Teicoplanin resistance

Other specific discovery assays have been used such as differential inhibition of a vancomycin resistant S. aureus strain and its susceptible parent, and an assay based on antagonism of the antibacterial activity by N,A/-diacetyl-L-Lys-D-Ala-D-Ala [24570-39-6] a tripeptide analogue of the dalbaheptides receptor. AppHcation of this latter test to 1936 cultures (90) led to the isolation of 42 dalbaheptides, six of which, including kibdelin (Table 3), parvodicin (Table 3), and actinoidin A2 (68) were novel. A colorimetric assay based on competition between horseradish peroxidase bound teicoplanin and the... 

This resistance, inducible by low concentrations of dalbaheptides, is plasmid mediated and is transferable. Concomitant with the induction of resistance is the appearance or increased expression of a protein having a molecular weight of either 39,500 or 39,000. The enzymatic activity of this material has been postulated (112). Although the mechanism of resistance induction by dalbaheptides is unknown, different dalhabaheptides have different induction capacity. Vancomycin (39) is the most powerful inducer teicoplanin is a very weak inducer. 

Acquired resistance to the glycopeptides is transposon-mediated and has so far been largely confined to the enterococci. This has been a problem clinically because many of these strains have been resistant to all other antibiotics and were thus effectively untreatable. Fortunately, the enterococci are not particularly pathogenic and infections have been confined largely to seriously ill, long-term hospital patients. Two types of acquired glycopeptide resistance have been described (Woodford et al. 1995). The VanA phenotype is resistant to vancomycin and teicoplanin, whereas VanB is resistant... 

Fig. 9.4 Organization of glycopeptide-resistance genes in transposon Tnl546. IR, invested repeats HPK, histidine protein kinase TcR, low level teicoplanin resistance.

VanB-type has been less well-characterized but essentially operates in a similar manner to VanA. Both inducible and constitutive forms of resistance have been described, but the reasons for susceptibility to teicoplanin are unclear. 

Vancomycin and teicoplanin display excellent activity against staphylococci and streptococci, but because of the wide availability of equally effective and less toxic drugs, they are second-line drugs in the treatment of most infections. As antistaphylococcal agents they are less effective than 3-lactam cephalosporin antibiotics, such as nafciUin and cefazoUn. They have attained much wider use in recent years as a consequence of the emergence of methicUlin-resistant S. aureus (MRSA) infections, in particular the growing importance of Staphylococcus epidermidis infections associated with the use of intravascular catheters and in patients with peritonitis who are on continuous ambulatory peritoneal dialysis. 

C. Teicoplanin, although used in Europe, is not approved for use in the United States. It can be used to treat a variety of gram-positive infections and should be considered in resistant gram-positive infections as well. Bacitracin and polymyxins are topical agents with potential for serious nephrotoxicity when used parenterally. Linezolid is recently approved for resistant gram-positive infections (VRE and MRSA) and is available in the United States. 

Mechanism of Resistance. Resistance to high levels of dalbaheptides has been described in enterococci. In some isolates, resistance is indutible. Transfer of resistance, in some cases plasmid-mediated, has been described. More recently, strains highly resistant to vancomycin but sensitive 10 teicoplanin have been isolated in the United States. Among the resistant... 

Apart from the above-discussed parameters for HPLC optimization of chiral resolution on antibiotic CSPs, some other HPLC conditions may be controlled to improve chiral resolution on these CSPs. The effect of the concentrations of antibiotics (on stationary phase) on enantioresolution varied depending on the type of racemates. The effect of the concentrations of teicoplanin has been studied on the retention (k), enantioselectivity (a), resolution (Rs), and theoretical plate number (N) for five racemates [21]. An increase in the concentration of teicoplanin resulted in an increase of a and Rs values. The most surprising fact is that the theoretical plate number (N) increases with the increase in the concentration of teicoplanin. It may be the result of the resistance of mass transfer resulting from analyte interaction with free silanol and/or the linkage chains (antibiotics linked with silica gel). This would tend to trap an analyte between the silica surface and the bulky chiral selector adhered to it. This is somewhat... 

Nakamura, T., Ushiyama, C., Suzuki, Y., Inoue, T., Shoji, H., Shimada, N., Koide, H. Combination therapy with polymyxin B-immobilized fibre haemoperfusion and teicoplanin for sepsis due to methicillin-resistant Staphylococcus aureus. J Hosp Infect 53 (2003) 58-63. 

In 76 patients receiving long-term teicoplanin for chronic osteomyelitis due to oxacillin-resistant Staphylococcus aureus, teicoplanin had to be withdrawn in only one subject because of low-grade fever, muscular pain, and sleeplessness these adverse effects abated after withdrawal (4). 

Severe thrombocytopenia occurred in a 46-year-old white man treated with teicoplanin 6 mg/kg/day for methicillin-resistant S. aureus bacteremia (30). The platelet count fell to 25 x 10 /1 on day 8 (baseline 110). After drug withdrawal the platelet count improved within 4 days. The trough teicoplanin concentrations were 17 pg/ml on day 4 and 15.4 pg/ml on day 9. 

---