MICRO PHARM Flashcards
Ribavirin
Mechanism:
- Inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase.
- It is a nucleoside analog that can act on both RNA and DNA viruses. Can act on both RNA and DNA viruses but is mechanism of action in DNA viruses remains unclear.
Clinical Use:
- Hepatitis C, RSV infection, and viral hemorrhagic fever (e.g., Lassa fever, Hantavirus infection).
- For hepatitis C, it is always used in combination with other medications such as simeprevir or PEG-interferon-α.
Adverse Effects:
Nausea, irritability, hemolytic anemia, and severe teratogenicity.
Carbapenems Clinical Use
IV imipenem (combined with cilastatin)
IV meropenem
IV ertapenem
IV doripenem
Imipenem is always given with cilastatin, which inhibits human dehydropeptidase I (a renal tubular enzyme that breaks down imipenem).
Meropenem is stable to dehydropeptidase I.
- Last-resort drugs (used only in life-threatening infections or after other antibiotics have failed) because of the significant adverse effects
- Broad-spectrum antibiotics with intrinsic beta-lactamase resistance
- Gram-positive cocci (except for MRSA and Enterococcus faecalis, which are intrinsically resistant)
- Gram-negative rods, including Pseudomonas aeruginosa (except ertapenem which has limited activity against Pseudomonas)
- Anaerobes
Azithromycin Mechanism
Macrolide IV or oral form Poor CNS penetration poor Route of elimination → biliary All macrolides (except azithromycin) have a short half-life.
Mechanism:
Bind to 23S ribosomal RNA molecule of the 50S subunit → blockage of translocation → inhibition of bacterial protein synthesis (bacteriostatic effect)
Tetracyclines
Oral or IV minocycline and tetracycline
Oral doxycycline and demeclocycline
CNS penetration → poor
Route of elimination: renal
Doxycycline → only gastrointestinal elimination (doxycycline is the only tetracycline that is not contraindicated in patients with renal failure)
Oral tetracyclines should not be taken with substances that contain large amounts of Ca2+, Mg2+, or Fe2+ (e.g., milk, antacids, iron supplements, respectively) because divalent cations inhibit the intestinal absorption of tetracyclines.
Mechanism:
Bind 30S subunit → aminoacyl-tRNA is blocked from binding to ribosome acceptor site → inhibition of bacterial protein synthesis (bacteriostatic effect)
Clinical Use:
Bacteria that lack a cell wall (e.g, Mycoplasma pneumoniae, Ureaplasma)
Intracellular bacteria, such as Rickettsia, Chlamydia, or Anaplasma (tetracyclines accumulate intracellularly and are, therefore, effective against intracellular pathogens)
Borrelia burgdorferi
Ehrlichia, Vibrio cholerae, Francisella tularensis
Cutibacterium acnes (topical tetracycline is used to treat acne)
Community-acquired MRSA (doxycycline)
Adverse Effects:
Hepatotoxicity
Deposition in bones and teeth → inhibition of bone growth (in children) and discoloration of teeth
Damage to mucous membranes (e.g., esophagitis, GI upset)
Photosensitivity (drug or metabolite in the skin absorbs UV radiation → photochemical reaction → formation of free radicals → damage to cellular components → inflammation (sunburn-like))
Demeclocycline can cause nephrogenic diabetes insipidus
Degraded tetracyclines are associated with Fanconi syndrome.
Rarely: pseudotumor cerebri
Contraindications: Children < 8 years of age (except doxycycline) Pregnant women (except doxycycline) Patients with renal failure (except doxycycline) Cautious use in patients with hepatic dysfunction
Mechanisms of Resistance:
Plasmid-encoded transport pumps increase efflux out of the bacterial cell and decrease uptake of tetracyclines.
Macrolides
Oral or IV → erythromycin, azithromycin, clarithromycin
CNS penetration → poor
Route of elimination → biliary
All macrolides (except azithromycin) have a short half-life.
Mechanism:
Bind to 23S ribosomal RNA molecule of the 50S subunit → blockage of translocation → inhibition of bacterial protein synthesis (bacteriostatic effect)
Clinical Use:
Atypical pneumonia caused by Mycoplasma pneumonia, Legionella pneumophila, Chlamydophila pneumoniae
Bordetella pertussis
STIs caused by Chlamydia
Gram-positive cocci (especially for the treatment of streptococcal infection in patients who are allergic to penicillin)
Neisseria spp.
Second-line prophylaxis for N. meningitidis
Dual therapy with ceftriaxone for N. gonorrhoeae (azithromycin)
Mycobacterium avium (prophylaxis: azithromycin; treatment: azithromycin, clarithromycin)
H. pylori (clarithromycin is the part of triple therapy)
Ureaplasma urealyticum
Babesia spp. (azithromycin in combination with atovaquone)
Erythromycin is used off-label for the treatment of gastroparesis because it increases GI motility.
Adverse Effects: Increased intestinal motility → GI upset QT-interval prolongation, arrhythmia Acute cholestatic hepatitis Eosinophilia Rash
Drug Interactions:
Erythromycin enhances the effect of oral anticoagulants (e.g., warfarin).
Erythromycin and clarithromycin increase theophylline serum concentrations due to CYP3A4 inhibition (cytochrome P450 inhibitors)
Contraindications:
Erythromycin estolate and clarithromycin are contraindicated in pregnant women (potentially hazardous to the fetus).
Azithromycin and clarithromycin are contraindicated in patients with hepatic failure (erythromycin should be used cautiously).
Cautious use of clarithromycin in patients with renal failure
Mechanisms of Resistance:
Methylation of the binding site of 23S rRNA prevents the macrolide from binding to rRNA.
Antipseudomonal penicillins
Piperacillin, ticarcillin, and carbenicillin.
Mechanism:
D-Ala-D-Ala structural analog.
Bind penicillin-binding proteins (transpeptidases). Block transpeptidase cross-linking of peptidoglycan in cell wall.
Activate autolytic enzymes.
Extended spectrum.
Penicillinase sensitive; use with β-lactamase inhibitors.
Clinical Use:
Pseudomonas spp. and gram ⊝ rods.
Adverse Reaction:
Hypersensitivity reactions.
Fidaxomicin
Macrocyclic antibiotic (related to macrolides)
Mechanism:
Inhibits the sigma subunit of RNA polymerase, leading to protein synthesis impairment and cell death (bactericidal activity against C difficile)
Clinical Use:
First-line therapy for initial episodes of C. difficile infection (WBC < 15,000)
Acyclovir
Mechanism:
Guanosine analogs.
Monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells –> few adverse effects.
Triphosphate formed by cellular enzymes.
Preferentially inhibit viral DNA polymerase by chain termination.
Clinical Use:
HSV and VZV. Weak activity against EBV.
No activity against CMV.
Used for HSV- induced mucocutaneous and genital lesions as well as for encephalitis.
Prophylaxis in immunocompromised patients.
Only affects actively replicating viruses and has no effect on latent infections of HSV and VZV.
Valacyclovir, a prodrug of acyclovir, has better oral bioavailability.
For herpes zoster, use famciclovir.
Adverse Effects: Obstructive crystalline nephropathy and acute renal failure if not adequately hydrated Thrombotic thrombocytopenic purpura Gastrointestinal symptoms (e.g., nausea) ↑ Transaminases
Mechanism of Resistance:
Mutated viral thymidine kinase.
Famciclovir
Mechanism:
Prodrug of penciclovir
Guanosine analog
Monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells –> few adverse effects.
Triphosphate formed by cellular enzymes.
Preferentially inhibit viral DNA polymerase by chain termination.
Clinical Use:
HSV and VZV. Weak activity against EBV.
No activity against CMV.
Used for HSV- induced mucocutaneous and genital lesions as well as for encephalitis.
Prophylaxis in immunocompromised patients.
No effect on latent forms of HSV and VZV.
For herpes zoster, use famciclovir.
Adverse Effects: Obstructive crystalline nephropathy and acute renal failure if not adequately hydrated. Thrombotic thrombocytopenic purpura Gastrointestinal symptoms (e.g., nausea) ↑ Transaminases
Mechanism of Resistance:
Mutated viral thymidine kinase.
Sofosbuvir
Mechanism:
NS5B inhibitor
Inhibition of NS5B (a RNA-dependent RNA polymerase) → chain termination and disruption of RNA synthesis → prevention of HCV replication
Clinical Use:
Used in combination with velpatasvir or ledipasvir for the treatment of chronic hepatitis C infection.
Adverse Effects: Fatigue, headache, nausea. Insomnia Pruritus Asthenia It is contraindicated in severe renal insufficiency.
Glycylcyclines
Tigecycline is only agent in this class
Mechanism:
Tetracycline derivative.
Binds to 30S, inhibiting protein synthesis.
Generally bacteriostatic.
Biliary elimination
Should not be taken with milk, antacids, or iron supplements because divalent cations inhibit the absorption of glycylcyclines in the intestines.
Clinical use:
Gram-positive aerobes (not effective against S. viridans or Enterococci; limited efficacy against MSSA)
Gram ⊝
MRSA
VRE
Anaerobes (broad spectrum)
Partially effective against gram-negative aerobes (no effect against Proteus species)
Gram-intermediate bacteria: Borrelia, Mycoplasma, Rickettsia, Chlamydia
Infections requiring deep tissue penetration.
Adverse Effects: GI upset (nausea, vomiting) Hepatotoxicity Deposition in bones and teeth Photosensitivity
Tigecycline
Glycylcycline class
Mechanism:
Tetracycline derivative.
Binds to 30S, inhibiting protein synthesis.
Generally bacteriostatic.
Biliary elimination
Should not be taken with milk, antacids, or iron supplements because divalent cations inhibit the absorption of glycylcyclines in the intestines.
Clinical use:
Gram-positive aerobes (not effective against S. viridans or Enterococci; limited efficacy against MSSA)
Gram ⊝
MRSA
VRE
Anaerobes (broad spectrum)
Partially effective against gram-negative aerobes (no effect against Proteus species)
Gram-intermediate bacteria: Borrelia, Mycoplasma, Rickettsia, Chlamydia
Infections requiring deep tissue penetration.
Adverse Effects: GI upset (nausea, vomiting) Hepatotoxicity Deposition in bones and teeth Photosensitivity
Albendazole
Mechanism:
Inhibit microtubule polymerization resulting in decreased glucose uptake and glycogen synthesis, degeneration of mitochondria and endoplasmic reticulum and lysosomal release
Clinical Use: Ascariasis Enterobiasis Trichuriasis Strongyloidiasis Hookworm infection Cysticercosis Trichinellosis Toxocariasis
Adverse Effects: Headache GI upset (especially in short term use) Increased liver enzymes Rash, urticaria Hair loss Agranulocytosis
Penicillin G
IV (crystalline) and IM (benzathine) form
Prototype β-lactam antibiotics.
Probenecid blocks the rebel tubular excretion (sometimes used to increase their serum levels or prolong their half life)
Often coadministered with aminoglycosides to aid their entry into the cell
Mechanism:
D-Ala-D-Ala structural analog. Bind penicillin-binding proteins (transpeptidases).
Block transpeptidase cross-linking of peptidoglycan in cell wall.
Activate autolytic enzymes.
Clinical Use:
Mostly used for gram ⊕ organisms (S pneumoniae, S pyogenes, Actinomyces, C. perfringens, S. agalactiae). Also used for gram ⊝ cocci (mainly N meningitidis) and spirochetes (mainly T pallidum).
Pasteurella
Rheumatic fever prophylaxis
Bactericidal for gram ⊕ cocci, gram ⊕ rods, gram ⊝ cocci, and spirochetes.
β-lactamase sensitive.
Adverse Effects:
Hypersensitivity reactions, direct Coombs ⊕ hemolytic anemia (binds to bacterial breakdown products that form haptens thus forming anti-IgG), drug-induced interstitial nephritis, cutaneous small vasculitis
Resistance:
β-lactamase cleaves the β-lactam ring.
Mutations in penicillin-binding proteins.
Penicillin V
Oral form
Prototype β-lactam antibiotics.
Probenecid blocks the rebel tubular excretion (sometimes used to increase their serum levels or prolong their half life)
Often coadministered with aminoglycosides to aid their entry into the cell
Mechanism:
D-Ala-D-Ala structural analog. Bind penicillin-binding proteins (transpeptidases).
Block transpeptidase cross-linking of peptidoglycan in cell wall.
Activate autolytic enzymes.
Clinical Use:
Mostly used for gram ⊕ organisms (S pneumoniae, S pyogenes, Actinomyces, C. perfringens, S. agalactiae). Also used for gram ⊝ cocci (mainly N meningitidis) and spirochetes (mainly T pallidum).
Pasteurella
Rheumatic fever prophylaxis
Bactericidal for gram ⊕ cocci, gram ⊕ rods, gram ⊝ cocci, and spirochetes.
β-lactamase sensitive.
Adverse Effects:
Hypersensitivity reactions, direct Coombs ⊕ hemolytic anemia (binds to bacterial breakdown products that form haptens thus forming anti-IgG), drug-induced interstitial nephritis, cutaneous small vasculitis
Resistance:
β-lactamase cleaves the β-lactam ring.
Mutations in penicillin-binding proteins.
Amoxicillin
Oral or IV
Combined with clavulanate
The molecular structure is similar to penicillin and therefore susceptible to degradation by β-lactamase (β-lactamase sensitive).
Oral bioavailability of amoxicillin is greater than that of ampicillin
D-Ala-D-Ala structural analog. Bind penicillin-binding proteins (transpeptidases).
Block transpeptidase cross-linking of peptidoglycan in cell wall.
Activate autolytic enzymes.
Clinical use:
Broader spectrum of activity than penicillin (extended-spectrum penicillin)
Gram-positive aerobes
Gram-negative rods (not effective against Enterobacter spp.)
Prophylaxis against encapsulated bacteria in asplenic patients and before dental procedures in patients with high risk for endocarditis
Otitis media and sinusitis caused by S. pneumonia, Moraxella and H influenzae
Most effective against:
H. pylori, H. influenzae, Enterococci, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, Spirochetes (Lyme disease in pregnant and children)
Adverse effects: Diarrhea Pseudomembranous colitis Hypersensitivity reactions Drug-induced rash (in patients with mononucleosis) Possibly acute interstitial nephritis
Mechanisms of resistance:
Cleavage of the β-lactam ring by penicillinases
Ampicillin
IV or IM form
With or without sulbactam
The molecular structure is similar to penicillin and therefore susceptible to degradation by β-lactamase (β-lactamase sensitive).
Oral bioavailability of ampicillin is lesser than that of amoxicillin
D-Ala-D-Ala structural analog. Bind penicillin-binding proteins (transpeptidases).
Block transpeptidase cross-linking of peptidoglycan in cell wall.
Activate autolytic enzymes.
Clinical use:
Broader spectrum of activity than penicillin (extended-spectrum penicillin)
Gram-positive aerobes
Gram-negative rods (not effective against Enterobacter spp.)
IV is good for aspiration pneumonia
Otitis media and sinusitis caused by S. pneumonia, Moraxella and H influenzae
Most effective against:
H. pylori, H. influenzae, Enterococci, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, Spirochetes (Lyme disease in pregnant and children)
Adverse effects: Diarrhea Pseudomembranous colitis Hypersensitivity reactions Drug-induced rash (in patients with mononucleosis) Possibly acute interstitial nephritis
Mechanisms of resistance:
Cleavage of the β-lactam ring by penicillinases
Dicloxacillin
Mechanism:
Same as penicillin.
D-Ala-D-Ala structural analog. Bind penicillin-binding proteins (transpeptidases). Block transpeptidase cross-linking of peptidoglycan in cell wall.
Activate autolytic enzymes.
Penicillinase resistant because bulky R group (e.g., isoxazolyl), which prevent bacterial β-lactamase from hydrolyzing the β-lactam ring
Clinical Use:
Narrow spectrum
Gram-positive aerobes, especially S. aureus (non-MRSA)
Penicillinase-resistant penicillins are not effective against Streptococcus viridans, Enterococci, or Listeria.
IV for systemic S aureus endocarditis and osteomelitis
Adverse Effect:
Interstitial nephritis (esp. associated with methicillin use)
Hypersensitivity reactions
Mechanism of Resistance:
Alteration of PBP binding site → reduced affinity → pathogen is not bound or inactivated by β-lactam (an altered PBP target site is one of the main virulence factors of MRSA)
Nafcillin
Mechanism:
Same as penicillin.
D-Ala-D-Ala structural analog. Bind penicillin-binding proteins (transpeptidases). Block transpeptidase cross-linking of peptidoglycan in cell wall.
Activate autolytic enzymes.
Penicillinase resistant because bulky R group (e.g., isoxazolyl), which prevent bacterial β-lactamase from hydrolyzing the β-lactam ring
Clinical Use:
Narrow spectrum
Gram-positive aerobes, especially S. aureus (non-MRSA)
Penicillinase-resistant penicillins are not effective against Streptococcus viridans, Enterococci, or Listeria.
IV for systemic S aureus endocarditis and osteomelitis
Adverse Effect:
Interstitial nephritis (esp. associated with methicillin use)
Hypersensitivity reactions
Mechanism of Resistance:
Alteration of PBP binding site → reduced affinity → pathogen is not bound or inactivated by β-lactam (an altered PBP target site is one of the main virulence factors of MRSA)
Oxacillin
Mechanism:
Same as penicillin.
D-Ala-D-Ala structural analog. Bind penicillin-binding proteins (transpeptidases). Block transpeptidase cross-linking of peptidoglycan in cell wall.
Activate autolytic enzymes.
Penicillinase resistant because bulky R group (e.g., isoxazolyl), which prevent bacterial β-lactamase from hydrolyzing the β-lactam ring
Clinical Use:
Narrow spectrum
Gram-positive aerobes, especially S. aureus (non-MRSA)
Penicillinase-resistant penicillins are not effective against Streptococcus viridans, Enterococci, or Listeria.
IV for systemic S aureus endocarditis and osteomelitis
Adverse Effect:
Interstitial nephritis (esp. associated with methicillin use)
Hypersensitivity reactions
Mechanism of Resistance:
Alteration of PBP binding site → reduced affinity → pathogen is not bound or inactivated by β-lactam (an altered PBP target site is one of the main virulence factors of MRSA)
Floxacillin
Mechanism:
Same as penicillin.
D-Ala-D-Ala structural analog. Bind penicillin-binding proteins (transpeptidases). Block transpeptidase cross-linking of peptidoglycan in cell wall.
Activate autolytic enzymes.
Penicillinase resistant because bulky R group (e.g., isoxazolyl), which prevent bacterial β-lactamase from hydrolyzing the β-lactam ring
Clinical Use:
Narrow spectrum
Gram-positive aerobes, especially S. aureus (non-MRSA)
Penicillinase-resistant penicillins are not effective against Streptococcus viridans, Enterococci, or Listeria.
IV for systemic S aureus endocarditis and osteomelitis
Adverse Effect:
Interstitial nephritis (esp. associated with methicillin use)
Hypersensitivity reactions
Mechanism of Resistance:
Alteration of PBP binding site → reduced affinity → pathogen is not bound or inactivated by β-lactam (an altered PBP target site is one of the main virulence factors of MRSA)
Methicillin
NO LONGER USED DUE TO HIGH ADVERSE EFFECTS
Mechanism:
Same as penicillin.
D-Ala-D-Ala structural analog. Bind penicillin-binding proteins (transpeptidases). Block transpeptidase cross-linking of peptidoglycan in cell wall.
Activate autolytic enzymes.
Penicillinase resistant because bulky R group (e.g., isoxazolyl), which prevent bacterial β-lactamase from hydrolyzing the β-lactam ring
Clinical Use:
Narrow spectrum
Gram-positive aerobes, especially S. aureus (non-MRSA)
Penicillinase-resistant penicillins are not effective against Streptococcus viridans, Enterococci, or Listeria.
IV for systemic S aureus endocarditis and osteomelitis
Adverse Effect:
Interstitial nephritis (esp. associated with methicillin use)
Hypersensitivity reactions
Mechanism of Resistance:
Alteration of PBP binding site → reduced affinity → pathogen is not bound or inactivated by β-lactam (an altered PBP target site is one of the main virulence factors of MRSA)
Mention Aminopenicillins (Penicillinase-Sensitive Penicillins)
Oral or IV: amoxicillin (combined with clavulanate )
IV or IM: ampicillin (with or without sulbactam)
Mention Antipseudomonal Penicillins
IV piperacillin (combined with tazobactam)
IV mezlocillin
IV ticarcillin
IV carbenicillin
Mention Penicillinase-Resistant Penicillins
Nafcillin Dicloxacillin Oxacillin Floxacillin Methicillin
Piperacillin
Antipseudomonal penicillins
IV form
Combined with tazobactam
Mechanism:
D-Ala-D-Ala structural analog.
Bind penicillin-binding proteins (transpeptidases). Block transpeptidase cross-linking of peptidoglycan in cell wall.
Activate autolytic enzymes.
Extended spectrum.
Penicillinase sensitive; use with β-lactamase inhibitors.
Clinical Use:
Pseudomonas spp. and gram ⊝ rods.
Also effective against anaerobes (e.g., Bacteroides fragilis)
Gram-positive aerobes (not effective against S. viridans)
Adverse Reaction:
Hypersensitivity reactions.
Mezlocillin
Antipseudomonal penicillins
IV form
Mechanism:
D-Ala-D-Ala structural analog.
Bind penicillin-binding proteins (transpeptidases). Block transpeptidase cross-linking of peptidoglycan in cell wall.
Activate autolytic enzymes.
Extended spectrum.
Penicillinase sensitive; use with β-lactamase inhibitors.
Clinical Use:
Pseudomonas spp. and gram ⊝ rods.
Also effective against anaerobes (e.g., Bacteroides fragilis)
Gram-positive aerobes (not effective against S. viridans)
Adverse Reaction:
Hypersensitivity reactions.
Ticarcillin
Antipseudomonal penicillins
IV form
Mechanism:
D-Ala-D-Ala structural analog.
Bind penicillin-binding proteins (transpeptidases). Block transpeptidase cross-linking of peptidoglycan in cell wall.
Activate autolytic enzymes.
Extended spectrum.
Penicillinase sensitive; use with β-lactamase inhibitors.
Clinical Use:
Pseudomonas spp. and gram ⊝ rods.
Also effective against anaerobes (e.g., Bacteroides fragilis)
Gram-positive aerobes (not effective against S. viridans)
Adverse Reaction:
Hypersensitivity reactions.
Carbenicillin
Antipseudomonal penicillins
IV form
Mechanism:
D-Ala-D-Ala structural analog.
Bind penicillin-binding proteins (transpeptidases). Block transpeptidase cross-linking of peptidoglycan in cell wall.
Activate autolytic enzymes.
Extended spectrum.
Penicillinase sensitive; use with β-lactamase inhibitors.
Clinical Use:
Pseudomonas spp. and gram ⊝ rods.
Also effective against anaerobes (e.g., Bacteroides fragilis)
Gram-positive aerobes (not effective against S. viridans)
Adverse Reaction:
Hypersensitivity reactions.
Mention Streptogramins
Quinupristin
Dalfopristin
Quinupristin
Streptogramin
Synergistic effect with Dalfopristin
Route of elimination → biliary and renal
Mechanism:
Inhibits the late phase of protein synthesis
Binds to 50S subunit → elongation of polypeptide is prevented → release of incomplete chains
Bacteriostatic when used separately, but bactericidal when used in combination with Dalfopristin
Clinical use: Skin and skin structure infection with: -S. aureus (methicillin-susceptible and resistant) -S. pyogenes -Vancomycin-resistant E. faecium (VRE) -Not effective against E. faecalis
Adverse effects: Inhibits CYP3A4 Nausea, vomiting Diarrhea Headache Arthralgia, myalgia Thrombophlebitis Rash, pruritus Pseudomembranous colitis
Mechanisms of resistance:
Modification of bacterial ribosome binding site
Enzyme-mediated methylation (cross resistance with clindamycin and macrolides)
Efflux pumps
Dalfopristin
Streptogramin
Synergistic effect with Quinupristin
Route of elimination → biliary and renal
Mechanism:
Inhibits the early phase of protein synthesis
Binds to 23S portion of 50S subunit → change of conformation → enhanced binding of quinupristin
Inhibits peptidyl transferase
Bacteriostatic when used separately, but bactericidal when used in combination with Quinupristin
Clinical use: Skin and skin structure infection with: -S. aureus (methicillin-susceptible and resistant) -S. pyogenes -Vancomycin-resistant E. faecium (VRE) -Not effective against E. faecalis
Adverse effects: Inhibits CYP3A4 Nausea, vomiting Diarrhea Headache Arthralgia, myalgia Thrombophlebitis Rash, pruritus Pseudomembranous colitis
Mechanisms of resistance:
Modification of bacterial ribosome binding site
Enzyme-mediated methylation (crossresistance with clindamycin and macrolides)
Efflux pumps
Mention 1st generation cephalosporins
Oral → cephalexin
IV, IM → cefazolin
Mention 2nd generation cephalosporins
Cefaclor Cefuroxime Cefoxitin Cefotetan Cefprozil
Mention 3rd generation cephalosporins
Cefixime Cefpodoxime Cefotaxime Ceftazidime Ceftriaxone Cefdinir Cefoperazone
Mention 4th generation cephalosporins
IV → cefepime
Mention 5th generation cephalosporins
IV → ceftaroline
Cephalexin
1st generation cephalosporin
Mechanism:
β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.
Bactericidal.
Clinical Use:
Gram ⊕ cocci, Proteus mirabilis, E coli, Klebsiella pneumoniae.
1st generation—PEcK.
Organisms typically not covered by 1st–4th generation cephalosporins are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci.
Adverse Effects:
Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency which increase the risk of bleeding. Low rate of cross- reactivity even in penicillin-allergic patients.
Increase nephrotoxicity of aminoglycosides.
Neurotoxicity (can lower seizure threshold)
Mechanism of resistance:
Inactivated by cephalosporinases (a type of β-lactamase).
Structural change in penicillin-binding proteins (transpeptidases).
Cefazolin
1st generation cephalosporin
Mechanism:
β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.
Bactericidal.
Clinical Use:
Gram ⊕ cocci, Proteus mirabilis, E coli, Klebsiella pneumoniae.
Perioperative wound infection prophylaxis (covers S. aureus)
1st generation—PEcK.
Organisms typically not covered by 1st–4th generation cephalosporins are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci.
Adverse Effects:
Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency which increase the risk of bleeding. Low rate of cross- reactivity even in penicillin-allergic patients.
Increase nephrotoxicity of aminoglycosides.
Neurotoxicity (can lower seizure threshold)
Mechanism of resistance:
Inactivated by cephalosporinases (a type of β-lactamase).
Structural change in penicillin-binding proteins (transpeptidases).
Cefaclor
2nd generation cephalosporin
Oral form
Mechanism:
β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.
Bactericidal.
Clinical Use:
Gram ⊕ cocci, Proteus mirabilis, E coli, Klebsiella pneumoniae, H. influenzae
Klebsiella aerogenes (previously known as Enterobacter aerogenes), Neisseria, Serratia marcescens
2nd generation—HENS PEcK.
Organisms typically not covered by 1st–4th generation cephalosporins are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci.
Adverse Effects:
Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency which increase the risk of bleeding. Low rate of cross- reactivity even in penicillin-allergic patients.
Increase nephrotoxicity of aminoglycosides.
Neurotoxicity (can lower seizure threshold)
Mechanism of resistance:
Inactivated by cephalosporinases (a type of β-lactamase).
Structural change in penicillin-binding proteins (transpeptidases).
Cefuroxime
2nd generation cephalosporin
Oral form
Mechanism:
β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.
Bactericidal.
Clinical Use:
Gram ⊕ cocci, Proteus mirabilis, E coli, Klebsiella pneumoniae, H. influenzae
Klebsiella aerogenes (previously known as Enterobacter aerogenes), Neisseria, Serratia marcescens
2nd generation—HENS PEcK.
Organisms typically not covered by 1st–4th generation cephalosporins are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci.
Adverse Effects:
Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency which increase the risk of bleeding. Low rate of cross- reactivity even in penicillin-allergic patients.
Increase nephrotoxicity of aminoglycosides.
Neurotoxicity (can lower seizure threshold)
Mechanism of resistance:
Inactivated by cephalosporinases (a type of β-lactamase).
Structural change in penicillin-binding proteins (transpeptidases).
Cefoxitin
2nd generation cephalosporin
IV form
Mechanism:
β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.
Bactericidal.
Clinical Use:
Gram ⊕ cocci, Proteus mirabilis, E coli, Klebsiella pneumoniae, H. influenzae
Klebsiella aerogenes (previously known as Enterobacter aerogenes), Neisseria, Serratia marcescens
2nd generation—HENS PEcK.
Organisms typically not covered by 1st–4th generation cephalosporins are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci.
Adverse Effects:
Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency which increase the risk of bleeding. Low rate of cross- reactivity even in penicillin-allergic patients.
Increase nephrotoxicity of aminoglycosides.
Neurotoxicity (can lower seizure threshold)
Mechanism of resistance:
Inactivated by cephalosporinases (a type of β-lactamase).
Structural change in penicillin-binding proteins (transpeptidases).
Cefotetan
2nd generation cephalosporin
IV form
Mechanism:
β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.
Bactericidal.
Clinical Use:
Gram ⊕ cocci, Proteus mirabilis, E coli, Klebsiella pneumoniae, H. influenzae
Klebsiella aerogenes (previously known as Enterobacter aerogenes), Neisseria, Serratia marcescens
2nd generation—HENS PEcK.
Organisms typically not covered by 1st–4th generation cephalosporins are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci.
Adverse Effects:
Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency which increase the risk of bleeding. Low rate of cross- reactivity even in penicillin-allergic patients.
Increase nephrotoxicity of aminoglycosides.
Neurotoxicity (can lower seizure threshold)
Mechanism of resistance:
Inactivated by cephalosporinases (a type of β-lactamase).
Structural change in penicillin-binding proteins (transpeptidases).
Cefprozil
2nd generation cephalosporin
Mechanism:
β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.
Bactericidal.
Clinical Use:
Gram ⊕ cocci, Proteus mirabilis, E coli, Klebsiella pneumoniae, H. influenzae
Klebsiella aerogenes (previously known as Enterobacter aerogenes), Neisseria, Serratia marcescens
2nd generation—HENS PEcK.
Organisms typically not covered by 1st–4th generation cephalosporins are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci.
Adverse Effects:
Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency which increase the risk of bleeding. Low rate of cross- reactivity even in penicillin-allergic patients.
Increase nephrotoxicity of aminoglycosides.
Neurotoxicity (can lower seizure threshold)
Mechanism of resistance:
Inactivated by cephalosporinases (a type of β-lactamase).
Structural change in penicillin-binding proteins (transpeptidases).
Cefixime
3rd generation cephalosporin
Oral form
Mechanism:
β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.
Bactericidal.
Clinical Use:
Least active among all cephalosporins against Gram ⊕ cocci
Serious gram ⊝ infections resistant to other β-lactams.
Perioperative wound infection prophylaxis (covers S. aureus)
Organisms typically not covered by 1st–4th generation cephalosporins are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci.
Adverse Effects:
Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency which increase the risk of bleeding. Low rate of cross- reactivity even in penicillin-allergic patients.
Increase nephrotoxicity of aminoglycosides.
Neurotoxicity (can lower seizure threshold)
Mechanism of resistance:
Inactivated by cephalosporinases (a type of β-lactamase).
Structural change in penicillin-binding proteins (transpeptidases).
Cefpodoxime
3rd generation cephalosporin
Oral form
Mechanism:
β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.
Bactericidal.
Clinical Use:
Least active among all cephalosporins against Gram ⊕ cocci
Serious gram ⊝ infections resistant to other β-lactams.
Perioperative wound infection prophylaxis (covers S. aureus)
Organisms typically not covered by 1st–4th generation cephalosporins are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci.
Adverse Effects:
Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency which increase the risk of bleeding. Low rate of cross- reactivity even in penicillin-allergic patients.
Increase nephrotoxicity of aminoglycosides.
Neurotoxicity (can lower seizure threshold)
Mechanism of resistance:
Inactivated by cephalosporinases (a type of β-lactamase).
Structural change in penicillin-binding proteins (transpeptidases).
Cefotaxime
3rd generation cephalosporin
IV form
Mechanism:
β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.
Bactericidal.
Clinical Use:
Least active among all cephalosporins against Gram ⊕ cocci
Serious gram ⊝ infections resistant to other β-lactams.
Perioperative wound infection prophylaxis (covers S. aureus)
Organisms typically not covered by 1st–4th generation cephalosporins are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci.
Adverse Effects:
Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency which increase the risk of bleeding. Low rate of cross- reactivity even in penicillin-allergic patients.
Increase nephrotoxicity of aminoglycosides.
Neurotoxicity (can lower seizure threshold)
Mechanism of resistance:
Inactivated by cephalosporinases (a type of β-lactamase).
Structural change in penicillin-binding proteins (transpeptidases).
Ceftazidime
3rd generation cephalosporin
IV form
Mechanism:
β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.
Bactericidal.
Clinical Use:
Least active among all cephalosporins against Gram ⊕ cocci
Serious gram ⊝ infections resistant to other β-lactams.
Perioperative wound infection prophylaxis (covers S. aureus)
Pseudomonas
Organisms typically not covered by 1st–4th generation cephalosporins are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci.
Adverse Effects:
Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency which increase the risk of bleeding. Low rate of cross- reactivity even in penicillin-allergic patients.
Increase nephrotoxicity of aminoglycosides.
Neurotoxicity (can lower seizure threshold)
Mechanism of resistance:
Inactivated by cephalosporinases (a type of β-lactamase).
Structural change in penicillin-binding proteins (transpeptidases).
Ceftriaxone
3rd generation cephalosporin
IM and IV form
Excreted in bile
Mechanism:
β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.
Bactericidal.
Clinical Use:
Serious gram ⊝ infections resistant to other β-lactams.
Can cross blood-brain barrier.
Perioperative wound infection prophylaxis (covers S. aureus)
Ceftriaxone—meningitis, gonorrhea, disseminated Lyme disease.
Organisms typically not covered by 1st–4th generation cephalosporins are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci.
Adverse Effects:
Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency which increase the risk of bleeding. Low rate of cross- reactivity even in penicillin-allergic patients.
Increase nephrotoxicity of aminoglycosides.
Neurotoxicity (can lower seizure threshold)
Mechanism of resistance:
Inactivated by cephalosporinases (a type of β-lactamase).
Structural change in penicillin-binding proteins (transpeptidases).
Cefdinir
3rd generation cephalosporin
Mechanism:
β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.
Bactericidal.
Clinical Use:
Least active among all cephalosporins against Gram ⊕ cocci
Serious gram ⊝ infections resistant to other β-lactams.
Perioperative wound infection prophylaxis (covers S. aureus)
Organisms typically not covered by 1st–4th generation cephalosporins are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci.
Adverse Effects:
Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency which increase the risk of bleeding. Low rate of cross- reactivity even in penicillin-allergic patients.
Increase nephrotoxicity of aminoglycosides.
Neurotoxicity (can lower seizure threshold)
Mechanism of resistance:
Inactivated by cephalosporinases (a type of β-lactamase).
Structural change in penicillin-binding proteins (transpeptidases).
Cefoperazone
3rd generation cephalosporin
Mechanism:
β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.
Bactericidal.
Clinical Use:
Least active among all cephalosporins against Gram ⊕ cocci
Serious gram ⊝ infections resistant to other β-lactams.
Pseudomonas
Organisms typically not covered by 1st–4th generation cephalosporins are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci.
Adverse Effects:
Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency which increase the risk of bleeding. Low rate of cross- reactivity even in penicillin-allergic patients.
Increase nephrotoxicity of aminoglycosides.
Neurotoxicity (can lower seizure threshold)
Mechanism of resistance:
Inactivated by cephalosporinases (a type of β-lactamase).
Structural change in penicillin-binding proteins (transpeptidases).
Cefepime
4th generation cephalosporin
IV form
Mechanism:
β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.
Bactericidal.
Clinical Use:
Gram ⊝ organisms, with increase activity against Pseudomonas and gram ⊕ organisms.
Penetrate CNS (so can be used in meningitis)
Broad spectrum
Used for severe life-threatening infections (including nosocomial)
Adverse Effects:
Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency which increase the risk of bleeding. Low rate of cross- reactivity even in penicillin-allergic patients.
Increase nephrotoxicity of aminoglycosides.
Neurotoxicity (can lower seizure threshold)
Mechanism of resistance:
Inactivated by cephalosporinases (a type of β-lactamase).
Structural change in penicillin-binding proteins (transpeptidases).
Ceftaroline
5th generation cephalosporin
IV form
Mechanism:
β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.
Bactericidal.
Clinical Use:
Broad gram ⊕ and gram ⊝ organism coverage
Unlike 1st–4th generation cephalosporins, ceftaroline covers Listeria, MRSA, and Enterococcus faecalis— does not cover Pseudomonas and atypicals (Chlamydia, Mycoplasma, Legionella)
Adverse Effects:
Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency which increase the risk of bleeding. Low rate of cross- reactivity even in penicillin-allergic patients.
Increase nephrotoxicity of aminoglycosides.
Neurotoxicity (can lower seizure threshold)
Mechanism of resistance:
Inactivated by cephalosporinases (a type of β-lactamase).
Structural change in penicillin-binding proteins (transpeptidases).
β-lactamase Inhibitors
Clavulanate (combined with amoxicillin)
Avibactam (combined with ceftazidime)
Sulbactam (combined with ampicillin)
Tazobactam (combined with piperacillin)
Prevent the destruction of β-lactam antibiotics by β-lactamases and increase the spectrum of the antibiotic activity.
Can be coadministered with β-lactamase-sensitive penicillins in order to treat β-lactamase-producing organisms
Aztreonam
Monobactam
IV form
Less susceptible to β-lactamases.
Prevents peptidoglycan cross-linking by binding to penicillin- binding protein 3.
Synergistic with aminoglycosides.
No cross-allergenicity with penicillins.
Clinical Use:
Effective against Gram ⊝ rods only, including nosocomial Pseudomonas, H. influenzae, and N. meningitidis
No activity against gram ⊕ rods or anaerobes
Alternative for penicillin-allergic patients (no cross-sensitivity with penicillins) and those with renal insufficiency who cannot tolerate aminoglycosides
Broad-spectrum coverage in combination with vancomycin or clindamycin
Adverse Effects:
Usually nontoxic; occasional GI upset.
Injection reactions
Rash
Vancomycin
Glycopeptide
Oral or IV form
Mechanism:
Bind terminal D-ala-D-ala of cell-wall precursor peptides → inhibition of cell wall synthesis (peptidoglycan formation) → bacterial death (bactericidal effect against most gram-positive bacteria)
Bacteriostatic against C. difficile
CNS penetration → only when there is increased permeability of the meningeal vessels (i.e., with meningeal inflammation)
Route of elimination → renal (via glomerular filtration)
Clinical Use:
Especially effective against multidrug-resistant organisms
Effective against a wide range of gram-positive bacteria only
MRSA
S. epidermidis
Enterococci (if not vancomycin resistant enterococci)
C. difficile (causing pseudomembranous colitis) → administered orally
Penetrate bone so its useful treatment for MRSA osteomyelitis
First line empiric treatment of endocarditis.
Adverse Effects:
Intravenous administration
Nephrotoxicity
Ototoxicity/vestibular toxicity
Thrombophlebitis
Red man syndrome (anaphylactoid reaction caused by rapid infusion of vancomycin; nonspecific mast cell degranulation → rapid release of histamine. Diffuse flushing of the skin, pruritus mainly of the upper body, muscle spasms and pain in the back and chest, possible hypotension and dyspnea. Can be prevented by slowing the rate of infusion and pretreating with antihistamines)
DRESS syndrome (drug reaction (anticonvulsant [hallopurinol] and sulfonamide) leading to eosinophilia and systemic symptoms)
Neutropenia
Dysgeusia and gastrointestinal side effects (e.g., nausea, vomiting, abdominal pain)
Oral administration → predominantly dysgeusia and gastrointestinal side effects
Mechanisms of Resistance:
Modification of amino acid D-Ala-D-Ala to D-Ala-D-Lac → occurs mainly in Enterococcus (e.g., E. faecium, less in E. faecalis)
Beta-lactamase resistant
Ricin
Castor oil toxin
Inhibits eukaryotic 60 subunit
Aminoglycosides
IV or IM gentamicin, amikacin, tobramycin, streptomycin
Oral neomycin, paromomycin
Poor CNS penetration
Route of elimination → renal (via glomerular filtration)
Mechanism:
Bind to 30S subunit of the bacterial ribosome → irreversible inhibition of initiation complex → inhibition of bacterial protein synthesis → cell death (bactericidal effect)
Misreading of mRNA
Blockage of translocation
Synergistic effect when combined with β-lactam antibiotics (β-lactams inhibit cell wall synthesis → facilitated entry of aminoglycoside drugs into the cytoplasm)
Clinical Use:
Severe gram-negative rod infections
Not effective against anaerobes (aminoglycosides require oxygen to be absorbed by cells)
Neomycin, which is not absorbed systemically, is administered orally to prepare the gut for bowel surgery.
Streptomycin is used as a second-line treatment for Mycobacterium tuberculosis and M. avium-intracellulare
Paromomycin is not significantly absorbed from the gastrointestinal tract, it is used as a luminal antibiotic in the treatment of hepatic encephalopathy and as a luminal amebicide (by eradicating intestinal cysts). First line treatment for amebiasis or giardiasis during pregnancy.
Gentamycin is the first line treatment of acute pyelonephritis in case of fluoroquinolone allergy or resistance
Adverse Effects:
Nephrotoxicity (proximal tubular injury and acute tubular necrosis visualized histologically as focal tubular epithelial necrosis, often with extensive granular casts that obstruct the tubular lumen and lead to rupture of the basement membrane)
Ototoxicity and vestibulotoxicity (risk of ototoxicity is higher when used concurrently with loop diuretics) resulting in tinnitus, ataxia, vertigo
Neuromuscular blockade (risk increases in the event of hypomagnesemia or myasthenia gravis, and in patients who use calcium channel blockers)
Teratogenicity
Contraindications: Myasthenia gravis Botulism Pregnancy Cautious use in patients with renal dysfunction
Mechanisms of resistance:
Inactivation via acetylation, phosphorylation, and/or adenylation by secreted bacterial transferase enzymes
Paromomycin
Aminoglycoside
Oral form
Poor CNS penetration
Route of elimination → renal (via glomerular filtration)
Mechanism:
Bind to 30S subunit of the bacterial ribosome → irreversible inhibition of initiation complex → inhibition of bacterial protein synthesis → cell death (bactericidal effect)
Misreading of mRNA
Blockage of translocation
Synergistic effect when combined with β-lactam antibiotics (β-lactams inhibit cell wall synthesis → facilitated entry of aminoglycoside drugs into the cytoplasm)
Clinical Use:
Because it is not significantly absorbed from the gastrointestinal tract, it is used as a luminal antibiotic in the treatment of hepatic encephalopathy and as a luminal amebicide (by eradicating intestinal cysts).
First line treatment for amebiasis or giardiasis during pregnancy.
Adverse Effects:
Nephrotoxicity (proximal tubular injury and acute tubular necrosis visualized histologically as focal tubular epithelial necrosis, often with extensive granular casts that obstruct the tubular lumen and lead to rupture of the basement membrane)
Ototoxicity and vestibulotoxicity (risk of ototoxicity is higher when used concurrently with loop diuretics) resulting in tinnitus, ataxia, vertigo
Neuromuscular blockade (risk increases in the event of hypomagnesemia or myasthenia gravis, and in patients who use calcium channel blockers)
Teratogenicity
Contraindications: Myasthenia gravis Botulism Pregnancy Cautious use in patients with renal dysfunction
Mechanisms of resistance:
Inactivation via acetylation, phosphorylation, and/or adenylation by secreted bacterial transferase enzymes
Gentamicin
Aminoglycoside
IV or IM form
Poor CNS penetration
Route of elimination → renal (via glomerular filtration)
Mechanism:
Bind to 30S subunit of the bacterial ribosome → irreversible inhibition of initiation complex → inhibition of bacterial protein synthesis → cell death (bactericidal effect)
Misreading of mRNA
Blockage of translocation
Synergistic effect when combined with β-lactam antibiotics (β-lactams inhibit cell wall synthesis → facilitated entry of aminoglycoside drugs into the cytoplasm)
Clinical Use:
Severe gram-negative rod infections
Not effective against anaerobes (aminoglycosides require oxygen to be absorbed by cells)
Gentamycin is the first line treatment of acute pyelonephritis in case of fluoroquinolone allergy or resistance
Adverse Effects:
Nephrotoxicity (proximal tubular injury and acute tubular necrosis visualized histologically as focal tubular epithelial necrosis, often with extensive granular casts that obstruct the tubular lumen and lead to rupture of the basement membrane)
Ototoxicity and vestibulotoxicity (risk of ototoxicity is higher when used concurrently with loop diuretics) resulting in tinnitus, ataxia, vertigo
Neuromuscular blockade (risk increases in the event of hypomagnesemia or myasthenia gravis, and in patients who use calcium channel blockers)
Teratogenicity
Contraindications: Myasthenia gravis Botulism Pregnancy Cautious use in patients with renal dysfunction
Mechanisms of resistance:
Inactivation via acetylation, phosphorylation, and/or adenylation by secreted bacterial transferase enzymes
Amikacin
Aminoglycoside
IV or IM form
Poor CNS penetration
Route of elimination → renal (via glomerular filtration)
Mechanism:
Bind to 30S subunit of the bacterial ribosome → irreversible inhibition of initiation complex → inhibition of bacterial protein synthesis → cell death (bactericidal effect)
Misreading of mRNA
Blockage of translocation
Synergistic effect when combined with β-lactam antibiotics (β-lactams inhibit cell wall synthesis → facilitated entry of aminoglycoside drugs into the cytoplasm)
Clinical Use:
Severe gram-negative rod infections
Not effective against anaerobes (aminoglycosides require oxygen to be absorbed by cells)
Adverse Effects:
Nephrotoxicity (proximal tubular injury and acute tubular necrosis visualized histologically as focal tubular epithelial necrosis, often with extensive granular casts that obstruct the tubular lumen and lead to rupture of the basement membrane)
Ototoxicity and vestibulotoxicity (risk of ototoxicity is higher when used concurrently with loop diuretics) resulting in tinnitus, ataxia, vertigo
Neuromuscular blockade (risk increases in the event of hypomagnesemia or myasthenia gravis, and in patients who use calcium channel blockers)
Teratogenicity
Contraindications: Myasthenia gravis Botulism Pregnancy Cautious use in patients with renal dysfunction
Mechanisms of resistance:
Inactivation via acetylation, phosphorylation, and/or adenylation by secreted bacterial transferase enzymes
Tobramycin
Aminoglycoside
IV or IM form
Poor CNS penetration
Route of elimination → renal (via glomerular filtration)
Mechanism:
Bind to 30S subunit of the bacterial ribosome → irreversible inhibition of initiation complex → inhibition of bacterial protein synthesis → cell death (bactericidal effect)
Misreading of mRNA
Blockage of translocation
Synergistic effect when combined with β-lactam antibiotics (β-lactams inhibit cell wall synthesis → facilitated entry of aminoglycoside drugs into the cytoplasm)
Clinical Use:
Severe gram-negative rod infections
Not effective against anaerobes (aminoglycosides require oxygen to be absorbed by cells)
Adverse Effects:
Nephrotoxicity (proximal tubular injury and acute tubular necrosis visualized histologically as focal tubular epithelial necrosis, often with extensive granular casts that obstruct the tubular lumen and lead to rupture of the basement membrane)
Ototoxicity and vestibulotoxicity (risk of ototoxicity is higher when used concurrently with loop diuretics) resulting in tinnitus, ataxia, vertigo
Neuromuscular blockade (risk increases in the event of hypomagnesemia or myasthenia gravis, and in patients who use calcium channel blockers)
Teratogenicity
Contraindications: Myasthenia gravis Botulism Pregnancy Cautious use in patients with renal dysfunction
Mechanisms of resistance:
Inactivation via acetylation, phosphorylation, and/or adenylation by secreted bacterial transferase enzymes
Streptomycin
Aminoglycoside
IV or IM form
Poor CNS penetration
Route of elimination → renal (via glomerular filtration)
Mechanism:
Bind to 30S subunit of the bacterial ribosome → irreversible inhibition of initiation complex → inhibition of bacterial protein synthesis → cell death (bactericidal effect)
Misreading of mRNA
Blockage of translocation
Synergistic effect when combined with β-lactam antibiotics (β-lactams inhibit cell wall synthesis → facilitated entry of aminoglycoside drugs into the cytoplasm)
Clinical Use:
Severe gram-negative rod infections
Not effective against anaerobes (aminoglycosides require oxygen to be absorbed by cells)
Streptomycin is used as a second-line treatment for Mycobacterium tuberculosis and M. avium-intracellulare
Adverse Effects:
Nephrotoxicity (proximal tubular injury and acute tubular necrosis visualized histologically as focal tubular epithelial necrosis, often with extensive granular casts that obstruct the tubular lumen and lead to rupture of the basement membrane)
Ototoxicity and vestibulotoxicity (risk of ototoxicity is higher when used concurrently with loop diuretics) resulting in tinnitus, ataxia, vertigo
Neuromuscular blockade (risk increases in the event of hypomagnesemia or myasthenia gravis, and in patients who use calcium channel blockers)
Teratogenicity
Contraindications: Myasthenia gravis Botulism Pregnancy Cautious use in patients with renal dysfunction
Mechanisms of resistance:
Inactivation via acetylation, phosphorylation, and/or adenylation by secreted bacterial transferase enzymes
Neomycin
Aminoglycoside
Oral form
Poor CNS penetration
Route of elimination → renal (via glomerular filtration)
Mechanism:
Bind to 30S subunit of the bacterial ribosome → irreversible inhibition of initiation complex → inhibition of bacterial protein synthesis → cell death (bactericidal effect)
Misreading of mRNA
Blockage of translocation
Synergistic effect when combined with β-lactam antibiotics (β-lactams inhibit cell wall synthesis → facilitated entry of aminoglycoside drugs into the cytoplasm)
Clinical Use:
Severe gram-negative rod infections
Not effective against anaerobes (aminoglycosides require oxygen to be absorbed by cells)
Neomycin, which is not absorbed systemically, is administered orally to prepare the gut for bowel surgery.
Adverse Effects:
Nephrotoxicity (proximal tubular injury and acute tubular necrosis visualized histologically as focal tubular epithelial necrosis, often with extensive granular casts that obstruct the tubular lumen and lead to rupture of the basement membrane)
Ototoxicity and vestibulotoxicity (risk of ototoxicity is higher when used concurrently with loop diuretics) resulting in tinnitus, ataxia, vertigo
Neuromuscular blockade (risk increases in the event of hypomagnesemia or myasthenia gravis, and in patients who use calcium channel blockers)
Teratogenicity
Contraindications: Myasthenia gravis Botulism Pregnancy Cautious use in patients with renal dysfunction
Mechanisms of resistance:
Inactivation via acetylation, phosphorylation, and/or adenylation by secreted bacterial transferase enzymes
Minocycline
Tetracycline IV and oral form CNS penetration → poor Route of elimination → renal Oral tetracyclines should not be taken with substances that contain large amounts of Ca2+, Mg2+, or Fe2+ (e.g., milk, antacids, iron supplements, respectively) because divalent cations inhibit the intestinal absorption of tetracyclines.
Mechanism:
Bind 30S subunit → aminoacyl-tRNA is blocked from binding to ribosome acceptor site → inhibition of bacterial protein synthesis (bacteriostatic effect)
Clinical Use:
Bacteria that lack a cell wall (e.g, Mycoplasma pneumoniae, Ureaplasma)
Intracellular bacteria, such as Rickettsia, Chlamydia, or Anaplasma (tetracyclines accumulate intracellularly and are, therefore, effective against intracellular pathogens)
Borrelia burgdorferi
Ehrlichia, Vibrio cholerae, Francisella tularensis
Adverse Effects:
Hepatotoxicity
Deposition in bones and teeth → inhibition of bone growth (in children) and discoloration of teeth
Damage to mucous membranes (e.g., esophagitis, GI upset)
DRESS syndrome
Photosensitivity: drug or metabolite in the skin absorbs UV radiation → photochemical reaction → formation of free radicals → damage to cellular components → inflammation (sunburn-like)
Degraded tetracyclines are associated with Fanconi syndrome.
Pseudotumor cerebri (rarely)
Contraindications: Children < 8 years of age (except doxycycline) Pregnant women (except doxycycline) Patients with renal failure (except doxycycline) Cautious use in patients with hepatic dysfunction
Mechanisms of Resistance:
Plasmid-encoded transport pumps increase efflux out of the bacterial cell and decrease uptake of tetracyclines.
Doxycycline
Tetracycline
Oral form
CNS penetration: poor
Gastrointestinal elimination (only tetracycline that is not contraindicated in patients with renal failure)
Oral tetracyclines should not be taken with substances that contain large amounts of Ca2+, Mg2+, or Fe2+ (e.g., milk, antacids, iron supplements, respectively) because divalent cations inhibit the intestinal absorption of tetracyclines.
Mechanism:
Bind 30S subunit → aminoacyl-tRNA is blocked from binding to ribosome acceptor site → inhibition of bacterial protein synthesis (bacteriostatic effect)
Clinical Use:
Bacteria that lack a cell wall (e.g, Mycoplasma pneumoniae, Ureaplasma)
Intracellular bacteria, such as Rickettsia, Chlamydia, or Anaplasma (tetracyclines accumulate intracellularly and are, therefore, effective against intracellular pathogens)
Borrelia burgdorferi
Ehrlichia, Vibrio cholerae, Francisella tularensis
Community-acquired MRSA (doxycycline)
Adverse Effects:
Hepatotoxicity
Deposition in bones and teeth → inhibition of bone growth (in children) and discoloration of teeth
Damage to mucous membranes (e.g., esophagitis, GI upset)
Photosensitivity: drug or metabolite in the skin absorbs UV radiation → photochemical reaction → formation of free radicals → damage to cellular components → inflammation (sunburn-like)
Degraded tetracyclines are associated with Fanconi syndrome.
Pseudotumor cerebri (rarely)
Contraindications: Children < 8 years of age (except doxycycline) Pregnant women (except doxycycline) Patients with renal failure (except doxycycline) Cautious use in patients with hepatic dysfunction
Mechanisms of Resistance:
Plasmid-encoded transport pumps increase efflux out of the bacterial cell and decrease uptake of tetracyclines.
Chloramphenicol
Mechanism:
Bind 50S subunit → blockage of peptidyltransferase → inhibition of bacterial protein synthesis (bacteriostatic effect)
CNS penetration → good
Route of elimination → renal elimination after hepatic metabolism
Clinical Use:
Meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae) and rickettsial diseases (eg, Rocky Mountain spotted fever [Rickettsia rickettsii]).
Limited use due to toxicity but often still used in developing countries because of low cost.
Adverse Effects:
Anemia (dose dependent), aplastic anemia (dose independent; due to bone marrow suppression), gray baby syndrome (in premature infants because they lack liver UDP-glucuronosyltransferase; hyponatremia, cyanosis, vomiting, flaccidity, hypothermia, and shock).
Potent inhibitory effect on cytochrome P450 isoforms CYP2C19 and CYP3A4
Contraindications:
Infancy
Pregnancy
Cautious use in patients with renal and/or hepatic dysfunction
Mechanism of resistance:
Plasmid-encoded acetyltransferase inactivates the drug.
Clindamycin
Mechanism:
Binds to 50S subunit → blockage of peptide translocation (transpeptidation) → inhibition of peptide chain elongation → inhibition of bacterial protein synthesis (bacteriostatic effect)
CNS penetration → poor
Route of elimination → both renal and biliary
Actively transported in macrophages so can have penetration in abscesses
Clinical Use:
Anaerobic infections (eg, Bacteroides spp., Clostridium perfringens) in aspiration pneumonia, lung abscesses, and oral infections.
Also effective against invasive group A streptococcal infection (especially invasive infections)
Partially effective against gram-positive aerobes
Can be used in MRSA infections
Babesia (together with quinine)
Gardnerella vaginalis
Acne
Not effective against Enterococci
Treats anaerobic infections above the diaphragm vs metronidazole (anaerobic infections below diaphragm).
Adverse Effects:
Pseudomembranous colitis (C difficile overgrowth), fever, diarrhea, teratogenicity
Associated with esophagitis due to low pH and irritant effects on the distal esophagus
Contraindications:
In pregnant women during the 1st trimester and breastfeeding women, clindamycin should be used only if benefits outweigh the risks.
Cross-resistance with macrolides
Fosfomycin
Oral and IV form
Mechanism:
Inhibits enolpyruvate transferase (MurA) → no formation of N-acetylmuramic acid (a component of bacterial cell wall) → inhibition of cell wall synthesis → cell death (bactericidal effect)
Route of elimination → renal
Clinical use:
Women with uncomplicated urinary tract infections (e.g., cystitis due to E. coli or E. faecalis)
Adverse Effects:
Mild electrolyte imbalances (e.g., hypernatremia, hypokalemia)
Diarrhea
Contraindications:
Hypersensitivity
Mechanisms of resistance:
MurA mutations
Linezolid
Oxazolidinone
Oral form
Mechanism:
Binds to 23S subunit of 50S bacterial ribosome → inhibition of initiation complex formation → inhibition of bacterial protein synthesis (bacteriostatic effect)
Unlike other antibiotics that inhibit later stages of bacterial protein synthesis (e.g., elongation), linezolid inhibits protein synthesis at the very first step of translation.
Nonselective monoamine oxidase inhibition (MAOI)
Bactericidal against streptococci
CNS penetration → good
Route of elimination → both biliary and renal elimination after hepatic metabolism
Clinical Use:
Gram ⊕ species including MRSA and VRE.
Adverse Effects:
Bone marrow suppression (especially thrombocytopenia), peripheral neuropathy, serotonin syndrome (increase risk with SSRIs, MAOIs, SNRIs, bupropion), optic neuropathy (decrease visual acuity, decrease color perception, scotomas), GI upset.
Contraindications:
Concurrent use with MAOIs and selective serotonin reuptake inhibitors (SSRIs)
Mechanism of resistance:
Point mutation of 23S rRNA
Erythromycin
Macrolide Oral or IV form CNS penetration → poor Route of elimination → biliary All macrolides (except azithromycin) have a short half-life.
Mechanism:
Bind to 23S ribosomal RNA molecule of the 50S subunit → blockage of translocation → inhibition of bacterial protein synthesis (bacteriostatic effect)
Clinical Use:
Atypical pneumonia caused by Mycoplasma pneumonia, Legionella pneumophila, Chlamydophila pneumoniae
Bordetella pertussis
STIs caused by Chlamydia
Gram-positive cocci (especially for the treatment of streptococcal infection in patients who are allergic to penicillin)
Neisseria spp.
Second-line prophylaxis for N. meningitidis
Ureaplasma urealyticum
Erythromycin is used off-label for the treatment of gastroparesis because it increases GI motility.
Adverse Effects: Increased intestinal motility → GI upset QT-interval prolongation, arrhythmia Acute cholestatic hepatitis Eosinophilia Rash
Drug Interactions:
Erythromycin enhances the effect of oral anticoagulants (e.g., warfarin).
Erythromycin and clarithromycin increase theophylline serum concentrations due to CYP3A4 inhibition (cytochrome P450 inhibitors)
Contraindications:
Erythromycin estolate and clarithromycin are contraindicated in pregnant women (potentially hazardous to the fetus).
Mechanisms of Resistance:
Methylation of the binding site of 23S rRNA prevents the macrolide from binding to rRNA.
Clarithromycin
Macrolide Oral or IV form CNS penetration → poor Route of elimination → biliary All macrolides (except azithromycin) have a short half-life.
Mechanism:
Bind to 23S ribosomal RNA molecule of the 50S subunit → blockage of translocation → inhibition of bacterial protein synthesis (bacteriostatic effect)
Clinical Use:
Atypical pneumonia caused by Mycoplasma pneumonia, Legionella pneumophila, Chlamydophila pneumoniae
Bordetella pertussis
STIs caused by Chlamydia
Gram-positive cocci especially for the treatment of streptococcal infection in patients who are allergic to penicillin)
Neisseria spp.
Second-line prophylaxis for N. meningitidis
Mycobacterium avium (prophylaxis: azithromycin; treatment: azithromycin, clarithromycin)
H. pylori (clarithromycin is the part of triple therapy)
Ureaplasma urealyticum
Adverse Effects: Increased intestinal motility → GI upset QT-interval prolongation, arrhythmia Acute cholestatic hepatitis Eosinophilia Rash
Drug Interactions:
Erythromycin and clarithromycin increase theophylline serum concentrations due to CYP3A4 inhibition (cytochrome P450 inhibitors)
Contraindications:
Erythromycin estolate and clarithromycin are contraindicated in pregnant women (potentially hazardous to the fetus) .
Azithromycin and clarithromycin are contraindicated in patients with hepatic failure (erythromycin should be used cautiously).
Cautious use of clarithromycin in patients with renal failure
Mechanisms of Resistance:
Methylation of the binding site of 23S rRNA prevents the macrolide from binding to rRNA.
Polymyxin B
IV or IM form
Mechanism: Cationic detergent (polypeptides) molecule that binds to phospholipids of the cytoplasmic membrane of gram-negative bacteria → increased membrane permeability → leakage of cell contents → cell death (bactericidal effect) Binds to and inactivates endotoxins CNS penetration → poor Route of elimination → mostly renal
Clinical Use:
Severe infections caused by multidrug-resistant gram-negative bacteria
Effective only against gram-negative bacteria including P. aeruginosa, K. pneumoniae, E. coli, Acinetobacter baumannii, and Enterobacteriaceae spp.
Proteus, Neisseria, and Serratia spp. are resistant to polymyxins.
Not effective against gram-positive bacteria (because gram-positive bacteria do not have an outer membrane)
Polymyxin B is a component of a triple antibiotic ointment (bacitracin, neomycin, and polymyxin B) used for superficial skin infections
Oral polymyxin B may be used to disinfect the bowel to prevent ICU infections (polymyxins have a poor oral absorption)
Adverse Effects:
Nephrotoxicity, neurotoxicity (e.g., paresthesias, weakness, speech disorders, neuromuscular blockage), respiratory failure.
Urticaria, eosinophilia, and/or anaphylactoid reactions
Contraindications:
Hypersensitivity to polymyxins
Cautious use in patients with renal dysfunction
Polymyxin E (Colistin)
IV or IM form
Mechanism: Cationic detergent (polypeptides) molecule that binds to phospholipids of the cytoplasmic membrane of gram-negative bacteria → increased membrane permeability → leakage of cell contents → cell death (bactericidal effect) Binds to and inactivates endotoxins CNS penetration → poor Route of elimination → mostly renal
Clinical Use:
Severe infections caused by multidrug-resistant gram-negative bacteria
Effective only against gram-negative bacteria including P. aeruginosa, K. pneumoniae, E. coli, Acinetobacter baumannii, and Enterobacteriaceae spp.
Proteus, Neisseria, and Serratia spp. are resistant to polymyxins.
Not effective against gram-positive bacteria (because gram-positive bacteria do not have an outer membrane)
Adverse Effects:
Nephrotoxicity, neurotoxicity (e.g., paresthesias, weakness, speech disorders, neuromuscular blockage), respiratory failure.
Urticaria, eosinophilia, and/or anaphylactoid reactions
Contraindications:
Hypersensitivity to polymyxins
Cautious use in patients with renal dysfunction
Nitrofurantoin
Mechanism:
Reduced by bacterial nitroreductases to reactive metabolites → bind to bacterial ribosomes → impaired metabolism, impaired synthesis of protein, DNA, and RNA → cell death (bactericidal effect)
Route of elimination → primarily renal (rapidly excreted after absorption), small amounts in feces
Clinical Use:
Urinary tract pathogens
Gram-positive → Enterococci, Staphylococcus saprophyticus, group B streptococcus, Staphylococcus aureus, Staphylococcus epidermidis
Gram-negative → E. coli, Enterobacter spp., Shigella spp., Salmonella spp., Citrobacter spp, Neisseria spp, Bacteroides spp., Klebsiella spp.
Not effective against Pseudomonas and/or Proteus
Treatment and prophylaxis of acute uncomplicated UTIs (e.g., urethritis, cystitis)
Asymptomatic bacteriuria or symptomatic UTI in pregnant women
Should not be used in (suspected) pyelonephritis because nitrofurantoin does not achieve adequate concentration in renal tissue
Adverse Effects: Pulmonary fibrosis Hemolytic anemia in patients with G6PD deficiency GI upset Reversible peripheral neuropathy
Contraindications:
Children < 1 month of age
Breastfeeding women
Women at 38–42 weeks’ gestation or during delivery (because of the risk of hemolytic anemia in an infant due to the lack of erythrocyte glutathione peroxidase)
Hepatic dysfunction
Renal dysfunction with a creatinine clearance < 60 mL/min (in renal failure, urinary drug levels do not reach concentrations required to treat UTIs, and the retention of nitrofurantoin in systemic circulation increases the risk of adverse effects.)
Sulfa Drugs
Antibiotics (sulfamethoxazole (SMX), sulfadiazine, sulfisoxazole)
Diuretics (thiazides, furosemide, acetazolamide)
Anti-inflammatory drugs (sulfasalazine, celecoxib)
Sulfonylureas
Probenecid
Trimethoprim (TMP)
Oral or IV cotrimoxazole (TMP/SMX)
Mechanism:
Inhibition of bacterial folic acid synthesis
Inhibit dihydrofolate reductase (DHFR) (DHFR uses NADPH to reduce dihydrofolic acid to tetrahydrofolic acid (THF); THF can be converted to methylene-THF; methylene-THF is an important cofactor for thymidylate synthetase, which catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP))
Bacteriostatic but become bactericidal when combined with sulfonamides
The combination of TMP and SMX also prevents antibiotic resistance.
CNS penetration → good
Route of elimination → primarily renal (via tubular secretion) (only a small amount is excreted with bile)
Clinical Use: Common indications include UTIs and acute otitis media. -TMP/SMX Shigella Salmonella Empiric treatment for simple UTI Prophylaxis and treatment of P. jirovecii Prophylaxis of toxoplasmosis
Adverse Effects:
Megaloblastic anemia
Leukopenia, granulocytopenia (can be prevented with concomitant folinic acid administration)
In high doses → hyperkalemia, particularly in HIV-positive patients
Artificially increased creatinine (despite unchanged GFR) (similar to the actions of amiloride TMP blocks the epithelial Na+ channel in the DCT and collecting duct, this reduces transepithelial voltage and impairs Na/K exchange, leading to reduced potassium excretion and hyperkalemia. This effect is often magnified elderly population, renal failure and those given other K sparing diuretics, ACE inhibitors and ARBs).
Contraindications: Children < 2 years of age Pregnant women Breastfeeding women Cautious use in people with hepatic failure, renal failure
Pyrimethamine
Oral sulfadiazine in combination with pyrimethamine
Mechanism:
Inhibition of bacterial folic acid synthesis
Inhibit dihydrofolate reductase (DHFR) (DHFR uses NADPH to reduce dihydrofolic acid to tetrahydrofolic acid (THF); THF can be converted to methylene-THF; methylene-THF is an important cofactor for thymidylate synthetase, which catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP))
Bacteriostatic but become bactericidal when combined with sulfonamides
The combination of TMP and SMX also prevents antibiotic resistance.
CNS penetration → good
Route of elimination → primarily renal (via tubular secretion) (only a small amount is excreted with bile)
Clinical Use: Common indications include UTIs and acute otitis media. -TMP/SMX Shigella Salmonella Empiric treatment for simple UTI Prophylaxis and treatment of P. jirovecii Prophylaxis of toxoplasmosis
Adverse Effects:
Megaloblastic anemia
Leukopenia, granulocytopenia (can be prevented with concomitant folinic acid administration)
In high doses → hyperkalemia, particularly in HIV-positive patients
Artificially increased creatinine (despite unchanged GFR)
Contraindications: Children < 2 years of age Pregnant women Breastfeeding women Cautious use in people with hepatic failure, renal failure
Sulfamethoxazole (SMX)
Sulfonamide
Oral or IV cotrimoxazole (TMP/SMX)
Mechanism:
Inhibition of bacterial folic acid synthesis
Inhibit dihydropteroate synthase.
Bacteriostatic but become bactericidal when combined with TMP
The combination of TMP and SMX also prevents antibiotic resistance.
CNS penetration → good
Route of elimination → primarily renal (via tubular secretion) (only a small amount is excreted with bile)
Metabolized in the liver via acetylation
Clinical Use: Common indications include UTIs and acute otitis media. -TMP/SMX Shigella Salmonella Empiric treatment for simple UTI Prophylaxis and treatment of P. jirovecii Prophylaxis of toxoplasmosis
Adverse Effects:
Fever
Photosensitivity
Sulfonamides hypersensitivity reactions (especially urticaria or hives) (sulfonamides are the second most common antibacterial to cause hypersensitivity reactions, after β-lactams)
Stevens-Johnson syndrome
Triggers hemolytic anemia in G6PD-deficient patients
Aplastic anemia, thrombocytopenia, and pancytopenia
Agranulocytosis
Hyperkalemia
GI upset
Nephrotoxicity (especially acute tubulointerstitial nephritis)
Kernicterus in infancy
Displacement of other drugs (e.g., warfarin) from albumin (SMX has a higher binding affinity to albumin, so it can displace drugs like warfarin from albumin, resulting in increased free plasma concentrations of the displaced drug)
Drug interactions due to CYP450 inhibition
Contraindications: Children < 2 years of age Pregnant women Breastfeeding women Cautious use in people with hepatic failure, renal failure
Mechanisms of Resistance:
Mutation in bacterial dihydropteroate synthase
Decreased uptake of sulfonamide
Increased para-aminobenzoate (PABA) synthesis (PABA is a substrate of dihydropteroate synthase and a precursor of folic acid)
