Rational use of antibiotics & problem of antibiotic resistense

1. Rational use of antibiotics
&
Problem of Antibiotic Resistance
Dr. Virendra Kumar Gupta
MD Pediatrics
Assistant Professor
Department of pediatric Gastroentero-Hepatology
& Liver Transplantation
NIMS Medical College & Hospital , Jaipur

2. We cannot outrun bacteria. So, we
must stop creating selective pressure
on them.
unnecessary
use of antibiotics
STOP
Bacteria/
Microbes
Picture source: http://www.geology.wisc.edu/homepages/g100s2/public_html/Geologic_Time/Time_Clock.gif

3. In his 1945 Nobel Prize lecture, Fleming himself warned of
the danger of resistance –
“It is not difficult to make microbes resistant to
penicillin in the laboratory by exposing them to
concentrations not sufficient to kill them, and the
same thing has occasionally happened in the body…
…and by exposing his microbes to non-lethal
quantities of the drug make them resistant.”
History
Nobel Lecture, December 11, 1945
Sir Alexander Fleming
The Nobel Prize in Physiology or Medicine 1945

4. Timeline of Antibiotic Resistance

6. Antibiotic resistance & Global warming
Picture source: http://ale1980italy.wordpress.com/
Similarities:
• Burning issue but well-
tolerated (no sense of
urgency)
• Everybody’s matters
• Effects on mankind
Difference:
Unlike the global
warming, antibiotic
resistance is not well-
recognized among
outsiders.

8. Why Rational Antibiotic Therapy ?
• Better care of patients.
• Combating antimicrobial resistance.
• Prevent misuse of antibiotics.
• Reduce cost of treatment.

9. Antibiotic Resistance
Defined as micro-organisms that are not
inhibited by usually achievable systemic
concentration of an antimicrobial agent with
normal dosage schedule and / or fall in the
minimum inhibitory concentration (MIC)
range.
Antibiotic Resistance (DR)
= MIC / MCC > Toxic Plasma Concentration

11. Myths of Antibiotic Resistance
1. Drugs (antibiotics) cause organisms
antibiotic resistant.
2. Antibiotic resistant organisms are
more virulent

12. Truth
• Antibiotics select out the resistant strain
• Faulty use of antibiotics or widespread use of
antibiotics increases the probability of such
selection.
• Antibiotic resistant strains appear to be more
virulent because we cannot kill them or stop
their growth.

13. Factors of Antibiotic Resistance
Environmental
Factors
Drug Related
Factors
Patient Related
Factors
Prescriber
Related Factors
Antibiotic
Resistance

15. Mechanism Antibiotic Resistance
Intrinsic (Natural) Acquired
Genetic Methods
Chromosomal Methods
Mutations
Extra chromosomal Methods
Plasmids

16. Bacterial Resistance
• Drug Resistance is a result of
exposure to drug
• It can be Genetic in origin
– Prevent Access to Site
• Decrease Influx
• Increase Efflux
– Inactivate Drug
– Change Site of Action
Does it matter?
http://www.sciam.com/1998/0398issue/0398levybox2.html

17. Perhaps it matters more than
we think it does
• Versatile Genetic Engineers
• Equalitarian and Social
Horizontal Transmission of Resistance
Genes among Species
http://www.sciam.com/1998/0398issue/0398levybox3.html
Gene Transfer in the Environment. Levy & Miller, 1989

18. Antibiotic Prescription
Antibiotic prescription should ideally
comprise of the following phases:
– Perception of need - is an antibiotic
necessary?
– Choice of antibiotic – which is the most
appropriate antibiotic?
– Choice of regimen : What dose, route,
frequency and duration are needed?
– Monitoring efficacy : is the antibiotic
effective?

19. What is our current practice?
Commonest reasons for antimicrobial drug use among
children in office practice are:
– Nonspecific upper respiratory tract infections
including Pharyngotonsillitis,
– Otitis media,
– Diarrhea
– Fever without focus
Most of the time these antimicrobials are often
unwarranted

20. Why do we err?
• Erroneous trust in our ability to treat all infections
(equated fever) with antibiotic prescription
– Many fevers are not due to infections
– Majority of infections seen in general practice are of viral
origin
• Antibiotics often prescribed in the belief that this will
prevent secondary bacterial infections
– No evidence except where chemoprophylaxis is advocated

21. Errors galore
• Using the “best” cover with the latest, potent, broad
spectrum higher generation antibiotic
– But it may not be the best and also not the safest too
• Injectables are used often than needed
• The duration of use is often not regulated
• Often upgrade or change the antibiotics for a patient
who continues to have fever despite antibiotic use
– Causes are many like incorrect diagnosis, incorrect dose
and/or route of administration or incorrect choice of drug,
phlebitis, antibiotic itself and not always due to antibiotic
resistance

22. ANTIBIOTIC PARADIGM
Excessive / inappropriate
antibiotic use
Failure of antibiotic
treatment
Antibiotic
resistance

23. The choice of antibiotics should largely be
determined by:
– source or focus of infection
– patient's age and immunologic status
– whether the infection is viral or bacterial
– is it community acquired or nosocomial
In office practice usual infections are community
acquired
Choice of Antibiotics

24. Case 1:
Apurva
Apurva, 1 yr 6 months old female,
• Brought with history of fever and cough with rhinorrhoea of
two days
• red eyes,
• diarrhea,
• No exanthema,
• cough ++
• H/o Similar case in
family
• O/E Throat congested
How will you manage?
Your thoughts……………

25. Clinically diagnosed :
Management:
Not needed
Viral URI – seasonal (pharyngotonsillitis)
General & Symptomatic Therapy
Antibiotics : ?

26. 41/2 year old Mehul - brought to your clinic with 2 days
history of high spiking fever and mild cough
From history and examination:
• Has no red eyes or rhinorrhea
• No exanthema
• Difficulty in swallowing,
• No history of similar case in the family
• He looks sick even when afebrile
2nd Case: Mehul

27. Mehul on examination……
• RR 28, HR 110
• perfusion and B.P normal
• Rt tonsil showed a purulent
discharge with inflammation of
both tonsils
• Bilateral tender cervical LN++
• Ear and Nose – Normal
• Other system examination –
normal
How will you manage?......

28. Apurva and Mehul – what difference?
Apurva
• Acute onset, Red eyes,
rhinorrhea, cough++, diarrhea
• No rashes
• Pharyngeal congestion but no or
scanty exudates and no cervical
lymphadenopathy
• Age less than 3 years
Most probably viral
Mehul
• Acute onset, throat pain, rapid
progression, very little
cough/cold
• Pharyngeal congestion more,
thick exudates or follicles,
purulent patchy lesions on
tonsils with tender enlarged LN
• Toxicity ++
• Age more than 3 years
Most probably bacterial

29. Viral vs Bacterial
Signs with good predictive values
– Presence of watery nasal discharge
– Absence of pharyngeal erythema
– Absence of tonsillar exudate or follicles
– Absence of tender lymphadenopathy
– Involvement of multiple systems
– Generalized maculopapular rashes
– H/o similar illness in family or community
Suggest Viral Pharyngotonsillitis
– More of these, better the predictability
– No single sign is definitive
– Age less than 3 years – more chance of viral

30. Etiology
Viral cause :
– Rhino virus (common cold) (60%),
– Enterovirus, Influenza virus, Para-influenza virus
– Adenovirus
– Special : HIV, Cytomegalovirus, Coxsackievirus, Herpes simplex,
Ebstein-barr virus, Bird flu?
Bacterial cause :
– Common - Group A ß-hemolytic streptococci (15-30% of age >3
years, <5% in age <3 yrs )
– Rare - C. diptheriae, Hemophilus influenzae, N. meningitides
– Special : Gonococcus,, Mycoplasma pneumoniae

31. In children with no Penicillin allergy
Antibiotic (route) (days) Children (< 30kg) Children ( > 30kg)
Penicillin V (Oral) (10d) 250 mg BID 500 mg BID
Amoxycillin (Oral) (10d) 40mg/kg/day
(Max 250 mg tid)
250 mg TID
Benzathine penicillin G (IM)
(single dose)
6 lakh Units 1.2 Million Units.
In children with Penicillin allergy (Non type 1)
Antibiotic ( route ) ( days) Children ( < 27 kg)
Erythromycin ethylsuccinate (oral) (10ds) 40-50 mg/kg/day TID
Azithromycin (oral ) ( 5days) 12 mg/kg OD
I generation Cephalosporin (oral) (10ds) Cephalexin/Cephadroxyl 25 to 30
mg/kg / 2nd gen cephalosporins*
in usual doses.
IInd Line: Clindamycin (oral) (10days) 10-20 mg / kg.
*early second generation

32. • 4 months later, Mehul is
back with fever, cough
and coryza. See his
throat
• Treating pediatrician
considers him to have
viral pharyngitis
DO YOU AGREE?
• HERPANGINA
Pharyngeal Erythema but not bacterial

33. Some more non-bacterial Pharyngeal
Inflammation

34. Case 3: Azhar
• Azhar, a 15 month otherwise healthy boy
had rhinorrhea, cough and fever of 1020F
for two days
• On day 3, he became fussy and woke up
crying multiple times at night
WHAT COULD BE WRONG?
HOW DOES ONE EVALUATE THIS CHILD ?

35. AZHAR HAS ACUTE OTITIS MEDIA
RIGHT EAR
On examination of Rt ear:
• Erythema
• Fluid
• Impaired mobility
• Acute symptoms
MANAGEMENT ?

36. Management AOM – Under 2 Yrs
• Analgesia
– Paracetamol in adequate doses as good as Ibuprofen
• Antibiotics in divided doses for 10 days
– Choice - first line Amoxycillin / Co-amoxyclav
– Second line
• Second generation cephalosporins e.g. Cefaclor,
cefuroxime.
• Co amoxyclav – if not used earlier
• Decongestants no role

37. • 10 month old jignesh, brought 2nd
December, 2006
• Illness 2 days
• Started with vomiting 6-7/day
• Fever
• Frequency of stool 12-15/day, watery, large
quantity
• On BF + Weaning diet
Case 4: Jignesh

38. • Ill look
• Depressed AF
• Dry skin and mucous membrane
• Sunken eyeballs
• Rapid, low volume pulse
How will you manage?
Jignesh....

39. • Winter season
• Infant
• Started with vomiting, mild fever and then
watery stool
• Think of Viral (Rota Virus) diarrhea
• Ask, Is he bottle fed?
What next?
Jignesh...

40. Child with Acute Diarrhea
Watery Diarrhea
without blood in stool
Diarrhea with
macroscopic blood in stool
in stool
Diarrhea with
Systemic infection
Assess
dehydration
Severe
dehydration
Mild to
moderate
dehydration
IV fluids
ORS(10)
Zinc (11)
Continued
frequent
feeding -
including BF
ORS (10)
Zinc (11)
Continued
frequent
feeding -
including BF
Pallor, Purpura,
Oliguria Hosptalise
No antibiotics

41. • Only when frequency of stool with macroscopic
blood and pus
• Common pathogens are shigella, enteroinvasive
E.coli, salmonella, campylobacter jejuni, yersenia
enterocolitis etc
• Shigella is the most common in age < 5 years
• Never a mixed etiology (amoebiasis)
• Peak in summer
• More severe in malnourished and non breast fed
infants
Dysentery

42. Antimicrobial agents in acute dysentery
Drug Mg/kg/day Divided doses
Duration in
days
Co-trimoxazole (TMP + SM)
(Resistance very high)
TMP 5
SM 25
2 5
Nalidaxic Acid 55 4 5
Norfloxacin 20 2 5
Ciprofloxacin 10-15 2 5
Cefixime 8 2 5
Ceftriaxone 80-100 2 5

43. Child with Acute Diarrhea
Watery Diarrhea
without blood in stool
Diarrhea with
macroscopic blood in stool
in stool
Diarrhea with
Systemic infection
Rule out risk factors &
noninfectious conditions
Treat with 3
rd
Gen
Oral Cephalosporins
ORS to treat &
prevent dehydration
Zinc
continued frequent
feeding including BF
Better in 2 days?*
No Yes
2
nd
line drugs:
ciprofloxacin
/ceftriaxone
Complete
3 days
treatment
Response in 2 days ? **
No Yes
Look for
trophoziotes of
E. histolytica in
stools
Complete
5 days
treatment
Absent Present
Treat with
Metronidazole
Antibiotics for
infection
ORS
Zinc
Continued
frequent feeding
including BF
Pallor, Purpura,
Oliguria
** Disappearance of fever,
less blood in stools - fewer
in no, improved appetite,
decreased abdominal
pain, return to normal
activity indicate good
response.
Hospitalise

44. Salmonella Typhi:
Suspect only when fever of more than 4 days,
without focus and primary reports suggestive
•MDR Strains still rampant
•Sensitivity to - 3rd gen cephalosporin – 98%
- Quinolones* – 90-95%
Always send Blood culture before starting antibiotics
*Recently some centers from apex institutes less sensitivity

45. Golden rules for Judicious use of
antimicrobials
Golden rule 1
Acute infection always presents with fever;
in acute illness, absence of fever does not justify
antibiotic

46. Golden rule 2
Infection is the most common cause of fever in office practice,
though not always bacterial infection
 - Viral infection in majority RTI
 - Viral infection should not be treated with antibiotic

47. Golden rule 3
Clinical differentiation is possible between bacterial and viral infection most of the times
• Viral infection is disseminated throughout the system
(URTI / LRTI)
- May affect multiple systems
- Fever is usually high at onset, settles by D3-4
- Child is comfortable and not sick during inter febrile state
• Bacterial infection is localized to one part of the system
(acute tonsillitis does not present with running nose or
chest signs)
- Fever is generally moderate at the onset and peaks by D3-4
• CBC does not differentiate between acute bacterial and
viral infection

48. Golden rule 4
Chronic infection may not be associated with Fever
 Diagnosis can be difficult
 Relevant laboratory tests are necessary
 Antibiotic is considered only after observing progress
 There is no need to hurry through antibiotic prescription

49. Golden rule 5
Choose single oral antibiotic, either covering suspected gram positive or
negative organism, as per site of infection and age of patient
 Combination of two antibiotics is justified only in serious
bacterial infection without proof of specific organism and
can be administered intravenously

50. Golden rule 6
At first visit (within 48 hrs of fever) antibiotic is justified only
if bacterial infection is clinically certain and
that does not call for any tests prior to starting the drug
(Acute tonsillitis / acute otitis media / bacillary dysentery
/ acute suppurative lymphadenitis)
 If bacterial infection is clinically strongly suspected but should
have confirmative tests prior to starting drug, then
order relevant tests and start appropriate antibiotic
(Acute UTI)
 In absence of clinical clue but not suspected to be serious
disease
observe without antibiotic and follow the progress

51. Recommendations for Antibiotic selection
Conditions First line drugs Second line
Pharyngotonsillitis Penicillin/1st gen ceph Amoxycillin
/Macrolides
Otitis/Sinusitis Amoxycillin Co-amoxyclav/
2nd gen ceph /Macrolides
Pneumonia High dose Amoxy/ 2nd/3rd gen Inj ceph
Co-amoxyclav/Clox /Vanco
Enteric fever 3rd gen oral ceph 3rd gen inj ceph/
Fluoroquinolones
Dysentery Norflox 2nd gen quinolones
/3rd gen oral ceph /Ceftriaxone
UTI Sulpha/Trimetho / Co-amoy Fluoroquinolones
/3rd gen oral ceph /Aminoglycosides

52. Key Messages:
• Resistance in community acquired infections very
low
- more perceived than real
• Irrational & Overuse of antibiotics – great concern
• Start antibiotic only if indicated
• Always use first line drugs
• Use Microbiology Lab more often
• Develop culture of culture
• Spend more time with parents
• Select proper empirical antibiotics
• Do not use antibiotics in nonbacterial conditions