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Osteomyelitis Due to Clostridium Innocuum in a Patient With CORE Metadata, citation and similar papers at core.ac.uk Provided by Springer - Publisher Connector Mutoh et al. SpringerPlus (2015) 4:385 DOI 10.1186/s40064-015-1176-3 CASE STUDY Open Access Osteomyelitis due to Clostridium innocuum in a patient with acute lymphoblastic leukemia: case report and literature review Yoshikazu Mutoh1,2*, Risen Hirai1, Akira Tanimura1, Takashi Matono2, Eriko Morino3, Satoshi Kutsuna2, Maki Nagamatsu4, Norio Ohmagari2 and Shotaro Hagiwara1* Abstract Introduction: Clostridium innocuum is an anaerobic Gram-positive bacterium, unable to produce toxins and rarely causes infections. We report the first case of C. innocuum osteomyelitis and bacteremia in a patient with acute lymphoblastic leukemia (ALL). Findings were compared with previously reported cases of C. innocuum infections in immunocompromised patients, e.g., patients with acquired immune deficiency syndrome, leukemia, and organ transplantation. Case description: A 32-year-old Japanese male was admitted for persistent low-grade fever and purpura lasting for 1 month. Complete blood counts and cytogenetic analysis identified Ph1-positive ALL, which was successfully treated using chemotherapy. However, the patient developed high fever and lumbar pain during complete remission. Fluoro- deoxyglucose-positron emission tomography and computed tomography demonstrated osteomyelitis. C. innocuum was identified as the causative agent and the patient was successfully treated using antibiotic therapy. Discussion and evaluation: We performed a literature review revealing a number of common aspects to the clinical presentation of C. innocuum infection and an association with various comorbidities. Further, we highlight the most efficient diagnostic and treatment strategies for C. innocuum osteomyelitis. Conclusions: Clostridium innocuum can be a causative pathogen of osteomyelitis and bacteremia in immunocom- promised patients. Keywords: Clostridium innocuum, Acute lymphoblastic leukemia, Osteomyelitis, Direct 16S-rRNA sequencing, Neutropenic enterocolitis Introduction such as those with acquired immune deficiency syn- Clostridial species are common anaerobic, spore-form- drome (AIDS), leukemia, and organ transplantation. ing, Gram-positive bacteria found in the normal flora of Because C. innocuum has intrinsic resistance to sev- the oropharynx and gastrointestinal tract. Among them, eral common antibiotics, including vancomycin, it may Clostridium innocuum is an unusual cause of infections cause intractable infections (Alexander et al. 1995; in humans. A few reports have described bacteremia David et al. 2004). We report the first case of pelvic due to C. innocuum in immunocompromised patients, osteomyelitis and sepsis due to C. innocuum infection in a patient with acute lymphocytic leukemia (ALL). We performed a literature review of previous reports *Correspondence: [email protected]; [email protected] to determine the most appropriate diagnostic strategies 1 Division of Hematology, Department of Internal Medicine, National Center for Global Health and Medicine, 1‑21‑1 Toyama, Shinjuku, and treatment regimens in cases of C. innocuum infec- Tokyo 162‑8655, Japan tion in patients with distinct comorbidities. 2 Disease Control and Prevention Center, National Center for Global Health and Medicine, 1‑21‑1 Toyama, Shinjuku, Tokyo 162‑8655, Japan Full list of author information is available at the end of the article © 2015 Mutoh et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Mutoh et al. SpringerPlus (2015) 4:385 Page 2 of 4 Review in the blood culture; however, the bacteria could not be Case description identified. For this reason, we tested the blood culture for A 32-year-old Japanese male with no previous medical direct 16S ribosomal RNA (16S rRNA) sequencing and history was admitted to our hospital for a persistent low- identified C. innocuum 2 days later. The presence of this grade fever and purpura lasting for 1 month. A complete pathogen was also confirmed by bone marrow culture blood count (CBC) revealed marked anemia, thrombo- from iliac crest. As a result of these findings, the patient cytopenia, and hyperleukocytosis (136,130/µL; blasts was treated with piperacillin/tazobactam, metronidazole, 97%, neutrophils 0%, lymphocytes 2%, and eosinophils and clindamycin. In this case, the causative pathogen was 1%). Bone marrow aspiration from iliac crest were hyper- sensitive to ampicillin, piperacillin/tazobactam, mero- cellular with 97.6% lymphoblasts. Cytogenetic analysis penem, clindamycin, and metronidazole. Intermediate revealed that blasts were positive for the Philadelphia sensitivity to penicillin G and cefmetazole was observed. chromosome (Ph1) with minor BCR/ABL mRNA tran- Further, the isolated strain was resistant to vancomycin scripts. Therefore, the patient was diagnosed with Ph1- with a minimum inhibitory concentration (MIC) of 8 μg/ positive ALL. mL. Combination chemotherapy with dasatinib was imme- Fever gradually resolved over the next 3 weeks, but diately initiated as remission induction. On treatment the lumbar pain persisted. CT imaging identified a small day 27, CBCs had normalized and bone marrow aspira- abscess in the iliacus muscle. Therefore, CT-guided tion from iliac crest analysis confirmed complete remis- drainage was performed. No pathogens were detected sion. On treatment day 39, consolidation chemotherapy in cultures of the abscess fluid or blood. The previ- with daunorubicin, cyclophosphamide, vincristine, pred- ously administered antibiotic regimen was consequently nisolone, methotrexate, and dasatinib was initiated. On deemed effective. After another 8 weeks of antibiotic treatment day 51, the patient became pyrexial (39.2°C) therapy, the lumbar pain subsided and treatment was ter- and reported severe lower back pain. The pain rapidly minated. On treatment day 104, the patient was asympto- worsened and radiated to the right axilla. WBC count matic and chemotherapy was reinitiated. was 430/mm3, with 8% segmented neutrophils, 2% bands, 80% lymphocytes, and 10% monocytes. We immediately Discussion and evaluation collected blood culture and started empiric antibiotic We identified previously published cases of C. innocuum therapy with meropenem, vancomycin, and liposomal infection by conducting a PubMed search of the literature amphotericin B. CT imaging revealed no apparent abnor- using the following keywords: Clostridium innocuum; mal findings; however, fluorodeoxyglucose (18F)- ALL; osteomyelitis; and anaerobic bacteria. PubMed que- positron emission tomography (FDG-PET) revealed ries also included infections that developed in immuno- increased uptake of FDG in the iliac bones and right side compromised patients during chemotherapy. of the sacrum. These findings suggested osteomyelitis The first human case of C. innocuum infection was of the iliac bone and sacrum and Gram-positive bacte- reported in the 1960s (Smith and King 1962). The term ria were detected by needle aspiration biopsy of the iliac “innocuum” is derived from “innocuous” (i.e., meaning bone (Fig. 1). Gram-positive bacterium was also found innocent) as the organism lacks the ability to produce Fig. 1 Diagnostic approach for a 32-year-old male with Clostridium innocuum osteomyelitis. a (18F)-Fluorodeoxyglucose positron emission tomog- raphy (FDG-PET) revealed marked uptake of FDG in the sacroiliac joint and iliac bone. b Bone marrow biopsy from iliac crest confirmed C. innocuum infection (Grambiopsy conf1000). Mutoh et al. SpringerPlus (2015) 4:385 Page 3 of 4 toxins. A PubMed search of the literature identified for the treatment of osteomyelitis (Howard et al. 1994; 16 previously reported cases of C. innocuum infection Spellberg and Lipsky 2012). (Smith and King 1962; Castiglioni et al. 2003; Crum- Comprehensive blood and bone marrow aspiration Cianflone 2009; Hung et al. 2014; Bodey et al. 1991; Cut- analysis revealed Ph1-positive ALL in our patient war- rona et al.1995). Details of these cases are summarized ranting immediate initiation of systemic chemotherapy. in Additional file 1: Table S1. Median age of patients The patient developed high fever and back pain, although was 38.0 years, and 66.7% were male. All but one patient complete remission of ALL was achieved. Therefore, we had a comorbid disorder, namely acute leukemia, AIDS, suspected that these symptoms were due to an infection chronic hepatitis, genitourinary malignancy, gastro- rather than related to a lymphoproliferative disease. intestinal malignancy, or organ transplantation (Crum- Systemic chemotherapy has been reported to induce Cianflone 2009; Hung et al. 2014; Bodey et al. 1991; neutropenic enterocolitis (NEC), a common complica- Cutrona et al. 1995; Shah et al. 2009). The most common tion in neutropenic cancer patients (Nesher and Rolston clinical symptom was fever of unknown origin followed 2013). Symptoms generally develop after the third week by the gastrointestinal tract disorder, such as diarrhea of chemotherapy and include neutropenic fever and or constipation, and/or respiratory disorder. Almost all abdominal pain (mainly in the right lower abdomen). patients developed bacteremia. Most commonly used The diagnostic criteria
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