Antibiotic resistance is an important consideration in the management of CARTIs. There is little doubt that widespread use of antibiotics leads to in vitro bacterial resistance.18-20 However, because clinical success has been observed in the presence of pathogens with low-level resistance, there is some debate as to whether low-level antibiotic resistance has a significant effect on clinical outcomes.18,21-29 Even so, the US Centers for Disease Control and Prevention has determined that people who attend or work at child-care centers and those who recently used antimicrobial agents are at increased risk for infection with drug-resistant S pneumoniae.30 Moreover, the WHO has stated that infection with resistant pathogens prolongs illness and increases the probability of a fatal outcome.31
Several surveillance programs that monitor antibiotic resistance patterns—including the Alexander Project32 and Tracking Resistance in the United States Today (TRUST)33-36 —have confirmed widespread resistance to antibiotics commonly used to treat CARTIs in the United States. β-Lactam resistance due to penicillin-binding protein changes in S pneumoniae has increased significantly over the past decade. Generally, more than 30% of S pneumoniae are now resistant to penicillins and macrolides (including azithromycin and clarithromycin, the ‘advanced’ agents in this group). A smaller number (6%) are resistant to amoxicillin/clavulanate, although this appears to be a result of in vitro test parameters involving primarily strains with high-level β-lactam resistance. Some cephalosporins also show greater activity than penicillin against intermediately susceptible S pneumoniae, but are not effective against highly resistant strains. In contrast, fewer than 1% of all pneumococci are resistant to newer fluoroquinolones (the so-called respiratory fluoroquinolones, such as gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin) and the ketolide telithromycin.
The prevalence of β-lactamase–producing strains of H influenzae appears to have leveled off. Approximately 30% of H influenzae strains are resistant to ampicillin, while fewer than 1% are resistant to amoxicillin/clavulanate, cefuroxime, macrolides, and newer fluoroquinolones.
More than 90% of M catarrhalis isolates produce β-lactamase, thereby conferring resistance to ampicillin and amoxicillin.
Significant geographical variation in resistance has been observed. The prevalence of penicillin-resistant S pneumoniae ranges from 8% in New England to 25% in the South Atlantic, while ampicillin-resistant H influenzae is seen most often in New England (35%) and least often in the Rocky Mountain region (24%).33,34,36 Significant differences within a community also have been observed.37 Thus, knowledge of local resistance patterns is necessary. This information generally is available from local hospitals, although such data may be more reflective of nosocomial pathogens, or state health departments.
Community-acquired pneumonia
The 2003 guidelines of the IDSA give advanced macrolides and respiratory fluoroquinolones a prominent role in the management of community-acquired pneumonia (TABLE 1).5 The IDSA reviewed data from more than 150 clinical trials conducted in adults over 15 years. The IDSA panel acknowledged the increasing in vitro resistance of S pneumoniae to the macrolides, but noted that reports of clinical failure have not paralleled this. The panel also pointed out the significantly lower rates of resistance to the respiratory fluoroquinolones and expressed concern that abuse of these agents could lead to increased resistance by S pneumoniae.
In a previously healthy person who has not taken an antibiotic in the last 3 months, the IDSA recommends a macrolide or doxycycline as first-line therapy, whereas a fluoroquinolone, high-dose amoxicillin/clavulanate, or a macrolide plus high-dose amoxicillin should be used if an antibiotic has been taken during the last 3 months. Patients with a significant comorbidity can be treated with a fluoroquinolone without regard to recent antibiotic use. Alternatively, a macrolide can be used alone in patients who have not taken an antibiotic in 3 months, but otherwise must be used in combination with high-dose amoxicillin. High-dose amoxicillin/clavulanate or cefpodoxime, cefprozil, or cefuroxime can be used in those with a significant comorbidity and recent antibiotic use.
TABLE 1
Initial empiric therapy in outpatients with community-acquired pneumonia
Clinical characteristics
No recent antibiotic therapy
Antibiotics during past 3 months
Previously healthy
Azithromycin, clarithromycin, or erythromycin
Doxycycline
Gatifloxacin, gemifloxacin, levofloxacin, or moxifloxacin
A panel of primary care physicians and specialists convened by the Canadian Thoracic Society (CTS) reviewed nearly 400 published articles on acute bacterial exacerbations of chronic bronchitis, including evidence-based reviews such as the Cochrane Database. The 2003 CTS guidelines recommend that treatment be based on the risk for treatment failure (TABLE 2).8
