Drugs 2007; 67 (16): Supplementary Material 0012-6667/07/0015-0001/$49.95/0 Review Article © 2007 Adis Data Information BV. All rights reserved.

Multidrug-Resistant Streptococcus pneumoniae Infections Current and Future Therapeutic Options Françoise Van Bambeke,1 René R. Reinert,2 Peter C. Appelbaum,3 Paul M. Tulkens,1 and Willy E. Peetermans4

1 Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de Louvain, Brussels, Belgium

2 Institute for Medical Microbiology, National Reference Center for Streptococci, University Hospital (RWTH), Aachen, Germany

3 Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania, USA

4 Department of Internal Medicine-Infectious Diseases, Katholieke Universiteit Leuven, University Hospital Gasthuisberg, Leuven, Belgium

Supplementary Material

This supplementary material contains the figures referred to in the full version of this article, which can be found at http://drugs.adisonline.com.

Figure 1. Chemical structures of reference cephalosporins and of derivatives in development that are characterised by a high in vitro activity towards S. pneumoniae.

H H R1 N S

O N R O 2

HO O

drug -R1 -R2

O ONH2 cefuroxime H C N 3 O O

H2N

S SN NH ceftriaxone N N O H3C N O O

S O

cefotaxime NH2 H3C N N O O

NH2

S

CH3 N cefditoren N S N

OCH3

NH2

S

NN N ceftobiprole NH

O N

OH

NH2

S

NN N cefmatilen N SSN H N

OH H N PO3H2 S S

NN S ceftaroline N N CH3 N

OEt NH2

S N N Cl RWJ-54428 S

NH N 3 S OH

Figure 2. Chemical structures of a reference carbapenem and of derivatives in development that are characterised by a high in vitro activity towards S. pneumoniae.

OH H H SR

N OH

O

O drug -R

S imipenem N NH H

faropenem O O NH

H S N

N N NH2 CS-023 H

N O

CH3

Figure 3. Chemical structures of reference glycopeptides and of derivatives in development that are characterised by a high in vitro activity towards S. pneumoniae.

HOHO

O OH O O CH R HN 3 1 O Cl R2

H3C O O R3 R4

O OH Cl O O O H H N N N N NH H H HN O O NHCH3 CONH2 O HOOC

OH HO OH

R5

drug -R1 -R2 -R3 -R4 -R5 vancomycin -H -OH -H -H -H

H2N HO Cl oritavancin -H -OH H3C O -H CH3

telavancin H -OH -H -H NH N

PO3H2

CO R1 HN HO HO O O R2 O O

R3 Cl O O O H H O N N NHCH3 N N N H H H HN O Cl O

R4

HO O OH OH HO O OH

O OH

OH OH

-R1 -R2 -R3 -R4

O OH HO teicoplanin -CH3OH HO O -COOH NHAc

dalbavancin -COOH -OH N NH CO

Figure 4. Chemical structures of a reference ketolide and of derivatives in development that are characterised by a high in vitro activity towards S. pneumoniae.

N N

O N O

H C H3C 3 CH3 CH3 N O OCH3 O O

H C N CH 3 3 H3C NH CH3 (H C) N 3 2 (H3C)2N H3C O HO O H3C H3CH2C O O HO O CH3 H3CH2C O O O CH3

O O O O CH3 CH3 telithromycin cethromycin N N N

N N O O N

N O O H3C CH3 H C N 3 CH3 O O HO O O H C CH 3 3 H3C NH CH3 (H3C)2N (H C) N H C 3 2 3 O H3C H CH C O OHO HO 3 2 O H3CH2C O O CH3 O CH3

O O O O F CH3 CH3 EDP-420 FMA-1485 Figure 5. Chemical structures of a reference lincosamide and of a derivative in development that is characterised by a high in vitro activity towards S. pneumoniae.

O R 1 R2

NH

O

HO SCH3

HO OH

drug -R1 -R2

Cl N clindamycin

VIC105555

N H

Figure 6. Chemical structures of a reference oxazolidinone and of a derivative in development that is characterised by a high in vitro activity towards S. pneumoniae.

O

HN

R N O

F O drug -R

linezolid O N

O2N

ranbezolid O

N N

Figure 7. Chemical structures of reference tetracyclines and of derivatives in development that are characterised by a high in vitro activity towards S. pneumoniae.

N R2 R1 R3 HH OH

NH2 R4 OH OH O OH O O

drug -R4 -R3 -R2 -R1 tetracycline -H -OH -H -H

doxycycline -H -CH3 -H -OH

O

H N -H -N(CH ) -CH tigecycline N 3 2 3 H

H PTK-0796 N -H -N(CH3)2 -CH3

Figure 8. Chemical structures of reference quinolones and of derivatives in development that are characterised by a high in vitro activity towards S. pneumoniae.

R5 O

R6 COOH

R7 X N

R8 R1

drug X -R8 -R1 -R5 -R6 -R7

C N levofloxacin -H -F NN O CH3 H H N N moxifloxacin C -O-CH3 -H -F

H

O

N -H -F N gemifloxacin N

NH2

HN garenoxacin C -O-CHF2 -H -H

N sitafloxacin C -Cl -H -F

F H2N

C N WCK-771 -H -F HO NN O CH3

CH3 H3C

WCK-1152 C -O-CH3 -H -F NH N 2

CH3 H3C

WCK-1153 C -O-CH3 -H -F H N N 2

DX-619 C -O-CH3 -H -F N

NH2 F

N

DK-507k C -O-CH3 -H -F

F H2N

N

DC-159a C -O-CH3 -H -F

F CH3 NH2 N HN DW-224a N -H -F

N O

NH2

PGE 9262932 C -O-CH3 -H -F N H

N olamufloxacin C -CH3 -NH2 -F

H2N

Figure 9. Chemical structures of a reference diaminopyridine and of derivatives in development that are characterised by a high in vitro activity towards S. pneumoniae.

H2NNNH2

N R drug -R

trimetoprim

O O

O

iclaprim

O O

O

O

O N AR-709 O

O NH

Cl