Recurrent penicillin-resistant pneumococcal sepsis after matched unrelated donor (MUD) transplantation for refractory T cell lymphoma

Abstract

Summary:Patients who undergo splenectomy and recipients of allogeneic marrow (alloBMT) or peripheral stem cell transplantation are at increased risk of overwhelming infection from encapsulated organisms such as Streptococcus pneumoniae, Haemophilus influenzae and Neiserria meningitidis. As prophylaxis against these pathogens splenectomised patients are immunised and may also receive antibiotics for life. We report relapsing overwhelming sepsis caused by penicillin-resistant pneumococcus in a patient who was immunised and received prophylactic phenoxymethylpenicillin for 8 months following splenectomy and matched unrelated donor (MUD) marrow transplantation for refractory T cell lymphoma. No obvious focus of sepsis was found during any of the three episodes and S. pneumoniae serogroup 6, subtype 6B was isolated from blood cultures on each occasion. He was treated with i.v. cephalosporins, as the organisms were resistant to penicillin with a minimum inhibitory concentration (MIC) of 2.0, and there was complete resolution of symptoms each time. In the light of recurrent sepsis with this penicillin-resistant organism the decision was made to give prophylactic levofloxacin for the next 12 months. This case illustrates that the choice of prophylactic regimen and the treatment of sepsis in immunocompromised patients remain difficult and challenging issues. 5 They are also immunised with 23-valent polysaccharide pneumococcal vaccine but the ability to generate an adequate antigen-specific immune response in recipients of alloBMT is time-dependent and may not be consistent. 6,7 To highlight the challenges in the primary prevention of sepsis with encapsulated bacteria in this group of patients, we report on the recurrence of serious penicillin-resistant pneumococcal sepsis in a patient, 8 months post-MUD transplantation for refractory T cell lymphoma. Case reportA 27-year-old man presented with splenomegaly and pancytopenia. A diagnosis of T cell NHL was made on trephine biopsy. He was treated with nine courses of CHOP chemotherapy. A splenectomy was performed 5 months after the initial diagnosis and nodular collections of small lymphocytic cells with slightly irregular nuclei and low mitotic rate, were detected on splenic sections. The cells expressed CD3, CD5 and CD43, thus confirming a diagnosis of lowgrade peripheral T cell lymphoma. Prior to the splenectomy he was immunised with 23-polyvalent polysaccharide pneumococcal vaccine, H. influenza type b (Hib) conjugate vaccine and meningococcal type A and C polysaccharide vaccine. He was subsequently treated with more chemotherapy (miniBEAM and subsequently a combination of idarubicin and cytosine arabinoside). However, marrow examination after completing chemotherapy continued to show infiltration with lymphoma, indicating refractory disease.Since the patient's sister was not HLA compatible, matched unrelated donor transplantation was performed 17 months after the initial diagnosis. The pretransplant conditioning regimen consisted of fractionated total body irradiation 1...

Invasive pneumococcal disease in adult hematopoietic stem cell transplant recipients: a decade of prospective population-based surveillance

“…14 Failure of pencillin with breakthrough penicillin-resistant IPD has been described. 15 This is an area that requires further study.…”

Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective

“…Antibiotic prophylaxis should be administered even to patients who have received pneumococcal vaccine, because not all strains are included in the vaccines, the immunogenicity of vaccines against the vaccine strains in HCT patients is only, at most, about 80% [194,195], and because of the theoretic concern that strains not included in the vaccine will replace vaccine strains. Oral penicillin remains the preferred choice, but antibiotic selection depends on the local pattern of pneumococcal resistance to penicillin and other antibiotics (ie, second-generation cephalosporins, macrolides, and quinolones) [196][197][198][199]. Early empirical antibiotic treatment is required in any HCT patient with suspected IPI, regardless of the time since transplant, the immunization status, and the use of chemoprophylaxis (AIII) [193].…”

Efficacy of donor vaccination before hematopoietic cell transplantation and recipient vaccination both before and early after transplantation

“…The percentage may rise in the 2000s due to the rapid emergence of resistant pneumococci. 34,35 Fortunately, vaccination of the donor pretransplant and the recipient pretransplant and early post transplant with the new heptavalent polysaccharide þ protein conjugate vaccine (Prevnar) appears to improve the post transplant antibody levels for the seven serotypes contained in the vaccine. 2 For the serotypes not contained in the heptavalent vaccine, the best prophylaxis continues to be antibiotic prophylaxis during the first year and immunization with the 23-valent polysaccharide vaccine at 1 year post transplant (see Figures 1 and 2 for the moderate efficacy of the 23-valent vaccine at 1 year post transplant).…”