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