rifampin and Hearing-Loss

The short treatment regimen (STR) achieves a >80% cure in rifampicin-resistant tuberculosis (RR-TB) patients. However, ototoxicity induced by the injectable is a concern. This is the first study to evaluate the replacement of injectables by linezolid in patients with audiometry abnormalities at baseline or during the treatment.We conducted a retrospective cohort study of all RR-TB patients started on the STR between 2016 and June, 2019, in Niger. Patients underwent audiometry every 2 months in 2016 and every month since 2017.Of 195 patients, 16.9% (33 out of 195) received linezolid from the start (n=17), or switched from injectables to linezolid during treatment (n=16), based on audiometry abnormalities. In 2016, two patients developed severe ototoxicity despite switching to linezolid. Since 2017, no patient developed severe hearing loss or complete deafness. Severe haematological toxicity was observed in 18.1% (six out of 33) of patients on linezolid, none of which was life threatening. The use of linezolid was associated with severe but manageable adverse events (hazard ratio 8.9, 95% CI 2.5-31.5; p=0.001). A total of 90.9% (30 out of 33) of patients on a linezolid-containing STR were cured, and none experienced treatment failure. Three died, but not due to adverse events.Baseline and monthly audiometry monitoring and using linezolid after detection of hearing abnormalities appears effective to prevent severe ototoxicity, while keeping high treatment success and manageable adverse events.

Topics: Antitubercular Agents; Deafness; Hearing Loss; Humans; Linezolid; Ototoxicity; Retrospective Studies; Rifampin; Treatment Outcome; Tuberculosis, Multidrug-Resistant

Exacerbation of cerebrospinal fluid (CSF) inflammation in response to bacteriolysis by beta-lactam antibiotics contributes to brain damage and neurological sequelae in bacterial meningitis. Daptomycin, a nonlytic antibiotic acting on Gram-positive bacteria, lessens inflammation and brain injury compared to ceftriaxone. With a view to a clinical application for pediatric bacterial meningitis, we investigated the effect of combining daptomycin or rifampin with ceftriaxone in an infant rat pneumococcal meningitis model. Eleven-day-old Wistar rats with pneumococcal meningitis were randomized to treatment starting at 18 h after infection with (i) ceftriaxone (100 mg/kg of body weight, subcutaneously [s.c.], twice a day [b.i.d.]), (ii) daptomycin (10 mg/kg, s.c., daily) followed 15 min later by ceftriaxone, or (iii) rifampin (20 mg/kg, intraperitoneally [i.p.], b.i.d.) followed 15 min later by ceftriaxone. CSF was sampled at 6 and 22 h after the initiation of therapy and was assessed for concentrations of defined chemokines and cytokines. Brain damage was quantified by histomorphometry at 40 h after infection and hearing loss was assessed at 3 weeks after infection. Daptomycin plus ceftriaxone versus ceftriaxone significantly (P < 0.04) lowered CSF concentrations of monocyte chemoattractant protein 1 (MCP-1), MIP-1α, and interleukin 6 (IL-6) at 6 h and MIP-1α, IL-6, and IL-10 at 22 h after initiation of therapy, led to significantly (P < 0.01) less apoptosis, and significantly (P < 0.01) improved hearing capacity. While rifampin plus ceftriaxone versus ceftriaxone also led to lower CSF inflammation (P < 0.02 for IL-6 at 6 h), it had no significant effect on apoptosis and hearing capacity. Adjuvant daptomycin could therefore offer added benefits for the treatment of pediatric pneumococcal meningitis.

Topics: Animals; Anti-Bacterial Agents; Apoptosis; Brain Damage, Chronic; Ceftriaxone; Chemokines; Cytokines; Daptomycin; Drug Administration Schedule; Drug Therapy, Combination; Hearing Loss; Inflammation; Meningitis, Pneumococcal; Random Allocation; Rats; Rats, Wistar; Rifampin

A 39-year-old man with a 4-month history of transient pins and needles sensations occurring below the waist while walking and difficulty walking presented to our outpatient clinic. He had an approximate 1-year history of bilateral hearing loss, the etiology of which was unknown. His symptoms had been progressive, and there was no significant family history. He demonstrated a spastic gait and required assistance for walking. Deep tendon reflexes were hypertonic; a sensation deficit was defined as originating from the 12th thoracic vertebra. Babinski's sign was positive bilaterally. Sphincter abnormalities were seen in the patient's bladder and bowel functions. Cerebral and spinal magnetic resonance images with contrast media were unremarkable. An analysis of the patient's cerebrospinal fluid was consistent with neurobrucellosis. Owing to spastic paraparesis and hearing loss, the diagnosis of neurobrucellosis was made. Combined antimicrobial therapy was started and continued 6 months. His neurologic condition improved, and he was able to walk without help after 3 months' treatment. Our case illustrates that acquired progressive spastic paraparesis may occur during the course of neurobrucellosis. Neurobrucellosis should be borne in mind when patients present with spastic paraparesis.

Topics: Adult; Anti-Bacterial Agents; Brucellosis; Ceftriaxone; Doxycycline; Hearing Loss; Humans; Male; Paraparesis, Spastic; Rifampin; Trimethoprim, Sulfamethoxazole Drug Combination

Tuberculous otitis media can provide a diagnostic challenge even to the most astute and experienced clinician. The rarity of the condition and its propensity to masquerade as commoner otological conditions further delays diagnosis and treatment. We present the case of a 22-year-old female who presented with chronic aural discharge, unilateral hearing loss and recurrent hemifacial paralysis. The paper highlights the difficulty in diagnosis and stresses the need for a high index of suspicion in cases resistant to the common methods of treatment.

Topics: Adult; Antitubercular Agents; Diagnosis, Differential; Drug Therapy, Combination; Ear Diseases; Facial Paralysis; Female; Hearing Loss; Hearing Loss, Conductive; Humans; Isoniazid; Mycobacterium Infections; Otitis Media; Pyrazinamide; Rifampin; Tinnitus; Tuberculosis