PRSP : WHAT’S NEW

Wibowo Suryatenggara

Bagian Pulmonologi & Kedokteran Respirasi

FKUI – RSUP Persahabatan
Jakarta
 PRSP
Penicillin Resistant
Streptococcus pneumoniae
Streptococcus pneumoniae
 Most common cause of pneumonia, otitis
media, and bacteremia in infants/children
 Most common cause of pneumonia in
adults
 A major cause of bronchitis and sinusitis
Sputum from a patient with pneumococcal pneumonia
 Key Bacterial Pathogens in
Community-Acquired Pneumonia:
A Global Meta-analysis

Other
11% • Global meta-analysis of English-
language studies
• Study cohorts: N=127
Legionella spp. S. pneumoniae
4% • Total patients: N= 33,148
Mycoplasma
66% • Total patients reporting data:
pneumoniae N=6,866
7%

Haemophilus
influenzae
12%
Fine MJ et al. JAMA 1996; 275:134.
Penicillin was discovered by
Alexander Flemming in 1928
1942 : First clinical trial were conducted
at Yale University and Mayo Clinic
with dramatic results
 1967 : First reported case of infection with
penicillin resistant S. pneumoniae
from Australia
 1974 : First reported isolates of penicillin
resistant S. pneumoniae from USA
 1983 : From Canada
 1977 : Multi drugs resistant S. pneumoniae
from South Africa
NCCLS breakpoints for
Penicillin Resistance
 Susceptible : MIC < 0,06 g/ml

 Relative resistant : MIC 0,1 – 1 g/ml

 Resistant : MIC > 2 g/ml

 Penicillin-Resistant S. pneumoniae 22

in Asia and the Pacific (1996-1997)

India
Australia *
Malaysia
Mainland China
Indonesia
Singapore
Sri Lanka
Taiwan†
Thailand
Vietnam
Japan
Korea

0 20 40 60 80 100
% Isolates

Song et al. Clin Infect Dis 1999;28:1206.

* Turnidge et al. Med J. Aust 1999;170:152.
† Fung et al. J Antimicrob Chemother 2000;45:49.
 Cross-Resistance of 24
S. pneumoniae Isolates to
Beta-Lactams in the Americas
Pen-S (n=2,605) Pen-I (n=869) Pen-R (n=476)
MIC90 Resistant (%) MIC90 Resistant (%) MIC90 Resistant (%)

Amox/clav 0.25 0 1 18 8 98
Cefuroxime <0.06 0.8 4 35 8 99
Cefepime <0.06 0.3 1 12 2 88
Cefotaxime 0.03 0.2 0.5 5 2 78

MIC90=MIC90 (µg/mL)
Pen-S=penicillin-susceptible; Pen-I=penicillin-intermediate; Pen-R=penicillin-resistant.
Amox/clav=amoxicillin/clavulanate

The SENTRY Database (North and South America), 1997 and 1998.
 Cross-Resistance of 25

S. pneumoniae to Macrolides

Pen-S (n=2,605) Pen-I (n=869) Pen-R (n=476)

MIC90 Resistant (%) MIC90 Resistant (%) MIC90 Resistant (%)

Erythromycin 0.25 0 4 24 >32 50

Azithromycin <0.12 0 4 21 >16 47

Clarithromycin <0.2 0 4 22 >32 50

Pen-S=penicillin-susceptible; Pen-I=penicillin-intermediate; Pen-R=penicillin-resistant.

The SENTRY Database (North and South America), 1997 and 1998.
Mechanism of bacterial resistance
to -lactam antibiotics
 Reduced affinity for target binding proteins
(penicillin-binding proteins)
 Increased production of -lactamases
 Reduced permeability of outer membrane
(Gram-negative organism only)
 Increased efflux of antibiotic
Streptococcus pneumoniae
resistance
 Due to altered penicliin binding proteins

(PBPs) with reduced affinity for penicillins

 Chromosomally mediated
Antibiotic
 Low resistance potential

 High resistance potential

Antibiotics with Low Resistance
Potential
 Most  -lactams except cefamandol and
ceftazidim
 Minocycline
 Doxycycline
 All third generation cephalosporins except
ceftazidim
 Meropenem
 All parenteral quinolone except ciprofloxacin


Antibiotic with High Resistance
Potential
 Ampicillin  Ciprofloxacin
 Carbenicillin  Imipenem
 Ceftazidim
 Gentamicin

 Tetracycline
Antibiotic Resistance

 Natural

 Acquired
Natural Resistance
Beyond the usual spectrum of an antibiotic

Ex : Aerobic gram negative bacilli are

naturally resistant to clindamycin

Acquired Resistance
Microbial resistance to a previously

sensitive organism

Ex : Ampicillin resistant H. influenzae

Intermediate or Relative
Resistance
Gradual increase in MIC of organisms
over time, but organisms still susceptible
to antibiotic at achievable serum and
tissue concentrations
Ex : Penicillin resistant S. pneumoniae
Antibiotic Resistance Control
Strategies
 National : - Resistant surveillance networks
- Stop antibiotic supplemented
animal feeds
 Hospital/
Institutional Restricted hospital formulary
 Clinician Preferentially prescribe
antibiotic with low resistance
potential
How to overcome infection
caused by PRSP ?
•
Anti S. pneumoniae Activity of
Commonly Use Antibiotics
Good activity
 Amoxicillin  Levofloxacin
 Clindamycin  Gatifloxacin
 Doxycycline  Moxifloxacin
 Minocycline  Imipenem
 Cephalosporin 1st, 2nd,  Meropenem
3rd generation  Vancomycin
 Cefepime
 Linezolid
Cunha BA : Seminars in Res Infections 2002; 17: 204-14
Anti S. pneumoniae Activity of
Commonly Used Antibiotics
Moderate activity Little or no activity
 TMP-SMX  Aminoglycosides
 Tetracycline  Polymyxin B
 Ciprofloxacin
 Macrolides
 Anti staphylococcal
penicillin
 Anti pseudomonal
penicillin
 Aztreonam
Cunha BA : Seminars in Res Infections 2002; 17: 204-14
Antibiotic with Good anti S.
pneumoniae Activity and Little or no
Resistance Potential

 Clindamycin  Carbopenem
 Doxycycline  Ofloxacin
 Cefadroxil  Levofloxacin
 Gatifloxacin
 Vancomycin
 Moxifloxacin
 Cefepime
What is the Antibiotic of Choice

 Levofloxacin

 Gatifloxacin

 Moxifloxacin