Rational use of antibiotics, Different approaches of antimicrobial therapy, Factors affecting the prescription of antibiotics

1. General Guidelines for Rational
use of Antibiotics
Dhaval Joshi

2. BACKGOUND
• Antibiotics are the most widely used
medications
• Perhaps the most irrationally used

3. Questions
• Is it infection?
• Is it bacterial Infection?
• If yes, take appropriate samples first
• What is likely etiologic agent?
• Which antibiotic?
• Also consider some evidence!

4. Case
• 5 yrs old boy
• Fever and cough for 8 days
• Admitted on day 2 of fever
• Chest X-ray: right lower zone pneumonia
• WBC count: 23,000/cumm
• Prescribed with Ceftriaxone, Amikacin

5. Case
• No improvement in chest x-ray, changed to
meropenam in 3 days
• Refereed on Day 3 meropenam for non
respone

6. Case
• Evidence of pneumococcal vaccines
• Amoxicillin

7. Indications for antibacterial therapy
1. Definitive therapy
2. Empirical therapy
3. Prophylactic therapy

8. Empirical therapy
• Empirical antibacterial therapy should be
restricted to critical cases, when time is
inadequate for identification and isolation of
the bacteria and reasonably strong doubt of
bacterial infection exists
• In such situations, drugs that cover the most
probable infective agent/s should be used

9. Definitive therapy
• This is for proven bacterial infections
• Attempts should be made to confirm the
bacterial infection by means of staining of
secretions/fluids/exudates, culture and
sensitivity, serological tests and other tests
• Based on the reports, a narrow spectrum, least
toxic, easy-to-administer and cheap drug should
be prescribed

10. Prophylactic therapy
• Antimicrobial prophylaxis is administered to
susceptible patients to prevent specific
infections that can cause definite detrimental
effect
• In all these situations, only narrow spectrum
and specific drugs are used. It should be
remembered that there is NO single prophylaxis
to 'prevent' all possible bacterial infections

11. What antibacterial?
• There are more than 100 antibacterials
available today, and each one has its own
spectrum of activity, adverse effect profile and
cost
• The prescriber should consider many factors
before prescribing an antibacterial agent so as
to make the treatment most effective with
least adverse effects and cost

12. Factors affecting Antibiotic
Prescribing
The following factors should be considered while
prescribing an antibacterial agent:
• Site of infection
• Type of infection
• Severity of infection
• Isolate and its sensitivity
• Source of infection
• Host factors
• Drug related factors

13. Site of infection
• As a Rule Of The Thumb, it can be
remembered that the infections above the
diaphragm are caused by Cocci and Gram
positive organisms and
• infections below the diaphragm are caused by
Bacilli and Gram negative organisms, although
there are exceptions

14. Infections above the diaphragm
• Respiratory tract infections- Streptococcus
pyogenes, S. pneumoniae, streptococci
• Managed with Penicillins, Cephalosporins,
Macrolides and Tetracyclines

15. Infections below the diaphragm
• Examples include urinary tract infection, intra-
abdominal sepsis, pelvic infections etc. and
these are caused by the organisms like E. coli,
Klebsiella, Proteus, Pseudomonas, etc.
• Quinolones, Aminoglycosides, 3rd generation
cephalosporins and Metronidazole, alone or in
combination are useful in these infections

16. Site of infection
• There are certain sites where the infection
tends to be difficult for treatment
• In such cases higher dose, more frequent
administration, longer duration, antibacterial
combinations and lipophilic antibacterials may
have to be used

17. Type of infection
• Infections can be localized or extensive; mild or
severe; superficial or deep seated; acute, sub
acute or chronic and extracellular or intracellular
• For extensive, severe, deep seated, chronic and
intracellular infections, higher and more frequent
dose, longer duration of therapy, combinations,
lipophilic drugs may have to be used

18. Severe infections
• (bacteremia / pyemia / sepsis syndrome /
septic shock; abscesses in lung/ brain/ liver/
pelvis/ intra-abdominal; meningitis/
endocarditis/ pneumonias/ pyelonephritis/ /
gangrene and hospital acquired infections) can
be life threatening and rapidly fatal

19. Severe infections
• In all such situations therefore, attempts
should be made to identify and isolate the
infecting organism from the site as well as
blood by staining culture
• In treating the severe infections, drugs should
be administered by only intravenous route to
ensure adequate blood levels

20. Severe infections
• Only bactericidal drugs should be used to ensure
faster clearance of the infection. If the site of
infection is known, narrow spectrum drugs
should be used
• A combination of Penicillins/3rd generation
cephalosporins, aminoglycosides and
metronidazole may be used. The dose should be
higher and more frequent. Whenever possible, a
switch to oral therapy should be made

21. Isolate and sensitivity
• Ideal management of any significant bacterial
infection requires culture and sensitivity study of
the specimen
• Blood culture: Febrile illness
• If the situation permits, antibacterials can be
started only after the sensitivity report is
available

22. Isolate and sensitivity
• Narrow spectrum, least toxic, easy to
administer and cheapest of the effective drugs
should be chosen
• If the patient is responding to the drug that
has already been started, it should not be
changed even if the in vitro report says
otherwise

23. Source of infection
• Community acquired infections are less likely
to be resistant whereas hospital acquired
infections are likely to be resistant and more
difficult to treat (e.g. Pseudomonas, MRSA
etc.)

24. Host factors

25. AGE
• The patient’s age is an important factor both
in trying to identify the likely etiologic agent
and in assessing the patient’s ability to
eliminate the drug(s) to be used
• In infants, chloramphenicol (can cause gray
baby syndrome) and sulfa (can cause
kernicterus) are contraindicated

26. AGE
• Elderly: Nephrotoxic drugs
• In the elderly, achlorhydria may affect absorption
of antibacterial agents; drug elimination is slower,
requiring dose adjustments; and ototoxicity of
aminoglycosides may be increased
• Increased absorption of penicillin G and
decreased absorption of Ketoconazole

27. Pregnancy
• In pregnancy, drugs with known toxicity or un-
established safety like tetracyclines,
quinolones, streptomycin, erythromycin and
Clarithromycin are contraindicated in all
trimesters
• Sulfa, nitrofurantoin and chloramphenicol are
contraindicated in the last trimester.

28. Pregnancy
• Drugs with limited data on safety like
aminoglycosides, azithromycin, clindamycin,
vancomycin, metronidazole, trimethoprim,
rifampicin and pyrazinamide
• Penicillins, cephalosporins, INH and ethambutol
are safe in pregnancy
• In lactating mothers sulfa, tetracyclines,
metronidazole, nitrofurantoin and quinolones are
contraindicated

29. Metabolic Abnormalities
• Inherited or acquired metabolic abnormalities
will influence the therapy of infectious
diseases in a variety of ways
• Slow acetylators
• G6PD deficiency

30. Organ Dysfunction
• In patients with renal failure,
tetracyclines are absolutely
contraindicated
• Aminoglycosides, cephalosporins,
fluroquinolones and sulfa are relatively
contraindicated; and

31. Organ Dysfunction
• Penicillins, Macrolides, vancomycin,
metronidazole, INH, ethambutol and
rifampicin are relatively safe
• It is better to avoid combinations of
cephalosporins and aminoglycosides in these
patients because both these classes of drugs
can cause nephrotoxicity.

32. Organ Dysfunction
• In patients with hepatic failure -
chloramphenicol, erythromycin,
fluroquinolones, pyrazinamide, rifampicin, INH
and metronidazole are relatively
contraindicated
• Penicillins, cephalosporins, ethambutol and
aminoglycosides are safe

33. Organ Dysfunction
• Significant accumulation can occur when both
liver dysfunction and renal dysfunction are
present for these drugs: cefotaxime, nafcillin,
piperacillin, and sulfamethoxazole

34. Concomitant Disease States
• Certain diseases will predispose patients to a
particular infectious disease or will alter the
type of infecting organism
• Patients with immunosuppressive diseases,
such as malignancies or acquired immunologic
deficiencies, are highly predisposed to
infections, and the types of organisms can be
vastly different from what would be expected

35. Concomitant Disease States
• Seizures-High doses of penicillin G
• Patients with myasthenia gravis or other
neuromuscular problems susceptible to the
neuromuscular blocking effect of the
aminoglycosides, polymyxins

36. Drug Factors

37. Pharmacokinetic and
Pharmacodynamic Considerations
• Integration of both pharmacokinetic and
pharmacodynamic properties of an agent is
important when choosing antimicrobial therapy
to ensure efficacy and to prevent resistance
• Aminoglycosides exhibit concentration-
dependent bactericidal effects
• β-Lactams display time-dependent bactericidal
effects

38. Tissue Penetration
• Cerebrospinal fluid (CSF) concentrations of
antimicrobial agents necessary to cure
bacterial meningitis have been defined
• Drugs that do not reach significant
concentrations in the CSF should either be
avoided or instilled directly, if feasible

39. Tissue Penetration
• The proper route of administration for an
antimicrobial depends on the site of infection
• Parenteral therapy: febrile neutropenia or deep-
seated infections such as meningitis,
endocarditis, and osteomyelitis
• Oral therapy: RTI, skin and soft tissue infections,
uncomplicated urinary tract infections, and
selected sexually transmitted diseases

40. Drug Toxicity
• CNS toxicities: penicillins, cephalosporins,
quinolones, and imipenem
• Hematologic: nafcillin, piperacillin, cefotetan,
chloramphenicol and trimethoprim
• Nephrotoxicity: aminoglycosides and
vancomycin

41. Drug Toxicity
• Ototoxicity: aminoglycosides or erythromycin
• Photosensitivity: azithromycin, quinolones,
tetracyclines, pyrazinamide, sulfamethoxazole,
and trimethoprim
• Gastric toxicities

42. Cost
• Lastly, the cost of therapy should be considered in
choosing the antibacterial agent and in a developing
country like India with limited spending on healthcare,
this does assume significance
• It should always be remembered that just because a
particular drug is expensive, it need not be superior
than the cheaper ones
• For example, cheaper drugs like doxycycline or co-
trimoxazole would be as effective as the costlier
clarithromycin or cephalosporins in the management
of LRTI

43. COMBINATION ANTIMICROBIAL
THERAPY
• Broadening the Spectrum of Coverage:
Intraabdominal and female pelvic infections
• Synergism: enterococcal endocarditis
• Preventing Resistance: TB

44. COMBINATION ANTIMICROBIAL
THERAPY
• The combination of two or more antibiotics
can result in antagonistic effects
• Increased cost
• Increased drug toxicity

45. General Guidelines To use Antibiotics
• Start antibiotics if there is evidence of
infection
• In starting antibiotics it is better not to use any
of the new ones,if you are not familiar with
their use
• Antibiotics should not be started in response
to patients pressure

46. General Guidelines To use Antibiotics
• No antibiotics- viral infections like Common
cold or diarrhea to satisfy the patients
• Antibiotics when used given for sufficient
long period, Inadequate duration and dose of
therapy should be discouraged
• Do not change an antibiotic before giving the
current antibiotic a fair trial

47. General Guidelines To use Antibiotics
• Cost effectiveness of therapy should be
considered especially while changing the
antibiotics, calculating for the full duration of
treatment.
• Wherever possible culture sensitivity of the
sample should be sent before the antibiotic
treatment started

48. General Guidelines To use Antibiotics
• Avoid using too many antimicrobials and drug
combinations as it encourages poor diagnosis and
its mismanagement
• Avoid use of multiple antibiotics, except where it
is indicate-TB
• Acquire adequate and unbiased information
about a limited number of antibiotics of proven
efficacy and be familiar with their side effects

49. General Guidelines To use Antibiotics
• Get a full drug history and history of allergy to the
chosen antibiotics, before starting the antibiotics
• Where possible and indicated,e.g.poor response
to therapy, repeat culture sensitivity
• Avoid the use of topical
antimicrobials,prophylactic antimicrobials and
antimicrobial combinations

50. THANK U !!