Journal of Antimicrobial Chemotherapy (1992) 29, Suppl. A, 13-17

Antibacterial activity in vitro of cefpirome against clinical isolates causing sexually transmitted diseases M. Limbert, G. Seibert, I. Winkkr, D. Isert, N. Klesel, A. Markos and E. Schrinner

The in-vitro activity of cefpirome was compared with other antibiotics against organisms causing sexually transmitted diseases (STD). The excellent activity of cefpirome against Neisseria gonorrhoeae (MIQo 1*0 mg/L), Haemophilia ducreyi (MIQm 0-5 mg/L), and Gardnerella vaginaJis (MIC» 10 mg/L) suggests that this agent might be useful in the empirical treatment of a variety of venereal diseases.

Introduction Cefpirome (HR 810) is a new cephalosporin intended exclusively for parenteral use. It has previously been shown to be active in vitro and in vivo against various Gram-positive and Gram-negative bacteria. Its spectrum includes Pseudomonas spp., Acinetobacter spp., Staphylococcus spp. and enterococci (Bauernfeind, 1983; Seibert, Klesel, Limbert et al., 1983; Seibert, Limbert, Winkler & Dick, 1983; Bertram, Bruckner & Young, 1984; Jones, Thornsberry & Barry, 1984; Bryskier, & Chantot, 1985; Chantot & Bryskier, 1985; Neu, Chin & Labthavikul, 1985), organisms that may pose problems for other cephalosporins. It is also highly active against Neisseria spp. (Jones et al., 1984; Neu et al., 1985). The aim of this study was to evaluate the in-vitro activity of cefpirome against bacteria implicated in sexually transmitted diseases (STD): Neisseria gonorrhoeae, Haemophilia ducreyi, Gardnerella vaginalis and Chlamydia spp. The activity of cefpirome was also compared with that of other cephalosporins as well as a selection of penicillins and quinolones. Methods Antibiotics Cefpirome was provided by Hoechst AG, Frankfurt/M. Germany. All other antibiotics were commercially available. Susceptibility testing Minimal inhibitory concentrations (MICs) were determined in participating laboratories by an agar dilution method. Recent clinical isolates and laboratory strains of the different organisms were studied. The sensitivity of N. gonorrhoeae was tested on 13

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© 1992 The British Society for Antimicrobial Chemotherapy

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Hoechst AG, SBU Anti-infectives Research, Postfach 800320. 6230 Frankfurt/M., Germany

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M. Lfanbert et aL

Sensitivity testing of Chlamydia spp. Monolayers of A-549 cells were prepared on coverglasses. Chlamydia suspensions (yolk sac material containing Chlamydia trachomatis or chorioallantoic fluid containing Chlamydia psittaci) were centrifuged on the A-549 layer to infect the cells. Varying concentrations of the antibiotics were prepared in complete culture medium (Eagle's Dulbecco Modification) supplemented with 10% fetal bovine serum and applied to the cultures. The infected and treated cell cultures were incubated for 48 h in 5% CO2 at 35-37°C. After staining with the fluorochrome, HOE 33258, the MIC was defined as the lowest concentration of the antimicrobial agent in the medium which prevented the formation of microscopically demonstrable inclusions. Results and discussion The in-vitro activities of cefpirome, six other cephalosporins, five penicillins and six quinolones against N. gonorrhoeae isolates, including 24 penicillin-resistant strains, are summarized in Table I. Of the cephalosporins, cefodizime was the most active (MIC*, 0-25 mg/L). Cefpirome (MIC*, 1-0 mg/L) was only slightly less active than cefotaxime (MIC*, 0-5 mg/L) against these strains. The activity of the penicillins was poor. However, the newer quinolones, enoxacin, norfloxacin, ofloxacin, and acrosoxacin, were highly active against all the strains tested (MIQo < 1*0 mg/L). With an MIQo of 0-5 mg/L, cefpirome was the most active of all the agents tested against H. ducreyi (Table II). Ofloxacin was the only quinolone which exhibited significant activity (MIC^ 2-0 mg/L) against this organism. The G. vaginalis isolates were highly sensitive to all /Mactams tested (Table III). With an MIC,,, of 1-0 mg/L, cefpirome was equivalent to ceftazidime, but the other cephalosporins were more active (MIQo as low as 0-063 mg/L). Of the quinolones, ofloxacin was again the most active compound (MIC^, 2-0 mg/L). The MICs of the various antibiotics against three strains of Chlamydia spp. are shown in Table IV. Ofloxacin was the most active (MIC < 1-0 mg/L). Cefpirome, cefodizime, and cefazolin possessed some activity against the two strains of C. trachomatis (MICs of 10 and 32 mg/L). However, these agents are unlikely to be effective in vivo against this species.

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GC-agar (Oxoid) supplemented with 0-2% autolyzed liver and 6% chocolated horse blood. H. ducreyi was tested on Mueller-Hinton agar (Oxoid) supplemented with 5% calf serum, 5% chocolated horse blood and 2% Iso Vitalex (BBL). For the sensitivity testing of G. vaginalis Columbia agar (Oxoid) supplemented with 7-5% horse blood was used. Doubling dilutions of the antibiotics were prepared in sterile physiological saline and incorporated into the appropriate agar to give final concentrations ranging from 0-008 to 128 mg/L. Overnight cultures freshly diluted in broth were used as inocula. The suspensions were transferred on to the surfaces of the antibioticcontaining agar plates by means of a multipoint inoculator (Denley). The density of the inocula were adjusted to obtain 5 x 10* cfu Neisseria or 5 x 10* cfu Haemophilus and Gardnerella spp. per spot. The plates were incubated for 24 h at 35°C in an aerobic atmosphere containing 5% {Neisseria spp.) or 10% CO2 {Haemophilus and Gardnerella spp.). The lowest concentration which allowed no visible growth on the plate was taken as the MIC. A single colony or a fine, barely visible haze of growth were disregarded.

Cefptrome and patfaogens causing STD

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Table L In vitro activity of cefpirome and other antimicrobials against N. gonorrhoeae (n = 29) Antibiotic Cefpirome Cefodizime Cefoperazone Cefotaxime Cefoxitin Ceftazidime Cefuroxime

Enoxacin Nalidixic acid Norfloxacin Ofloxacin Pipemidic acid Acrosoxacin

0062 0062 0125 0031

10 10 0125 >32O >32O

160 >32O

80 0062

40 0062 1280 40- > 1280

1016O-

201O-

80 320 16-0

2O

16O- > 1280

10-

80

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Ampicillin Azlocillin Mezlocillin Penicillin G Piperacillin

1vUCjoOng/L) 1vile*, (mg/L)

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M. limbert et aL Table IIL In vitro activity of cefpiromc and other antimicrobials against G. vaginalis (n - 13) Antibiotic

ft4ICjo(mg/L) ^rfIC* (mg/L)

Range (mg/L)

0-25 0063 0016 0031 0-125 0-5 0O63

10 0-5 0-125 0063 0-5 10 0-25

0O63-1O 0031-0-5 0O08-4O 0O31-O-125 0O63-0-5 0-5 - 1 0 0O63-0-25

Ampicillin Penicillin G Piperacillin

0031 0008 0063

0-125 0063 0-25

0008-0-25 0O04-0-25 0O16-2O

Enoxacin Nalidixic acid Norfloxacin Ofloxacin Pipcmidic acid Acrosoxacin

80 640 160 20 640 160

160 1280 320 20 1280 16O

40 320 80 20 320 80

-320 ->128O -320 -40 -1280 -320

Table IV. In vitro activity of cefpirome and other antimicrobials against single strains of Chlamydia spp.

Antibiotic Cefpirome Cefazolin Cefodizime Cefotaxime Cefuroxime Nalidixic acid Norfloxacin Ofloxacin Pipemidic acid

MIC (mg/L) C. trachomatis C. trachomatis BOUR/E Tang/L2

C. psittad SAV

10O 10O 100 > 1000 > 100O

100 100 320 > 1000 > 1000

> 100O > 10OO > 1000 > 1000 >100O

1000 10 10 1000

100O 20 0-5 320

10OO 20 0-5 320

Our investigations suggest that cefpirome, due to its high in-vitro activity against N. gonorrhoeas, H. ducreyi and G. vaginalis, might be useful in the treatment of a variety of sexually transmitted diseases caused by these pathogens. Acknowledgement This work was presented in part at the 14th International Congress of Chemotherapy, Kyoto, 1985.

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Cefpirome Cefodizime Cefoperazone Cefotaxime Cefoxitin Ceftazidime Cefuroxime

Cefpirotne and pathogens causing STD

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References

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Bauernfcind, A. (1983). Susceptibility of Gram-positive aerobic cocci to the new cephalosporin HR 810. European Journal of Clinical Microbiology 2, 354-5. Bertram, M. A., Bruckner, D. A. & Young, L. S. (1984). In vitro activity of HR 810, a new cephalosporin. Antimicrobial Agents and Chemotherapy 26, 277-9. Bryskier, A. & Chantot, J. F. (1985). Cefpirome (HR 810): une nouvelle cephalosporine a large spectre. Pathologie Biologie 33, 477-81. Chantot, J. F. & Bryskier, A. (1985). Evaluation experimentale de Factivite antibiotique in vitro et in vivo d*une nouvelle amino-2-thiazole methoxy-imino cephalosporine. Pathologie Biologie 33, 482-6. Jones, R. N., Thomsberry, C. & Barry, A. L. (1984). In vitro evaluation of HR 810, a new widespectrum aminothiazolyl alpha-methoxyimino cephalosporin. Antimicrobial Agents and Chemotherapy 25, 710-8. Neu, H. C , Chin, N. X. & Labthavikul, P. (1985). The in vitro activity and beta-lactamase stability of cefpirome (HR 810), a pyridine cephalosporin agent active against staphylococci, Enterobacteriaceae and Pseudomonas aeruginosa. Infection 13, 146-55. Seibert, G., Kksel, N., Limbert, M., Schrinner, E., Seeger, K., Winkjer, I. et al.. (1983). HR 810, a new parenteral cephalosporin with broad antibacterial spectrum. Arxneimittel-Forschung/Drug Research 33, 1084-6. Seibert, G., Limbert, M., Winkler, I. & Dick, T. (1983). The antibacterial activity in vitro and /J-lactamase stability of the new cephalosporin HR 810 in comparison with five other cephalosporins and two aminoglycosides. Infection 11, 275-9.

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Antibacterial activity in vitro of cefpirome against clinical isolates causing sexually transmitted diseases.

The in-vitro activity of cefpirome was compared with other antibiotics against organisms causing sexually transmitted diseases (STD). The excellent ac...
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