Community-Acquired Pneumonia: March 2006

Treatment Guidelines

Menendez R, Torres A, Zalacain R, et al; NEUMOFAIL Group. Guidelines for the treatment of community-acquired pneumonia: predictors of adherence and outcome. Am J Respir Crit Care Med. 2005;172:757-762. This report from Spain was designed to evaluate adherence to guidelines for the treatment of community-acquired pneumonia (CAP) and to correlate adherence with outcome. The analysis included 1288 patients with CAP who were admitted to 13 Spanish hospitals. The results were restricted to empiric antibiotic treatment according to Spanish guidelines, which are first-line treatment with cefotaxime, ceftriaxone, or amoxicillin-clavulanate, to which a macrolide or fluoroquinolone may be added. For patients admitted to the intensive care unit (ICU), the recommendation was a third- or fourth-generation cephalosporin combined with either an intravenous (IV) macrolide or an IV fluoroquinolone. The results showed that 979 patients (nearly 80%) were treated with antibiotics selected according to the guidelines for hospitalization on the general ward and 67% adherence for those admitted to the ICU. There were substantial differences in adherence to guidelines according to hospital (47% to 97%) and physician specialty. With regard to outcome, measured as treatment failure and mortality, there was a statistically significant better outcome in patients treated according to guidelines. These data are shown in Table 1 .

Conclusion: The study authors conclude that there is a substantial difference between hospitals and practitioners for adherence to CAP guidelines, and that adherence to these guidelines is associated with a favorable outcome compared with nonadherence.

Comment: This study has undergone editorial review by Drahomir Aujesky, MD, Master of Science (MSc), University of Lausanne, Lausanne, Switzerland, and Michael J. Fine, MD, MSc, Veterans Administration (VA), Pittsburgh Healthcare System, Pittsburgh, Pennsylvania,^[1] with several concerns:

• The results are limited to the assessment only for antibiotic selection and do not include other important variables, such as timely administration;
  
  

• Patients who died within the first 48 hours were excluded; and
  
  

• The improved outcome was shown only for those who were not seriously ill, although this cannot be explained.

In addition, there was no assessment of "collateral damage" in the form of antibiotic resistance, which may be a penalty when everyone uses the same antibiotics to treat a relatively common infection.

Schouten JA, Hulscher ME, Wollersheim H, et al. Quality of antibiotic use for lower respiratory tract infections at hospitals: (how) can we measure it? Clin Infect Dis. 2005;41:450-460. This report from The Netherlands is by authorities who designed a novel method to assess and improve guidelines and quality indicators for patients with either CAP or acute exacerbations of chronic bronchitis (AECB).

Methods: Sequential steps in the process were as follows:

• Assessment of national and international guidelines, including the Infectious Diseases Society of America (IDSA), American Thoracic Society (ATS), European Respiratory Society, and British Thoracic Society, combined with a literature review. This review was designed to determine potential indicators for the quality of antibiotic use in treating hospitalized patients with lower respiratory tract infections.
  
  

• Review of the literature to determine the quality of evidence to support these indicators resulting in the grading of A through D.
  
  

• Expert panel consisting of 11 opinion leaders in microbiology, infectious diseases, respiratory medicine, and quality-of-care medicine developed a consensus procedure for preselected indicators with a 5-category Likert scale. Only indicators with over 70% agreement on each criterion were selected.
  
  

• Assessment of applicability of quality indicators was completed with a prospective observational audit performed at 8 hospitals.
  
  

• Characteristics of quality indicators were assessed for feasibility, reliability, opportunity for improvement, and case-mix stability.

Results: The following quality indicators for antibiotic use in lower respiratory tract infections were chosen.

CAP:

• Initiate antibiotic therapy within 4 hours after presentation;
  
  

• Prescribe empiric antibiotics according to national guidelines;
  
  

• Adapt dose and dose interval of antibiotics according to renal function;
  
  

• Switch from IV to oral antibiotics according to existing criteria and clinical stability;
  
  

• Change broad-spectrum empiric treatment to pathogen-directed therapy when culture results become available;
  
  

• Stop antibiotic therapy if there is no fever for 3 days;
  
  

• Change antibiotic therapy if there is no clinical improvement within 72 hours;
  
  

• Perform gram stain and culture on sputum sample;
  
  

• Obtain 2 blood cultures before empiric treatment;
  
  

• Perform gram stain before empiric treatment; and
  
  

• Perform urine antigen test for Legionella on clinical suspicion.

Exacerbation of chronic bronchitis:

• Prescribe antibiotic treatment for exacerbation of chronic bronchitis only when indicated;
  
  

• Do not use a macrolide as the first choice of antibiotic;
  
  

• Adapt dose and dose interval of antibiotics to renal function;
  
  

• Switch from IV to oral antibiotics according to existing criteria and clinical stability;
  
  

• Change broad-spectrum empiric treatment to pathogen-directed therapy when culture results become available;
  
  

• Perform gram stain and culture of sputum sample; and
  
  

• Optimal duration of antibiotic treatment should be 5-7 days.

Conclusion: The study authors conclude that quality indicators for antibiotic use in hospitalized patients with lower respiratory tract infections were successfully developed on the basis of evidence and expert opinion following a carefully crafted procedure.

Comment: This is an interesting process that has resulted in a set of performance indicators. It is quite obvious in comparing their conclusions with those of the IDSA^[2] and ATS^[3] guidelines for CAP that there is substantial divergence of opinion. For example, the ATS guidelines do not require sputum gram stain and culture for all patients, and the IDSA guidelines recommend initiation of antibiotics within 8 hours of presentation. Also, the ATS and IDSA guidelines use severity of illness to guide decisions for obtaining Legionella Urinary Antigen; IDSA, for example, recommends this test for those requiring ICU admission for CAP.

Bodi M, Rodriguez A, Sole-Violan J, et al; Community-Acquired Pneumonia Intensive Care Units (CAPUCI) Study Investigators. Antibiotic prescription for community-acquired pneumonia in the intensive care unit: impact of adherence to Infectious Diseases Society of America guidelines on survival. Clin Infect Dis. 2005;41:1709-1716. The study, conducted by the Community-Acquired Pneumonia Intensive Care Units (CAPUCI) Study Investigators, is a prospective multicenter analysis of all patients with CAP who were admitted to ICUs in 33 Spanish hospitals between 2001 and 2002.

The IDSA guidelines used in this analysis recommended a beta lactam (cefotaxime, ceftriaxone, ampicillin-sulbactam, or ertapenem) plus an advanced macrolide (clarithromycin or azithromycin) or a respiratory fluoroquinolone; coverage for Pseudomonas aeruginosa was to be added if there were risks for this pathogen on the basis of severe structural lung disease, recent antibiotic therapy, or recent hospitalization.

During the 15-month study period, 529 patients were hospitalized in ICUs with severe CAP. The overall mortality was 148 cases (28%), and the rate of nonadherence to the IDSA guidelines was just over 42%. The mortality was higher among those with nonadherence to the guidelines (33.2% vs 24.2%, P > .05).

The microbiology results and an analysis of deaths are summarized in Table 2 and Table 3 .

Conclusion: Better adherence to the IDSA guidelines would improve survival in patients with severe CAP.

Comment: There are some misunderstandings and possibly late changes in the IDSA guidelines that are relevant to this study:

• The guidelines apply only to immunocompetent adults. This study included 49 immunocompromised patients, including 6 with infections by Pneumocystis jiroveci, who were considered immunocompetent.
  
  

• There is now a new category of patients who have "healthcare-associated CAP" who are supposed to be treated according to the nosocomial pneumonia guidelines; these actually account for 20% to 30% of cases in most series.
  
  

• The IDSA guidelines for empiric treatment apply only to the patients who have no etiologic diagnosis. Recommendations would be much more specific once the etiologic agent is known. It is not clear how often this information applied here, but 45 cases (16%) were believed to have an established diagnosis by urinary antigen detection, which is usually information that is rapidly available.
  
  

• The investigators were unable to find any difference in outcome on the basis of timely administration of antibiotics, something that is now considered a critical variable that is based on Medicare data.

Despite these concerns, this study is added to others that show better outcomes when using IDSA or ATS guidelines.^[4,5,6]

Hedlund J, Stralin K, Ortqvist A, Holmberg H; Community-Acquired Pneumonia Working Group of the Swedish Society of Infectious Diseases. Swedish guidelines for the management of community-acquired pneumonia in immunocompetent adults. Scand J Infect Dis. 2005;37:791-805. The Swedish Society of Infectious Diseases has provided 2005 guidelines for the management of CAP. The analysis was based on assessments of 519 publications considered relevant, and the structure used was based on methods of the British Thoracic Society with an evidence level (I-IV) and guideline statement grade (A-D). The guidelines are summarized as follows.

Nonmicrobiological lab studies:

• X-ray;
  
  

• O₂ saturation; blood gas if SaO₂ < 95 or severe CAP; and
  
  

• Blood chemistries: blood urea nitrogen (BUN), complete blood count (CBC), C-reactive protein (CRP), creatinine, sodium (Na), potassium (K), and alanine aminotransferase (ALT).

Severity evaluation -- CURB-65:

• Confusion: new disorientation or reduced consciousness;
  
  

• Urea value > 7 mmol/L;
  
  

• Respiratory rate ≥ 30/minute;
  
  

• Blood pressure: systolic < 90 or diastolic < 60; and
  
  

• 65: age > 65 years.

Site of care based on CURB-65 score:

• 0-1: Home treatment;
  
  

• 2: Hospital or supervised home treatment;
  
  

• 3-5: Hospital; and
  
  

• 4-5: Consider ICU.

Microbiology studies:

• All patients: 2 pretreatment blood cultures and pretreatment sputum culture with cytologic screening; must be pretreatment and must be cultured quantitatively or semiquantitatively;
  
  

• Severe pneumonia (CURB-65 score of 3-5): pneumococcal urinary antigen, Legionella urinary antigen, Legionella sputum culture, and polymerase chain reaction (PCR) or serology for Mycoplasma pneumoniae;
  
  

• Critically ill: consider bronchoscopy; and
  
  

• Isolation for M pneumoniae, influenza, adenovirus, and Mycoplasma tuberculosis.
  
  

Antibiotic treatment:

• Not severe (CURB-65, 0-2):
  
  

  • Penicillin V (1 g 3 times daily) or amoxicillin (0.5-1 g 3 times daily)
    
    

  • Penicillin allergy: erythromycin (1 g 3 times daily) or clindamycin (300 mg 3 times daily)
    
    

  • Atypical pathogen suspected: erythromycin (500 mg twice daily) or doxycycline (200 mg, then 100 mg each day )
    
    

• Severe pneumonia (CURB-65, 3-5):
  
  

  • Preferred: penicillin 3 g 3 times daily
    
    

  • Alternative: cefuroxime (1.5 g 3 times daily) or cefotaxime (1 g 3 times daily) (especially with influenza or severe cold)
    
    

  • Atypical suspected (especially Legionella): cefotaxime/cefuroxime and erythromycin (1 g 3 times daily) or penicillin (3 g 3 times daily) and moxifloxacin (400 mg every day) or levofloxacin (500 mg every day or twice daily)
    
    

  • Severe penicillin allergy: clindamycin 600 mg 3 times daily and moxifloxacin/levofloxacin
    
    

• Legionella confirmed: moxifloxacin or levofloxacin (above doses)
  
  

• Switch from IV to oral: clinically improved, afebrile, and able to take oral medication
  
  

• Switch to specific pathogen: when culture results are known
  
  

• Duration of antibiotics:
  
  

  • Not severe (CURB 0-2), 7 days
    
    

  • Severe (CURB 3-5), 10 days
    
    

  • Legionella, 10-14 days
    
    

  • Staphylococcus aureus or gram-negative bacilli, 14-21 days
    
    

Treatment failure, defined as no improvement in 48-72 hours:

• Lab tests that should be done include:
  
  

  • Blood chemistry: BUN, CBC, CRP, creatinine, Na, K, calcium (Ca), ALT, bilirubin, lactate dehydrogenase (LDH), creatine phosphokinase (CPK), D-dimer
    
    

  • Imaging: x-ray, computerized tomographic (CT) scan
    
    

  • Microbiology: urine culture, urinary antigen, Streptococcus pneumoniae and Legionella, PCR, or serology for M pneumoniae
    
    

  • Bronchoscopy
    
    

• Antibiotic changes:
  
  

  • Oral penicillin to amoxicillin, IV penicillin, doxycycline, or macrolide
    
    

  • Macrolide/doxycycline to penicillin or amoxicillin
    
    

  • Penicillin G to IV cephalosporin or macrolide
    
    

  • IV penicillin to IV cephalosporin + macrolide or add macrolide or moxifloxacin/levofloxacin
    
    

  • IV cephalosporin -- add IV macrolide or moxifloxacin/levofloxacin.

Discharge: When improved and clinically stable for 24 hours.

Follow-up:

• Hospitalized patients: at 6-8 weeks by clinic visit or phone;
  
  

• X-ray if recurrent CAP, complicated course, persisting symptoms, immunocompromised, or risk for malignancy (smokers); and
  
  

• Persistent symptoms or infiltrates on x-ray: CT scan or bronchoscopy.

Prevention:

• Smoking cessation.
  
  

• Influenza vaccination: age > 65, nursing home resident, chronic disease, healthcare workers.
  
  

• Pneumococcal vaccine: age > 65, nursing home resident, aspiration-prone, chronic disease, and asplenia. Consider revaccination after 5 years.

Comment: These Swedish guidelines have at least 3 major differences from guidelines for the United States from IDSA and the ATS:

• There is extensive use of CURB-65 for decision making.
  
  

• Antibiotic recommendations are quite different with heavy dependence on penicillin as the preferred drug because of the assumption that the major treatable pathogen is S pneumoniae. The absence of empiric treatment directed against atypical bacteria is based on several studies that show that such treatment is not a benefit. The primary references were the meta-analyses published this year by Mills and colleagues^[7] and a Cochrane review by Shefet and coworkers.^[8]
  
  

• Recommendations for microbiological analysis are much more rigorous.

One particularly admirable feature of these guidelines is the simplicity and clarity of the presentation.

Medscape Infectious Diseases. 2006;8(1) © 2006  Medscape

Cite this: Community-Acquired Pneumonia: March 2006 - Medscape - Mar 01, 2006.