Manel Luján

Severity of Pneumococcal Pneumonia Associated with Genomic Bacterial Load

BACKGROUND There is a clinical need for more objective methods of identifying patients at risk for septic shock and poorer outcomes among those with community-acquired pneumonia (CAP). As viral load is useful in viral infections, we hypothesized that bacterial load may be associated with outcomes in patients with pneumococcal pneumonia. METHODS Quantification of Streptococcus pneumoniae DNA level by real-time polymerase chain reaction (rt-PCR) was prospectively conducted on whole-blood samples from a cohort of 353 patients who were displaying CAP symptoms upon their admission to the ED. RESULTS CAP caused by S pneumoniae was documented in 93 patients (36.5% with positive blood culture findings). A positive S pneumoniae rt-PCR assay finding was associated with a statistically significant higher mortality (odds ratio [OR], 7.08), risk for shock (OR, 6.29), and the need for mechanical ventilation (MV) [OR, 7.96]. Logistic regression, adjusted for age, sex, comorbidities, and pneumonia severity index class, revealed bacterial load as independently associated with septic shock (adjusted odds ratio [aOR], 2.42; 95% CI, 1.10 to 5.80) and the need for MV (aOR, 2.71; 95% CI, 1.17 to 6.27). An S pneumoniae bacterial load of >or= 10(3) copies per milliliter occurred in 29.0% of patients (27 of 93 patients; 95% CI, 20.8 to 38.9%) being associated with a statistically significant higher risk for septic shock (OR, 8.00), the need for MV (OR, 10.50), and hospital mortality (OR, 5.43). CONCLUSION In patients with pneumococcal pneumonia, bacterial load is associated with the likelihood of death, the risk of septic shock, and the need for MV. High genomic bacterial load for S pneumoniae may be a useful tool for severity assessment.

PIRO score for community-acquired pneumonia: a new prediction rule for assessment of severity in intensive care unit patients with community-acquired pneumonia.

Objective:To develop a severity assessment tool to predict mortality in community-acquired pneumonia (CAP) patients in intensive care unit (ICU), comparing its performance with Acute Physiology and Chronic Health Evaluation (APACHE) II score and American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) criteria as a prognostic index in CAP patients requiring ICU admission. Design:Secondary analysis of prospective observational cohort study. Setting:Thirty-three ICUs. Patients:Five hundred and twenty-nine adult patients with CAP requiring ICU admission. Measurements and Main Results:A severity assessment score was developed based on the PIRO (predisposition, insult, response, and organ dysfunction) concept including the presence of the following variables: Comorbidities (chronic obstructive pulmonary disease, immunocompromise); age >70 years; multilobar opacities in chest radiograph; shock, severe hypoxemia; acute renal failure; bacteremia and acute respiratory distress syndrome. PIRO score was obtained at ICU within 24 hours from admission, and one point was given for each present feature (range, 0–8 points). The mean PIRO score was significantly higher in nonsurvivors than in survivors (4.6 ± 1.2 vs. 2.3 ± 1.4). Considering the observed mortality for each PIRO score, the patients were stratified in four levels of risk: a) Low, 0–2 points; b) Mild, 3 points; c) high, 4 points; and d) Very high, 5–8 points. Mild-risk (hazard ratio [HR] 1.8; 95% confidence interval [CI] 1.1–2.9; p < 0.05), high-risk (HR 3.1; 95% CI = 2.0–4.7; p < 0.001), and very high risk levels (HR 6.3; 95% CI = 4.2–9.4; p < 0.001) were significantly associated with higher risk of death in Cox proportional hazards regression analysis. Furthermore, analysis of variance showed that higher levels of PIRO score were significantly associated with higher mortality (p < 0.001), prolonged length of stay in the ICU (p < 0.001), and days of mechanical ventilation (p < 0.001). Receiver operating characteristic curves showed that PIRO score (area under the curve [AUC] = 0.88) performed better than APACHE II (AUC = 0.75, p < 0.001) and ATS/IDSA criteria (AUC = 0.80, p < 0.001) to predict 28-day mortality. Conclusions:The PIRO score performed well as 28-day mortality prediction tool in CAP patients requiring ICU admission with a better performance than APACHE II and ATS/IDSA criteria in this subset of patients. Furthermore, PIRO score also is associated with increased healthcare resource utilization in CAP patients admitted in the ICU.

LATE-ONSET CONGENITAL CYSTIC ADENOMATOID MALFORMATION OF THE LUNG

Background: Congenital cystic adenomatoid malformation of the lung (CCAM) is an embryonic developmental anomaly of an unknown etiology usually diagnosed antenatally by imaging techniques. A minority of cases may not be identified by prenatal imaging techniques and may go unnoticed for the first 6 months of their extrauterine life. Due to its rarity, physicians are unlikely to suspect the condition. Objectives: To highlight the embryology, clinical symptomatology, diagnostic procedures, therapeutic approach and clinical follow-up of a series of 12 patients with late-onset CCAM. Methods: An observational study which offers the description of the clinical presentation, diagnostic methods, treatment and follow-up of 12 patients with late-onset CCAM. Setting: A 600-bed teaching hospital in a reference area of 350,000 inhabitants. Patients: 12 patients from 1983 to 1999. Results: Twelve diagnosed cases of late-onset CCAM. Mean age at diagnosis: 6.7 years (range: 6 months to 23 years). Clinical presentation: 9 out of 12 (75%) with repeated lung infections, 2 out of 12 (16%) chance finding, and 1 case (8%) with pneumothorax. On pathological examination, 7 were found to be CCAM type I and 4 CCAM type II according to Stocker’s classification; 1 patient is currently awaiting surgery. The diagnostic method of choice nowadays is a computed tomography (CT) scan performed in the 7 more recent cases; in the former 5 cases an isotopic lung scan was done (and in 2 of them a bronchography was also performed). Treatment: 11 patients were operated: 8 lobectomies, 2 segmentectomies and 1 localized resection. Mean follow-up: 8 years (range: 6 months to 16 years). Complications: One reintervention due to a reappearance of the lesion in the patient who underwent localized resection of the CCAM. No cases of malignancy were found. Conclusions: Late-onset CCAM is an infrequent illness which requires a high level of clinical suspicion. It usually presents in the form of repeated infections. The most frequent pathological forms are type I and II (Stocker). The diagnostic method of choice is the CT scan. The recommended treatment is radical surgery of the lesion once diagnosis has been established. Malignancy and relapses are very infrequent when radical surgery is not postponed.

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.

Why Mortality Is Increased in Health-Care-Associated Pneumonia: Lessons From Pneumococcal Bacteremic Pneumonia

BACKGROUND A cohort of patients with bacteremic Streptococcus pneumoniae pneumonia was reviewed to assess why mortality is higher in health-care-associated pneumonia (HCAP) than in community-acquired pneumonia (CAP). METHODS A prospective cohort of all adult patients with bacteremic pneumococcal pneumonia attended at the ED was used. RESULTS One hundred eighty-four cases were classified as CAP and 44 (19%) as HCAP. Fifty-two (23%) were admitted to the ICU. Three (1.5%) isolates were resistant to beta-lactams, and only two patients received inappropriate therapy. The CAP cohort was significantly younger (median age 68 years, interquartile range [IQR] 42-78 vs 77 years, IQR 67-82, P < .001). The HCAP cohort presented a higher Charlson index (2.81 +/- 1.9 vs 1.23 +/- 1.42, P < .001) and had higher severity of illness at admission (altered mental status, respiratory rate > 30/min, Pao(2)/Fio(2) < 250, and multilobar involvement). HCAP patients had a lower rate of ICU admission (11.3% vs 25.5%, P < .05), and a trend toward lower mechanical ventilation (9% vs 19%, P = .17) and vasopressor use (9% vs 18.4%, P = .17) were documented. More patients in the HCAP cohort presented with a pneumonia severity index score > 90 (class IV-V, 95% vs 65%, P < .001), and 30-day mortality was significantly higher (29.5% vs 7.6%, P < .001). A multivariable regression logistic analysis adjusting for underlying conditions and variables related to severity of illness confirmed that HCAP is an independent variable associated with increased mortality (odds ratio = 5.56; 95% CI, 1.86-16.5). CONCLUSIONS Pneumococcal HCAP presents excess mortality, which is independent of bacterial susceptibility. Differences in outcomes were probably due to differences in age, comorbidities, and criteria for ICU admission rather than to therapeutic decisions.

The Spectrum of Pneumococcal Empyema in Adults in the Early 21st Century

BACKGROUND Increased rates of empyema have been reported in children after the introduction of the pneumococcal conjugate vaccine (PCV7). Our objective was to describe the risk factors for pneumococcal empyema in adults and to analyze the differences in the incidence, disease characteristics, and serotype distribution between the pre- and post-PCV7 eras. METHODS An observational study of all adults hospitalized with invasive pneumococcal disease (IPD) who presented with empyema in 2 Spanish hospitals was conducted during the periods 1996-2001 (prevaccine period) and 2005-2009 (postvaccine period). Incidences of empyema were calculated. A multivariate analysis was performed to identify variables associated with pneumococcal empyema. RESULTS Empyema was diagnosed in 128 of 1080 patients with invasive pneumococcal disease. Among patients aged 18-50 years, the rates of pneumococcal pneumonia with empyema increased from 7.6% to 14.9% (P = .04) and the incidence of pneumococcal empyema increased from 0.5 to 1.6 cases per 100,000 person-years (198% [95% confidence interval {CI}, 49%-494%]). The incidence of empyema due to serotype 1 increased significantly from 0.2 to 0.8 cases per 100,000 person-years (253% [95% CI, 67%-646%]). Serotype 1 caused 43.3% of cases of empyema during the postvaccine period. Serotypes 1 (odds ratio [OR], 5.88; [95% CI, 2.66-13]) and 3 (OR, 5.49 [95% CI, 1.93-15.62]) were independently associated with development of empyema. CONCLUSIONS The incidence of pneumococcal empyema in young adults has increased during the postvaccine period, mainly as a result of the emergence of serotype 1. Serotypes 1 and 3 are the main determinants of development of this suppurative complication.

Feasibility of real-time polymerase chain reaction in whole blood to identify Streptococcus pneumoniae in patients with community-acquired pneumonia.

We assessed a real-time quantitative polymerase chain reaction (PCR) assay targeting the lytA and ply gene of Streptococcus pneumoniae. Both assays were applied to whole blood samples from 28 adult patients with community-acquired pneumonia. Our findings suggest the lytA PCR is more sensitive, and the quantitative aspect of the assay shows promise as an aid to clinical judgment.

Effect of Leak and Breathing Pattern on the Accuracy of Tidal Volume Estimation by Commercial Home Ventilators: A Bench Study

BACKGROUND: New home ventilators are able to provide clinicians data of interest through built-in software. Monitoring of tidal volume (VT) is a key point in the assessment of the efficacy of home mechanical ventilation. OBJECTIVE: To assess the reliability of the VT provided by 5 ventilators in a bench test. METHODS: Five commercial ventilators from 4 different manufacturers were tested in pressure support mode with the help of a breathing simulator under different conditions of mechanical respiratory pattern, inflation pressure, and intentional leakage. Values provided by the built-in software of each ventilator were compared breath to breath with the VT monitored through an external pneumotachograph. Ten breaths for each condition were compared for every tested situation. RESULTS: All tested ventilators underestimated VT (ranges of −21.7 mL to −83.5 mL, which corresponded to −3.6% to −14.7% of the externally measured VT). A direct relationship between leak and underestimation was found in 4 ventilators, with higher underestimations of the VT when the leakage increased, ranging between −2.27% and −5.42% for each 10 L/min increase in the leakage. A ventilator that included an algorithm that computes the pressure loss through the tube as a function of the flow exiting the ventilator had the minimal effect of leaks on the estimation of VT (0.3%). In 3 ventilators the underestimation was also influenced by mechanical pattern (lower underestimation with restrictive, and higher with obstructive). CONCLUSIONS: The inclusion of algorithms that calculate the pressure loss as a function of the flow exiting the ventilator in commercial models may increase the reliability of VT estimation.

Twelve years’ experience with methotrexate for GINA treatment step 5 asthma patients

ABSTRACT Background: Certain studies have shown the beneficial effects of methotrexate (MTX) in asthma patients. Here we describe the drugs tolerance and oral corticosteroid sparing capacity in a long-term observational study. Methods: Forty-four patients with steroid-dependent asthma treated with 10 mg per week of oral MTX were prospectively followed for 91.3 ± 39.5 months. Intervention: blood analysis each 3 months; spirometry monthly during the first 3 months and then every 3–6 months; liver ultrasound when an accumulated dose of 1500 mg was reached or whenever hepatic function was altered. Results: Two patients who dropped out early were excluded. Mean accumulated dose of MTX was 3.499 ± 2.207 mg. Corticosteroid use was reduced from 15.1 ± 8.2 to 2.64 ± 5.35 mg (p < 0.008) and was withdrawn in 25 patients. In the remaining 17 patients, the dose was reduced from 17.1 ± 9.1 mg to 6.5 ± 6.8 mg. FEV1 (% predicted) was 66.2 ± 19.7 at the beginning and 65.7 ± 19.1 at the end. Haematology was normal and only a mild increase in hepatic enzymes was observed in four patients, which normalized after treatment discontinuation. Hair loss was observed in one case. Conclusions: In our series, a substantial, safe decrease in oral corticosteroid requirements was observed, probably due, to some extent, to MTX therapy. Oral corticosteroids were withdrawn completely in 59% of patients. Liver function was impaired in some patients; however, it recovered after MTX withdrawal and MTX could be safely reintroduced. The association of oral corticosteroids and MTX did not increase the number of side-effects and immunity was not affected. We were unable to identify a factor that could predict which patients would benefit most from MTX treatment. Some limitations of the study include the lack of control of asthma exacerbations and the lack of booster courses of corticosteroids.

Healthcare-associated infections. A useful concept?

Purpose of reviewTo provide an overview of the importance of healthcare-associated infections (HCAI) as a new concept in infectious diseases. Although described originally in bacteremia, the concept has also been applied to other infections such as pneumonia and endocarditis. Recent findingsTherapeutic protocols recommend treating HCAI with broad-spectrum antibiotics to cover infection due to multidrug-resistant pathogens (MDR). Nonetheless, the prevalence of MDR pathogens may vary considerably in different subgroups of HCAI and in different countries. Patients categorized as having HCAI usually present atypical symptoms that may delay diagnosis; moreover, outcome is worse than community-acquired infections. Although several studies have reported that inappropriate empiric therapy may explain adverse outcomes in HCAI, careful adjustment for other conditions should be taken into account, such as baseline comorbidities, therapeutic limitations, and delay in the initiation of antibiotic treatment. SummaryIn patients with HCAI, complementary workup should be systematically performed in search of a microbiologic diagnosis. Broad-spectrum antibiotics should not be prescribed automatically, especially in countries with lower prevalence of MDR pathogens. Some refinements of the definition are needed and specific risk factors for infection by MDR microorganisms should be assessed.