Antimicrobial therapy
folic acid synthesis
- Sulfonamides
- Trimethoprim
Antimicrobial therapy
DNA Topoisomerases
- Fluoroquinolones
- Quinolone
Antimicrobial therapy
damages DNA
Metronidazole
Antimicrobial therapy
mRNA synthesis
Rifampin
Antimicrobial therapy
protein synthesis (50S)
- Chloramphenicol
- Clindamycin
- Linezolid
- Macrolides
- Streptogramins
Antimicrobial therapy
protein synthesis (30S)
- Aminoglycosides
- Tetracyclines
Antimicrobial therapy
cell wall synthesis (peptidoglycan cross linking)
- penicillinase-sensitive penicillins
- penicillinase-resistant penicillins
- antipseudomonals
- cephalosporins
- carbapenems
- monobactams
Antimicrobial therapy
cell wall synthesis (peptidoglycan synthesis)
Glycopeptides
Penicillin G, V
administration
- prototype ß-lactam antibiotics
- penicillin G - IV & IM
- penicillin V - oral
Penicillin G, V
mechanism
- bind PBPs (transpeptidases)
- block transpeptidase cross-linking of peptidoglycan
- activate autolytic enzymes
Penicillin G, V
clinical use
penicillinase
- gram (+) organisms
- S. pneumoniae, S. pyogenes, Actinomyces
- N. meningitidis, T. pallidum
- bactericidal: gram (+) cocci, gram (+) rods, gram (-) cocci, spirochetes
- penicillinase sensitive
Penicillin G, V
toxicity
- hypersensitivity rxns
- hemolytic anemia
Penicillin G, V
resistance
penicillinase in bacteria cleaves ß-lactam ring
type of ß-lactamase
Ampicillin, amoxicillin
mechanism
- same as penicillin
- wider spectrum
- penicillinase sensitive
- combine w/ clavulanic acid to protect against ß-lactamase
Ampicillin, amoxicillin
clinical use
HELPSS kill enterococci
- extended-spectrum penicillin
- Haemophilus influenzae
- E. coli
- Listeria monocytogenes
- Proteus mirabilis
- Salmonella
- Shigella
- enterococci
Ampicillin, amoxicillin
toxicity
- hypersensitivity rxns
- rash
- psuedomembranous colitis
Ampicillin, amoxicillin
resistance
- penicillinase in bacteria cleaves ß-lactam ring
- ß-lactamase
Oxacillin, nafcillin, dicloxacillin
mechanism
- same as penicillin
- narrow spectrum
- **penicillinase resistant **
- bulky R group
- blocks access of ß-lactamase to ß-lactam ring
Oxacillin, nafcillin, dicloxacillin
clinical use
S. aureus (except MRSA)
Oxacillin, nafcillin, dicloxacillin
toxicity
- hypersensitivity rxns
- interstitial nephritis
Ticarcillin, piperacillin
mechanism
- same as penicillin
- extended spectrum
Ticarcillin, piperacillin
clinical use
- Pseudomonas spp.
- gram-negative rods
- susceptible to penicillinase
- **use w/ ß-lactamase inhibitors **
Ticarcillin, piperacillin
toxicity
hypersensitivity rxns
ß-lactamase inhibitors
CAST
- Clavulanic Acid
- Sulbactam
- Tazobactam
Cephalosporins
mechanism
- ß-lactams
- **inhibit cell wall synthesis **
- less susceptible to penicillinases
- bactericidal
1st generation cephalosporins
**cefazolin, cephalexin **
- gram (+) cocci
- PEcK
- Proteus mirabilis
- E. coli
- Klebsiella
_______ used prior to surgery to prevent S. aureus wound infections.
Cefazolin
2nd generation cephalosporins
**cefoxitin, cefaclor, cefuroxime **
- gram (+) cocci
- HEN PEcKS
- Haemophilus influenzae
- Enterobacter aerogenes
- Neisseria spp.
- Proteus mirabilis
- E. coli
- Klebsiella pneumoniae
- Serratia marcescens
3rd generation cephalosporins
**ceftriaxone, cefotaxime, ceftazidime **
- serious gram (-) infections resistant to other ß-lactams
- Ceftriaxone - meningitis & gonorrhea
- Ceftazidime - Psuedomonas
4th generation cephalosporins
cefepime
- increased activity against Pseudomonas & gram (+) organisms
5th generation cephalosporins
ceftaroline
- broad gram (+) & gram (-) organism coverage
- MRSA, not Pseudomonas
Cephalosporins
toxicity
- hypersensitivity rxns
- vitamin K deficiency
- low cross-reactivity w/ penicillins
- increased nephrotoxicity of aminoglycosides
Aztreonam
mechanism
- monobactam
- resistant to ß-lactamases
- prevents peptidoglycan cross-linking
- binds PBP
- synergistic w/ aminoglycosides
- no cross-allergy w/ penicillins
Aztreonam
clinical use
- gram (-) rods only
- penicillin-allergic patients
- patients w/ renal insufficiency who can’t tolerate aminoglycosides
Aztreonam toxicity
- usually non-toxic
- occasional GI upset
Carbapenems
- Imipenem
- Meropenem
- Ertapenem
- Doripenem
Carbapenems
mechanism
Imipenem
- broad-spectrum, ß-lactamase resistant
- admin w/ cilastatin
- inhibitor of renal dehydropeptidase I
- decreased inactivation of drug in renal tubules
Carbapenems
clinical use
- gram (+) cocci, gram (-) rods, anaerobes
- wide spectrum
- **life-threatening infections or when other drugs have failed **
- Meropenam has decreased risk of seizures
Carbapenems
toxicity
- GI distress
- skin rash
- CNS toxicity (seizures)
Vancomycin
mechanism
- inhibits cell wall peptidoglycan formation
- binds D-ala-D-ala
- bactericidal
Vancomycin
clinical use
- gram (+) only
- serious, multidrug-resistant organisms
- MRSA, enterococci, C. difficile
Vancomycin
toxicity
NOT trouble-free
- Nephrotoxicity
- Ototoxicity
- Thrombophlebitis
- diffuse flushing
- red man syndrome
Vancomycin
resistance
- aa modification of D-ala-D-ala to D-ala-D-lac
Protein synthesis inhibitors
- 30S inhibitors
- 50S inhibitors
Buy AT 30, CCEL (sell) at 50
- 30S inhibitors
- Aminoglycosides
- Tetracyclines
- 50S inhibitors
- Chloramphenicol, Clindamycin
- Erythromycin (macrolides)
- Linezolid
Aminoglycosides
GNATS
- Gentamicin
- Neomycin
- Amikacin
- Tobramycin
- Streptomycin
Aminoglycosides
mechanism
- bactericidal
- **inhibits formation of initiation complex **
- misreading of mRNA
- blocks translocation
- requires O2 (aerobes)
Aminoglycosides
clinical use
- severe gram (-) rod infections
- synergistic w/ ß-lactam antibiotics
________ for bowel surgery.
Neomycin
Aminoglycosides
toxicity
NNOT
- Nephrotoxicity
- Neuromuscular blockade
- Ototoxicity
- Teratogen
Aminoglycosides
resistance
- bacterial transferase enzymes inactivate drug
- acetylation
- phosphorylation
- adenylation
Tetracyclines
- Tetracycline
- Doxycycline
- Minocycline
Tetracyclines
mechanism
- bacteriostatic
- binds 30S & prevents attachment of aminoacyl tRNA
- limited CNS penetration
________ is fecally eliminated & can be used in patients w/ renal failure.
Doxycycline
Do not take tetracyclines w/ ______, _____, or ____-containing preparations b/c divalent cations inhibit its absorption in the gut.
- milk (Ca2+)
- antacids (Ca2+, Mg2+)
- iron
Tetracyclines
clinical use
- Borrelia burgdorferi
- M. pneumoniae
- Rickettsia & Chlamydia (intracellular)
- treats acne
Tetracyclines
toxicity
- GI distress
- _discoloration of teeth & inhibition of bone growth _
- children
- photosensitivity
- contraindicated in pregnancy
Tetracyclines
resistance
decreased uptake or increased efflux out of bacterial cells by _plasmid-encoded transport pumps _
Macrolides
- Azithromycin
- Clarithromycin
- Erythromycin
Macrolides
mechanism
- inhibit protein synthesis
- **block translocation **
- bind 23S rRNA of 50S ribosomal subunit
- bacteriostatic
Macrolides
clinical use
- atypical pneumonias
- Mycoplasma
- Chlamydia
- Legionella
- STDs
- Chlamydia
- gram (+) cocci
- Strep in patients allergic to penicillin
Macrolides
toxicity
MACRO
- GI Motility issues
- Arrhythmia (prolonged QT)
- acute Cholestatic hepatitis
- Rash
- eOsinophilia
- Increases serum conc of theophyllines, oral anticoagulants
Macrolides
resistance
methylation of 23S rRNA-binding site
Chloramphenicol
mechanism
blocks peptidyltransferase at 50S ribosomal subunit
Chloramphenicol
clinical use
- meningitis
- Haemophilus influenzae
- Neisseria meningitidis
- Streptococcus pneumoniae
- rocky mountain spotted fever
- Rickettsia rickettsii
- limited use due to toxicity (but low cost)
Chloramphenicol
toxicity
- anemia (dose dependent)
- aplastic anemia (dose independent)
- **gray baby syndrome **
- premature infants
- lack liver UDP-glucuronyl transferase
Chloramphenicol
resistance
plasmid-encoded acetyltransferase inactivates the drug
Clindamycin
mechanism
blocks peptide transfer (translocation) at 50S ribosomal subunit
Clindamycin
clinical use
- anaerobic infections (Bacteroides, Clostridium perfringens) in…
- aspiration pneumonia
- lung abscesses
- oral infections
- invasive group A strep infection
______ treats anaerobes above the diaphragm.
______ treats anaerobes below the diaphragm.
Clindamycin
Metronidazole
Clindamycin
toxicity
- Pseudomembranous colitis (C. diff overgrowth)
- fever
- diarrhea
Sulfonamides
- sulfamethoxazole (SMX)
- sulfisoxazole
- sulfadiazine
Sulfonamides
mechanism
- inhibit folate synthesis
- PABA antimetabolites inhibit dihydropteroate synthase
- bacteriostatic
Sulfonamides
clinical use
- gram (+)
- gram (-)
- Nocardia
- Chlamydia
- triple sulfas or SMX for simple UTI
Sulfonamides
toxicity
- hypersensitivity rxns
- hemolysis if G6PD deficient
- nephrotoxicity (tubulointerstitial nephritis)
- photosensitivity
- kernicterus in infants
- displace other drugs from albumin (warfarin)
Sulfonamides
resistance
- altered enzyme (bacterial dihydropteroate synthase)
- decreased uptake
- increased PABA synthesis
Trimethoprim
mechanism
inhibits bacterial DHFR
bacteriostatic
Trimethoprim
clinical use
- combination w/ sulfonamides (TMP-SMX)
- sequential blockade of folate synthesis
- combination used for UTIs, Shigella, Salmonella, PCP pneumonia treatment & prophylaxis, toxoplasmosis prophylaxis
Trimethoprim
toxicity
- megaloblastic anemia
- leukopenia
- granulocytopenia
Fluoroquinolones
- ciprofloxacin
- norfloxacin
- levofloxacin
- ofloxacin
- sparfloxacin
- moxifloxacin
- gemifloxacin
- enoxacin
- nalidixic acid (quinolone)
Fluoroquinolones
mechanism
- inhibit DNA gyrase (topoisomerase II) & topoisomerase IV
- bactericidal must NOT be taken w/ antiacids
Fluoroquinolones
clinical use
- gram (-) rods of urinary & GI tracts
- includes Pseudomonas
- Neisseria
- some gram (+)
Fluoroquinolones
toxicity
- GI upset
- superinfections
- skin rashes
- headache
- dizziness
- less common: tendonitis, tendon rupture, leg cramps, myalgias
- contraindicated in pregnant women, nursing mothers, children <18 YO –> possible damage to cartilage
- prolonged QT interval
- tendon rupture in >60 YO & patients taking prednisone
Fluoroquinolones
resistance
- chromosome-encoded mutation in DNA gyrase
- plasmid-mediated resistance
- efflux pumps
Metronidazole
mechanism
- free radical toxic metabolites in bacterial cell that damage DNA
- bactericidal
- antiprotozoal
Metronidazole
clinical use
**GET GAP **
- Giardia
- Entamoeba
- Trichomonas
- Gardnerella vaginalis
- Anaerobes (Bacteroides, C. difficile)
- H. Pylori (triple therapy)
- metronidazole + PPI + clarithromycin
Metronidazole
toxicity
- disulfiram-like rxn w/ alcohol
- severe flushing
- tachycardia
- hypotension
- headache
- metallic taste
Antimycobacterial drugs
- M. tuberculosis
- M. avium-intracellulare
- M. leprae
- M. tuberculosis
- Prophylaxis: Isoniazid
- Treatment: RIPE
- Rifampin
- Isoniazid
- Pyrazinamide
- Ethambutol
- M. avium-intracellulare
- Prophylaxis: azithromycin, rifabutin
- Treatment: azithromycin/clarithromycin + ethambutol
- M. leprae
- Prophylaxis: N/A
- Treatment: dapson & rifampin (T); + clofazimine (L)
Isoniazid
mechanism
- decreases synthesis of mycolic acids
- bacterial catalase-peroxidase needed to convert to active metabolite
Isoniazid
toxicity
INH Injures Neurons & Hepatocytes
- neurotoxicity
- hepatotoxicity
- pyridoxine (vit B6) can prevent neurotoxicity, lupus
Rifamycins
- Rifampin
- Rifabutin
4 R’s of Rifampin
Rifampin ramps up CYP450, but rifabutin does not
- RNA polymerase inhibitor
- Ramps up microsomal CYP450
- Red/orange body fluids
- Rapid resistance if used alone
Rifamycins
_____ favored over _____ in patients w/ HIV infection due to less CYP450 stimulation.
rifabutin
rifampin
Pyrazinamide
mechanism
- uncertain
- **thought to acidify intracellular environment **
- conversion to pyrazinoic acid
- effective in acidic pH of phagolysosomes (TB engulfed by macrophages)
Pyrazinamide
clinical use
toxicity
- Mycobacterium tuberculosis
- Hyperuricemia, hepatotoxicity
Ethambutol
mechanism
decreases carb polymerization of mycobacterium cell wall by blocking arabinosyltransferase
Ethambutol
clinical use
toxicity
- Mycobacterium tuberculosis
- Optic neuropathy (red-green color blindness)
antimicrobial prophylaxis
endocarditis w/ surgical or dental procedures
penicillins
antimicrobial prophylaxis
gonorrhea
ceftriaxone
antimicrobial prophylaxis
history of recurrent UTIs
TMP-SMX
antimicrobial prophylaxis
meningococcal infection
ciprofloxacin
rifampin (children)
antimicrobial prophylaxis
pregnant woman carrying group B strep
ampicillin
antimicrobial prophylaxis
prevention of gonococcal or chlamydial conjunctivitis of the newborn
erythromycin ointment
antimicrobial prophylaxis
prevention of postsurgical infection due to S. aureus
cefazolin
antimicrobial prophylaxis
prophylaxis of strep pharyngitis in child w/ prior rheumatic fever
oral penicillin
antimicrobial prophylaxis
syphilis
benzathine penicillin G
