Antibiotic resistance is a Global Threat, Antibiotic prescription practices are varied and rationalization of usage can find a way to reduce! Understanding ideal prescription practice for antibiotics shall help clinician improvise outcomes.

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Rational Use of Antibiotics
Parthiv Mehta
Pulmonologist - Intensivist
Ahmedabad

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Acknowledgements

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Acknowledgements..
TEAM Pulmocare

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Increasing Diseases…

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Background :
Antibiotic Resistance
• Since 1998, spread of concerns on
resistance
• Loss of once-good and cheap
treatment for infections
• Increasing mortality in ICU set up
for infection resistance to first line
empirical therapy.
• Increase in the cost of treatment
and hospital stay.
• Emerging pathogens

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Background :
Irrational Use of Medicines
Examples of irrational use of medicines:
• No drug needed e.g. unnecessary & ineffective
antimicrobials or anti-diarrhoeals given instead of Oral
Rehydration Solution.
• Unsafe drugs e.g. Analgin (Dipyrone) banned in most
developed countries, is used in many developing countries.
• Under use of available effective drugs e.g. ORS not used
effectively.
• Ineffective drugs & drugs with doubtful efficacy e.g.
unnecessary excessive use of tonics & multivitamin
preparations
• Incorrect use of drugs e.g. overuse of Injections
Drugs used in unwarranted situations
Dr. Parthiv Mehta

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Background :
Irrational Use of Antibiotics
• Overuse, under-use, and misuse of medicines
- antimicrobials remains a world wide hazard.
• Over 15 billion injections per year,
– Half unsterile, many unneeded,
– 25-75% of antibiotic prescriptions inappropriate,
– 50% of people worldwide fail to take medicines
correctly
(Health quick 2003)
Dr. Parthiv Mehta

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Background :
Irrational Use of Antibiotics
• Misuse and overuse of antibiotics, overuse
and unsafe use of injections has been
reported in Southeast Asian countries.
– All over the world 30-60% of PHC patients receive
antibiotics which may be twice as high as it may
be clinically required.
– Large number of viral URTI and diarrhoea are
treated with antibiotics in the world and
inappropriate use is also being used in teaching
hospitals all over the world.
Dr. Parthiv Mehta

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Background :
Irrational Use of Antibiotics

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Antibiotics and Fluoroquinolones
are ore First Love

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S 98250 31615
Clinician’s Problems….
• Too many formulations
• Repeated “DISTRACTIONS”
• Standard guideline
• Updates too little
• BUGS are too smart
Excuses?

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Rational – Meaning..
Dr. Parthiv Mehta

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Antibiotic - Meaning
Dr. Parthiv Mehta

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Use - Meaning
Dr. Parthiv Mehta

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Rational Use of Antibiotic..
• Sensible
• Safe
• Sincere
Effort to control Microbial Infection
HOW DO I DO IT?
Dr. Parthiv Mehta

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Rational Use of Antibiotic..
Checklist
 Indicated?
 Appropriately identified?
 What organism?
 Which agent?
 Combination?
 Host factor?
 Route of administration?
 Dose?
 Modification?
 Duration?
Dr. Parthiv Mehta

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Rational Use of Antibiotic..
Checklist
 Indicated?
 Appropriately identified?
 What organism?
 Which agent?
 Combination?
 Host factor?
 Route of administration?
 Dose?
 Modification?
 Duration?
Dr. Parthiv Mehta

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Problems with Antibiotic Usage: As Common as Common Cold
Indicated?
Anti
Biotic

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Indicated?
Dr. Parthiv Mehta

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Antibiotics -Indicated only when…
• Proven infection : Empiric / Definitive
• Higher chances of acquiring infection :
Prophylaxis
Is it Bacterial Infection?
Dr. Parthiv Mehta

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Antimicrobial therapy - Goal
• Rapid eradication of infecting
organism
– Empiric coverage of common pathogens
 Culture
Selective coverage for specific pathogens
• Avoid major organ systemic side
effects
Unfortunately, goal is OUR safety
Dr. Parthiv Mehta

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Indicated?
Dr. Parthiv Mehta

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Vicious cycle of Antibiotic Resistances
Excessive/inappropriate
antibiotic use
Failure of
antibiotic
therapy
Antibiotic
resistance
PROPHYLACTIC
EMPIRICAL
Dr. Parthiv Mehta

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Conditions in which AB Prophylaxis
had been proved to be of value
Conditions Antimicrobial agents
GAS in children with Rheumatic Fever Penicillins
Endocarditis in children with CHD Amoxicillin
GBS in neonates Penicillin or Ampicillin
Gonococcal Ophthalmia in neonates Silver nitrate or Erythromycin
TB in household contacts Rifampicin + Isoniazid
Recurrent UTI Trimethoprim-Sulfamethoxazole
Sepsis in Asplenia Penicillin
PCP in transplants recipients or AIDS Trimethoprim-Sulfamethoxazole

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Rational Use of Antibiotic..
Checklist
 Indicated?
 Appropriately identified?
 What organism?
 Which agent?
 Combination?
 Host factor?
 Route of administration?
 Dose?
 Modification?
 Duration?
98250 31615

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Identification of
Infecting Organism
• Gram stain
– Buffy coat -- phagocytosed bact. or fungi
– stool -- sheets of G(+) cocci in Staph.
enterocolitis; PMN in bact. enterocolitis
• Antigen detection-- latex agglutination
• PCR
• Culture
• Bacteriological statistics
Dr. Parthiv Mehta

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Determining Anti-microbial
Susceptibility - Culture
• Disk diffusion
– Simple, cheap
• E-test
– Diffusion of continuous conc. gradient from plastic
strip into agar medium
• Minimal inhibitory conc. (MIC)
– no visible growth
• Minimal bactericidal conc. (MBC)
– >99.9% suppression after subculture to agar
Local susceptibility pattern - Antibiogram
Unfortunately,
To Culture is NOT OUR CULTURE
Dr. Parthiv Mehta

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Rational Use of Antibiotic..
Checklist
 Indicated?
 Appropriately identified?
 What organism?
 Which agent?
 Combination?
 Host factor?
 Route of administration?
 Dose?
 Modification?
 Duration?
Dr. Parthiv Mehta

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Common pathogens
• UTI
• Catheter
• Cellulitis & STI
• Septic arthritis
• CAP
-E. coli, Klebsiella, Proteus
-S. aureus, S. epidermidis
-S. aureus, Streptococci
-S. aureus, Group B Strep
- Pneumococcus, H. Influenza
Dr. Parthiv Mehta

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Rational Use of Antibiotic..
Checklist
 Indicated?
 Appropriately identified?
 What organism?
 Which agent?
 Combination?
 Host factor?
 Route of administration?
 Dose?
 Modification?
 Duration?
Dr. Parthiv Mehta

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Antimicrobial agents of choice
Community-Acquired Pneumonia
Age Drug of choice Pathogens
<2m Ampicillin + Aminoglycoside GBS, E. coli
2m-2y Amoxicillin + Clavulanic Acid Pneumococcus
2º cephalosporins Haemophilus influenzae
2y-5y Amoxicillin + Clavulanic Acid Pneumococcus, H. influenzae
2º cephalosporins Mycoplasma, Chlamydia
± Macrolides
5y- 18y Penicillin  Macrolides Pneumococcus
Mycoplasma
>18y 3º Cephalosporins Pneumococcus
 Macrolides Mycoplasma

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Antimicrobial agents of choice
Bacterial Meningitis
Age Pathogens Drug of choice
Neonate, early-onset GBS, L. monocytogenes,
enterococci,
GNB
Ampicillin and
cefotaxime
Aminoglycoside
Neonate, late-onset S. aureus, GNB,
P. aeruginosa
Oxacillin, Vanco and
Ceftazidime
1-3 months infant All of above Ampicillin and
Cefotaxime
Child N. meningitides,
S. pneumoniae,
H. influenzae
Ceftriaxone or
Cefotaxime

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Antimicrobial agents of choice
Pathogen Specific
• Staph. aureus
• Gr. -Streptococci
• Gr. -Streptococci
(Viridans)
• Pneumococcus
-Oxacillin, Vanco, LNZ
-Penicillin
-Penicillin
-Penicillin, Cefotaxime,
Vanco
Dr. Parthiv Mehta

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Antimicrobial agents of choice
Pathogen Specific
• Neisseria
• E. coli
• H. influenzae
• Kleb. pneumoniae
- Penicillin
- Carbapenems,
3rd cephalosporins
- Amoxicillin + Clav.,
3rd cephalosporin
- 3rd cephalosporin
Dr. Parthiv Mehta

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Antimicrobial agents of choice
Pathogen Specific
• P. aeruginosa
• Salmonella
• Acinetobacter
• Brucella
• Enterobacter
• Proteus
- Ticarcillin + Genta,
Ceftazidime
- Ceftriaxone,
Fluoroquinolone
- Imipenem
- Doxycycline
- Imipenem
- Ampicillin, 3rd Ceph.
Dr. Parthiv Mehta

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Fluoroquinolones - WARNING
• Another one for Fluoroquinolones!!
Dr. Parthiv Mehta

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Fluoroquinolones - WARNING

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Fluoroquinolones - WARNING
• Paul Auwaerter – Professor, Infectious
Diseases at Johns Hopkins University School of
Medicine.
– US Food and Drug Administration (FDA) recently
announced[1] upgrade of its package warnings on
fluoroquinolones. To include instructions that they
should not be used for routine respiratory tract
infections or uncomplicated urinary tract
infections unless there is no suitable alternative
agent.
Dr. Parthiv Mehta

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Rational Use of Antibiotic..
Checklist
 Indicated?
 Appropriately identified?
 What organism?
 Which agent?
 Combination?
 Host factor?
 Route of administration?
 Dose?
 Modification?
 Duration?
Dr. Parthiv Mehta

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Irrational Fixed Dose Combinations
Dr. Parthiv Mehta

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Irrational Fixed Dose Combinations
• For instance, there are at least 100 brands of
combination of norfloxacin or ciprofloxacin
(antibiotics) with metronidazole or tinidazole
(anti-diarrhoeal drugs) in the Indian market.
• The Indian Journal of Pharmacology had in 2006
reported that these combinations were
irrational because a patient suffers only from one
type of diarrhoea and using this combination
adds to costs, adverse effects and may encourage
drug resistance. But these combinations are still
sold in the market.
Dr. Parthiv Mehta

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Irrational Fixed Dose Combinations
• The Indian pharmaceutical market has about
2,000 brands of fixed-dose combinations in
the antibiotics segment alone.
• Of these, at least 1,800 brands are irrational
in terms of wrong or unnecessary
composition of multiple drugs, according to
market data compiled by CDSCO for a
proposed ban on such combination brands
manufactured by both small and large drug
makers.
Dr. Parthiv Mehta

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Indications for combination
• Need for Broad spectrum
– Neutropenia, severe sepsis
• Multiple organisms
• Preventing the emergence
of resistance
• Synergism
Dr. Parthiv Mehta

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Indications for combination
Synergism
• Penicillin and Gentamicin
– Viridans Streptococci and enterococci
• Ticarcillin and Aminoglycosides
– Pseudomonas
• Cephalosporins and Aminoglycosides
– K. pneumoniae
• Penicillin and Clindamycin
– Toxic shock syndrome
Dr. Parthiv Mehta

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Disadvantages of Combination
Antagonism
• Penicillin and Tetracycline
– Meningitis
• Chloramphenicol and Aminoglycoside
Dr. Parthiv Mehta

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Disadvantages of Combination

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Rational Use of Antibiotic..
Checklist
 Indicated?
 Appropriately identified?
 What organism?
 Which agent?
 Combination?
 Host factor?
 Route of administration?
 Dose?
 Modification?
 Duration?
Dr. Parthiv Mehta

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Host Factors
H/O previous usage
H/O adverse reactions to antibiotics
• Chloramphenicol -- poor gluc-uronylation in
neonates --> Gray syndrome (shock, collapse,
death)
• Sulfonamide compete albumin binding with
bilirubin --> Kernicterus
• Tetracycline bind developing bone and tooth -->
purplish or brown Discoloration of teeth, Enamel
Hypoplasia
Dr. Parthiv Mehta

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Host Factors
Liver & Renal function
• Tetracycline contraindicated in impaired
renal function except Doxycycline,
Minocycline
• Aminoglycoside in renal impairment
Consideration of Creatinine Clearance is
MUST
Dr. Parthiv Mehta

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Host Factors
Sites of infection
• Dose of choice of antibiotics
– Local conc. > MIC
• Vegetation, bone, devitalized tissue
– Inaccessible to antibiotic
– High dose, prolonged treatment
• Purulent material
– Inactivate Aminoglycoside, Polymyxin
Dr. Parthiv Mehta

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Host Factors
Sites of infection
• CNS penetration
– Good
• Rifampicin, chloramphenicol, trimethoprim,
sulfamethoxazole
– Good when Meninges inflammed
• Penicillin G, Ampicillin, Cefotaxime, Ceftriaxone,
Ceftazidime, Imipenem, Meropenem
– Unreliable
• Amikacin, Gentamicin, Tobramycin, Vancomycin
Dr. Parthiv Mehta

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Host Factors
Sites of infection
• Low local oxygen tension
– O2 required for transport of Aminoglycoside into
bacterial cell
• Low local pH (abscess, lysosome)
– Poor activity of Aminoglycoside
• Foreign body
– Protect bacteria
Dr. Parthiv Mehta

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Host Factors
Pregnancy and nursing
• All antibiotics cross the placenta in varying
degree, appear in breast milk
• Safe
– Penicillins, Cephalosporins, Macrolide
• Teratogenic
– Metronidazole, Ticarcillin
• Higher dose needed
Dr. Parthiv Mehta

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Rational Use of Antibiotic..
Checklist
 Indicated?
 Appropriately identified?
 What organism?
 Which agent?
 Combination?
 Host factor?
 Route of administration?
 Dose?
 Modification?
 Duration?
Dr. Parthiv Mehta

58. R
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E
O
F
A
N
T
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B
I
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I
C
S 98250 31615
Route of Administration
• Oral or parenteral?
– Higher and consistent serum concentrations of
drugs are achieved by parenteral route
– Parenteral-oral
• Pneumonia, Pyelonephritis, Skeletal infection
• Push? Drip?
– Side effect  if infused too rapidly
• Aminoglycosides, cephalosporins, F.Q.
– Deteriorate of activity if kept long
• Penicillin, Amoxycillin + Clav
Inhaled AB has an important place

59. R
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A
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Dose
• Important aspects
– According to body weight
– Never to under dose for the fear of side
effects
Inadequate AB a GLOBAL issue
Dr. Parthiv Mehta

60. R
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N
A
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E
O
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Checklist
 Indicated?
 Appropriately identified?
 What organism?
 Which agent?
 Combination?
 Host factor?
 Route of administration?
 Dose?
 Modification?
 Duration?
Dr. Parthiv Mehta

61. R
A
T
I
O
N
A
L
U
S
E
O
F
A
N
T
I
B
I
O
T
I
C
S
Rational Use of Antibiotic..
Checklist
 Indicated?
 Appropriately identified?
 What organism?
 Which agent?
 Combination?
 Host factor?
 Route of administration?
 Dose?
 Modification?
 Duration?
Dr. Parthiv Mehta

62. R
A
T
I
O
N
A
L
U
S
E
O
F
A
N
T
I
B
I
O
T
I
C
S
Modifications
• According to renal & Hepatic Functions
– Aminoglycosides
– Carbapenams
– Rifampicin
• According to severity
– Severe sepsis, ARDS
Dr. Parthiv Mehta

63. R
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Duration
• According to indication
– LRTI : 5 – 7 - 14 days
– URTI : 3 – 5 - 7 days
– UTI : 5 – 7 – 14 days
– S & STI : 7 – 14 – 28 days
• Must to use According labelled directive
and guidelines
– Aminoglycosides : 5-7 days
– Cephalosporins: 7-14 days
– Macrolides: 3 – 5 – 7 days
– MOX/Clav: 7-10 days

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What to do?

65. R
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Patients and Antibiotics

66. R
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Selection of Antibacterial Therapy…
CAREFUL CONSIDERATION
• Site of infection
• Age
• Renal/hepatic fn
• Immune status
• Pregnancy
• Previous antibacterial
experience
• Genetic / Metabolic
abnormalities
• Gram
Staining
• Antibiotic
Resistance

67. R
A
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A
N
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REMEMBER….Checklist
 Indicated?
 Appropriately cultured?
 What organism?
 Which agent?
 Combination?
 Host factor?
 Route of administration?
 Dose?
 Modification?
 Duration?
Dr. Parthiv Mehta

68. R
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REMEMBER….Checklist
 Indicated?
 Appropriately cultured?
 What organism?
 Which agent?
 Combination?
 Host factor?
 Route of administration?
 Dose?
 Modification?
 Duration?
Dr. Parthiv Mehta

69. R
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N
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E
O
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A
N
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S
Optimizing Usage and
Antibiotic Resistance
• Where do we stand?
Dr. Parthiv Mehta

70. R
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Optimization of Antibiotic Use
Dr. Parthiv Mehta

71. R
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Raising Awareness
Dr. Parthiv Mehta

72. R
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Training of Professionals
Dr. Parthiv Mehta

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Multi-sector Involvement
Dr. Parthiv Mehta

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The determinants of irrational
antibiotic use
• Very short consultation time - does not allow
proper diagnosis
• Prescription of antibiotics for non-bacterial
infections: Clinicians prescribe antibiotics to
patients with non-bacterial infections, a practice
that has important repercussions
• Polypharmacy - Too many medicines are
prescribed per patient (Lack of trust in or delayed
lab results, fear of clinical failure)
• Antibiotic injections - are used where oral
formulations would be more appropriate
Dr. Parthiv Mehta

75. R
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A
N
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S
The determinants of irrational
antibiotic use
• Prolonged empiric antimicrobial treatment
without clear evidence of infection
• Failure to narrow antimicrobial therapy when
a causative organism is identified
• Prescriptions do not follow clinical guidelines
• Patients self-medicate inappropriately
• Patients do not adhere to prescribed
treatment
Dr. Parthiv Mehta

76. R
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Optimization of Antibiotic Use
• Evidence based prescribing through effective,
rapid, low-cost diagnostic tools are needed to
optimize use of antimicrobials.
• In addition to better prescribing practices, the
global community must restrict inappropriate
and unregulated use / dispensing of
antimicrobial agents.
Dr. Parthiv Mehta

77. R
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Optimization of Antibiotic Use
• Stronger compliance to antibiotic treatment
regimes, quality assurance measures to
prevent consumption of substandard
medications, and restrictions of non-
therapeutic uses of antibiotics will provide a
foundation for antimicrobial stewardship.
• Regulations for antibiotic distribution,
quality, and use could preserve the
effectiveness of antibiotics as a public good.
Dr. Parthiv Mehta

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Prevention of Resistance..

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My requests…
• Understand and Justify Reason of USING BIG GUNS!!!
• Improving it can SPARE BIG GUNS!!!!!
• Practice Simple ways to AVOID MURDUR of
ANTIBIOTICS!!!!!
Dr. Parthiv Mehta

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S Dr. Parthiv Mehta
My requests…

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82. R
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My requests…Ask yourself
Dr. Parthiv Mehta

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Thank
you…for
Saving Me…

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Let us be Friends…for Better..

85. R
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Arise, Awake..
Stop Not Till the Goal is Reached..