Int J Clin Exp Med 2018;11(8):8672-8676 www.ijcem.com /ISSN:1940-5901/IJCEM0066200

Case Report Vertebral caused by Scedosporium apiospermum in an immunocompetent male: a case report

Dan Cao1,2*, Dajiang Li1,2*, Le Yu1,2, Hongxia Bi1,2, Rong Deng1,2, Lichun Wang1,2

1Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, P.R. China; 2Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, P.R. China. *Equal contribu- tors. Received September 25, 2017; Accepted April 25, 2018; Epub August 15, 2018; Published August 30, 2018

Abstract: We describe an extremely rare case in which Scedosporium apiospermum caused vertebral osteomy- elitis in an immunocompetent 47-year-old man after he nearly drowned in a pond. The patient was admitted to West China Hospital complaining of lower back pain. Computed tomography (CT) of the chest revealed a chest-wall abscess, and CT of the lumbar spine revealed destruction in the L-3, L-4, and L-5 vertebrae. S. apiospermum was cultured from a paravertabral necrotic secretion, and therapy with was initiated. The lower back pain disappeared after antifungal treatment, and the previously elevated white blood cell count, pro-calcitonin level, and erythrocyte sedimentation rate returned to normal. Moreover, CT showed improvement in the condition of the chest wall and lumbar spine. We report this case to advise physicians that lower back pain in near- victims should raise suspicion of vertebral osteomyelitis due to the ubiquitous S. apiospermum.

Keywords: Vertebral osteomyelitis, Scedosporium apiospermum, near-drowning, antifungal therapy

Introduction Case description

Scedosporium apiospermum, is the asexual A motorcycle was submerged in a pond owing form of the filamentous fungus Pseudallesche- to a traffic accident. The driver, a 47-year-old ria boydii [1]. It is highly invasive and opportu- healthy man, was trapped head-down under nistic pathogen and can withstand high tem- the sewage. After being rescued, he was admit- peratures, high salinity, and hypoxia. It is found ted to the Affiliated Hospital of Southwest Me- most commonly in soil, sewage, and stagnant dical University (first hospital), at which time he water [2]. In recent years, the incidence of S. was diagnosed with aspiration pneumonia and apiospermum infections has tended to increase respiratory failure. Antibiotics including moxi- in immunocompromised individuals, HIV/AIDS floxacin and biapenem were administered for patients, sufferers, transplant the pneumonia. Acinetobacter Baumanii was recipients, and patients who received immuno- detected in endotracheal sputum cultures. Cli- suppressants for long periods of time. S. apio- nical symptoms improved after administration spermum infection can also occur in immuno- of naproxen, vancomycin, and moxifloxacin to competent individuals in situations such as control the infection in the lungs. One week trauma and near-drowning [3-6]. S. apiosper- after treatment, the patient experienced right mum causes soft tissue infections, pneumonia, eye blindness and lower-back pain. Radiography arthritis (most often in knee ), and brain revealed destruction, disc bulging, and abscesses [7-10]. In near-drowning victims, endplate osteochondritis at the L-4 and L-5 ver- pneumonia and brain abscesses are its most tebral levels. He was diagnosed with vertebral common effects, whereas osteomyelitis is rare osteomyelitis, and extensive debridement, par- [11]. Here, we describe a rare case of verteb- tial corpectomy, and internal fixation were per- ral osteomyelitis in an immunocompetent man formed at the L-4 and L-5 levels. Surgical find- who contracted S. apiospermum infection after ings included the presence of a necrotic secre- nearly-drowning. tion. Although the Mucor was detected in cul- S. apiospermum-induced vertebral osteomyelitis

notransferase: 23 U/L, albumin: 33.2 g/L. CT of the lumbar spine showed destruction of the L-3, L-4, and L-5 vertebrae (Figures 1 and 6), and CT of the chest showed the lungs scatter- ing in the infected focus, inflammatory nodules, and an abscess in the chest-wall (Figure 2). An orbital CT scan of the anterior and posterior diameters of the right eye revealed that the density of the vitreous body was slightly above normal and that the lens was invisible. In etio- logical examinations, the following were nega- tive: blood and chest-wall pus cultures; Asper- Figure 1. CT of the lumbar spine demonstrating bone gillus galactomannan, fungal (1,3)-beta-D dex- destruction of the L5 vertebral body in April 21, 2016. tran tests, and interferon gamma release tests; acid-fast staining; and gram staining of the pa- ravertebral necrotic secretion. A biopsy of the chest-wall abscess was negative. Percutaneous needle aspiration biopsy of the L-4 and L-5 ver- tebrae revealed a large number of neutrophils, monocytes, lymphocytes, and plasma cells, but no septate hyphae.

After admission to West China Hospital, the patient’s temperature fluctuated from 38°C to 38.5°C between April 20th and April 25th. Levofloxacin and carbenin were administered to control the infection. S. apiospermum was present in cultures of the paravertebral necrot- ic secretion, and antifungal therapy (200 mg voriconazole intravenously for 12 hours) was initiated. The patient’s temperature and inflam- Figure 2. CT revealing the lungs scattering with nodu- matory indexes (white blood cell count, neutro- lar, hyper-dense shadows and local abscess of the phil ratio, pro-calcitonin level, and erythrocyte right anterior inferior wall in April 19, 2016. sedimentation rate) decreased gradually. His lower back pain subsided, and less pus was secreted in the sinuses. These findings indi- tures, the patient refused antifungal treatment cated that the infection had been controlled. and the fever recurred, as did infection of the During treatment, liver enzyme levels increased L-3 and L-4 vertebrae as shown via CT. For fur- to 102 U/L, but then returned to normal after ther care, the patient was admitted to West liver protective therapy. Eight weeks after re- China Hospital (Secondary Hospital), with a ceiving antifungal therapy, the patient was dis- description of “a traffic injury 3 months ago and charged home. He required oral administration lower back pain for 2 months”. Physical exami- of voriconazole (200 mg bid for 12 months) out- nation revealed right eye blindness and tender- side the hospital. In a telephone follow-up 6 ness on the right side of the chest without local months after discharge, the patient stated that swelling. Sinuses were 1×1 cm in size at the L-4 he no longer had a fever or lower back pain. CT and L-5 levels, with tiny amounts of pus, mild showed that his condition had improved. tenderness, and knocking pain. Heart and abdominal physical examinations showed no All procedures performed in these studies abnormal findings. involving human participants were in accor- dance with the ethical standards of the institu- Laboratory examination revealed the following tional and/or national research committee and white blood cell count: 6.11×109/L, neutrophil with the 1964 Declaration of Helsinki and its ratio: 73.6%, pro-calcitonin level: 1.52 ng/mL, later amendments or comparable ethical stan- erythrocyte sedimentation rate: 70 mm/h, ala- dards. Informed consent was obtained from the nine aminotransferase: 24 U/L, aspartate ami- patient included in the study.

8673 Int J Clin Exp Med 2018;11(8):8672-8676 S. apiospermum-induced vertebral osteomyelitis

Figure 3. Sabouraud dextrose agar showing growth Figure 5. S. apiospermum conidiophores bearing of S. apiospermum (multiple fungal colonies). one celled obovoid conidia produced singly under electron microscope.

Figure 4. Photomicrograph of S. apiospermum (wet mount, lactophenol aniline blue stain) demonstrat- Figure 6. ing multiple obovoid conidia with truncate bases, Reconstructed CT of the lumbar spine dem- arising from short conidiophores or directly from hy- onstrating bone destruction of the L-3, L-4 and L-5 phae. vertebral bodies.

Discussion are rare. S. apiospermum is a rare fungal patho- gen hat can invade multiple organs, sometimes Suppurative spondylitis, which includes verte- fatally. S. apiospermum infections typically oc- bral osteomyelitis and epidural abscesses, cur in immunocompromised patients and com- mainly occurs in young adults [12]. Because it mon infection sites include the skin, lungs, has no specific symptoms, its early-stage diag- joints, and nervous system. In our case, the pa- nosis is difficult, and its consequences include tient had nearly drowned and was predisposed spinal deformities, neurological damage, paral- to infection. Our case is of interest for two rea- ysis, and even death [13]. It is primarily caused sons: the patient was a young immunocompe- by a hematogenous infection, followed by trau- tent man, and the S. apiospermum infection ma and local spread of the infection [13]. The occurred in the lumbar vertebrae. Because he pathogens responsible for infection are usual- had no previous history of lumbar trauma or ly bacterial (Staphylococcus aureus [14] and chronic lumbar spine disease, this case sug- Escherichia coli [15]), whereas fungal sources gests that S. apiospermum can cause a dis-

8674 Int J Clin Exp Med 2018;11(8):8672-8676 S. apiospermum-induced vertebral osteomyelitis seminated infection in immunocompetent indi- spermum infection. In support, S. apiosper- viduals. mum was detected in cultures of the paraver- tebral necrotic secretion. Direct contact of the At present, diagnosis of an S. apiospermum in- eyes with S. apiospermum-infested sewage fection is difficult because its clinical features can cause ocular and corneal infections, which and histopathology resemble those of infect- can be painful and vision impairing. Indeed, the ions caused by other filamentous fungi such as patient in our study became blind in the right and Fusarium spp. Microorganism- eye after crashing his motorcycle into a sew- detecting cultures are a reliable diagnostic age-containing pond. We could not rule out tool. In the first hospital, Mucor was evident in infection as the cause of the blindness without patient-derived cultures. Unlike Aspergillus and performing fungal staining or culturing. In addi- Fusarium, Mucor resides in soil, feces, and wet tion, long-term use of broad-spectrum antibiot- environments, has thick hyphae and spores, ics and the resistivity drop of the patient after and its mycelia are white in the early stages, near-drowning were associated with the spread turning black after maturity. S. apiospermum of fungi. thrives in similar environments as Mucor, and its mycelia undergo similar changes (Figure 3). Voriconazole appears to be efficacious and It has thin-walled, septate, transparent hyphae, generally well-tolerated and is the agent of and one or more conidiophorebores at the ends choice for treatment of fungal vertebral osteo- of the mycelia (Figures 4 and 5). Amphotericin myelitis. In the study by Troke et al. [20], vori- B and its lipid derivatives are the most common conazole achieved a successful therapeutic first-line anti-Mucortherapies [16], while flucy- response in 57% of patients with scedosporio- tosine, itraconazole, and voriconazole have no sis (n = 107); skin/subcutaneous (91%) and bo- intrinsic activity, as demonstrated in multiple ne (79%) infections responded best. Side effe- trials [17]. Two case studies report successful cts of voriconazole include transient visual dis- treatment of Scedosporium infections with vori- turbances, skin rashes, and hepatotoxicity [21, conazole [18, 19]. In our study, the patient’s 22]. In our case, voriconazole effectively treat- symptoms were relieved and inflammation gra- ed acute vertebral osteomyelitis, but was ac- dually declined after almost 8 weeks of voricon- companied by hepatotoxicity. Hence, we should azole treatment. We believe that the misdiag- examine hepatic function regularly during anti- nosis by the first hospital (i.e., a Mucor infec- fungal therapy. tion rather than an S. apiospermum infection) reflects the experience of the specialist, and In summary, we believe that near-drowning vic- the technical experience of the staff. This tims with subacute or chronic lower back pain attests to the difficulty of detecting S. apios- should be rigorously examined for spondylodis- permum in patient samples and the need for citis resulting from fungal infection, especially a greater understanding of S. apiospermum S. apiospermum infections. Combined histo- infections by hospital and laboratory person- logical and microbiological analyses and anti- nel. Of note, Katragkou et al. [11] reported that fungal therapies can reduce the risk of mortal- the median time to diagnosis of a Scedospo- ity in cases in which microorganism-induced rium infection was 28 days, perhaps owing to infections are historically difficult to diagnose the low sensitivity of routine culture methods. and treat.

The mode of S. apiospermum invasion and sub- Disclosure of conflict of interest sequent spread to the vertebrae remain ambig- uous. The development of suppurative spon- None. dylitis presumably involves the aspiration of pathogens in polluted water and their dissemi- Address correspondence to: Lichun Wang, Center of nation from the lungs to the lumbar vertebrae Infectious Diseases, West China Hospital, Sichuan via the bloodstream. Although biopsy of the University, Division of Infectious Diseases, State right chest-wall abscess showed no fungal in- Key Laboratory of Biotherapy, Sichuan University, fection in our patient, voriconazole markedly 37 Guoxue Alley, Chengdu 610041, Sichuan, China. reduced the size of abscess. Therefore, we Tel: +86-189-806-01326; E-mail: mindywang0218@ believe that the abscess was due to S. apio- 163.com

8675 Int J Clin Exp Med 2018;11(8):8672-8676 S. apiospermum-induced vertebral osteomyelitis

References [13] Shiban E, Janssen I, Da CP, Rainer J, Stoffel M, Lehmberg J, Ringel F and Meyer B. Safety and [1] Gilgado F, Gené J, Cano J and Guarro J. Hetero- efficacy of polyetheretherketone (PEEK) cages thallism in Scedosporium apiospermum and in combination with posterior pedicel screw description of its teleomorph Pseudallescheria fixation in pyogenic spinal infection. Acta Neu- apiosperma sp. nov. Med Mycol 2010; 48: rochir (Wien) 2016; 158: 1851-7. 122-128. [14] Harada Y, Tokuda O and Matsunaga N. Mag- [2] Guarro J, Kantarcioglu AS, Horré R, Rodriguez- netic resonance imaging characteristics of tu- Tudela JL, Estrella MC, Berenguer J and Hoog berculous spondylitis vs. pyogenic spondylitis. GSD. Scedosporium apiospermum: changing Clin Imaging 2008; 32: 303-309. clinical spectrum of a therapy-refractory op- [15] Rutges JP, Kempen DH, Dijk MV and Oner FC. portunist. Medical Mycology 2006; 44: 295. Outcome of conservative and surgical treat- [3] Walsh TJ, Groll A, Hiemenz J, Fleming R, Roi- ment of pyogenic spondylodiscitis: a system- lides E and Anaissie E. Infections due to atic literature review. Eur Spine J 2015; 25: emerging and uncommon medically important 983-999. fungal pathogens. Clin Microbiol Infect 2004; [16] Lewis RE, Albert ND, Liao G, Hou J, Prince RA 10: 48-66. and Kontoyiannis DP. Comparative pharmaco- [4] He XH, Wu JY, Wu CJ, Halm-Lutterodt NV, Zhang dynamics of lipid complex and J, Li CS. Scedosporium apiospermum infection liposomal amphotericin B in a murine model of after near-drowning. Chin Med J (Engl) 2015; pulmonary mucormycosis. Antimicrob Agents 128: 412-421. Chemother 2010; 54: 1298-1304. [5] Nakamura Y, Yu U, Suzuki N, Nakajima Y, Mu- [17] Gómez-López A, Cuenca-Estrella M, Monzón A rata O, Sasaki N, Nitanai H, Nagashima H, Mi- and Rodriguez-Tudela JL. In vitro susceptibility yamoto S and Yaegashi J. Multiple Scedospo- of clinical isolates of Zygomycota to amphoteri- rium apiospermum abscesses in a woman survivor of a tsunami in northeastern Japan: a cin B, flucytosine, itraconazole and voricon- case report. J Med Case Rep 2011; 5: 526. azole. J Antimicrob Chemother 2001; 48: 919- [6] Nakadate T, Nakamura Y, Yamauchii K and 921. Endo S. Two cases of severe pneumonia after [18] Ananda-Rajah MR, Grigg A and Slavin MA. the 2011 Great East Japan Earthquake. West- Breakthrough disseminated Scedosporium ern Pac Surveill Response J 2012; 3: 67-70. prolificans infection in a patient with relapsed [7] Eldin C, Chiche L, Thomas G, Dicostanzo MP, leukaemia on prolonged voriconazole followed Durand JM, Harle JR and Ranque S. Scedospo- by prophylaxis. Mycopathologia rium apiospermum catheter-related soft-tis- 2008; 166: 83-86. sue infection: a case report and review of the [19] Walsh TJ, Lutsar I, Driscoll T, Dupont B, Roden literature. Med Mycol 2012; 50: 627-630. M, Ghahramani P, Hodges M, Groll AH and Per- [8] Chen TC, Ho MW, Chien WC and Lin HH. Dis- fect JR. Voriconazole in the treatment of asper- seminated Scedosporium apiospermum infec- gillosis, scedosporiosis and other invasive fun- tion in a near-drowning patient. J Formos Med gal infections in children. Pediatr Infect Dis J Assoc 2016; 115: 213-214. 2002; 21: 240-248. [9] Tirado-Miranda R, Solera-Santos J, Brasero JC, [20] Troke P, Aguirrebengoa K, Arteaga C, Ellis D, Haro-Estarriol M, Cascales-Sánchez P and Heath CH, Lutsar I, Rovira M, Nguyen Q, Slavin Igualada JB. Septic arthritis due to Scedospo- M and Chen SC; Global Scedosporium Study rium apiospermum: case report and review. J Group. Treatment of scedosporiosis with vori- Infect 2001; 43: 210-212. conazole: clinical experience with 107 pa- [10] Buzina W, Feierl G, Haas D, Reinthaler FF, Holl tients. Antimicrob Agents Chemother 2008; A, Kleinert R, Reichenpfader B, Roll P and 52: 1743-1750. Marth E. Lethal due to the fun- [21] Lazarus HM, Blumer JL, Yanovich S, Schlamm gus Scedosporium apiospermum (teleomorph H, Romero A. Safety and pharmacokinetics of ) after a near-drowning oral voriconazole in patients at risk of fungal incident: case report and review of the litera- infection: a dose escalation study. J Clin Phar- ture. Medical Mycology 2006; 44: 473-477. macol 2002; 42: 395-402. [11] Katragkou A, Dotis J, Kotsiou M, Tamiolaki M [22] Tan DK, Brayshaw MN, Tomaszewski DK, Troke and Roilides E. Scedosporium apiospermum DP and Wood DN. Investigation of the potential infection after near-drowning. Mycoses 2007; relationships between plasma voriconazole 50: 412-421. concentrations and visual adverse events or [12] Bornemann R, Müllerbroich JD, Deml M, Sand- liver function test abnormalities. J Clin Phar- er K, Wirtz DC and Pflugmacher R. [Diagnosis macol 2006; 46: 235-243. and treatment of spondylodiscitis/spondylitis in clinical practice]. Z Orthop Unfall 2015; 153: 540-545.

8676 Int J Clin Exp Med 2018;11(8):8672-8676