ANTIBIOTICS USED IN SURGERY (1.....).pptx

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1. ANTIBIOTICS USED IN SURGERY PRESENTER - MANOHAR MODERATOR – DR T R RAVI MOHAN (HOD AND PROFESSOR) DEPARTMENT OF GENERAL SURGERY

2. Antibiotics used in treatment and prophylaxis of surgical infection PENICILLIN AMPICILLIN, AMOXICILLIN PIPERACILLIN CEPHALOSPORINS CARBAPENEMS VANCOMYCIN AMINOGLYCOSIDES CLINDAMYCIN LINEZOLID FLUOROQUINOLONES METRONIDAZOLE NITROFURANTOIN

3. MECHANISM OF ACTION

4. PENICILLIN-G Narrow spectrum. CLINICAL USE – Gram positive cocci (most streptococci), Neisseria gonorrhea, Actinomycetes, Spirochetes, clostridium tetani. RESISTANCE – 1)Beta lactamase cleaves the Beta lactam ring. 2)Mutations in PBPs. PHARMACOKINETICS – Destroyed by gastric acid, peak plasma volume in 30 mins, renal excretion plasma t1/2 is 30 mins. DOSE – 0.6-2.4 MU IM every 2-4 weeks as aqueous suspension. ADVERSE EFFECTS – Local irritancy,Hypersensitivity reactions, Direct coombs positive hemolytic anemia, drug induced interstitial nephritis.

5. AMPICILLIN, AMOXICILLIN Extended spectrum. CLINICAL USE – H.pylori , E.coli, Salmonella, Shigella Used for Meningitis, Cholecystitis, Septicemias, Component of triple drug therapy for H.pylori . RESISTANCE – Beta lactamase cleaves the Beta lactam ring. PHARMACOKINETICS – 1)Ampicillin – Food interferes with absorption, Renal excretion, Partially excreted in bile, plasma t1/2 – 1hr 2)Amoxicillin – oral bioavailability is better. DOSE – 1)Ampicillin – 0.5 – 2 g oral/ i.m / i.v every 6 hours. Children – 50-100mg/kg/day 2)Amoxicillin – 0.25 -1 g TDS oral/ i.m . Children – 25-75mg/kg/day ADVERSE EFFECTS – Diarrhea,Hypersensitivity reactions, rash, pseudomembranous colitis.

6. PIPERACILLIN Extended spectrum. CLINICAL USE – Good coverage against pseudomonas, klebsiella , many enterobacteriaceae . Often employed in treating serious gram negative infections in neutropenic/immunocompromised or burn patients RESISTANCE – Beta lactamase cleaves the Beta lactam ring. PHARMACOKINETICS – Elimination t1/2 – 1 hour. DOSE – 100-150mg/kg/day in 3 divided doses i.m / i.v. ADVERSE EFFECTS – Hypersensitivity reactions.

7. CEPHAZOLIN Use: Susceptible to staphylococcal beta lacatamase Pharmacokinetics : T1/2 -2 hrs Dose - For surgical prophylaxis 1gm 30 mins before surgery CEFOTETAN and CEFOXITIN For surgical prophylaxis against anaerobic organisms in colorectal and pelvic surgeries

8. CEPHALOSPORINS CEFIXIME -orally active III gen cephalosporin. Plasma t1/2 – 3 hour. Dose – 100 or 200 mg tab. CEFTRIAXONE – III gen cephalosporin. Plasma t1/2 – 8 hours. Dose – 1-2 gm i.m / i.v per day. Severe side effects- hypoprothrombinemia and thrombocytopenia(bleeding), pseudolithiasis,kernicterus . CEFOPERAZONE – III gen cephalosporin Plasma t1/2 – 2 hours Dose – 1-3 gm i.m / i.v 8-12 hourly.

9. CARBAPENEMS Broad spectrum CLINICAL USE – Gram positive cocci, Enterobacteriaceae , pseudomonas aeruginosa, listeria, anaerobes. Used for serious nosocomial infections like septicemia, febrile neutropenia, intra abdominal and pelvic surgeries, diabetic foot. RESISTANCE – Inactivated by carbapenemases . PHARMACOKINETICS – Elimination t1/2 – 1 hour. Imipenem is renally excreted and inactivated by dehydropeptidase 1 (inhibited by cilastatin ). DOSE – 1) Imipenem – 250 – 500 mg/vial injection. 2) Meropenem– 0.5 – 2.0 gm slow I.V injection. ADVERSE EFFECTS – GI distress, rash, CNS toxicity (seizures) at high levels.

10. SIDE EFFECTS OF BETA LACTAMS Rash,anaphylaxis Hypoprothombinemia ( methylthiotetrazole ) Disulfiram like action Psuedomembranous enterocolitis Hepatotoxicity and nephrotoxicity(cephaloridine) Renal failure except cefoperazone,cefpiramide

11. VANCOMYCIN CLINICAL USE – Gram positive cocci including MRSA, sensitive Enterococcus species, C.difficile . RESISTANCE – Amino acid modification of D-Ala-D- Ala to D-Ala – D-lac. PHARMACOKINETICS – Renal excretion, Elimination t1/2 – 6 hour. DOSE – 125-500mg oral 6 th hourly. ADVERSE EFFECTS – Nephrotoxicity, ototoxicity, Thrombophlebitis, red man syndrome.

12. AMINOGLYCOSIDES Gentamycin, Neomycin, Amikacin CLINICAL USE – Gram – ve rods. RESISTANCE – Bacterial transferase enzyme inactivate the drug by acetylation PHARMACOKINETICS – Renal excretion, Elimination t1/2 – 24 hours. DOSE – Gentamycin – 3-5 mg/kg/day Amikacin – 15 mg/kg/day ADVERSE EFFECTS – Nephrotoxicity, ototoxicity, Neuromuscular blockade (contraindicated in myasthenia gravis)

13. TOXICITY OF AMINOGLYCOSIDE

14. LINEZOLID CLINICAL USE – Gram + ve species including MRSA and VRE RESISTANCE – point mutation of ribosomal RNA. PHARMACOKINETICS – Renal excretion, Plasma t1/2 – 5 hours DOSE – 600mg tab ADVERSE EFFECTS – Bone marrow suppression( especially thrombocytopenia), mitochondrial toxicity, SSRI syndrome.

15. FLUOROQUINOLONES CLINICAL USE – Gram – ve rods of urinary and GI tract RESISTANCE – chromosome encoded mutation in DNA gyrase. PHARMACOKINETICS – Renal excretion, Plasma t1/2 – 5 hours DOSE – 1)Ciprofloxacin – 500mg PO/BD 2)Ofloxacin – 200 – 400 mg PO/BD ADVERSE EFFECTS – GI upset, skin rashes, myalgias, tendonitis or tendon rupture, QT prolongation.

16. CLINDAMYCIN Uses: Gram positive aerobes and anaerobes, gram negative anaerobes Pharmacokinetics: T ½ -3hrs, dose: 150-300 mg QID oral Side effects: Pseudomembaranous enterocolitis, neuromuscular toxicity , thrombophlebitis on IV

17. METRONIDAZOLE MECHANISM OF ACTION – Free radical formation in the bacterial cell which damages DNA. CLINICAL USE – Anaerobes, Used in triple therapy for H.pylori , Giardia, Amoebiasis . PHARMACOKINETICS – Renal excretion, Plasma t1/2 – 5 hours DOSE – 400 mg PO/TID 500 mg i.v infusion

18. SIDE EFFECTS OF METRONIDAZOLE ADVERSE EFFECTS – Disulfiram like reaction (severe flushing, tachycardia, hypotension) with alcohol, metallic taste, tinnitus, emesis, reddish brown urine, ototoxicity, nephrotoxicity, deranged INR, peripheral neuropathy, Thrombophlebitis.

19. Preoperative use of antibiotics Not required in clean surgery unless a prosthesis is implanted. Use antibiotics that are effective against expected pathogens within local hospital guidelines. Plan for a single shot intravenous administration at induction of anesthesia. Repeat only during long operations or if there is excessive blood loss. Patient with heart valve disease or a prosthesis should be protected from bacteremia caused by dental work, urethral instrumentation or visceral surgery.

20. Post operative use of antibiotics Choice of antibiotic therapy – empirical and later modified depending on microbiological findings. There are 2 approaches to antibiotic therapy – A narrow spectrum antibiotic for a known sensitive infection Combination of broad spectrum antibiotics. Antibiotics do not replace surgical drainage of infections.