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BACKGROUND: Despite the burden of pyelonephritis after kidney transplantation, there is no consensus on initial empirical antibiotic management. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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OBJECTIVES: Nocardiosis is a rare but life-threatening infection after hematopoietic cell transplantation (HCT). We aimed at identifying risk factors for nocardiosis after allogeneic HCT and clarifying the effect of trimethoprim-sulfamethoxazole prophylaxis on its occurrence. METHODS: We performed a retrospective multicenter case-control study of patients diagnosed with nocardiosis after allogeneic HCT between January 2000 and December 2018. For each case, two controls were matched by center, transplant date, and age group. Multivariable analysis was conducted using conditional logistic regression to identify potential risk factors for nocardiosis. Kaplan-Meier survival curves of cases and controls were compared using log-rank tests. RESULTS: Sixty-four cases and 128 controls were included. Nocardiosis occurred at a median of 9 months after allogeneic HCT (interquartile range: 5-18). After adjustment for potential confounders in a multivariable model, Nocardia infection was associated with tacrolimus use (adjusted odds ratio [aOR] 9.9, 95 % confidence interval [95 % CI]: 1.6-62.7), lymphocyte count < 500/µL (aOR 8.9, 95 % CI: 2.3-34.7), male sex (aOR 8.1, 95 % CI: 2.1-31.5), recent use of systemic corticosteroids (aOR 7.9, 95 % CI: 2.2-28.2), and recent CMV infection (aOR 4.3, 95 % CI: 1.2-15.9). Conversely, use of trimethoprim-sulfamethoxazole prophylaxis was associated with a significantly decreased risk of nocardiosis (aOR 0.2, 95 % CI: 0.1-0.8). HCT recipients who developed nocardiosis had a significantly decreased survival, as compared with controls (12-month survival: 58 % and 90 %, respectively; p < 0.0001). CONCLUSIONS: We identified six factors independently associated with the occurrence of nocardiosis among allogeneic HCT recipients. In particular, trimethoprim-sulfamethoxazole prophylaxis was found to protect against nocardiosis.
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Trasplante de Células Madre Hematopoyéticas , Nocardiosis , Combinación Trimetoprim y Sulfametoxazol , Humanos , Nocardiosis/epidemiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Femenino , Estudios de Casos y Controles , Factores de Riesgo , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Trasplante Homólogo/efectos adversos , Anciano , Receptores de Trasplantes/estadística & datos numéricos , Nocardia/aislamiento & purificación , Profilaxis AntibióticaAsunto(s)
Antibacterianos , Cefepima , Infecciones , Combinación Piperacilina y Tazobactam , Adulto , Humanos , Enfermedad Aguda , Antibacterianos/uso terapéutico , Cefepima/uso terapéutico , Hospitalización , Infecciones/tratamiento farmacológico , Combinación Piperacilina y Tazobactam/uso terapéuticoRESUMEN
BACKGROUND: Whether trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis prevents nocardiosis in solid organ transplant (SOT) recipients is controversial. OBJECTIVES: 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. METHODS: A systematic review and individual patient data meta-analysis. DATA SOURCES: 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. STUDY ELIGIBILITY CRITERIA: (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. PARTICIPANTS: SOT recipients. INTERVENTION: TMP-SMX prophylaxis versus no prophylaxis. ASSESSMENT OF RISK OF BIAS: Risk Of Bias In Non-randomized Studies-of Exposure (ROBINS-E) for comparative studies; dedicated tool for non-comparative studies. METHODS OF DATA SYNTHESIS: 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. RESULTS: 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). CONCLUSIONS: In SOT recipients, TMP-SMX prophylaxis likely reduces the risk of nocardiosis. Resistance appears uncommon in case of breakthrough infection.
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Nocardiosis , Trasplante de Órganos , Humanos , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Infección Irruptiva , Estudios Retrospectivos , Revisiones Sistemáticas como Asunto , Nocardiosis/microbiología , Trasplante de Órganos/efectos adversos , Receptores de TrasplantesRESUMEN
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.
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Criptococosis , Cryptococcus gattii , Cryptococcus neoformans , Infecciones por VIH , Meningitis , Humanos , VIH , Estudios Retrospectivos , Nueva Zelanda/epidemiología , Australia/epidemiología , Criptococosis/diagnóstico , Criptococosis/epidemiología , Hospitales , Antígenos Fúngicos , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiologíaRESUMEN
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.
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Gripe Humana , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Adulto , Estudios de Cohortes , Mortalidad Hospitalaria , Hospitalización , Humanos , Gripe Humana/complicaciones , Gripe Humana/diagnóstico , Gripe Humana/epidemiología , Unidades de Cuidados Intensivos , Infecciones por Virus Sincitial Respiratorio/complicaciones , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones por Virus Sincitial Respiratorio/epidemiología , Estudios RetrospectivosRESUMEN
The objectives of this study were to assess the immunogenicity and safety of COVID-19 vaccines in patients with hematologic malignancies. A systematic review and meta-analysis of clinical studies of immune responses to COVID-19 vaccination stratified by underlying malignancy and published from January 1, 2021, to August 31, 2021, was conducted using MEDLINE, EMBASE, and Cochrane CENTRAL. Primary outcome was the rate of seropositivity after 2 doses of COVID-19 vaccine with rates of seropositivity after 1 dose, rates of positive neutralizing antibodies, cellular responses, and adverse events as secondary outcomes. Rates were pooled from single-arm studies while rates of seropositivity were compared against the rate in healthy controls for comparator studies using a random effects model and expressed as a pooled odds ratios with 95% confidence intervals. Forty-four studies (16 mixed group, 28 disease specific) with 7064 patients were included in the analysis (2331 after first dose, 4733 after second dose). Overall seropositivity rates were 62% to 66% after 2 doses of COVID-19 vaccine and 37% to 51% after 1 dose. The lowest seropositivity rate was 51% in patients with chronic lymphocytic leukemia and was highest in patients with acute leukemia (93%). After 2 doses, neutralizing antibody response rates were 57% to 60%, and cellular response rates were 40% to 75%. Active treatment, ongoing or recent treatment with targeted and CD-20 monoclonal antibody therapies within 12 months were associated with poor immune responses to COVID-19 vaccine. New approaches to prevention are urgently required to reduce COVID-19 infection morbidity and mortality in high-risk patient groups that respond poorly to COVID-19 vaccination.
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COVID-19 , Neoplasias Hematológicas , Anticuerpos Neutralizantes , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/terapia , Humanos , SARS-CoV-2RESUMEN
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.
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Bacteriemia , Enfermedades Transmisibles , Trasplante de Células Madre Hematopoyéticas , Enfermedades Pulmonares , Nocardiosis , Nocardia , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Médula Ósea , Enfermedades Transmisibles/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Enfermedades Pulmonares/microbiología , Nocardiosis/diagnóstico , Nocardiosis/tratamiento farmacológico , Nocardiosis/epidemiología , Estudios Retrospectivos , Receptores de TrasplantesRESUMEN
BACKGROUND: 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). Aim To evaluate the epidemiology, clinical characteristics and outcomes of CMV infection in this population. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Coinfección , Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Leucemia Linfocítica Crónica de Células B , Linfopenia , Mieloma Múltiple , Humanos , Citomegalovirus/genética , Inhibidores de Puntos de Control Inmunológico , ADN Viral , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/epidemiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Linfopenia/etiología , Receptores de Antígenos , CorticoesteroidesRESUMEN
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.
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Absceso Encefálico , Nocardiosis , Nocardia , Encéfalo , Absceso Encefálico/tratamiento farmacológico , Humanos , Huésped Inmunocomprometido , Nocardiosis/diagnóstico , Nocardiosis/tratamiento farmacológicoRESUMEN
There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.
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Bacteriemia , Trasplante de Riñón , Infecciones Urinarias , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Estudios de Cohortes , Ertapenem , Humanos , Puntaje de Propensión , Estudios Retrospectivos , Infecciones Urinarias/tratamiento farmacológico , beta-LactamasasRESUMEN
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.
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Nocardiosis , Trasplante de Órganos , Neumonía por Pneumocystis , Humanos , Nocardiosis/tratamiento farmacológico , Nocardiosis/epidemiología , Trasplante de Órganos/efectos adversos , Estudios Retrospectivos , Receptores de Trasplantes , Combinación Trimetoprim y Sulfametoxazol/efectos adversosRESUMEN
PURPOSE OF REVIEW: This review aims to summarize available guidelines as well as the emerging evidence for the prevention and treatment of invasive fungal diseases in high-risk haematology patients. RECENT FINDINGS: Primary mould-active prophylaxis is the strategy used in many centres to manage the risk of invasive fungal disease in high-risk haematology patients, and posaconazole remains the antifungal of choice for most of these patients. Data on the use of other antifungals for primary prophylaxis, including isavuconazole, are limited. There is considerable interest in identifying a strategy that would limit the use of mould-active agents to the patients who are the most likely to benefit from them. In this regard, a recent trial demonstrated that the preemptive strategy is noninferior to the empiric strategy. For primary treatment of invasive aspergillosis, two randomized trials found isavuconazole and posaconazole to be noninferior to voriconazole. Isavuconazole does not appear to require therapeutic drug monitoring. SUMMARY: Prophylaxis and treatment of invasive fungal diseases in high-risk haematology patients is a rapidly evolving field. Critical clinical questions remain unanswered, especially regarding the management of suspected invasive fungal diseases breaking through mould-active prophylaxis, and the duration of antifungal therapy for invasive mould infections.