What are the main classes of antibiotics, such as penicillins (e.g. amoxicillin), macrolides (e.g. azithromycin), and cephalosporins (e.g. ceftriaxone)?

Main Classes of Antibiotics

Beta-Lactam Antibiotics

Beta-lactam antibiotics are characterized by the presence of a beta-lactam ring and exert their antibacterial effect by inhibiting bacterial cell wall synthesis, producing autolysis through binding to penicillin-binding proteins (PBPs) in the cell wall 1.

Penicillins

Penicillins are bicyclic ring compounds containing a 4-membered beta-lactam ring fused to a 5-membered thiazolidine ring 2.

Natural Penicillins:

• Benzylpenicillin (penicillin G) and penicillin V have potent activity against gram-positive pathogens, gram-negative cocci, some spirochetes and actinomycetes 2.
• Penicillin V remains the drug of choice for pharyngitis caused by group A streptococci 3.

Aminopenicillins:

• Amoxicillin and ampicillin have improved oral bioavailability and superior activity against Haemophilus influenzae, certain gram-negative bacilli, salmonellae, enterococci and Listeria monocytogenes 2.
• Amoxicillin is generally considered the most active of all oral beta-lactams against streptococci, including pneumococci, due to its intrinsic activity and excellent bioavailability 1.
• Amoxicillin is first-line therapy for acute otitis media 3.

Beta-Lactamase Inhibitor Combinations:

• Amoxicillin-clavulanate, ampicillin-sulbactam, ticarcillin-clavulanate, and piperacillin-tazobactam combine a penicillin with a beta-lactamase inhibitor 1.
• The beta-lactamase inhibitors (clavulanic acid, sulbactam, tazobactam) have no intrinsic antibacterial activity but confer greater stability to beta-lactamases and hence a broader spectrum of activity 2.
• Amoxicillin-clavulanate is most effective for animal and human bites 3.

Antistaphylococcal Penicillins:

• Methicillin, nafcillin, oxacillin, and flucloxacillin are penicillinase-resistant and are the principal antistaphylococcal treatments 1, 2.

Antipseudomonal Penicillins:

• Ureidopenicillins (piperacillin, ticarcillin) have better activity against Pseudomonas aeruginosa while retaining activity against gram-negative and gram-positive bacteria, including enterococci and anaerobes 2.

Cephalosporins

Cephalosporins have been modified to broaden antimicrobial spectrum and increase stability in the presence of beta-lactamases 1.

First-Generation Cephalosporins:

• Examples include cefazolin (parenteral), cephalexin, cefadroxil, and cefprozil (oral) 1, 4.
• Indicated for surgical prophylaxis and treatment of most staphylococcal and streptococcal infections in penicillin-allergic patients 4.
• Bactericidal against most gram-positive cocci and some gram-negative bacilli 4.

Second-Generation Cephalosporins:

• Examples include cefuroxime (oral and parenteral), cefoxitin, and cefaclor 1.
• Have increased activity against gram-negative organisms compared to first-generation agents 1.

Third-Generation Cephalosporins:

• Examples include ceftriaxone, cefotaxime, ceftazidime, cefixime, cefpodoxime, and cefdinir 1.
• Ceftriaxone and cefotaxime have excellent activity against Streptococcus pneumoniae and gram-negative bacilli but have no activity against anaerobic bacteria, Pseudomonas aeruginosa, Enterococcus species, or atypical organisms 5, 6.
• Ceftazidime has antipseudomonal activity but must be combined with penicillin G for coverage of S. pneumoniae 1.
• Activity against gram-negative bacilli increases from first- to third-generation drugs 4.

Important Cephalosporin Limitations:

• Cephalosporins are inherently less active than penicillin/amoxicillin against S. pneumoniae—many have baseline MICs fourfold higher than amoxicillin 1.
• No cephalosporin is active against enterococci 1, 4.
• Treatment of Bacteroides fragilis and Pseudomonas aeruginosa infections is not entirely satisfactory with currently available cephalosporins 4.

Carbapenems

• Examples include imipenem, meropenem, ertapenem, and doripenem 1.
• Carbapenems (imipenem, meropenem, ertapenem) are the most active beta-lactams against penicillin-resistant S. pneumoniae 1.
• Ertapenem (group 1 carbapenem) lacks antipseudomonal activity, while imipenem and meropenem (group 2 carbapenems) cover Pseudomonas 1.
• Carbapenems are the drug of choice for extended-spectrum beta-lactamase (ESBL) producers 1.

Macrolides and Azalides

Macrolides have a similar spectrum of antimicrobial activity to erythromycin and are valuable alternatives to penicillins and cephalosporins 7.

Erythromycin

• The original macrolide with activity against gram-positive organisms and atypical pathogens 1, 7.
• Less active than newer macrolides against H. influenzae and Moraxella catarrhalis 7.

Clarithromycin

• Much better activity than erythromycin against H. influenzae and M. catarrhalis, making it a better choice for community-acquired pneumonia 7.
• Clarithromycin is the macrolide of choice for treatment and prophylaxis of Mycobacterium avium complex (MAC) in AIDS patients 7.
• Preferred for Helicobacter pylori treatment 7.

Azithromycin

• More active than erythromycin against many gram-negative pathogens including H. influenzae, H. parainfluenzae, M. catarrhalis, Neisseria gonorrhoeae, Ureaplasma urealyticum, and Borrelia burgdorferi 8.
• Marginally less active than erythromycin against gram-positive organisms, though this is of doubtful clinical significance 8.
• Serum concentrations are lower than erythromycin, but tissue concentrations exceed those of erythromycin due to extensive intracellular distribution 8.
• Long terminal elimination half-life allows single-dose or once-daily dosing 8.
• Preferred macrolide for Chlamydia trachomatis infections and effective for prophylaxis of MAC 7.
• Azithromycin is more active in vitro than clarithromycin against H. influenzae 1.

Common Macrolide Characteristics:

• Macrolides are preferred for atypical pathogens (Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella species) 1.
• Erythromycin-resistant organisms are also resistant to azithromycin and clarithromycin 8.
• Activity is unaffected by beta-lactamase production 8.

Fluoroquinolones

Respiratory fluoroquinolones (levofloxacin, moxifloxacin, gemifloxacin) have the greatest in vitro activity against predominant respiratory pathogens among oral agents 1.

• Levofloxacin, moxifloxacin, and gatifloxacin have 99% activity against S. pneumoniae based on pharmacokinetic/pharmacodynamic breakpoints 1.
• Ciprofloxacin is appropriate for Legionella and most gram-negative bacilli including H. influenzae but is not a first-line choice for penicillin-susceptible strains 1.
• Fluoroquinolones are preferred for Legionella species infections 1.
• Antipseudomonal fluoroquinolones (ciprofloxacin, levofloxacin 750 mg daily) are used in combination therapy for P. aeruginosa 1.

Other Important Antibiotic Classes

Lincosamides

• Clindamycin has activity against gram-positive cocci and anaerobes 1.
• Clindamycin affects toxin production and may be considered for necrotizing pneumonias associated with Panton-Valentine leukocidin-producing Staphylococcus aureus 1.

Tetracyclines

• Doxycycline is effective against atypical pathogens (Mycoplasma, Chlamydophila, Coxiella burnetii) 1.
• Tetracyclines are alternatives for penicillin-allergic patients 1.

Sulfonamides/Trimethoprim

• Trimethoprim-sulfamethoxazole has activity against S. pneumoniae (63-75% based on PK/PD breakpoints), H. influenzae (70-85%), and MRSA 1.

Oxazolidinones

• Linezolid is effective against MRSA and affects toxin production 1.

Glycopeptides

• Vancomycin and teicoplanin are used for MRSA and other resistant gram-positive infections 1.

Nitroimidazoles

• Metronidazole provides anaerobic coverage, particularly Bacteroides fragilis and other anaerobic gram-negative bacilli 1, 5.
• Metronidazole must be combined with other antibiotics as it has no activity against aerobic bacteria 1, 5.