Page 826 - Basic _ Clinical Pharmacology ( PDFDrive )

812 SECTION VIII Chemotherapeutic Drugs

SUMMARY Beta-Lactam & Other Cell Wall- & Membrane-Active Antibiotics

Subclass, Mechanism of Pharmacokinetics,
Drug Action Effects Clinical Applications Toxicities, Interactions
PENICILLINS
• Penicillin G Prevents bacterial cell Rapid bactericidal activity Streptococcal infections, IV administration • rapid renal clearance (half-life
wall synthesis by binding against susceptible bacteria meningococcal infections, 30 min, so requires dosing every 4 h) • Toxicity:
to and inhibiting cell wall neurosyphilis Immediate hypersensitivity, rash, seizures
transpeptidases

• Penicillin V: Oral, low systemic levels limit widespread use
• Benzathine penicillin, procaine penicillin: Intramuscular, long-acting formulations
• Nafcillin, oxacillin: Intravenous, added stability to staphylococcal β-lactamase, biliary clearance
• Ampicillin, amoxicillin, piperacillin: Greater activity versus Gram-negative bacteria; addition of β-lactamase inhibitor restores activity against many β-lactamase-producing bacteria
CEPHALOSPORINS
• Cefazolin Prevents bacterial cell Rapid bactericidal activity Skin and soft tissue IV administration • renal clearance (half-life 1.5 h)
wall synthesis by binding against susceptible bacteria infections, urinary tract • given every 8 h • poor penetration into the
to and inhibiting cell wall infections, surgical central nervous system (CNS) • Toxicity: Rash,
transpeptidases prophylaxis drug fever
• Cephalexin: Oral, first-generation drug used for treating skin and soft tissue infections and urinary tract infections
• Cefuroxime: Oral and intravenous, second-generation drug, improved activity versus pneumococcus and Haemophilus influenzae
• Cefotetan, cefoxitin: Intravenous, second-generation drugs, activity versus Bacteroides fragilis allows for use in abdominal/pelvic infections
• Ceftriaxone: Intravenous, third-generation drug, mixed clearance with long half-life (6 hours), good CNS penetration, many uses including pneumonia, meningitis,
pyelonephritis, and gonorrhea
• Cefotaxime: Intravenous, third-generation, similar to ceftriaxone; however, clearance is renal and half-life is 1 hour
• Ceftazidime: Intravenous, third-generation drug, poor Gram-positive activity, good activity versus Pseudomonas aeruginosa
• Cefepime: Intravenous, fourth-generation drug, broad activity with improved stability to chromosomal β-lactamases
• Ceftaroline: Intravenous, active against methicillin-resistant staphylococci, broad Gram-negative activity not including Pseudomonas aeruginosa
• Ceftazidime-avibactam, ceftolozane-tazobactam: Intravenous, cephalosporin-β-lactamase inhibitor combination drugs, broad activity with improved stability to
chromosomal β-lactamase and some extended-spectrum β-lactamases
CARBAPENEMS
• Imipenem- Prevents bacterial cell Rapid bactericidal activity Serious infections such as IV administration • renal clearance (half-life 1 h),
cilastatin wall synthesis by binding against susceptible bacteria pneumonia and sepsis dosed every 6–8 h, cilastatin added to prevent
to and inhibiting cell wall hydrolysis by renal dehydropeptidase • Toxicity:
transpeptidases Seizures especially in renal failure or with high
doses (>2 g/d)
• Meropenem, doripenem: Intravenous, similar activity to imipenem; stable to renal dehydropeptidase, lower incidence of seizures
• Ertapenem: Intravenous, longer half-life allows for once-daily dosing, lacks activity versus Pseudomonas aeruginosa and Acinetobacter
MONOBACTAMS
• Aztreonam Prevents bacterial cell Rapid bactericidal activity Infections caused by aerobic, IV administration • renal clearance half-life 1.5 h
wall synthesis by binding against susceptible bacteria Gram-negative bacteria in • dosed every 8 h • Toxicity: No cross-allergenicity
to and inhibiting cell wall patients with immediate with penicillins
transpeptidases hypersensitivity to penicillins
GLYCOPEPTIDE
• Vancomycin Inhibits cell wall synthesis Bactericidal activity against Infections caused by Oral, IV administration • renal clearance (half-life
by binding to the d-Ala-d- susceptible bacteria, slower Gram-positive bacteria 6 h) • starting dose of 30 mg/kg/d in two or three
Ala terminus of nascent kill than β-lactam including sepsis, endocarditis, divided doses in patients with normal renal
peptidoglycan antibiotics and meningitis • C difficile function • trough concentrations of
colitis (oral formulation) 10–15 mcg/mL sufficient for most infections
• Toxicity: “Red man” syndrome • nephrotoxicity
• Teicoplanin: Intravenous, similar to vancomycin except that long half-life (45–70 h) permits once-daily dosing
• Dalbavancin: Intravenous, very long half-life (>10 days) permits once-weekly dosing
• Oritavancin: Intravenous, very long half-life (>10 days) permits once-weekly dosing
• Telavancin: Intravenous, once-daily dosing

LIPOPEPTIDE
• Daptomycin Binds to cell membrane, Bactericidal activity against Infections caused by Gram- IV administration • renal clearance (half-life 8 h)
causing depolarization susceptible bacteria • more positive bacteria including • dosed once daily • inactivated by pulmonary
and rapid cell death rapidly bactericidal than sepsis and endocarditis surfactant so cannot be used to treat pneumonia
vancomycin • Toxicity: Myopathy • monitoring of weekly
creatine phosphokinase levels recommended