Elías Cañas

Comparison of a repetitive extragenic palindromic sequence-based PCR method and clinical and microbiological methods for determining strain sources in cases of nosocomial Acinetobacter baumannii bacteremia.

ABSTRACT Using a repetitive extragenic palindromic PCR (REP-PCR), we genotypically characterized strains causing nosocomial Acinetobacter baumannii infections and analyzed the source of bacteremia in 67 patients from an institution in which infections by this bacterium were endemic. Six different genotypes were found, including 21, 27, 3, 9, 3, and 4 strains. The probable source of bacteremia, according to clinical and/or microbiological criteria, was known in 42 patients (63%): respiratory tract (n = 19), surgical sites (n = 12), intravascular catheters (n = 5), burns (n = 3), and urinary tract (n = 3). The definite source of bacteremia, according to REP-PCR, could be established in 30 (71%) out of the 42 patients with strains from blood and other sites; in these cases clinical and microbiological criteria for the source of bacteremia were thus confirmed. In the remaining 12 patients (29%) the probable source was refuted by the REP-PCR method. The definite sources of bacteremia according to genotype were as follows: respiratory tract in 13 patients (31%), surgical sites in 8 (19%), intravascular catheters in 4 (9%), burns in 3 (7%), and urinary tract in 2 (5%). A comparison of strains from blood cultures and other sites with regard to their REP-PCR and antimicrobial resistance profiles was also made. Taking the REP-PCR as the “gold standard,” the positive predictive value of antibiotype was 77% and the negative predictive value was 42%. In summary, the utility of the diagnosis of the source of nosocomial A. baumannii bacteremia using clinical and/or microbiological criteria, including antibiotyping, is limited, as demonstrated by REP-PCR.

Infections in Renal Transplant Recipients Receiving Mycophenolate Versus Azathioprine-Based Immunosuppression

Differences in the incidence, etiology, type, and outcome of infections occurring during the first 6 months after transplantation were evaluated in two consecutive cohorts of kidney recipients who received immunosuppressive regimens based on either azathioprine (plus antilymphocyte globulin, cyclosporine A, and prednisone) (ATG-AZA cohort) or mycophenolate-mofetil (plus cyclosporine A and prednisone) (MMF cohort). The overall incidence of infections in the two cohorts was similar (0.99±1.06 infections/patient in the MMF cohort and 1.04±0.99 in the ATG-AZA cohort, P=0.3), as was the incidence of bacterial and fungal infections. In patients who received mycophenolate, cytomegalovirus disease occurred at a higher incidence (0.3±0.54 vs. 0.1±0.34 episodes/patient, P=0.005) and affected the upper gastrointestinal tract more frequently (0.21±0.48 vs. 0.025±0.16 episodes of cytomegalovirus ulcerative esophagitis, gastritis, or duodenitis per patient; P=0.001). A nonsignificant trend toward a higher recipient survival for patients receiving mycophenolate was noted (100% vs. 95%, P=0.07). In multivariate analysis, the following factors were independently associated with a higher risk of cytomegalovirus disease: the serostatus R–/D+ (seronegative recipients who received a kidney from a seropositive donor) (RR=35.7 [95%CI, 7.4–166.7]), treatment with mycophenolate (RR=10.4 [95%CI, 2.7–38.4]), and the development of any episodes of acute rejection (RR=10.1 [95%CI, 2.5–41.6]). These data show that kidney recipients receiving mycophenolate have a higher incidence of cytomegalovirus disease, mainly affecting the upper gastrointestinal tract, compared to those receiving azathioprine-based immunosuppression.

The changing etiology of fever of intermediate duration

BACKGROUND Fever of intermediate duration (FID) is a common condition. Currently, its most frequent causes are not well defined. METHODS Prospective study of FID cases attended at a hospital in 2 periods: 1983-1989 and 2004-2005. Blood cultures and serologic studies for Brucella melitensis, Coxiella burnetii, Rickettsia typhi, Rickettsia conorii, cytomegalovirus, and Epstein-Barr virus were performed on all patients. Other microbiological, serological, radiological, or invasive procedures were performed according to clinician-in-charge criteria. RESULTS A total of 505 patients were included from 1983 to 1989, and 179 from 2004 to 2005. A diagnosis was reached in 410 (81.1%) and 109 patients (60.9%), respectively. The cause of FID was an infectious disease in 389 patients from the first period (94.8% of those with a final diagnosis) and 92 from the second (84.4%). Most were systemic infections, 328 (80%) in 1983-1989 and 74 (67.8%) in 2004-2005, followed by focal infections, 9.5% and 16.5%, respectively. Q fever was the most frequent etiology in both periods. In 2004-2005, brucellosis decreased and HIV infection emerged as a cause of FID. The origin of FID was non-infectious in 5.1% and 15.5%, respectively. CONCLUSIONS Q fever is the most frequent cause of FID in southern Spain. Studies over time are needed to identify changes in the etiologic spectrum of this condition. Important viral etiologies, such as HIV infection, may be detected as causes of FID. Further studies are needed to determine the importance of other agents as causes of FID.

Pharmacokinetics of zidovudine in end-stage renal disease: influence of haemodialysis.

Objective.To study the pharmacokinetics of zidovudine (ZDV) and its glucoronide metabolite (C-ZDV) in a patient with end-stage renal disease in haemodialysis. Design.Pharmacokinetics study performed during and between haemodialysis sessions. Methods.The patient was treated with oral ZDV (100 mg every 8 h). Concentrations of ZDV and G-ZDV were measured by radioimmunoassay. A monocompartmental model was used to calculate pharmacokinetic parameters. Results.The peak plasma concentrations of ZDV and C-ZDV after drug administration between haemodialysis sessions were 0.57 and 10.01 μg/ml, respectively. The half-lives of ZDV and C-ZDV rose to 3.2 and 14.2 h, respectively. The total body clearance for ZDV in the period between haemodialysis sessions (0.44 l/kg/h) was 66% lower than normal values. The ZDV half-life was normalized by haemodialysis, the total body clearance of ZDV increased (1.12 l/kg/h) and the C-ZDV half-life shortened (5.9–7.9 h). Neither C-ZDV accumulation nor derived ZDV toxicity occurred. Conclusions.Our data suggest that ZDV is safe and an efficient drug when administered at a dosage of 100 mg three times daily in patients with end-stage renal disease in haemodialysis sessions, and that ZDV and C-ZDV are cleared by haemodialysis.

Las infecciones en el trasplante hepático del siglo veintiuno

La incidencia de infecciones postrasplante sigue siendo muy elevada y, al contrario que la mortalidad, no se ha reducido. Las numerosas medidas aplicadas para su prevencion no han tenido el exito esperado porque con frecuencia se han basado mas en el temor al elevado riesgo de infeccion que en la demostracion de su eficacia. La descontaminacion intestinal selectiva es un buen ejemplo de ello, a pesar de una larga experiencia en el trasplante hepatico, no ha conseguido prevenir las infecciones bacterianas ni fungicas y, por el contrario, favorece el desarrollo de resistencias. En el estudio de Losada et al, que utilizan profilaxis universal con norfloxacino, la resistencia de Escherichia coli a quinolonas alcanza el 76%. Estos datos hacen razonable limitar el uso de la descontaminacion intestinal selectiva a nuevos proyectos de investigacion clinica. En general, la profilaxis universal postrasplante hepatico ha dejado paso a la profilaxis seleccionada en pacientes de alto riesgo, que es mas eficiente y segura, con la excepcion de la profilaxis de la herida quirurgica y de la neumonia por Pneumocystis carinii. Con ello, la identificacion de nuevos factores de riesgo de infeccion, como el de la anastomosis de la arteria hepatica con sutura diferente a la terminoterminal descrita por Losada et al se hace mas necesaria. Desde el comienzo del trasplante hepatico, citomegalovirus ha sido el microorganismo estrella por su elevada morbimortalidad. La aparicion del ganciclovir ha eliminado practicamente la mortalidad por citomegalovirus y ha reducido la frecuencia de infeccion (30%) y de enfermedad (6-10%). El proximo reto esta en saber si el citomegalovirus tiene efectos indirectos sobre el trasplante como algunos estudios sugieren, en concreto su relacion con el rechazo agudo y cronico y, si el control de la infeccion previene el rechazo y mejora la supervivencia. Si asi fuese, seria necesario cambiar la estrategia preventiva actual, encaminada a evitar el desarrollo de la enfermedad, por una estrategia menos tolerante dirigida a evitar la infeccion activa. El valganciclovir reune las caracteristicas farmacocineticas apropiadas para ser ensayado en la prevencion de la infeccion activa por citomegalovirus durante largos periodos de tiempo. La resistencia de citomegalovirus a ganciclovir, que por ahora esta limitada a los receptores citomegalovirus (–) con donante citomegalovirus (+) que realizaron profilaxis prolongada con ganciclovir oral, es una nueva llamada de atencion sobre los riesgos de la profilaxis y para el desarrollo de antivirales con mecanismos de accion diferentes frente a citomegalovirus. La relacion de los virus de la hepatitis con el trasplante hepatico es una historia inacabada de exitos y de fracasos. La recurrencia del virus de la hepatitis B (VHB) durante los primeros meses postrasplante era la norma en los El pasado ano se realizaron en Espana mas de 900 trasplantes hepaticos con una supervivencia esperada superior al 80% a los 5 anos (http://www.msc.es/ont/esp/registro/f_registro.htm). El progreso del trasplante hepatico ha estado estrechamente ligado al control del rechazo y de las infecciones. La importancia de las infecciones en el trasplante hepatico quedo establecida en la decada de los anos 80, con el estudio de Kusne et al en el que la incidencia de infeccion postrasplante fue de 1,3 episodios por paciente y la mortalidad secundaria a la misma del 23%. En este numero de la revista, Losada et al analizan las infecciones precoces de 149 trasplantes hepaticos realizados en el Hospital Universitario Puerta de Hierro durante los anos 90. La lectura de ambos trabajos invita a reflexionar sobre la evolucion de las infecciones en el trasplante hepatico y a imaginar el futuro de estas. De esta comparacion asimetrica la mejor noticia es la reduccion de la mortalidad relacionada con las infecciones en casi el 50% (23% frente a 12%). La peor que su frecuencia sigue siendo muy elevada (1,1 episodios por paciente). Pero, ademas, hay otras diferencias cualitativas entre ambos periodos, referidas a la etiologia de las infecciones, a la sensibilidad de los microorganismos causales, y al diagnostico y tratamiento de los mismos, que demuestran la rapida evolucion de esta area del saber medico. Los avances en la inmunosupresion, en la cirugia, y en el conocimiento de las infecciones han sido factores determinantes en la reduccion de la mortalidad infecciosa en el trasplante hepatico. Es decir, la suma de un progreso multidisciplinario, como no podia ser de otra manera en un procedimiento tan vasto como el trasplante. Fruto del trabajo en estas unidades funcionales que conforman los grupos de trasplante, integradas por especialistas diversos, incluidos los infectologos, es la elaboracion de dos documentos por el Grupo para el Estudio de las Infecciones en el Trasplante (GESITRA) de la Sociedad Espanola de Enfermedades Infecciosas (SEIMC). En el primero de ellos se definen los criterios para la seleccion del donante de organos respecto a la transmision de infecciones y en el segundo, que se publica en este numero de la revista, la evaluacion de las enfermedades infecciosas en el candidato a trasplante de organo solido. En ambos se puede comprobar la complejidad de la microbiologia y de la infectologia del trasplante.

Zika Virus Screening among Spanish Team Members After 2016 Rio de Janeiro, Brazil, Olympic Games

We evaluated the risk for the Spanish Olympic Team acquiring Zika virus in Rio de Janeiro, Brazil, during 2016. We recruited 117 team members, and all tested negative for Zika virus. Lack of cases in this cohort supports the minimum risk estimates made before the Games.

Malaria and Travel to the Dominican Republic

To the Editor: The rise in international travel to malaria-endemic areas in recent years has been followed by an increase in the number of cases diagnosed in countries where malaria is not endemic (1). Tourist areas of the Dominican Republic have traditionally been considered to be low risk for malaria transmission. However, over the past few years, sporadic descriptions of imported falciparum malaria in travelers to these destinations have been described (2,3). In spite of these findings, neither the World Health Organization nor the Centers for Disease Control and Prevention recommend antimalarial chemoprophylaxis for trips to the Dominican Republics main tourist resorts (4,5).1 We report a new case of imported malaria caused by mixed Plasmodium vivax and P. malariae infection, with unique clinical features, after a standard tourist trip to Puerto Plata (on the northern coast of the Dominican Republic). A 31-year-old man with no relevant medical history was treated in the internal medicine department of our hospital. He reported a history of poorly defined malaise, night sweats, sleeplessness, tinnitus, and episodic diarrhea with no pathologic products during the previous 6 days. He did not report fever, chills, or headache. Two weeks earlier, he had spent 10 days in Puerto Plata in a tourist resort, without traveling to any other place. He had not received any antimalarial chemoprophylaxis. Physical examination showed no abnormalities. Laboratory values, including levels of sodium, potassium, liver enzymes, creatinine, and coagulation factors, as well as results of hemogram and chest radiograph, were within normal limits. A blood film showed trophozoytes of P. vivax and P. malariae. In a stool specimen, Entamoeba histolytica, Trichiuris trichura, Endolimax nana, and Blastocystis hominis were observed; stool cultures were negative. Treatment was initiated with chloroquine (4 doses) and primaquine for a period of 14 days; metronidazole and paromomycin were administered for the intestinal infestations. Symptoms resolved in 48 hours, and control blood films showed clearance of the parasitemia. Two months after the end of treatment, the patient remained asymptomatic. We describe a new and unusual case of imported vivax-malariae malaria. Two characteristics of our patients case bear mention. First, the place of acquisition of the infection and the species of Plasmodium involved are notable. The Dominican Republic is considered a low-risk area for malaria, although some places in the west, on the Haitian border, are malaria-endemic. In addition, according to available information, autochthonous malaria cases increased after Hurricane George (3,003 cases in 1999, compared to 2,000 in 1998) (6). Previously described sporadic cases of imported malaria from the Dominican Republic included those in tourists who traveled to Punta Cana, in the eastern part of the country. All these cases were caused by P. falciparum. To our knowledge, no cases of P. vivax or mixed P. vivax/P. malariae infection have been described after travel to the Dominican Republic (2,3). From January 1999 to September 2003, TropNetEurop (a European surveillance network of tropical and imported diseases) noted 618 cases of P. vivax infection imported to Europe. The most common areas of acquisition of P. vivax infection were the Indian subcontinent (17%), Indonesia (12.1%), South America (11.4%), and West Africa (11.4%). Only 0.2% of the cases of P. vivax infection were acquired in the Caribbean, none of them in the Dominican Republic (7). Second, the clinical features were atypical. Malaria usually starts as a febrile syndrome, accompanied by chills, headache, malaise, and arthromyalgia. However, sometimes symptoms are unspecific. In fact <10% of patients do not exhibit fever or chills, and some report only poorly defined complaints or other atypical symptoms. Among these, gastrointestinal symptoms are the most frequently reported (8). In the present case, the syndrome could have been easily explained by the intestinal infestations detected in stool studies, and malaria would have been overlooked if the clinician had not taken into account this disease in the diagnostic workup. In summary, clinicians should include malaria in the diagnostic workup of tourists who become ill after traveling to the Dominican Republic. Species other than P. falciparum may be the cause of the disease; these species likely induce more atypical forms of malaria.

Neumonía por Pneumocystis carinii y cáncer de órgano sólido

Pneumocystis carinii pneumonia is associated with immunodepression processes of cellular origin, such as haematological neoplasia, solid organ transplant, or HIV infection. Patients with solid organ tumours under chemotherapy treatment develop P. carinii pneumonia with much lower frequency. We report a case of P. carinii pneumonia in a patient with advanced prostatic neoplasia under chemotherapy treatment. The patient was treated with cotrimoxazol and methylprednisolone for two weeks, and with cotrimoxazol during the remaining chemotherapy treatment. Full recovery from pneumonia was achieved.