COMBATING THE ANTIBIOTICS

(AB) RESISTANCE IN PICU

 OBJECTIVE

1. Understanding of AB resistance problem in PICU

2. National strategy to combat the emergence and

spread AB resistance
- Prevent selection : Wisely use of AM
- Prevent transmission : General precaution
standard
3. The importance of Antimicrobial Stewardship
Program (ASP)
 AB RESISTANCE PROBLEM IN PICU

• The most common causes of community-acquired neonatal and

infant bacteraemic infection in developing countries
Staphylococcus aureus, Escherichia coli and Klebsiella sp.
Downie L, et al. Arch Dis Child 2013

• Antibiotic resistance is an example of Darwinian selection

• Human use and misuse of antibiotics  expression and
transmission of resistance genes in pathogenic bacteria
• Widely used penicillin (1948)  β-lactamase- (penicillinase-)
producing strains
• Antibiotic resistance has been a major clinical problem
• AB resistance : global thread & challenge
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Vancomycin-resistant Enterococcus (VRE)
- MDR Pseudomonas aeruginosa beta-lactamases, carbapenemases
- Imipenem-resistant Acinetobacter baumannii
- Third-generation cephalosporin-resistant Escherichia coli
- Klebsiella pneumonia
Yeoh, SF. ACCP, Singapore 2010

Lee C, et al. Int. J. Environ. Res. Public Health 2013

• Appropriate changes in AB use can lead to recovery of susceptibility

Ballow et al. Microbiol Infect Dis, 1992
Diseases severity
Comorbidity
Immune system
Organ dysfunction
 FACT…

Sepsis
AB resistance

LOS ↑

High cost

Mortality
Morbidity
 MRSA & PAN-RESISTANCE

Period Jan-June July-Dec 2011 Jan-June 2012 July-Dec 2012

2011
n % n % n % n %
MRSA 26/136 19 36/163 22 46/242 19 35/192 18
Pan 7 12 60 178
resistance
 PAN-RESISTANCE BACTERIA
Period Jan- July- Jan-
June Dec June
2012 2012 2013
Organism n % n % n %
Acinetobacter sp 26 84 4
A. Baumanii 2 46.7 15 55.6 57 74.3

Pseudomonas sp 19 31.7 71 39.9 1 1.2

K.Pneumoniae 7 11.7 4 2.2 8 9.8

E.Coli 2 1 3
K. Oxytoca 1 1 1
S. Liquifaciens 1 0 1
E.aerogenes 2 2 3
60 100 178 100 82 100
 EMERGENCE OF ANTIMICROBIAL
RESISTANCE
- Increase - AM resistance
use - Collateral damage
- Over use Inappropriate ....
- Increase morbidity/
,...-
use
- Misuse mortality
- Under use - Higher cost

Need AM policy to control

AM usage!

Ref. WHO policy perspective on medicines:

containing antimicrobial resistance.
WHO, Geneva, 2005
Prevent AM/ AB resistance in health care settings

---
Prevent !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!9..,
Wisely use
!!! !! N I seIection - of AM/AB

--- Prevent ff
GENERAL
--- transmission -- PRECAUTION
STANDARD

* WHO report in infectious disease. WHO / CDS / 20 00.2

* CDC campaign to prevent AM resistance in health care
settings.
http://www.cdc.gov/drugresistance/ healthcare/
ha/12steps HA.htm
 WISELY USE OF
ANTIBIOTICS

Guidelines for selecting

P-drugs :
– Efficacy
– Safety
– Suitability
– Cost
 ANTIBIOTIC EMPIRICAL THERAPY

• Epidemiology data of antibiotics

• Clinical conditions  Severe infections :
- Broad spectrum AB
- Timelines  ASAP : Evaluation
- Length of treatment

Lawrence KL et al. Am J Respir-Crit Care Med. 2009

Peterson LR. CRIDTRHOPHID-ARCP. Faculty of Medicine Univ. of Indon. March 10, 2012
 ANTIBIOTIC EMPIRICAL
STRATEGIES
PATIENT

Ambulatory Admission

Stable Critical

Escalation Deescalation

AB based on :
AB pattern resistency
Immunological st comorbidity and organ dysfunction

AB : monotherapy or combination

Pohan HT, 2005

 IDEAL
AB

• Provides empiric coverage for all community

and nosocomial pathogens
• Capable of tissue penetration
• Resistant to inactivation by bacterial enzymes
• High affinity for site target
• Must not readily stimulate bacterial resistance
• Minimum side effect
• Proven clinical efficacy
 PRUDENT USE OF AB

- Adequate data for diagnosis of infection(s)

- Right indication  treat infection not colonization
- AB selection: efficacy, safety, suitability, cost
- Right . dose
. interval
. route of administration
. duration
. Time of initiation
- Anaphylactic reaction?
- Patient education

- Gyssens 2005
- de Vries et al. Guide to good prescribing. WHO 1994
HOSPITAL GUIDELINES ANTIBIOTIC USE
1. Wisely use of AB
2. Surgical & non surgical prophylactic AB
3. Empirical treatment of AB
4. Definitive treatment of AB
5. Combination therapy
6. Antibiotic categories
7. Pharmaceutical aspect
8. Monitoring of effectivenes of AB

Ref. PPRA-RSCM, 2009

 AB CATEGORIES

Class A Class B Class C

Aminoglicoside Cephalosporine gen III Teicoplanin
Penicillin Fluoroquinolonegen III-IV Linezolide
Cephalosporin gen.I,II Cefepime
Chloramphenicol Cefpirome
Fucidic acid Carbapenem
Lincosamide Tygecycline
Macrolide Ceftazidime
Nitroimidazol Pip-Tazo
Fluoroquinolone Vancomycin
gen.I,II Aztreonam
Tetracyline
TMP-SMX
Fosfomicin
Polypeptide
 CONTROL OF ANTIBIOTIC USAGE

• Avoid antibiotic homogeneity

• Promote appropriate use of multiple drug class
• Apply formulary control and restrict of specific
agent or drug class that resistant
• Consider antibiotic cycling, rotation or mixed
use of antibiotic classes
• Develop and promote antibiotic guidelines and
protocol based on local data
PEDOMAN PENGGUNAANANTIBIOTIK

TIM POKJA PPRA

DEPARTEMEN ILMU KESEHATAN ANAK
RSUPN DR CIPTO MANGUI\TKUSUMO
2013
 AB HETEROGENECITY : CYCLING OR
MIXING CONCEPTS
• Cycling (Rotation)
- AB are withdrawn from use for a period of time to be
reintroduced later
- One AB is replaced by one from another class (similar
spectrum of activity, but different mechanisms of antibiotic
resistance (β-lactams, aminoglycosides, and fluoroquinolones
- Purpose : to limit resistance to the cycled agent
• Mixing
- Simultaneous, mixed use of different antimicrobial class for
different patients in a unit
- Allows for greater antibiotics heterogeneity than cycling
Ref. Peterson LR. CRID-TROPHID-ARCP. Faculty of Medicine Univ. Indon, March 10, 2012
M Microbiology guides therapy
wherever possible
I Indications should be evidence based
N Narrowest spectrum required
D Dosage appropriate to the site and
t y pe of infection
M Minimise duration of therapy
E Ensure monotherapy in most situations
ANTIBIOTIC STEWARDSHIP
PROGRAM
 SUMMARY

• AB resistance  major problem across the world

• Widespread use of AB  increased incidence of AB resistance

• Appropriate changes in AB use  recovery of susceptibility

• Two strategies to prevent AM/AB resistance

- prevent selection: wisely use of AB
- prevent transmission: general precaution standard
• ASPs