Abstract
Flavobacterium lindanitolerans, a gram-negative, non-spore forming predominantly aerobic rod, is an unusual cause of disease in humans. It has previously been described as an opportunistic pathogen in immunocompromised hosts. Here we described a case of meningitis and bacteraemia, in an immunocompetent individual who had undergone recent neurosurgical intervention.
1. Case report
A 53-year-old immunocompetent male presented with fevers, headache, photophobia, and vomiting. He was diagnosed with a nasopharyngeal basaloid squamous cell carcinoma six months previously and underwent surgical resection.
Admission bloods revealed a white cell count (WCC) of 12.5 × 109/L and C-reactive protein (CRP) of 114 mg/L. He commenced empirical meningitis treatment with cefotaxime and aciclovir. Metronidazole was added due to the recent neurosurgical intervention.
Cerebrospinal fluid (CSF) revealed a white cell count (WCC) of 11/mm3 (100 % lymphocytes), elevated protein (0.6 g/L), and glucose of 3.8 mmol/L (serum glucose 8.3 mmol/L). Both CSF and admission blood cultures grew Flavobacterium lindanitolerans, identified with Matrix-assisted laser desorption/ionisation (MALDI-TOF) mass spectrometry; once this was known, aciclovir was stopped. The literature [1] suggests ceftriaxone resistance in Flavobacterium species; whilst co-trimoxazole has been demonstrated to be an effective treatment [2].Considering this, empirical intravenous co-trimoxazole 1.44g BD was started; pending final sensitivities of the isolate, available the following day.
Antibiotic susceptibility testing was unable to be interpreted owing to lack of available data (Table 1). Once antibiotic sesnsitivies had been performed, both oral rifampicin 600mg BD and moxifloxacin 400mg OD were added to the co-trimoxazole. This was based upon the in vitro results (rifampicin had a 24 mm zone of inhibition, similar to earlier data [2]), and previous success in treating F.lindanitolerans meningitis with quinolone therapy [3]. After four days, the patient clinically improved. Intravenous antibiotics were changed to oral preparations, and he was discharged to complete a 21-day course of all three antibiotics whilst undergoing radiotherapy.
Table 1.
Sensitivity profile of F.lindanitolerans (zone diameters and minimum inhibitory concentrations (MICs)).Both zone diameters and MICs are uninterpretable due to the lack of data available.
| Sample type | Antibiotic | Zone size (mm) | MIC (mg/L) | Sample type | Antibiotic | Zone size (mm) | MIC (mg/L) |
|---|---|---|---|---|---|---|---|
| Blood | Gentamicin | 6 | Cerebrospinal fluid (CSF) | Chloramphenicol | 21 | ||
| Ciprofloxacin | 19 | Clindamycin | 0.38 | ||||
| Meropenem | 11 | Moxifloxacin | 0.38 | ||||
| Piperacillin-tazobactam | 17 | Vancomycin | 32 | ||||
| Ceftazidime | 6 | Teicoplanin | 24 | ||||
| Ampicillin | 11 | Colistin | 64 | ||||
| Co-amoxiclav | 20 | Doxycycline | 1.5 | ||||
| Trimethoprim-sulfamethoxazole | 6 | Rifampicin | 25 | ||||
| Cefotaxime | 6 | ||||||
| Rifampicin | 24 | ||||||
| Ertapenem | 6 | ||||||
| Moxifloxacin | 0.19 | ||||||
| Doxycycline | 0.75 | ||||||
| Cefotaxime | 48 | ||||||
| Clindamycin | 0.25 |
Seven days later, the patient re-presented with fevers. Serum inflammatory markers had improved (WCC 3.0 × 109/L, CRP 37 mg/L). Liver enzymes were deranged (alanine transferase 120 U/L (previously 41 U/L), alkaline phosphatase 240 U/L (previously 86 U/L), gamma-glutamyltransferase 255 U/L (previously 80 U/L)), this was presumed to be secondary to rifampicin.
Repeat CSF had a WCC of 33/mm3 (95 % lymphocytes). Both blood cultures and CSF were negative for bacterial growth. A transthoracic echocardiogram excluded infective endocarditis.
Rifampicin was stopped. After 11 days, his fevers resolved. He was discharged to complete his radiotherapy course and continued the co-trimoxazole and moxifloxacin for the entirety of his radiotherapy.
On completion of radiotherapy and antibiotics, he underwent chemotherapy, making a good clinical recovery. A follow-up MRI head revealed no disease recurrence.
2. Discussion
F.lindanitolerans was first isolated in 2008 from a waste site in India contaminated with hexachlorocyclohexane. It belongs to the genus ‘Flavobacterium’ [4], part of the family Flavobacteriaceae.
Flavobacteria are aerobic, non-spore forming, gram-negative bacilli. Found in soil and freshwater habitats, most Flavobacteria are unlikely to be pathogenic to humans but may cause opportunistic infections [5,6].
A previous case described F.lindanitolerans-associated bacteraemia and meningoencephalitis [3], although the patient involved was immunosuppressed (splenectomised). Our patient was, in contrast, immunocompetent.
The source of this patient's infection remains unclear. Whilst there was no clear exposure to freshwater or soil in the patient's history, his previous occupation involved domestic waste water handling, which may account for some (although not fresh) water exposure. However, the timing of this patient's recent neurosurgery and subsequent CSF leak (one month prior to his presentation) make the nosocomial acquisition of infection more likely in this case.
Antibiotic resistance of F.lindanitolerans and few data describing optimal treatment duration makes selecting therapy difficult. Initial antibiotic duration followed guidelines for community-acquired gram-negative bacterial meningitis (21 days) [7]. However, the patient's readmission with fevers and susceptibility to disease recurrence led to an extended duration.
The patient's re-presentation with fevers and increasing CSF WCC remains unexplained; the absence of bacterial growth from repeat CSF suggests the infection was responding to treatment. A third CSF sample after completing antibiotics may have been useful to confirm response.
We believe this is the first UK case of F.lindanitolerans-associated meningitis and bacteraemia in an immunocompetent host. F.lindanitolerans is a potential human pathogen, more likely to cause meningitis in the context of neurosurgical intervention.
CRediT authorship contribution statement
Amelia Benjamin: Conceptualization, Writing – original draft. Robert Gray: Writing – review & editing. Madhuri Vidwans: Conceptualization, Writing – review & editing.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Handling Editor: Patricia Schlagenhauf
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