This document discusses principles of antibiotic therapy and treatment of infections. It covers: - Factors that influence infection like the host, environment, and causative agent - Principles of antibiotic prescribing including obtaining cultures, using the narrowest effective spectrum, and conforming to treatment guidelines - The growing problem of antibiotic resistance due to overuse and misuse of antibiotics - Examples of optimal treatment for different types of infections like community-acquired pneumonia, bone infections, and skin/soft tissue infections

1. PRINCIPLES OF ANTIBIOTIC
THERAPY
Dr jigar mehta

2. Causative
agent
host
environment
INFECTION/
DISEASE
•Age
•prior illness
•level of
nutrition
•pregnancy
•coexisting
illness,immunoc
ompromised
state
•Community acquired:
environment,geography
•Hospital acquired
Evolution of variety of
antiobiotics/AMAs to
kill/supress the causative
agents.
The problem of antibiotic
resistance

3. Principles of Antibiotic prescribing
• Fever may not always indicate infection
• Community or Hospital acquired
• Status of host
• Site of infection
• Document reason for starting antibiotics
• Obtain microbiological specimens, ask for early Gram stain
reports
• Gram +ve, Gram -ve, anerobes, fungus?
• Use the narrowest spectrum with imp. exceptions
• Conform to established treatment guidelines
• Use newer antibiotics when absolutely necessary and only
when indicated

4. Principles of Antibiotic prescribing…….
Fever may not always indicate infection
• Infections- bacterial,viral, fungal,protozoal
• collagen vascular diseases
• malignancies
• a stressful event-
– CVA, AMI, PE
– Post operative surgical stress
– thrombophlebitis
– hemorrhage- GI,Brain
• others-
– LCF, CAH, thyroiditis, FMF
– Drug fever, factitious fever

5. Principles of Antibiotic prescribing
• Fever may not always indicate infection
• Community or Hospital acquired
• Status of host
• Site of infection
• Document reason for starting antibiotics
• Obtain microbiological specimens, ask for early Gram stain
reports
• Gram +ve, Gram -ve, anerobes, fungus?
• Use the narrowest spectrum with imp. exceptions
• Conform to established treatment guidelines
• Use newer antibiotics when absolutely necessary and only
when indicated

6. Principles of Antibiotic prescribing……. Community or Hospital acquired
Epidemiology of ICU Nis.
Infection site
FOLEYS CATHETER
(95%)
Main Nis.
UTI 31%
Pathogen distributn
Fungal:candida
MECHANICAL
VENTILATION
(86%)
Pneumonia 27% G-ve aerobic 64%
Staphylococci 20%
CVP (87%) Blood stream
infection (19%)
CoNS 36%
Enterococci (16%
Staph aureus13%
Fungus 12%

7. Principles of Antibiotic prescribing
• Fever may not always indicate infection
• Community or Hospital acquired
• Status of host
• Site of infection
• Document reason for starting antibiotics
• Obtain microbiological specimens, ask for early Gram stain
reports
• Gram +ve, Gram -ve, anerobes, fungus?
• Use the narrowest spectrum with imp. exceptions
• Conform to established treatment guidelines
• Use newer antibiotics when absolutely necessary and only
when indicated

8. Principles of Antibiotic prescribing…….
Status of host
• Immunocompromised patient
– Severe underlying illness
– Malnutrition
– DM
– Repeated hospitalisations
– HIV, others
• Use of devices
Such patients are colonized with resistant
organisms due to prior antibiotic use

9. Principles of Antibiotic prescribing
• Fever may not always indicate infection
• Community or Hospital acquired
• Status of host
• Site of infection
• Document reason for starting antibiotics
• Obtain microbiological specimens, ask for early Gram stain
reports
• Gram +ve, Gram -ve, anerobes, fungus?
• Use the narrowest spectrum with imp. exceptions
• Conform to established treatment guidelines
• Use newer antibiotics when absolutely necessary and only
when indicated

10. • Use newer antibiotics when absolutely necessary
and only when indicated
WHY?
BECAUSE OF THE GROWING PROBLEM OF
ANTIBIOTIC RESISTANCE
Principles of Antibiotic
prescribing

11. “we know everything about antibiotics except
how much to give” Maxwell Finland
(The 500 mg 6hrly era)
Bacterial Killing is a function of drug
concentration and time of exposure
Concentration independent Killing
Concentration dependant Killing
Optimal Dose

13. Time dependant killing
• B lactams
• Clindamycin
Dose more frequently rather than increasing single
dose (or continuous infusion)
Ceftriaxone 1 gm as good as higher dose for most
community acquired respiratory, uti, abdominal
infections

14. Optimal Duration
• Most antibiotics are being given for far
too long
• Stop antimicrobial treatment:
• -When infection is cured.
(if patient is afebrile & well for 48hrs)
• -When cultures are negative and infection is
unlikely.

15. OPTIMAL SELECTION
Presumed Site of infection
(e.g. respiratory tract, urinary tract, a
subdiaphragmatic collection, or whatever)
address any surgically remediable
pathology right away

16. Community Acquired v/s hospital
acquired
Community acquired usually sensitive (even
if severe)
Hospital acquired likely to be caused by
resistant bugs (even if mild)
e.g. pneumonia, abdominal infections, skin & soft
tissue infections

17. Optimal antibiotic Selection
Always culture
Start antibiotics immediately
Hit Hard & high
De escalate

18. History
Penicillin - first antibiotic
1929, Alexander Flemming
late ‘40’s and early 50”s (golden
age of discovery)
streptomycin,
chloramphenicol,
tetracycline,sulfonamides
80% staph aureus resistant
PRSP
1953 - Shigella outbreak in Japan
1950’s - Mycobacterium
tuberculosis largely resistant to
streptomycin

19. IT IS A GLOBAL
PROBLEM
THE BUGS HAVE BEEN THERE EVER SINCE AND
THEY ARE GETTING CLEVERER BY THE MINUTE

20. Factors in Antimicrobial Resistance in
hospitalised patients
Cross transmission
Lack of Asepsis
Unwashed hands
Care of devices
Level of crowding
Transfer of critically ill patients from other facilities
Host defense
Immunocompromised patient
Severe underlying illness
Malnutrition
DM
Repeated hospitalisations
HIV, others
Use of devices
Antimicrobial use
ANTIMICROBIAL
RESISTANCE

21. Antimicrobial Use
• Direct, consistent correlation between antibiotic
use and resistance patterns
• development of resistance is correlated with level
of antibiotic use
– overuse has increased the incidence of and selection
for resistance-conferring mutations
– McGowan et al Rev. Inf. Dis 1983
– Ballow C.H., Schentag J.J. - National Nosocomial Resistance
Surveillance Group 1992
– Fridkin S.K. et al Antimicrobial Resistance in ICU’s, Clinics in
Chest Medicine 1999

22. Evolution of Antimicrobial Resistance
in Gram-Positive Cocci
S. aureus
Penicillin
[1940s] Penicillin-resistant
S. aureus
Methicillin
[1960s] Methicillin-resistant
S. aureus (MRSA)
Vancomycin-resistant
enterococcus (VRE)
Vancomycin
[1997]
Vancomycin
(glycopeptide)
intermediate-resistant
S. aureus
Vancomycin-
resistant
S. aureus
Ciprofloxacin
1987
[2002]
Adapted from: CDC. Prevent Antimicrobial Resistance: A Campaign for Clinicians. April 2002.

23. What should we do?
Prevent overuse /misuse
Optimize use of antimicrobial
agents
Prevent cross-transmission

24. Examples of overuse/misuse
“DOES MY PATIENT NEED AN
ANTIBIOTIC?”
• prophylactic use after elective surgery
• empiric use (no known etiologic agent)
• increased use of broad spectrum agents
• antibiotics in animal feeds
• pediatric use for viral infections
• patients who do not complete course
(TB,AIDS)

25. Prevent cross transmission
• Hand washing
• Gloves
• Gowns
• Face masks
• Patient isolation or cohorting
• Traffic control

26. Other Strategies
• New Drugs
– currently about 100 antibiotics on market
– three main mechanisms of action
• inhibition of protein synthesis
• inhibition of cell wall synthesis/maintenance
• inhibition of DNA replication

27. New Antibiotics
• Cell Wall inhibitors - based on beta lactam skeleton
– carbapenems - broad spectrum
• imipenem usually given with cilastatin (prevents degradation
by renal enzymes)
• meropenem - enhaced anti-Pseudomonas activity
• ertapenem
– monobactams - beta lactamase stable
• Aztreonam
• Moxalactam

28. New Antibiotics
• Betalactamase inhibitors
– clavulanate
– sulbactam
– tazobactam
• piperacillin/tazobactam
• ticarcillin/clavulanate
• do not penetrate meninges thus may not
potentiate the action of extended spectrum
penicillins.
• Fourth generation cephalosporins

29. New Antibiotics
• New Quinolones
– gatifloxacin
– moxifloxacin
– trovafloxacin
– gemifloxacin
– sitafloxacin
– Clinafloxacin
• isolates of S.pneumoniae less resistant to these as
compared to penicillin,amox-clav, cefuroxime,
erythromycin
• very effective against L.pneumophilia,M. catarrhalis, H
influenzae.

30. New Antibiotics-
enhanced activity against GPC
Sr.No Class examples activity versus
VRE MRSA PRSP
1 GLYCOPEPTIDES BI- 397,
LY333328
+ + +
2 EVERNINOMICINS Ziracin + + +
3 LIPOPEPTIDES daptomycin + + +
4 OXAZOLIDINONES linezolid + + +
5 STREPTOGRANINS quinupristin/
dalfopristin
+ + +
6

31. 3rd Gen Cephalosporins
Enterococcus
Klebsiella sp E
coli/enterobacteriaceae with
ESBL’s
Vancomycin
Meropenem
Imipenem/Cilastatin
Acinetobacter Fungi, Yeast
VRE
Overuse
Resistance
Overgrowth
Escalating drug therapy and its hazards
Piperacillin/tazobactam
ticarcillin/clavulanate

32. Principles of Antibiotic prescribing
• Fever may not always indicate infection
• Community or Hospital acquired
• Status of host
• Site of infection
• Document reason for starting antibiotics
• Obtain microbiological specimens, ask for early Gram stain
reports
• Gram +ve, Gram -ve, anerobes, fungus?
• Use the narrowest spectrum with imp. exceptions
• Conform to established treatment guidelines
• Use newer antibiotics when absolutely necessary and only
when indicated

33. Skin, soft tissue infections
• Amoxycillin/clavulanate +
cefoxitin/cloxacillin or
• Clinda or Metro + amoxy/amoxycillin-
clavulanate + Genta
• * Penicillin treatment alone carries 30 -
50% mortality

34. Bone infections
• Oxacillin, nafcillin, cephalosporin like
cefpirome or glycopeptide like vanco` or
teicoplanin to cover Staph aureus well
• If Gram -ve org are suspected - 3rd gen
cephalosporin or aminoglycoside or
fluoroquinolone is added
• For P. aeruginosa :Aminglycoside like
Tobramycin + ticarcillin-clavulanate
/ceftazidime /fluoroquinolone
• Duration of therapy - 6 weeks

35. COMMUNITY ACQUIRED PNEUMONIAS
Out Patients: No Cardiopulmonary Disease,
No Modifying Factors
Advanced generation
macrolide:azithromycin /
clarithromycin
Or
Doxycycline
•Strep. Pneumoniae
•M.Pneumoniae
•Chlamydia pneumoniae
•Hemophilus influenzae
•Respiratory viruses
•Miscellaneous
•Legionella spp
Therapy
Organism

36. Out Patients: With Cardiopulmonary Disease /
Modifying Factors
Β-Lactam (oral cefpodoxime,
cefuroxime,high-dose amoxicillin/clavulanate;
or parenteral ceftriaxone followed by oral
cefpodoxime)
+
Macrolide / Doxyclcline
Or
Antipneumococcal fluroquinolones
(used alone)
Add Clindamycin/Metronidazole
when anaerobes are suspected
•Strep. Pneumoniae(including PRSP)
•M.Pneumoniae
•Chlamydia pneumoniae
•Mixed infection (bacteria plus atyrpical
pathogen or virus)
•Hemophilus influenzae
•Enteric Gram Negatives
•Anaerobes
• Respiratory viruses
•Miscellaneous
•Legionella spp
Therapy
Organism

37. In Patients: No Cardiopulmonary Disease /
Modifying Factors
I.V Azithromycin alone
If macrolide allergic or intolerant:
Doxycycline and a β-lactam
Or
Monotherpay with an
antipneumococcal fluroquinolone
•Strep. Pneumoniae
•Hemophilus influenzae
•M.Pneumoniae
•Chlamydia pneumoniae
•Mixed infection (bacteria plus atyrpical
pathogen)
•Viruses
•Legionella spp
•M.Tuberculosis
•Endemic fungi
Therapy
Organism

38. In Patients: With Cardiopulmonary Disease /
Modifying Factors
I.V Β-Lactam (cefotaxime,
ceftriaxone, amox-clav)
Plus
I.V or oral Macrolide / Doxyclcline
Or
I.V Antipneumococcal
fluroquinolones alone
Add Clindamycin/Metronidazole
when anaerobes are suspected
•Strep. Pneumoniae(including DRSP)
•Hemophilus influenzae
•M.Pneumoniae
•Chlamydia pneumoniae
•Mixed infection (bacteria plus atyrpical
pathogen)
•Enteric Gram Negatives
•Aspiration (Anaerobes)
•Viruses
•Staph
•Legionella spp
Therapy
Organism

39. Urinary infections
• Acute uncomplicated cystitis-
– cotrimoxazole, norflox/ciplox/oflox
• acute urethritis-chlamydial
– doxycycline
• Complicated urinary infection requires
– ampi/sulbactam +/- aminoglycoside
– 3rd gen cephalosporin like ceftazidime/ cefoperazone
– cefoperazone/sulbactam
– piperacillin/tazobactam or ticarcillin/clavulanate
• Prolonged duration of therapy usually required 7-
21 days

40. CNS infections
• Meningitis
– <1month - Ampi, cefotaxime
– 4 -12 weeks - Ampi + 3rd gen ceph.
– 3mths - 6yrs - 3rd gen ceph + Vanco
– young adult - 3rd gen ceph Cefotaxime or
ceftriaxone.
– >50yrs - Ampi +3rd gen ceph +/- Vanco
– Postneurosurgical - Vanco + ceftazidime+/-
intrathecal aminoglycosides +/- rifampin

41. Sepsis of unkown origin
• Broad spectrum cover
• HIT HARD HIT FAST especially severe
sepsis with septicemic shock
• Is host immunocompromised?
• What prior antibiotics has he received?
• Where was he admitted?-does he have a
nosocomial infection
• How ill is the patient?

42. Immunocompromised/Septic host
• III/IV gen cephalosporin + Vanco/linezolid +Metro
+Antifungal or any other broad spectrum combn
• Specific situation may require specific workup and
specific drugs

43. Conclusion
• Fever may not always indicate infection
• The interaction between host, agent and environment must
be understood and targeted in controlling disease
• Resistance to antimicrobials is currently and will continue to
be a problem
• Have an antibiotic policy
– To provide the most effective treatment for the individual
patient
– To advise on rational prescribing
– To limit the use of prophylactic antibiotics
– To delay the emergence of resistance
– To minimise adverse events
– To maintain a cost effective strategy