-The ability of a chemical or a drug to kill a microorganism without being harmful to its host

Low = more toxic to host 

High = less toxic to host

Why must one consider the following when choosing an antimicrobial drug for a patient:

1-Selective toxicity 

2-Spectrum of activity 

3-Tissue distribution 

4-Metabolism & excretion of the drug 

5-Adverse effects 

6-Synergistic combinations 

7-Microbial resistance

1-If the patient's system can handle a drug with a low selective toxicity, if the choice can be made

2-If the infectious agent is known, a narrow spectrum antibiotic would be the best choice because it would target the problem organism. Less is best. 

3-If an infection is systemic, a drug with a high tissue distribution rate would be preferrable. 

4- The rate of excretion is expressed in the half-life - how long it tastes for the body to eliminate one half the original dose in serum. This dictates the frequency of the dose.

5-Are any possible adverse effects/toxicity associated with the drug a danger to the patient? known allergies?

6-Are there any other drugs which could supplement your choice that could work synergistically to kill any of th bacteria who may be resistant/ or have better resutsl?

7-If the bacteria is known, are they known to carry a high resistance rate against any particular drugs? 

-Inhibition of cell wall synthesis

-Inhibition of protein synthesis 

-Inhibition of nucleic acid synthesis 

-Inhibition of metabolic pathways 

-Interference with cell membrane integrity 

-Interference with essential processes of M. tuberculosis

-Part of a group of drugs which have beta-lactam rings

-Inhibits cell wall formation by interefering with the formation of the peptide side chains between PTG by inhibiting penicillin-binding proteins.

-Broad spectrum, mainly G+ but some modified to deal with G- 

- Resisted against through production of beta-lactamase enzyme, which breaks the beta-lactam ring

-Cephalosporins more resistant to inactivation by beta-lactamases

-Inhibits the formation of glycan chains; inhibits formation of PTG and cell wall construction.

-Does not cross the lipid membrane of G-, g- innately resistant 

-Important for treating infectioncs caused by penicillin resistant G+ organisms 

-Strictly IV, poor GI absorption 

-Resistance most often due to alterations in side chain of NAM molecule, which prevcents vancomycin from binding to NAM component of glycan

-Interferes with transport of PTG precursors across cytoplasmic membrane

-Toxicity limits use to topical only 

-Irreversibly binds to 30S ribosomal subunit, which causes distortion and malfunction of ribosome, and misreading of mRNA by bloking translation

-Not effective against anaerobes, enterococci, and streptococci 

-Often used synergistically with beta-lactam drugs to allow the aminoglycosides to enter cells which are often resistant

-Reversibly binds to 30S ribosomal subunit, which blocks attachment of tRNA to ribosome, which in turn prevents continuation of protein synthesis

-Effective against certain G+ & G- 

-New tetracyclines such as doxycyline have longer half-lives which allows for less frequent dosing 

-Resistance is due to decreased accumulation of the drug in bacterial cells

-Reversibly binds to 50S ribosome, which prevents continuation of protein synthesis

-Effective against many G+ organisms and those responsible for atypical pneumonia 

-Good choice for patients allergic to penicillin 

-Resistance can occur via modification of RNA target. Other mechanisms inclue an enzyme that chemically modifies drug as well as alterations that result in decreaed uptake of drug

-Binds to 50S ribosomal subunit, which prevents peptide bonds from forming and blocks protein synthesis

-Broad spectrum 

-Last resort drug for life-threatening infections 

-Last resort drug because of its rare but lethal side effect of aplastic anemia (inability to make WBC & RBC)

-Binds to 50S subunit which prevents continuation of protein synthesis

-Broad spectrum 

-Useful in treating infections due to intestinal perforation 

-New class of antimicrobials

-Binds to 50S ribosomal subunit which intereferes with the initiation of protein synthesis 

-Effective against many G+ bacteria, especially those resistant to beta-lactams and vancomycin

-Bonds to two different sides on 50S ribosomal subunit

-Acts synergistically through the combination of quinupristin and dalfopristin 

-Effective against many G+ bacteria, especially those resistant to beta-lactams and vancomycin

-Inhibits actions of topoisomerase DNA gyrase, which causes DNA to supercoil

-Broad spectrum 

-Resistance due to alteration of DNA gyrase

-Blocks prokaryotic RNA polymerase, which blocks the initiation of transcription

-Broad spectruml effective against Mycobacterium 

-Primarily used to treat TB and leprosy (hansen's Disease), as well as preventing meningitis after exposure 

-Resistance is due to mutation coding RNA polymerase, and develops rapidly

-Group of related compounds called sulfa drugs 

-Broad spectrum 

-Inhibits growth through competitive inhibition of the enzyme that aids in the production of folic acid 

-Structurally similar to para-aminobenzoic acid, which is a substrate in the folic acid pathway 

-Humans cannot synthesize folic acid, highly selective toxicity 

-Resistance is due to plasmid which codes for enzyme with a lower affinity to the drug

-Inhibits folic acid production by interfering with the activity of the enzyome following enzyme inhibited by sulfonamides

-Often used synergistically with sulfonamide 

-Most common mechanism of resistance is plasmid encoded alternative enzyme

-Damages the cell membrane

-Topical

-Binds membrane of G- cells, which alters permeability 

-Rifamycin, Streptomycin, Isoniazid, Ethambutol, Pyrazinamide

-These are the 'first line drugs' against M. tuberculosis

-Not many drugs are used against this genus because of chronic nature of disease, slow growth, and waxy lipid in cell wall (mycolic acid, which is impervious to many drugs)

-Minimum inhibitory concentration is a quantitiative test which determines the lowst concentration of a specific antimicrobial drug needed to prevent growth of said organism

-Determined by examining strain's ability to grow in broth containing different concentrations of test drug 

- Tubes set up withdecreating concentrations of test drugs and known concentrations ofa specific strain are added to each tube. They are then incubated andthe growth is examined for(by turbidity). 

-The lowest concentration of the drug to prevent growth is the MIC

-Kirby-Bauer disc diffusion is routinely used to qualitatively determine susceptibility

-Standard concentration of strain is spread evenly over entire suface of media 

-Discs impregnanted with specific concentrations of antibiotic placed on plate and incubated 

-Clear zone of inhibition around disc reflects susceptibility (based on size, organism can be described as sucspetible or resistant)

-The E-test is a modification of the disc diffusion test

-Uses strips impregnanted with gradient concentration of antibiotic (from highest to lowest) 

-Test organism will grow and form zone of inhibition 

-Zone will intersect strip at inhibitory concentration

1) Drug inactivating enzymes - some organisms produce enzymes which chemically modify drug (penicillinase breaks beta-lactam ring of penicillin antibiotics)

2)  Alteration of target molecule - minor structural changes in antibiotic target can prevent binding (changes in ribosomal RNA preven macrolids from binding to ribosomal subunits)

3)  Decreased uptake of drug - alterations in porin proteins decrease permability of cells (prevents certain drugs from entering)

4) Increased elimination of the drug - Some organisms produce efflux pumps, which increased overall capacity of organism to eliminate drug (enables organism to resist higher concentrations of drug; tetracycline)

-Acquisition of resistance: 

*Can be due to spontaneous mutation: occurs at a relatively low rate,  some mutations have profound effect on population. Broad spectrum antibiotics make it more difficult for an organism to achieve resistance through spontaneous mutation.

*Can be due to acquiring new genes through gene transfer: most common mechanism of transfer is through conjugation, transfer of R plasmid. Plasmid often carries many resistances, so organism acquires resistance to several different drugs at the same time.

-Responsible physicians and healthcare workers who increase efforts to prescribe narrow spectrum antibiotics for specific organisms, and educate pateints on proper antibiotic use.

-Responsible patients who follow instructions carefully and complete prescribed course of treatment 

-Educating the public on misuse of antibiotics (not taking full dose, taking antibotics for random illnesses that are often viral) 

- Lowering amount of antimicrobials available in unneeded things without a prescription.