Bloodstream infections caused by Escherichia coli producing AmpC ß-lactamases: epidemiology and clinical features.

The aim of the study was to investigate the epidemiology and clinical features of bloodstream infections due to Escherichia coli producing AmpC ß-lactamases (AmpC-Ec-BSI). In a multi-centre case-control study, all third-generation-cephalosporin-resistant Escherichia coli BSI (3GC-Ec-BSI) isolates were analysed. Acquired bla AmpC (bla ac-AmpC) detection was done by polymerase chain reaction (PCR) and sequencing. Chromosomal bla AmpC (bla c-AmpC) expression was quantified by real-time PCR. Cases were patients with AmpC-Ec-BSI. Controls were patients with cephalosporin-susceptible E. coli BSI, matched 1:1 by sex and age. Demographics, comorbidities, intrinsic and extrinsic risk factors for antimicrobial resistance, clinical presentation and outcomes were investigated. Among 841 E. coli BSI, 17 were caused by AmpC-Ec (2 %). Eleven isolates (58.8 %) had bla ac-AmpC and six were bla c-AmpC overproducers. The mean age of cases was 66.2 years and 71 % were men. Cases were more frequently healthcare-related (82 vs. 52 % controls, p < 0.05) and presented more intrinsic and extrinsic risk factors. At least one risk factor was present in 94.1 % of cases vs. 41.7 % of controls (p = 0.002). Severity and length of stay (LOS) were higher among cases (mean Pitt Score 2.6 vs. 0.38 in controls, p = 0.03; LOS 17.5 days vs. 6 in controls, p = 0.02). Inappropriate empirical therapy (IET) was administered to 70.6 % of cases and 23.5 % of controls (p < 0.003). No differences were found in terms of cure rate at the 14th day and mortality. Bloodstream infections due to AmpC-Ec (mostly plasmid-mediated) are infrequent in our area. AmpC-Ec-BSI affects mainly patients with intrinsic risk factors and those with previous antibiotic exposure. A high proportion received IET.

Prevention strategies for cytomegalovirus disease and long-term outcomes in the high-risk transplant patient (D+/R-): experience from the RESITRA-REIPI cohort.

BACKGROUND: Cytomegalovirus (CMV)-negative recipients of a graft from a CMV-positive donor (D+/R-) are at high risk of CMV disease. Current preventive strategies include universal prophylaxis (UP) and preemptive therapy (PT). However, the best strategy to prevent CMV disease and achieve better long-term outcomes remains a matter of debate. METHODS: We analyzed the incidence of CMV disease and long-term outcomes including graft dysfunction and patient mortality at 5 years after transplantation with both preventive strategies. High-risk (D+/R-) kidney and liver transplant recipients from the RESITRA cohort were included. RESULTS: Of 2410 kidney or liver transplant patients, 195 (8.3%) were D+/R-. The final cohort included 58 liver and 102 kidney recipients. UP was given in 92 patients and 68 received PT; 10.9% and 36.8% developed CMV disease, respectively (P < 0.01). The independent risk factors for CMV disease were PT strategy (hazard ratio [HR], 3.30; 95% confidence interval [CI], 1.6-6.9), kidney transplantation (HR, 3.8; 95% CI, 1.4-9.9), and cyclosporine immunosuppression (HR, 2.4; 95% CI, 1.2-4.7). PT strategy was also a risk factor for CMV disease in both liver transplantation (HR, 11.0; 95% CI, 1.2-98.7) and kidney transplantation (HR, 2.7; 95% CI, 1.3-6.0), independently. The development of CMV replication during the first 2 years after transplantation was a risk factor for graft dysfunction at 5 years after transplantation (odds ratio, 3.4; 95% CI, 1.3-9.0). Nevertheless, no significant differences were seen in either graft dysfunction or mortality between the 2 strategies. CONCLUSIONS: The study supports the benefit of the UP strategy to prevent CMV disease in D+/R- liver or kidney transplant patients. The development of CMV replication during the first 2 years after transplantation was associated with graft dysfunction at 5 years after transplantation.

Bacterial urinary tract infection after solid organ transplantation in the RESITRA cohort.

BACKGROUND: Urinary tract infection (UTI) is the most common infection in renal transplant patients, but it is necessary to determine the risk factors for bacterial UTI in recipients of other solid organ transplants (SOTs), as well as changes in etiology, clinical presentation, and prognosis. METHODS: In total, 4388 SOT recipients were monitored in 16 transplant centers belonging to the Spanish Network for Research on Infection in Transplantation (RESITRA). The frequency and characteristics of bacterial UTI in transplant patients were obtained prospectively from the cohort (September 2003 to February 2005). RESULTS: A total of 192 patients (4.4%) presented 249 episodes of bacterial UTI (0.23 episodes per 1000 transplantation days); 156 patients were kidney or kidney-pancreas transplant recipients, and 36 patients were liver, heart, and lung transplant recipients. The highest frequency was observed in renal transplants (7.3%). High frequency of cystitis versus pyelonephritis without related mortality was observed in both groups. The most frequent etiology was Escherichia coli (57.8%), with 25.7% producing extended-spectrum ß-lactamase (ESBL). In all transplants but renal, most cases occurred in the first month after transplantation. Cases were uniformly distributed during the first 6 months after transplantation in renal recipients. Age (odds ratio [OR] per decade 1.1, 95% confidence interval [CI] 1.02-1.17), female gender (OR 1.74, 95% CI 1.42-2.13), and the need for immediate post-transplant dialysis (OR 1.63, 95% CI 1.29-2.05) were independent variables associated with bacterial UTI in renal and kidney-pancreas recipients. The independent risk factors identified in non-renal transplants were age (OR per decade 1.79, 95% CI 1.09-3.48), female gender (OR 1.7, 95% CI 1.43-2.49), and diabetes (OR 1.02, 95% CI 1.001-1.040). CONCLUSIONS: UTI was frequent in renal transplants, but also not unusual in non-renal transplants. Because E. coli continues to be the most frequent etiology, the emergence of ESBL-producing strains has been identified as a new problem. In both populations, most cases were cystitis without related mortality. Although the first month after transplantation was a risk period in all transplants, cases were uniformly distributed during the first 6 months in renal transplants. Age and female gender were identified as risk factors for UTI in both populations. Other particular risk factors were the need for immediate post-transplant dialysis in renal transplants and diabetes in non-renal transplants.

Immunosuppressive therapy and infection after kidney transplantation.

BACKGROUND: The role of immunosuppressive drugs in the development of infection in transplant recipients has been poorly analyzed. OBJECTIVE: To evaluate the possible association between infection and immunosuppression regimens in a large cohort of renal transplant recipients. METHODS: All renal transplant recipients included in the RESITRA prospective cohort from August 2003 to February 2005 with a minimum follow-up of 3 months were studied. An intention-to-treat analysis was performed and patients were analyzed in groups according to the type of induction and initial maintenance therapy. Viral, bacterial, and fungal infections occurring during this period were evaluated. RESULTS: A total of 1398 renal transplant recipients were studied. A maintenance regimen containing sirolimus was independently associated with a lower risk of cytomegalovirus (CMV) infection (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.05-0.54) and with a higher rate of surgical site infection (OR, 3.21; 95% CI, 1.26-8.21). Excluding treatment used for acute rejection episodes, no other factors related to the immunosuppression regimens were associated with the development of bacteremia, urinary infections, pneumonia, or other infections. CONCLUSION: The use of sirolimus as maintenance therapy in kidney recipients is associated with a low rate of CMV infection and with a higher risk of surgical site infection.

Incisional surgical infection in heart transplantation.

BACKGROUND: Incisional surgical site infections (ISSIs) are common bacterial infections in heart transplantation (HT). The purpose of this study was to determine the incidence, etiology, timing, and risk factors for ISSIs. METHODS: A prospective study was performed, which included all heart transplants carried out in the participating hospitals (pertaining to the Spanish National Hospital Network RESITRA) between August 2003 and February 2005. A population of 292 consecutive patients was included (84.9% males). The definition of ISSI used in the study was based on the Centers for Disease Control criteria. RESULTS: Seventeen episodes of ISSIs were recorded in 14 patients (4.8%; confidence interval [CI] 95% 2.7-7.7%). The median time from transplant to ISSI was 14 days (range 3-75). Two patients (14%) died; fatality was related to ISSI (mediastinitis) in 1 patient (7%). Coagulase-negative staphylococci (7 cases), methicillin-resistant Staphylococcus aureus (3 cases), Proteus mirabilis, extended-spectrum beta-lactamase-producing Escherichia coli, Candida albicans, and Candida glabrata, 1 case each, were the isolated pathogens. The duration of extracorporeal circulation was longer in patients with ISSI, although the difference did not reach statistical significance. Antibiotic prophylaxis with ciprofloxacin alone (odds ratio, 15.8; 95% CI, 1.2-216.9) was independently associated with the development of ISSI. CONCLUSIONS: ISSIs in HT are frequently caused by resistant bacteria and Candida, but are associated with good prognosis.

Clinical and microbiological features of nocardiosis 1997-2003.

Nocardiosis has been believed to be caused by the members of the Nocardia asteroides complex and the Nocardia brasiliensis species. However, recent advances in genotypic identification have shown that the genus exhibits considerable taxonomic complexity and the phenotypic markers used in the past for its identification can be ambiguous. The aim of this study was to assess the species distribution of Nocardia isolates and to determine whether there are differences in pathogenicity or antimicrobial susceptibility between the different species identified. Nocardia isolates obtained over a 7 year period were retrospectively reviewed. The isolates were identified genotypically, their antibiotic susceptibility was tested and the clinical data of the 27 patients were retrieved. Eight different Nocardia species were identified: Nocardia farcinica (n=9), Nocardia abscessus (n=6), Nocardia cyriacigeorgica (n=6), Nocardia otitidiscaviarum (n=2), Nocardia nova (n=1), N. nova complex (n=1), Nocardia carnea (n=1) and Nocardia transvalensis complex (n=1). All species were susceptible to co-trimoxazole but different patterns of susceptibility to other agents were observed. All patients had active comorbidities at the time of infection. A total of 19 patients were immunosuppressed, due to human immunodeficiency virus infection, chronic corticosteroid therapy, immunosuppressive therapy or haematological malignancies. Six patients displayed a Charlson comorbidity index score above 4. Global mortality was 50 % while attributable mortality was 34.6 %. Patients infected with N. farcinica--the most resistant species--had the highest Charlson index score and the highest mortality rate. Accurate identification of the species and susceptibility testing of Nocardia isolates may play an important role in diagnosis and treatment.

Investigation of the ability of the Pneumonia Severity Index to accurately predict clinically relevant outcomes: a European study.

In order to confirm the validity of the Pneumonia Severity Index (PSI) for patients in Europe, data from adults with pneumonia who were enrolled in two prospective multicentre studies, conducted in France (Pneumocom-1, n = 925) and Spain (Pneumocom-2, n = 853), were compared with data from the original North American study (Pneumonia PORT, n = 2287). The primary outcome was 28-day mortality; secondary outcomes were subsequent hospitalisation for outpatients, and intensive care unit admission and length of stay for inpatients. All outcomes within individual risk classes, and mortality rates in low-risk (PSI I-III) and higher-risk patients, were compared across the three cohorts. Overall mortality rates were 4.7% in Pneumonia PORT, 6.3% in Pneumocom-2 and 10.6% in Pneumocom-1 (p <0.01), ranging from 0.4% to 1.6% (p 0.06) for low-risk patients and from 13.0% to 19.1% (p 0.24) for high-risk patients. Despite significant differences in baseline patient characteristics, none of the study outcomes differed within the low-risk classes. The sensitivity and negative predictive value of low-risk classification for mortality exceeded 93% and 98%, respectively. Thus, in two independent European cohorts, the PSI predicted patient outcomes accurately and reliably, particularly for low-risk patients. These findings confirm the validity of the PSI when applied to patients from Europe.

Clinical efficacy of ß-lactam/ß-lactamase inhibitor combinations for the treatment of bloodstream infection due to extended-spectrum ß-lactamase-producing Enterobacteriaceae in haematological patients with neutropaenia: a study protocol for a retrospective observational study (BICAR).

INTRODUCTION: Bloodstream infection (BSI) due to extended-spectrum ß-lactamase-producing Gram-negative bacilli (ESBL-GNB) is increasing at an alarming pace worldwide. Although ß-lactam/ß-lactamase inhibitor (BLBLI) combinations have been suggested as an alternative to carbapenems for the treatment of BSI due to these resistant organisms in the general population, their usefulness for the treatment of BSI due to ESBL-GNB in haematological patients with neutropaenia is yet to be elucidated. The aim of the BICAR study is to compare the efficacy of BLBLI combinations with that of carbapenems for the treatment of BSI due to an ESBL-GNB in this population. METHODS AND ANALYSIS: A multinational, multicentre, observational retrospective study. Episodes of BSI due to ESBL-GNB occurring in haematological patients and haematopoietic stem cell transplant recipients with neutropaenia from 1 January 2006 to 31 March 2015 will be analysed. The primary end point will be case-fatality rate within 30 days of onset of BSI. The secondary end points will be 7-day and 14-day case-fatality rates, microbiological failure, colonisation/infection by resistant bacteria, superinfection, intensive care unit admission and development of adverse events. SAMPLE SIZE: The number of expected episodes of BSI due to ESBL-GNB in the participant centres will be 260 with a ratio of control to experimental participants of 2. ETHICS AND DISSEMINATION: The protocol of the study was approved at the first site by the Research Ethics Committee (REC) of Hospital Universitari de Bellvitge. Approval will be also sought from all relevant RECs. Any formal presentation or publication of data from this study will be considered as a joint publication by the participating investigators and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE). The study has been endorsed by the European Study Group for Bloodstream Infection and Sepsis (ESGBIS) and the European Study Group for Infections in Compromised Hosts (ESGICH).

Risk factors for invasive aspergillosis in solid-organ transplant recipients: a case-control study.

BACKGROUND: To facilitate the design of strategies for prevention of invasive aspergillosis in solid-organ transplant recipients, this study investigates whether the development of early-onset and late-onset aspergillosis are related to different risk factors, thereby distinguishing 2 risk populations for this serious complication. METHODS: A retrospective case-control study was performed, including 156 cases of proven or probable invasive aspergillosis in patients recruited from 11 Spanish centers since the start of the centers' transplantation programs. RESULTS: Among all patients, 57% had early-onset IA (i.e., occurred during the first 3 months after transplantation). Risk factor analysis in this group identified as significantly associated risk factors a more complicated postoperative period, repeated bacterial infections or cytomegalovirus disease, and renal failure or the need for dialysis. Among patients with late-onset infections (i.e., occurred > 3 months after transplantation), who comprised 43% of cases, the patients at risk were older, were in an overimmunosuppressed state because of chronic transplant rejection or allograft dysfunction, and had posttransplantation renal failure. CONCLUSIONS: Risk factors in patients with early-onset cases and patients with late-onset cases of posttransplantation invasive aspergillosis are not the same, a fact that could have implications for the preventive approaches used for this infection.

Antiviral susceptibility of Herpes simplex viruses and its clinical correlates: a single center's experience.

The in vitro susceptibility to acyclovir of 204 herpes simplex virus isolates from 165 immunocompromised patients treated at our hospital was determined by the cytopathic effect reduction assay. Approximately 95% of herpes simplex virus 1 and 73% of herpes simplex virus 2 isolates were inhibited by acyclovir at concentrations of <2 microgram/mL. From 8 patients (5%), an isolate with low susceptibility to acyclovir (50% inhibitory dose, >3 microgram/mL) was recovered. Medical records of 83 patients were reviewed. Lesions resolved in most of the patients, independent of treatment. Treatment failures were not always associated with isolation of an in vitro-resistant virus. On the contrary, when a virus with low susceptibility to acyclovir was isolated, resolution of the lesion was the rule. In 9 of 10 patients with subsequent recurrent episodes of disease, the susceptibility of the viruses isolated was similar to that of the first episode. Routine susceptibility testing in our geographic area is not encouraged because of the low incidence of acyclovir-resistant herpes simplex viruses.

Streptococcus agalactiae infective endocarditis: analysis of 30 cases and review of the literature, 1962-1998.

We describe 30 cases (1.7%) of community-acquired penicillin-susceptible Streptococcus agalactiae endocarditis among 1771 episodes of endocarditis diagnosed in 4 Spanish hospitals from 1975 through 1998. Endocarditis affected a native valve (most often the mitral valve) in 25 cases (83%). Surgical valve replacement was performed for 12 patients (40%). Fourteen patients (47%) died. Mortality rates for patients with native and prosthetic valve endocarditis were 36% and 100%, respectively (P=.01). The mortality rate for native valve endocarditis decreased during the last 6 years of the study (from 61% in 1975-1992 to 8% in 1993-1998; P<.05). Additionally, 115 cases in the literature from 1962-1998 were reviewed. During 1980-1998, the percentage of patients who underwent cardiac surgery increased from 24% (in the previous period, 1962-1979) to 43% (P=.05) and the mortality rate decreased from 45% to 34% (P=NS). S. agalactiae is an uncommon cause of endocarditis with a high mortality rate, although the prognosis of native valve endocarditis has improved in recent years, probably because of an increased use of cardiac surgery.

Clinical presentation and outcome of tuberculosis in kidney, liver, and heart transplant recipients in Spain. Spanish Transplantation Infection Study Group, GESITRA.

BACKGROUND: Tuberculosis is unusual in transplant recipients. The incidence, clinical manifestations, and optimal treatment of this disease in this population has not been adequately defined. The present study was undertaken to assess the incidence, clinical features, and response to therapy of Mycobacterium tuberculosis infection in solid-organ transplant recipients. METHODS: We evaluated retrospectively the incidence, clinical characteristics, diagnostic procedures, antituberculous treatment, clinical course, and factors influencing mortality in 51 solid-organ transplant recipients who developed tuberculosis after transplantation. We also reviewed the world literature on tuberculosis in solid-organ transplantation. RESULTS: The overall incidence of tuberculosis was 0.8%. The localization was pulmonary in 63% of the cases, disseminated in 25%, and extrapulmonary in 12%. Tuberculosis developed from 15 days to 13 years after surgery (mean, 23 months). In one third of the cases, diagnosis was not suspected initially, and in three cases, diagnosis was made at necropsy. Fever was the most frequent symptom, followed by constitutional symptoms, cough, respiratory insufficiency, and pleuritic pain. Fifteen patients (33%) developed hepatotoxicity during treatment; hepatotoxicity was severe in seven cases. Hepatotoxicity was higher in patients receiving four or more antituberculous drugs (50%) than in patients receiving three drugs (21%; P=0.03). Serum levels of cyclosporine decreased in the 26 patients under the simultaneous use of rifampin. Nine of them (35%) developed acute rejection, and five (56%) died, in comparison with 3 of 17 patients (18%) who did not develop rejection after the use of cyclosporine and rifampin (P=0.03). Although microbiological response was favorable in 94% of the 35 patients who completed 6 or more months of treatment, 16 other patients (31%) died before diagnosis or in the course of treatment. None of the patients treated for more than 9 months died as a consequence of tuberculosis, whereas the mortality rate was 33% among those treated for 6 to 9 months (P=0.03). Use of antilymphocyte antibodies or high doses of steroids for acute rejection before tuberculosis was associated with a higher mortality rate. CONCLUSIONS: M tuberculosis causes serious and potentially life-threatening disease in solid-organ transplant recipients. Treatment with at least three drugs during 9 months or more, avoiding the use of rifampin, appears to be appropriate.

Epidemiologic evidence of transmission of donor-related bacterial infection through a transplanted heart.

This study describes a patient who had fulminant infectious myocarditis as a result of methicillin-resistant Staphylococcus aureus after receiving a heart transplant from an infected donor. There was complete concordance of typing results between donor and recipient strains that were different from the 20 isolates with which they were compared. Molecular epidemiologic study provided compelling evidence that a transplanted organ can transmit a bacterial infection from the donor to the recipient.

Polymicrobial bacteremia in critically ill patients.

OBJECTIVE: To characterize the epidemiology of polymicrobial bacteremia (PMB) among critically ill patients. DESIGN: Prospective clinical study. SETTING: University medical center. PATIENTS: All patients with positive blood cultures in a medical-surgical ICU. MEASUREMENTS: PMB represents 8.4% of all true bacteremia in our ICU. Most of these patients were postoperative but none had malignancies or significant immunodepression. Over three-quarters of the episodes were nosocomial. No significant differences in factors associated with PMB were found when they were compared with a cohort of 154 monomicrobial episodes. Enterobacteriaceae were the most common organisms. Intravascular devices (42.8%) were the most common source of PMB, followed by intra-abdominal origin (21.4%). The overall mortality was 7.1%, a lower rate than has previously been described. CONCLUSIONS: We suggest catheter replacement in patients who develop PMB and improving techniques of catheter maintenance in order to reduce its incidence.

Nosocomial bacteremia in a medical-surgical intensive care unit: epidemiologic characteristics and factors influencing mortality in 111 episodes.

OBJECTIVE: To analyze the epidemiology and factors influencing mortality of ICU-acquired bacteremia. DESIGN: Prospective clinical study. SETTING: A medical-surgical ICU in an university hospital. PATIENTS: We recorded variables from 111 consecutive ICU-acquired episodes for a 3-year period. RESULTS: The attack rate was 1.9 episodes per 100 patient-days. The commonest isolates were coagulase-negative staphylococci, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. Intravascular catheters were the most frequent source of infection. Overall mortality was 31.5%, and 65.7% of all deaths were directly attributable to infection. Bacteremia from intra-abdominal, lower respiratory tract or unknown origin were associated with a poor prognosis. A logistic regression analysis defined intraabdominal origin (p = 0.01, OR = 15.7) and presence of shock (p = 0.04, OR = 3.3) as independently influencing the risk of death. No significant differences were found for the remaining variables studied. CONCLUSIONS: Epidemiology and etiology of ICU-acquired bacteremia does not differ seriously in respect to nosocomial bacteremia among unselected populations, although it is associated with a greater incidence and overall mortality. Presence of shock is the most important modificable variable affecting the outcome.

[Complications associated with nonfunctioning pacemaker electrodes retained within the cardiovascular system]. / Complicaciones asociadas con electrodos de marcapasos no funcionantes retenidos en el sistema cardiovascular.

INTRODUCTION AND OBJECTIVE: The aim of the present study was to evaluate the complications in patients with functionless pacing leads retained in the cardiovascular system. PATIENTS AND METHODS: We retrospectively studied 39 patients: 31 underwent surgery for electrical or mechanical failure (group I) and eight for cutaneous pocket infection (group II). The follow-up was 45 +/- 34 months. RESULTS: Only one patient (3%) from group I presented infectious complications probably related to the retained pacing lead. Seven patients (87%) in group II presented recurrence of the infection with persistent fever and/or septicemia due to skin erosion and unnoticed pacing lead infection (p < 0.0005). Removal of the infected generator was performed in 8/39 (21%) of the patients. Thoracotomy to explant the infected retained leads was required in five of them (62%). No patient presented lead migration or venous thrombosis during the follow-up. CONCLUSIONS: Retained pacing leads in the cardiovascular system are well tolerated. However, in spite of adequate antibiotic treatment, patients with local and pacemaker system infection may present recurrence of the infection with persistent fever and/or septicemia. Early surgical pacemaker system removal is recommended in these patients due to the high morbidity.

[The prognostic factors of invasive pulmonary aspergillosis in patients with chronic pneumopathy]. / Factores pronósticos de la aspergilosis pulmonar invasiva en pacientes con neumopatía crónica.

OBJECTIVES: a) To determine in patients with chronic respiratory disease the risk factors for death due to semi-invasive and invasive pulmonary aspergillosis (SIPA), and b) to describe the clinical features of SIPA in such patients. METHOD: Twenty-one patients with chronic respiratory disease were enrolled (9 with chronic obstructive pulmonary disease, 2 asthmatics and 3 with bronchiectasis, 5 with post-tubercular sequelae and 2 mixed cases). A diagnosis of SIPA was established in our hospital when, in a patient with a clinical picture consistent with such a diagnosis, the fungus was isolated in bronchial secretions or parenchymal pulmonary specimens were obtained during autopsy. RESULTS: The most common symptoms were dyspnea (81%), cough (67%) and expectoration (62%) increasing over the levels usual for patients with chronic respiratory disease. Hemoptysis was present in only 14%. Eight patients (38%) died as a result of SIPA. A comparison of those surviving and non-surviving patients revealed that the latter had significantly higher LDH levels and white cell counts, and significantly lower total plasma protein and platelet counts. CONCLUSIONS: a) Low protein levels and high LDH levels and white cell counts with thrombopenia are indicators of poor prognosis in chronic respiratory disease patients with SIPA, and b) such patients do not usually present signs or symptoms that lead to a suspicion of SIPA given that such signs are typical of failing compensatory mechanisms in the disease itself.

[Invasive pulmonary aspergillosis: a study of 33 cases]. / Aspergilosis pulmonar invasiva: estudio de 33 casos.

Invasive pulmonary aspergillosis (IPA) is an infectious complication appearing mainly in immunosuppressed patients, whose diagnosis is often difficult and lately made, and that usually bears a dismal prognosis. Patients diagnosed as having IPA from 1989 to 1994 were retrospectively analyzed. Probable IPA was diagnosed on the basis of a positive culture for Aspergillus together with a consistent radiological image. Confirmed IPA was diagnosed if there was, in addition to the former, a pathological examination showing Aspergillus hifae invading pulmonary parenchyma and/or pulmonary vessels. There were 25 men and 8 women with a mean age of 53.7 +/- 16.9 years (range: 22-86 years). IPA was confirmed in 11 cases and probable in 22. Sixty three percent of the patients had hematologic malignancy or solid cancer, whereas 30.3% did not have prior granulocytopenia or immunosuppressive therapy. The mean (SD) interval between admission and diagnosis was 40.2 (37.1) days (range: 1-180 days), and the diagnosis was made while the patient was still alive in 75% of the cases. Fifteen percent of the patients had extrapulmonary aspergillosis. The most frequent finding both on X-ray film of the chest and pulmonary computed tomography were bilateral multiple pulmonary nodules. Thirteen patients were treated with itraconazole, 6 with amphotericin B, 5 received both drugs, and 2 received fluconazole. Nineteen patients (57.6%) died and the case-fatality rate among treated patients was 46.1%. IPA presents mainly in immunosuppressed patients, but there was a not negligible proportion of patients lacking the classical risk factors. IPA is often a lately made diagnosis and in a quarter of the patients it is not made when the patient is alive. The most frequent radiological presentation are multiple bilateral nodules. The case-fatality rate of IPA is exceedingly high, even when if the patient has been adequately treated.

[Emergency valvular replacement in infective endocarditis: hospital and long term clinical course. Analysis of 45 patients]. / Sustitución valvular urgente en la endocarditis infecciosa: evolución hospitalaria y a largo plazo. Análisis de 45 pacientes.

BACKGROUND: To define the evolution of patients with infective endocarditis who require urgent valve replacement in our environment. PATIENTS AND METHODS: We followed 45 consecutive cases of infective endocarditis that require valve replacement during their hospitalization. 32 patients had native valve infective endocarditis, 7 early prosthesis valve endocarditis and 6 late prosthesis valve endocarditis. Patients were followed for a long-term period, clinical and echocardiographycally. RESULTS: In 39 cases valve replacement was performed before ending antibiotic therapy. The main indications for surgery were refractory heart failure (24 patients) and shock (11 patients). The mortality rate was 24%: 19% in native valve infective endocarditis, 43% in early prosthetic valve endocarditis and 33% in late prosthesis valve endocarditis. The first cause of death was septic shock (46%). We followed 31 over 34 survivors for a mean time 65 (DS 49) months. We found two relapses and six deaths (1 sudden death, 2 endocarditis) and 72% of patients presented class I NYHA. We detected 17% prosthetic leaks (34% in the prosthetic valve endocarditis group). CONCLUSIONS: The need of urgent valve replacement in the context of infective endocarditis is associated with a high mortality rate, and should be considered a serious condition. Long term prognosis is, however, acceptable, although 17% of patients had prosthesis leak, specially those with prosthetic valve endocarditis.

A lipid anchor improves the protective effect of ectoine in inflammation.

Others and we have shown in several studies that the natural tetrahydropyrimidine ectoine protects mammalian cells and tissues against various stress factors including ischemia/reperfusion injury, UV-irradiation, and inflammation. Since little is known about the molecular mechanism of this protective effect, which was ascribed exclusively to an extracellular action of this small water-soluble molecule, we asked whether and how a hydrophobic anchor modulates the inflammation protective properties of ectoine. We therefore investigated the influence of ectoine and of its semi-synthetic derivative lauryl-ectoine on inflammation in RAW 264.7 macrophages and primary cultured rat intestinal smooth muscle (RISM) cells. Both, ectoine and lauryl-ectoine considerably decreased lipopolysaccharide (LPS)-induced interleukin (IL)- 1, IL-6, tumor necrosis factor (TNF)- α, and cyclooxygenase (COX)-2 gene expression in macrophages as well as TNF-α- induced IL-1, IL-6 and COX-2 expression in RISM cells. This reduction of inflammatory agents was accompanied on the one hand by a significant decrease of nuclear translocation of nuclear factor (NF)-κB and on the other hand by a reduction of cellular ceramide content. Interestingly, lauryl- ectoine was much more active exerting its effect at about 10-fold lower concentrations than its natural counterpart. Note that ectoine was almost completely recovered in the medium whereas lauryl-ectoine was found to be cell-associated. Together our data indicate that a lipid anchor considerably improves a possible preventive and/or therapeutic implementation of ectoine in inflammatory processes.