Sir

During a randomized trial of linezolid versus teicoplanin in the treatment of Gram-positive infection in the critically ill, isolates of Staphylococcus aureus were tested by Etest (AB Biodisk, Solna, Sweden) for susceptibility to teicoplanin and linezolid. The breakpoints for teicoplanin recommended by the British Society for Antimicrobial Chemotherapy are susceptible ≤4 mg/L and resistant ≥8 mg/L; those of the NCCLS are susceptible ≤8 mg/L, intermediate 16 mg/L and resistant ≥32 mg/L. S.aureus with reduced susceptibility to teicoplanin was isolated from four of 204 patients enrolled in the study, two of whom were given teicoplanin and two linezolid, all within a period of 8 weeks. Another patient not in the study was found to harbour a strain with reduced teicoplanin susceptibility. Only one patient acquired the organism during his ICU stay. The organisms were detected on nasal/perineal screens in all five patients and in the sputum from two; bacteraemia occurred in one patient.

Twenty-five isolates from these five patients demonstrated teicoplanin MICs of at least 8 mg/L, as determined with Etests; the median MIC was 16 mg/L (range 8–32 mg/L). Disc testing of teicoplanin did not detect resistance. Subsequent testing of the isolates at the Antibiotic Resistance Monitoring and Reference Laboratory by agar dilution showed only seven isolates from two patients with teicoplanin MICs of 16 mg/L and one isolate from another patient with an MIC of 8 mg/L. Of these eight isolates, five were from screens, one from the patient’s environment, one from sternal tissue and one from blood. All 25 isolates were susceptible to linezolid (MIC 1–1.5 mg/L), vancomycin (1–2 mg/L), gentamicin (≤1 mg/L), rifampicin (≤0.25 mg/L), tetracycline (1–2 mg/L), clindamycin (≤0.25 mg/L) and fusidic acid (1–2 mg/L). The methicillin MICs were all >32 mg/L. All eight isolates with confirmed teicoplanin resistance and seven other of the 25 isolates (MIC 2–4 mg/L by reference laboratory testing) were EMRSA-16 and were indistinguishable on sub-typing (lysed by phage 52,75,77). Four isolates were urease positive. Pulsed-field gel electrophoresis (PFGE) of SmaI (Boehringer-Mannheim, Mannheim, Germany) macrodigested genomic DNA was consistent with a single strain.

Of the two patients with isolates confirmed to be teicoplanin-resistant (or intermediate on NCCLS criteria), the index case (case 1) was a 62-year-old man with diabetes, pulmonary oedema and periph-eral vascular disease. MRSA had been isolated from a perianal abscess 10 days earlier and he had then been treated with a low dose of teicoplanin for 6 days (200 mg every 2 days) followed by flucloxacillin. He was treated with linezolid for 1 week after MRSA was re-isolated, and subsequently recovered. Patient 2 was present in the ICU at the same time as patient 1, and had an infected sternal wound for which he had received a 10-day course of teicoplanin. The teicoplanin-resistant MRSA strain was detected in his wound, sputum and pleural fluid 3 weeks after that in the first patient. Two other strains of MRSA, susceptible to teicoplanin, were also present during this time (Table 1). He was treated with linezolid for 1 week and then vancomycin for 2 weeks, but died of multi-organ failure. MRSA was present in tracheal aspirate, wound swab and central line catheter specimens just before death. The MRSA with a confirmed teicoplanin MIC of 8 mg/L came from a screening swab from an uninfected patient 4 days after patient 1 was admitted. As regards the other two patients, whose isolates appeared resistant by Etests but not reference testing, one isolate was detected within 1 week of that of patient 1 and the other 1 week after that of patient 2.

Prolonged therapy of MRSA infections with teicoplanin has been associated with development of resistance (MIC 16–32 mg/L) in earlier reports.1,2 In a recent study, an EMRSA-16 strain was shown to become increasingly resistant to teicoplanin (MIC rising from 1 to 16 mg/L) during treatment, and to have spread to one other patient; both patients died from their infections.3 Screening of 72 MRSA and 143 MSSA isolates from blood cultures found seven representatives of each that were teicoplanin-resistant.4 The MRSA were all EMRSA-16 of two PFGE subtypes. The majority of isolates of a new UK epidemic strain, EMRSA-17, have been reported to be resistant to teicoplanin.5 Teicoplanin resistance in MRSA has been reported in ICUs that use this glycopeptide as a first-line antibiotic but before this study, Etests were used in our laboratory only in cases of doubtful susceptibility. Etests, or agar dilution methodology, rather than disc testing, are essential to detect resistant or intermediately resistant isolates and should be introduced at least for patients with persistent infection in units where teicoplanin is used.6

Acknowledgements

We thank Dr B. Cookson and Dr T. Pitt of the Laboratory of Hospital Infection, CPHL, Colindale, for assistance in typing the MRSA isolates.

*

*Corresponding author. Tel: +44-20-7380-9516; Fax: +44-20-7388-8514; E-mail: peter.wilson@uclh.org

Table 1.

Characteristics of S. aureus isolates from patients yielding teicoplanin-resistant organisms

Days from admission of index case  Epidemic type  MIC (mg/L)a 
Sample type  teicoplanin linezolid vancomycin 
Index case (case 1)       
screen E-16  16 
screen E-16  16 
screen E-16  16 
Case 2       
–5 screen E-16   4 
–5 catheter tip 16D   4 
–3 screen 16D   4 
screen 16D   4 
22 tissue wound E-16  16 
23 screen E-16  16 
24 environmental E-16  16 
25 leg E-16   4 
31 blood E-16  16 
Days from admission of index case  Epidemic type  MIC (mg/L)a 
Sample type  teicoplanin linezolid vancomycin 
Index case (case 1)       
screen E-16  16 
screen E-16  16 
screen E-16  16 
Case 2       
–5 screen E-16   4 
–5 catheter tip 16D   4 
–3 screen 16D   4 
screen 16D   4 
22 tissue wound E-16  16 
23 screen E-16  16 
24 environmental E-16  16 
25 leg E-16   4 
31 blood E-16  16 

aDetermined by agar dilution at ARMRL.

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Author notes

1Department of Clinical Microbiology, University College London Hospitals, London; 2Bloomsbury Institute of Intensive Care Medicine, Dept. of Medicine, UCL, London; 3Department of Medical Microbiology, Royal Free Hospital London, London; 4Antibiotic Resistance Monitoring & Reference Laboratory, Health Protection Agency, Colindale, London, UK