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Background: The treatment of tuberculosis (TB) in solid organ transplant (SOT) recipients is challenging owing to interactions between rifampin and immunosuppressive drugs. Rifabutin, a rifamycin with excellent activity against Mycobacterium tuberculosis and that induces cytochrome p450 less, may facilitate treatment. We report our experience with rifabutin for treating TB in SOT recipients and review the available literature. Methods: A retrospective observational study of all SOT recipients with TB between January 2000 and December 2019. The clinical characteristics and outcomes of patients treated with and without rifabutin‐containing regimens were compared and a literature review was conducted. Results: We included 31 SOT recipients with TB, among whom 22 (71%) were men and the median age was 62 years (interquartile range 50‐20). There were no significant differences between patients treated with rifabutin (n = 12), rifampin (n = 14), and non‐rifamycins (n = 5) in clinical cure rates (83.3%, 64.3%, and 100%, respectively; P =.21), side effects (25%, 37.5%, and 20%, respectively; P =.74), or mortality (16.7%, 35.7%, and 0%, respectively; P =.21). Only one patient, treated with rifampin, suffered graft rejection. The literature review identified 59 SOT recipients with TB treated with rifabutin‐containing regimens from 8 publications. Overall, the clinical cure, graft rejection, and mortality rates were 93.2%, 5.1%, and 6.8%, respectively. Conclusions: Rifabutin‐containing regimens offer a reliable alternative to rifampin when treating TB in SOT recipients. [ABSTRACT FROM AUTHOR]

Background: The management and outcomes of nontuberculous mycobacterial (NTM) infections in solid organ transplant (SOT) recipients are poorly characterized. We aimed to describe the management and 1-y mortality of these patients., Methods: Retrospective, multinational, 1:2 matched case-control study included SOT recipients aged 12 y old or older diagnosed with NTM infection between January 1, 2008, and December 31, 2018. Controls were matched on transplanted organs, NTM treatment center, and posttransplant survival at least equal to the time to NTM diagnosis. The primary aim was 1-y mortality after NTM diagnosis. Differences between cases and controls were compared using the log-rank test, and Cox regression models were used to identify factors associated with mortality at 12 mo among cases., Results: In 85 patients and 169 controls, the median age at the time of SOT was 54 y (interquartile range, 40-62 y), 59% were men, and the lungs were the most common site of infection after SOT (57.6%). One-year mortality was significantly higher in cases than in controls (20% versus 3%; P < 0.001), and higher mortality was associated with lung transplantation (hazard ratio 3.27; 95% confidence interval [1.1-9.77]; P = 0.034). Median time (interquartile range) from diagnosis to treatment initiation (20 [4-42] versus 11 [3-21] d) or the reduction of net immunosuppression (36% versus 45%, hazard ratio 1.35 [95% CI, 0.41-4.43], P = 0.618) did not differ between survivors and those who died., Conclusions: NTM disease in SOT recipients is associated with a higher mortality risk, especially among lung transplant recipients. Time to NTM treatment and reduction in net immunosuppression were not associated with mortality., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Interferon-y Release Assays (IGRA) reversions have been reported in different clinical scenarios for the diagnosis of tuberculosis (TB) infection. This study aimed to determine the rate of QuantiFERON-TB Gold Plus (QFT-Plus) reversions during contact investigation as a potential strategy to reduce the number of preventive treatments., Methods: Prospective, multicentre cohort study of immunocompetent adult contacts of patients with pulmonary TB tested with QFT-Plus. Contacts with an initial positive QFT-Plus (QFT-i) underwent a second test within 4 weeks (QFT-1), and if negative, underwent a repeat test 4 weeks later (QFT-2). Based on the QFT-2 result, we classified cases as sustained reversion if they remained negative and as temporary reversion if they turned positive., Results: We included 415 contacts, of whom 96 (23.1%) had an initial positive test (QFT-i). Following this, 10 had negative QFT-1 results and 4 (4.2%) of these persisted with a negative result in the QFT-2 (sustained reversions). All four sustained reversions occurred in contacts with IFN-γ concentrations between ≥0.35 and ≤0.99 IU•mL-1 in one or both QFT-i tubes., Conclusion: In this study, TB contact investigations rarely reveal QFT-Plus reversion. These results do not support retesting cases with an initial positive result to reduce the number of preventive treatments., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: M. S. received fees for participating in an advisory board with Pfizer Ltd (2 hours). The remaining authors declare no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Pérez-Recio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Risk factors for nontuberculous mycobacteria (NTM) infections after solid organ transplant (SOT) are not well characterized. Here we aimed to describe these factors., Methods: Retrospective, multinational, 1:2 matched case-control study that included SOT recipients ≥12 years old diagnosed with NTM infection from 1 January 2008 to 31 December 2018. Controls were matched on transplanted organ, NTM treatment center, and post-transplant survival greater than or equal to the time to NTM diagnosis. Logistic regression on matched pairs was used to assess associations between risk factors and NTM infections., Results: Analyses included 85 cases and 169 controls (59% male, 88% White, median age at time of SOT of 54 years [interquartile range {IQR} 40-62]). NTM infection occurred in kidney (42%), lung (35%), heart and liver (11% each), and pancreas transplant recipients (1%). Median time from transplant to infection was 21.6 months (IQR 5.3-55.2). Most underlying comorbidities were evenly distributed between groups; however, cases were older at the time of NTM diagnosis, more frequently on systemic corticosteroids and had a lower lymphocyte count (all P < .05). In the multivariable model, older age at transplant (adjusted odds ratio [aOR] 1.04; 95 confidence interval [CI], 1.01-1.07), hospital admission within 90 days (aOR, 3.14; 95% CI, 1.41-6.98), receipt of antifungals (aOR, 5.35; 95% CI, 1.7-16.91), and lymphocyte-specific antibodies (aOR, 7.73; 95% CI, 1.07-56.14), were associated with NTM infection., Conclusions: Risk of NTM infection in SOT recipients was associated with older age at SOT, prior hospital admission, receipt of antifungals or lymphocyte-specific antibodies. NTM infection should be considered in SOT patients with these risk factors., Competing Interests: Potential conflicts of interest. C. M. C. reports the following grants or contracts unrelated to this work: Centers for Disease Control and Prevention (CDC) subaward from Johns Hopkins University to the Washington University in St. Louis (funding by the CDC grant number 1U54CK000617-01-00), vendor/individual agreement with Wayne State University for a case registry, and Associate Editor for Open Forum Infectious Diseases (1 May 2022 through 30 April 2023). D. F. P. reports payment or honoraria as a speaker for an antibiotic course for UMC Utrecht and as a teacher for Hospital Pharmacists in training for PAO; and participation on DSMB for the COBRA trial (Very short-course versus standard course antibiotic therapy in patients with acute Cholangitis after adequate endoscopic biliaRy drainage) in the Netherlands. M. J. M. reports consulting fees from Insmed and Biomerieux; payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from Microsoft Diagnostics (MSD), Insmed, and Teva; support for attending meetings and/or travel from MSD, Berlin Chemie; and participation on a Data Safety Monitoring Board or Advisory Board for Biomerieux, Insmed, MSD. J. T. S. reports payment or honoraria for manuscript writing for Gilead on subjects not related to this manuscript. M. B. reports support from Pfizer for attending a congress. N. K. reports royalties or licenses from Up To Date; consulting fees from Astellas, AstraZeneca, Biotest, ExeViR, Hansa, Merck Sharp and Dohme, Glasgow Smith Kline, Novartis Pharma, Takeda; payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from Astellas, Biotest, CSL Behring, Chiesi, Novartis Pharma, Sanofi, Sandoz, Takeda; and support for attending meetings and/or travel from Astellas, Novartis Pharma, Takeda. N. J. M. reports support for attending meetings and/or travel paid to author from Biotest; unpaid participation on a Data Safety Monitoring Board or Advisory Board for a CTX3 Study and paid participation on Advisory Boards for Takeda, MSD, and Pfizer. N. M. T. reports payment or honoraria for guest lecture for Boston Medical Center and Beth Israel Medical Center; payment for expert testimony for record review for Ficksman & Conley, LLP, in Boston, Massachusetts; participation on a Data Safety Monitoring Board or Advisory Board for United Network for Organ Sharing HIV Organ, Policy Equity (HOPE) Act Safety Review, and Workgroup (unpaid); role as Chair of the American Society of Transplantation and leadership or fiduciary role with Infectious Diseases Community of Practice (unpaid). O. M. reports payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from MSD; and participation on a Data Safety Monitoring Board or Advisory Board for MSD. S. Be. reports grants or contracts unrelated to this work from Vancouver Costal Health Research Institute and Transplant Research Foundation of BC; payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from Merck; and participation on an Advisory Board for Evusheld (AstraZeneca). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To evaluate the real-world clinical efficacy of ceftolozane/tazobactam (C/T) in difficult-to-treat infections caused by multi-drug resistant Gram-negative microorganisms, including carbapenem-resistant Pseudomonas aeruginosa., Methods: Retrospective cohort study of adult patients treated with C/T for at least 48 hours for infections caused by multi-drug resistant Gram-negative bacteria in a tertiary hospital from May 2016 until August 2019. The primary outcome analysed was clinical failure, defined as a composite of symptomatology persistence after 7 days of C/T treatment, infection recurrence, and/or all-cause mortality within 30 days of follow-up., Results and Discussion: 96 episodes of C/T treatment were included, mostly consisting of targeted treatments (83.9%) for the following sources of infection: intra-abdominal (22.6%), urinary tract (25.8%), skin and soft tissue (19.4%), hospital-acquired pneumonia (14%), and other (6.4%). The most frequently isolated bacteria were carbapenem-resistant (88, 94.6%). Clinical failure rate was 30.1%, due to persistent infection at day 7 (4.3%), recurrence of the initial infection (16.1%), or 30-day all-cause mortality (8.6%). Adverse events most frequently reported were Clostridium difficile infection (9%) and cholestasis (8%)., What Is New and Conclusion: C/T showed a favourable clinical profile for difficult-to-treat multidrug-resistant and carbapenem-resistant Gram-negative infections, regardless of the source of infection., (© 2022 John Wiley & Sons Ltd.)

We investigated whether the difference of antigen tube 2 (TB2) minus antigen tube 1 (TB1) (TB2-TB1) of the QuantiFERON-TB gold plus test, which has been postulated as a surrogate for the CD8 + T-cell response, could be useful in identifying recent tuberculosis (TB) exposure. We looked at the interferon gamma (IFN-γ) responses and differences in TB2 and TB1 tubes for 686 adults with QFT-plus positive test results. These results were compared among groups with high (368 TB contacts), low (229 patients with immune-mediated inflammatory diseases [IMID]), and indeterminate (89 asylum seekers or people from abroad [ASPFA]) risks of recent TB exposure. A TB2-TB1 value >0.6 IU·ml -1 was deemed to indicate a true difference between tubes. In the whole cohort, 13.6%, 10.9%, and 11.2% of cases had a TB2>TB1 result in the contact, IMID, and ASPFA groups, respectively ( P  = 0.591). The adjusted odds ratios (aORs) for an association between a TB2-TB1 result of >0.6 IU·ml -1 and risk of recent exposure versus contacts were 0.71 (95% confidence interval [CI], 0.31 to 1.61) for the IMID group and 0.86 (95% CI, 0.49 to 1.52) for the ASPFA group. In TB contact subgroups, 11.4%, 15.4%, and 17.7% with close, frequent, and sporadic contact had a TB2>TB1 result ( P  = 0.362). The aORs versus the close subgroup were 1.29 (95% CI, 0.63 to 2.62) for the frequent subgroup and 1.55 (95% CI, 0.67 to 3.60) for the sporadic subgroup. A TB2-TB1 difference of >0.6 IU·ml -1 was not associated with increased risk of recent TB exposure, which puts into question the clinical potential as a proxy marker for recently acquired TB infection. IMPORTANCE Contact tuberculosis tracing is essential to identify recently infected people, who therefore merit preventive treatment. However, there are no diagnostic tests that can determine whether the infection is a result of a recent exposure or not. It has been suggested that by using the QuantiFERON-TB gold plus, an interferon gamma (IFN-γ) release assay, a difference in IFN-γ production between the two antigen tubes (TB2 minus TB1) of >0.6 IU·ml -1 could serve as a proxy marker for recent infection. In this large multinational study, infected individuals could not be classified according to the risk of recent exposure based on differences in IFN-γ in TB1 and TB2 tubes that were higher than 0.6 IU·ml -1 . QuantiFERON-TB gold plus is not able to distinguish between recent and remotely acquired tuberculosis infection, and it should not be used for that purpose in contact tuberculosis tracing.

Background: Systematic screening for, and treatment of, latent tuberculosis (TB) infection is recommended prior to kidney transplant. However, little is known about patient compliance with, or the safety profile of, preventive therapies used in clinical practice., Methods: This was a retrospective observational study of patients who were eligible for kidney transplant and were evaluated for TB infection between January 2013 and June 2019 at the TB clinic of a tertiary care teaching hospital. All patient data were registered prospectively as part of our nurse-led program before kidney transplant. We assessed completion rates, tolerance with therapy, development of TB, and associated workload., Results: In total, 1568 patients were referred to our TB clinic for evaluation. Preventive therapy was given to 385 patients and completed by 340 (88.3%). Of these, 89 (23.1%) experienced some intolerance, with 27 requiring full discontinuation. After a median follow-up of 45 months (1426 patient-years), 206 (53.5%) of the treated patients received a kidney transplant; only one patient, who failed to complete treatment, developed post-transplant TB (7.01 cases per 10 000 patient-years; 95% confidence interval, 0.35-34.59). Extra nurse or medical visits were required by 268 (69.6%) patients., Conclusion: Despite the complexity and workload generated by patients with ESRD awaiting kidney transplant, preventive therapy for TB is effective in most cases. Our experience provides important evidence on the feasibility of preventive therapy for TB before kidney transplant when delivered as part of a comprehensive nurse-led program., (© 2021 Wiley Periodicals LLC.)