Comparison of the activities of ceftriaxone and penicillin G against experimentally induced syphilis in rabbits

Self Cite

136

The antimicrobial susceptibility of Borrelia burgdorferi isolated from human spinal fluid was determined in vitro and in vivo. A broth dilution technique was used to determine the MBCs of four antimicrobial agents. The Lyme disease spirochete was most susceptible to ceftriaxone (MBC, 0.04 ,ug/ml) and erythromycin (MBC, 0.05 ,ug/ml), then tetracycline (MBC, 0.8 ,ug/ml), and finally penicillin G (MBC, 6.4 ,g/ml). Syrian hamsters were used to determine the 50% curative doses (CD_0s) of the four antimicrobial agents. Ceftriaxone and tetracycline had the highest activities, with CD50s of 240 and 287 mg/kg, respectively. Both erythromycin and penicillin G possessed low activities. The CD50 of erythromycin was 2,353 mg/kg, and the CD50 of penicillin G was >1,975 mg/kg.

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo susceptibility of the Lyme disease spirochete, Borrelia burgdorferi, to four antimicrobial agents

Johnson¹,

Kodner²,

Russell³

1987

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136

“…Agents Chemother., in press); and in vivo studies with T. pallidum-infected rabbits (5,12,25,27). Each of these methods has limitations.…”

mentioning

confidence: 99%

In vitro culture system to determine MICs and MBCs of antimicrobial agents against Treponema pallidum subsp. pallidum (Nichols strain)

Norris

Edmondson

1988

A new procedure for determining the susceptibility of Treponema pallidum subsp. pallidum to antimicrobial agents was developed, utilizing a tissue culture system which promotes the in vitro multiplication of this organism. In the absence of antibiotics, T. pallidum (Nichols virulent strain) multiplied an average of 10-fold when incubated for 7 days in the presence of SflEp cottontail rabbit epithelial cell cultures. Varied concentrations of penicillin G, tetracycline, erythromycin, and spectinomycin were added to triplicate cultures to determine their effects on treponemal multiplication, motility, and virulence. The MIC of each antibiotic was defined as the lowest concentration which prevented treponemal multiplication, whereas the MBC was defined as the lowest concentration which abrogated the ability of the cultured treponemes to multiply and cause lesions in rabbits. The in vitro culture technique provided highly reproducible MICs and (in parentheses) MBCs of each of the antibiotics tested: aqueous penicillin G, 0.0005 (0.0025) ,ug/ml; tetracycline, 0.2 (0.5) ,ug/ml; erythromycin, 0.005 (0.005) ,ug/mI; and spectinomycin, 0.5 (0.5) ,Ig/mI. The significance of these results in light of the in vivo activities and the previous in vitro evaluations of these antibiotics is discussed. The T. pallidum in vitro cultivation system shows promise as a method for studying the interaction between T. pallidum and antimicrobial agents and for screening new antibiotics for syphilis therapy.

“…pallidum infection frequently occurs concomitantly with H. ducreyi. Ceftriaxone has been shown to be bactericidal for T. pallidum (6), and the single-dose regimen prescribed for gonococcal infection may be effective for incubating syphilis infections. However, more prolonged treatment regimens are required to cure patients with T. pallidum infection (E. W. Hook III, R. E. Roddy, and H. H. Handsfield, Meet.…”

Section: Discussionmentioning

confidence: 99%

Single-dose ceftriaxone for chancroid

Bowmer¹,

Nsanze²,

D'Costa³

et al. 1987

Men with genital ulcers that were culture positive for Haemophiluss ducreyi were treated with intramuscular ceftriaxone and randomized to three different dose regimens. All but 1 of 50 men treated with 1 g of intramuscular ceftriaxone were cured. Similarly, 0.5 and 0.25 g cured 43 of 44 men and 37 of 38 men, respectively. A single dose of 250 mg of intramuscular ceftriaxone is an effective treatment for chancroid. Increasing awareness of antimicrobial agent-resistantHaemophilus ducreyi strains has led us' to search for alternate treatment regimens for chancroid (7). A 10-day course of erythromycin and a 1-week course of amoxicillin in combination with clavulanic acid are each satisfactory treatments, with cure rates of over 95% (2,10). More recently, we have shown that a single dose of trimethoprimsulfametrole (11) or of rifampin in combination with trimethoprim (12) can cure most patients with chancroid in Kenya. However, additional effective single-dose treatment regimens are necessary due to the recent emergence of trimethoprim-resistant H. ducreyi strains in Thailand (13).Ceftriaxone is remarkably effective -against H. ducreyi in vitro, with MICs of 0.015 mg/liter or'less for all isolates tested. In the present study, we compared three different single-dose intramuscular ceftriaxone regimens for the treatment of men with genital ulcer disease due to H. ducreyi. MATERIALS AND METHODSBetween April and December 1982, male patients presenting at the Nairobi Special Treatment Clinic with a clihical syndrome compatible with chancroid were enrolled in the study. Men were eligible if'they were older than 18 years, had had no antimicrobial therapy in the preceding week, were willing to return for follow-up, and were negative for Treponema pallidum on dark-field examination. The external genitalia were examined, and the number, size, and clinical characteristics of the ulcers were noted. Buboes, defined as tender inguinal or femoral lymph nodes enlarged to more than 1 cm, were examined for fluctuance, consistency, and size. Ulcers were cultured for H. ducreyi and herpes simplex virus by techniques described in an earlier publication (11). All ulcers were cultured on two different media, which in combination have been shown to support the growth of H. ducreyi from samples of ulcers from over 80% of patients with clinical chancroid (8). Agar dilution ceftriaxone and other cephalosporin MICs for H. ducreyi were determined as described previously (4). One or more dark-field examinations were performed on samples of all ulcers. Serum was obtained for serologic tests for syphilis initially and at 10 and 28 days.Patients who had positive cultures for H. ducreyi and no evidence of T. pallidum infection were assigned by a preconstructed random sequence to treatment with ceftriax-* Corresponding author.one in a dose of 1.0, 0.5, or 0.25 g. The ceftriaxone was administered intramuscularly after dilution in 1% xylocaine. The evaluator' was unaware of the treatment regimen selected.The men were requested to return for follow-up vi...