Beta-lactam antibiotics

Natural and semisynthetic penicillins

Penicillins are divided into natural and semisynthetic.

Natural penicillins The main representative is benzylpenicillin (penicillin G). It is active primarily 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 — penicillinases.

Semisynthetic penicillins They are produced by chemically attaching various radicals to 6-aminopenicillanic acid. This overcomes the shortcomings of natural drugs and broadens their spectrum of activity.

Classification of semisynthetic penicillins:

• Depot preparations (e.g., benzathine benzylpenicillin) — form a depot in the muscles and act for up to 4 weeks. Used for syphilis and rheumatic fever prophylaxis.
• Acid-resistant (phenoxymethylpenicillin) — suitable for oral administration as they are not destroyed in the stomach.
• Penicillinase-resistant (methicillin, oxacillin) — not destroyed by bacterial enzymes, but have a narrow spectrum of activity.
• Broad-spectrum drugs (ampicillin, amoxicillin).
• Antipseudomonal — carboxypenicillins (carbenicillin) and ureidopenicillins (piperacillin, azlocillin).
• Combined or protected — contain an antibiotic and a β-lactamase inhibitor (e.g., amoxicillin + clavulanic acid, ampicillin + sulbactam). Inhibitors bind bacterial enzymes, preventing them from destroying the main antibiotic.

Cephalosporins: generations and evolution

Cephalosporins are β-lactams with a broad spectrum of activity directed primarily against Gram-negative bacteria. Depending on their market release time, activity spectrum, and resistance to β-lactamases, they are divided into four generations. It is important to remember that newer generations do not replace, but complement previous ones.

1. 1st generation (cefazolin, cephalothin): active mainly against Gram-positive flora, but destroyed by β-lactamases.
2. 2nd generation (cefuroxime, cefaclor): possess greater activity against Gram-negative bacteria and better resistance to β-lactamases.
3. 3rd generation (cefotaxime, ceftazidime): demonstrate even higher efficacy against Gram-negative flora and have high resistance to bacterial enzymes.
4. 4th generation (cefepime): possess combined activity — work against Gram-positive microbes, certain Gram-negative bacteria, and Pseudomonas aeruginosa. Resistant to β-lactamases.

Carbapenems and monobactams

In addition to penicillins and cephalosporins, the group of β-lactam antibiotics includes two other important drug classes:

• Carbapenems (representative — imipenem). Feature the broadest spectrum of antimicrobial activity among all β-lactams. Furthermore, they are resistant to the action of destructive enzymes — β-lactamases.
• Monobactams (representative — aztreonam). Have a narrow yet very potent spectrum of activity. They are highly effective against Gram-negative bacteria, including Pseudomonas aeruginosa. Like carbapenems, monobactams are resistant to β-lactamases.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• The mechanism of β-lactam ring destruction by bacterial enzymes (penicillinases, β-lactamases)
• Pharmacokinetics of depot preparations (benzathine benzylpenicillin) and their role in the treatment of syphilis
• Properties of 6-aminopenicillanic acid as a basis for the synthesis of semisynthetic penicillins
• Special considerations for the use of carbapenems in severe infections

Other topics in the section "Chemotherapeutic Antimicrobial Drugs"

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