Antimicrobials Flashcards
Penicillin V
Prototype B lactam antibiotic–Oral form
MOA: binds PBPs and blocks transpeptidase crosslinking
Uses: mostly gram positive (s. Pneumo, s. Pyogenes, actinomyces); Also used for N? Meningitidis and T. pallidum. Bactericidal for gram positive cocci, gram positive rods, gram negative cocci, and spirochetes. Penicillinase sensitive.
TOXICITY: hypersensitivity reactions, hemolytic anemia.
RESISTANCE: penicillinase in bacteria (a type of B lactamase) cleaves B lactam ring
Penicillin G
Prototype B lactam antibiotic–IV and IM form
MOA: binds PBPs and blocks transpeptidase crosslinking
Uses: mostly gram positive (s. Pneumo, s. Pyogenes, actinomyces); Also used for N? Meningitidis and T. pallidum. Bactericidal for gram positive cocci, gram positive rods, gram negative cocci, and spirochetes. Penicillinase sensitive.
TOXICITY: hypersensitivity reactions, hemolytic anemia.
RESISTANCE: penicillinase in bacteria (a type of B lactamase) cleaves B lactam ring
Ampicillin
Penicillinase-sensitive penicillin
MOA: same as penicillin. Wider spectrum; penicillinase sensitive. Also combine with clavulanic acid to protect against B-lactamase.
USES: extended-spectrum penicillin–Haemophilus influenzae, E. Coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci (ampicillin/amoxicillin HELPSS kill enterococci)
TOXICITY: hypersensitivity reactions; rash; pseudo membranous colitis
RESISTANCE: penicillinase in bacteria (a type of B lactamase) cleaves B-lactam ring
Oxacillin
Penicillinase-resistant penicillin
MOA: same as penicillin. Narrow spectrum; penicillinase resistant because bulky R group blocks access of B lactamase to B lactam ring.
USE: S. aureus (except MRSA; resistant because of altered PBP target site)
TOXICITY: hypersensitivity reactions, interstitial nephritis
Pipercillin
Antipsuedomonal
MOA: same as penicillin. Extended spectrum.
USES: Pseudomonas spp. And gram negative rods; susceptible to penicillinase; use with B lactamase inhibitors.
TOXICITY: hypersensitivity reactions
Cephalosporins
Inhibits peptidoglycan cross-linking; less susceptible to penicillinase than penicillin
1st generation: cefazolin, cephalexin
2nd generation: cefaclor, cefprozi, cefoxitin
3rd generation: cefpodoxime, cefotaxime, ceftriaxone
4th generation: cefepime
1st generation cephalosporins
Cefazolin, cephalexin
PEcK: Proteus mirabilis, E. coli, Klebsiella pneumoniae
Don’t penetrate CNS
2nd generation cephalosporins
Cefaclor, cefprozi, cefoxitin; extended gram negative spectrum
HEN PEcKS: Haemophilus influenzae, Enterobacter, Neisseria, Proteus, E. Coli, Klebsiella, Serratia
3rd generation cephalosporins
Cefpodoxime, cefotaxime, ceftriaxone
Serious gram negative infections resistant to other beta lactams
Penetrates the CNS-meningitis, gonorrhea, pseudomonas
Less effective against gram positive than 1st
4e generation cephalosporins
Cefepime
Increased activity against pseudomonas and gram positive
Enhanced resistance to beta lactamase
Crosses the BBB
Imipenem
Cabapenem
MOA: broad-spectrum, B-lactamase-resistant capbapenem. Inhibit cell wall synthesis. Always administered with cilastatin (inhibitor of renal dehydropeptidase I) to decreased inactivation of drug in renal tubules.
USES: gram positive cocci, gram negative rods, and anaerobes. Wide spectrum, but significant side effects limit use to life threatening infections or after other drugs have failed.
TOXICITY: GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels.
Vancomycin
MOA: inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors. Bacteriocidal.
USES: gram positive only–serious, multidrug-resistant organisms, including MRSA, enterococci, and Clostridium difficile (oral dose for pseudomembranous colitis)
TOXICITY: well tolerated in general–but NOT trouble free. Nephrotoxicity, ototoxicity, thrombophlebitis, diffuse flushing–red many syndrome (can largely prevent by pretreatment with antihistamines and slow infusion rate)
RESISTANCE: occurs in bacterial via amino acid modification of D-ala D-ala to D-ala D-lac
Tobramycin
Aminoglycoside–30S inhibitor
MOA: bactericidal; inhibits formation of inititation complex and causes misreading of mRNA. Also blocks translocation. Requires O2 for uptake; therefore ineffective against anaerobes.
USES: severe, gram negative rod infections. Synergistic with B lactam antibiotics.
TOXICITY: nephrotoxicity, neuromuscular blockade, ototoxicity (especially when used with loop diuretics), teratogenic.
RESISTANCE: bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation.
Doxycycline
MOA: bacteriostatic; binds 30s and prevents attachment of aminoacyl-tRNA; limited CNS penetration. Doxycycline is fecally eliminated and can be used in patients with renal failure. Do not take with milk (calcium), antacids (calcium or magnesium), or iron-containing preparations because divalent cations inhibit absorption in gut.
USES: Borrelia burgdorferi, M pneumoniae. Drug’s ability to accumulate intracellularly makes it very effective against Rickettsia and Chlamydia. Also used to treat acne.
TOXICITY: GI distress, discoloration of Teeth and inhibition of bone growth in children, photosensitivity. Contraindicated in pregnancy.
RESISTANCE: decreased uptake or increased efflux out of bacterial cells by plasmid-encoded transport pumps.
Erythromycin
Macrolide
MOA: binds 50S subunit and inhibits translocation. Bacteriostatic.
Uses: atypical pneumonias-mycoplasma, chlamydia, legionella, STDs (chlamydia), gram positive cocci (strep if allergic to penicillin)
TOXICITY: GI motility issues, arrhythmia caused by prolonged QT, Canute cholestatic hepatitis, rash, eosinophilia. Increases serum concentration of theophyllines, oral anticoagulants.
RESISTANCE: methylation of 23s rRNA-binding site prevents binding of drug.
Clindamycin
MOA: blocks peptide transfer (translocation) at 50s ribosomal subunit. Bacteriostatic.
USES: anaerobic infections (e.g. Bacteroides spp., Clostridium perfringens) in aspiration pneumonia, lung abscesses, and oral infections. Also effective against invasive Group A strep infection. **treats anaerobes above the diaphragm vs metronidazole
TOXICITY: pseudomembranous colitis (C. Difficile overgrowth), fever, diarrhea
Linezolid
Oxazolidinone
MOA: inhibits protein synthesis by binding to 50S subunit and preventing formation of the initiation complex.
USES: gram positive species including MRSA and VRE
TOXICITY: bone marrow suppression (especially thrombocytopenia), peripheral neuropathy, serotonin syndrome
RESISTANCE: point mutation of ribosomal RNA
Sulfamethoxazole
Sulfonamide
MOA: inhibits folate synthesis. Para-aminobenzoic acid (PABA) antimetabolites inhibit dihydropteroate synthase. Bacteriostatic.
Uses: gram positive, gram negative, Nocardia, Chlamydia. Triple sulfas or SMX for simple UTI.
TOXICITY: hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (Tubulointerstitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin (e.g. Warfarin)
RESISTANCE: altered enzyme (bacterial dihydropteroate synthase), decreased uptake, or increased PABA synthesis
Trimethoprim
MOA: Inhibitor of dihydrofolate reductase. Bacteriostatic.
USES: used in combination with sulfonamides, causing sequential block of folate synthesis. Combination used for UTIs, shigella, salmonella, pneumocystis jirovecii pneumonia treatment and prophylaxis, toxoplasmosis prophylaxis.
TOXICITY: megaloblastic anemia, thrombocytopenia, leukopenia
Ciprofloxacin
fluoroquinolone
MOA: inhibits DNA gyrate (topoisomerase II) and topoisomerase IV. bactericidal. Must not be taken with antacids.
Uses: gram negative rods of urinary and GI tracts, Neisseria, some gram positive organisms
TOXICITY: GI upset, super infections, skin rashes, headache, dizziness. Less commonly, can cause tendonitis, tendon rupture, leg cramps, and myalgias. Contraindicated in pregnancy, nursing mothers, and children under 18 due to possible damage to cartilage. Some may cause prolonged QT interval. May cause tendon rupture in people over 60y and in patients taking prednisone.
RESISTANCE: chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.
Metronidazole
MOA: Forms free radical toxic metabolites in bacterial cell that Damage DNA. Bactericidal, antiprotozoal.
USES: treats GET GAP–Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (Bacteroides, C. Difficile). Used with a proton pump inhibitor and clarithromycin for “triple therapy” against H. Pylori.
TOXICITY: disulfiram-like reaction (severe flushing, tachycardia, hypotension) with alcohol (thought to be due to its inhibition of alcohol oxidizing enzymes–>accumulation of acetaldehyde); headache, metallic taste
Amoxicillin
Penicillinase-sensitive penicillin
MOA: same as penicillin. Wider spectrum; penicillinase sensitive. Also combine with clavulanic acid to protect against B-lactamase.
USES: extended-spectrum penicillin–Haemophilus influenzae, E. Coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci (ampicillin/amoxicillin HELPSS kill enterococci)
TOXICITY: hypersensitivity reactions; rash; pseudo membranous colitis
RESISTANCE: penicillinase in bacteria (a type of B lactamase) cleaves B-lactam ring
Nafcillin
Penicillinase-resistant penicillin
MOA: same as penicillin. Narrow spectrum; penicillinase resistant because bulky R group blocks access of B lactamase to B lactam ring.
USE: S. aureus (except MRSA; resistant because of altered PBP target site)
TOXICITY: hypersensitivity reactions, interstitial nephritis
Dicloxacillin
Penicillinase-resistant penicillin
MOA: same as penicillin. Narrow spectrum; penicillinase resistant because bulky R group blocks access of B lactamase to B lactam ring.
USE: S. aureus (except MRSA; resistant because of altered PBP target site)
TOXICITY: hypersensitivity reactions, interstitial nephritis