Community-Acquired Pneumonia (CAP) Antibiotic Selection and Management Update

Nurse Editor: Reneé Semonin Holleran, RN, PhD, Chief Flight Nurse, Clinical Nurse Specialist, University Hospital, Cincinnati.

Peer Reviewer: Darlene Bradley, RN, MSN, MAOM, CNS, CCRN, CEN, CNS, MICN, University of California Irvine Medical Center, Orange.

Introduction

Community-acquired pneumonia (CAP) is the sixth leading cause of death overall and the most common cause of death from infection1,2 with an overall case-fatality rate of about 5%. Mortality is substantially greater (about 13.6%) among hospitalized patients.3 Expert committees have published treatment guidelines, but the guidelines have not been prospectively validated.4,5 Prior studies using pneumonia guidelines have reported decreased admission rates, lengths of hospital stay, and costs, but no change in clinical outcomes.6-8

The introduction of antibiotic agents dramatically reduced mortality from pneumococcal pneumonia. However, the mortality rate from bacteremic pneumococcal CAP has shown little improvement in the past three decades, remaining between 19% and 28%, depending on the population and institution studied. Factors such as the aging population, increased prevalence of comorbid illnesses, human immunodeficiency virus, and increasing microbial resistance probably have contributed to maintaining the high mortality rate despite advances in medical care.

Signs and Symptoms. The signs and symptoms of pneumonia, which include respiratory distress, coughing, fever, and pulmonary infiltrates, can be mimicked by many other causes. Diseases such as pulmonary embolism, congestive heart failure (CHF), lung cancer, tuberculosis, chronic obstructive pulmonary disease (COPD), and systemic lupus erythematosus may produce pneumonia-like symptoms. Cytotoxic agents; nonsteroidal anti-inflammatory (NSAIDS); some antibiotics, including sulfonamides; and certain antiarrhythmics, such as amiodarone, can mimic pulmonary infection. Common analgesics such as salicylates, propoxyphene, and methadone also may precipitate acute respiratory symptoms.

Initial Treatment. Prompt, aggressive, and adequate supportive care must be provided to patients who present to the hospital with pneumonia, especially the elderly and immunocompromised. Among initial stabilization measures, managing the airway and ensuring adequate breathing, oxygenation, ventilation, and perfusion are of paramount importance.

Upon arrival to the hospital, oxygenation status should be assessed immediately using pulse oximetry. Patients with an arterial oxygen saturation of less than 90% should receive supplemental oxygen and should be considered candidates for admission, prompt evaluation, and treatment if the diagnosis is confirmed. Arterial blood gases (ABG) are especially helpful in patients suspected of hypercarbia and respiratory failure. ABG may be useful in patients with COPD, decreased mental status, and fatigue.

Patients who are hypoxic and do not respond to supplemental oxygen, as well as those with hypercarbia accompanied by respiratory acidosis, may be candidates for mechanical ventilation. This patient population also has a poorer prognosis. Support may be accomplished with intubation and mechanical ventilation or noninvasive ventilation (bilevel positive pressure ventilation [BiPAP]). Recent studies have shown BiPAP to be successful for treatment of patients with respiratory failure due to pneumonia.5 When this technique is available, it may avert the need for endotracheal intubation and its potential complications. Finally, patients with evidence of bronchospasm on physical exam, as well as those with a history of obstructive airway disease (asthma or COPD), may benefit from inhaled bronchodilator therapy.

Complications related to pneumonia range from mild dehydration to septic shock. Patients in septic shock show evidence of decreased tissue perfusion manifested by confusion and oliguria. Initial therapy consists of fluid resuscitation, but patients should be closely monitored to avoid fluid overload.

Antibiotic Therapy. The Antibiotic Selection for Community-Acquired Pneumonia (ASCAP) 2002 Consensus Panel concurred that appropriate use of antibiotics require radiographic confirmation of the diagnosis of CAP. Treatment options are recommended for outpatient and in hospital patients. (See ASCAP 2002 Guidelines.)

Antibiotic therapy for patients who will be treated as an outpatient should cover on an empiric basis six respiratory tract pathogens to include Streptococcus pneumoniae, Haemophilus influenza, Moraxella catarrhalis, Chlamydia pneumoniae, Mycoplasma pneumonia, and Legionella pneumonphila. Two safe and effective advanced generation macrolides azithromycin and clarithromycin are available for oral-based outpatient treatment.

Patients should be prescribed antibiotics for CAP at the time of diagnosis, and they must fill their prescription and take the medication as prescribed. Ideally, patients should initiate their first course of oral therapy within eight hours of diagnosis, a time frame that appears reasonable based on studies in hospitalized patients indicating improved survival in patients who received their first intravenous (IV) dose within eight hours of diagnosis.4

Clinicians are urged to instruct patients in medication compliance, and in the case of short (five-day) courses of therapy, educate their patients that, although they are only consuming medications for a five-day period, the antibiotic remains at the tissue site of infection for about seven to 10 days and continues to deliver therapeutic effects during that period.

Verbal or on-site re-evaluation of patients is recommended within a three-day period following diagnosis and treatment. Follow-up in the office or clinic especially is recommended for elderly patients, those with comorbid illness, and those whose medication compliance may be compromised. More urgent follow-up may be required in patients with symptoms including dyspnea, fever, or other systemic signs and symptoms. A follow-up radiograph generally is not recommended in outpatient CAP, except in high-risk groups and those in whom the diagnosis may have been uncertain.

The in-hospital management of the patient with CAP begins with prompt administration of IV antibiotics in the emergency department. Research has shown improved clinical outcomes in patients with CAP when the antibiotics are administered in the ED once the diagnostic tests including radiographs and cultures are completed.4,7, 8,9

Although antibiotic recommendations based on risk-stratification criteria, historical features, sites where the infection was acquired, allergies, and other modifying factors play a role, institutional protocols, hospital-based critical pathways, resistance features, and other factors also will influence antibiotic selection. Despite variations in hospital or departmental protocols, certain requirements regarding drug selection for CAP are relatively consistent.

When combination cephalosporin/macrolide therapy is selected hospital protocol, among the beta-lactams available, IV ceftriaxone is recommended by the ASCAP 2002 Consensus Panel because of evidenced-based efficacy in moderate to severe CAP. The advantages of this treatment regimen include once daily administration, spectrum of coverage, and support by all major guideline panels.

Azithromycin is recommended as the cotherapeutic macrolide agent in patients with CAP for the following reasons: 1) it can be administered on a once-daily basis; 2) it is the only macrolide indicated for in-hospital, IV-to-oral step-down in some pneumonias caused by specific infective agents; 3) it is cost-effective; 4) the IV-to-oral step-down dose of 500 mg has been established as effective in clinical trials evaluating hospitalized patients with CAP; 5) azithromycin has excellent activity against L. pneumonphila, a common pathogen in geriatric patients with CAP.

The ASCAP Consensus Panel recommends IV azithromycin therapy as the preferred initial, empiric agent in combination with ceftriaxone. The panel acknowledges, however, that some institutions will use IV ceftriaxone in combination with oral macrolide in patients who are not in the intensive care unit, which is an approach supported by a number of national panels.

Antimicrobial Therapy and Medical Outcomes. One study has helped assess the relationship between initial antimicrobial therapy and medical outcomes for elderly patients hospitalized with pneumonia.9 In this retrospective analysis, hospital records for 12,945 Medicare inpatients (65 years of age) with pneumonia were reviewed. Associations were identified between the choice of the initial antimicrobial regimen and three-day mortality, and there was an adjustment for baseline differences in patient profiles, illness severity, and process of care. Comparisons were made between the antimicrobial regimens and a reference group consisting of patients treated with a nonpseudomonal third-generation cephalosporin alone.9

The national study demonstrated that, compared to a reference group receiving a nonpseudomonal third-generation cephalosporin alone, initial therapy with a nonpseudomonal plus a macrolide, a second-generation cephalosporin plus a macrolide, or a fluoroquinolone alone was associated with 26%, 29%, and 36% lower 30-day mortality, respectively. Despite the fact that regimens are compatible with those recommended by the Infectious Disease Society of America (IDSA) and Centers for Disease Control and Prevention (CDC), only 15% of patients received one of the three aforementioned regimens associated with reduced mortality rates.

For reasons that are not entirely clear, patients treated with a beta-lactam/beta-lactamase inhibitor plus a macrolide or an aminoglycoside plus another agent had mortality rates that were 77% and 21% higher than the reference group, respectively.

Consensus Report Guidelines: Infectious Disease Society of America. The IDSA, through its Practice Guidelines Committee, provides assistance to clinicians in the diagnosis and treatment of CAP. The targeted patient groups are imunocompetent adult patients. Criteria are specified for determining whether the inpatient or outpatient setting is appropriate for treatment. Differences from other guidelines written on this topic include use of laboratory criteria for diagnosis and approach to antimicrobial therapy.

The guidelines are evidenced-based when possible. A standard ranking system is used for the strength of recommendations and the quality of the evidence cited in the literature reviewed. The Practice Guidelines Committee has subjected the document to external review by peer reviewers, and it was approved by the IDSA Council in September 2000. (See guidelines.)

Summary

It should be stressed that there is no absolute or consistent consensus about precisely which drug, or combination of drugs, constitutes the most outcome-effective choice for pneumonia in patients with CAP, although a recent study suggests improved mortality rates with regimens using two-drug combinations rather than monotherapy in patients with bacteremic pneumonoccal pneumonia.10,11,12

Most panels and guideline documents agree that antimicrobial coverage must include sufficient activity against the principle bacterial pathogens, as well as against atypical pathogens. Currently, recommended regimens include ceftriaxone/cefotaxime plus azithromycin, or monotherapy with advanced generation fluoroquinolones — given some qualifications regarding outcomes and resistance issues — have emerged as preferred treatment of inpatients with CAP.

Beyond this non-negotiable caveat mandating coverage for the six aforementioned pathogens, there are important differences among the recommendations and expert panels for empiric treatment of pneumonia.

Research needs to continue using evidence-based guidelines, protocols, and critical pathways to ensure that patients with CAP are appropriately treated and to decrease the mortality and morbidity related to CAP for the patients that are cared for in the emergency department.

[Editor’s note: This article originally was written by Gideon Bosker, MD, FACEP, Assistant Clinical Professor, Section of Emergency Services, Yale University School of Medicine; Associate Clinical Professor, Oregon Health Sciences University, Portland, and published in Emergency Medicine Reports. It was peer reviewed by Steven M. Winograd, MD, FACEP, Attending Physician, Emergency Department, Jeannette (PA) District Memorial Hospital, St. Clair Memorial Hospital and University of Pittsburgh Medical Center; and James A. Wilde, MD, FAAP, Assistant Professor, Emergency Medicine and Pediatrics, Research Director, Department of Emergency Medicine, Medical College of Georgia in Augusta.]

References

1. Niederman MS, McCombs JS, Unger AN, et al. The cost of treating community-acquired pneumonia. Clin Therapeut 1998;2:820-837.

2. Medicare and Medicaid statistical supplement, 1995. Health Care Finance Rev 1995;16.

3. Fine MJ, Smith MA, Carson CA, et al. Prognosis and outcomes of patients with community-acquired pneumonia. JAMA 1995;274:134-141.

4. American Thoracic Society: Guidelines for the Initial Management of Adults with Community-Acquired Pneumonia: Diagnosis, assessment of severity, and initial antimicrobial therapy. Am Rev Respir Dis 1993;148:1418-1426.

5. Confalonieri M, Potena A, Carbone G, et al. Acute respiratory failure in patients with severe community-acquired pneumonia. A prospective randomized evaluation of noninvasive ventilation. Am J Respir Crit Care Med 1999;160:1585-1591.

6. Hoe LK, Keang LT. Hospitalized low-risk community-acquired pneumonia: Outcome and potential for cost-savings. Respirology 1999;4:307-309.

7. Marrie TJ, Lau CY, Wheeler SL, et al. A controlled trial of a critical pathway for treatment of community-acquired pneumonia. JAMA 2000;283:749-755.

8. Dean NC, Suchyta MR, Bateman KA. Implementation of admission decision support for community-acquired pneumonia. A pilot study. Chest 2000;117:1368-1377.

9. Gleason PP, Meehan TP, Fine JM, et al. Associations between initial antimicrobial therapy and medical outcomes for hospitalized elderly patients with pneumonia. Arch Intern Med 1999;159:2562-2572.

10. Kaplan SL, Mason Jr. EO, Barson WJ, et al. Outcome of invasive infections outside the central nervous system caused by Streptococcus pneumoniae isolates nonsusceptible to ceftriaxone in children treated with beta-lactam antibiotics. Pediatr Infect Dis J 2001;20:392-396.

11. Heffelfinger JD, Dowell SF, et al. A report from the Drug-resistant Streptococcus pneumoniae Therapeutic Working Group. Management of community-acquired pneumonia in the era of pneumonoccal resistance. Arch Intern Med 2001;161:1837-1842.

12. Waterer GW, Somes GW, Wunderink RG. Monotherapy may be suboptimal for severe bacteremic pneumonoccal pneumonia. Arch Intern Med 2001;161:1837-1842.

13. Marie TJ. Community-acquired pneumonia: Epidemiology, etiology, treatment. Infect Dis Clinic North Am 1998;12:723-740.

14. Bartlett JG, Mundy M. Community-acquired pneumonia. N Engl J Med 1995;333:1618-1624.

15. Bates JH, Campbell AL, et al. Microbial etiology of acute pneumonia in hospitalized patients. Chest 1992;101:1005-1002.

16. Plouffe J, Schwartz DB, Kolokathis A, et al. Clinical efficacy of intravenous followed by oral azithromycin monotherapy in hospitalized patients with community-acquired pneumonia. Antimicrob Agents Chemother 2000;44:1796-1802.

17. Vergis EN, Indorf A, et al. Azithromycin vs cefuroxime plus erythromycin for prospective, randomized, multicenter trial. Arch Int Med 2000;160:1294-1300.

18. The choice of antibacterial drugs. Med Lett Drugs Ther 1996;38:25-34.

19. Clarithromycin and azithromycin. Med Lett Drugs Ther 1992;34:45-47.

20. Fang GD, Fine M, Orloff, et al. New and emerging etiologies for community-acquired pneumonia with implications for therapy-prospective multicenter study of 359 cases. Medicine 1990;69:307-316.

21. Antibiotic Update 1998: Outcome-effective treatment for bacterial infections managed in the primary care and emergency department setting. Emerg Med Rep 1997;18:1-24.

22. File TM, Dunbar L, et al. A multicenter, randomized study comparing the efficacy and safety of intravenous and/or oral levofloxacin versus ceftriaxone and/or cefuroxime in treatment of adults with community-acquired pneumonia. Antimicrob Agents Chemother 1997;41:1965-1972.


CE Objectives

After reading this issue of Emergency Nursing Reports, the continuing education participant will be able to:

  • Discuss the guidelines for the management of CAP.
  • Identify the common agents that cause CAP.
  • Describe the failure rate of the identification of the cause of CAP in the elderly.
  • Identify the time period in which treatment for CAP should begin for optimal patient treatment.

CE Questions

1. Prior studies of pneumonia guidelines have reported all of the following, except:

A. decreased lengths of stay.

B. admission rates.

C. costs.

D. change in clinical outcomes.


2. Empiric coverage for community-acquired pneumonia (CAP) must provide activity against which of the follow- ing pathogens, at a minimum?

A. S. pneumoniae, H. influenza, and M. catarrhalis

B. Mycoplasma, Legionella, and C. pneumoniae

C. H. influenza, M. catarrhalis, and Mycoplasma

D. S. pneumoniae, H. influenza, and M. catarrhalis, as well as against atypical pathogens M. pneumoniae, L. pneumoniae, and C. pneumoniae


3. Prospective studies evaluating the causes of CAP in elderly adults have failed to identify the cause in what percent of the cases?

A. 4-6 %

B. 14-16%

C. 20%

D. 40-60%


4. Patients with CAP should initiate their first course of oral therapy within what time period, ideally?

A. Eight hours of diagnosis

B. 12 hours of diagnosis

C. 18 hours of diagnosis

D. 24 hours of diagnosis