Antimicrobials Flashcards
penicillin G, V
penicillin G (IV and IM form), penicillin V (oral); prototype B-lactam antibiotics
MOA: D-Ala-D-Ala structural analog => binds penicillin-binding proteins (PBPs, transpeptidases) => block transpeptidase cross-linking of peptidoglycan in cell wall => activate autolytic enzymes (bactericidal)
use: gram positive organisms (S. pneumoniae, S. pyogenes, Actinomyces), gram negative cocci (N. meningitidis), and spirochetes (T. pallidum)
AE: hypersensitivity reactions, direct Coombs positive hemolytic anemia, drug-induced interstitial nephritis
amoxicillin, ampicillin, aminopenicillins
penicillinase-sensitive penicillins
MOA: same as penicillin (D-Ala-D-Ala analog => prevents cross-linking of peptidoglycan in cell wall); can combine with clavulanic acid to protect against destruction by B-lactamase
use: H. influenzae, H. pylori, E. coli, Enterococci, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella (“HHEELPSS kill enterococci”)
AE: hypersensitivity reactions, rash, pseudomembranous colitis
dicloxacillin, nafcillin, oxacillin
penicillinase-resistant penicillins
MOA: same as penicillin (D-Ala-D-Ala analog => prevents cross-linking of peptidoglycan in cell wall); bulky R group blocks access of B-lactamase to B-lactam ring
use: S. aureus (except MRSA)
AE: hypersensitivity reactions, interstitial nephritis
piperacillin
antipseudomonal penicillin
MOA: same as penicillin (D-Ala-D-Ala analog => prevents cross-linking of peptidoglycan in cell wall); penicillinase sensitive (use with B-lactamase inhibitors)
use: Pseudomonas species and gram negative rods
AE: hypersensitivity reactions
cefazolin, cephalexin
first generation cephalosporins
MOA: B-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases; bactericidal
use: gram positive cocci, Proteus mirabilis, E. coli, Klebsiella pneumoniae; cefazolin used prior to surgery to prevent S. aureus wound infections (“positive PEcK”)
AE: hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency
DDI: increase nephrotoxicity of aminoglycosides
cefaclor, cefoxitin, cefuroxime, cefotetan
second generation cephalosporins (“2nd graders wear fake fox fur to tea parties”)
MOA: B-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases; bactericidal
use: gram positive cocci, H. influenzae, Enterobacter aerogenes, Neisseria species, Serratia marcescens, Proteus mirabilis, E. coli, Klebsiella pneumoniae (“positive HENS PEcK”)
AE: hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency
DDI: increase nephrotoxicity of aminoglycosides
ceftriaxone, cefotaxime, cefpodoxime, ceftazidime, cefixime
third generation cephalosporins
MOA: B-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases; bactericidal; can cross BBB
use: serious gram negative infections resistant to other B-lactams; ceftriaxone = meningitis, gonorrhea, disseminated Lyme disease; ceftazidime = Pseudomonas
AE: hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency
DDI: increase nephrotoxicity of aminoglycosides
cefepime
fourth generation cephalosporin (“four vowels”)
MOA: B-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases; bactericidal
use: gram negative organisms, increased activity against Pseudomonas and gram positive orgamisms
AE: hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency
DDI: increase nephrotoxicity of aminoglycosides
ceftaroline
fifth generation cephalosporin
MOA: B-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases; bactericidal
use: broad gram positive and gram negative organism coverage; UNLIKE 1st-4th generation, 5th generation covers MRSA and Enterococcus faecalis but DOES NOT cover Pseudomonas
AE: hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency
DDI: increase nephrotoxicity of aminoglycosides
clavulanic acid, avibactam, sulbactam, tazobactam
B-lactamase inhibitors
MOA: added to penicillin antibiotics to protect the antibiotic from destruction by B-lactamase
doripenem, imipenem, meropenem, ertapenem
carbapenems (“Pens cost a DIME”)
MOA: B-lactamase-resistant; binds PBPs => inhibition of cell wall synthesis => cell death; always administered with cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules
use: gram positive cocci, gram negative rods, anaerobes; use limited to life-threatening infections or when other drugs have failed
AE: GI distress, rash, CNS toxicity (seizures)
aztreonam
monobactam antibiotic
MOA: less susceptible to B-lactamases; prevents peptidoglycan cross-linking by binding to PBP3; synergistic with aminoglycosides; no cross-allergenicity with penicillins
use: gram negative rods ONLY; for penicillin-allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides
AE: usually nontoxic; occasional GI upset
vancomycin
glycopeptide antibiotic
MOA: inhibits cell wall peptidoglycan formation by binding D-Ala-D-Ala portion of cell wall precursors; bactericidal against most bacteria (bacteriostatic against C. difficile); not susceptible to B-lactamases
use: gram positive bugs ONLY; for serious, multidrug resistant organisms (MRSA, S. epidermidis, sensitive Enterococcus species, and C. difficile)
AE: nephrotoxicity, ototoxicity, thrombophlebitis, diffuse flushing (vancomycin infusion reaction), DRESS syndrome
gentamicin, neomycin, amikacin, tobramycin, streptomycin
aminoglycosides (“mean GNATS cannot kill anaerobes”)
MOA: bind 30S subunit => irreversible inhibition of initiation complex; can cause misreading of mRNA and block translocation; require O2 for uptake - do NOT work against anaerobes
use: severe gram negative rod infections; synergistic with B-lactam antibiotics; neomycin for bowel surgery
AE: nephrotoxicity, neuromuscular blockade, ototoxicity, teratogenicity
tetracycline, doxycycline, minocycline
tetracyclines
MOA: bacterioSTATIC; bind to 30S and prevent attachment of aminoacyl-tRNA; limited CNS penetration
use: Borrelia burgdorferi, M. pneumoniae; Rickettsia, Chlamydia; community-acquired MRSA (doxycycline); doxycycline used for patients with renal failure (fecally eliminated)
AE: GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity, teratogenic; do not take tetracyclines with milk, antacids, or iron-containing preparations because divalent cations inhibit drugs’ absorption in the gut
tigecycline
tetracycline derivative
MOA: binds to 30S, inhibiting protein synthesis; also bacterioSTATIC
use: broad-spectrum anaerobic, gram negative and gram positive coverage; multidrug-resistant organisms (MRSA, VRE)
AE: nausea, vomiting
chloramphenicol
MOA: blocks peptidyltransferase at 50S ribosomal unit; bacterioSTATIC
use: meningitis (H. influenzae, N. meningitidis, S. pneumoniae) and rickettsial diseases (Rocky Mountain spotted fever); limited use due to toxicity
AE: anemia (dose-dependent), aplastic anemia (dose-independent), gray baby syndrome (premature infants lack liver UDP-glucuronosyltransferase)
clindamycin
lincomycin antibiotic
MOA: blocks peptide transfer (translocation) at 50S ribosomal subunit; bacterioSTATIC
use: anaerobic infections (Bacteroides species, C. perfringens) in aspiration pneumonia, lung abscesses, and oral infections; treats anaerobic infections ABOVE the diaphragm
AE: pseudomembranous colitis, fever, diarrhea
linezolid
oxazolidinone antibiotic
MOA: inhibits protein synthesis by binding to 50S subunit and preventing formation of initiation complex
use: gram positive species including MRS and VRE
AE: myelosuppression (especially thrombocytopenia), peripheral neuropathy, serotonin syndrome (partial MAO inhibition)
azithromycin, clarithromycin, erythromycin
macrolides
MOA: inhibit protein synthesis by blocking translocation; bind to 23S rRNA of 50S ribosomal subunit; bacterioSTATIC
use: atypical pneumonias (Mycoplasma, Chlamydia, Legionella), STIs (Chlamydia), gram positive cocci (streptococcal infections in patients allergic to penicillin), B. pertussis
AE: gastrointestinal Motility issues, Arrhythmia caused by prolonged QT interval, acute cholestatic hepatitis, Rash, eOsinophilia (“MACRO”)
DDI: increases serum concentration of theophylline and oral anticoagulants
colistin (polymyxin E), polymyxin B
polymyxins
MOA: cation polypeptides that bind to phospholipids on cell membrane of gram negative bacteria; disrupt cell membrane integrity => leakage of cellular components => cell death
use: salvage therapy for multidrug-resistant gram negative bacteria (P. aeruginosa, E. coli, K. pneumoniae); polymyxin B is used in triple antibiotic ointments
AE: nephrotoxicity, neurotoxicity (slurred speech, weakness, paresthesias, respiratory failure
sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine
sulfonamides
MOA: inhibit dihydropteroate synthase => inhibits folate synthesis; bacterioSTATIC (bactericidal when combined with trimethoprim)
use: gram positive and negative, Nocardia; TMP-SMX for simple UTI
AE: hypersensitivity reaction, hemolysis of G6PD deficiency, nephrotoxicity (tubulointerstitial nephritis), photosensitivity, Stevens-Johnson syndrome, kernicterus in infants, displaces other drugs from albumin (e.g., warfarin)
dapsone
sulfone antibiotic
MOA: similar to sulfonamides (inhibit folate synthesis), but structurally distinct
use: leprosy (lepromatous and tuberculoid), Pneumocystis jirovecii prophylaxis or treatment (when combined with TMP)
AE: hemolysis in G6PD deficiency, methemoglobinemia, agranulocytosis
trimethoprim
MOA: inhibits bacterial dihydrofolate reductase; bacterioSTATIC (bactericidal when combined with SMX - sequential block of folate synthesis)
use: UTIs, Shigella, Salmonella, Pneumocystis jirovecii pneumonia treatment and prophylaxis, toxoplasmosis prophylaxis
AE: hyperkalemia (high doses), megaloblastic anemia, leukopenia, granulocytopenia (avoided with coadministration of leucovorin)
ciprofloxacin, enoxacin, norfloxacin, ofloxacin; gemifloxacin, levofloxacin, moxifloxacin
fluoroquinolones
MOA: inhibit prokaryotic enzymes topoisomerase II (DNA gyrase) and topoisomerase IV; bactericidal
use: gram negative rods of urinary and GI tracts (including Pseudomonas), some gram positive organisms, otitis externa
AE: GI upset, superinfections, skin rashes, headache, dizziness, leg cramps and myalgia; must not be taken with antacids; may cause tendonitis or rupture, possible damage to cartilage - contraindicated in pregnancy and children <18; may prolong QT interval
daptomycin
MOA: lipoprotein that disrupts cell membranes of gram positive cocci by creating transmembrane channels
use: S. aureus skin infections (especially MRSA), bacteremia, infective endocarditis, VRE; NOT used for pneumonia (avidly binds and is inactivated by surfactant)
AE: myopathy, rhabdomyolysis
metronidazole
MOA: forms toxic free radical metabolites in the bacterial cell that damage DNA; bactericidal, antiprotozoal
use: Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (Bacteroides, C. difficile); can be used in place of amoxicillin in H. pylori “triple therapy” if penicillin allergy (“GET GAP on the Metro”)
AE: disulfiram-like reaction (severe flushing, tachycardia, hypotension) with alcohol, headache, metallic taste
treatment and prophylaxis: M. tuberculosis
prophylaxis: rifamycin-based regimen for 3-4 months
treatment: Rifampin, Isoniazid, Pyrazinamide, Ethambutol (“RIPE for treatment”)
treatment and prophylaxis: M. avium-intracellulare
prophylaxis: azithromycin, rifabutin
treatment: azithromycin or clarithromycin + ethambutol; can add rifabutin or ciprofoxacin
