These are the principles of the use of antimicrobial therapy in management of disease conditions

1. PRINCIPLES OF ANTIMICROBIAL
THERAPY
By
Ngwogu Kelechi K.

2. The Basic Challenge
• Increasing number of multiresistant bacteria
and only few antibiotics in the pipelines of
companies (the present)
• a great number of new – but very expensive –
antibiotics (the future)

3. BACTERICIDAL OR BACTERIOSTATIC
ANTIBIOTIC
Bactericidal agent is recommended in cases of:
• severe infection
• immunocompromised patient
• infections in sites with poor antibiotic
penetration

4. ANTIBACTERIAL SPECTRUM
A broad spectrum antibiotic is recommended in cases of:
• wide spectrum of pathogens
• critical clinical situation
• known mixed infection
A narrow spectrum antibiotic is recommended in cases of
• infections caused by only a few pathogens
• of isolated pathogen with known
sensitivity

5. TARGETED (DIRECTED, SENSITIVITY BASED)
THERAPY
Administration of an antibiotic
- against the proved pathogen
- with known antibiotic sensitivity

6. EMPIRIC (PRESUMED) THERAPY
Administration of an antibiotic, if
- the clinical symptoms, lab tests indicate microbial
infection, and
- the pathogen and its sensitivity can only be
presumed
In case of empiric therapy the proper selection should
be based on the knowledge of:
- the potential pathogen spectrum,
- local antibiotic sensitivity of the possible pathogens

7. FACTORS TO BE CONSIDERED FOR THE
CHOICE OF ANTIBIOTICS
1.Community versus hospital-acquired
infections
• the pathogens are different in term of
spectrum and antibiotic sensitivity
• the pathogens of the nosocomial infections
are more resistant or even multiresistant

8. FACTORS TO BE CONSIDERED FOR THE
CHOICE OF ANTIBIOTICS
2. The anatomical site of the focus of sepsis
• the anatomical site determines the types of
possible pathogens, especially in community-
acquired infections

9. FACTORS TO BE CONSIDERED FOR THE
CHOICE OF ANTIBIOTICS
3. The presence of underlying diseases
• diabetes mellitus
• alcoholism
• cardiac failure, chronic lung disease
• immunosuppression
• liver and renal failure

10. FACTORS TO BE CONSIDERED FOR THE
CHOICE OF ANTIBIOTICS
4. Diagnostic or surgical intervention in the
recent past
• iv lines
• indwelling catheter
• Implantations
• surgical intervention

11. FACTORS THAT INFLUENCE THE OUTCOME
OF AN INFECTION
• type, virulence and number of pathogens
• the site of infections
• host factors

12. Virulent bacteria (obligate pathogens):
• bacteria having special virulence factors, toxins
that enable them to invade healthy human
organism (S. aureus, V.cholerae, S pneumoniae)
Non-virulent bacteria (facultative pathogens):
• cause infection mainly in hosts with (transiently)
impaired host defense

13. HOST FACTORS
• Age (infants and elderly are more prone to
unfavorable outcome)
• Underlying conditions, comorbidity
• Genetic variability
• Immune status (congenital or acquired
immunodeficiency, malignancies, steroid
treatment)
• Medical interventions (diagnostic, therapeutic
invasive methods)

14. THE SITE OF INFECTION
Infections with high mortality
• Pneumonia (the most frequent infectious
cause of death)
• Meningitis
• Endocarditis
• Peritonitis

15. Infections with low mortality
• Lower urinary tract infections
• Pelvic infections
• Osteomyelitis
Difficult to treat infections due to the poor penetration of
antibiotics
• Meningitis
• Endocarditis
• Osteomyelitis
• Prostatitis

16. INDICATIONS OF ANTIBIOTIC
COMBINATIONS
1. To assure broader antimicrobial spectrum
• mixed infections, if the selected antibiotic
does not cover the whole spectrum
(secondary peritonitis)
• severe infections of unknown etiology
• infections possible due to multiresistant
bacteria (nosocomial pneumonia, infections of
neutropenic patients)

17. INDICATIONS OF ANTIBIOTIC
COMBINATIONS
2. To enhance the antibacterial effect and/or to
prevent the development of resistance
• synergistic effect in case of some bacteria
(M.tuberculosis, enterococci, P.aeruginosa)
• if the number of bacteria (CFU) is particularly
high or/and the antibiotics poorly penetrate to
the site of infection

18. POTENTIAL CAUSES OF THERAPEUTIC
FAILURE
• The pathogen is not covered by the antibiotic
or resistant
• The daily dose is low or the method of
administration is inappropriate
• The antibiotic treatment does not correspond
to the clinical situation
• The antibiotic does not penetrate to the site of
infection

19. POTENTIAL CAUSES OF THERAPEUTIC
FAILURE
• The pathogen develops resistance during the
treatment
• New pathogens emerge
• Misinterpretation of lab test (the isolated
bacterium is not the pathogen)
• Poor immune status, advanced disease or fatal
underlying disease

20. PREREQUISITES OF THE SUCCESSFUL
ANTIBIOTIC THERAPY
• activity against the pathogen
• effective antibiotic concentration (higher than
MIC)

21. STRATEGY OF ANTIBIOTIC TREATMENT IN
SEVERE INFECTIONS
De-escalation therapy
• begin with the most effective therapy
• streamline the therapy later, when the patient
is already getting better and/or the pathogen
and its antibiotic sensitivity are known

22. AUGMENTED RENAL CLEARANCE
• Critically ill patients (such as trauma patients, burns
patients, in general, younger patients) are known to
experience augmented renal clearance that is clearly
associated with faster elimination of antibiotics and
lower than expected serum concentration.
• Infected critically ill patients may have adverse
outcomes as a result of inadequate antibiotic
exposure; a paradigm change to more personalized
antibiotic dosing may be necessary to improve
outcomes for these most seriously ill patients.

23. SUMMARY
• The clinical challenge remains to find the
balance between ensuring that each individual
patient is appropriately covered for the most
likely pathogens of their infection, while
avoiding the use of overtly broad-spectrum
antimicrobials in order to preserve them for
future use.

24. SUMMARY
• The basic principles of antimicrobial therapy work in
the clinical practice
• The use of combination therapy is indicated in
empiric therapy, however its value is not clear in
directed therapy
• De-escalation strategy is associated with good
clinical results and decreased antibiotic consumption
• Personalized antibiotic therapy should be introduced
in the treatment of critically ill patients

25. THANKS
FOR
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