Natural and Semisynthetic Penicillins
Penicillins are divided into natural and semisynthetic agents.
Natural Penicillins The primary representative is benzylpenicillin (penicillin G). It is primarily active against gram-positive bacteria. However, natural penicillins have significant drawbacks: they are rapidly eliminated from the body, destroyed in the acidic environment of the stomach, and inactivated by bacterial enzymes called penicillinases.
Semisynthetic Penicillins These are produced by chemically attaching various side chains to 6-aminopenicillanic acid (6-APA). This modification overcomes the limitations of natural agents and broadens the antimicrobial spectrum.
Classification of semisynthetic penicillins:
- Repository (Depot) preparations (e.g., benzathine benzylpenicillin) — form a depot in muscle tissue, providing prolonged action for up to 4 weeks. They are used in syphilis treatment and rheumatic fever prophylaxis.
- Acid-stable penicillins (phenoxymethylpenicillin) — suitable for oral administration as they resist gastric acid degradation.
- Penicillinase-resistant penicillins (methicillin, oxacillin) — resistant to bacterial beta-lactamases, but possess a narrower spectrum of activity.
- Broad-spectrum penicillins (ampicillin, amoxicillin).
- Antipseudomonal penicillins — carboxypenicillins (carbenicillin) and ureidopenicillins (piperacillin, azlocillin).
- Combined or protected penicillins — contain an antibiotic combined with a β-lactamase inhibitor (e.g., amoxicillin + clavulanic acid, ampicillin + sulbactam). Inhibitors bind to bacterial enzymes, preventing them from destroying the core antibiotic.
Cephalosporins: Generations and Evolution
Cephalosporins are β-lactams with a broad spectrum of activity targeting predominantly gram-negative bacteria. Based on their chronological development, spectrum of activity, and resistance to β-lactamases, they are classified into four generations. Newer generations do not replace older ones but rather expand the spectrum of coverage.
- 1st Generation (cefazolin, cephalothin): highly active against gram-positive flora, but susceptible to β-lactamases.
- 2nd Generation (cefuroxime, cefaclor): exhibit greater activity against gram-negative bacilli and enhanced resistance to β-lactamases.
- 3rd Generation (cefotaxime, ceftazidime): show even higher efficacy against gram-negative flora (including Pseudomonas aeruginosa for ceftazidime) and strong resistance to bacterial enzymes.
- 4th Generation (cefepime): possess combined activity — effective against gram-positive microbes, a wide range of gram-negative bacteria, and Pseudomonas aeruginosa. Highly resistant to β-lactamases.
Carbapenems and Monobactams
In addition to penicillins and cephalosporins, the β-lactam antibiotic family includes two other critical classes:
- Carbapenems (representative: imipenem). They feature the broadest spectrum of antimicrobial activity among all β-lactam classes. Furthermore, they are highly resistant to degradation by most β-lactamases.
- Monobactams (representative: aztreonam). They possess a narrow, highly targeted spectrum of activity. They are exceptionally effective against aerobic gram-negative bacteria, including Pseudomonas aeruginosa. Like carbapenems, monobactams are resistant to β-lactamases.