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Evaluation of in vitro activity of quinupristin/dalfopristin and comparator antimicrobial agents against worldwide clinical trial and other laboratory isolates

      Abstract

      This report summarizes the activities of quinupristin/dalfopristin (Q/D) and appropriate comparator antibiotics, including ciprofloxacin, erythromycin, gentamicin, rifampin, teicoplanin, and vancomycin, against selected gram-positive pathogens, including Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus agalactiae, and Streptococcus pyogenes. The study pathogens were obtained from 2 sources: (1) clinical isolates taken from patients participating in Q/D worldwide Phase III comparative and noncomparative (emergency-use program) clinical trials; and (2) other isolates collected from the laboratories of 45 geographically distinct medical centers around the world. Q/D was highly active, with minimum inhibitory concentrations (MICs) ≤1.0 μg/mL against most isolates, including those known to be resistant to methicillin, vancomycin, or erythromycin. Q/D was active (MICs ≤1 μg/mL) against 95% of the vancomycin-resistant E. faecium strains, for example, whereas ciprofloxacin was active against 6%. Q/D was equally active against methicillin-susceptible or -resistant S. aureus strains (MIC90 = 1 μg/mL), as was vancomycin (MIC90 = 2 μg/mL), whereas ciprofloxacin was much less active against methicillin-resistant strains than against methicillin-susceptible strains (MIC90 = 32 vs 1 μg/mL). Given its spectrum of activity, Q/D may provide a viable option for the treatment of severe respiratory and skin and skin-structure infections caused by gram-positive bacteria, especially when strains with known or suspected resistance to other commonly used antibiotics are present.
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      References

        • CDC
        Nosocomial enterococci resistant to vancomycin—United States, 1989-1993.
        MMWR. 1993; 42: 597-599
        • Leclerq R
        • Derlot E
        • Weber M
        • Duval J
        • Courvalin P
        Transferable vancomycin and teicoplanin resistance in Enterococcus faecium.
        Antimicrob Agents Chemother. 1989; 33: 10-15
        • CDC
        Reduced susceptibility of Staphylococcus aureus to vancomycin—Japan 1996.
        MMWR. 1997; 46: 624-626
        • Hiramatsu K
        The emergence of Staphylococcus aureus with reduced susceptibility to vancomycin in Japan.
        Am J Med. 1998; 104: 7-10
        • CDC
        Staphylococcus aureus with reduced susceptibility to vancomycin—United States, 1997.
        MMWR. 1997; 46: 765-766
        • CDC
        Update.
        MMWR. 1997; 46: 813-815
        • Wilkinson B.J
        • Maxwell S
        • Schaus S.M
        Classification and characteristics of coagulase-negative, methicillin-resistant staphylococci.
        J Clin Microbiol. 1980; 12: 161-166
        • Poyart C
        • Pierre C
        • Quesne G
        • et al.
        Emergence of vancomycin resistance in the genus streptococcus.
        Antimicrob Agents Chemother. 1997; 41: 24-29
        • Boswell T.C
        • Frodsham D
        • Nye K.J
        • Smith E.G
        Antibiotic resistance and serotypes of Streptococcus pneumoniae at Birmingham Public Health Laboratory, 1989-94.
        J Infect. 1996; 33: 17-22
        • Johnson A.P
        • Speller D.C
        • George R.C
        • et al.
        Prevalence of antibiotic resistance and serotypes in pneumococci in England and Wales.
        BMJ. 1996; 312: 1454-1456
        • Ednie L.M
        • Visalli M.A
        • Jacobs M.R
        • Appelbaum P.C
        Comparative activities of clarithromycin, erythromycin, and azithromycin against penicillin-susceptible and penicillin-resistant pneumococci.
        Antimicrob Agents Chemother. 1996; 40: 1950-1952
        • Cornaglia G
        • Ligozzi M
        • Mazzariol A
        • Valentini M
        • Orefici G
        • Fontana R
        Rapid increase of resistance to erythromycin and clindamycin in Streptococcus pyogenes in Italy, 1993-1995.
        Emerg Infect Dis. 1996; 2: 339-342
        • Lee H.J
        • Park J.Y
        • Jang S.H
        • Kim J.H
        • Kim E.C
        • Choi K.W
        High incidence of resistance to multiple antimicrobials in clinical isolates of Streptococcus pneumoniae from a university hospital in Korea.
        Clin Infect Dis. 1995; 20: 826-835
        • DiGiambattista M
        • Chinali G
        • Cocito C
        The molecular basis of the inhibitory activities of type A and type B synergimycins and related antibiotics on ribosomes.
        J Antimicrob Chemother. 1989; 24: 485-506
        • DiGiambattista M
        • Engelborghs Y
        • Nyssen E
        • Cocito C
        Kinetics of binding of macrolides, lincosamides, and synergimycins to ribosomes.
        J Biol Chemistry. 1987; 262: 8591-8597
        • Aumercier M
        • Bouhallab S
        • Capmau M.L
        • Le Goffic F
        RP 59500.
        J Antimicrob Chemother. 1992; 30: 9-14
        • Andrews J.M
        • Wise R
        The in vitro activity of a new semi-synthetic streptogramin compound, RP 59500, against staphylococci and respiratory pathogens.
        J Antimicrob Chemother. 1994; 33: 849-853
        • Neu H.C
        • Chin N.X
        • Gu J.W
        The in vitro activity of new streptogramins, RP 59500, RP 57669 and RP 54476, alone and in combination.
        J Antimicrob Chemother. 1992; 30: 83-94
        • Hoban D.J
        • Weshnoweski B
        • Palatnick L
        • Zhanel C.G
        • Davidson R.J
        In vitro activity of streptogramin RP 59500 against staphylococci, including bactericidal kinetic studies.
        J Antimicrob Chemother. 1992; 30: 59-65
        • Leclerq R
        • Nantas L
        • Soussy C.J
        • Duval J
        Activity of RP 59500, a new parenteral semisynthetic streptogramin, against staphylococci with various mechanisms of resistance to macrolide-lincosamide-streptogramin antibiotics.
        J Antimicrob Chemother. 1992; 30: 67-75
        • Archer G.L
        • Auger P
        • Doern G.V
        • et al.
        RP 59500, a new streptogramin highly active against recent isolates of North American staphylococci.
        Diagn Microbiol Infect Dis. 1993; 16: 223-226
        • Barry A.L
        • Fuchs P.C
        In vitro activities of a streptogramin (RP59500), three macrolides, and an azalide against 4 respiratory tract pathogens.
        Antimicrob Ag Chemother. 1995; 39: 238-240
      1. Casewell M, Seyed-Akhavani M, Wade J. In vitro activity of RP 59500 against vancomycin-resistant Enterococcus faecium also resistant to ≥512 mg/L of gentamicin. 33rd Annual Meeting, Interscience Conference on Antimicrobial Agents and Chemotherapy; 1993; New Orleans, Louisiana.

        • Collins L.A
        • Malanoski G.J
        • Eliopoulos G.M
        • Wennersten C.B
        • Ferraro M.J
        • Moellering Jr, R.C
        In vitro activity of RP59500, an injectable streptogramin antibiotic, against vancomycin-resistant gram-positive organisms.
        Antimicrob Agents Chemother. 1993; 37: 598-601
        • Freeman C
        • Robinson A
        • Cooper B
        • Mazens-Sullivan M
        • Quintiliani R
        • Nightingale C
        In vitro antimicrobial susceptibility of glycopeptide-resistant enterococci.
        Diagn Microbiol Infect Dis. 1995; 21: 47-50
        • Fremaux A
        • Sissia G
        • Cohen R
        • Geslin P
        In-vitro antibacterial activity of RP 59500, a semisynthetic streptogramin, against Streptococcus pneumoniae.
        J Antimicrob Chemother. 1992; 30: 19-23
        • Pankuch G.A
        • Jacobs M.R
        • Appelbaum P.C
        Study of comparative antipneumococcal activities of penicillin G, RP 59500, erythromycin, sparfloxacin, ciprofloxacin, and vancomycin by using time-kill methodology.
        Antimicrob Agents Chemother. 1994; 38: 2065-2072
      2. Auckenthaler RA, Baquero F, Braveny I, et al. In vitro activity of RP 59500 against staphylococci: a European multicenter study. 31st Annual Meeting, Interscience Conference on Antimicrobial Agents and Chemotherapy; 1991; Chicago, Illinois.

      3. Silber JL, Patel M, Paul SM, Kostman JR. Statewide surveillance of isolates of vancomycin-resistant gram-positive cocci: genotyping of vancomycin resistance and activity of RP 59500 (Synercid) and other antimicrobials. 34th Annual Meeting, Interscience Conference on Antimicrobial Agents and Chemotherapy; 1994; Orlando, Florida.

      4. Data on file at Rhône-Poulenc Rorer, Collegeville, PA.

      5. National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 3rd edition. Approved standard M7-A3. Villanova, PA: National Committee for Clinical Laboratory Standards.

        • Barry A.L
        • Fuchs P.C
        • Brown S.D
        Provisional interpretive criteria for quinupristin/dalfopristin susceptibility tests.
        J Antimicrob Chemother. 1997; 39: 87-92
      6. Mahayni R, Perri MB, Dembry LM, Zervos, MJ. Comparative in vitro and bactericidal activity of RP 59500 (Synercid) against multiply-resistant Enterococcus faecium 34th Annual Meeting, Interscience Conference on Antimicrobial Agents and Chemotherapy; 1994; Orlando, Florida.

      7. Scriver SR, Willey BM, Matsumura S, Tyrrell G, Kreisuirth BN, Low DE. Susceptibility of glycopeptide-resistant enterococci, including variant species, to RP 59500. 1st Annual Meeting. International Conference on Macrolides, Azalides, and Streptogramins; 1994; Venice, Italy.

        • Ristow T
        • Noskin G
        • Warren J
        • Peterson L
        In vitro activity of RP 59500 (Synercid) and ramoplanin against vancomycin-resistant Enterococcus faecium.
        Microb Drug Resist. 1995; 1: 335-339
        • Johnson C.C
        • Slavoski L
        • Schwartz M
        • et al.
        In vitro activity of Synercid against antibiotic-resistant strains of Streptococcus pneumoniae and enterococci.
        Diagn Microbiol Infect Dis. 1995; 21: 169-173
      8. Scriver SR, Lai STF, Chong Y, Gonsales A, Levi M, Low DE. In vitro activity of RP 59500 against Streptococcus pneumoniae including isolates moderately susceptible and resistant to penicillin. 1st Annual Meeting, International Conference on Macrolides, Azalides, and Streptogramins; 1994; Venice, Italy.

        • Tarasi A
        • Dever L
        • Tomasz A
        Activity of quinupristin/dalfopristin against Streptococcus pneumoniae in vitro and in vivo in the rabbit model of experimental meningitis.
        J Antimicrob Chemother. 1997; 39: 121-127