Journal of Antimicrobial Chemotherapy (1992) 30, Suppl. A. 77-81
In-vitro activity of RP 59500, a new synergic antibacterial agent, against LegioneUa spp. J. DnbofaT* and J. R. Joly*
The in-vitro activity of RP 59500, a new semiiynthetk injectable streptogramin, was compared with that of erythromycin, rifampicin and ciprofloxacin against 189 LegioneUa spp. Rifampicin was the most active agent tested. RP 59500 was found to be more active than erythromycin against most strains, but less active than ciprofloxacin. LegioneUa pneumophUa serogroups 1, 3,4, 5 and 6 were more susceptible to RP 59500 than were L. pneumophUa serogroups 2, 7, and 8. LegioneUa micdadei was the least susceptible species to RP 59500 and erythromycin. RP 59500 was similar in activity against isolates obtained from both patients and environmental sources. This activity was generally better than that of erythromycin.
Introduction
RP 59500 is a member of the streptogramin family of antimicrobial agents. RP 59500 consists of a well-defined mixture (30:70) of derivatives of pristinamycin IA and IIB. Separately, each of the 2 components has in-vitro bacteristatic activity against Gram-positive organisms, Haemophilus spp. and many genital pathogens, such as Neisseria spp., Mycoplasma spp., Ureaplasma spp., Chlamydia spp. and anaerobes (Lafaix et al., 1985; Laforest et al., 1988; Lefevre et al., 1989; Weber et al., 1989). However, the combination of the two components has synergic bactericidal activity. RP 59500 is a new semisynthetic injectable streptogramin. It is active against a range of bacilli resistant to aminoglycosides and methicillin-rcsistant staphylococci (Fass, 1991). In this study, we have determined the MICs of RP 59500, erythromycin, ciprofloxacin and rifampicin against a variety of legionclla strains isolated either from nosocomial or community-acquired respiratory tract infections, or from environmental sources. Materials and methods
Strains A total of 189 strains of LegioneUa spp., isolated from nosocomial or communityacquired respiratory tract infections or from environmental sources, were identified by standard methods, such as those described by Edelstein (1985). •Correipooding author. 0305-7453/92/30A077+05 $03.00/0
77 © 1992 The British Society for Anumicrobiil Chemotherapy
Downloaded from http://jac.oxfordjournals.org/ at University of Manitoba on August 25, 2015
"Centre Hospitalier Hdtel-Dieu de Sherbrooke, 580 Bowen sud, Sherbrooke, Quibec, Canada, JIG 2E8 and bDipartement de Microbiologie, Faculti de midecine, Unhersiti Laval, Quibec, Canada, JIG 7P4
78
J. Dnbois and J. R. JoJy
Drugs The antimicrobial agents were kindly provided as follows: RP 59500 (Rhone-Poulenc Rorer, Montreal, Quebec), ciprofloxacin (Miles Pharmaceuticals, West Haven, USA), rifampicin (Merrel Dow, Richmond, Ontario) and erythromycin (Abbott Laboratories, Mississauga, Ontario). Determination of MICs
Results The activity of RP 59500 against L. pnewnophila serogroups 1 to 8 is shown in Table I. The MIQo of rifampicin against L. pnewnophila strains was less than or equal to 0-008 mg/L. RP 59500 was twice as active as erythromycin against most L. pnewnophila strains tested. The MICs of RP 59500 ranged from 0-008 mg/L to 1-0 mg/L. L. pnewnophila serogroups 1,3,4, 5, and 6 were found to be more susceptible to RP 59500 than L. pnewnophila serogroups 2, 7 and 8. The MIC,,, of erythromycin for L. pnewnophila serogroup 1 was 0-5 mg/L. The susceptibilities of other Legionella spp. to RP 59500 are shown in Table II. Against Legionella dumoffii, rifampicin was less active than against other Legionella spp. In the case of Legionella micdadei, RP 59500 was less active than erythromycin. Ciprofloxacin was intermediate in activity between erythromycin and rifampicin against all strains tested. Discussion In this study, rifampicin and ciprofloxacin showed impressive activity against Legionella spp. Rifampicin is often prescribed in combination with erythromycin, but should not be used as a single agent because resistant strains emerge readily. Ciprofloxacin and other quinolones may prove clinically useful (Chin et al., 1988), but there is little clinical data to support their use in man. In contrast to the findings of Edelstein et al. (1980), the results in this study indicate erythromycin to be less active than RP 59500 against most Legionella spp. tested. However, RP 59500 was less active than ciprofloxacin and rifampicin. The results of this study differ from those obtained by Washington et al. (1985). The lowest MIQo values obtained in this study are explained by the absence of charcoal in our medium; charcoal interacts unfavourably with antimicrobial agents, such as rifampicin and macrolides (Barker et al., 1986).
Downloaded from http://jac.oxfordjournals.org/ at University of Manitoba on August 25, 2015
MICs were determined by a standard agar dilution procedure using doubling dilutions of antibiotic. The medium used was buffered yeast extract agar (BYE). The inoculum was prepared from an overnight culture and colonies were added to .sterile water to a turbidity of no. 1 McFarland standard. This inoculum was diluted ten-fold and, by means of a replicating device, about 104 cfu were inoculated on to BYE containing doubling dilutions of antibiotics from 0.004 mg/L to 8 mg/L. The plates were incubated aerobically at 35°C for 48 h. The MIC was defined as the lowest concentration of antimicrobial agent that completely inhibited visible growth. Legionella pnewnophila ATCC 33152 was included as a control.
In-vttro acttrity of RP 59500 against IcgkmcOa
79
Table L Susceptibility of Legionella pneumophila serogroups 1 to 8 to RP 59500, erythromycin, ciprofloxacin and rifampidn Organism (no. of strains)
MIC so
RP 59500 erythromycin ciprofloxacin rifampicin RP 59500 erythromycin ciprofloxacin rifampicin
0-12 0-25 0O3
In-vitro activity of RP 59500, a new synergic antibacterial agent, against LegioneUa spp. J. DnbofaT* and J. R. Joly*
The in-vitro activity of RP 59500, a new semiiynthetk injectable streptogramin, was compared with that of erythromycin, rifampicin and ciprofloxacin against 189 LegioneUa spp. Rifampicin was the most active agent tested. RP 59500 was found to be more active than erythromycin against most strains, but less active than ciprofloxacin. LegioneUa pneumophUa serogroups 1, 3,4, 5 and 6 were more susceptible to RP 59500 than were L. pneumophUa serogroups 2, 7, and 8. LegioneUa micdadei was the least susceptible species to RP 59500 and erythromycin. RP 59500 was similar in activity against isolates obtained from both patients and environmental sources. This activity was generally better than that of erythromycin.
Introduction
RP 59500 is a member of the streptogramin family of antimicrobial agents. RP 59500 consists of a well-defined mixture (30:70) of derivatives of pristinamycin IA and IIB. Separately, each of the 2 components has in-vitro bacteristatic activity against Gram-positive organisms, Haemophilus spp. and many genital pathogens, such as Neisseria spp., Mycoplasma spp., Ureaplasma spp., Chlamydia spp. and anaerobes (Lafaix et al., 1985; Laforest et al., 1988; Lefevre et al., 1989; Weber et al., 1989). However, the combination of the two components has synergic bactericidal activity. RP 59500 is a new semisynthetic injectable streptogramin. It is active against a range of bacilli resistant to aminoglycosides and methicillin-rcsistant staphylococci (Fass, 1991). In this study, we have determined the MICs of RP 59500, erythromycin, ciprofloxacin and rifampicin against a variety of legionclla strains isolated either from nosocomial or community-acquired respiratory tract infections, or from environmental sources. Materials and methods
Strains A total of 189 strains of LegioneUa spp., isolated from nosocomial or communityacquired respiratory tract infections or from environmental sources, were identified by standard methods, such as those described by Edelstein (1985). •Correipooding author. 0305-7453/92/30A077+05 $03.00/0
77 © 1992 The British Society for Anumicrobiil Chemotherapy
Downloaded from http://jac.oxfordjournals.org/ at University of Manitoba on August 25, 2015
"Centre Hospitalier Hdtel-Dieu de Sherbrooke, 580 Bowen sud, Sherbrooke, Quibec, Canada, JIG 2E8 and bDipartement de Microbiologie, Faculti de midecine, Unhersiti Laval, Quibec, Canada, JIG 7P4
78
J. Dnbois and J. R. JoJy
Drugs The antimicrobial agents were kindly provided as follows: RP 59500 (Rhone-Poulenc Rorer, Montreal, Quebec), ciprofloxacin (Miles Pharmaceuticals, West Haven, USA), rifampicin (Merrel Dow, Richmond, Ontario) and erythromycin (Abbott Laboratories, Mississauga, Ontario). Determination of MICs
Results The activity of RP 59500 against L. pnewnophila serogroups 1 to 8 is shown in Table I. The MIQo of rifampicin against L. pnewnophila strains was less than or equal to 0-008 mg/L. RP 59500 was twice as active as erythromycin against most L. pnewnophila strains tested. The MICs of RP 59500 ranged from 0-008 mg/L to 1-0 mg/L. L. pnewnophila serogroups 1,3,4, 5, and 6 were found to be more susceptible to RP 59500 than L. pnewnophila serogroups 2, 7 and 8. The MIC,,, of erythromycin for L. pnewnophila serogroup 1 was 0-5 mg/L. The susceptibilities of other Legionella spp. to RP 59500 are shown in Table II. Against Legionella dumoffii, rifampicin was less active than against other Legionella spp. In the case of Legionella micdadei, RP 59500 was less active than erythromycin. Ciprofloxacin was intermediate in activity between erythromycin and rifampicin against all strains tested. Discussion In this study, rifampicin and ciprofloxacin showed impressive activity against Legionella spp. Rifampicin is often prescribed in combination with erythromycin, but should not be used as a single agent because resistant strains emerge readily. Ciprofloxacin and other quinolones may prove clinically useful (Chin et al., 1988), but there is little clinical data to support their use in man. In contrast to the findings of Edelstein et al. (1980), the results in this study indicate erythromycin to be less active than RP 59500 against most Legionella spp. tested. However, RP 59500 was less active than ciprofloxacin and rifampicin. The results of this study differ from those obtained by Washington et al. (1985). The lowest MIQo values obtained in this study are explained by the absence of charcoal in our medium; charcoal interacts unfavourably with antimicrobial agents, such as rifampicin and macrolides (Barker et al., 1986).
Downloaded from http://jac.oxfordjournals.org/ at University of Manitoba on August 25, 2015
MICs were determined by a standard agar dilution procedure using doubling dilutions of antibiotic. The medium used was buffered yeast extract agar (BYE). The inoculum was prepared from an overnight culture and colonies were added to .sterile water to a turbidity of no. 1 McFarland standard. This inoculum was diluted ten-fold and, by means of a replicating device, about 104 cfu were inoculated on to BYE containing doubling dilutions of antibiotics from 0.004 mg/L to 8 mg/L. The plates were incubated aerobically at 35°C for 48 h. The MIC was defined as the lowest concentration of antimicrobial agent that completely inhibited visible growth. Legionella pnewnophila ATCC 33152 was included as a control.
In-vttro acttrity of RP 59500 against IcgkmcOa
79
Table L Susceptibility of Legionella pneumophila serogroups 1 to 8 to RP 59500, erythromycin, ciprofloxacin and rifampidn Organism (no. of strains)
MIC so
RP 59500 erythromycin ciprofloxacin rifampicin RP 59500 erythromycin ciprofloxacin rifampicin
0-12 0-25 0O3
