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Bacteremia and Possible Septic Arthritis Following Peripheral Blood Stem Cell Transplantation

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Bacteremia and Possible Septic Arthritis Following Peripheral Blood Stem Cell Transplantation Bone Marrow Transplantation (2000) 26, 101–104 2000 Macmillan Publishers Ltd All rights reserved 0268–3369/00 $15.00 www.nature.com/bmt Case report Agrobacterium yellow group: bacteremia and possible septic arthritis following peripheral blood stem cell transplantation Y Chalandon1, DL Roscoe2 and SH Nantel1 1Division of Hematology and Leukemia/Bone Marrow Transplantation Program of British Columbia; and 2Division of Microbiology, Vancouver General Hospital, British Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada Summary: Case report A 47-year-old male patient developed sepsis and A 47-year-old male developed recurrent nodular sclerosing monoarticular arthritis following autologous stem cell Hodgkin’s disease 2 years after attaining CR with multiag- transplantation for recurrent Hodgkin’s disease. Blood ent chemotherapy (mechlorethamine, vincristine, procarba- cultures were positive for Agrobacterium yellow group. zine, prednisone (MOPP)/adriamycin, bleomycin, vinblas- The knee pain and swelling responded promptly to the tine (ABV) hybrid × 6 cycles). At relapse he had evidence institution of empirical broad-spectrum antibiotics. of disease in the abdomen and right inguinal region. Recurrent bacteremia developed necessitating Hickman He received two cycles of standard chemotherapy line removal for eventual resolution of the infection. (cyclophosphamide, vincristine, procarbazine, prednisone Transplant physicians should be aware of this unusual (CVPP)/MOPP) and had peripheral blood stem cells pathogen and the potential for both persistent line- (PBSC) collected following mobilization with G-CSF 10 related sepsis and possible septic arthritis. Bone Marrow ␮g/kg/day × 6 days. In November 1998, he underwent auto- Transplantation (2000) 26, 101–104. logous PBSC transplant following conditioning with cyclo- Keywords: Agrobacterium; septic arthritis; autologous; phosphamide, carmustine (BCNU), etoposide (VP-16) and transplantation; stem cell cisplatin (CBVP). He did not receive any antibiotic prophy- laxis. On day +2 he developed fever to 38.4°C, diarrhea and left knee pain. He had no previous history of arthritis. He was neutropenic (ANC = 0) and empirical broad spec- Febrile neutropenia and central venous catheter-associated trum antibiotics were commenced (ceftazidime 2 g i.v. bacteremia are common complications following intensive every 8 h, tobramycin 110 mg i.v. every 8 h, vancomycin chemotherapy and stem cell transplantation. Septic arthritis 1 g i.v. every 12 h. Tobramycin and vancomycin doses and is distinctly unusual in these patients suggesting that com- intervals were then adjusted to maintain therapeutic blood monly encountered organisms do not typically cause joint- levels). On day +3 in the face of progressive knee swelling, related complications. Agrobacteria are anaerobic nonfer- the knee joint was aspirated. Gram stain and cultures were mentative gram-negative bacilli found worldwide in soils negative. Crystals were not detected. Synovial fluid WBC and known to be plant pathogens, but infrequently have count was 61 × 106/l with 66% neutrophils, 30% monocytes been reported to cause infections in humans. Some authors and 4% lymphocytes. Within 48 h the fever and knee have described Agrobacteria as emerging opportunistic pain/swelling resolved. Blood cultures drawn at the time of 1–3 pathogens, primarily Agrobacterium radiobacter. fever grew gram-negative bacilli, subsequently identified as Reported infection due to Agrobacterium yellow group is Agrobacterium yellow group, and reported to be susceptible rare, with only one report in the literature describing four to ceftazidime and tobramycin (Table 1). Blood cultures 4 cases. Infection with unusual organisms may present with were collected by aseptic technique into two aerobic and unique clinical problems. In this report we describe a case two anaerobic culture bottles and incubated in the BAC- of Agrobacterium yellow group bacteremia associated with TEC 9240 (BD Biosciences, Sparks, MD, USA). At 48 h, a possible septic arthritis, which required removal of slender gram-negative bacilli were detected in the aerobic the central venous catheter in addition to antibiotics for bottles, which were subcultured in 5% sheep’s blood and resolution. MacConkey agars. After overnight incubation in 5% CO2, circular convex colonies 1–2 mm in diameter notable for a bright yellow pigment were present on the blood agar plate. There was no growth on the MacConkey agar. The oxidase Correspondence: Dr Y Chalandon, Division of Hematology and and catalase tests were positive. Initial identification and Leukemia/Bone Marrow Transplantation Program of British Columbia, Vancouver Hospital and Health Sciences Centre, 950 West 10th Avenue, susceptibility tests were done on an automated system Vancouver, British Columbia, V5Z 4E3, Canada (MicroScan, West Sacramento, CA, USA). The preliminary Received 6 April 1999; accepted 11 February 2000 identification of the isolate was Chryseobacterium spp., but Agrobacterium septic arthritis and autologous stem cell transplantation Y Chalandon et al 102 Table 1 Antibiotic susceptibility of Agrobacterium yellow group Discussion Antibiotics Isolate No 1 Isolate No 2 We describe the case of an immunocompromised patient who developed Agrobacterium yellow group bacteremia MicroScana Etest MIC MicroScan post-PBSC transplant for recurrent Hodgkin’s disease. ␮ g/ml Agrobacterium yellow group has only previously been reported in patients receiving peritoneal dialysis.4 Agrobac- Cefazolin R ND R Ceftazidime S 24.0 I teria are gram-negative, aerobic bacteria found ubiquitously Ceftriaxone S ND I in soil. Recognized as plant pathogens, human infections Cefuroxime I 24.0 R have rarely been reported. Best known for its ability to Ciprofloxacin I 3.0 R induce tumors in susceptible plants, Agrobacterium tumefa- Gentamicin S 1.0 S ciens is now known to be genetically identical to A. radio- Imipenem S 1.0 S Tobramycin S 1.0 S bacter, the most commonly reported species associated TMP-SMX S 0.25 S with human infections. Agrobacteria have biochemical characteristics similar to other gram-negative bacilli com- aSusceptibility interpretations are not available for this organism and were monly isolated from the environment and often require tests based on interpretation for non-Enterobacteriaceae. not routinely available in the clinical diagnostic laboratory, = = = MIC minimum inhibitory concentrations; R resistant; I intermediate; as occurred in this instance. Agrobacterium yellow group S = susceptible; TMP-SMX = trimethoprim-sulfamethoxazole; ND = not determined. are a distinct entity without species designation and are commonly confused with Sphingomonas paucimobilis.7 The actual incidence of infection with this organism may be under reported due to the difficulty in making an due to the relative biochemical inertness on this system the exact identification. isolate was sent to our reference laboratory (Provincial Lab- This presentation of Agrobacterium infection was oratory, British Columbia Center for Disease Control) who unusual due to the association of a possible septic arthritis made the identification of Agrobacterium yellow group of the left knee, which to our knowledge has not been based on the following biochemical reactions: oxidative uti- described previously. Despite the negative synovial fluid lization (OF) of glucose, xylose, lactose, sucrose and malt- culture, Agrobacterium-induced septic arthritis was ose, but not mannitol; negative reactions for indole, citrate, strongly suspected. First, the fluid was inflammatory show- lysine and ornithine decarboxylase, arginine dihydrolase, ing 61 × 103/ml WBC with a majority of neutrophils with gelatinase and DNAse; weakly positive delayed urea no crystals seen at a time when the patient was profoundly (Christensen’s); growth at 25° and 35°C, but not at 42°C; neutropenic and febrile. Second, the patient had good and no zone of inhibition to a polymixin disk. Tests for response to antibiotics and did not receive non-steroidal motility were positive and the isolate demonstrated one anti-inflammatory agents or steroids. The negative culture polar flagellum. Flexirubin pigment was not demonstrated. results in this case may have been due to the antibiotic Susceptibility results for both isolates from both episodes therapy which was started 18 h prior to joint aspiration. It of bacteremia are reported in Table 1. Only the first isolate is also possible that Agrobacterium is difficult to culture was available for susceptibility testing by an agar gradient from synovial fluid, with local factors in the joint fluid, diffusion method (Etest, ABBiodisk, Solna, Sweden) such as defensin, humoral factors or neutrophils impairing according to the manufacturer’s recommendations. Results growth of Agrobacterium in culture, and organisms may are reported in Table 1. Specific interpretations for suscepti- have been trapped in the clotted synovial fluid sample. The bility testing of this organism are not available and guide- possibility that this could have been a reactive arthritis to lines for interpretations were based on those for non- Agrobacterium as occurs during infection with other patho- Enterobacteriaceae.5 Antibiotics were continued and on day gens such as Chlamydia (Reiter’s syndrome) or enteric bac- +9 fever recurred. Therapeutic dose amphotericin B (0.5 teria was also considered.8 The presumed mechanism for mg/kg/day i.v. every 24 h) was added. Ceftazidime was reactive arthritis is an immune-mediated inflammatory
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