Invasive Trichosporon infection in solid organ transplant patients: a report of two cases identified using IGS1 ribosomal DNA sequencing and a review of the literature.

Trichosporon species are rare etiologic agents of invasive fungal infection in solid organ transplant (SOT) recipients. We report 2 well-documented cases of Trichosporon inkin invasive infection in SOT patients. We also conducted a detailed literature review of Trichosporon species infections in this susceptible population. We gathered a total of 13 cases of Trichosporon species infections. Any type of organ transplantation can be complicated by Trichosporon infection. Bloodstream infections and disseminated infections were the most common clinical presentations. Liver recipients with bloodstream or disseminated infections had poor prognoses. Although the most common species was formerly called Trichosporon beigelii, this species name should no longer be used because of the changes in the taxonomy of this genus resulting from the advent of molecular approaches, which were also used to identify the strains isolated from our patients. Antifungal susceptibility testing highlights the possibility of multidrug resistance. Indeed, Trichosporon has to be considered in cases of breakthrough infection or treatment failure under echinocandins or amphotericin therapy. Voriconazole seems to be the best treatment option.

Bacterial and fungal pneumonias after lung transplantation.

OBJECTIVE: The aim of this study was to evaluate the epidemiology of bacterial and fungal pneumonia in lung transplant (LT) recipients and to assess donor-to-host transmission of these microorganisms. MATERIALS AND METHODS: We retrospectively studied all positive cultures from bronchoalveolar lavage (BAL) of 49 lung transplant recipients and their donors from August 2003 to April 2007. RESULTS: There were 108 episodes of pneumonia during a medium follow-up of 412 days (range, 1-1328 days). The most frequent microorganisms were: Pseudomonas aeruginosa (n = 36; 33.3%), Staphylococcus aureus (n = 29; 26.8%), and Aspergillus spp. (n = 18; 16%). Other fungal infections were due to Fusarium spp., Cryptococcus neoformans, and Paracoccidioides brasiliensis. Of the 31 donors with positive BAL, 15 had S. aureus. There were 21 pretransplant colonized recipients (43%) and 16 of them had suppurative underlying lung disease. P. aeruginosa was the most frequent colonizing organism (59% of pretransplant positive cultures). There were 11 episodes of bacteremia and lungs were the source in 5 cases. Sixteen deaths occurred and 6 (37.5%) were due to infection. Statistical analyses showed association between pretransplant colonizing microorganisms from suppurative lung disease patients and pneumonias after lung transplantation (RR = 4.76; P = .04; 95% CI = 1.02-22.10). No other analyzed factor was significant. CONCLUSIONS: Bacterial and fungal infections are frequent and contribute to higher mortality in lung transplant recipients. P. aeruginosa is the most frequent agent of respiratory infections. This study did not observe any impact of donor lung organisms on pneumonia after lung transplantation. Nevertheless, we demonstrated an association between pretransplant colonizing microorganisms and early pneumonias in suppurative lung transplant recipients.

Systemic availability of prophylactic cefuroxime in patients submitted to coronary artery bypass grafting with cardiopulmonary bypass.

Cardiopulmonary bypass and hypothermia (HCPB) is a procedure commonly used during heart surgery, representing a risk factor for the patient by promoting extensive haemodilution and profound physiological changes. Cefuroxime is used for the prevention of infection following heart surgery, and several dose schemes have been suggested for prophylaxis with cefuroxime. The objective of the present study was to assess, in a comparative manner, the systemic availability of cefuroxime administered intravascularly as a bolus dose of 1.5 g to 17 patients having heart surgery with or without HCPB. Plasma cefuroxime concentrations were determined by high-pressure liquid chromatography-UV, and the following values, expressed as medians, were obtained for the study group compared with controls: 69.1 vs. 62.7 mg/L (1st h), 35.8 vs. 26.0mg/L (3rd h), 14.6 vs. 8.7 mg/L (6th h, P<0.05), 6.1 vs. 3.0mg/L (9th h, P<0.05) and 2.6 vs. 1.0mg/L (12th h, P<0.05). Despite the differences recorded during the study period as a consequence of HCPB, low antibiotic concentrations were found as early as 6h post dose for both groups investigated. Thus, the low systemic availability of cefuroxime after the administration of a 1.5-g dose may not protect against postoperative infections. The data obtained permit us to recommend a change in the dose scheme in order to maintain adequate plasma levels of cefuroxime.

Later evolution after cardiac transplantation in Chagas' disease.

OBJECTIVE: This research reported the accumulated experience with cardiac transplantation in Chagas' disease, emphasizing reactivation, immunosuppression, and mortality. METHODS: Fifty-nine patients undergoing cardiac transplantation had Chagas' disease with classically accepted recipient selection criteria. In this series, 84.7% of the patients were functional class IV; 36.0% used vasopressor support; and 13.5% mechanical circulatory assistance. One patient received a heart and kidney transplantation. RESULTS: After the initial experience the doses of immunosuppressants were significantly reduced with improvement in outcomes. The diagnosis of the reactivation of disease was documented by the identification of parasite in the myocardium, or on subcutaneous or serological exams. Reactivation of disease was significantly reduced by decreasing the immunosuppression. Immediate mortality occurred in 10 cases: three infections, two allograft dysfunction, two rejections, and two sudden deaths. Subsequent mortality happened in 14 patients: four by lymphoma, three by infection, two by Kaposi's sarcoma two by rejection, two by constrictive pericarditis, and one by reactivation of disease in the brain. CONCLUSIONS: There's no correlation between the disease and pre- or postoperative prophylaxis. The early diagnosis and specific treatment of reactivation did not leave functional sequelae in the myocardium. Reduction in immunosuppression significantly reduced reactivation of disease and neoplasms. The combined transplantation can be realized safely with more care about the immunosuppressants.

Staphylococcus aureus bacteremia: what is the impact of oxacillin resistance on mortality?

In order to analyse the impact of oxacillin resistance on the mortality of Staphylococcus aureus bacteremia, and to assess the antimicrobial susceptibility of community-acquired strains in two large university hospitals (the Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo and the Instituto Central do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo), we carried out a four-month-long prospective cohort study, which included 163 consecutive cases of S. aureus bacteremia. Of these, 140 (85.9%) were hospital-acquired, 9 (5.5%) were community-acquired and 14 (8.6%) were of indeterminate origin. No cases of community-acquired infection by oxacillin-resistant S. aureus was identified. Among hospital-acquired infections, oxacillin-resistant S. aureus was responsible for 64.3% of cases. Mortality up to 15 days after diagnosis of bacteremia was 27% (18/67) for infections caused by susceptible strains and 33% (32/96) for infections caused by oxacillin-resistant strains (p=0.10). The following independent risk factors for the acquisition of oxacillin-resistant S. aureus were identified in multiple logistical regression analysis: age over 60 years, use of corticoids; presence of a central vascular catheter, and previous use of antibiotics.

Hepatic and pulmonary biopsy by mini-thoracotomy and transdiaphragmatic access.

Frequently, immunodeficient patients have more than one organ or system affected by opportunistic infection or neoplasia, requiring quick and precise diagnostic investigation. In some situations, different invasive diagnostic procedures may be necessary. Open lung biopsy is sometimes necessary to clarify the pulmonary diagnosis. Laparoscopy may be useful to clarify liver or other peritoneal diseases. Some specific patients might require both procedures. In this way it is proposed that the surgeon, through a microthoracotomy used for the pulmonary biopsy, has access to the diaphragm. A small phrenotomy is performed and then a liver needle biopsy under direct vision. The described technique of simultaneous open lung and hepatic biopsy permits better handling of the needle and hemostasis of the hepatic lesion at the puncture site. This method has been used since 1994 on 16 HIV-positive patients, all having clinical and laboratory manifestations of lung disease associated with liver disease of unknown etiology. No complications related to the method were observed. It is significant that different etiologies for the lung and liver disease were found in 50% of the cases. We conclude that the presented technique is simple, useful, and safe.

Epidemiologic investigation of an outbreak of coagulase-negative Staphylococcus primary bacteremia in a newborn intensive care unit.

Infections due to coagulase-negative Staphylococcus (CNS) are an ever-increasing nosocomial problem, particularly in the pediatric population. The authors describe a cluster of three primary bloodstream infections due to CNS in a newborn intensive care unit that occurred between November 23 and December 2, 1992. Two children died as a direct consequence of the bacteremia; at autopsy, one had a large bacteria-containing thrombus extending from the insertion site of a central catheter to the superior vena cava. The children were placed in isolation, and the nursing and medical staff were given topical nasal mupirocin. Plasmid analysis performed later disclosed three different blood isolates that also were different from any of the staff's nasal isolates. The authors concluded that molecular methods such as plasmid analysis are important tools in identifying true outbreaks and can prevent needless interventions, such as those during this cluster.

Significance of the human immunodeficiency virus infection in patients submitted to cardiac surgery.

BACKGROUND: To realize if cardiac surgery could interfere with the evolution of HIV infected patients to the acquired immunodeficiency syndrome (AIDS). METHODS: The study group consisted of 30 HIV positive patients (0.21%) among 14,785 who underwent cardiac surgery at the Heart Institute of University of Sao Paulo Medical School (Incor-FMUSP) from November 1988 to December 1994. Patients were followed up until they were discharged from hospital and a new contact was kept at the end of the first semester of 1995. RESULTS: All patients were asymptomatic at the time they were operated. Two patients progressed to death during hospitalization due to non-infectious complications and other three patients could not be traced. After all 25 patients had their progression evaluated. Six patients (24%) died within a period ranging from 1 to 46 months (average=17 months): 2 due to bacterial pneumonia and 04 due to AIDS-related complications. The average follow-up period for the 19 surviving patients was 33.6 months (ranging from 13 to 74 months), and only one of them (5.3%) saw the infection progress to AIDS. In summary, 5/25 (20%) saw HIV infection progress to AIDS within a maximum period of 74 months. CONCLUSIONS: Data available up to now show no conclusive evidence of acceleration of HIV into AIDS associated with cardiac surgery.

Hyperlipidemia related to the use of HIV-protease inhibitors: natural history and results of treatment with fenofibrate.

Hyperlipidemia has been frequently recorded as a side effect of treating HIV patients with protease inhibitors (PI). This study was initiated to analyze the modifications on blood lipids in HIV-patients receiving PI and the safety and efficacy of the treatment with fenofibrate. Total (TC) and HDL-cholesterol, triglycerides (TG), and CD(4)(+) T-cell counts were measured in 30 HAART-naive patients (Group I) before and after PI introduction. In a second phase of the study, the effects of fenofibrate on lipids, CPK, CD(4)(+), and viral load were determined in 13 patients (Group II) with elevated TC or TG. In Group I, 60% of the patients showed TC or TG elevations. Average increments of 31% and 146% in TC and TG respectively (p<0.0006 and p<0.0001) were observed. In Group II, fenofibrate treatment was associated with decrements of 6.6% (TC) and 45.7% (TG) (p=0.07 and 0.0002) and no modifications on CPK, CD(4)(+), and viral load. In conclusion, hyperlipidemia is common during the treatment of HIV with protease inhibitors, and fenofibrate appears to be an effective and safe choice for its treatment.

Cytomegalovirus and other herpesviruses infections in heart and bone marrow transplant recipients.

From January 1988 to January 1989 all the heart transplant and bone marrow recipients at the Instituto do Coração of the Hospital das Clínicas of the University of São Paulo Medical School were studied for the incidence and morbidity associated with herpesviruses infections after transplantation. Five bone marrow and 5 heart transplant recipients were followed for a mean of 4.2 months post-transplantation. All the patients were seropositive for cytomegalovirus (CMV) before admission and 80% experienced one or more recurrences during the observation period. Of the 12 episodes of CMV infection, that were identified in this study, 83% were accompanied by clinical or laboratory abnormalities. However, there was only one case of severe disease. The overall incidence of infection for herpes simplex (HSV) was 50%. Although most of HSV reactivations were oral or genital, one case of HSV hepatitis occurred. One of the 6 episodes of HSV infections that were treated with acyclovir showed an unsatisfactory response and was successfully managed with ganciclovir. All the individuals had anti-varicella zoster virus antibodies, but none of them developed infection. The study emphasizes the importance of active diagnostic surveillance of herpesvirus infections in transplant patients. Both CMV and HSV reactivations showed high incidence and important morbidity and thus, deserve prophylactic therapy.

[Infections caused by virus in 100 patients submitted to heart transplantation]. / Infecções causadas por vírus em 100 pacientes submetidos a transplante cardíaco.

PURPOSE: To analyse prevalence, clinical features and organ involvement in viral infections occuring after heart transplantation. METHODS: One hundred consecutive heart transplantation patients were studied. The follow-up was three to 90 (mean 23.32 +/- 25.97) months. Viral infections were diagnosed using the Center for Disease Control criteria. RESULTS: Viral infections were responsible for 51 infections, 19.6% of all infections in this patient population. Herpesvirus infection was the most common etiology: 32 (59.25%) of all viral infections were caused by reactivation of or reinfection by cytomegalovirus. Of those infections 27 (84.37%) occurred in the first three weeks following surgery. Only 4 (12.50%) of those showed clinical signs of cytomegalovirus disease. Other herpesvirus causing infections were herpes simplex and varicella-zoster virus. CONCLUSION: Infections are common after heart transplantation and viral infections of herpesviridae family are important causes of those infections; usually as reactivation in an immune suppressed patient. The most important viral infections were caused by reactivation of or reinfection by cytomegalovirus.

[Preoperative HIV infection in cardiovascular surgery]. / Infecção pré-operatória pelo vírus HIV em cirurgia cardiovascular.

PURPOSE: To evaluate patients in the preoperative period of cardiovascular surgery for HIV antibody in the serum. MATERIAL AND METHODS: 1200 patients older than 15 years tested for HIV antibody before cardiovascular surgery with an enzyme immunoassay test (ELISA). When the results were ELISA positive ou inconclusive, another sample was collected for confirmatory test (Western Blot). We also analysed risk factors, clinical status of HIV infection and postoperative evolution. RESULTS: ELISA test for HIV antibody were negative in 1180 (98.3%) patients, inconclusive in 14 and positive in 6. One ELISA inconclusive and six ELISA positive patients resulted Western Blot positive. All of the seven patients were asymptomatic (group II) in relation to HIV infection, including four bisexual men, two transfusion recipients men and a woman with an undetermined source of infection. Only the two transfusion recipients had their risk factor identified before testing. All of them were submitted to surgery with no immediate postoperative complication. CONCLUSION: Seven (0.58%) patients had HIV antibody (Western Blot assay) but in only two risk factors were identified by routine preoperative anamnesis.

[Infections in 100 heart transplantation patients]. / Infecções em 100 pacientes submetidos a transplante cardíaco.

PURPOSE: A prospective study of infective agents in diagnosed infections and deaths by specific agents in cardiac transplant patients. METHODS: Infections occurring in a series of 100 consecutive cardiac transplant patients after transplantation with definite infectious diagnosis were studied; follow-up after transplantation was 3 to 90 (medium 25.38 +/- 25.97) months. Diagnostic criteria for defining infections were those used in the Epidemiology and Quality Control Division of the INCOR, that are the same published by the Centers for Disease Control. The following parameters were analysed: infections/patient/time, causes of infection and organs infected, clinical presentation and clinical aspects of infections, methods used for the infective diagnosis and relationship between rejection episodes and infection. Death caused by infections and survival rates per infection were also studied. RESULTS: Bacterial infections were more frequent (56.3% of all infections), followed by viral infections (19.6%), fungal infections (18%) and protozoal infections (6.1%). Of all deaths after transplantation, 25% were caused by infections. CONCLUSION: Infections are an important cause of mortality and morbidity in this patient population; our data are in accordance to the other reported series.

[Bacterial infections in 100 patients submitted to heart transplantation]. / Infecções bacterianas em 100 pacientes submetidos a transplante cardíaco.

PURPOSE: To evaluate clinical findings and etiology of bacterial infections diagnosed in 100 consecutive heart transplantations. METHODS: One hundred consecutive heart transplant patients were studied. Follow-up after heart transplantation varied from 3 to 90 (mean 25.38 +/- SD 25.97) months. Etiology of bacterial infection was established using the Centers for Disease Control criteria. RESULTS: Bacterial infection was the most common cause of infection after heart transplantation; diagnosis was difficult. Infection sites were skin, mucous, membranes, soft tissue, surgical scar, pericardial and pleural spaces, soft tissue around heart pacing devices, urinary tract; bacteremias and endocarditis were also found. All bacterial agents recovered were fully identified. CONCLUSION: Bacterial infections are the most common infections in the first month after heart transplantation. They are important and also common after the treatment of the rejection episodes. Rapid diagnosis and adequate treatment are essential to prevent morbidity and death.

[Fungal infections in 100 patients subjected to heart transplantation]. / Infecções fúngicas em 100 pacientes submetidos a transplante cardíaco.

PURPOSE: To evaluate prevalence, causes, clinical aspects, topography and deaths due to fungal infections diagnosed in a series of patients submitted to heart transplantation. METHODS: 100 consecutive patients submitted to heart transplantation were studied. Follow-up was three to 90 (mean 25.38 +/- 25.97) months. Fungal infections were diagnosed by the Centers for Disease Control criteria. RESULTS: Forty seven fungal infections were found, with three deaths caused mainly by fungal infection. The most common infection in this series was oral infection by Candida albicans, Acremonium sp, Aspergillus sp, Candida tropicalis, Histoplasma capsulatum and Pneumocystis carinii were also responsible for infections in this patient population. CONCLUSION: Fungal infections caused three deaths in this series, and were responsible for increased morbidity. The authors suggest prophylactic and therapeutic recommendations.

[Infective endocarditis in 100 patients subjected to heart transplantation]. / Endocardite infecciosa em 100 pacientes submetidos a transplante cardíaco.

PURPOSE: An analysis of occurence, etiology, clinical aspects and death rate of infectious endocarditis cases involving patients who underwent heart transplantation. METHODS: 100 consecutive heart transplant patients were analysed; follow-up varied from three to 90 (medium of 25.38, SD +/- 27.97) months. Diagnostic criteria for endocarditis were those of the epidemiology and quality control service, Heart Institute, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, that agree with those of the Center for Disease Control. Diagnosis was established mostly by blood cultures, echocardiograms, either transthoracic or esophageal and autopsy. RESULTS: Six cases of endocarditis were recognized, with four deaths; in three of those we found severe systemic compromise. All cases had fever as an important symptom. CONCLUSION: Death risk seems high of infectious endocarditis after heart transplantation. The cause of this high risk appears to be linked to the bacteria themselves, to association with other clinical situations and to the use of immunosuppresive agents. We recommend a high index of suspition when risk factors are present in order to make a rapid diagnosis soon enough in the natural history of the disease; treatment has to be started as soon as possible.

Histoplasmosis as a late infectious complication following heart transplantation in a patient with Chagas' disease.

Infectious complications following heart transplantation are an important cause of morbidity and mortality. Generally, bacterial infections are predominant; however, fungal infections can be responsible for up to 25% of infectious events. We report the case of a patient who presented with histoplasmosis as an infectious complication five years after heart transplantation due to a chagasic cardiopathy. This association has rarely been reported in the international literature.

Nosocomial outbreak of Pantoea agglomerans bacteraemia associated with contaminated anticoagulant citrate dextrose solution: new name, old bug?

We describe an outbreak investigation of Pantoea agglomerans bacteraemia associated with anticoagulant citrate-dextrose 46% (ACD) solution prepared in-house. A healthy man presented with septic shock during plasmapheresis for granulocyte donation. The solution used for priming and blood samples were sent for culture. Identification of the isolate to species level was performed by gyrB sequencing. Typing was performed by pulsed-field gel electrophoresis (PFGE). In total, eight cases were identified during a three-week period. P. agglomerans was also cultured from six ACD solution bags. Isolates from patients and ACD bags were identical by PFGE. All isolates were susceptible to ampicillin, cephazolin, gentamicin, ciprofloxacin, cefepime and imipenem.

Mycobacterium chelonae valve endocarditis resulting from contaminated biological prostheses.

OBJECTIVES: A rapid-growing mycobacteria biological prosthetic valve (BPV) endocarditis related to prosthetic manufacturing process is described in Brazil. METHODS: From 1999 to 2008, thirty-nine patients underwent BPV replacement due to culture-negative suspected endocarditis. All these cases had histological sections stained by Ziehl-Neelsen method. Clinical and microbiological data were reviewed in all acid-fast bacilli (AFB) positive cases. The 16S-23S internal transcribed sequence (ITS) was amplified using DNA extracted from paraffin-embedded samples, digested with restrictions enzymes and/or sequenced. RESULTS: Eighteen AFB positive BPV (18/39)(46%) were implanted in 13 patients and were from the same manufacturer. Four of them were implanted in other hospitals. Thirteen BPV were histologically proven endocarditis and five showed a colonization pattern. The examination of six non-implanted "sterile" BPV from this manufacturer resulted in 5 AFB positive. Mycobacterium chelonae was the AFB identified by ITS restriction analysis and sequencing. CONCLUSIONS: Rapid-growing mycobacteria infections must be suspected and Ziehl-Neelsen stain always performed on histology of either early or late BPV endocarditis, particularly when blood cultures are negative.

Impact of cytomegalovirus infection in lung transplant patients under universal prophylaxis: single-center experience in Brazil.

INTRODUCTION: Cytomegalovirus (CMV) infection, a common complication in lung transplant (LT) patients, is associated with worse outcomes. Therefore, prophylaxis and surveillance with preemptive treatment is recommended. OBJECTIVES: Describe the epidemiology and impact on mortality of CMV infection in LT patients receiving CMV prophylaxis. METHODS: Single-center retrospective cohort of LT recipients from August 2003 to March 2008. We excluded patients with survival or follow-up shorter than 30 days. We reviewed medical charts and all CMV pp65 antigen results. RESULTS: Forty-seven patients met the inclusion criteria and 19 (40%) developed a CMV event: eight CMV infections, seven CMV syndromes, and 15 CMV diseases. The mean number of CMV events for each patient was 1.68 +/- 0.88. Twelve patients developed CMV events during prophylaxis (5/12 had CMV serology D+/R-). Forty-six of the 47 patients had at least one episode of acute rejection (mean 2.23 +/- 1.1). Median follow-up was 22 months (range = 3-50). There were seven deaths. Upon univariate analysis, CMV events were related to greater mortality (P = .04), especially if the patient experienced more than two events (P = .013) and if the first event occurred during the first 3 months after LT (P = .003). Nevertheless, a marginally significant relationship between CMV event during the first 3 months after LT and mortality was observed in the multivariate analysis (hazards ratio: 7.46; 95% confidence interval: 0.98-56.63; P = .052). Patients with CMV events more than 3 months post-LT showed the same survival as those who remained CMV-free. CONCLUSION: Prophylaxis and preemptive treatment are safe and effective; however, the patients who develop CMV events during prophylaxis experience a worse prognosis.