Previously Healthy Patients Without Comorbidities
Key Points:
- Azithromycin is usually adequate therapy for younger and otherwise healthy patients who have not received these antimicrobials in the previous 3 months.
- Erythromycin and clarithromycin are not recommended as first-line drugs, and safer and better tolerated antimicrobials should be used.
- Doxycycline, although effective against the "atypical" pathogens, is increasingly less useful in Streptococcus pneumoniae infections due to resistance.
- For previously healthy patients without comorbidities who have received antimicrobials in the previous 3 months, the possibility of resistance to those antimicrobials is a potential concern. Thus, if the patient has recently received a macrolide, a recommended respiratory fluoroquinolone is a good option.
Azithromycin is usually adequate therapy for younger and otherwise healthy patients who have not received these antimicrobials in the previous 3 months. Azithromycin provides adequate coverage for most Streptococcus pneumoniae, Haemophilus influenzae, and the "atypical" pathogens: Mycoplasma, Chlamydia pneumoniae, and Legionella. Consistent with IDSA guidelines, the workgroup recommends use of azithromycin rather than a fluoroquinolone in this setting, to minimize overuse and development of quinolone resistance.
Erythromycin has been used for CAP in the past, but requires more frequent dosing and has a higher degree of gastrointestinal side effects than the newer agents. Because of a large number of drug interactions and a recent report suggesting an increased risk of sudden cardiac death (presumably due to QT prolongation) when used in combination with drugs that can increase their serum levels, erythromycin and clarithromycin are not recommended as first-line drugs, and safer and better tolerated antimicrobials should be used. [Conclusion Grade II: See Conclusion Grading Worksheet B -- Annotation #10 (Erythromycin and Clarithromycin) in the original guideline document].
Doxycycline, although effective against the "atypical" pathogens, is increasingly less useful in S. pneumoniae infections due to resistance. It can be used, but caution should be exercised and another agent substituted if the patient does not show prompt response.
For previously healthy patients without comorbidities who have received antimicrobials in the previous 3 months, the possibility of resistance to those antimicrobials is a potential concern. Thus, if the patient has recently received a quinolone, azithromycin plus high dose amoxicillin or amoxicillin-clavulanate would be a good treatment option. Similarly, if the patient has recently received a macrolide, a respiratory quinolone (moxifloxacin or levofloxacin) is a good option.
Among the quinolones, this work group suggests moxifloxacin may be preferred over levofloxacin. Pharmacodynamic parameters (AUC/MIC) favor moxifloxacin for S. pneumoniae; additionally, moxifloxacin concentrations exceed the mutant prevention concentration and may be less likely to cause resistance. There is evidence that levofloxacin-induced first-step mutants of S. pneumoniae may not be detected with current susceptibility testing methods and use of levofloxacin in this setting can potentially lead to high level resistance with cross-resistance to other quinolones.
Due to a lack of randomized comparative trials demonstrating clear superiority of moxifloxacin and the availability of several studies supporting levofloxacin efficacy, levofloxacin has been included in the guideline as an option. Note that ciprofloxacin does not have adequate coverage for S. pneumoniae and should not be used in this setting. Gemifloxacin was recently U.S. Food and Drug Administration (FDA) approved but has a higher incidence of rash and has been less studied than other options. Gatifloxacin is contraindicated in diabetic patients due to reports of hypo and hyperglycemia. Thus, the use of gemifloxacin and gatifloxacin has not been included in the guideline.
If the patient has recently received a recommended respiratory fluoroquinolone, azithromycin plus high dose amoxicillin or amoxicillin-clavulanate would be good treatment options. High dose amoxicillin or amoxicillin-clavulanate used for respiratory infections can overcome intermediate resistance seen in S. pneumoniae, while the macrolide conveys activity for atypical organisms.
Telithromycin is a new ketolide antibiotic recently approved by the FDA for treatment of mild-moderate community-acquired pneumonia, including macrolide resistant strains of S. pneumoniae. It also has activity against
H. influenzae, Moraxella catarrhalis, and atypical organisms. Similar to erythromycin, it has numerous drug interactions and should be avoided in patients predisposed to prolongation of the QT interval. In addition, it can cause visual disturbances in some patients and should be avoided in patients with myasthenia gravis. It is also fairly expensive and for now should be reserved as a second-line agent where intolerance to alternatives exists or resistant organisms are suspected. Until further safety and efficacy data are available, the workgroup did not include it in the algorithm.
Most recently the FDA issued a statement that it is continuing to evaluate the issue of liver problems in association with use of telithromycin in order to determine if labeling changes or other actions are warranted. As a part of this, the FDA is continuing to work to better understand the frequency of liver-related adverse events reported for approved antibiotics, including telithromycin.
See Appendix A, "Pneumonia Antibiotics," in the original guideline document for detail on doses and comparative costs.
Comment: Antibiotic therapy may need to be tailored to known local antibiotic resistance patterns.
Evidence supporting this recommendation is of classes: C, D, R