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Basic Principles of
   Antimicrobial Therapy

      Javed Iqbal,        FCPS, FRCS
          Professor of Surgery
Quaid-e-Azam medical College, Bahawalpur


             www.surgeonjaved.com
Antibiotics are being used
very injudiciously




      www.surgeonjaved.com
They are being used for
non-infective diseases




      www.surgeonjaved.com
They are being used when
surgical intervention is the
answer, not the antibiotics
(alone)




        www.surgeonjaved.com
They are being used for a
period less/more then
required




      www.surgeonjaved.com
They are being used as a
replacement of basic
aseptic principals




      www.surgeonjaved.com
Hand washing


  Centers for Disease Control and Prevention
 (CDC) has stated: "It is well-documented that
   one of the most important measures for
preventing the spread of pathogens is effective
                 hand aing."

               www.surgeonjaved.com
Pre-operative preparation


Bath, Shaving, Change of cloths



         www.surgeonjaved.com
Theater environment


General cleanliness, Fomites, Air
handling, anaesthesia machines,
  sponges, surgical techniques


          www.surgeonjaved.com
So, it is thought that a
   breach in any of above
   can be compensated with:
     An “ACHEE” ANTIBIOTICS
Which is synonymous with a “Mahngee”
               antibiotic


            www.surgeonjaved.com
The problem arises:

  When the antibiotics is used when not
                 needed
or is not used appropriately when needed


             www.surgeonjaved.com
This presentation must be
interpreted this context




      www.surgeonjaved.com
www.surgeonjaved.com
No two human
beings are the
same




www.surgeonjaved.com
The choice of antibiotics is
never very straight forward


It needs careful assessment and
         thoughtfulness


         www.surgeonjaved.com
Which
antibiotic
   www.surgeonjaved.com
pharma                          Back ground
                                knowledge




                                 Hospital
cost                             policy




         www.surgeonjaved.com
General
Principles
   www.surgeonjaved.com
1       The best antibiotic is one
        which is appropriate for a
        particular clinical scenario.

    There is no such thing as “achhi antibiotic”
     Costly antibiotic is not synonymous with
                 “Achhi antibiotic”


                   www.surgeonjaved.com
The best basis to
    choose an
2   antibiotic is the
    microbial culture
    and sensitivity
    pattern.




        Along with the under standing of drug
                  pharmacokinatics


                        www.surgeonjaved.com
Community
3
         Acquired
                      vs

    Hospital Acquired
         www.surgeonjaved.com
Community Acquired
 Community Acquired infections are in their
  “pure” form
 They are usually not resistant to standard
  antimicrobials
 Their behavior is predictable
        Gram positive in throat
        Gram negative in UTI etc.




                     www.surgeonjaved.com
Hospital Acquired
 The infection is usually by resistant microbes
 The pattern in not predictable
 The infection is usually by mixed flora




           Hospital
       Hospital antibiogram
         antibiogram
                  www.surgeonjaved.com
www.surgeonjaved.com
www.surgeonjaved.com
Infections can come
 From staff
 From Patient to patient
 From fomites
 In OT




                 www.surgeonjaved.com
4
        If we know the bug….


     The narrow spectrum antibiotic against
    which the bug is sensitive should be used


                    www.surgeonjaved.com
5   If we don’t know the
    bug….(empirical therapy)

    *Drug should be broad spectrum
      *Multiple drugs can be used
             www.surgeonjaved.com
Broad spectrum antibiotics
 3rd generation cephalolosporins
 Carbapanum group
 Qunalones
      Ofloxacin
      Ciprofloxacin

      Levofloxacin

      Getifloxacin


                 www.surgeonjaved.com
Antibiogram
                 Selection of an
6       antibiotic for a particular
        scenario is not a static
        phenomenon

    The antibiotics should be rotated from one
      generic to another of the same group


                  www.surgeonjaved.com
7      If antibiotic is not giving
       desired results


    Please remember that there might be pus
            some where in the body


                 www.surgeonjaved.com
8   Changing the drug            vs



    Changing the dose

          www.surgeonjaved.com
9
Prophylactic
    vs
Treatment
     www.surgeonjaved.com
Prophylaxis
 Peri-operative period needs to be covered
 The drugs should be broad spectrum
 The resistant pattern should be kept in mind
 Dose may be repeated if procedure is
  prolonged ( After 1-2 times of the half life of the
  drug)
 Best time for prophylaxis is just at the time of
  intubation
 In some cases the prophylaxis can be started
  24 hours before
                    www.surgeonjaved.com
 Clean surgery needing skin and soft infection
            First generation cephalosporin
 Surgery involving opening of a body
  cavity…...       3rd generation cepalosporin
 If gut has to be opened       mitronidazole has
  to be added.
 Cardiac surgery         Vancomycine



                  www.surgeonjaved.com
10


     Immunological status
            www.surgeonjaved.com
 Diabetes
 Steroids
 Anti cancer drugs
 AIDS
 Lympho-reticular disorders
 Anaemia




                 www.surgeonjaved.com
11
     SEPSIS
     Hospital Acquired Pneumonia
      Ventilator related infections


             www.surgeonjaved.com
 Sepsis is a serious medical condition

 Whole-body is in inflammatory state

 Systemic inflammatory response syndrome or

  SIRS
 A lay term for sepsis is blood poisoning,

  more aptly applied to septicemia

                 www.surgeonjaved.com
Sepsis has systemic implications:

 Decreased tissue perfusion.

 MOD    leading to death
 The mortality rate from septic shock is

  approximately 50%.




                 www.surgeonjaved.com
THE TRADITIONAL APPROACH

 Initial Use of narrow spectrum antibiotic
 Most potent drugs reserved
    Severely immunocompromised
    Nonresponders
    Resistant pathogen

 Aim is to avoid antibiotic exposure when
  infection is not confirmed
 Limiting the development of resistance
 Allowing the control of cost
                      www.surgeonjaved.com
There is a need for Initial
Appropriate Therapy in the
Treatment of Serious
Infection

    The new consences



       www.surgeonjaved.com
Initial antibiotic therapy:

 Inappropriate: The microbiological
  documentation of infection in the blood culture
  that was not effectively treated at the time, the
  causative microorganism and its antibiotic
  susceptibility were known.
 Appropriate: when at least one effective drug
  was included in the empirical antibiotic treatment
  within 24 h of the identification of bacteremia.
  This definition is in agreement with recent statements issued by the
               Centers for Disease Control and Prevention.

                                www.surgeonjaved.com
  Chest: May 2003,vol 123,1615-1624
 The traditional approach may no longer be
  appropriate in the current era of
  increasing antibiotic resistance

 It is important to recognize that the
  excess mortality associated with
  inadequate initial therapy occurred even
  though the antibiotic could be switched
  once the culture and susceptibility data
  became available.

 The delay may have been only 2-3 days
  but by that time, it was already too late.
                     www.surgeonjaved.com
INCREASING ANTIBIOTIC
RESISTANCE REQUIRES A
NEW TREATMENT
APPROACH




      www.surgeonjaved.com
Factors involved in optimal initial antibiotic therapy.
                           www.surgeonjaved.com
DE-ESCALATIONn
THERAPY




    www.surgeonjaved.com
De-escalation therapy
Changing from the broad spectrum
antibiotic to an agent with a narrow focus
based on culture data ;changing the focus
from multiple antibiotics to a single drug
when the suspected organism is not
detected by culture; and without fever




              www.surgeonjaved.com
DE-ESCALATION
           THERAPY
 STAGE 1
 Administer the broadest-spectrum
  antibiotic therapy to improve outcomes
  (decrease mortality, prevent organ
  dysfunction, and decrease hospital length
  of stay).

STAGE 2
 Focus on de-escalation as a means to
  minimize resistance and improve cost-
  effectiveness

                    www.surgeonjaved.com
Carbapenems: A Good Choice for Initial
Appropriate Therapy in ICU Patients
with Serious Nosocomial Infection

 The carbapenem of choice for initial appropriate
 therapy should offer:
  Broad-spectrum activity
  Proven efficacy
  Low potential for resistance
  Good tolerability




                      www.surgeonjaved.com
www.surgeonjaved.com
www.surgeonjaved.com
www.surgeonjaved.com
www.surgeonjaved.com
Conclusions: While choosing an
antibiotic:
   Consider the patient
   Consider the site
   Consider the type of bug/s
   Consider the drug pharmacokinetics
   Consider the dosage
   Consider the route
   Consider the combination of drugs
   Consider the side effects
   Consider the cost

                  www.surgeonjaved.com
Thank
Thank you
very much
 you


            www.surgeonjaved.com

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Basic principles of antimicrobial therapy

  • 1.
  • 2. Basic Principles of Antimicrobial Therapy Javed Iqbal, FCPS, FRCS Professor of Surgery Quaid-e-Azam medical College, Bahawalpur www.surgeonjaved.com
  • 3. Antibiotics are being used very injudiciously www.surgeonjaved.com
  • 4. They are being used for non-infective diseases www.surgeonjaved.com
  • 5. They are being used when surgical intervention is the answer, not the antibiotics (alone) www.surgeonjaved.com
  • 6. They are being used for a period less/more then required www.surgeonjaved.com
  • 7. They are being used as a replacement of basic aseptic principals www.surgeonjaved.com
  • 8. Hand washing Centers for Disease Control and Prevention (CDC) has stated: "It is well-documented that one of the most important measures for preventing the spread of pathogens is effective hand aing." www.surgeonjaved.com
  • 9. Pre-operative preparation Bath, Shaving, Change of cloths www.surgeonjaved.com
  • 10. Theater environment General cleanliness, Fomites, Air handling, anaesthesia machines, sponges, surgical techniques www.surgeonjaved.com
  • 11. So, it is thought that a breach in any of above can be compensated with: An “ACHEE” ANTIBIOTICS Which is synonymous with a “Mahngee” antibiotic www.surgeonjaved.com
  • 12. The problem arises: When the antibiotics is used when not needed or is not used appropriately when needed www.surgeonjaved.com
  • 13. This presentation must be interpreted this context www.surgeonjaved.com
  • 15. No two human beings are the same www.surgeonjaved.com
  • 16. The choice of antibiotics is never very straight forward It needs careful assessment and thoughtfulness www.surgeonjaved.com
  • 17. Which antibiotic www.surgeonjaved.com
  • 18. pharma Back ground knowledge Hospital cost policy www.surgeonjaved.com
  • 19. General Principles www.surgeonjaved.com
  • 20. 1 The best antibiotic is one which is appropriate for a particular clinical scenario. There is no such thing as “achhi antibiotic” Costly antibiotic is not synonymous with “Achhi antibiotic” www.surgeonjaved.com
  • 21. The best basis to choose an 2 antibiotic is the microbial culture and sensitivity pattern. Along with the under standing of drug pharmacokinatics www.surgeonjaved.com
  • 22. Community 3 Acquired vs Hospital Acquired www.surgeonjaved.com
  • 23. Community Acquired  Community Acquired infections are in their “pure” form  They are usually not resistant to standard antimicrobials  Their behavior is predictable  Gram positive in throat  Gram negative in UTI etc. www.surgeonjaved.com
  • 24. Hospital Acquired  The infection is usually by resistant microbes  The pattern in not predictable  The infection is usually by mixed flora Hospital Hospital antibiogram antibiogram www.surgeonjaved.com
  • 27. Infections can come  From staff  From Patient to patient  From fomites  In OT www.surgeonjaved.com
  • 28. 4 If we know the bug…. The narrow spectrum antibiotic against which the bug is sensitive should be used www.surgeonjaved.com
  • 29. 5 If we don’t know the bug….(empirical therapy) *Drug should be broad spectrum *Multiple drugs can be used www.surgeonjaved.com
  • 30. Broad spectrum antibiotics  3rd generation cephalolosporins  Carbapanum group  Qunalones  Ofloxacin  Ciprofloxacin  Levofloxacin  Getifloxacin www.surgeonjaved.com
  • 31. Antibiogram Selection of an 6 antibiotic for a particular scenario is not a static phenomenon The antibiotics should be rotated from one generic to another of the same group www.surgeonjaved.com
  • 32. 7 If antibiotic is not giving desired results Please remember that there might be pus some where in the body www.surgeonjaved.com
  • 33. 8 Changing the drug vs Changing the dose www.surgeonjaved.com
  • 34. 9 Prophylactic vs Treatment www.surgeonjaved.com
  • 35. Prophylaxis  Peri-operative period needs to be covered  The drugs should be broad spectrum  The resistant pattern should be kept in mind  Dose may be repeated if procedure is prolonged ( After 1-2 times of the half life of the drug)  Best time for prophylaxis is just at the time of intubation  In some cases the prophylaxis can be started 24 hours before www.surgeonjaved.com
  • 36.  Clean surgery needing skin and soft infection First generation cephalosporin  Surgery involving opening of a body cavity…... 3rd generation cepalosporin  If gut has to be opened mitronidazole has to be added.  Cardiac surgery Vancomycine  www.surgeonjaved.com
  • 37. 10 Immunological status www.surgeonjaved.com
  • 38.  Diabetes  Steroids  Anti cancer drugs  AIDS  Lympho-reticular disorders  Anaemia www.surgeonjaved.com
  • 39. 11 SEPSIS Hospital Acquired Pneumonia Ventilator related infections www.surgeonjaved.com
  • 40.  Sepsis is a serious medical condition  Whole-body is in inflammatory state  Systemic inflammatory response syndrome or SIRS  A lay term for sepsis is blood poisoning, more aptly applied to septicemia www.surgeonjaved.com
  • 41. Sepsis has systemic implications:  Decreased tissue perfusion.  MOD leading to death  The mortality rate from septic shock is approximately 50%. www.surgeonjaved.com
  • 42. THE TRADITIONAL APPROACH  Initial Use of narrow spectrum antibiotic  Most potent drugs reserved  Severely immunocompromised  Nonresponders  Resistant pathogen  Aim is to avoid antibiotic exposure when infection is not confirmed  Limiting the development of resistance  Allowing the control of cost www.surgeonjaved.com
  • 43. There is a need for Initial Appropriate Therapy in the Treatment of Serious Infection The new consences www.surgeonjaved.com
  • 44. Initial antibiotic therapy:  Inappropriate: The microbiological documentation of infection in the blood culture that was not effectively treated at the time, the causative microorganism and its antibiotic susceptibility were known.  Appropriate: when at least one effective drug was included in the empirical antibiotic treatment within 24 h of the identification of bacteremia. This definition is in agreement with recent statements issued by the Centers for Disease Control and Prevention. www.surgeonjaved.com Chest: May 2003,vol 123,1615-1624
  • 45.  The traditional approach may no longer be appropriate in the current era of increasing antibiotic resistance  It is important to recognize that the excess mortality associated with inadequate initial therapy occurred even though the antibiotic could be switched once the culture and susceptibility data became available.  The delay may have been only 2-3 days but by that time, it was already too late. www.surgeonjaved.com
  • 46. INCREASING ANTIBIOTIC RESISTANCE REQUIRES A NEW TREATMENT APPROACH www.surgeonjaved.com
  • 47. Factors involved in optimal initial antibiotic therapy. www.surgeonjaved.com
  • 48. DE-ESCALATIONn THERAPY www.surgeonjaved.com
  • 49. De-escalation therapy Changing from the broad spectrum antibiotic to an agent with a narrow focus based on culture data ;changing the focus from multiple antibiotics to a single drug when the suspected organism is not detected by culture; and without fever www.surgeonjaved.com
  • 50. DE-ESCALATION THERAPY STAGE 1  Administer the broadest-spectrum antibiotic therapy to improve outcomes (decrease mortality, prevent organ dysfunction, and decrease hospital length of stay). STAGE 2  Focus on de-escalation as a means to minimize resistance and improve cost- effectiveness www.surgeonjaved.com
  • 51. Carbapenems: A Good Choice for Initial Appropriate Therapy in ICU Patients with Serious Nosocomial Infection The carbapenem of choice for initial appropriate therapy should offer:  Broad-spectrum activity  Proven efficacy  Low potential for resistance  Good tolerability www.surgeonjaved.com
  • 56. Conclusions: While choosing an antibiotic:  Consider the patient  Consider the site  Consider the type of bug/s  Consider the drug pharmacokinetics  Consider the dosage  Consider the route  Consider the combination of drugs  Consider the side effects  Consider the cost www.surgeonjaved.com
  • 57. Thank Thank you very much you www.surgeonjaved.com

Editor's Notes

  1. There are two stages in the process of DE-ESCALATION THERAPY ™ † . The first stage involves administering the broadest-spectrum antibiotic. This is done to decrease morbidity and mortality, prevent organ dysfunction, and potentially decrease hospital length of stay. DE-ESCALATION THERAPY ™ works on the principle that the best possible regimen for critically ill patients is empiric therapy with a broad-spectrum agent that provides full coverage of all identified pathogens. The concept is that a broad-spectrum antimicrobial that is effective against both gram-negative and gram-positive bacteria needs to be administered as soon as infection is suspected. 9 This is done to avoid the high mortality and resistance development associated with inadequate antibiotic therapy. 9,11 Of course, it is very important for every institution to have local, current microbiological data in order to assess the likely infecting pathogens and the susceptibility patterns. 8,9 In the early and mid-1990s, several studies were published which suggested that the appropriateness of initial antibiotic therapy was a major factor in hospital mortality rates. 12-16 These studies found that patients who did not receive appropriate initial therapy had higher hospital mortality rates than those patients who received empiric therapy, which provided full antimicrobial coverage. Moreover, once therapy was initiated, switching from inadequate to appropriate therapy did not lower mortality rates. 12,14,17,18 In other words, the consequences of initial inadequate therapy were irreversible. † Trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA. Ref 8 p 471 par 1 L31-34 p 473 par 1 L24-30 Ref 9 p 1474 par 1 L25-33 Ref 10 p 236 par 2 L3-9 Ref 12 p 392 par 1 Table 6 p 393 par last L12-13 Ref 13 p 680 par 1 L6-11 par 2 l3-11 p 682 par last L22-25 p 684 par last L13-17 Ref 14 p 198 par 1 L11-end par 2 table 5 p 199 par 1 L10-12 Ref 15 p 1353 par 2 l7-8 Ref 16 p 374 par 7 L1-8 Ref 17 p 416 par last L1-6 p 417 par 1 L1-6 p 418 fig 2 Ref 18 p 149 par 1 l11-15 p 150 fig 1 p 152 par 1 L1-6
  2. The carbapenem of choice should offer: A broad antimicrobial spectrum Proven efficacy A low potential for resistance Good tolerability. Ref 1 WPC Title slide—to be covered in slide set