Antibiotics

Beta-lactams: mechanism

Beta-lactams inhibit bacterial cell wall synthesis by binding penicillin-binding proteins and are generally bactericidal.

ESBL-producing Enterobacterales preferred therapy

Meropenem, imipenem-cilastatin, or ertapenem are preferred for infections outside the urinary tract caused by ESBL-producing Enterobacterales.

Beta-lactam adverse effects

Common adverse effects include allergic reactions, gastrointestinal symptoms, C. difficile infection, interstitial nephritis, neurologic toxicity, and hematologic abnormalities.

Vancomycin spectrum

Vancomycin has activity against Gram-positive organisms including MRSA, streptococci, susceptible enterococci, and C. difficile; NO effect on gram neg

Oral vancomycin

Oral vancomycin is used for C. difficile infection because it remains concentrated in the intestinal lumen.

Vancomycin concentration-related toxicity

Ototoxicity and nephrotoxicity are associated with higher vancomycin serum concentrations.

Vancomycin non-concentration-related adverse effects

Red-man syndrome, drug fever, chills, thrombophlebitis, neutropenia, and thrombocytopenia are not primarily related to serum concentration.

What is Red-man syndrome

Red-man syndrome is a histamine-mediated infusion reaction characterized by flushing, pruritus, rash, tachycardia, and hypotension.

Fosfomycin mechanism

Fosfomycin inhibits bacterial cell wall synthesis through a unique early step in peptidoglycan synthesis.

Fosfomycin spectrum

Fosfomycin has activity against many Gram-positive and Gram-negative organisms, including E. coli, Klebsiella, Proteus, and Enterobacter.

Fosfomycin adverse effects

Common adverse effects include gastrointestinal symptoms and sodium loading.

Daptomycin class

Daptomycin is an intravenous cyclic lipopeptide antibiotic active against Gram-positive organisms.

Daptomycin mechanism

Daptomycin disrupts the bacterial cell membrane, causing rapid depolarization and cell death.

Daptomycin spectrum

Daptomycin covers MRSA, VRE, coagulase-negative staphylococci, streptococci, and other Gram-positive organisms.

Daptomycin major toxicities

Daptomycin can cause rhabdomyolysis and eosinophilic pneumonia, particularly at higher doses.

Polymyxin spectrum

Polymyxins primarily target aerobic Gram-negative bacilli including Pseudomonas, Acinetobacter, Klebsiella, and E. coli.

Polymyxin intrinsic resistance

Proteus, Providencia, Serratia, Burkholderia cepacia, and anaerobic Gram-negative organisms are intrinsically resistant to polymyxins.

Polymyxin major toxicity

Nephrotoxicity is the major toxicity associated with polymyxins.

Linezolid mechanism

Linezolid inhibits bacterial protein synthesis by binding the 50S ribosomal subunit and preventing formation of the initiation complex.

Linezolid spectrum

Linezolid is active against most clinically important Gram-positive organisms including MRSA and VRE.

Linezolid adverse effects

Major adverse effects include bone marrow suppression, thrombocytopenia, peripheral neuropathy, lactic acidosis, and serotonin syndrome.

Macrolide mechanism

Macrolides reversibly bind the 50S ribosomal subunit and block peptide translocation from the A-site to the P-site.

Macrolide bactericidal activity

Macrolides are generally bacteriostatic but may become bactericidal at high concentrations against susceptible organisms.

Macrolide agents

The major macrolides are erythromycin, clarithromycin, and azithromycin.

Azithromycin advantages

Azithromycin has less gastrointestinal toxicity, fewer drug interactions, and a much longer half-life than erythromycin.

Macrolide AE

GI disturbance, QT prolongation, CYP interactions

Lincosamide mechanism

Lincosamides inhibit protein synthesis by binding the 50S ribosomal subunit near the macrolide binding site.

Clindamycin spectrum

Clindamycin is active against many Gram-positive organisms and anaerobes including Bacteroides fragilis.

Clindamycin major use

Clindamycin is useful for Gram-positive and anaerobic infections but does not cover aerobic Gram-negative bacilli.

Clindamycin adverse effects

Common adverse effects include nausea, vomiting, diarrhea, C. difficile infection, transaminase elevation, and cytopenias.

Tetracycline mechanism

Tetracyclines reversibly bind the 30S ribosomal subunit and block aminoacyl-tRNA binding to the acceptor site.

Tetracycline agents

Major tetracyclines include tetracycline, doxycycline, minocycline, and tigecycline.

Doxycycline spectrum

Doxycycline covers many Gram-positive and Gram-negative organisms as well as atypical pathogens, Rickettsiae, Borrelia, and some parasites.

Tigecycline spectrum

Tigecycline covers many Gram-positive, Gram-negative, anaerobic, and atypical organisms including MRSA and VRE.

Tetracycline adverse effects

Common adverse effects include gastrointestinal irritation, photosensitivity, and vestibular toxicity, Fanconi syndrome, tooth discoloration

Tetracycline resistance

Important resistance mechanisms include decreased bacterial influx and increased efflux through active transport pumps.

Aminoglycoside mechanism

Aminoglycosides irreversibly bind the 30S ribosomal subunit, causing misreading of mRNA, impaired initiation, and bacterial death.

Aminoglycoside spectrum

Aminoglycosides primarily cover aerobic Gram-negative bacilli and have synergistic activity against selected Gram-positive organisms.

Aminoglycoside post-antibiotic effect

Aminoglycosides suppress bacterial growth even after concentrations fall below the MIC, producing a post-antibiotic effect.

Aminoglycoside major toxicities

The major aminoglycoside toxicities are nephrotoxicity and ototoxicity, NMJ blockade

Fluoroquinolone mechanism

Fluoroquinolones inhibit bacterial DNA gyrase and topoisomerase IV, preventing DNA replication and transcription.

Fluoroquinolone antipseudomonal activity

Ciprofloxacin and levofloxacin have antipseudomonal activity, whereas moxifloxacin does not reliably cover Pseudomonas.

Fluoroquinolone adverse effects

Major adverse effects include gastrointestinal symptoms, CNS toxicity, QT prolongation, tendinitis, arthropathy, retinal concerns, and dysglycemia.

TMP-SMX mechanism

TMP-SMX sequentially inhibits bacterial folate synthesis by blocking dihydropteroate synthase and dihydrofolate reductase.

TMP-SMX spectrum

TMP-SMX covers many Enterobacterales, Stenotrophomonas, Nocardia, Pneumocystis, and some Gram-positive organisms including MRSA.

TMP-SMX major adverse effects

Important adverse effects include rash, photosensitivity, bone marrow suppression, hemolysis in G6PD deficiency, hyperkalemia, and renal effects.

Rifamycin mechanism

Rifamycins inhibit the beta subunit of DNA-dependent RNA polymerase and therefore block bacterial RNA synthesis.

Rifamycin agents

Rifamycin antibiotics include rifampin, rifabutin, rifapentine, and rifaximin.

Rifamycin spectrum

Rifamycins are active against organisms including Staphylococcus, Streptococcus, Listeria, Legionella, Mycobacterium tuberculosis, and some nontuberculous mycobacteria.

Rifamycin adverse effects

Important adverse effects include cholestatic jaundice, hemolytic anemia, thrombocytopenia, interstitial nephritis, uveitis, and lupus-like symptoms.

Metronidazole spectrum

Metronidazole is highly active against anaerobic bacteria, particularly Gram-negative anaerobes and Clostridium species.

Metronidazole common adverse effect

Metallic taste = GI AE, neurologic toxicity