Enterococcus Faecium Bacteremia Does Vancomycin Resistance Make a Difference?

ORIGINAL INVESTIGATION Enterococcus faecium Bacteremia Does Vancomycin Resistance Make a Difference?

Valentina Stosor, MD; Lance R. Peterson, MD; Michael Postelnick, RPh; Gary A. Noskin, MD

Background: Enterococcus faecium has received in- eters (P=.01). Fifty-nine percent of the patients with VSE creased attention, primarily due to the emergence of van- bacteremia survived vs 24% with VRE (P=.009), despite comycin resistance. The purpose of this investigation was similar severity-of-illness scores. In 62% of the patients to study the epidemiological characteristics of vancomy- with VRE sepsis, death was related to the bacteremia cin-resistant E faecium (VRE) bacteremia and to deter- (P=.01). Patients infected with VRE had longer hospi- mine the clinical impact of vancomycin resistance on the talizations than those with VSE (34.8 vs 16.7 days, re- outcome of patients with this infection. spectively) (P=.004), were more likely to be on the medical service (P=.03), and on the average, had hospitalization Methods: We retrospectively analyzed the clinical features costs of more than $27 000 per episode than did pa- and outcome of 53 patients with E faecium bacteremia. tients with VSE bloodstream infection ($83 897 vs $56 707, respectively) (P=.04). Results: From January 1992 until December 1995, there were 32 episodes of bacteremia caused by vancomycin- Conclusions: Vancomycin-resistant E faecium bactere- susceptible E faecium (VSE) and 21 caused by VRE. An mia is a complication of prolonged hospitalization in de- intra-abdominal site was the most common source of bac- bilitated patients. Vancomycin resistance has a negative teremia in both groups. All of the VRE and 78% of VSE impact on survival in patients with E faecium bactere- bacteremia cases were nosocomially acquired. Previous mia and leads to higher health care costs. administration of vancomycin was associated with VRE bacteremia (PϽ.001), as were indwelling bladder cath- Arch Intern Med. 1998;158:522-527

NTEROCOCCUS faecium has In some medical centers, VRE have be- grown in importance as a come endemic.18 Vancomycin-resistant nosocomial pathogen dur- enterococci were first identified at our ing the past decade.1,2 While medical center in 1991, and remain a sig- there once was controversy nificant problem despite attempts to cur- regardingE the pathogenic role of entero- tail the prevalence by formulary manage- cocci in causing infection, mounting evi- ment strategies19 and the institution of dence has now established E faecium as a increasingly more stringent infection con- cause of significant morbidity and mor- trol practices.20 Since treatment options are tality in hospitalized patients who are in- limited, much attention has been fo- fected with this organism.3-6 Notorious for cused on trying to understand the epide- resistance to multiple antimicrobial agents, miological features of VRE and the im- the acquisition of vancomycin resistance pact that vancomycin resistance has had has made this organism a formidable on the ability to care for patients infected From the Division of Infectious pathogen. with this organism. It is only through this Diseases, Department of Vancomycin-resistant enterococci understanding that more effective means Medicine, and the Clinical (VRE), first described in 1988,7 are a grow- to control further dissemination of VRE Microbiology Section, ing problem as more hospitals throughout will be identified. For these reasons, we Department of Pathology, the United States and Europe report signifi- performed a retrospective comparison of Northwestern University cant outbreaks associated with this organ- vancomycin-susceptible E faecium (VSE) Medical School (Drs Stosor, 8-16 Peterson, and Noskin), and the ism. The National Nosocomial Infec- and VRE bacteremia in our hospital to Department of Pharmacy, tions Surveillance System has reported that study the clinical and epidemiological as- Northwestern Memorial the incidence of VRE increased from 0.3% pects of this infection, as well as to define Hospital (Mr Postelnick), of all enterococci in 1989 to 7.9% in 1993, the clinical and economic significance of Chicago, Ill. with larger increases in intensive care units.17 vancomycin resistance in enterococci.

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Downloaded From: https://jamanetwork.com/ on 10/01/2021 PATIENTS AND METHODS indwelling bladder catheters or central venous catheters and hyperalimentation therapy was also recorded. A severity-of-illness score22 was calculated for each pa- PATIENTS tient at the onset of bacteremia. This grading system as- signs points on the following basis: change in mental sta- Northwestern Memorial Hospital in Chicago, Ill, is a 588- tus with disorientation, 1 point; change in mental status bed, university-affiliated, tertiary care hospital with active with stupor, 2 points; change in mental status with coma, surgical, trauma, solid organ transplantation, and bone mar- 4 points; body temperature of 37.8°C or higher, 1 point; row transplantation units. Medical records were reviewed body temperature of 40°C or higher, 2 points; body tem- for all patients who had a blood culture positive for E fae- perature of 35.6°C or lower, 2 points; hypotension (sys- cium during the 4-year period from January 1992 through tolic blood pressure Յ90 mm Hg, decrease in systolic blood December 1995, as identified by the Clinical Microbiology pressure by Ն20 mm Hg, or use of intravenous pressor Laboratory of Northwestern Memorial Hospital. Seventy-two agents), 2 points; use of mechanical ventilation, 2 points; cases of E faecium bacteremia were identified; of these, com- and cardiac arrest, 4 points. This index has previously been plete medical records were available for 59 patients. Four shown to be predictive of outcome for patients with bac- of these bacteremias were only identified from autopsy speci- teremia. mens and were not included in the final analysis. Two cases were excluded because the patients were neonates and fi- MICROBIOLOGICAL DETERMINATIONS nal outcomes were unknown due to patient transfer to other hospitals. Overall, 53 patients with bacteremia were included From January 1992 through March 1993, blood was cul- in the final analysis: 32 patients with VSE and 21 patients with tured aerobically with the use of a processing system (Iso- VRE bacteremia. Clinically significant bacteremia was defined lator system, Wampole Laboratories, Cranberry, NJ) and as the presence of 2 or more blood cultures positive for E fae- anaerobically in broth (Thiol, Difco Laboratories, Detroit, cium, or a single positive blood culture coupled with a clini- Mich). Throughout the remainder of the study period, the cally evident, or culture-positive, other site of infection.3 Isolator processing system and an automated system (ESP, Difco Laboratories) were used to culture blood aerobi- CLINICAL DATA COLLECTION cally and anaerobically. Identification of E faecium was based on standard methods, including the ability of the organ- Clinical information obtained for each patient included the ism to hydrolyze esculin in the presence of bile and grow following: age, sex, length of hospital stay prior to the on- in 6.5% sodium chloride, demonstration of a lack of pig- set of bacteremia, and hospital unit where the patient was mentation and motility, and fermentation of arabinose.23 admitted. A determination was also made regarding Susceptibility testing was performed by agar dilution on community vs nosocomial acquisition of the bacteremia. Mueller-Hinton agar according to reference methods.24 Nosocomial acquisition was defined as those patients whose first positive blood culture occurred more than 72 hours TREATMENT DATA after admission to the hospital, or when the patient was transferred from another hospital or chronic care facility. Therapy recorded for E faecium bacteremia included in- The source of bacteremia was identified from a culture- formation on the dosage and duration of all antimicrobial positive site or a clinically apparent site of infection. If an- agents used. Documentation was made if single, dual, or other site of infection was not evident, the source was con- no drug therapy was attempted. Data were also collected sidered unknown and the bacteremia primary in origin. If if other interventions (such as central venous catheter re- E faecium was isolated from multiple body sites, this was moval or surgical drainage of infected tissues) were made documented. Information regarding previous antimicro- in attempt to treat the infection and/or bacteremia. bial agent therapy was also obtained for each patient, as well as data pertaining to the management of the infection. OUTCOME DATA All medical records were reviewed for potential underlying risk factors or predisposing conditions for the ac- Outcome determinations were based on mortality: death quisition of E faecium bacteremia. This information in- was considered directly caused by the E faecium bactere- cluded liver disease, renal dysfunction, neutropenia, mia if the patient died following a positive blood culture significant corticosteroid therapy, infection with the hu- with a clinical picture consistent with sepsis; death was in- man immunodeficiency virus, malignant neoplasms, bone directly caused by the bacteremia if the patient died of mul- marrow transplantation, solid organ transplantation, dia- tifactorial causes, including further organ compromise by betes mellitus, pulmonary disease, debilitating neurologic the current septic episode; and death was considered un- disease, recent trauma, recent surgical procedures, and con- related to the bacteremia if the patient died following the comitant Clostridium difficile–associated diarrhea or coli- bacteremia of causes independent of the infectious pro- tis.3,9,11-13,16,18,21 Liver disease was defined as the presence cess. Survival was defined as the patient recovering from of a total bilirubin level greater than 43 µmol/L (2.5 mg/dL) the bacteremia and eventually being discharged from the and aminotransferase levels greater than twice normal. Re- hospital. nal dysfunction was defined as moderate if the calculated creatinine clearance was less than 1.0 mL/s (60 mL/min) COST DATA or severe if it was less than 0.25 mL/s (15 mL/min). Ab- solute neutropenia was defined as less than 500ϫ106/L of Through the hospital management engineering database, polymorphonuclear leukocytes. A daily prednisone dos- information was collected to determine the total cost of age of 20 mg (or equivalent) for at least 2 weeks was considered significant corticosteroid therapy. The presence of Continued on next page

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Downloaded From: https://jamanetwork.com/ on 10/01/2021 Table 1. Clinical Features of inpatient care for 53 patients with E faecium bacter- Enterococcus faecium Bacteremia* emia. One liver transplant recipient with VRE was excluded from analysis because of excessive hospi- No. (%) of Patients† talization costs related to complications from transplantation, and 1 patient with VSE was excluded be- VSE VRE cause of excessive costs related to surgery. The final Feature (n=32) (n=21) P calculations were based on 31 patients with VSE bac- Sex M 26 (81) 9 (43) teremia and 20 patients with VRE bacteremia. From .004 these data, the average cost of hospitalization was de- F 6 (19) 12 (57) termined for each group of patients. Mean (±SD) SIS 4.2±3.8 4.5±3.4 .76 SIS Ն5 13 (41) 8 (38) .22 STATISTICAL ANALYSIS Clinically significant 26 (81) 18 (86) .27 Unit of acquisition‡ All clinical, microbiological, and outcome data were ICU 12 (38) 12 (57) .09 Surgical 3 (9) 2 (10) .36 assessed for statistical significance by the use of the Medical 9 (28) 1 (5) .03 Fisher exact test (2-tailed) and computation of P val- Oncology 8 (25) 6 (29) .24 ues. The Student t test was used to compare continu- Nosocomial 25 (78) 21 (100) .02 ous variables. PϽ.05 was considered statistically sig- Mean (±SD) length of stay, d§ 16.7±16.1 34.8±23.3 .004 nificant. *VSE indicates vancomycin-susceptible enterococci; VRE, vancomycin-resistant enterococci; SIS, severity-of-illness score; and ICU, intensive care unit. †Unless otherwise indicated. RESULTS ‡Unit where patient was hospitalized at the onset of bacteremia. §Median length of stay prior to onset of bacteremia. DEVELOPMENT OF BACTEREMIA

During the 4-year study period, 32 episodes of VSE bac- Table 2. Features of Enterococcus faecium Bacteremia* teremia and 21 episodes of VRE bacteremia were reviewed. Of these, 26 VSE bacteremias (81%) compared No. (%) of with 18 VRE bacteremias (86%) were determined to be Patients† clinically significant. The annual number of VRE bacte- VSE VRE remias slowly increased throughout the study period; from Feature (n=32) (n=21) P January 1992 through December 1993, 8 VRE bactere- Mean (±SD) positive blood cultures 1.6±0.7 2.3±1.1 .02 mias were identified. However, 13 VRE bacteremias oc- Polymicrobial bacteremia 14 (44) 9 (43) .22 curred during the last 2 years of the study period. In con- Source of bacteremia trast, the number of VSE bacteremias declined from 13 Intra-abdominal 15 (47) 8 (38) .18 cases in 1992 to 6 cases in 1993, 6 cases in 1994, and 7 Urinary tract 1 (3) 1 (5) .49 cases in 1995. Wound 1 (3) 0 (0) .60 Soft tissue 1 (3) 0 (0) .60 The mean age of patients with VSE was 56.7 years, Vascular catheter 4 (13) 3 (14) .31 and that of patients with VRE was 58.3 years. Nosoco- Multiple sources 1 (3) 4 (19) .07 mial acquisition of bacteremia occurred in 25 patients Unknown source 9 (28) 5 (24) .24 with VSE (78%) compared with all of the patients with VRE (P=.02). Patients with VRE had longer hospital stays *VSE indicates vancomycin-susceptible enterococci; prior to the onset of bacteremia than did patients with VRE, vancomycin-resistant enterococci. †Unless otherwise indicated. VSE, with a mean of 34.8 days vs 16.7 days, respectively (P=.004). The intensive care units were the most frequent hospital location for development of enterococcal bac- equal frequency in both the VSE and VRE bacteremic teremia: 38% (12/32) of patients with VSE compared with episodes: 14 patients with VSE (44%) vs 9 patients with 57% (12/21) of those with VRE (P=.09). Table 1 sum- VRE (43%) had more than 1 organism recovered from marizes the clinical features of the patients with E fae- blood cultures. The mean number of blood cultures cium bacteremia. positive for E faecium was higher in the VRE group In Table 2, the various sources of infections iden- (Table 2). The mean (±SD) severity-of-illness scores at tified in these patients and their microbiological fea- the onset of the bacteremic episodes were equivalent for tures are listed. There were no statistically significant dif- both groups (4.2±3.8 for the VSE group vs 4.5±3.4 for ferences in the sources of the bacteremia. An intra- the VRE group). In addition, the VSE and VRE groups abdominal site was the most common source of bacteremia had comparable numbers of patients with a severity-of- for both the VSE and VRE groups: 15 (47%) and 8 (38%), illness score greater than or equal to 5: 13 (41%) and 8 respectively. A trend toward multiple sources for the bac- (38%), respectively. teremia was seen in the patients with VRE, but this did Data pertaining to antimicrobial agent therapy not reach statistical significance (P=.07). prior to the development of bacteremia were retrievable Microbiological data revealed that polymicrobial for 29 VSE and 20 VRE cases (Table 3). Patients in bacteremia was relatively common, and occurred with both groups frequently received antimicrobial chemo-

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Downloaded From: https://jamanetwork.com/ on 10/01/2021 Table 3. Antimicrobial Agent Exposure Prior to the Table 4. Predisposing Factors in Development of Enterococcus faecium Bacteremia* Enterococcus faecium Bacteremia*

No. (%) of Patients No. (%) of Patients

VSE VRE VSE VRE Agent (n=29) (n=20) P Factor (n=32) (n=21) P Vancomycin hydrochloride 10 (34) 16 (80) .002 Malignancy 18 (56) 11 (52) .21 Aminoglycoside† 20 (69) 20 (100) .005 Solid tumor 9 (28) 2 (10) .08 Aztreonam 7 (24) 6 (30) .23 Hematologic 9 (28) 9 (43) .13 Third-generation cephalosporin‡ 11 (38) 5 (25) .16 Transplantation Ampicillin and/or sulbactam 6 (21) 6 (30) .20 Solid organ 0 (0) 3 (14) .06 Piperacillin sodium and/or tazobactam 12 (41) 10 (50) .19 Bone marrow 2 (6) 3 (14) .24 Fluoroquinolone§ 9 (31) 4 (20) .18 Neutropenia 6 (19) 8 (38) .08 Trimethoprim-sulfamethoxazole 12 (41) 7 (35) .21 Corticosteroid therapy 7 (22) 6 (29) .22 Metronidazole 12 (41) 10 (50) .19 HIV infection 7 (22) 0 (0) .02 Clindamycin 3 (10) 2 (10) .36 Surgery 10 (31) 8 (38) .20 Trauma 3 (9) 0 (0) .21 *VSE indicates vancomycin-susceptible enterococci; Diabetes mellitus 4 (13) 6 (29) .10 VRE, vancomycin-resistant enterococci. Hepatic dysfunction 6 (19) 6 (29) .18 †Either gentamicin, tobramycin, or amikacin. Renal dysfunction ‡Either ceftriaxone, cefotaxime, ceftazidime, cefoperazone, or ceftizoxime. Moderate 8 (25) 5 (24) .25 §Either ciprofloxacin or ofloxacin. Severe 8 (25) 4 (19) .24 Neurologic disease 6 (19) 3 (14) .27 therapy prior to the development of enterococcal bac- Pulmonary disease 4 (13) 1 (5) .26 Central venous catheter 22 (69) 18 (86) .10 teremia. Previous administration of vancomycin was Indwelling bladder catheter 9 (28) 13 (62) .01 more commonly associated with VRE bacteremia com- Clostridium difficile diarrhea 2 (6) 3 (14) .23 pared with VSE bacteremia (16 [80%] vs 10 [34%] Hyperalimentation 10 (31) 10 (48) .11 patients, respectively; PϽ.002). Aminoglycoside use was also associated with the development of VRE bac- *VSE indicates vancomycin-susceptible enterococci; teremia (P=.005). There were no significant differences VRE, vancomycin-resistant enterococci; and HIV, human immunodeficiency virus. between the enterococcal bacteremia groups observed with the use of third-generation cephalosporins, aztreonam, or fluoroquinolones. otic or vancomycin plus an aminoglycoside, was given Table 4 summarizes the serious underlying con- equally to the patients of both groups. Not surprisingly, ditions and risk factors for the acquisition of E faecium use of vancomycin therapy was significantly higher in the bacteremia. Although both groups had many underly- VSE group, with 18 (56%) patients with VSE receiving ing illnesses, there were few statistically significant dif- this agent compared with 4 (19%) patients with VRE ferences between those with VRE and VSE bacteremia. (P=.006). Ampicillin, given at high doses as a continu- Malignant neoplasms and surgical procedures were com- ous infusion, was used more frequently in the treatment mon to both groups. A known malignant neoplasm was of bloodstream infections caused by VRE. Unconven- present in more than half of the patients with E faecium tional and investigational therapies, such as a combina- bacteremia. Recent surgery was documented in 10 (31%) tion product of quinupristin and dalfopristin,25 an ex- vs 8 (38%) of the patients in the VSE and VRE groups, perimental streptogramin, were used to treat patients in respectively. Interestingly, infection with the human im- the VRE group. Central venous catheter removal as an munodeficiency virus was seen significantly more often additional therapy was significantly more common in pa- in the VSE group: 7 (22%) compared with 0 (0%) in the tients with VRE bacteremia (10 [48%] vs 6 [19%] for VSE VRE group (P=.02). Although neutropenia (6 [19%] in cases; P=.02). There was no difference in surgical de- VSE vs 8 [38%] in VRE; P=.08) and solid organ trans- bridement of infected tissue between the 2 groups. plantation (0 [0%] in VSE vs 3 [14%] in VRE; P=.06) were identified more frequently in patients with VRE, these OUTCOME AND HOSPITAL COST ANALYSIS did not reach statistical significance. There was no difference in the use of central venous catheters; however, Overall mortality for the VSE group was 41% (n=13), but indwelling urinary catheter use was significantly higher only one fourth of these deaths (9% mortality rate [n=3]) in patients with VRE compared with those with VSE (13 could be directly attributed to the bacteremia. Mortality [62%] vs 9 [28%], respectively; P=.01). for the VRE group was significantly higher, with death occurring in 16 patients (76%) (P=.009). One half (38% TREATMENT OF BACTEREMIA mortality rate) of these deaths were directly caused by VRE bacteremia, and in an additional 5 cases (24%), VRE With respect to treatment, patients with VRE bactere- contributed indirectly to the mortality of the patient. In- mia were just as likely to receive some form of specific terestingly, while there was no significant difference in antimicrobial agent therapy as their VSE counterparts: mortality between patients in whom enterococci were 15 (71%) vs 24 (75%) patients, respectively (Table 5). isolated in multiple as opposed to a single blood cul- Combination therapy, usually with a ␤-lactam antibi- ture, there was a trend toward more directly attribut-

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Downloaded From: https://jamanetwork.com/ on 10/01/2021 Table 5. Treatment of Enterococcus faecium Bacteremia* Table 6. Outcomes of Enterococcus faecium Bacteremia*

No. (%) of Patients No. (%) of Patients†

VSE VRE VSE VRE Treatment (n=32) (n=21) P Outcome Measure (n=32) (n=21) P Antimicrobial agent therapy 24 (75) 15 (71) .23 Mortality 13 (41) 16 (76) .009 Vancomycin hydrochloride 18 (56) 4 (19) .006 Directly related 3 (9) 8 (38) .01 Ampicillin 1 (3) 8 (38) .001 Indirectly related 6 (19) 5 (24) .24 Ampicillin plus sulbactam 4 (13) 2 (10) .33 Unrelated 4 (13) 3 (14) .31 Piperacillin sodium 8 (25) 0 (0) .01 Survival 19 (59) 5 (24) .009 Gentamicin sulfate 16 (50) 13 (62) .16 Total cost of hospitalization, $‡ 83 897 56 707 .04 Tobramycin 4 (13) 0 (0) .12 Imipenem 2 (6) 0 (0) .36 *VSE indicates vancomycin-susceptible enterococci; Ciprofloxacin 0 (0) 2 (10) .15 VRE, vancomycin-resistant enterococci. Quinupristin plus dalfopristin 0 (0) 2 (10) .15 †Unless otherwise indicated. No therapy 8 (25) 6 (29) .24 ‡Average total cost of hospitalization for 31 patients with VSE bacteremia Surgical de´bridement 5 (16) 1 (5) .18 and 20 patients with VRE bacteremia. See “Results” section of the text for details. Removal of venous catheter 6 (19) 10 (48) .02

*VSE indicates vancomycin-susceptible enterococci; VRE, vancomycin-resistant enterococci. ing shorter lengths of hospitalization (average, 8 days; range, 4-14 days) for these patients. The use of indwelling bladder catheters was also as- able mortality in the group with VRE (7 cases vs 0 VSE sociated with VRE bacteremia, although the urinary tract cases; P=.09). However, no death was found to be di- was not found to be a common source for VRE blood- rectly attributable to VRE bacteremia when the organism stream infections. This may be explained in part by the was isolated from only a single blood culture. Table 6 serious underlying diseases in the patients with VRE. summarizes outcome and costs associated with entero- However, Morris and colleagues18 found that urinary tract coccal bacteremia. Average cost of hospitalization for a pa- catheterization was a risk factor for the development of tient with VRE bacteremia was $83 897 compared with urinary tract infections caused by this organism. $56 707 for a patient with VSE bacteremia (P=.04). A 32.4% Broad-spectrum antimicrobial agent therapy ap- cost difference was identified between these 2 cohorts. pears to be an important predisposing factor to E faecium bacteremia. We found a strong correlation be- COMMENT tween parenteral vancomycin use and the subsequent development of VRE. This supports previous findings by Our study confirms and extends what has been ob- Morris and coworkers,18 who found that patients with served in patients with VRE bacteremia: that this is cur- urinary tract infection caused by VRE were more likely rently a nosocomial infection acquired by patients who to have prior exposure to parenteral vancomycin than have severe underlying medical conditions, who have pro- those with VSE urinary tract infections. Our findings dif- longed hospital stays, and who have been previously fer from those of Linden et al,25 who report similar pa- treated with broad-spectrum antimicrobial agents, espe- tient exposure to vancomycin prior to the development cially vancomycin.3,13,25,26 Additionally, vancomycin re- of VRE and VSE bloodstream infection. Aminoglyco- sistance directly adds to the cost of care of these pa- side use was also found to correlate with VRE bactere- tients, accompanied by an increase in infection-related mia. However, our data may have been influenced by an- mortality. Most patients in our series were hospitalized tibiotic formulary changes that occurred during the study for more than 2 weeks prior to the onset of the bactere- period.19 Early in 1993, a policy restricting the use of third- mia. Interestingly, men acquired VRE more frequently generation cephalosporins at our medical center re- than women; however, our data contained no explana- sulted in substantial decreases in cephalosporin use and tion for this finding. Patients often acquired the organ- increases in aminoglycoside use. Our finding may be ex- ism in an intensive care unit, and no one was admitted plained by this and the fact that VRE bacteremia has been with community-acquired VRE. increasingly common at our center since the beginning As for the presence of underlying illness, both groups of 1994. For similar reasons, we did not find a strong cor- of patients had numerous but similar comorbidities and relation between third-generation cephalosporin use and equivalent severity-of-illness scores. Malignant neo- the acquisition of VRE. However, previous investigations plasms, neutropenia, corticosteroid therapy, recent sur- at our medical center did find use of third-generation cepha- gery, liver dysfunction, and renal impairment were com- losporins as a risk factor for enterococcal bacteremia.3,6 monly present. Many of these same underlying conditions While we were not able to identify many dif- have been associated with bacteremia and other infec- ferences in the patient populations who developed tions caused by VRE.3,26 Although not statistically sig- E faecium bacteremia, we were able to highlight dra- nificant, neutropenia and solid organ transplantation were matic differences in the outcomes of these groups. De- present more frequently in patients who acquired VRE. spite similar comorbidities and comparable severity-of- We did not find VRE bacteremia in our patients infected illness scores, mortality was much higher in patients with the human immunodeficiency virus, likely reflect- with VRE bloodstream infection. Although our patients

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Downloaded From: https://jamanetwork.com/ on 10/01/2021 with VRE were just as likely to receive aggressive antibi- Reprints: Valentina Stosor, MD, Northwestern Uni- otic therapy combined with removal of foreign bodies versity Medical School, Division of Infectious Diseases, 303 and surgical drainage, the high mortality in this group E Superior St–8E, Chicago, IL 60611. likely reflects the lack of effective therapy for VRE bloodstream infection. Similarly, data collected by 25 Linden and colleagues, the National Nosocomial Infec- REFERENCES tions Surveillance System,17 and Montecalvo and col- 26 leagues also show higher mortality rates with E faecium 1. Moellering RC Jr. Emergence of enterococcus as a significant pathogen. Clin In- bacteremia when vancomycin resistance is present. In fect Dis. 1992;14:1173-1178. contrast, Wells et al27 found comparable and overall 2. Murray BE. The life and times of the enterococcus. 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MMWR Morb Mortal Wkly Rep. 1993; resistant organism is crucial since controlling infection 42:597-599. with VRE becomes both medically necessary and eco- 18. Morris JG Jr, Shay DK, Hebden JN, et al. Enterococci resistant to multiple antimicrobial agents, including vancomycin: establishment of endemicity in a uni- nomically important. versity medical center. Ann Intern Med. 1995;123:250-259. In conclusion, VRE bacteremia is a serious and costly 19. Noskin GA, Postelnick M, Peterson LR. Control of enterococci by restriction of complication of prolonged hospitalization in severely de- third generation cephalosporins. Clin Infect Dis. 1994;19:597. 20. Bodnar UR, Noskin GA, Suriano T, Cooper I, Reisberg BE, Peterson LR. Use of bilitated patients. Previous treatment with parenteral van- in-house molecular epidemiology and full species identification for controlling comycin appears to be a major factor in the acquisition spread of vancomycin resistant Enterococcus faecalis isolates. J Clin Microbiol. of VRE bacteremia. As a medical community we must be 1996;34:2129-2132. 21. Lam S, Siger C, Tucci V, Morthland VH, Pfaller MA, Isenberg HD. The challenge more judicious in the use of this antibiotic as well as other of vancomycin-resistant enterococci: a clinical and epidemiologic study. Am J extended-spectrum antimicrobial agents. This study re- Infect Control. 1995;23:170-180. 22. Chow JW, Fine MJ, Shlaes DM, et al. Enterobacter bacteremia: clinical features inforces the serious nature of the problem of reemerg- and emergence of antibiotic resistance during therapy. Ann Intern Med. 1991; ing pathogens with multiple drug resistance and sug- 115:585-590. gests that future resources and efforts must be directed 23. Facklam RR, Collins MD. Identification of enterococcus species isolated from human infections by a conventional test scheme. J Clin Microbiol. 1989;27:731- at finding more efficacious therapy plus preventing fur- 734. ther nosocomial spread of this pathogen. 24. National Committee for Clinical Laboratory Standards. Methods for Dilution: An- timicrobial Susceptibility Tests for Bacteria That Grow Aerobically. 4th ed. Vil- lanova, Pa: National Committee for Clinical Laboratory Standards; 1997. NCCLS Accepted for publication July 17, 1997. document M7-A4. This work was supported in part by Northwestern 25. Linden PK, Pasculle AW, Manez R, et al. Differences in outcome for patients with bacteremia due to vancomycin-resistant Enterococcus faecium or vancomycin- University Medical School and Northwestern Memorial susceptible Enterococcus faecium. Clin Infect Dis. 1996;22:663-670. Hospital. 26. Montecalvo MA, Shay DK, Patel P, et al. Bloodstream infections with vancomycin- Presented in part as an abstract at the 36th Inter- resistant enterococci. Arch Intern Med. 1996;156:1458-1462. 27. Wells CL, Juni BA, Cameron SB, et al. Stool carriage, clinical isolation, and mor- science Conference on Antimicrobial Agents and Chemo- tality during an outbreak of vancomycin-resistant enterococci in hospitalized medi- therapy Meeting, New Orleans, La, September 16, 1996. cal and/or surgical patients. Clin Infect Dis. 1995;21:45-50.

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