Table 4.
Recommended antibiotic therapy for adults with ABRS
| Initial therapy | Calculated clinical efficacy(%)∗ | Calculated bacteriologic efficacy(%)∗ | Switch therapy options (no improvement or worsening after 72 hours)† |
|---|---|---|---|
| Mild disease‡ with no recent antimicrobial use (past 4–6 weeks)§ | |||
| Amoxicillin/clavulanate (1.75–4 g/250 mg/d)§, ∥ | 90–91 | 97–99 | |
| Amoxicillin (1.5–4 g/d)∥ | 87–88 | 91–92 | Gatifloxacin, levofloxacin, moxifloxacin |
| Cefpodoxime proxetil | 87 | 91 | Amoxicillin/clavulanate 4g/250 mg |
| Cefuroxime axetil | 85 | 87 | Ceftriaxone |
| Cefdinir | 83 | 85 | Combination Therapy¶ |
| β-Lactam allergic# | |||
| TMP/SMX | 83 | 84 | |
| Doxycycline | 81 | 80 | Gatifloxacin, levofloxacin, moxifloxacin |
| Azithromycin, clarithromycin, erythromycin | 77 | 73 | Rifampin plus clindamycin |
| Telithromycin∗∗ | 77 | 73 | |
| Mild disease‡ with recent antimicrobial use (past 4–6 weeks) or moderate disease‡ | |||
| Gatifloxacin/levofloxacin/moxifloxacin | 92 | 100 | |
| Amoxicillin/clavulanate (4 g/250 mg) | 91 | 99 | Reevaluate patient‡‡ |
| Ceftriaxone | 91 | 99 | |
| (Combination therapy)¶ | |||
| β-Lactam allergic# | |||
| Gatifloxacin, levofloxacin, moxifloxacin | 92 | 100 | Reevaluate patient†† |
| Clindamycin and rifampin†† | Reevaluate patient†† | ||
Clinical and bacterial efficacy (ie, clinical and microbiologic adequacy) is represented by the calculation from the Poole Therapeutic outcome model (see text) using the mean values of two surveillance data sets: the US component of the Alexander project (1998 to 2001) and SENTRY surveillance data. These values do not guarantee clinical success or failure.
When a change in antibiotic therapy is made, the clinician should consider the limitations in coverage of the initial antibiotic. The respiratory fluoroquinolones (gatifloxacin, levofloxacin, and moxifloxacin), ceftriaxone, and amoxicillin/clavulanate (4 g/250 mg) currently have the best coverage for both S pneumoniae and H influenzae. The terms mild and moderate are designed to aid in selecting antibiotic therapy.
The difference in severity of disease does not imply the presence or absence of antimicrobial resistance. Rather, this terminology indicates the relative degree of acceptance of possible therapeutic failure, and the likelihood of achieving spontaneous resolution of symptoms. The determination of disease severity lies with the clinician’s evaluation of the patient’s history and clinical presentation. Severe, life-threatening infection, with or without complications, is not addressed in these guidelines.
Prior antibiotic therapy within 4 to 6 weeks is a risk factor for infection with resistant organisms. Antibiotic choices should be based on this and other risk factors.
The total daily dose of amoxicillin and the amoxicillin component of amoxicillin/clavulanate can vary from 1.5 to 4 g/day. Lower daily doses (1.5 g/day) are more appropriate in mild disease in patients with no risk factors for infection with a resistant pathogen (including recent antibiotic use). Higher daily doses (4 g/day) may be advantageous in areas with a high prevalence of penicillin-resistant S pneumoniae or DRSP, for patients with moderate disease, for patients who may need better H influenzae coverage or for patients with risk factors for infection with a resistant pathogen. There is a greater potential for treatment failure or resistant pathogens in these patient groups.
Based on in vitro spectrum of activity; combination therapy using appropriate gram-positive and -negative coverage may be appropriate. Examples of combination therapy regimens include high-dose amoxicillin (4 g/day) or clindamycin plus cefixime, or high-dose amoxicillin (4 g/day) or clindamycin, plus rifampin. There is no clinical evidence at this time, however, of the safety or efficacy of these combinations.
Cephalosporins should be considered initially for patients with penicillin intolerance/non-Type I hypersensitivity reactions (eg, rash). TMP/SMX, doxycycline, macrolides, azalides, and ketolides are not recommended unless the patient is β-lactam allergic. Their effectiveness against the major pathogens of ABRS is limited, and bacterial failure of 20% to 25% is possible. A respiratory fluoroquinolone (eg, gatifloxacin, levofloxacin, moxifloxacin) is recommended for patients who have allergies to β-lactams or who have recently failed other regimens.
Telithromycin is not approved for use by the FDA (at the time of writing).
Reevaluation is necessary because the antibiotics recommended for initial therapy provide excellent activity against the predominant ABRS pathogens, including S pneumoniae and H influenzae. Additional history, physical examination, cultures, and/or CT scan may be indicated, and the possibility of other less common pathogens considered.
Rifampin is a well-known inducer of several cytochrome p450 isoenzymes and therefore has a high potential for drug interactions.