Journal of Antimicrobial Chemotherapy (1992) 30, Suppl. A, 39-44

Comparative in-vitro activity of RP 59500 Lodo Verbist and Jan Verhaegen

The in-vitro activity of RP 59500 was compared with that of other appropriate antibiotics against 131 staphylococci, 97 streptococci, 20 enterococci, 68 Neisseria spp., 68 Haemophilia inftuenzae, 21 Moraxella catarrhalis and 250 Gram-negative bacilli. RP 59500 was more active than oxacillin, vancomycin and crythromycin against staphylococci (MIC 0-03-4 mg/L). RP 59500 inhibited streptococci between 0-03-1 mg/L and enterococci between 1-8 mg/L, but was less active than ampicillin and erythromycin. However, its activity remained unchanged against strains with acquired resistance to ampicillin, erythromycin and oxacillin. It was as active as ampicillin against Neisseria spp., but less active against H. influenxae and M. catarrhalis. All enterobacteria and non-fermenters were resistant to RP 59500.

Introduction

RP 59500 is a new semisynthetic streptogramin derivative that is water-soluble and injectable. RP 59500 is a mixture of RP 57669 (30%) and RP 54476 (70%), two watersoluble derivatives of pristinamycin I and II, respectively. The parent compound pristinamycin was described originally in 1962 (Benazet et al., 1962; Monnier & Bourse, 1962). In this study we compared the in-vitro activity of RP 59500 with that of other appropriate antibiotics against a variety of Gram-positive and Gram-negative bacteria. Materials and methods Micro-organisms The organisms used in this study were recent clinical isolates. Some of the strains were selected on the basis of resistance to specific antibiotics: i.e. staphylococci resistant to oxacillin, pneumococci resistant to erythromycin, and gonococci and Haemophilia influenzae which produced ft-lactamases. The number of strains used is shown in parentheses in Table I. Antibiotics Antibiotics of known potency were obtained from the manufacturers: RP 59500 (Rhone-Poulenc, Rorer); erythromycin, cefazolin and vancomycin (Eli Lilly); oxacillin and ampicillin (Beecham); gentamicin (Schering-Plough); cundamycin (Upjohn); cefotaxime (Hoechst); ciprofloxacin (Bayer). Except indicated below, antibiotics were prepared as stock solutions in water to a concentration of 1-28 g/L. RP 59500 was 0305-7453/92/30A039+06 $03.00

39 ©1992 The British Society for Antimicrobial Chemotherapy

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Diagnostic Microbiology Laboratory, University Hospital St Rafael, Kapucijnenvoer 35, B-3000 Leuven, Belgium

40

L. VetWtt and J. Verhaegen

Table L In-vitro activity of RP 59500 and other antibiotics (mg/L) Bacteria (no.) and antibiotics tested

MIC range

MIC*

05 025 1 05 003 025 025

05 16 1 1 012 1 025

> 16

32 1 025

025 012 2 025 006 012 006

18-33

075 034 2-20 8-75

05

023

1 025 2 05 05 16 05

029 019 O97 017 014 054 010

> 16

32 2 025 16

034 054 075 051 005 037 018 >16

>64 1 1

> 16

>16 025

Mean MIC

>64 2 05

> 16 11-07 1-74

028

> 16

1-97 5-69

006

1

O10

1 012 05 025 025 012 1

8 16 1 05 4 16 4

056 057 019 O40 035 087

05 1 1 4

05 2 32 4

047 097 303 318

> 16

006 025 05 012 025

006 025 05 012 05

1-23

005 017 048 013 029

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S. aureus oxacillin-susccptible (31) 006-1 oxarilbn 0-12- > 64 gcntamicin 025-2 vancomycin 012-1 ciprofloxacin 0 0 3 - > 16 dindamycin 006->16 erythromycin 003-0-25 RP 59500 S. aureus oxacillin-resistant (45) 4 - > 16 oxacillin 0 1 2 - > 64 gentamicin 025-2 vancomycin 012-1 ciprofloxacin 0 0 3 - > 16 dindamycin 012- > 16 crythromycin 003-4 RP 59500 S. epidermidis oxacillin-susceptiblc (20) oxaciUin 006-2 gentamicin 012-64 vancomycin 025-2 ciprofloxacin 006-O5 dindamycin 0 0 3 - > 16 erythromycin 003- > 16 RP 59500 003-4 5. epidermidis oxacilUn-resistant(25) oxacillin 8-> 16 gentamicin 012- > 64 vancomycin 025-2 ciprofloxacin 006-8 dindamycin 0 0 3 - > 16 erythromycin 0 0 6 - > 16 RP 59500 003-4 5. saprophyticus (10) oxacillin 0 1 2 - > 16 gentamicin 012-64 vancomycin 025-1 ciprofloxacin 006-05 dindamycin 0 0 3 - > 16 crythromycin 0 0 6 - > 16 RP 59500 012-4 E.faecalis (20) ampicillin 025-1 vancomycin 025-4 erythromycin 05-32 RP 59500 1-8 S. pyogenes (21) ampicillin 0008-012 cefazolin 006-05 vancomycin 025-0-5 erythromycin 006-0-25 RP 59500 006-05

MICJO

41

RP 59500 m-rhro actfrtty Table I—continued Bacteria (no.) and antibiotics tested S. agalactiae (20) ampicillin cefazolin vancomycin erythromycin RP 59500

MIC range

MIC

MIC*

Mean MIC

0O08 012 05 003 012

0O15 012 05 006 025

001 Oil 041 003 008

S. pneumoniae erythromycin-susceptible (20) ampicillin 0-008-0-5 cefazolin 0-03-0-5 vancomycin 0-25-1 erythromycin 0-06-0-25 RP 59500 0-12-0-5

0015 006 05 O06 025

003 006 05 012 05

0O1 0O5 039 O09 034

S. pneumoniae erythromycin-resistant (16) ampicillin 0008-0015 cefazolin 0O3-0-12 vancomycin 0-25-0-5 erythromycin 4->32 RP 59500 0-25-1

0O15 006 025 16 05

0O15 012 05 >32 1

001 006 034 12-88 044

025 025 025 O06 05

2 2 05 4 05

026 025 029 021 047

006 0008 0004 05 003

O06 0015 0008 2 012

005