Download - Principles of Antibiotic Use in ICU
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