Management of community-acquired pneumonia: a review and update

Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide, affecting approximately 5.6 million patients annually in the USA, where the annual cost exceeds US$12 billion. Optimal management should be based on knowledge of the most likely etiologic pathogens for each patient, based on an assessment of specific risk factors. It is also essential to assess severity of illness, to determine the appropriate site of care, and to order appropriate diagnostic testing. New developments in CAP management have focused on recognizing newly identified pathogens, such as methicillin-resistant Staphylococcus aureus and novel H1N1 influenza, understanding when to utilize new microbiological diagnostic techniques, and how to use biomarkers to direct the appropriate utilization of antibiotics and to define the duration of therapy. This paper reviews recent advances in our knowledge about the diagnosis and optimal management of CAP.     

Community-acquired pneumonia

This seminar reviews important features and management issues of community-acquired pneumonia (CAP) that are especially relevant to immunocompetent adults in light of new information about cause, clinical course, diagnostic testing, treatment, and prevention. Streptococcus pneumoniae remains the most important pathogen; however, emerging resistance of this organism to antimicrobial agents has affected empirical treatment of CAP. Atypical pathogens have been quite commonly identified in several prospective studies. The clinical significance of these pathogens (with the exception of Legionella spp) is not clear, partly because of the lack of rapid, standardised tests. Diagnostic evaluation of CAP is important for appropriate assessment of severity of illness and for establishment of the causative agent in the disease. Until better rapid diagnostic methods are developed, most patients will be treated empirically. Antimicrobials continue to be the mainstay of treatment, and decisions about specific agents are guided by several considerations that include spectrum of activity, and pharmacokinetic and pharmacodynamic principles. Several factors have been shown to be associated with a beneficial clinical outcome in patients with CAP. These factors include administration of antimicrobials in a timely manner, choice of antibiotic therapy, and the use of a critical pneumonia pathway. The appropriate use of vaccines against pneumococcal disease and influenza should be encouraged. Several guidelines for management of CAP have recently been published, the recommendations of which are reviewed.     

The role of new therapies for severe community-acquired pneumonia

PURPOSE OF REVIEW: Community-acquired pneumonia (CAP) is associated with significant morbidity and mortality and is the most common cause of death from infectious diseases. CAP patients requiring intensive care unit (ICU) admission carry the highest mortality rates. This paper aims to review the current literature regarding epidemiology, risk factors, severity criteria and reasons for admitting the hospitalized patient to the ICU, and the empiric and specific antibiotic therapeutic regimens employed. RECENT FINDINGS: Multiple sets of clinical practice guidelines have been published in the past few years addressing the treatment of CAP. The guidelines all agree that CAP patients admitted to the hospital represent a major concern, and appropriate empiric therapy should be instituted to improve clinical outcomes. SUMMARY: The cost, morbidity and mortality of CAP patients requiring ICU admission remain unacceptably high. These are heterogeneous groups of patients, so it is important to use risk-stratification based on clinical parameters and prediction tools. Appropriate antibiotic therapy is an important component in the management of both groups of patients. In particular, it is essential to administer an appropriate antimicrobial agent from the initiation of therapy, so that the risks of treatment failure and the morbidity of CAP may be minimized.     

Schwere, ambulant erworbene Pneumonie

For several decades, severe community-acquired pneumonia (CAP) has been associated with a high, unchanged mortality rate despite improvements in ICU management, diagnostics, antibiotic therapy, and adjunctive measures. This acute illness is not only a threat for older people with severe comorbidities, but also to the young without comorbidities or immunodeficiency, because nearly half of the affected patients will die. Decisive to improving the outcome is rapid diagnosis, risk stratification according the CRB-65 scoring system, immediate start of a risk-adapted antibiotic therapy, and the use of further adjunctive measures, such as non-invasive or invasive mechanical ventilation. Diagnostic procedures should not delay the start of the antibiotic treatment. Most important for the empirical usage of antimicrobials in this setting is the evaluation of the individual risk for a P. aeruginosa infection. In each case, the antibiotic empiric regime should cover pneumococci; a combination regime with macrolides might improve survival.     

The antibiotic treatment of severe community-acquired pneumonia admitted to the critical care unit

Community-acquired pneumonias (CAP) are still caused by Streptococcus pneumoniae, Hemophilus influenzae, or Moraxella catarrhalis. Legionella and Chlamydia pneumoniae have been defined as important atypical pathogens causing CAP. Klebsiella causes CAP primarily in patients with chronic alcoholism or in chronic care facilities. Normal hosts do not present with "unusual pathogens' e.g., Staphylococcus aureus or Pseudomonas aeruginosa. The clinical severity of a bacterial pneumonia has important prognostic implications and predicts admission to intensive care units, duration of therapy, and complications. The factors that determine the severity of a CAP are less related to the pathogen than the underlying cardiopulmonary status of the patient as well as the patient's humoral immunity. Relatively avirulent pathogens may result in severe CAP in patients with diminished/absent splenic function or significant cardiopulmonary disease. A critical concept is to appreciate that the selection of antimicrobial therapy is not dependent on co-morbidities since the antimicrobial therapy is directed against the pathogen and not the co-morbidities. Therefore the treatment of CAP, whether moderate or severe is with the same antibiotic at the same dose. Many antibiotic regimens are equally efficacious in the treatment of CAP. The most cost effective optimal regimen covers both typical and atypical pathogens, e.g., levofloxacin, and is currently the preferred antibiotic approach to moderate or severe CAP in the CCU.     

Clinical impact of broad-spectrum empirical antibiotic therapy in patients with healthcare-associated pneumonia: a multicenter interventional study

Healthcare-associated pneumonia (HCAP) has been proposed as a new category of pneumonia distinct from community-acquired pneumonia (CAP). A multicenter observational study in 2008 finds that patients with HCAP have a mortality rate significantly higher than patients with CAP, and a worse outcome is associated at logistic regression analysis with a low adherence to empirical antibiotic therapy recommended by ATS/IDSA guidelines. We designed a prospective interventional study to establish whether administration of a broad-spectrum antibiotic therapy consistent with the 2005 ATS/IDSA guidelines has an effect on the clinical outcome of hospitalized patients with HCAP. All patients with HCAP prospectively admitted in 25 medical wards of 20 Italian hospitals during a 1-month period were included in the study. All patients were assigned to receive an empirical therapy including a fluoroquinolone plus an anti-MRSA agent plus either piperacillin?Ctazobactam or a carbapenem. Main measures for improvement were duration of antibiotic therapy, length of hospital stay, and in-hospital mortality rate. Patients were compared with a historical control group of 90 patients, and followed up to discharge or death. HCAP patients receiving a guideline-concordant therapy had a shorter duration of antibiotic therapy (median 15 vs. 12?days, p?=?0.0002), a shorter duration of hospitalization (median 18 vs. 14?days, p?=?0.02), and a lower mortality rate (17.8 vs. 7.1?%, p?=?0.03). Our results suggest that an empirical broad-spectrum therapy is associated with improved outcome in patients with HCAP.     

Pneumonia in the developing world: Characteristic features and approach to management

Community‐acquired pneumonia (CAP) is a common cause of morbidity and mortality in adults worldwide, but its epidemiology varies markedly by region. Whilst in high‐income countries, the predominant burden of CAP is in the elderly and those with chronic cardiovascular and pulmonary co‐morbidity, CAP patients in low‐income settings are often of working age and, in sub‐Saharan Africa, frequently HIV‐positive. Although region‐specific aetiological data are limited, they are sufficient to highlight major trends: in high‐burden settings, tuberculosis (TB) is a common cause of acute CAP; Gram‐negative pathogens such as Klebsiella pneumoniae are regionally important; and HIV‐associated opportunistic infections are common but difficult to diagnose. These differences in epidemiology and aetiological profile suggest that modified approaches to diagnosis, severity assessment and empirical antimicrobial therapy of CAP are necessary, but tailored individualized management approaches are constrained by limitations in the availability of radiological and laboratory diagnostic services, as well as medical expertise. The widespread introduction of the Xpert MTB/RIF platform represents a major advance for TB diagnosis, but innovations in rapid diagnostics for other opportunistic pathogens are urgently needed. Severity assessment tools (e.g. CURB65) that are used to guide early management decisions in CAP have not been widely validated in low‐income settings and locally adapted tools are required. The optimal approach to initial antimicrobial therapy choices such as the need to provide early empirical cover for atypical bacteria and TB remain poorly defined. Improvements in supportive care such as correcting hypoxaemia and intravenous fluid management represent opportunities for substantial reductions in mortality.     

Assessing severity of patients with community-acquired pneumonia

Despite all advances in its management, community-acquired pneumonia (CAP) is still an important cause of morbidity and mortality requiring a great consumption of health, social, and economic resources. An early and adequate severity assessment is of paramount importance to provide optimized care to these patients. In the last 2 decades, this issue has been the subject of extensive research. Based on 30 day mortality, several prediction rules have been proposed to aid clinicians in deciding on the appropriate site of care. In spite of being well validated, their sensitivity and specificity vary, which limits their widespread use. The utility of biomarkers to overcome this problem has been investigated. At this moment, their full clinical value remains undetermined, and no single biomarker is consistently ideal for assessing CAP severity. Biomarkers should be seen as a complement rather than superseding clinical judgment or validated clinical scores. The search for a gold standard is not over, and new tools, like bacterial DNA load, are in the pipeline. Until then, CAP severity assessment should be based in three key points: a pneumonia-specific score, biomarkers, and clinical judgment.     

Nonchemotherapy drug-induced agranulocytosis: experience of the Strasbourg teaching hospital (1985-2000) and review of the literature

Agranulocytosis is a life-threatening disorder that frequently occurs as an adverse reaction to drugs. The overall incidence of nonchemotherapy drug-induced agranulocytosis (DIA) ranges from 2.6 to 10 cases per million patients exposed to drugs per year. Although patients experiencing DIA may initially be asymptomatic, the severity of the neutropenia usually leads to severe sepsis, requiring intravenous broad-spectrum antibiotic therapy. In this setting, old age, septicaemia, shock, and the metabolic complications of infection, such as renal failure, are poor prognostic variables. The severity of neutropenia (< 0.1 x 10(9))/l) and its duration (> 10 days) may also impact negatively on the outcome. With appropriate management using pre-established procedures, the mortality rate is now around 5%. Haematopoietic growth factors have been shown to shorten the duration of neutropenia in DIA. However, it has yet to be determined whether their use translates into a better outcome in DIA patients experiencing sepsis. DIA still remains a rare event. However, given the increased life expectancy and subsequent longer exposure to drugs, as well as the development of new agents, physicians should be aware of this complication and its management.     

New trends in patient management: risk-based therapy for febrile patients with neutropenia.

Standard management of febrile neutropenia includes the prompt administration of empirical, broad-spectrum, parenteral antibiotic therapy. This is generally done in a hospital-based setting. Although effective (overall survival of >90%), such therapy leads to prolonged hospitalization, excessive resource utilization, and increased costs. Recently, risk-assessment models have been developed that reliably differentiate febrile patients with neutropenia that are at low risk for morbidity and/or mortality. This has enabled clinicians to administer risk-based treatment to such patients. High-risk patients still receive standard, hospital-based, parenteral treatment. Many patients, however, defervesce promptly and can be discharged home with parenteral or oral antibiotics. Low-risk patients need not be hospitalized at all and can be safely treated with parenteral or oral antibiotics in the outpatient or home setting. Careful risk assessment and patient selection, appropriate antimicrobial regimen(s), and meticulous monitoring for response or the development of complications or toxicity are essential for the success of risk-based therapy.     

Severe community-acquired pneumonia: an Australian perspective

BACKGROUND: Severe community-acquired pneumonia (CAP) is a common disease with a relatively high mortality. The initial treatment is empirical, based on a broad range of potential pathogens. There are minimal published data describing microbiological causes of pneumonia in Australia. AIMS: To describe the aetiology and characteristics of severe CAP in patients requiring intensive care unit (ICU) admission, to identify factors predicting mortality and to audit current practices of investigation and antibiotic management of these patients from an Australian perspective. METHODS: A retrospective analysis of patient case notes was performed for 96 consecutive patients admitted to two ICU with severe CAP. Data recorded included patient demographics, comorbidities, antimicrobial treatment, investigations and outcome (mortality, length of stay). RESULTS: Overall, mortality was 32%. A microbiological diagnosis was made in 46% of patients. The most frequent causative organisms were Streptococcus pneumoniae (13 cases), influenza A (9), Haemophilus influenzae (5) and Staphylococcus aureus (4); aerobic Gram-negative bacilli collectively accounted for five cases. Blood cultures were positive in 20% of patients. Seventy patients (73%) required mechanical ventilation and 61 patients (63%) required inotropic support. Laboratory abnormalities including acute renal failure, metabolic acidosis and coagulopathy were frequent. Factors associated with mortality on multivariate analysis were age, antibiotic administration prior to hospital presentation, delay in hospital antibiotic administration of more than 4 h, and presence of multilobar or bilateral consolidation on chest X-ray. CONCLUSIONS: Severe CAP requiring ICU admission was associated with a mortality rate of 32%, despite appropriate antimicrobial therapy including a beta-lactam and a macrolide antibiotic in most cases. Causative organisms identified were similar to those found in previous studies. High rates of viral causes (28% of identified pathogens) were noted. Low rates of legionellosis and other atypical causes were found, most probably due to a lack of systematic testing for these agents.     

Nonchemotherapy drug‐induced agranulocytosis: experience of the Strasbourg teaching hospital (1985–2000) and review of the literature

Agranulocytosis is a life‐threatening disorder that frequently occurs as an adverse reaction to drugs. The overall incidence of nonchemotherapy drug‐induced agranulocytosis (DIA) ranges from 2.6 to 10 cases per million patients exposed to drugs per year. Although patients experiencing DIA may initially be asymptomatic, the severity of the neutropenia usually leads to severe sepsis, requiring intravenous broad‐spectrum antibiotic therapy. In this setting, old age, septicaemia, shock, and the metabolic complications of infection, such as renal failure, are poor prognostic variables. The severity of neutropenia (< 0.1 × 10⁹/l) and its duration (> 10 days) may also impact negatively on the outcome. With appropriate management using pre‐established procedures, the mortality rate is now around 5%. Haematopoietic growth factors have been shown to shorten the duration of neutropenia in DIA. However, it has yet to be determined whether their use translates into a better outcome in DIA patients experiencing sepsis. DIA still remains a rare event. However, given the increased life expectancy and subsequent longer exposure to drugs, as well as the development of new agents, physicians should be aware of this complication and its management.     

New determinants of prognosis in bacterial infections in cirrhosis

Despite major advances in the knowledge and management of liver diseases achieved in recent decades, decompensation of cirrhosis still carries a high burden of morbidity and mortality. Bacterial infections are one of the main causes of decompensation. It is very important for clinical management to be aware of the population with the highest risk of poor outcome. This review deals with the new determinants of prognosis in patients with cirrhosis and bacterial infections reported recently. Emergence of multiresistant bacteria has led to an increasing failure rate of the standard empirical antibiotic therapy recommended by international guidelines. Moreover, it has been recently reported that endothelial dysfunction is associated with the degree of liver dysfunction and, in infected patients, with the degree of sepsis. It has also been reported that relative adrenal insufficiency is frequent in the non-critically ill cirrhotic population and it is associated with a higher risk of developing infection, severe sepsis, hepatorenal syndrome and death. We advise a change in the standard empirical antibiotic therapy in patients with high risk for multiresistant infections and also to take into account endothelial and adrenal dysfunction in prognostic models in hospitalized patients with decompensated cirrhosis.     

Comparing the pneumonia severity index with CURB-65 in patients admitted with community acquired pneumonia

Pneumonia severity assessment systems such as the pneumonia severity index (PSI) and CURB-65 were designed to direct appropriate site of care based on 30-d mortality. Increasingly they are being used to guide empirical antibiotic therapy and also possibly to detect patients who will require admission to the intensive care unit (ICU). We retrospectively reviewed the records of all patients admitted to our institution with confirmed community acquired pneumonia (CAP) for the 12 months from January 2002. 408 episodes were studied with an overall 30-d mortality of 15.4% and ICU admission of 10.5%. PSI classes IV/V were significantly better than CURB-65 score > or = 3 for predicting patients who died within 30 d (94% vs 62%; p < 0.001), and those that needed ICU (86% vs 61%; p = 0.01). In addition, for the patients identified as 'low risk' by PSI (classes I/II), there was only 1 death and 1 admission to an ICU compared to 8 deaths and 7 ICU admissions with CURB-65 scores of 0-1. Although easier to use, CURB-65 is neither sensitive nor specific for predicting mortality in CAP patients. Neither rule was sufficiently accurate for predicting need for an ICU, even when patients with 'not for resuscitation' orders were excluded.     

Community-acquired pneumonia

Community-acquired pneumonia (CAP) remains a leading cause of morbidity and mortality worldwide and has significant financial implications for health-care systems. The epidemiology and fundamental biology of the disease has evolved, reflecting the human immunodeficiency virus pandemic, increasing world travel, and, as always, poverty. The promise held out by molecular diagnostic technology has yet to deliver in this arena, and antibiotic resistance continues to drive the quest for new antimicrobial agents. The emergence of multidrug-resistant Streptococcus pneumoniae, the microorganism most often implicated as a cause of CAP, continues to threaten treatment options. The evolution of this organism, the persistently high mortality rate associated with CAP, and increasing health-care costs have prompted the publication of guidelines by various authorities that can be used to assist in the initial assessment of the patient and then guide empirical antimicrobial therapy. It is unclear whether these guidelines will have significant impact on cost and mortality, although the trend toward a rational and evidence-based approach to antimicrobial therapy must be a goal to aspire to.     

Performance of PSI, CURB-65, and SCAP scores in predicting the outcome of patients with community-acquired and healthcare-associated pneumonia

The objective was to compare three score systems, pneumonia severity index (PSI), the Confusion-Urea-Respiratory Rate-Blood pressure-65 (CURB-65), and severe community-acquired pneumonia (SCAP), for prediction of the outcomes in a cohort of patients with community-acquired (CAP) and healthcare-associated pneumonia (HCAP). Large multi-center, prospective, observational study was conducted in 55 hospitals. HCAP patients were included in the high classes of CURB-65, PSI and SCAP scores have a mortality rate higher than that of CAP patients. HCAP patients included in the low class of the three severity rules have a significantly higher incidence of adverse events, including development of septic shock, transfer into an ICU, and death (p < 0.01). At multivariate Cox regression analysis, inclusion in the severe classes of PSI, CURB-65, or SCAP scores and receipt of an empirical therapy not adherent to international guidelines prove to be risk factors independently associated with poor outcome. PSI, CURB-65, and SCAP score have a good performance in patients with CAP but are less useful in patients with HCAP, especially in patients classified in the low-risk classes.     

Prognostic factors in severe community-acquired pneumonia in patients without co-morbid illness

OBJECTIVES: We wished to determine the prognostic factors and the impact of initial empirical antibiotic therapy on the outcome of severe community-acquired pneumonia in patients without underlying co-morbid illness. METHODOLOGY: This is a retrospective record review of consecutive patients with severe community-acquired pneumonia who were divided into those with and without underlying co-morbid illness. RESULTS: There were 182 patients including 112 primary (no co-morbid illness) and 70 secondary (underlying co-morbid illness) pneumonias. The overall mortality was 41.8% and there were no differences in APACHE II score or mortality when comparing cases with primary (37.5%) and secondary infections (48.6%). The mortality was significantly higher in patients with negative microbiology. Univariate analysis identified a number of parameters and various antibiotic regimens, which appeared to be associated with a significantly poorer outcome. On multivariate analysis multilobar pulmonary consolidation, need for mechanical ventilation, inotropes and dialysis were documented to be independent predictors of mortality. Only in their absence could different antibiotic regimens be shown to have an apparent impact on outcome and further analysis suggested that the reason for these differences related predominantly to differences in the severity of the infection. CONCLUSIONS: Markers of disease severity appear to be the most important predictors of outcome in patients with severe community-acquired pneumonia.     

Community-acquired pneumonia in the central desert and north-western tropics of Australia

Background: Community-acquired pneumonia (CAP) results in significant morbidity in central and north-western Australia. However, the nature, management and outcome of CAP are poorly documented. The aim of the study was to describe CAP in the Kimberley and Central Desert regions of Australia.
Methods: Prospective and retrospective cohort studies of inpatient management of adults with CAP at Alice Springs Hospital and six Kimberley hospitals were carried out. We documented demographic data, comorbidities, investigations, causes, CAP severity, outcome and concordance between prescribed and protocol-recommended antibiotics.
Results: Two hundred and ninety-three subjects were included. Aboriginal Australians were overrepresented (relative risk 8.1). Patients were notably younger (median age 44.5 years) and disease severity lower than in urban Australian settings. Two patients died within 30 days of admission compared with expected mortality based on Pneumonia Severity Index predictions of seven deaths (χ², P = 0.09). Disease severity and outcome did not differ between regions. Management differences were identified, including significantly more investigations, higher rates of critical care and broader antibiotic cover in Central Australia compared with the Kimberley. Sputum culture results showed Gram-negative organisms in both regions. However, Streptococcus pneumoniae was the most frequent organism isolated in the Kimberley and Haemophilus influenzae in Central Australia.
Conclusion: CAP in this setting is an Aboriginal health issue. The low mortality observed and results of microbiology investigations support the use of existing antibiotic protocols. Larger studies investigating CAP aetiology are warranted. Addressing social and environmental disadvantage remains the key factors in dealing with the burden of CAP in this setting.     

重症社区获得性肺炎9项次要诊断标准权重分析

治疗地点的抉择是治疗社区获得性肺炎(CAP)的关键,而这又取决于起始病情评估.在过去10年里,许多病情评估系统问世,获得证实,并应用于临床.如何定义重症CAP尚未定论.美国感染性疾病学会/美国胸科学会在2007年颁布成人CAP管理指南,并定义凡符合2项主要诊断标准之一或9项次要诊断标准中至少3项者为重症CAP.每项次要诊断标准预测病死率和人住重症监护病房的权重不一,且不同研究间存在显著分歧.重症监护病房资源的稀缺性要求临床医师能甄别入住者中孰能真正或最大程度受益,而探明每项次要诊断标准的权重无疑是甄别的核心.

Abstract：

A key step in the management of community-acquired pneumonia (CAP) is the initial assessment of the severity of the disease. An accurate assessment helps clinicians determine the site of care. Over the past decade, a number of prognostic (severity) scores have been derived and validated, and subsequently incorporated into clinical practice. However, how severe CAP should be defined remains unclear. The Infectious Disease Society of America and the American Thoracic Society issued guidelines in 2007 which defined severe CAP: when one of two major criteria or three of nine minor criteria are fulfilled. The individual minor criteria for severe CAP are of unequal weight in predicting mortality and intensive care unit (ICU) admission. A marked discrepancy with the weight between studies is observed. Because ICU resources are often scarce in many institutions, patients with CAP who would really or maximumly benefit from ICU care should be identified by clinicians. The determination of the weight of the nine minor criteria provides pivotal discriminative information.     

Die schwere ambulant erworbene Pneumonie

Background

Hospitalized patients with community-acquired pneumonia (CAP) still have a high mortality rate in Germany; therefore, selected patients with severe CAP should be regarded and treated as medical emergency cases.

Objectives

Recent advances in risk stratification for identification of high risk patients and management approaches, including adequate treatment of infection and septic organ dysfunction in order to improve the prognosis of these patients are discussed.

Results and discussion

Early identification of high risk patients focusses on identification of organ dysfunction related to acute sepsis or comorbidities; therefore, vital parameters and so-called minor criteria must be continuously evaluated. Patients with severity criteria require adequate management of severe sepsis including individualized volume therapy, guideline-conform treatment of pulmonary and extrapulmonary organ failure and rapid antibiotic treatment. The spectrum of the empirical therapy should include pneumococci, Legionella spp., Staphylococcus aureus and Enterobacteriaceae and the recommended treatment regimen consists of a parenteral broad spectrum beta-lactam combined with a macrolide. Study results regarding adjuvant therapies including steroids are so far conflicting. Cardiovascular complications make an essential contribution to the prognosis and should therefore be systematically monitored and treated.