In Vitro Activity of Retapamulin and Comparators
13665 Dulles Technology Drive
against 1690 Recent Gram-Positive Clinical Isolates
Herndon, VA 20171
Tel: +1 703 480 2500
Fax: +1 703 480 2654
D. Draghi,1 N. Scangarella,2 R. Shawar2 & D. Sahm1
1Focus Bio-Inova, Herndon, VA, USA; 2GlaxoSmithKline Pharmaceuticals, Collegeville, PA, USA.
however, some of the organisms tested, not typically associated with
Table 3. In Vitro Activity of Retapamulin and Comparator Antimicrobials
points were read visually and MICs were interpreted as susceptible,
SSSIs, were derived from other specimen sources (Table 1).
intermediate, or resistant using the 2004 CLSI M100-S14 published
Retapamulin (SB-275833) is the first pleuromutilin formulated as a
breakpoints, where available.2 VISA and VRSA isolates were tested
topical antibacterial for treating skin and skin structure infections (SSSIs). It has
The following comparator antibacterial agents were tested: bacitracin,
in triplicate using fresh broth microdilution panels prepared at Focus
a unique mode of action and shows no target-specific cross-resistance to other
cephalothin, ciprofloxacin, erythromycin, gentamicin, mupirocin,
antibacterial classes. The aim of this study was to assess the in vitro
retapamulin and other antibacterial agents against clinical isolates from Gram-
positive bacterial species commonly associated with SSSIs. Methods:
In addition to the isolates described, 11 vancomycin-intermediate
retapamulin, bacitracin, cephalothin, ciprofloxacin, erythromycin, gentamicin,
(VISA; vancomycin MICs = 8 µg/mL) and 2 vancomycin-resistant (VRSA;
mupirocin, oxacillin and penicillin were determined by broth microdilution
● Retapamulin maintained a high level of activity (based on MIC )
vancomycin MICs >32 µg/mL) isolates were selected from the Network
according to the Clinical and Laboratory Standards Institute (CLSI, formerly the
against all key Gram-positive species associated with skin infections.
National Committee for Clinical Laboratory Standards [NCCLS]) methodology.
on Antimicrobial Resistance in Staphylococcus aureus
This level of activity did not appear to be impacted by the
A total of 1690 recent clinical isolates (1998–2004) from the USA and Europe
repository based on their vancomycin MIC as reported by NARSA. The
organism’s resistance phenotypes to other drug classes (Table 2).
were selected for testing, the majority of which were chosen from SSSI sources.
following comparator agents were tested against the VISA and VRSA
● For S. aureus
, Streptococcus pyogenes
, Staphylococcus saprophyticus
isolates: fusidic acid, moxifloxacin and mupirocin.
and other coagulase-negative staphylococci, retapamulin exhibited
the comparator agents (for S. aureus
, retapamulin and mupirocin
exhibited the same MIC ). For Streptococcus agalactiae
Isolates were tested by broth microdilution at Focus Bio-Inova central
group streptococci, retapamulin activity was greater than that of
laboratory (Herndon, VA, USA). Testing was done using commercially
comparators and equal to that of penicillin (Table 3).
prepared frozen broth microdilution panels (TREK Diagnostic Systems,
● With regard to specific S. aureus
-resistant phenotypes, retapamulin
Inc., Cleveland, OH, USA) according to Clinical and Laboratory Standards
activity was maintained regardless of the methicillin status of the
Institute (CLSI, formerly National Committee for Clinical Laboratory
isolates tested. In contrast, the activity of several comparators was
Standards [NCCLS]) standard methodology (M7-A6).1 Inhibition end-
● Similarly, retapamulin exhibited strong in vitro
activity against all
RE, retapamulin; BA, bacitracin, CE, cephalothin; CI, ciprofloxacin; ER, erythromycin; GE, gentamicin;
Table 1. Breakdown of Organisms by Specimen Source
the VISA and VRSA strains tested (Table 5).
MU, mupirocin; OX, oxacillin; PE, penicillin.
On the basis of MIC s, retapamulin had the most potent in vitro
profile against staphylococci and streptococci. With the exception of Bacillus
the in vitro
activity of retapamulin indicates potential in the treatment of SSSIs
● Retapamulin exhibited promising activity against clinically relevant
caused by these Gram-positive organisms.
Gram-positive organisms associated with SSSIs and this in vitro
activity was not impacted by resistance to other antimicrobial
● These in vitro
findings strongly support retapamulin’s clinical
Staphylococcal, streptococcal and facultative aerobic Gram-positive
potential. Clinical trial data are required in order to assess its
organisms are of serious concern for clinicians treating skin and soft
tissue infections. Resistance to currently marketed antibacterial agents is
rising for patients with these types of infections. Retapamulin (Figure 1,
SB-275833) is the first, novel, semi-synthetic pleuromutilin, representing
This study was sponsored by a grant from GlaxoSmithKline
a new class of antibacterial agent, which has been formulated as a
topical antibacterial for the treatment of skin and skin structure
Table 2. Overall Summary of Retapamulin In Vitro Activity
infections (SSSIs). It inhibits protein synthesis by interacting at a unique
site on the 50S ribosomal subunit and shows no target-specific cross-
National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests
resistance to other antibacterial classes. The aim of this study was to
for Bacteria that Grow Aerobically, Approved Standard, 6th Edition. M7-A6. Wayne, PA, USA: NCCLS, 2003.
National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Susceptibility
assess the in vitro
activity of retapamulin and other antibacterial agents
Testing, 14th Informational Supplement. M100-S14. Wayne, PA, USA: NCCLS, 2004.
against clinical isolates from Gram-positive bacterial species, some of
Table 4. Comparative In Vitro Activity of Retapamulin and Comparators against
which are commonly associated with SSSIs.
Methicillin-susceptible and Methicillin-resistant S. aureus
Bacterial isolates and antimicrobials
In total, 1690 recent clinical isolates (1998–2004) from the USA and
Europe were selected for testing. All isolates were consecutively
collected and only one isolate per patient was tested. Isolates were
chosen from skin and skin structure specimen sources where possible;
Table 5. Comparative In Vitro Activity of Retapamulin and Comparators against
VISA and VRSA
aCephalothin was tested to predict the activity of cephalexin.
Figure 1. Chemical Structure of Retapamulin
aMIC and MIC not reported for isolate subsets with n<10.
bNCCLS interpretations are unavailable to determine percent resistant.
Presented at the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, 16–19 December 2005, Washington, DC, USA
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