ANTIBIOTICS

What are antibiotics ?

 Substances produced by micromicroorganisms which supress the growth of or kill the other micro-organisms at very microlow concentrations.

Classification based on chemical structure:

1. Sulphonamides sulphadiazine , sulphonessulphonesPAS , Dapsone 2. Diaminopyrimidines- Trimethoprime, DiaminopyrimidinesPyrimethamine 3. Quinolones Nalidixic acid, Norfloxacin, Ciprofloxacin 4. Beta lactam- Penicilline, cephalosporins, lactamMonobactams, Carbapenems

5. Tetracycline- Oxy-tetracycline, Doxycycline Tetracycline- Oxy6. Nitrobenzene derivatives- Chloramphenicol derivatives7. Aminoglycoside- Neomycin, streptomycin, Aminoglycosidegentamycin 8. Macrolides- Erythromycin , azithromycin Macrolides9. Poly peptides- Polymyxin-B , Bacitracin peptides- Polymyxin10. Glycopeptides- vancomycin Glycopeptides11. Nitrofuran derivative- Nitrofurantoin derivative12. Nitroimidazole- Metronidazole , tinidazole Nitroimidazole-

Prophylactic antibiotics in surgery :

 Decisive period in first 4 hrs after a breach in a epithelial surface and underlying connective tissues, made during surgery or trauma , there is a delay before host defences can become mobilized through acute inflammatory , humoral and cellular processes.

 Ideally Prophylactic antibiotics are given i.v at induction of anaesthesia except in elective colonic surgery in which case oral antibiotics are given 8-10hrs before surgery 8 In long or prosthetic operations or unexpected contaminations , antibiotics are repeated 8 and 16hrs later.  But danger of indiscriminate use of antibiotics should be kept in mind.

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Wide spread sensitization of the population with resulting hypersensitivity , anaphylaxis , fever , rashes , blood disorders , cholestatic hepatitis Changes in the normal flora of the body with disease resulting from superinfection due to over growth of drug resistant organisms. Masking serious infection without eradicating it e.g clinical manifestation of abscess may be supressed while the infectious process continues Direct drug toxicity e.g granulocytopenia or thrombocytopenia with cephalosporin and penicillin and renal or auditory damage due to aminoglycosides . Development of drug resistance in microbial population chiefly through the elimination of drug sensitive micromicroorganisms from antibiotic saturated environments like hospital and their replacement by drug resistant micromicroorganisms.

Antibiotic Prophylaxis guidelines

 Single preoperative dose of antibiotics is as effective as full 5days course of therapy assuming uncomplicated procedure.  Prophylatic antibiotics should target anticipated organisms.

 Prophylaxis should not be extended beyond 24hrs following surgery.  One preoperative and 2 or 3 postoperative doses are sufficient in clean surgery .  Contaminated and dirty procedures should additionally receive additional postoperative coverage .  During prolonged procedures antibiotics prophylaxis should be administered every 3 hrs.  Use of antibiotics in procedure classified as contaminated or infected should be used as therapeutic and not prophylactic .

 Traumatically injured patients antibiotics can be given before bacterial contamination occurs.  Cephalosporins especially cephazolin is 1st line drug is used as prophylactic agent for most surgical procedures because of their low toxicity , long serum half life , broad spectrum of activity , low cost . 3rd generation should not be used for routine prophylaxis because they promote emergence of resistance.

Procedure Likely Recom Availabl Organism memded e Drugs CardioCardioThoracic Staph. Aureus, Staph. Epidermid is, Strept. , Gram ve Baccili Staph. , Enterococ cus , Gram ve Baccili

Altenativ e

Cefazoli Cephrad Clindam ine ycin , ne , Vancom Cefama ycin ndolec, Cefuroxi me Cefazoli Cephrad Clindam ycin ine ne, Cefuroxi me

Vascular Surgery

Organis m are Anerobe s , Staph Aureus, Gram ve Urology Gram (high ve risk) , Baccili , Diabetics Enterocc , ocus Catheriz ed Head and Neck Surgery

Clindamy cin is recomme nded

Available includes Metronid azole + Cephradi ne

Alternativ e Cephazo line + Metronid azole

Cefazolin Ciproflox Ciproflox e acin acin , Gentamy cin

Orthopedic Common 1st Line s surgery Organism s 1) Closed Fracture

Availabl e

2nd Line

Cefazoli Cephrad Clindam Staph. ycin ine Aureus , ne Staph. Epididerm is Staph. , Strept. , Gram ve Baccili, Anearobe s Cefazoli n+ Gentaci n Cephrad ine + Gentaci n Clindam ycin + Gentaci n

2) Open Fracture

Amputati Clostridia, ons Gram ve Baccili , Gram +ve Other Anearobes General Surgery Gastrodu odenal , Oesopha geal (high risk only) Organism Enteric Gram ve Baccili , Gram +ve Ccci

Metroni dazole _ Gentaci n+ Flucoxa cilin 1st Line Cephaz oline

Augmenti n+ Gantacin + Metronid azole Available Cephradi ne , Augmenti n+ Gentacin 2nd Line Clinda mycin + Gentaci n

Billiary Tract Surgery

Enteric GramGramve Baccili

Cefotaxime Cefotaxim single dose e , Cefazoline Cephradi Cefoxiti ne + n Metronida zole

Appendic Enteric Cefazoline ectomy Gram + ve Metronidaz Baccili ole 03 doses in non perforated , 5days in perforated

Colon surgery ( Elective )

Enteric Gram ve Baccili , Enteroc occus , Anaero bes

Oral Prophylaxis - Oral Neomycin + Erythrocin in base 1gm Each at 1300, 1400, 2100hrs in prepre-op i.v Cefazoline + Metronidaz ole

Oral Neomycin i.V Cefotaxi + Metronida me + Metronid zole i.v Ampicilin azole + One Dose or Gentacin Gentaci + Metronida n+ Metronid zole azole

Non Elective

Cefoxitin 1gm prepreop + 3 post op doses 8hrly No antibiotic s prophyla xis required

Laprosco pic Cholecys tectomy

Hernial Repair without Mesh Repair With Mesh

No Prophyla xis is required Cefazolin Cephradi single ne Dose Cefotaxi me + Metronid azole

Strangul Anearobi Cefoxitin ated c and 1gm Hernia Gram 8hrly ve Baccili

Penetrati ng Abdomin al Trauma

Enteric Gram ve Baccili , Enteroco ccus , Anaerob es

Cefazolin e+ Metronid azole

Metronid Metronid azole + azole + Cefotaxi Gentacin me

Breast Surgery

Augment in

Acute GramGram-ve Ciproflox Cholecys Baccili + acin tectomy Anearob 500mg es BD + Metronid azole 400mg TDS Acute Cefuroxi Cefotaxi Pancreat me me itis (low risk) high risk Imipenu m

Gram negative cocci

Suspected or proved etiological agents Neisseria gonorrhoeae (gonococcus) Drugs of 1st choice Alternative Drugs

Ceftriaxone , ciprofloxacin or ofloxacin

Spectinomycin, cefpodoxime proxetil Cefotaxime , ceftizoxime , ceftriaxone , ampicillin , chloramphenic ol

Neisseria Penicillin meningitidis (meningococcus )

Gram positive cocci

Streptococcus pneumoniae(pneumo coccus) Penicillin Erythromycin, cephalosporin, vancomycin, clindamycin, azithromycin,tetracyclin, certain fluroquinolones , imipenems Erythromycin, cephalosporin, vancomycin, clindamycin, azithromycin, clarithromycin Cephalosporin, vancomycin

Streptococcus hemolytic grp A,B,C,G Viridian Streptococci

Penicillin

Penicillin+/Penicillin+/Gentamycin

Staphylococcus methicillin -resistant

Vancomycin+/Vancomycin+/Gentamycin+/Gentamycin+/rifampicin

TMPTMP-SMZ, minocycline , fluroquinolones , clindamycin

Staphylococcus nonnonpencillinase producing

Penicillin

Cephalosporin , vancomycin, imipenem, meropenem , fluroquinolones, clindamycin Vancomycin, cephalosporin, clindamycin, amoxicillinamoxicillin-clavulanic acid, ampicillin sulbactam

Staphylococcus penicillinase producing

Penicillinase resistant penicillin

Enterococcus faecalis

Ampicillin+ gentamycin Vancomycin +gentamycin

Gram negative rods:

Bacteriods GI strains Metronidazole Cefoxitin, Chloramphenicol,clinda mycin, imipenem , meropenem,cefotetan aminoglycoside, fluroquinolones, cefepime Imipenem or meropenem, aminoglycoside, fluroquinolones Chloramphenicol, meropenem

Enterobacter

TMP- SMZ, imipenem, TMPmeropenem

Escherichia coli (sepsis) Cefotaxime, ceftriaxone , ceftrizoxime, cefepime,ceftazidime Haemophilus (meningitis and other serious infection) Cefotaxime, ceftriaxone , ceftrizoxime, ceftazidime

Escherichia coli (uncomplicated UTI)

Fluoroquinolones, nitrofurantoin

TMPTMP- SMZ, oral contraceptives, fosfomycin Clarithromycin + bismuth subsalicylate (pepto bismol) + tetracycline ; Amoxicillin + clarithromycin ; Amoxicillin + metronidazole + bismuth subsalicylate Ceftazidime+/Ceftazidime+/aminoglycoside; imipenem or meropenem+/meropenem+/aminoglycoside; ciprofloxacin+/ciprofloxacin+/ceftazidine

Helicobacter pylori

Amoxicillin + clarithromycin + omeprazole or tetracycline + metronidazole + bismuth subsalicylate

Pseudomonas aeruginosa

Aminoglycoside + antipseudomonal penicillin

Salmonella (bacteremia)

Ceftriaxone , fluoroquinolones

TMPTMP- SMZ, ampicillin , chloramphenicol

Shigella

Fluoroquinolones

ampicillin , TMPTMPSMZ, ceftriaxone

Vibrio (cholera , sepsis)

Tetracycline

TMP- SMZ , TMPfluoroquinolones

Gram positive rods

Clostrdium (gas gangrene , tetanus) penicillin Metronidazole , chloramphenic ol, clindamycin, imipenem or meropenem TMPTMP-SMZ

Listeria

Ampicillin +/+/aminoglycoside

Adverse effects of commonly used antibiotics:

1. Fluoroquinolones Ciprofloxacin - good safety records ~ 10% patients side effects seen GIT- nausea , vomiting , anorexia, bad taste GITCNSCNS- impairment of concentration, dizziness, headache , anxiety,rarely seizures SKIN- hypersensitivity reaction , urticaria , rash SKINNSAIDS enhance the CNS toxicity of ciprofloxacin and precipitate seizure in predisposed individuals

2. Penicillin- pain at i.m sight , Penicillinthrombophlebitis of injected vein, use with care in patients with renal impairment as it may lead to CNS toxicity Hypersensitivity reaction seen in 1-10% pts 1esp Pn G(rash, itching, urticaria, fever)

3. Cephalosporins- diarrhoea due to Cephalosporinsalteration of gut ecology Hypersensitivity reaction , bleeding esp in pts with Ca , intra abdominal infection , renal failure CefoperazoneCefoperazone- disulfiram like rxn with alcohol

4. Carbapenem imipenem , meropenem Induces seizures in predisposed pts when given at higher doses 5. Glycopeptides- Vancomycin- High systemic Glycopeptides- Vancomycintoxicity , plasma concentration dependent nerve deafness, fall in BP during i.v injections 6. Metronidazole anorexia , nausea , metallic taste in mouth, due to prolonged administration can cause peripheral neuropathy and CNS effects

7. Tetracycline irrtative nausea , vomiting diarrhoea DoxycyclineDoxycycline- oesophageal ulceration Dose related toxicity liver damage , can precipitate acute hepatic necrosis in pregnancy fatal ,Renal damage( all tetracycline exp doxycycline enhance renal failure) , phototoxicity , due to chelating property affects teeth and bones thus C/I in pregancy and young children, has anti-anabolic effects- decreased protein antieffectssynthesis, negative nitrogen balance and subsequent increased blood urea , increased ICP in neonates.

8. Aminoglycosides notorious for Ototoxicity cochlear and vestibular damage , hearing loss Nephrotoxicity Neuromuscular blockade- myasthenic blockadeweakness is increased by aminoglycosides, to be used cautiously esp with muscle relaxants

9. Clindamycin- similar in activity to Clindamycinerythromycin Causes diarrhoea and pseudomembranous enteocolitis due to clostridium difficile superinfection can prove fatal Treat this with stopping clindamycin and giving metronodazole 800mg TDS