cooper.cpmc.org

Macrolide resistance is an emerging problem in AIDS patients who receive these agents for treatment or prophylaxis against Mycobacterium avium (MAC) infection. We compared the emergence of resistant MAC strains during therapy with clarithromycin (clarithromycin resistance was defined as MIC > or = 32 microg/ml) and azithromycin [Zithromax] (azithromycin [Zithromax] resistance was defined as MIC > or = 128 microg/ml) in C57BL/6 beige mice. Treatment with clarithromycin and azithromycin [Zithromax] resulted in a decrease of 98.5% in the number of viable bacteria in spleens at week 8 and 99% at week 12 compared with the number of bacteria present in spleen before the initiation of therapy (P < 0.001). Splenic homogenates were also plated onto 7H11 agar plus clarithromycin at 32 microg/ml or azithromycin [Zithromax] at 128 microg/ml. Resistance emerged significantly more often in mice treated with clarithromycin (100% of treated mice at both 8 and 12 weeks) than in those receiving azithromycin [Zithromax] (0% at week 8 and 14% at week 12). The frequencies of resistance of the MAC population in the spleen to clarithromycin were 2.1 x 10(-3) at week 8 and 1.1 x 10(-2) at week 12, whereas resistance to azithromycin [Zithromax] was absent at week 8 (all mice) and was approximately 3.5 x 10(-5) (mean for the three positive animals) at week 12. Clarithromycin was more effective in initial reduction of MAC burden in tissue after 8 and 12 weeks of treatment, but resistant strains emerged significantly more frequently after treatment with clarithromycin than after treatment with azithromycin.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9449283&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1998 Jan;42(1):194-6.
Microbiologic efficacy of azithromycin [Zithromax] and susceptibilities to azithromycin [Zithromax] of isolates of Chlamydia pneumoniae from adults and children with community-acquired pneumonia.

Roblin PM, Hammerschlag MR.

Department of Pediatrics, State University of New York Health Science Center at Brooklyn, 11203-2098, USA.

Chlamydia pneumoniae was eradicated from the nasopharynges of 26 of 33 (78.8%) evaluable children and adults with community-acquired pneumonia who were treated with azithromycin. We tested 55 isolates of C. pneumoniae obtained from 46 of these patients against azithromycin. The MIC at which 90% of the isolates were inhibited and the minimal chlamydiacidal concentration at which 90% of strains tested were killed of azithromycin [Zithromax] for these isolates were both 0.5 microg/ml. Seven patients remained culture positive after treatment. The MICs of azithromycin [Zithromax] for isolates from two patients increased fourfold after therapy. However, all the patients with persistent infection improved clinically. Further studies of treatment of C. pneumoniae infection, utilizing culture, are needed both to assess efficacy and to monitor for the possible development of antibiotic resistance.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9449287&dopt=Abstract Zithromax azithromycin




Rev Med Chir Soc Med Nat Iasi. 1996 Jul-Dec;100(3-4):128-34.
[The postantibiotic effect of azithromycin [Zithromax] on respiratory pathogens]

[Article in Romanian]

Diculencu D, Andrews JM, Boswell FJ, Wise R.

Facultatea de Medicina, Disciplina de Microbiologie, Universitatea de Medicina si Farmacie Gr. T. Popa, Iasi.

Azithromycin [Zithromax] has in vitro activity which includes important respiratory pathogens and is successful in treatment of respiratory tract infections. We assessed postantibiotic effect (PAE) of azithromycin [Zithromax] against 3 stains of Streptococcus pneumoniae, 2 strains of Haemophilus influenzae and 2 strains of Moraxella catarrhalis. The strains were exposed for 2 hours to an azithromycin [Zithromax] concentration of 0.5 mg/L (maximum serum concentration achieved by azithromycin [Zithromax] after the usual dosing regimen). A stationary phase inoculum of 1 x 10(6)-5 x 10(6) UFC/ml in IsoSensitest Broth with 5% lysed horse blood and 20 mg/L NAD was used and shaken for the duration of the experiment. Antibiotic was neutralised by dilution 1:1000 into pre-warmed medium. Viable counts were determined before and after antibiotic exposure and then hourly for 7 hours by Miles and Misra method. The experiment was performed in triplicate. Even at such low concentration as that achieved in serum, azithromycin [Zithromax] exhibits a PAE of 119 min for pneumococci, 130 min for haemophili and 155 min for moraxellae, fact which could allow the use of usual oral regimen in bacteraemic respiratory infection, as well.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9455450&dopt=Abstract Zithromax azithromycin




Circulation. 1998 Feb 24;97(7):633-6.
Infection with Chlamydia pneumoniae accelerates the development of atherosclerosis and treatment with azithromycin [Zithromax] prevents it in a rabbit model.

Muhlestein JB, Anderson JL, Hammond EH, Zhao L, Trehan S, Schwobe EP, Carlquist JF.

University of Utah, LDS Hospital, Salt Lake City 84143, USA.

BACKGROUND: Chlamydia pneumoniae infection has been associated with atherosclerosis by serological studies and detection of bacterial antigen within plaque. We sought to evaluate a possible causal role in an animal model. METHODS AND RESULTS: Thirty New Zealand White rabbits were given three separate intranasal inoculations of either C pneumoniae (n = 20) or saline (n = 10) at 3-week intervals and fed chow enriched with a small amount (0.25%) of cholesterol. Immediately after the final inoculation, infected and control rabbits were randomized and begun on a 7-week course of azithromycin [Zithromax] or no therapy. Three months after the final inoculation, rabbits were euthanatized and sections of thoracic aortas were blindly evaluated microscopically for maximal intimal thickness (MIT), percentage of luminal circumference involved (PLCI), and plaque area index (PAI) of atherosclerosis. Vascular chlamydial antigen was assessed by direct immunofluorescence. MIT differed among treatment groups (P=.009), showing an increase in infected rabbits (0.55 mm; SE = 0.15 mm) compared with uninfected controls (0.16 mm; SE = 0.06 mm) and with infected rabbits receiving antibiotics (0.20 mm; SE = 0.03 mm) (both P<.025), whereas MIT in infected/treated versus control rabbits did not differ. PLCI also tended to differ (P<.1) and PAI differed significantly (P<.01) among groups with a similar pattern. Chlamydial antigen was detected in 2 untreated, 3 treated, and 0 control animals. CONCLUSIONS: Intranasal C pneumoniae infection accelerates intimal thickening in rabbits given a modestly cholesterol-enhanced diet. In addition, weekly treatment with azithromycin [Zithromax] after infectious exposure prevents accelerated intimal thickening. These findings strengthen the etiologic link between C pneumoniae and atherosclerosis and should stimulate additional animal and human studies, including clinical antibiotic trials.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9495296&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1998 Jan;41(1):127-30.
The combination of amphotericin B and azithromycin [Zithromax] as a potential new therapeutic approach to fusariosis.

Clancy CJ, Nguyen MH.

Department of Medicine, University of Florida College of Medicine, Gainesville 32610, USA.

We investigated the interaction between amphotericin B and azithromycin [Zithromax] in vitro against 26 clinical isolates of Fusarium. Synergy was demonstrated in all isolates. Amphotericin B MICs were reduced from a mean of 1 mg/L when tested alone to a mean of 0.37 mg/L when tested in combination with azithromycin. Azithromycin [Zithromax] demonstrated no activity against Fusarium when tested alone (MIC > 128 mg/L). When combined with amphotericin B the mean MIC was reduced to 5.5 mg/L, a level readily achieved in tissue. Given the resistance of Fusarium to conventional therapy, the in-vitro synergy between amphotericin B and azithromycin [Zithromax] might prove to be important in therapy for fusariosis.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9511049&dopt=Abstract Zithromax azithromycin

BACL.AZR.NL

In this study, we determined the efficacy of various dosing regimens for erythromycin and azithromycin [Zithromax] against four pneumococci with different susceptibilities to penicillin in an in vitro pharmacokinetic model and in a mouse peritonitis model. The MIC was 0.03 microg/ml, and the 50% effective doses (determined after one dose) of both drugs were comparable for the four pneumococcal strains and were in the range of 1.83 to 6.22 mg/kg. Dosing experiments with mice, using regimens for azithromycin [Zithromax] of one to eight doses/6 h, showed the one-dose regimen to give the best result; of the pharmacodynamic parameters tested (the maximum drug concentration in serum [Cmax], the times that the drug concentration in serum remained above the MIC and above the concentration required for maximum killing, and the area under the concentration time curve), Cmax was the best predictor of outcome. The bacterial counts in mouse blood or peritoneal fluid during the first 24 h after challenge were not correlated to survival of the mice. The serum concentration profiles obtained with mice for the different dosing regimens were simulated in the in vitro pharmacokinetic model. Here as well, the one-dose regimen of azithromycin [Zithromax] showed the best result. However, the killing curves in vivo in mouse blood and peritoneal fluid and in the vitro pharmacokinetic model were not similar. The in vitro killing curves showed a decrease of 2 log10 within 2 and 3 h for azithromycin [Zithromax] and erythromycin, respectively whereas the in vivo killing curves showed a bacteriostatic effect for both drugs. It is concluded that the results in terms of predictive pharmacodynamic parameters are comparable for the in vitro and in vivo models and that high initial concentrations of azithromycin [Zithromax] favor a good outcome.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9527789&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1998 Feb;42(2):414-8.
Postanitbiotic and sub-MIC effects of azithromycin [Zithromax] and isepamicin against Staphylococcus aureus and Escherichia coli.

Fuentes F, Izquierdo J, Martin MM, Gomez-Lus ML, Prieto J.

Department of Microbiology, Faculty of Medicine, Complutense University of Madrid, Spain.

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.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9527796&dopt=Abstract Zithromax azithromycin