Case Report Mycobacterial Central Venous Catheter Tunnel Infection: a Difficult Problem
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Bone Marrow Transplantation, (1999) 24, 325–329 1999 Stockton Press All rights reserved 0268–3369/99 $12.00 http://www.stockton-press.co.uk/bmt Case report Mycobacterial central venous catheter tunnel infection: a difficult problem MS Ward, KV Lam, PK Cannell and RP Herrmann Haematology Department, Royal Perth Hospital, Perth, Australia Summary: Case reports We report our experience of non-tuberculous myco- Case 1 bacterial infection associated with the tunnel of Hick- man–Broviac central venous catheters in immunosup- A 28-year-old woman with AML achieved complete pressed patients with haematological malignancies remission with the first course of standard induction chemo- undergoing high-dose chemotherapy supported by therapy. Prolonged aplasia for several months complicated BMT. The problem is rare and difficult to treat. Our the first consolidation therapy. One year after diagnosis an cases are unique in developing tunnel site mycobac- abscess developed adjacent to the site of the previously terial infection well after the tunnelled catheters were removed Groshong catheter, with persistently negative removed. We diagnosed one case of Mycobacterium microbiological cultures (Figure 1). chelonae, which is a well-documented cause of such Fifteen months after initial diagnosis the AML relapsed. infections, and two cases of Mycobacterium haemophi- She went on to allogeneic bone marrow transplantation lum, which are the first reported cases in this setting. (1992) using busulphan and cyclophosphamide condition- Early wide surgical excision of the infected tunnel site ing with short-course methotrexate and cyclosporin graft- and prolonged antibiotic therapy is necessary. Despite versus-host disease (GVHD) prophylaxis. Grade II/III these measures recurrence occurred in two cases. Close cutaneous, hepatic and gastrointestinal GVHD was treated liaison with the microbiology laboratory is needed to with prednisolone 25 mg daily and Psoralen Ultra Violet A (PUVA) therapy. ensure the appropriate culture media and conditions Three months later the left chest wall lesion had deterio- are used for these fastidious organisms. Empiric anti- rated and numerous granulomata and acid-fast bacilli, later biotic regimens should be based on the likely organism. identified as Mycobacterium chelonae (abscessus), was Drugs active against M. chelonae and M. haemophilum isolated at biopsy. Wide surgical excision was undertaken. should be included. The lesion penetrated to within 0.5 cm of the pectoralis Keywords: mycobacteria; central venous catheter; Hick- major muscle and was extensive, necessitating subtotal man line; infection; M. chelonae; M. haemophilum mastectomy. Anti-mycobacterial therapy was i.v. amikacin 500 mg once daily and i.v. cefoxitin 2 g four times a day. A few months later M. chelonae recurred, just above the Tunnelled venous access devices are used commonly in scar, with 2–3 cm of induration. Local excision and imip- bone marrow transplantation to allow long-term venous enem were used initially and later amikacin and clarithro- access. These lines are associated with infectious and mycin (1 g twice a day). The area remained ulcerated for thrombotic complications. Mycobacterial infections are months, but was slowly healing. Intensive immunosuppres- rarely encountered. Tunnel-related infection is even less sion was continued because of progressive GVHD includ- frequently reported. We discuss the problem, outline our ing obliterative bronchiolitis. experience and review the literature. One year later a further lesion developed which was indurated, red and tender; the old lesion ulcerated. Amika- cin and cefoxitin were employed as the organism had become resistant to clarithromycin. Deafness was noted, probably due to cumulative toxicity of amikacin; although amikacin levels were never toxic. Death occurred 3 years after initial presentation from respiratory failure (obliterative bronchiolitis), disseminated mycobacterial Correspondence: Dr MS Ward, Haematology Department, Royal Perth sepsis (blood cultures positive for M. chelonae) and Hospital, Wellington Street, Perth WA 6000, Australia chronic GVHD. Received 15 September 1998; accepted 11 March 1999 Mycobacterial CVC tunnel infection MS Ward et al 326 Figure 1 Photograph of ulcerated area adjacent to previous Groshong catheter site (case 1). Case 2 and no sign of recurrence. Immunosuppressive or immunomodulating therapy has been withheld indefinitely. A 29-year-old woman was diagnosed with intermediate- grade non-Hodgkin’s lymphoma (diffuse mixed small and large cell) at 26 weeks gestation. Skin, lung, liver and spleen were involved. The baby was delivered early, and Case 3 CEOP chemotherapy was commenced, without improve- ment. A salvage regimen containing dexamethasone, high- A 26-year-old woman with a past history of epilepsy was dose cytarabine and carboplatin was used, followed by dou- diagnosed with blastic transformation of CML and received ble autologous peripheral blood stem cell transplantation at two cycles of idarubicin, high-dose cytarabine and etopo- 3 and 5 months after diagnosis (1998). Interleukin-2 and side chemotherapy. Matched unrelated BMT was perfor- interferon-alpha were then employed. Three months after med 5 months after diagnosis (1998) using total body the second autograft an inflamed mass developed in the irradiation and cyclophosphamide conditioning followed by right supraclavicular region with some inflammation at the short-course methotrexate, Campath 1G, steroid and cyclo- CVC site. Cellulitis with lymphadenopathy were suspected sporin GVHD prophylaxis. and flucloxacillin commenced. The lesion became harder Three months after transplant the site of a previous Hick- and less inflamed but did not disappear. Fine needle aspir- man catheter (removed after only a few hours because of ation (FNA) cytology failed to demonstrate recurrent lym- accidental dislodgement) became ulcerated and infected, phoma or any microbial organism. Only neutrophils were associated with a purulent discharge. Flucloxacillin was seen. Since the lesions failed to respond, antibiotics were prescribed but swabs demonstrated leucocytes with no changed to ciprofloxacin and cephalexin. The lesion slowly microbial growth. The ulcer persisted and cultures from deteriorated, and new ulcerated lesions developed along the swabs grew abundant Proteus and Pseudomonas, which track of the previous catheter. Further FNA was perfomed were treated with ciprofloxacin. Numerous rapid-growing which demonstrated acid-fast bacilli. Wide surgical exci- mycobacteria were also detected after 5 days. Wide surgical sion of the catheter track and two adjacent lymph nodes excision was performed down to 2 cm from the muscle. confirmed granulomata with multi-nucleate giant cells. Oral clarithromycin 500 mg twice a day, i.v. amikacin One of the nodes contained a few acid-fast bacilli. Culture 500 mg daily and i.v. meropenem 500 mg three times a day confirmed Mycobacterium haemophilum after 7 (subsequently changed to i.v. cefoxitin 2 g twice a day) weeks incubation. Therapy consisted of amikacin, clari- were commenced. The immunosuppression was reduced. thromycin, ciprofloxacin and meropenem for 3 weeks, Identification of Mycobacterium haemophilum took 7 then amikacin and meropenem were ceased and ethambutol weeks. Figure 2 demonstrates numerous mycobacteria in started. She continues on this regimen with a healed wound the biopsy specimen. Mycobacterial CVC tunnel infection MS Ward et al 327 Table 1 Summary of published cases of catheter-related Mycobacterial infection Study Cases Setting Species Site Therapy Roy et al7 6/2241 BMT 3 M. chelonae 3 tunnel infection 1–6 months Ab: amik, clar, cipro, adult and paediatric 3 M. fortuitum 3 CRB cotrim. ± line removal. Surgery not mentioned. Raad et al8 15 Cancer 9 M. fortuitum 4 local line sepsis CRB: Catheter removal + Ab. 6 M. chelonae 11 CRB Tunnel infection: required surgical excision. Exit site infection: catheter removal only. Amik, cotrim, cefox. Flynn et al9 6 Haematological 4 M. chelonae Hickman 3 cases of tunnel infection recurred with malignancy (paediatric) 2 M. fortuitum catheter removal and Ab, which resolved with surgical excision. Holland et al10 1 BMT M. neoaurum Hickman catheter Ab (tic/clav, tob) then line removal. Esteban et al11 1 HD chemo, NHL M. aurum Tunnelled catheter line removal + Ab: amik, clari. Skeitz12 1 Cancer M. smegmatis CRB line removal + Ab. Groeger et al3 1/1431 Cancer M. chelonae tunnel infection No details. Ward et al (this 3/401 BMT 1 M. chelonae tunnel site infection surgical excision + Ab. paper) 2 M. haemophilum (catheter previously Amik, cefox, imip, cipro, clar. removed) Amik, clar, cipro, mero, etham. Amik, clar, rif, cipro. CRB = catheter-related bacteraemia; Ab = antibiotic therapy; amik = amikacin; clar = clarithromycin; cotrim = co-trimoxazole (sulphamethoxazole/trimethoprim); cefox = cefoxitin; rif = rifampicin; tic/clav = ticarcillin/clavulanic acid; tob = tobramycin; imip = imipenem; mero = meropenem; etham = ethambutol; cipro = ciprofloxacin. Two months later the ulcer reappeared and a few AFB relied upon catheter removal and antibiotics. They also were isolated. Repeat surgical excision (to the pectoralis noted, as we have, that tunnel infection required surgical muscle including a cuff of muscle) was undertaken. excision. Flynn et al9 also found that in three patients the The drugs were changed to oral rifampicin 600 mg daily, local infection relapsed after the catheter was removed and ciprofloxacin 750 mg twice a day and clarithromycin