Managing community-acquired pneumonia during flu season
ABSTRACTThe clinical findings of influenza overlap those of community-acquired bacterial pneumonia (CABP), and influenza infection can be complicated by bacterial infections. Reviewed here are the epidemiology, pathophysiology, diagnosis, and management of community-acquired pneumonia (CAP) with special emphasis on considerations during influenza season.
KEY POINTS
- Especially during flu season, clinicians should consider influenza in patients with respiratory symptoms.
- The diagnosis of CAP is based primarily on clinical factors: a combination of signs and symptoms such as cough, fever, chills, sputum production, dyspnea, pleuritic pain, tachypnea, tachycardia, hypoxemia, consolidation or rales on auscultation, and a new infiltrate on chest imaging.
- Empiric outpatient treatment of a previously healthy patient with CABP should include either a macrolide or doxycycline. A fluoroquinolone or beta-lactam plus a macrolide should be used for patients with comorbid conditions.
- Several indices have been validated for use in deciding on inpatient vs outpatient treatment and whether a patient with pneumonia should be admitted to an intensive care unit.
TREATMENT
Multiple studies have shown that treatment of CAP in accordance with guidelines has led to improved clinical outcomes.21,68–70
How fast must antibiotics be started?
Based on studies that showed a lower mortality rate when antibiotics were started sooner, Medicare and Medicaid adopted a quality measure calling for starting antibiotics within 4 hours in patients being admitted to the hospital.50,71 However, several subsequent studies showed that the diagnosis of pneumonia is often incorrect and that rapid administration of antibiotics could lead to misdiagnosis, overuse of antibiotics, and a higher risk of Clostridium difficile infection.72,73
The current IDSA/ATS guidelines21 recommend that the first antibiotic dose be given while the patient is still in the emergency department, but do not give a specific time within which it should be given. Medicare and Medicaid later updated their quality measure to antibiotic administration within 6 hours.
Which antibiotics should be used?
The selection of antimicrobial agent depends upon the patient’s severity of illness and comorbid conditions.
Although most studies of combination antibiotic therapy have been retrospective and observational, they suggest that a macrolide (ie, one of the “mycins”) added to a beta-lactam antibiotic is beneficial, possibly by covering atypical organisms or via anti-inflammatory action.74–76 The choice of one antibiotic over another appears to be less important, and a recent Cochrane review concluded that there was no significant difference in efficacy among five antibiotic pairs studied.77
Empiric outpatient treatment of a previously healthy patient with CAP and no risk factors for drug-resistant S pneumoniae should include either a macrolide (azithromycin [Zithromax], clarithromycin [Biaxin], or erythromycin) or doxycycline. If the patient has a chronic comorbid condition such as heart, lung, liver, or renal disease, diabetes mellitus, alcoholism, malignancy, asplenia, or immunosuppression or has received antimicrobials within the preceding 3 months, then treatment should include either a respiratory fluoroquinolone (moxifloxacin [Avelox] or levofloxacin [Levaquin]) or a beta-lactam plus a macrolide.21
Overall, published data suggest that the survival rate is about the same with fluoroquinolone monotherapy as with beta-lactam plus macrolide combination therapy, and better than with beta-lactam monotherapy.78
Selection of antibiotics for inpatient treatment of CAP is influenced by severity of illness. Inpatients who do not require intensive care should be treated with either a respiratory fluoroquinolone or combination therapy with a beta-lactam (cefotaxime [Claforan], ceftriaxone [Rocephin], ampicillin, or ertapenem [Invanz]) plus a macrolide or doxycycline.21,76,79
If a specific microbiologic diagnosis is made, then treatment can be narrowed. However in certain cases, such as invasive pneumococcal infection, combination therapy may still be superior.80,81 For patients who need intensive care, treatment should always include a beta-lactam plus either azithromycin or a respiratory fluoroquinolone.21 In certain situations, additional antibiotics may be added as well, such as agents to treat Pseudomonas, community-acquired MRSA, or both.
Switching to oral therapy; short-course therapy
In the interest of avoiding unnecessary antibiotics, numerous studies have addressed the issue of an “early switch” to oral antibiotics and “short-course” therapy for CAP. In general, once clinically stable, patients with CAP, including bacteremic S pneumoniae pneumonia, can be safely switched to oral antibiotics.82
The issue of short-course therapy is more complicated, and the appropriate length of therapy for CAP is not well established. However, 5 days of levofloxacin 750 mg was shown to be as successful as 7 to 10 days of levofloxacin 500 mg.83 In another study, in patients who improved after 3 days of intravenous therapy for CAP, there was no difference in clinical outcome between those who were changed to oral therapy for 5 more days and those who received an oral placebo.84
Most patients who achieve clinical stability in the first week do not need prolonged antibiotic therapy. However, certain conditions, such as S aureus bacteremic pneumonia, complicated pneumonia, and pneumonia due to unusual organisms, may require prolonged treatment.
Other therapies
Additional therapies studied in patients with pneumonia include early mobilization, adjunctive corticosteroids, and statin drugs.
Early mobilization was shown in one study to decrease hospital length of stay without increasing adverse effects.85
Corticosteroids are not supported as a standard of care for patients with severe CAP according to current available studies.86,87 Furthermore, a randomized, controlled trial showed that prednisolone daily for a week did not improve outcomes in hospitalized patients with CAP, and it was associated with increased late failure.88
Statin trials under way. Several observational studies have suggested that statins might be beneficial in managing sepsis through their effects on endothelial cell function, antioxidant effects, anti-inflammatory effects, and immunomodulatory effects.89 However, a recent large prospective multicenter cohort study of hospitalized patients with CAP did not find evidence of a protective effect of statins on clinically meaningful outcomes in CAP or significant differences in circulating biomarkers.90 Several randomized trials of statin therapy in patients with both ventilator-associated pneumonia and CAP are under way.
INFLUENZA TREATMENT: MOST EFFECTIVE WITHIN 48 HOURS
Treatment with antiviral drugs is most effective if started within 48 hours after symptom onset, although some patients with confirmed influenza who are either not improving or who are critically ill may still benefit from treatment started later.
Treatment should be considered in patients with laboratory-confirmed or suspected influenza who are at risk of developing complicated influenza and in otherwise healthy patients who wish to reduce the duration of illness or who have close contact with patients who are at high risk of complications.
Antiviral medications are oseltamivir (Tamiflu), zanamivir (Relenza), and the adamantines amantadine (Symmetrel) and rimantadine (Flumadine).
Due to evolving viral resistance patterns, the choice of antiviral drug depends on the strain. Seasonal H1N1 is best treated with zanamivir or an adamantine, while pandemic 2009 H1N1 and H3N2 are best treated with zanamivir or oseltamivir. When strain typing is not available, empiric therapy should be with either zanamivir monotherapy or a combination of oseltamivir plus rimantadine. Influenza B viruses are resistant to adamantines and should be treated only with either zanamivir or oseltamivir.45
