PRINCIPLE

OF
PRUDENT USE
OF ANTIBIOTICS

Abu Tholib Aman

Dept of Microbiology
FM UGM

Disampikan pada Annual Sxcien?c Mee?ng (ASM), FM UGM.

Yogyakarta, April 8, 2017.
 Introduction

Antimicrobials are the great discovery of the 20th

century.
Sulfonamides and penicillin were launched in the
30s and the 1940s respectively. with Since then,
many antibiotic drugs have been developed,
mainly for treatment of bacterial infections
These drugs have played an important role in the
dramatic decrease in morbidity and mortality due
to infectious diseases.
 Introduction

The miracle may come to an end.

Inappropriate use (misuse) of an?bio?cs as tool
for treatment has produced many problems.
Since the 1980s not many new an?bio?cs have
been discovered.
Nowadays, the misuse (or irra?onal use) of
an?bio?cs must be control, otherwise an?bio?cs
may become irrelevant as life saving i.nstrument
Cause of Emerging Resistant Strains

Any use of an?microbials (e.g. in human,

veterinary medicine and othres) can result in the
development of Resistant strains.
The risk increases if such an?microbials are used
inappropriately / misuse them.
 Mechanisms of Emergence of
Resistant strain
Intrinsic: the R factor reside in their
Chromosome.
MutaCon (random, mistake during
replicaCon).
Gene Transfer: TransformaCon,
TransposisCon, conjugaCon, TransducCon
..> followed by: Selection.
 MutaCon in Bacteria
Susceptible Bacteria

Resistant Bacteria

Mutations

XX

Resistance Gene Transfer

New Resistant Bacteria
hPp://www.cdc.gov
 SelecCon for AnCmicrobial-resistant Strains

The Major factor that cause

increase the resistant strain
Resistant Strains
Rare

Antimicrobial xx
Exposure xx

Resistant Strains
Dominant

hPp://www.cdc.gov
 Misuse of An?bio?cs
Include :
An?bio?cs are prescribed unnecessarily.
An?bio?c treatment is not streamlined according
to Suscep?bility data.
The dose is lower or higher than appropriate for
the specic pa?ent.
The dura?on of treatment is too short /long.
An?bio?c treatment is delayed in cri?cally ill
pa?ents.
Broad-spectrum or narrow-spectrum an?bio?cs
are used incorrectly.
 Gram-Posi?ve Resistance in the US, 1980-99

100

80
MRCNS
Percentage of
Pathogens 60
Resistant to
MRSA
AnCbioCcs 40
PRSP
20
VRE
0 GISA
1975 1980 1985 1990 1995 2000
1997

Paladino JA. Am J Health Syst Pharm 2000;57 Suppl 2:S10-2. 9

 % fluoroquinolone resistance

0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
50%
NO (1117)

EE (116)

2006
2005
2004
2003
2002
2001

SE (2904)

FI (1543)

IS (99)

NL (2140)

FR (4610)

GR (950)

SI (526)

HR (527)

BE (1118)

LU (191)

UK (1879)

PL (153)

IE (1184)

AT (1336)

CZ (1809)

BG (155)

HU (723)
Country code (average number of isolates reported per year)

IT (826)

IL (862)

PT (754)

ES (2816)

DE (1040)

MT (84)
Fluoroquinlone-Resistant E.coli in Europe, 2001-2006

CY (57)

RO (47)

TR (782)
CorrelaCon: Macrolide Use and Macrolide-Resistant
S. pneumoniae
60

Erytromycin resistant S. pneumoniae (%) FR

50

40 ESBE
GR

IT
30
LU
DE

20

PT
FI UK
IE
10
AT
SE
NL NO DK
0
0 1 2 3 4 5 6

Consumption of macrolides (J01FA) in DID, AC 1998

Organism Spearman
Antibiotic use -
year of isolation Antibiotic No. of correlation (r)
ATC group P-value
[source of resistance countries (confidence
(year of data)
information] interval)
S. pneumoniae
Macrolides - J01FA 0.83
1999/2000 Erythromycin 16 < 0.001
(1998) (0.67-0.94)
[8]

Goossens et al, Lancet 2005

 Clostridium difficile Infection (CDI)
Antibiotics are the single
most important risk
factor for CDI

Annual Mortality Rate per Million Population

Incidence and mortality

# of CDI Cases per 100,000 Discharges

increasing
A more virulent NAP1/BI
strain also seen with
increasing frequency

Redelings, et al. EID, 2007;13:1417, CDC. www.cdc.gov/Getsmart/healthcare

Fluoroquinolone Use and Resistance among
Gram-Negative Isolates, 1993-2000
National ICU Surveillance Study
35 250
Strains Resist. Ciprofloxacin (%)

30
200

FQ Use (kg X 1000)

25

150
20

15
100

10 P. aeruginosa
GNR 50
5 Fluoroquinolone Use

0 0
1993 1994 1995 1996 1997 1998 1999 2000

Neuhauser, et al. JAMA 2003; 289:885

 Limited Number of New Antibiotics to Combat
Antibiotic Resistance
New Systemic Antibiotics Approved by the FDA

Clin Infect Dis. 2011;52:S397-S428

 Prudent Use of An?microbials

WHO: Prudent Use of AnCmicrobials is the

use which maximizes therapeuCc eect of
the anCmicrobial agent while minimizing the
development of anCmicrobial resistance.
Principles of Prudent use of
AnCmicrobial
 Principles of Prudent use of An?microbial
Conrm presence of infec?on.
Iden?fy the cause of infec?on
Select AB base on An?bio?c suscep?bility data.
Treat Bacterial Infection, not Colonization nor
contamination.
Do not treat sterile inflammation or Abnormal
Imaging Without Infection.
Do not Treat Viral Infections with Antibiotics.
Select the most suitable antibiotics for the patient.
Limit duration of antibiotic therapy to the
appropriate Length.
Antibiotic Stewardship
1. Conrm presence of infec?on

@. Clinical diagnosis supported

by lab. data.
@. Agreement between clinical
features and laboratory data.

 Not all fevers are infecCon.
Common non-infecCous causes of fever:
Drugs
Immunologically-based disorders (Temporal
arteri?s; Vasculi?s, Lupus)
Inammatory and granulomatous condi?ons
(Inammatory bowel disease, Sarcoidosis)
Neoplasms
Endocrine disorder (Thyroid disease)
Other: Thrombophlebi?s and pulmonary embolis;
Liver disease/cirrhosis; CNS disorders
 2. Identify the cause of infection.

@. Collec?on of infected material before

beginning an?microbial therapy .
>. An?bio?c can be administered in
some cases ( Empirical Therapy. eg: Sepsis).

@. IdenCcaCon of the pathogen. (Cri?cal
aspect: Spesimen selec?on, collec?on and
handling).
 3. Select AnCbioCc/anCmicrobial base on:

A. SuscepCbility data:
@. Culture and/ or other test and
An?bio?cs/ An?microbial
Suscep?bility Test as needed.
#. Disc Diu?on
#. MIC
#. Molecular iden?ca?on
of R factor
#. Etc.
 B. Other AnCbioCcs Factors

Spectrum Drug interaction

Mechanisms of Side effect

action Drug

Pharmacokinetic
monitoring
Toxicity
Pharmacodynamic
Others
 anCbioCc selecCon

>. An?bio?c coverage should be kept to the

narrowest spectrum,, least toxic agent(s), least
expensive that will adequately treat the most
likely pathogens.

>. When a causa?ve infec?ous agent has been

iden?ed, an?bio?c coverage should be
narrowed to treat that organism.
>. Avoid overlapping an?bio?cs

 Antibiotic Selection

Consider Host factor:

Allergy, Age,
Pregnancy,
Metabolic abnormali?es,
Organ dysfunc?on, ect.
 4. Treat Bacterial Infection, not
contamination or colonization.
@. Patients may be colonized with potentially pathogenic
bacteria but are not infected
@. A major cause of antimicrobial overuse is treatment
of contaminated cultures or colonization.
Blood culture positif of non-pathogenic bacteria (normal flora
of skin).
Asymptomatic bacteriuria or foley catheter colonization
Tracheostomy colonization in chronic respiratory failure
Chronic wounds and decubiti; Chronic bronchitis
Can be difficult to differentiate
Presence of WBCs not always indicative of infection
Fever may be due to another reason, not the positive culture
.
Prevalence of Asymptomatic Bacteriuria

Age (years) Women Men

20 1% 1%
70 20% 15%
>70 + long-term care 50% 40%
Spinal cord injury 50% 50%
(with intermittent catheterization)
Chronic urinary catheter 100% 100%
Ileal loop conduit 100% 100%

Nicolle LE. Int J Antimicrob Agents. 2006 Aug;28 Suppl 1:S42-8.

5. Do not Treat Sterile Inflammation or
Abnormal Imaging Without Infection

Example: community-acquired pneumonia

(CAP)
CAP: often a difficult diagnosis
X-rays can be difficult to interpret. Infiltrates
may be due to non-infectious causes.
Examples:
Malignancy
Hemorrhage
Pulmonary edema
6. Do not Treat Viral Infections with Antibiotics

Acute bronchitis
Common colds
Rotavirus under < 5 yrs
Influenza
Sinusitis with symptoms less than 7
days
Sinusitis not localized to the maxillary
sinuses

Gonzales R, et al. Annals of Intern Med 2001;134:479; Gonzales R, et al. Annals of

Intern Med 2001;134:400; Gonzales R, et al. Annals of Intern Med 2001;134:521
 8. Limit Duration of Antibiotic Therapy
to the Appropriate Length

Ventilator-associated pneumonia (8 days?)

Most community-acquired pneumonia (5 days).
Cystitis.
Cellulitis: 5-7 days

Hayashi Y, Paterson DL. Clin Infect Dis 2011; 52:1232

 9. Antibiotic Stewardship

Re-evaluate, de-escalate or stop therapy in due

course based on diagnosis and microbiologic results
Re-evaluate, de-escalate or stop therapy with
transitions of care (e.g. ICU to step-down or ward)
Do not give antibiotic with overlapping activity
Do not double-cover gram-negative rods (i.e.
Pseudomonas sp.) with 2 drugs with overlapping
activity
Use rapid diagnostics if available (e.g. respiratory viral
PCR)
Result of Prudent use of
anCbioCcs
 Outpatient consumption of amoxicillin/clavulanate
before and after restriction
2
AMC
restriction pre-trend
post-trend
1,5
DDD/1000 inhabitants

0,5

0
1996 1998 2000 2002 2004 2006 2008 2010
quartiles
 Outpatient consumption of fluoroquinolones
before and after restriction
0,5
FQ
restriction pre-trend
0,4 post-trend
DDD/1000 inhabitants

0,3

0,2

0,1

0
1996 1998 2000 2002 2004 2006 2008 2010
quartiles
 Concluding Remark
Discoveries of An?bio?cs has produced Huge
improvement in controlling Infec?ous disease
and safe live. However, con?nuing uncontrol
use and misuse of an?bio?cs can not be
tolerate.
Therefore, implemen?ng prudent use of
an?bio?cs is an urgently needed, otherwise
An?bio?c may soon become irrelevant in
trea?ng infec?ous diseases.
THANK YOU VERY MUCH