De novo daptomycin non-susceptible enterococci causing urinary tract infection: a study from north India

Introduction: Daptomycin is a bactericidal agent active against vancomycin resistant enterococci (VRE) which are emergent nosocomial uropathogens. There is limited data available on daptomycin non-susceptible enterococci (DNSE) in India. Herein we describe the emergence of de novo DNSE causing urinary tract infections (UTI) from India. Materials and Methods: We prospectively screened, consecutive enterococci (n=140) grown in significant numbers (≥105cfu/ml) from urine cultures in hospitalized patients (n=12434) over 6 months. Isolates with daptomycin minimum inhibitory concentration (MIC) >4µg/ml by E-test and no history of daptomycin exposure were defined as DNSE. Colonization and symptomatic UTI was defined as per the Centre for Disease Control and Prevention guidelines. Results: Prevalence of DNSE was 12.1% (17/140) and all were E. faecium. In 6 cases (35.2%) DNSE isolates were colonizers while 11(64.71%) were from UTI cases. Urosepsis occurred in 4 cases, of which 3 died. History of immunocompromise, recent urogenital surgery and indwelling per-urethral catheter were present in 47%, 58.8% and 64.7% cases respectively. Exposure to third generation cephalosporin and metronidazole was seen in nine (52.9%) and 3 (17.65%) cases respectively, while one patient each had vancomycin and teicoplanin exposure. Daptomycin MIC range was 6 to >256 µg/ml. Resistance to ciproflocaxin, amoxicillin, high level gentamicin, tetracycline, nitrofurantoin and vancomycin was seen in 100%, 94.1%, 88.2%, 52.9%, 41.1% and 23.5% respectively. All DNSE were susceptible to linezolid. Conclusions: A high prevalence of DNSE warrants further case control studies, molecular and epidemiological studies to elucidate the risk factors, molecular mechanisms of resistance and epidemiological origin of these isolates.