Antibiotics are naturally occurring substances produced by a fungus or bacteria

Used to treat bacterial infections

Alternate Forms

Synthetic Totally manufactured or artificial

Semi-synthetic compounds • Naturally occurring substances that have been chemically

altered

Bacteriocidal

› Kills the bacteria Kill bacteria

Most useful in situations when host defenses cannot control pathogen

Bacteriostatic

› Inhibit microbial growth Inhibit bacterial growth

depend on host immunity

Spectrum of activity Antimicrobials vary with respect to

range of organisms controlled Narrow spectrum

Work on narrow range of organisms

Gram-positive only OR Gram-negative only

Advantage: effects pathogen only

Disadvantage: requires identification of pathogen

Broad spectrum Advantage: Work on broad range of organisms

Disadvantage : disruption of normal flora

Empirical therapy Initiation of therapy prior to organism ID

Additive Effects

› Combining two antimicrobials causes twice the effect of the two drugs by themselves

Indifference

› No effect of combining antimicrobial therapies

Synergy

› Combined effect is greater than the two individual effects added together

Antagonism

› One drug counteracts the other

Synergism occurs when the effect of two drugs together is greater than the effect of either alone. › E.g. Sulfamethoxazole and trimethoprim

› Penicillin with beta-lactamase inhibitor (clav. acid)

› Alcohol and sleeping pills

Antagonism occurs when the effect of two drugs together is less than the effect of either alone. › E.g. Ibuprofen (anti-diuretic properties) + diuretic

Adverse effects Allergic reactions

Toxic effects

Suppression of normal flora

Antimicrobial resistance

What is the targeted bacteria?

Where is it located? Can the antimicrobial reach that site in sufficient concentration?

Can the antimicrobial be retained in the body long enough to be effective?

What are the side effects? How is it excreted?

What is the cost?

Mechanisms of action › Effects on Cell Wall Synthesis

› Interruption of Cell Membrane Structure and Function

› Inhibition of Protein Synthesis

› Inhibition of Folate Synthesis

› Interference with Nucleic Acid Metabolism

Cell wall protects the bacteria cytoplasmic membrance

Cell wall primarily composed of a peptidoglycan layer

Inactivating or interfering with enzymes that synthesize the cell wall can destroy the bacteria

› Effect cell wall synthesis

› Sizable portion of antibacterial agents used today

› Includes penicillins, monobactams, and carbapenems, and cephalosporins

Bind specific enzymes known as penicillin-binding proteins (PBPs)

› PBPs mediate peptidoglycan cross-linking

If PBPs are bound by the beta-lactam, the cross-linking of the cell wall is incomplete, results in cell death

Penicillins › Simple penicillins are effective against many streps, Neisseria,

Pasteurella, and a number of anaerobes

Monobactams › Limited to aerobic Gram negative bacilli

Carbapenems › Broadest antimicrobial spectrum › Effective against gram positive and negative organisms, and

anaerobes › Resistant to beta-lactamase

Cephalosporins

› Classified by their spectrum of activity and are spoken of in terms of “generations

First-generation › Have good GP and GN activity

Second-generation › Have better GN, and anerobes activity

Third-generation › Better with Enterobacteriaceae and Pseudomonas spp.

Fourth –generation › Effective against GNR that are resistant to 3rd generation

cephalosporins

Fifth-generation › Spectrum of activity includes the 3rd and 4th generation

Combination of a β-lactam and a β-lactamase inhibitor act in synergy › Bind to beta-lactamase produced by certain

microbes

β-Lactamase Inhibitors › Offer no antibacterial activity by themselves Examples include: clavulanic acid, sulbactam,

tazobactam

Glycopeptides

› Bind certain amino acids and inhibit eznymes in the developing peptidoglycan layer

› Vancomycin Most clinically important

Effective against MRSA, other GP organisms, and organisms resistant to penicillin

Damages the cytoplasmic membrane of the organism

Bacitracin

› Prevents the addition of peptidogylcan to the cell wall

› Disrupts the cell membrane

› Primarily effective against GP organism

› Because of toxicity, these are limited to topical medications (ex. Neosporin, etc.)

Polymyxins › Bind to outer surface of cell membrane,

affecting phospholoid

› Leads to leakage of intracellular contents and cell death

› Effective against gram negative bacteria

These antimicrobials bind to ribosomal subunits

This binding is either irreversible, resulting in cell death(bactericidal), or reversible, resulting in bacteriostatic effects

Antibiotics › Aminoglycosides, tetracyclines, macrolides,

clindamycin chloramphennicol.

Aminoglycosides › Bactericidal

› Used primarily against GN bacteria

Tetracyclines › Bacteriostatic

› Broad spectrum

› Effective against GP and GN organisms

› Tetracycline is NOT used in young children or in pregnancy, as it affects tooth and bone development

Macrolides

› Bacteriostatic

› Broad spectrum

› Effective against GP and some GN organisms, spirochetes, Mycoplasma, Legionella, and Chlamydia

› Agents include: erythromycin, azithromycin, clarithromycin

Clindamycin

Bacteriostatic Excellent activity against aerobic

GP organisms Extremely potent against

anaerobes “D” test Detects resistance to clindamycin

based on past treatment with erythromycin

Chloramphenicol

Bacteriostatic

Has broad activity but is extremely toxic

Interfere with either DNA or RNA metabolism

Inhibit enzymes required in the replication process

Agents: quinolones/fluoroquinolones, rifamycins

RNA Synthesis Interference

Rifampicin

Mainly used for M. tuberculosis and M. avium complex

Has a broad spectrum of activity

DNA Synthesis Interference Quinolones/Fluoroquinolones Bactericidal Used to treat GN organisms Agents- ciprofloxacin, levofloxacin

Metronidzole Activates under anaerobic conditions Effective against anaerobes and protozoa,

bacterial vaginosis Nitrofurantoin Used against GP and GN organisms Concentrates well in urine

Modify target

› If target is altered, reduction or prevention of antimicrobial binding can occur

› End result- antimicrobial is ineffective › How does the microbe modify the target? Chromosomal mutations Transposons Plasmids

Inactivation of Antimicrobial Agent › Genes of the microbe encode enzymes that

convert active antimicrobial agents to an inactive form Encoding of enzymes via chromosomal or

plasmid-mediated genes

Example: beta-lactamase producing organisms

Blockage of antimicrobial entry into the cell

Mechanisms › Decreased permeability

› Decreased uptake

› Increased ability to pump antimicrobial out of cell