In vitro activity of clavulanic acid, amoxicillin, and ticarcillin against Chlamydia trachomatis

Abstract

In vitro, growth of Chlamydia trachomatis was not entirely eliminated by 960 ,ig of ticarcillin per ml, 64 ,ug of amoxicillin per ml, 32 ,ug of clavulanic acid per ml, a combination of ticarcillin (480 ,ig/ml) and clavulanic acid (32 ,ig/ml), and a combination of amoxicillin (32 ,ig/ml) and clavulanic acid (8 ,ig/ml). However, a -99% decrease in the number of inclusions was obtained at concentrations readily attainable in serum.Penicillins have partial activity against Chlamydia trachomatis both in vitro and in vivo (2-7, 9, 16). For most antimicrobial agents, MICs are well defined and the number of inclusions in cell cultures declines dramatically from numbers near those in controls without antimicrobial agents to nil over only a few dilutions (6,10,14,15). In contrast, with penicillins there are occasional inclusions over a wide range of concentrations (6,10,14,15). This probably accounts for the large discrepancies in published reports of MICs of penicillins (4,6,9,10,(13)(14)(15)(16). In vivo, single-dose penicillin treatment does not usually eradicate C. trachomatis (7, 10), but multiple-dose penicillin treatment often results in negative follow-up cultures for weeks or longer (2,5,7,12). Because of this activity, penicillins have been considered for use in the treatment of uncomplicated chlamydial infections in pregnancy (2). Clavulanic acid, in combination with amoxicillin or ticarcillin, has been used in the treatment of genital syndromes or infections such as the frequencydysuria syndrome and pelvic inflammatory disease (1,8) that are sometimes caused by C. trachomatis (11,17). Consequently, it is important to know whether the addition of clavulanic acid to amoxicillin or ticarcillin enhances in vitro activity against C. trachomatis. In this study, the activities of amroxicillin, ticarcillin, and clavulanic acid alone, clavulanic acid in combination with amoxicillin, and clavulanic acid in combination with ticarcillin were evaluated in vitro against C. trachomatis in cell cultures.Twenty-one strains of C. trachomatis were used, including three typed strains (B, DE, and FG) initially isolated from men with nongonococcal urethritis in Seattle, Wash., one LGV2 strain kindly provided by Julius Schachter, and 17 genital isolates from men and women in Vancouver or Edmonton, Alberta, Canada. Isolates were passed in cycloheximide-treated McCoy cells and stored at -70°C when not in use. All strains were in passage 7 to 10 at the time of use.Antimicrobial agents were reconstituted and diluted with 0.4 M sucrose phosphate the day of use (6, 15). The final concentrations evaluated for ticarcillin were 960, 480, 30, 7.5, 1.875, and 0.469 ,uggml; for amoxicillin they were 64, 16, 4, 1, and 0.25 ,ug/ml; for clavulanic acid they were 32, 16, 4, 1, and 0.25 ,ug/ml; for the combination of ticarcillin and clavulanic acid in a 15:1 ratio they were 480 and 32, 30 and 2, 7.5 and 0.5, 1.875 and 0.125, and 0.469 and 0.031 p.g/ml;and for the combination of amoxicillin with clavulanic acid in a 4:1 ratio they were 32 and 8, 8 an...

Characteristics of murine model of genital infection with Chlamydia trachomatis and effects of therapy with tetracyclines, amoxicillin-clavulanic acid, or azithromycin

“…Our studies showed that this organism was highly susceptible to minocycline and doxycycline, as are human strains (4,24). Likewise, amoxicillin, clavulanic acid, and amoxicillin-clavulanic acid were inhibitory at low concentrations but, in keeping with other penicillins, failed to exert a complete bactericidal effect in cell culture, as was demonstrated by Bowie with clinical isolates (6). The susceptibility of C. trachomatis MoPn to azithromycin was similar to that of human strains (23).…”

In vitro activities of lomefloxacin, tetracycline, penicillin, spectinomycin, and ceftriaxone against Neisseria gonorrhoeae and Chlamydia trachomatis

“…These aberrant inclusions have decreased infectivity. The effect of P-lactams on C. trachomatis and the MIC discrepancies has been well documented (2,6,9,10). In our study, the aberrant inclusions at 0.06 to 0.5 ,ug/ml in cultures incubated with penicillin failed to significantly infect new monolayers, but a few inclusions persisted.…”

Effect of Azithromycin plus Rifampin versus Amoxicillin Alone on Eradication and Inflammation in the Chronic Course of Chlamydia pneumoniae Pneumonitis in Mice

“…Amoxicillin is not a treatment of choice for chlamydial infection. However, in vitro experiments have shown that ampicillin and amoxicillin each have a definite, but incomplete, inhibitory effect on C. trachomatis and C. pneumoniae at concentrations attainable in vivo (4,5,8,15,16). Masson et al (20) have shown some activity of amoxicillin-clavulanate in reducing isolation rates of C. pneumoniae from lungs in experimental mouse pneumonitis 1 day after cessation of treatment.…”