micro_drugs

functions as competitive inhibitor of transpeptidase activity

G+ & G-

pen derivatives:cephalosporins, monobactams, carbapenems, and lactamase inhibitors

competitive inhibition of transpeptidase activity

hydrolysis of B-Lac ring

G+ & G-

1st GEN PRIMARILY G+ COCCI

2nd ON PRIMARILY G- RODS

new generation drugs better against res G-

6-RING, PEN IS 5-RING

• Binds to D-ala-D-ala portion of UDP-muramylpentapeptide after transfer out of
• cytoplasm; inhibits both transglycosylation and
• transpeptidation

replacement of D-ala-D-ala with D-ala-D-lac (2)

binds to the a-subunit of DNA gyrase causing immediate cessation of DNA synthesis (3)

PROT SYNTH

REVERSIBLY BINDS TO 50S ribosomal subunit, blocking peptide bond formation (3)

G+; CHLAMYDIA, MYCOPLASM, TREPONEMA, RICKETTIA

RESP INFECTIONS

ex ERYTHROMYCIN, AZITHROMYCIN, CLIRITHROMYCIN

methylation of adenine residues in 23S ribo RNA (3)

binding to 50S subunit of 70S ribosomes

acetylation

TRI - competitive inhibition of dihydrofolate reductase

SULFA - ANALOG OF PABA - COMP INH DIHYDROPTEROIC ACID SYNTHASE

G+ & G-

ALSO PNEUMO JIROVECII (P. CARNII)

TRI RESISTANCE - PLASMID production of MODIFIED dihydrofolate reductase IN G+ & G- RODS(3).

Sulfa RESISTANCE - plasmid production of modified dihydropteroic acid synthetase.

Enterococcus RES- ability to utilize exogenous thymine & thymidine to escape inhibition of folate pathway, confering resistance

• competitive
• inhibition of dihydrofolate reductase

PROT SYNTH

G+; TB

forms complexes with the b-subunit of RNA polymerase, preventing transcription (3)

Binds to DNA-dependent RNA polymerase of bacteria preventing initiation of DNA transcription

G+, TB

RESISTANCE -- CHROM MUTATIONS -- SINGLE AA CHANGES IN THE b-SUBUNIT OF RNA POLYMERASE

affect cell wall synthesis at a different site than penicillins

INTERFERES WITH COMPLEXING OF PEPTIDOGLYCAN PRECURSOR

G+ (MRSA)

ex VANCOMYCIN

• gram neg are resistant b/c impermeability of the outer
• cell membrane to the large, hydrophobic glycopeptide molecules. Enterococcus species modify the D-ala-D-ala to either D-ala-D-lac or D-ala-D-ser.

An antibiotic that resembles nicotinamide in structure and competes with it for incorporation into NAD

DNA gyrase

• EF-G
• (elongation factor G)

PROT SYNTH

REVERSIBLY BINDS TO 30S ribosomal subunit

G+ & G-

ex DOXYCYCLINE, MINOCYCLINE

active efflux - energy dep pump removes Ab from cell before ribosomal target can be affected. Ribosome protection & altered permeability - porin modification --> MAR system

production of resistant dihydrofolate reductase (3)

Binds 30S bacterial ribosomal subunit causing distortions in the A site

• ultimately inhibits elongation of the growing
• peptide chain

PROT SYNTH -- Binds irreversibly to 30S ribosomal subunit

AEROBIC G- RODS, TB, OR SYNERGISTIC AGAINST RES G+ (ENTEROCOCCI)

STREPOMYCIN, GENTAMYCIN

• intrinsic resistance - fail to actively transport aminoglycosides across the cell membrane into the
• cytoplasm where ribosomal targets are (enterococci, anaerobes & streptococci)

Acquired resistance - by plasmid or transposon - acetylate AA, adenylate hydroxyl groups, phosphorylate hydroxyl groups

• natural
• inhibitory product of microorganism

• non-antibiotic,
• antimicrobial agent

irreversible b-lactamase inhibitor

UTI

inhibtis protein synthesis at multiple levels

inhibitory, but non-lethal effect

killing of 99.9% of bacterial population

extrachromosomal genetic element

targets of b-lactam antibiotic

effect of two drugs together better than combined separate drug effects

production of drug-inactivating enzymes

irreversible binding to a target enzyme or molecule

alteration of antibiotic target site

inhibition of cell wall peptidoglycan cross-linking.

four-membered b-lactam ring

an extracellular protein

Antibiotic must have high affinity for its microbial agent

Non-toxic to mammalian systems at concentrations similar to those required for its antimicrobial activity

Should not induce resistance to itself during therapy and should be chemically stable

using antibiotics only when indicated

Know This

Vancomycin

Vancomycin

acquisition of b-lactamase encoding plasmids

cell wall synth

broth dilution

Beta-lactam like mech, but different central ring structure (carbon-sulfur switch).

Better against bacteria with beta-lactamase

G+ & G-

ex IMIPENEM

Broadest spectrum

BAC WITH CARBAPENEMASES can destroy all current b-lac drugs

B-LAC - UNIQUE MONOCYCLIC STRUCTURE

AEROBIC G- ONLY (PSEUDOMONAS, ENTEROBACTER)

AZTREONAM ONLY

CELL MEM SYNTH (DAPTOMYCIN DEPOLERIZE CELL MEM)

INTERACT WITH PHOPHOLIPIDS IN G- MEMs CAUSING LEAKAGE

G-

USED TOPICALLY

TOXIC TO HUMANS

- only used systematically if infection is life threatening

ex P. auruginosa, A. baumannii, b/c toxic to humans

Lipopeptide antibiotic causing CA++ mediated depolarization of cell membrane (POLYMYXIN -- CELL SYNTH)

G+ (MRSA, VRE)

INJECTABLE FOR SEVERE DRUG RES G+

MACRILIDES, KETOLIDES LINCOSAMIDES, STREPTOGRAMINS

Active efflux of macrolides but no clindamycin. Target modification by methylation of 50S ribosomal subunit (ketolides are less susceptible to this)

PROT SYNTH

Like Macrolides, but better against macrolids resistant strep and staph

G+

FOR MACROLIDE RES STRAINS

TELITHROMYCIN

PROT SYNTH

Like Macrolides, broader spectrum, prevent polypeptide chain elongation

G+

GOOD FOR ANAEROBIC G-

ex CLINDAMYCIN

PROT SYNTH

• Given as quinupristin and dalfopristin combo (SYNERGY). Quin targets same 50S as Macrolides, but Dalfo. Targets
• 50S at different site

G+

GOOD FOR VRE AND MRSA

ex QUINUPRISTIN, DALFORPRISTIN

PROT SYNTH

Targets 50S ribosome, and inhibits the initiation of translation, but is not bacteriocidal.

AEROBIC G+

For REALLY resistant stuff like MRSA, VRSA, VISA

ex LINEZOLID

PROT SYNTH

Inhibits tRNA synthetase

G+

TOPICAL APPLICATION

DNA REPLICATION

Inhibits DNA-gyrase or bacterial topoisomerase IV

G+ & G-

MOST FREQUENTLY PRESCRIBED - BROAD SPECTRUM

ex - CIPROFLOXIN, LEVOFLOXACIN, MOXIFLOXACIN

Alteration of the structure of the target A subunit of the DNA gyrase enzyme - Ab cannot bind to active site. Efflux pumps -- G-

DNA REPLICATION

Reduction of the nitro group on antibiotic causes toxic intermediate in bacteria - distrupts DNA

ANEROBIC ONLY

INTESTINAL PROTAZOA (GIARDIA AND HISTOLYTICA) AND ANAEROBIC BACTERIA

ex METRONIDAZOLE

UTI - INHIBITS PROTEIN SYNTH

G+ & G-

ANTI-FUNGAL

binds to ergosterol in fungal cell membrane - osmotic instability and loss of membrane integrity

ONLY FOR VERY SERIOUS FUNGAL INFECTION -- TOXIC

ex AMPHOTERICIN B

ANTI-FUNGAL

interfere with fungal cell membrane ergosterol synthesis

NON-TOXIC, IV OR ORAL

• Fluconazole,
• itraconazole,
• voriconazole,
• posaconazole

ANTI-FUNGAL

inhibit glucan synthesis in cell wall of yeasts and some mold fungi

IV

• Caspofungin,
• micafungin,
• anidulofungin

ANTI-FUNGAL

inhibits DNA and RNA synthesis of some fungi

orally, bone marrow toxicity - only for serious infections

Flucytosine or 5FC