Continuity of Care: Pneumonia: Targeting Treatments and Monitoring the Response

Author: Cheryl A. Grandinetti, PharmD

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Dr. Grandinetti is a senior clinical research pharmacist at the National Cancer Institute, National Institutes of Health, Rockville, Maryland. The views expressed are those of the author and not those of any government agency.

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Infected or inflamed lung parenchyma is generally described as community-acquired pneumonia (CAP) or nosocomial pneumonia (NP).^1-3 Influenza and pneumonia combined is the seventh leading cause of death in the United States. Pneumonia-associated mortality remains high in patients who are elderly, critically ill, immunocompromised, and with preexisting cardiopulmonary disease.^1,4

Types of Pneumonia

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Pneumonia Risk Factors Alcoholism Chronic liver or lung disease Smoking Heart failure Coronary artery disease Dementia Diabetes Drug abuse Elderly Immunosuppression Malignancy Medications that alter consciousness Renal failure Seizures Strokes Additional risk factors for NP and NHAP Dysphagia Enteral feedings Impaired mental status Inadequate oral care Malnutrition Medication or therapies that impair lung defenses Medications that reduce gastric acidity (ie, proton pump inhibitors, histamine2 antagonists) Nasogastric and endotracheal tubes Surgery Trauma NP = nosocomial pneumonia; NHAP = nursing home?acquired pneumonia. Adapted from references 2,4,5.

Each type of pneumonia is associated with causative bacteria, viruses, parasites, or fungi with unique clinical presentations but similar risk factors. Difficulty obtaining sputum samples and results confounded by oropharyngeal colonization make identifying the causative microorganism difficult. Antimicrobial therapy, therefore, is often empiric.^5,6

Community-Acquired Pneumonia
CAP is acquired more than 14 days from a stay in a hospital or long-term care facility. Most CAP patients can be treated safely as outpatients, and mortality is <5%; however, some patients needing close observation, respiratory support, or intravenous (IV) antibiotics require admission to the hospital. Mortality approaches 40% in patients who require intensive care. Prompt treatment (within 4 hours of admission) can improve mortality.^1,7,8

Nosocomial Pneumonia
NP, occurring 48 hours or more after hospitalization, is the leading hospital-acquired cause of mortality. NP includes ventilator-associated pneumonia and health care?associated pneumonia (HCAP). HCAP occurs in patients who were hospitalized in an acute care hospital for ≥2 days within 90 days of infection; resided in a long-term care facility; received IV antibiotics, chemotherapy, or wound care within 30 days of infection; or attended a hospital or hemodialysis clinic. Recent antibiotic therapy, hospitalization (within 3 months), and late-onset NP (≥5 days after admission), increase the risk for colonization with a multidrug resistant (MDR) organism.^2,5,9,10

Nursing Home?Acquired Pneumonia
Nursing home residents are at greater risk for pneumonia with antibiotic-resistant organisms, and pneumonia is the leading cause of death among residents.² The elderly are prone to conditions causing aspiration and reflux (ie, oversedation, excessive narcotic use, supine positioning, and confusion). Respiratory care interventions and good oral care are important to reduce oropharyngeal colonization with potential respiratory pathogens that can be aspirated.

Monitoring and Counseling Tips for Pharmacists In All Settings: Recommend antibiotics with longer half-lives that permit once-daily administration, improve adherence and outcomes, and decrease costs Counsel patients on: Completing entire treatment course Maintaining adequate nutrition and exercise for recovery and to prevent subsequent infections Preventing and spreading CAP: hand washing, using masks or tissues, and vaccinations Smoking cessation programs, if applicable Assess adherence In the Hospital: Ensure accurate pneumonia diagnosis Recognize patients at risk for MDR Ensure use of most appropriate, safe, and cost-effective antibiotic; avoid indiscriminate antibiotic use Administer antibiotics as early as possible Assess vaccination status Switch patients to oral therapy when clinically indicated Discharge patients as soon as they are clinically stable At Discharge: Vaccinate at discharge or during outpatient treatment Remind patients of the importance of annual influenza vaccine In Long-Term Care Facilities: Emphasize the importance of good oral hygiene Use central nervous system depressants cautiously CAP = community-acquired pneumonia; MDR = multidrug resistance. Adapted from references 2,4-6.

Treatment

Treatment goals are to eradicate causative pathogens, resolve clinical signs and symptoms, minimize hospitalization, and prevent reinfection. The Infectious Diseases Society of America/American Thoracic Society consensus guidelines recommend empiric therapy with macrolides, fluoroquinolones, or doxycycline.^4-6 The Centers for Disease Control and Prevention recommends fluoroquinolone use only when patients fail first-line regimens, are allergic to alternative agents, or have a documented drug-resistant pneumococcal infection. Clinicians should consider local epidemiologic and resistant patterns and patient circumstances when basing therapy choices on published guidelines.^5,6

Prolonged and unnecessary broad-spectrum anti-infectives are associated with development of resistant organisms. Clinicians should avoid antibiotic overuse and tailor empiric treatment to the causative microorganism as soon as possible. Antibiotics are generally administered for 7 to 14 days; longer treatment durations may be necessary in immunocompromised patients or those infected with atypical pathogens (Legionella pneumophilia, Mycoplasma pneumoniae, Chlamydia pneumoniae). Oral therapy is indicated once patients are clinically stable and able to tolerate oral intake.^1,7,9

Preventive Strategies

For patients ≥50 years of age, those with chronic medical conditions, long-term care facility residents, household contacts of high-risk persons, and health care workers, annual vaccination with inactivated influenza vaccine is crucial. The intranasal live attenuated vaccine is indicated for healthy persons aged 5 to 49 years. A one-time pneumococcal vaccine is indicated for patients aged ≥65 and younger patients who are immunocompromised or have long-term medical conditions.¹¹

Pharmacists can influence patient care by ensuring that therapy is initiated quickly with the most appropriate, cost-effective anti-infective, monitoring patient response, and suggesting conversion to oral therapy to shorten hospitalization.

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Risk Factors for Multi-Drug Resistant Pathogens Hospitalization for ≥2 days or antimicrobials in preceding 90 days Current hospitalization of ≥5 days High frequency of antibiotic resistance in the community or specific hospital unit Resident in extended care facility Home infusion therapy Chronic dialysis within 30 days Home wound care Family member with MDR pathogen Immunosuppression MDR=multidrug resistant Adapted from reference 5.

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Empiric Therapy Choices for Pneumonia Treatment Types of Pneumonia Patient Type and Setting Common Pathogens Empiric Therapy Recommendations CAP Previously healthy outpatients, no risk factors for MDR pathogens Streptococcus pneumoniae; Haemophilus influenzae; Mycoplasma pneumoniae; Chlamydia pneumoniae; Moraxella catarrhalis; Staphylococcus aureus Azithromycin, clarithromycin, or erythromycin Alternatives: doxycycline Outpatients with comorbidities or macrolide-resistant infection Fluoroquinolonea or high-dose amoxicillin or amoxicillin/clavulanate plus a macrolide or doxycycline Alternatives: ceftriaxone, cefpodoxime, and cefuroxime plus a macrolide or doxycycline Inpatient, non-ICU treatment S pneumoniae; M pneumoniae; C pneumoniae; H influenzae Legionella species Fluoroquinolone,a beta-lactam (cefotaxime, ceftriaxone, or ampicillin; ertapenem for selected patients) plus a macrolide or doxycycline Penicillin-allergic patients: fluoroquinolonea Inpatient, ICU treatment S pneumoniae; S aureus; Legionella pneumophilia; Gram-negative bacilli; H influenzae; Pseudomonas aeruginosa Cefotaxime, ceftriaxone, or ampicillin-sulbactam plus azithromycin or fluoroquinolonea Penicillin-allergic patients: fluoroquinolonea and aztreonam For pseudomonas infection: piperacillin/tazobactam, cefepime, imipenem, or meropenem plus ciprofloxacin or levofloxacin OR beta-lactam plus an aminoglycoside and azithromycin or fluoroquinolonea; penicillin-allergic patients: substitute aztreonam for a beta-lactam. For MRSA infection: add vancomycin or linezolid. Viral CAP Outpatient/inpatient non-ICU treatment Influenza; Respiratory syncytial virus; Adenovirus; Parainfluenza virus Oseltamivir, zanamavir (within 48 hours of the onset of symptoms) Alternatives: amantadine, rimantadine NHAP Nursing home Klebsiella pneumoniae; S aureus; Escherichia coli; MRSA; Anaerobes Fluoroquinolone or amoxicillin/clavulanate plus azithromycin or clarithromycin Hospital ward Parenteral third-generation cephalosporin or ampicillin/sulbactam plus azithromycin or clarithromycin or parenteral levofloxacin, gatifloxacin, or moxifloxacin NP, VAP, HCAP Early onset, no risk factors for MDR pathogens, any disease severity S pneumoniae; H influenzae; Methicillin-sensitive S aureus; Antibiotic-sensitive enteric gram-negative bacilli; E coli; K pneumoniae; Enterobacter species; Proteus species; Serratia marcescens Ceftriaxone, levofloxacin, moxifloxacin, ciprofloxacin, ampicillin/sulbactam, or ertapenem Late-onset disease or risk factors for MDR pathogens All microorganisms listed under early onset plus MDR pathogens: P aeruginosa; E coli; K pneumoniae; Acinectobacter species; MRSA; Legionella species Cefepime, ceftazidime, imipenem, meropenem, or piperacillin/tazobactam, plus Ciprofloxacin, levofloxacin, or aminoglycoside plus If MRSA+: linezolid or vancomycin If legionella+: replace aminoglycoside with a macrolide or a fluoroquinolone *The Infectious Diseases Society of America recommends moxifloxacin, gemifloxacin, and levofloxacin. Avoid ciprofloxacin and ofloxacin because they lack activity against S pneumoniae. CAP = community-acquired pneumonia; HCAP = health care associated?pneumonia; ICU = intensive care unit; MDR = multidrug resistant; MRSA = methicillin-resistant Staphylococcus aureus; NP = nosocomial pneumonia; NHAP = nursing home?acquired pneumonia; VAP = ventilator-associated pneumonia. Adapted from references 2,5,6.