Dolors Mariscal

Type III protein secretion is associated with poor clinical outcomes in patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa.

OBJECTIVE Pseudomonas aeruginosa is a frequent cause of ventilator-associated pneumonia. Recent evidence suggests that production of type III secretion proteins is correlated with increased pathogenicity in both cellular and animal models of infection. The objective of this study was to determine whether this system contributes to disease severity in humans with ventilator-associated pneumonia. DESIGN Retrospective pilot cohort study. SETTING University hospital. PATIENTS Thirty-five mechanically ventilated patients with bronchoscopically confirmed ventilator-associated pneumonia caused by P. aeruginosa. MEASUREMENTS AND MAIN RESULTS Ventilator-associated pneumonia was categorized as severe (patients died or had a recurrence of their pneumonia despite appropriate antibiotic therapy) or mild (patients uneventfully recovered from their pneumonia). The type III secretion genotypes and phenotypes of isolates cultured from the patients with ventilator-associated pneumonia were determined. Whereas every examined isolate harbored type III secretion genes, only 27 (77%) were capable of secreting detectable amounts of type III proteins in vitro. Twenty-two (81%) of the patients infected with these 27 isolates had severe disease. Of the eight isolates that did not secrete type III proteins, only three (38%) were cultured from patients with severe disease. Thus, infection with a type-III-secreting isolate correlated with severe disease (p < .05). In vitro assays indicated that ExoU, the type III effector protein most closely linked to mortality in animal models, was secreted in detectable amounts in vitro by 10 (29%) of the 35 examined isolates. Nine (90%) of these 10 isolates were cultured from patients with severe disease (p < .05 when compared with the nonsecreting isolates). In contrast, ExoS was secreted by 16 (46%) of the 35 examined isolates. Twelve (75%) of these 16 isolates were cultured from patients with severe disease (p = .14 when compared with the nonsecreting isolates). CONCLUSIONS In patients with ventilator-associated pneumonia, type-III-secreting isolates were associated with worse clinical outcomes, suggesting that this secretion system plays an important role in human disease. Our findings support the hypothesis that antibodies targeted against these proteins may be useful as adjunctive therapy in intubated patients with P. aeruginosa colonization or infection.

A clinical trial on the prevention of catheter-related sepsis using a new hub model.

BACKGROUND Catheter hub contamination is being increasingly recognized as a source of catheter-related sepsis. The authors have investigated the efficacy of a new hub design in preventing endoluminal catheter contamination and catheter-related sepsis arising at the hub. METHODS Adult surgical and intensive care patients requiring a subclavian catheter for at least 1 week were randomly assigned to receive catheters with standard connectors (control group, n=73) or equipped with a new hub model (new hub group, n=78). Skin, catheter tip, and hub cultures were performed at the time the catheter was withdrawn because therapy was terminated or because of suspicion of sepsis, in which case peripheral blood cultures were taken. RESULTS Of the 151 patients included, 15 (10%) developed catheter-related sepsis. Catheters were more often withdrawn because suspicion of infection in the control group (42 vs. 19%, p<0.005). Catheter sepsis rate was higher in the control group (16 vs. 4%, p<0.01) because of the low rate of catheter sepsis arising at the hub observed in the new hub group (1 vs. 11%, p<0.01). The prevalence of culture-positive catheter hubs without associated bacteremia (colonization) was higher in the control group (18 vs. 5%, P<0.03). CONCLUSIONS A new catheter hub has proved to be useful in preventing endoluminal bacterial colonization and catheter-related sepsis in subclavian lines inserted for a mean of 2 weeks.

Pulmonary Nocardiosis: Clinical Experience in Ten Cases

Background: Pulmonary nocardiosis is an infrequent infection whose incidence seems to be increasing due to a higher degree of clinical suspicion and the increasing number of immunosuppressive factors. Objective: To study the predisposing factors, clinical characteristics, diagnostic procedures, treatment and progress of pulmonary nocardiosis (PN). Methods: Review of 10 patients (9 male, 1 female, mean age 61) with PN in a 600-bed teaching hospital, diagnosed from 1992 to 1999. Results: Associated diseases observed were chronic obstructive pulmonary disease (COPD) in 6 patients, human immunodeficiency virus (HIV) infection in 3 and polymyalgia rheumatica in 1. Four patients had received oral corticotherapy for COPD for over a year (mean dose 13 mg/day of prednisone or equivalent). The main reason for consultation was an increase in dyspnea in the patients with COPD (6/6) and fever in those with HIV (3/3). Mean time between onset of symptoms and diagnosis was 5 weeks. In 8 patients, the infection occurred outside the hospital setting. The infection was restricted to the lung in 9/10; in the remaining case, the central nervous system (CNS) and subcutaneous tissue were affected. Lobar or multilobar consolidation was the most frequent radiographic pattern found (6/10). Sputum culture was positive when performed (8 cases). Diagnosis was made or confirmed by bronchoscopy (bronchoaspirate or protected specimen brush) in 5 patients. Germs isolated were: Nocardia asteroides (8/10), Nocardia farcinica (1/10), Nocardia otitidiscaviarum (1/10). Cotrimoxazole was the most used empirical treatment (6/10). Resolution was achieved in 5 cases. Four subjects died: 1 HIV patient with disseminated nocardiosis, and 3 COPD patients, 2 of whom had received long-term corticotherapy. Illness recurred in only 1 case, due to failure to comply with treatment. Conclusions: (1) In our geographical setting Nocardia presents as a subacute or chronic pulmonary infection, mainly outside the hospital. (2) It tends to affect only the lung. (3) Diagnosis requires a high clinical suspicion, and can be made on the basis of a sputum culture. (4) Nocardia tends to attack patients with underlying COPD, or immunodepressed patients treated with glucocorticoids, or patients with HIV infection. (5) Mortality is high in both COPD and HIV patients. (6) In our area, cotrimoxazole seems to be the most commonly prescribed treatment.

A 7-year study of severe hospital-acquired pneumonia requiring ICU admission

ObjectiveTo examine the characteristics, prognostic factors, and outcome of patients with severe hospital-acquired pneumonia admitted to the ICU.Design and settingProspective observational clinical study in two medical-surgical ICUs with 16 and 20 bedsPatients and participantsDuring a 7-year period all hospitalized patients requiring admission to either ICU for hospital-acquired pneumonia were followed up.Measurements and resultsWe diagnosed 96 episodes of severe hospital-acquired pneumonia, and in 67 cases a causal diagnosis was made. Most episodes were late-onset pneumonia. Gram-negative micro-organisms were isolated in 51% of episodes diagnosed, and Pseudomonas aeruginosa was the most frequent pathogen isolated (24%). Clearly significant variations happened between hospitals, particularly affecting the incidence of Aspergillus spp. and Legionella pneumophila. Forty-nine patients developed septic shock (51%). Fifty-one patients died (53%). Aspergillosis and pneumonia due to P. aeruginosa were associated with the highest mortality. Septic shock (OR: 14.27) and chronic obstructive pulmonary disease (OR: 6.11) were independently associated with a poor prognosis.ConclusionsPatients with severe hospital-acquired pneumonia admitted to the ICU present high mortality. The presence of septic shock and chronic obstructive pulmonary disease in conjunction with specific microorganisms are associated with a poor prognosis. Local epidemiological data combined with a patient-based approach may allow a more accurate therapy decision making.

Invasive Aspergillosis: A Life-Threatening Complication of Short-Term Steroid Treatment

Objective: To describe a patient with invasive pulmonary aspergillosis related to short-term steroid treatment. Case Summary: A 78-year-old man with chronic obstructive pulmonary disease (COPD) developed an invasive pulmonary aspergillosis after short-term (less than 1 week) intravenous steroid therapy. The diagnosis was established by recovering Aspergillus fumigatus from a bronchoalveolar lavage and was confirmed by autopsy, with the additional finding of an aspergilloma. Discussion: This case is of interest for 3 reasons: (1) it illustrates that invasive aspergillosis may be followed by a rapidly progressive respiratory failure, even in the absence of a fever; (2) this patient had simultaneously an aspergilloma and an invasive aspergillosis; and (3) it confirms reports indicating that short-term steroid therapy for COPD represents a significant risk factor for opportunistic lung infections. Conclusions: In patients with COPD who receive even short-term steroid therapy and who have progressive respiratory failure caused by pneumonia, invasive aspergillosis should be suspected early and acted upon accordingly.

Micobacteriosis genitourinaria: estudio retrospectivo de 45 casos en un hospital general

Introduccion La tuberculosis genitourinaria (TGU) es la afeccion extrapulmonar mas frecuente tras la pleural y ganglionar. Dada su escasa sintomatologia clinica su diagnostico y tratamiento son, a menudo, tardios. Metodos Estudio de las caracteristicas clinicas, epidemiologicas y evolutivas de los pacientes diagnosticados de TGU en nuestro centro los ultimos 10 anos. Se han incluido los pacientes con cultivo de Lowenstein positivo, en orina o en muestras de biopsies o con estudio anatomopatologico compatible con tuberculosis. Los casos de tuberculosis multifocal, Lowenstein positivo sin clinica urinaria ni alteraciones radiologicas se consideraron micobacteriuria. Resultados Se han analizado 45 pacientes (el 62% hombres con una edad media de 49,4 anos). En el 33% coexistia enfermedad de base (14 infectados por el virus de la inmunodeficencia humana). Se diagnosticaron de tuberculosis renal 26 pacientes (57%), 5 (11%) de orquiepididimitis y 14 (31%) se catalogaron como micobacteriuria. La sintomatologia mas frecuente fue sindrome miccional (60%), dolor lumbar (44%) y hematuria macroscopica (12%). La tincion de Ziehl fue positiva en el 38% de los casos. El urocultivo fue positivo para otros germenes en 9 pacientes (20%). La urografia intravenosa oriento el diagnostico en 28/32 casos (87,5%). El intervalo medio de sintomas previos al diagnostico fue de 15 meses. La curacion sin secuelas se logro en el 60%. Se indico cirugia en 10 casos. Conclusiones Se debe incrementar el grado de sospecha de TGU ante sindromes urinarios de repeticion. La menor utilizacion actual de la urografia frente a otras pruebas de imagen y el hallazgo de otros germenes en el urocultivo pueden retrasar el diagnostico.

Effect of enriched thioglycolate on direct examination of respiratory specimens and guiding initial empirical therapy in intubated patients with pneumonia: a prospective, randomized study.

Objective To evaluate the use of enriched thioglycolate as a transport medium of protected specimen brush samples, in particular its value in direct examination of respiratory specimens and in guiding initial antibiotic prescription. Design Prospective, randomized, pilot study. Setting Medical-surgical teaching intensive care unit. Subjects Thirty adults with suspected ventilator-associated pneumonia. Intervention Bronchoscopy was performed by using standard techniques, and two consecutive protected specimen brush samples were taken. Transport medium consisted of 1 mL of sterile saline or thioglycolate. Gram stains were performed in all samples. Randomization was used to select which transport medium was used first. Each patient served as his or her own control. The laboratory was blind to the choice. Measurements and Main Results Causative agents were cultured in 16 episodes, and no significant differences were observed when the transport media were compared. Anaerobes were identified in only one episode. Direct staining in thioglycolate samples anticipated the presumptive diagnosis (in presence of false-negative cultures) in three additional patients in whom prior antibiotic therapy was prescribed; this was also the case in one patient with saline solution. The etiology was anticipated by direct Gram staining and permitted a more targeted initial empirical treatment in 75% of samples transported in thioglycolate, compared with only 37.5% of samples transported in saline solution (p < .05). Conclusion When protected specimen brush samples are obtained, thioglycolate may contribute to early identification of the pathogen and may guide the initial empirical therapy.

Neumonía por Pseudomonas aeruginosa

Pseudomonas aeruginosa es uno de los principales bacilos gramnegativos que causa con mayor frecuencia neumonia nosocomial. Es ademas el patogeno mas comun causante de neumonia asociada a ventilacion mecanica y el que se asocia a una mayor mortalidad entre las infecciones adquiridas en el hospital. P. aeruginosa produce un elevado numero de toxinas y tiene en su superficie diversos componentes que lo hacen especialmente virulento comparado con otros microorganismos. Entre estos se incluyen los pili, flagelos lipopolisacarido y otros productos excretados como exotoxina A, S y U, elastasa, proteasa alcalina, citotoxinas y fosfolipasas. La via mas comun de infeccion en los pacientes ventilados mecanicamente es a traves de la aspiracion de secreciones procedentes del tracto respiratorio superior y previamente colonizadas debido a la manipulacion de la via respiratoria artificial o a traves de las manos contaminadas del personal sanitario. El tratamiento antibiotico frente a P. aeruginosa debe de establecerse de forma precoz ante la sospecha o confirmacion de la neumonia. Debe de iniciarse tratamiento empirico frente a P. aeruginosa, especialmente en los pacientes que han recibido previamente tratamiento antibiotico o que desarrollan una neumonia tardia.

Presence of polyclonal Pseudomonas aeruginosa in an intensive care unit: A 27-month prospective study on molecular epidemiology

Pseudomonas aeruginosa was isolated in 22.2% of 305 intensive care unit environmental cultures. A high genetic heterogeneity (18 pulsotypes) was evident. Taps and related surfaces were a stable reservoir for certain pulsotypes. The 15.4% of the P. aeruginosa-positive cultures were polyclonal. Different colony morphotypes should be assayed in surveillance studies.