In vitro evaluation of the activities of azithromycin ( Zithromax ) alone and combined with pyrimethamine against Toxoplasma gondii.

By using an in vitro microassay to assess drug interaction, azithromycin ( Zithromax ) combined to pyrimethamine was found more active than pyrimethamine alone against Toxoplasma gondii, and additivity between those drugs was demonstrated. Our results show that the combination of azithromycin ( Zithromax ) and pyrimethamine may lead to a more rapid control of T. gondii.

Microbiologic effect of bovine cerebrospinal fluid and azithromycin ( Zithromax ) against Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae.

Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of azithromycin ( Zithromax ) against reference strains of Streptococcus pneumoniae ATCC 49619, Neisseria meningitidis ATCC 13090, and Haemophilus influenzae ATCC 49247 were determined by the macrodilution broth method with and without 10% bovine cerebrospinal fluid (CSF) supplementation. The MICs and MBCs were within one to two dilutions for N. meningitidis and S. pneumoniae, and no difference was observed for H. influenzae. Time-kill curves demonstrated enhanced killing by azithromycin ( Zithromax ) when 10% bovine CSF was added to media for N. meningitidis. The minimum azithromycin ( Zithromax ) concentration for a greater than 3 log10 reduction in inoculum with bovine CSF was 0.03 microg/ml and without CSF was 0.12 microg/ml, a 3-fold difference. Killing was not significantly different for either H. influenzae nor S. pneumoniae.

Postanitbiotic and sub-MIC effects of azithromycin ( Zithromax ) and isepamicin against Staphylococcus aureus and Escherichia coli.

Investigations of pharmacodynamic parameters (postantibiotic effect [PAE], sub-MIC effects [SMEs], etc.) have been progressively employed for the design of dosing schedules of antimicrobial agents. However, there are fewer in vivo than in vitro data, probably because of the simplicity of the in vitro procedures. In this study, we have investigated the in vitro PAE, SME, and previously treated (postantibiotic [PA]) SME (1/2 MIC, 1/4 MIC and 1/8 MIC) of azithromycin ( Zithromax ) and isepamicin against standard strains of Staphylococcus aureus and Escherichia coli by using centrifugation to remove the antibiotics. In addition, the in vivo PAE and SME have been studied with the thigh infection model in neutropenic mice. Finally, in vivo killing curves with two dosing schedules were determined to examine whether the PAE can cover the time that antimicrobial agents are below the MIC. The two antimicrobial agents induced moderate-to-high in vitro PAEs, SMEs, and PA SMEs against S. aureus (>8 h) and E. coli (3.38 to >7.64 h). The in vivo PAEs were also high (from 3.0 to 3.6 h), despite the fact that isepamicin had lower times above the MIC in serum. Only azithromycin ( Zithromax ) showed a high in vivo SME against the two strains (1.22 and 1.75 h), which indicated that the in vivo PAEs were possibly overestimated. In the killing kinetics, no great differences (<0.5 log10) were observed between the schedule that took the PAE into account and the continuous administration of doses. These results are comparable with those of other authors and suggest that these antimicrobial agents could be administered at longer intervals without losing effectiveness.

Inhibitory activity of azithromycin ( Zithromax ) on biofilm synthesis and synergism between azithromycin ( Zithromax ) and fleroxacin on Pseudomonas aeruginosa in biofilms

OBJECTIVE: The influence of azithromycin ( Zithromax ) (AZT) on the production of glycocalyx (GLX) from P. aeruginosa biofilms and synergism of antibacterial activities between AZT and fleroxacin (FLX) on P. aeruginosa were investigated. METHOD: GLX production was measured by using a L-tryptophan method and viable counts in biofilms was determined by using a methylthiazolyldiphenyltetrazolium(MTT) method. RESULT: GLX production was reduced significantly from 28.0 +/- 8.1 micrograms/ml at 0MIC to 21.8 +/- 8.2 micrograms/ml at 1/16MIC and 16.7 +/- 7.9 micrograms/ml at 1/4MIC respectively (P = 0.0002). 1/16MIC and 1/4MIC AZT showed no bactericidal activities to P. Aeruginosa in biofilms. Viable counts in biofilms were 6.2 +/- 0.61 Lg/cm2 at 0MIC, 6.1 +/- 0.4 Lg/cm2 at 1/16MIC and 6.2 +/- 0.4 Lg CFU/cm2 at 1/4 MIC respectively (P = 0.63). However, AZT could enhance bactericidal activity of FLX on P. aeruginosa in biofilms. When 1/4MIC FLX was combined with 1/16MIC and 1/4 MIC AZT, viable counts were reduced significantly from 6.1 +/- 0.5 Lg CFU/cm2 to 5.9 +/- 0.3 Lg CFU/cm2 and 5.8 +/- 0.4 Lg CFU/cm2 respectively (P = 0.02). When 1/2MIC FLX was combined with 1/16MIC and 1/4MICAZT, viable counts were reduced significantly from 6.3 +/- 0.7 Lg CFU/cm2 to 5.8 +/- 0.5 LgCFU/cm2 and 5.7 +/- 0.6 Lg CFU/cm2 respectively (P = 0.03). CONCLUSION: Because AZT did not have direct bactericidal activities on P. aeruginosa in biofilms but could inhibit GLX production, We considered that AZT could enhance antibacterial activities of FLX by enhancing permeability of FLX into biofilms.