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Microbiology
Antibiotic lecture
46
Medical
Professional
04/15/2009

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Term
Antimicrobial agent: 
Definition

 

 A general term for drugs, chemicals, or other 

substances that either kill or slow the growth of microbes. 

 

Term
Antibiotic:
Definition

A drug used to treat infections caused by bacteria and 

other microorganisms. Includes synthetically produced drugs

Term
Bacteriostatic
Definition

a compound that inhibits growth or reproduction of a 

microorganism, but does not directly kill the organism.

Term
Bactericidal
Definition
capable of killing bacteria outright.
Term
Prodrug
Definition

a drug that is administered in an inactive form. Activation 

occurs in vivo upon it being metabolized. (e.g. Isoniazid is activated by 

Mycobacterium’s catalase enzyme)

Term
Broad-spectrum antibiotics
Definition

 capable of targeting both Gram-

negative and Gram-positive bacteria.

Term
Antimicrobial Sensitivity Assays: Kirby‐Bauer Disc Diffusion
Definition
Qualitative measurement of Minimum Inhibitory Concentration (MIC)
Term
Determining Quantitative Minimal Inhibitory Concentration (MIC)
Definition

Commercially available strips. 

Serial dilution of antibiotic 

across strip. Placed on agar 

plate containing bacteria. View 

edge of clearing at lowest 

concentration of antibiotic.

Term
Determining Minimal Bactericidal Concentration (MBC)
Definition

Inoculate from MIC cultures 

into fresh growth medium 

lacking antibiotics

MBC will always be greater-

than or equal-to MIC.

Term
Antibiotics targeting cell wall biosynthesis
Definition

Fosfomycin, Ramoplanin, Mersacidin, Moenomycin, Chlorobiphenylvancomycin, Vancomycin, Penicillin, Cephalosporin, Bacitracin, Carbapenems

 

Cycloserine, vancomycin, bacitracin, fosfomycin, penicillins, cephaolosporin, carbapenems

Term
Antiobiotics that target protein synthesis
Definition

Macrolides, Lincosamides, Streptogramins, Everninomycins, Oxazolidones (50s)

Aminoglycosides, Tetracyclines (30s)

 

50s - erythromycin, chloramphenicol, clindamycin

30s - tetracycline, spectinomycin, streptomycin, gentamicin, tobramycin, amikacin

Term
Antiobiotics that target DNA replication/RNA synthesis
Definition

Rifampin, Ciprofloxacin, Novobiocins

 

nalidixic acid, quinolines (DNA gyrase)

 

rifampin (DNA dependent RNA polymerase)

Term
Metabolic analogs
Definition

Sulfamethoxazole, Trimethoprim

Structural analogs and competitive antagonists to PABA and dihydrofolate

TMP+SMX = bactrim

work synergistically to block different steps in same pathway that is used for folate metabolism/thymine biosynthesis

Term
Target Cell Membrane
Definition

 Lipopolysacharide (LPS), polymyxin B, E

 

cyclic peptide binds LPS and hydrophobic tail interacts with membrane to form pore

Term

Beta Lactams

 

(penicillin, cephalosporin)

Definition
[image]
Term

Ampicillin

 

(amino penicillin)

Definition

A beta lactam - penicillin with altered R group that allows it to target a wider range of bacterial species

 

Broad gram negative coverage, enterococci

Term
Penicillinase resistant (IV)
Definition

Nafcillin, Oxacillin

 

use penicillinase resistant antibiotics for staphylococcal skin infections when suspect that staph produces Beta-lactamase

Term
Penicillinase resistant (oral)
Definition
Cloxacillin, Dicloxacillin
Term
Anti-pseudomonal
Definition

Ticarcillin, Piperacillin

 

anaerobic coverage

Term
Penicillin G
Definition

IV or IM (cannot survive stomach acid)

 

Group A strep, syphilis, listeria, neisseria meningitidis, streptococcus pneumoniae

Term
Penicillin V
Definition

Oral administration (acid resistant)

 

Strep throat

Term
Combined penicillin and beta lactamase inhibitors
Definition

Augmentin (amoxicillin + clavulanate)

 

Timentin (ticarcillin + clavulanate), Unasyn, Zosyn

 

Augmentin is oral, others are IV

 

Very broad coverage, anaerobic coverage

Term
Key points to remember for penicillins
Definition

1. Can cause allergenic reactions and lead to superinfections

2. Not all are resistant to stomach acid, some given IV.

3. Non-MRSA and GAS infections can be treated with Nafcillin and 

Dicloxacillin

4. Anti-pseudomonal drug of choice is Ticarcillin (contains β-lactamase

inhibitor).

5. Augmentin is another combinatorial drug (Amoxacillin + clavulanic

acid)

Term
Cephalosporins
Definition

Benefits over penicillin: more resistant to lactamases, R2 group offers more manipulation for changing specificity (2 R groups on penicillin ring)

 

Term
1st generation cephalosporins
Definition

Best for gram positives (strep and staph)

 

Cefazolin

Term
2nd generation cephalosporins
Definition

 broader Gram-negative spectrum; respiratory tract infections, sinusitis 

and otitis media; urinary tract infections from E. coli, Klebsiella and Proteus

 

Cefprozil, cefuroxime, cefaclor, cefaxitin

Term
3rd generation Cephalosporins
Definition

 further increased effectiveness against Gram-negatives, but decreased 

against many Gram-positives (exception Streptococcus pneumoniae - Ceftriaxone)

 

Best for gram-negatives

 

 

Term
4th generation Cephalosporins
Definition

 Broadest coverage against Gram-negatives and positives; best 

resistance to β-lactamases; some can cross blood-brain barrier (treat meningitis)

 

Cefquinome, Cefpirome, Cefozopran, Cefluprenam

Term
Problems with Cephalosporins
Definition

Many not effective against most hospital acquired infections:

•     Clostridium difficile (C.dif)

•     Methicillin Resistant Staphylococcus aureus (MRSA)

•     Vancomycin Resistant Enterococcus (VRE)

•     β-lactam resistant Streptococcus pneumoniae

Term
Carbapenems
Definition

(Imipenem)

 Very small β-lactam.  Broadest antibacterial 

coverage.  Often given with cilastin (inhibitor of liver enzyme that breaks down this 

drug)

Making it small allows to get into smaller pores at the cell wall in gram-negatives

Term
Monobactams (Aztreonam)
Definition

 

Great against Gram-negatives. Broad spectrum 

when given with vancomycin or clindomycin.

 

cell wall inhibitor

 

Term
Bacitracin
Definition
Topical use only, cyclic peptide (not a beta lactam)
Term
Vancomycin
Definition

Glycopeptide

 

MRSA, C diff, VRE

Term
Isoniazid
Definition

Cell wall inhibitor

 

used against mycobacterium tuberculosis (MTB)

 

inhibits synthesis of mycolic acid in cell wall

Term
Cycloserine
Definition

Used against mycobacterium tuberculosis as a second line drug 

 

cell wall inhibitor

Term
Target 50s ribsomal subunit
Definition
Chloramphenicol: toxicity is severe (aplastic anemia). Not used in U.S. except topically or eye drops.
Macrolides: (Erythromycin, Azithromycin) good against Gram-positives and negatives; low toxicity.
Clindamycin: covers Anaerobes and Gram-positives, not negatives
Linezolid (zyvox): best against MRSA and VRE. Very expensive.
Streptogramins (combination drug quinupristin+dalfopristin); last choice drug due to high occurance of toxicity.
Term
Target 30s subunit
Definition
Tetracyclines (doxycycline, minocycline); chelates Ca2+; treats Chlamydia, tick-borne disease, acne; phototoxic

Spectinomycin: treats gonorrhea
Term
Target 30s and 50s subunits
Definition

Aminoglycosides: (Streptomycin, Gentamycin, Tobramycin, Amikacin). Renal 

and cochlear toxicity at high rates.

Term
Target nucleic acid biosynthesis
Definition
Trimethoprim/sulfamethoxazole (TMP/SMX)= Sulfa drugs. Treats UTIs and Pneumocystis carinii in AIDS patients.
Quinolones/fluoroquinolones (ciprofloxacin): treat UTIs, lower respiratory infections, many Gram-negatives.
Rifampin: treats carriage of Haemophilus influenza B (Hib) and Neisseria meningitidis
Term
Polymyxin B
Definition

Targets cell membrane, topical treatment only

 

treats skin, ear, and eye infections

 

high toxicity if ingested

Term

Combination anti-microbial therapy

 

Synergistic

Definition

Combination use of 2 antibiotics reduces the MIC of either alone

 

Penicillin and aminoglycosides

Term

Combination anti-microbial therapy

 

Additive

Definition

decreasing concentration of drugs (due to toxicity) may be applied 

if two different drugs are administered.

Term

Combination antimicrobial therapy

 

Antagonistic 

Definition

 (reduction of activity of one or both)

Penicillin and Erythromycin or tetracycline (if you inhibit protein 

synthesis (i.e. erythromycin) cell wall synthesis stops. Penicillin only 

works on growing bacteria.

Term
Mechanisms of bacterial antibiotic resistance
Definition
1. Alteration of bacterial protein targets (ribosomes, cell wall precursors
2. Alteration of bacterial membrane (physical barrier) - changing permeability of membrane keeps out larger molecules (gram negative resistance to B lactams)
3. Enzymatic inhibition of antibiotic (beta lactamases, aminoglycosidases)
4. Bypass pathways targeted by antibiotics - acquire metabolite from environment instead of synthesizing it (trimethoprim resistance if acquire thymidine from host instead of synthesizing)
5. Efflux of antibiotics from bacterial cell - pump out toxic compound (tetracyline efflux common in staphylococcus and pseudomonas
Term
Means of acquiring bacterial resistance 
Definition
1. Single BP mutations
2. Large DNA rearrangements
3. Horizontal gene transfer (conjugation, bacteriophage transfer, endocytosis of exogenous DNA)
Term
Indiscriminate use of antibiotics leads to:
Definition
toxic effects, allergic reactions, antibiotic resistance, alteration of immune response, imbalance of normal body flora (opens up to disease by opportunistic infections that recolonize - candida albicans (oral and vaginal), C diff (GI)) 
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