Treatment of community-acquired pneumonia in an ambulatory setting

Community-acquired pneumonia continues to be a significant cause of morbidity and mortality despite broad-spectrum antibiotics and advances in critical care. Frequently, the diagnosis is confounded by coexisting cardiac or pulmonary conditions. Recognition of patients at risk for complications from pneumonia is critical when making the decision of how and where to treat. This review summarizes the diagnosis and treatment of community-acquired pneumonia with oral antibiotics in an outpatient setting. Specific pathogens and clinical presentations in certain at-risk populations are highlighted. Also presented are validated algorithms for evaluating and identifying patients who may be at risk for serious complications of pneumonia and require treatment in an inpatient setting.     

Treatment failure in community-acquired pneumonia

Treatment failure (TF) is defined as a clinical condition with inadequate response to antimicrobial therapy. Clinical response should be evaluated within the first 72 h of treatment, whereas infiltrate images may take up to 6 weeks to resolve. Early failure is considered when ventilatory support and/or septic shock appear within the first 72 h. The incidence of treatment failure in community-acquired pneumonia is 10 to 15%, and the mortality is increased nearly fivefold. Resistant and unusual microorganisms and noninfectious causes are responsible for TF. Risk factors are related to the initial severity of the disease, the presence of comorbidity, the microorganism involved, and the antimicrobial treatment implemented. Characteristics of patients and factors related to inflammatory response have been associated with delayed resolution and poor prognosis. The diagnostic approach to TF depends on the degree of clinical impact, host factors, and the possible cause. Initial reevaluation should include a confirmation of the diagnosis of pneumonia, noninvasive microbiological samples, and new radiographic studies. A conservative approach of clinical monitoring and serial radiographs may be recommended in elderly patients with comorbid conditions that justify a delayed response. Invasive studies with bronchoscopy to obtain protected brush specimen and BAL are indicated in the presence of clinical deterioration or failure to stabilize. BAL processing should include the study of cell patterns to rule out other noninfectious diseases and complete microbiological studies. The diagnostic yield of imaging procedures with noninvasive and invasive samples is up to 70%. After obtaining microbiological samples, an empirical change in antibiotic therapy is required to cover a wider microbial spectrum.     

Treatment of community-acquired pneumonia in adults

Appropriate antibiotic treatment reduces the duration of symptoms associated to pneumonia, the risk of complications and mortality. In most cases, it is not possible to identify the etiologic agent so antibiotic treatment is empirically prescribed. In Chile, one third of Streptococcus pneumoniae strain isolates has diminished susceptibility to penicillin; in-vitro erythromycin resistance is about 10-15% and cefotaxime resistance 2-10%. It is recommended to classify patients with community acquired pneumonia in four risk categories: Group 1: patients under 65 years without co-morbidities, in ambulatory attendance. Treatment: oral amoxicillin 1 g TID, 7 days. Group 2: patients over 65 years and / or co-morbidities, in ambulatory attendance. Treatment: oral amoxicillin/clavulanate 500/125 mg TID or 875/125 mg BID, or cefuroxime 500 mg BID, 7 days. Group 3: patients admitted to general wards with criteria of moderate severity. Treatment: ceftriaxone 1-2 g once a day or cefotaxime 1 g TID, IV, 7-10 days. Group 4: patients with severe CAP that must be interned into ICU. Treatment: ceftriaxone 2 g once a day or cefotaxime 1 g TID, IV, associated to erythromycin 500 QID, levofloxacin 500-1.000 mg once a day, or moxifloxacin 400 mg/once a day, IV, 10-14 days. In the presence of allergy to or treatment failure with betalactam drugs and/or positive serology for Mycoplasma, Chlamydia or Legionella sp it is recommended to add: erythromycin 500 mg QID, IV or oral, oral clarithromycin 500 mg BID, or oral azythromycin 500 mg once a day.     

Comparative validation of prognostic rules for community-acquired pneumonia in an elderly population.

The aim of the study was to validate the prediction rule of M.J. Fine and coworkers for clinical outcome variables and three prognostic rules for the individual outcome of community-acquired pneumonia in an elderly population (rule 1: respiratory frequency > or =30 breaths x min(-1), diastolic blood pressure < or =60 mmHg, blood urea nitrogen >7 mM; rule 2: respiratory frequency > or =30 breaths x min(-1), diastolic blood pressure < or =60 mmHg, mental confusion; and rule 3: systolic blood pressure < or =80 mmHg, cardiac frequency > or =90 beats x min(-1), lactate dehydrogenase activity > or =260 IU x L(-1); death was predicted in the presence of at least two of three parameters). Overall 168 consecutive episodes of community-acquired pneumonia in patients aged > or =65 yrs and hospitalized in a primary care hospital were studied prospectively. Fine's rule was tested for its ability to predict length of hospital stay, requirement for intensive care unit (ICU) admission and death. For the three prognostic rules of individual outcome, performance regarding predicting death was determined. Mortality was 17/168 (10%). Fine's rule accurately predicted length of stay, the requirement for ICU admission and the risk of death from pneumonia as compared to the original derivation and validation cohorts. All three rules achieved moderate-to-high specificity (73%, 88% and 80%, respectively) and high negative predictive values (95%, 94% and 93%, respectively) but had a low sensitivity (65%, 47% and 47%, respectively). Rule 2 most closely reflected the risk of death from pneumonia when Fine's classification was used as reference. Fine's rule proved to give valid estimations regarding clinical outcome variables of community-acquired pneumonia in the elderly. The prognostic rules may be useful in determining individual patients at lower risk of death caused by pneumonia.     

Treatment with anti-inflammatory drugs in community-acquired pneumonia

Pneumonia exhibits a broad range of severity, from mildly symptomatic at one end to fulminant septic shock and death at the other. Although an adequate inflammatory response is necessary for the clearance of microorganisms, excessive inflammation can lead to ongoing local and systemic damage. Because of this extended inflammatory response despite appropriate antibiotic therapy, as well as increasing antibiotic resistance, adjuvant therapy for pneumonia that can favourably modify the immune response has become an increasingly relevant approach to improve prognosis. Different adjuvant treatment options for pneumonia have recently been proposed. Promising treatment options include corticosteroids, statins, macrolides and Toll-like receptor antagonists. The aim of this review is to summarize the inflammatory response during pneumonia and discuss the current knowledge and future perspectives regarding the anti-inflammatory treatment options for patients with pneumonia.     

Outcomes and costs among seniors requiring hospitalization for community-acquired pneumonia in Alberta

OBJECTIVES: To determine the age-specific rates of hospital discharge, cost per day, and overall in-hospital 1- and 4-year mortality for seniors who required hospitalization for the treatment of community-acquired pneumonia (CAP). DESIGN: Retrospective analysis of two administrative health service databases. SETTING: Province of Alberta, Canada. PARTICIPANTS: Residents of Alberta aged 18 and older. MEASUREMENTS: Hospital abstracts and vital statistics from April 1, 1994, to March 31, 1999, were analyzed, and mortality and cost outcomes statistically modeled by regression. RESULTS: There were 8,500 annual hospital discharges for CAP costing more than $40 million per year. The overall in-hospital all-cause mortality rate was 12%, and the 1-year mortality rate was 26%. The mean age of pneumonia cases increased (P<.000) from 62.8 in 1994/1995 to 67.2 in 1998/1999. The proportion of hospital discharges in those aged 85 and older was 13% in 1994/1995, increasing to 18% in 1998/1999 (P<.000). The age-specific hospital discharge rate and length of hospitalization increased with age. After adjustment for other factors using modeling, it was found that the relative risk (RR) of in-hospital and 1-year mortality increased with age, the RR of using special medical care and higher-than-average daily hospital cost decreased with age, and the RR of greater-than-average daily hospital cost was not associated with an increase in comorbidity. Total costs per hospital stay were similar in patients aged 85 and older to those in patients aged 65 to 74, despite a one-third longer length of stay, which was consistent with reduced use of special medical care in those aged 85 and older. CONCLUSION: The increased use of hospital resources for CAP in the setting of an aging population may have been partially avoided because of limitations in care provided for seniors aged 85 and older.     

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.     

Etiology of community-acquired pneumonia treated in an ambulatory setting

BACKGROUND: Very few studies have addressed the etiology of community-acquired pneumonia (CAP) treated in an ambulatory setting. METHODS: Patients were recruited from physicians' offices and from Emergency Rooms in Canada. Pneumonia was defined as two or more respiratory symptoms and signs and a new opacity on chest radiograph interpreted by a radiologist as pneumonia. Blood and sputum for culture as well as acute and convalescent serum samples for serology were obtained. Antibodies to Mycoplasma pneumoniae and Chlamydia pneumoniae were determined using enzyme-linked immunosorbent assays. RESULTS: Five hundred and seven patients were enrolled in the study; 419 (82%) had blood cultures done, seven (1.4%) of which were positive for Streptococcus pneumoniae; 241 (47.5%) had a sputum processed for culture, 31% of which were positive for a potential respiratory pathogen. 437 (86.2%) had both acute and convalescent serum samples obtained, 148 (33.8%) of which gave a positive result. Overall an etiological diagnosis was made in 48.4% of the patients. M. pneumoniae accounted for 15% of the cases, C. pneumoniae 12%, S. pneumoniae 5.9% and Haemophilus influenzae 4.9%. CONCLUSIONS: Despite considerable effort an etiological diagnosis of CAP treated on an ambulatory basis was made in only half the patients. The most commonly identified pathogens were M. pneumoniae, C. pneumoniae, S. pneumoniae,     

Genetics of community-acquired pneumonia

The variable clinical presentation of community-acquired pneumonia (CAP) suggests a genetic predisposition. Specific mutations or polymorphisms in host response genes such as pattern recognition molecules (PRMs), inflammatory molecules, and the coagulation system are likely to play a role in this variable response to CAP. Mannose-binding lectin polymorphisms appear to play a more dominant role in CAP than other PRMs, such as the Toll-like receptors (TLRs). The role of tumor necrosis factor (TNF) and lymphotoxin alpha (LTA) polymorphisms remain unclear despite extensive study whereas interleukin (IL)-10 and IL-1 receptor antagonist polymorphisms appear to play an important role in the anti-inflammatory response. Coagulation gene polymorphisms are likely important as well. The real value of these genetic studies in CAP and other severe infections will be when the management of an individual patient can be optimized by therapy based on the individual's genotype for molecules important in outcome.     

Etiology of community-acquired pneumonia

Community-acquired pneumonia (CAP) is a serious lower respiratory tract infection associated with significant morbidity and mortality that is characterized by disputes over diagnostic evaluations and therapeutic decisions. With the widespread use of broad-spectrum antimicrobial agents and the increasing number of immunocompromised hosts, the etiology and the drug resistance patterns of pathogens responsible for CAP have changed. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis remain the leading causes of CAP in immunocompetent patients. Opportunistic infections with organisms such as Pneumocystis jiroveci and Mycobacterium tuberculosis and other opportunistic fungal pneumonias should also be considered in the differential diagnosis of CAP in immunocompromised patients. This article examines the current peer-reviewed literature on etiology, risk factors, and outcomes of patients with CAP.     

Adjunctive therapy in community-acquired pneumonia

Despite potent antibiotics, community-acquired pneumonia (CAP) remains the most common cause of death from infection and the eighth overall leading cause of death in the United States. For this reason, adjunctive therapeutic measures directed at the host response rather than the pathogen are attractive. The immunomodulatory effects of macrolide antibiotics may play a significant role in management of severe CAP. The existing literature does not demonstrate a clear benefit for corticosteroids, but larger prospective randomized trials are needed. Nonsteroidal antiinflammatory drugs may benefit oxygenation but have no documented effect on mortality. Statin use before CAP diagnosis is associated with improved outcome but requires further research to determine if initiation at the time of diagnosis will affect outcome positively. Activation of the coagulation system appears to be a major pathophysiological event in severe pneumonia, but neither drotrecogin alfa activated nor tifacogin (recombinant tissue factor pathway inhibitor) have demonstrated a survival benefit. Other therapies have theoretical benefit but are not yet in the stage of clinical trials.