The median age of patients with DNSE was 52.2
years, with 14 of 25 (56%) being female (Table
). DNSE was identified in 25 patients and found in 32 clinical samples from 4 specimen sources including; blood (9 patients; 12 isolates), urine (12 patients; 14 isolates), peritoneal fluid or intra-abdominal abscess (3 patients; 4 isolates), and wounds (2 patients; 2 isolates). One patient had DNSE identified from both urine and blood (Table
). Multiple isolates from the same patient were always of the same species, PFGE type or subtype, and had an identical antimicrobial susceptibility pattern.
Clinical characteristics of patients with DNSE colonization or infection
Infection due to DNSE was confirmed by both laboratory and chart review in 17 of 25 (68%) patients. In the remaining 8 patients, DNSE was isolated from urine alone and represented colonization based on the absence of documented clinical symptoms and/or negative urinalysis. A bloodstream infection was identified in 9 patients, a genitourinary infection such as UTI, pyelonephritis, or kidney abscess in 3 patients, bacterial peritonitis in 3 patients, and a skin and soft tissue infection and/or osteomyelitis in 2 patients.
A concomitant gastrointestinal or intra-abdominal process was identified in 19 of 25 (76%) patients, including Clostridium difficile infection, graft-versus-host-disease of the gut, neutropenic enterocolitis/perforation, traumatic bowel perforation, bowel ischemia, bacterial peritonitis, ascending cholangitis, gastroparesis, pyelonephritis and/or kidney abscess, or other gastrointestinal surgery with complications. Twenty-one patients (84%) were immunosuppressed, including: 12 (48%) with underlying cancer and/or ongoing chemotherapy; 12 (48%) with diabetes mellitus (including 4 with an associated malignancy, 2 requiring hemodialysis for end-stage renal disease, 2 requiring immunosuppressive therapy for prior kidney-pancreas transplants, and 1 with hip osteomyelitis); and 1 patient requiring dialysis for end-stage renal disease due to hypertension. In-hospital mortality of patients with DNSE infection or colonization was high, occurring in 10 of 25 patients (40%).
Daptomycin exposure was confirmed in 15 of 25 (60%) patients prior to the isolation of DNSE. Of these, 10 of 15 (67%) had DNSE isolated during treatment with daptomycin after receiving an average of 13.9
days of therapy (range 3–40
days). The remaining 5 patients had recently received daptomycin with an average drug-free interval of 7.8
days (range 3–14
days) prior to DNSE isolation. In patients with prior daptomycin exposure, the total days of daptomycin therapy in the year prior to isolation of DNSE varied between 5–67
days, with a mean of 20.9
days and median of 16
days. Ten patients had no documented daptomycin exposure at our institution, and no evidence in their medical records that they received daptomycin prior to admission at UIHC. However, detailed records of care prior to UIHC admission were not always available and therefore daptomycin exposure could not be completely excluded in these cases.
Of patients with prior daptomycin exposure, 8 of 15 (53%) were female, compared to 6 of 10 (60%) of patients without prior daptomycin exposure (Table
). Compared to patients without prior daptomycin exposure, patients with prior daptomycin exposure were less likely to harbor E. faecalis
(0% vs. 33%; p
0.019). In patients with DNSE and prior daptomycin exposure, there was a non-significant trend toward having a bloodstream isolate (47% vs. 20%; p
0.174), a history of immunosuppression from any cause (93% vs. 70%; p
0.119), and death (53% vs. 20%; p
Characteristics of patients with respect to prior daptomycin exposure
The number of patients with DNSE colonization or infection at UIHC increased from 2.33 cases per year for the time period 2005–2007 to 4.33 cases per year for the time period 2008–2010 (Figure
). An additional five cases were identified in the first 6
months of 2011 alone – as many as had been noted over any 12-month period previously. Rates of daptomycin usage at UIHC increased during the study period as well, from approximately 0.2% of inpatients in 2005 receiving daptomycin to 0.9% in 2011 (Figure
Figure 1 Number of patients with colonization/infection due to daptomycin non-susceptible enterococci (solid bars; left vertical axis), and percentage of all discharged in-patients prescribed daptomycin during their hospital stay (solid line; right vertical axis) (more ...)
Twenty-one patients had enterococcal isolates available for species identification. Of these, eighteen patients (86%) had E. faecium
, and two (10%) had E. faecalis
). Vancomycin resistance was common, occurring in DNSE isolates from 18 of 25 patients (72%), including 16 of 18 (89%) E. faecium
isolates. Ampicillin resistance was detected in DNSE isolates from 18 of 25 patients (72%), and in 17 of 18 (94%) E. faecium
isolates. Linezolid resistance was uncommon, occurring in only 1 DNSE isolate from 21 patients. Linezolid susceptibility was not performed for 4 patient’s isolates, as they were not available for further susceptibility testing.
Antimicrobial resistance profile of enterococcal isolates to selected antimicrobial agents by species
PFGE revealed significant genetic heterogeneity, with 16 PFGE types and 24 subtypes represented among the 29 patient isolates available for typing (results not shown). Multiple isolates from the same patient were always of the same type or subtype. There were only four instances in which more than one patient shared the same PFGE type with the most common PFGE type shared among 4 patients. In only one instance did two patients share the same PFGE subtype.