1TETRACYCLINES AND CHLORAMPHENICOL Bacteriostatic NOT bactericidalModified from Dr LebretonTetracyclines2II. Mechanism of antimicrobial activity:competes with tRNA for the A site on 30s ribosomeTetracyclineIII. Bacterial active transport system increases the intracellular concentration of antibiotic 50x more than surrounding medium. This results in enhanced antibacterial activity and specificity at a dose which is harmless to animal tissues.3II. Spectrum: very wide includes Gram (+) and Gram (-) Mycoplasma, Rickettsia, Chamydia spp., spirochaetes and some protozoa (amoeba)Minocycline is also effective against N. meningitidisIII. Resistance to antimicrobial activity:i. inhibition of protein-mediated transport of antibiotic into bacterial cellii. developed resistance usually affects all tetracycline derivatives4IV. Absorption:Oralabsorbed in GI tract mostly from stomach and upper small intestineabsorption impaired by milk products, aluminum hydroxide gels, calcium and magnesium salts, and iron preparations due to chelating action of tetracyclineMinocycline and doxycycline are completely absorbedV. Distribution:i. ready access to most tissuesii. cross placental barrier and enter fetal circulation and amniotic fluidiii. high concentration can appear in milkiv. can reach significant concentrations in CSF when given I.V.v. accumulate in dentine and enamel of unerupted teeth and in liver, spleen, bone marrow and bone5VI. Excretion:i. excreted in urine and fecesii. primary route of elimination is glomerular filtrationiii. exceptions are minocycline which is excreted in urine to a much smaller extent,and doxycycline which is not excreted in urineiv. doxycycline can be of value in treating patients with impaired renal functionXI. Side Effects:• GI irritation• Phototoxicity (Sun burn)more particularly with demeclocycline• Minocycline can produce dose-related vestibular disturbances such as dizziness and nausea• hepatic toxicity• renal toxicity: High doses of tetracycline can decrease protein synthesis in the host cells-an anti-anabolic effect6• discoloration of teeth in children • drug interaction with penicillins (do not use concurrently)• Superinfection with yeast or resistant pathogenic bacteria may occur with the tetracyclines.Chloramphenicol (Chloramycetin)7ChloramphenicolII. Mechanism: Inhibits transpeptidases can also block mitochondrial protein synthesis in mammalian cells, especially in erythropoetic cellsIII. Because of potential toxicity, should be employed only in well defined and indicated conditions.8IV. Spectrum: Gram (-) : H. influenzae (bacteriocidal), N. meningitidis, N. gonorrhoea, Salmonella typhis, Brucella and Bordetella pertussis anaerobic bacteria Gram (+) cocci; clostridium Gram(-) rods: E. coli, V. cholerae, Shingella, Chlamydia and Mycoplasmanot effective against pseudomonas, histolylica, EntamoebaV. Resistance:i. acetylation of chloramphenicol by acetyl-tranferase ribosome ii. decreased cellular permeabilityiii. mutation leading to ribosomal insensitivity9VI. Absorption:i. parent drug readily absorbed in GI tractii. prodrug (chloramphenicol palmitate) hydrolyzed in duodenumiii. chloramphenicol succinate used for parenteral administrationV. Distribution:i. readily accessible to tissues and bodily fluidsii. high concentration achieved in brainiii. enters CSF at therapeutic concentrationsiv. crosses placental barrierv. present in milk and bile enzyme; vi. acetylated form cannot bind10VI. Excretion:i. metabolized in liver and inactive glucuronide metabolite excreted in urineii. exercise caution in treating patients with hepatic cirrhosisiii. reduced renal function can increase half-life of chloramphenicol succinateVII. Side effectsHematological toxicity: most important side effect is on bone marrow : irreversible idiosynchratic reactions: aplastic anemia reversible: interferes with iron metabolism Neonatal toxicity: "gray baby syndrome"Therapeutic use of antibiotics for common or important microorganismsCiprofloxacin or amacrolideVancomycin +gentamicinMethicillin -resistantCephalosporin or vancomycinor macrolideβ-lacatamaseresistant penicillin (flucloxacillin)β-lacatamase-insensitiveCephalosporin orvancomycin or macrolidePenicillin G or V +an aminoglycosideStaphylococcus hemolytic typesseptic infections e.g., bacteremia, scarlet fever, toxic shock syndromeCephalosporinPenicillin G or V or ampicillin, or amacrolidePneumococcuspneumoniavancomycinPenicillin G +gentamicinEnterococcusCephalosporin orvancomycinPenicillin G or VStaphylococcusβ-lacatamase-sensitiveendocarditisGram (+) cocciIind choiceIst choicemicroorganismconditionboils, infection of wounds etcChloramphenicol or Cefotaxime or minocyclinePenicillin VNeisseria meningitidismeningitisCefotaxime or a quinoloneAmoxicillin +clavulanic acid or ceftriaxoneNeisseria gonorrhoeagonorrhoeaCiprofloxacinAmoxicillin + clavulanic acidMorasella catarrhalissinusitisCephalosporinPenicillin G or V or ampicillin, or amacrolidePneumococcuspneumoniaGram (-) cocciIind choiceIst choicemicroorganismconditionErythromycin + an aminoglycosideAmoxycillin + an aminoglycoside Listeria monocytogenesRare cause of meningitis and generalized infection in neonatesTetracycline or a cephalosprinsPenicillin VClostridium Tetanus, gangrenePenicillin VA macrolideCorynebacterium diphtheriaGram (+) rodsIind choiceIst choicemicroorganismconditionAmoxycillin or chloramphenicol, trimethoprim Quinolone or ceftriaxoneSalmonellaTyphoid, paratyphoidchloramphenicolAmpicillin or cefuroximeHaemophillus influenzaeInfections of the respiratory tract, ear, sinuses; meningitisAmpicillin or trimethoprimA quinoloneShigelladysentryImipenem or a quinoloneAn aminoglycoside (i.v) or cefuroximeEnterobacteriaceae, E coli,Enterobacter, Klebsiella septicaemiaExtended spectrum penicilinAn oral Cephalosporin or a quinoloneEnterobacteriaceae, E coli, Enterobacter, KlebsiellaInfections of urinary tractGram (-) rodsIind choiceIst choicemicroorganismconditionAntipseudomonal penicillinA quinolonePseudomonas aeruginosaUrinary tract infectionImipenem +an aminoglycoside or ceftazidimeAntipseudomonalpenicillin + tobramycinPseudomonas aeruginosaOther infections (of burns)Clarithromycin + methoprimAmoxycillin + ranitidine + MetronidazoleAssociated withHelicobacter pyloriPeptic ulcerA macrolide+rifampicinLegionella pneumophilaPneumonia, Legionnaires diseaseA quinoloneA tetracyclineVibrio choleraecholeraAmpicillinAmoxycillin + clavulanic acidPasteurella
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