Staphylococci macrolides

Hydrolysis of macrolides by products of the ere genes detected in enterobacteria is only of scientific interest, while esterases VGB-A and VGB-B encoded by the vgb type genes mediate clinically relevant resistance in staphylococci to the B compound (quinupristin) of the streptogramin combination quinu-pristin-dalfopristin. 

Another group of antibiotics that can be inactivated by hydrolysis are 14- and 15- membered macrolides [2]. Esterases cleave the lactone ring. The plasmid encoded ere genes are found in members of the Enter-obacteriaceae and increase the intrinsic resistance. Furthermore, these esterases can also be found in some isolates of erythromycin resistant staphylococci. 

MsrA 14-, 15-Membered macrolides, streptogramin type B Staphylococci Plasmid... 

The lincosamides, another group of anti-infectives, are effective against many gram-positive organisms, such as streptococci and staphylococci. However, because of their high potential for toxicity, the lincosamides are usually used only for the treatment of serious infections in which penicillin or erythromycin (a macrolide) is not effective... 

Clarithromycin is better absorbed and irritates the gastrointestinal tract less than erythromycin. It is presumed that its activity exceeds that of erythromycin by 2-4 times with respect to a number of streptococci and staphylococci, and to a few other microorganisms. It is used for treating bacterial bronchitis, pneumonia, skin and sexual infections. It is believed that clarithromycin is the most active macrolide for treating atypical mycobacteria. Synonyms of this drug are biaxin and others. 

Multiply resistant coagulase-negative staphylococci are frequently the cause of postoperative endophtalmitis and require the use of a glycopep-tide (e.g. vancomycin). For topical treatment fusidic acid eye gel, tetracycline or chloramphenicol ointment are available, and can be administered 2 t.d. for 7 days. Trachoma should be treated with an oral macrolide (e.g. a single oral dose of 20 mg/kg azithromycin) or doxycyclin for 3 weeks (for moderate to severe cases). Keratitis needs hourly administration of fortified antibiotic eye drops for 2 weeks. Endophtalmitis needs specialist treatment for 6 weeks. 

Rx of pneumonia, skin, soft tissue Infxns, osteomyelitis caused by penicillinase-producing staphylococci Action Bactericidal X cell wall synth Dose Adults. 250-500 mg qid Feds <40 kg, 12.5-100 mg/kg/d - qid take on empty stomach Caution [B, ] Contra Component orPCN sensitivity Disp Caps 125, 250, 500 mg soln 62.5 mg/5 mL SE N/D, abd pain Interactions T Effects W/ disulfiram, probenecid T effects OF MRX, X effects W/ macrolides, tetracyclines, food X effects OF OCPs, warfarin EMS Monitor for signs of electrolyte disturbances and hypovolemia d/t D OD May cause N/V/D, behavior changes, urinary retention, skin rash and Szs symptomatic and supportive... 

As this category of penicillins was used for treatment, S. aureus and S. epidermidis became resistant to them through the production of altered penicillin-binding proteins. These strains of staphylococci are called methicillin resistant, which denotes resistance not only to all penicillinase-resistant penicillins but to all penicillin drugs. Methicillin-resistant staphylococci have become a major problem in treatment because they are also resistant to the cephalosporins, aminoglycosides, and macrolides. For this reason vancomycin, a more toxic antibiotic, is the drug of choice for these organisms. 

Lina G, Quaglia A, Reverdy ME, Leclercq R, Vandenesch F, Etienne J. Distribution of genes encoding resistance to macrolides, lincosamides, and streptogramins among staphylococci. Antimicrob Agents Chemother 1999 43(5) 1062-6. 

The macrolide antibiotics include erythromycin, clarithromycin, azithromycin, tylosin, tilmicosin and tiamulin. Clindamycin and lincomycin are related lincosamides. Susceptible bacteria include staphylococci, streptococci, Campylobacter jejunii, Clostridium spp., R. equi, Mycoplasma pneumoniae and Chlamydia spp. Drugs in this group are only effective against a few Gram-negative bacteria in cattle, namely some strains of Pasteurella and Haemophilus spp. Macrolides and lincosamides are associated with causing colitis in horses, so their use is usually restricted to p.o. erythromycin for the treatment of R. equi infections in foals. Subantimicrobial doses of erythromycin are administered i.v. to horses for gastrointestinal prokinetic action. 

Ketolides and macrolides have very similar antibacterial properties. Telithromycin is active against staphylococci, streptococci, S. pneumoniae, Haemophilus spp., Moraxella catarrhalis. Mycoplasma, Chlamydia, and Legionella. It is slightly more active by weight than erythromycin. MIC breakpoints for telithromycin are <0.25 pg/ml for S. aureus, <1 pg/ml for S. pneumoniae, and pg/ml for H. influenzae. 

Macrolide Resistance Due to Decreased Accumulation (Enhanced Efflux) in Staphylococci and Streptococci... 

In recent years, new resistance phenotypes (macrolide and streptogramin B antibiotics [MS] or partial macrolide and streptogramin B antibiotics [PMS], and macrolide antibiotics [M]) have been observed in elinical isolates of staphylococci and streptococci. Ross et al. [61, 125, 193] and Goldman and Capobianco [126] reported that MS-resistant strains of Staphylococcus epidermidis were resistant to 14- or 15-membered-ring macrolides and streptogramin B, but were susceptible to 16-membered-ring macrolide and lincosamide antibiotics. 

Thakker-Varia, S., Jenssen, W. D., Moon-McDermott, L., Weinstein, M. P., and Dubin, D. T. (1987). Molecular epidemiology of macrolide-lincosamide-streptogramin B resistance in Staphylococcus aureus and coagulase-negative staphylococci. Antimicrob. Agents Chemother. 31, 735-743. 

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