Antibiotics

ANTIBIOTICSANTIBIOTICS

What are antibiotics ?What are antibiotics ?

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

Classification based on Classification based on chemical structure:chemical structure:

1.1. Sulphonamides – sulphadiazine , sulphones- Sulphonamides – sulphadiazine , sulphones- PAS , DapsonePAS , Dapsone

2.2. Diaminopyrimidines- Trimethoprime, Diaminopyrimidines- Trimethoprime, PyrimethaminePyrimethamine

3.3. Quinolones – Nalidixic acid, Norfloxacin, Quinolones – Nalidixic acid, Norfloxacin, CiprofloxacinCiprofloxacin

4.4. Beta –lactam- Penicilline, cephalosporins, Beta –lactam- Penicilline, cephalosporins, Monobactams, CarbapenemsMonobactams, Carbapenems

5. Tetracycline- Oxy-tetracycline, Doxycycline5. Tetracycline- Oxy-tetracycline, Doxycycline6. Nitrobenzene derivatives- Chloramphenicol6. Nitrobenzene derivatives- Chloramphenicol7. Aminoglycoside- Neomycin, streptomycin, 7. Aminoglycoside- Neomycin, streptomycin,

gentamycingentamycin8. Macrolides- Erythromycin , azithromycin8. Macrolides- Erythromycin , azithromycin9. Poly peptides- Polymyxin-B , Bacitracin9. Poly peptides- Polymyxin-B , Bacitracin10. Glycopeptides- vancomycin10. Glycopeptides- vancomycin11. Nitrofuran derivative- Nitrofurantoin11. Nitrofuran derivative- Nitrofurantoin12. Nitroimidazole- Metronidazole , tinidazole12. Nitroimidazole- Metronidazole , tinidazole

Prophylactic antibiotics Prophylactic antibiotics in surgery :in surgery :

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

Ideally Prophylactic antibiotics are given i.v Ideally Prophylactic antibiotics are given i.v at induction of anaesthesia except in at induction of anaesthesia except in elective colonic surgery in which case oral elective colonic surgery in which case oral antibiotics are given 8-10hrs before surgeryantibiotics are given 8-10hrs before surgery

In long or prosthetic operations or In long or prosthetic operations or unexpected contaminations , antibiotics are unexpected contaminations , antibiotics are repeated 8 and 16hrs later.repeated 8 and 16hrs later.

But danger of indiscriminate use of But danger of indiscriminate use of antibiotics should be kept in mind.antibiotics should be kept in mind.

1.1. Wide spread sensitization of the population with resulting Wide spread sensitization of the population with resulting hypersensitivity , anaphylaxis , fever , rashes , blood hypersensitivity , anaphylaxis , fever , rashes , blood disorders , cholestatic hepatitis disorders , cholestatic hepatitis

2.2. Changes in the normal flora of the body with disease Changes in the normal flora of the body with disease resulting from superinfection due to over growth of drug resulting from superinfection due to over growth of drug resistant organisms.resistant organisms.

3.3. Masking serious infection without eradicating it e.g clinical Masking serious infection without eradicating it e.g clinical manifestation of abscess may be supressed while the manifestation of abscess may be supressed while the infectious process continuesinfectious process continues

4.4. Direct drug toxicity e.g granulocytopenia or Direct drug toxicity e.g granulocytopenia or thrombocytopenia with cephalosporin and penicillin and thrombocytopenia with cephalosporin and penicillin and renal or auditory damage due to aminoglycosides .renal or auditory damage due to aminoglycosides .

5.5. Development of drug resistance in microbial population Development of drug resistance in microbial population chiefly through the elimination of drug sensitive micro-chiefly through the elimination of drug sensitive micro-organisms from antibiotic saturated environments like organisms from antibiotic saturated environments like hospital and their replacement by drug resistant micro-hospital and their replacement by drug resistant micro-organisms. organisms.

Antibiotic Prophylaxis Antibiotic Prophylaxis guidelinesguidelines

Single preoperative dose of antibiotics is Single preoperative dose of antibiotics is as effective as full 5days course of as effective as full 5days course of therapy assuming uncomplicated therapy assuming uncomplicated procedure.procedure.

Prophylatic antibiotics should target Prophylatic antibiotics should target anticipated organisms.anticipated organisms.

Prophylaxis should not be extended beyond 24hrs Prophylaxis should not be extended beyond 24hrs following surgery.following surgery.

One preoperative and 2 or 3 postoperative doses are One preoperative and 2 or 3 postoperative doses are sufficient in clean surgery .sufficient in clean surgery .

Contaminated and dirty procedures should additionally Contaminated and dirty procedures should additionally receive additional postoperative coverage .receive additional postoperative coverage .

During prolonged procedures antibiotics prophylaxis During prolonged procedures antibiotics prophylaxis should be administered every 3 hrs.should be administered every 3 hrs.

Use of antibiotics in procedure classified as Use of antibiotics in procedure classified as contaminated or infected should be used as contaminated or infected should be used as therapeutic and not prophylactic . therapeutic and not prophylactic .

Traumatically injured patients antibiotics can Traumatically injured patients antibiotics can be given before bacterial contamination occurs.be given before bacterial contamination occurs.

Cephalosporins especially cephazolin is 1Cephalosporins especially cephazolin is 1stst line line drug is used as prophylactic agent for most drug is used as prophylactic agent for most surgical procedures because of their low surgical procedures because of their low toxicity , long serum half life , broad spectrum toxicity , long serum half life , broad spectrum of activity , low cost . 3of activity , low cost . 3rdrd generation should not generation should not be used for routine prophylaxis because they be used for routine prophylaxis because they promote emergence of resistance.promote emergence of resistance.

ProcedureProcedure Likely Likely OrganismOrganism

RecomRecommemded memded DrugsDrugs

AvailablAvailable e

AltenativAltenativee

Cardio- Cardio- ThoracicThoracic

Staph. Staph. Aureus, Aureus, Staph. Staph. EpidermidEpidermidis, is, Strept. , Strept. , Gram –ve Gram –ve BacciliBaccili

CefazoliCefazoline , ne , CefamaCefamandolec, ndolec, CefuroxiCefuroximeme

CephradCephradineine

ClindamClindamycin , ycin , VancomVancomycinycin

Vascular Vascular SurgerySurgery

Staph. , Staph. , EnterococEnterococcus , cus , Gram –ve Gram –ve BacciliBaccili

CefazoliCefazoline, ne, CefuroxiCefuroximeme

CephradCephradineine

ClindamClindamycinycin

Head Head and and Neck Neck SurgerySurgery

OrganisOrganism are m are AnerobeAnerobes , Staph s , Staph Aureus, Aureus, Gram –Gram –ve ve

ClindamyClindamycin is cin is recommerecommendednded

Available Available includes includes MetronidMetronidazole + azole + CephradiCephradinene

AlternativAlternative e CephazoCephazoline + line + MetronidMetronidazoleazole

Urology Urology (high (high risk) , risk) , DiabeticsDiabetics, , CatherizCatherizeded

Gram –Gram –ve ve Baccili , Baccili , EnteroccEnteroccocusocus

CefazolinCefazolinee

CiprofloxCiprofloxacinacin

CiprofloxCiprofloxacin , acin , GentamyGentamycincin

OrthopedicOrthopedics surgerys surgery

Common Common OrganismOrganisms s

11stst Line Line AvailablAvailable e

22ndnd Line Line

1) Closed 1) Closed FractureFracture

Staph. Staph. Aureus , Aureus , Staph. Staph. EpididermEpididermis is

CefazoliCefazolinene

CephradCephradineine

ClindamClindamycinycin

2) Open 2) Open FractureFracture

Staph. , Staph. , Strept. , Strept. , Gram –ve Gram –ve Baccili, Baccili, AnearobeAnearobess

CefazoliCefazolin + n + GentaciGentacinn

CephradCephradine + ine + GentaciGentacinn

ClindamClindamycin + ycin + GentaciGentacinn

AmputatiAmputationsons

Clostridia, Clostridia, Gram –ve Gram –ve Baccili , Baccili , Gram +ve Gram +ve Other Other AnearobesAnearobes

MetroniMetronidazole dazole _ _ GentaciGentacin + n + FlucoxaFlucoxacilincilin

AugmentiAugmentin + n + Gantacin Gantacin + + MetronidMetronidazoleazole

General General Surgery Surgery GastroduGastroduodenal , odenal , OesophaOesophageal geal (high risk (high risk only)only)

Organism Organism Enteric Enteric Gram –ve Gram –ve Baccili , Baccili , Gram +ve Gram +ve CcciCcci

11stst Line Line CephazCephazoline oline

Available Available CephradiCephradine , ne , AugmentiAugmentin + n + GentacinGentacin

22ndnd Line Line ClindaClindamycin + mycin + GentaciGentacinn

Billiary Billiary Tract Tract SurgerySurgery

Enteric Enteric Gram-Gram-ve ve BacciliBaccili

Cefotaxime Cefotaxime single dose single dose , Cefazoline , Cefazoline

CefotaximCefotaximee

AppendicAppendicectomyectomy

Enteric Enteric Gram Gram –ve –ve Baccili Baccili

Cefazoline Cefazoline + + MetronidazMetronidazole 03 ole 03 doses in doses in non non perforated , perforated , 5days in 5days in perforatedperforated

CephradinCephradine + e + MetronidaMetronidazole zole

CefoxitiCefoxitinn

Colon Colon surgery surgery ( Elective )( Elective )

Enteric Enteric Gram –Gram –ve ve Baccili , Baccili , EnterocEnterococcus , occus , AnaeroAnaerobes bes

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

i.V i.V CefotaxiCefotaxime + me + MetronidMetronidazole azole One One Dose or Dose or Gentacin Gentacin + + MetronidMetronidazole azole

Oral Oral Neomycin Neomycin + + MetronidaMetronidazole i.v zole i.v Ampicilin Ampicilin + + Gentacin Gentacin + + MetronidaMetronidazolezole

Non – Non – Elective Elective

Cefoxitin Cefoxitin 1gm pre-1gm pre-op + 3 op + 3 post – op post – op doses doses 8hrly 8hrly

LaproscoLaproscopic pic CholecysCholecystectomytectomy

No No antibioticantibiotics s prophylaprophylaxis xis required required

Hernial Hernial Repair Repair without without MeshMesh

No No ProphylaProphylaxis is xis is required required

Repair Repair With With MeshMesh

Cefazolin Cefazolin single single DoseDose

CephradiCephradinene

StrangulStrangulated ated Hernia Hernia

AnearobiAnearobic and c and Gram –Gram –ve ve Baccili Baccili

Cefoxitin Cefoxitin 1gm 1gm 8hrly 8hrly

CefotaxiCefotaxime + me + MetronidMetronidazole azole

PenetratiPenetrating ng AbdominAbdominal al TraumaTrauma

Enteric Enteric Gram –Gram –ve ve Baccili , Baccili , EnterocoEnterococcus , ccus , AnaerobAnaerobes es

CefazolinCefazoline + e + MetronidMetronidazole azole

MetronidMetronidazole + azole + CefotaxiCefotaxime me

MetronidMetronidazole + azole + GentacinGentacin

Breast Breast Surgery Surgery

AugmentAugmentinin

Acute Acute CholecysCholecystectomytectomy

Gram-ve Gram-ve Baccili + Baccili + AnearobAnearobeses

CiprofloxCiprofloxacin acin 500mg 500mg BD + BD + MetronidMetronidazole azole 400mg 400mg TDSTDS

Acute Acute PancreatPancreatitis (low itis (low risk) high risk) high riskrisk

CefuroxiCefuroxime me

ImipenuImipenumm

CefotaxiCefotaximeme

Gram negative cocciGram negative cocciSuspected or Suspected or proved proved etiological etiological agentsagents

Drugs of 1Drugs of 1stst choicechoice

Alternative Alternative DrugsDrugs

Neisseria Neisseria gonorrhoeae gonorrhoeae (gonococcus)(gonococcus)

Ceftriaxone , Ceftriaxone , ciprofloxacin or ciprofloxacin or ofloxacinofloxacin

Spectinomycin, Spectinomycin, cefpodoxime cefpodoxime proxetilproxetil

Neisseria Neisseria meningitidis meningitidis (meningococcus(meningococcus))

Penicillin Penicillin Cefotaxime , Cefotaxime , ceftizoxime , ceftizoxime , ceftriaxone , ceftriaxone , ampicillin , ampicillin , chloramphenicchloramphenicolol

Gram positive cocciGram positive cocciStreptococcus Streptococcus pneumoniae(pneumopneumoniae(pneumococcus)coccus)

PenicillinPenicillin Erythromycin, cephalosporin, Erythromycin, cephalosporin, vancomycin, clindamycin, vancomycin, clindamycin, azithromycin,tetracyclin, azithromycin,tetracyclin, certain fluroquinolones , certain fluroquinolones , imipenemsimipenems

Streptococcus Streptococcus hemolytic grp hemolytic grp A,B,C,GA,B,C,G

PenicillinPenicillin Erythromycin, cephalosporin, Erythromycin, cephalosporin, vancomycin, clindamycin, vancomycin, clindamycin, azithromycin, clarithromycinazithromycin, clarithromycin

Viridian Streptococci Viridian Streptococci Penicillin+/- Penicillin+/- GentamycinGentamycin

Cephalosporin, vancomycinCephalosporin, vancomycin

Staphylococcus Staphylococcus methicillin -resistantmethicillin -resistant

Vancomycin+/- Vancomycin+/- Gentamycin+/- Gentamycin+/- rifampicinrifampicin

TMP-SMZ, minocycline , TMP-SMZ, minocycline , fluroquinolones , clindamycinfluroquinolones , clindamycin

Staphylococcus non-Staphylococcus non-pencillinase producing pencillinase producing

PenicillinPenicillin Cephalosporin , Cephalosporin , vancomycin, imipenem, vancomycin, imipenem, meropenem , meropenem , fluroquinolones, fluroquinolones, clindamycinclindamycin

Staphylococcus Staphylococcus penicillinase producing penicillinase producing

Penicillinase resistant Penicillinase resistant penicillinpenicillin

Vancomycin, Vancomycin, cephalosporin, cephalosporin, clindamycin, clindamycin, amoxicillin-clavulanic amoxicillin-clavulanic acid, ampicillin acid, ampicillin sulbactamsulbactam

Enterococcus faecalis Enterococcus faecalis Ampicillin+ gentamycinAmpicillin+ gentamycin Vancomycin Vancomycin +gentamycin+gentamycin

Gram negative rods:Gram negative rods:Bacteriods GI strainsBacteriods GI strains MetronidazoleMetronidazole Cefoxitin, Cefoxitin,

Chloramphenicol,clindaChloramphenicol,clindamycin, imipenem , mycin, imipenem , meropenem,cefotetanmeropenem,cefotetan

Enterobacter Enterobacter TMP- SMZ, imipenem, TMP- SMZ, imipenem, meropenemmeropenem

aminoglycoside, aminoglycoside, fluroquinolones, fluroquinolones, cefepimecefepime

Escherichia coli (sepsis)Escherichia coli (sepsis) Cefotaxime, Cefotaxime, ceftriaxone , ceftriaxone , ceftrizoxime, ceftrizoxime, cefepime,ceftazidimecefepime,ceftazidime

Imipenem or Imipenem or meropenem, meropenem, aminoglycoside, aminoglycoside, fluroquinolonesfluroquinolones

Haemophilus Haemophilus (meningitis and other (meningitis and other serious infection) serious infection)

Cefotaxime, Cefotaxime, ceftriaxone , ceftriaxone , ceftrizoxime, ceftrizoxime, ceftazidimeceftazidime

Chloramphenicol, Chloramphenicol, meropenem meropenem

Escherichia coli Escherichia coli (uncomplicated UTI)(uncomplicated UTI)

Fluoroquinolones, Fluoroquinolones, nitrofurantoinnitrofurantoin

TMP- SMZ, oral TMP- SMZ, oral contraceptives, contraceptives, fosfomycin fosfomycin

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

Clarithromycin + Clarithromycin + bismuth subsalicylate bismuth subsalicylate (pepto bismol) + (pepto bismol) + tetracycline ; Amoxicillin tetracycline ; Amoxicillin + clarithromycin ; + clarithromycin ; Amoxicillin + Amoxicillin + metronidazole + metronidazole + bismuth subsalicylate bismuth subsalicylate

Pseudomonas Pseudomonas aeruginosaaeruginosa

Aminoglycoside + Aminoglycoside + antipseudomonal antipseudomonal penicillinpenicillin

Ceftazidime+/- Ceftazidime+/- aminoglycoside; aminoglycoside; imipenem or imipenem or meropenem+/- meropenem+/- aminoglycoside; aminoglycoside; ciprofloxacin+/- ciprofloxacin+/- ceftazidine ceftazidine

Salmonella Salmonella (bacteremia)(bacteremia)

Ceftriaxone , Ceftriaxone , fluoroquinolones fluoroquinolones

TMP- SMZ, TMP- SMZ, ampicillin , ampicillin , chloramphenicolchloramphenicol

Shigella Shigella FluoroquinolonesFluoroquinolones ampicillin , TMP- ampicillin , TMP- SMZ, ceftriaxoneSMZ, ceftriaxone

Vibrio (cholera , Vibrio (cholera , sepsis)sepsis)

TetracyclineTetracycline TMP- SMZ , TMP- SMZ , fluoroquinolonesfluoroquinolones

Gram positive rodsGram positive rods

Clostrdium Clostrdium (gas (gas gangrene , gangrene , tetanus)tetanus)

penicillinpenicillin Metronidazole , Metronidazole , chloramphenicchloramphenicol, clindamycin, ol, clindamycin, imipenem or imipenem or meropenem meropenem

ListeriaListeria Ampicillin +/- Ampicillin +/- aminoglycosideaminoglycoside

TMP-SMZTMP-SMZ

Adverse effects of Adverse effects of commonly used antibiotics:commonly used antibiotics:

1.1. FluoroquinolonesFluoroquinolones – –Ciprofloxacin Ciprofloxacin - good - good safety records ~ 10% patients side effects safety records ~ 10% patients side effects seen seen

GIT- nausea , vomiting , anorexia, bad taste GIT- nausea , vomiting , anorexia, bad taste CNS- impairment of concentration, dizziness, CNS- impairment of concentration, dizziness,

headache , anxiety,rarely seizuresheadache , anxiety,rarely seizures SKIN- hypersensitivity reaction , urticaria , rash SKIN- hypersensitivity reaction , urticaria , rash NSAIDS – enhance the CNS toxicity of NSAIDS – enhance the CNS toxicity of

ciprofloxacin and precipitate seizure in ciprofloxacin and precipitate seizure in predisposed individuals predisposed individuals

2. Penicillin- pain at i.m sight , 2. Penicillin- pain at i.m sight , thrombophlebitis of injected vein, use thrombophlebitis of injected vein, use with care in patients with renal with care in patients with renal impairment as it may lead to CNS impairment as it may lead to CNS toxicitytoxicity

Hypersensitivity reaction seen in 1-10% pts Hypersensitivity reaction seen in 1-10% pts esp Pn G(rash, itching, urticaria, fever)esp Pn G(rash, itching, urticaria, fever)

3. Cephalosporins- diarrhoea due to 3. Cephalosporins- diarrhoea due to alteration of gut ecology alteration of gut ecology

Hypersensitivity reaction , bleeding esp in Hypersensitivity reaction , bleeding esp in pts with Ca , intra abdominal infection , pts with Ca , intra abdominal infection , renal failure renal failure

Cefoperazone- disulfiram like rxn with Cefoperazone- disulfiram like rxn with alcoholalcohol

4. 4. Carbapenem Carbapenem – – imipenem , meropenemimipenem , meropenemInduces seizures in predisposed pts when given Induces seizures in predisposed pts when given

at higher dosesat higher doses5. 5. Glycopeptides-Glycopeptides- VancomycinVancomycin- High systemic - High systemic

toxicity , plasma concentration dependent toxicity , plasma concentration dependent nerve deafness, fall in BP during i.v injectionsnerve deafness, fall in BP during i.v injections

6. Metronidazole – anorexia , nausea , metallic 6. Metronidazole – anorexia , nausea , metallic taste in mouth, due to prolonged administration taste in mouth, due to prolonged administration can cause peripheral neuropathy and CNS can cause peripheral neuropathy and CNS effectseffects

7. Tetracycline – irrtative –nausea , vomiting diarrhoea7. Tetracycline – irrtative –nausea , vomiting diarrhoeaDoxycycline- oesophageal ulceration Doxycycline- oesophageal ulceration Dose related toxicity – liver damage , can precipitate Dose related toxicity – liver damage , can precipitate

acute hepatic necrosis in pregnancy – fatal ,Renal acute hepatic necrosis in pregnancy – fatal ,Renal damage( all tetracycline exp doxycycline enhance renal damage( all tetracycline exp doxycycline enhance renal failure) , phototoxicity , due to chelating property affects failure) , phototoxicity , due to chelating property affects teeth and bones thus C/I in pregancy and young teeth and bones thus C/I in pregancy and young children, has anti-anabolic effects- decreased protein children, has anti-anabolic effects- decreased protein synthesis, negative nitrogen balance and subsequent synthesis, negative nitrogen balance and subsequent increased blood urea , increased ICP in neonates.increased blood urea , increased ICP in neonates.

8. Aminoglycosides – notorious for8. Aminoglycosides – notorious forOtotoxicity – cochlear and vestibular Ototoxicity – cochlear and vestibular

damage , hearing lossdamage , hearing loss Nephrotoxicity Nephrotoxicity Neuromuscular blockade- myasthenic Neuromuscular blockade- myasthenic

weakness is increased by weakness is increased by aminoglycosides, to be used cautiously aminoglycosides, to be used cautiously esp with muscle relaxants esp with muscle relaxants

9. Clindamycin- similar in activity to 9. Clindamycin- similar in activity to erythromycin erythromycin

Causes diarrhoea and pseudomembranous Causes diarrhoea and pseudomembranous enteocolitis due to clostridium difficile enteocolitis due to clostridium difficile superinfection can prove fatal superinfection can prove fatal

Treat this with stopping clindamycin and Treat this with stopping clindamycin and giving metronodazole 800mg TDSgiving metronodazole 800mg TDS