There are 3 major mechanisms of resistance to penicillins:
• Porin channel changes resulting in “blockage” (e.g., used by Pseudomonas spp. to resist carbapenems)
• Production of beta-lactamase (e.g., by H. influenzae and M. catarrhalis)
• Alteration in the penicillin-binding protein site (e.g., used by S. pneumoniae)
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Beta-lactamase Production
Production of beta-lactamase is one of the most important mechanisms of penicillin resistance. Several aerobic and anaerobic beta-lactamase producing bacteria (BLPB) occur in sinusitis.
• BLPB have been recovered from more than one third of patients with acute and chronic sinusitis
• In polymicrobial infection, BLPB may shield penicillin-susceptible organisms from the activity of penicillin, thereby contributing to their persistence.
• The ability of BLPB to protect penicillin-sensitive microorganisms has been demonstrated in vitro and in vivo.
• The phenomenon of “shielding” and the actual activity of the enzyme beta-lactamase were demonstrated in acutely and chronically inflamed sinus fluids. Antimicrobial therapy should be directed at the eradication of BLPB whenever present.
Beta-lactamase detected in four acute bacterial sinusitis aspirates obtained from patients treated with amoxicillin | ||||
Organism | Patient | |||
1* | 2* | 3 | 4 | |
S. pneumoniae | + | + | ||
M. catarrhalis (beta-lactamase positive) | + | + | ||
H. influenzae (beta-lactamase positive) | + | + | ||
Beta-lactamase activity in pus | + | + | - | + |
*Shielding of S. pneumoniae by beta-lactamase producers is evident in patients 1 and 2. Data from Brook et al.1996. | ||||
Beta-lactamase detected in four chronic bacterial sinusitis aspirates obtained from patients treated with amoxicillin | ||||
Organism | Patient | |||
1 | 2 | 3 | 4 | |
S. aureus BL (+) | + | + | ||
S. pneumoniae | + | |||
Peptostreptococcus spp. | + | + | ||
Propionibacterium acnes | + | |||
Fusobacterium spp. BL (+) | + | + | ||
Fusobacterium spp. BL (-) | + | + | ||
Prevotella spp. BL (+) | + | |||
Prevotella spp. BL (-) | + | + | + | |
Bacteroides fragilis group BL (+) | + | + | ||
Beta-lactamase activity in pus | + | + | + | + |
*Shielding is present in all cases. BL (+) = beta-lactamase–producing organism. Data from Brook et al. 1996. | ||||
• Oral antimicrobial agents effective against the aerobic BLPB in acute bacterial sinusitis include amoxicillin and clavulanic acid, the second- and third-generation cephalosporins, and the “newer” quinolones.
• Oral agents effective against BLPB in chronic bacterial sinusitis are the combination of amoxicillin and clavulanic acid, clindamycin, and metronidazole (effective only against anaerobes).
Gram stain of Streptococcus pneumoniae
Streptococcus pneumoniae Resistance
• S. pneumoniae is resistant to penicillins through changes in penicillin-binding proteins.
• The national rate of resistance has increased steadily in the past decade and is over 35% of all isolates.
• Approximately a third of the penicillin-resistant strains are currently intermediately resistant (minimal inhibitory concentration [MIC] of 0.12–1.0 mg/ml) and the rest are highly resistant (MIC 2.0 mg/ml).
• Penicillin-resistant strains are often also resistant to other antimicrobial agents, but they are generally susceptible to vancomycin, and the “newer” quinolones.
• Clindamycin, some of the oral second-generation cephalosporins ( e.g. cefuroxime-axetil and cefprozil), a high concentration of penicillin or amoxicillin are also effective in-vitro against most intermediately penicillin-resistant strains but not the highly resistant strains.
Cross-resistance of penicillin-resistant S. pneumoniae | ||
Antimicrobial agent | Cross-resistance (%) | |
Intermediately resistant* | Highly resistant† | |
Trimethoprim-sulfamethoxazole | 52 | 91.9 |
Tetracycline | 22.8 | 47.4 |
Macrolides | 49.8 | 80.4 |
Clindamycin | 13.1 | 25.3 |
Third-generation cephalosporins: | ||
Oral (cefixime, ceftibuten) | 60 | 95 |
Parenteral (ceftriaxone) | 5 | 10 |
Rifampin | 10 | 20 |
Levofloxacin | 2.2 | 2.2 |
*MIC 0.12-1.0 mg/mL. †MIC ³ 2.0 mg/mL. | ||
Treatment of sinus infection associated with the recovery of MRSA
• It is important to provide coverage against these organisms as well as other potential aerobic and anaerobic pathogens.
•Although vancomycin is considered the gold standard for therapy of MRSA infections, reports of increasing in -vitro resistance to vancomycin combined with reports of clinical failures underscore the need for alternative therapies.
• Older agents with favorable in vitro activity available in both oral and intravenous dose forms include trimethoprim-sulfamethoxazole and clindamycin.
•Newer treatment options of therapies for MRSA include linezolid, quinupristin-dalfopristin, daptomycin, and tigecycline.
Risk Factors for infection due to antimicrobial resistant bacteria
The observed increase in bacterial resistance to antibiotics is related to several risk factors. These include: Prior direct or indirect antibiotic exposure, including prophylaxis, daycare attendance, < 2 years of age, recent hospitalization, recurrent infection (especially at extreme ages), high prevalence of resistance in the community, winter season, and a smoker in family.
Antimicrobial susceptibility testing
