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dalfopristin (RP 59500) against a large collection of infrequently isolated or tested species
ELSEVIER
In Vitro Activity of Quinupristin/ Dalfopristin (RI? 59500) Against a Large Collection of Infrequently Isolated or Tested Species Mary S. Barrett and Ronald N. Jones
Quinuprisfin/dalfoprisfin (RP 59500, Synercid@) is a parenferal streptogramin combination antimicrobial that possesses a synergistic and often bactericidal action against many Grampositive species. In this study, a collection of 1270 uncommonly isolated OY tested strains were evaluated for suscepfibilify to quinuprisfin/dalfoprisfin using agar dilution minimum inhibitory concentration (MIC) methods described in fke National Committee for Clinical Laboratory Standards. The greafesf antimicrobial activity observed for quinuprisfin/dalfoprisfin was against staphylococci, streptococci, the pathogenic neisseria, Legionella spp., Lactobacillus spp., and Peptostreptococcus spp. (ME,, range, 0.5-2 ug/mlI. Marginal activity (M&&s, 4 to 8 ug/ml) was identified for the rarer enferococci,
INTRODUCTION Quinupristin/dalfopristin (formerly RP 59500) is a parenteral combination antimicrobial of the macrolide-lincosamide-streptogramin family that possesses a synergistic antibacterial action. The components are semisynthetic pristinamycin derivatives, quinupristin (formerly RI’ 57669) and dalfopristin (formerly RI? 54476), in the 30:70 (w/w> ratio. Published studies have demonstrated excellent in vitro activity against many commonly encountered Grampositive species including StuphyZococcus spp. [Neu et al., 1992; Soussy et al., 1992; Archer et al., 19931, Streptococcus pneumoniae [Neu et al., 1992; Soussy et al., 19921, Enterococcus fuecium [Goto et al., 1992; FreeFrom the Medical Microbiology Division, Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa, U.S.A. Address reprint requests to Mary S. Barrett, Department of Pathology, 251 MRC, University of Iowa College of Medicine, Iowa City, Iowa 52242. Received 1 July 1996; revised and accepted 1 August 1996.
DIAGN MICROBIOL INFECT DIS 1996;25:147-149 0 1996 Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
Leuconostoc spp., Pediococcus spp., and Streptococcus bovis. Against Haemophilus parainfluenzae, Bacteroides thetaiotaomicron, Fusobacterium spp., and Prevotella spp., the sfreptogramin was inactive. Although no susceptible breakpoint has been approved for quinuprisfin/dalfopristin, three possible breakpoints (s 2, G 2, OY G 4 ug/mL) were evaluated. Acceptance of the lower breakpoints C< 1 or G 2 pg/mL) would limit quinupristin/dalfopristin use to staphylococci, streptococci, gonococci, meningococci, and Legionella spp. These results markedly expand the understanding of the usable spectrum of quinupristin/dalfopristin. 0 1996 Elsevier Sci-
ence Inc. man et al., 19951, and streptococci [Goto et al., 1992; Neu et al., 19921. Several respiratory tract pathogens have also been reportedly inhibited in vitro: Huemophilus influenzae [Neu et al., 19921, Moraxella catavrhalis [Neu et al., 19921, Legionella spp. [Soussy et al., 19921, and Mycoplasma spp. [Renaudin et al., 19911. Quinupristin/dalfopristin has been shown to be bactericidal against most susceptible isolates of staphylococci, streptococci, and enterococci [Neu et al., 1992; Soussy et al., 1992; Johnson et al., 19951 and has an extended postantibiotic effect [Chin and Neu, 19911. In this study we expand the antimicrobial activity information for quinupristin/dalfopristin against infrequently isolated or tested strains using reference in vitro methods. Quinupristin and dalfopristin were received from Rhone-Poulenc Rorer (Collegeville, PA). A collection of 1270 strains was studied that are uncommonly isolated or not routinely tested under clinical conditions. Several species with various well-defined mechanisms of resistance were included (See Table 1). The agar dilution antimicrobial susceptibility
0732~8893/96/$15.00 PI1 SO732-8893(96)00129-O
M.S. Barrett
148
TABLE
and R.N. Jones
Interim Report of Infrequently Isolated Bacterial Species Tested Against Quinupristin/DaIfopristin, 1270 Strains
1
% inhibited at MIC (kg/mL)
MIC (yg/mL) Organism
Enterococcus avium (27) Enterococcus casseliflavus (30) Entevococcus dumns (20) Enterococcus galli?zarum (33) Streptococcus bovis (14) Leucorzostoc spp. (20) Pediococcus spp. (21) Staphylococcus azlrezls
oxacillin-resistant Staphylococcus Staphylococcus Streptococcus, Streptococcus, Streptococcus, Sfreptococcus
90%
4 4
2
4 4 4 8 4 4 4
0.5 0.25 0.5 0.25 0.5 0.5
0.5 2 1 0.5 0.5 1
1
4 2 1
(105)
simulans (17) wanzeri (18) gr A (105) gr B (51) viridans
50%
gr (105)
Sl
Range
2-8 1-8 0.5-4 0.5->8 14 l-8 0.54 0.25-l 0.25-2 0.25-l 0.06-0.5 0.5-l
<2 0 3
70 12 36 75 29
19 27 80 27 79 90 71
G4 93 97 100 79 100 95 100
100
100
88
100
100 100
100
100
100
100
100
100
100
100
100
0.12-2
99
100
100
1 16
0.5-2
97
100
100
0
2
16
1
0.5-2
99
100
100
pneumoniae,
fluoroquinolone-resistant
(35)”
Haemophilzts parainfluenzae (56) Legionella spp. (105jb Neisseria gonorrkoeae (205) Neisseria menirzgitidis (105) Bacteroides fketaiotaomicrozz (30) Clostridium dificile (3) Fusobacterium spp. (10) Lactobacillus spp. (40) Peptostreptococcz4s spp. (58) Prevotelfa spp. (57)
0.5 8 0.5 0.25 0.25 16 1 1
0.5 0.5 2
0.5 0.5 32 16 2 1 16
2->16 0.015-l 0.06-0.5
100
100
100
100
100
100
8-32
0
0
0
1-16
67
67
67
0.25->16
60
60
70
0.12-2
68
100
100
0.254
98
98
100
23
60
88
l-32
“Defined as a ciprofloxacin MIC of a2 kg/ml. bIncludes L. pneumoniae (98 strains), L. micdadei (two strains), L. gormnnii (one strain), L. bazetnarzi (one strain), L. dumofii (one strain), L. jordanus (one strain), and L. longbeackae (one strain).
methods used in the evaluation were outlined in the procedures described in the National Committee for Clinical Laboratory Standards (NCCLS) documents [NCCLS 1993a,b, 19951. In brief, all organisms were tested using 5% sheep blood supplemented MuellerHinton gar in 3-5% CO, with a lo5 CFU/spot inoculum and interpreted at 24 hours of incubation unless otherwise specified. Deviations from the above cited testing conditions were as follows: Anaerobic organisms = 5% sheep blood Brucella agar, anaerobic atmosphere, incubated 48 hours; Gonococci = GC agar; Serogroup A streptococci and Neisseria meningitidis = lo4 CFU/spot; Haemophilus parainfluenzae = Haemophilus Test Media; and Legionella spp. = buffered charcoal yeast extract media, 10% CO,, incubated 48 hours. Table 1 summarizes the antimicrobial activity of quinupristin/dalfopristin (30:70) tested against 1270 bacteria. The greatest antimicrobial activity exhibited by the streptogramin combination was observed against staphylococci (MI&s, 0.5 to 2 kg/ml), streptococci (MI&,, 0.5 to 1 kg/mL), pathogenic nesseria
(MI&, 0.5 yg/mL), LegioneHa spp. (MI&, 1 pg/ mL), Lactobacillus spp. (MI&,, 2 kg/mL), and Peptostreptococcus spp. (MI&, 1 pg/mL). Previous reports of quinupristin/dalfopristin activity generally agreed within + two-fold of the value reported here [Goto et al., 1992; Neu et al., 1992; Soussy et al., 19921. Discord with earlier study results were those from Goto et al. [1992] that reported a significantly greater activity against serogroup A streptococci (MI&,, c 0.063 pg/ mL) and Soussy et al. 119921 that reported a MI& of 2 pg/ml for gonococci that was four-fold greater than our results. This difference may be due to the use of a different agar medium (GC agar base) or to the organism populations found in Japan and France. Marginal activity (MI&+, 4 to 8 Fg/mL) for quinupristin/dalfopristin was documented for serogroup D streptococci, rarer Enterococcus spp., and species having intrinsic resistance to glycopeptides (Leucolzostuc spp., Pediococcus spp.). The degree of spectrum could vary from 0% to 100% for these species depending upon that selected breakpoint concentration indicating susceptibility.
Note
Poor antimicrobial activity was displayed by quinupristin/dalfopristin against H. p~~upinfhen~ae, Bacteroides thetaiotaomicron, Fusobacterium spp., and 2 16 &mL). Previous pubPreuotellaspp. (MI&, lications [Neu et al., 19921 have reported MIC,,s of 4 k.g/mL for Haemophilus injluenzae, which indicated greater antibacterial activity than that detected here against H. puruinfluenzae. Neu et al. 119921 has reported a MIC,, of 8 kg/mL for a set of Bacteroides strains that inchtded B. thetaiotaomicron e.g. four-fofd greater activity than reported here. No susceptible breakpoint criteria has been approved for quinupristin/dalfopristin in the United States. Peak human serum levels as high as 24 pg/ mL have been obtained, however, a lower dose of 5 to 15 mg/kg administered twice daily has been suggested that yields a Cmax of only 4 to 10 kg/mL [Etienne et al., 19921. In this study, three possible susceptible breakpoints (~1, ~2, or ~4 t.Lg/mL) were utilized to calculate the percentage inhibition of strains (spectrum). At <4 pg/mL, quinupristin/ dalfopristin was usable versus more than 90% of strains tested (except for E. gallinarum, Z-I.parupiulflu-
149
enzae, and some anaerobes). Lower breakpoints (~1 or ~2 kg/ml) would focus the quinupristin/dalfopristin use toward staphylococci, streptococci, N. gonorrhoeae, N. meningitidis, and Legionella spp. The excellent Gram-positive spectrum and potency of quinupristin/dalfopristin has been well documented against common species as well as its favorable killing qualities and postantibiotic effects [Chin and Neu, 1991; Goto et al., 1992; Neu and Chin, 1992; Soussy et al., 1992; Archer et al., 19931. Furthermore, several studies have outlined the potential role of this streptogramin combination against emergent antimicrobial-resistant species [Freeman et al., 1995; Johnson et al., 19951, but few investigations have addressed the extent of its spectrum against rarer bacteria [Renaudin et al., 19911. This study expands the spectrum characterization of this compound to 30 additional species including a large collection of oxacillin-resistant S. Rureus and fluoroquinolone (ciprofloxacin)-resistant pneumococci. Quinupristin/dalfopristin appears to be an excellent candidate for the therapy of infections caused by Gram-positive organisms that may be refractory to contemporary drugs.
REFERENCES Archer G, Auger P, Doern G, Ferraro MJ, Fuchs P, Jorgensen J, Low D, Murray I’, Reller LB, Stratton C, Wennersten C, Moellering RC (1993) RI’ 59500, a new streptogramin highly active against recent isoIates of North American staphylococci. Diagn Microbiol Infect Dis 16: 223-226. Chin NX, Neu HC (1991) Post-antibiotic effect of RP 59500 against Gram-positive bacteria compared to other agents. 3Ist ICAAC, Chicago, US: Abstract 899. Etienne SD, Montay G, LeLibaux A, Frydman A, Garaud JJ (1992) A phase I, double-blind, placebo-controlled study of the tolerance and pharmacokinetic behavior of RF’ 59500. J Antimicrob Chemother 3O(Suppl A):123-131. Freeman C, Robinson A, Cooper 8, Mazens-Sullivan M, Quintilliani R, Nightingale C (1995) In vitro antimicrobial susceptibility of glycopeptide-resistant enterococci. Diagn Microbial Infect Dis 21:47-50.
National Committee for Clinical Laboratory Standards (NCCLS). (1993a) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 3rd ed. Approved standard M7-A3. Villanova, PA: NCCLS. National Committee for Clinical Laboratory Standards (NCCLS). (1993b) Methods for antimicrobial susceptibility testing of an aerobic bacteria, 3rd ed. Approved standard Ml 1 -A3. Villanova, PA: NCCLS. National Committee for Clinical Laboratory Standards (NCCLS) (1995) Performance standards for antimicrobial susceptibility testing. Sixth Information Supplement MlOO-S6. Villanova, PA: NCCLS. Neu HC, Chin N, Gu J. (1992) The in vitro activity of new streptogramins, RP 59500, RI’ 57669, and RI’ 54476, alone and in combination. J Antimicrob Chemofher 3O(Suppl A):83-94.
Goto S, Miyazaki S, Kaneko Y (1992) The in vitro activity of RP 59500, a new semisynthetic streptogramin antibiotic against Gram-positive bacteria. ] Antimicrob Chemother 3O(Suppl A):25-28.
Renaudin H, Boussens B, Bebear C (1991) In vitro activity of RI’ 59500 against mycoplasma. 31st ICAAC, Chicago, US: Abstract 893.
Johnson CC, Slavoski L, Schwartz M, May I’, Pitsakis PG, Shur AL, Levison ME (1995) In vitro activity of RP 59500 (quinupristin/dalfopristin) against antibiotic-resistant strains of Streptococcus pneumoniae and enterococci. Diagn Microbial Infect Dis 21;169-173.
Soussy CJ, Acar JF, Cluzel R, Courvalin P, Duval J, Fleurette J, Megraud, Meyran M, Thabaut A (1992) A collaborative study of the in vitro sensitivity to RP 59500 of bacteria isolated in seven hospitals in France. J Antimicrab Chemother 3O(Suppl A):53-58.
In Vitro Activity of Quinupristin/ Dalfopristin (RI? 59500) Against a Large Collection of Infrequently Isolated or Tested Species Mary S. Barrett and Ronald N. Jones
Quinuprisfin/dalfoprisfin (RP 59500, Synercid@) is a parenferal streptogramin combination antimicrobial that possesses a synergistic and often bactericidal action against many Grampositive species. In this study, a collection of 1270 uncommonly isolated OY tested strains were evaluated for suscepfibilify to quinuprisfin/dalfoprisfin using agar dilution minimum inhibitory concentration (MIC) methods described in fke National Committee for Clinical Laboratory Standards. The greafesf antimicrobial activity observed for quinuprisfin/dalfoprisfin was against staphylococci, streptococci, the pathogenic neisseria, Legionella spp., Lactobacillus spp., and Peptostreptococcus spp. (ME,, range, 0.5-2 ug/mlI. Marginal activity (M&&s, 4 to 8 ug/ml) was identified for the rarer enferococci,
INTRODUCTION Quinupristin/dalfopristin (formerly RP 59500) is a parenteral combination antimicrobial of the macrolide-lincosamide-streptogramin family that possesses a synergistic antibacterial action. The components are semisynthetic pristinamycin derivatives, quinupristin (formerly RI’ 57669) and dalfopristin (formerly RI? 54476), in the 30:70 (w/w> ratio. Published studies have demonstrated excellent in vitro activity against many commonly encountered Grampositive species including StuphyZococcus spp. [Neu et al., 1992; Soussy et al., 1992; Archer et al., 19931, Streptococcus pneumoniae [Neu et al., 1992; Soussy et al., 19921, Enterococcus fuecium [Goto et al., 1992; FreeFrom the Medical Microbiology Division, Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa, U.S.A. Address reprint requests to Mary S. Barrett, Department of Pathology, 251 MRC, University of Iowa College of Medicine, Iowa City, Iowa 52242. Received 1 July 1996; revised and accepted 1 August 1996.
DIAGN MICROBIOL INFECT DIS 1996;25:147-149 0 1996 Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
Leuconostoc spp., Pediococcus spp., and Streptococcus bovis. Against Haemophilus parainfluenzae, Bacteroides thetaiotaomicron, Fusobacterium spp., and Prevotella spp., the sfreptogramin was inactive. Although no susceptible breakpoint has been approved for quinuprisfin/dalfopristin, three possible breakpoints (s 2, G 2, OY G 4 ug/mL) were evaluated. Acceptance of the lower breakpoints C< 1 or G 2 pg/mL) would limit quinupristin/dalfopristin use to staphylococci, streptococci, gonococci, meningococci, and Legionella spp. These results markedly expand the understanding of the usable spectrum of quinupristin/dalfopristin. 0 1996 Elsevier Sci-
ence Inc. man et al., 19951, and streptococci [Goto et al., 1992; Neu et al., 19921. Several respiratory tract pathogens have also been reportedly inhibited in vitro: Huemophilus influenzae [Neu et al., 19921, Moraxella catavrhalis [Neu et al., 19921, Legionella spp. [Soussy et al., 19921, and Mycoplasma spp. [Renaudin et al., 19911. Quinupristin/dalfopristin has been shown to be bactericidal against most susceptible isolates of staphylococci, streptococci, and enterococci [Neu et al., 1992; Soussy et al., 1992; Johnson et al., 19951 and has an extended postantibiotic effect [Chin and Neu, 19911. In this study we expand the antimicrobial activity information for quinupristin/dalfopristin against infrequently isolated or tested strains using reference in vitro methods. Quinupristin and dalfopristin were received from Rhone-Poulenc Rorer (Collegeville, PA). A collection of 1270 strains was studied that are uncommonly isolated or not routinely tested under clinical conditions. Several species with various well-defined mechanisms of resistance were included (See Table 1). The agar dilution antimicrobial susceptibility
0732~8893/96/$15.00 PI1 SO732-8893(96)00129-O
M.S. Barrett
148
TABLE
and R.N. Jones
Interim Report of Infrequently Isolated Bacterial Species Tested Against Quinupristin/DaIfopristin, 1270 Strains
1
% inhibited at MIC (kg/mL)
MIC (yg/mL) Organism
Enterococcus avium (27) Enterococcus casseliflavus (30) Entevococcus dumns (20) Enterococcus galli?zarum (33) Streptococcus bovis (14) Leucorzostoc spp. (20) Pediococcus spp. (21) Staphylococcus azlrezls
oxacillin-resistant Staphylococcus Staphylococcus Streptococcus, Streptococcus, Streptococcus, Sfreptococcus
90%
4 4
2
4 4 4 8 4 4 4
0.5 0.25 0.5 0.25 0.5 0.5
0.5 2 1 0.5 0.5 1
1
4 2 1
(105)
simulans (17) wanzeri (18) gr A (105) gr B (51) viridans
50%
gr (105)
Sl
Range
2-8 1-8 0.5-4 0.5->8 14 l-8 0.54 0.25-l 0.25-2 0.25-l 0.06-0.5 0.5-l
<2 0 3
70 12 36 75 29
19 27 80 27 79 90 71
G4 93 97 100 79 100 95 100
100
100
88
100
100 100
100
100
100
100
100
100
100
100
100
0.12-2
99
100
100
1 16
0.5-2
97
100
100
0
2
16
1
0.5-2
99
100
100
pneumoniae,
fluoroquinolone-resistant
(35)”
Haemophilzts parainfluenzae (56) Legionella spp. (105jb Neisseria gonorrkoeae (205) Neisseria menirzgitidis (105) Bacteroides fketaiotaomicrozz (30) Clostridium dificile (3) Fusobacterium spp. (10) Lactobacillus spp. (40) Peptostreptococcz4s spp. (58) Prevotelfa spp. (57)
0.5 8 0.5 0.25 0.25 16 1 1
0.5 0.5 2
0.5 0.5 32 16 2 1 16
2->16 0.015-l 0.06-0.5
100
100
100
100
100
100
8-32
0
0
0
1-16
67
67
67
0.25->16
60
60
70
0.12-2
68
100
100
0.254
98
98
100
23
60
88
l-32
“Defined as a ciprofloxacin MIC of a2 kg/ml. bIncludes L. pneumoniae (98 strains), L. micdadei (two strains), L. gormnnii (one strain), L. bazetnarzi (one strain), L. dumofii (one strain), L. jordanus (one strain), and L. longbeackae (one strain).
methods used in the evaluation were outlined in the procedures described in the National Committee for Clinical Laboratory Standards (NCCLS) documents [NCCLS 1993a,b, 19951. In brief, all organisms were tested using 5% sheep blood supplemented MuellerHinton gar in 3-5% CO, with a lo5 CFU/spot inoculum and interpreted at 24 hours of incubation unless otherwise specified. Deviations from the above cited testing conditions were as follows: Anaerobic organisms = 5% sheep blood Brucella agar, anaerobic atmosphere, incubated 48 hours; Gonococci = GC agar; Serogroup A streptococci and Neisseria meningitidis = lo4 CFU/spot; Haemophilus parainfluenzae = Haemophilus Test Media; and Legionella spp. = buffered charcoal yeast extract media, 10% CO,, incubated 48 hours. Table 1 summarizes the antimicrobial activity of quinupristin/dalfopristin (30:70) tested against 1270 bacteria. The greatest antimicrobial activity exhibited by the streptogramin combination was observed against staphylococci (MI&s, 0.5 to 2 kg/ml), streptococci (MI&,, 0.5 to 1 kg/mL), pathogenic nesseria
(MI&, 0.5 yg/mL), LegioneHa spp. (MI&, 1 pg/ mL), Lactobacillus spp. (MI&,, 2 kg/mL), and Peptostreptococcus spp. (MI&, 1 pg/mL). Previous reports of quinupristin/dalfopristin activity generally agreed within + two-fold of the value reported here [Goto et al., 1992; Neu et al., 1992; Soussy et al., 19921. Discord with earlier study results were those from Goto et al. [1992] that reported a significantly greater activity against serogroup A streptococci (MI&,, c 0.063 pg/ mL) and Soussy et al. 119921 that reported a MI& of 2 pg/ml for gonococci that was four-fold greater than our results. This difference may be due to the use of a different agar medium (GC agar base) or to the organism populations found in Japan and France. Marginal activity (MI&+, 4 to 8 Fg/mL) for quinupristin/dalfopristin was documented for serogroup D streptococci, rarer Enterococcus spp., and species having intrinsic resistance to glycopeptides (Leucolzostuc spp., Pediococcus spp.). The degree of spectrum could vary from 0% to 100% for these species depending upon that selected breakpoint concentration indicating susceptibility.
Note
Poor antimicrobial activity was displayed by quinupristin/dalfopristin against H. p~~upinfhen~ae, Bacteroides thetaiotaomicron, Fusobacterium spp., and 2 16 &mL). Previous pubPreuotellaspp. (MI&, lications [Neu et al., 19921 have reported MIC,,s of 4 k.g/mL for Haemophilus injluenzae, which indicated greater antibacterial activity than that detected here against H. puruinfluenzae. Neu et al. 119921 has reported a MIC,, of 8 kg/mL for a set of Bacteroides strains that inchtded B. thetaiotaomicron e.g. four-fofd greater activity than reported here. No susceptible breakpoint criteria has been approved for quinupristin/dalfopristin in the United States. Peak human serum levels as high as 24 pg/ mL have been obtained, however, a lower dose of 5 to 15 mg/kg administered twice daily has been suggested that yields a Cmax of only 4 to 10 kg/mL [Etienne et al., 19921. In this study, three possible susceptible breakpoints (~1, ~2, or ~4 t.Lg/mL) were utilized to calculate the percentage inhibition of strains (spectrum). At <4 pg/mL, quinupristin/ dalfopristin was usable versus more than 90% of strains tested (except for E. gallinarum, Z-I.parupiulflu-
149
enzae, and some anaerobes). Lower breakpoints (~1 or ~2 kg/ml) would focus the quinupristin/dalfopristin use toward staphylococci, streptococci, N. gonorrhoeae, N. meningitidis, and Legionella spp. The excellent Gram-positive spectrum and potency of quinupristin/dalfopristin has been well documented against common species as well as its favorable killing qualities and postantibiotic effects [Chin and Neu, 1991; Goto et al., 1992; Neu and Chin, 1992; Soussy et al., 1992; Archer et al., 19931. Furthermore, several studies have outlined the potential role of this streptogramin combination against emergent antimicrobial-resistant species [Freeman et al., 1995; Johnson et al., 19951, but few investigations have addressed the extent of its spectrum against rarer bacteria [Renaudin et al., 19911. This study expands the spectrum characterization of this compound to 30 additional species including a large collection of oxacillin-resistant S. Rureus and fluoroquinolone (ciprofloxacin)-resistant pneumococci. Quinupristin/dalfopristin appears to be an excellent candidate for the therapy of infections caused by Gram-positive organisms that may be refractory to contemporary drugs.
REFERENCES Archer G, Auger P, Doern G, Ferraro MJ, Fuchs P, Jorgensen J, Low D, Murray I’, Reller LB, Stratton C, Wennersten C, Moellering RC (1993) RI’ 59500, a new streptogramin highly active against recent isoIates of North American staphylococci. Diagn Microbiol Infect Dis 16: 223-226. Chin NX, Neu HC (1991) Post-antibiotic effect of RP 59500 against Gram-positive bacteria compared to other agents. 3Ist ICAAC, Chicago, US: Abstract 899. Etienne SD, Montay G, LeLibaux A, Frydman A, Garaud JJ (1992) A phase I, double-blind, placebo-controlled study of the tolerance and pharmacokinetic behavior of RF’ 59500. J Antimicrob Chemother 3O(Suppl A):123-131. Freeman C, Robinson A, Cooper 8, Mazens-Sullivan M, Quintilliani R, Nightingale C (1995) In vitro antimicrobial susceptibility of glycopeptide-resistant enterococci. Diagn Microbial Infect Dis 21:47-50.
National Committee for Clinical Laboratory Standards (NCCLS). (1993a) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 3rd ed. Approved standard M7-A3. Villanova, PA: NCCLS. National Committee for Clinical Laboratory Standards (NCCLS). (1993b) Methods for antimicrobial susceptibility testing of an aerobic bacteria, 3rd ed. Approved standard Ml 1 -A3. Villanova, PA: NCCLS. National Committee for Clinical Laboratory Standards (NCCLS) (1995) Performance standards for antimicrobial susceptibility testing. Sixth Information Supplement MlOO-S6. Villanova, PA: NCCLS. Neu HC, Chin N, Gu J. (1992) The in vitro activity of new streptogramins, RP 59500, RI’ 57669, and RI’ 54476, alone and in combination. J Antimicrob Chemofher 3O(Suppl A):83-94.
Goto S, Miyazaki S, Kaneko Y (1992) The in vitro activity of RP 59500, a new semisynthetic streptogramin antibiotic against Gram-positive bacteria. ] Antimicrob Chemother 3O(Suppl A):25-28.
Renaudin H, Boussens B, Bebear C (1991) In vitro activity of RI’ 59500 against mycoplasma. 31st ICAAC, Chicago, US: Abstract 893.
Johnson CC, Slavoski L, Schwartz M, May I’, Pitsakis PG, Shur AL, Levison ME (1995) In vitro activity of RP 59500 (quinupristin/dalfopristin) against antibiotic-resistant strains of Streptococcus pneumoniae and enterococci. Diagn Microbial Infect Dis 21;169-173.
Soussy CJ, Acar JF, Cluzel R, Courvalin P, Duval J, Fleurette J, Megraud, Meyran M, Thabaut A (1992) A collaborative study of the in vitro sensitivity to RP 59500 of bacteria isolated in seven hospitals in France. J Antimicrab Chemother 3O(Suppl A):53-58.