ROTHIA MUCILAGINOSA MENINGITIS AFTER SINUS SURGERY: a CASE REPORT and LITER- ATURE REVIEW Introduction Rothia Mucilaginosa, Whic

Acta Medica Mediterranea, 2019, 35: 1245

ROTHIA MUCILAGINOSA MENINGITIS AFTER SINUS SURGERY: A CASE REPORT AND LITER- ATURE REVIEW

Bahar Akgün Karapınar1, Cömert Şen2, Bora Başaran2, Derya Aydın3 1Department of Medical Microbiology, İstanbul Faculty of Medicine, İstanbul University, İstanbul, Turkey - 2Department of Otorhinolaryngology, İstanbul Faculty of Medicine, İstanbul University, İstanbul, Turkey - 3Department of Medical Microbiology, Faculty of Medicine, Biruni University, İstanbul, Turkey

ABSTRACT

Introduction: Rothia mucilaginosa, a member of the family Micrococcaceae, which is a normal flora member of the upper respiratory tract. Infections are very rare, but often causes opportunistic infections in immunosuppressed patients. We report the first case of Rothia mucilaginosa meningitis due to sinus surgery in a healty adult in Turkey. A literature research was done for the meningitis caused by Rothia mucilaginosa until recently. Materials and methods: Pubmed and Google Scholar databases were investigated between January 1990 and March 2018 using the keywords Stomatococcus mucilaginosus, Rothia mucilaginosa and meningitis, respectively. Results: A total of 25 patients, including this report, were reached. The mean age was 18 years (range: 28th gestational week-46 years) and 34,7% female, 65,2% were male. The underlying diseases were acute myeloid leukemia (n:9), acute lymphoblastic leukemia (n:8), chronic myeloid leukemia (n:2), non-Hodgkin lymphoma (n:1), multiple myeloma (n:1) and neuroectodermal cancer (n:1). No neutropenia was detected in the three patients. Totally 13 patients were revovered, 11 patients died and the outcome of one patient was not reported. Conclusion: Rothia mucilaginosa infections, which are mostly caused by underlying factors, are rarely seen in the literature. This report has been presented to attract attention especially to this bacteria which can easily be overlooked in conventional identifi - cation.

Keywords: Rothia mucilaginosa, Stomatococcus mucilaginosa, meningitis, sinus surgery, antibiotic susceptibility.

DOI: 10.19193/0393-6384_2019_3_190

Received November 30, 2018; Accepted February 20, 2019

Introduction non-hemolytic. R.mucilaginosa is differentiated from Staphylococci and Micrococci with the presence of Rothia mucilaginosa, which is a member of the capsule and no growth in a 5% NaCl containing me- Micrococcaceae family that has been previously re- dium(4,5), and generally leads to opportunistic infec- ferred as Micrococcus mucilaginosus, Staphylococ- tions such as pneumonia in immunosuppressed pa- cus salivarius, and Stomatococcus mucilaginosus, is tients(6,7). Furthermore, it may cause infections such as a member of the normal upper respiratory system flo- bacteremia, endocarditis, meningitis, peritonitis etc. ra(1-3). It is a catalase positive (although some species although they are more frequently encountered in the are catalase negative), oxidase negative, fermentative presence of risk factors(5,8,9). This study presents a case and nonmotile microorganism in a Gram positive of meningitis in a healthy adult following endocopic coccus structure that presents in pairs or clusters (2). It sinus surgery caused by R.mucilaginosa, which has grows easily in a non-selective medium and its col- never before been reported as a cause of meningitis in onies are mucoid and sticky, white to a greyish and Turkey to the date. 1246 Bahar Akgün Karapınar, Cömert Şen et Al

The study makes a literature review of cases of the results were evaluated considering the Staphylo- meningitis caused by this same bacteria. coccus breakpoints, since no standard breakpoints were defined. According to this, penicillin (10 unit), Case Presentation erythromycin (15 µg), clindamycin (2 µg), gentamicin (10 µg), tetracycline (30 µg), ciprofloxacin (5 µg), A 45-year-old male patient with no known ad- levofloxacin (5 µg), norfloxacin (10 µg), rifampicin ditional disease, and who had previously been oper - (5 µg) and linezolid (30 µg) were evaluated using the ated on for the same reason 5 and 3 years ago, was disk diffusion method, and vancomycin and ceftriax- operated for nasal polyposis in December 2017. The one minimum inhibitor concentrations was evaluated patient, who had been administered routine preopera- using a gradient test (E TEST, bioMérieux, France). tive 1 g ampicillin-sulbactam IM once for prophylaxis with minimum inhibitor concentrations. The bacteria and who had no intraoperative complications, had a was found to be sensitive to penicillin, erythromycin, clear nasal discharge on postoperative day 1 that was linezolid, levofloxacin, tetracycline, rifampicin, van- considered to be cerebrospinal fluid (CSF) rhinor - comycin (1.5 mg/L) and ceftriaxone (0.50 mg/L), and rhea, as a complication of the operation. According- was intermediate to clindamycin, while being found ly, a paranasal sinus tomography was performed and to be resistant to gentamicin and norfloxacin. The a defect on the lateral lamella of the cribriform plate ceftriaxone treatment was continued, and the blood was observed on the anterior skull base. Intravenous culture was analyzed according to the BACTEC 9120 ceftriaxone 2 g daily was administered for proph- (Becton Dickinson, USA) system. ylaxis, converted to IV cefuroxime-axetil, 750 mg, twice daily after three days. An anterior skull base CSF rhinorrhea repair was performed after CSF rhinorrhea continued in spite of conservative therapy for one week. The patient complained of headache, nau- sea and vomiting three days after the CSF rhinorrhea repair. A cranial magnetic resonance imaging (MRI) was carried out with preliminary diagnoses of meningitis and intracranial hypotension. A lumbar puncture was performed and IV ceftriaxone was started at 2 g twice daily. The cranial MRI showed no pathology and the CSF cell count of the patient was 2.332 leukocytes/ mm3 and 240 lymphocytes/mm 3, which was inter - preted as meningitis. A Gram stain of the CSF sample revealed polymorphonuclear leukocytes, and no microorganisms were seen. The samples were cul- tured in sheep blood agar (Becton Dickinson, USA), chocolate agar, brain heart infusion broth and tryptic Fig. 1A: Gram positive cocci seen in Gram stain (x1000); soy broth (Oxoid, United Kingdom). The agars were Fig. 1B: Mucoid, greyish colonies on blood agar of Rothia mucilaginosa, which were grown at 35 °C for 48 hours. incubated in a medium at 35°C with 5% CO 2 for 72 hours. Growth was detected at the 48th hour of the cul- An alpha hemolytic streptococcus was isolated ture, and Gram staining was performed on the grayish in the culture of two simultaneously obtained blood sticky colonies and large Gram positive cocci in pairs samples, and so IV vancomycin 1 g twice daily was or clusters were observed (Figure 1A-B). added to the treatment. A viral meningitis panel was The catalase and oxidase test negative, L-Pyrro- applied to the CSF sample using the multiplex PCR lidonyl-β-naphthylamide (PYR) test and esculin hy- method, and the result was negative. Antibiotherapy drolysis positive bacteria was identified as Rothia was stopped after 14 days of treatment in the patient, mucilaginosa using Matrix Assisted Laser Desorption who showed clinical and laboratory improvement. The Ionization Time-of-Flight (MALDI-TOF) (VITEK patient was discharged without complications. MS, France) technology. The antibiotic susceptibility Using the Medline and Google scholar data- test was performed by recommendations of the Clini- bases, a search was carried out using the key words cal and Laboratory Standards Institute (CLSI) (10), and Stomatococcus mucilaginosus, Rothia mucilagino- Rothia mucilaginosa meningitis after sinus surgery: a case report and literature review 1247

Author Gen- Underlying Results of CSF Gram CSF cell count-WBCb CSF cell count- Year Age Bacteremia Treatmentd Outcome [Reference] der diseasea stain; culture (n/mm3) RBCc (n/mm3)

Gram (+) cocci in AK,CAZ,RIF, Weinblott 410 1990 Øe F AML clusters; Ø (-)f TOB,IPM,C, TCA,NAF, Ex (11,12,13) (%85 PMNL) S.mucilaginosa VA(IV)

Gram stain (-); Clausen 1992 10 M ALL S.mucilaginosa 0-1 0 (-) CAZ,TCA,TOB,RIF,VA(IV) (24) Ex

Gram (+) cocci in Souillet FOS,CRO,GN, 1992 11 M ALL clusters; Ø Ø S.mucilaginosa Ex (18) T,VA(IV,IT) S.mucilaginosa

McWhinney Gram (+) coccus; ATM,PEN,F, 1992 29 M AML Ø Ø (-) Ex (25) S.mucilaginosa C,VA(IV)

Langbaum Gram stain Ø; 360 AMP,GN, 1992 28 wg Ø No neutropenia 8.700 S.mucilaginosa Revovered (26 S.mucilaginosa (%52 PMNL) VA(IV)

Gram (+) cocci in Heinwick 60 1993 17 F AML clusters; 10.000 S.mucilaginosa CRO,VA(IV) Revovered (19) (%76 neutrophil) S.mucilaginosa

Chanock No cell, Gram (+) coccus; PEN,CAZ, 1993 2.5 F NHL 0 (-) (-) Ex (11,12,13) S.mucilaginosa AMF-B,VA(IV)

Ben Salah Ø; 1994 2 M NEC 27 0 S.mucilaginosa CAZ,AK,IPM, VA (IV,IT) Revovered (11,12) S.mucilaginosa

Al-Fiar Intra/extracellular S.mucilaginosa, 1995 (27) 14 M ALL Gram (+) coccus; Ø Ø CAZ,AK,CRO,RIF,VA(IV,IT) Ex S.mitis S.mucilaginosa

Guarmazi Gram (+) coccus; 1995 14 M AML Ø Ø S.mucilaginosa VA(IV) Revovered (28) S.mucilaginosa

Guarmazi Gram (+) coccus; S.mucilaginosa, 1995 46 M AML Ø Ø VA(IV) Revovered (28) S.mucilaginosa Staphylococcus

Granlund Ø; 1996 31 M CML Ø Ø S.mucilaginosa CIP,VA,CTX Ex (29) S.mucilaginosa

Park Gram (+) coccus; S.mucilaginosa, CRO,AMP, 1997 5 F ALL 1.130 10 Revovered (30) S.mucilaginosa S.mitis VA(IV)

Gram (+) cocci in Abraham 1997 48 M MM clusters; 1.318 28 (-) SXT,OX,PEN G, C,VA(IV) Revovered (31) S.mucilaginosa

Intracellular CAZ,CTX, Goldman 1998 60 F ALL Gram (+) coccus; 490-34.750 Ø S.mucilaginosa RIF,CLA, Revovered (11) S.mucilaginosa VA(IV,IT,IVT)

Gram (+) coccus Skogen 2001 2.5 M ALL (pairs&tetrats); 36-27.880 Ø S.mucilaginosa CTX,RIF,VA(IV) Ex (23) S.mucilaginosa

Gram (+) cocci in Rizvi 2008 2 m F (-) clusters; Ø Ø S.mucilaginosa CTX,AK,VA Revovered (20) S.mucilaginosa

Intra/extracellular Lee Gram (+) cocci in 2008 11 M AML 20-1.010 114-30.700 (-) AMP,CAZ,MEM, VA(IV,IT) Revovered (12) clusters; R.mucilaginosa

Intracellular Lee Gram (+) cocci in 2008 13 F AML 9-92 0-22.25 (-) RIF,MEM,CAZ,VA(IV,IVT) Ex (12) clusters; R.mucilaginosa

Gram (+) cocci in Faiad ALLh 198 CRO,RIF, 2011 21 M clusters; Ø Ø Revovered (9) (%95 PMNL) VA(IV,IT) R.mucilaginosa

Chavanı 2013 13 M AML Ø; No growthi Ø Ø R.mucilaginosa VA(IV),TCA,GN Ex (13)

Chavan Ø; R.mucilaginosa 2013 7 F ALL 70 0 R.mucilaginosa VA(IV),CTX,RIF Revovered (13)

Chavan 2013 21 M CML Ø; No growthj 0 0 (-) VA(IV),TCA,GN Ex (13)

Wang 2016 <18 Ø AML Ø Ø Ø (-) Ø Ø (32)

Akgün Kara- (-) PMNLk (+), microorgan- 2.332 PMNL, Alpha hemolytic CRO,CXM, 2018 45 M 0 Revovered pınar ism (-); R.mucilaginosa 240 lymphocyte streptococcus VA(IV) Table 1:Clinical characteristics of patients with Stomatococcus mucilaginosa/Rothia mucilaginosa meningitis. aAML: Acute myeloid leukemia, ALL: Acute lymphoblastic leukemia, NHL: NonHodgkin lymphoma, NEC: Neuroectodermal cancer, MM: Multiple myeloma, CML: Chronic myeloid leukemia; bWBC: White blood cell; c:RBC: Red blood cell; dAK: Amikacin, CAZ: Ceftazidime, RIF: Rifampicin, TOB: Tobramycin, IPM: Imipenem, C: Chloramphenicol, TCA: Ticarcillin-clavulanic acid, NAF: Nafcillin, VA: Vancomycin, FOS: Fosfomycin, CRO: Ceftriaxone, GN: Gentamicin, T: Thiamphenicol, ATM: Aztreonam, PEN: Peni- cillin, F: Flucloxacillin, AMP: Ampicillin, AMF-B: Amphotericin B, CIP: Ciprofloxacin, CTX: Cefotaxime, SXT: Trimethoprim-sul- famethoxazole, OX: Oxacillin, CLA: Clarithromycin, MEM: Meropenem, CXM: Cefuroxime-Axetil, IV: Intravenous, IT: Intrathecal, IVT: Intraventricular; eØ: Not specified;f (-): Negative; g28 week of gestation; hThe patient is, however, not neutropenic in the presence of this infection ; ıIsolated in CSF and postmortem brain tissue in a total of 7 and 2 patients, respectively. The study provides informa- tion only on patients with underlying malignancy. iNo isolation in CSF. Postmortem; Rothia mucilaginosa in meninx, stomach, lung and spleen; jNo growth in CSF. Postmortem; Rothia mucilaginosa in leptomeninx kPMNL: Polymorphonuclear leukocytes 1248 Bahar Akgün Karapınar, Cömert Şen et Al sa and meningitis between January 1990 and March In the present case, a meningitis infection with 2018, and a total of 18 references were found. In ad- the causative agent R.mucilaginosa, a member of the dition, the results of three studies were obtained au- normal flora was reported following endoscopic sinus thored by reference 11-13. The age and gender of the surgery performed for nasal polyposis with no under- patients, underlying disease, microbiological and bio- lying diseases. chemical laboratory results of the cerebrospinal fluid, Rothia mucilaginosa has been reported to be presence of accompanying bacteremia, the antibiotics generally sensitive to beta lactams especially, high used in the treatment and the results of the treatment dose ampicillin, cefotaxime, penicillin, imipenem were analyzed (Table 1). and rifampicin, cloramphenicol, although antibiotic sensitivity tests have not been standardized for R.mu- Discussion cilaginosa(7,12,22). Furthermore, as a result of difficul- ties in the preservation of CSF levels and decreased Rothia mucilaginosa is present in the normal flo- sensitivities, rifampicin and high dose ampicillin is ra of humans and may cause opportunistic infections. recommended instead of vancomycin as a first-line R.mucilaginosa, as a rare cause of infection, is detect- treatment, since it passes the blood brain barrier at a ed as an effective agent in patients under immunosup- higher level and has high in vitro activity, especial- pression, with neutropenia, hematologic malignancies ly in neutropenic patients with meningitis (12,22,23). The and solid organ cancers, and in the presence of under- species isolated in the present case was found to be lying factors such as diabetes mellitus, hypertension, sensitive to penicillin, rifampicin, vancomycin and chronic renal diseases and chronic lung disease in im- ceftriaxone, and so the patient was treated using IV munocompetent patients(4,7,14-16). ceftriaxone and IV vancomycin. Rothia mucilaginosa was isolated in Turkey in a To the best of our knowledge, this is the first case 44 year-old male patient with Still’s disease and pul- of meningitis in Turkey in whichRothia mucilaginosa monary hypertension, and in a 75 year-old female pa- was isolated as the causative agent in a healthy adult. tient with diabetes mellitus, chronic liver disease and The aim of this report is to draw attention to this bac- chronic renal disease, as the cause of bacteremia in teria, which is in a coccus form in pairs or clusters, 2013(4), in a 68 year-old male patient with lung can- forming sticky colonies and that could easily be over- cer undergoing chemotherapy and radiotherapy as the looked during conventional identification due to their cause of pneumonia in 2014 (6), and in a 75 year-old catalase variable structure. patient with chronic obstructive pulmonary disease as the cause of pneumonia and in another patient with neuroblastoma as the cause of bacteremia in 2016(8,17). Rothia mucilaginosa has been reported world- References wide as the causative agent in various infections. As a cause of meningitis, it has been reported predom- 1) Collins MD, Hutson RA, Baverud V, et al. Characteri - inantly under its former name, S.mucilaginosa, and zation of a Rothia-like organism from a mouse: descrip- tion of Rothia nasimurium sp. nov. and reclassification later as R.mucilaginosa in neutropenic patients, and of Stomatococcus mucilaginosus as Rothia mucilagino- in patients with hematologic malignancies, since the sa comb. nov. Int J Syst Evol Microbiol 2000; 50: 1247- 1990s.(18,19). Similar to the case reported here, menin- 51. gitis has been observed on rare occasions in healthy 2) Bergan T, Kocur M. Stomatococcus mucilaginosus gen. nov., sp.nov., ep. rev., a member of the family Micrococ- individuals with nor underlying diseases or neutro- caceae. Int J Syst Bacteriol 1982; 32: 374-7. (20) penia. Rizvi et al. detected S.mucilaginosa as the 3) Gordon DF. Reisolation of Staphylococcus salivarius causative agent of meningitis that developed in a from the human oral cavity. J Bacteriol 1967; 94: 1281- healthy 2-month-old baby and reported that oral flora 6. bacteria had passed to the CSF due to an underlying 4) Kayman T, Akalin T, Ugur H, et al. Two bacteremia cases associated with Rothia mucilaginosa. Clin Lab 2013; oral infection. Furthermore, bacteremia was report- 59: 1167-70. ed in an immuncompetent pediatric patient in 2017, 5) Ruoff KL. Miscellaneous catalase-negative, gram-pos- and the immune system was suggested to be evaluat- itive cocci: emerging opportunists. J Clin Microbiol ed in patients who were detected to have this agent, 2002; 40: 1129-33. 6) Sadıç B, Başaran S, Kuşkucu M, et al. Nosocomial although the test results (immunoglobulin levels and pneumonia caused by Rothia mucilaginosa in a lung lymphocyte subgroups) in the patient were found to cancer patient. Klimik Journal 2014; 27: 121-3. be within normal ranges(21). 7) Maraki S, Papadakis IS. Rothia mucilaginosa pneumo- Rothia mucilaginosa meningitis after sinus surgery: a case report and literature review 1249

nia: a literature review. Infect Dis (Lond) 2015; 47: 125- Stomatococcus mucilaginosus. Clin Microbiol Newsl 9. 1992; 14: 87-8. 8) Turhanoğlu NM, Koyuncu E, Tekay F, et al. Pneumonia 25) McWhinney PHM, Kibbler CC, Gillespie SH, et al. caused by Rothia mucilaginosa: case report. Flora 2016; Stomatococcus mucilaginosus: an emerging pathogen in 21: 186-90. neutropenic patients . Clin Infect Dis 1992; 14: 641-6. 9) Faiad G, Singh M, Narasimhan A, et al. Rothia muci - 26) Langbaum M, Eyal FG. Stomatococcus mucilaginosus laginosa life threatening infections in non-neutropenic septicemia and meningitis in a premature infant. Pediatr hosts. Open Journal of Internal Medicine 2011; 1: 68-71. Infect Dis J 1992; 11: 334-5. 10) CLSI. Performance standards for antimicrobial suscepti- 27) Al-Fiar F, Ellis M, Hussain Qadri SM, et al. Stomato - bility testing. 28th ed. CLSI supplement M100. Wayne, coccus mucilaginosus meningitis in a patient with acute PA: Clinical and Laboratory Standards Institute; 2018. lymphoblastic leukemia. Ann Saudi Med 1995; 15: 393- 11) Goldman M, Chaudhary UB, Greist A, et al. Central 5. nervous system infections due to Stomatococcus muci - 28) Guermazi A, Miaux Y, Laval-Jeantet M. Imaging of laginosus in immunocompromised hosts. Clin Infect Dis Choroid Plexus Infection by Stomatococcus. AJNR Am 1998; 27: 1241-6. J Neuroradiol 1995; 16: 1331-4. 12) Lee AB, Harker-Murray P, Ferrieri P, Schleiss MR, To- 29) Granlund M, Linderholm M, Nogren M, et al. Stomato- lar J. Bacterial meningitis from Rothia mucilaginosa in coccus mucilaginosus septicemia in leukemic patients. patients with malignancy or undergoing hematopoietic Clin Microbiol Infect 1996; 2: 179-85. stem cell transplantation. Pediatr Blood Cancer 2008; 30) Park MK, Khan J, Stock F, et al. Successful treatment 50: 673-6. of Stomatococcus mucilaginosus meningitis with intra - 13) Chavan RS, Pannaraj PS, Luna RA, et al. Significant venous vancomycin and intravenous ceftriaxone. Clin morbidity and mortality attributable to Rothia mucilag - Infect Dis 1996; 24: 278. inosa infections in children with hematological malig - 31) Abraham J, Bilgrami S, Dorsky D, et al. Stomatococcus nancies or following hematopoietic stem cell transplan- mucilaginosus meningitis in a patient with multiple my- tation. Pediatr Hematol Oncol 2013; 30: 445-54. eloma following autologous stem cell transplantation. 14) Bruminhent J, Tokarczyk MJ, Jungkind D, DeSimone Bone Marrow Transplant 1997; 19: 639-41. JA Jr. Rothia mucilaginosa prosthetic device infections: 32) Wang JY, Brossard J, Cellot S, et al. Invasive Rothia a case of prosthetic valve endocarditis. J Clin Microbiol infections in children with acute myeloid leukemia: a 2013; 51: 1629-32. report from the Canadian infections in AML research 15) Ascher DP, Zbick C, White C, Fischer GW. Infections group. Pediatr Hematol Oncol 2016; 33: 277-81. due to Stomatococcus mucilaginosus: 10 cases and review. Rev Infect Dis 1991; 13: 1048-52. 16) Ramanan P, Barreto JN, Osmon DR, Tosh PK. Rothia bacteremia: a 10-Year experience at Mayo Clinic, Roch- ester, Minnesota. J Clin Microbiol 2014; 52: 3184-9. 17) Bayhan C, Öncel EK , Cengiz AB, et al. Bacteremia caused by Rothia mucilaginosa after pneumonia, in a patient with hematopoietic stem cell transplantation. Arch Argent Pediatr 2016; 114: 343-5. 18) Souillet G, Chomarat M, Barbé G, et al. Stomatococcus mucilaginosus meningitis in a child with leukemia. Clin Infect Dis 1992; 15: 1045. 19) Henwick S, Koehler M, Patrick CC. Complications of bacteremia due to Stomatococcus mucilaginosus in neutropenic children. Clin Infect Dis 1993; 17: 667-71. 20) Rizvi M, Fatima N, Shukla I, et al. Stomatococcus mucilaginosus meningitis in a healthy 2-month-old child. J Med Microbiol 2008; 57: 382-3. 21) Luque-Pérez S, Cobos-Carrascosa E, Guarino-Narváez J, et al. Rothia mucilaginosa bacteraemia in an immu - nocompetent paediatric patient: a new pathogen to take into account: a case report. Infez Med 2017; 25: 371-3. 22) Von Eiff C, Herrmann M, Peters G. Antimicrobial sus- ceptibilities of Stomatococcus mucilaginosus and of Mi- crococcus spp. Antimicrob Agents Chemother 1995; 39: ––––––––– 268-70. Corresponding Author: 23) Skogen PG, Kolmannskog S, Bergh K. Bactericidal Bahar Akgün Karapınar activity in cerebrospinal fluid by treating meningitis İstanbul Üniversitesi, İstanbul Tıp Fakültesi Temel Bilimler caused by Stomatococcus mucilaginosus with rifampic- Binası 1. Kat Tibbi Mikrobiyoloji Anabilim Dalı Çapa/Fatih/ in, cefotaxime and vancomycin in a neutropenic child. İstanbul Clin Microbiol Infect 2001; 7: 39-42. Email: [email protected] (Turkey) 24) Clausen CR. Central nervous system infection due to