ABSTRACT Acinetobacter baumannii most often causes pneumonia in critically ill patients. However, A. baumannii is also an important cause of a broader range of infections, including skin/wound and urinary tract infections. This study aims to evaluate the in vitro activity of sulbactam-durlobactam and comparator antibiotics, including meropenem and cefiderocol against A. baumannii-calcoaceticus complex isolates from non-respiratory and non-bloodstream sources. Samples included 285 A. baumannii-calcoaceticus complex isolates enriched for carbapenem resistance collected across 17 states in the United States (January 2023–May 2025). Antimicrobial susceptibility tests were conducted by manual broth microdilution and interpreted according to Clinical and Laboratory Standards Institute (CLSI) and Food and Drug Administration (FDA) (cefiderocol) standards. A. baumannii complex isolates were primarily cultured from skin/wound (58.6%), urinary tract (31.6%), and other sources (9.8%), including cerebrospinal and peritoneal fluid. Carbapenem resistance was observed in approximately 70% of isolates and more common among skin/wound cultures. Sulbactam-durlobactam was observed to be highly active (96.9% susceptible [S]; MIC90 4 mg/L) and demonstrated greater activity than sulbactam (37.9% S; MIC90 32 mg/L). Sulbactam-durlobactam also displayed high susceptibility rates across isolate sources, ranging from 96.4 (skin/wound) to 97.8% (urine). Cefiderocol demonstrated similar in vitro activity across culture sources and patient location, inhibiting >90 and >80% of isolates at CLSI and FDA susceptible breakpoints, respectively. Minocycline susceptibility was 69.1%, while tigecycline and eravacycline MICs50/90 were 1/4 and 0.5/1 mg/L, respectively. The observed data are consistent with results from surveillance studies among respiratory and bloodstream isolates and show that sulbactam-durlobactam demonstrates potent in vitro activity against clinical A. baumannii complex isolates from a variety of culture sources.IMPORTANCEAcinetobacter baumannii is a difficult-to-treat pathogen that often affects hospitalized patients and is known for a high level of multi-drug resistance. While commonly associated with pneumonia, it also causes infections in wounds, the urinary tract, and other parts of the body. This study shows that sulbactam-durlobactam is highly effective against A. baumannii from various infection sites. The results are important because they can inform clinicians on the susceptibility profiles of A. baumannii from a variety of infection sources, not just lung and bloodstream. As new antibiotics come onto the market, it is important to continuously assess resistance patterns to inform patient and system-wide health decisions.
Acinetobacter baumannii most often causes nosocomial bacteremia and pneumonia. However, A. baumannii is becoming an important cause of a broader range of infections including skin and soft tissue infection (SSTI) and urinary tract infections (UTI). This study aims to evaluate the in vitro activity of sulbactam-durlobactam and other clinically utilized antibiotics against A. baumannii-calcoaceticus complex isolates isolated from non-respiratory and non-bloodstream sources. Samples included 193 A. baumannii-calcoaceticus complex isolates collected from 2023-2025 across 19 states. Susceptibility tests for sulbactam-durlobactam (durlobactam fixed concentration of 4 mg/L), and comparator agents were conducted by manual broth microdilution and interpreted according to CLSI and FDA (cefiderocol) standards. A. baumannii complex isolates were primarily cultured from skin and soft tissue (56.5%), followed by urinary tract (31.6%) and other sources (11.9%) including bone biopsy, fluid aspirate etc. ICU patients contributed 20% of the isolates. Sulbactam-durlobactam was observed to be highly active (98.5% susceptible [S]; MIC50/90 1/4 mg/L), demonstrating greater activity than ampicillin-sulbactam (41.5% S; MIC50/90 8/32 mg/L) and meropenem (32.1% S; MIC50/90 32/128 mg/L). Sulbactam-durlobactam also displayed high susceptibility rates across sample sources, ranging from 97.3% (skin and soft tissue) to 100% (urine). The MIC50/90 and susceptibility rates for all other agents including tetracycline derivatives are shown in Table 1. Notably, among the carbapenem-resistant A. baumannii (CRAB) isolates (n=130) in the collection, sulbactam-durlobactam retained high activity (97.7% S) relative to ampicillin-sulbactam (16.2% S). Cefiderocol inhibited 97.7% and 75.4% of isolates at CLSI and FDA susceptible breakpoints, respectively. The data reported here are consistent with results from surveillance studies among non-respiratory and bloodstream isolates and show that sulbactam-durlobactam demonstrates in vitro activity against clinical A. baumannii complex isolates from urinary tract and SSTI sources, including isolates that are resistant to ampicillin-sulbactam, carbapenems, and cefiderocol. Tomefa E. Asempa, PharmD, Innoviva: Grant/Research Support Robin R. Chamberland, PhD D(ABMM), bioMerieux: Advisor/Consultant|Pattern Bioscience, Inc.: Advisor/Consultant|Pattern Bioscience, Inc.: Grant/Research Support Jonathan Hand, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|Ferring: Grant/Research Support|Innoviva: Advisor/Consultant|Janssen: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Scynexis: Grant/Research Support|The Antibiotic Resistance Leadership Group (ARLG): Grant/Research Support|The Antibiotic Resistance Leadership Group (ARLG): Honoraria Amanda Harrington, PhD, Beckman Coulter: Grant/Research Support|bioMerieux/BioFire: Advisor/Consultant|bioMerieux/BioFire: Grant/Research Support|bioMerieux/BioFire: Honoraria|BioRad: Advisor/Consultant|Selux: Grant/Research Support Wesley D. Kufel, Pharm.D., BCPS, BCIDP, Merck & Co.: Grant/Research Support|Shionogi, Inc: Grant/Research Support|Shionogi, Inc: Honoraria Lars Westblade, PhD, Elements Materials Technology: Grant/Research Support|Hardy Diagnostics: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Selux Diagnostics: Grant/Research Support|Shionogi: Advisor/Consultant|SNIPRBIOME: Grant/Research Support Thomas Kirn, MD PhD, BD: Advisor/Consultant|BD: Honoraria Brian Mochon, PhD, D(ABMM), Shionogi: Advisor/Consultant Mark Fisher, PhD, Shionogi Inc.: Advisor/Consultant Rebekah Dumm, PhD D(ABMM), BD: Advisor/Consultant|BD: Grant/Research Support|Biomerieux: Advisor/Consultant|Biomerieux: Grant/Research Support|Diasorin: Grant/Research Support|Pattern Biosciences: Grant/Research Support|Qiagen: Grant/Research Support|Roche Diagnostics: Advisor/Consultant|Shionogi: Advisor/Consultant David P. Nicolau, PharmD, CARB-X: Grant/Research Support|Innoviva: Advisor/Consultant|Innoviva: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support
Background:The clinical and microbiological features of infection due to non-tuberculous mycobacteria (NTM) after hematopoietic stem-cell transplantation (HSCT) remain poorly understood. Methods:We performed a retrospective, multinational case-control study that included HSCT recipients (≥12 years) diagnosed with NTM disease between January 2008 and December 2018. Controls were HSCT recipients with no evidence of NTM disease, matched (1:2 ratio) by participating center and post-transplant survival. Logistic regression on matched pairs was used to investigate risk factors for NTM disease. Results:We included 25 cases of NTM disease. The most common HSCT type was allogeneic from unrelated donor (72.0%) after myeloablative conditioning (76.0%). Predominant hematological conditions were acute myelogenous leukemia (28.0%) and myelodysplastic syndrome (24.0%). Most patients (88.0%) had previously received immunosuppressive therapy. The most common species identified were Mycobacterium avium complex (64.0%) and rapidly growing mycobacteria (20.0%). Most patients (68.0%) had pulmonary disease. All but one received antimycobacterial therapy for a median of 267.5 days. Macrolides (83.3%), rifamycins (58.3%) and ethambutol (62.5%) were the most commonly used drugs. Four patients (16.7%) developed adverse events requiring therapy discontinuation. All-cause and attributable mortality rates were 28.0% and 4.0%, respectively. One patient experienced relapse after 464 days. Diagnosis of a non-NTM infection (adjusted odds ratio [aOR]: 3.11; 95% confidence interval [95% CI]: 1.25-7.78) and corticosteroid therapy (aOR: 2.88; 95% CI: 1.16-7.17), both within the previous 90 days, were associated with NTM disease. Conclusions:NTM disease is a serious complication among heavily immunocompromised HSCT recipients associated with prior non-NTM infection and corticosteroid therapy.
Patients with mechanical circulatory support (MCS) devices and those who undergo heart transplants are at risk for invasive fungal infections (IFI). Though Candida and Aspergillus spp. account for most infections, the evolving epidemiology of resistant-Candida spp. such as Candida auris, endemic mycoses, and other molds impacted by climate change, threaten MCS and transplant patients. Fungal diagnostics are overall limited, and current, widely used antifungal agents are suboptimal with significant toxicities. However, innovative diagnostic strategies coupled with novel antifungal agents for prevention and treatment of invasive fungal disease encourage optimism for MCS and transplant patients and clinicians.
BACKGROUND Transplanting kidneys from donors with HIV to recipients with HIV has become standard clinical practice. However, donors with HIV may have higher prevalence of viral and bacterial infections and autoimmunity that could increase allograft rejection in recipients. METHODS We included deceased kidney donors (60 with HIV and 41 without HIV) who participated in a multicenter prospective study of HIV kidney transplantation between April 2018 and September 2021. Using phage immunoprecipitation sequencing, we compared the human antibody repertoire (allergens, autoantibodies, viruses, and bacterial toxins) between donors with and without HIV and evaluated their association with recipient allograft rejection. Moderated t tests were used to assess reactivity and a multivariate logistic regression model adjusted for donor sex and kidney donor profile index assessed the association between donor adenovirus reactivity and recipient allograft rejection. RESULTS Compared with donors without HIV, donors with HIV had lower BMI and were more likely to be African American. The median number of positive autoantibodies was marginally higher among donors with HIV (499 [IQR, 357, 579]) compared with that of donors without HIV (395 [IQR, 256, 538], P = 0.058). Donors with HIV additionally had significantly higher antibody reactivity to Epstein-Barr virus and cytomegalovirus ( q < 0.05). Among all donors with and without HIV, antibodies against adenovirus were significantly associated with increased rejection among recipients, including after adjusting for false discovery ( q < 0.05) and also adjusting for demographic factors using multivariable logistic regression (odds ratio = 4.97; 95% CI = 1.89–13.61). CONCLUSION The presence of antibodies against adenovirus infection in kidney donors with HIV may be associated with allograft rejection. TRIAL REGISTRATION ClinicalTrials.gov NCT03500315. FUNDING US NIH.
Background: The 2013 HIV Organ Policy Equity Act facilitated HIV-to-HIV organ transplants, enabling people with HIV to receive transplants more quickly. However, managing drug interactions between ART and immunosuppressive regimens remains a challenge. Objective: This study assesses the safety and effectiveness of cabotegravir/rilpivirine (CAB/RPV), an injectable ART, in maintaining HIV virologic suppression in kidney and liver transplant recipients. Methods: A retrospective review of three clinical studies evaluated CAB/RPV in transplant recipients with HIV. Participants had suppressed HIV RNA levels before transplant and were monitored post-transplant every six months. Results: Nine transplant recipients (7 kidney, 2 liver) received CAB/RPV. All maintained HIV suppression, with no allograft loss, although one liver recipient experienced acute rejection. One participant died from trauma unrelated to the transplant or HIV. Conclusion: CAB/RPV shows promise for HIV management after transplantation. Further research is needed using a larger cohort.
Background Strongyloides stercoralis infection can be associated with high mortality in solid organ transplant (SOT) recipients, yet global practices regarding screening and management remain poorly characterized. We conducted an international survey to evaluate knowledge, screening, and management practices among healthcare workers (HCWs) involved in SOT care.Methods We performed a cross-sectional, web-based survey of HCWs caring for SOT candidates and recipients. The survey assessed provider characteristics, knowledge of strongyloidiasis, as well as screening and management practices. Descriptive statistics were used to summarize responses.Results A total of 101 HCWs responded, including 65 (64%) infectious diseases (ID) providers and 36 (36%) non-ID providers. Knowledge gaps were identified regarding transmission and mortality, particularly among non-ID providers. Overall, 85% of respondents reported screening SOT candidates for S. stercoralis; among those who screen, serology is the most commonly used method. Screening strategies varied by geographic region, with universal screening more common in endemic areas and targeted screening in non-endemic regions. Management practices, including approaches to indeterminate or negative test results, showed substantial heterogeneity.Conclusions This international survey demonstrates considerable variability in knowledge, screening, and management of strongyloidiasis among HCWs involved in SOT care. These findings highlight opportunities for improved education, clearer guidance, and greater standardization of practices related to Strongyloides infection to avoid unnecessary morbidity.
Background:Norovirus infection causes significant morbidity in solid organ transplant (SOT) recipients, yet few treatments are available, and evidence for efficacy is sparse. In this scoping review, we identify and evaluate potential interventions for managing norovirus infections in SOT recipients. Methods:We searched electronic databases from inception to July 6, 2025. Eligible studies were analyzed for participants' characteristics, intervention types, and reported outcomes. Results:After screening 245 abstracts, 58 studies were included (1 randomized controlled trial, 27 cohort studies, 5 case series and 25 case reports), mainly from the United States. Transplant types included kidney (n = 36), liver (n = 12), cardiac (n = 12), pulmonary (n = 7), pancreas (n = 6), small bowel (n = 7), and multiorgan (n = 13) transplants. The most frequently reported primary outcome was resolution of gastrointestinal (GI) symptoms. Interventions were diverse: immunosuppression modification (n = 14), nitazoxanide (n = 6), IVIG (n = 3), oral immunoglobulin (n = 10), combination of these (n = 19), fecal transplant (n = 2), supportive management (n = 4), and others not classified (n = 5). Limited quality evidence for the resolution of gastrointestinal symptoms was reported for immunosuppression modification (n = 7/14), nitazoxanide (n = 4/6), IVIG (n = 2/3), oral immunoglobulin alone (n = 10/10), fecal transplant (n = 2/2), supportive treatment (n = 4/4), and a combination of treatments (n = 10/19). A lack of clinical improvement was described in 13 of 58 studies. Conclusions:A wide range of interventions has been used to manage norovirus infections in SOT recipients; however, the evidence is limited to observational studies, and the findings are uncertain. High-quality randomized controlled trials are needed to establish treatment efficacy and safety.
BACKGROUND:Few studies have examined pretransplant CD4 count and risk of post-kidney transplant (KT) infection in persons with HIV (PWH). METHODS:This multi-center, retrospective cohort study included adult PWH undergoing KT from 2004 to 2019. The primary outcome was infection in the first year post-KT in PWH with pretransplant CD4 < 350 cells/µL versus CD4 ≥ 350 cells/µL. Relative risk was assessed using modified Poisson modeling. Restricted mean survival time analysis was used to assess 5-year posttransplant outcomes. RESULTS:Of the 75 patients included, 27% had a pretransplant CD4 < 350 cells/µL. Those with CD4 < 350 versus CD4 ≥ 350 were more likely to be hospitalized for infection in the first year (55% versus 16%, p = 0.001). There were no significant differences in relative risk of infection in the first-year posttransplant (RR: 1.31, p = 0.053), 5-year overall survival (87.5% vs. 93%, p = 0.49) or 5-year graft loss (29.4% vs. 23.1%, p = 0.61) between groups. CONCLUSION:These findings suggest that pretransplant CD4 count alone may not reflect the true risk of post-KT infection in PWH.
Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract illnesses (LRI) worldwide, particularly affecting high-risk groups such as cancer patients, solid organ transplant (SOT) recipients, older adults, and those with significant comorbidities. The Advisory Committee on Immunization Practices (ACIP) recommends vaccinating adults aged ≥75 years, and those aged 60-74 at greater risk for severe RSV disease (1). Recently, they proposed expanding this recommendation to at-risk patients aged 50-59 (2). Our study aims to investigate outcomes of RSV infection and identify risk factors for complications in various populations.Table 1:Baseline characteristics and clinical outcomes of patients with RSV-related respiratory viral infection by underlying conditions.aData are no. (%) unless otherwise specified; bn=528; cn=419; dn=435; en=159; fn=298; gn=332; hn=263; in=512; jn=520; kn=443; ln=379=; mn=214.*In post-hoc analysis, the comparisons between the cancer and the non-cancer/SOT groups, and the SOT and non-cancer/SOT groups were statistically significant (p < 0.05).**The HCT indication was primary immunodeficiency disorder.***Coinfections included rhinovirus (n=18), endemic human coronavirus (n=9), SARS-CoV-2 (n=8), parainfluenza virus (n=3), adenovirus (n=1), influenza virus (n=3), CMV pneumonitis (n=2), Pseudomonas aerogenes (n=10), Streptococcus pneumonia (n=4), Stenotrophomonas melophilia (n=3), Haemophilus influenza (n=3), staphylococcus aureus (MSSA) (n=4), staphylococcus aureus (MRSA) (n=1), Legionella pneumophila (n=1), Nocardia (n=1), Escherichia coli (n=1), Aspergillus (n=4), Zygomycete (n=1), Pneumocystis jirovecii (n=1) .Abbreviations: ALL, acute lymphocytic leukemia; AML, acute myeloid leukemia; BiPAP, bilevel positive airway pressure; BITE, Bispecific T cell Engager; BMI, body mass index; CAR-T, chimeric antigen receptor T-cell therapy; CKD, chronic kidney disease; CLL, chronic lymphocytic leukemia; CMML, Chronic myelomonocytic leukemia; CML, Chronic myeloid leukemia; HCT, hematopoietic stem cell transplantation; HFNC, high-flow nasal cannula; HIV, human immunodeficiency virus; HM, haematologic malignancy; ICU, intensive care unit; IQR, intra-quartile range; IVIG, intravenous immunoglobulin; LRI, lower respiratory tract infection; MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasms; RSV, respiratory syncytial virus; RVI, respiratory virus infection; SOT, solid organ transplantation; SD, standard deviation; TIA, transient ischemic attack; URI, upper respiratory tract infection.Table 2a:Multivariable analysis (logistic regression) for risk factors of lower respiratory tract infection. Table 2b: Multivariable analysis (logistic regression) for risk factors of 30-day all-cause mortality.Abbreviations: aOR, adjusted odds ratio; LRI, lower respiratory tract infection; RVI, respiratory viral infection; SOT, solid organ transplantation; 95% CI, 95% confidence interval. We conducted an international multicenter retrospective observational study including adults with RSV infection across six centers in the USA, the Netherlands, Israel, and Taiwan from October 2018 to April 2024. Patients were categorized based on underlying conditions: cancer, SOT recipients, and those without either. Primary outcomes included LRI and 30-day all-cause and RSV-related mortality.Figure 1:RSV infection outcomes stratified by age groupsAbbreviations: LRI, lower respiratory tract infection; RSV, respiratory syncytial virus; SOT, solid organ transplantation. * In the SOT group, only one patient was aged over 80. This patient progressed to LRI and died from another etiology after 19 days of follow-up.Figure 2:30-day all-cause mortality according to the underlying condition type and the infection site.Abbreviations: LRI, lower respiratory tract infection; RVI, respiratory virus infection; SOT, solid organ transplantation; URI, upper respiratory tract infection We analyzed 562 patients: 425 (75.6%) with cancer, mainly hematologic malignancies (HMs), and 53 (9.4%) SOT recipients (Table 1). Most patients without either cancer or SOT (84 patients, 15.0%) had significant comorbidities, with 73.8% having a Charlson comorbidity index (CCI) ≥4. Overall LRI rates were 46.8% (48.9% in cancer patients, 35.8% in SOT recipients, and 42.9% in others), with 30-day mortality of 8.0% (7.3% in cancer patients, 11.3% in SOT recipients, and 9.5% in others). LRI and mortality by age group and underlying condition are presented in Figure 1. Independent risk factors for LRI were older age, higher CCI, HMs, smoking, recent steroid use, lymphopenia, and elevated creatinine levels, but the type of underlying condition was not independently associated with LRI (Table 2a). Independent risk factors for 30-day mortality were SOT (compared to cancer), metastatic solid malignancy, nosocomial infection, neutropenia, respiratory co-infection, and LRI (Table 2b, Figure 2). The study highlights significant morbidity and mortality from RSV in patients with cancer and SOT recipients, as well as in patients without these conditions who are over 50 years of age. Jonathan Hand, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|Ferring: Grant/Research Support|Innoviva: Advisor/Consultant|Janssen: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Scynexis: Grant/Research Support|The Antibiotic Resistance Leadership Group (ARLG): Grant/Research Support|The Antibiotic Resistance Leadership Group (ARLG): Honoraria Lior Nesher, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Honoraria|F2G: Grant/Research Support|GSK: Advisor/Consultant|GSK: Honoraria|Medison: Advisor/Consultant|Moderna: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Pfizer: Grant/Research Support|Pfizer: Honoraria|Takeda: Honoraria Roy F. Chemaly, MD, MPH, FIDSA, FACP, FESCMID, ADMA Biologics: Advisor/Consultant|AiCuris: Advisor/Consultant|AiCuris: Grant/Research Support|Ansun Biopharma: Advisor/Consultant|Ansun Biopharma: Grant/Research Support|Assembly Bio: Advisor/Consultant|Astellas: Advisor/Consultant|Eurofins Viracor: Advisor/Consultant|Eurofins Viracor: Grant/Research Support|Genentech: Grant/Research Support|Gilead: Advisor/Consultant|InflaRX: Advisor/Consultant|IntegerBio: Advisor/Consultant|Karius: Advisor/Consultant|Karius: Grant/Research Support|Merck/MSD: Advisor/Consultant|Merck/MSD: Grant/Research Support|Moderna: Advisor/Consultant|Oxford Immunotec: Advisor/Consultant|Pfizer: Advisor/Consultant|Shionogi: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Grant/Research Support|Tether: Advisor/Consultant
BACKGROUND:Due to high prevalence of Kaposi sarcoma-associated herpesvirus (KSHV) among people with human immunodeficiency virus (HIV), KSHV-associated disease (KAD) may be increased after kidney transplantation from donors with HIV (HIV D+) to recipients with HIV (HIV R+). METHODS:Anti-KSHV antibodies were measured in HIV R+ and donors with and without HIV (HIV D-) using a 30-antigen multiplex assay within 3 multicenter kidney transplantation studies. KSHV seropositivity was defined as reactivity to conventional KSHV antigens (≥1 ORF73 or K8.1); reactivity to expanded 5-antigen and 30-antigen panels were also reported. Risk factors were identified using modified Poisson regression. Recipients were monitored for posttransplant anti-KSHV antibody changes and KAD. RESULTS:KSHV seroprevalence was 40.6% (143/352) among HIV R+, 25.2% (33/131) among HIV D+, and 7.5% (4/53) among HIV D-. In the multivariable model, only men who have sex with men (MSM) status was associated with KSHV seropositivity (relative risk, 1.51 [95% confidence interval {CI}, 1.07-2.14] in recipients and 2.39 [95% CI, 1.03-5.53] in donors). Among 418 HIV R+ (215 HIV D+/R+, 203 HIV D-/R+), there were 5 KAD cases (incidence, 0.63 cases/100 person-years [95% CI, .26-1.52]): 3 skin-only Kaposi sarcoma (KS), 1 multicentric Castleman disease, and 1 allograft KS. The allograft KS occurred in a female HIV D+/R+ and was likely donor derived. Remaining KAD cases occurred in male HIV D-/R+ and were likely recipient KSHV reactivation or acquisition. CONCLUSIONS:In the United States, KSHV seroprevalence in donors and recipients with HIV was high, particularly among MSM. Reassuringly, KSHV-associated disease was rare and primarily attributed to recipient rather than donor-derived KSHV.
BACKGROUND:Kidney transplantation (KT) from donors with human immunodeficiency virus (HIV-1) to recipients with HIV (HIV D+/R+) is noninferior to KT from donors without HIV (HIV D-/R+) with regard to safety. However, there may be differences in posttransplant infections. METHODS:We performed a secondary analysis of the HOPE in Action KT Study (NCT02602262) comparing the time to first clinically relevant infection within 24 months posttransplantation in 99 HIV D+/R+ versus 99 HIV D-/R+. Secondary outcomes included incidence rates, infection-related death, and timing of clinically relevant infection, each stratified by donor HIV status. RESULTS:The cumulative incidence of a clinically relevant infection at 24 months posttransplantation was 73.8% (95% confidence interval [CI]: 63.1%-81.2%) for HIV D+/R+ versus 64.7% (95% CI: 53.0%-73.4%) for HIV D-/R+. Comparing time to first clinically relevant infection in HIV D+/R+ versus HIV D-/R+, the adjusted hazard ratio (aHR) was 1.44 (95% CI: 1.01-2.04) at 24 months posttransplantation; for infections associated with hospitalization, the aHR was not significantly higher (1.21 [95% CI: .78-1.86). There were no significant differences in the number of infections, death from infection, duration, or site of infection between HIV D+/R+ versus HIV D-/R+, though viral infections were numerically more common in HIV D+/R+ (40% vs 35%). CONCLUSIONS:Although there was a statistically significant association between receipt of a kidney from a donor with HIV and time to first clinically relevant infection in the 24 months posttransplantation, there were no differences in infections associated with hospitalization. These data are overall reassuring as this emerging practice expands into clinical care. Clinical Trials Registration. NCT02602262.
The worldwide shortage of donor hearts necessitates transplant programs reassess organs once declined due to infection-related concerns. Donor-derived infections (DDIs) are rare, complicating fewer than 0.2 % of solid-organ transplants, whereas wait-list mortality for advanced heart failure reaches 10-15 % annually. This review synthesizes modern epidemiology, transmission rates, and management for major pathogen groups, integrating guideline updates, Disease Transmission Advisory Committee (DTAC) ten-year surveillance, and recent CDC investigations. With transparent risk communication, recipient screening, and targeted prophylaxis or pre-emptive therapy, many donors with infections can be safely utilized, while others may pose risks that preclude acceptance. Infection transmission fears, uncertainty, and inconsistent protocols likely contribute to variations in center-to-center donor utilization. The objective of this review is, therefore, practical: to delineate which infections are acceptable with mitigation, quantify true transmission probability, and offer an evidence-based playbook for clinicians.
BACKGROUND:Lower allograft survival has been demonstrated in kidney transplant recipients without HIV whose donors have 2 apolipoprotein L1 ( APOL1 ) renal risk variants (RRVs). The effects of APOL1 RRV on kidney transplant outcomes in people with HIV have not been fully assessed. METHODS:Genomic DNA was analyzed for APOL1 RRV genotype using a probe-based assay in HIV-positive kidney transplant recipients (R + ) and their respective HIV-negative (D - ) or HIV-positive (D + ) kidney donors participating in HIV transplantation studies in South Africa (SA) and the United States (US). Allograft outcomes (time to first rejection, HIV-associated nephropathy, graft failure, or death) were compared by both donor and recipient RRV status. RESULTS:Genomic DNA was available for 21 donors with HIV and 38 HIV D + /R + recipients in the SA cohort, and 57 donors (40 D + and 17 D - ) and 119 recipients (49 HIV D + /R + and 70 D - /R + ) in the US cohort. Recipient outcomes were not associated with recipient APOL1 genotype. However, recipients whose donor carried 1 versus 0 APOL1 RRV were significantly more likely to experience a negative composite outcome ( P < 0.02 for both cohorts independently), which led to an adjusted hazard ratio of a poor composite outcome of 2.9 (95% confidence interval, 1.1 to 7.4) and 10.1 (95% confidence interval, 2.4 to 42.7) in the SA and US cohorts, respectively. CONCLUSIONS:In two independent cohorts, the presence of 1 APOL1 RRV in a donor kidney led to significantly worse posttransplant outcomes. Further research into the interaction between the allograft environment and donor APOL1 genotype in people with HIV is required.
Kidney transplantation from donors with HIV has recently become standard clinical practice, but the plasma inflammatory profile is not well characterized. Thirty-two cytokines and chemokines were evaluated among donors with HIV (n = 63) and without HIV (n = 41). Wilcoxon rank sum test was used to compare cytokines between groups. Donors with and without HIV were generally similar in terms of characteristics, except those with HIV had a non-significantly lower kidney donor profile index, reflecting better graft survival, creatinine, and body mass index. Most cytokine and chemokine levels were similar between groups. However, median IL-8 levels were higher (p < 0.0015) in donors without HIV (32.6 pg/mL, IQR = 13.8-394.9) compared to donors with HIV (15.1 pg/mL, IQR = 8.4-35.5). There were no significant correlations between cytokine and chemokine concentrations and CD4 counts or HIV viral load. In summary, inflammatory profiles were similar or lower among donors with HIV compared to donors without HIV supporting the safety of this emerging kidney transplantation practice.
Historically, liver transplant (LT) candidates with human immunodeficiency virus (HIV) have experienced high waitlist mortality. Since the HIV Organ Policy Equity (HOPE) Act expands access to organs from donors with HIV, we assessed the impact of HOPE on LT rate and wait time for this population. We linked data from a multicenter HOPE in Action study to Scientific Registry of Transplant Recipients (February 21, 2019 to June 1, 2024) and used Poisson regression to compare transplant rates among 99 candidates willing to accept HOPE donors (HOPE candidates) to 13 495 candidates with or without HIV not listed as willing to accept HOPE donors (non-HOPE candidates) matched on transplant center. The median time to any deceased donor liver transplant (DDLT) was 2.3 months for HOPE and 1.1 years for non-HOPE candidates. Within 2 years of listing, 90.9% of HOPE versus 58.5% of non-HOPE candidates received a DDLT (P < .001). HOPE was associated with an overall 3.11-fold higher DDLT incident rate ratio (95% CI 2.48-3.88, P < .001). Stratified by model for end-stage liver disease score categories 6 to 14, 15 to 24, 25 to 34, and 35 to 40/status 1; HOPE candidates had 10.12-fold, 5.31-fold, 1.41-fold and 2.90-fold higher DDLT rates, respectively. Willingness to accept livers from donors with HIV improves access to liver transplantation for candidates with HIV.
Infections caused by carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (ABC) are associated with high mortality rates and limited treatment options. This study aims to evaluate the in vitro activity of clinically utilized antimicrobials against a contemporary collection of ABC isolates with a predominant carbapenem-resistant phenotype. Geographically dispersed US medical centers (n = 22) provided non-duplicate respiratory and bloodstream ABC isolates for surveillance testing. Antimicrobial susceptibility testing was conducted by broth microdilution and interpreted according to Clinical & Laboratory Standards Institute (CLSI) and Food and Drug Administration (FDA) breakpoints. ABC isolates (n = 523) from respiratory tract (74.4%) and blood (25.6%) sources were recovered from patients (2023-2024). Forty percent were obtained from intensive care unit patients. Carbapenem non-susceptibility was observed in 76.9% of isolates and was more common among respiratory tract cultures. The addition of durlobactam to sulbactam decreased the MIC90 by three-doubling dilutions from 32 to 4 µg/mL, increasing the susceptibility rate to 96.9% from 33.8%. Genome sequencing of sulbactam-durlobactam non-susceptible isolates (16/523; n = 3.1%) revealed MBL and non-enzymatic resistance mechanisms. Cefiderocol inhibited 93.5% and 76.1% of isolates at CLSI and FDA susceptible breakpoints, respectively. Minocycline susceptibility was <50%, while tigecycline and eravacycline MIC50/90 were 1/2 and 0.5/1 µg/mL, respectively. Sulbactam-durlobactam displayed high activity against sulbactam (95.4%), carbapenem (96.3%), and cefiderocol (95.2%) non-susceptible isolates. Susceptibility rates of clinically utilized antimicrobials against a US collection of ABC isolates ranged from 23% to 97%, with meropenem displaying the lowest rate and sulbactam-durlobactam demonstrating the highest overall rate. Sulbactam-durlobactam activity was preserved against sulbactam, carbapenem, and cefiderocol non-susceptible isolates among respiratory tract and bloodstream isolates.