CASE REPORT Open Access

Meningitis in a patient with neutropeniadue to Rothia mucilaginosa: a case reportMaxim Clauwaert* , Patrick Druwé and Pieter Depuydt

Abstract

Background: Rothia mucilaginosa is a Gram-positive bacterium occurring as a commensal in the oral cavity andupper respiratory tract. Although rarely pathogenic in an immunocompetent host, it can cause severe opportunisticinfections in immunocompromised individuals.

Case presentation: A 67-year-old white woman had a routine blood analysis before undergoing knee surgery. Theresults showed leukopenia for which bone marrow examination was performed, showing an underlying acutemyeloid leukemia. During the neutropenic phase after a second induction with cytarabine/idarubicin, shedeveloped fever, headaches, and photophobia. Cultures of cerebrospinal fluid were positive for Rothia mucilaginosa.Despite full therapy with antibiotics, neurosurgical interventions, and intensive care support, our patient died due torefractory intracranial hypertension and transtentorial herniation.

Conclusions: Meningitis due to Rothia mucilaginosa is a rare but potentially lethal infection in patients withneutropenia, and evidence-based guidelines for the treatment of this disease are lacking. We suggest an empiricaltherapy with amoxicillin/rifampicin until adjustments can be made based on an antibiogram. Intrathecal orintraventricular administration of antibiotics can be considered if neurosurgical access is already obtained becauseof disease-associated complications.

Keywords: Rothia mucilaginosa, Meningitis, Acute myeloid leukemia, Neutropenia

BackgroundOpportunistic infections are a major cause of morbidityand mortality in patients going through a neutropenicphase following chemotherapy or bone marrow trans-plantation as a treatment for acute myeloid leukemia(AML) [1]. Rothia mucilaginosa is a Gram-positive bac-terium that occurs as a commensal in the oral cavity andupper respiratory tract. However, in the context of neu-tropenia, this bacterium causes invasive infections suchas bacteremia, endocarditis, peritonitis, pneumonia, for-eign body infections, and meningitis [2]. However, be-cause of its rarity as an invasive pathogen, there is littleliterature on Rothia mucilaginosa. The literature onmeningitis caused by this bacterium is limited to a fewcase descriptions almost exclusively within a pediatricpopulation [1–3]. Here we present an adult patient withneutropenia who developed meningitis with Rothiamucilaginosa, showing insufficient response to therapy

and further clinical deterioration after admission to ourintensive care unit. We hope other clinicians can usethis article as a guideline when they are confronted withRothia mucilaginosa meningitis.

Case presentationOur patient was a 67-year-old white woman with norelevant medical history. She was on no medication attime of admission. She did not smoke tobacco and con-sumed no alcohol. She was retired at time of admissionand worked as a librarian before. She was married andhad two children, both healthy. Her mother was88-years old and still alive; her father died at the age of94, cause not known. None of them had malignancies intheir past. At time of admission she felt perfectly nor-mal, had no B-symptoms, no bleedings, and no signs ofinfections. She was 152 cm in height and weighed 72 kg,with a body surface area of 1.7 m2. Her temperature was36.7 °C (98 °F), blood pressure 128/79 mmHg, and pulse73 beats per minute. No cardiac, respiratory, gastrointes-tinal, urological, dental, or neurological anomalies were

* Correspondence: maxim.clauwaert@ugent.beIntensive Care Unit, Universitair Ziekenhuis Gent, C. Heymanslaan 10, 9000Ghent, Belgium

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Clauwaert et al. Journal of Medical Case Reports (2019) 13:84 https://doi.org/10.1186/s13256-018-1947-x

Fig. 1 Peripheral blood count at time of diagnosis. ANC: absolute neutrophil count, MCH: mean corpuscular hemoglobin, MCHC: mean corpuscularhemoglobin concentration, MCV: mean corpuscular volume, WBC: white blood cells. Translations: absolute neutrofielen telling: absolute neutrophilcount, basofiele granulocyten: basophils, blasten: blasts, bloedplaatjes: platelets, commentaar plaatjes: comment platelets, differentiatie: differentiation,eenheid: unit, eosinofiele granulocyten: eosinophils, hematocriet: hematocrit, hemoglobine: hemoglobin, hypochromie: hypochromia, lymfocyten:lymphocytes, microscopische: microscopic, monocyten: monocytes, neutrofiele granulocyten: neutrophils, normoblasten: normoblasts, perifeer bloed:peripheral blood, polychromasie: polychromasia, refwaarde: reference interval, resultaat: result, reuze: giant, rode bloedcellen: red blood cells, stopgezet:stopped, uitzicht serum/plasma: sight serum/plasma, witte bloedcellen: white blood cells

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detected at physical examination. The reason for her ad-mission at our Hematology department was a routineblood analysis, performed before undergoing knee sur-gery, which showed leukopenia (Fig. 1). A bone marrowexamination was performed, revealing an underlyingAML (Table 1 and Fig. 2).Induction therapy with cytarabine (200 mg/m2, con-

tinuous infusion over 24 hours, on days 1–7) and idaru-bicin (12 mg/m2, once daily, infusion over 1 hour, ondays 1–3) was initiated, and given her neutropenic con-dition from the start, she stayed in protective isolation atthe Hematology department. She received levofloxacin500 mg once daily for intestinal decontamination and in-fectious prophylaxis. Since no complications occurred,the second induction was initiated with cytarabine(1000 mg/m2, twice daily, infusion over 3 hours, on days1–3) and idarubicin (12 mg/m2, once daily, infusion over1 hour, on days 3–5). After this therapy, she developed

general weakness and diarrhea. At day 35 after the firstinduction, she developed neutropenic fever for whichceftazidime (2000 mg intravenously every 8 hours, con-tinuous infusion over 8 hours) and Colimycin (colisti-methate sodium; 2 × 106 international unitsintravenously every 6 hours) were started, guided by thepresence of a resistant Pseudomonas aeruginosa strain inthe fecal cultures. Two days later she started vomitingand reported headaches and photophobia. Analysis ofher cerebrospinal fluid (CSF) was compatible with bac-terial meningitis (Table 2). She was transferred to our in-tensive care unit receiving empirical antibiotic therapywith ceftazidime, Colimycin (colistimethate sodium),amoxicillin (2000 mg intravenously every 4 hours), andvancomycin (loading dose 1400 mg intravenously over 2hours, maintenance dose 2500mg intravenously over 24hours); although the plasma concentration of this lastone only reached therapeutic levels after 2 days. Gram

Table 1 Subtype of leukemia

Cytomorphology 75% blasts, no Auer rods

Flow cytometry (leukemia-associated immunophenotype) CD15-/CD13-/CD34-/CD117+/CD33+/CD10-/HLADR-/CD45+

Molecular analysis NPM1+/FLT3-

Genetics Normal: 46,XXNo t(15,17)

Conclusion AML, favorable risk [9]

AML acute myeloid leukemia

Fig. 2 Microscopy of bone marrow aspirate. Because of peripheral blood admixture only peripheral blood cells can be seen. The colored cellsare myeloblasts

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staining on the CSF showed Gram-positive cocci, whichwere presumed to represent Staphylococci at first. How-ever, cultures identified Rothia mucilaginosa as the re-sponsible pathogen and after 2 days of empiricaltherapy, antibiotics were switched to amoxicillin (2000mg intravenously every 4 hours) and rifampicin (600 mgintravenously every 12 hours) bi-therapy based on anantibiogram (Fig. 3) and the (limited) available literature[1, 2, 4, 5]. Blood cultures remained negative. She wasstable for 1 week until she developed significant lethargyand anisocoria. Hydrocephalus was diagnosed with com-puted tomography (CT) imaging for which external ven-tricular drainage was provided. Because of anon-communicating hydrocephalus due to ventriculi-tis, a second drainage was performed. In spite of this,our patient developed bilateral mydriasis without

reactivity to light and increasing edema on brain CT,leading to the placement of two more external ventri-culostomies in the temporal horns (Fig. 4). Despitethese neurosurgical interventions and medical therapywith hypertonic salt and mannitol, intracranial pres-sure continued to rise, resulting in progressive brainedema and transtentorial herniation. In consultationwith her family, further therapy was discontinued andshe died on day 49 after the first induction chemo-therapy. An autopsy was considered, but, given theclear medical context, this would not have led toother conclusions (Additional file 1).

DiscussionThe fight against aggressive forms of leukemia such asAML, does not only consist of eradicating the malignantcells, but also requires effective treatment of potentiallylethal complications of the disease and its antineoplastictherapy. These complications include mainly infectiousepisodes resulting from the destruction of the immunesystem [6]. We presented a case of a 67-year-old patientwho was diagnosed as having AML and died of an op-portunistic infection despite obtaining a molecular re-mission after the second induction course withchemotherapy. More specifically, she developed

Table 2 Analysis of the cerebrospinal fluid at time of diagnosis

Result Reference interval

Glucose (mg/dL) 15.7 49–80

Protein (mg/dL) 77.4 15–50

Lactate (mg/dL) 92.2 10–22

Leukocytes (/μL) 132 < 10

Erythrocytes (/μL) 14.7 0

Fig. 3 Antibiogram of Rothia mucilaginosa at time of diagnosis. IV intravenous

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meningitis with Rothia mucilaginosa, a condition ofwhich little is known and only a few case reports areavailable and most of them in a pediatric population.We proposed a way to treat this condition becauseevidence-based guidelines are lacking.Rothia mucilaginosa is a commensal Gram-positive

bacterium in the oral cavity and upper respiratory tract. Inan immunocompetent host it has low virulence, but it canbehave as an opportunistic pathogen in the presence offavorable host factors [2]. Chemotherapy in the treatmentof AML not only induces long-term neutropenia, but alsoextensive mucositis and it requires a central catheter: allthese facilitate the invasive character of a germ. In addition,repeated or prolonged exposure to prophylactic or thera-peutic broad-spectrum antibiotics may lead to the selectionof pathogenic germs [1]. More specifically, a significantassociation was seen between Rothia bacteremia and theuse of fluoroquinolones [7]. In our patient, levofloxacin forintestinal decontamination was provided at the start ofinduction. Although blood cultures remained negative inthis case, hematogenous dissemination is assumed.Diagnosis of meningitis in patients with neutropenia can

be delayed because of less pronounced symptomatology asa result of agranulocytosis. In addition, antimicrobialagents penetrate the blood–brain barrier less since there islittle or no meningeal inflammation. Because meningitisdue to Rothia mucilaginosa is rare and only a few cases in

an adult population have been described, it was difficult tochoose the most adequate therapy. Selection of the antibi-otics could be based on the cultures obtained by lumbarpuncture. Taking into account the penetration of theagents into the CSF and recommendations from previouscase reports, a combination antibiotherapy with amoxicil-lin and rifampicin was given. Vancomycin had been thefirst choice in the majority of case reports [1], but a higherminimum inhibitory concentration (MIC) was reported bythe laboratory compared to amoxicillin (1 μg/mL versus0.064 μg/mL). In addition, the penetration of vancomycinin the CSF is thought to be low because of its hydrophilicnature and high molecular weight, although recent re-search could not confirm this [8]. The question of whetherthere is additional benefit of intrathecally administered an-tibiotics is at present unanswered. Given the need forneurosurgical intervention to achieve this, this is, in gen-eral, discouraged and only considered when disease com-plications necessitate a ventricular drainage [1, 4, 5].However, in our patient, despite the surgical intervention,no intraventricular antibiotics were administered sinceanalysis of the perioperative CSF showed decreasing whiteblood cell counts as compared to the result at diagnosis,and because of the absence of bacteria on microscopicevaluation. Furthermore, the rapidly declining medicalcondition of our patient did not allow us to consider anyadditional intracerebral manipulation.

Fig. 4 a Brain computed tomography at time of diagnosis, without particular complications. b Supratentorial hydrocephalus with loss of gyri. cPlacement of ventriculostomies (bilateral, cannot be seen on the image) with reduction of the volume of the ventricular system. dVentriculostomies in situ, although further development of edema and cerebellar herniation

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ConclusionsRothia mucilaginosa meningitis is a rather rare compli-cation with a high mortality risk in patients with neutro-penia. The lack of therapeutic guidelines makes itdifficult to maintain evidence-based medicine. Empiricaltherapy with amoxicillin/rifampicin may be a reasonableinitial choice until adjustments can be made based onthe antibiogram. Intrathecal or intraventricular adminis-tration of antibiotics may be considered if neurosurgicalaccess is already obtained because of disease-associatedcomplications.

Additional file

Additional file 1: Timeline. (DOCX 57 kb)

AbbreviationsAML: Acute myeloid leukemia; CSF: Cerebrospinal fluid; CT: Computedtomography; MIC: Minimum inhibitory concentration

AcknowledgementsNot applicable.

FundingNone.

Availability of data and materialsData sharing not applicable to this article as no datasets were generated oranalyzed during the current study.

Authors’ contributionsMC wrote the paper and PDr and PDe revised the final manuscript. Allauthors read, corrected, and approved the final manuscript.

Ethics approval and consent to participateNot applicable.

Consent for publicationWritten informed consent was obtained from the patient’s next of kinfor publication of this case report and any accompanying images. Acopy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interestsThe authors declare that they have no competing interests.

Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.

Received: 4 August 2018 Accepted: 10 December 2018

References1. Lee AB, Harker-Murray P, Ferrieri P, Schleiss MR, Tolar J. Bacterial

Meningitis From Rothia mucilaginosa in Patients With Malignancy orUndergoing Hematopoietic Stem Cell Transplantation. Pediatr BloodCancer. 2008;50:673–6.

2. Ramanana P, Barretob JN, Osmona DR, Tosha PK. Rothia Bacteremia: a 10-Year Experience at Mayo Clinic, Rochester, Minnesota. J Clin Microbiol. 2014;52(9):3184–9.

3. Chavan RS, Pannaraj PS, Luna RA, Szabo S, Adesina A, Versalovic J, etal. Significant Morbidity and Mortality Attributable to RothiaMucilaginosa Infections in Children with Hematological Malignancies

or Following Hematopoietic Stem Cell Transplantation. PediatrHematol Oncol. 2013;30(5):445–54.

4. Abraham J, Bilgrami S, Dorsky D. Stomatococcus mucilaginosusmeningitis in a patient with multiple myeloma following autologousstem cell transplantation. Bone Marrow Transplant. 1997;19:639–41.

5. Goldman M, Chaudhary UB, Greist A, Fausel CA. Central nervous systeminfections due to Stomatococcus mucilaginosus in immunocompromisedhosts. Clin Infect Dis. 1998;27(5):1241–6.

6. Blijlevens NMA, Rijdners BJ. Behandeling van infecties bij deimmuungecompromitteerde patient. In: Löwenberg B, OssenkoppeleGJ, Blijlevens NMA, Leebeek FWG, Zweegman S, editors. LeerboekHematologie. Utrecht: De Tijdstroom; 2015. p. 687–708.

7. Abidi MZ, Ledeboer N, Banerjee A, Hari P. Morbidity and mortalityattributable to Rothia bacteremia in neutropenic and nonneutropenicpatients. Diagn Microbiol Infect Dis. 2016;85:116–20.

8. Beach JE, Perrott J, Turgeon RD, Ensom MHH. Penetration of Vancomycininto the Cerebrospinal Fluid: A Systematic Review. Clin Pharmacokinet. 2017;56(12):1479–90.

9. Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, et al.Diagnosis and management of AML in adults: 2017 ELN recommendationsfrom an international expert panel. Blood. 2017;129:424–47.

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