The first linezolid-resistant Enterococcus faecium in India: High level resistance in a patient with no previous antibiotic exposure
We report a case of a 72-year-old female, known diabetic for last 16 years, was admitted to the intensive care unit (ICU) of a tertiary care hospital with sudden onset unconsciousness for approximately 12 h first noticed when patient was not responding when her family tried to wake her up from sleep, patient was on oral hypoglycemic drugs with poor glycemic control. The patient was also hypertensive, which was controlled on medication. Patient did not have any history of convulsions, fever, vomiting, headache, trauma or any neurodeficit in the past.\nAt the time of admission, the patient neurological score was 5/15 as per Glasgow Coma scale. The pulse was 88/min, blood pressure-140/80 mm Hg, respiratory rate of 16/min and was irregular with bilateral vesicular breath sounds. The capillary blood glucose was 28 mg/dL. The other blood investigations were as follows: Total leukocyte count-16,200/mm3 with neutrophil predominance, serum alanine aminotransferase (ALT) -31 IU/mL, serum aspartate aminotransferase (AST) -71 IU/mL, alkaline phosphatase-22 IU/L, total protein-4.8 g/dL, albumin-2.4 g/dL, urea-54 mg/dL, creatinine-1.2 mg/dL, total bilirubin-0.6 mg/dL, conjugated bilirubin 0.3 mg/dL. Computerized tomographic scan on admission showed signs of focal ischemia. She was diagnosed as a case of hypoglycemic encephalopathy with hypoxic brain damage. She was intubated and put on ventilator support. The patient's glycemic status was restored and the patient was started on piperacillin + tazobactam empirically, to cover against any aspiration pneumonia, given the long period of unconsciousness of the patient.\nOn day 3 of treatment, she was showing some response to a painful stimulus, but the blood sugar was remaining uncontrolled fluctuating in between 221 mg/dL and 350 mg/dL. On day 4 of treatment, she developed low grade fever for which the endotracheal secretions were sent for culture. Acinetobacter baumanii with significant colony count (>106 colony forming units) was isolated, which was sensitive to netilmicin and polymixin B. The blood cultures sent on day 3 showed no growth and the chest X-ray showed mild right sided basal opacity. Patient was started on netilmicin and cefepime.\nOn day 7 of treatment, the patient developed high grade fever. The blood investigations were showed total leukocyte count of 8400/mm3 with neutrophilic predominance and serum creatinine of 2 mg/dL. The catheterized urine sample and blood were sent for culture. The urine culture showed a significant growth of Escherichia coli which was sensitive to meropenem, poymyxin B, cotrimoxazole and nitrofurantoin. On the basis of the culture reports, meropenem was added to the treatment regimen, but the general condition of the patient deteriorated, with total leukocyte counts dropping to 4000/mm3.\nThe blood cultures sent on day 7 and day 8 showed growth of E. faecium, which was identified by standard laboratory procedures.[] The antibiotic susceptibility of the isolate was performed by Kirby Bauer disc diffusion technique as per Clinical and Laboratory Standards Institute (CLSI guidelines), which showed the organism to be sensitive to vancomycin, but more remarkably the isolate was resistant to linezolid showing no zone around the disc by the disc diffusion technique [].[] Disk diffusion testing was performed with 30-μg linezolid disks (BBL, Becton Dickinson). E-test linezolid strips with a concentration gradient corresponding to 0.016-256 μg/mL were utilized with Mueller-Hinton agar as described by the manufacturer (Hi Media laboratories Mumbai) to determine the MIC of theisolate, but the isolate did not show any zone of inhibition, indicating that the MIC of the isolate was more than 256 μg/mL []. The MIC of the isolate was further determined by agar dilution method (using 0.5, 1, 2, 4, 8, 16, 32, 64, 128, 256, 512 and 1024 μg/mL) was conducted in accordance with CLSI standards[] using a linezolid preparation obtained from the manufacturer (Pfizer, India) which showed the MIC of the isolate was 1024 μg/mL. Automated susceptibility testing by the Vitek 2 system using the antimicrobial susceptibility testing (AST) GP-61 card (bioMérieux) was performed according to the manufacturers’ instructions. The categorical interpretation of results was based on CLSI guidelines.\nPatient was started on vancomycin but her condition further deteriorated and she was declared dead on day 15 of admission.\nThe cultures from the other patients in the ICU, did not reveal any similar organisms, unlike other case reports where isolation of linezolid resistant enterococci from one patient was usually associated with clonally related isolates, being isolated from other patients in the same wards.[]