Antibiotics use and overuse

Antibiotics : Use and overuse

KM MuraliMD (Med), DM (Neph), DNB (Neph), F Neph (Canada)

Consultant NephrologistMIMS, Kozhikode

First world war

Second world war

Cold war

Man

vs

Microbe

Timeless war

Spread of “jewish poison”

Anton V Leeuwenhock : “animalcules”

1674 AD

Louis Pasteur: “germ theory of disease”

1857

1822 - 1895

Gram Staining

Gram Positive

Staphylococci Coagulase + ve

Coagulase - ve

Streptococci

Enterococci

Gram +ve bacilli

Gram +ve anaerobes

Gram Positive Gram Negative

EnterobacteriaceaeEschericiae

Klebsiellae Proteaceae

Pseudomonas

Vibrio

Hemophilus

Others

Gram Staining

Staphylococci Coagulase + ve

Coagulase - ve

Streptococci

Enterococci

Gram +ve bacilli

Gram +ve anaerobes

The “antibiotic surge”

• Penicillin 1941

• Streptomycin 1944

• Tetracycline 1948

• Erythromycin 1952

• Vancomycin 1958

• Methicillin 1959

• Gentamicin 1962

“...... It’s time to close the book on infectious

diseases, the war against pestilence is over”

William Stewart, Surgeon General

Message to US Congress, 1969

Antibacterial weaponry

Penicillins Fluoroquinolones

Cephalosporins Macrolides

Monobactams Sulfonamides

Carbopenams Streptogramins

Aminoglycosides Oxazolidinediones

Glycopeptides Others

+

DNA

DNA-RNA polymerase

Cell wall

Cell membrane

Protein synthesis

Folate synthesis

PABA

DHFA

THFA

Penicillin and beta-lactam ring

• The prototype Penicillin G

• Acid resistant Penicillin V

• Penicillinase resistant Methicillin, Oxacillin

• “Broad Spectrum” Amoxicillin, Ampicillin

• “Antipseudomonas” Azlocillin, piperacillin• Combinations Augmentin, Timentin• (+ -lactamase inhibitor)

The big penicillin family

Penicillin vs Cephalosporin

Penicillin vs Cephalosporin vs Carbapenams

Penicillin vs Aztreonam

Penicillin vs Vancomycin

“Excessive use of penicillin can lead to its resistance”

- Sir Alexander Fleming (1941)

Preliminary reports of resistance

• Penicillin 1941 1942

• Streptomycin 1944 1946

• Tetracycline 1948 1952

• Erythromycin 1952 1955

• Vancomycin 1958 1990

• Methicillin 1959 1968

• Gentamicin 1962 1975

• Ciprofloxacin 1988 1989

Staphylococcus aureus PCN resistance

0

5

10

15

20

25

30

1990 1992 1994 1996 1998 2000

Year

Non ICU

ICU

Enterococcus Vancomycin resistance

0

5

10

15

20

25

30

35

40

Ove

rall

Per

cent

Res

ista

nce

PCN ERY CLINDA TET TMP-SMX

1994-19951997-19981999-2000

Streptococcus antibiotic resistance

RESISTANCE : Survival of the fittest

Revertant

ResistantCompensatory mutations

Passages

Categories of resistance

Acquired

Staphylococci

Streptococci

Gram –ve cocci

Enterobacteriaceae

Intrinsic

Pseudomonas

Enterococci

Categories of acquired resistance

• Mutational

• Single drug

• Low level resistance

• Surpassable

Transferable

Often multiple drugs

High level resistance

Unsurpassable

• Enzymatic inactivation of drug

Biochemical basis of drug resistance

Beta – lactamase opens penicillin ring

Beta - lactamase

Penicillinase

Oxacilinase

Cephalosporinase

Carbenicilinase

Carbapenamase

ESBL

Beta – lactamase inhibitors

• Flucloxacillin

• Clavulanate

• Sulbactam

• Tazobactam

• Enzymatic inactivation of drug

• Alteration of drug target

Biochemical basis of drug resistance

• Penicillin binding proteins (PBPs)– Streptococcus pneumoniae (penicillin)– Staphylococcus aureus (MRSA, nafcillin; mecA gene)

• Ribosomal binding site (23S rRNA)– Streptococcus pneumoniae, Helicobacter pylori (macrolides)

• DNA gyrase– Gram negative bacteria (quinolones)

• Cell wall precursor targets– Vancomycin resistant enterococci (VRE)

Alteration of Drug Target

Vancomycin resistance in enterococcus

• Enzymatic inactivation of drug

• Alteration of drug target

• Changes in drug uptake or efflux

Biochemical basis of drug resistance

The toughest enemy: Pseudomonas

Pseudomonas: Efflux pump

Conspiracy: Sharing of intelligence

Pseudomonas

Enterobacteriacea

Campylobacter

Staphylococci

Enterococci

Streptococci

Man vs Microbe : Are we lost ??

• We are not winning

• But let us not lose

• Let us not overuse antibiotics

Physician practices in antibiotic use

• 2/3 of outpatient antibiotic use is avoidable

• 40% inpatient antibiotic selection incorrect

• Costly antibiotics being overused

Ground realities in Indian scenario

• Poor awareness about sample collection

• Poor microbiological infrastructure

• Low yield of blood culture

• Low yield of anaerobic bacteriae

• Lack of faith in laboratory reports

EMPIRICAL ANTIBIOTIC THERAPY

IS DIRECTED AGAINST THE MOST PROBABLE PATHOGEN……………..

NOT AGAINST ALL PATHOGENS !!!

BUT THEN CULTURES SHOULD FOLLOW

Empirical initiation of therapyEmpirical completion of therapy

ICU Antibiotic cocktail

• One for gram positive

• One for gram negative

• One for anaerobe

• One for ‘atypical’

• One for the master and one for the dame !!

Practical solutions

• Prevention of infection

• Give only essential treatment

• Monitoring policies

Preventing infections

• Universal precautions

• Hand washing

• Avoid non-essential lines and tubes

• Isolation of patients infected with muti-drug resistant pathogens

Essential treatment

• Use the right antibiotic

• Avoid broad spectrum antibiotic

• Use the right dose

• Use for the right time

Monitoring policies

• Infection control surveillance

• Bacteriological surveillance

• Prescription surveillance

Thank you Thank you