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Acute bacterial endocarditis during granulocytopenia in an allogenic marrow transplant recipient

      To the Editor
      Although granulocytopenia resulting from chemotherapy predisposes patients to a wide variety of infectious complications, endocarditis has seldom been described (
      • Rosen P.
      • Armstrong D.
      Infective endocarditis in patients treated for malignant neoplastic diseases a post-mortem study.
      ). We report a case of bacterial endocarditis on a native valve after allogenic marrow transplantation with subsequent neutropenia.
      A 53-year-old man underwent an allogenic marrow transplant from an HLA-matched, unrelated donor as treatment for myelodysplastic syndrome (FAB subtype refractory anemia with excess blasts in transformation). Pretransplant cytoreduction consisted of hyperfractionated whole-body radiotherapy (1,350 cGy) and cyclophosphamide (120 mg/kg). Graft-versus-host disease prophylaxis consisted of intravenous cyclosporine (1.5 mg/kg twice daily) and methotrexate (15 mg/m2 on day 1 and 10 mg/m2 on days 3 and 6 posttransplantation).
      Five days posttransplant, the patient developed severe oral pain and gingival bleeding. Three days later he had a new fever (39.6°C), accompanied by rigors. On examination, he appeared ill, with extensive hemorrhagic buccal mucositis. The left subclavicular fossa was erythematous, tender, and indurated along the subcutaneous course of the central venous catheter tract. His absolute neutrophil count was 0.0 cells/mm3, the hemoglobin was 9.1 g/dL, and the platelet count 13,000 cells/μL. Serum aminotransferase and creatinine levels and a chest radiograph were normal.
      Intravenous ticarcillin-clavulanic acid (3 g every 4 hours), gentamicin (5 mg/kg daily), and vancomycin (1 g every 12 hours) were instituted. The fever resolved within 48 hours. On day 12 after transplantation, blood cultures from all central venous catheter ports grew a gram-negative bacteria (from anaerobic cultures at 70 hours and from aerobic cultures at 88 hours). Haemophilus parainfluenzae was isolated. Transthoracic and transesophageal echocardiography for evaluation of a new pansystolic murmur showed a single 8-mm vegetation on an otherwise normal aortic valve.
      The patient continued to improve and all subsequent blood cultures were sterile. The neutropenia resolved 21 days after transplantation. The left central venous catheter tract infection improved. Broad-spectrum antibiotics were changed to intravenous ceftriaxone (2 g daily), and he was discharged home to complete 6 weeks of therapy. There was no evidence of relapse at 6-month follow-up.
      Endovascular infections associated with Haemophilus species are uncommon and account for about 1% of all cases of infectious endocarditis (
      • Lynn D.J.
      • Kane J.G.
      • Parker R.H.
      Haemophilus parainfluenzae and influenzae endocarditis a review of forty cases.
      ,
      • Chunn C.J.
      • Jones S.R.
      • McCutchan J.A.
      • et al.
      Haemophilus parainfluenzae infective endocarditis.
      ,
      • Cates J.E.
      • Christie R.V.
      Subacute bacterial endocarditis review of 442 patients treated in 14 centers appointed by Penicillin Trials Committee of Medical Research Council.
      ). Haemophilus species associated with endocarditis include H. influenzae, H. parainfluenzae, H. aphorpholus, and H. paraphropholus. The latter three organisms, in the context of current understanding of endocarditis, are grouped as “HACEK” organisms (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella) because of their common clinical and microbiologic features: slow-growing, fastidious bacteria; large vegetations; and frequent embolic occlusion of medium-sized and even large arteries. The primary sources of bacteremia associated with Haemophilus species endovascular infection include dental procedures, upper respiratory tract infections, and pneumonia (
      • Chunn C.J.
      • Jones S.R.
      • McCutchan J.A.
      • et al.
      Haemophilus parainfluenzae infective endocarditis.
      ,
      • Cates J.E.
      • Christie R.V.
      Subacute bacterial endocarditis review of 442 patients treated in 14 centers appointed by Penicillin Trials Committee of Medical Research Council.
      ,
      • Geraci J.E.
      • Wilkowske C.J.
      • Wilson W.R.
      • Washington J.A.
      Haemophilus endocarditis. Report of 14 patients.
      ,
      • Craven E.B.
      • Lexington N.C.
      • Poston M.A.
      • Orgain E.S.
      Haemophilus para-influenzae endocarditis. A report of two cases and a review of the literature of the influenzal endocarditides.
      ,
      • Julander I.
      • Lindberg A.A.
      • Svanbom M.
      Haemophilus parainfluenzae. An uncommon cause of septicemia and endocarditis.
      ).
      Although neutrophils are not an essential component of valvular vegetations, bacterial endocarditis is rarely encountered in granulocytopenic subjects, even in those with persistent bacteremia due to Streptococcus, Staphylococcus, or Enterococcus species. We suspect that severe mucositis in our patient was the portal of entry for the H. parainfluenzae blood stream infection. Secondary infection of the central venous catheter tract might have led to high-grade bacteremia, promoting endocarditis; however, we were able to “treat through” the tunnel infection without removal of the catheter.

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