Antibiotics (Properties, Administration, Interactions) - Posokhova K.A., Viktorov O.P. 2005

Glycopeptide, lipopeptide, and polypeptide antibiotics
Glycopeptide antibiotics

Glycopeptide Antibiotics include vancomycin, ristomycin, teicoplanin, and daptomycin.

MECHANISM OF ACTION: inhibition of peptidoglycan synthesis, which is a structural component of the Introduction/37.html">Bacterial Cell wall. Glycopeptides exhibit a bacteriostatic effect against enterococci, coagulase-negative staphylococci, and certain streptococci, and a bactericidal effect against other microorganisms.

Spectrum of antibacterial activity. One of the most valuable properties of this group of antibiotics is their high activity against multidrug-resistant pathogens (staphylococci, enterococci, pneumococci, meningococci, corynebacteria), and most importantly, against methicillin-resistant (MRS) and coagulase-negative (MRCNS) staphylococcal strains.

Over the past decade, the proportion of purulent Infections caused by Gram-positive microorganisms has been rapidly increasing, notably MRS (S. aureus) and MRCNS (S. epidermidis, S. saprophyticus, S. pyogenes, etc.). These pathogens exhibit multiple resistances to Major Groups of modern antibiotics (beta-lactams, Tetracyclines, Aminoglycosides, macrolides) and often show low susceptibility to fusidic acid and rifampicin. The isolation rate of MRS and MRCNS varies across different inpatient facilities from 6% to 50%. Methicillin-resistant staphylococci are frequent causative agents of severe hospital-acquired infections (generalized wound infection, angiogenic Sepsis, valve replacement endocarditis, etc.), particularly in intensive care units and cardiothoracic surgery departments.

Another group of microorganisms whose role in causing severe nosocomial infections (urosepsis, angiogenic sepsis, endocarditis, etc.) has sharply increased nowadays is enterococci: E. faecalis and E. faecium. These microorganisms possess intrinsic resistance to most antibiotic groups.

Glycopeptide antibiotics remain the only Class of agents that maintain high activity against multi-resistant staphylococci and enterococci, proving effective in treating infections caused by them. However, in foreign hospitals, the isolation rate of vancomycin-resistant enterococci (VRE) exceeds 10% and shows an upward trend.

Bacteria also susceptible to glycopeptide antibiotics include Listeria monocytogenes and most Corynebacterium species, including C. jeikeium (one of the causative agents of opportunistic infections in AIDS).

Among anaerobes, most Clostridium species are susceptible to these antibiotics, including C. perfringens, C. difficile, and Propionibacterium acnes. These antibiotics are inactive against Gram-negative bacteria.

The susceptibility criteria of microorganisms to vancomycin are as follows (MIC):

- for staphylococci and enterococci: < 4 mg/L - susceptible, < 8-16 mg/L - intermediate, > 32 mg/L - resistant;

- for strepto- and pneumococci: 1 mg/L - susceptible.

Susceptibility criteria for teicoplanin (MIC):

- for staphylococci and enterococci: < 8 mg/L - susceptible, < 16 mg/L - intermediate, > 32 mg/L - resistant;

- for strepto- and pneumococci: < 8 mg/L - susceptible.

Pharmacokinetics. Vancomycin penetrates well into Tissues and

fluids, with limited penetration into the CEREBROSPINAL FLUID. T_1/2 is 6 hours. It is administered via intravenous infusion (over at least 1 hour) 2-3 times daily.

In severe purulent-septic conditions, teicoplanin is initially administered intravenously at a dose of 12 mg/kg three times at 12-hour intervals, followed by intravenous (or intramuscular) administration at the same dose once daily. These antibiotics are prescribed orally solely for the Treatment of pseudomembranous colitis: vancomycin at 2 g daily for 10-14 days; teicoplanin at 100 mg twice daily for 10 days or 50 mg four times daily for 7 days.

Indications for use. Glycopeptides are used for infections of any localization caused by microorganisms that are multiply resistant to Other Antibiotics:

- penicillin-resistant pneumococci (meningitis);

- methicillin-susceptible staphylococci (in case of allergy to beta-lactam antibiotics, particularly Penicillins and Cephalosporins);

- methicillin-resistant staphylococci;

- E. faecium;

- E. faecalis (ampicillin-resistant strains), including in the treatment of infective endocarditis (in combination with gentamicin);

- penicillin-resistant pneumococci (in the treatment of meningitis).

Glycopeptide antibiotics are also indicated for infections involving shunts, Valves, and catheters (catheter-associated sepsis, post-traumatic or postoperative Purulent meningitis, infective endocarditis).

They are used for enterocolitis caused by staphylococci, enterococci, or clostridia (pseudomembranous colitis).

Side effects. Severe complications, which are more common with prolonged (exceeding 10 days) administration of high doses of glycopeptides, include ototoxicity and nephrotoxicity. The risk of nephrotoxic effects also increases in patients with a history of renal disease, congestive Heart Failure, hypovolemia, concurrent use of glycopeptides with other potentially nephrotoxic drugs, and in elderly and senile patients. To prevent this complication, glycopeptides should be prescribed taking creatinine clearance into account; Kidney function (diuresis, serum creatinine concentration) must be monitored during treatment, and Blood drug concentrations should be monitored whenever possible (the permissible level is no more than 50 mg/L). To prevent the ototoxic effects of glycopeptides—which may manifest as vestibular disorders, reversible Hearing loss, or permanent deafness—they must not be combined with other ototoxic agents.

Rapid intravenous administration of glycopeptides may lead to thrombophlebitis (to prevent this, the intravenous infusion should last at least one hour), while intramuscular administration causes pain at the injection site.

Glycopeptide therapy may be associated with "red man syndrome" ("red neck syndrome"): itching and flushing of the face and upper torso, pruritus, angioedema, bronchospasm, hypotension, chest pain, and tachycardia. These symptoms are caused by histamine release from mast Cells. It occurs upon rapid administration of glycopeptides or when they are used concomitantly with local anesthetics.

Allergic reactions during glycopeptide treatment cannot be excluded, including rashes, urticaria, fever, and, rarely, anaphylactic Shock. Laboratory abnormalities may be observed, such as leukopenia, eosinophilia, thrombocytopenia, and elevated transaminase levels. Regardless of the route of administration, these drugs may cause nausea, vomiting, and diarrhea.

Although there are no reports of teratogenic effects from glycopeptides, their use is not recommended in pregnant or lactating women unless strictly indicated for life-saving reasons. This is due to the potential risk of toxic effects on the fetus and newborn (as they readily cross the Placenta and pass into breast milk).

Interactions. The combination of glycopeptides with aminoglycosides or rifampicin produces a synergistic antibacterial effect. At the same time, the risk of nephrotoxicity increases when they are combined with aminoglycosides, amphotericin B, polymyxin, cyclosporine, or loop Diuretics; the risk of ototoxicity increases when combined with aminoglycosides or loop diuretics (furosemide, ethacrynic acid). Vancomycin and heparin are pharmaceutically incompatible and therefore must not be combined in infusion solutions. The results of interactions between glycopeptides and certain medicinal products are presented in Table 34.

Table 34. Interactions of glycopeptide antibiotics (vancomycin and teicoplanin) with other drugs (V.P. Yakovlev, S.V. Yakovlev et al., 2003)