Microbiology Chemotherapy 1992;38:303-307
J.C. Lefèvre R. Bauriaud E. Gaubert M.C. Escaffre M.B. Lareng
In vitro Activity of Sparfloxacin and Other Antimicrobial Agents against Genital Pathogens
Groupe ‘Etude et Prévention des Maladies Transmissibles Sexuellement’, Laboratoire Central de Microbiologie, Hôpital Purpan, Toulouse, France
Abstract The in vitro activity of sparfloxacin was determined for 60 strains of Neisseria gonorrhoeae, 15 strains of Chlamydia tracho matis and 40 strains each of Gardnerella vaginalis, Mycoplasma hominis, and Ureaplasma urealyticum and compared with those of ampicillin, azithromycin, clarithromycin, erythromycin, ofloxacin, temafloxacin and tetracycline. Sparfloxacin was ac tive against all the strains studied and appeared to be the most potent quinolone tested. Sparfloxacin had the lowest MICs against N. gonorrhoeae (MICs 0.002-0.06 pg/ml). Its MICs against C. trachomatis (0.03-0.06 ug/ml) were higher than those of clarithromycin but lower than those of the other anti microbial agents. Sparfloxacin was particularly active against tetracycline-susceptible as well as resistant strains of M. homi nis (MICs, 0.06 pg/ml) and U. urealyticum (MICs 0.125-1 pg/ ml). Because of this in vitro activity and its tissue distribution, sparfloxacin might be a valuable therapeutic agent for treating major bacterial sexually transmitted diseases.
Introduction Although most bacterial sexually transmit ted diseases can be effectively treated, antimi crobial resistance to penicillins, tetracyclines and erythromycins, limits the use of these anti
biotics. Since sexually transmitted diseases caused by different pathogens are frequently concurrent, treatment with a single antibiotic with a broad spectrum of activity against these pathogens would be of great clinical value. Fluoroquinolones represent a class of broad-
J.C. Lefèvre Groupe ‘Etude et Prévention des Maladies Transmissibles Sexuellement', Laboratoire Central de Microbiologie Hôpital Purpan. Place du Docteur Baylac F-31059 Toulouse Cedex (France)
© 1992 S. Karger AG, Bascl 0009-3157/92/ 0385-0303 $ 2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/3/2018 7:49:28 PM
Key Words Sparfloxacin Genital pathogens Susceptibility, in vitro
CO, at 37 °C, the MIC was determined by observing the lowest concentration of antibiotic in which bacte rial growth was inhibited. In each experiment, World Health Organization N. gonorrhoeae reference strains A, B. C, D and E were included; the MICs of tetra cycline for these strains were similar to those obtained by Riou ct al. |8] with peptone agar. The MICs for M. hominis and U. urealyticum were determined in microdilution plates (12x8 wells). The growth medium was Shepard broth without penicillin in U. urealyticum tests and modified Hayflick medium without penicillin in M. hominis tests. The plates con taining serial dilutions of antibiotics (0.016-128 pg/l) were inoculated with 104 color change units per millili ter and incubated in 5% CO, for 48 h. The MIC was de fined as the lowest concentration of antibiotic which prevented color change. In each experiment a refer ence strain, M. hominis PG21 or U. urealyticum 2K160 was included. The MICs of tetracycline for strain PG21 were 32 ug/ml and for strain 2K160,0.5 ug/ml. The MIC for C. trachomatis was determined by a modification of a previously described method [9). All the clinical isolates and a laboratory strain of C. tracho matis (LGV-II ATCC VR-902) used as a control were passaged extensively in the laboratory and at least twice in antibiotic-free maintenance medium (Eagle minimum essential medium with 10% fetal bovine se rum. 1% glutamine, and 5 g of glucose per liter). Monolayers of antibiotic-free McCoy cells were grown in 96well microdilution plates seeded at a concentration of Materials and Methods 2.0 x 10’ cells/ml. After 48 h of incubation, the C. tra chomatis strains were each inoculated (250-500 inclu A total of 20 penicillinase-producing N. gonor sion-forming units/well). Monolayers were then cen rhoeae, 40 non-penicillinasc-producing N. gonor trifuged for 60 min at 1,500 g, aspirated, and overlaid rhoeae, 40 M. hominis, 40 U. urealyticum, 15 C. tracho with appropriate serial dilutions of the antibiotic being matis and 40 C. vaginalis strains were used. All the tested (0.004-64 pg/ml). All dilutions were made with strains were isolated from specimens obtained from the above-mentioned antibiotic-free maintenance me patients attending the Sexually Transmitted Diseases Clinic of Purpan Hospital in Toulouse, France (1988— dium containing 0.5 pg of cyclohcximide per milliliter. Appropriate antibiotic-free controls were included on 1990). The organisms were stored at -7 0 °C until use. each plate. Cultures were incubated for 48 h at 35 °C The antimicrobial agents used were ampicillin and then fixed and stained for enumeration of inclu (Bristol Laboratories), tetracycline,ofloxacin (Roussel sions by using a fluorescein-conjugated monoclonal Laboratories), erythromycin, clarithromycin, temaantibody (Ortho Diagnostics, Inc.). The lowest concen floxacin (Abbott Laboratories), azithromycin (Pfizer tration of each antibiotic with completely inhibited in Laboratories) and Sparfloxacin (Rhöne-Poulcnc). clusion formation was defined as the MIC. In each ex MIC tests with N. gonorrhoeae and G. vaginalis periment. the reference strain (LGV-II) was included; were performed by an agar dilution technique with the MIC of tetracycline for this strain was 0.06 pg/ml. Mucllcr-Hinton agar supplemented with 5% horse blood, as described previously [7). Twofold serial con centrations from 0.001 to 128 ug/ml were incorporated into the medium. The inocula were prepared from a 24-hour culture on agar medium and diluted to obtain Hf CFU per spot in N. gonorrhoeae and G. vaginalis tests. After incubation of the inocula for 48 h in 10%
304
Lefevre/Bauriaud/Gaubert/Escaffre/ Lareng
Sparfloxacin and Other Antimicrobial Agents against Genital Pathogens
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/3/2018 7:49:28 PM
spcctrum antimicrobial agents active against many gram-positive and gram-negative or ganisms. However, some genital pathogens such as mycoplasmas, Chlamydia trachomatis and Gardnerella vaginalis are not sufficiently susceptible to many of the quinolones test ed to date [1-3]. Sparfloxacin, a new difluoro quinolone antibiotic (previously designated AT4140) has been shown to have a spectrum of activity including not only the common bacte rial pathogens but also C. trachomatis and my coplasmas [4-6]. However, very few compari sons were made between Sparfloxacin and other classes of antimicrobial agents used in the treatment of genital infections. Moreover, there are no data available about its activity against G. vaginalis. We have therefore exam ined the in vitro activity of Sparfloxacin against clinical isolates of Neisseria gonorrhoeae, Mycoplasma homiis, Ureaplasma urealyticum, C. trachomatis, G. vaginalis and compared it with those of seven appropriate antibiotics.
Table 1. In vitro susceptibilities of genital pathogens to sparfloxacin and seven other antibiotics Antimicrobial agent
N. gonorrhoeae non penicillinase-producing (40)
ampicillin tetracycline erythromycin azithromycin clarithromycin ofloxacin tcmafloxacin sparfloxacin ampicillin tetracycline erythromycin azithromycin clarithromycin ofloxacin temafloxacin sparfloxacin ampicillin tetracycline erythromycin azithromycin clarithromycin ofloxacin tcmafloxacin sparfloxacin ampicillin tetracycline erythromycin azithromycin clarithromycin ofloxacin temafloxacin sparfloxacin tetracycline erythromycin azithromycin clarithromycin ofloxacin temafloxacin sparfloxacin tetracycline erythromycin azithromycin clarithromycin ofloxacin temafloxacin sparfloxacin
N. gonorrhoeae penicillinase-producing (20)
C. trachomatis (15)
G. vaginalis (40)
M. hominis (40)
U. urealyticum (40)
MIC, pg/ml range 0.03-1 0.125-64 0.03-1 0.008-0.25 0.03-1 0.008-0.25 0.004-0.03 0.002-0.008 >2 0.5-4 0.06-2 0.016-0.5 0.06-1 0.008-0.5 0.004-0.25 0.002-0.06 >32 0.06 0.06-0.125 0.06-0.125 0.008-0.016 0.5-1 0.25-0.5 0.03-0.06 0.06-1 0.125-128 0.008-0.125 0.004-0.125 0.016-0.06 1-4 0.25-2 0.125-1 0.125-32 > 128 32-128 > 128 0.25-1 0.06-0.25 0.06 0.125-64 0.25-4 0.5-4 0.03-0.25 1-4 0.5-4 0.125-1
50%
90%
0.25 0.5 0.25 0.016 0.25 0.016 0.008 0.004 >2 1 0.25 0.06 0.25 0.016 0.(X)8 0.004 >32 0.06 0.06 0.06 0.008 0.5 0.25 0.03 0.25 2 0.03 0.03 0.03 1 0.5 0.25 0.125 > 128 64 > 128 0.5 0.125 0.06 0.5 1 2 0.06 2 1 0.25
1 2 1 0.15 0.5 0.06 0.03 0.008 >2 2 1 0.25 1 0.03 0.016 0.008 >32 0.125 0.125 0.125 0.016 1 0.5 0.06 1 64 0.06 0.06 0.06 2 1 0.5 16 > 128 128 > 128 0.5 0.125 0.06 32 2 2 0.125 4 2 0.5
305
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Organisms (number of isolates)
The MICs of Sparfloxacin and the other antimicrobial agents for isolates of N. gonorrhoeae, C. trachomatis, U. urealyticum, M. ho minis and G. vaginalis are shown in table 1. Sparfloxacin had a spectrum of activity grea ter than all other antimicrobial agents we studied. Sparfloxacin had a high intrinsic ac tivity against each strain of N. gonorrhoeae tested. No difference was observed between penicillinase- and non penicillinase-produc ing strains. Our results are in agreement with those previously reported [5,10,11]. C. tracho matis was inhibited by Sparfloxacin at MICs of 0.03-0.06 pg/ml which were higher than those of clarithromycin, a new macrolide, and lower than those of the other antimicrobial agents. Pharmacokinetic studies revealed that Spar floxacin was well absorbed orally, had a rela tively long half-life in plasma (19 h) and showed good tissue distribution (12]. Our find ings of the potent antichlamydial activity of Sparfloxacin suggest that it could be of benefit in the therapy of chlamydial infections. The tetracyclines and macrolides are the drugs most frequently used to treat infections asso ciated with mycoplasmas. These compounds are not ideal, because of the spread of Tct-Mmediated resistance and, in the case of 14- and 15-membered macrolides, lack of activity against M. hominis. Fluoroquinolones were the only compounds used in this series which demonstrated potentially useful activity against mycoplasmas, including those strains resistant to tetracycline. Sparfloxacin ap peared to be the most active quinolonc tested. Our results were similar to those reported re cently [4, 6], Furthermore, for mixed infec tions involving M. hominis (bacterial vaginosis and pelvic inflammatory disease), Sparfloxa cin appears very promising. This antibiotic has been reported to show valuable in vitro activ ity against anaerobic bacteria (5, 10, 11]. It
306
showed relatively good activity against G. vag inalis in our series with an MIC of 0.5 pg/ml for 90% of strains tested. Although discrepancies have been found between the in vitro and in vivo susceptibilities of G. vaginalis, clinical studies of sparfloxacin in bacterial vaginosis appear justified. A number of problems compromise the ef ficacy of currently available regimens in the antimicrobial therapy of bacterial sexually transmitted diseases. These include antimi crobial resistance, frequent side effects, lack of alternative for patients with drug allergies and ineffectiveness of most regimens against all pathogens in polymicrobial infections or in simultaneously occurring infections. The re sults of our in vitro study show the broad spec trum of activity of sparfloxacin against major genital pathogens. This antibiotic has in vitro activity superior to that of ofloxacin which is effective in the treatment of gonococcal and chlamydial infections [13-15] and to that of temafloxacin, a newer fluoroquinolone. More over, sparfloxacin may be useful in the treat ment of genital tract infections because of its tissue distribution and prolonged half-life. Preliminary studies have shown that the to xicity of sparfloxacin is low enough to allow the initiation of clinical trials which will be re quired to evaluate its clinical usefulness against genital pathogens [12].
Lefdvre/Bauriaud/Gaubert/Escaffre/ Lareng
Sparfloxacin and Other Antimicrobial Agents against Genital Pathogens
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/3/2018 7:49:28 PM
Results and Discussion
References 6 Waites KB, Duffy LB. Schmid T, Crabb D, Pate MS, Cassel GH: In vitro susceptibilities of Mycoplasma pneumoniae. Mycoplasma hominis and Ureaplasma urealyticum to Spar floxacin and PD-127391. Antimicrob Agents Chemother 1991 ;35:1181 — 1185. 7 Lefèvre JC Bauriaud R: Compara tive in vitro activities of pristinamycin and other antimicrobial agents against genital pathogens. Antimi crob Agents Chemother 1989:26: 2152-2154. 8 Riou JY, Lind I, Guibourdenche M: Antibiotic susceptibility of 83 peni cillinase-producing Neisseria gonor rhoeae strains isolated in France. J Antimicrob Chemother 1985:16 (suppl 1):209—212. 9 Stamm WE, Suchland R: Antimi crobial activity of U-70138F (paldimycin), roxithromycin (RU-965). and ofloxacin (ORF-18489) against Chlamydia trachomatis) in cell cul ture. Antimicrob Agents Chemo ther 1986;30:806-807. 10 Chin NX, Gu JV. Yu KW, Zhang YX. Neu HC: In vitro activity of Sparfloxacin. Antimicrob Agents Chemother 1991;35:567-571. 11 Cooper MA. Andrews JM, Ashby JP. Matthews RS, Wise R: In vitro activity of Sparfloxacin, a new quino lone antimicrobial agent. J Antimi crob Chemother 1990;26:667-676.
12 Hashimoto M. Minami A, Nakata K. Nakamura S, Ohnishi K, Shimizu M: Program Abstr 28th Intersci Conf Antimicrob Agents Chemother 1988. Abstr 1488. 13 Corrado ML: The clinical experi ence with ofloxacin in the treatment of sexually transmitted diseases. Am J Obstet Gynecol 1991:164:13961399. 14 Hooper DC, Wolfson JS: Treatment of genitourinary tract infections with fluoroquinolones: Clinical effi cacy in genital infections and ad verse effects. Antimicrob Agents Chemother 1989;33:1662-1667. 15 Mardh PA, Lowing C: Treatment of chlamydial infection. Scand J Infect Dis 1990:58:23-30.
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1 Aznar J, Caballero MC, Lozano MC, De Miguel C, Palomares JC, Perea RJ: Activities of quinolone derivatives against genital patho gens. Antimicrob Agents Chcmothcr 1985:27:75-78. 2 Liebowitz LD, Saunders J, Fehler G. Rallard RC. Koornhof HJ: In vitro activity of A-56619 (Difloxacin), A-56620, and other new quinolone antimicrobial agents against genital pathogens. Antimicrob Agents Chemother 1986;30:948-950. 3 Tjiam KH. Wagenvoort JHT, van Klingeren B. Piot P. Stolz E, Michel MF: In vitro activity of two new 4 quinolones A-56619 and A-56620 against Neisseria gonorrhoeae. Chla mydia trachomatis. Mycoplasma ho minis, Ureaplasma urealyticum and GardnereUa vaginalis. Eur J Clin Mi crobiol 1986;5:498-501. 4 Kenny GE, Cartwright FD: Suscep tibilities of Mycoplasma hominis and Ureaplasma urealyticum to two new quinolones, Sparfloxacin and WIN57273. Antimicrob Agents Chemother 1991;35:1515-1516. 5 Nakamura S. Minami A, Nakata K, Kurobe N, Kouno K, Sakaguchi Y. Kashimoto S, Yoshida H. Kojima T, Ohue T. Foujimoto K. Nakamura M, Hashimoto M. Shimizu M: In vitro antibacterial activities of AT-4140, a new broad-spectrum quinolone. Antimicrob Agents Chemother 1989:33:1167-1173.
J.C. Lefèvre R. Bauriaud E. Gaubert M.C. Escaffre M.B. Lareng
In vitro Activity of Sparfloxacin and Other Antimicrobial Agents against Genital Pathogens
Groupe ‘Etude et Prévention des Maladies Transmissibles Sexuellement’, Laboratoire Central de Microbiologie, Hôpital Purpan, Toulouse, France
Abstract The in vitro activity of sparfloxacin was determined for 60 strains of Neisseria gonorrhoeae, 15 strains of Chlamydia tracho matis and 40 strains each of Gardnerella vaginalis, Mycoplasma hominis, and Ureaplasma urealyticum and compared with those of ampicillin, azithromycin, clarithromycin, erythromycin, ofloxacin, temafloxacin and tetracycline. Sparfloxacin was ac tive against all the strains studied and appeared to be the most potent quinolone tested. Sparfloxacin had the lowest MICs against N. gonorrhoeae (MICs 0.002-0.06 pg/ml). Its MICs against C. trachomatis (0.03-0.06 ug/ml) were higher than those of clarithromycin but lower than those of the other anti microbial agents. Sparfloxacin was particularly active against tetracycline-susceptible as well as resistant strains of M. homi nis (MICs, 0.06 pg/ml) and U. urealyticum (MICs 0.125-1 pg/ ml). Because of this in vitro activity and its tissue distribution, sparfloxacin might be a valuable therapeutic agent for treating major bacterial sexually transmitted diseases.
Introduction Although most bacterial sexually transmit ted diseases can be effectively treated, antimi crobial resistance to penicillins, tetracyclines and erythromycins, limits the use of these anti
biotics. Since sexually transmitted diseases caused by different pathogens are frequently concurrent, treatment with a single antibiotic with a broad spectrum of activity against these pathogens would be of great clinical value. Fluoroquinolones represent a class of broad-
J.C. Lefèvre Groupe ‘Etude et Prévention des Maladies Transmissibles Sexuellement', Laboratoire Central de Microbiologie Hôpital Purpan. Place du Docteur Baylac F-31059 Toulouse Cedex (France)
© 1992 S. Karger AG, Bascl 0009-3157/92/ 0385-0303 $ 2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/3/2018 7:49:28 PM
Key Words Sparfloxacin Genital pathogens Susceptibility, in vitro
CO, at 37 °C, the MIC was determined by observing the lowest concentration of antibiotic in which bacte rial growth was inhibited. In each experiment, World Health Organization N. gonorrhoeae reference strains A, B. C, D and E were included; the MICs of tetra cycline for these strains were similar to those obtained by Riou ct al. |8] with peptone agar. The MICs for M. hominis and U. urealyticum were determined in microdilution plates (12x8 wells). The growth medium was Shepard broth without penicillin in U. urealyticum tests and modified Hayflick medium without penicillin in M. hominis tests. The plates con taining serial dilutions of antibiotics (0.016-128 pg/l) were inoculated with 104 color change units per millili ter and incubated in 5% CO, for 48 h. The MIC was de fined as the lowest concentration of antibiotic which prevented color change. In each experiment a refer ence strain, M. hominis PG21 or U. urealyticum 2K160 was included. The MICs of tetracycline for strain PG21 were 32 ug/ml and for strain 2K160,0.5 ug/ml. The MIC for C. trachomatis was determined by a modification of a previously described method [9). All the clinical isolates and a laboratory strain of C. tracho matis (LGV-II ATCC VR-902) used as a control were passaged extensively in the laboratory and at least twice in antibiotic-free maintenance medium (Eagle minimum essential medium with 10% fetal bovine se rum. 1% glutamine, and 5 g of glucose per liter). Monolayers of antibiotic-free McCoy cells were grown in 96well microdilution plates seeded at a concentration of Materials and Methods 2.0 x 10’ cells/ml. After 48 h of incubation, the C. tra chomatis strains were each inoculated (250-500 inclu A total of 20 penicillinase-producing N. gonor sion-forming units/well). Monolayers were then cen rhoeae, 40 non-penicillinasc-producing N. gonor trifuged for 60 min at 1,500 g, aspirated, and overlaid rhoeae, 40 M. hominis, 40 U. urealyticum, 15 C. tracho with appropriate serial dilutions of the antibiotic being matis and 40 C. vaginalis strains were used. All the tested (0.004-64 pg/ml). All dilutions were made with strains were isolated from specimens obtained from the above-mentioned antibiotic-free maintenance me patients attending the Sexually Transmitted Diseases Clinic of Purpan Hospital in Toulouse, France (1988— dium containing 0.5 pg of cyclohcximide per milliliter. Appropriate antibiotic-free controls were included on 1990). The organisms were stored at -7 0 °C until use. each plate. Cultures were incubated for 48 h at 35 °C The antimicrobial agents used were ampicillin and then fixed and stained for enumeration of inclu (Bristol Laboratories), tetracycline,ofloxacin (Roussel sions by using a fluorescein-conjugated monoclonal Laboratories), erythromycin, clarithromycin, temaantibody (Ortho Diagnostics, Inc.). The lowest concen floxacin (Abbott Laboratories), azithromycin (Pfizer tration of each antibiotic with completely inhibited in Laboratories) and Sparfloxacin (Rhöne-Poulcnc). clusion formation was defined as the MIC. In each ex MIC tests with N. gonorrhoeae and G. vaginalis periment. the reference strain (LGV-II) was included; were performed by an agar dilution technique with the MIC of tetracycline for this strain was 0.06 pg/ml. Mucllcr-Hinton agar supplemented with 5% horse blood, as described previously [7). Twofold serial con centrations from 0.001 to 128 ug/ml were incorporated into the medium. The inocula were prepared from a 24-hour culture on agar medium and diluted to obtain Hf CFU per spot in N. gonorrhoeae and G. vaginalis tests. After incubation of the inocula for 48 h in 10%
304
Lefevre/Bauriaud/Gaubert/Escaffre/ Lareng
Sparfloxacin and Other Antimicrobial Agents against Genital Pathogens
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/3/2018 7:49:28 PM
spcctrum antimicrobial agents active against many gram-positive and gram-negative or ganisms. However, some genital pathogens such as mycoplasmas, Chlamydia trachomatis and Gardnerella vaginalis are not sufficiently susceptible to many of the quinolones test ed to date [1-3]. Sparfloxacin, a new difluoro quinolone antibiotic (previously designated AT4140) has been shown to have a spectrum of activity including not only the common bacte rial pathogens but also C. trachomatis and my coplasmas [4-6]. However, very few compari sons were made between Sparfloxacin and other classes of antimicrobial agents used in the treatment of genital infections. Moreover, there are no data available about its activity against G. vaginalis. We have therefore exam ined the in vitro activity of Sparfloxacin against clinical isolates of Neisseria gonorrhoeae, Mycoplasma homiis, Ureaplasma urealyticum, C. trachomatis, G. vaginalis and compared it with those of seven appropriate antibiotics.
Table 1. In vitro susceptibilities of genital pathogens to sparfloxacin and seven other antibiotics Antimicrobial agent
N. gonorrhoeae non penicillinase-producing (40)
ampicillin tetracycline erythromycin azithromycin clarithromycin ofloxacin tcmafloxacin sparfloxacin ampicillin tetracycline erythromycin azithromycin clarithromycin ofloxacin temafloxacin sparfloxacin ampicillin tetracycline erythromycin azithromycin clarithromycin ofloxacin tcmafloxacin sparfloxacin ampicillin tetracycline erythromycin azithromycin clarithromycin ofloxacin temafloxacin sparfloxacin tetracycline erythromycin azithromycin clarithromycin ofloxacin temafloxacin sparfloxacin tetracycline erythromycin azithromycin clarithromycin ofloxacin temafloxacin sparfloxacin
N. gonorrhoeae penicillinase-producing (20)
C. trachomatis (15)
G. vaginalis (40)
M. hominis (40)
U. urealyticum (40)
MIC, pg/ml range 0.03-1 0.125-64 0.03-1 0.008-0.25 0.03-1 0.008-0.25 0.004-0.03 0.002-0.008 >2 0.5-4 0.06-2 0.016-0.5 0.06-1 0.008-0.5 0.004-0.25 0.002-0.06 >32 0.06 0.06-0.125 0.06-0.125 0.008-0.016 0.5-1 0.25-0.5 0.03-0.06 0.06-1 0.125-128 0.008-0.125 0.004-0.125 0.016-0.06 1-4 0.25-2 0.125-1 0.125-32 > 128 32-128 > 128 0.25-1 0.06-0.25 0.06 0.125-64 0.25-4 0.5-4 0.03-0.25 1-4 0.5-4 0.125-1
50%
90%
0.25 0.5 0.25 0.016 0.25 0.016 0.008 0.004 >2 1 0.25 0.06 0.25 0.016 0.(X)8 0.004 >32 0.06 0.06 0.06 0.008 0.5 0.25 0.03 0.25 2 0.03 0.03 0.03 1 0.5 0.25 0.125 > 128 64 > 128 0.5 0.125 0.06 0.5 1 2 0.06 2 1 0.25
1 2 1 0.15 0.5 0.06 0.03 0.008 >2 2 1 0.25 1 0.03 0.016 0.008 >32 0.125 0.125 0.125 0.016 1 0.5 0.06 1 64 0.06 0.06 0.06 2 1 0.5 16 > 128 128 > 128 0.5 0.125 0.06 32 2 2 0.125 4 2 0.5
305
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Organisms (number of isolates)
The MICs of Sparfloxacin and the other antimicrobial agents for isolates of N. gonorrhoeae, C. trachomatis, U. urealyticum, M. ho minis and G. vaginalis are shown in table 1. Sparfloxacin had a spectrum of activity grea ter than all other antimicrobial agents we studied. Sparfloxacin had a high intrinsic ac tivity against each strain of N. gonorrhoeae tested. No difference was observed between penicillinase- and non penicillinase-produc ing strains. Our results are in agreement with those previously reported [5,10,11]. C. tracho matis was inhibited by Sparfloxacin at MICs of 0.03-0.06 pg/ml which were higher than those of clarithromycin, a new macrolide, and lower than those of the other antimicrobial agents. Pharmacokinetic studies revealed that Spar floxacin was well absorbed orally, had a rela tively long half-life in plasma (19 h) and showed good tissue distribution (12]. Our find ings of the potent antichlamydial activity of Sparfloxacin suggest that it could be of benefit in the therapy of chlamydial infections. The tetracyclines and macrolides are the drugs most frequently used to treat infections asso ciated with mycoplasmas. These compounds are not ideal, because of the spread of Tct-Mmediated resistance and, in the case of 14- and 15-membered macrolides, lack of activity against M. hominis. Fluoroquinolones were the only compounds used in this series which demonstrated potentially useful activity against mycoplasmas, including those strains resistant to tetracycline. Sparfloxacin ap peared to be the most active quinolonc tested. Our results were similar to those reported re cently [4, 6], Furthermore, for mixed infec tions involving M. hominis (bacterial vaginosis and pelvic inflammatory disease), Sparfloxa cin appears very promising. This antibiotic has been reported to show valuable in vitro activ ity against anaerobic bacteria (5, 10, 11]. It
306
showed relatively good activity against G. vag inalis in our series with an MIC of 0.5 pg/ml for 90% of strains tested. Although discrepancies have been found between the in vitro and in vivo susceptibilities of G. vaginalis, clinical studies of sparfloxacin in bacterial vaginosis appear justified. A number of problems compromise the ef ficacy of currently available regimens in the antimicrobial therapy of bacterial sexually transmitted diseases. These include antimi crobial resistance, frequent side effects, lack of alternative for patients with drug allergies and ineffectiveness of most regimens against all pathogens in polymicrobial infections or in simultaneously occurring infections. The re sults of our in vitro study show the broad spec trum of activity of sparfloxacin against major genital pathogens. This antibiotic has in vitro activity superior to that of ofloxacin which is effective in the treatment of gonococcal and chlamydial infections [13-15] and to that of temafloxacin, a newer fluoroquinolone. More over, sparfloxacin may be useful in the treat ment of genital tract infections because of its tissue distribution and prolonged half-life. Preliminary studies have shown that the to xicity of sparfloxacin is low enough to allow the initiation of clinical trials which will be re quired to evaluate its clinical usefulness against genital pathogens [12].
Lefdvre/Bauriaud/Gaubert/Escaffre/ Lareng
Sparfloxacin and Other Antimicrobial Agents against Genital Pathogens
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/3/2018 7:49:28 PM
Results and Discussion
References 6 Waites KB, Duffy LB. Schmid T, Crabb D, Pate MS, Cassel GH: In vitro susceptibilities of Mycoplasma pneumoniae. Mycoplasma hominis and Ureaplasma urealyticum to Spar floxacin and PD-127391. Antimicrob Agents Chemother 1991 ;35:1181 — 1185. 7 Lefèvre JC Bauriaud R: Compara tive in vitro activities of pristinamycin and other antimicrobial agents against genital pathogens. Antimi crob Agents Chemother 1989:26: 2152-2154. 8 Riou JY, Lind I, Guibourdenche M: Antibiotic susceptibility of 83 peni cillinase-producing Neisseria gonor rhoeae strains isolated in France. J Antimicrob Chemother 1985:16 (suppl 1):209—212. 9 Stamm WE, Suchland R: Antimi crobial activity of U-70138F (paldimycin), roxithromycin (RU-965). and ofloxacin (ORF-18489) against Chlamydia trachomatis) in cell cul ture. Antimicrob Agents Chemo ther 1986;30:806-807. 10 Chin NX, Gu JV. Yu KW, Zhang YX. Neu HC: In vitro activity of Sparfloxacin. Antimicrob Agents Chemother 1991;35:567-571. 11 Cooper MA. Andrews JM, Ashby JP. Matthews RS, Wise R: In vitro activity of Sparfloxacin, a new quino lone antimicrobial agent. J Antimi crob Chemother 1990;26:667-676.
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