Flashcards in Antibiotics Deck (132):
Which penicillin is oral? IV/IM?
oral: pen V. IV/IM: pen G.
1) bind PBPs (transpeptidases) 2) block transpeptidase cross-linking of peptidoglycan. 3) Activate autolytic enzymes.
Clinical use of Penicillin
Gram + organisms (S. pneumoniase, S. pyogenes, Actinomyces). Also used for N. Meningitidis and T. Pallidum. Bactericidal for gram positive cocci, gram positive rods, gram negative cocci, and spirochetes. Penicillinase sensitive.
Hypersensitivity reactions. Hemolytic anemia
Penicillinase in bacteria (a type of beta lactamase) cleaves beta lactam ring
Ampicillin, amoxicillin (aminopenicillins, penicillinase sensitive penicillins) Mechanism?
Same as penicillin but wider spectrum; penicillinase sensitive. Also combine with clavulonic acid to protect against beta lactamase.
Which has better oral bioavailability, ampicillin or amoxicillin?
amOxicillin (O for oral)
What is the clinical use of Ampicillin, amoxicillin (aminopenicillins, penicillinase sensitive penicillins)?
Extended-spectrum penicillin : HELPSS kill enterococci: Haemophilus influenzae, E. Coli, Listeria monocytogenes (meningitis in the elderly) Proteus mirabilis, Salmonella, Shigella, enterococci
Ampicillin, amoxicillin (aminopenicillins, penicillinase sensitive penicillins) SE?
Hypersensitivity reactions; rash; pseudomembranous colits
Ampicillin, amoxicillin (aminopenicillins, penicillinase sensitive penicillins) Mechanism of resistance?
Penicillinase in bacteria (a type of beta lactamase) cleaves beta lactam ring
Oxacillin, nafcillin, dicloxacillin (penicillinase resistance penicillins) mechanism?
same as penicillin. Narrow spectrum; penicillinase resistant because bulky R group blocks access of beta lactamase to beta lactam ring
Oxacillin, nafcillin, dicloxacillin (penicillinase resistance penicillins) clinical use?
S. aureus ( except MRSA; resistant because of altered PBP target site). Use naf (naficillin for staph)
Oxacillin, nafcillin, dicloxacillin (penicillinase resistance penicillins) toxicity?
hypersensitivity reactions, interstitial nephritis
Ticarcillin, piperacillin mech?
Same as penicillin. Extended spectrum.
Ticarcillin, piperacillin clinical use?
Pseudomonas spp. and gram-negative rods; susceptible to penicillinase; use with beta lactamase inhibitors.
Ticarcillin, piperacillin toxicity?
What are the beta lactamase inhibitors?
Clavulanic Acid, Sulbactam, Tazobactam. Often added to penicillin antibiotics to protect the antibiotic from destruction by beta lactamase (penicillinase).
what are cephalosporins
beta lactam drugs that inhibit cell wall synthesis but are less susceptible to penisillinases
What organisms are typically not covered by cephalosporins?
they are LAME: Listeria, Atypicals (chlamydia, mycoplasma), MRSA, and Enterococci.
What Cephalosporin will cover MRSA?
What is the clinical use of 1st generation Cephalosporins?
gram positive cocci: PEcK : Proteus mirabilis, E. Coli, Klebsiella pneumoniae.
What are the 1st generation Cephalosporins?
which 1st generation cephalosporin is used prior to surgery to prevent S. aureus wound infections?
What are the 2nd generation cephalosporin drugs/indications?
cefoxitin, cefaxcor, cefuroxime (gram positive cocci): HEN PEcKS: Haemophilius influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E. coli, Klebsiella pneumoniae, Serratia
What are the 3rd generation cephalosporin drugs/indications?
Ceftriazone (meningitis and gonorrhea), Ceftazidime (Pseudomonas), Cefotaxime: Serious gram negative infections resistant to other beta lactams
What is the 4th generation cephalosporin drug/indications?
Cefepime - increased activity against Pseudomonas (G-) and other gram positive organisms
What is a 5th generation cephalosporin, and what is the indication?
Ceftaroline: broad gram positive and gram negative organism coverage including MRSA ; does NOT cover Pseudomonas
What toxicites can cephalosporins cause?
Hypersensitivity reactions, vitamin K deficiency. Low cross reactivity with penicillins. Increased nephrotoxicity of aminoglycoside
A monobactam; resistant to beta lactamases. Prevent peptidoglycan cross linking by binding to PBP 3. Synergisitc with aminoglycosides. No cross allergenicity with penicillins.
What is the clinical use of Aztreonam?
Gram negative rods only. no activity against gram positives or anaerobes. Used for penicillin allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides.
What is the toxicity of Aztreonam?
generally none. occasional GI upset
What are the carbapenems?
Imipenem, meropenem, ertapenem, doripenem
What is the mechanism of carbapenems, specifically imipenem?
broad spectrum beta lactamase resistance carbapenem.
What drug is alway administered with Imipenem? Why?
Cilastin (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules.
The kill is lastin with cilastin!
What carbapenem has limited psuedomonas coverage?
What is the clinical use of the carbapenems?
Gram-positive cocci, gram-negative rods (enterobacter cloacae, serratia marcescens, klebsiella pneumonia) and anaerobes. Wide spectrum, but significant SE limit use to life threatening infection or after other rgus have failed.
What carbapenem has resistance to dehydropeptidase I?
What carbapenem has a decreased risk of seizures?
What are the SE/Toxicities of carbapenems?
GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels.
inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors. Bactericidal.
What is the use of Vancomycin?
Gram positive only. serious, multi-drug resistant organisms including MRSA, enterococci, and C diff - Oral dose for pesudomembrane colitis!
What are the toxicites of Vancomycin?
Well tolderated in general but NOT trouble free: Nephrotoxicity, Ototoxicity, Thrombophlebitis, diffuse flushing (RED MAN SYNDROME)
how can RED MAN syndrome be prevented?
Vanco + antihistamines and slow infusion
What is the mech of resisitance to Vancomycin?
Ocurrs in bacteria via amino acid modification of D-Ala D-ala to D-ala D-lac.
Protein synthesis inhibitors
Specifically target smaller bacterial ribosome 70S, made of 30S and 50S subunits, leaving human ribosomes 80s unaffected
buy AT 30, CCEL at 50
1) 30s inhibitors: Aminoglycosides (bactericidal), Tetracyclines (bacteriostatic)
2) 50s inhibitors: Chloramphenicol, Clindamycin (bacteriostatic), Erythromycin (macrolide, bacteriostatic), Linezolid (variable)
What are the Aminoglycosides?
Mean (aminoglycoside) GNATS caNNOT kill anaerobes. Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin
Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin mechanism
Bactericidal; inhibit formation of initiation complex and cause misreading of mRNA. Also block translocation. Require O2 for uptake; therefore ineffective against anaerobes.
A INITIATES the Alphabet
What is the SE's of Aminoglycosides?
Mean (aminoglycoside GNATS caNNOT kill anaerobes. Nephrotoxicity (especially when used with cephalosporins), Neuromuscular blockase, Ototoxicity (especially with loop diuretics). Teratogen
What is the mechanism of resistance to Aminoglycosides?
Bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation
What are the Tetracyclines?
Tetracycline, doxycline, minocycline
Mechanism of Tetracyclines
Bacteriostatic: bind to 30S and prevent attachment of aminoacyl-tRNA; limited CNS penetration. Doxycycline is fecally eliminated and can be used in patient with renal failure.
What should you NOT take with the Tetracyclines?
milk (Ca++), antacids (Ca++ or Mg++), or iron-containing preparations because divalent cations inhibit its absorption in the gut
What is the clinical use of Tetracyclines?
Borrelia burgdorferi, M. pneumoniae, vibrio cholera, chlamydia urea plasm, urealyticum, francisella tularenesis, H pylori, rickettsia. Drugs ability to accumulate intracellulary makes it very effective against Rickettsia and Chlamydia. Also used to treat Acne
GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity.
Who should NOT take Tetracyclines?
mechanism of resistance to Tetracyclines
Decrease uptake or Increased efflux out of bacterial cells by plasmid-encoded transport pumps
What are the Macrolides?
(MAC is an ACE) Azithromycin, Clarithromycin, Erythromycin
Mechanism of the Macrolides?
Inhibit protein synthesis by blocking translocation (macroSLIDES); bind to the 23S rRNA of the 50s ribosomal subunit. Bacteriostatic.
Clinical use of Macrolides?
Atypical Pneumonias (Mycoplasma, Chlamydia, Legionella), STDs (for Chlamydia), and gram positive cocci (streptococcal infections in patients allergic to penicillin)
SE/Toxicities of Macrolides?
MACRO: Gatrointestinal Motility issues, Arrhythmia causing prolonged QT, acute Cholestatic hepatitis, Rash, eOsinophilia.
Macrolides increase the serum concentration of what drugs?
Theophyllines, oral anticoagulants
What is the mech of resistance to macrolides?
Methylation of 23S rRNA-binding site prevents binding of drug
blocks peptidytransferase at 50S ribosomal subunit. bacteriostatic.
Meningitis (Haemophius influenze, Neisseria meningitidis, Streptococcus pneumoniae), and Rocky Mountain spotted fever (Rickettsia Ricketsii).
What limits Chloramphenicol's use?
toxicities; still used in developing countries because of low cost
Toxicity/SE of Chloramphenicol?
Anemia (dose dependent), aplastic anemia (dose dependent), gray baby syndrome (in premature infant because they lack liver UDP glucuronyl transferase)
What is the mech of resistance to chloramphenicol?
plasmid encoded acetyltransferase inactivates the drug
Blocks peptide transfer (translocation) at 50S ribosomal subunit. Bacteriostatic.
Clinical use of Clindaslidosin?
Anaerobic infections (Bacteroides spp., C. Perfringens) in aspiration pneumonia, lung abscess, and oral infections. Also effective against invasive Group A Strep (GAS) infection.
Helpful tip for clinda
Treats anaerobes ABOVE the diaphragm vs Metrondiazole (anaerobic infections below the diaphragm)
Toxicity of Clindamycin?
Pseudomembranous colitis (C. Diff overgrowth), fever, diarrhea
What are the sulfonamides?
Sulfamethoxazole (SMX), Sulfisoxazole, Sulfadiazine
inhibit folate synthesis. Para aminobenzoic acid (PABA) antimetabolites inhibit dihydropteroate synthase. Basteriostatic.
Clinical use of sulfonamides?
Gram +, Gram -, Nocardia, Chlamydia. Triple sulfas or SMX for simple UTI
What are the SE/toxities of the sulfonamides?
Hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (tubulointersitial nephritis), photosensiivity, kernicterus in infants, displace other drugs from albumin (i.e. warfarin)
What is the mechanism of resistance to sulfonamides?
Altered enzyme (bacterial dihydropteroate synthase), decrease uptake, or increase PABA synthesis
Inhibits bacterial dihydrofolate reductase. bacteriostatic
What is the clinical use of Trimethoprim?
Used in combination with sulfonamides (TMP-SMX), causing a sequential block of folate synthesis. Combination used for UTIs, Shigella, Salmonella, Pneumocystis Jirovecii pneumonia treatment and phophylaxis, toxoplasmosis prophylaxis
Megaloblastic anemia, leukopenia, granulocytopenia. (may alleviate with supplemental folinic acid).
Trimethoprim mneumonic: TMP
Treats Marrow Poorly
What are the Fluroquinolones?
Ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, sparfloxacin, moxifloxacin, gemifloxacin, enoxacin, nalidixic acid (a quinolone)
mech of the Fluoroquinolones (floxacin):
Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV. bactericidal.
What should not be taken with the fluoroquinolones?
What is the clinical use of Fluroquinolones?
Gram-negative rods of urinary and GI tracts (including Pseudomonas, salmonella typhi), Neisseria, some gram-positive oranisms.
What is the toxicity of Fluoroquinolones?
Gi upset, superinfections, skin rashes, headache, dizziness. Less commonly, can cause tendonitis, tendon rupture, leg cramps, and myalgias. Some may cause prolonged QT interval. May cause tendon rupture in people >60 yo and people taking prednisone
Fluoroquinolones are contraindicated in whom?
Pregnant bitches, nursing mothers, and children
Pregnant woman should not take what antibiotics?
Tetracycline and Fluoroquinolones
Which two antimicrobials can cause a prolonged QT interval?
Macrolides and Fluoroquinolones
What is the mech of resistance to Fluoroquinolones?
Chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.
What is the mech of Metrondiazole?
Binds DNA and unwinds helical structure then causes stand breaks to ultimately decrease protein synthesis
M. TB Prophylaxis? Treatment?
Isoniazid. Rifampin, Isoniazid, Pyrazinamide, Ethambutol
M. avium-intracellulare Prophylaxis? Treatment?
P: Azithromycin, rifabutin. Treatment: More drug resistant than M. TB. Azithromycin or clarithromycin + ethambutol. Can add rifabutin or ciprofloxacin
M. Leprae Treatment?
Long term treatment with dapsone and rifampin for FB form. Add clofazimine for lepromatous form.
decreases synthesis of mycolic acids. bacterial catalse-peroxidase (encoded by KatG) needed to convert INH to active metabolite
Clinical use of Isoniazid?
M. TB. The only agent used as solo prophylaxis against TB.
What determines the half life of Isoniazid?
Fast vs. Slow acetylators
Neurotoxicity, hepatotoxicity. Pyridoxine (Vit b6) can prevent neurotoxicity, lupus.
mneumonic for Isoniazic?
INH Injures Neurons Hepatocytes
Inhibits DNA-dependent RNA polymerase
What is the clinical use of Rifamycins?
M. TB; delays resistance to dapsone when used for leprosy. Used for meningococcal prophylaxis (neisseria) and chemoprophylaxis in contacts of children with Haemophilus influenzae type B
menumonic for Rifampin's 5 R's
1) RNA polymerase inhibitor 2) Ramps up microsomal cytochrome P-450 3) Red/orange bodily fluids 4) Rapid resistance if used alone 5) Rifampin ramps up cytochrome P-450, but rifabutin does not
What are the toxicities of Rifamycins?
Minor hepatotoxicity and drug interaction (Increased P-450); orange body fluids (nonhazardous SE).
What drug is favored in HIV patients: Rifampin or Rifabutin?
Rifabutin due to less CYP indution
Mech uncertain. Through to acidify intracellular environment via conversion to pyrazinoic acid. Effective in acidic pH of phagolysosomes, where TB engulfed by macrophages is found
Clinical use of pyrazinamide
Toxicity/SE of Pyrazinamide
decrease carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase.
Clinical use of Ethambutol
Optic Neuropathy (red-green color blindness)
Prophylaxis for Endocarditis with surgical or dental procedures?
Prophylaxis for Gonorrhea?
Prophylaxis for Hs of recurrent UTIs?
Prophylaxis for meningococcal infection?
Ciprofloxacin, rifampin for children ***
Prophylaxis for pregnant woman carrying group B strep?
Prophylaxis for preventino of gonococcal or chlamydial conjunctivitis in newborn?
Prophylaxis of strep pharyngitis in child with prior rheumatic fever?
Prophylaxis for Syphilis?
Benzathine Pen G
Treatment of MRSA?
Vancomycin, daptomycin, linezolid, tigecycline, ceftaroline
SE of linezolid?
Treatment of Vancomycin Resistant Enterococci?
Linezolid and streptogranins (quinupristin/dalfopristin)
Which antibiotics are bactericidal?
Penicillin, Vancomycin, Aminoglycosides, Fluoroquinolones, Metrondiazole
What treatment do you give for N. Gohnorrhea?
Ceftriaxone for the gonhorreah and must give a macrolide (azithromycin) for Claudia because of co infection
What is the treatment of listeria monocytogenes?
What is the treatment for yersini?
Tetracycline and Aminoglycosides (streptomycin)
What is the treatment of pseudomonas?
Piperacillin + tazobactam, Aminoglycosides (in combo with beta lactams), or fluoroquinolones (pseudomonas uti). Coproflixacin in CF patients
Treatment for proteus?
What is the indication of piperacillin-tazobactam?
Pseudomonas infection, resistant staph aureus infection, gram negative rods