Azithromycin antibacterial activity

Matsunaga, T., and Ogawa, M. (1995). Antibacterial activity of azithromycin against fresh clinical isolates. Jpn. J. Chemother 43 (S-6), 84-94. 

Macrolide antibiotics are a homogeneous group of antimicrobial drugs that have been used to treat clinical infections for several decades. The most clinically useful classification of the macrolides is based on the size of the lactone ring that forms the chemical nucleus of each macrolide molecule [1, 2]. The 14- and 15-membered macrolides include erythromycin, clarithromycin, dirithromycin, roxithromycin, and azithromycin. Erythromycin is the oldest and still the most important of the macrolide antibiotics because it is a useful alternative to penicillin G. It is one of the safest antibiotics available. Clarithromycin and azithromycin have shown some advantages over erythromycin in their antibacterial activity,... 

Erythromycin is active against gram-positive cocci with the exception of enterococci. Erythromycin is also active against Mycoplasma pneumoniae, Chlamydia trachomatis, Chlamydia pneumoniae, and Borrelia burgdorferi. Clarithromycin and azithromycin have antibacterial spectra similar to that of erythromycin except that they have enhanced activity against H. influenzae. 

The antibacterial spectrum of these macrolides is broader. For example, the clinical modification at C6 [e.g., O-methylation (clarithromycin)] or at C9 [e.g., some 9-ether oxime derivatives (roxithromycin and dirithromycin)] stabilizes 14-membered lactone rings in acidic media, even when the modified drugs have been orally administered. Drugs with an expanded erythromycin A-lactone ring (e.g., azithromycin) are also more stable in acidic media and display better antigram-negative activity than does erythromycin A. 

McFarland JW, Berger CM, Froshauer SA, Hayashi SF, Hecker SJ, Jaynes BH, Jefson MR, Kamicker BJ, Lipinski CA, Lundy KM, Reese CP and Vu CB, Quantitative Structure-activity relationships among macrolide antibacterial agents In vitro and in vivo potency against Pasteurella multocida, /. Med. Chem., 40, 1340-1346 (1997). NB See Azithromycin for details average standard deviation of 0.07 for the pKa value. 

Erythromycin is a known inhibitor of the cytochrome P450 isoenzyme CYP3A4. However, this isoenzyme has only a minor role in the metabolism of warfarin , (p.358), specifically the less active R-isomer of warfarin. Consequently, only minor increases in the levels of warfarin have been seen in pharmacokinetic studies, which would generally not be expected to be clinically relevant. However, it is possible that even these small changes might be important in a very few patients, particularly those with a low prothrombin complex aetivity. Other macrolides (azithromycin, clarithromycin, dirithromycin, roxithromycin) have less effect on CYP3A4 than erythromycin, and consequently would be expected to have even less effect on the pharmacokinetics of warfarin or acenocoumarol, which is borne out in the few studies available. Nevertheless, cases of interactions have been reported for nearly all these macrolides. Moreover, one cohort study found that clarithromycin increased the risk of an interaction and erythromycin did not. It is possible that there is some other, as yet unidentified, mechanism involved. Alternatively, it is equally possible that the relatively few cases just represent idiosyncratic effects attributable to other factors, and not to any interaction (see also Coumarins -i- Antibacterials , p.365). 

Azithromycin is a widely used antibacterial agent whose immunomodulatoiy activity is well known. The activity of AZI in pulmonaiy disease provides substantial insight into the drug s biological activity for modulating immune responses. These uses are summarized in Table 6.4 along with the number of patients in studies and the outcomes observed. 

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