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Background: Nocardiosis is rare after hematopoietic cell transplantation (HCT). Little is known regarding its presentation, management, and outcome in this population., Methods: This retrospective international study reviewed nocardiosis episodes in HCT recipients (1/1/2000-31/12/2018; 135 transplant centers; 33 countries) and described their clinical, microbiological, radiological, and outcome characteristics., Results: We identified 81 nocardiosis episodes in 74 allo- and 7 auto-HCT recipients. Nocardiosis occurred a median of 8 (IQR: 4-18) months post-HCT. The most frequently involved organs were lungs (70/81; 86%) and brain (30/81; 37%); 29 (36%) patients were afebrile; 46/81 (57%) had disseminated infections. The most common lung imaging findings were consolidations (33/68; 49%) or nodules (32/68; 47%); brain imaging findings were multiple brain abscesses (19/30; 63%). Ten of 30 (33%) patients with brain involvement lacked neurological symptoms. Fourteen of 48 (29%) patients were bacteremic. Nocardia farcinica was the most common among molecularly identified species (27%; 12/44). Highest susceptibility rates were reported to linezolid (45/45; 100%), amikacin (56/57; 98%), trimethoprim-sulfamethoxazole (57/63; 90%), and imipenem (49/57; 86%). One-year and last follow-up (IQR: 4-42.5 months) all-cause mortality were 40% (32/81) and 52% (42/81), respectively. In the multivariable analysis, underlying disease not in complete remission (HR: 2.81; 95% CI: 1.32-5.95) and prior bacterial infection (HR: 3.42; 95% CI: 1.62-7.22) were associated with higher 1-year all-cause mortality., Conclusions: Nocardiosis is a late post-HCT infection usually manifesting as a pulmonary disease with frequent dissemination, brain infection, and bacteremia. Brain imaging should be performed in HCT recipients with nocardiosis regardless of neurological symptoms. Overall mortality is high., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Purpose of Review: Brain nocardiosis is a rare but severe infection mostly occurring among immunocompromised patients. In this review, we present recent data on this infection and address some of the common clinical dilemmas encountered in patients with brain nocardiosis., Recent Findings: Strategies used to approach a patient with suspected brain nocardiosis include the 'conservative strategy' (without early neurosurgery) and the 'neurosurgical strategy' (with early aspiration or excision of brain abscess[es]). The advantages and disadvantages of both strategies are summarised. Our opinion is that the use of the 'conservative strategy' should be limited to well-selected patients presenting with an easily accessible extra-neurological lesion(s) and have brain abscesses at low risk of treatment failure. In terms of antimicrobial therapy, we summarise the data supporting the use of a multidrug regimen in patients with brain nocardiosis.Last, we list possible reasons for treatment failure in patients with brain nocardiosis and suggest interventions to overcome them., Summary: Literature is scarce regarding brain nocardiosis, as a consequence of the rarity of this disease. A multidisciplinary and individualised management is required to optimise the outcome of patients with brain nocardiosis., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Transplant recipients are at risk of pulmonary nocardiosis, a life-threatening opportunistic infection caused by Nocardia species. Given the limitations of conventional diagnostic techniques (i.e., microscopy and culture), a polymerase chain reaction (PCR)-based assay was developed to detect Nocardia spp. on clinical samples. While this test is increasingly being used by transplant physicians, its performance characteristics are not well documented. We evaluated the performance characteristics of this test on bronchoalveolar lavage (BAL) fluid samples from lung transplant recipients (LTRs)., Methods: We prospectively included all BAL samples from LTRs undergoing bronchoscopy at our institution between December 2016 and June 2017 (either surveillance or clinically-indicated bronchoscopies). Presence of microbial pathogens was assessed using techniques available locally (including microscopy and 10-day culture for Nocardia). BAL samples were also sent to the French Nocardiosis Observatory (Lyon, France) for the Nocardia PCR-based assay. Transplant physicians and patients were blinded to the Nocardia PCR results., Results: We included 29 BAL samples from 21 patients (18 surveillance and 11 clinically-indicated bronchoscopies). Nocardiosis was not diagnosed in any of these patients by conventional techniques. However, Nocardia PCR was positive in five BAL samples from five of the patients (24%, 95% confidence interval: 11-45%); four were asymptomatic and undergoing surveillance bronchoscopy, and one was symptomatic and was later diagnosed with influenza virus infection. None of the five PCR-positive patients died or were diagnosed with nocardiosis during the median follow-up of 21 months after the index bronchoscopy (range: 20-23 months)., Conclusions: In this prospective study, Nocardia PCR was positive on BAL fluid from one fourth of the LTRs. Nocardia PCR-based assays should be used with caution on respiratory samples from LTRs because of the possible detection of airway colonization using this technique. Larger studies are required to determine the usefulness of the Nocardia PCR-based assay in transplant recipients., Competing Interests: The authors have declared that no competing interests exist.

Purpose of Review: Nocardia spp. is a gram-positive bacteria that may cause infections in humans. Nocardiosis has been described since the early years of transplantation. This review aims to provide an overview of present knowledge regarding posttransplant nocardiosis, with a focus on recent findings., Recent Findings: Nocardiosis is not rare among transplant recipients, especially after thoracic transplantation and/or in case of intense immunosuppressive regimen or use of tacrolimus. Low-dose cotrimoxazole is not effective to prevent nocardiosis. Although lung is the most common site of infection, more than 40% of organ transplant patients have a disseminated infection. As central nervous system involvement is frequent (about 1/3 of the patients) and possibly asymptomatic, brain imaging is mandatory. Diagnosis relies on direct examination and culture; molecular species identification is useful to guide treatment. Although cotrimoxazole is the drug for which we have the strongest clinical experience, other antibiotics such as linezolid, parenteral cephalosporins, carbapenems, and amikacin can be used to treat nocardiosis. Although treatment duration has historically been set to at least 6 months, shorter durations (<120 days) seem associated with a good outcome in selected patients., Summary: Physicians in charge of transplant patients should be aware of nocardiosis. Diagnosis and management of transplant recipients with nocardiosis require a multidisciplinary approach.

Background: Nocardiosis is a rare, life-threatening opportunistic infection, affecting 0.04% to 3.5% of patients after solid organ transplant (SOT). The aim of this study was to identify risk factors for Nocardia infection after SOT and to describe the presentation of nocardiosis in these patients., Methods: We performed a retrospective case-control study of adult patients diagnosed with nocardiosis after SOT between 2000 and 2014 in 36 European (France, Belgium, Switzerland, the Netherlands, Spain) centers. Two control subjects per case were matched by institution, transplant date, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors for nocardiosis., Results: One hundred and seventeen cases of nocardiosis and 234 control patients were included. Nocardiosis occurred at a median of 17.5 (range, 2-244) months after transplant. In multivariable analysis, high calcineurin inhibitor trough levels in the month before diagnosis (odds ratio [OR], 6.11; 95% confidence interval [CI], 2.58-14.51), use of tacrolimus (OR, 2.65; 95% CI, 1.17-6.00) and corticosteroid dose (OR, 1.12; 95% CI, 1.03-1.22) at the time of diagnosis, patient age (OR, 1.04; 95% CI, 1.02-1.07), and length of stay in the intensive care unit after SOT (OR, 1.04; 95% CI, 1.00-1.09) were independently associated with development of nocardiosis; low-dose cotrimoxazole prophylaxis was not found to prevent nocardiosis. Nocardia farcinica was more frequently associated with brain, skin, and subcutaneous tissue infections than were other Nocardia species. Among the 30 cases with central nervous system nocardiosis, 13 (43.3%) had no neurological symptoms., Conclusions: We identified 5 risk factors for nocardiosis after SOT. Low-dose cotrimoxazole was not found to prevent Nocardia infection. These findings may help improve management of transplant recipients., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

The article discusses the impact of sulfonamide allergy labels on the risk of opportunistic infections after solid organ transplantation (SOT). SOT recipients with a sulfonamide allergy label were found to have an increased risk of Toxoplasma and Nocardia infections compared to those without the label. The study highlights the importance of reassessing sulfonamide allergy labels in SOT recipients to optimize prophylactic treatment and reduce the risk of opportunistic infections. Efforts should be made to identify safe delabeling strategies and promote the use of trimethoprim/sulfamethoxazole (TMP‐SMX) in eligible SOT recipients. [Extracted from the article]

Nocardiosis is a rare infection that is often difficult to treat and may be life-threatening. There is no consensus on its management. Our aim was to provide the current evidence for the diagnosis and management of individuals with nocardiosis, and to propose a management approach for this uncommon infection. We systematically searched the medical literature on nocardiosis for studies published between 2010 and 2020 and describing ten or more individuals. Nocardiosis, a primarily opportunistic infection which may occur in immunocompetent persons, most commonly involves the lungs and frequently disseminates to other sites including the central nervous system. The reference standard for Nocardia species identification is molecular biology, and the preferred method for antibiotic susceptibility testing (AST) is broth microdilution. Monotherapy seems appropriate for patients with primary skin nocardiosis or non-severe pulmonary disease; we reserve a multidrug regimen for more severe infections. Species identification and AST results are often missing at initiation of antibiotics. Trimethoprim-sulfamethoxazole is the preferred agent for initial therapy, because Nocardia is very often susceptible to this agent, and because it has been the keystone of nocardiosis treatment for years. Linezolid, to which Nocardia is almost always susceptible, may be an alternative. When combination therapy is required, the repertoire of companion drugs includes third-generation cephalosporins, amikacin and imipenem. Therapeutic modifications should take into account clinical response to initial therapy and AST results. Treatment duration of 6 months is appropriate for most situations, but longer durations are preferred for disseminated nocardiosis and shorter durations are reasonable in low-risk situations. Secondary prophylaxis may be considered in selected individuals with permanent immunosuppression. We hereby provide the clinician with an easy-to-use algorithm for the management of individuals with nocardiosis. We also illuminate gaps in evidence and suggest future research directions. [ABSTRACT FROM AUTHOR]