JAC

Journal of Antimicrobial Chemotherapy (2001) 48, 315–329

Correspondence Clindamycin treatment of Staphylococcus aureus expressing inducible clindamycin resistance J Antimicrob Chemother 2001; 48: 315–316 Dragana Drinkovica*, Elizabeth R. Fullerb, Keith P. Shorea, David J. Hollanda,b and Rod Ellis-Peglerb Departments of aMicrobiology and bInfectious Disease, Auckland Hospital, Auckland, New Zealand *Corresponding author. Tel: 64-9-307-4949; Fax: 64-9-307-8922; E-mail: [email protected] Sir, We read with interest the correspondence regarding the use of clindamycin in the treatment of patients with infections caused by erythromycin-resistant staphylococci, expressing inducible clindamycin resistance (ICR).1,2 We have been unsure as to the clinical significance of ICR in the treatment of patients with infection due to these organisms. We have recently treated three such patients with clindamycin; two patients were cured but the other was not. Patient 1, an 87-year-old woman, was admitted with a 6 week history of pain and swelling of the right mid-foot. She was afebrile, but the dorsum of the right foot was warm and tender, with erythema and swelling. Pus obtained by needle aspiration of the talo-navicular joint yielded Staphylococcus aureus resistant to erythromycin and expressing ICR. The patient was allergic to penicillin, so oral clindamycin (300 mg, 8 hourly) was begun, and following a 6 week course, a successful outcome resulted. Patient 2, a previously well 38-year-old man, presented with an infected scalp wound after a cut sustained during a haircut. The infection was unresponsive to oral erythromycin and co-trimoxazole treatment and after 3 days of fever and right flank pain, the patient was admitted with hypotension and tachycardia. A head CT revealed a subgaleal collection and chest X-ray showed a right pleural effusion. An intercostal drain was inserted for presumed empyema, and the scalp incised. The patient was treated with iv flucloxacillin and gentamicin. Methicillin-resistant S. aureus (MRSA) was isolated from scalp wound pus, sputum and blood cultures, but not from the pleural fluid. The isolate was resistant to erythromycin and expressed ICR. Flucloxacillin and gentamicin were discontinued and iv clindamycin (600 mg, 8 hourly) was given for 2 weeks followed by 2 weeks of oral medication; the patient was cured of invasive MRSA disease.

Patient 3, an 84-year-old man, was admitted after fracturing his right neck of femur. A right hemiarthroplasty was performed, with a successful post-operative course and satisfactory wound healing. Three weeks later he complained of increasing right hip pain, and the wound was discharging pus from which an erythromycin-resistant MRSA expressing ICR was isolated. The patient developed signs of sepsis syndrome and iv vancomycin was started, which was changed to iv clindamycin (600 mg, 8 hourly) on the second day of treatment when an urticarial rash developed. An ultrasound scan of the hip showed a large fluid collection and open debridement, washout and removal of hemiarthroplasty was performed. There was a good clinical response and after 12 days he was switched to oral clindamycin (450 mg, 8 hourly). However, 5 days later he again became febrile and the hip wound started to discharge. Further surgical debridement and washout was performed, and iv clindamycin recommenced. However, clindamycinresistant MRSA was isolated from the surgical specimens and again the patient developed sepsis syndrome. After discussion with his family, all treatment was withdrawn owing to his poor pre-morbid condition and prognosis. Clindamycin-resistant MRSA with the same phage pattern as the wound isolate was isolated from blood cultures and the patient died several days later. Resistance to macrolide, lincosamide and streptogramin B (MLS) antibiotics most commonly results from acquisition of erythromycin resistance methylase (erm) genes, which encode enzymes that methylate the 23S rRNA. Expression of MLS resistance may be constitutive or inducible. Constitutively resistant strains are resistant to all MLS antibiotics and are readily detected by standard susceptibility methods. Inducible resistance is expressed in the presence of strong inducers of methylase synthesis, such as 14-membered (e.g. erythromycin) and 15-membered (e.g. azithromycin) macrolides. The 16-membered macrolides (e.g. spiramycin), lincosamides (e.g. clindamycin) and streptogramin B antibiotics may appear active using standard susceptibility methods, because they are weak inducers of methylase synthesis,3 but inducible resistance can be detected by the disc diffusion induction test.4 It was shown recently that erythromycin-resistant, clindamycin-susceptible S. aureus isolates expressing ICR rapidly developed clindamycin resistance in vitro.1 Recently, one of three patients with MRSA expressing ICR failed clindamycin treatment2 (although the author suggested all were successful), as did one of three described above by us. Likewise in 1976, a patient with endocarditis due to S. aureus, initially susceptible to erythromycin, failed treat-

315 © 2001 The British Society for Antimicrobial Chemotherapy

Correspondence ment with clindamycin, again with the development of clindamycin resistance.5 Just how often and how quickly resistant mutants develop in vivo where host, bacterial and antimicrobial factors interact is unknown. The conclusion is that this event certainly occurs and the accumulating clinical evidence indicates that it is not rare. We will now be very cautious about using clindamycin in patients with major infections due to S. aureus expressing ICR, especially where treatment is likely to be prolonged or infection difficult to eradicate.

2. Gopal Rao, G. (2000). Should clindamycin be used in treatment of patients with infections caused by erythromycin-resistant staphylococci? Journal of Antimicrobial Chemotherapy 45, 715.

References

5. Watanakunakorn, C. (1976). Clindamycin therapy of Staphylococcus aureus endocarditis. Clinical relapse and development of resistance to clindamycin, lincomycin and erythromycin. American Journal of Medicine 60, 419–25.

1. Panagea, S., Perry, J. D. & Gould, F. K. (1999). Should clindamycin be used in treatment of patients with infections caused by erythromycin-resistant staphylococci? Journal of Antimicrobial Chemotherapy 44, 581–2.

3. Leclerq, R. & Courvalin, P. (1991). Bacterial resistance to macrolide, lincosamide, and streptogramin antibiotics by target modification. Antimicrobial Agents and Chemotherapy 35, 1267–72. 4. Sanchez, M. L., Flint, K. K. & Jones, R. N. (1993). Occurrence of macrolide-lincosamide-streptogramin resistance among staphylococcal clinical isolates at a university medical center: is false susceptibility to new macrolides and clindamycin a contemporary clinical and in vitro testing problem? Diagnostic Microbiology and Infectious Disease 16, 205–13.

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