Prognostic factors for early clinical failure in patients with severe community-acquired pneumonia

For patients with community-acquired pneumonia (CAP), clinical response during the first days of treatment is predictive of clinical outcome. As risk assessments can improve the efficiency of pneumonia management, a prospective cohort study to assess clinical, biochemical and microbiological predictors of early clinical failure was conducted in patients with severe CAP (pneumonia severity index score of >90 or according to the American Thoracic Society definition). Failure was assessed at day 3 and was defined as death, a need for mechanical ventilation, respiratory rate >25/min, PaO2 <55 mm Hg, oxygen saturation <90%, haemodynamic instability, temperature >38 degrees C or confusion. Of 260 patients, 80 (31%) had early clinical failure, associated mainly with a respiratory rate >25/minute (n = 34), oxygen saturation <90% (n = 28) and confusion (n = 20). In multivariate logistic regression analysis, failure was associated independently with altered mental state (OR 3.19, 95% CI 1.75-5.80), arterial PaH <7.35 mm Hg (OR 4.29, 95% CI 1.53-12.05) and PaO2 <60 mm Hg (OR 1.75, 95% CI 0.97-3.15). A history of heart failure was associated inversely with clinical failure (OR 0.30, 95% CI 0.10-0.96). Patients who failed to respond had a higher 28-day mortality rate and a longer hospital stay. It was concluded that routine clinical and biochemical information can be used to predict early clinical failure in patients with severe CAP.     

Antibacterial treatment of community-acquired pneumonia: the role of therapeutic agents other than the macrolide

The optimal guidelines for the treatment of community-acquired pneumonia are not well established, and the relevant pathogen is often unknown. Initial choice of an antimicrobial agent should depend on the initial severity of the patient's illness, site of acquisition, age, coexisting illness and treatment setting. Few reliable studies have been performed to establish the supremacy of any antibiotic agent in this condition, either for ambulatory or hospital treatment.     

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.     

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。     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Transthoracic fine-needle aspiration in the aetiological diagnosis of community-acquired pneumonia

To investigate the safety and practicability of conducting transthoracic fine-needle aspiration (TFNA) in a general hospital setting, we applied the TFNA procedure to 20 patients hospitalized with community-acquired pneumonia (CAP) within 36 h of admission. Also, a preliminary assessment was made of the potential value of adding TFNA to conventional methods of diagnostic microbiology. TFNA was easy to perform and caused little discomfort, and no serious adverse events were observed. In spite of ongoing antimicrobial treatment, a likely aetiological diagnosis was established for 14 of 20 (70%) of the patients. TFNA may provide important additional information on the aetiology of CAP.     

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.     

Effect of positive microbiological testing on antibiotic de-escalation and outcomes in community-acquired pneumonia: a propensity score analysis

ObjectivesThe usefulness of routine microbiological testing for rationalising antibiotic use in hospitalised patients with community-acquired pneumonia (CAP) continues to be a subject of debate. We aim to determine the effect of positive microbiological testing on antimicrobial de-escalation and clinical outcomes in CAP.MethodsA retrospective analysis of a prospectively collected cohort of non-immunosuppressed adults hospitalised with CAP was performed. The primary study outcome was antimicrobial de-escalation. Secondary outcomes included 30-day case-fatality rate, adverse events, and CAP recurrence. Adjustment for confounders was performed by inverse probability weighting propensity score, logistic regression, and cause-specific Cox model.ResultsOf 3677 patients with CAP, 1924 (52.3%) had any positive microbiological test. Antimicrobial de-escalation was performed in 648/1924 (33.7%) of patients with positive microbiological testing and in 179/1753 (10.2%) of those with non-positive results. When propensity score was entered into the multivariate analysis, positive microbiological testing (adjusted OR (AOR)], 2.59; 1.96–3.41) and clinical stability at day 3 (AOR 1.87; 1.45–2.10) were two of the main factors independently associated with antimicrobial de-escalation. After applying an adjusted cause-specific Cox model, antimicrobial de-escalation was not associated with a higher 30-day case-fatality rate (adjusted hazard ratio (AHR), 0.44 (95% CI, 0.14–1.43)), higher frequency of adverse events (AHR, 0.77 (95% CI, 0.53–1.12)), or CAP recurrence (AHR, 0.65 (95% CI, 0.35–1.14)).DiscussionAntimicrobial de-escalation was more often performed in hospitalised patients with CAP who had positive microbiological tests than in those with non-positive results, and it did not adversely affect relevant clinical outcomes.     

Utility of C-reactive protein in assessing the disease severity and complications of community-acquired pneumonia

Previous studies on the usefulness of C-reactive protein (CRP) in patients with community-acquired pneumonia (CAP) have yielded somewhat inconsistent results. Our aim was to assess the value of CRP in estimating the severity and complications of CAP. CRP levels during the first 5 days of hospitalization were measured in 384 adult patients with CAP, and the data were evaluated using comprehensive statistical analyses. Significantly higher CRP levels on admission were detected in Pneumonia Severity Index (PSI) classes III–V than in classes I and II (p <0.001). An increment of 50 mg/L CRP on admission was associated with a 1.22-fold odds for a patient to be in PSI classes III–V as compared with classes I and II (OR 1.22, 95% CI  1.11–1.34; p <0.001). CRP levels were significantly higher in bacteraemic pneumonia than in non-bacteraemic pneumonia (p <0.001). An increment of 50 mg/L CRP was associated with a 1.67-fold odds for a patient to be bacteraemic (OR 1.67, 95% CI  1.46–1.92; p <0.001). CRP levels >100 mg/L on day 4 after the admission were significantly associated with complications (p <0.01). There was a trend for an association between the level of CRP on admission and the time to reach clinical stability (p <0.01). In conclusion, CRP may be valuable for revealing the development of complications in CAP. It may also be useful to assess the disease severity, thus being complementary to the assessment of the PSI. In our patients, high CRP levels were associated with a failure to reach clinical stability.     

Mixed microbial aetiology of community-acquired pneumonia in children

Seven paediatric studies on community-acquired pneumonia with serological methods for both viruses and bacteria have been published, allowing the evaluation of concomitant multiple etiological findings. In these studies, dual viral infection has been present in 0-14%, dual bacterial infection likewise in 0-14%, and mixed viral-bacterial infection in 3-30% of the pneumonia cases. The results confirm former clinical observations that respiratory viruses often pave the way for airway-colonising bacteria. The measured frequency of multiple infections has been dependent on the available test panel, mainly on the tests used for pneumococcal aetiology. Mixed viral-bacterial infections have been especially common in young children under 2 years of age, reflecting the high frequency of respiratory syncytial virus infections and their tendency to induce bacterial co-infections. No microbe-specific viral-bacterial associations have been demonstrated. The clinical implications of mixed viral-bacterial infections, compared with viral infections alone or bacterial infections alone, have so far remained unresolved. Current guidelines recommend antibiotic therapy for all community-acquired pneumonia cases in children.     

The impact of 13-valent pneumococcal conjugate vaccination on virus-associated community-acquired pneumonia in elderly: Exploratory analysis of the CAPiTA trial

ObjectivesOur objective was to evaluate whether vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) prevents the incidence of community-acquired pneumonia (CAP) caused by influenza (influenza-associated CAP, IA-CAP) or other respiratory viruses in the elderly.MethodsThis analysis was part of the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA); a double blind, randomized, placebo-controlled trial in 84 496 immunocompetent individuals aged ≥65 years. CAP was defined by clinical and radiological criteria, and oropharyngeal swabs were collected from all individuals referred to a sentinel centre with a clinical suspicion of pneumonia. Presence of influenza A and B, parainfluenza 1, 2, 3 and 4, human adeno-, boca-, corona-, metapneumo-, rhino- and respiratory syncytial viruses was determined by real-time PCR.ResultsOf 3209 episodes of suspected pneumonia, viral aetiology was tested in 2917 and proportions with influenza virus, human metapneumovirus and respiratory syncytial virus were 4.6%, 2.5% and 3.1%, respectively. There were 1653 oropharyngeal swabs for PCR testing available from 1814 episodes that fulfilled criteria for CAP, yielding 23 first episodes of IA-CAP in the PCV13 and 35 in the in placebo group—vaccine efficacy for IA-CAP of 34.4% (95% CI –11.1% to 61.2%; p 0.117). Annual influenza vaccination was received by 672 (87.2%) in the PCV13 group and 719 (87.7%) in the placebo group of the confirmed CAP cases.ConclusionIn a randomized study of 84 496 elderly individuals with a high uptake of influenza vaccination, PCV13 was not associated with a statistically significant reduction of influenza or virus-associated CAP. Overall incidence of non-influenza viral pneumonia was low.     

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).