rational use of antibiotics & problem of antibiotic resistense
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Rational use of antibiotics&
Problem of Antibiotic Resistance
Dr. Virendra Kumar GuptaMD Pediatrics
Assistant Professor Department of pediatric Gastroentero-Hepatology
& Liver Transplantation NIMS Medical College & Hospital , Jaipur
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
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 FlemingThe Nobel Prize in Physiology or Medicine 1945
Timeline of Antibiotic Resistance
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.
Why Rational Antibiotic Therapy ?
• Better care of patients.
• Combating antimicrobial resistance.
• Prevent misuse of antibiotics.
• Reduce cost of treatment.
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
Myths of Antibiotic Resistance
1. Drugs (antibiotics) cause organisms antibiotic resistant.
2. Antibiotic resistant organisms are more virulent
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.
Factors of Antibiotic ResistanceEnvironmental
FactorsDrug Related
Factors
Patient Related Factors
Prescriber Related Factors
Antibiotic Resistance
Mechanism Antibiotic Resistance
Intrinsic (Natural) Acquired
Genetic Methods
Chromosomal Methods Mutations
Extra chromosomal Methods Plasmids
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
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
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?
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
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
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
ANTIBIOTIC PARADIGM
Excessive / inappropriateantibiotic use
Failure of antibiotic treatment
Antibiotic resistance
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
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……………
Clinically diagnosed :
Management:
Not needed
Viral URI – seasonal (pharyngotonsillitis)
General & Symptomatic Therapy
Antibiotics : ?
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
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?......
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 yearsMost probably bacterial
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
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
In children with no Penicillin allergyAntibiotic (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
• 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
Some more non-bacterial Pharyngeal Inflammation
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 ?
AZHAR HAS ACUTE OTITIS MEDIA RIGHT EAR
On examination of Rt ear:• Erythema• Fluid• Impaired mobility• Acute symptoms
MANAGEMENT ?
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
• 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
• Ill look• Depressed AF• Dry skin and mucous membrane• Sunken eyeballs• Rapid, low volume pulse
How will you manage?
Jignesh....
• 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...
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
• 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
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
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 3rd Gen Oral Cephalosporins ORS to treat & prevent dehydration Zinc continued frequent feeding including BF
Better in 2 days?*
No
Yes
2nd 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
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
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
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
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
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
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
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
diseaseobserve without antibiotic and follow the
progress
Recommendations for Antibiotic selectionConditions First line drugs Second line
Pharyngotonsillitis Penicillin/1st gen ceph Amoxycillin /MacrolidesOtitis/Sinusitis Amoxycillin Co-amoxyclav/ 2nd gen ceph /MacrolidesPneumonia High dose Amoxy/ 2nd/3rd gen Inj ceph Co-amoxyclav/Clox /VancoEnteric fever 3rd gen oral ceph 3rd gen inj ceph/ FluoroquinolonesDysentery Norflox 2nd gen quinolones /3rd gen oral ceph /CeftriaxoneUTI Sulpha/Trimetho / Co-amoy Fluoroquinolones /3rd gen oral ceph /Aminoglycosides
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
THANK YOU
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