Antibiotics. Asmaa.A

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Antibiotics

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Antibiotics

Are antibacterial substances produced by various species of microorganisms (bacteria, fungi, and actinomycetes) that suppress the growth of other microorganisms or kill it.

Common usage often extends the term antibiotics to include synthetic antimicrobial agents, such as sulfonamides and quinolones.

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Classification and Mechanism of Action

Antimicrobial agents are classified based on chemical structure and proposed mechanism of action, as follows: (1) agents that inhibit synthesis of bacterial cell walls, including the β-lactam class (e.g., penicillins, cephalosporins, and carbapenems) and dissimilar agents such as cycloserine, vancomycin, and bacitracin;

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(2) agents that act directly on the cell membrane of the microorganism, increasing permeability and leading to leakage of intracellular compounds, including detergents such as polymyxin; polyene antifungal agents (e.g., nystatin and amphotericin B) which bind to cell-wall sterols.

(3) agents that disrupt function of 30S or 50S ribosomal subunits to reversibly inhibit protein synthesis, which generally are bacteriostatic (e.g., chloramphenicol, tetracyclines, erythromycin, clindamycin, streptogramins, and linezolid);

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(4) Agents that bind to the 30S ribosomal subunit and alter protein synthesis, which generally are bactericidal (e.g., the aminoglycosides).

(5) Agents that affect bacterial nucleic acid metabolism, such as the rifamycins (e.g., rifampin and rifabutin), which inhibit RNA polymerase, and the quinolones, which inhibit topoisomerases.

(6) the antimetabolites, including trimethoprim and the sulfonamides, which block essential enzymes of folate metabolism.

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* Infections are often categorized as community acquired are less severe and easier to treat or hospital acquired (nosocomial) more severe and difficult to manage because they often result from drug-resistant microorganisms and occur in people whose resistance to disease is impaired.

Drug-resistant strains of staphylococci, Pseudomonas, and Proteus are common causes of nosocomial infections

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Cell Wall Inhibitors:

The most important members of this group of drugs

are the beta-lactam antibiotics.

Beta-lactam antibacterial drugs inhibit synthesis of

bacterial cell walls by binding to proteins

(penicillin-binding proteins) in bacterial cell membranes. This

binding produces a defective cell wall that allows

intracellular contents to leak out, destroying the

microorganism.

They are inactive against organisms devoid of this

structure, such as mycobacteria, protozoa, fungi, and

viruses.

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Penicillins

Several natural penicillins can be produced depending on the chemical composition of the fermentation medium used to culture Penicillium.

Penicillin G (benzylpenicillin) has the greatest antimicrobial activity of these and is the only natural penicillin used clinically.

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Classification of the Penicillins

1.Penicillin G and its close congener penicillin V are highly active against sensitive strains of gram-positive cocci.

2.The penicillinase-resistant penicillins [methicillin, nafcillin, oxacillin, cloxacillin and dicloxacillin have less potent antimicrobial activity against microorganisms that are sensitive to penicillin G.

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3.Ampicillin, amoxicillin, and others make up a group

of penicillins whose antimicrobial activity is extended

to include such gram-negative microorganisms as

Haemophilus influenzae, E. coli, and Proteus mirabilis.

Frequently these drugs are administered with a

beta-lactamase inhibitor such as clavalanate or salbactam are

found with increasing frequency in clinical isolates of

these gram-negative bacteria.

4.The antimicrobial activity of (carbenicillin), and

ticarcillin

is

extended

to

include

Pseudomonas,

Enterobacter, and Proteus spp. These agents are inferior

to ampicillin against gram-positive cocci and Listeria.

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5.Mezlocillin, azlocillin, and piperacillin have excellent antimicrobial activity against Pseudomonas, Klebsiella, and certain other gram-negative microorganisms.

Adverse reactions

Penicillins are among the safest drugs, and blood levels are not monitored. However, the following adverse reactions may occur. 1. Hypersensitivity: 2. Diarrhea: 3. Nephritis: 4. Neurotoxicity. 5. Hematologic toxicities 6. Cation toxicity.

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Cephalosporins

The cephalosporins are beta-lactam antibiotics that are closely related both structurally and functionally to the penicillins.

Antibacterial spectrum

Cephalosporins have been classified as first, second, third, or fourth generation, based largely on their bacterial susceptibility patterns and resistance to beta-lactamases

• First generation: The first-generation cephalosporins act as

penicillin G substitutes. They are resistant to the

staphylococcal penicillinase and also have activity against Proteus mirabilis, E. coli, and Klebsiella pneumoniae.

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• Second generation: The second-generation cephalosporins display greater activity against three additional gram-negative organisms: H. influenzae, Enterobacter aerogenes, and some Neisseria species.

• Third generation: Third-generation cephalosporins have enhanced activity against gram-negative bacilli,

Ceftriaxone

or

cefotaxime

have become agents of choice in the treatment of meningitis.

Ceftazidime

has activity against P. aeruginosa.

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• Fourth generation: Cefepime is classified as a fourth-generation cephalosporin and must be administered parenterally. Cefepime has a wide antibacterial spectrum, being active against streptococci and staphylococci (but only those that are methicillin-susceptible). Cefepime is also effective against aerobic gram-negative organisms, such as enterobacter, E. coli, K. pneumoniae, P. mirabilis, and P. aeruginosa.

Adverse reactions

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Carbapenems

Carbapenems are synthetic beta-lactam antibiotics .Meropenem and ertapenem are the only drugs of this group currently available alone. While Imipenem is combined with cilastatin .

Antibacterial spectrum: The drug plays a role against gram-positive and gram-negative organisms, anaerobes, and P. aeruginosa.

*Note :Imipenem and meropenem are administered IV and penetrate well into body tissues and fluids, including the CSF when the meninges are inflamed. They are excreted by glomerular filtration.

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Monobactams

Aztreonam acts against aerobic gram-negative rods, including P. aeruginosa. It lacks activity against gram-positive organisms and anaerobes.

Aztreonam is relatively nontoxic, but it may cause phlebitis, skin rash, and occasionally, abnormal liver function tests. Thus, this drug may offer a safe alternative for treating patients who are allergic to penicillins and/or cephalosporins.

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Beta-Lactamase Inhibitors

Beta-Lactamase inhibitors, such as clavulanic acid, sulbactam, and tazobactam, contain a beta-lactam ring they bind to and inactivate beta-lactamases, thereby protecting the antibiotics that are normally substrates for these enzymes.

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PROTEIN SYNTHESIS INHIBITORS Tetracyclines

Mechanism of action

The drug binds reversibly to the 30S subunit of the bacterial ribosome, By this mechanism, bacterial protein synthesis is inhibited.

Antibacterial spectrum

As broad-spectrum, bacteriostatic antibiotics, the tetracyclines are effective against positive and gram-negative bacteria as well as against organisms other than bacteria

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Adverse effects Gastric discomfor.

Effects on calcified tissues Fatal hepatotoxicity

Phototoxicity

Vestibular problems Superinfections.

Contraindications:

Renally impaired patients should not be treated with any of the tetracyclines except doxycycline.

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Aminoglycosides

Used for treatment of serious infections due to aerobic gram-negative bacilli. However, because their use is associated with serious toxicities, they have been replaced to some extent by safer antibiotics, such as the third- and fourth-generation cephalosporins, the fluoroquinolones, and the carbapenems.

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Mechanism of action

Susceptible gram-negative organisms. The antibiotic then binds to the 30S ribosomal subunit prior to ribosome formation.

The aminoglycosides are effective against aerobic gram-negative bacilli, including Pseudomonas aeruginosa. To achieve an additive or synergistic effect, aminoglycosides are often combined with a beta-lactam antibiotic, or vancomycin, or a drug active against anaerobic bacteria.

Adverse effects Ototoxicity

Nephrotoxicity Allergic reactions

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Macrolides

Erythromycin was an alternative to penicillin in individuals who are allergic to beta-lactam antibiotics. The newer members of this family, like clarithromycin and azithromycin.

The macrolides bind irreversibly to a site on the 50S subunit of the bacterial ribosome, thus inhibiting the translocation steps of protein synthesis. Generally considered to be bacteriostatic, they may be bactericidal at higher doses.

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Erythromycin: This drug is effective against many of the same organisms as penicillin G therefore; it is used in patients who are allergic to the penicillins.

Clarithromycin: This antibiotic has a spectrum of antibacterial activity similar to that of erythromycin, but it is also effective against Haemophilus influenzae.

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Azithromycin: Although less active against streptococci and staphylococci than erythromycin. azithromycin is far more active against respiratory infections due to H. influenzae and Moraxella catarrhalis.

Azithromycin is now the preferred therapy for urethritis caused by Chlamydia trachomatis

Adverse effects Epigastric distress Cholestatic jaundice Ototoxicity.

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Chloramphenicol

It is active against a wide range of positive and gram-negative organisms.

The drug binds to the bacterial 50S ribosomal subunit and inhibits protein synthesis.

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Antimicrobial spectrum

Chloramphenicol, a broad-spectrum antibiotic, is active not only against bacteria but also against other microorganisms, such as rickettsiae. Pseudomonas aeruginosa is not affected. Chloramphenicol has excellent activity against anaerobes.

Adverse effects • Anemias