Epidemiology of community-acquired pneumonia in adult patients at the dawn of the 21st century: a prospective study on the Mediterranean coast of Spain

This study presents data from a prospective study of adult patients with community-acquired pneumonia (CAP). Of 493 patients included in the study, 223 (45.2%) were aged > or = 65 years, and 265 (53.7%) had one or more underlying diseases, mostly chronic obstructive pulmonary disease, diabetes mellitus or dementia. In total, 281 microorganisms were identified in 250 (50.7%) patients, with two or more pathogens detected in 28 (5.7%) cases. Microbial diagnosis varied according to age, severity, co-morbidity and site-of-care, but there was much overlap among groups. Streptococcus pneumoniae was the single most prevalent organism in outpatients, patients admitted to hospital, and patients who died, either as a single pathogen or combined with another organism. Infections caused by 'atypical' pathogens were seen across all groups, including the elderly and patients with co-morbidities. Mortality varied according to the pneumonia severity index (PSI) of the pneumonia patient outcomes research team. Shock (OR 34.48), an age of > 65 years (OR 25) and altered mental status (OR 9.92) were factors associated independently with 30-day mortality. Key findings from this study were the advanced age of the population with CAP, and the high prevalence of dementia as an underlying disease. The study also revealed that microbiological diagnosis of CAP remains problematic. Although certain epidemiological features may help to predict the microbial aetiology, the overlap among groups reduces the usefulness of this information in guiding therapeutic decisions. Greater effort should be made to improve identification methods for microbial pathogens causing CAP.     

Community-acquired pneumonia: causes of treatment failure in patients enrolled in clinical trials

In order to determine the causes of treatment failure in community-acquired pneumonia (CAP) clinical trials, a MEDLINE search for all CAP studies published between 1990 and 1997 was performed. Prospective, randomized studies comparing the efficacy of two or more antibiotics in CAP were selected. Treatment failure was defined as persistent fever, deterioration of patient's condition, or a change in the prescribed antibiotic regimen. In 16% of the cases included in the clinical trials, the treatment of CAP is unsuccessful. A significant number of identified failure cases were owing to antibiotic side-effects. Resistant pathogens are an unusual cause of failure whatever the antibiotic used.     

Impact of pre-hospital antibiotic use on community-acquired pneumonia

Information on the influence of pre-hospital antibiotic treatment on the causative organisms, clinical features and outcomes of patients with community-acquired pneumonia (CAP) remains scarce. We performed an observational study of a prospective cohort of non-immunosuppressed adults hospitalized with CAP between 2003 and 2012. Patients were divided into two groups: those who had received pre-hospital antibiotic treatment for the same episode of CAP and those who had not. A propensity score was used to match patients. Of 2179 consecutive episodes of CAP, 376 (17.3%) occurred in patients who had received pre-hospital antibiotic treatment. After propensity score matching, Legionella pneumophila was more frequently identified in patients with pre-hospital antibiotic treatment, while Streptococcus pneumoniae was less common (p <0.001 and p <0.001, respectively). Bacteraemia was less frequent in pre-treated patients (p 0.01). The frequency of positive sputum culture and the sensitivity and specificity of the pneumococcal urinary antigen test for diagnosing pneumococcal pneumonia were similar in the two groups. Patients with pre-hospital antibiotic treatment were less likely to present fever (p 0.02) or leucocytosis (p 0.001). Conversely, chest X-ray cavitation was more frequent in these patients (p 0.04). No significant differences were found in the frequency of patients classified into high-risk Pneumonia Severity Index classes, in intensive care unit admission, or in 30-day mortality between the groups. In conclusion, L. pneumophila occurrence was nearly three times higher in patients who received pre-hospital antibiotics. After a propensity-adjusted analysis, no significant differences were found in prognosis between study groups. Pre-hospital antibiotic use should be considered when choosing aetiological diagnostic tests and empirical antibiotic therapy in patients with CAP.     

喹诺酮类药物治疗社区获得性肺炎疗效观察与安全性评价

目的探讨3种喹诺酮类药物治疗社区获得性肺炎的疗效和安全性,为临床治疗性用药提供科学依据。方法采用随机、开放对照的研究方法,选取120例社区获得性肺炎患者,随机分为莫西沙星组、左氧氟沙星组和环丙沙星组3组,每组各40例,治疗7d后比较3组临床与细菌学疗效和安全性。结果莫西沙星组总有效率为93%,细菌清除率为88.9%,不良反应的发生率为7.5%;左氧氟沙星总有效率为88%,细菌清除率为76.5%,不良反应的发生率为73.3%;环丙沙星总有效率为88%,细菌清除率为73.3%,不良反应的发生率为7.5%。3组总有效率和不良反应发生率比较差异无统计学意义,细菌清除率莫西沙星组要高于左氧氟沙星组和环丙沙星组,差异有统计学意义（P〈0.05）。结论经验性莫西沙星、左氧氟沙星与环丙沙星治疗社区获得性肺炎的总的临床疗效和安全性基本一致,但莫西沙星具有更强的细菌清除率。     

Once-daily oral gatifloxacin vs. three-times-daily co-amoxiclav in the treatment of patients with community-acquired pneumonia

A double-blind, double-dummy, multicentre, multinational, parallel-group study was designed to establish proof of equivalence between oral gatifloxacin and oral co-amoxiclav in the treatment of 462 patients with mild-to-moderate community-acquired pneumonia. Eligible patients were randomised equally to either gatifloxacin 400 mg once-daily plus matching placebo for 5-10 days, or amoxycillin 500 mg + clavulanic acid 125 mg three-times-daily for 5-10 days. The primary efficacy endpoint was clinical response (clinical cure plus improvement) at the end of treatment. Overall, a successful clinical response was achieved in 86.8% of gatifloxacin-treated patients, compared with 81.6% of those receiving co-amoxiclav, while corresponding rates of bacteriological efficacy (eradication plus presumed eradication) were 83.1% and 78.7%, respectively. The safety and tolerability profile of gatifloxacin was comparable to that of co-amoxiclav, with adverse gastrointestinal events, e.g., diarrhoea and nausea, being the most common treatment-related adverse events in both groups. The study showed no evidence of gatifloxacin-induced phototoxicity, musculoskeletal disorders, or hepatic and renal problems. Overall, this study showed that gatifloxacin was equivalent clinically to a standard course of co-amoxiclav in patients with community-acquired pneumonia, and that gatifloxacin was safe and well-tolerated.     

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.     

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.     

Doxycycline vs. macrolides in combination therapy for treatment of community-acquired pneumonia

We assessed the comparative efficacy of empirical therapy with beta-lactam plus macrolide vs. beta-lactam plus doxycycline for the treatment of community-acquired pneumonia (CAP) among patients in the Australian Community-Acquired Pneumonia Study. Both regimens demonstrated similar outcomes against CAP due to either ‘atypical’ (Chlamydophila, Legionella or Mycoplasma spp.) or typical bacterial pathogens.     

Clinical features and outcome of patients with community-acquired Pseudomonas aeruginosa bacteraemia

Cases of community-acquired Pseudomonas aeruginosa bacteraemia (n = 39) that occurred at a tertiary-care hospital during a 5-year period were analysed retrospectively. The commonest underlying diseases were solid tumour (41%) and haematological malignancy (18%). Most (44%) of the patients were neutropenic, and 39% had septic shock at initial presentation. The 30-day attributable mortality rate was 39%. Two previously healthy patients were identified with fatal P. aeruginosa pneumonia with bacteraemia. P. aeruginosa bacteraemia is a fatal infection that should be considered in the differential diagnosis of patients presenting from the community with rapidly progressive sepsis.     

Prognostic factors of mid-term clinical outcome in congestive heart failure patients discharged after acute decompensation

Introduction

Risk stratification in congestive heart failure (CHF) patients is based on a variety of clinical and laboratory variables. We analysed renal function, BNP, water composition, echocardiographic and functional determinations in predicting mid-term outcome in CHF patients discharged after decompensation.

Material and methods

All subjects with NYHA class II-IV were enrolled at hospital discharge. NYHA class, BNP, water body composition, non-invasive cardiac output and echocardiogram were analysed. Death, cardiac transplantation and hospital readmission for CHF were scheduled.

Results

Two-hundred and thirty-seven (64.5% males, age 71.1±10.1) patients were discharged after obtaining normal hydration; left ventricular ejection fraction (LVEF) was 43.2±16.2%, cardiac output was 3.8±1.1 l/min and BNP at discharge resulted 401.3±501.7 pg/ml. During the 14-month follow-up 15 patients (6.3%) died, 1 (0.4%) underwent cardiac transplantation and 18 (7.6%) were readmitted for CHF (event group); in 203 (85.6%) no events were observed (no-event group). Higher NYHA class (2.1±0.7 vs. 1.9±0.4, p=0.01), BNP at discharge (750.2±527.3 pg/ml vs. 340.7±474.3 pg/ml, p=0.002) and impaired LVEF (33.7±15.7% vs. 44.5±15.8%, p=0.0001) and creatinine (1.7±0.6 vs. 1.2±0.8 mg/dl, p=0.004) were noticed in the event group. At multivariate Cox analysis LVEF (p=0.0009), plasma creatinine (p=0.006) and BNP at discharge (p=0.001) were associated with adverse mid-term outcome. Kaplan-Meier survival curves demonstrated that adding cut-off points for creatinine 1.5 mg/dl and discharged BNP of 250 pg/ml discriminated significantly prognosis (p=0.0001; log rank 21.09).

Conclusions

In predicting mid-term clinical prognosis in CHF patients discharged after acute decompensation, BNP at discharge ≥ 250 pg/ml added with plasma creatinine > 1.5 mg/dl are strong adverse predictors.     

The effect of age on the systemic inflammatory response in patients with community-acquired pneumonia

Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide. Increasing age has been associated with elevated circulating levels of pro-inflammatory mediators. We aimed to determine the impact of ageing on the systemic inflammatory response to CAP. In total 201 CAP patients were enrolled. Blood samples were obtained upon presentation, and on days 2, 3 and 5. For the current analysis patients ≤50 and ≥80 years were included. The Pneumonia Severity Index (PSI) score was calculated at presentation. The study encompassed 46 CAP patients aged ≤50 years (median 37 years) and 41 CAP patients aged ≥80 years (median 84 years). In both groups Streptococcus pneumoniae was the common causative microorganism. Whereas most young patients had a PSI score of I (54%), 98% of elderly patients had a PSI score ≥III (p <0.001). Four elderly patients died vs. none of the young patients (p 0.045). Older patients demonstrated lower serum C-reactive protein levels on admission and during the course of their hospitalization (p 0.001) in spite of more severe disease. Serum concentrations of pro-inflammatory (interleukin (IL)-6 and IL-8) and anti-inflammatory cytokines (IL-10 and IL-1 receptor antagonist) did not differ between age groups, although admission IL-8 levels tended to be higher in elderly patients (p 0.05). Cytokine levels were positively correlated with PSI in young but not in elderly patients. These results suggest that elderly patients show an absolute (C-reactive protein) or relative (cytokines) reduction in their systemic inflammatory response on admission for CAP.     

A randomised, double-blind, double-dummy comparative study of gatifloxacin with clarithromycin in the treatment of community-acquired pneumonia

Eligible patients were randomised in this multicentre, randomised, double-blind, double-dummy parallel-group study in a ratio of 1:1 to either gatifloxacin 400 mg once-daily for 5-14 days plus matching placebo, or clarithromycin 500 mg twice-daily for 5-14 days. The primary outcome measure was clinical response (clinical cure plus improvement) at the end of treatment. Secondary endpoints were clinical response at end of study, clinical cure at end of treatment and end of study, bacteriological response at end of treatment and end of study, and treatment duration. The overall clinical response was similar in the two treatment groups, with 92.2% of gatifloxacin-treated patients cured or improved at the end of treatment, compared with 93.1% of those receiving clarithromycin. Corresponding bacteriological response rates (eradication plus presumed eradication) were 96.7% and 87.5%, respectively. The study drugs were well-tolerated, with nausea (gatifloxacin) and bitter taste (clarithromycin) being the only treatment-related adverse events with a frequency of > 5%. No patients experienced phototoxicity, hepatic or renal dysfunction, tendonitis or crystalluria. Oral gatifloxacin 400 mg once-daily appeared to be a safe and effective alternative to clarithromycin in the treatment of community-acquired pneumonia.     

Prognostic factors associated with severe leptospirosis

Leptospirosis is an anthropozoonosis caused by Leptospira interrogans. It occurs worldwide and is endemic in French Polynesia. Leptospirosis is associated with a large variety of clinical symptoms. Most infections caused by leptospires are either sub-clinical or of very mild severity, but 5-10% of infections result in multiple organ damage, including kidney, liver and lung lesions. Among 71 patients hospitalised in Papeete for severe leptospirosis during a period of 2 years, the main risk-factors for a severe outcome were hypotension, oliguria and an abnormal chest auscultation at the first physical examination. Survival depends on rapid diagnosis and early appropriate management. Well-defined criteria may help physicians to improve the timely treatment of high-risk patients.     

Compliance with severe sepsis bundles and its effect on patient outcomes of severe community-acquired pneumonia in a limited resources country

Introduction

Validation of compliance with severe sepsis bundles is still needed. The purpose of this study was to determine compliance and its outcomes in severe community-acquired pneumonia (CAP) patients in a limited resources country.

Material and methods

A prospective cohort study of 212 severe CAP patients was carried out. The implementation programme was organized into two continuous phases. The primary outcomes were compliance and hospital mortality.

Results

Compliance with administration of antibiotics and vasopressors as well as plateau pressure on average < 30 cm H₂O was high in both groups. In the bundles group, patients received more serum lactate monitoring (62.3% vs. 11.3%), more blood cultures (47.1% vs. 24.5%), more fluid resuscitation (63.2% vs. 26.4%) and volumes infused (1319.8 ±1107.4 ml vs. 461.9 ±799.3 ml), more inotropic dobutamine and/or packed red blood cells (21.7% vs. 10.0%), more low-dose steroids (56.5% vs. 15.0%), and more glucose control (51.9% vs. 6.6%) compared with such patients in the control group. The rates of total compliance with 6-hour, 24-hour, and 6/24-hour bundles in the prospective period were 47.1%, 51.9%, and 42.5%, respectively. Hospital mortality was reduced from 44.3% to 29.2% (p = 0.023) in the bundles group, and the compliant subgroup had a more than twofold decrease in mortality (17.8% vs. 37.7%, p = 0.003). Serum lactate measured, blood cultures, and fluid resuscitation showed independent relationships with decreased mortality.

Conclusions

Total compliance was relatively low, but the implementation of severe sepsis bundles could clearly reduce mortality from severe CAP.     

CD4 T-lymphocyte subset counts in HIV-seropositive patients during the course of community-acquired pneumonia caused by Streptococcus pneumoniae

Total lymphocyte counts, CD4 T-lymphocyte counts and CD4/CD8 ratios were measured in 30 anti-retroviral-naive HIV-seropositive patients upon hospital admission for acute community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae, and again 1 month after resolution of infection. There was a significant depression of the total lymphocyte count (p < 0.005) and CD4 T-lymphocyte count (p < 0.001) in the acute stage of CAP caused by S. pneumoniae, with a subsequent increase in 90% (27/30) of cases after resolution of the infection. There was no significant difference in the CD4/CD8 T-lymphocyte ratio on admission compared with 1 month later (p 0.9).     

Microbiological etiology in clinically diagnosed community-acquired pneumonia in primary care in Örebro, Sweden

Objective  To study the etiology of clinically diagnosed community-acquired pneumonia (CAP) in antibiotically naive patients attending a primary care center and treated at their homes.
Methods  A three-year prospective study was carried out, and 177 patients presenting with clinical signs of CAP were included. All patients had chest X-rays after inclusion, and 82 (46%) showed infiltrates. Nasopharyngeal swab culture was performed on all patients, and 51% produced a representative sputum sample. Paired sera were obtained from 176 patients.
Results  Among the 82 patients with radiographically proven CAP, Streptococcus pneumoniae was detected in 26 patients (32%), Haemophilus influenzae in 23 (28%), Mycoplasma pneumoniae in 15 (18%), and Chlamydia pneumoniae in four (5%). Serologic evidence of a viral infection was found in 13 patients (16%). Among the 95 patients without infiltrates, S. pneumoniae was found in 21 (22%), H. influenzae in 14 (15%), M. pneumoniae in two (2%), and C. pneumoniae in five (5%). Viral infection was detected in 19 (20%) of these 95 patients.
Conclusion  In primary care in Sweden, the initial antibiotic treatment in any patient with pneumonia should be effective against S. pneumonia and H. influenzae . In addition, M. pneumoniae should be targeted during recurrent epidemics. C. pneumoniae , and especially Legionella , seem to be uncommon in primary care.     

中性粒细胞-淋巴细胞比值和C-反应蛋白在细菌性社区获得性肺炎诊断中的临床价值

目的:探讨中性粒细胞-淋巴细胞比值(neutrophil-lymphocyte count ratio,NLCR)和CRP在细菌性社区获得性肺炎诊断中的临床价值.方法:采用回顾性病例对照研究方法,分析115例细菌性肺炎、64例非细菌性肺炎和61例健康体检者外周血白细胞总数、中性粒细胞计数、淋巴细胞计数、NLCR和CRP含量,并对检测结果进行统计学分析.结果:细菌性肺炎患者外周血NLCR和CRP水平显著高于非细菌组和健康对照组,差异有统计学意义(P＜0.05).ROC曲线分析显示NLCR和CRP在细菌性肺炎诊断中的曲线下面积分别为0.700和0.794,且对细菌性肺炎具有良好的敏感性和特异性.结论:联合检测外周血NLCR和CRP对细菌性肺炎的诊断具有重要的临床价值.     

Comparative study of levofloxacin and amoxycillin/clavulanic acid in adults with mild-to-moderate community-acquired pneumonia

Objective: To compare the efficacy and safety of two different doses of levofloxacin with amoxycillin/clavulanic acid in the treatment of community-acquired pneumonia.
Methods: A double-blind, randomized (1:1:1), double-dummy, three-arm parallel design, multicenter study was conducted in adult patients with mild-to-moderate community-acquired pneumonia. In total, 518 patients were randomized to receive levofloxacin 500 mg once daily, levofloxacin 500 mg twice daily or amoxycillin/clavulanic acid 625 mg three times daily for 7–10 days.
Results: The clinical cure rates post-therapy (2–5 days after the end of treatment) in the intent-to-treat population were 84.2% (144/171) in the levofloxacin once-daily group, 80.2% (142/177) in the levofloxacin twice-daily group and 85.7% (144/168) in the amoxycillin/clavulanic acid group. In the per-protocol population, the clinical cure rates post-therapy were 95.2% (138/145), 93.8% (137/146) and 95.3% (141/148), respectively. The total pathogen eradication rates were 97.8%, 100% and 97.5%, respectively. Both drugs were equally well tolerated and no major adverse events were observed.
Conclusions: Levofloxacin was effective, safe and well tolerated in the treatment of mild-to-moderate community-acquired pneumonia. A complementary analysis indicated that there was no difference in therapeutic outcome between levofloxacin 500 mg once daily and twice daily. Levofloxacin 500 mg once daily, for 7–10 days, is an effective and safe treatment for mild-to-moderate community-acquired pneumonia in adults.