Miguel Salavert

Early infections in adult patients undergoing unrelated donor cord blood transplantation

Early transplant-related mortality after cord blood transplantation from unrelated donors (UD-CBT) is close to 50%, mainly due to infectious complications. We have studied the incidence and characteristics of early infections (before day 100) in a series of 27 adult patients (median age 30 years, range 16–46) undergoing UD-CBT at a single institution. All 27 patients experienced at least one infectious episode and 18 (66%) suffered a severe infection. Bacteremia occurred in 55% of patients (13 with Gram-positive and 11 with Gram-negative microorganisms). Eleven of 19 CMV-seropositive patients (58%) developed CMV antigenemia and one patient had CMV disease. Fungal infections were documented in three patients (11%), comprising invasive fungal infections in two cases and a localized esophagitis in one. Ten patients (37%) died before day 100 after transplantation. Infection was considered the primary cause of death in four patients (sepsis by Acinetobacter spp. bacteremia in three cases) and contributed to death in another four. The most striking findings in this series were the high incidence of, and mortality due to multiresistant Acinetobacter spp. and the low incidence of and lack of mortality due to CMV disease. This report confirms that infection is a major complication in adults undergoing UD-CBT.

Blastoschizomyces capitatus Infection in Patients with Leukemia: Report of 26 Cases

Twenty-six cases of Blastoschizomyces capitatus infection were diagnosed in 25 patients at 7 tertiary care hematology units in Spain over a 10-year period. Most patients (92%) had acute leukemia and developed infection during a period of severe and prolonged neutropenia. Two patients had esophagitis, and the rest had invasive infection. Fungemia (20 cases) was a common finding, with frequent visceral dissemination. The 30-day mortality associated with this infection was 52%, compared with 57% among patients with systemic infection. In a univariate analysis, the following 3 variables had a positive impact on 30-day survival: removal of the central venous catheter within 5 days after the onset of infection (P=.02), a good performance status (P=.003), and receipt of systemic prophylactic or empirical antifungal therapy before infection onset (P=.006). Outcome for neutropenic patients with B. capitatus infection is still poor. Rapid removal of the central venous catheter and novel antifungal therapies are recommended for treatment of this rare infection.

Fungal infections after lung transplantation

Lung transplantation (LT) is now considered to be the standard therapeutic intervention in some patients with end-stage pulmonary disease. Infectious complications after LT are relatively common due to the aggressive immunosuppression used in these receptors and local host factors derived from this type of transplant. The incidence of fungal infections after LT ranges up to 30%. However, the incidence of invasive mycoses has declined over the past decade. These mycoses are associated with high overall mortality rates despite increase of the antifungal armamentarium in the last years. Candida and Aspergillus spp produce most of these infections, but unusual moulds such as Scedosporium spp are increasingly recognized as opportunistic pathogens in LT. This review highlights the changing spectrum of invasive fungal infections, risk factors, antifungal prophylaxis, diagnosis, and treatment after LT.

Initial Use of Echinocandins Does Not Negatively Influence Outcome in Candida parapsilosis Bloodstream Infection: A Propensity Score Analysis

BACKGROUND Concerns have arisen regarding the optimal antifungal regimen for Candida parapsilosis bloodstream infection (BSI) in view of its reduced susceptibility to echinocandins. METHODS The Prospective Population Study on Candidemia in Spain (CANDIPOP) is a prospective multicenter, population-based surveillance program on Candida BSI conducted through a 12-month period in 29 Spanish hospitals. Clinical isolates were identified by DNA sequencing, and antifungal susceptibility testing was performed by the European Committee on Antimicrobial Susceptibility Testing methodology. Predictors for clinical failure (all-cause mortality between days 3 to 30, or persistent candidemia for ≥72 hours after initiation of therapy) in episodes of C. parapsilosis species complex BSI were assessed by logistic regression analysis. We further analyzed the impact of echinocandin-based regimen as the initial antifungal therapy (within the first 72 hours) by using a propensity score approach. RESULTS Among 752 episodes of Candida BSI identified, 200 (26.6%) were due to C. parapsilosis species complex. We finally analyzed 194 episodes occurring in 190 patients. Clinical failure occurred in 58 of 177 (32.8%) of evaluable episodes. Orotracheal intubation (adjusted odds ratio [AOR], 2.81; P = .018) and septic shock (AOR, 2.91; P = .081) emerged as risk factors for clinical failure, whereas early central venous catheter removal was protective (AOR, 0.43; P = .040). Neither univariate nor multivariate analysis revealed that the initial use of an echinocandin-based regimen had any impact on the risk of clinical failure. Incorporation of the propensity score into the model did not change this finding. CONCLUSIONS The initial use of an echinocandin-based regimen does not seem to negatively influence outcome in C. parapsilosis BSI.

Patients' characteristics and clinical implications of suboptimal CD4 T-cell gains after 1 year of successful antiretroviral therapy.

To describe characteristics and prognosis of patients with suboptimal immunological response to combined antiretroviral therapy (CART). Using data from a multicenter cohort study, we selected patients who initiated CART and showed suboptimal CD4-T cell response (defined as <50 cells/L increase) after 1 year of therapy, despite sustained virological suppression. Characteristics of those patients were compared with subjects who showed optimal immunological response. Of 650 patients with virological suppression, 108 (16.6%) showed suboptimal CD4-T cell response. Independent predictors of suboptimal response were previous injection drug use (OR, 1.85; 95% CI, 1.12-2.98) and age at CART initiation (OR, 1.04 per year increase; 95%CI, 1.01-1.06). Hepatitis C virus coinfection was not associated with impaired immunological response. As compared with patients with optimal immunological response, those with suboptimal response had a higher mortality rate (3.22 versus 0.71 per 100 person-years; p=.001), but a similar rate of new AIDS-defining events. In patients with sustained virological suppression with CART, previous injection drug use, but not hepatitis C virus coinfection, and older age at initiation of therapy were associated with suboptimal CD4 T-cell responses. Patients with suboptimal response had a higher mortality over time, mainly due to diseases other than AIDS-defining events.

Incidence, risk factors, and outcome of cytomegalovirus infection and disease in patients receiving prophylaxis with oral valganciclovir or intravenous ganciclovir after umbilical cord blood transplantation.

There is no information on the efficacy and safety of anticytomegalovirus (CMV) prophylaxis with intravenous ganciclovir or oral valganciclovir after unrelated cord-blood transplantation (UCBT). This issue was addressed in 151 adults (117 CMV-seropositive) undergoing UCBT at a single institution. The first 38 CMV-seropositive recipients were assigned to receive prophylactic ganciclovir, and the next 79 were given valganciclovir after engraftment. The cumulative incidence (CI) of CMV infection and disease was similar in patients receiving valganciclovir or ganciclovir (59% versus 55%, P = .59; and 9% versus 18%, P = .33, respectively). The toxicity profile and CI of nonrelapse mortality (CMV) and infection-related mortality did not differ between drugs. Patients receiving valganciclovir required fewer visits to the day hospital (P = .04). The CI of CMV infection and disease in 34 CMV-seronegative recipients was 12% and 6%, indicating that tight CMV monitoring is mandatory in this subset. The recipients CMV serostatus, acute and extensive chronic graft-versus-host disease (aGVHD, cGVHD) were the main risk factors for CMV infection, and aGVHD for CMV disease. This study suggests that prophylaxis with oral valganciclovir is as safe and effective as intravenous ganciclovir for preventing CMV infection and disease after UCBT, but valganciclovir reduces the use of hospital resources.

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients. Prophylaxis, empirical, preemptive or targeted therapy, which is the best in the different hosts?

The high morbidity, mortality, and health care costs associated with invasive fungal infections, especially in the critical care setting and immunocompromised host, have made it an excellent target for prophylactic, empiric, and preemptive therapy interventions principally based on early identification of risk factors. Early diagnosis and treatment are associated with a better prognosis. In the last years there have been important developments in antifungal pharmacotherapy. An approach to the new diagnosis tools in the clinical mycology laboratory and an analysis of the use new antifungal agents and its application in different clinical situations has been made. Furthermore, an attempt of developing a state of the art in each clinical scenario (critically ill, hematological, and solid organ transplant patients) has been performed, trying to choose the best strategy for each clinical situation (prophylaxis, pre-emptive, empirical, or targeted therapy). The high mortality rates in these settings make mandatory the application of early de-escalation therapy in critically ill patients with fungal infection. In addition, the possibility of antifungal combination therapy might be considered in solid organ transplant and hematological patients.

EBV-associated post-transplant lymphoproliferative disorder after umbilical cord blood transplantation in adults with hematological diseases

We analyzed the incidence, clinicopathological features, risk factors and prognosis of patients with EBV-associated post-transplant lymphoproliferative disorder (EBV-PTLD) in 288 adults undergoing umbilical cord blood transplantation (UCBT) at a single institution. Twelve patients developed proven EBV-PTLD at a median time of 73 days (range, 36–812). Three-year cumulative incidence (CI) of EBV-PTLD was 4.3% (95% CI: 1.9–6.7). All patients presented with extranodal involvement. Most frequently affected sites were the liver, spleen, central nervous system (CNS), Waldeyer’s ring and BM in 7, 6, 4, 3 and 3 patients, respectively. One patient had polymorphic and 11 had monomorphic EBV-PTLD (7 diffuse large B-cell lymphomas not otherwise specified, 4 plasmablastic lymphomas). We confirmed donor origin and EBV infection in all histological samples. EBV-PTLD was the cause of death in 11 patients at a median time of 23 days (range, 1–84). The 3-year CI of EBV-PTLD was 12.9% (95% CI: 3.2–22.5) and 2.6% (95% CI: 0.5–4.7) for patients receiving reduced-intensity conditioning (RIC) and myeloablative conditioning, respectively (P<0.0001). In conclusion, adults with EBV-PTLD after UCBT showed frequent visceral and CNS involvement. The prognosis was poor despite routine viral monitoring and early intervention. An increased risk of EBV-PTLD was noted among recipients of RIC regimens.

Bacteriemia por Pasteurella spp.: una entidad infrecuente durante los ´ultimos 8 años en nuestro centro

Objectivos Revisar y actualizar el conocimiento epidemiologico y clinico relacionado con la enfermedad bacteriemica causada por especies de Pasteurella en nuestro entorno Metodos Estudio retrospectivo en un unico centro hospitalario terciario de los episodios de bacteriemia por Pasteurella spp. en enfermos atendidos durante el periodo comprendido entre enero de 1994 y diciembre de 2001 Resultados De las 31 muestras clinicas remitidas al laboratorio de microbiologia en las que se identifico alguna especie de Pasteurella en el periodo del estudio, cinco correspondieron a hemocultivos positivos (16%) de 5 pacientes con bacteriemia por Pasteurella spp. Globalmente, P. multocida fue la especie predominante en el 70% de todos los aislamientos, al igual que en los hemocultivos donde todas, excepto una, se identificaron como tal. Todos los enfermos eran adultos de mas de 50 anos y presentaban enfermedades de base subyacentes causantes de comorbilidad o cierto grado de inmunocompromiso sobre todo enfermedad cardiovascular e hipertensiva; solo una paciente tenia cirrosis hepatica. En todos los casos, excepto uno, existio contacto o convivencia con perros o gatos. La forma de presentacion clinica de la bacteriemia por Pasteurella spp. fue inespecifica y solo dos episodios se relacionaron con un posible foco de origen (localizado en tejidos blandos). No hubo complicaciones graves en forma de shock septico, fallo multiorganico o enfermedad invasiva (meningitis o endocarditis). Todos los pacientes se curaron con el tratamiento antimicrobiano, aunque en 2 casos fue necesario desbridamiento quirurgico de la infeccion de herida por mordedura. Los betalactamicos, y otras familias de antibioticos, mostraron una excelente actividad in vitro frente a las cinco cepas de Pasteurella aisladas en hemocultivos Conclusiones La bacteriemia por Pasteurella spp. ocurre en pacientes adultos con distintos y variados factores de comorbilidad; la mayoria han contactado con animales domesticos, aunque no siempre con lesion traumatica, y la presentacion clinica no es diferente a la de otras sepsis no graves. Aunque la sensibilidad y la respuesta al tratamiento de eleccion (penicilinas y derivados) sigue siendo excelente, deberia realizarse un mayor enfasis preventivo relacionado con las medidas de higiene y limpieza en este grupo de enfermos que conviven con animales de compania

Spondylodiscitis Caused by Candida krusei: Case Report and Susceptibility Patterns

ABSTRACT A 62-year-old man with amphotericin B-resistant Candida krusei spondylodiscitis, following an episode of candidemia caused by the same strain, was successfully treated with caspofungin plus voriconazole. Amphotericin B fungicidal concentrations were better predictors of the clinical outcome than were MICs. This is the first case of C. krusei spondylodiscitis reported in the literature.