Acute respiratory distress syndrome in mechanically ventilated patients with community-acquired pneumonia.

Our aim was to assess the incidence, characteristics, aetiology, risk factors and mortality of acute respiratory distress syndrome (ARDS) in intensive care unit (ICU) patients with community-acquired pneumonia (CAP) using the Berlin definition.We prospectively enrolled consecutive mechanically ventilated adult ICU patients with CAP over 20 years, and compared them with mechanically ventilated patients without ARDS. The main outcome was 30-day mortality.Among 5334 patients hospitalised with CAP, 930 (17%) were admitted to the ICU and 432 required mechanical ventilation; 125 (29%) cases met the Berlin ARDS criteria. ARDS was present in 2% of hospitalised patients and 13% of ICU patients. Based on the baseline arterial oxygen tension/inspiratory oxygen fraction ratio, 60 (48%), 49 (40%) and 15 (12%) patients had mild, moderate and severe ARDS, respectively. Streptococcus pneumoniae was the most frequent pathogen, with no significant differences in aetiology between groups. Higher organ system dysfunction and previous antibiotic use were independent risk factors for ARDS in the multivariate analysis, while previous inhaled corticosteroids were independently associated with a lower risk. The 30-day mortality was similar between patients with and without ARDS (25% versus 30%, p=0.25), confirmed by propensity-adjusted multivariate analysis.ARDS occurs as a complication of CAP in 29% of mechanically ventilated patients, but is not related to the aetiology or mortality.

A multiplex real-time PCR assay for identification of Pneumocystis jirovecii, Histoplasma capsulatum, and Cryptococcus neoformans/Cryptococcus gattii in samples from AIDS patients with opportunistic pneumonia.

A molecular diagnostic technique based on real-time PCR was developed for the simultaneous detection of three of the most frequent causative agents of fungal opportunistic pneumonia in AIDS patients: Pneumocystis jirovecii, Histoplasma capsulatum, and Cryptococcus neoformans/Cryptococcus gattii. This technique was tested in cultured strains and in clinical samples from HIV-positive patients. The methodology used involved species-specific molecular beacon probes targeted to the internal transcribed spacer regions of the rDNA. An internal control was also included in each assay. The multiplex real-time PCR assay was tested in 24 clinical strains and 43 clinical samples from AIDS patients with proven fungal infection. The technique developed showed high reproducibility (r(2) of >0.98) and specificity (100%). For H. capsulatum and Cryptococcus spp., the detection limits of the method were 20 and 2 fg of genomic DNA/20 µl reaction mixture, respectively, while for P. jirovecii the detection limit was 2.92 log10 copies/20 µl reaction mixture. The sensitivity in vitro was 100% for clinical strains and 90.7% for clinical samples. The assay was positive for 92.5% of the patients. For one of the patients with proven histoplasmosis, P. jirovecii was also detected in a bronchoalveolar lavage sample. No PCR inhibition was detected. This multiplex real-time PCR technique is fast, sensitive, and specific and may have clinical applications.

Community-acquired polymicrobial pneumonia in the intensive care unit: aetiology and prognosis.

INTRODUCTION: The frequency and clinical significance of polymicrobial aetiology in community-acquired pneumonia (CAP) patients admitted to the ICU have been poorly studied. The aim of the present study was to describe the prevalence, clinical characteristics and outcomes of severe CAP of polymicrobial aetiology in patients admitted to the ICU. METHODS: The prospective observational study included 362 consecutive adult patients with CAP admitted to the ICU within 24 hours of presentation; 196 (54%) patients had an established aetiology. RESULTS: Polymicrobial infection was present in 39 (11%) cases (20% of those with defined aetiology): 33 cases with two pathogens, and six cases with three pathogens. The most frequently identified pathogens in polymicrobial infections were Streptococcus pneumoniae (n = 28, 72%), respiratory viruses (n = 15, 39%) and Pseudomonas aeruginosa (n = 8, 21%). Chronic respiratory disease and acute respiratory distress syndrome criteria were independent predictors of polymicrobial aetiology. Inappropriate initial antimicrobial treatment was more frequent in the polymicrobial aetiology group compared with the monomicrobial aetiology group (39% vs. 10%, P < 0.001), and was an independent predictor of hospital mortality (adjusted odds ratio = 10.79, 95% confidence interval = 3.97 to 29.30; P < 0.001). The trend for higher hospital mortality of the polymicrobial aetiology group compared with the monomicrobial aetiology group (n = 8, 21% versus n = 17, 11%), however, was not significantly different (P = 0.10). CONCLUSIONS: Polymicrobial pneumonia occurs frequently in patients admitted to the ICU. This is a risk factor for inappropriate initial antimicrobial treatment, which in turn independently predicts hospital mortality.

Assessment of a Loop-Mediated Isothermal Amplification (LAMP) Assay for the Rapid Detection of Pathogenic Bacteria from Respiratory Samples in Patients with Hospital-Acquired Pneumonia.

Rapid identification of the causative agent of hospital-acquired pneumonia (HAP) will allow an earlier administration of a more appropriate antibiotic and could improve the outcome of these patients. The aim of this study was to develop a rapid protocol to identify the main microorganisms involved in HAP by loop-mediated isothermal amplification (LAMP) directly from respiratory samples. First of all, a rapid procedure (<30 min) to extract the DNA from bronchoalveolar lavage (BAL), endotracheal aspirate (EA) or bronchoaspirate (BAS) was set up. A specific LAMP for Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter baumannii was performed with the extracted solution at 65 °C for 30-40 min. Overall, 58 positive BAL and 83 EA/BAS samples were tested. The limits of detection varied according to the microorganism detected. Validation of the LAMP assay with BAL samples showed that the assay was 100% specific and 86.3% sensitive (positive predictive value of 100% and a negative predictive value of 50%) compared with culture. Meanwhile for BAS/EA samples, the assay rendered the following statistical parameters: 100% specificity, 94.6% sensitivity, 100% positive predictive value and 69.2% negative predictive value. The turnaround time including sample preparation and LAMP was circa 1 h. LAMP method may be used to detect the most frequent bacteria causing HAP. It is a simple, cheap, sensitive, specific and rapid assay.

Cutaneous infection by Phaeoacremonium parasiticum.

BACKGROUND: Phaeoacremonium parasiticum is considered a rare infectious agent that is part of a heterogeneous group of fungi causing phaeohyphomycosis. This organism is capable of producing subcutaneous infections, eumycetomas, osteomyelitis, arthritis, myositis and also disseminated diseases, such as fungemia and endocarditis. CASE REPORT: We describe a case of cutaneous infection by P. parasiticum in a kidney transplant patient. The identification of this microorganism was performed by microbiological and histopathological studies and confirmed with the sequence of the gene encoding ß-tubulin and a real time panfungal PCR targeting 18S ribosomal RNA gene. The microorganism was correctly identified by phenotypic and molecular methods. The patient was treated with oral antifungal therapy and a debulking surgery and evolved without any complication. CONCLUSIONS: The diagnosis of this infection is difficult and usually affects kidney transplant patients, but the reasons of this association are still unknown.

[Clinical features and outcome in patients with mucormycosis in a tertiary hospital (2012-2016)]. / Características clínicas y evolución de los pacientes diagnosticados de mucormicosis en un hospital de tercer nivel (2012-2016).

BACKGROUND: The most common presentation of mucormycosis in the past was the nasosinusal involvement in patients with diabetic ketoacidosis. However, in the last few years, new groups of patients with risk of mucormycosis have emerged. AIMS AND METHODS: Retrospective analysis of the characteristics, treatment and evolution of patients with mucormycosis in a tertiary hospital in the years 2012-2016. RESULTS: Of the 12 patients included in the study, 7 had a haematological disease as a predisposing factor, most of them (6 patients) related to transplantation of haematopoietic progenitors. Only one patient had diabetic ketoacidosis. Seven out of the twelve patients were receiving an antifungal treatment at the onset of symptoms, and 9 patients had received them three months before. The clinical presentation was rhinosinusal (16.6%), localised lung disease (33.3%), and musculoskeletal (25%) and disseminated disease (25%). Surgical debridement was performed on 8 patients. Combination therapy with amphotericin B and posaconazole was received by 6 patients (16% mortality), and 4 patients were treated with amphotericin B alone (50% mortality), with an overall mortality of 41%. The mortality of patients with pulmonary involvement was 71%, increasing to 100% in the case of disseminated disease. None of the patients with only musculoskeletal involvement died. CONCLUSIONS: Mucormycosis has a high mortality rate, especially the pulmonary forms. Musculoskeletal involvement had a better prognosis. The main group at risk was that of patients with haematopoietic stem cell transplantation. Combination therapy had better results than monotherapy, although more experience is needed to define the most appropriate treatment.

Community-Acquired Pneumonia Due to Multidrug- and Non-Multidrug-Resistant Pseudomonas aeruginosa.

BACKGROUND: Pseudomonas aeruginosa is not a frequent pathogen in community-acquired pneumonia (CAP). However, in patients with severe CAP, P aeruginosa can be the etiology in 1.8% to 8.3% of patients, with a case-fatality rate of 50% to 100%. We describe the prevalence, clinical characteristics, outcomes, and risk factors associated with CAP resulting from multidrug-resistant (MDR) and non-MDR P aeruginosa. METHODS: Prospective observational study of 2,023 consecutive adult patients with CAP with definitive etiology. RESULTS: P aeruginosa was found in 77 (4%) of the 2,023 cases with microbial etiology. In 22 (32%) of the 68 cases of P aeruginosa with antibiogram data, the isolates were MDR. Inappropriate therapy was present in 49 (64%) cases of P aeruginosa CAP, including 17/22 (77%) cases of MDR P aeruginosa CAP. Male sex, chronic respiratory disease, C-reactive protein <12.35 mg/dL, and pneumonia severity index risk class IV to V were independently associated with P aeruginosa CAP. Prior antibiotic treatment was more frequent in MDR P aeruginosa CAP compared with non-MDR P aeruginosa (58% vs 29%, P = .029), and was the only risk factor associated with CAP resulting from MDR P aeruginosa. In the multivariate analysis, age ≥65 years, CAP resulting from P aeruginosa, chronic liver disease, neurologic disease, nursing home, criteria of ARDS, acute renal failure, ICU admission, and inappropriate empiric treatment were the factors associated with 30-day mortality. CONCLUSIONS: P aeruginosa is an individual risk factor associated with mortality in CAP. The risk factors described can help clinicians to suspect P aeruginosa and MDR P aeruginosa.

Influence of age in renal transplant infections: cases and controls study.

Kidney transplantation in elderly patients is a good therapeutic option, but the incidence of infections compared to younger patients must be studied. Case and control study was performed with 40 cases (patients older than 65) and 40 controls (younger than 65) receiving a kidney transplant between January 2000 and August 2002. In 32 cases (80%) and in 14 controls (32%), some type of infection appeared during the follow-up (odds ratio [OR] 5; 95% CI 1.6-20). The percentage of patients with bacterial infections was higher in the cases (70% vs. 28%; OR 5.7; 95% CI 1.9-20), especially for urinary infections. No differences for viral and fungal infections were observed in the two groups. Mortality rate was 13% in the cases (5% due to infections), whereas there was no controls' mortality. Although the number of bacterial infections was higher, kidney transplantation in elderly patients is a secure procedure.

Bronchial colonization and postoperative respiratory infections in patients undergoing lung cancer surgery.

STUDY OBJECTIVES: To evaluate the risk factors associated with postoperative respiratory infection in patients undergoing lung cancer surgery, with special emphasis on the perioperative pattern of airway colonization. DESIGN: Prospective cohort study. SETTING: Department of Pneumology and Thoracic Surgery of a tertiary hospital. PATIENTS: Seventy-eight consecutive patients undergoing lung cancer surgery were evaluated. Patients were followed up until hospital discharge or death. INTERVENTIONS: Fiberoptic bronchoscopies with bilateral protected specimen brush or bronchial aspirates were performed during anesthesia prior to the initiation of the surgical procedure. RESULTS: Sixty-five patients (83%) had perioperative bronchial colonization by either potentially pathogenic microorganisms (PPMs) [28 patients, 36%] or non-potentially pathogenic microorganisms (56 patients, 72%). The 24 patients (31%) with a postoperative respiratory infection (pneumonia, purulent tracheobronchitis, or pleural empyema) had significantly higher perioperative bronchial colonization by PPMs (15 patients [63%] vs 13 patients [24%], p = 0.003) and a higher bacterial index (mean +/- SD, 3.6 +/- 3.3 vs 0.9 +/- 1.4; p = 0.003), compared to patients without infection. The agreement between pathogens found in perioperative evaluation and during postoperative infection was total in 5 patients (21%), partial in 5 patients (21%), and no concordance in 14 patients (58%). In the multivariate analysis, the presence of perioperative airway colonization by a PPM (odds ratio [OR], 6.9; p = 0.001) and a higher postoperative pain score (OR, 4.1; p = 0.014) were independent predictors of postoperative respiratory infection. CONCLUSION: Adequate control of postoperative pain, as well as the conditions that potentially cause airway colonization by PPMs, could be beneficial in preventing postoperative respiratory infections after lung cancer surgery.

Risk factors associated with potentially antibiotic-resistant pathogens in community-acquired pneumonia.

RATIONALE: To identify pathogens that require different treatments in community-acquired pneumonia (CAP), we propose an acronym, "PES" (Pseudomonas aeruginosa, Enterobacteriaceae extended-spectrum ß-lactamase-positive, and methicillin-resistant Staphylococcus aureus). OBJECTIVES: To compare the clinical characteristics and outcomes between patients with CAP caused by PES versus other pathogens, and to identify the risk factors associated with infection caused by PES. METHODS: We conducted an observational prospective study evaluating only immunocompetent patients with CAP and an established etiological diagnosis. We included patients from nursing homes. We computed a score to identify patients at risk of PES pathogens. MEASUREMENT AND MAIN RESULTS: Of the 4,549 patients evaluated, we analyzed 1,597 who presented an etiological diagnosis. Pneumonia caused by PES was identified in 94 (6%) patients, with 108 PES pathogens isolated (n = 72 P. aeruginosa, n = 15 Enterobacteriaceae extended-spectrum ß-lactamase positive, and n = 21 methicillin-resistant Staphylococcus aureus). These patients were older (P = 0.001), had received prior antibiotic treatment more frequently (P < 0.001), and frequently presented with acute renal failure (P = 0.004). PES pathogens were independently associated with increased risk of 30-day mortality (adjusted odds ratio = 2.51; 95% confidence interval = 1.20-5.25; P = 0.015). The area under the curve for the score we computed was 0.759 (95% confidence interval, 0.713-0.806; P < 0.001). CONCLUSIONS: PES pathogens are responsible for a small proportion of CAP, resulting in high mortality. These pathogens require a different antibiotic treatment, and identification of specific risk factors could help to identify these microbial etiologies.

[Aspergillus galactomannan detection in allogenic hematopoietic cell transplantation]. / Detección de antígeno galactomanano de Aspergillus en el trasplante alogénico de progenitores hematopoyéticos.

Invasive aspergillosis has become the leading cause of death after allogeneic hematopoietic stem cell transplantation. This is partially due to the lack of a prompt diagnosis. Recently the detection of Aspergillus galactomannan antigen by means an ELISA technique in serum has been described. The objective of this study was to validate its usefulness in the allogeneic hematopoietic stem cell transplantation setting.

Cutaneous infection by Phaeoacremonium parasiticum / Infección cutánea por Phaeoacremonium parasiticum

Background: Phaeoacremonium parasiticum is considered a rare infectious agent that is part of a heterogeneous group of fungi causing phaeohyphomycosis. This organism is capable of producing subcutaneous infections, eumycetomas, osteomyelitis, arthritis, myositis and also disseminated diseases, such as fungemia and endocarditis. Case report: We describe a case of cutaneous infection by P. parasiticum in a kidney transplant patient. The identification of this microorganism was performed by microbiological and histopathological studies and confirmed with the sequence of the gene encoding β-tubulin and a real time panfungal PCR targeting 18S ribosomal RNA gene. The microorganism was correctly identified by phenotypic and molecular methods. The patient was treated with oral antifungal therapy and a debulking surgery and evolved without any complication. Conclusions: The diagnosis of this infection is difficult and usually affects kidney transplant patients, but the reasons of this association are still unknown

Antecedentes: Phaeoacremonium parasiticum es considerado un agente infeccioso poco común que forma parte de un grupo heterogéneo de hongos causantes de feohifomicosis. Este microorganismo es capaz de producir infección cutánea, eumicetoma, osteomielitis, artritis, miositis e incluso enfermedad diseminada como fungemia y endocarditis. Caso clínico: Se describe un caso de infección cutánea por P. parasiticum en un paciente trasplantado renal. Para la identificación del microorganismo se realizaron pruebas microbiológicas e histopatológicas, y se confirmó la identificación con la secuenciación del gen de la β-tubulina y una PCR a tiempo real para la detección del gen 18S rRNA. El microorganismo fue identificado correctamente por métodos fenotípicos y moleculares. El paciente recibió tratamiento con antifúngicos orales y citorreducción quirúrgica, y evolucionó sin ninguna complicación. Conclusiones: El diagnóstico de esta infección es difícil y se presenta habitualmente en pacientes trasplantados renales. Sin embargo, la asociación de esta infección con este tipo de pacientes no ha sido aún explicada

[Microbiological diagnosis of bacterial lower respiratory tract infections]. / Diagnóstico microbiológico de las infecciones bacterianas del tracto respiratorio inferior.

Microbiological diagnosis of bacterial lower respiratory tract infections has relevant limitations and related controversy, depending on the clinical setting and diagnostic methods used, and its value is contingent on an accurate clinical diagnosis and previous antimicrobial therapy. The limitations reside in a low diagnostic yield of the causative agent and the difficulty of determining the clinical significance of the agents recovered. This report examines the current microbiological diagnostic yield of the main clinical entities and etiological agents, indications for invasive or non-invasive specimen collection procedures, and proper specimen processing and culture in the appropriate media. Criteria regarding specimen suitability and indications for quantitative cultures are established. Criteria for evaluating the results are provided, and the current fast diagnostic techniques are described.

Bronchoscopic validation of the significance of sputum purulence in severe exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Antibiotics are commonly prescribed in exacerbations of chronic obstructive pulmonary disease (COPD). However, the role of bacteria in these exacerbations is controversial. OBJECTIVE: To identify clinical predictors of bacterial infection as a cause of exacerbation, considering the protected specimen brush (PSB) as the gold standard. METHODS: Clinical data, sputum and PSB samples were collected from 40 patients with COPD requiring hospitalisation due to severe exacerbations who had not received previous antibiotic treatment. RESULTS: Quantitative cultures of PSB samples (n = 40) yielded 23 potential pathogenic microorganisms (PPMs) at concentrations of > or =10(2) colony-forming units/ml in 18 (45%) patients. Sputum samples were obtained from all 40 patients. Culture of good-quality sputum samples (n = 18) yielded 16 PPMs corresponding to 14 (35%) patients. The concordance between the PSB and sputum rate was high (kappa = 0.85, p < 0.002). The self-reporting patient observation of sputum purulence (odds ratio (OR) 27.20 (95% confidence interval (CI) 4.60 to 60.69), p = 0.001), the percentage predicted forced expiratory volume in 1 s (FEV(1)%) <50 (OR 2.27 (95% CI 1.55 to 3.21), p = 0.014), >4 exacerbations in the past year (OR 6.9 (95% CI 0.08 to 1.08), p = 0.028) and previous hospitalisations due to COPD (OR 4.13 (95% CI 1.02 to 16.07), p = 0.041) were associated with the presence of PPMs in the distal airways. The operative characteristics for predicting distal airway infection when patients presented with purulent exacerbation were as follows: sensitivity 89.5%, specificity 76.2%, positive predicted value 77.3% and negative predicted value 88.9%. CONCLUSIONS: The self-reporting presence of purulence in the sputum, as well as common previous exacerbations and hospitalisations due to COPD in patients with severe airflow obstruction (FEV1% <50) predict the presence of bacterial infection in the distal airways. The use of these clinical variables may help in selecting candidates to receive antibiotic treatment.

Prospective evaluation of procalcitonin in adults with febrile neutropenia after haematopoietic stem cell transplantation.

Serum procalcitonin (PCT) levels have been proposed as a new discriminative marker for bacterial and fungal infections. We analysed the diagnostic relevance of PCT in febrile episodes of neutropenic adult patients after haematopoietic stem cell transplantation (HSCT). PCT was determined prospectively in 92 febrile episodes, classified according to the final diagnosis as: neutropenic fever of unknown origin (n = 51), microbiological (n = 26) or clinical (n = 5) documented infection and non-infectious febrile episodes (n = 10). On first day of fever, mean (+/- SD) PCT level was 0.3 ng/ml (0.2) in neutropenic fever of unknown origin, 0.5 ng/ml (0.7) in microbiologically confirmed infections, 0.2 ng/ml (0.2) in clinically documented infections and 1.7 (4.2) in non-infectious fever (P = not significant). Five days after the antibiotic therapy was started, fever persisted in 29 neutropenic episodes (32%). Cases that were eventually diagnosed with invasive aspergillosis had PCT values significantly higher [10.1 ng/ml (6.7)] than all remaining groups (P = 0.027; Kruskal-Wallis). Our analysis indicates that the PCT level on first day of fever did not facilitate the differential diagnosis of neutropenic febrile episode. However, when fever persisted for more than 5 d, PCT values > or = 3 ng/ml had a high sensitivity and specificity for the diagnosis of invasive aspergillosis.

Pulmonary infiltrates in immunosuppressed patients: analysis of a diagnostic protocol.

A diagnostic protocol was started to study the etiology of pulmonary infiltrates in immunosuppressed patients. The diagnostic yields of the different techniques were analyzed, with special emphasis on the importance of the sample quality and the role of rapid techniques in the diagnostic strategy. In total, 241 patients with newly developed pulmonary infiltrates within a period of 19 months were included. Noninvasive or invasive evaluation was performed according to the characteristics of the infiltrates. Diagnosis was achieved in 202 patients (84%); 173 patients (72%) had pneumonia, and specific etiologic agents were found in 114 (66%). Bronchoaspirate and bronchoalveolar lavage showed the highest yields, either on global analysis (23 of 35 specimens [66%] and 70 of 134 specimens [52%], respectively) or on analysis of each type of pneumonia. A tendency toward better results with optimal-quality samples was observed, and a statistically significant difference was found in sputum bacterial culture. Rapid diagnostic tests yielded results in 71 of 114 (62.2%) diagnoses of etiological pneumonia.

Diagnóstico microbiológico de las infecciones bacterianas del tracto respiratorio inferior / Microbiological diagnosis of bacterial lower respiratory tract infections

El diagnóstico microbiológico de las infecciones bacterianas del tracto respiratorio inferior (TRI) presenta importantes limitaciones y controversias según los diferentes cuadros clínicos y los métodos diagnósticos, y su valor depende, a su vez, de un diagnóstico clínico correcto y de un tratamiento antibiótico previo. Las limitaciones estriban en la baja rentabilidad del aislamiento del agente causal y en la difícil valoración de los microorganismos aislados en relación con su significación clínica. Se examina aquí el rendimiento actual del diagnóstico microbiológico de los principales cuadros clínicos y agentes etiológicos, los procedimientos de recogida invasivos o no invasivos de los diferentes tipos de muestras, y su procesamiento y siembra en medios de cultivo. Se establecen los criterios de aceptación de las muestras y la indicación de realización de cultivos cuantitativos. Se exponen los criterios para la interpretación de los resultados y, por último, se describen las técnicas de diagnóstico rápido actuales (AU)

Microbiological diagnosis of bacterial lower respiratory tract infections has relevant limitations and related controversy, depending on the clinical setting and diagnostic methods used, and its value is contingent on an accurate clinical diagnosis and previous antimicrobial therapy. The limitations reside in a low diagnostic yield of the causative agent and the difficulty of determining the clinical significance of the agents recovered. This report examines the current microbiological diagnostic yield of the main clinical entities and etiological agents, indications for invasive or non-invasive specimen collection procedures, and proper specimen processing and culture in the appropriate media. Criteria regarding specimen suitability and indications for quantitative cultures are established. Criteria for evaluating the results are provided, and the current fast diagnostic techniques are described (AU)