unit 10.4: beta-lactam - other drugs

Aztreonam

Aztreonam

• Monobactam

• limited to aerobic Gr(-) organisms

• Resistant to beta-lactamases by some organisms

  • Klebsiella, Pseudomonas, Serratia

• An inhibitor of cell wall synthesis binding to PBP3

• No activity against gram (+) and anaerobes

• Synergistic with aminoglycosides

• No cross-allergenicity with penicillin

renal tubular secretion

Aztreonam:

Eliminated via ___

prolonged

Aztreonam:

Half-life is ___ in renal failure

Carbapenems

• Low susceptibility to beta-lactamases

• Resistant to most β –lactamases, ESBL (extended-spectrum BL)

• Wide activity against Gram(+) cocci, Gram (-) rods, Anaerobes

• Pseudomonal infections

• Drug of choice for Enterobacter

renal (kidney)

Carbapenems:

Excretion

Imipenem

Carbapenems:

• Rapidly inactivated by renal dehydropeptidases I

• Partial cross-allergenicity with penicillins

Cilastatin

• Inhibitor of the enzyme

• Increases the half-life

• Inhibits formation of nephrotoxic metabolites

Carbapenems: Imipenem

imipenem is combined with ___ which inhibits dehydropeptidase enzymes in renal tubules that inhibit imipenem

Meropenem

cot metabolized by renal dehydropeptidases

• Less likely to cause seizure

Ertapenem

Carbapenems:

• Less active against pseudomonas

• IM injection causes pain and irritation

Clavulanic acid, Sulbactam, Tazobactam

• Used in fixed combination with certain hydrolyzable penicillins

• Plasmid-encoded beta-lactamases

Vancomycin

Inhibitors of Cell Wall Synthesis:

• Bactericidal Against Gram-positive cocci and anaerobes

• Isolated from the bacterium Amycolatopsis orientalis

• Inhibits transglycosylation

• drug of choice for methicillin-resistant S. aureus (MRSA)

D-Ala-D-Ala terminal

Inhibitors of Cell Wall Synthesis: Vancomycin

• Binds to the ___ of the nascent peptidoglycan pentapeptide side chain

Red Man Syndrome

Inhibitors of Cell Wall Synthesis: Vancomycin

• Rapid IV infusion may cause diffuse blushing a syndrome known as ___

Teicoplanin

Inhibitors of Cell Wall Synthesis: Vancomycin

Similar drug

Fosfomycin

Inhibitors of Cell Wall Synthesis:

• Prevents the formation of N-acetylmuramic acid which is essential in peptidoglycan chain formation

• Synergistic with beta-lactam and quinolones in specific infections

decreased intracellular accumulation of the drug

Inhibitors of Cell Wall Synthesis: Fosfomycin

• Resistance occurs via ___

Antimetabolite inhibitor of cytosolic enolpyruvate transferase

Inhibitors of Cell Wall Synthesis: Fosfomycin

• Inhibits addition of phosphoenolpyruvate to UDP-N-acetylglucosamine

kidney with urinary levels exceeding the MICs for many urinary tract pathogens

Inhibitors of Cell Wall Synthesis: Fosfomycin

Excretion

uncomplicated cystitis (UTI)

Inhibitors of Cell Wall Synthesis: Fosfomycin

Clinical Use

fluoroquinolones

Inhibitors of Cell Wall Synthesis: Fosfomycin

Drug is less effective than the 7-day course of treatment with ___

Bacitracin

Inhibitors of Cell Wall Synthesis:

• Peptide antibiotic

• Interferes with a late stage in cell wall synthesis in gram (+) organisms

• Topical only

• highly nephrotoxic when administered systemically

• Tracy strain of Bacillus subtilis

lipid carrier that transfers peptidoglycan subunits

Inhibitors of Cell Wall Synthesis: Bacitracin

• Inhibits cell wall formation by interfering with the ___ to the growing cell wall

Cycloserine

Inhibitors of Cell Wall Synthesis:

• Antimetabolite

• Used only in TB caused by organisms resistant to first-line antituberculous drugs

• Produced by Streptomyces orchidaceous

D-alanine (tetrapeptide cross linker)

Inhibitors of Cell Wall Synthesis: Cycloserine

Inhibits incorporation of ___ into peptidoglycan pentapeptide by inhibiting alanine racemase, which converts l-alanine to d-alanine, and d-alanyl-d-alanine ligase

Daptomycin

Inhibitors of Cell Wall Synthesis:

• Lipopeptide

• vancomycin-resistant strains of enterococci and S aureus (VRE, VRSA)

• Fermentation product of Streptomyces roseosporus

• myopathy

Depolarization

Inhibitors of Cell Wall Synthesis: Daptomycin

• ___ of the cell membrane with potassium efflux and rapid cell death

Pulmonary surfactant

Inhibitors of Cell Wall Synthesis: Daptomycin

• ___ antagonizes daptomycin, and it should not be used to treat pneumonia