Antimicrobials - First Aid Flashcards
Penicillin G and V (prototype Beta-lactams) MOA
Bind penicillin-binding proteins to block transpeptidase cross-linking of peptidoglycan.
They also activate autolytic enzymes.
Penicillin G and V Use
- mostly for gram-positive organisms
- also for N. meningitidis and T. pallidum
Penicillin G, V are bactericidal for…
gram-positive cocci and rods, gram-negative cocci and spirochetes.
Toxicity of Penicillin G, V
HSRs and hemolytic anemia
Resistance to Penicillin G, V
penicillinase in bacteria (a type of beta-lactamase) cleaves the beta-lactam ring
Ampicillin/Amoxicillin MOA
same as penicillin
Ampicillin/Amoxicillin Use
extended spectrum penicillins
- H. influenzae
- E. coli
- Listeria
- Proteus
- Salmonella
- Shigella
- enterococci
Ampicillin/Amoxicillin Toxicity
- HSRs
- rash
- pseudomembranous colitis
Ampicillin/Amoxicillin Resistance
-penicillinase
Oxacillin, Nafcillin, Dicloxacillin MOA
same as penicillin; penicillinase resistant because bulky R group blocks access of beta-lactamase
Oxacillin, Nafcillin, Dicloxacillin Use
S. aureus (narrow spectrum)
Oxacillin, Nafcillin, Dicloxacillin Toxicity
HSRs, interstitial nephritis
MRSA is resistant because of….
altered PBP target site.
Ticarcillin, Piperacillin MOA
same as penicillin
Ticarcillin, Piperacillin Use
extended spectrum; Pseudomonas and gram-negative rods
Beta-lactamse inhibitors are often…
added to penicillin antibiotics to protect the antibiotic from destruction by beta-lactamase.
(Clavulanic Acid, Sulbactam, Tazobactam)
Cephalosporins MOA
Beta-lactam drugs that inhibit cell wall synthesis but are less suceptible to penicillinases; bactericidal
Organisms typically not covered by cephalosporins are…
LAME:
- Listeria
- Atypicals
- MRSA
- Enterococci
(Exception: ceftaroline covers MRSA)
1st generation Cephalosporins Use
Cefazolin, Cephalexin
- gram positive cocci
- Proteus
- E. coli
- Klebsiella
Cefazolin is used prior to…
surgery to prevent S. aureus wound infections.
2nd generation Cephalosposrins Use
Cefoxitin, Cefaclor, Cefuroxime
- gram positive cocci
- H. influenza
- Enterobacter
- Neisseria
- Proteus
- E. coli
- Klebsiella
- Serratia
3rd genreation Cephalosporins Use
Ceftriaxone, Cefotaxime, Ceftazidime
-serious gram negative infections resistant to other beta-lactams
(Ceftriaxone for Neisseria and Ceftazidime for Pseudomonas)
4th generation Cephalosporins Use
Cefepime
-increased activity against pseudomonas and gram-positives
5th generation Cephalosporins Use
Ceftaroline
- broad gram positive and negative coverage
- including MRSA
- does NOT cover pseudomonas
Cephalosporins toxicity
- HSRs
- vitamin K deficiency
- increased nephrotoxicity of aminoglycosides
Aztreonam MOA
a monobactam; resistant to beta-lactamases; prevents peptidoglycan cross-linking by binding to PBP3
Aztreonam Use
gram-negative rods only; for penicillin allergic pts and those with renal insufficiency who cannot tolerate aminoglycosides
Carbapenems (4)
- Imipenem
- Meropenem
- Ertapenem
- Doripenem
Carpabenem (Imipenem) MOA
broad-spectrum, beta-lactamase reistant; always admisistered with Cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of the drug in the renal tubules
Clinical use of carbapenems
- gram positive cocci
- gram negative rods
- anaerobes
Toxicity
GI distress, rash, CNS toxicity (seizures) - limits use
Meropenem has decreased risk of seizures
Vancomycin MOA
inhibits cell wall peptidoglycan formation by binding D-ala-D-ala portion of cell wall precurors; bactericidal
Use of Vancomycin
gram positive only (serious, multidrug resistant organisms including MRSA, enterococci and C. diff)
Toxicity of Vancomycin
- Red Man Syndrome
- Nephrotoxicity
- Ototoxicity
- Thrombophlebitis
Mechanism of resistance to Vancomycin
-amino acid modification of D-ala-D-ala to D-ala-D-lac
Protein synthesis inhibitors specifically target…
the smaller bacterial ribosome (70S (30S+50S)) leaving the human ribosome (80S) unaffected.
30S Inhibitors
Aminoglycosides (bactericidal)
Tetracyclines (bacteriostatic)
50S Inhibitors
Chloramphenicol, Clindamycin (bacteriostatic)
Erythromycin (macrolides - bacteriostatic)
Linezolid
Aminoglycosides (5)
- Gentamicin
- Neomycin
- Amikacin
- Tobramycin
- Streptomycin
Aminoglycosides MOA
inhibit formation of initiation complex and cause misreading of mRNA; also block translocation
Aminoglycosides are ineffective against…
anaerobes bc they require O2 for uptake.
Aminoglycosides Use
- severe gram-negative rod infections
- neomycin for bowel surgery
Aminoglycosides Toxicity
- Nephrotoxicity (esp. with cephalosporins)
- Neuromuscular blockade
- Ototoxicity (esp. with loop diuretics)
- Teratogen
Aminoglycosides resistance
bacterial transferase enyzmes inactivate the drug by acetylation, phosphorylation or adenylation
Tetracyclines (3)
- Tetracycline
- Doxycycline
- Minocycline
MOA of Tetracyclines
bind to 30S and prevent attachment of aminoacyl-tRNA
Doxycycline is eliminated…
fecally and can be used in pts with renal failure.
Tetracyclines should not be taken with…
milk, antacids or iron-containing preps because divalent cations inhibit its absorption in the gut.
Clinical use of tetracyclines
- Borrelia
- M. pneumoniae
- Rickettsia and Chlamydia (bc it can accumulate intracellularly)
Toxicity of Tetracycline
- GI
- discoloration of teeth-
- inhibition of bone growth
- photosensitivity
(contraindicated in pregnancy)
Resistance to Tetracycline
decreased uptake or increased efflux out of bacterial cells by plasmid-encoded transport pumps
Macrolides (3)
- Azithromycin
- Clarithromycine
- Erythromycine
Macrolides MOA
inhibit protein synthesis by blocking translocation; binds to the 23S rRNA of the 50S ribosomal subunit
Macrolides Use
- atypical pneumonias
- STDs (Chlamydia)
- gram-positive cocci (strep infxns in pts allergic to penicillin)
Toxicity of Macrolides
- GI motility issues
- Arrhythmia (prolonged QT)
- acute cholestatic hepatitis
- rash
- eosinophilia
Macrolides increase the concentration of…
theophyllines and oral anticoagulants.
Resistance to Macrolides
methylation of 23S rRNA binding site prevents binding of drug
Chloramphenicol Mechanism
blocks peptidyltransferase at 50S ribosomal subunit; bacteriostatic
Chloramphenicol Use
Meningitis
Rocky Mountain Spotted Fever
Toxicity of Chloramphenicol
- anemia (dose dependent)
- aplastic anemia (dose independent)
- gray baby syndrome
Chloramphenicol causes gray baby syndrome in premature infants because…
they lack liver UDP-glucuronyl transferase.
Chloramphenicol resistance
plasmid-encoded acetyltransferase inactivates the drug
Clindamycin MOA
blocks peptide transfer (translocation) at 50S ribosomal subunit; bacteriostatic
Clindamycin Use
- anaerobic infxns (Bacteroides, C. perfringens) in aspiration pneumonia
- lung abscesses
- oral infxns
- Group A Strep
Clindamycin Toxicity
- pseudomembranous colitis
- fever
- diarrhea
Treat anaerobes above the diaphragm with…
Clindamycin and below the diaphragm with Metronidazole.
Sulfonamides (3)
- Sulfamethoxazole (SMX)
- Sulfisoxazole
- Sulfadiazine
Sulfonamides MOA
- inhibits folate synthesis
- para-aminobenzoic acid (PABA) antimetabolites inhibit dihydropteroate synthase; bacteriostatic
Sulfonamides Use
- gram positive
- gram negative
- Nocardia
- Chlamydia
- simple UTI
Toxicity of Sulfonamides
- HSRs
- hemolysis if G6PD deficient
- tubulointerstitial nephritis
- photosensitivity
- kernicterus in infants
- displaces other drugs from albumin (warfarin)
Resistance to Sulfonamides
- altered enzyme (bacterial dihydropteroate synthase)
- decreased uptake
- increased PABA synthesis
Trimethoprim MOA
inhibits bacterial dihydrofolate reductase; bacteriostatic
Trimethoprim Use
in combo with sulfonamides causing sequential block of folate synthesis; UTIs, Shigella, Salmonella, Pneumocystis jirovecii, pneumonia tx/prophylasis, toxoplasmosis prophylaxis
Trimethoprim Toxicity
- megaloblastic anemia
- leukopenia
- granulocytopenia
Fluoroquinolones (9)
- Ciprofloxacin
- Norofloxacin
- Levofloxacin
- Ofloxacin
- Sparfloxacin
- Moxifloxacin
- Gemifloxacin
- Enoxacin
- Nalidixic Acid (a quinolone)
MOA of Fluoroquinolones
inhibit DNA gyrase (topoisomerase II) and topoisomerase IV; bactericidal
Use of Fluoroquinolones
gram-negative rods of urinary and GI tracts (including pseudomonas), Neisseria
Fluoroquinolones Toxicity
- superinfections
- tendonitis
- tendon rupture (in people over 60 and people taking prednisone)
- leg cramps
- QT prolonagation
Fluoroquinolones are contraindicated in…
pregnant women, nursing mothers, and children under 18 due to risk of cartilage defect.
Resistance to Fluoroquinolones
chromosome-encoded mutation in DNA gyrase, plasma-mediated reissitance, efflux pumps
Metronidazole MOA
forms free radical toxic metabolites in the bacterial cell taht damage DNA; bactericidal; antiprotozoal
Metronidazole Use
Giardia Entamoeba Trichomonas Gardnerella Anaerobes H. pylori (w/ a proton pump inhibitor and clarithromycin)
Metronidazole Toxicity
Disulfiram like rxn (flushing, tachycardia, hyoptension)
Mycobacterium tuberculosis prophylaxis
Isoniazid
Mycobacterium tuberculosis treatment
Rifampin
Isoniazid
Pyrazinamide
Ethambutol
Mycobacterium avium-intracellulare prophylaxis
Azithromycin
Rifabutin
Mycobacterium avium-intracellulare treatment
- more drug resistant than M. tuberculosis
- Azithromycin or Clarithromycin + Ethambutol
Mycobacterium leprae treatment
long-term treatment with dapsone and rifampin for tuberculoid form; add clofazimine for lepromatous form
Isoniazid MOA
decreased synthesis of mycolic acids; bacterial catalase-peroxidase needed to convert INH to the active metabolite
Isoniazid Use
M. tuberculosis
Toxicity of Isoniazid
-neurotoxicity, hepatotoxicity
B6 can prevent the neurotoxicity
Rifampin, Rifabutin MOA
inhibits DNA-dependent RNA polymerase
Use of Rifampin, Rifabutin Use
M. tuberculosis; delays resistance to dapsone when used for leprosy; used for meningococcal prophylaxis and prophylaxis in contacts of kids w/ Hib
Toxicity of Rifampin, Rifabutin
-orange body fluids
-hepatotoxicity/drug interaction
(Rifabutin favored in pts with HIV due to less CYP450 stimulation.)
Pyrazinamide MOA
thought to acidify intracellular environment via conversion to pyrazinoic acid; effective in acidic pH of phagolysosomes where TB engulfed by macrophages is found
Pyrazinamide Use
M. tuberculosis
Toxicity of Pyrazinamide
Hyperuricemia, hepatotoxicity
Ethambutol MOA
decreased carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase
Ethambutol Use
M. tuberculosis
Ethambutol toxicity
optic neuropathy (red-green color blindness)
Prophylaxis for endocarditis with surgical or dental procedures
Penicillins
Prophylaxis for gonorrhea
Ceftriaxone
Prophylaxis for recurrent UTIs
TMP-SMX
Prophylaxis for meningococcal infxn
Ciprofloxacin
Rifampin for children
Prophylaxis for pregnant women carrying group B strep
Ampicillin
Prevention of gonococcal or chlamydial conjunctivitis in the newborn
erythromycin ointment
Prevention of postsurgical infxn due to S. aureus
Cefazolin
Prophylaxis of strep pharyngitis in a child with prior rheumatic fever
oral penicillin
Prophylaxis for syphilis
benzathine penicillin G
Prophylaxis of Pneumocystis pneumonia in HIV pts with CD4
TMP-SMX
Prophylaxis of Pneumocystis pneumonia and toxoplasmosis in HIV pts with CD4
TMP-SMX
Prophylaxis of M. avium in HIV pts with CD4
Azithromycin
MRSA treatments
- vancomycin
- daptomycin
- linezolid (can cause serotonin syndrome)
- tigecycline
- ceftaroline
VRE treatments
- linezolid
- streptogramins (quinupristin/dalfopristin)
Amphotericin B MOA
binds ergosterol (unique to fungi); forms membrane pores that allows leakage of electrolytes
Amphotericin B Use
- Cryptococcus
- Blastomyces
- Coccidioides
- Histoplasma
- Candida
- Mucor
(give supplemental K+ and Mg2+ bc of altered renal tubule permeability)
Amphotericin B toxicity
- fevers/chills
- nephrotoxicity
- arrhythmias
- anemia
- IV phlebitis
Nystatin MOA
same as amphotericin B; topical form only!
Nystatin Use
“swish and swallow” for oral candidiasis; topical for diaper rash or vaginal candidiasis
Azoles (6)
- Fluconazole
- Ketoconazole
- Clotrimazole
- Miconazole
- Itraconazole
- Voriconazole
Azoles MOA
inhibit fungal sterol synthesis by inhibiting the CYP450 that converts lanosterol to ergosterol
Azoles Use
local/less serious systemic mycoses
- Fluconazole for chronic suppression of cryptococcal meningitis in AIDS pts and candidal infections of all types
- Itraconazole for Blasto, Cocci, and Histo
- Clotrimazole/Miconazole for topical fungal infxns
Azoles toxicity
-testosterone synthesis inhibition (gyencomastia, esp. w/ ketoconazole), liver dysfunction (inhibits CYP450)
Flucytosine MOA
inhibits DNA and RNA biosynthesis by conversion to 5-FU by cytosine deaminase
Use of Flucytosine
systemic funcgal infections (esp. meningitis caused by Crypto) in combo w/ amphotericin B
Toxicity of flucytosine
bone marrow suppression
Echinocandins (3)
- Caspofungin
- Micafungin
- Anidulafungin
Echinocandins MOA
inhibits cell wall synthesis by inhibiting synthesis of beta-glucan
Use of Echinocandins
invasive aspergillosis, Candida
Terbinafine MOA
inhibits the fungal enzyme squalene epoxidase
Terbinafine Use
dermatophytoses (esp onychomycosis)
Griseofulvin MOA
interferes w/ microtubule fxn; disrupts mitosis; deposits keratin-containing tissues
Use of Griseofulvin
oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm)
Griseofulvin toxicity
teratogenic, carcinogenic, confusion, headaches, increased P450 and warfarin metabolism
Toxoplasmosis tx
pyrimethamine
Trypanosoma brucei tx
Suramin and Meelarsoprol
T. cruzi tx
Nifurtimox
Leishmaniasis tx
Sodium Stibogluconate
Chloroquine MOA
blocks detoxification of heme into hemozoin; heme accumulates and is toxic to plasmodia
Chloroquine Use
treatment of plasmodial species other than P. falciparum (resistance to P. falciparum due to membrane pump that decreases intracellular concentration of the drug)
Treat P. falciparum with…
artemether/lumefantrine or atovaquone/proguanil.
For life-threatening malaria, use…
quinidine or artesunate.
Toxicity of chloroquine
retinopathy
pruritis
Antihelminthic therapy (5)
- Mebendazole
- Pyrantel pamoate
- Ivermectin
- Diethylcarbamazine
- Praziquantel
(immobilize helminths)
Treatment for flukes (trematodes) such as Schistosoma
Praziquantel
Zanamivir, Oseltamivir MOA
inhibit influenza neuraminidase leading to decreased release of progeny virus
Zanamivir, Oseltamivir Use
treatment/prevention of influenza A and B
Ribavirin MOA
inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase
Ribavirin Use
RSV, chronic hep C
Ribavirin toxicity
- hemolytic anemia
- severe teratogen
Acyclovir, Famciclovir, Valacyclovir MOA
guanosine analog; triphosphate formed by cellular enzymes; preferentially inhibits DNA polymerase by chain termination
Acyclovir, Famciclovir and Valacyclovir have few adverse effects because…
they are monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells.
Use of Acyclovir, Famciclovir and Valacyclovir
HSV and VZV
-HSV induced mucocutaneous/genital lesions and encephalitis
-prophylaxis in immunocompromised
-
Acyclovir, Famciclovir and Valacyclovir have no effect on..
latent forms of HSV and VZV.
Toxicity of Acyclovir, Famciclovir and Valacyclovir
obstructive crystalline nephropathy and acute renal failure
Mechanism of resistance to Acyclovir, Famciclovir and Valacyclovir
mutated viral thymidine kinase
Ganciclovir MOA
5’ monophosphate formed by a CMV viral kinase; guanosine analog; triphosphate formed by cellular kinases; preferentially inhibits viral DNA polymerase
Use of Ganciclovir
CMV, esp. in immunocompromised pts
Toxicity of Ganciclovir
leukopenia, neutropenia, thrombocytopenia, renal toxicity
Resistance to Ganciclovir
mutated CMV DNA polymerase or lack of viral kinase
Foscarnet MOA
viral DNA polymerase inhibitor that binds to the pyrophosphate-binding site of the enzyme; does not require activation by viral kinase
Foscarnet Use
CMV retinitis in immunocompromised pts when ganciclovir fails; acyclovir resistant HSV
Toxicity of Foscarnet
Nephrotoxicity
Resistance to Foscarnet
mutated DNA polymerase
Cidofovir MOA
preferentially inhibits viral DNA polymerase; does not require phosphorylation by viral kinase
Use of Cidofovir
CMV retinitis in immunocompromised pts; acyclovir-resistant HSV
Toxicity of Cidofovir
nephrotoxicity (administer with probenecid and IV saline to decrease toxicity)
Highly Active Antiretroviral Therapy (HAART) is initiated when…
pts present with an AIDs defining illness, low CD4 cell counts (
HAART regimen consists of..
3 drugs to preven resistance:
- 2 nucleoside reverse transcriptase inhibitors
- 1 non-nucleoside reverse transcriptase inhibitor OR 1 protease inhibitor OR 1 integrase inhibitor
Protease Inhibitors (7)
- Atazanavir
- Darunavir
- Fosamprenavir
- Indinavir
- Lopinavir
- Ritonavir
- Saquinavir
(Navir tease a protease)
The assembly of HIV virions depends on…
HIV-1 protease (pol gene) which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses.
Ritonavir can boost…
other drug concentrations by inhibiting CYP450.
Toxicity of protease inhibitors
hyperglycemia, lipodystrophy, nephropathy, hematuria
NRTIs (nucleoside reverse transcriptase inhibitors) (7)
- Abacavir
- Didanosine
- Emtricitabine
- Lamivudine
- Stavudine
- Tenofovir
- Zidovudine
(Have you dined (vudine) w/ my nuclear (nucleoside) family?)
NRTIs MOA
competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain
NRTIs need to be…
phosphorylated to be active (except for tenofovir which is a nucleotide).
Zidovudine is used for…
general prophylaxis and during pregnancy to decrease risk of fetal transmission.
Toxicity of NRTIs
bone marrow suppression (give G-CSF and EPO), neuropathy, lactic acidosis, anemia (ZDV), pancreatitis (didanosine)
NNRTIs (non-nucleoside reverse transcriptase inhibitors) (3)
- Efavirenz
- Nevirapine
- Delavirdine
NNRTIs MOA
bind to reverse transcriptase at a site different from NRTIs; do not require phosphorylation for activation
Toxicity of NNRTIs
- rash, hepatotoxicity
- vivid dreams and CNS symptoms (Efavirenz)
Delavirdine and Efavirenz are contraindicated in…
pregnancy.
Raltegravir MOA
inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase
Raltegravir Toxicity
hypercholesterolemia
Fusion inhibitors
Enfuvirtide
Maraviroc
Enfuvirtide MOA
binds gp41, inhibiting viral entry
Maraviroc MOA
binds CCR-5 on surface of T cells/monocytes inhibiting interaction with gp120
Interferons MOA
glycoproteins normally synthesized by virus-infected cells, exhibiting a wide range of antiviral and antitumoral properties
Use of INF-alpha
chronic Hep B/C, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, RCC and malignant melanoma
Use of IFN-beta
MS
Use of IFN-gamma
CGD
Toxicity of interferons
neutropenia
myopathy
Antibiotics to avoid in pregnancy
SAFe Children Take Really Good Care Sulfonamides Aminoglycosides Fluoroquinolones Clarithromycin Tetracyclines Ribavirin Griseofulvin Chloramphenicol
Sulfonamides teratogenecity
Kernicterus
Aminoglycosides teratogenecity
ototoxicity
Fluoroquinolones teratogenecity
cartilage damage
Clarithromycin teratogenecity
embryotoxic
Tetracyclines teratogenecity
discolored teeth, inhibition of bone growth