 of 170 participants (19.4%). Mean ALC in relapse-free patients was 1.08 ± 0.69 vs 0.73 ± 0.42 × 103 cells/µL in those who relapsed, corresponding to an unadjusted hazard ratio of 1.11 (95% confidence interval, 1.03-1.21; P = .009, n = 133) for every decrease of 100 cells/µL. After adjusting for potential confounders, the association between ALC and relapse remained significant (HR, 1.11 [1.03-1.20]; P = .009). Conclusions: Low ALC at the time of CMV treatment completion was a strong independent predictor for recurrent CMV disease. This finding is biologically plausible given the known importance of T-cell immunity in maintaining CMV latency. Future studies should consider this inexpensive, readily available marker of host immunity.

Role of Secondary Prophylaxis With Valganciclovir in the Prevention of Recurrent Cytomegalovirus Disease in Solid Organ Transplant Recipients.

BACKGROUND: Cytomegalovirus (CMV) is a major contributor to morbidity and mortality in solid organ transplant recipients (SOTRs). Ganciclovir and valganciclovir are highly effective antiviral drugs with a well-established role in primary prophylaxis and treatment of CMV disease. Our objective in this study was to examine the effect of secondary prophylaxis (SP) on the risk of relapse in SOTRs following an episode of CMV disease. METHODS: We performed a retrospective cohort study of SOTRs from 1995 to 2015 and used propensity score-based inverse probability of treatment weighting methodology to control for confounding by indication. A weighted Cox model was created to determine the effect of SP on time to relapse within 1 year of treatment completion. RESULTS: Fifty-two heart, 34 liver, 79 kidney, and 5 liver-kidney transplant recipients who completed treatment for an episode of CMV infection/disease were included. A total of 120 (70.6%) received SP (median duration, 61 days; range, 5-365) and 39 (23%) relapsed. SP was protective against relapse from 0 to 6 weeks following treatment completion (hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.05-0.69). However, after 6 weeks, risk of relapse did not significantly differ between the 2 groups (HR, 1.18; 95% CI, 0.46-2.99). CONCLUSIONS: Our findings demonstrate that use of SP following treatment of CMV disease did not confer long-term protection against relapse, although it did delay relapse while patients were receiving antivirals. This suggests that SP has limited clinical utility in the overall prevention of recurrent CMV disease.

Characteristics and outcomes of neutropenia after orthotopic liver transplantation.

Neutropenia after orthotopic liver transplantation (LT) is relatively common, but the factors associated with its development remain elusive. We assessed possible predictors of neutropenia (absolute neutrophil count [ANC] ≤ 1000/mm(3) ) within the first year of LT in a cohort of 304 patients at a tertiary medical center between 1999 and 2009 using time-dependent survival analysis to identify risk factors for neutropenia. In addition, we analyzed neutropenia as a predictor of the clinical outcomes of death, bloodstream infection (BSI), invasive fungal infection, cytomegalovirus (CMV) disease, and graft rejection within the first year of LT. Of the 304 LT recipients, 73 (24%) developed neutropenia, 5 (7%) of whom had grade 4 neutropenia (ANC < 500/mm(3) ). The following were independent predictors for neutropenia: Child-Turcotte-Pugh score (hazard ratio [HR] 1.15; 95% confidence interval [CI], 1.03-1.30; P = 0.02), BSI (HR, 2.89; 95% CI, 1.63-5.11; P < 0.001), CMV disease (HR, 4.28; 95% CI, 1.55-11.81; P = 0.005), baseline tacrolimus trough level (HR, 1.02; 95% CI, 1.01-1.03; P = 0.007), and later era LT (2004-2009 versus 1999-2003; HR, 2.28; 95% CI, 1.43-3.65; P < 0.001). Moreover, neutropenia was found to be an independent predictor for mortality within the first year of LT (HR, 3.76; 95% CI, 1.84-7.68; P < 0.001). In conclusion, our data suggest that neutropenia within a year after LT is not unusual and is an important predictor of mortality.

Pretransplant lymphopenia is a novel prognostic factor in cytomegalovirus and noncytomegalovirus invasive infections after liver transplantation.

Infection after liver transplantation (LT) remains a leading cause of morbidity and mortality. The risk of infection after LT is highest in those who are most immunosuppressed, but to date, no standard blood marker of one's degree of immunosuppression or risk index has been established. The purpose of this study was to determine whether pretransplant lymphopenia (absolute lymphocyte count < 500 cells/mm3 within 24 hours before LT) is a candidate marker of immunosuppression and could be useful in predicting the risk of cytomegalovirus (CMV) disease and non-CMV invasive infections after LT. Data were extracted from medical records for all primary, solitary LT procedures performed at Tufts Medical Center from 1999 to 2009. Two hundred seventy-six patients had sufficient data to be included in the analysis. Among these patients, 52% developed CMV or non-CMV invasive infections within 5 years of LT. Within 2 years, 23 (8%) had CMV disease, and 103 (37%) at least 1 non-CMV invasive infection. More lymphopenic patients than nonlymphopenic patients developed CMV (21% versus 4%, P < 0.001) and non-CMV invasive infections (50% versus 33%, P = 0.02). In a multivariate survival analysis, pretransplant lymphopenia was the strongest independent predictor of CMV disease [hazard ratio (HR) = 5.52, 95% confidence interval (CI) = 2.31-13.1, P = 0.001] after adjustments for known risk factors, including CMV serostatus (HR = 4.72, 95% CI = 2.01-11.1, P < 0.001). Both pretransplant lymphopenia (HR = 1.64, 95% CI = 1.14-2.53, P = 0.03) and CMV (HR = 2.93, 95% CI = 1.23-6.92, P = 0.02) independently predicted non-CMV infections. Our results suggest that pretransplant lymphopenia is a novel independent predictor of both CMV disease and non-CMV invasive infections after LT and is a candidate marker of immunosuppression in LT recipients.

Infectious Aspects of Chronic Wounds.

The treatment, maintenance, and suppression of infection in chronic wounds remain a challenge to all practitioners. From an infectious disease standpoint, knowing when a chronic wound has progressed from colonized to infected, when to use systemic antimicrobial therapy and when and how to culture such wounds can be daunting. With few standardized clinical guidelines for infections in chronic wounds, caring for them is an art form. However, there have been notable advances in the diagnosis, treatment, and management of infected wounds. This article will discuss the pathophysiology of infection in older adults, including specific infections such as cutaneous candidiasis, necrotizing soft tissue infection, osteomyelitis, and infections involving hardware.

Multidisciplinary expert consensus statements and recommendations for use of hypochlorous acid as a solution for negative pressure wound therapy with instillation.

BACKGROUND: HOCl (eg, pHAp) preserved solutions have antimicrobial properties and are considered safe and effective for wound management. NPWTi-d (or NPWTi) is an established adjunctive wound modality for a variety of wound etiologies in various anatomic locations in which an instillate solution dwells on the surface of the wound to assist in wound bed preparation. A variety of solutions have been used, including 0.9% normal saline wound cleansers and antiseptics. pHAp is growing in popularity as the solution of choice for NPWTi-d. OBJECTIVE: To evaluate consensus statements on the use of NPWTi-d with pHAp. METHODS: A 15-member multidisciplinary panel of expert clinicians in the United States, Canada, and France convened in person in April 2023 in Washington, D.C. and/or corresponded later to discuss 10 statements on the use of pHAp with NPWTi-d. The panelists then replied "agree" or "disagree" to each statement and had the option to provide comments. RESULTS: Ten consensus statements are presented, along with the proportion of agreement or disagreement and summary comments. Although agreement with the statements on NPWTi-d with pHAp varied, the statements appear to reflect individual preferences for use rather than concerns about safety or efficacy. CONCLUSION: The consensus indicates that NPWTi-d with pHAp can have a beneficial effect in wound care.

Voriconazole use and pharmacokinetics in combination with interferon-gamma for refractory cryptococcal meningitis in a patient receiving low-dose ritonavir.

We present a case of relapsing cryptococcal meningitis unresponsive to standard therapy. Voriconazole induction, including the utilization of voriconazole therapeutic drug monitoring in both serum and CSF, with transition to voriconazole plus interferon-gamma (IFN-gamma) was successfully used in a patient receiving antiretroviral therapy with abacavir/lamivudine and lopinavir/ritonavir. Initial voriconazole levels at standard doses of 4 mg/kg twice daily intravenously were low when co-administered with lopinavir/ritonavir but increased to recommended therapeutic levels with an increase of the voriconazole dose to 7 mg/kg twice daily. This case highlights the utility of voriconazole therapeutic drug monitoring when prescribed concurrently with a ritonavir boosted protease inhibitor and the potential role of combination therapy with IFN-G for refractory cryptococcal meningitis.