Chcooh

r—ch + 6-Aminopenicillanic acid

Penicilloic acids

FIGURE 44-1 Structure of penicillins and products of their enzymatic hydrolysis.

plasmids can be transferred between bacteria by conjugation. These enzymes can hydrolyze penicillins, cephalosporins, or both.

OTHER FACTORS THAT INFLUENCE THE ACTIVITY OF ß-LACTAM ANTIBIOTICS

Microorganisms adhering to implanted prosthetic devices (e.g., catheters, artificial joints, prosthetic heart valves) produce biofilms. Bacteria in biofilms are much less sensitive to antibiotic therapy, in part owing to decreased growth rates. The ß-lactam antibiotics are most active against bacteria in the logarithmic phase of growth and have little effect on microorganisms in the stationary phase. Similarly, intracellular bacteria that survive inside host cells generally are protected from the action of the ß-lactam antibiotics.

Classification of the Penicillins and Summary of Their Pharmacological Properties

Penicillins are classified according to their spectra of antimicrobial activity (Table 44-1).

1. Penicillin G and its close congener penicillin V are highly active against sensitive strains of gram-positive cocci but are readily hydrolyzed by penicillinase and therefore ineffective against most strains of S. aureus.

2. The penicillinase-resistant penicillins (methicillin [discontinued in the U.S.], nafcillin, oxacillin, cloxacillin [not marketed in the U.S.], and dicloxacillin) have less potent antimicrobial activity against microorganisms that are sensitive to penicillin G but are the agents of first choice for treatment of penicillinase-producing S. aureus and S. epidermidis that are not methicillin-resistant.

3. Ampicillin, amoxicillin, and others comprise a group of penicillins whose antimicrobial activity is extended to include such gram-negative microorganisms as Haemophilus influenzae, Escherichia coli, and Proteus mirabilis. Frequently these drugs are administered with a ß-lactamase inhibitor to prevent hydrolysis by broad-spectrum ß-lactamases that are found with increasing frequency in clinical isolates of these gram-negative bacteria.

4. The antimicrobial activity of carbenicillin (discontinued in the U.S.), its indanyl ester (carbenicillin indanyl), and ticarcillin includes Pseudomonas, Enterobacter, and Proteus spp. These agents are inferior to ampicillin against gram-positive cocci and Listeria monocytogenes and are less active than piperacillin against Pseudomonas.

5. Mezlocillin, azlocillin (both discontinued in the U.S.), and piperacillin have excellent antimicrobial activity against Pseudomonas, Klebsiella, and certain other gram-negative microorganisms. Piperacillin retains the activity of ampicillin against gram-positive cocci and L. monocytogenes.

Certain useful generalizations can be made. Following oral or parenteral administration, these agents distribute widely throughout the body. Therapeutic concentrations of penicillins are achieved

Chemical Structures and Major Properties of Various Penicillins

R—C—NH2_CH—CH C\ Penicillins are substituted 6-aminopenicillanic acids

Major Properties

Nonproprietary Name

Absorption after Oral Administration

Resistance to Penicillinase

Useful Antimicrobial Spectrum

Penicillin V

Methicillin

Penicillin G

Penicillin V

Methicillin

Oxacillin

Cloxacillin

Dicloxacillin

Variable (poor) No

Streptococcus species, * Enterococci,* Listeria, Neisseria meningitidis, many anaerobes (not Bacteroides fragilis),* spirochetes, Actinomyces, Erysipelothrix spp., Pasteurella multocida**

Good

Poor (not given orally)

Good

Indicated only for non-methicillin-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis. Compared to other penicillins, these penicillinase-resistant penicillins lack activity against Listeria monocytogenes and Enterococcus spp.

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