A 23-year-old Pakistani male biomedical engineer, with no significant past or present medical history, presented to the emergency department (ED) with a 3-day history of severe hearing loss that was associated with fever and disorientation. The patient appeared anxious and agitated due to his apparent hearing impairment based on his father. According to him, the patient had reported a history of fever, worsening headache, neck pain, and flu-like symptoms 7 days prior to his presentation. It was treated as an upper respiratory tract infection with minimal improvement. One week before his presentation, he returned to Qatar after a short vacation in Islamabad, Pakistan, with a history of eating local food from roadside stalls. He denied hiking, camping, tick bites, mosquito bites, exposure to lice, mites, animals, and their body fluids.
His father also reported that the patient had diarrhea and abdominal pain while in Pakistan, 10 days prior to his presentation, but without nausea or vomiting. The patient denied history of earache, ear discharge, tinnitus, recent upper respiratory tract infection, vertigo, and dizziness. He denied history of smoking, alcohol intake, and illicit drug use.
In the ED, he was febrile with an oral temperature of 38.9 C, pulse rate of 95 beats/min, respiratory rate of 20 breaths/min, and blood pressure of 115/67 mm Hg. Upon physical examination, the patient appeared anxious and disoriented to place. He also showed bilateral impaired hearing ability, raising his voice in order to communicate and struggling to hear questions from the medical team. Otherwise, systematic examination was normal.
Initial investigation showed mild thrombocytopenia with normal white blood cell count and hemoglobin level. He had mild elevation in creatinine at 162 umol/L (normal <100 umol/L), hyponatremia at 127 mmol/L (normal range 135-145 mmol/L), elevated serum alanine aminotransferase (ALT) at 134 U/L (normal <41 U/L), elevated serum aspartate aminotransferase (AST) at 240 U/L (normal <40 U/L), and elevated C-reactive protein (CRP) at 185 mg/L (normal <10 mg/L). Alkaline phosphatase (ALP) and total bilirubin were normal. Malaria screening was negative. Initial imaging with chest X-ray and head CT (computed tomography) were normal.
Acute meningitis with or without encephalitis was the top differential diagnosis; lumbar puncture (LP) failed in the ED due to the patient's agitation and non-cooperation. Intravenous normal saline and empirical antibiotics (ceftriaxone 2 g every 12 h, vancomycin 1 g/day, and acyclovir 750 mg every 8 h) were initiated after sending cultures and investigations for sepsis workup. Intravenous dexamethasone (initial loading dose of 3 mg/kg, then 1 mg/kg every 6 h) was also added to the regimen, then shifted to oral prednisolone (60 mg/day) after 2 days.
Pure tone audiometry (PTA) was performed at presentation and 15 days later in the outpatient clinic. The result from the left ear audiometry is shown in Figure 1. It showed moderate bilateral sensorineural hearing loss, to nearly all frequencies during his inpatient admission (shown in Figure 1(a)). PTA was repeated after 15 days and showed marked improvement with mild hearing loss only to high frequencies (shown in Figure 1(b)). Tympanometry and tone decay test were normal upon admission.
One day after admission, the patient's blood culture demonstrated growth of Salmonella Typhi. Due to the high prevalence of extensively drug-resistant (XDR) strains in Pakistan, antibiotics were changed to meropenem (2 g every 8 h) and azithromycin (500 mg/day) to ensure coverage of possible drug-resistant strains. According to the World Health Organization (WHO), 5274 (64.4%) cases of XDR typhoid fever were reported out of 8188 typhoid fever cases from 1 November 2016 to 9 December 2018 in Pakistan. The XDR strains of Salmonella Typhi have shown resistance to first- and second-line antibiotics (e.g. fluoroquinolones) as well as third-generation cephalosporins (e.g. ceftriaxone). Therefore, current treatment options for Pakistani XDR strains of Salmonella Typhi are limited to oral azithromycin, and intravenous meropenem or tigecycline.
Two days after admission, blood culture sensitivity results showed Salmonella Typhi sensitive to ceftriaxone but resistant to ciprofloxacin. Therefore, antibiotics were de-escalated to intravenous ceftriaxone only, to complete the total duration of 14 days of antibiotics. Head MRI (magnetic resonance imaging) was normal and fluoroscopic guided LP was performed; results showed high protein level without leukocytosis. Cerebrospinal fluid (CSF) culture and viral screen, including herpes simplex viruses, were negative. Workup for tuberculosis from sputum and CSF was negative. Urine analysis and microscopy were normal.
Clinically, the patient improved quite rapidly; fever subsided and hearing loss gradually improved 5 days after the treatment had commenced. The patient's hearing loss continued to improve and almost completely resolved by the end of the first month of treatment. Audiometry was not done after 1 month because the patient had traveled back to his home country and was thus contacted over the phone. Oral prednisolone was gradually tapered down from 60 mg/day and stopped within 3 weeks.