Antimicrobial Therapy Flashcards
What does bacteriostatic mean?
antimicrobial drug that requires host defense mechanism to get rid of bug. Use in healthy people
What does bactericidal mean?
Antimicrobial that eradicates bug without use of host defense
What is minimum inhibitory concentration?
lowest concentration of antimicrobial drug that can inhibit growth of organism on a defined medium. This will vary from person to person
What patient factors affect MIC to kill bug
Pregnancy and lactation, immune system, age, disease
What drugs are avoided in pregnancy?
tetracycline - causes tooth dysplasia and inhibits bone growth
with what type of drugs is a compromised immune system problematic?
bacteriostatic drugs
What differs typically in young and old patients compared to older children and adults?
rental, hepatic and CV function differs
Which drugs block cell wall synthesis by inhibition of peptidoglycan cross-linking
penicillin, methicillin, ampicillin, piperacillin, cephalosporins, azteronam, imipenem
Which drugs block peptidoglycan synthesis of cell wall?
Bacitracin, vancomycin
Which drugs block nucleotide synthesis (metabolism)?
sulfonamides, trimethoprim
Which drugs block DNA topoisomerases, nucleic acid function or synthesis
Fluoroquinolones and rifampin
Which drugs inhibit cell membrane function?
isoniazide, amphotericin B
Which drugs block protein synthesis at 50S ribosomal subunit?
Chloramphenicol, macrolides, clindamycin, streptogramins, linezolid
Which drugs block protein synthesis at 30 S ribosomal subunit
Aminoglycosides, tetracyclines
What is the mechanism of penicillin?
- binds PCPs (penicillin-binding proteins)
- Blocks transpeptidase cross-linking of peptidoglycan
- Activates autolytic enzymes
What is the clinical use of penicillin?
Used for gram positive organisms mostly: S. pneumoniae, S. pyogenes, Actinomyces and syphilis. Bactericidal for gram + cocci & rods, gram-negative cocci, spirochetes.
What has penicillin resistance?
Beta Lactamases - cleave Beta lactam ring
What are the penicillinase-resistant penicillins and what are they used to treat?
Methicillin, Nafcillin, dicloxacillin. Use Naf for Staph. (not MRSA)
How do ampillicin/amoxicillin differ from penicillin?
Wider spectrum, but still penicillinase sensitive. Combine with clavulanic acid to protect against beta lactamase. AmOxicillin = greater Oral bioavailability than ampicillin.
What are aminopenicillins (amox/amp) used to treat?
HELPSS kill enterococci
Haemophilus influenza, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, Enterococci.
What are Ticarcillin, carbenicillin, and piperacillin used for?
anti-pseudomonals. TCP - takes care of pseudomonas (and gram - rods).
Penicillinase sensitive, use with clauvulanic acid.
What are the beta lactamase inhibitors?
CAST: Clauvulanic Acid Sulfbactam Tazobactam - often added to penicillin antibiotics to evade destruction
What are the beta lactam drugs that inhibit cell wall synthesis and are less susceptible to penicillinases
Cephalosporins
Which organisms are not covered by cephalosporins?
LAME! Listeria Atypicals (Chlamydia, Mycoplasma) MRSA Enterococci
What are the clinical use of first generation cephalosporins and what are the names of these drugs?
Drugs: cefazolin, cephalexin PEcK P - proteus mirabilis E. coli Klebsiella
What do the 2nd generation cephalosporins treat and what are the drug names?
Drugs: cefoxitin, cefaclor, cefuroxime HEN PEcKS H- H.influenza E - enterobacter aerogenes N - neisseria P =- proteus mirabilis E. coli K - Kleibsiella S - serratia
What are the third generation cephalosporins and what are they used to treat?
Drugs: ceftriaxone - used for meningitis and gonorrhea
cefotaxime,
ceftazidime - used for pseudomonas
Treat serious gram negative infections resistant to other beta lactams
What are the 4th generation cephalosporins and what are they used for?
Drugs: cefepime. Increased activity against pseudomonas and gram positive organisms.
What is aztronam used to treat?
Gram-negative rods only. No effect on gram-positives or anaerobes. It is resistant to beta lactamases, inhibits cell wall synthesis by binding to PBP.
What is Imipenem combined with and what is it used for?
the kill is “lastin” with ciLASTatIN
combined with cilastatin to decrease inactivation of drug in renal tubules.
Wide spectrum but used to treat nosocomial infections and multiple infections of unknown origin. Low susceptibility to beta lactamases
What is the mechanism of action of vancomycin?
inhibits cell wall formation by binding to D-ala D-ala to D-ala D-lac. Bacteriocidal. “pay back 2 D-ala’s for VANdalizing”
What is vancomycin used to treat?
Gram positive only, serious, multidrug resistant Staph Aureus, enterococci and C diff.
What is the toxicity of Vancomycin?
does NOT have many problems except N - nephrotoxicity O- ototoxicity T- thrombophlebitis and diffuse flushing - red man syndrome
Buy AT 30, CCEL at 50
30S inhibitors:
A: Aminoglycosides (SIDAL)
T: Tetracyclines (bacteriostatic)
50S inhibitors: C: Chloramphenicol C: Clinamycin E: erythromycin (macrolides) L: Linezolid
What are the aminoglycosides?
MIN GNATS canNOT kill anaerobes G: gentamicin N: neomycin A: amikacin T: tobramycin S: streptomycin
What is the mechanism of action of Aminoglycosides?
Bactericidal - inhibit formation of initation complex and cause misreading of mRNA. “A” “initiates” the alphabet. Require oxygen for uptake, therefore ineffective against anaerobes
What is the toxicity of aminoglycosides?
NOT
Nephrotoxicity (especially when combined with cephalosporins), Ototoxicity (especially when used with loop diuretics), and Teratogen.
What are the tetracyclines?
Tetracycline, doxycycline, tigecycline, minocycline
What is the mechanism of action of the tetracyclines.
Bacteriostatic, binds to 30S and prevents attachment of aminoacyl-tRNA. Limited CNS penetration. Doxy is fecally eliminated so can be used in patients with renal failure
What is the clinical use of tetracyclines?
Borrelia Burgdorferi, Mycoplasma pneumoniae, rickettsia, Chlamydia.
What is toxicity of tetracyclines>
GI distress (C diff), bone and tooth irregularities in children, photosensitivity, hepatotoxicity, bone deformities in fetuses - crosses placenta, vestibular toxicity
How is resistance conferred in tetacyclines?
decreased uptake into cells or increased efflux out of cells by plasmid-encoded transport pumps
What are the macrolides?
Erythromycin, Azithromycin, Clarithromycin, Telithromycin, Clindamycin
What are the macrolides mechanism of action?
bind to 50S subunit to inhibit translocation and stop peptide synthesis
how is resistance conferred in the macrolides
increased synthesis of methylase (methylation of 50S rRNA binding site); increased efflux
What is the clinical use of the macrolides?
Atypical pneumonias (Mycoplasma, Chlamydia, Legionella), URIs, STDs, Gram + cocci (strep and syphilis in patients allergic to penicillin), Neisseria
What is the toxicity of the Macrolides?
Prolonged QT interval, especially erythromycin. GI discomfort, acute cholestatic hepatitis, eosinophilia, skin rash
What is the mechanism of Chloramphenicol
Blocks peptide bond formation at 50S ribosomal subunit. Bacteriostatic
What is the clinical use of Clindamycin?
Blocks peptide bond formation at 50S. Bacteriostatic.
What are the clinical uses for clindamycin?
anaerobic infections like bacteroides fragilis, clostridium perfringens in aspiration pneumonia or lung abcesses
What are the sulfonamides?
Sulfasalazine, sulfadiazine, sulfapyridine, Sulfamethoxazole, Sulfisoxazole
What is the mechanism of sulfonamides?
PABA antimetabolites inhibit dihydropteroate synthetase. Bacteriostatic. Blocks bacterial folate synthesis.
What is the clinical use for sulfonamides?
Nocardia, Chlamydia, active against enterobacteria in urinary tract (UTI)
What is sulfasalazine broken up into in the body?
Sulfapyridine &
Amino salicylate
What sulfa drug is used to treat chronic bowel disorders?
sulfasalazine - poor oral absorption, stays in gut
What are the adverse effects of Sulfonamides?
- crysalluria - crystallize in bladder
- Hypersensitivty - rashes, angioedema
- Hemolytic anemia in G6PD deficiency
- Kernicterus in infants caused by increased bilirubin
What is the function of trimethoprim?
Inhibits bacterial dihydrofolate reductase. Bacteriostatic.
What is the clinical use of trimethoprim?
combine with sulfonamides to create cotrimoxazole “Bactrim”
What is the mechanism of Cotrimoxazole?
Blocks dihydropteroate (sulfonamide)
Blocks dihydrofolate reductase
penetrates CSF
What adverse effects does trimethoprim alone cause?
megaloblastic anemia, leukopenia, granulocytopenia
What can trimethoprim be used to treat?
UTIs, prostatitis, vaginitis
What are the 1st generation fluoroquinolones?
Nalidixic acid, norfloxacin. Used for gram negatives typically uncomplicated UTIs.
What are the 2nd generation fluoroquinolones?
Ciprofloxacin, Ofloxaxin. Expanded gram negative activity and atypical mycoplasma and chlamydia pneumoniae.
What are the 3rd and 4th generation fluoroquinolones?
3- levofloxacin, gemifloxacin. Gram neg, Gram pos, and atypical pneumoniae.
4 - moxifloxacin - gains anaerobic coverage
What are the fluoroquinolines used for?
gram negative rods of urinary and GI tracts (pseudomonas, neisseria, and some gram + organisms)
What is the drug of choice for anthrax?
Ciprofloxacin
Why is ciprofloxacin not used for pneumonia or sinusitis? What should you use instead?
Because it was weak activity against strep pneumoniae. Use Levofloxacin or moxifloxacin instead.
What is the mechanism of action of fluroquinolones
inhibits topoisomerase II in gram negative (inhibiting DNA gyrase) and inhibits topoisomerase IV in gram positive (interferes with separation of strands). Decreases bacterial DNA synthesis.
What is the “black box” warning for fluoroquinolones?
increased risk of tendonitis, tendon rupture after systemic use.
Why are fluoroquinolones not recommended in growing children?
Lones are bad for the Bones. affect cartilage formation, increases joint pain.
What are other adverse effects of fluoroquinolones?
diarrhea, nausea, headache, dizziness, nephrotoxicity - reduce kidney function
Which drug is not appropriate in the treatment of Legionella pneumonia out of erythromycin, gentamicin, ciprofloxin, doxycyclin, azithromycin?
gentamicin