Pulmonary Actinomyces graevenitzii Infection Diagnosed by Bronchoscopy using Endobronchial Ultrasonography with a Guide Sheath
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1 doi: /internlmedicine Intern Med 57: , CASE REPORT Pulmonry Actinomyces grevenitzii Infection Dignosed y Bronchoscopy using Endoronchil Ultrsonogrphy with Guide Sheth Disuke Himeji, Schik Hr, Tkeshi Kwguchi nd Gen-ichi Tnk Astrct: A 75-yer-old mn visited our hospitl complining of low-grde fever, dry cough, nd chest norml shdow. Chest computed tomogrphy reveled nodule with cvity in the right upper loe. Endoronchil ultrsonogrphy (EBUS) of the lesion suggested tht the lesion ws enign. Actinomyces grevenitzii ws cultured from the specimen otined y ronchoscopy using endoronchil ultrsonogrphy with guide sheth technique nd ws identified y mtrix-ssisted lser desorption/ioniztion time-of-flight mss spectrometry nd 16S rrna sequencing. The ptient ws treted with intrvenous mpicillin; susequently, his condition improved. We elieve tht creful oservtion of EBUS findings my e useful for the differentil dignosis. Key words: pulmonry ctinomycosis, Actinomyces grevenitzii, endoronchil ultrsonogrphy with guide sheth (EBUS-GS), ronchoscopy (Intern Med 57: , 2018) () Introduction Pulmonry ctinomycosis is n indolent, slowly progressive infection cused y the neroic Actinomyces cteri (1). Becuse the clinicl nd rdiologicl findings of pulmonry ctinomycosis mimic mlignncy, it is frequently misdignosed, nd dequte tretment is delyed. In ddition, the identifiction of Actinomyces from clinicl smples is difficult. Therefore, pulmonry ctinomycosis is often dignosed s result of surgicl opertion. We herein report cse of pulmonry A. grevenitzii infection, which ws identified y the neroic culture of smples otined y ronchoscopy using endoronchil ultrsonogrphy with guide sheth (EBUS-GS). Cse Report A 75-yer-old mn visited regionl hospitl with 10- dy history of low-grde fever nd dry cough. He hd smoking history of 40 cigrettes per dy for 35 yers. His medicl history included pneumoni nd Guillin-Brré syndrome, nd he hd periodontitis. He underwent chest rdiogrphy, which reveled infiltrte in the right upper loe. He ws referred to Miyzki Prefecturl Miyzki Hospitl for n exmintion under suspicion of lung cncer. His vitl signs were s follows: temperture, 35.6 ; lood pressure, 117/73 mmhg; pulse, 69/min; respirtory rte, 20/min with n O2 sturtion of 94% on room ir. The results of hemogrm reveled norml leucocyte count of 6,590/μL, nd the renl nd liver prmeters were norml. The C-rective protein level ws 4.38 mg/dl. The tumor mrkers CEA, CYFRA, NSE, nd progrp were negtive (Tle). A sputum Grm stin ws negtive, while sputum nd lood cultures reveled no growth. Chest rdiogrph reveled nodule with cvity in the right upper loe, while chest computed tomogrphy (CT) demonstrted nodule with cvity (Fig. 1). We considered lung cncer, n cid-fst cillus infection, nd pulmonry ctinomycosis s the differentil dignoses sed on his smoking history nd the presence of periodontitis. For the dignosis, we performed ronchoscopy using Deprtment of Internl Medicine, Miyzki Prefecturl Miyzki Hospitl, Jpn Received: July 12, 2017; Accepted: Jnury 24, 2018; Advnce Puliction y J-STAGE: April 27, 2018 Correspondence to Dr. Disuke Himeji, himeji@pref-hp.miyzki.miyzki.jp 2547
2 Tle. Lortory Findings on Admission. Hemtology Biochemistry Tumor mrker WBC 6,590 /mm 3 TP 7.4 g/dl CEA 1.4 ng/dl Bnd 0.0 % Al 3.3 g/dl CYFRA 1.2 ng/dl Seg 65.0 % T-Bil 0.4 mg/dl progrp pg/ml Eo 2.0 % AST 23 U/L NSE ng/ml B 0.0 % ALT 11 U/L Mo 9.0 % LDH 187 U/L Bcteriology Ly 24.0 % ALP 258 U/L T-SPOT (-) H 13.2 g/dl γ-gtp 28 U/L Ht 39.7 % BUN 18.0 mg/dl Serology Plt /mm 3 Cr 0.77 mg/dl HBsAg (-) CRP 4.38 mg/dl HCVA (-) Cogultion Glu 105 mg/dl PT 11.2 s HA1c 6.3 %(NGSP) PT-INR 0.93 APTT 41.0 s Firinogen 850 mg/dl Figure 1. Chest X-ry nd computed tomogrphy (CT). : The rdiogrph shows nodule with cvity in the right upper lung. : The chest CT imge shows nodule with cvity in the right upper loe. EBUS-GS, s descried previously (2). After loclizing the lesion using rdil proe, we otined EBUS internl echo imges (Fig. 2). The internl echo imge of the lesion ws homogeneous, prompting designtion of type I under Kurimoto s clssifiction (2). After oserving the EBUS findings, we performed ronchil rushing (BB), trnsronchil iopsy (TBB), nd ronchil wshing. After rushing, the rush ws withdrwn, nd the mteril s cells were trnsferred directly onto clen glss slides. Susequently, we wshed the rush in sline (BB wshing). We then performed TBB five times. After BB nd the TBB, ronchil wshings ws otined y lvge with 20 ml of norml sline. The ronchil wshing ws mixed with the BB wshing, nd 5 ml of the mixture ws trnsferred immeditely into continer for neroic culture. Primry culturing of tht mixture ws performed with lood, chocolte, nd Brucell gr with hemin nd vitmin K1 (Brucell HK gr). Brucell HK gr ws incuted t 35 under neroic conditions. After 96 hours of incution, only molr-tooth-like colonies were oserved on Brucell HK gr. The orgnism ws coryneform Grmpositive rod tht did not produce ctlse. Mtrix-ssisted lser desorption/ioniztion time-of-flight mss spectrometry (MALDI-TOF MS) ws performed for identifiction, nd we identified the isolte s A. grevenitzii. For confirmtion, we performed moleculr identifiction y polymerse chin rection (PCR) mplifiction nd sequencing nlysis of the 16S rrna gene using DNA extrcted from the isolted orgnism. We performed the sequencing nlysis using Gen- Bnk BLAST serch. The sequence of the 16S rrna gene ws 99.0% identicl to tht of the type strin of A. grevenitzii. No other cteri or fungi were detected in this specimen, nd the results of the cid-fst stining nd PCR tests of the 2548
3 Figure 2. Fluoroscopy nd endoronchil ultrsonogrphy (EBUS) internl echo imge. : The proe is inserted into the lesion in the right upper loe. : EBUS demonstrtes hypoechoic homogeneous lesion. Figure 3. Chest X-ry nd computed tomogrphy fter tretment. : The rdiogrph shows remission of the nodule in the right upper lung. : The nodule with cvity in the right upper loe hs disppered. ptient s smple for Mycocterium tuerculosis, M. vium, nd M. intrcellulre were negtive. The histologicl findings of the TBB specimen nd the cytologicl findings of BB reveled only nonspecific inflmmtion, nd the chrcteristic histology of pulmonry ctinomycosis, such s grnulom or sulphur grnules, ws not oserved. In ddition, no microorgnisms were detected y Grm or PAS stins. These results indicted tht the pulmonry lesion of our ptient ws cused y A. grevenitzii. The ptient ws treted with 9,000 mg mpicillin/sulctm intrvenously for 1 week. After the identifiction of A. grevenitzii, he ws treted with 6,000 mg of mpicillin intrvenously for 1 week. Susequently, he ws treted with 1,500 mg of mpicillin orlly for 2 months. The clinicl sttus grdully improved. The lung nodule disppered in drmtic response to the ntiiotics (Fig. 3). We pln to continue tretment for the next 10 months. Discussion We encountered cse of pulmonry A. grevenitzii infection dignosed y ronchoscopy using EBUS-GS nd y moleculr identifiction of the smple. In ddition, we demonstrted tht pproprite neroic culture of ronchil rushing smples nd wshing fluid were useful for the identifiction of the pthogen of pulmonry ctinomycosis. Pulmonry ctinomycosis proly results from the spirtion of orophryngel or gstrointestinl secretions into the respirtory trct (3). Insufficient introrl hygiene nd ssocited dentl disese my increse the risk (4). Pulmonry ctinomycosis is rrely cused y distnt hemtogenous seeding (5). The ptient in our cse hd periodontitis, so his poor orl hygiene my hve een relted to the pthogenesis of pulmonry ctinomycosis infection. 2549
4 Six species of this genus re considered pthogenic in humns: A. isreli, A. neslundii, A. odontolyticus, A. viscosus, A. meyeri, nd A. gerencserie (6, 7). A. grevenitzii ws first isolted in 1997 from respirtory nd one specimens (8), while cses of pulmonry infection cused y A. grevenitzii hve een reported efore (9, 10). However, little is known out the clinicl fetures nd pthogenesis of this cterium. Becuse of its rrity, more studies on such cses re required to determine the pthogenesis of A. grevenitzii. The dignosis of pulmonry ctinomycosis cn e quite chllenging. In one series, the dignosis ws suspected upon hospitl dmission in 7% of ptients who lter turned out to hve the infection (11). Severl reports found tht 25-49% of cses of pulmonry ctinomycosis were initilly suspected of hving lung mlignncy t hospitl dmission (6, 12, 13). Even when the clinicl suspicion of pulmonry ctinomycosis is high, microiologicl confirmtion cn e difficult. Medicl intervention lone is sufficient for tretment; therefore, creful dignosis cn void unnecessry surgery. Bronchoscopy is vile dignostic method; however, the cteriologicl identifiction of Actinomyces species from the smples otined y ronchoscopy is reportedly very difficult. The smple should e hndled neroiclly with cution, s the culture of Actinomyces species cn e flsely negtive if the smple is exposed to ir for more thn 20 minutes (6). To dignose pulmonry ctinomycosis ppropritely, it is importnt to consider pulmonry ctinomycosis s differentil dignosis of lung tumor-relted shdow. In ddition, to identify cteri, we must ensure tht we hndle specimens ppropritely nd culture them under neroic conditions. In the present cse, we performed ronchoscopy using EBUS-GS. The utility of EBUS hs een reported for the dignosis of not only mlignnt lung diseses ut lso enign ones (14). Cses of ctinomycosis of the lung dignosed using EBUS hve lso een reported (15, 16). However, in those reports, EBUS ws used only to confirm the lesions. Notly, we used EBUS not only for the identifiction of the lesion ut lso to oserve its internl structure. Kurimoto et l. reported tht the clssifiction of ultrsonogrms suggests the pthology nd histology of the lesions (2). EBUS reveled tht this lesion hd homogeneous pttern without vessels or ronchioles, which is type I pttern under Kurimoto s clssifiction. Type I is sid to primrily reflect orgnized pneumoni or tuerculom. The pthologicl feture of pulmonry ctinomycosis is chronic inflmmtion comprising grnulomtous chnge (17); therefore, the EBUS findings of our ptient my reflect the pthologicl fetures, prticulrly the grnulomtous chnges of the lesion. More studies reporting EBUS findings in cses of ctinomycosis re necessry. In ddition, creful nlysis of the EBUS findings will encourge physicins to consider the possiility of ctinomycosis s the differentil dignosis, even if it hd not een considered efore ronchoscopy, therey leding physicins to perform pproprite smpling nd smple processing. To our knowledge, this is the first report descriing the usefulness of EBUS internl echo imging in dignosing pulmonry ctinomycosis cused y A. grevenitzii, which ws dignosed using moleculr nlysis of the smple otined y ronchoscopy. In conclusion, for the pproprite dignosis of pulmonry ctinomycosis, it is importnt tht the smples e prepred nd hndled while considering the possiility of pulmonry ctinomycosis. In ddition, the creful oservtion of the EBUS findings my e useful for the differentil dignosis. The uthors stte tht they hve no Conflict of Interest (COI). Acknowledgement We re grteful to Kzuhiro Skd, Issku Ymmoto, Akir St (Deprtment of Clinicl Lortory, Miyzki prefecturl Miyzki Hospitl), Nmi Tsuru, nd Shuji Yoshino (Miyzki Prefecturl Institute for Pulic Helth nd Environment) for their ssistnce in identifying A. grevenitzii. References 1. Russo TA. Actinomycosis nd Whipple s disese. In: Hrrison s Principles of Internl Medicine. 19th ed. Ksper DL, Huser SL, Jmeson JL, et l., Eds. McGrw-Hill, New York, 2015: Kurimoto N, Murym M, Yoshiok S, Nishisk T. Anlysis of the internl structure of peripherl pulmonry lesions using endoronchil ultrsonogrphy. CHEST 122: , Bennhoff DF. Actinomycosis: dignostic nd therpeutic considertions nd review of 32 cses. Lryngoscope 94: , Russo TA. Agents of ctinomycosis. In: Principles nd Prctice of Infectious Disese. 5th ed. Mndell GL, Ed. Churchill Livingstone, New York, 1995: Apothloz C, Regmey C. Disseminted infection due to Actinomyces myeri - cse report nd review. Clin Infect Dis 22: , Mez GF, Mcfrlne J. Pulmonry ctinomycosis. Eur Respir J 21: , Smego RA, Fogli G. Actinomycosis. Clin Infect Dis 26: , Rmos CP, Flsen E, Alvrez N, Akervll E, Sjoden B, Collins MD. Actinomyces grevenitzii sp. nov., isolted from humn clinicl specimens. Int J Syst Bcteriol 47: , Tietz A, Aldridge KE, Figuero JE. Disseminted coinfection with Actinomyces grevenitzii nd Mycocterium tuerculosis: cse report nd review of the literture. J Clin Microiol 43: , Glig S, Devux M, Gosset Woimnt M, Mompoint D, Perronne C, Dvido B. Actinomyces grvenitzii pulmonry scess mimicking tuerculosis in helthy young mn. Cn Respir J 21: 75-77, Weese WC, Smith IM. A study of 57 cses of ctinomycosis over 36-yer period. Arch Intern Med 135: , Kolditz M, Bickhrdt J, Mtthiessen W, Holotiuk O, Höffken G, Koschel D. Medicl mngement of pulmonry ctinomycosis: dt from 49 consecutive cses. J Antimicro Chemother 63: , Song JU, Prk HY, Jeon K, Um SW, Kwon OJ. Tretment of tho- 2550
5 rcic ctinomycosis: retrospective nlysis of 40 ptients. Ann Thorc Med 5: 80-85, Shingw N, Nkno K, Ashin H, et l. Endoronchil ultrsonogrphy with guide sheth in the dignosis of enign peripherl diseses. Ann Thorc Surg 93: , Fujit Y, Iikur M, Horio Y, Ohkusu K, Koyshi N. Pulmonry Actinomyces grevenitzii infection presenting s orgnizing pneumoni dignosed y PCR nlysis. J Med Microiol 61: , Arimur Y, Kitmur A, Tsuchid S, et l. A cse of pulmonry ctinomycosis dignosed y ronchoscopy using endoronchil ultrsonogrphy with guide sheth method. J Jpn Soc Respir Endosc 38: , 2016 (in Jpnese, Astrct in English). 17. Kim TS, Hn J, Koh WJ, et l. Thorcic ctinomycosis: CT fetures with histopthologic correltion. Am J Roentgenol 186: , The Internl Medicine is n Open Access rticle distriuted under the Cretive Commons Attriution-NonCommercil-NoDerivtives 4.0 Interntionl License. To view the detils of this license, plese visit ( y-nc-nd/4.0/) The Jpnese Society of Internl Medicine Intern Med 57: ,
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