Ricard Verdaguer

Community-acquired pneumonia in very elderly patients: causative organisms, clinical characteristics, and outcomes.

We performed an observational analysis of pro-spectively collected data on 1,474 adult patients who were hospitalized for community-acquired pneumonia; 1,169 patients were under 80 years of age and 305 (21%) patients were over 80 years (“very elderly”). Mean patient ages were 60 years in the former group and 85 years in the latter group. Severely immunosuppressed patients and nursing-home residents were not included. Comorbidities significantly associated with older age were chronic obstructive pulmonary disease, chronic heart disease, and dementia. The most common causative organism was Streptococcus pneumoniae (23% in both groups). Aspiration pneumonia was more frequent in the very elderly (5% in younger patients versus 10% in the very elderly);Legionella pneumophila (8% in younger patients versus 1% in the very elderly) and atypical agents (7% in younger patients versus 1% in the very elderly) were rarely recorded in the very elderly. While very elderly patients complained less frequently of pleuritic chest pain, headache, and myalgias, they were more likely to have absence of fever and altered mental status on admission. No significant differences were observed between groups as regards incidence of classic bacterial pneumonia syndrome (60% versus 59%) in 343 patients with pneumococcal pneumonia. The development of inhospital complications (26% in younger versus 32% in very elderly patients) as well as early mortality (2% in younger versus 7% in very elderly patients) and overall mortality (6% in younger versus 15% very elderly patients) were significantly higher in very elderly patients. Acute respiratory failure and shock/multiorgan failure were the most frequent causes of death, especially of early mortality. Factors independently associated with 30-day mortality in the very elderly were altered mental status on admission (odds ratio, 3.69), shock (odds ratio, 10.69), respiratory failure (odds ratio, 3.50), renal insufficiency (odds ratio, 5.83), and Gram-negative pneumonia (odds ratio, 20.27).

Contribution of a Urinary Antigen Assay (Binax NOW) to the Early Diagnosis of Pneumococcal Pneumonia

We evaluated the usefulness of a rapid urinary antigen test (Binax NOW; Binax) to detect Streptococcus pneumoniae for the early diagnosis of community-acquired pneumococcal pneumonia (PP) in 220 nonseverely immunosuppressed adults. We compared results of this test with those of sputum Gram staining. The rapid urinary antigen test showed limited sensitivity (65.9%; 95% confidence interval [CI], 51.4-80.4) but high specificity (100%; 95% CI, 99.7-100) for diagnosing PP. The test was more sensitive for patients with versus those without high-risk pneumonia (94% vs. 63%; P<.001) and for patients without versus those with demonstrative results of a sputum Gram stain (97% vs. 55%; P<.001), and it tended to be more sensitive for patients with versus those without bacteremic PP (92% vs. 74%; P=NS). Rapid urinary antigen testing permitted early diagnosis of PP in 26% more patients than did Gram staining but missed 22% of the rapid diagnoses initially identified by Gram staining. On the basis of our results, a sequential approach is proposed, with reservation of urinary antigen testing for high-risk patients for whom demonstrative results of a sputum Gram stain are unavailable.

Prospective Study of the Usefulness of Sputum Gram Stain in the Initial Approach to Community-Acquired Pneumonia Requiring Hospitalization

From February 1995 through May 1997, we prospectively studied 533 patients with community-acquired pneumonia requiring hospitalization in order to assess the current usefulness of sputum Gram stain in guiding the etiologic diagnosis and initial antibiotic therapy when applied routinely. Sputum samples of good quality were obtained in 210 (39%) patients, 175 of whom showed a predominant morphotype. Sensitivity and specificity of Gram stain for the diagnosis of pneumococcal pneumonia were 57% and 97%, respectively; the corresponding values for Haemophilus influenzae pneumonia were 82% and 99%. Patients with a predominant morphotype were more frequently treated with monotherapy than were patients without a demonstrative sputum sample (89% vs. 75%; P<.001). Analysis of our data shows that a good-quality sputum sample can be obtained from a substantial number of patients with community-acquired pneumonia. Gram stain was highly specific for the diagnosis of pneumococcal and H. influenzae pneumonia and may be useful in guiding pathogen-oriented antimicrobial therapy.

Clinical Outcomes for Hospitalized Patients with Legionella Pneumonia in the Antigenuria Era: The Influence of Levofloxacin Therapy

BACKGROUND Although the reduction in case-fatality rate recently observed among patients with Legionella pneumonia has been largely attributed to the progressive utilization of urine antigen testing, other factors, such as changes in empirical antibiotic therapy, may also have contributed. We have analyzed more-recent outcomes of Legionella pneumonia in an institution where urine antigen testing was reflexly performed in cases of community-acquired pneumonia without an etiological diagnosis. METHODS From a prospective series of 1934 consecutive cases of community-acquired pneumonia in nonimmunocompromised adults, 139 cases of Legionella pneumophila pneumonia were selected for observational review. Legionella cases were analyzed for outcome with respect to antibiotic treatment, mortality, complications, length of stay, time to defervescence, and stability. RESULTS The early case-fatality rate was 2.9% (4 of 139 patients), and the overall case-fatality rate was 5% (7 of 139 patients). One hundred twenty patients (86.3%) received an appropriate initial therapy, which included macrolides (i.e., erythromycin or clarithromycin) in 80 patients and levofloxacin in 40. Levofloxacin progressively replaced macrolides as the initial therapy during the study period. Compared with patients who received macrolides, patients who received levofloxacin had a faster time to defervescence (2.0 vs. 4.5 days; P<.001) and to clinical stability (3 vs. 5 days; P=.002). No differences were found regarding the development of complications (25% vs. 25%; P=.906) and case-fatality rate (2.5% vs. 5%; P=.518). The median length of hospital stay was 8 days in patients treated with levofloxacin and 10 days in those who received macrolides (P=.014). CONCLUSIONS Legionella pneumonia is still associated with significant complications in hospitalized patients, but recent mortality is substantially lower than that found in earlier series. Levofloxacin may produce a faster clinical response than older macrolides, allowing for shorter hospital stay.

Community-acquired bacterial meningitis in elderly patients: experience over 30 years.

Clinical characteristics, etiologies, evolution, and prognostic factors of community-acquired bacterial meningitis in elderly patients are not well known. To improve this knowledge, all episodes of community-acquired bacterial meningitis were prospectively recorded and cases occurring in patients ≥65 years old were selected. During the period 1977-2006, 675 episodes in adults (aged ≥18 yr) were recorded, with 185 (27%) in patients aged ≥65 years old; 76 were male and 109 were female, with a mean age of 73 ± 6 years (range, 65-93 yr). Causative microorganisms were Streptococcus pneumoniae 74, Neisseria meningitidis 49, Listeria monocytogenes 17, other streptococcal 9, Escherichia coli 6, Haemophilus influenzae 4, Klebsiella pneumoniae and Staphylococcus aureus 2 each, Capnocytophaga canimorsus and Enterococcus faecalis 1 each, and unknown in 20. On admission 91% had had fever, 32% were in a coma (Glasgow Coma Scale ≤8), 9% presented with seizures, and 8% with shock. Thirty patients (16%) presented with seizures during therapy. Mortality was 58/185 (31%). Compared with patients aged 18-65 years, there were significant differences among older patients (aged ≥65 yr), who showed a higher frequency of diabetes and malignancy as underlying disease; pneumonia, otitis, and pericranial fistula as predisposing factors; and S. pneumoniae and L. monocytogenes as etiology. There were also differences in clinical presentation, complications, sequelae, and mortality. Factors independently related with mortality were age, pneumonia as a predisposing factor, coma on admission, and heart failure and seizures after therapy. Dexamethasone therapy was a protective factor. In conclusion, bacterial meningitis in elderly patients is associated with greater diagnostic difficulties and neurologic severity and more complications, as well as with increased mortality. Antiseizure prophylaxis might be useful in these patients. Abbreviations: CSF = cerebrospinal fluid, ICP = intracranial pressure.

Community-acquired Legionella pneumophila pneumonia: a single-center experience with 214 hospitalized sporadic cases over 15 years.

AbstractLegionella pneumophila has been increasingly recognized as a cause of community-acquired pneumonia (CAP) and an important public health problem worldwide. We conducted the present study to assess trends in epidemiology, diagnosis, clinical features, treatment, and outcomes of sporadic community-acquired L. pneumophila pneumonia requiring hospitalization at a university hospital over a 15-year period (1995–2010). Among 3934 nonimmunosuppressed hospitalized patients with CAP, 214 (5.4%) had L. pneumophila pneumonia (16 cases were categorized as travel-associated pneumonia, and 21 were part of small clusters). Since the introduction of the urinary antigen test, the diagnosis of L. pneumophila using this method remained stable over the years (p = 0.42); however, diagnosis by means of seroconversion and culture decreased (p < 0.001 and p = 0.001, respectively).The median age of patients with L. pneumophila pneumonia was 58.2 years (SD 13.8), and 76.4% were male. At least 1 comorbid condition was present in 119 (55.6%) patients with L. pneumophila pneumonia, mainly chronic heart disease, diabetes mellitus, and chronic pulmonary disease. The frequency of older patients (aged >65 yr) and comorbidities among patients with L. pneumophila pneumonia increased over the years (p = 0.06 and p = 0.02, respectively). In addition, 100 (46.9%) patients were classified into high-risk classes according to the Pneumonia Severity Index (groups IV–V). Twenty-four (11.2%) patients with L. pneumophila pneumonia received inappropriate empirical antibiotic therapy at hospital admission. Compared with patients who received appropriate empirical antibiotic, patients who received inappropriate therapy more frequently had acute onset of illness (p = 0.004), pleuritic chest pain (p = 0.03), and pleural effusion (p = 0.05). The number of patients who received macrolides decreased over the study period (p < 0.001), whereas the number of patients who received levofloxacin increased (p < 0.001). No significant difference was found in the outcomes between patients who received erythromycin and clarithromycin. However, compared with macrolide use during hospital admission, levofloxacin therapy was associated with a trend toward a shorter time to reach clinical stability (median, 3 vs. 5 d; p = 0.09) and a shorter length of hospital stay (median, 7 vs. 10 d; p < 0.001).Regarding outcomes, 38 (17.8%) patients required intensive care unit (ICU) admission, and the inhospital case-fatality rate was 6.1% (13 of 214 patients). The frequency of ICU admission (p = 0.34) and the need for mechanical ventilation (p = 0.57) remained stable over the study period, but the inhospital case-fatality rate decreased (p = 0.04). In the logistic regression analysis, independent factors associated with severe disease (ICU admission and death) were current/former smoker (odds ratio [OR], 2.96; 95% confidence interval [CI], 1.01–8.62), macrolide use (OR, 2.40; 95% CI, 1.03–5.56), initial inappropriate therapy (OR, 2.97; 95% CI, 1.01–8.74), and high-risk Pneumonia Severity Index classes (OR, 9.1; 95% CI, 3.52–23.4).In conclusion, L. pneumophila is a relatively frequent causative pathogen among hospitalized patients with CAP and is associated with high morbidity. The annual number of L. pneumophila cases remained stable over the study period. In recent years, there have been significant changes in diagnosis and treatment, and the inhospital case-fatality rate of L. pneumophila pneumonia has decreased.

Changing Trends in the Epidemiology of Pyogenic Vertebral Osteomyelitis: The Impact of Cases with No Microbiologic Diagnosis

OBJECTIVES The observed higher incidence of pyogenic vertebral osteomyelitis (PVO) may entail an increasing number of patients with no microbiologic diagnosis. The true incidence of these cases, how exhaustive the etiologic diagnostic efforts must be, and the usefulness of an empirical antibiotic therapy are not well defined. METHODS Retrospective analysis of all cases of vertebral osteomyelitis in our center (1991-2009) and retrospective analysis of cases of PVO (2005-2009). Clinical data, diagnostic procedures, treatment, and outcome were reviewed. A comparative analysis between microbiologically confirmed PVO (MCPVO) and probable PVO (PPVO) was performed. RESULTS Increasing incidence of PVO (+0.047 episodes/100,000 inhabitants-year). During the last decade, there was an increase of PPVO (+0.059 episodes/100,000 inhabitants-year) with stable incidence of MCPVO. During 2005-2009, there were 72 patients [47 (65%) MCPVO and 25 (35%) PPVO]. 60% men; mean age was 66 years. Bacteremia was found in 59%. Computed tomographic guided vertebral biopsy, positive in 7/36 (19%), was more successful among patients with bacteremia. Among MCPVO, there was an increasing proportion of less virulent bacteria. Cases of MCPVO presented more frequently with sepsis, fever, and high acute-phase reactants, and PPVO cases were mostly treated with oral fluoroquinolones plus rifampin. No differences were found between both groups in outcome (93% success, 22% sequelae). CONCLUSIONS An epidemiologic change of PVO is suggested by a higher incidence of PPVO and the isolation of less virulent microorganisms among MCPVO. In this setting, the availability of an oral and effective empirical antibiotic therapy may challenge an exhaustive prosecution of the etiology.

Community-acquired pneumonia in patients with liver cirrhosis: clinical features, outcomes, and usefulness of severity scores.

We performed an observational analysis of a prospective cohort of nonimmunocompromised hospitalized adults with community-acquired pneumonia (CAP) to determine the epidemiology, clinical features, and outcomes of patients with liver cirrhosis. We also analyzed the prognostic value of several severity scores. Of 3420 CAP episodes, 90 occurred in patients with liver cirrhosis. The median value of the Model for End-Stage Liver Disease (MELD) was 14 (range, 6-36). On the Child-Pugh (CP) score, 56% of patients were defined as grade B and 22% as grade C. Patients with liver cirrhosis were younger (61.8 vs. 66.8 yr; p = 0.001) than patients without cirrhosis, more frequently presented impaired consciousness at admission (33% vs. 14%; p < 0.001) and septic shock (13% vs. 6%; p = 0.011), and were more commonly classified in high-risk Pneumonia Severity Index (PSI) classes (classes IV-V) (74% vs. 58%; p = 0.002). Streptococcus pneumoniae (47% vs. 33%; p = 0.009) and Pseudomonas aeruginosa (4.4% vs. 0.9%; p = 0.001) were more frequently documented in patients with cirrhosis. Bacteremia was also more common in these patients (22% vs. 13%; p = 0.023). Areas under the curve (AUCs) from disease-specific scores (MELD, CP, PSI, and CURB-65 [confusion, urea, respiratory rate, blood pressure, and age ≥65 yr]) were comparable in predicting severe disease (30-d mortality and intensive care unit [ICU] admission). A new score based on MELD, multilobar pneumonia, and septic shock at admission (MELD-CAP) had an AUC of 0.945 (95% confidence interval [CI], 0.872-0.983) for predicting severe disease and was significantly different from other scores. Early (5.6% vs. 2.1%; p = 0.048) and overall (14.4% vs. 7.4%; p < 0.024) mortality rates were higher in cirrhotic patients than in patients without cirrhosis. Factors associated with mortality were impaired consciousness, multilobar pneumonia, ascites, acute renal failure, bacteremia, ICU admission, and MELD score. Among the severity scores, MELD-CAP was the only score associated with severe disease (odds ratio [OR], 1.33; 95% CI, 1.09-1.52) and mortality (OR, 1.21; 95% CI, 1.03-1.42).In conclusion, CAP in patients with liver cirrhosis presents a distinctive clinical picture and is associated with higher mortality than is found in patients without cirrhosis. The severity of hepatic dysfunction plays an important role in the development of adverse events. Cirrhosis-specific scores may be useful for predicting and stratifying cirrhotic patients with CAP who have a high risk of severe disease.Abbreviations: AUC = area under the curve, CAP = community-acquired pneumonia, CI = confidence interval, CP = Child-Pugh score, CURB-65 = confusion, urea, respiratory rate, blood pressure, and age ≥65 years, HIV = human immunodeficiency virus, ICU = intensive care unit, LR = likelihood ratio, MELD = Model for End-Stage Liver Disease, OR = odds ratio, PSI = Pneumonia Severity Index, ROC = receiver operating characteristic, SBP = spontaneous bacterial peritonitis

Epidemiology, clinical features and outcomes of pneumonia in patients with chronic kidney disease

BACKGROUND Although infection remains among the most common causes of morbidity and mortality in patients with chronic kidney disease (CKD), data on epidemiology, clinical features and outcomes of pneumonia in this population are scarce. METHODS Observational analysis of a prospective cohort of hospitalized adults with pneumonia, between 13 February 1995 and 30 April 2010, in a tertiary teaching hospital. CKD patients, defined as patients with a baseline glomerular filtration rate <60 mL/min/1.73 m(2), were compared with non-CKD patients. RESULTS During the study period, 3800 patients with pneumonia required hospitalization. Two-hundred and three (5.3%) patients had CKD, of whom 46 were on dialysis therapy. Patients with CKD were older (77 versus 70 years; P < 0.001), were more likely to have comorbidities (82.3 versus 63.3%; P < 0.001) and more commonly classified into high-risk pneumonia severity index classes (89.6 versus 57%; P < 0.001) than were the remaining patients. Streptococcus pneumoniae was the most frequent pathogen (28.1 versus 34.7%; P = 0.05). Mortality was higher in patients with CKD (15.8 versus 8.3%; P < 0.001). Among CKD patients, age [+1 year increase; adjusted odds ratio, 1.25; 95% confidence interval (CI) 1.07-1.46] and cardiac complications during hospitalization (adjusted odds ratio, 9.23; 95% CI 1.39-61.1) were found to be independent risk factors for mortality, whereas prior pneumococcal vaccination (adjusted odds ratio, 0.05; 95% CI 0.005-0.69) and leukocytosis at hospital admission (adjusted odds ratio, 0.10; 95% CI 0.01-0.64) were protective factors. CONCLUSIONS Pneumonia is a serious complication in CKD patients. Independent factors for mortality are older age and cardiac complications, whereas prior pneumococcal vaccination and leucokytosis at hospital admission are protective factors. These findings should encourage physicians to increase pneumococcal vaccine coverage among CKD patients.

Efficacy of linezolid alone and in combination with rifampin in staphylococcal experimental foreign-body infection

OBJECTIVES The knowledge about efficacy of linezolid alone or in combination with rifampin in device infections is limited. We test their in vitro and in vivo efficacy in a rat model of foreign-body infection by methicillin-susceptible S. aureus. METHODS In vitro studies for logarithmic and stationary bacteria were performed. In vivo efficacy (decrease in bacterial counts in tissue cage fluid) was evaluated at: (i) after 7-day therapy (groups: linezolid, cloxacillin, rifampin, linezolid-rifampin and cloxacillin-rifampin); and (ii) after 10-day therapy (groups: rifampin and linezolid-rifampin). RESULTS After 7-day therapy all groups were significantly better than controls; linezolid (Delta log cfu/ml: -0.59, no resistant strains) and cloxacillin (-0.85) were the least effective therapy; linezolid was significantly less active (P<0.05) than rifampin (-1.22, resistance 90%), cloxacillin-rifampin (-1.3) and linezolid-rifampin (-1.14). After 10-day therapy linezolid-rifampin was the most effective treatment (Delta log -1.44, no resistance, P<0.05); in contrast, rifampin resulted ineffective (Delta log 0.1) due to the growth of resistant strains (100%). CONCLUSIONS Linezolid alone showed moderate efficacy, whereas its combination with rifampin prevented the emergence of rifampin resistance. The efficacy of linezolid-rifampin combination was initially similar to that of rifampin alone, but in contrast to rifampin, it increased over time revealing the impact of protection against rifampin resistance and the benefits of rifampin activity.