Elisa Vidal

Tuberculosis in the transplant candidate: importance of early diagnosis and treatment.

Background. Transplantation is contraindicated in candidates with active tuberculosis. The present study was undertaken to determine the clinical manifestations of tuberculosis in the transplant candidate and the prognosis of cases that inadvertently undergo transplantation. Methods. This study was a retrospective study of tuberculosis cases diagnosed among 3,889 transplant candidates. All cases were diagnosed from respiratory or tissue samples obtained in the pretransplant period or during transplantation. Results. We observed 7 cases (0.18%) of active tuberculosis among 3,889 candidates. Two patients had a history of tuberculosis. Tuberculosis was frequently asymptomatic. Three patients had extrapulmonary tuberculosis. Chest radiographs showed residual fibrotic lesions in three patients and noncavitated consolidation in two patients. All of the patients in which the purified protein derivative test was performed were anergic. All patients that inadvertently underwent transplantation were cured. Conclusions. Aggressive management is required to prevent tuberculosis in transplant candidates. Patients that inadvertently undergo transplantation can be effectively treated when diagnosed early.

Tuberculosis Prophylaxis With Levofloxacin in Liver Transplant Patients Is Associated With a High Incidence of Tenosynovitis: Safety Analysis of a Multicenter Randomized Trial

BACKGROUND It is necessary to develop a safe alternative to isoniazid for tuberculosis prophylaxis in liver transplant recipients. This study was designed to investigate the efficacy and safety of levofloxacin. METHODS An open-label, prospective, multicenter, randomized study was conducted to compare the efficacy and safety of levofloxacin (500 mg q24h for 9 months) initiated in patients awaiting liver transplantation and isoniazid (300 mg q24h for 9 months) initiated post-transplant when liver function was stabilized. Efficacy was measured by tuberculosis incidence at 18 months after transplantation. All adverse events related to the medication were recorded. RESULTS CONSORT guidelines were followed in order to present the results. The safety committee suspended the study through a safety analysis when 64 patients had been included (31 in the isoniazid arm and 33 in the levofloxacin arm). The reason for suspension was an unexpected incidence of severe tenosynovitis in the levofloxacin arm (18.2%). Although the clinical course was favorable in all cases, tenosynovitis persisted for 7 weeks in some patients. No patients treated with isoniazid, developed tenosynovitis. Only 32.2% of patients randomized to isoniazid (10/31) and 54.5% of patients randomized to levofloxacin (18/33, P = .094) completed prophylaxis. No patient developed tuberculosis during the study follow-up (median 270 days). CONCLUSIONS Levofloxacin prophylaxis of tuberculosis in liver transplant candidates is associated with a high incidence of tenosynovitis that limits its potential utility.

Identical Rearranged Forms of JC Polyomavirus Transcriptional Control Region in Plasma and Cerebrospinal Fluid of Acquired Immunodeficiency Syndrome Patients with Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system (CNS) caused by the human polyomavirus JC (JCV). JCV has a hypervariable noncoding transcriptional control region (TCR) that spans the origin of replication of the JCV genome through to the first ATG start codon for late gene transcription. The archetype form of TCR is frequently found in the urine and kidneys of healthy and immunocompromised subjects. However the rearranged forms, whose prototype is Mad-1, possibly generated by deletion and duplication of segments of the archetype sequence, are found in the brain and cerebrospinal fluid (CSF) of PML patients. In this study the authors compared JCVTCR detected in paired CSF, plasma, and urine samples of 11 acquired immunodeficiency syndrome (AIDS) patients affected by PML to try to determine where the rearranged JCV TCRs are selected. In one patient, it was also possible to amplify and sequence the TCR in the brain and lymphocytes. Moreover, in 5/11 patients, the CSF, plasma, and urine samples corresponding to 2 months after PML development were available; and in another patient, it was possible to sequence the TCR in plasma and lymphocytes sampled 8 months before the onset of PML. The presence of the same TCR sequences in all the CSF and plasma samples taken from individual patients could strengthen the hypothesis that the blood is a compartment where JCV may replicate and undergo rearrangement of the TCR. This further supports the hypothesis that JCV reaches the brain by a hematogenous route and indicates that the JCV TCR sequences detected in plasma could be used as an early marker of JCV pathogenicity before the clinical appearance of PML in immunocompromised patients.

Infection prevention in solid organ transplantation

As complications from infection are a major cause of morbidity and mortality following transplantation, infection prevention is a cornerstone of any modern solid organ transplantation program. There is no doubt that, among other measures, antimicrobial prophylaxis has decreased the incidence and severity of posttransplant infections, and it is a major contributor to the currently improved survival rates of solid organ transplant recipients. This chapter is not a thorough analysis of all studies examining the prevention of infection following organ transplantation, but a practical guide to widely accepted recommendations regarding the prevention of common infections in the transplant setting, such as bacterial infections, including tuberculosis, cytomegalovirus, hepatitis viruses or invasive fungal infections.

Epidemiology and clinical impact of infection in patients awaiting heart transplantation

OBJECTIVES The aim of this study was to determine the epidemiology and clinical impact of infections in patients awaiting heart transplantation. METHODS We evaluated all patients considered for a heart transplant in our center over a period of 18 months over a period of 18 months from 2007 to 2009. The patients were followed up for 8 months or until death, transplant, or loss to follow-up. RESULTS Ninety patients were included in the study. During follow-up, 25 infections were recorded in 22 heart transplant candidates (24.4%). Respiratory infections were the most frequent infection (12 bronchitis; 48.0%), followed by skin and soft tissue infections (four infections; 16.0%), intra-abdominal infections (four infectious diarrhea; 16.0%), bacteremia (three infections; 12.0%), and urinary tract infections (two infections; 2.0%). Age, comorbidity, sex, and diabetes were not found to be risk factors for infection. Twenty-four patients (26.7%) were transplanted during follow-up. Infection before transplantation was not associated with an increased risk of mortality or a higher rate of infection in the immediate post-transplant period. CONCLUSIONS Infections are common in heart transplant candidates, affecting almost 25% of them. Respiratory tract infections are the most frequent type of infection. However, they are not associated with increased mortality in the immediate post-transplant period.

Paciente procedente de la República del Congo con dolor ocular intermitente

Paciente varon de 27 anos, natural de la Republica del Congo, sin antecedentes de interes, que reside en Espana desde hace 8 meses, acudio al servicio de urgencias, con sensacion de cuerpo extrano, fotofobia y dolor ocular en su ojo derecho. El paciente fue valorado por el oftalmologo de guardia que en su exploracion ocular mediante retinografo detecto la presencia de un verme de aproximadamente 3 cm de longitud en la conjuntiva del globo ocular (fig. 1). Se procedio a su extraccion mecanica en el quirofano de urgencia tras la aplicacion de anestesicos locales para inmovilizarlo. La muestra fue remitida al laboratorio de microbiologia para su identificacion. El paciente fue citado a la manana siguiente para su valoracion por el Servicio de Medicina Interna-Infecciosas, y se procedio a la extraccion de sangre venosa para estudio de microfilarias sanguineas y otras posibles parasitosis. Al mismo tiempo se instauro tratamiento antiparasitario con albendazol (200 mg/12 h, 3 semanas).

Infections by Carbapenemase Producing Klebsiella Pneumoniae Bacteria in Solid Organ Transplant Recipients

Introduction Infections caused by Klebsiella pneumoniae (Kp), specifically Kp producing Klebsiella pneumoniae carbapenemases (Kp-KPC), are an emerging problem worldwide with an increased incidence of infections by these microorganisms in recent years. Recipients of a solid organ transplant constitute a population at high risk to suffer infections by this type of germs. Our objective was to describe the clinical and microbiological characteristics of the infections caused by K. pneumoniae-KPC in kidney transplant patients (KT) in the context of an outbreak detected in our hospital in July 2012. Materials and Methods Clinical and microbiological data were collected from KT recipients, in which K. pneumoniae-KPC was isolated in any location, carrying out the identification and genetic characterization of the responsible clone by the use of pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). After data collection was completed, patients were followed up to the present time. Results Thirteen patients with Kp-KPC infection were collected: 9 men and 4 women with a median age of 70 years (range 27-78). 11 were recipients of a KT, 1 of simultaneous pancreas-kidney and 1 of simultaneous liver-kidney transplant. 46% had previous intestinal colonization. 62% had received antibiotic treatment in the previous month. The most frequent source of infection was the urinary tract (8/15), followed by respiratory (3/15), abdominal (2/15), venous catheter (1/15) and primary bacteremia (1/15). Blood cultures were positive in 39% of these subjects. Infection was more frequent along the first year after transplantation, with an increase in incidence from the second month post-transplant. Combined treatment was performed in 92% of the cases: fosfomycin + tigecycline (5/13), fosfomycin + gentamicin (3/13), tigecycline + gentamicin (2/13) and tigecycline + fosfomycin + gentamicin (2/13); only 1 patient was treated using monotherapy with fosfomycin. In one case, rescue therapy with ceftazidime/avibactam was used. Cure was achieved in 62% of patients. Crude mortality at 30 days was 23% and that related to Kp-KPC infection was of 15%. The ST512 clone, producer of the carbapenemic resistance enzyme KPC-3, has been identified as the one responsible for the outbreak originated in our hospital. Conclusions In our series, episodes of Kp-KPC infection in kidney transplant patients have been more frequent since the 2nd month post-transplant, with the urinary tract being the most frequent focus and requiring combined treatment in most cases, achieving clinical cure and microbiological eradication in most patients.

Fosfomycin for the Treatment of Asymptomatic Bacteriuria and Cystitis in Kidney Transplantation: new uses of an old antibiotiotic in the era of multidrug-resistance

Background The number of urinary tract infections (UTI) caused by multidrug-resistant (MDR) Gram-negative bacilli (GNB) in kidney transplant recipients (KTR) is increasing. Fosfomycin could be a suitable alternative, especially when other effective oral antibiotics are absent. Materials and Methods We performed a retrospective study including 14 Spanish hospitals. KTR treated with oral fosfomycin for cystitis or asymptomatic bacteriuria (AB) between 2005 and 2017 were included. Patients that concomitantly received another active antibiotic were excluded. We defined “clinical cure” of patients with cystitis as the remission of UTI symptoms at the end of treatment. Results A total of 326 KTR (42% males) developed 353 episodes of UTI (40.5% cystitis and 59.5% AB) treated with fosfomycin (11.9% of cases after the failure of a previous antibiotic treatment). 79 recipients (22.4%) had a urinary catheter (double J stent [14.4%]; urethral catheter [9.6%]). 333 episodes were produced by a GNB (94.3%), 57.0% were identified as MDR (16.5% extended-spectrum &bgr;-lactamase (ESBL)-producing Enterobacteriaceae; 3.3% of carbapenemase-producing bacilli). Gram-positive cocci accounted for 20 UTI (5.7%), especially Enterococcus spp. (12 episodes [60.0%]). A median dose of 2 g daily of fosfomycin (IQR: 1.5-3) was prescribed, for a median of 7 days (IQR: 3-9). There was clinical cure in 119 KTR (83.8%) treated for cystitis. Only 56 of these recipients had a urine culture performed within the first two weeks after stopping fosfomycin; in 44 (78.6%) it was sterile. In the case of AB, 99 KTR (48.3%) had a urine culture performed within the first two weeks after stopping fosfomycin; it was sterile in 50 (50.5%). No serious adverse events related to fosfomycin were reported. Conclusion Fosfomycin appears to be safe and effective for the treatment of cystitis and AB in KTR. Its availability is especially important for the treatment of infections produced by MDR bacteria with poor alternative antibiotic options. Countries in which oral fosfomycin is not available should consider its commercialization. On behalf of the Spanish Network for Research in Infectious Diseases (REIPI) and the Group for the Study of Infection in Transplantation of the Spanish Society of Infectious Diseases and Clinical Microbiology (GESITRA-SEIMC).

Detection of cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance

BACKGROUND Current guidelines recommend that treatment of resistant cytomegalovirus (CMV) in solid organ transplant (SOT) recipients must be based on genotypic analysis. However, this recommendation is not systematically followed. OBJECTIVES To assess the presence of mutations associated with CMV resistance in SOT recipients with suspected resistance, their associated risk factors and the clinical impact of resistance. STUDY DESIGN Using Sanger sequencing we prospectively assessed the presence of resistance mutations in a nation-wide prospective study between September 2013-August 2015. RESULTS Of 39 patients studied, 9 (23%) showed resistance mutations. All had one mutation in the UL 97 gene and two also had one mutation in the UL54 gene. Resistance mutations were more frequent in lung transplant recipients (44% p=0.0068) and in patients receiving prophylaxis ≥6 months (57% vs. 17%, p=0.0180). The mean time between transplantation and suspicion of resistance was longer in patients with mutations (239 vs. 100days, respectively, p=0.0046) as was the median treatment duration before suspicion (45 vs. 16days, p=0.0081). There were no significant differences according to the treatment strategies or the mean CMV load at the time of suspicion. Of note, resistance-associated mutations appeared in one patient during CMV prophylaxis and also in a seropositive organ recipient. Incomplete suppression of CMV was more frequent in patients with confirmed resistance. CONCLUSIONS Our study confirms the need to assess CMV resistance mutations in any patient with criteria of suspected clinical resistance. Early confirmation of the presence of resistance mutations is essential to optimize the management of these patients.

Tumoración lumbar en un paciente con sida

Se solicito tomografia computarizada abdominopelvica (fig. 2). Dados los antecedentes del paciente, se inicio tratamiento anti-MAC con rifabutina, claritromicina y etambutol, asi como tratamiento antirretrovirico con estavudina, lamivudina y nelfinavir. Se decidio abordaje quirurgico, con drenaje y colocacion de tubo. El postoperatorio curso de forma favorable, excepto por la persistencia de fiebre diaria. Al septimo dia de la intervencion se recibio el resultado del cultivo del material obtenido del drenaje, identificandose Aspergillus niger. Se inicio tratamiento con amfotericina B intravenosa a dosis de 1 mg/kg/dia, y la fiebre remitio en las siguientes 48 h. En el dia 11, y tras un postoperatorio sin complicaciones de relevancia, el paciente solicito el alta voluntaria. Se aconsejo tratamiento domiciliario con itraconazol, antirretroviricos, anti-MAC y trimetropim-sulfametoxazol. El paciente abandono todo el tratamiento, acudio al hospital 28 dias despues en situacion de fallo multiorganico y fallecio el mismo dia de su ingreso.