Antibiotics 2

• antibiotics • contents - Antibiotics - Anti-bacterial classes - Antibiotic misuse - Resistance to Antibiotics - What can you do to delay the spread of antibiotic resistance? - Requirements for Successful Antimicrobial Therapy Antibiotics An antibiotic is a substance or compound (also called chemotherapeutic agent) that kills or inhibits the growth of bacteria. • Anti-bacterial classes 1-antibiotics which interfere with cell-wall synthesis beta-lactams, including penicillins and cephalosporins;carbapenems,monobactam; non beta-lactams, such as vancomycin . 2-antibiotics which interfere with bacterial protein synthesis *antibiotics which bind to the 50S ribosomal unit lincosamides/lincosides ; chloramphenicol & macrolides **antibiotics which interfere the 30S ribosomal unit tetracyclines; aminoglycosides . 3-drugs which inhibit nucleic acid synthesis *drugs which inhibit folate synthesis: sulfonamides and trimethoprim **drugs which interfere with DNA &RNA synthesis: rifampin, metronidazole, quinolines, novobiocin. 4-drugs which interfere with cell membrane function: polymyxin B, gramicidin

Drugs that inhibit cell wall synthesis includes: 1.B-lactams antibacterials: 1.penicillines 2.cephalosporines 3.carbapenems 4.monobactams 2.Non B-lactams antibacterials: as* vancomycin, cycloserine &bacitracin .

penicillines Pen..are bactricidal ,act by inhibiting the enzyme transpeptidase that is involved in the formation of the bacterial cell wall . the absorption of most penicillines is affected by food( except amoxicillin ). they are mostly exc.. Unchanged in urine. • Classification of penicillins

1- narrow spectrum pen: Benzyl pen(pen G) , procain pen.,pen.V, antistaph..pen(flucloxacillin, cloxacillin) 2- broad spectrum : • Ampicillin • Amocxicillin • Co-amoxiclav (amoxicillin + clavulanic acid) • Antipseudomonal CLINICAL CONCERNS

Adverse effects of penicillines 1. 2. 3. 4.

Hypersensitivity reaction. large doses of pen.. Lead to GIT upset ( N, V & D..). In patients with renal failure or in high doses penicillins can cause seizures. Neutropenia is a risk of high doses of penicillins and for a peroid longer than 10 days.

Drug Interactions 1- Penicillins are displaced from plasma-protein binding sites and tubular secretion is delayed by salicylates, sulfonamides. 2- penicillins potentiate the action of anticoagulants by depressing vitamin K production by gut flora. 3- tetracyclines may decrease the effect of penicillins.

Cephalosporines Are structurally related to pen..&having a wide range of activity & low toxicity. they are primarily exc.. through glumerular filteration except ceftrixone exc.. in bile. • Classification of cephalosporines st 1 generation Cephalexine,cephazoline,cephadroxil. Active against gr+ve cocci , E.coli , klebsiella &proteous. 2nd generation Cefoxitin, cefuroxime. Less active against gr+ve & more active against gr-ve bacteria 3rd generation: Cefotaxime, ceftrixone &cefixime.more active against gr –ve bacteria than the 2nd gener… 4th generation: Cefepime is more resistant to hydrolysis by beta-lactamase producing bacteria (enterobacter..) It has good activity against p.aerog., enterobactriace,H.influ &neiseria. 5th gener.. ceftobiprol

Adverse effects of cephalosporines 1- allergic reactions. 2- severe pain & thrombophlebitis after i.v. inj. 3- if are used more than 2 weeks itll cause thromocytopenia, interstitial nephritis & neutropenia.

Carbapenems e.g. Imipenem & meropenem. They are active against gr+ve , gr-ve &anaerobic bacteria. they are mostly used for septicemia intra-abdominal infections.

Monobactams They are relatively resistant to beta-lactamases and are active against gr-ve rods (including psedomonas) ,but have no activity against gr+ve bacteria nor anaerobics. e.g.:aztreonam. NOTE:Penecillin & cephalosporine allergic pts. tolerate aztreonam without reaction.

Other antibiotcs that inhibit cell wall synthesis: 1.Vancomycin:used in prophylaxis &treat.. of gr+ve ,clostridium & staphylo.. S.E.:allergy,red man syndrome,nephrotoxicity & auditory damage. :2.Cycloserine Effective against mycobacterium.

Inhibition of protein synthesis: 1.Tetracyclines. 2.Macrolides. 3.Chloramphenicol. 4.Aminoglycosides.

Tetracyclines They act by inhibiting bacterial protein synthesis at 30S subunit. they are bacteriostatic against: Gr+ve & gr-ve bact. Including: (anaerobics, clamydia, mycoplasma & helicobacter pylori ). • :Classification of Tetracyclines 1.Short acting: tetracycline (dose:250-500mg/6hrs), oxytetracyclin. 2.Intermediat acting: demeclocycline. 3.Long acting: doxycyclin(dose: 100-200mg/24 hrs). CLINICAL CONCERNS

Side effects of tetracyclines 1.Hypersensitivity reactions. 2.GI s.e. 3.Effects on bone & teeth. 4.Liver toxicity. 5.Kidney toxicity”renal tubular necrosis”. 6.Photosensitization “demeclocycline”.

Drug – interactions of tetracyclines 1. Dairy products. 2. Antacids containing Ca or AL. 3. Iron preparations. All reduce the absorption of tetracyclines .

Macrolides They inhibit bac.pr. Synthesis at 50S subunit on ribosomal RNA. : -Erythromycin

-Clarithromycin -Azithromycin • -*Erythromycin: active against gr+ve,coryne bac. infection(diphtheria), mycoplasma, clamydia & helicobacter. Dose: 250-500mg/6hrs. *Azithromycin: less active than erythro..& clarithro..against staph..&strepto but highly active against clamydia. given as 250mg/24hr. *Clarithromycin:it is identical to erythromycin with respect to antibacterial activity but it is more active against mycobacterium. Dose:250-500mg/12hrs.

Adverse effects of Macrolides 1.GI s.e. (N. ,V. , dia. & anorexia). 2.Liver toxicity (erythro.. estolate can cause chloestatic hepatitis).

Drug-interactions of Macrolides: Erythromycin or its metabolites & clarithromycin can increase the serum conc. of : - theophylline - warfarin - digoxin - Prednisolone - verapamil & diltiazem - cyclosporine.

lincosamides/lincosides clindamycin Clinda.. like eryhro.. inhibit 50s subunit of bacteria it is active active againststaph..,strepto..& pnemococci & anaerobic bacteria. There is a cross reistance between clinda.. & erythro.. oral adult dose is 150- 300mg /6hrs. S.E. :dia.. ( colitis ),nau..& impaired liver function.

Chloramphenicol Is a potent inhibitor of microbial protein synthesis at 50s subunit. It is a wide spectrum antibiotic that has bactricidal and bactristatic activity (so active against aerobic & anaerobic gr+ve & gr-ve bacteria). Dose: orally 250-500mg/6hrs • Adverse effects of chloram… 1. GI disturbances. 2. BM disturbances: *RBC suppression(dose related: if it is more than 50mg/kg/day & for 1-2 weeks). *aplastic anaemia( not dose related & is irreversible). 3. Toxicity of new born infants (gray baby syndrome). • Drug- interactions of Chloram.. :1.Chloram.. Can increase the serum conc. of - phenytoin. - tolbutamide. - warfarine. 2. Chloramphenicol should not be administered concurrently with other antibacterial agents that bind to the 50S ribosomal subunit (eg, the macrolides and lincosamides).

Aminoglycosides They are bactricidal antibiotcs that inhibit bacterial protein at 30s subunit. These agents are mainly active against aerobic gr-ve m.o. & staphylococci. Note: aminoglycosides are eleminated unchanged by kidney. • Individual aminoglycosides -Gentamycin:it is the drug of choice for gr-ve septicaemia & enterococcal endocarditis. Dose : 2-5mg/kg/day in 3 divided doses. -Tobramycin: it is similar to gentamycin but less nephrotoxic. -Amikacin: it is useful for gentamycin-resistant m.o.. -Neomycin: mainly used for topical infections. • Adverse effects of Aminoglycosides 1- ototoxicity. 2- nephrotoxicity. 3-Haemolytic anemia & bleeding ( due to antagonism of factor 5). 4-neuromuscular blockade( mysthenic syndrome ). • Drug- interactions of aminoglycosieds 1. If given with diuretics there is increased risk of nephrotoxicity. 2. Neuromuscular blockade is more likely when aminoglycosides are administered at the same time with skeletal muscle relaxants and gas anesthetics.