Nosocomial isolates of coagulase-negative staphylococci (CNS) are often resistant to multiple antibiotics, including anti-staphylococcal penicillins. As a result, the glycopeptides, vancomycin and teicoplanin, have acquired increasing importance in the treatment of patients with infections caused by these microorganisms. Reduced susceptibility of CNS to glycopeptides (MIC ≥ 8 mg/L) has been documented, but is usually limited to decreased effectiveness of teicoplanin against such species.1–4 We report here the recent isolation in Greece of two Staphylococcus haemolyticus strains that were fully resistant to teicoplanin (MIC ≥ 64 mg/L).
Two S. haemolyticus strains (S-652 and S-671) resistant to teicoplanin were recovered for the first time in our hospital during the first 3 months of 2000. They were isolated from different departments and were not epidemiologically related. The organisms were identified with the Vitek system (bioMérieux Vitek, Hazelwood, MO, USA). Susceptibility to 18 antimicrobial agents was evaluated with the same system according to the recommendations of the manufacturer. Susceptibility to teicoplanin and vancomycin was also determined by an agar incorporation method.5 The strains were incubated for 24 h before reading the MICs and resistance to any glycopeptide was confirmed by repeating the test. Staphylococcus aureus ATCC 29213 was used as a control and susceptibility categories were assigned according to NCCLS interpretative criteria.5
Strain S-652 was recovered from blood cultures of a 67-year-old male who had suffered a subarachnoid haemorrhage and had had an episode of sepsis due to an iv line infection; this was treated with ceftazidime 500 mg bd and teicoplanin 200 mg od. The strain was resistant to oxacillin, aminoglycosides, quinolones, macrolides, tetracyclines, fusidic acid and teicoplanin, but remained susceptible to vancomycin (MICs of 64 and 4 mg/L, respectively). The patient remained afebrile after line removal and intravenous administration of vancomycin.
The second patient was a 70-year-old female with type II diabetes mellitus, coronary artery disease and peripheral vascular disease who was treated for a necrotizing soft tissue infection. A multi-resistant oxacillin-resistant strain of S. aureus was cultured from the first wound swab and teicoplanin 200 mg od was given intramuscularly. Two weeks later an oxacillin-resistant S. haemolyticus strain (S-671) was found to predominate in the wound. It was fully resistant to teicoplanin (MIC 128 mg/L) but susceptible to vancomycin (MIC 4 mg/L). The strain was also resistant to other alternative antibiotics but remained susceptible to macrolides.
Teicoplanin resistance among CNS has usually been detected in methicillin-resistant strains after administration of glycopeptides.1,3 Although high rates of methicillin-resistant staphylococci are commonly detected in our region, this is the first report of infections caused by glycopeptide-resistant CNS in Greece. In our hospital, since 1990, vancomycin use has increased significantly as a result of the prevalence of methicillin-resistant staphylococci. Teicoplanin was introduced in 1993, but its use has been kept to a minimum in most wards. However, since 1998, the agent has replaced vancomycin in many departments of the hospital. The strains described in this study were acquired nosocomially and in both cases teicoplanin was administered before detection.
Although there are various studies describing CNS with reduced susceptibility to teicoplanin, data on the existence of isolates with high-level resistance (MIC ≥ 64 mg/L) is rather limited.2–4 In this report, the teicoplanin MICs for strains S-671 and S-652 were repeatedly 128 and 64 mg/L, respectively. With an automated system the former strain was characterized as resistant (MIC ≥ 32 mg/L) while the latter fell within the intermediate susceptibility category (MIC 16 mg/L). Previous studies2,4,6 have shown that standard disc diffusion testing and automated susceptibility systems may not define precisely the susceptibility status of staphylococci with reduced susceptibility to glycopeptides. Thus, it has been considered that susceptibility to teicoplanin should be carefully monitored with an agar or broth dilution method. This is of more value for seriously ill patients who have failed to respond to therapy with glycopeptides. In our clinical setting, resistance to methicillin is predominant among CNS and glycopeptides remain one of the limited choices for the treatment of infections caused by these microorganisms. Routine dilution susceptibility testing is recommended for all clinically significant CNS in order to clarify the incidence of glycopeptide resistance and restrain potential outbreaks.