A rare case of nocardial pachymeningitis and osteomyelitis of frontal bone in an immunocompetent young patient

A 36-year-old Caucasian man fell six meters in April 2010. At admission, the Glasgow coma scale was 14/15with stable vital signs. His past medical history was unremarkable. A head computer tomography (CT) scan documented multiple cranio-facial fractures, including the right orbital roof and the right zygomatic arch, the frontal sinus, the bilateral maxillary sinus, associated with thin right acute subdural hematoma and pneumocephalus. The patient underwent maxillofacial surgery to reduce multiple fractures, without complication. Ten days after, the patient experienced a progressive decrease of consciousness with body temperature of 39.5°C. CT scan showed a right frontal epidural and parenchymal collection with ring enhancement after contrast administration, suggestive for an infective process [Figure 1].{Figure 1} Cerebrospinal fluid (CSF) analysis revealed: cell count of 3000/mcL, protein 317 mg/dL, glucose 15 mg/dL, with cultures negative for bacteria and/or mycobacteria. Blood, urinary and bronchoalveolar lavage culture were negative. Intravenous antibiotic therapy with Meropenem (3 g/day) started immediately. The patient underwent bifrontal craniotomy, frontal sinus cranialization by pericranial flap and excision of the abscess. Intraoperatively, right frontal meningeal appeared covered by dense pus with negative culture for bacteria. Intravenous antibiotic therapies were increased with Teicoplanin (800 mg/day) for two weeks. Fever was resolved after 6 days and the 3-month follow-up CT scans confirmed the healing of the infective process. The patient was discharged on day 43, without neurological deficit. In January 2015, the patient was newly admitted to evaluate a right frontal dehiscence of the surgical scar and throbbing headache for 10 days. Physical and neurological examinations were normal. CT scan showed frontal meningeal enhancement and frontal bone flap reabsorption, suggestive for a new infection. Laboratory blood tests documented: white blood cell count of 8600/mm3 (neutrophils 55.7%, lymphocytes 36.6%, monocytes 0.45%), erythrocyte sedimentation rate of 10 mm/hr, and C-reactive protein level of 0.9 mg/dL. Human Immunodeficiency Virus (HIV) antibody was negative. Chest X-Ray was normal. The patient underwent surgery to remove the reabsorbed bone flap and a polyetheretherketone cranioplasty was positioned to repair the bone defect. Under the bone flap, yellowish and turbid pus was evident in the left frontal sinus, associated to a diffuse pachymeningitis [Figure 2]a and [Figure 2]b. Empirical intravenous antibiotics were started with Meropenem (6 g/day). Six days later, gram-positive bacilli were reported growing from the surgical specimens' culture but, only after 4 days, Nocardia asteroides was identified [Figure 2]c. The therapy was increased with Trimethoprim and Sulfameyhoxazole (TMP-SMX) (15 mg/kg TMP and 75 mg/kg SMX per day) and Meropenem (6 g/day) for three weeks, according with the Minimal inhibitory concentration (MIC) testing. The patient was discharged home and continued with oral TMP-SMX therapy for further 6 months. Six and twelve-month follow-up CT scan confirmed meningeal infection resolution [Figure 3].{Figure 2}{Figure 3} Nocardia species are filamentous, Gram-positive, partially acid-fast, branched bacteria ubiquitous in the environment, particularly in the soil and water.[1]Nocardia is considered an opportunistic microorganism because it occurs in immuno compromised patients, particularly those with cell-mediated immunity defects. There are more than 50 species of Nocardia, but Nocardia asteroides group is responsible for the majority of human nocardial infections.[1],[2],[3] Infection mainly occurs by direct inhalation or skin inoculation. The most common clinical manifestations are pulmonary, cutaneous and soft tissue (8.1%) and systemic nocardiosis (13.5%), including central nervous system (CNS) dissemination (5.4%).[2] Regarding CSN, nocardiosis may present with cerebral abscesses and meningitis, nevertheless meningitis is extremely rare. CNS infection may be secondary to hematogenous dissemination from a primary site, usually the lungs, or may exist on its own.[2] Osteomyelitis is an unusual manifestation.[1],[2],[3] Most cases are associated with infections of the vertebral bodies,[4],[5],[6] femur and tibia but other, less frequent locations include skull, ilium, fibula and metatarsal bones. A pub med search revealed two cases in literature,[1],[2],[3] but only one of them was similar: a 34-year-old man presented skull vault osteomyelitis and pachymeningitis, successfully treated with prolonged antibiotic therapy.[3] As in our case, bone infection and pachymeningitis had probably spread from overlying soft tissue infection, where there was a surgical scar. Diagnosis of Nocardia is extremely difficult because these species are slow-growing organism and are easily contaminated. An optimal treatment for cerebral nocardiosis has not been established. Clinical experience has shown that successful therapy requires appropriate surgical drainage in combination with antimicrobial drugs for a prolonged period. Synergy against Nocardia has been demonstrated between TMP-SMX, which is the first line therapy, due to good tolerance for the patient and better cerebrospinal fluid penetration.[3] Our patient received a combination regimen of TMP-SMX plus Meropenem, which was switched to oral TMP-SMX, for 6 months with a successful outcome. An interesting point in our case was the completely asymptomatic course of infection, despite cerebral nocardiosis has a high mortality and morbidity. Our case highlights how the diagnosis of nocardiosis remains extremely difficult in an immunocompetent patient. Prolonged and specific