PRINCIPLES OFANTIBIOTIC USE IN

ICU Dr. R.K.Sisodia Senior Consultant Critical care Kailash Hospital Ltd Greater Noida

INTRODUCTION-

--THE MODERN AGE OF ANTIBIOTIC THERAPEUTICS WAS LAUNCHED IN 1930S WITH SULPHONAMIDES AND IN 1940S WITH PENICILLINS.

--SINCE THEN MANY ANTIBIOTIC DRUGS HAVE BEEN DEVELOPED MOSLTY AIMED AT

THE TREATMENT OF BACTERIAL INFECTIONS.

--THESE DRUGS HAVE PLAYED AN IMPORTANT ROLE IN THE DRAMATIC DECREASE IN THE MORBADITY AND MORTALITY DUE TO INFECTIOUS DISEASES.

--WHILE THE ABSOLUTE NUMBER OF ANTIBIOTIC DRUGS ARE LARGE, THERE ARE FEW UNIQUE ANTIBIOTIC TARGETS

DEFINATION

ANTIBIOTICS ARE THE TYPES OF MEDICATION

THAT DESTROYS OR SLOWS DOWN THE

GROWTH OF BACTERIA

QUALITIES OF A GOOD ANTIBIOTIC AGENT

-KILL OR INHIBIT THE GROWTH OF MICROORGANISM.-CAUSE NO DAMAGE TO THE HOST.-CAUSE NO ALLERGIC REACTION TO THE HOST.-STABLE ON STORAGE.-REMAIN IN SPECIFIC TISSUE ENOUGH TO BE EFFECTIVE.-KILL THE PATHOGEN BEFORE THEY MUTATE AND BECOME RESISTANT TO IT.

WITHIN THE LAST 15 YEARSA VARIETY OF NEW ANTIBIOTICS HAS

BEEN INTRODUCED FOR USE IN CLINICAL PRACTICE

BUTTHE IDEAL ANTIBIOTIC MAY STILL BE IN

FUTURE…

MAIN ANTIBIOTICS USED IN ICU

DESPITE THE AVAILABILITY OF

NUMEROUS ANTIBIOTICS, MOST PATHOGENS ARE

OPTIMALLY TREATED WITH ONLY A FEW DRUGS

THESE ARE A BROAD CLASS OF ANTIBIOTICS THAT CONTAIN A BETA LACTUM RING IN THEIR MOLECULAR STRUCTURE… Ex- PENICILLINS CEPHALOSPORINS CARBAPENUMS MONOBECTUMS

BETA LACTAMS:

--BETA LACTUM ANTIBIOTICS ARE THE MOST WIDELY USED GROUP OF ANTIBIOTICS,

--BACTERIA OFTEN DEVELOP RESISTANCE BY SYNTHESIZING A BETA LACTAMASE, AN ENZYME THAT ATTACKS BETA LACTUM RING

--TO OVERCOME THIS RESISTANCE THESE ANTIBIOTICS ARE PRESCRIBED WITH THE BETA LACTUM INHIBITORS…

PENICILLINS NATURAL PENICILLINS- Ex- BENZYLPENICILLINS -PHENOXYMETHYLPENICILLIN SEMISYNTHETIC PENICILLINS 1-ANTISTAPHYLOCOCCI PENICILLINASE RESISTANT PENICILLIN Ex- OXACILLIN, DICLOXACILLIN,METHICILLIN 2-ANTIPSEUDOMONAS PENICILLINS Ex-PIPERACILLIN 3-WIDE SPECTRUM Ex-AMPICILLIN, AMOXICILLIN

BETA LACTAMASE INHIBITORS

-CLAVULANIC ACID

-SULBACTAM

-TAZOBACTAM

BETA-LACTAMASE PROTECTED PENICILLINS

AMOXICILLIN / CLAVULANATE

AMPICILLIN / SUBACTUM

TICARCILLIN / CLAVULANATE

PIPERACILLIN / TAZOBACTUM

CEPHALOSPORINS: 1ST GENERATION:- Ex-CEPHAZOLIN CEPHALOTHIN CEPHALORIDINE

2ND GENERATION:- Ex-CEFAMYCIN C CEFOXITIN CEFOTITAN CEFMETAZOLE

CEPHALOSPORINS: 3RD GENERATION:- Ex-CEFTRIAXONE -CEFOTAXIME -CEFTAZIDIME 4TH GENERATION:- Ex-CEFEPIME -CEFPIROME

CEPHALOSPORINES ARE NOT RECOMMONDED TO COMBINE WITH

OTHER NEPHROTOXIC DRUGS (AMINOGLYCOSIDES)

CEPHALOSPORINES ARE CONTRADICTED TO COMBINE WITH

LOOP DIURETICS...

CARBAPENUMS: ACT BY INHIBITING THE CELL WALL

SYNTHESIS AND ARE KNOWN TO BE MOST EFFECTIVE AGAINST GRAM NEGATIVE INFECTION.

Ex- IMIPENUM MERUPENUM DORIPENUM ERTAPENUM

THE WIDEST SPECTRUM OF ANTIBACTERIAL ACTION MOST OF AEROBE AND

ANAEROBE, GRAM +VE AND GRAM –VE BACTERIA

INCLUDING THOSE WHICH PRODUCE BETA-

LACTAMASE

FLOUROQUINILONES: EXERT THEIR ANTIBACTERIAL EFFECT BY PREVENTING BACTERIAL DNA FROM DUPLICATIONG. Ex-CIPROFLOXACIN -LEVOFLOXACIN -OFLOXACIN -PAZUFLOXACIN -SPARFLOXACIN -MOXIFLOXACIN

MACROLIDES: -THE MECHANISM OF ACTION OF

MACROLIDES IS INHIBITION OF BACTERIAL PROTEIN BIOSYNTHESIS.

-THIS ACTION IS BACTEROSTATIC.

CLASSIFICATION OF MACROLIDES

1- NATURAL SUBSTANCES Ex- ERYTHROMYCIN

2- SEMI-SYNTHETIC SUBSTANCES Ex-CLARITHROMYCIN

3- AZALIDE Ex- AZITHROMYCIN

AMINOGLYCOSIDES: -MAINLY GRAM NEGATIVE BACTERICIDAL AGENT WORK BY INHIBITING PROTEIN BIOSYNTHESIS. 1st GENERATION- Ex-STREPTOMYCIN, NEOMYCIN,KENAMYCIN 2ND GENERATION- Ex-GENTAMICIN, TOBRAMYCIN 3RD GENERATION- Ex- AMIKACIN, NETILMICIN

GLYCOPEPTIDES: - THESE DRUGS INHIBIT THE SYNTHESIS

OF CELL WALL. - DUE TO TOXICITY THEIR USE IS

RESTRICTED TO PATIENTS WHO HAVE HYPERSENSITIVE TO BETA LACTUMS. - EFFECTIVE MAINLY AGAINT GRAM POSITIVE COCCI. Ex- VANCOMYCIN - TEICOPLANIN

MONOBACTUM- AZTREONUM - -ACTION SPECTRUM- GRAM NEGATIVE BACTERIA INCLUDING E-COLI, KLEBSIELLA. HAEMOPHILLUS INFLUEZAE… -ACTIVITY EQUAL TO 3RD GENERATION

CEPHALOSPORINES… -CLINCAL USES- SEPSIS, UTI, SSTI,

MENINGITIS -OFTENCOMBINEAMINOGLYCOSIDES,

CLINDAMYCIN, METRONIDAZOLE,VANCOMYCIN….

LINCOSAMIDES-CLINDAMYCIN -ACTION SPECTRUM: GRAM+VE AEROBIC COCCI, GRAM+VE & GRAM –VE ANAEROBES

-PENETRATE ALL THE TISSUES

-A LOT OF SIDE EFFECTS

CLASSIFICATION OF

ANTIBIOTICS

ACCORDING TO ACTIVITY1-BACTERICIDAL: THEY KILL BACTERIA DIRECTLY.Ex- BETA LACTUMS CEPHALOSPORINS CARBAPENUMS AMINOGLYCOSIDES.......2-BACTERIOSTATIC: THEY STOP BACTERIA FROM GROWING.Ex- TETRACYCLINE CHLORAMPHENICOL SULPHONAMIDES MACROLIDES LINCOSAMIDES

ACCORDING TO SPECTRUM

1-BROAD SPECTRUM: THEY WORK AGAINST VARIETY OF BACTERIAEx:- PENICILLINS CARBAPENUMS FLOROQUINILONES CEPHALOSPORINS...............2-NARROW SPECTRUM: THEY WORK AGAINST A SMALL RANGE OF BACTERIAEx:- MACROLIDES LINCOSAMIDES GLYCOPEPTIDES.........

ACCORDING TO MECHANISMOF ACTION

1-CELL WALL SYNTHESIS INHIBITORS:

Ex:- PENICILLINS CEPHALOSPORINS BETA LACTUMS CARBAPENUMS MACROLIDES VANCOMYCIN........

2- PROTEIN SYNTHESIS INHIBITORS: A-INHIBIT 30S SUBUNIT:-

Ex- AMINOGLYCOSIDES TETRACYCLINE

B-INHIBIT 50S SUBUNIT:-

Ex- MACROLIDES - CHLORAMPHENICOL - CLINDAMYCIN - LINEZOLID

3- DNA SYNTHESIS INHIBITORS: Ex- FLOROQUINOLONES - METRONIDAZOLE

4- RNA SYNTHESIS INHIBITORS: Ex- RIFAMPICIN

5- FOLIC ACID SYNTHESIS INHIBITORS: Ex- SULPHONAMIDES - TRIMETHOPRIM

ACCORDING TO FREQUENCY OF DOSING

1- TIME DEPENDENT

Ex- CARBAPENUMS - MACROLIDES - BETA LACTUMS2- CONCENTRATION DEPENDENT

Ex- AMINOGLYCOSIDES

GLYCYLCYCLINES: TIGICYCLINE ---SPECTRUM INCLUDED GRAM+VE AND

GRAM –VE AEROBIC AND ANAEROBIC BACTERIA,INCLUDING SOME WITH RESISTANT TO OTHER CLASSES e.g.

VRE, MRSA AND MDR ACINETOBACTER.

---BUT HAS LIMITED ACTIVITY AGAINST P. AERUGINOSA.

RIGHT TIME

1- EMPIRICALLY- FOR PRESUMED INFECTION WITH

CULTURE REPORT PENDING.

2- PROPHYLECTALLY- MAINLY PEROPERATIVELY TO

PREVENT INFECTION.

3-DEFINITIVELY- WITH POSITIVE CULTURE REPORT.

EMPIRICAL ANTIBIOTIC THERAPY

- IN CRITICALLY ILL PATIENTS, EMPIRICAL ANTIBIOTIC THERAPY SHOULD BE

INITIATED IMMEDIATELY OR CONCURRENTLY WITH COLLECTION OF

DIAGNOSTIC SPECIMENS.

GUIDELINESEMPIRICAL ANTIBIOTIC THERAPY

1- SITE OF INFECTION2- PATIENT'S FACTORS RENAL HEPATIC IMMUNE SYSTEM AGE3-SEFTY OF ANTIBIOTIC4-COST OF THERAPY

USING ANTIBIOTICS RESPONSIBILY

RIGHT DOSE WITH RIGHT FREQUENCY:

MONOTHERAPYOR

COMBINATION THERAPY

ADVANTAGESOF

COMBINATION THERAPY1- PREVENTION OF DEVELOPMENT OF ANTIBIOTIC RESISTANCE.

2- ACHIEVING ANTIBIOTIC SYNERGISM Ex- SULPHONAMIDE+ TRIMETHOPRIM - VANCOMYCIN+ AMINOGLYCOSIDE

3- WIDE ANTIBIOTIC COVERAGE

4- DECREASED INCIDENCE OF TOXICITY

GENERAL PRINCILES OF ANTIBIOTIC THERAPY

USING ANTIBIOTICS RESPONSIBLY

RIGHT DRUGRIGHT TIMERIGHT DOSE

RIGHT DURATION

DISADVANTAGES OF COMBINATION THERAPY

1- INCREASED COST OF THERAPY.2- MORE CHANCES OF SUPERINFECTION.3- DRUG ANTAGONISM Ex- IF TWO BETA LACTUMS GIVEN TO

GETHER ONE WILL BECOME INEFFECTIVE4- DIRECT INTERACTION OF DRUGS. Ex- MIXING TICARCILLIN WITH AMONO- GLYCOSIDE RESULTS IN INACTIVATION OF AMINOGLYCOSIDE.

USING ANTIBIOTICS RESPONSIBLY

TIME DEPENDENT OR

CONCENTRATIONDEPENDENT

TIME DEPENDENT DOSING

THOSE CLASSES OF ANTIBIOTICS WHOSEKILLING RESPONSE IS DEPENDENT ON TIMEARE TERMED AS TIME DEPENDENT

ANTIBIOTICS. HIGHER CONCENTRATION OF SUCH DRUGS DOES NOT RESULTS IN HIGHER KILLING OF BACTERIA.

Ex- CARBAPENUMS - PENICILLINS - CEPHALOSPORINS.......

CONCENTRATION DEPENDENT DOSING

THOSE CLASSES OF ANTIBIOTICS WHICH EREDICATE BACTERIA BY ACHIEVING HIGH CONCENTRATION AT THE SITE OF BONDING IS KNOWN AS CONCENTRATION DEPENDENT ANTIBIOTICS.

Ex- AMINOGLYCOSIDES FLOUROQUINOLONES

USING ANTIBIOTICS RESPONSIBLY

RIGHT DURATION OF THERAPY

ASCALATION OR

DEASCALATION THERAPY

ASCALATION OR TRADITIONAL APPROACH

TRADITIONAL APPROACH TO ANTIBIOTIC THERAPY SUGGESTS THAT YOU SHOULD

CHOOSE THE NARROWEST SPECTRUMANTIBIOTIC AGAINST THE BACTERIA YOUSUSPECT ARE CAUSING THE INFECTION.THIS WOULD THEN BE MODIFIED BASEDON DEFINITIVE CULTURE RESULTS.

EMPIRICAL ANTIBIOTIC

THERAPYACCORDING

TO SITEOF

INFECTION

CENTRAL NERVOUS SYSYEMMENINGITIS;

CEFTRIAXONE- 2 GM IV q12h +VANCOMYCIN- 500-750 MG IV q6hALTERNATIVEMERUPENUM 2 GM IV q8h

POST HEAD TRAUMA:CEFEPIME 2 GM IV q8h +VANCOMYCIN 500-750 MG IV q6hALTERNATIVEMERUPENUM 2 GM IV q8hVANCOMYCIN 1 GM IV q6-8h

PNEUMONIA

COMMUNITY ACQUIRED:CEFTRIAXONE 1 GM IV q12h +AZITHROMYCIN 500 MG IV q24h ORERTAPENUM 1 GM IV q24h +AZITHROMYCIN 500 MG IV q24h

PNEUMONIA

HOSPITAL ACQUIRED:IMIPENUM- 500 MG IV q6h ORMERUPENAM- 1 GM IV q8h OR DORIPENUM- 500 MG IV q8h +LEVO 750 MG IV q24h ORMOXI 400 MG IV q24h

ASPIRATION PNEUMONITIS:

-PIP+TAZO 4.5 GM IV q8h ALTERNATIVE CEFTRIAXONE 1 GM IV q12h + METRONIDAZOLE 500 MG IV q8h

PERITONITIS

SPONTANEOUS BACTERIAL PERITONITIS

CEFOTAXIME 2 GM IV q8h OR PIP+TAZO 4.5GM IV q8h OR CEFTRIOXONE 2GM IV q8h OR ERTAPENUM 1GM IV q24h

PERITONITIS PERFORATION PERITONITIS PIP+TAZO 4.5GM IV q8h OR ERTAPENUM 1GM IV q24h LIFE THREATENING PERITONITIS IMIPENUM 500MG IV q8h OR MERUPENUM 1GM IV q8h OR DORIPENUM 500MG IV q8h

BURN WOUND SEPSIS-

PIP+TAZO 4.5GM IV q8h + VANCOMYCIN 1 GM IV q12h + AMIKACIN 7.5GM / KG IV q12h

BONE AND JOINT INFECTION:

--FLUCLOXACILLIN 2 GM IV q8h IF ALLERGIC TO PINICILLINS --CEFUROXIME 2GM IV q8h OR ---CLINDAMYCIN 600MG IV q6h IF MRSA IS A POSSIBILITY ---PIP+TAZO 4.5GM IV q8h + ----VANCOMYCIN 1GM IV q8h IF RISK OF MDRGNB ---MERUPENUM 1GM IV q8h

TYPHOIDAL SYNDROME

CIPROFLOX 500MG IV q12h OR LEVOFLOX 500 MG IV q12h OR CEFTRIAXONE 2 GM IV q8h OR AZITHROMYCIN 500 MG PO q24h

INAPPROPRIATE USE OF ANTIBIOTICS IS A WORLD WIDE PROBLEM

* MORE THAN 50% OF ALL MEDICINES ARE PRESCRIBED,DISPENSED OR SOLD INAPPROPRIATELY.

* HALF OF ALL PATIENTS FAIL TO TAKE MEDICINES CORRECTLY.

*THE OVERUSE,UNDER USE OR MISUSE HARM PEOPLE AND WASTE RESOURSES. *MORE THAN 50% OF ALL COUNTRIES DO NOT IMPLEMENT BASIC POLICIES TO PROMOTE RATIONAL USE OF MEDICINES. *LESS THAN 30% OF ALL PATIENTS ARE TREATED ACCORDING TO CLINICAL GUIDELINES.

WHAT WENT WRONG WITH ANTIBIOTIC USES

-TREATING TRIVIAL / VIRAL INFECTIONS WITH ANTIBIOTICS HAS BECOME ROUTINE.

- MANY USE ANTIBIOTICS WITHOUT KNOWING THE BASIC PRINCIPLES OF ANTIBIOTIC THERAPY. - MANY PRACTIONERS ARE UNDER PRESSURE FOR SHORT TERM SOLUTIONS. -EMERGING RESISTANCE DUE TO UNAPPROPRIATE USE OF ANTIBIOTICS. -COMMERCIAL INTERESTS OF PHARMACEUTICAL INDUSTRY PUSHING THE USE OF ANTIBIOTICS.

NEED FOR NEWER ANTIBIOTICS

NEWER ANTIBIOTICS ARE NEEDED DESPERATELYBECAUSE:

-- EMERGENCE BACTERIAL RESISTANCE

--RESERGENCE AND NEW INFECTIOUS DISEASES

SINCE 2000 ONLY 3 NEW CLASSES OF ANTIBIOTICS

HAVE BEENINTRODUCED FOR HUMAN USE..

NEW CLASSES OF ANTIBIOTICS:

1- OXAZOLIDIONELINEZOLID:-APPROVED FOR ADULT USE IN 2000.

-NEWER OXAZOLIDIONE IN PIPELINE. RADEZOLID TOREZOLID

NEWER CLASSES OF ANTIBIOTICS

2-LIPOPEPTIDES-DEPTOMYCIN

APPROVED IN 2003 RAPIDLY BACTERICIDAL NO CROSS RESISTANCE

NEWER CLASSES OF ANTIBIOTICS

3-KETOLIDESTELITHROMYCIN-APPROVED IN 2004-FOR COMMUNITY

ACCQUIRED PNEUMONIA

WHY WE NEED ANTIBIOTIC

POLICY

- REDUCE THE ANTIBIOTIC RESISTANCE- INITIATE BEST EFFORTS IN THE HOSPITAL AREA AS MANY RESISTANCE BACTERIA GENERATED IN HOSPITALS.-INITIATE GOOD HYGIENIC PRACTICES SO BACTERIA DO NOT SPREAD.-PRACTICE BEST EFFORTS TO PREVENT SPREAD OF RESISTANT STRAINS.-TO PREVENT SPILL INTO SOCIETY AS THEY PRESENT AS COMMUNITY ACQIURED INFECTIONS.

A MEDICAL DOCTOR HAS TO KNOWDEFINITE CLINICAL PHARMACOLOGY

OFANTIBIOTICS

HOW TO SELECTANDUSE

THEM RATIONALLY

TENETS OF

APPROPRIATEANTIBIOTIC

USE

TENET-1TREAT

INFECTIONNOT

COLONIZATION

MANY PATIENTS BECOME COLONIZEDWITH POTENTIALLY PATHOGENIC BACTERIA BUT ARE NOT INFECTED---ASYMPTOMATIC BACTERIURIA OR CATHETER COLONIZATION.---TRACHEOSTOMY COLONIZATION.---CHRONIC WOUNDS.---CHRONIC BRONCHITIS.---PRESENCE OF WBC NOT ALWAYS INDICATIVE OF INFECTION.---FEVER MAY BE DUE TO ANOTHERV REASON, NOT THE POSITIVE CULTURE….

TENET-2

DO NOT

TREAT STERILE INFLAMMATION

OR ABNORMAL IMAGING

WITHOUT INFECTION

X-RAYS CAN BE DIFFICULT TO INTERPRIT

INFILTRATE MAY BE DUE TO NON-INFECTIOUS CAUSE

TENET-3 DO NOT

USE ANTIBIOTICS TO TREAT VIRAL

INFECTIONS THERE IS NO DEFINITE PROOF

THAT ANTIBIOTICS CAN PREVENT

SECONDARY INFECTION

TENET-4

A GOOD

ANTIBIOTIC DOES NOT NECESSARILY MEANS

A COSTLY

ANTIBIOTIC.

TO SUMMARISE -THERE IS A GREAT NEED OF NEWER ANTIBIOTICS BECAUSE OF INCREASING MICRIBIAL RESISTANCE.

-BECAUSE OF GREAT COST OF DEVELOP- MENT ONLY FEW DRUGS ARE IN PIPELINE.

-RATIONAL USE OF ANTIBIOTICS REMAINS THE MOST IMPORTANT MEASURE.

THANK YOU