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Principles of Antibiotic Use in ICU
1. PRINCIPLES OF
ANTIBIOTIC USE IN
ICU
Dr. R.K.Sisodia
Senior Consultant
Critical care
Kailash Hospital Ltd
Greater Noida
2. 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.
3. --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
5. 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.
6. WITHIN THE LAST 15 YEARS
A VARIETY OF NEW ANTIBIOTICS HAS
BEEN INTRODUCED FOR USE IN
CLINICAL PRACTICE
BUT
THE IDEAL ANTIBIOTIC MAY STILL BE IN
FUTURE…
7. MAIN ANTIBIOTICS USED IN ICU
DESPITE THE AVAILABILITY
OF
NUMEROUS ANTIBIOTICS,
MOST PATHOGENS ARE
OPTIMALLY TREATED
WITH ONLY A FEW DRUGS
8. THESE ARE A BROAD CLASS OF ANTIBIOTICS
THAT CONTAIN A BETA LACTUM RING IN THEIR
MOLECULAR STRUCTURE…
Ex- PENICILLINS
CEPHALOSPORINS
CARBAPENUMS
MONOBECTUMS
BETA LACTAMS:
9. --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…
15. CEPHALOSPORINES ARE NOT
RECOMMONDED TO COMBINE WITH
OTHER NEPHROTOXIC DRUGS
(AMINOGLYCOSIDES)
CEPHALOSPORINES ARE
CONTRADICTED TO COMBINE WITH
LOOP DIURETICS...
16. CARBAPENUMS:
ACT BY INHIBITING THE CELL WALL
SYNTHESIS AND ARE KNOWN TO BE MOST
EFFECTIVE AGAINST GRAM NEGATIVE
INFECTION.
Ex- IMIPENUM
MERUPENUM
DORIPENUM
ERTAPENUM
17. THE WIDEST SPECTRUM OF
ANTIBACTERIAL ACTION
MOST OF AEROBE AND
ANAEROBE, GRAM +VE AND
GRAM –VE BACTERIA
INCLUDING THOSE WHICH
PRODUCE BETA-LACTAMASE
18. FLOUROQUINILONES:
EXERT THEIR ANTIBACTERIAL EFFECT BY
PREVENTING BACTERIAL DNA FROM
DUPLICATIONG.
Ex-CIPROFLOXACIN
-LEVOFLOXACIN
-OFLOXACIN
-PAZUFLOXACIN
-SPARFLOXACIN
-MOXIFLOXACIN
19. MACROLIDES:
-THE MECHANISM OF ACTION OF
MACROLIDES IS INHIBITION OF BACTERIAL
PROTEIN BIOSYNTHESIS.
-THIS ACTION IS BACTEROSTATIC.
21. 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
22. 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
26. 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
27. ACCORDING TO SPECTRUM
1-BROAD SPECTRUM:
THEY WORK AGAINST VARIETY OF BACTERIA
Ex:- PENICILLINS
CARBAPENUMS
FLOROQUINILONES
CEPHALOSPORINS...............
2-NARROW SPECTRUM:
THEY WORK AGAINST A SMALL RANGE OF BACTERIA
Ex:- MACROLIDES
LINCOSAMIDES
GLYCOPEPTIDES.........
28. ACCORDING TO MECHANISM
OF ACTION
1-CELL WALL SYNTHESIS INHIBITORS:
Ex:- PENICILLINS
CEPHALOSPORINS
BETA LACTUMS
CARBAPENUMS
MACROLIDES
VANCOMYCIN........
31. ACCORDING TO FREQUENCY OF DOSING
1- TIME DEPENDENT
Ex- CARBAPENUMS
- MACROLIDES
- BETA LACTUMS
2- CONCENTRATION DEPENDENT
Ex- AMINOGLYCOSIDES
32. 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.
33. RIGHT TIME
1- EMPIRICALLY-
FOR PRESUMED INFECTION WITH
CULTURE REPORT PENDING.
2- PROPHYLECTALLY-
MAINLY PEROPERATIVELY TO
PREVENT INFECTION.
3-DEFINITIVELY-
WITH POSITIVE CULTURE REPORT.
34. EMPIRICAL ANTIBIOTIC THERAPY
- IN CRITICALLY ILL PATIENTS, EMPIRICAL
ANTIBIOTIC THERAPY SHOULD BE
INITIATED IMMEDIATELY
OR
CONCURRENTLY WITH COLLECTION OF
DIAGNOSTIC SPECIMENS.
37. ADVANTAGES
OF
COMBINATION THERAPY
1- PREVENTION OF DEVELOPMENT OF
ANTIBIOTIC RESISTANCE.
2- ACHIEVING ANTIBIOTIC SYNERGISM
Ex- SULPHONAMIDE+ TRIMETHOPRIM
- VANCOMYCIN+ AMINOGLYCOSIDE
3- WIDE ANTIBIOTIC COVERAGE
4- DECREASED INCIDENCE OF TOXICITY
38. GENERAL PRINCILES OF ANTIBIOTIC
THERAPY
USING ANTIBIOTICS RESPONSIBLY
RIGHT DRUG
RIGHT TIME
RIGHT DOSE
RIGHT DURATION
39. 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 INEFFECTIVE
4- DIRECT INTERACTION OF DRUGS.
Ex- MIXING TICARCILLIN WITH AMONO-
GLYCOSIDE RESULTS IN INACTIVATION
OF AMINOGLYCOSIDE.
41. TIME DEPENDENT DOSING
THOSE CLASSES OF ANTIBIOTICS WHOSE
KILLING RESPONSE IS DEPENDENT ON TIME
ARE TERMED AS TIME DEPENDENT
ANTIBIOTICS. HIGHER CONCENTRATION OF
SUCH DRUGS DOES NOT RESULTS IN
HIGHER KILLING OF BACTERIA.
Ex- CARBAPENUMS
- PENICILLINS
- CEPHALOSPORINS.......
42. 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
44. ASCALATION OR TRADITIONAL
APPROACH
TRADITIONAL APPROACH TO ANTIBIOTIC
THERAPY SUGGESTS THAT YOU SHOULD
CHOOSE THE NARROWEST SPECTRUM
ANTIBIOTIC AGAINST THE BACTERIA YOU
SUSPECT ARE CAUSING THE INFECTION.
THIS WOULD THEN BE MODIFIED BASED
ON DEFINITIVE CULTURE RESULTS.
46. CENTRAL NERVOUS SYSYEM
MENINGITIS;
CEFTRIAXONE- 2 GM IV q12h
+
VANCOMYCIN- 500-750 MG IV q6h
ALTERNATIVE
MERUPENUM 2 GM IV q8h
POST HEAD TRAUMA:
CEFEPIME 2 GM IV q8h
+
VANCOMYCIN 500-750 MG IV q6h
ALTERNATIVE
MERUPENUM 2 GM IV
q8h
VANCOMYCIN 1 GM IV q6-8h
53. 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
55. 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.
56. 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.
57. NEED FOR NEWER
ANTIBIOTICS
NEWER ANTIBIOTICS ARE
NEEDED DESPERATELYBECAUSE:
-- EMERGENCE BACTERIAL
RESISTANCE
--RESERGENCE AND NEW
INFECTIOUS DISEASES
58. SINCE 2000
ONLY 3 NEW CLASSES OF ANTIBIOTICS
HAVE BEEN
INTRODUCED FOR HUMAN USE..
59. NEW CLASSES OF ANTIBIOTICS:
1- OXAZOLIDIONE
LINEZOLID:
-APPROVED FOR ADULT USE IN 2000.
-NEWER OXAZOLIDIONE IN PIPELINE.
RADEZOLID
TOREZOLID
60. NEWER CLASSES OF ANTIBIOTICS
2-LIPOPEPTIDES
-DEPTOMYCIN
APPROVED IN 2003
RAPIDLY BACTERICIDAL
NO CROSS RESISTANCE
61. NEWER CLASSES OF ANTIBIOTICS
3-KETOLIDES
TELITHROMYCIN
-APPROVED IN 2004
-FOR COMMUNITY
ACCQUIRED PNEUMONIA
63. - 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.
64. A MEDICAL DOCTOR HAS TO KNOW
DEFINITE CLINICAL PHARMACOLOGY
OF
ANTIBIOTICS
HOW TO SELECT
AND
USE
THEM RATIONALLY
67. MANY PATIENTS BECOME COLONIZED
WITH 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….
72. 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.