1. ANTIBIOTIC THERAPY IN
THE INTENSIVE CARE
UNIT
Dr amrita
Moderator : dr amit rastogi

2. THE ACTION OF ANTIMICROBIAL DRUGS
Figure 20.2

3. PROTEIN SYNTHESIS INHIBITORS
Figure 20.4

4. BETA LACTAMS
• Narrow spectrum
• Narrow spectrum pEnicillinase susceptible. Penicillin
• Very-narrow-spectrum penicillinase-resistant drugs
• Methicillin
• Nafacillin
• Oxacillin

5. • Wide spectrum
• Wider-spectrum penicillinase-susceptible drugs
• Ampicillin and amoxicillin.
• Piperacillin and ticarcillin.
• Wide spectrum pEnicillinase resistant drugs
• Carbapenem
• Imipinem
• Meropenem
• Doripinem
• Ertapenem

6. THE CEPHALOSPORIN FAMILY

7. OTHER CELL WALL INHIBITORS
• Monobactams
• Aztreonams
• Vancomycin
• Telavancin
• Dalacin
• teichoplanin

8. AMINOGLYCOSIDES
• Gentamycin
• Tobramcin
• Amikacin
• Toxicity profile
• Ototoxicity
• Nephrotoxicity
• Blocking neuromuscular transmission
• hypersensitivity

9. PROTEIN SYNTHESIS INHIBITORS
• Linezolid
• Quinupristin/Dalfopristin
• Daptomycin
• Tigecycline

10. ANTIMICROBIALS WITH ACTIVITY AGAINST
ANAEROBES
• Metronidazole
• clindamycin

11. PHARMACOKINETICS AND
PHARMACODYNAMICS OF ANTIBIOTICS

12. SPECIAL CONSIDERATIONS IN THE
CRITICALLY ILL PATIENT
• Volume of distribution
• Metabolism
• Clearance : ranal hyper and hypo filtration
• hypoalbunaemia

13. HOW TO START
• Loading dose = target plasma conc * volume of distribution
• High loading doses for hydrophilic drugs like beta lactams , vancomycin , and
aminoglycosides
• Lipophilic drugs like macrolides,linezolid,tetracyclins do not require a high loading
dose
• Renal and hepatic function do not affect loading dose

14. PHARMACOKINETIC AND PHARMACODYNAMICS
PROPERTIES OF ANTIBIOTICS
• Minimum inhibitory concentration : The MIC is the lowest concentration of an
antibiotic that completely inhibits the growth of a microorganism in vitro. While the
MIC is a good indicator of the potency of an antibiotic, it indicates nothing about the
time course of antimicrobial activity
• Parameters quantifying serum level :
• Peak serum level : Cmax
• Trough level : Cmin
• Area Under the serum concentration time Curve (AUC) : indicates the amount of drug

16. PARAMETERS INDICATING ANTIBIOTIC
ACTIVITY
• he Peak/MIC ratio, Cpmax divided by the MIC.
• the T>MIC, percentage of a dosage interval in which the serum level exceeds the
MIC.
• and the 24h-AUC/MIC ratio. determined by dividing the 24-hour-AUC by the MIC

17. Pattern of Activity Antibiotics Goal of Therapy PK/PD Parameter
Type I
Concentration-dependent killing and
Prolonged persistent effects
Aminoglycosides
Daptomycin
Fluoroquinolones
Ketolides
Maximize concentrations
24h-AUC/MIC
Peak/MIC
Type II
Time-dependent killing and
Minimal persistent effects
Carbapenems
Cephalosporins
Erythromycin
Linezolid
Penicillins
Maximize duration of exposure T>MIC
Type III
Time-dependent killing and
Moderate to prolonged persistent effects.
Azithromycin
Clindamycin
Oxazolidinones
Tetracyclines
Vancomycin
Maximize amount of drug 24h-AUC/MIC

18. DOSING OF A CONCENTRATION
DEPENDANT ANTIBIOTIC

19. DOSING OF A TIME DEPENDANT
ANTIBIOTIC
• Multiple small dosing to obtain the
maximum t > MIC
• Role of prolonged infusions

20. ANTIBIOTIC RESISTANCE
• Common mechanisms
• Impermeability of the drug:
• alteration in target molecules
• enzymatic drug modifications
• Efflux
• both chromosomal mutations or genetic transfer ( plasmids ) can be responsible for
the resistance acquisition,

21. FACTORS RESPONSIBLE FOR ANTIBIOTIC
RESISTANCE
• Lack of education
• Hospital acquired infections
• Use of antibiotics in agriculture or aquaculture
• Environmental factors
• Use in household products

22. SOME COMMON RESISTANT STRAINS :
GRAM POSITIVE
• Methicillin resistant Staplylococcus aureus (MRSA)
• Vancomycin intermediate staph. Aureus ( VISA )
• Enterococcus- HLAR
• Multi drug resistant strep pneumoniae

23. SOME COMMON RESISTANT STRAINS :
GRAM NEGATIVE
• Extended-Spectrum b-Lactamase –Producing Enterobacteriaceae
• Antibiotic options carbapenems,
• tigecycline
• Carbapenemase producing enterobacteriaciae
• The delhi metalloprotease
• No susceptibility to any beta lactam or other higher antibiotics
• Susceptible to tigecycline and colistin

24. • Multi drug resistant pseudomonas MDR P aeruginosa are strains that are
resistant to 2 or more classes of antibiotics
• Antipseudomonal Penicillins with or with out beta lactamases
• Piperacillin tazobactum
• Ticarcillin
• Aztreonam
• Caeftazidime in combination with aminoglycosides
• Carbapenems : imipinem > doripinem > meropenem.etrapenem has no role against
pseudomonas.
• colistin

25. ANTIBIOTIC THERAPY IN THE ICU

26. ANTIBIOTIC STEWARDSHIP
• The Centers for Disease Control and Prevention (CDC) estimates more than two
million people are infected with antibiotic-resistant organisms, resulting in
approximately 23,000 deaths annually.
• Has recommended the setting up of special bodies in all acute care hospitals for the
optimization of antibiotic use-called antibiotic stewardship programmes.

27. SPECIFIC INTERVENTIONS TO IMPROVE
ANTIBIOTIC USE
• formal procedure for all clinicians to review the appropriateness of all antibiotics 48
hours after the initial orders (e.g. antibiotic time out)
• specified antibiotic agents need to be approved by a physician or pharmacist prior to
dispensing
• physician or pharmacist to review courses of therapy for specified antibiotic agents
(i.e., prospective audit with feedback)
• Automatic changes from intravenous to oral antibiotic therapy in appropriate
situations
• Dose adjustments in cases of organ dysfunction

28. • Dose optimization (pharmacokinetics/pharmacodynamics) to optimize the treatment
of organisms with reduced susceptibility
• Automatic alerts in situations where therapy might be unnecessarily duplicative
• Time-sensitive automatic stop orders for specified antibiotic prescriptions
• track rates of C. difficile infection
• Monitor total amounts of antibiotics used

29. ANTIBIOTIC STRATEGIES TO COMBAT
RESISTANCE
Blast them

30. Fool them

31. Stop irritating them.

32. ANTIBIOTIC STRATEGY FOR SKIN AND
SOFT TISSUE INFECTION

34. ANTIBIOTIC STRATEGY FOR COMMUNITY
ACQUIRED PNEUMONIA
• A b-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam)
+
azithromycin (level II evidence) or a respiratory fluoroquinolone
• If Pseudomonas is a consideration
• An antipneumococcal, antipseudomonal b-lactam (piperacillintazobactam,
cefepime, imipenem, or meropenem) plus
• either ciprofloxacin or levofloxacin (750 mg)

35. • Or
• The above b-lactam plus an aminoglycoside and azithromycin
• or
• The above b-lactam plus an aminoglycoside and an antipneumococcal
fluoroquinolone (for penicillin-allergic patients,
substitute aztreonam for above b-lactam)

39. ANTIBIOTIC INFECTION FOR INTRA
ABDOMINAL INFECTIONS