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Background Methods Results Conclusion Despite the burden of pyelonephritis after kidney transplantation, there is no consensus on initial empirical antibiotic management.We surveyed clinicians throughout the world on their practice and opinions about the initial empirical therapy of post‐transplant pyelonephritis, using clinical vignettes. A panel of experts from 19 countries on six continents designed this survey, and invited 2145 clinicians to participate.A total of 721 clinicians completed the survey (response rate: 34%). In the hypothetical case of a kidney transplant recipient admitted with pyelonephritis but not requiring intensive care, most respondents reported initiating either a 3rd‐generation cephalosporin (37%) or piperacillin‐tazobactam (21%) monotherapy. Several patient‐level factors dictated the selection of broader‐spectrum antibiotics, including having a recent urine culture showing growth of a resistant organism (85% for extended‐spectrum ß‐lactamase‐producing organisms, 90% for carbapenemase‐producing organisms, and 94% for Pseudomonas aeruginosa). Respondents attributed high importance to the appropriateness of empirical therapy, which 87% judged important to prevent mortality. Significant practice and opinion variations were observed between and within countries.High‐quality studies are needed to guide the empirical management of post‐transplant pyelonephritis. In particular, whether prior urine culture results should systematically be reviewed and considered remains to be determined. Studies are also needed to clarify the relationship between the appropriateness of initial empirical therapy and outcomes of post‐transplant pyelonephritis. [ABSTRACT FROM AUTHOR]

This document is a meeting report summarizing the presentations and discussions from the 2023 GTI Annual Meeting, which focused on new approaches to manage infectious complications in transplant recipients. Topics covered included new anti-infective agents and non-antibiotic approaches to manage infections caused by multidrug-resistant bacteria, staphylococci, and fungi, as well as new approaches to manage urinary tract infections in kidney transplant recipients. The report highlights the need for innovative strategies to address the challenges of treating infections in transplant recipients, who are at high risk of difficult-to-treat infections and side effects associated with anti-infective agents. The document also consists of a list of references to various scientific articles related to the treatment of infections in specific populations, such as kidney transplant recipients and patients with hematologic malignancies. The articles cover topics such as the use of antibiotics, the efficacy of different treatments, and the impact of gut microbiota on infection development. Some articles discuss the emergence of antibiotic resistance and potential solutions, such as bacterial vaccines. The document provides a comprehensive list of recent research in the field of infection treatment and prevention. It is a valuable resource for researchers and healthcare professionals interested in the field of infectious disease treatment. [Extracted from the article]

This document is a meeting report summarizing the presentations and discussions from the 2023 GTI Annual Meeting, which focused on new approaches to manage infectious complications in transplant recipients. Topics covered included new anti-infective agents and non-antibiotic approaches to manage infections caused by multidrug-resistant bacteria, staphylococci, and fungi, as well as new approaches to manage urinary tract infections in kidney transplant recipients. The report highlights the need for innovative strategies to address the challenges of treating infections in transplant recipients, who are at high risk of difficult-to-treat infections and side effects associated with anti-infective agents. The report also discusses the use of fecal microbiota transplantation and the development of molecules to protect the gut microbiota from the effects of antibiotics. Additionally, it provides an overview of new antibiotics that have been developed to combat carbapenem-resistant bacteria. The document also consists of a list of references to various scientific articles related to antibiotic resistance and treatment in different contexts, including solid organ transplant recipients and kidney transplant recipients. The articles cover topics such as the efficacy of specific antibiotics, the management of multidrug-resistant infections, the treatment of asymptomatic bacteriuria, and the use of probiotics and fecal microbiota transplantation. The articles provide valuable insights into the current research and practices in the field of antibiotic treatment and resistance. [Extracted from the article]

Background Patients without human immunodeficiency virus (HIV) are increasingly recognized as being at risk for cryptococcosis. Knowledge of characteristics of cryptococcosis in these patients remains incomplete. Methods We conducted a retrospective study of cryptococcosis in 46 Australian and New Zealand hospitals to compare its frequency in patients with and without HIV and describe its characteristics in patients without HIV. Patients with cryptococcosis between January 2015 and December 2019 were included. Results Of 475 patients with cryptococcosis, 90% were without HIV (426 of 475) with marked predominance in both Cryptococcus neoformans (88.7%) and Cryptococcus gattii cases (94.3%). Most patients without HIV (60.8%) had a known immunocompromising condition: cancer (n = 91), organ transplantation (n = 81), or other immunocompromising condition (n = 97). Cryptococcosis presented as incidental imaging findings in 16.4% of patients (70 of 426). The serum cryptococcal antigen test was positive in 85.1% of tested patients (319 of 375); high titers independently predicted risk of central nervous system involvement. Lumbar puncture was performed in 167 patients to screen for asymptomatic meningitis, with a positivity rate of 13.2% where meningitis could have been predicted by a high serum cryptococcal antigen titer and/or fungemia in 95% of evaluable cases. One-year all-cause mortality was 20.9% in patients without HIV and 21.7% in patients with HIV (P =.89). Conclusions Ninety percent of cryptococcosis cases occurred in patients without HIV (89% and 94% for C. neoformans and C. gattii , respectively). Emerging patient risk groups were evident. A high level of awareness is warranted to diagnose cryptococcosis in patients without HIV. [ABSTRACT FROM AUTHOR]

Background: The characteristics and outcomes of adult patients with respiratory syncytial virus (RSV) infection who require ICU admission are poorly defined. Although several studies in adults with RSV infection have been published in recent years, they did not focus specifically on patients with critical illness.Research Question: What are the characteristics and outcomes of adult patients in the ICU with RSV infection and how do they compare with those of patients in the ICU with influenza infection?Study Design and Methods: This retrospective, multicenter study in France and Belgium (17 sites) compared the characteristics and outcomes of adult patients in the ICU with RSV infection vs those with influenza infection between November 2011 and April 2018. Each patient with RSV infection was matched by institution and date of diagnosis with a patient with influenza infection. In-hospital mortality was compared between the two groups, with adjustment for prognostic factors in a multivariate model (sex, age, main underlying conditions, and concurrent bloodstream infection).Results: Data from 618 patients (309 with RSV infection and 309 with influenza infection) were analyzed. Patients with RSV infection were significantly more likely to have an underlying chronic respiratory condition (60.2% vs 40.1%; P < .001) and to be immunocompromised (35% vs 26.2%; P = .02) than patients with influenza infection. Several differences in clinical signs and biological data at diagnosis were found between the groups. In-hospital mortality was not significantly different between the two groups (23.9% in the RSV group vs 25.6% in the influenza group; P = .63), even after adjustment for prognostic factors in a multivariate model.Interpretation: Adult patients in the ICU with RSV infection differ from adult patients in the ICU with influenza in terms of comorbidities and characteristics at diagnosis. RSV infection was associated with high in-hospital mortality, approaching 25%. In multivariate analysis, RSV infection was associated with a similar odds of in-hospital death compared with influenza infection. [ABSTRACT FROM AUTHOR]

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]

Many transplant physicians screen for and treat asymptomatic bacteriuria (ASB) during post-kidney-transplant surveillance. We investigated whether antibiotics are effective in reducing the occurrence of symptomatic urinary tract infection (UTI) in kidney transplant recipients with ASB. We performed this multicentre, randomized, open-label trial in kidney transplant recipients who had ASB and were ≥2 months post-transplantation. We randomly assigned participants to receive antibiotics or no therapy. The primary outcome was the incidence of symptomatic UTI over the subsequent 12 months. One hundred and ninety-nine kidney transplant recipients with ASB were randomly assigned to antibiotics (100 participants) or no therapy (99 participants). There was no significant difference in the occurrence of symptomatic UTI between the antibiotic and no-therapy groups (27%, 27/100 versus 31%, 31/99; univariate Cox model: hazard ratio 0.83, 95%CI: 0.50–1.40; log-rank test: p 0.49). Over the 1-year study period, antibiotic use was five times higher in the antibiotic group than in the no-therapy group (30 antibiotic days/participant, interquartile range 20–41, versus 6, interquartile range 0–15, p < 0.001). Overall, 155/199 participants (78%) had at least one further episode of bacteriuria during the follow-up. Compared with the participant's baseline episode of ASB, the second episode of bacteriuria was more frequently caused by bacteria resistant to clinically relevant antibiotics (ciprofloxacin, cotrimoxazole, third-generation cephalosporin) in the antibiotic group than in the no-therapy group (18%, 13/72 versus 4%, 3/83, p 0.003). Applying a screen-and-treat strategy for ASB does not reduce the occurrence of symptomatic UTI in kidney transplant recipients who are more than 2 months post-transplantation. Furthermore, this strategy increases antibiotic use and promotes the emergence of resistant organisms. [ABSTRACT FROM AUTHOR]

Background: During routine post-kidney transplant care, most European transplant physicians screen patients for asymptomatic bacteriuria. The usefulness of this strategy is debated. To make screening cost-effective, asymptomatic bacteriuria should be prevalent enough to justify the expense, and antibiotics should improve patient outcomes significantly if asymptomatic bacteriuria is detected. Regrettably, the prevalence of asymptomatic bacteriuria among kidney transplant recipients is not well defined. Methods: To determine the prevalence of asymptomatic bacteriuria among kidney transplant recipients, we did a cross-sectional study among kidney transplant recipients undergoing routine surveillance in three outpatient transplant clinics in Belgium and France. We excluded patients who were in the first two months post-transplantation and/or had a urinary catheter. Asymptomatic participants who had a urine culture with one organism isolated at ≥ 105 CFU/mL were asked to provide a confirmatory urine specimen. Asymptomatic bacteriuria was defined per Infectious Diseases Society of America guidelines. Results: We screened 500 consecutive kidney transplant recipients. Overall, the prevalence of asymptomatic bacteriuria was 3.4% (17/500 patients). It was similarly low among kidney transplant recipients who were between 2 and 12 months after transplantation (1.3%, 1/76 patients) and those who were farther after transplantation (3.8%, 16/424 patients: p = 0.49). Asymptomatic bacteriuria was significantly associated with female gender (risk ratio 3.7, 95% CI 1.3–10.3, p = 0.007) and older age (mean age: 61 ± 12 years [bacteriuric participants], versus 53 ± 15 years [non-bacteriuric participants], p = 0.03). One participant’s colistin-resistant Escherichia coli isolate carried the globally disseminated mcr-1 gene. Conclusions: Among kidney transplant recipients who are beyond the second month post-transplant, the prevalence of asymptomatic bacteriuria is low. Further studies are needed to ascertain the cost-effectiveness of a screen-and-treat strategy for asymptomatic bacteriuria in this population. [ABSTRACT FROM AUTHOR]

Background Urinary tract infection is the most common infection among kidney transplant recipients (KTRs). Many transplant physicians fear that host compromise will allow low-virulence strains to cause pyelonephritis in KTRs, so they often treat asymptomatic bacteriuria with antibiotics. Identification of the host/microbe factors that determine the clinical presentation (i.e. pyelonephritis versus asymptomatic bacteriuria) once an Escherichia coli strain enters a KTRs bladder could inform management decisions. Methods We prospectively collected all E. coli isolates causing either pyelonephritis or asymptomatic bacteriuria in KTRs at our institution (December 2012–June 2015). Whole-genome sequencing was used to assess bacterial characteristics (carriage of 48 virulence genes and phylogenetic and clonal background). Host parameters were also collected. Results We analysed 72 bacteriuria episodes in 54 KTRs (53 pyelonephritis, 19 asymptomatic bacteriuria). The pyelonephritis and asymptomatic bacteriuria isolates exhibited a similar total virulence gene count per isolate [median 18 (range 5–33) and 18 (5–30), respectively; P = 0.57] and for individual virulence genes differed significantly only for the prevalence of the pap operon (pyelonephritis 39%,versus asymptomatic bacteriuria 0%; P = 0.002). No other significant between-group differences were apparent for 86 other bacterial and host variables. Conclusions Our findings suggest that bacterial adherence plays a role in the pathogenesis of pyelonephritis in KTRs despite significantly altered host urinary tract anatomy and weakened immunity. Whether KTRs might benefit from targeted therapies (e.g. vaccination or inhibitors of fimbrial adhesion) has yet to be studied. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The survey done by Kumar and colleagues also shows that infectious diseases physicians and transplant physicians have different perspectives on the management of kidney transplant recipients with pyelonephritis. Dear Editor, The kidney is by far the most commonly transplanted organ, and urinary tract infection is the most common infection after kidney transplantation.[1] Despite that, many clinical questions remain understudied, and therefore unanswered, regarding the optimal management of kidney transplant recipients with urinary tract infection.[2] This is particularly true for pyelonephritis, that is, a major event that generally requires hospital admission, decreases kidney graft function, and reduces quality of life among kidney transplant recipients. [Extracted from the article]

Nocardiosis is a rare but potentially severe bacterial opportunistic infection that may occur after solid organ transplantation (SOT), typically among thoracic transplant recipients and/or in recipients with a high degree of immunosuppression due to anti-rejection therapy [1]. The physiopathology of post-transplant nocardiosis remains poorly understood, and it is unclear why nocardiosis sometimes occur late after transplantation among minimally immunosuppressed SOT recipients. Sera from nocardiosis cases were sampled around the transplantation date (Tx) or around the date of nocardiosis diagnosis (Noc). [Extracted from the article]

Background Asymptomatic bacteriuria is frequent in kidney transplant recipients (KTRs). However, there is no consensus on diagnosis or management. We conducted a European survey to explore current practice related to the diagnosis and management of asymptomatic bacteriuria in adult KTRs. Methods A panel of experts from the European Renal Association–European Dialysis Transplant Association/Developing Education Science and Care for Renal Transplantation in European States working group and the European Study Group for Infections in Compromised Hosts of the European Society of Clinical Microbiology and Infectious Diseases designed this cross-sectional, questionnaire-based, self-administered survey. Invitations to participate were e-mailed to European physicians involved in the care of KTRs. Results Two hundred and forty-four participants from 138 institutions in 25 countries answered the survey (response rate 30%). Most participants [72% (176/244)] said they always screen for asymptomatic bacteriuria in KTRs. Six per cent (15/240) reported never treating asymptomatic bacteriuria with antibiotics. When antimicrobial treatment was used, 24% of the participants (53/224) said they would start with empirical antibiotics. For an episode of asymptomatic bacteriuria caused by a fully susceptible microorganism and despite no contraindications, a majority of participants (121/223) said they would use a fluoroquinolone (n  = 56), amoxicillin/clavulanic acid (n  = 38) or oral cephalosporins (n  = 27). Conclusions Screening for and treating asymptomatic bacteriuria are common in KTRs despite uncertainties around the benefits and harms. In an era of antimicrobial resistance, further studies are needed to address the diagnosis and management of asymptomatic bacteriuria in these patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Whether trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis prevents nocardiosis in solid organ transplant (SOT) recipients is controversial. To assess the effect of TMP-SMX in the prevention of nocardiosis after SOT, its dose-response relationship, its effect on preventing disseminated nocardiosis, and the risk of TMP-SMX resistance in case of breakthrough infection. A systematic review and individual patient data meta-analysis. MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science Core Collection, and Scopus up to 19 September 2023. (a) Risk of nocardiosis between SOT recipients with and without TMP-SMX prophylaxis, or (b) sufficient details to determine the rate of TMP-SMX resistance in breakthrough nocardiosis. SOT recipients. TMP-SMX prophylaxis versus no prophylaxis. Risk Of Bias In Non-randomized Studies-of Exposure (ROBINS-E) for comparative studies; dedicated tool for non-comparative studies. For our primary outcome (i.e. to determine the effect of TMP-SMX on the risk of nocardiosis), a one-step mixed-effects regression model was used to estimate the association between the outcome and the exposure. Univariate and multivariable unconditional regression models were used to adjust for the potential confounding effects. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Individual data from three case-control studies were obtained (260 SOT recipients with nocardiosis and 519 uninfected controls). TMP-SMX prophylaxis was independently associated with a significantly decreased risk of nocardiosis (adjusted OR = 0.3, 95% CI 0.18–0.52, moderate certainty of evidence). Variables independently associated with an increased risk of nocardiosis were older age, current use of corticosteroids, high calcineurin inhibitor concentration, recent acute rejection, lower lymphocyte count, and heart transplant. Breakthrough infections (66/260, 25%) were generally susceptible to TMP-SMX (pooled proportion 98%, 95% CI 92–100). In SOT recipients, TMP-SMX prophylaxis likely reduces the risk of nocardiosis. Resistance appears uncommon in case of breakthrough infection. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Therapeutic drug monitoring of mycophenolic acid (MPA) is usually performed with a limited sampling strategy (LSS), which relies on a limited number of blood samples and subsequent extrapolation of the global exposure to MPA. LSS is usually performed successfully with mycophenolate mofetil (MMF), but data on enteric-coated mycophenolate sodium (ECMPS) are scarce. Here, we evaluated the feasibility of 6-h LSS therapeutic drug monitoring with EC-MPS compared with MMF monitoring among kidney transplant recipients. Methods: Sixty-two patients who received EC-MPS during the first 6 months of transplantationwere compared with a matched group of 64 MMF-treated kidney transplant recipients. The area under the curve (AUC) was computed by LSS using multiple concentration time points (0, 1, 2, 3 and 6 h post-dose) and a trapezoidal rule. Patients had MPA therapeutic drug monitoring performed on two occasions, one within 2 weeks and the second after 3-4 months of transplantation. Results: EC-MPS monitoring and MMF therapeutic drug monitoring were not interpretable in 34.5% (n = 40/116) and 1.8% (n = 2/112) of patients, respectively {relative risk [RR] 19.3 [95% confidence interval (CI) 4.8-78.0]; P < 0.0001}. The main cause of abnormal EC-MPS therapeutic drug monitoring was delayed absorption of both the previous evening and the morning dose, resulting in MPA plasma levels before the next morning dose being higher than MPA plasma levels measured at 1, 2 and 3 h after taking EC-MPS. Cyclosporin in association with MMF significantly increased the risk of low AUC values (<30 mg h/L) in comparison with tacrolimus [55% (n = 11/20) and 10% (n = 9/88), respectively; RR 5.4 (95% CI 2.6-11.2); P < 0.0001]. Conclusions: The risk of therapeutic drug monitoring failure with EC-MPS is >30% during the first 6 months of renal transplantation. Delayed pharmacokinetics was the main reason. In contrast, the risk of therapeutic drug monitoring failure was substantially lower with MMF. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion High‐intensity chemotherapy and advances in novel immunotherapies have seen the emergence of cytomegalovirus (CMV) infections in cancer patients other than allogeneic haemopoietic cell transplantation (HCT).AimTo evaluate the epidemiology, clinical characteristics and outcomes of CMV infection in this population.A retrospective review of cancer patients other than allogeneic HCT who had CMV DNAemia and/or disease from July 2013 till May 2020 at a quaternary cancer centre was performed.Of 11 485 cancer patients who underwent treatment during this period, 953 patients had CMV DNA testing performed and 238 of them had CMV DNAemia. After excluding patients with allogeneic HCT, 62 patients with CMV DNAemia were identified, of whom 10 had concurrent CMV disease. The most frequent underlying malignancies were B‐cell lymphoproliferative disease (LPD) (31%; 19/62), T‐cell LPD (21%; 13/62), chronic lymphocytic leukaemia (11%; 7/62) and multiple myeloma (10%; 6/62). Most patients had lymphopenia (77%; 48/62), multiple cancer therapies (63%; 39/62 received ≥2 previous therapies), co‐infection (56%; 35/62 had ≥1 co‐infection) and corticosteroid therapy (48%; 30/62) within 1 month before CMV diagnosis. CMV DNAemia and disease were observed in patients receiving novel immunotherapies, including bispecific antibody therapy, chimeric‐antigen receptor T‐cell therapy and immune checkpoint inhibitors.Patients with haematological malignancy, particularly B‐cell LPD, T‐cell LPD, chronic lymphocytic leukaemia and multiple myeloma, were frequently identified to have CMV DNAemia and disease. Lymphopenia, multiple cancer therapies, co‐infection and recent receipt of systemic corticosteroids were also commonly observed. Future studies are necessary to determine optimal identification and management of CMV in these patients. [ABSTRACT FROM AUTHOR]

Background: Little is known regarding the optimal management of nocardiosis among solid organ transplant (SOT) recipients. It is often suggested to avoid trimethoprim/sulfamethoxazole (TMP‐SMX) monotherapy in heavily immunocompromised patients (such as SOT recipients) and/or in case of severe or disseminated nocardiosis. Our aim was to report our experience with TMP‐SMX monotherapy in SOT recipients with nocardiosis. Methods: Using data from a previously published European study, we assessed the incidence of adverse events in SOT recipients receiving TMP‐SMX monotherapy and assessed its effectiveness. Results: Thirty‐one SOT recipients with nocardiosis were included, mostly kidney transplant recipients (20/31, 65%). Eleven (36%) had disseminated infection, and four (13%) had brain nocardiosis. Most patients had lung and/or pleural involvement (26/31, 84%). Daily dose of trimethoprim at initiation was 10 [6.4‐14.8] mg/kg. The median estimated glomerular filtration rate at time of diagnosis of nocardiosis was 44 [30‐62] ml/min/1.73 m². TMP‐SMX was discontinued prematurely in one third of the patients (10/31, 32%, mostly for hematological toxicity [n = 3] or increased serum creatinine [n = 3]). Focusing on the 24 (77%) patients who completed at least 30 days of TMP‐SMX monotherapy, 4 had late (>30 days) drug discontinuation, 1 experienced treatment failure, and 19 completed planned TMP‐SMX monotherapy. Clinical outcome was favorable in these 19 patients, despite the fact that 8 (42%) had disseminated infection and 2 (11%) brain nocardiosis. Overall, all‐cause 1‐year mortality was 10% (3/31). Conclusions: TMP‐SMX monotherapy appears to be effective for the treatment of most nocardiosis among SOT recipients. Interventional studies are needed to compare its safety and effectiveness with those of other regimens used to treat posttransplant nocardiosis. [ABSTRACT FROM AUTHOR]

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]

Background The incidence of nosocomial infections due to carbapenem-resistant Klebsiella pneumoniae is increasing worldwide. Whole-genome sequencing (WGS) can help elucidate the transmission route of nosocomial pathogens. Methods We combined WGS and epidemiological data to analyze an outbreak of New Delhi metallo-β-lactamase (NDM)–producing K. pneumoniae that occurred in 2 Belgian hospitals situated about 50 miles apart. We characterized 74 NDM-producing K. pneumoniae isolates (9 from hospital A, 24 from hospital B, and 41 contemporary isolates from 15 other Belgian hospitals) using pulsed-field gel electrophoresis and WGS. Results A K. pneumoniae sequence type 716 clone was identified as being responsible for the outbreak with all 9 strains from hospital A and 20 of 24 from hospital B sharing a unique pulsotype and being clustered together at WGS (compared with 1 of 41 isolates from other Belgian hospitals). We identified the outpatient clinic of hospital B as the probable bridging site between the hospitals after combining epidemiological, phylogenetic, and resistome data. We also identified the patient who probably caused the transmission. In fact, all but 1 strain from hospital A carried a Tn 1331-like transposon, whereas none of the hospital B isolates did. The patient from hospital A who did not have the Tn 1331-like transposon was treated at the outpatient clinic of hospital B on the same day as the first NDM-producing K. pneumoniae –positive patient from hospital B. Conclusions The results from our WGS-guided investigation highlight the importance of implementing adequate infection control measures in outpatient settings, especially when healthcare delivery moves from acute care facilities to outpatient clinics. [ABSTRACT FROM AUTHOR]

Background. Solid organ transplant (SOT) recipients are at risk of nocardiosis, a rare opportunistic bacterial infection, but prognosis and outcome of these patients are poorly defined. Our objectives were to identify factors associated with 1-year mortality after nocardiosis and describe the outcome of patients receiving short-course antibiotics (≤120 days). Methods. We analyzed data from a multicenter European case-control study that included 117 SOT recipients with nocardiosis diagnosed between 2000 and 2014. Factors associated with 1-year all-cause mortality were identified using multivariable conditional logistic regression. Results. One-year mortality was 10-fold higher in patients with nocardiosis (16.2%, 19/117) than in control transplant recipients (1.3%, 3/233, P < .001). A history of tumor (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.8), invasive fungal infection (OR, 1.3; 95% CI, 1.1-1.5), and donor age (OR, 1.0046; 95% CI, 1.0007-1.0083) were independently associated with 1-year mortality. Acute rejection in the year before nocardiosis was associated with improved survival (OR, 0.85; 95% CI, 0.73-0.98). Seventeen patients received short-course antibiotics (median duration 56 [24-120] days) with a 1-year success rate (cured and surviving) of 88% and a 5.9% risk of relapse (median follow-up 49 [6-136] months). Conclusions. One-year mortality was 10-fold higher in SOT patients with nocardiosis than in those without. Four factors, largely reflecting general medical condition rather than severity and/or management of nocardiosis, were independently associated with 1-year mortality. Patients who received short-course antibiotic treatment had good outcomes, suggesting that this may be a strategy for further study. [ABSTRACT FROM AUTHOR]

Background: Scedosporium species and Lomentospora prolificans (S/L) are the second most common causes of invasive mold infections following Aspergillus in lung transplant recipients. Methods: We assessed the current practices on management of S/L colonization/infection of the lower respiratory tract before and after lung transplantation in a large number of lung transplant centers through an international practice survey from October 2016 to March 2017. Results: A total of 51 respondents from 45 lung transplant centers (17 countries, 4 continents) answered the survey (response rate 58%). S/L colonization was estimated to be detected in candidates by 48% of centers. Only 18% of the centers used a specific medium to detect S/L colonization. Scedosporium spp. colonization was a contraindication to transplantation in 10% of centers whereas L prolificans was a contraindication in 31%; 22% of centers declared having had 1‐5 recipients infected with S/L in the past 5 years. Conclusions: This survey gives an overview of the current practices regarding S/L colonization and infection in lung transplant centers worldwide and underscores the need of S/L culture procedure standardization before implementing prospective studies. [ABSTRACT FROM AUTHOR]

Background: There is no consensus on the optimal management of immunosuppression during bacterial infections among solid organ transplant recipients. Methods: A multicenter, cross‐sectional survey, of high‐volume kidney and liver transplant centers across US and Europe. Structured questionnaires including six multiple‐choice questions concerning the management of immunosuppression during infection were distributed among 381 centers. Results: A total of 124 (33%) centers fully completed the questionnaire: 67 liver, 57 kidney centers. Participating centers reported heterogenous approaches to immunosuppression management for all types of immunosuppressive drugs. Notably, kidney centers reported similar frequencies of either discontinuation (19%), continuation (19%), or dose reduction (17.5%) of antimetabolites; discontinuation only for life‐threatening infection (17.5%) or case by case decisions (27%). Calcineurin inhibitors (CNI) management was heterogenous mostly among liver centers, with 8% discontinuing the CNI, 18% continuing, and 22% reducing dose. Heterogenous approaches to management of steroids and inhibitors of the mammalian target of rapamycin were also demonstrated. Conclusions: Immunosuppression management during bacterial infection is heterogenous in US and European centers. Immunosupression reduction (ISR) during infection is a common practice, though supported by limited evidence. Demonstrating high heterogeneity in the approach to ISR, together with the equivocal results of clinical studies, support consideration of an interventional clinical trial. [ABSTRACT FROM AUTHOR]