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
treatment and prophylaxis: M. leprae
no prophylaxis
treatment: long-term treatment with dapsone and rifampin for tuberculoid form; add clofazimine for lepromatous form
rifampin, rifabutin, rifapentine
rifamycins
MOA: inhibit DNA-dependent RNA polymerase
use: Mycobacterium tuberculosis; delays resistance to dapsone when used for leprosy; meningococcal prophylaxis and chemoprophylaxis in contacts of children with H. influenzae type b
AE: minor hepatotoxicity and drug interactions; orange body fluids
“4 Rs of Rifampin = RNA polymerase inhibitor, Ramps up microsomal CYP450, Red/orange body fluids, Rapid resistance if used alone”
note: rifabutin does NOT ramp up CYP450
isoniazid
MOA: decreased synthesis of mycolic acids; bacterial catalase-peroxidase (encoded by KatG) needed to convert INH to active metabolite
use: M. tuberculosis; also as a monotherapy for latent TB
AE: hepatotoxicity, cytochrome P450 inhibition, drug-induced SLE, anion gap metabolic acidosis, vitamin B6 deficiency (peripheral neuropathy, sideroblastic anemia), seizures
pyrazinamide
MOA: uncertain; works best at acidic pH (e.g., in host phagolysosomes)
use: M. tuberculosis
AE: hyperuricemia, hepatotoxicity
ethambutol
MOA: decreased carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase
use: M. tuberculosis
AE: optic neuropathy (red-green colorblindness, usually reversible)
streptomycin (for TB)
MOA: interferes with 30S component of ribosome
use: M. tuberculosis (second line)
AE: tinnitus, vertigo, ataxia, nephrotoxicity
prophylaxis treatment for:
exposure to meningococcal infection
ceftriaxone, ciprofloxacin, or rifampin
prophylaxis treatment for:
high risk for infective endocarditis and undergoing surgical or dental procedures
amoxicillin
prophylaxis treatment for:
history of recurrent UTIs
TMP-SMX
prophylaxis treatment for:
malaria prophylaxis for travelers
atovaquone-proguanil, mefloquine, doxycycline, primaquine, or chloroquine
prophylaxis treatment for:
pregnant patients carrying group B strep
intrapartum penicillin G or ampicillin
prophylaxis treatment for:
prevention of gonococcal conjunctivitis in newborn
erythromycin ointment on eyes
prophylaxis treatment for:
prevention of postsurgical infection due to S. aureus
cefazolin; vancomycin if positive for MRSA
prophylaxis treatment for:
prophylaxis of strep pharyngitis in child with prior rheumatic fever
benzathine penicillin G or oral penicillin V
[?] is used as prophylaxis against Pneumocystis pneumonia and toxoplasmosis in patients with HIV
TMP-SMX
amphotericin B
antifungal
MOA: binds ergosterol; forms membrane pores that allow leakage of electrolytes
use: serious, systemic mycoses; Cryptococcus, Blastomyces, Coccidioides, Histoplasma, Candida, Mucor
AE: fever/chills, hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis
supplement K+ and Mg+ because of altered renal tubule permeability; hydration decreases nephrotoxicity
nystatin
antifungal
MOA: same as amphotericin B (binds ergosterol and forms membrane pores)
use: “swish and swallow” for oral candidiasis (thrush), topical for diaper rash or vaginal candidiasis
flucytosine
antifungal
MOA: inhibits DNA and RNA biosynthesis by conversion to 5-fluorouracil by cytosine deaminase
use: systemic fungal infections (especially meningitis caused by Cryptococcus) in combination with amphotericin B
AE: myelosuppression
clotrimazole, fluconazole, isavuconazole, itraconazole, ketoconazole, miconazole, voriconazole
azoles
MOA: inhibit fungal sterol synthesis by inhibiting cytochrome P450 enzyme that converts lanosterol to ergosterol
use: local and less serious systemic mycoses
-fluconazole: chronic suppression of cryptococcal meningitis in people living with HIV and candidal infections of all types
-itraconazole: Blastomyces, Coccidioides, Histoplasma, Sporothrix schenckii
-clotrimazole, miconazole: topical fungal infections
-voriconazole: Aspergillus and some Candida
-isavuconazole: serious Aspergillus and Mucor infections
AE: testosterone synthesis inhibition (gynecomastia, especially ketoconazole), liver dysfunction (inhibits cytochrome P450), QT interval prolongation
terbinafine
MOA: inhibits fungal enzyme squalene epoxidase
use: dermatophytosis (especially onychomycosis - fungal infections of finger or toe nails)
AE: GI upset, hepatotoxicity, taste disturbance
anidulafungin, caspofungin, micafungin
echinocandins
MOA: inhibit cell wall synthesis by inhibiting synthesis of B-glucan
use: invasive aspergillosis, Candida
AE: GI upset, flushing (by histamine release)
griseofulvin
MOA: interferes with microtubule function, disrupts mitosis; deposits in keratin-containing tissues
use: oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm)
AE: teratogenic, carcinogenic, confusion, headaches, disulfiram-like reaction, increased P450 and warfarin metabolism
antiprotozoal therapy:
-toxoplasmosis = ?
-T. brucei = ?
-T. cruzi = ?
-leishmaniasis = ?
toxoplasmosis = pyrimethamine
T. brucei = suramin and melarsoprol
T. cruzi = nifurtimox
leishmaniasis = sodium stibogluconate
permethrin, malathion, ivermectin
used to treat scabies and lice
chloroquine
MOA: blocks detoxification of heme into hemozoin; heme accumulates and is toxic to plasmodia
use: plasmodial species other than P. falciparum (resistance due to membrane pump that decreases intracellular concentration of drug)
AE: retinopathy (cumulative dose-dependent), pruritis
P. falciparum infections treated with [?]
artemether/lumefantrine or atovaquone/proguanil
antihelminthic therapy
pyrantel pamoate, ivermectin, mebendazole, praziquantel, diethylcarbamazine
oseltamivir, zanamivir
antiviral
MOA: inhibit influenza neuraminidase => decrease release of progeny virus
use: influenza A and B
baloxavir
antiviral
MOA: inhibits “cap snatching” (transfer of 5’ cap from cell RNA onto viral RNA) endonuclease activity of influenza virus RNA polymerase => decreased viral replication
use: influenza
remdesivir
antiviral
MOA: prodrug of an ATP analog; active metabolite inhibits viral RNA-dependent RNA polymerase and evades proofreading by viral exoribonuclease (ExoN) => decreased viral RNA production
use: COVID-19
acyclovir, famciclovir, valacyclovir
antivirals
MOA: guanosine analogs; monophosphorylated by HSV/VZV thymidine kinase => preferentially inhibit viral DNA polymerase by chain termination
use: HSV-induced mucocutaneous and genital lesions and encephalitis; prophylaxis for immunocompromised patients or those with recurrent infection
NO effect on CMV because CMV lacks thymidine kinase necessary to activate guanosine analogs; no effect on latent forms of HSV, VZV
AE: obstructive crystalline nephropathy and acute kidney injury if not properly hydrated
ganciclovir
antiviral
MOA: guanosine analog; 5’-monophosphate formed by CMV viral kinase => preferentially inhibits viral DNA polymerase
use: CMV, especially in immunocompromised
AE: myelosuppression, renal toxicity
foscarnet
antiviral
MOA: viral DNA/RNA polymerase inhibitor and HIV reverse transcriptase inhibitor; binds to pyrophosphate-binding site of enzyme, does not require kinase activation
use: CMV retinitis in immunocompromised (if ganciclovir fails), acyclovir-resistant HSV
AE: nephrotoxicity, multiple electrolyte abnormalities that can lead to seizures
cidofovir
antiviral
MOA: preferentially inhibits viral DNA polymerase; does not require phosphorylation by viral kinase
use: CMV retinitis in immunocompromised (if ganciclovir fails), acyclovir-resistant HSV
AE: nephrotoxicity (co-administer with probenecid and IV saline to decrease toxicity)
abacavir, emtricitabine, lamivudine, tenofovir, zidovudine
nucleotide reverse transcriptase inhibitors (NRTIs)
MOA: competitively inhibit nucleotide binding to reverse transcriptase and terminate DNA chain; tenofovir is a nucleotide, the others are nucleosides
use: HIV therapy (2 NRTIs and 1 integrase inhibitor); zidovudine can be used for general prophylaxis and during pregnancy to reduce the risk of transmission
AE: myelosuppression (reversed with G-CSF), nephrotoxicity
abacavir contraindicated in patients with HLA-B*5701 mutation (increased risk of hypersensitivity)
[?] is contraindicated in patients with HLA-B*5701 mutation
abacavir - increased risk of hypersensitivity
efavirenz, nevirapine
non-nucleotide reverse transcriptase inhibitors (NNRTIs)
MOA: bind to reverse transcriptase at site different from NRTIs; do not require phosphorylation to be active or compete with nucleotides
use: HIV
AE: rash and hepatotoxicity; vivid dreams and CNS symptoms (efavirenz)
bictegravir, dolutegravir, elvitegravir, raltegravir
integrase inhibitors
MOA: inhibit HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase
use: HIV therapy (2 NRTIs and 1 integrase inhibitor)
AE: increased creatine kinase, weight gain
atazanavir, darunavir, lopinavir, ritonavir
protease inhibitors
MOA: inhibits HIV protease - assembly of virions depends on HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into their functional parts
AE: hyperglycemia, GI intolerance
DDI: rifampin decreases protease inhibitor concentrations (use ribabutin instead); ritonavir (CYP450 inhibitor) increases other drug concentrations
enfuvirtide, maraviroc
entry inhibitors
MOA:
-enfuvirtide: binds gp41, inhibiting entry/fusion
-maraviroc: binds CCR-5 on T cells/monocytes, inhibits interaction with gp120 (inhibits attachment)
AE: skin reaction at injection site
ledipasvir, ombitasvir, velpatasvir
NS5A inhibitors
MOA: inhibits NS5A (viral phosphoprotein involved in RNA replication)
use: hepatitis C
AE: headache, diarrhea
sofosbuvir, dasabuvir
NS5B inhibitors
MOA: inhibits NS5B (RNA-dependent RNA polymerase), acting as chain terminator; prevents viral RNA replication
use: hepatitis C
AE: fatigue, headache
grazoprevir, simeprevir
NS3/4A inhibits
MOA: inhibit NS3/4A (viral protease), preventing viral replication
use: hepatitis C
AE: headache, fatigue (grazoprevir); photosensitivity reactions, rash (simepravir)
ribavirin
MOA: inhibits synthesis of guanine nucleotides by competitively inhibiting IMP dehydrogenase
use: adjunct in hepatitis C cases refractory to newer medications
AE: hemolytic anemia, severe teratogen
antimicrobials to avoid in pregnancy
“SAFe Children Take Really Good Care”
sulfonamides (kernicterus), aminoglycosides (ototoxicity), fluroquinolones (cartilage damage), clarithromycin (embryotoxic), tetracyclines (discolored teeth, inhibition of bone growth), ribavirin (teratogenic), griseofulvin (teratogenic), chloramphenicol (gray baby syndrome)
