Timing of antibiotic administration and outcomes of hospitalized patients with community-acquired and healthcare-associated pneumonia.

The effects of antibiotic timing on outcomes of patients with community-acquired pneumonia (CAP) are controversial. Moreover, no information is available regarding this issue in healthcare-associated pneumonia (HCAP). We aimed to determine the impact of antibiotic timing on 30-day mortality of patients with CAP and HCAP. Non-immunocompromised adults admitted to hospital through the emergency department (ED) with community-onset pneumonia were prospectively observed from 2001 to 2009. Patients who received prior antibiotics were excluded. Of 1593 patients with pneumonia who were analyzed, 1274 had CAP and 319 HCAP. The mean time from patient arrival at the ED until antibiotic administration was 5.8 h (standard deviation (SD) 3.5) in CAP and 6.1 h (SD 3.8) in HCAP (p 0.30). Mortality was higher in patients with HCAP (5.5% vs. 13.5%; p <0.001). After adjusting for confounding factors in a logistic regression analysis, the antibiotic administration ≤4 h was not associated with decreased 30-day mortality in patients with CAP (odds ratio (OR) 1.12, 95% confidence interval (CI) 0.57-2.21) and in patients with HCAP (OR 0.59, 95% CI 0.19-1.83). Similarly, antibiotic administration ≤8 h was not associated with decreased 30-day mortality in CAP (OR 1.58, 95% CI 0.64-3.88) and HCAP patients (OR 0.59, 95% CI 0.19-1.83). In conclusion, antibiotic administration within 4 or 8 h of arrival at the ED did not improve 30-day survival in hospitalized adults for CAP or HCAP.

Impact of antibiotic therapy on systemic cytokine expression in pneumococcal pneumonia.

The aim of this study was to compare the evolution of systemic cytokine levels over time in patients with pneumococal pneumonia treated either with ß-lactam monotherapy or with combination therapy (ß-lactam plus fluoroquinolone). Prospective observational study of hospitalized non-immunocompromised adults with PP. Concentrations of IL-6, IL-8, IL-10, and TNF-α were determined on days 0, 1, 2, 3, 5, and 7. Patients on ß-lactam monotherapy were compared with those receiving combination therapy. Fifty-two patients were enrolled in the study. Concentrations of IL-6, IL-8, and IL-10 decreased rapidly in the first days after admission, in accordance with the mean time to defervescence. High levels of IL-6 were found in patients with the worst outcomes, measured by the need for intensive care unit admission and mortality. No major differences in demographic or clinical characteristics or severity of disease were found between patients treated with ß-lactam monotherapy and those treated with combination therapy. IL-6 levels fell more rapidly in patients with combination therapy in the first 48 h (p = 0.016). Our data suggest that systemic expression of IL-6 production in patients with PP correlates with prognosis. Initial combination antibiotic therapy produces a faster decrease in this cytokine in the first 48 h.

Aetiology of, and risk factors for, recurrent community-acquired pneumonia.

Recurrent community-acquired pneumonia (CAP) requiring hospitalization is a matter of particular concern. However, current information on its prevalence, aetiology and risk factors is lacking. To address these issues, we performed an observational analysis of a prospective cohort of hospitalized adults with CAP. Recurrence was defined as two or more episodes of CAP 1 month apart within 3 years. Patients with severe immunosuppression or local predisposing factors were excluded. Of the 1556 patients, 146 (9.4%) had recurrent CAP. The most frequent causative organism was Streptococcus pneumoniae, both in patients with recurrent CAP and in those without recurrence. Haemophilus influenzae, other Gram-negative bacilli and aspiration pneumonia were more frequent among patients with recurrent CAP, whereas Legionella pneumophila was rarely identified in this group. Independent factors associated with recurrent CAP were greater age, lack of pneumococcal vaccination, chronic obstructive pulmonary disease (COPD) and corticosteroid therapy. In a sub-analysis of 389 episodes of pneumococcal pneumonia, the only independent risk factor for recurrence was lack of pneumococcal vaccination. Recurrence of CAP is not a rare clinical problem and it occurs mainly in the elderly, patients with COPD, and those receiving corticosteroids. Our study provides support for recommending pneumococcal vaccination for adults at risk of pneumonia, including those with a first episode of CAP.

Early mortality in patients with community-acquired pneumonia: causes and risk factors.

The first 48 h of evolution of patients with community-acquired pneumonia (CAP) are critical. The aim of the present study was to determine the frequency, causes and factors associated with early mortality in CAP. Nonimmunocompromised adults hospitalised with CAP were prospectively observed from 1995 to 2005. Early deaths, defined as death due to any cause < or = 48 h after admission, were compared with all patients who survived > 48 h. Furthermore, early deaths were compared with late deaths (patients who died > 48 h) and with survivors. Of 2,457 patients, 57 (2.3%) died < or = 48 h after admission. Overall mortality was 7.7%. The main causes of early mortality were respiratory failure and septic shock/multiorgan failure. Independent factors associated with early deaths were increased age, altered mental status at presentation, multilobar pneumonia, shock at admission, pneumococcal bacteraemia and discordant empiric antibiotic therapy. Currently, early mortality is relatively low and is caused by pneumonia-related factors. It occurs mainly among the elderly and in patients presenting with altered mental status, multilobar pneumonia and septic shock. Pneumococcal bacteraemia and discordant antibiotic therapy, mainly due to lack of coverage against Pseudomonas aeruginosa are also significant risk factors.

Noninvasive positive pressure ventilation prevents postoperative pulmonary complications in chronic ventilators users.

OBJECTIVE: To evaluate the postoperative pulmonary complications and the long-term impact on pulmonary function of different surgical procedures with general anaesthesia in chronic respiratory failure (CRF) patients who were using noninvasive positive pressure ventilation (NPPV). DESIGN: We retrospectively studied 20 stable patients on NPPV for CRF secondary to: kyphoscoliosis (eight), morbid obesity (six), thoracoplasty (four), neuromuscular diseases (two), who underwent surgical procedures with general anaesthesia, between January 1998 and December 2003. MATERIAL AND METHODS: The variables studied were: type of surgery, hours of orotracheal intubation, hours of stay in the postsurgical reanimation unit (PRU), postoperative pulmonary complications and days of hospital stay. These results were compared with those obtained in patients without respiratory pathology and who were submitted to the same type of surgical interventions during the study period. All patients were tested for: arterial blood gases, forced vital capacity (FVC) and forced expiratory volume in 1s (FVE1). These tests were carried out both prior to surgical intervention and 12 months after this intervention, and the use of medical assistance resources the year prior to and the year after the surgical intervention were also analysed. RESULTS: Sixteen patients were using NPPV at home at the time of the intervention and four patients were adapted to NPPV before surgery. The surgical procedures were: gastroplasty: six; mastectomy: five; septoplasty: three; hip prosthesis: two; cholecystectomy: one; Gasserian ganglion thermocoagulation: one; hysterectomy: one; and endoscopic retrograde cholangiopancreatography (ERCP): one. The mean postoperative intubation time was 3.8+/-3.2h, and only one patient remained intubated for more than 12h. The mean stay in the PRU was 19+/-9h (vs 19+/-6h in the general population, p>0.05). The days of hospital stay for the different pathologies were in the majority of cases greater than in the general population. We did not find significant differences on comparing the arterial blood gases, in pulmonary function or in use of assistance resources between the year previous to and the year following the surgical intervention. CONCLUSIONS: In high-risk patients with chronic respiratory failure as a consequence of a restrictive lung pathology, NPPV can play an important role to confront surgical procedure with general anaesthesia with greater security. To obtain these results, it was fundamental to coordinate between the Pulmonary Services and the Anaesthesia Services as well as to follow up jointly in the PRU.

Effect of prior pneumococcal vaccination on clinical outcome of hospitalized adults with community-acquired pneumococcal pneumonia.

The aim of this study was to evaluate the effect of prior pneumococcal vaccination on the clinical outcome of 554 consecutive hospitalized adults with community-acquired pneumococcal pneumonia from 1995 to 2004, 61 of whom had been vaccinated in the 5 years before admission. Outcome variables that were compared in vaccinated and unvaccinated adults included the occurrence of bacteremia, the time to resolution of pneumonia symptoms, the length of hospital stay, and mortality. Prior pneumococcal vaccination was associated with a lower risk of bacteremia (odds ratio 0.46, 95% CI 0.22-0.98). Compared with unvaccinated patients, vaccine recipients had better clinical outcomes, which included a faster resolution of pneumonia symptoms. The median length of hospital stay was shorter in vaccinated patients (8.0 vs. 9.0 days; p=0.032). Overall case-fatality rates did not differ significantly between groups (1.6% vs. 6.2%; p=0.233). In conclusion, prior pneumococcal vaccination appears to be associated with a lower risk of bacteremia, a faster time to resolution of symptoms, and a shorter hospital stay in adults with pneumococcal pneumonia. The findings presented here provide additional support to the current vaccine recommendations and should encourage healthcare providers to increase pneumococcal vaccine coverage among targeted adult populations.

[Analysis of oxidative stress in exhaled breath condensate from patients with severe pulmonary infections]. / Estrés oxidativo en el condensado exhalado de pacientes con infección pulmonar grave.

OBJECTIVE: Oxidative stress is an intrinsic part of the chain of events leading to inflammation of the airways caused by bacterial infection. The aim of this study was to determine whether analysis of exhaled breath condensate from patients with severe lung infections reveals changes in the redox state at the airway surface. PATIENTS AND METHODS: The study included a total of 48 subjects divided into 4 groups: individuals without respiratory disease (n=14), patients with multilobar pneumonia (n=13), patients who had chronic obstructive pulmonary disease with superinfection (n=14), and mechanically ventilated patients with severe pneumonia (n=7). A sample of exhaled breath condensate was obtained within the first 72 hours of hospital admission and the concentrations of nitrite, nitrate, 8-isoprostane, and myeloperoxidase (MPO) were determined. RESULTS: Significant differences in the concentrations of nitrite, 8-isoprostane, and MPO were observed between patients and individuals without respiratory disease but no differences were found between the 3 patient groups. The concentration of MPO was correlated with the concentrations of 8-isoprostane and nitrate, which were normalized to the nitrite concentration. CONCLUSIONS: Analysis of the concentrations of 8-isoprostane and MPO in exhaled breath condensate allows assessment of oxidative stress in the airways of patients with severe lung infections.

Efficacy and safety of sequential amoxicillin-clavulanate in the treatment of anaerobic lung infections.

In order to assess the efficacy and safety of amoxicillin-clavulanate for the treatment of anaerobic lung infection, 40 patients with lung abscess or necrotizing pneumonia were given sequential amoxicillin-clavulanate therapy. All patients received intravenous amoxicillin-clavulanate (2 g/200 mg/8 h), which was switched to oral form (1 g/125 mg/8 h) after clinical improvement. Mean duration of antibiotic therapy was 43.5 days. Microbiological documentation was obtained in 53% of cases. All but 1 of the 48 microorganisms isolated were susceptible to amoxicillin-clavulanate. The drug was well tolerated by the patients and no severe adverse effects were observed. At the end of treatment all patients were considered cured. The 35 patients assessed at long-term follow-up visit remained disease-free.

Effects of antibiotics on protected specimen brush sampling in ventilator-associated pneumonia.

The effects of antibiotic treatment on the results of protected specimen brushing (PSB) in ventilator-associated pneumonia were prospectively assessed by performing this procedure before antibiotic treatment, and 12, 24, 48 and 72 h after initiation of antibiotic treatment, in 35 ventilated patients who developed pneumonia during mechanical ventilation. The number of micro-organisms isolated, their concentration (colony-forming units (cfu) mL(-1)), and the number of cases with a positive PSB (> or =10(3) cfu x mL(-1)) were evaluated. Within 12 h of the initiation of effective antibiotic treatment a rapid, significant decrease in the numbers of organisms isolated, their individual concentrations and the percentage of positive PSB results were observed. Certain bacterial species (Streptococcus pneumoniae, Haemophilus influenzee) appeared to be more vulnerable to antibiotics than others (Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumanni). This data confirms that prior antibiotic treatment, even after only a few hours of activity, significantly decreases the sensitivity of protected brush specimen; this effect appears to be particularly marked among the species involved in early ventilator associated pneumonia.

Etiology, reasons for hospitalization, risk classes, and outcomes of community-acquired pneumonia in patients hospitalized on the basis of conventional admission criteria.

We performed an observational analysis of prospectively collected data on 533 nonseverely immunosuppressed adult patients who were hospitalized for community-acquired pneumonia on the basis of conventional admission criteria. For this population, we correlated etiology, reasons for admission, and outcomes using the Pneumonia Severity Index (PSI), to identify major discrepancies between the PSI risk class and the conventional criteria for deciding the site of care. PSI classes and corresponding mortality rates were as follows: class I, 51 patients (0%); class II, 62 (2%); class III, 117 (3%); class IV, 198 (10%); and class V, 105 (29%). We identified significant discrepancies between both methods. Overall, 230 patients (40%) who were hospitalized according to conventional criteria were assigned to low-risk classes. Of these 230 patients, 137 (60%) needed supplementary oxygen or had pleural complications; for the remaining patients, there were no irrefutable reasons for admission. This latter group deserves prospective evaluation in randomized studies that compare ambulatory and in-hospital management.

Usefulness of betalactam therapy for community-acquired pneumonia in the era of drug-resistant Streptococcus pneumoniae: a randomized study of amoxicillin-clavulanate and ceftriaxone.

Empirical antibiotic therapy of community-acquired pneumonia (CAP) has been complicated by the worldwide emergence of penicillin resistance among Streptococcus pneumoniae. The impact of this resistance on the outcome of patients hospitalized for CAP, empirically treated with betalactams, has not been evaluated in a randomized study. We conducted a prospective, randomized trial to assess the efficacy of amoxicillin-clavulanate (2 g/200 mg/8 hr) and ceftriaxone (1 g/24 hr) in a cohort of patients hospitalized for moderate-to-severe CAP. Three-hundred seventy-eight patients were randomized to receive amoxicillin-clavulanate (184 patients) or ceftriaxone (194 patients). Efficacy was assessed on Day 2, after completion of therapy and at long term follow-up. There were no significant differences in outcomes between treatment groups, both in intention-to-treat and per-protocol analysis. Overall mortality was 10.3% for amoxicillin-clavulanate and 8.8% for ceftriaxone (NS). There were 116 evaluable patients with proven pneumococcal pneumonia. Rates of high-level penicillin resistance (MIC of penicillin > or = 2 microg/mL) were similar in the two groups (8.2 and 10.2%). Clinical efficacy at the end of therapy was 90.6% for amoxicillin-clavulanate and 88.9% for ceftriaxone (95% C.I. of the difference: -9.3 to +12.7%). No differences in outcomes were attributable to differences in penicillin susceptibility of pneumococcal strains. Sequential i.v./oral amoxicillin-clavulanate and parenteral ceftriaxone were equally safe and effective for the empirical treatment of acute bacterial pneumonia, including penicillin and cephalosporin-resistant pneumococcal pneumonia. The use of appropriate betalactams in patients with penumococcal pneumonia and in the overall CAP population, is reliable at the current level of resistance.

Impact of a hospital-based home-care program on the management of COPD patients receiving long-term oxygen therapy.

STUDY OBJECTIVES: To analyze the influence of a hospital-based home-care program (HCP) on the management of patients with COPD receiving long-term oxygen therapy. DESIGN AND SETTING: Randomized, controlled study in a 1,000-bed university hospital. INTERVENTION: The HCP applied to patients in the intervention group (HCP group) consisted of a monthly telephone call, home visits every 3 months, and home or hospital visits on a demand basis. Patients in the control group were given conventional medical care. MEASUREMENTS: Pulmonary function data, gas exchange, use of hospital resources (emergency department visits, admissions, and hospital stay) and the cost of medical assistance were investigated in both groups before and after 1 year of study. Quality of life was analyzed using the chronic respiratory questionnaire in the first 40 consecutive patients included in the study. Survival throughout the study was also assessed. RESULTS: One hundred twenty-two patients were enrolled in the study, and 94 patients (46 in the HCP group and 48 in the control group) completed the 1-year follow-up period: 83 patients (88%) were men, and mean (+/- SD) age was 68 +/- 8 years. During the follow-up period, there was a highly significant decrease in the mean number of emergency department visits (0.45 +/- 0.83 vs 1.58 +/- 1.96; p = 0.0001) and also a significant decrease in hospital admissions (0.5 +/- 0.86 vs 1.29 +/- 1.7; p = 0.001) and days of hospital stay (7.43 +/- 15.6 vs 18.2 +/- 24.5; p = 0.01) in the HCP group. Patients in the intervention group required a total of 221 home visits (mean per patient, 4.8 +/- 0.8) and 69 hospital visits (mean per patient, 1.5 +/- 1.07). In spite of the cost of the program, cost analysis showed a total saving of 8.1 million pesetas ($46,823) in the HCP group, mainly due to a decrease in the use of hospital resources. There was no difference in pulmonary function, gas exchange, quality of life, and survival between the two groups. CONCLUSIONS: Hospital-based home care is an effective alternative to hospital admission. It reduces the use of hospital resources and the cost of health care.

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.

[Effectiveness of a mandibular advancement prosthesis in the treatment of obstructive sleep apnea syndrome]. / Eficacia de una prótesis de avance mandibular en el tratamiento del síndrome de apneas obstructivas del sueño.

OBJECTIVE: To assess the efficacy of a mandibular advancement prosthesis for treating obstructive sleep apnea syndrome (OSAS). METHOD: Mandibular advancement appliances were prescribed for 21 patients (20 men) with OSAS diagnosed by polysomnography. Mean age was 51 (8) years, BMI was 30 (4) kg/m2, and the apnea-hypopnea index (AHI) per hour was 48 (17). If the device was well tolerated, regardless of clinical response, polysomnography was repeated between 1 to 3 months after start of treatment. The device was considered effective if the AHI decreased to < 15/h and symptoms related to OSAS disappeared. RESULTS: Seven patients withdrew from treatment after only a few days. The remaining 14 (66%) tolerated treatment well and the second polysomnogram was performed. In six of the 14 (43%), the device proved effective for correcting OSAS. In six more patients, the AHI decreased but failed to become normal. In the remaining two patients, no improvement was observed. Improvement in the AHI was unrelated to severity of OSAS. CONCLUSION: The mandibular advancement prosthesis is effective for some patients with OSAS, including those in whom the AHI is high. Larger studies are needed to allow us to define the type of patients that might benefit.

[The internal consistency and content validity of the Spanish version of the Asthma Autonomy Questionnaire]. / Consistencia interna y validez de contenido de la versión española del Asthma Autonomy Questionnaire.

The Asthma Autonomy Questionnaire (AAQ) was designed to evaluate asthmatics' desire to learn about their disease and to make decisions. The AAQ consists of 26 items distributed in two scales: Preferences in the Search for Information (PSI, 8 items) and Preferences in Decision Making (PDM, 6 general items and 12 related to 3 scenarios depicting asthma in stable phase, during mild exacerbation and during severe exacerbation). The aim of this study was to analyze the internal consistency (Cronbach's-coefficient) and content validity (factorial analysis of principal components) of the AAQ. After translation and back translation, the Spanish version of the AAQ was administered to 115 adult asthmatics of both sexes and differing levels of severity. The alpha coefficients for the two scales and 3 scenarios ranged from 0.42 (PSI) to 0.73 (stable phase scenario); only for the stable-phase scenario were values high or statistically acceptable. Factorial analysis reproduced the content of the scales only approximately, with some items proving to relate to factors that were different from the scale they originally belonged to. These results indicate that, in its current formulation, the AAQ presents important measurement problems and revision is advisable.

[Information seeking and decision making in asthmatic patients]. / Búsqueda de información y toma de decisiones en pacientes asmáticos.

Patient cooperation in controlling asthma is a key element for achieving the most efficient therapy possible according to current guidelines. Cooperation requires that the patient be adequately informed about his disease and able to make certain decisions. The aim of this study was to analyze whether patients really desire information about asthma and to what point they are disposed to cooperate actively in managing their disease. Ninety-five adult asthmatics with different levels of severity of disease were studied in stable condition. All responded to the Spanish version of the questionnaire on autonomy in asthma, an instrument with a scoring range of 0 to 100 and 26 items grouped in two subscales: preferences in the search for information (PSI) and preferences in decision making (PDM). The second subscale was based on three scenarios describing stable asthma, slight exacerbation and severe exacerbation. The results obtained indicate that although patients are greatly interested in receiving information (PSI scores of 86.4 +/- 8.7) they express substantially less desire to make decisions (PDM 45 +/- 10.2) (p < 0.01). Attitudes did not change in relation to education, number of exacerbations during the last year, duration of disease or severity as assessed by the patient. Only patient age (with older patients scoring higher on PSI) and presence of severe asthma (according to consensus guidelines) increased the desire for information (but not the preference for decision making). These data indicate the need to implement educational programs about asthma, components of which promote effective desire for self-management.

Löfgren's syndrome revisited: a study of 186 patients.

PURPOSE: To evaluate the clinical features, the results of noninvasive tests and biopsies, and the outcome of patients with Löfgren's syndrome. SUBJECTS AND METHODS: Patients diagnosed as having Löfgren's syndrome at a university hospital in Barcelona, Spain, from 1974 to 1996, were prospectively followed. Löfgren's syndrome was defined as the association of erythema nodosum or periarticular ankle inflammation with unilateral or bilateral hilar or right paratracheal lymphadenopathy. RESULTS: Löfgren's syndrome was diagnosed in 186 patients. The mean age was 37 +/- 11 years, and 157 (85%) were women. In 91 patients (49%), symptoms started during the spring (P < 0.0001). Erythema nodosum, periarticular ankle inflammation, or both were present at onset in 173 patients (93%). At the time of diagnosis, 161 patients (87%) had no respiratory symptoms; 151 (81%) had stage I abnormalities on chest radiograph, 29 (16%) stage II, and 6 (3%) stage 0. Five percent of patients had decreased forced vital capacity, and 15% had decreased carbon monoxide diffusing capacity. Extrathoracic involvement was infrequent. Serum angiotensin-converting enzyme levels were increased in 50% of patients. Gallium-67 scans showed hilar uptake in all the studied patients, but it yielded useful additional diagnostic information only in those with normal chest radiographs or with unilateral hilar lymphadenopathy. The diagnosis was proven with biopsy results in 63% of patients. None of the patients without histologic confirmation were subsequently found to have a diagnosis other than sarcoidosis. In the 133 patients who were followed for a mean of almost 5 years, 11 (8%) continued to have active disease, and 8 (6%) had several recurrences between 18 months and 20 years after a complete resolution. A normal serum angiotensin-converting enzyme level at diagnosis was associated with disease resolution without recurrence. CONCLUSION: Löfgren's syndrome is usually a self-limiting form of sarcoidosis. Histologic confirmation is not necessary in typical cases. In a small number of patients, the disease may remain active or recur long after its onset, although usually with mild organ dysfunction.

Microbial etiology and bacterial resistance.

The nature of the causative organisms involved in community-acquired pneumonia has always attracted the interest of investigators. Despite multiple studies using different methodological approaches, it remains a matter of controversy because a reliable cause cannot be obtained in a significant percentage of cases, even when using more sophisticated diagnostic procedures. The recent discovery of new pathogens such as the Legionella species or Chlamydia pneumoniae, highly prevalent worldwide shows the limitations of our knowledge in that field. Recently, common respiratory pathogens such as the pneumococcus or Haemophilus influenzae, among others, showed a progressive tendency to develop resistance to penicillins and other antibiotics. Although this phenomenon has a variable impact among different countries, its growing importance is changing the classical therapeutic approach to community-acquired pneumonia.