Infección del torrente sanguíneo en pacientes receptores de trasplante de precursores hematopoyéticos. Siete años de experiencia con adultos y niños / Bloodstream infection in patients receiving hematopoietic stem cell transplant. Seven years of experience with adults and children

Resumen Introducción: La infección del torrente sanguíneo es una complicación usual, que puede comprometer la vida de los pacientes que recibieron trasplante de precursores hematopoyéticos. Objetivo: Analizar las características de las infecciones del torrente sanguíneo en receptores de trasplante de precursores hematopoyéticos. Materiales y Métodos: Estudio observacional, retrospectivo. Se revisaron los registros de 451 pacientes (trasplantes autólogos y alogénicos), desde enero de 2009 a octubre de 2015. Resultados: Hubo 99 hemocultivos positivos en 73 pacientes con infección del torrente sanguíneo (16%). Mortalidad atribuible a causas infecciosas: 17%. De las 99 infecciones sanguíneas, 63% fueron provocados por bacilos gramnegativos (Escherichia coli 45%, Klebsiella spp 23%, Pseudomonas spp 11%, Acinetobacter spp 6% y otros bacilos gramnegativos 15%), 33% por cocáceas grampositivas, 3% por hongos y 1% por bacilos grampositivos. Se observó resistencia a ciprofloxacina (81%), piperacilina/tazobactam (48%), Enterobacteriaceae productoras de β-lactamasa de espectro extendido (BLEE) (40%), cefepime (39%) y ausencia de resistencia a amikacina. Discusión: Existe mayor frecuencia de infección por bacilos gramnegativos, con un importante porcentaje de aislados multi-resistentes, y consecuente, alta resistencia al tratamiento antimicrobiano empírico.

Background: Bloodstream infection is a common complication, which can be life-threatening for hematopoietic stem cells transplant recipients. Objective: To analyze the characteristics of bloodstream infections in hematopoietic stem cell transplant recipients. Materials and Methods: Observational, retrospective study. We reviewed the records of 451 patients (autologous and allogeneic transplants) from January 2009 to October 2015. Results: 99 positive blood cultures in 73 patients with bloodstream infection (16%) were found. Mortality attributable to infectious causes was 17%. From the 99 bloodstream infection, 63% were caused by gram-negative bacilli (Escherichia coli 45%, Klebsiella spp 23%, Pseudomonas spp 11% Acinetobacter spp % and other bacilli 15%), 33% by gram-positive cocci, 3% by fungi and 1% by gram-positive bacilli. The gram-negative bacilli were ciprofloxacin resistant (81%), piperacillin/tazobactam resistant (48%), extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae (40%), cefepime resistant (39%) and there was no resistance noted to amikacin. Discussion: There is a higher frequency of gram-negative bacilli infection, with a high percentage of multiresistant microorganisms and high resistance to empirical antibiotic treatment.

Rol de la cirugía en el manejo de la infección invasora por Saprochaete capitata / Role of surgery in Saprochaete capitata (S. capitata) sepsis in a patient with acute myeloid leukemia

Saprochaete capitata (S. capitata) fungal sepsis is a severe condition with a clinical presentation that is similar to other yeast originated fungal sepsis. It is observed in patients with hematological malignancies such as acute myeloid leukemia and neutropenia. We report a 23 year old male presenting with cough, fever and malaise. A bone marrow biopsy led to the diagnosis of acute myeloid leukemia. During the first cycle of chemotherapy the patient presented fever: blood cultures were positive for Klebsiella pneumoniae. Despite antimicrobial treatment, fever persisted; a computed tomography showed a focal splenic lesion; a left exudative pleural effusion appeared. A Matrix Assisted Laser Desorption Ionization-Time of Flight mass spectrometry identified the presence of S. capitata. After multiple antifungal treatments and pleural cavity cleansing by means of videothoracoscopy and laparoscopic splenectomy, the infection resolved and the patient completed his chemotherapy.

Perfil de suscetibilidade de Candida tropicalis a antfúngicos sistêmicos / Susceptibility profile of Candida tropicalis to systemic antifungals

Infecções fúngicas invasivas são uma ameaça crescente à saúde humana. Tem ocorrido um aumento considerável na taxa de infecções nosocomiais no sangue, causadas por espécies de Candida. C. albicans é a principal levedura isolada de candidemias, no entanto o isolamento de C. tropicalis e C.parapsilosis também tem sido frequente. Este estudo teve como objetivos isolar, identificar e avaliaro perfil de suscetibilidade de C. tropicalis a antifúngicos sistêmicos. Foram utilizadas 50 cepas de C.tropicalis provenientes de amostras clínicas de sangue, urina e lavado bronco alveolar de pacientes atendidos no Ceará. Foi avaliado o perfil de sensibilidade das cepas aos antifúngicos sistêmicos anfotericina B, fluconazol, itraconazol e voriconazol pela metodologia de microdiluição em caldoRPMI. As cepas de C. tropicalis não apresentaram resistência, mas foram encontradas cepas com CIM elevada para o fluconazol, portanto deve ter continuidade o monitoramento de Candida spp. isoladas no Ceará com o fim de avaliar a evolução da resistência.

Species distribution and susceptibility profile of yeasts isolated from blood cultures: results of a multicenter active laboratory-based surveillance study in Argentina

The Mycology Department of the Instituto Nacional de Enfermedades Infecciosas "Dr. C. Malbrán", conducted the Second National Multicenter Survey on Fungemia due to Yeasts in Argentina. The aim was to obtain updated data of the frequency of the causative species encountered and their in vitro susceptibility to seven antifungal agents. Yeast species were identified by micromorphological and biochemical studies. Antifungal susceptibility testing was performed by the reference microdilution method E.Def 7.1 of the European Committee on Antibiotic Susceptibility Testing (EUCAST). A total of 461 viable yeasts were identified. The most frequent species were: Candida albicans (38.4 %), Candida parapsilosis (26 %), Candida tropicalis (15.4 %) and Candida glabrata (4.3 %). Other uncommon species, such as Candida viswanathii (0.6 %), Candida haemulonii (0.4 %), Candida inconspicua (0.2 %) and Candida fermentati (0.2 %) were also isolated. Among the Candida spp., 5.4 % and 1.6 % were resistant to fluconazole and voriconazole, respectively. Itraconazole and caspofungin were the most efficient agents against all Candida spp. tested (MIC < 1 mg/l). For anidulafungin, 21.6 % of C. parapsilosis showed a MIC value of 4 mg/l. Fluconazole was less active against 53.1 % of Cryptococcus neoformans (MIC > 8 mg/l), 75 % of Trichosporon spp., and 100 % of Rhodotorula spp., Geotrichum candidum, Saccharomyces cerevisiae. The global percentage of mortality was 20 %. The presence of uncommon species reinforces the need for performing continuous laboratory surveillance in order to monitor possible changes, not only in the epidemiological distribution of species, but also in the resistance to antifungal drugs.

Distribución de especies y perfil de sensibilidad de levaduras aisladas de hemocultivos: resultados de un estudio multicéntrico de vigilancia de laboratorio en Argentina. El Departamento Micología del Instituto Nacional de Enfermedades Infecciosas "Dr. Carlos G. Malbrán" condujo el segundo estudio multicéntrico nacional sobre funge- mias debidas a levaduras. El objetivo fue obtener datos actualizados sobre la distribución de especies y la sensibilidad in vitro frente a siete antifúngicos. Las levaduras fueron identificadas mediante el estudio de la micromorfología y la realización de pruebas bioquímicas. La determinación de la sensibilidad se realizó según el método de referencia E.Def 7.1 del European Committee on Antibiotic Susceptibility Testing (EUCAST). Se identificaron 461 levaduras. Las especies más frecuentes fueron Candida albicans (38,4 %), Candida parapsilosis (26 %), Candida tropicalis (15,4 %) y Candida glabrata (4,3 %). Se aislaron otras especies menos comunes, como Candida viswanathii (0,6 %), Candida haemulonii (0,4 %), Candida inconspicua (0,2 %) y Candida fermentati (0,2 %). Entre las especies del género Candida, el 5,4 % y el 1,6 % fueron resistentes al fluconazol y al voriconazol, respectivamente. El itraconazol y la caspofungina fueron los antifúngicos más eficaces in vitro frente a las especies de Candida evaluadas (CIM < 1 mg/l). Para la anidulafungina, el 21,6 % de los aislamientos de C. parapsilosis mostraron una CIM de 4 mg/l. El fluconazol fue menos activo para el 53,1 % de los aislamientos de Cryptococcus neoformans (CIM > 8 mg/l), el 75 % de los aislamientos de Trichosporon spp. y el 100 % de los aislamientos de Rhodotorula spp., Geotrichum candidum y Saccharomyces cerevisiae. El porcentaje de mortalidad fue del 20 %. La presencia de especies infrecuentes refuerza la necesidad de realizar la continua vigilancia de laboratorio con el fin de monitorear posibles cambios, no solo en la epidemiología de las especies causantes de fungemia, sino también en la resistencia a los antifúngicos.

Invasive candidiasis in pediatric intensive care units.

Candidemia and disseminated candidiasis are major causes of morbidity and mortality in hospitalized patients especially in the intensive care units (ICU). The incidence of invasive candidasis is on a steady rise because of increasing use of multiple antibiotics and invasive procedures carried out in the ICUs. Worldwide there is a shifting trend from C. albicans towards non albicans species, with an associated increase in mortality and antifungal resistance. In the ICU a predisposed host in one who is on broad spectrum antibiotics, parenteral nutrition, and central venous catheters. There are no pathognomonic signs or symptoms. The clinical clues are: unexplained fever or signs of severe sepsis or septic shock while on antibiotics, multiple, non-tender, nodular erythematous cutaneous lesions. The spectrum of infection with candida species range from superficial candidiasis of the skin and mucosa to more serious life threatening infections. Treatment of candidiasis involves removal of the most likely source of infection and drug therapy to speed up the clearance of infection. Amphotericin B remains the initial drug of first choice in hemodynamically unstable critically ill children in the wake of increasing resistance to azoles. Evaluation of newer antifungal agents and precise role of prophylactic therapy in ICU patients is needed.

Central venous catheter-related bloodstream infection and Cryptococcus neoformans

This is the first case reported of central venous catheter-related fungemia due to C. neoformans. A patient with chronic renal failure developed a fungemia during the treatment of a dialysis-associated bacteremia. Cryptococcus neoformans grew in the catheter tip and blood culture. We addressed questions about this catheter-related fungemia.

Kodamaea ohmeri infection in a neonate.

Kodamaea ohmeri is an extremely uncommon human pathogenic yeast. It causes opportunistic infection in immunocompromised hosts. We report a case of Kodamaea ohmeri fungemia in a preterm neonate who succumbed despite antifungal therapy.

Blood Stream Infections by Candida glabrata and Candida krusei: A Single-Center Experience

BACKGROUND/AIMS: The increasing incidence of Candida glabrata and Candida krusei infections is a significant problem because they are generally more resistant to fluconazole. We compared the risk factors associated with C. glabrata and C. krusei fungemia with Candida albicans fungemia and examined the clinical manifestations and prognostic factors associated with candidemia. METHODS: We retrospectively reviewed demographic data, risk factors, clinical manifestations, and outcomes associated with C. glabrata and C. krusei fungemia at a tertiary-care teaching hospital during a 10-years period from 1997 to 2006. RESULTS: During the study period, there were 497 fungemia episodes. C. glabrata fungemia accounted for 23 episodes and C. krusei fungemia accounted for 8. Complete medical records were available for 27 of these episodes and form the basis of this study. Compared to 54 episodes of C. albicans fungemia, renal insufficiency and prior fluconazole prophylaxis were associated with development of C. glabrata or C. krusei fungemia. The overall mortality was 67%. The fungemia-related mortality of C. glabrata and C. krusei was higher than that of C. albicans (52 vs. 26%, p=0.021). Empirical antifungal therapy did not decrease the crude mortality. Multiple logistic regression analysis showed that high APACHE II scores, catheter maintenance, and shock were independently associated with an increased risk of death. CONCLUSIONS: Renal insufficiency and prior fluconazole prophylaxis were associated with the development of C. glabrata or C. krusei fungemia. Fungemia-related mortality of C. glabrata or C. krusei was higher than that of C. albicans. Outcomes appeared to be related to catheter removal, APACHE II scores, and shock.

Neonatal septicaemia in a premature infant due to Candida dubliniensis.

Candida dubliniensis is a recently described species that shares many features with Candida albicans. There are very few reports of isolation of this species from bloodstream in adults and paediatric population. Here we report a case of neonatal septicaemia produced by C. dubliniensis in a premature infant admitted to neonatal intensive care unit. The preterm male neonate with a gestational age of 30 weeks and a birth weight of 1.2 kg presented with respiratory distress syndrome for which mechanical ventilation was provided. In spite of receiving antibiotics, the patient developed fever. C.dubliniensis was repeatedly isolated from the blood culture of the patient collected aseptically from different sites. The patient was successfully treated with amphotericin B.

Pattern of Candida isolates in hospitalized children.

Nosocomial candidemia is the 4(th) most common pathogen in blood stream infection. Emergence of non-albicans Candida species with often intrinsically resistance fluconazole pattern may lead to difficulty in management of septicemia. Although the present study isolated 80% of non albicans candida species with C.tropicalis as the most common (35%) species, 96% of our Candida species isolated were sensitive to fluconazole. The probable causes of low resistance pattern to fluconazole in our institute are discussed. It is however necessary to identify the complete clinical response to the given treatment. Therefore, appropriate identification of species with susceptibility testing would be advisable before start of anti-fungals. This would prevent emergence of fluconazole resistance.

Fungemia caused by Verticillium species in an immunocompromised child.

The incidence of fungal infections is increasing due to immunocompromised states. We report a case of fungaemia due to a rare fungus - Verticillium, in a 6 year old child diagnosed as a case of acute lymphoblastic leukaemia- L1 with high grade fever. The patient was treated with amphotericin B with a good clinical response.

Estudio multicéntrico de fungemias por levaduras en la República Argentina / Multicenter study of bloodstream infections due to yeasts in Argentina

La incidencia de candidemias aumentó aproximadamente en un 500% en hospitales de alta complejidad y se observó un cambio en la distribución de especies del género Candida, con un incremento de las levaduras no Candida albicans. Con el objeto de conocer la distribución de especies asociadas a fungemias por levaduras en Argentina y determinar su sensibilidad a los antifúngicos de uso convencional, se realizó un estudio multicéntrico durante el período abril 1999 a abril 2000. Participaron 36 instituciones del país. Se colectaron 265 aislamientos de levaduras provenientes de hemocultivos, que se identificaron utilizando pruebas morfológicas, fisiológicas y bioquímicas y la determinación de la concentración inhibitoria mínima se realizó en base al estándar del NCCLS. La distribución de especies fue: Candida albicans (40,75%), Candida parapsilosis (28,67%), Candida tropicalis (15,84%), Candida famata (3,77%), Cryptococcus neoformans (3,77%), Candida glabrata (2,64%) y otras (4,53%). La mayoría de los aislamientos fueron sensibles a anfotericina B, fluconazol e itraconazol. La mortalidad asociada a las fungemias por levaduras estudiadas (n=265) fue del 30%, siendo más baja a lo descrito (33-54%) y fue menor en los pacientes que recibieron tratamiento antifúngico (26,3%), que en los no tratados (47%).

The incidence of candidemia has increased approximately 500% in high-complexity hospitals. A change in the spectrum of Candida infections due to species other than Candida albicans has also been detected. Between April 1999 and April 2000 a multicenter study was performed in order to determine the species distribution associated to candidemias in Argentina and the susceptibility profile of the isolates to the current antifungal drugs. Thirty six institutions have participated. All the 265 yeast strains isolated from blood cultures were identified by morphological, physiological, and biochemical tests. The antifungal susceptibility testing of isolates was performed based on the reference NCCLS procedure. The distribution of species was: Candida albicans (40.75%), Candida parapsilosis (28.67%), Candida tropicalis (15.84%), Candida famata (3.77%), Cryptococcus neoformans (3.77%), Candida glabrata (2.64%), and others (4.53%). Most of the isolates were susceptible to amphotericin B, fluconazole and itraconazole. Mortality associated to the fungemia by yeasts episodes (n=265) was 30%, lower than results previously determined (33-54%). The mortality percentage in patients who received antifungal therapy versus patients without treatment was 26.3% and 47%, respectively.

Treatment of Candida Chorioretinitis with Voriconazole

A 63-year-old female with candidemia following necrotizing pancreatitis developed clinical signs of chorioretinitis and underwent the systemic administration of voriconazole, after which anterior chamber inflammation and multiple, white, fluffy, chorioretinal lesions, under 1mm in diameter, were gradually resolved and visual acuity improved. We report the first Korean case of candida chorioretinitis successfully treated with the systemic administration of voriconazole.

Candidemia in neonatal intensive care unit.

The present study was conducted over a period of 6 months to determine the Candida species causing candidemia in a neonatal intensive care unit and to analyse the risk factors associated with acquisition of significant fungemia. Speciation of the 19 isolated Candida spp was done by the standard techniques. Antimicrobial susceptibility of these isolates was determined by disc diffusion method against Amphotericin B, Fluconazole, Ketoconozole and 5-Flucytosine. Candida glabrata was the most common species involved (42.1%). Other species isolated were C. tropicalis (31.6%). Calbicans (21.1%) and C.parapsilosis (5.2%). All the isolates were sensitive to Amphotericin B. Resistance to other antigungal agents was seen only in C. globrata. Significant candidemia was seen in 14/19 (72.6%) of neonates. Risk factors found to be associated with significant candidemis in these neonates included intake of multiple broad-spectrum antibiotics (p<0.0001), use of total parenteral nutrition (p<0.045) and ventilators (p<0.0001).

Recent trends in antifungal therapy: focus on systemic mycoses.

Amphotericin B (AmB) remains the 'gold standard' for systemic antifungal therapy and newer drug delivery systems have been effectively developed for this drug. The newer azoles e.g. itraconazole, voriconazole and their derivatives are viable alternatives to AmB, and are suitable for oral administration. Combination antifungal therapy has been tried successfully. For instance, AmB plus flucytosine is preferred in cryptococcal meningitis and candidemia. A liquid preparation of itraconazole and cyclodextrin is pharmacokinetically superior to the conventional dosage form of itraconazole, and is particularly effective in mycoses following cytotoxic chemotherapy and bone marrow transplants. Newer potential antifungals such as echinocandins, benanomicins/pradimicins, aureobasidins and nikkomycins are under clinical trials. The role of -immunomodulation in systemic anti-fungal therapy has been proposed and recombinant cytokine therapy (G-CSF, GM-CSF, IFN-g, IL-I, TNF-a) either alone or in combination with AmB have shown good results.

Antifungal agents and immunomodulators in systemic mycoses.

The rising incidence of fungal infections and the emergence of several fungi as opportunistic pathogens have reawakened interest in chemotherapeutic and prophylactic agents for mycoses. During the past decades significant advances have been made in the development of novel antifungal agents for treatment of systemic mycoses. This brief review presents an update of the available information on polyenes, imidazoles, triazoles, flucytosine, allylamines, echinocandins, nikkomycins, sordarins and immunomodulators. A reference has also been made to the work in antifungals done or in progress at the Central Drug Research Institute (CDRI), Lucknow. Currently, antifungals represent more than 6% of the total world market for anti-infective agents and with 20% annual expansion they are expected to cross the 15 billion US Dollars in value within a decade.