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Erythromycin and related macrolide antibiotics have recently enjoyed a resurgence of clinical interest. This is a result of activity against organisms which are becoming more prevalent, particularly in immunocompromised hosts and, in addition, better understanding of the unique tissue penetration properties and potential immunomodulating properties of macrolides. Other features of clinical interest possessed by certain of the newer macrolides include the potential for once-daily dosing, resistance to acid degradation in the stomach without enteric coating, and possibly reduced gastrointestinal side effects. The new macrolides are expected to retain the clinical indications of erythromycin, which include upper and lower respiratory tract infections, skin and skin structure infections, and genital tract infections caused by erythromycin-susceptible organisms. In addition, enhanced activity has been demonstrated in animal models and in vitro against toxoplasma, Legionella, Haemophilus, and Campylobacter spp. New macrolide derivatives also show promise to expand the antimicrobial spectrum of erythromycin to include Mycobacterium and Borrelia spp.

A plasmid conferring resistance to the aminocyclitol antibiotic hygromycin B was isolated from Escherichia coli. The gene conferring resistance to this drug was cloned in pBR322, and the gene was localized to a fragment of ca. 1,510 base pairs. Resistance to hygromycin B is determined by an aminocyclitol phosphotransferase that modifies hygromycin B and structurally related antibiotics. The specific modification of hygromycin B is a phosphorylation of the hydroxyl on the 4 position of the cyclitol ring (hyosamine). The presence of the phosphotransferase in E. coli correlates with reduced accumulation of [14C]hygromycin B.

Aminoglycoside-2"-O-adenylyltransferase was inhibited by 7-hydroxytropolone. Inhibition was competitive with respect to the cosubstrate ATP and appeared to require the unique vicinal arrangement of oxygens found in 7-hydroxytropolone. Combinations of 7-hydroxytropolone plus the appropriate aminoglycoside substrates were active against resistant bacteria possessing the adenylyltransferase. No potentiation was observed against other aminoglycoside-resistant or -susceptible strains. The fact that the inhibition of an aminoglycoside-modifying enzyme overcomes the poor uptake of aminoglycosides in resistant strains points to the singular importance of the inactivating enzyme as a determinant of resistance.