Other Macrolides

Four macrolides, 11-undecanolide (12-membered,UDL) [85,86], 12-dodeca-nolide (13-membered,DDL) [86,87], 15-pentadecanolide (16-membered, PDL) [85,86,88,89], and 16-hexadecanolide (17-membered, HDL) [90], were subjected to the lipase-catalyzed polymerization. For the polymerization of DDL, lipases CC, PC, PF, and PPL showed the high catalytic activity and the activity order in the bulk polymerization was as follows lipase PC > lipase PF > lipase CC> PPL. These enzymes were also active for the polymerization of other macrolides. NMR analysis showed that the terminal structure of the polymer was of carboxylic acid at one end and of alcohol at the other terminal. 

Secondary metabolites generated via the propionate route are quite unusual in nature. Relevant exceptions are some antibiotic macrolides from Streptomycetes [42], but wholly propionate-derived macrolides are rare. This biosynthetic pathway has been well proved for erythromycin (13), where the aglycone is produced by assembling seven propionate units [43, 44], and for a few related antibiotics [45]. However, very sophisticated biosynthetic experiments [46] have established that some apparent propionate units in other macrolides (e.g., aplasmomycin [46]) from Streptomycetes could be formed either by C-methylation through S-adenosylmethionine or from glycerol. 

It is 2-A times less active than erythromycin with respect to a number of streptococci and staphylococci, and to a number of other organisms however, it is more active than other macrolides with respect to certain anaerobic organisms. Like other macrolides, it is active with respect to pathogens of the respiratory tract and pathogens transmitted sexually. It is used for treating bacterial bronchitis, pneumonia, skin, and sexual infections. Synonyms of this drug are zithromax and others. 

Erythromycin and the other macrolides prevent release of tRNAs from the ribosomal A site after peptide bond formation. 

Community-acquired pneumonia PO 500 mg once a day for 14 days. Contraindications Flypersensitivity to other macrolide antibacterials... 

Like fluoxetine, erythromycin and other macrolides inhibit the CYP-3A isoenzyme and increase the levels and effects of the triazolobenzodiazepines (Shader and Greenblatt, 1995 Chouinard et ah, 1999). Midazolam should be avoided or the dosage dropped by 50% in patients receiving erythromycin (Olkkola et ah, 1993). Ketoconazole and itraconazole may also interact with triazolam and midazolam, and combinations of these drugs should be avoided (Varhe et ah, 1994 Chouinard et ah, 1999). 

It is more stable in acid media than other macrolides. Roxithromycin is found... 

Nefazodone substantially decreases the clearance rate for triazolam, which results in a 400% increase in triazolam s serum levels (131). Erythromycin can also interfere with the metabolism of triazolam, resulting in decreased clearance and increased plasma levels, possibly causing toxicity. Troleandomycin and other macrolide antibiotics, such as clarithromycin, flurithromycin, josamycin, midecamycin, or roxithromycin, also may inhibit triazolam s metabolism (132). The coadministration of itraconazoie and triazolam can produce a marked elevation of triazolam plasma levels associated with statistically significant impairment of psychomotor tests and a prolongation of other effects (e.g., amnesia, lethargy, and confusion) for hours after awakening ( 133). 

With the important exception of additive effects when combined with other CNS depressants, including alcohol, BZDs interact with very few drugs. Disulfiram (see the section The Alcoholic Patient in Chapter 14) and cimetidine may increase BZD blood levels, and diazepam may increase blood levels of digoxin and phenytoin. Antacids may reduce the clinical effects of clorazepate by hindering its biotransformation to desmethyidiazepam. Coadministration of a BZD and another drug known to induce seizures may possibly increase seizure risk, especially if the BZD is abruptly withdrawn. Furthermore, as noted earlier, important interactions have been reported among nefazodone, erythromycin, troleandomycin, and other macrolide antibiotics, as well as itraconazole. In each case, metabolism is inhibited, and triazolam levels can increase significantly. 

M scrofuiaceum Cervical adenitis in children Amikacin, erythromycin (or other macrolide), rifampin, streptomycin (Surgical excision is often curative and the treatment of choice.)... 

Tilmicosin is a macrolide antibiotic exclusively used in veterinary medicine and resembling tylosin. It is approved for treatment of respiratory diseases in beef cattle and sheep by the subcutaneous route (100, 101). It is also indicated for treatment and control of respiratory diseases associated with mycoplasma in broiler chickens, but not in laying hens. Of major significance is that in contrast to other macrolides, tilmicosin is not safe for use in swine since fatalities may occur at dosage as low as 20 mg/kg bw (7). 

Data from the literature suggest that spiramycin produces more persistent residues than the other macrolides (95). However, due to the microbiological... 

Other macrolides have been prepared which represent hybrids of structures within the 14-membered family, within the 16-membered family, or between the two families. These hybrids have been made by chemical, bioconversion, or genetic manipulations. 

Erythromycin and the other macrolides exhibit a very broad spectrum of antibacterial activities and are active against many gram-positive bacteria, as well as some gram-negative bacteria. These agents are often used as the primary or alternative drug in a variety of clinical conditions (see Table 33-5). Macrolides may be especially useful in patients who are allergic to penicillin. 

Tinel M, Descatoire V, Larrey D, et al. Effects of clarithromycin on cytochrome P-450. Comparison with other macrolides. J Pharmacol Exp Ther 1989 250 746-751. 

Lindstrom T, Hanssen B, Wrighton S. Cytochrome P-450 complex formation by dirithromycin and other macrolides in rat and human livers. Antimicrob Agents Chemother 1993 37 265-269. 

Erythromycin Erythromycin is incompatible with preparations that are highly acidic or alkaline in nature. Pancreatitis disorders are reported with erythromycin overdose. Erythromycin and other macrolides interact with other drugs and are detailed elsewhere.6... 

As indicated in Scheme VII/32, cyclononanone (VII/165) is transformed into hydroperoxide hemiacetal, VII/167, which is isolated as a mixture of stereoisomers. The addition of Fe(II)S04 to a solution of VII/167 in methanol saturated with Cu(OAc)2 gave ( )-recifeiolide (VII/171) in quantitative yield. No isomeric olefins were detected. In the first step of the proposed mechanism, an electron from Fe2+ is transferred to the peroxide to form the oxy radical VII/168. The central C,C-bond is weakened by antiperiplanar overlap with the lone pair on the ether oxygen. Cleavage of this bond leads to the secondary carbon radical VII/169, which yields, by an oxidative coupling with Cu(OAc)2, the alkyl copper intermediate VII/170. If we assume that the alkyl copper intermediate, VII/170, exists (a) as a (Z)-ester, stabilized by n (ether O) —> <7 (C=0) overlap (anomeric effect), and (b) is internally coordinated by the ester to form a pseudo-six-membered ring, then only one of the four -hydrogens is available for a syn-//-elimination. [111]. This reaction principle has been used in other macrolide syntheses, too [112] [113]. 

Plasmid (or transposon)-encoded enzymes are thus responsible for the degradation of several different types of antibiotics. The inactivation of several /J-lactams, AGACs, 14-membered macrolides, other macrolides, lin-cosamides and streptogramis (MLS) and chloramphenicol is a major resistance mechanism it has yet to be shown that inactivation of other antibiotics falls into this category. 

A third possibility is that the differences in macrolide binding between these sets of experiments result from inaccuracies in the models. Relevant to this possibility, the 14-membered macrolide stmctures are based on lower resolution data and have higher free R values than do the other macrolide structures. 

Other macrolides (clarithromycin, flurithromycin, Carbamazepine High risk of carbamazepine toxicity Inhibition of carbamazepine metabolism... 

When azithromycin is used concomitantly with digoxin, serum digoxin concentrations need to be monitored (47). While data on the effects of azithromycin on the intestinal metabolism of digoxin have not been reported so far, it is likely that it will affect Eubacterium lentum, like other macrolides. 

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