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283 Cards in this Set
- Front
- Back
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beta-lactams: mechanism of action
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kill bacteria by inhibiting or weakening cell wall (bactericidal) penicillin binding proteins (PBPs): binding sites for β-lactam AB’s
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beta-lactams: bacterial resistance mechanisms
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failure to penetrate outer bacterial cell layer (ex. gram neg. bacteria) altered target: PBPs can mutate & ↓ their affinity for AB --> resistance production of β-lactamase: most common mechanism
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beta-lactams a. bactericidal or bacteriostatic? b. time or conc. dependent?
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a. bactericidal b. time dep.
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penicillins: spectrum
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primarily Gram positive, some obligate anaerobes
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penicillins: 3 formulations
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Penicillin G Potassium, Penicillin G Sodium: short lived plasma conc. Procaine Penicillin G: lasts ~24 hrs Benzathine Penicillin G: can last up to 14 days (not used much d/t residues)
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penicillins a. oral absorption b. volume of distribution c. half life d. method of elimination e. routes of administration
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a. poor (<10%) b. small (doesn't cross mems well) c. short (0.5-1.2 hrs) d. renal e. IM, IV, SQ only
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penicillins: adverse effects
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allergic rxns vomiting/diarrhea
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penicillins: regulatory considerations
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high doses in cattle not approved --> extended withdrawal times
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aminopenicillins a. 2 most common b. spectrum
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a. Amoxicillin, Ampicillin b. same as Penicillin + some gram negative bacteria (acquired resistance common)
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aminopenicllins a. oral absorption b. volume of distribution c. half life
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a. poor in horses & ruminants, good in other animals (Amoxicillin 2x > Ampicillin) b. low c. short
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aminopenicillins: adverse effects
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allergy vomiting/diarrhea
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beta-lactamase inhibitors: 2 primary drugs added to aminopenicillins
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clavulanic acid (potassium clavulanate) sulbactam
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Clavamox a. components b. species c. uses
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a. amoxicillin, clavulanic acid b. dogs & cats c. used to tx infection in most tissues: UTI, skin infection, pneumonia, systemic infection
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Unasyn a. components b. species c. routes of administration
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a. sulbactam, ampicillin b. dogs, horses, cattle c. IM, IV, SQ
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advantages of beta-lactamase inhibitors
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low toxicity & good safety profile of other beta-lactams may be useful for infections caused by β-lactamase producing bacteria (ex. Staph, Gram neg. bacilli, Gram neg. anaerobes)
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cephalosporins: spectrum
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similar to aminopenicillins; have activity against: Staph (β-lactamase positive) Strep Gram neg. bacteria (including E. coli, Proteus, Klebsiella), except Pseudomonoas anaerobic bacteria, except Bacteroides fragilis resistance common
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cephalosporins: a. routes of administration b. oral absorption c. metabolism d. elimination e. half life f. volume of distribution
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a. SC, IM, IV, oral, intramammary b. good in small animals, poor in large animals c. liver (minimal) d. renal e. variable (short to long) f. small, but good distribution into ECF of most tissues
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Cephalexin a. generation b. uses
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a. 1st generation cephalosprin b. commonly used for many infections, including pyoderma, UTI, pneumonia, soft tissue infection, & osteomyelitis
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Cefazolin a. generation b. uses
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a. 1st generation cephalosporin b. most commonly used injectable cephalosporin in vet med
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1st generation cephalosporins: spectrum
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Staph Strep Anaerobes Gram neg. bacteria (may develop resistance)
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3rd generation cephalosporins: spectrum
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Strep (variable) Anaerobes Gram neg. bacteria (more active than other generations) greater CNS penetration
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Cefpodoxime-proxetil a. trade name b. generation c. activity d. uses e. dosing
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a. Simplicef b. 3rd generation cephalosporin c. more active than many other 3rd generation cephalosporins against Staph - not active against Pseudomonas aeruginosa, Enterococcus, or MRSA d. tx of cutaneous infections e. SID; prodrug
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Ceftiofur a. generation b. uses c. Excede
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a. 3rd generation cephalosporin c. tx respiratory infections in cattle, pigs, & horses d. crystalline free acid form: slow-releasing drug that is injected at base of ear of cattle & neck of pigs
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cephalosporins: adverse effects
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allergy: less common than in penicillins vomiting, diarrhea
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carbapenems: spectrum
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broad spectrum: gram pos. & gram neg. highly resistant to β-lactamase enzymes & penetrate most gram neg. bacteria readily more bactericidal than other β-lactam ABs against gram neg. bacteria produce post-antibiotic effect (PAE) not seen w/ other β-lactams
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carbapenems a. uses b. example drug
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a. use limited to serious infections caused by bacteria resistant to other ABs b. Meropenem (Merrem): given IV or SQ to dogs & cats - not likely to cause seizures, as Imipenem, another drug in class, can
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aminoglycosides: mechanism of action
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bind 30-S ribosomal subunit --> inhibit bacterial protein synthesis
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aminoglycosides: a. bactericidal or bacteriostatic? b. concentration or time dependent? c. dosing
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a. bactericidal b. concentration dependent c. SID (long PAE)
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aminoglycosides: spectrum
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effective against most gram neg. bacteria, including Enterobacteriaceae (E. coli, Klebsiella, Proteus, Enterobacter) & Pseudomonas aeruginosa somewhat effective against Staph (resistance can occur) anaerobic bacteria are resistant
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aminoglycosides: effects of tissue environ. on activity a. pH b. cellular debris c. O2 tension d. cations
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a. activity is less at low pH (optimum: 6-8) b. aminoglycosides are bound to & inactivated by cellular debris --> poor activity in abscesses c. low O2 tension, such as found in anaerobic tissue or decaying tissue --> ↓ activity d. divalent cations (ex. Ca2+, Mg2+) interfere w/ uptake into bacteria
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aminoglycosides: bacterial resistance mechanisms
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anaerobic bacteria are intrinsically resistant failure to penetrate cell wall altered target (ribosome) that resists binding synthesis of bacterial enzymes that inactivate drug
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aminoglycosides a. volume of distribution b. half life c. oral absorption d. elimination
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a. small: poor distribution into respiratory fluids, eye, prostate, CNS -VD larger in young animals b/c of ↑ proportion of extracellular fluid --> higher doses need for neonates to maintain effective plasma concentrations b. short (1-2 hrs) c. poor d. renal
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aminoglycosides: adverse effects
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renal toxicosis: toxicity most severe in proximal tubules b/c drug is actively taken up there -animals that are dehydrated, have electrolyte imbalances, endotoxemia, or existing renal dz, or are taking the drug for longer than 7-10 days are at a higher risk for toxicity -assess renal function BEFORE beginning tx ototoxicity, vestibulotoxicity: may result from prolonged use neuromuscular blockade: rare (only at high doses)
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aminoglycosides: clinical uses
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acute overwhelming sepsis tx of resistant gram neg. organisms (ex. Pseudomonas, E. coli, Staph) topical preparations: skin infections, eyes, ears (no systemic absorption)
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aminoglycosides: prototype & formulations
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Gentamicin IV, SC, IM, topical (ears, eyes, skin)
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aminoglycosides: regulatory status
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not registered for systemic use in food animals (very long withdrawal times for slaughter)
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tetracyclines: mechanism of action
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bind 30-S ribosomal subunit --> inhibit bacterial protein synthesis
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tectracylines a. bactericidal or bacteriostatic? b. time or conc. dependent?
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a. bacteriostatic (binding to ribosome is reversible) b. time dependent
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tetracyclines: spectrum
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BROAD active against gram neg. & gram pos. bacteria, Chlamydia, rickettsia, spirochetes, mycoplasma, L-form bacteria, & some protozoa (Plasmodium, Entameba) Pseudomonas spp., Enterobacteracae usually resistant
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tetracyclines: bacterial resistance mechanisms
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caused by failure in active transport required to enter bacterial cell
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tetracyclines a. oral absorption b. half life c. volume of distribution d. elimination
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a. good in most species - Ca2+ & other divalent cations chelate tetracyclines --> inhibit oral absorption b. moderately long c. well distributed to most tissues, except CNS - passively diffuse into cells --> effective for treating intracellular infections d. renal
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tetracyclines: adverse reactions
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diarrhea (esp. horses) -horses: oral administration of oxytetracycline has been assoc. w/ proliferation of Clostridium perfringens or Salmonella in colon (“Colitis X”) esophageal lesions: doxycyline hyclate capsule or broken tablet administered to cat can become lodged in esophagus --> esophageal lesions & stricture (try to give w/ water or food in cats) tooth discoloration in young animals renal tubular necrosis: high doses (rare) toxic hepatatis: rare
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tetracyclines a. large animal drug b. small animal drug
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a. oxytetracycline (parenteral) - IM absorption delayed by addition of “viscosity excipient” --> long acting forms b. doxycycline hyclate - can be given orally or IV - drug of choice for rickettsial infections
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tetracyclines: clinical uses a. cattle & sheep b. swine c. small animals d. birds e. horses
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a. oxytetracycline used to tx lung infections assoc. w/ bovine respiratory dz (BRD) b. Mycoplasma, atrophic rhinitis, pneumonic pasteurellosis c. Ehrlichiosis, Rickettsia, Mycoplasma, Chlamydia, UTIs, respiratory infections d. tx of choice for psittacosis caused by Chlamydophila psittaci (oral, add doxycline to drinking water) e. oxytetracycline has been used to tx Potomac Horse Fever (Neorickettsia risticii) - IV administration of doxycycline in horses has caused acute death
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chloramphenicol: mechanism of action -bactericidal or bacteriostatic?
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binds 50-S ribosomal subunit --> inhibits bacterial protein synthesis -bacteriostatic
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chloramphenicol: spectrum
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good activity against Gram neg., Gram pos., anaerobes, Rickettsia, Chlamydia, Mycoplasma poor activity against Pseudomonas, unpredictable activity against Enterobacteracae (resistance common)
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chloramphenicol: bacterial resistance mechanisms
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inactivation by bacterial enzymes, inhibited entry into bacteria
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chloramphenicol a. oral absorption b. volume of distribution
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a. good oral absorption in most animals, except ruminants b. high volume of distribution: penetrates some tissues, such as eye & CNS, better than many other ABs
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chloramphenicol: regulatory status
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banned for use in cattle b/c of risk of residues in treated animals very few preparations currently on market
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chloramphenicol: adverse reactions
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bone marrow toxicity - dose relation anemia & pancytopenia: dogs & cats - ↓ in protein synthesis in bone marrow may be assoc. w/ chronic tx - reversible if discontinued - idiosyncratic aplastic anemia: described only in humans (rare, but severe) - irreversible - not dose related - led to ban in food animals WEAR GLOVES WHEN HANDLING
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Florfenicol a. class b. spectrum c. uses
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a. newer analogue of chloramphenicol that does NOT produce aplastic anemia in people b. similar spectrum to chloramphenicol, but more active c. cattle, swine: tx of respiratory infections
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macrolides: mechanism of action
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bind 50-S ribosomal subunit --> inhibit bacterial protein synthesis
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macrolides a. bactericidal or bacteriostatic? b. time or conc. dependent?
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a. bacteriostatic (bactericidal for some Gram pos. bacteria) b. time dependent
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macrolides: spectrum
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NARROW good activity against Gram pos. bacteria, Rhodococcus, Mycoplasma, Chlamydia poor activity against most Gram neg. bacteria, except some Pasteurella & Mannheimia haemolytica
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macrolides: bacterial resistance mechanisms
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gram neg. bacteria inherently resistant other bacteria can develop resistance w/ repeated exposure ↓ entry into bacteria, altered target site on ribosomal RNA, inactivation by bacterial enzymes
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macrolides a. oral absorption b. volume of distribution
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a. good in monogastrics, 15-20% in horses b. good tissue distribution -concentration in most tissues are higher than in plasma -drugs concentrate in WBCs --> WBCs carry drug to infected tissues -high concentrations in tissues persistent for much longer than plasma concentrations
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macrolides: prototype, routes of administration
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Eryhtromycin: clinical use has ↓ in recent years oral, IM (painful infection)
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macrolides: adverse rxns
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serious changes in bacterial intestinal flora --> diarrhea in rodents, horses - DO NOT give orally to rodents ↑ upper GI motility - can cause vomiting & regurgitation in small animals - at small doses, can be used as a motility-stimulating drug - mechanism: ↑ activation of motilin receptors via release of endogenous motilin or via cholingeric mechanisms in upper GI tract
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macrolides: clinical uses a. small animals b. horses c. cattle, pigs
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a. pyoderma, respiratory infections, osteomyelitis, soft tissue infections b. resp. infections (esp. w/ Rhodococcus equi) c. respiratory infections
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Tilmicosin a. class b. species c. precaution
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a. macrolide (injectable: SQ only) b. cattle, sheep c. DON'T GIVE IV -IV administration has caused deaths in animals d/t negative inotropic effects on heart -do not give to any species other than cattle or sheep -accidental injection into humans has caused death by cardiovascular toxicity
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Azithromycin a. class b. comparative pharmacokinetics c. uses in dogs, cats, horses
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a. macrolide b. better tolerated, better oral absorption, ↑ volume of distribution, ↑ half life, ↑ tissue concentrations compared to erythromycin - concentrations in WBCs may be 200x concentrations in serum --> allows intermittent dosing c. dogs: respiratory, skin, refractory infections -cats: respiratory, skin, Bartonella infections -horses: Rhodococcus equi infections
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Tulathromycin a. class b. uses c. comparative pharmacokinetics
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a. macrolide b. used to tx respiratory infections in cattle & pigs c. improved gram neg. activity compared to other drugs in group -long half life in tissues --> long withdrawal times (cannot use in lactating dairy cows)
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lincosamides: mechanism of action
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bind 50-S ribosomal subunit --> inhibit bacterial protein synthesis
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lincosamides a. bactericidal or bacteriostatic? b. time or conc. dependent?
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a. bacteriostatic b. time dependent
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lincosamides: spectrum
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NARROW -good activity against Gram pos. bacteria, Mycoplasma, most anaerobic bacteria -little activity against Gram neg. bacteria
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lincosamides a. oral absorption b. volume of distribution
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a. good b. good tissue distribution
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lincosamides: adverse effects
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can cause bacterial overgrowth, particularly of Clostridium difficle, d/t activity against anaerobes -serious & fatal diarrhea reported in humans, rabbits, ruminants, horses following oral administration --> DO NOT GIVE TO HORSES, RUMINANTS, RODENTS
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lincosmaides a. prototype b. uses in small animals
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a. Clindamycin b. oral cavity infections, pyoderma, osteomyelitis, soft tissue infections, Staph infections
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trimethoprim-sulfonamide combinations: mechanism of action
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inhibit formation of tetrahydrofolic acid (active form of folic acid): step in synthesis of nucleotides
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trimethoprim-sulfonamide combinations: how it targets bacteria
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- microorgs more selectively inhibited than animal cells - sulfonamide serves as a “false substrate” for PABA, which is used by micro-orgs to synthesize folic acid - mammals use dietary folate, thus bypassing this step - bacterial form of enzyme dihydrofolate reductase has much higher affinity for trimethropin than does mammalian form
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trimethoprim-sulfonamide combinations: spectrum
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BROAD good activity against Gram pos., Gram. neg., & some protozoa (Toxoplasma, intestinal coccidian, Sarcocystis neurona) resistance common
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trimethoprim-sulfonamide combinations a. oral absorption b. volume of distribution c. elimination
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a. good in most animals b. good: penetrates tissues, cells, CNS c. renal: high urine concentration (used to tx UTIs)
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trimethoprim-sulfonamide combinations: bacterial resistance mechanisms
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mutation of dihydrofolate reductase enzyme to become resistant to trimethoprim utilization of other pathways by bacteria to make folic acid
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trimethoprim-sulfonamide combinations: clinical uses a. horses b. small animals
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a. commonly used b/c of good oral absorption & inexpensive - respiratory, joint, abdominal infections; EPM b. respiratory, skin, urinary tract infections; Toxoplasmosis, Coccidia
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trimethoprim-sulfonamide combinations: adverse effects
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hypersensitivity rxns: DOGS DO NOT GIVE SULFONAMIDE TO DOBERMANS!! - caused by sulfonamide component -lesions: polyarthritis, skin rash, fever, hepatitis, thrombocytopenia, pancytopenia, anemia -may be d/t inability of dogs to acetylate drugs --> most of drug directed to liver (cytochrome p450) for conversion to a toxic metabolite --> metabolites usually detoxified by glutathione conjugation (some patients may lack this ability) -toxic metabolites react w/ cell membranes --> cell injury KCS: DOGS -lacrimotoxic effect of sulfonamide -check tear production in dogs on these meds folate antagonism: HORSES (rare; --> anemia) diarrhea: HORSES UT obstruction, hepatitis, hypothyroidism, skin rxns
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Pyrimethamine a. structurally related to what drug? b. comparative spectrum c. uses
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a. trimethoprim (same mechanism of action) b. more potent in terms of inhibition of dihydrofolate reductase of PROTOZOA than bacteria c. (w/ sulfonamide): EPM in horses, Neospora, Toxoplasma
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fluoroquinolones: mechanism of action
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inhibit DNA gyrase (topoisomerase II) or topoisomerase IV, which catalyze conversion of circular DNA to superhelical form
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fluoroquinolones a. bactericidal or bacteriostatic? b. time or conc. dependent?
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a. bactericidal b. conc. dependent
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fluoroquinolones: factors affecting AB activity a. pH b. cations
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a. less active in acid environ (pH ≤ 6) - acid environ such as urine may ↓ effectiveness for treating UTIs b. activity may be inhibited by di- or tri- valent cations (ex. Mg, Fe, Ca, Al)
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fluoroquinolones: spectrum
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BROAD good activity: Gram neg. (esp. E. coli, Salmonella, Enterobacter, Klebsiella), Gram pos., Chlamydia, Mycoplasma, Rickettsia moderate activity: Pseudomonas aeruginosa poor activity: Strep, Enteroccocus, anaerobes
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fluoroquinolones: bacterial resistance mechanisms
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chromosomal mutation of DNA gyrase or topoisomerase IV efflux pump via outer membrane protein --> prevents accumulation of drug in bacteria (less common) - bacteria may also exclude other ABs --> multi-drug resistance
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fluoroquinolones a. oral absorption b. volume of distribution c. elimination d. PAE?
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a. good in all species b. achieves high concentrations in most tissues & WBCs (exceeds plasma concentrations) - enrofloxacin converted to ciprofloxacin in liver - additive effect from both drugs (enrofloxacin is still active on its own) c. renal d. prolonged PAE
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fluoroquinolones: prototype & formulations
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Enrofloxacin (Baytril) tablets, injectable, otic preparations
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fluoroquinolones: adverse effects
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GI effects: vomiting at high doses; transient diarrhea (rare d/t poor activity vs. anaerobes --> doesn’t alter gut flora as much as other ABs) CNS effects: high doses can cause excitement, confusion, seizures (mostly reported in people) - avoid using in epileptic patients young animals: can produce arthropathy in dogs 8-28 wks old & foals 2-3 wks old - cats, calves appear resistant - joint damaged related to drug’s ability to chelate magnesium - may be reversible if recognized early enough blindness in cats - Enrofloxacin only: do not exceed 5 mg/kg in cats - mydriasis, acute blindness d/t retinal degeneration
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fluoroquinolones: drug interactions
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di- & tri-valent cations may inhibit oral absorption - ex. sucralfate, Fe supplements, oral antacids (contain Al, Mg) fluoroquinolones may inhibit hepatic metabolism of some drugs (ex. theophylline)
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fluoroquinolones: clinical uses in small animals
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soft tissue infections, skin infections, pneumonia, osteomyelitis, prostatitis, UTIs commonly used in many species, esp. exotics
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fluoroquinolones: regulatory issues a. food animals b. poultry
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a. cattle: Enrofloxacin, Danofloxacin approved ONLY for tx of respiratory dz - all other use is ILLEGAL in food animals b. withdrawn by FDA d/t resistance possibly being transmitted to humans who eat poultry (ex. resistance of Campylobacter to fluoroquinolones in humans)
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metronidazole: mechanism of action bactericidal or bacteriostatic?
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rapidly taken up by bacteria --> metabolized by a reduction process --> cytotoxic derivatives aerobic bacteria lack reductive pathway needed to produce the cytotoxic compounds bactericidal
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metronidazole: spectrum
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NARROW highly effective against anaerobes good activity against many protozoa (incl. Giardia), Helicobacter
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metronidazole a. oral absorption b. volume of distribution
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a. rapid & complete oral absorption in small animals & horses b. high: distributes well into all tissues
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metronidazole: adverse effects
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broken or crushed tablets have unpleasant taste - Metronidazole benzoate is more insoluble & lacks unpleasant taste neurotoxicosis: at high doses only -inhibition of GABA --> ataxia, lethargy, proprioceptive deficits, nystagmus, seizure-like signs in dogs -dogs recover if drug administration is discontinued carcinogenicity & mutagenicity: some studies show that metronidazole causes mutations in bacteria -no reported problems in human or vet med
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metronidazole: clinical uses
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-rational choice for anaerobic bacterial infections, incl. oral infections, osteomyelitis, pneumonia, intra-abdominal infections -colitis -giardiasis
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metronidazole: regulatory status
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food animals: prohibited b/c it is considered a potential carcinogen
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Aminoglycosides
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1. 30S 2. Bactericidal 3. Results in premature release of aberrant protein
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Tetracylines
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1. 30S Subunit 2. Bacteriostatic 3. Prevents elongation
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Oxazolidinone
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1. 50S Subunit 2. Bacteriostatic 3. Inhibits initiation complex
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Macrolides
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1. 50S Subunit 2. Bacteriostatic 3. Prevents elongation
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Chloramphenicol
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1. 50S Subunit 2. Bacteriostatic 3. Prevents elongation
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Daptomycin acts on ____ of gram ____ cells
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Daptomycin acts on CELL MEMBRANE of gram POSITIVE cells
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Polymyxin
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Works on outer membrane of Gram Negative bacteria.
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Mechanism of vancomycin
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Prevents crosslinking by binding 5th a.a., preventing it from getting clipped.
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Beta Lactams 1. Where do they work? 2. Function? 3. Common beta lactam?
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1. Cell wall (peptidoglycan) 2. The cell sees them as D-alanine + D-alanine and irreversibly inserts this segment into peptidoglycan 3. Penicillin is a common lactam
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Sulfonamides & Trimethoprim
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Block tetrahydrofolate pathway needed for the production of nucleic acids (Thymine)
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Rifampin
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Stops bacterial RNA polymerase
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Do beta lactams work on Gram+ or Gram-
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Both!
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Linezolid is an example of which antibiotic class?
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Oxazoldinones
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Erythromycin is an example of which class?
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Macrolides
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PENICILLINS (PCN) 4 Compounds Function
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Beta Lactams Disrupt cell wall synthesis Penicillin Oxacillin Ampicillin Piperacillin
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Penicillin - Drug of choice for (2):
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Strep syphilis
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What is the super penicillin? Why is it called this?
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Piperacillin It's a super penicillin because it is very broad spectrum (even against Gram-)
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Adverse effects of penicillin
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Allergy (anaphylaxis / immediate& delayed hypersensitivity) Bone marrow probs nephritis seizures
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Beta Lactam / lactamase inhibitor (4)
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Amoxicillin/ clavulanic acid ampicillin/sulbactam ticarcillin/clavulanic acid piperacillin/tazobactam
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Where do you see the largest activity gain using beta lactam / lactamase inhibitors
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Anaerobic bacteria and Gram negative rods (pseudomonas)
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Problem with lactam/lactamase inhibitors:
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They won't work if resistance is not mediated through Beta lactamase
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Cephalosporins: Mode of action Resistance Excretion Administered? Side effects?
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Block cell wall synthesis - Resistance similar to PCN Renal excretion Can be given orally and parenterally Side effects similar to PCN (note cross allergies)
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Cephalosporins - 5 drugs For each state generation and any Drug of Choice
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Cefazolin (1st gen.) DOC= Staph, strep. E. coli (mostly Gram+, note E.Coli is Gram-) Cefuroxime (2nd gen) good for Staph/strep, more Gram- (esp. respiratory) Ceftriaxone, Cefotaximine & Ceftazidime (3rd gen) Gram+&- BACT MENINGITIS Cefepime (4th gen) PSEUDOMONAS AERUGINOSA
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What is cefepime ineffective against?
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Enterococcus
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Carbapenems (CARBAP) 4 drugs:
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1. Imipenem/cilastatin 2. Meropenem 3. Doripenem 4. Ertapenem (all end in "penem")
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Carbapenems: -Mode of action -Resistance -Excretion -Administration
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Action = Stop cell wall Beta lactamase stable, although bact can aquire resistance via carbapenemase Excretion via kidneys No oral dosage
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Carbapenems: Adverse reactions Any cross allergies?
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Similar to PCN (rash/marrow/seizures) Can have cross allergies with PCN Also see seizures and superinfection
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What bugs are Carbapenems good at fighting?
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Very broad spectrum Both Gram+ and Gram- as well as anaerobes However, only used for severe and/or complex infections
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Ampicillin is the drug of choice for what (2)?
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1.Enterococcus 2.Listeria
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Monobactam (MONOB) -Drug (1) -Function -Resistance (2) -Administration -Excretion Side effects? Cross allergy to PCN?
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Aztreonam Stops cell wall synthesis -Resistance through (1) Altering binding sites & (2) enzyme degredation No oral dosage Excreted through urine. Rxn similar to PCN although they can be given to patients allergic to PCN. There is NO cross allergy to PCN
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Which bacteria can monobactam (MONOB) treat?
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Only gram negative organisms. Use where GNR's are isolated "1/2 the molecule with 1/2 the activity"
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Aminoglycosides (AMINOG): 4 drugs in this family:
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1. Streptomycin 2.Gentamicin 3. Tobramycin 4.Amikacin
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Aminoglycosides (AMINOG): Mechanism Resistance Excretion Administration
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Mechanism: Binds to 30s of ribosomes Resistance via (1) Inactivating enzymes & (2) Decr. Uptake Excretion: Via the kidneys Admin: No oral dosage (Tobramycin can be inhaled)
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What are aminoglycosides effective against? How can they be synnergistic?
|
Good for fighting gram netative bacilli & some mycobacterial (TB) Synergy with beta lactams (especially pseudomonus)
|
|
|
Adverse effects of aminoglycosides(3): Which ones are reversible and which are irreversible?
|
Nephrotoxicity/Ototoxicity/Neuromuscular blockade Nephro = reversible Oto = irreversible (both deafness and balance loss)
|
|
|
What is the post antibiotic effect? Which classes of drugs does it pertain to? Why is it beneficial for clinicians?
|
Post antibiotic effect means drug will work below min level of antibiotics (MIC) needed to kill bacteria (Drug lingers) Helpful for dosing Pertains to aminoglycosides & quinupristin/dalfopristin
|
|
|
Tetracycline (TET): 3 drugs in family (besides tetracycline):
|
1. Doxycycline 2. Minocycline 3.Tigecycline
|
|
|
Tetracycline (TET): Mechanism Resistance Excretion Administration
|
Mechanism: Binds to 30S (bacteriostatic) Resistance through decr. Uptake and EFFLUX Excretion = Renal for TET itself, billiary for other drugs in this class Can be taken IV or orally
|
|
|
Which bacteria can tetracyclines treat?
|
Tetracycline itself is good for acne Drugs in this class are good for CHLAMYDIA and bizarro ARTHROPOD BORNE diseases Drugs are generally broad spectrum
|
|
|
Adverse effects of Tetracyclines (TET) Who can these drugs not be perscribed to?
|
Upset stomach/Diarrhea Also photosensitivty, depressed bone growth, discolored teeth (permanent) Pregnant women and children should not take it
|
|
|
Chloramphenicol (CHLORO): -Mechanism -Resistance -Excretion -Administration
|
Binds to 50S -Bacteriostatic/cidal depending on bacteria Resistance by (1) Decr. Permeability & (2) Acetylating enzyme Liver and renal excretion Can be given orally and by IV
|
|
|
Which bacteria can chloramphenicol (CHLORO) treat?
|
Broad range against both Gram+ and Gram- organisms. Excellent against anaerobes. Good against rickets, spirochetes, mycoplasma, chlamydia
|
|
|
Adverse effects of chloramphenicol:
|
Aplastic anemia Bone marrow toxicity (reversible) Gray Baby syndrome Optic neuritis For these reasons, these drugs are not used in the USA too often
|
|
|
Which bacteria can chloramphenicols be used for as an alternative here in the USA (3)?
|
1. Meningitis 2.RMSF 3.Typhoid fever
|
|
|
MACROLIDES (MACRO): Name 3 drugs in this family
|
Erythromycin Azithromycin Clarithromycin Note all end in Mycin
|
|
|
Macrolides (MACRO): -Mechanism -Resistance -Administration -Excretion
|
Mechanism: Binds to 50S (bacteriostatic) Resistance: (1) Decr perm. (2) Altering binding sites on ribosomes Can be given orally and through IV Excretion: Biliary
|
|
|
Which bacteria are macrolides effective against?
|
Mostly gram positive (newer ones are also Gram-) DRUG OF CHOICE FOR: LEGIONELLA, MYCOPLASMA, DIPTHERIA, PERTUSIS
|
|
|
Adverse effects of macrolides:
|
Upset stomach, gout exacerbation, rash
|
|
|
Quinupristin/Dalfopristin: -Mechanism -Excretion -Resistance -Administration
|
Stops 50S protein synthesis -Biliary excretion -Resistance???? -IV administration only Drug is very similar to Macrolides
|
|
|
What is quinupristin/dalfopristin used for? What is the special exception?
|
Selective against Gram+ organisms Generally restricted to VRE faecium Not active against E faecalis
|
|
|
Adverse effects to Quinupristin/Dalfopristin:
|
Very expensive! Causes arthralgias/myalgias Causes hyperbilirubinemia Needs to be infused through central vein Antagonistic to erythromycin
|
|
|
Linezolid: -Mechanism -Excretion -Resistance
|
Mechanism: Binds 50s blocks initiation (fMEt-tRNA) Excretion: Mostly by biliary, some by renal -Resistance: Who knows?
|
|
|
Administration of Linezolid:
|
Can be taken orally or through IV. Cleared by dialysis so those patients must be given drug after dialysis In the body it is protein bound
|
|
|
Drug/food interactions with linezolid:
|
It's an MAO inhibitor so be careful with px on SSRI antidepressants. Also with pseudoephedrine & phenylpropalolamine Food interactions with high tyramine (Asain ruben sandwich with beer)
|
|
|
Which bacteria is linezolid good at treating?
|
Only gram positive (especially strep) DOC for VRE, MRSA, PNEUMONIA
|
|
|
Adverse effects of linezolid:
|
It's an MAO inhibitor. It enhances adrenergic and serotenergic meds Also GI distress & thromocytopenia
|
|
|
Daptomycin: -Mechanism -Excretion -Administration -Resistance
|
Mechanism: Lipophilic & protein bound. Depolarizes PM of Gram positive bacteria (bactericidal). Excretion: Mostly renal Administered by IV only Very little resistance
|
|
|
What is daptomycin good at treating?
|
Gram Positives- DOC for MRSA & VRE & SOFT TISSUE/SKIN INFECTIONS Also good for both E faecalis and E faecium unlike Quinupristin
|
|
|
What is daptomycin approved for? What disease can daptomycin NOT be used for? Why?
|
Approved for complicated skin and soft tissue infections. Cannot be used for Pneumonia -Binds to lung surfactant
|
|
|
Adverse effects of daptomyin:
|
Mild & self-limiting -Muscle discomfort & weakness Elevation of CPK (asymptomatic)
|
|
|
Trimethoprim-Sulfamethoxazole (TMP-SMX) -Mechanism Resistance Excretion Administered?
|
Mechanism: Stops folic acid synthesis (bacteriostatic) Resistance: (1) decr permeability or (2) enzyme affinity Excreted: Via urine Administered: Can be given orally or by IV
|
|
|
Which bacteria are sulfamethoxazoles good at treating?
|
What aren't they good at? Can treat pretty much everything except (1) anaerobes (2) Enterococcus (3) P. aeruginosa. DOC FOR PNEUMOCYSTIS CARINII, STENOTOPHOMONAS MALTOPHILIA, NOCARDIA
|
|
|
Adverse effects of sulfamethoxazoles:
|
Stevens-Johnson Syndrome (dermatologic hypersensitivity) Renal and liver dysfunction Bone marrow suppression Crystalluria
|
|
|
Quinolones (Q) Name 3 drugs in this class:
|
Ciprofloxacin (Gen 2) Levofloxacin (Gen 2) Moxifloxacin (gen 3) "Note floxacins"
|
|
|
Quinolones (Q): -Mechanism -Resistance -Excretion Administration
|
Mechanism: Inhibits DNA gyrase Resistance: Via (1) Altered binding site & (2) Active efflux -Excretion varies by compound -Admin: Can be given orally or by IV
|
|
|
Quinolones (Q) are good for treating which bacteria?
|
In general, excellent Gram Negative activity, Good gram positive activity 3rd Generation (Moxifloxacin) is good at anaerobes as well Also, second line of defense against TB
|
|
|
Adverse effects of Quinolones (Q)
|
Rash, GI distress Also problems with CNS toxicity Alters glucose metabolism Bound by cations and metals (interacts with antacids) Interferes with developing cartilage (so you can't give to children or pregnant women)
|
|
|
Vancomycin (VANCO) -Mechanism -Resistance Excretion Administration
|
Mechanism: Inhibits cell wall synthesis (works on Gram+ only!) Resistance: Via alteration of end molecule binding site -Note resistance from overuse. Excretion: Renal Administered: Parenteral (oral only for c. dif colitis)
|
|
|
Vancomycin (VANCO) is good for treating which bacteria?
|
Used for gram positive bacteria only! DOC for PENICILLIN RESISTANT MENINGITIS (PRSP), MRSA
|
|
|
Clindamycin: -Mechanism -Resistance -Excretion -Administered
|
Mechanism: Binds to 50 S subunits Resistance: From altered binding site Excretion: Biliary Administered: Orally or by IV (the oral form is miserable for patients)
|
|
|
What is Clindamycin good at fighting?
|
Good for anaerobic activity Good for Gram+ (although not enterococcus or MSA) Microaerophilic organisms Also good for head and neck infections, aspiration pneumonia, intraabdominal infxn, pelvic infxn
|
|
|
Adverse effects of clindamycin
|
Rash & GI distress Greatest association with pseudomembranous colitis
|
|
|
Metronidazole: -Mechanism -Resistance -Excretion -Administration
|
Mechanism: Interrupt DNA synthesis Resistance: Who knows? Excreted: Biliary Admin: Can be taken orally or through IV
|
|
|
What is metronidazole (METRO) good at fighting?
|
Gold standard for anaerobes (DOC) - Includes Bacteroides and clostridium -Some antiparasitic action (Giardia, Entamoeba, Trichomona, Gardnerella vaginais) -NO aerobic action
|
|
|
Adverse effects of metronidazole (METRO):
|
Bad metallic taste Neuropathy (peripheral) Disulfiram-like rxn Pancreatitis Patients will vomit if they take it with alcohol
|
|
|
Adverse effects of Vancomycin
|
Ototoxicity (like aminogycosides) Nephrotoxicity Vein sclerosis Rash/Redman syndrome
|
|
|
Gram stain of Clostridium difficile?
|
Gram (+) rod
|
|
|
Gram stain of Clostridium perfringens?
|
Gram (+) rod
|
|
|
Gram stain of S. Viridans?
|
Gram (+) cocci (chain)
|
|
|
Gram stain of Pseudomonas aeroginosa?
|
Gram (-) rod, non-lactose fermenter
|
|
|
Gram stain of Staph. epidermis?
|
Gram (+) cocci, cluster, coagulase (-)
|
|
|
Gram stain of Bacteroids fragilis?
|
Gram negative rod
|
|
|
C. difficile is most often seen clinically as ___?
|
pseudomembranous colitis
|
|
|
S. viridians is most often seen clinically as ____?
|
dental work-related SBE
|
|
|
Enterococcus Faecium is most often seen clinically as ___?
|
VRE
|
|
|
Staph epidermis is most often seen clinically as ___?
|
line infections
|
|
|
Bacteroids fragilis is most often seen clinically as ___?
|
septic abortion, aspiration pneumonia, pelvic abscess
|
|
|
3 examples of bacteria with defective cell walls?
|
Chlamydia, Mycoplasma, Rickettsia
|
|
|
Clostridium perfringens is most commonly seen clinically as ___?
|
gas gangrene
|
|
|
C. difficile: aerobe or anaerobe?
|
C. diff is an anaerobe
|
|
|
B. fragilis: aerobe or anaerobe?
|
Bacteroids fragilis is an anaerobe
|
|
|
Ticarcillin should be used cautiously in what pt. population?
|
CHF (has a high Na+ load)
|
|
|
Examples of 1st generation cephalosporins?
|
Cefazolin, cephalexin
|
|
|
Examples of 2nd generation cephalosporins?
|
Cefotetan, Cefoxitin, Cefuroxime
|
|
|
Examples of 3rd generation cephalosporins?
|
Ceftriaxone, ceftazidime, cefotaxime
|
|
|
Which cephalosporin is associated with acalculous cholestasis and bilirubin displacement from albumin?
|
ceftriaxone
|
|
|
Examples of 4th generation cephalosporins?
|
Cefepime
|
|
|
Name 3 examples of antibiotics that work by inhibiting cell wall synthesis
|
PCNs, cephalosporins, Vancomycin
|
|
|
Name 2 examples of antibiotics which inhibit bacterial DNA
|
fluoroquinolines, flagyl
|
|
|
Name 4 examples of antibiotics which work by inhibiting protein synthesis
|
aminoglycosides, clindamycin, macrolides, tetracyclines
|
|
|
Name 2 examples of antibiotics which are antimetabolites
|
sulfonamides, trimethoprim
|
|
|
Name 3 examples of antibiotics which work by disrupting cell membranes
|
amphotericin B, ketaconazole, nystatin
|
|
|
Example of beta-lactam antibiotics?
|
PCNs, cephalosporins, carbapenems (imipenem), monobactams (aztreonam)
|
|
|
Uses for natural PCN?
|
mostly G(+), mostly streptococci (most mouth anaerobes)
|
|
|
Uses for PCNase-resistant PCNs?
|
Most streptococci; beta-lactamase producing S. aureus; not good for gram (-)
|
|
|
Examples of PCNase-resistant PCNs?
|
Nafcillin, Oxacillin
|
|
|
Examples of aminopenicillins?
|
Ampicillin, Amoxacillin
|
|
|
Uses for aminopenicillins?
|
Most streptococci, basic G(-) coverage
|
|
|
Name 2 aminopenicillins that have some G(+)/G(-) coverage but are not effective against beta lactamase producing organisms
|
Ampicillin, Amoxacillin
|
|
|
Name 2 aminopenicillin preparations that have some G(+)/G(-) coverage and are effective against beta lactamase producing organisms
|
Ampicillin/sulbactam (Unasyn), Amoxacillin/Clavulanate (Augmentin)
|
|
|
Examples of Anti-pseudomonas PCNs?
|
ticarcillin, piperacillin
|
|
|
Uses of anti-pseudomonas PCNs?
|
G(-) rod bacteria, especially pseudomonas; aminopenicillin-resistant Proteus
|
|
|
Sulfanilamide
|
PABA analog. Competitively inhibits a folic acid synthesizing enzyme. The action of sulfanilamide is reversible, thus it is bacteriostatic. (Antimetabolite)
|
|
|
Trimethoprim
|
Inhibits dihydrofolate reductase. Synergism with sulfonamides. (Antimetabolite)
|
|
|
Isoniazid
|
Specific against TB, and probably acts by interfering with mycolic acid synthesis, specifically by inhibiting InhA, essential for FA elongation. (Antimetabolite)
|
|
|
Penicillin
|
Inactivate transpeptidases responsible for cross linking peptidoglycans. (Cell wall synthesis inhibitor)
|
|
|
Penicillin G
|
Sensitive to penicillinase, limited spectrum, effective against G+ and G- cocci but not G- enterics. Acid labile. (Cell wall synthesis inhibitor)
|
|
|
Penicillin V
|
Sensitive to penicillinase, limited spectrum, effective against G+ and G- cocci but not G- enterics. Relatively acid-stable. (Cell wall synthesis inhibitor)
|
|
|
Ampicillin
|
Sensitive to penicillinase, broader spectrum, typically aminopenicillins. Acid stable. (Cell wall synthesis inhibitor)
|
|
|
Amoxicillin
|
Same as ampicillin but higher serum levels. (Cell wall synthesis inhibitor)
|
|
|
Ticarcillin
|
Sensitive to penicillinase, extended spectrum; it is a carboxypenicillin. (Cell wall synthesis inhibitor)
|
|
|
Piperacillin
|
A ureidopenicillin, the most effective one against G- enteric bacilli, including anaerobes. (Cell wall synthesis inhibitor)
|
|
|
Methicillin
|
Resistant to penicillinase. Antistaphylococcal. (Cell wall synthesis inhibitor)
|
|
|
Oxacillin
|
Resistant to penicillinase. Antistaphylococcal. Available orally. (Cell wall synthesis inhibitor)
|
|
|
Cephalosporins
|
Broad spectrum bactericidal agents. (Cell wall synthesis inhibitor)
|
|
|
Aztreonam
|
Beta-lactam, but otherwise not similar to penicillin. (Cell wall synthesis inhibitor)
|
|
|
Imipenem
|
Beta-lactam, but otherwise not similar to penicillin. (Cell wall synthesis inhibitor)
|
|
|
Clavulanic acid
|
Beta-lactamase inhibitor. (Cell wall synthesis inhibitor)
|
|
|
Sulbactam
|
Beta-lactamase inhibitor. (Cell wall synthesis inhibitor)
|
|
|
Augmentin
|
Combination of amoxicillin and clavulanic acid. (Cell wall synthesis inhibitor)
|
|
|
Vancomycin
|
Glycopeptide. Binds R-D-ala-D-ala structures, like petidoglycan precursors.
|
|
|
Cycloserine
|
D-ala analog. (Cell wall synthesis inhibitor)
|
|
|
Bacitracin
|
Inactivates the phosphatase responsible for regenerating the active form of the carrier lipid in murein (peptidoglycan) precursor synthesis.
|
|
|
Polymyxin B
|
Causes membrane leakage. Anti-fungal. (Affects membrane permeability)
|
|
|
Streptomycin
|
Aminoglycoside. Bactericidal. Binds to 30S subunit. (Protein synthesis inhibitor)
|
|
|
Gentamicin
|
Aminoglycoside. Bactericidal. Binds to 30S subunit. (Protein synthesis inhibitor)
|
|
|
Tetracycline
|
Blocks binding of aminoacyl-RNA to 30S subunit. Bacteriostatic. Broad spectrum. (Protein synthesis inhibitor)
|
|
|
Erythromycin
|
Inhibits 50S subunit. (Protein synthesis inhibitor)
|
|
|
Azithromycin
|
Inhibits 50S subunit. (Protein synthesis inhibitor)
|
|
|
Chloramphenicol
|
Inhibits 50S subunit. (Protein synthesis inhibitor)
|
|
|
Clindamycin
|
Inhibits 50S subunit (peptidyl transfer). (Protein synthesis inhibitor)
|
|
|
Oxazolidinones
|
Inhibits both 30S and 50S subunits. (Protein synthesis inhibitor)
|
|
|
Streptogramins
|
Binds 50S subunit. New class. (Protein synthesis inhibitor)
|
|
|
Dalfopristin
|
Streptogramin. Binds 50S subunit. New class. (Protein synthesis inhibitor)
|
|
|
Quinupristin
|
Streptogramin. Binds 50S subunit. New class. (Protein synthesis inhibitor)
|
|
|
Synergin
|
Combination of Dalfopristin and Quinupristin. (Protein synthesis inhibitor)
|
|
|
Mupirocin
|
Binds a specific tRNA synthetase. (Protein synthesis inhibitor)
|
|
|
Ciprofloxacin
|
DNA gyrase inhibitor (DNA replication inhibitor)
|
|
|
Metronidazole
|
Binds and causes fragmentation of DNA. (DNA replication inhibitor)
|
|
|
Rifampin
|
Binds beta subunit of bacterial RNA polymerase, inhibiting specific binding to DNA. (RNA synthesis inhibitor)
|
|
|
Ethambutol
|
Bacteriostatic against TB. Mechanism unknown
|
|
|
Pyrazinamide
|
Bactericidal against TB. Mechanism unknown
|
|
|
Amphotericin B
|
Polyene compound that binds to ergosterols in fungal cell membrane. (Antifungal)
|
|
|
Nystatin
|
Polyene compound that binds to ergosterols in fungal cell membrane. (Antifungal)
|
|
|
Flucanazole
|
Inhibits ergosterol synthesis by inhibiting cytochrome P450. Fungistatic effect. (Inhibits cell membrane synthesis)
|
|
|
Ketconazole
|
Inhibits ergosterol synthesis by inhibiting cytochrome P450. Fungistatic effect. (Inhibits cell membrane synthesis)
|
|
|
Caspofungin
|
Inhibits glucan synthesis. (Fungal cell wall inhibitor)
|
|
|
Flucytosine
|
Fungal antimetabolite
|
|
|
This antibiotic is inhibited under anaerobic or acidic conditions
|
Streptomycin
|
|
|
In contrast to cell-wall inhibitors, this antibiotic is effective in non-dividing cell populations
|
Polymyxin B
|
|
|
* ANTIMETABOLITES * (4)
|
*ANTIMETABOLITES are those that interfere with the synthesis or function of a substance involved in normal cell function- - and it's usually similar to natural substance. We study the following: 1) SULFONAMIDE 2) TRIMETHOPRIM 3) BACTRIM 4) ISONIAZID
|
|
|
1) SULFONAMIDE
|
C/S: static TARGET: act against a wide range of bacteria including PROTOZOA - some are concentrated in the urine, so may use in UTIs MECHANISM: - penetrates sensitive bacteria to inhibit FOLIC ACID production by inhibiting one of the enzymatic steps - there is NO DNA SYNTHESIS - it is REVERSIBLE, so that when you stop using the drug, the growth of teh bacteria resumes
|
|
|
2) TRIMETHOPRIM
|
C/S: static TARGET: MECHANISM: - it acts of DIHYDROFOLATE REDUCTASE to inhibit its activity so that you can't get THF - you may use this with SULFONAMIDE and together they have SYNERGISTIC action and are sometimes used in conjunction to treat UTIs
|
|
|
3) BACTRIM
|
C/S: static TARGET: UTIs MECHANISM: combination of trimethoprim and bactrim is common
|
|
|
4) ISONIAZID
|
C/S: cidal!! TARGET: TB! MECHANISM: - takes specific action against TB (has a narrow spectrum) - it interferes iwth mycolic acid which is unique to the cell wall of mycobacteria - it inhibits the action of anyme InhA, which is essential for fatty acid elongation - it's good drug because it may penetrate through the human cytoplasmic membrane, impor because many mycobacteria are intracellular
|
|
|
* PENICILLIN *
|
* penecillin causes bacteria to lyse, and it can prevent slow or lethal action to bacteria in medium * all cell wall synthesis inhibitors are BACTERICIDAL as they INHIBIT THE STEPS OF PEPTIDOGLYCAN SYNTHESIS 1) PENICILLIN G 2) PENICILLIN V 3) AMPICILLIN 4) AMOXICILLIN 5) TICARCILLIN 6) PIPERACILLIN 7) METHACILLIN 8) OXACILLIN
|
|
|
1) PENECILLIN G*
|
TYPE: - SENSITIVE to penicillinase - also SENSITIVE to acid hydrolysis - LIMITED spectrum TARGET: - gram +ve and -ve cocci (like neisseria meningitis and treponema pallidum) - INEFFECTIVE against gram -ve enterics
|
|
|
2) PENECILLIN V*
|
same as PENICILLIN G except it is ACID STABLE!
|
|
|
3) AMPICILLIN**
|
TYPE: - SENSITIVE to penicillinase - BROADER spectrum TARGET: - active against gram -ve enterics - retains most activity against gram +ve bacteria *ACID STABLE! an aminopenicillin
|
|
|
4) AMOXICILLIN**
|
*just like AMPICILLIN but has higher serum levels
|
|
|
5) TICARCILLIN***
|
TYPE: - SENSITIVE to penicillinase - EXTENDED spectrum TARGET: - active against gram -ve bacteria such as p. aeruginose - LESS ACTIVE against cocci *B- lactam effective against p. aeruginosa, carboxypenicillin
|
|
|
6) PIPERACILLIN***
|
*just like TICARCILLIN - most active against gram -ve eneteric bacilli including p. aeruginosa and anaerobes
|
|
|
7) METHACILLIN*
|
TYPE: - acid labile - avoid usage in adults because it causes an increase in intestinal nephritis TARGET: - has slightly lower activity against gram +ve bacteria, but still effective - little against gram -ve
|
|
|
8) OXACILLIN*
|
*just same as methacillin, newer more potent derivative - acid labile and availble only orally
|
|
|
* CEPHALOSPORINS * (4)
|
*They are similar to penicillins in mechanism of action, in that they target the cell wall with a 4- membered lactam ring, BUT substitute a dihidrothiazine ring instead of thiazolidine of the penicillins
|
|
|
Important points about CEPHALOSPORINS? (5)
|
1) bactericidal 2) differ from penicillins in that they have greater acid stability and are resistent to penicillinases 3) BROAD SPECTRUM antibiotics against both gram +ve and -ve bacilli 4) useful when patients are allergic to penicillin because they are antigenically dissimilar 5) as new members of the class of cephalosporins were developed, they were called 1st, 2nd, and 3rd generations- - differing in the spectrum of bacteria they could be used to treat against *the newer agents are active against pseudomonas, and can better penetrate the cerebral spinal fluid
|
|
|
1) CEFAZOLIN
|
TYPE: FIRST GENERATIONS TARGET: - this is most active aginst gram +ve cocci - it is active against most gram -ve eneterics BUT NOT PSEUDOMONAS
|
|
|
2) CEFUROXINE
|
TYPE: 2ND GENERATION TARGET: - improved pharmacologic spectrum - most effective against gram (-) ve bacteria - less effecitve against gram +ve - NOT EFFECTIVE AGAINST PSEUDOMONAS
|
|
|
3) CEFTRIAXONE 4) CEFTAZIDIME
|
TYPE: THIRD GENERATION TARGET: - improved B- lactamase stability - BROADER gram -ve spectrum - it is effective against pseudomonas - SUPERIOR CNS penetration
|
|
|
* OTHER B- LACTAM RINGS * (2)
|
1) AZTREONAM (MONOBACTAMS) 2) IMIPENEM (CARBAPENEM)
|
|
|
1) AZTREONAM
|
TYPE: - resistant to B- lactamases and - minimal cross immunogenicity with other B- lactams TARGET: - effective against gram -ve bacteria and p. aeruginosa - INEFFECTIVE against gram +ve anaerobic bacteria
|
|
|
2) IMIPENEM
|
TYPE: - BROADEST ANTIMICROBIAL SPECTRUM - resistant to most lactamases - BUT it is susceptible to MRSA - acid is susceptible to dipeptidase
|
|
|
*B- LACTAMASE INHIBITORS * (2)
|
1) CLAVULONIC ACID 2) SULBACTAM
|
|
|
1) CLAVULONIC ACID
|
currently available in fixed combination with amoxicillin (augmentin)
|
|
|
2) SULBACTAM
|
available in fixed combo with ampicillin
|
|
|
* GLYCOPEPTIDES * (2)
|
1) VANCOMYCIN 2) TEICOPLANIN
|
|
|
1) VANCOMYCIN
|
TYPE: - only gram -ve MRSE, VSE TARGET: - activity restricted to gram +ve complex glycopeptides - binds to R-D-ALA-D-ALA block - somewhat toxic, BUT when less toxic drugs are ineffective or contraindicated, used against serious systemic staph/ enterococcal infections or orally for C. difficile enterocolitis - SIDE EFFECTS: hearing and kidney damage - available for MRSA AND MRE - VRE transfer resistance to MRSA and increase in VRE is an increasing problem
|
|
|
2) TEICOPLANIN
|
TYPE: - increase in LIPOPHILICITY - can penetrate the tissue well - less toxic TARGET: - chemically similar to vancomycin - greter lipophilicity over vancomycin and has a long elimnation 1/2 life - less toxic than vancomycin - DISADVANTAGE: no oral form - NOT APPROVED BY FDA
|
|
|
*CYCLOSERINE*
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TYPE: secondary TB drug, TOXIC!! TARGET: - it's a D- ALA analog which inhibits L- ALA- - thus inhibiting cell wall synthesis
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*BACITRACIN*
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TYPE: TARGET: - restricted to gram +ve organisms - it inactivates the phosphatase responsible for regenerating the active form of the carrier lipid in murein precursor synthesis - TOXIC and restricted to TOPICAL therapy, often in conjunction with POLYMYXIN B and NEOMYCIN (like neosporin)
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