RESUMEN
In 2023, published research on COVID-19 remains prominent. The aim of this article is to highlight important developments in infectious disease evidence unrelated to COVID-19 that were published in 2023. The literature was screened for sound new evidence relevant to internal medicine specialists and subspecialists whose focus of practice is not infectious diseases. The highlighted publications relate to various organisms and patient populations. One article provides insight into the updated guidelines for the diagnosis and management of infective endocarditis. Several articles address the management of sepsis and bacteremia: comparison of cefepime versus piperacillin-tazobactam, ceftobiprole for the treatment of complicated Staphylococcus aureus bacteremia, and early switch from intravenous to oral antibiotics in patients with gram-negative bacteremia. Another article examines differences in all-cause mortality in patients with Clostridioides difficile infection who receive different treatments. Additional articles provide evidence about the treatment of patients with HIV infection: the utility of preexposure prophylaxis to prevent HIV infection, the efficacy of pitavastatin in reducing cardiovascular disease, and the efficacy of dexamethasone for the treatment of tuberculous meningitis in persons with HIV.
Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/complicaciones , Antibacterianos/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Enfermedades Transmisibles/tratamiento farmacológicoRESUMEN
In 2022, COVID-19 remained the infectious disease at the top of most internal medicine physicians' minds. However, it was not the only infectious disease that was the topic of clinically relevant research that year. This article highlights some important infectious disease evidence unrelated to COVID-19 that was published in 2022. The literature was screened for sound new evidence relevant to internal medicine specialists and subspecialists whose focus of practice is not infectious diseases. The publications highlighted relate to various organisms in different patient populations. One article provides insight into the role of Helicobacter pylori eradication in the treatment of functional dyspepsia. The descriptive epidemiology of bacterial (Staphylococcus aureus) and viral (mpox) infections are the focus of 2 other articles. Several articles address the management of resistant and difficult-to-treat infections: multidrug-resistant gram-negative infections, resistant HIV-1, rifampin-resistant tuberculosis, cryptococcal meningitis, and invasive fungal infection in the setting of neutropenia. Another article provides data on effective HIV preexposure prophylaxis in women, an understudied population. Finally, given the urgent need to reduce inappropriate use of antibiotics, an article on antibiotic stewardship for hospitalized patients with presumed sepsis in a non-intensive care unit setting is also included.
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COVID-19 , Enfermedades Transmisibles , Sepsis , Infecciones Estafilocócicas , Humanos , Femenino , Enfermedades Transmisibles/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Antibacterianos/uso terapéutico , Sepsis/tratamiento farmacológicoRESUMEN
BACKGROUND: Liver tumours observed in rats exposed to micafungin led to a black box warning upon approval in Europe in 2008. Micafungin's risk for liver carcinogenicity in humans has not been investigated. We sought to describe the risk of fatal hepatocellular carcinoma (HCC) among persons who received micafungin and other parenteral antifungals (PAFs) with up to 12 years of follow-up. METHODS: We assembled a US multicentre cohort of hospitalized patients who received micafungin or other PAFs between 2005 and 2012. We used propensity score (PS) matching on patient characteristics from electronic medical records to compare rates of HCC mortality identified through the National Death Index though to the end of December 2016. We computed HRs and 95% CIs. RESULTS: A total of 40110 patients who received a PAF were identified; 6903 micafungin recipients (87% of those identified) were successfully matched to 16317 comparator PAF users. Ten incident HCC deaths, one in the micafungin-exposed group and nine among comparator PAF users, occurred in 71285 person-years of follow-up. The HCC mortality rate was 0.05 per 1000 person-years in micafungin patients and 0.17 per 1000 person-years in comparator PAF patients. The PS-matched HR for micafungin versus comparator PAF was 0.29 (95% CI 0.04-2.24). CONCLUSIONS: Both micafungin and comparator PAFs were associated with HCC mortality rates of <0.2 per 1000 person-years. Given the very low event rates, any potential risk for HCC should not play a role in clinical decisions regarding treatment with micafungin or other PAFs investigated in this study.
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Antifúngicos/efectos adversos , Carcinoma Hepatocelular/mortalidad , Fungemia/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Micafungina/efectos adversos , Adulto , Anciano , Carcinoma Hepatocelular/microbiología , Registros Electrónicos de Salud , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Infusiones Parenterales , Neoplasias Hepáticas/microbiología , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
Invasive fungal infections (IFI) are a significant source of morbidity and mortality for patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Given the heterogeneity of the population receiving hypomethylating agents (HMA), it is difficult for clinicians to accurately assess their patients' risk of infection. Literature on the incidence of IFI following HMA is limited to several studies of azacitidine. The primary objective of this retrospective study was to establish the incidence of IFI in HMA treated AML/MDS patients at a large U.S. comprehensive cancer center. Secondary objectives included comparing incidence of IFI among pre-specified subgroups to identify potential risk factors for IFI. Two hundred three patients with AML, intermediate to very high risk MDS or chronic myelomonocytic leukemia who received at least two cycles of HMA were included. The incidence of IFI, as defined by the European Organization for Research and Treatment of Cancer / Invasive Fungal Infections Cooperative Group criteria, was 9.6%, with 20 IFI diagnosed following HMA (three proven, four probable, 13 possible). Among the proven cases of IFI, molds included Scedosporium and Fusarium spp. Eleven patients who developed IFIs were neutropenic upon initiating HMA. The majority (17/20) of infections occurred during the first four cycles. Given this incidence, mold-active prophylaxis can be considered in patients who are neutropenic at the start of therapy.
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Antineoplásicos/efectos adversos , Fusariosis , Fusarium , Infecciones Fúngicas Invasoras , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Scedosporium , Anciano , Antineoplásicos/administración & dosificación , Femenino , Fusariosis/inducido químicamente , Fusariosis/epidemiología , Fusariosis/prevención & control , Humanos , Incidencia , Infecciones Fúngicas Invasoras/inducido químicamente , Infecciones Fúngicas Invasoras/epidemiología , Infecciones Fúngicas Invasoras/prevención & control , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/epidemiología , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Clostridium difficile infection (CDI) is a leading cause of infectious complications in allogeneic hematopoietic cell transplant recipients (alloHCT). We sought to evaluate whether prophylactic oral vancomycin reduces the incidence of CDI in alloHCT recipients. METHODS: We conducted a retrospective cohort study to examine the effectiveness of CDI prophylaxis with oral vancomycin, as compared to no prophylaxis, in 145 consecutive adult alloHCT recipients at the University of Pennsylvania between April 2015 and November 2016. Patients received oral vancomycin 125 mg twice daily, starting on admission and continuing until discharge. The primary outcome of interest was the association between oral vancomycin prophylaxis and CDI diagnosis. Secondary outcomes included graft-versus-host disease (GVHD) and relapse. RESULTS: There were no cases of CDI in patients that received prophylaxis (0/90, 0%), whereas 11/55 (20%) patients who did not receive prophylaxis developed CDI (P < .001). Oral vancomycin prophylaxis was not associated with a higher risk of acute, grades 2-4 GVHD (subhazard ratio [sHR] 1.59; 95% confidence interval [CI] 0.88-2.89; P = .12), acute, grades 3-4 GVHD (sHR 0.65; 95% CI 0.25-1.66; P = .36), or acute, grades 2-4 gastrointestinal GVHD (sHR 1.95; 95% CI 0.93-4.07; P = .08) at day 180 post-transplant. No associations between oral vancomycin and relapse or survival were observed. CONCLUSIONS: Prophylaxis with oral vancomycin is highly effective in preventing CDI in alloHCT recipients without increasing the risk of graft-versus-host disease or disease relapse. Further evaluation via a prospective study is warranted.
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Profilaxis Antibiótica , Clostridioides difficile/efectos de los fármacos , Infecciones por Clostridium/etiología , Infecciones por Clostridium/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hipersensibilidad/complicaciones , Receptores de Trasplantes , Vancomicina/administración & dosificación , Administración Oral , Adulto , Anciano , Profilaxis Antibiótica/métodos , Clostridioides difficile/inmunología , Infecciones por Clostridium/mortalidad , Femenino , Enfermedad Injerto contra Huésped/etiología , Humanos , Hipersensibilidad/inmunología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tiempo de Tratamiento , Trasplante Homólogo/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: Most studies of post-transplant CMV infection have focused on either solid organ or hematopoietic cell transplant (HCT) recipients. A large prospective cohort study involving both lung and HCT recipients provided an opportunity to compare the epidemiology and outcomes of CMV infections in these 2 groups. METHODS: Patients were followed up for 30 months in a 6-center prospective cohort study. Data on demographics, CMV infections, tissue-invasive disease, recurrences, rejection, and immunosuppression were recorded. RESULTS: The overall incidence of CMV infection was 83/293 (28.3%) in the lung transplant group and 154/444 (34.7%) in the HCT group (P = .0706). Tissue-invasive CMV disease occurred in 8/83 (9.6%) of lung and 6/154 (3.9%) of HCT recipients with CMV infection, respectively (P = .087). Median time to CMV infection was longer in the lung transplant group (236 vs 40 days, P < .0001), likely reflecting the effects of prophylaxis vs preemptive therapy. Total IgG levels of < 350 mg/dL in lung recipients and graft vs host disease (GvHD) in HCT recipients were associated with increased CMV risk. HCT recipients had a higher mean number of CMV episodes (P = .008), although duration of viremia was not significantly different between the 2 groups. CMV infection was not associated with reduced overall survival in either group. CONCLUSIONS: Current CMV prevention strategies have resulted in a low incidence of tissue-invasive disease in both lung transplant and HCT, although CMV viremia is still relatively common. Differences between the lung and HCT groups in terms of time to CMV and recurrences of CMV viremia likely reflect differences in underlying host immunobiology and in CMV prevention strategies in the modern era.
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Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Pulmón/efectos adversos , Receptores de Trasplantes/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/administración & dosificación , Citomegalovirus/efectos de los fármacos , Citomegalovirus/inmunología , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/mortalidad , Femenino , Ganciclovir/administración & dosificación , Enfermedad Injerto contra Huésped/epidemiología , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Humanos , Incidencia , Trasplante de Pulmón/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Viremia/epidemiología , Viremia/prevención & controlRESUMEN
It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
Asunto(s)
Candidiasis/diagnóstico , Candidiasis/tratamiento farmacológico , Animales , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , Candidiasis/microbiología , HumanosRESUMEN
It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
Asunto(s)
Candidiasis/diagnóstico , Candidiasis/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , HumanosRESUMEN
Infection is a major complication of hematopoietic cell transplantation. Prolonged neutropenia and graft-versus-host disease are the 2 major complications with an associated risk for infection, and these complications differ according to the graft source. A phase 3, multicenter, randomized trial (Blood and Marrow Transplant Clinical Trials Network [BMT CTN] 0201) of transplantation of bone marrow (BM) versus peripheral blood stem cells (PBSC) from unrelated donors showed no significant differences in 2-year survival between these graft sources. In an effort to provide data regarding whether BM or PBSC could be used as a preferential graft source for transplantation, we report a detailed analysis of the infectious complications for 2 years after transplantation from the BMT CTN 0201 trial. A total of 499 patients in this study had full audits of infection data. A total of 1347 infection episodes of moderate or greater severity were documented in 384 (77%) patients; 201 of 249 (81%) of the evaluable patients had received a BM graft and 183 of 250 (73%) had received a PBSC graft. Of 1347 infection episodes, 373 were severe and 123 were life-threatening and/or fatal; 710 (53%) of these episodes occurred on the BM arm and 637 (47%) on the PBSC arm, resulting in a 2-year cumulative incidence 84.7% (95% confidence interval [CI], 79.6 to 89.8) for BM versus 79.7% (95% CI, 73.9 to 85.5) for PBSC, P = .013. The majority of these episodes, 810 (60%), were due to bacteria, with a 2-year cumulative incidence of 72.1% and 62.9% in BM versus PBSC recipients, respectively (P = .003). The cumulative incidence of bloodstream bacterial infections during the first 100 days was 44.8% (95% CI, 38.5 to 51.1) for BM versus 35.0% (95% CI, 28.9 to 41.1) for PBSC (P = .027). The total infection density (number of infection events/100 patient days at risk) was .67 for BM and .60 for PBSC. The overall infection density for bacterial infections was .4 in both arms; for viral infections, it was .2 in both arms; and for fungal/parasitic infections, it was .04 and .05 for BM and PBSC, respectively. The cumulative incidence of infection before engraftment was 47.9% (95% CI, 41.5 to 53.9) for BM versus 32.8% (95% CI, 27.1 to 38.7) for PBSC (P = .002), possibly related to quicker neutrophil engraftment using PBSC. Infections remain frequent after unrelated donor hematopoietic cell transplantation, particularly after BM grafts.
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Trasplante de Médula Ósea/efectos adversos , Trasplante de Médula Ósea/métodos , Infecciones/etiología , Infecciones/virología , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Trasplante de Células Madre de Sangre Periférica/métodos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Donante no EmparentadoRESUMEN
Transplant recipients are at a high risk for developing invasive fungal infections. The agents of phaeohyphomycosis are environmental molds found worldwide, and they cause a broad spectrum of disease including skin and subcutaneous lesions, pneumonia, central nervous system disease, fungemia, and disseminated disease. Using data from the Transplant Associated Infection Surveillance Network (TRANSNET), we evaluated patients with proven and probable phaeohyphomycosis. Centers collected data on demographics, co-morbid conditions, clinical features, treatment, and three-month mortality. Fifty-six patients with phaeohyphomycosis were identified from 15 centers, comprising 26 stem cell transplant (SCT) and 30 solid organ transplant (SOT) recipients. Median time to diagnosis post-transplant was 358 days (SCT 100 days; SOT 685 days; P = <.001). The most frequent pathogen was Alternaria species (32%). Disseminated disease was found in 55.4%. Cutaneous infection was more common in SOT (53.3% vs 23.1%; P = .021), while pulmonary disease was more common in SCT (57.7 vs. 26.7; P = .019). Voriconazole (44.6%) and amphotericin B preparations (37.5%) were the most common antifungal therapies. Overall mortality was 25% and was higher in SCT than in SOT (42% vs 10%; P = <.001). A wide variety of organisms encompass phaeohyphomycosis contributing to varying types of infection in transplant recipients. Site of infection, time to disease, and mortality varies significantly between SCT and SOT recipients. Lipid formulations of amphotericin B and voriconazole were the most common antifungals used to treat this disorder.
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Infecciones Oportunistas/epidemiología , Feohifomicosis/epidemiología , Receptores de Trasplantes , Adulto , Anciano , Antifúngicos/uso terapéutico , Monitoreo Epidemiológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones Oportunistas/tratamiento farmacológico , Infecciones Oportunistas/mortalidad , Infecciones Oportunistas/patología , Feohifomicosis/tratamiento farmacológico , Feohifomicosis/mortalidad , Feohifomicosis/patología , Estudios Prospectivos , Análisis de SupervivenciaRESUMEN
BACKGROUND: Invasive candidiasis is the third most common bloodstream infection in the intensive care unit (ICU) and is associated with morbidity and mortality. Prophylaxis and preemptive therapy are attractive strategies for this setting. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial of caspofungin as antifungal prophylaxis in 222 adults who were in the ICU for at least 3 days, were ventilated, received antibiotics, had a central line, and had 1 additional risk factor (parenteral nutrition, dialysis, surgery, pancreatitis, systemic steroids, or other immunosuppressants). Subjects' (1,3)-ß-d-glucan levels were monitored twice weekly. The primary endpoint was the incidence of proven or probable invasive candidiasis by EORTC/MSG criteria in patients who did not have disease at baseline. Patients who had invasive candidiasis were allowed to break the blind and receive preemptive therapy with caspofungin. The preemptive approach analysis included patients all patients who received study drug, including those positive at baseline. RESULTS: The incidence of proven/probable invasive candidiasis in the placebo and caspofungin arms was 16.7% (14/84) and 9.8% (10/102), respectively, for prophylaxis (P = .14), and 30.4% (31/102) and 18.8% (22/117), respectively, for the preemptive approach (P = .04); however, this analysis included patients with baseline disease. There were no significant differences in the secondary endpoints of mortality, antifungal use, or length of stay. There were no safety differences. CONCLUSIONS: Caspofungin was safe and tended to reduce the incidence of invasive candidiasis when used for prophylaxis, but the difference was not statistically significant. A preemptive therapy approach deserves further study. CLINICAL TRIALS REGISTRATION: NCT00520234.
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Antifúngicos/uso terapéutico , Candidiasis Invasiva/prevención & control , Equinocandinas/uso terapéutico , Unidades de Cuidados Intensivos , Adulto , Anciano , Antifúngicos/efectos adversos , Candidiasis Invasiva/epidemiología , Caspofungina , Método Doble Ciego , Equinocandinas/efectos adversos , Femenino , Humanos , Incidencia , Lipopéptidos , Masculino , Persona de Mediana Edad , Profilaxis Pre-Exposición , Factores de Riesgo , Resultado del TratamientoRESUMEN
Invasive Fusarium infections occur in immunosuppressed patients, especially those with haematological malignancies. We conducted a descriptive analysis of data from patients with invasive fusariosis identified in the Prospective Antifungal Therapy Alliance registry, which collected data on invasive fungal infections in the United States and Canada from 2004 to 2008. In this series of 65 patients with proven (83.1%) and probable (16.9%) invasive fusariosis, the most common underlying condition was haematological malignancy, in which neutropenia and corticosteroid usage frequently occurred. Seven patients with invasive Fusarium infections had cross-reactive galactomannan assay results. The survival rate for all patients at 90 days was 44%, which was an improvement compared with historical data. Disseminated disease occurred frequently (35.4%), and patients with and without disseminated disease had survival rates of 33% and 50%, respectively. Posaconazole and voriconazole were the most frequently employed therapies and may be linked to the improved survival rate observed in this patient series. In summary, patients with invasive Fusarium infections continue to have high fatality rates, especially those with disseminated disease. Fusarium infections should be strongly considered in the absence of Aspergillus isolation in patients at high risk of mould infections with positive galactomannan assay test results.
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Antifúngicos/uso terapéutico , Fusariosis/tratamiento farmacológico , Fusarium/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Canadá/epidemiología , Femenino , Fusariosis/epidemiología , Fusariosis/microbiología , Fusariosis/mortalidad , Fusarium/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sistema de Registros , Análisis de Supervivencia , Resultado del Tratamiento , Triazoles/uso terapéutico , Estados Unidos/epidemiología , Voriconazol/uso terapéutico , Adulto JovenRESUMEN
The epidemiology of invasive aspergillosis (IA) is evolving. To define the patient groups who will most likely benefit from primary or secondary Aspergillus prophylaxis, particularly those whose medical conditions and IA risk change over time, it is helpful to depict patient populations and their risk periods in a temporal visual model. The Sankey approach provides a dynamic figure to understand the risk of IA for various patient populations. While the figure depicted within this article is static, an internet-based version could provide pop-up highlights of any given flow's origin and destination nodes. A future version could highlight links to publications that support the color-coded incidence rates or other actionable items, such as bundles of applicable pharmacologic or non-pharmacologic interventions. The figure, as part of the upcoming Infectious Diseases Society of America's aspergillosis clinical practice guidelines, can guide decision-making in clinical settings.
RESUMEN
The impact of antifungal therapy on economic outcomes in patients with invasive aspergillosis (IA) needs further exploration. The purpose of this study was to describe antifungal therapy and factors associated with hospital length of stay (LOS) in transplant patients with IA. Patients were enrolled from March 2001 to October 2005 and IA cases identified through March 2006 from a sub-group of patients in the Transplant Associated Infection Surveillance Network (TRANSNET). Factors associated with hospital LOS were determined by logistic regression analysis. Of 361 patients, the mean age was 49 years, 60.7% were male, and 63% were hematopoietic stem cell transplantation (HSCT) recipients. Primary monotherapy was used in 233 (64.5%) patients, of which voriconazole (93/233, 39.9%) was most commonly used antifungal. Primary combination therapy was used in 128 (35.4%) of 361 patients, with voriconazole plus caspofungin (81/361, 22.4%) the most frequently employed. Mean duration of therapy was 115 days (HSCT 109.7; solid organ transplant [SOT] 125.3). Mean hospital LOS was 35.3 days (HSCT 38.7; SOT 29.7). Regression analysis identified disseminated IA, neutropenia, malnutrition and length of ICU stay as factors associated with increased hospital LOS. Initial voriconazole use was associated with decreased LOS. Further investigation on impact of antifungal therapy on economic outcomes is needed.
Asunto(s)
Antifúngicos/uso terapéutico , Aspergilosis/tratamiento farmacológico , Aspergillus/efectos de los fármacos , Equinocandinas/uso terapéutico , Pirimidinas/uso terapéutico , Triazoles/uso terapéutico , Adulto , Anciano , Aspergilosis/microbiología , Aspergilosis/mortalidad , Caspofungina , Estudios de Cohortes , Demografía , Quimioterapia Combinada , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Control de Infecciones , Tiempo de Internación , Lipopéptidos , Pulmón/microbiología , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Factores de Tiempo , VoriconazolRESUMEN
Ecthyma gangrenosum (EG) is a skin infection that is classically associated with Pseudomonas aeruginosa septicemia in immunocompromised patients. Other bacterial, viral, and fungal pathogens also have been implicated in EG. Both bacteremic and nonbacteremic forms of EG have been described. We describe a case of EG associated with methicillin-resistant Staphylococcus aureus (MRSA) in a 35-year-old woman with acute lymphoblastic leukemia (ALL) and review the literature.
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Ectima/microbiología , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas/complicaciones , Adulto , Antibacterianos/uso terapéutico , Ectima/tratamiento farmacológico , Femenino , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Vancomicina/uso terapéuticoRESUMEN
Patients undergoing haploidentical or mismatched unrelated donor (haplo/MMUD) allogeneic hematopoietic cell transplantation (alloHCT) receiving post-transplant cyclophosphamide (PTCy) are at high risk of cytomegalovirus (CMV) infection. Experience with letermovir (LET) in this population is limited. This single center retrospective cohort study compared CMV and transplant outcomes between LET and a historical control with high-dose valacyclovir (HDV) prophylaxis in adults undergoing haplo/MMUD alloHCT. Thirty-eight CMV seropositive patients were included, 19 in each arm. LET reduced the incidence of CMV infection (5% vs. 53%, RR 0.01, 95% CI 0.014-0.71, p = .001) and need for CMV treatment by day +100 (5% vs. 37%, RR 0.14, 95% CI 0.18-0.99, p = .017) compared to HDV. Median CMV event-free-survival was improved with LET (not reached vs. 80 days, HR 0.114, 95% CI 0.07-0.61, p = .004). These data support the efficacy of LET in alternative donor transplants.
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Infecciones por Citomegalovirus , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Acetatos , Adulto , Ciclofosfamida/efectos adversos , Citomegalovirus , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/prevención & control , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Quinazolinas , Estudios Retrospectivos , Donante no Emparentado , Valaciclovir/uso terapéuticoRESUMEN
Recent reports describe increasing incidence of non-Aspergillus mold infections in hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients. To investigate the epidemiology of infections with Mucorales, Fusarium spp., and Scedosporium spp. molds, we analyzed data from the Transplant-Associated Infection Surveillance Network, 23 transplant centers that conducted prospective surveillance for invasive fungal infections during 2001-2006. We identified 169 infections (105 Mucorales, 37 Fusarium spp., and 27 Scedosporium spp.) in 169 patients; 124 (73.4%) were in HCT recipients, and 45 (26.6%) were in SOT recipients. The crude 90-day mortality rate was 56.6%. The 12-month mucormycosis cumulative incidence was 0.29% for HCT and 0.07% for SOT. Mucormycosis incidence among HCT recipients varied widely, from 0.08% to 0.69%, with higher incidence in cohorts receiving transplants during 2003 and 2004. Non-Aspergillus mold infections continue to be associated with high mortality rates. The incidence of mucormycosis in HCT recipients increased substantially during the surveillance period.
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Micosis/epidemiología , Infecciones Oportunistas/epidemiología , Trasplante , Adulto , Antifúngicos/uso terapéutico , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Micosis/tratamiento farmacológico , Micosis/microbiología , Infecciones Oportunistas/tratamiento farmacológico , Infecciones Oportunistas/microbiología , Trasplante/efectos adversos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Invasive aspergillosis (IA) is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. The purpose of this study was to evaluate factors associated with mortality in transplant patients with IA. METHODS: Transplant patients from 23 US centers were enrolled from March 2001 to October 2005 as part of the Transplant Associated Infection Surveillance Network. IA cases were identified prospectively in this cohort through March 2006, and data were collected. Factors associated with 12-week all-cause mortality were determined by logistic regression analysis and Cox proportional hazards regression. RESULTS: Six-hundred forty-two cases of proven or probable IA were evaluated, of which 317 (49.4%) died by the study endpoint. All-cause mortality was greater in HSCT patients (239 [57.5%] of 415) than in SOT patients (78 [34.4%] of 227; P<.001). Independent poor prognostic factors in HSCT patients were neutropenia, renal insufficiency, hepatic insufficiency, early-onset IA, proven IA, and methylprednisolone use. In contrast, white race was associated with decreased risk of death. Among SOT patients, hepatic insufficiency, malnutrition, and central nervous system disease were poor prognostic indicators, whereas prednisone use was associated with decreased risk of death. Among HSCT or SOT patients who received antifungal therapy, use of an amphotericin B preparation as part of initial therapy was associated with increased risk of death. CONCLUSIONS: There are multiple variables associated with survival in transplant patients with IA. Understanding these prognostic factors may assist in the development of treatment algorithms and clinical trials.
Asunto(s)
Aspergilosis/mortalidad , Trasplante de Células Madre Hematopoyéticas/mortalidad , Trasplante de Órganos/mortalidad , Adulto , Antifúngicos/uso terapéutico , Aspergilosis/complicaciones , Aspergilosis/tratamiento farmacológico , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/mortalidad , Factores de RiesgoRESUMEN
BACKGROUND: Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among organ transplant recipients. Multicenter prospective surveillance data to determine disease burden and secular trends are lacking. METHODS: The Transplant-Associated Infection Surveillance Network (TRANSNET) is a consortium of 23 US transplant centers, including 15 that contributed to the organ transplant recipient dataset. We prospectively identified IFIs among organ transplant recipients from March, 2001 through March, 2006 at these sites. To explore trends, we calculated the 12-month cumulative incidence among 9 sequential cohorts. RESULTS: During the surveillance period, 1208 IFIs were identified among 1063 organ transplant recipients. The most common IFIs were invasive candidiasis (53%), invasive aspergillosis (19%), cryptococcosis (8%), non-Aspergillus molds (8%), endemic fungi (5%), and zygomycosis (2%). Median time to onset of candidiasis, aspergillosis, and cryptococcosis was 103, 184, and 575 days, respectively. Among a cohort of 16,808 patients who underwent transplantation between March 2001 and September 2005 and were followed through March 2006, a total of 729 IFIs were reported among 633 persons. One-year cumulative incidences of the first IFI were 11.6%, 8.6%, 4.7%, 4.0%, 3.4%, and 1.3% for small bowel, lung, liver, heart, pancreas, and kidney transplant recipients, respectively. One-year incidence was highest for invasive candidiasis (1.95%) and aspergillosis (0.65%). Trend analysis showed a slight increase in cumulative incidence from 2002 to 2005. CONCLUSIONS: We detected a slight increase in IFIs during the surveillance period. These data provide important insights into the timing and incidence of IFIs among organ transplant recipients, which can help to focus effective prevention and treatment strategies.