Principles of Antibiotic Use in ICU

PRINCIPLES OF
ANTIBIOTIC 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 YEARS
A VARIETY OF NEW ANTIBIOTICS HAS
BEEN INTRODUCED FOR USE IN
CLINICAL PRACTICE
BUT
THE 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

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 BACTERIA
Ex:- PENICILLINS
CARBAPENUMS
FLOROQUINILONES
CEPHALOSPORINS...............
2-NARROW SPECTRUM:
THEY WORK AGAINST A SMALL RANGE OF BACTERIA
Ex:- MACROLIDES
LINCOSAMIDES
GLYCOPEPTIDES.........

ACCORDING TO MECHANISM
OF 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 LACTUMS
2- 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.

GUIDELINES
EMPIRICAL ANTIBIOTIC THERAPY
1- SITE OF INFECTION
2- PATIENT'S FACTORS
RENAL
HEPATIC
IMMUNE SYSTEM
AGE
3-SEFTY OF ANTIBIOTIC
4-COST OF THERAPY

USING ANTIBIOTICS RESPONSIBILY
RIGHT DOSE WITH RIGHT
FREQUENCY:
MONOTHERAPY
OR
COMBINATION THERAPY

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

GENERAL PRINCILES OF ANTIBIOTIC
THERAPY
USING ANTIBIOTICS RESPONSIBLY
RIGHT DRUG
RIGHT TIME
RIGHT 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 INEFFECTIVE
4- DIRECT INTERACTION OF DRUGS.
Ex- MIXING TICARCILLIN WITH AMONO-
GLYCOSIDE RESULTS IN INACTIVATION
OF AMINOGLYCOSIDE.

TIME DEPENDENT
OR
CONCENTRATION
DEPENDENT

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.......

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

RIGHT DURATION OF THERAPY
ASCALATION
OR
DEASCALATION THERAPY

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.

EMPIRICAL
ANTIBIOTIC
THERAPY
ACCORDING
TO
SITE
OF
INFECTION

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

PNEUMONIA
COMMUNITY ACQUIRED:
CEFTRIAXONE 1 GM IV q12h
+
AZITHROMYCIN 500 MG IV q24h
OR
ERTAPENUM 1 GM IV q24h
+
AZITHROMYCIN 500 MG IV q24h

PNEUMONIA
HOSPITAL ACQUIRED:
IMIPENUM- 500 MG IV q6h
OR
MERUPENAM- 1 GM IV q8h
OR
DORIPENUM- 500 MG IV q8h
+
LEVO 750 MG IV q24h
OR
MOXI 400 MG IV q24h

ASPIRATION PNEUMONITIS:
-PIP+TAZO 4.5 GM IV q8h
ALTERNATIVE
+
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
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-
+
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
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 BEEN
INTRODUCED FOR HUMAN USE..

NEW CLASSES OF ANTIBIOTICS:
1- OXAZOLIDIONE
LINEZOLID:
-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-KETOLIDES
TELITHROMYCIN
-APPROVED IN 2004
-FOR COMMUNITY
ACCQUIRED PNEUMONIA

- 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 KNOW
DEFINITE CLINICAL PHARMACOLOGY
OF
ANTIBIOTICS
HOW TO SELECT
AND
USE
THEM RATIONALLY

TENETS
OF
APPROPRIATE
ANTIBIOTIC
USE

TENET-1
TREAT
INFECTION
NOT
COLONIZATION

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….

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.

Principles of Antibiotic Use in ICU

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Principles of Antibiotic Use in ICU