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.