Meningitis in a patient with neutropenia due to Rothia mucilaginosa: a case report
Rothia mucilaginosa is a Gram-positive bacterium occurring as a commensal in the oral cavity and upper respiratory tract. Although rarely pathogenic in an immunocompetent host, it can cause severe opportunistic infections in immunocompromised individuals.
A 67-year-old white woman had a routine blood analysis before undergoing knee surgery. The results showed leukopenia for which bone marrow examination was performed, showing an underlying acute myeloid leukemia. During the neutropenic phase after a second induction with cytarabine/idarubicin, she developed 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 to refractory intracranial hypertension and transtentorial herniation.
Meningitis due to Rothia mucilaginosa is a rare but potentially lethal infection in patients with neutropenia, and evidence-based guidelines for the treatment of this disease are lacking. We suggest an empirical therapy with amoxicillin/rifampicin until adjustments can be made based on an antibiogram. Intrathecal or intraventricular administration of antibiotics can be considered if neurosurgical access is already obtained because of disease-associated complications.
KeywordsRothia mucilaginosa Meningitis Acute myeloid leukemia Neutropenia
Acute myeloid leukemia
Minimum inhibitory concentration
Opportunistic infections are a major cause of morbidity and mortality in patients going through a neutropenic phase following chemotherapy or bone marrow transplantation as a treatment for acute myeloid leukemia (AML) . Rothia mucilaginosa is a Gram-positive bacterium that occurs as a commensal in the oral cavity and upper respiratory tract. However, in the context of neutropenia, this bacterium causes invasive infections such as bacteremia, endocarditis, peritonitis, pneumonia, foreign body infections, and meningitis . However, because of its rarity as an invasive pathogen, there is little literature on Rothia mucilaginosa. The literature on meningitis caused by this bacterium is limited to a few case descriptions almost exclusively within a pediatric population [1, 2, 3]. Here we present an adult patient with neutropenia who developed meningitis with Rothia mucilaginosa, showing insufficient response to therapy and further clinical deterioration after admission to our intensive care unit. We hope other clinicians can use this article as a guideline when they are confronted with Rothia mucilaginosa meningitis.
Subtype of leukemia
75% blasts, no Auer rods
Flow cytometry (leukemia-associated immunophenotype)
AML, favorable risk 
Analysis of the cerebrospinal fluid at time of diagnosis
The fight against aggressive forms of leukemia such as AML, does not only consist of eradicating the malignant cells, but also requires effective treatment of potentially lethal complications of the disease and its antineoplastic therapy. These complications include mainly infectious episodes resulting from the destruction of the immune system . We presented a case of a 67-year-old patient who was diagnosed as having AML and died of an opportunistic infection despite obtaining a molecular remission after the second induction course with chemotherapy. More specifically, she developed meningitis with Rothia mucilaginosa, a condition of which little is known and only a few case reports are available and most of them in a pediatric population. We proposed a way to treat this condition because evidence-based guidelines are lacking.
Rothia mucilaginosa is a commensal Gram-positive bacterium in the oral cavity and upper respiratory tract. In an immunocompetent host it has low virulence, but it can behave as an opportunistic pathogen in the presence of favorable host factors . Chemotherapy in the treatment of AML not only induces long-term neutropenia, but also extensive mucositis and it requires a central catheter: all these facilitate the invasive character of a germ. In addition, repeated or prolonged exposure to prophylactic or therapeutic broad-spectrum antibiotics may lead to the selection of pathogenic germs . More specifically, a significant association was seen between Rothia bacteremia and the use of fluoroquinolones . In our patient, levofloxacin for intestinal decontamination was provided at the start of induction. Although blood cultures remained negative in this case, hematogenous dissemination is assumed.
Diagnosis of meningitis in patients with neutropenia can be delayed because of less pronounced symptomatology as a result of agranulocytosis. In addition, antimicrobial agents penetrate the blood–brain barrier less since there is little or no meningeal inflammation. Because meningitis due to Rothia mucilaginosa is rare and only a few cases in an adult population have been described, it was difficult to choose the most adequate therapy. Selection of the antibiotics could be based on the cultures obtained by lumbar puncture. Taking into account the penetration of the agents into the CSF and recommendations from previous case reports, a combination antibiotherapy with amoxicillin and rifampicin was given. Vancomycin had been the first choice in the majority of case reports , but a higher minimum inhibitory concentration (MIC) was reported by the laboratory compared to amoxicillin (1 μg/mL versus 0.064 μg/mL). In addition, the penetration of vancomycin in the CSF is thought to be low because of its hydrophilic nature and high molecular weight, although recent research could not confirm this . The question of whether there is additional benefit of intrathecally administered antibiotics is at present unanswered. Given the need for neurosurgical intervention to achieve this, this is, in general, discouraged and only considered when disease complications necessitate a ventricular drainage [1, 4, 5]. However, in our patient, despite the surgical intervention, no intraventricular antibiotics were administered since analysis of the perioperative CSF showed decreasing white blood cell counts as compared to the result at diagnosis, and because of the absence of bacteria on microscopic evaluation. Furthermore, the rapidly declining medical condition of our patient did not allow us to consider any additional intracerebral manipulation.
Rothia mucilaginosa meningitis is a rather rare complication with a high mortality risk in patients with neutropenia. The lack of therapeutic guidelines makes it difficult to maintain evidence-based medicine. Empirical therapy with amoxicillin/rifampicin may be a reasonable initial choice until adjustments can be made based on the antibiogram. Intrathecal or intraventricular administration of antibiotics may be considered if neurosurgical access is already obtained because of disease-associated complications.
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MC wrote the paper and PDr and PDe revised the final manuscript. All authors read, corrected, and approved the final manuscript.
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