Concise Communication

Epidemiology of Infection and Colonization With Vancomycin‐Resistant Enterococci and Frequency of Cocolonization With Methicillin‐Resistant Staphylococcus aureus in Children

Lacey Benson, BA; Bruce Sprague, BA; Joseph Campos, PhD; Nalini Singh, MD, MPH  

From Case Western Medical School, Cleveland, Ohio (L.B.); and the Center for Health Services and Community Research, Children's National Medical Center (B.S.), the Departments of Pediatrics (J.C., N.S.), Pathology (J.C.), and Microbiology–Tropical Medicine (J.C.), The George Washington University School of Medicine, and the Department of Laboratory Medicine (J.C.) and Division of Infectious Diseases (N.S.), Children’s National Medical Center, The George Washington University School of Medicine, Washington, DC.

Address reprint requests to Nalini Singh, MD, MPH, Departments of Pediatrics, Epidemiology, and Global Health, The George Washington University Schools of Medicine and Public Health, 111 Michigan Avenue NW, Washington, DC 20010 (Nsingh@cnmc.org).

We report the descriptive and molecular epidemiology of vancomycin‐resistant enterococci (VRE) infection and colonization and cocolonization with methicillin‐resistant Staphylococcus aureus (MRSA) in children. Interunit and intraunit spread of VRE was detected, and 8 cases of VRE‐MRSA cocolonization were identified. Seven of these cases were identified only via active surveillance, because clinical evidence of VRE colonization was absent.

Received September 5, 2006; accepted November 29, 2006; electronically published May 31, 2007.

Vancomycin‐resistant enterococci (VRE) are an important cause of healthcare‐associated infections in US hospitals. The National Nosocomial Infections Surveillance System of the Centers for Disease Control and Prevention reported a vancomycin resistance rate of 28.5% among enterococci that caused hospital‐associated infections in intensive care unit patients in 2004, representing a 12% increase since 1991.1

With the increasing number of community‐associated methicillin‐resistant Staphylococcus aureus (MRSA) infections and frequency of MRSA infection outbreaks among infants,2 there is a growing need for the recognition of VRE and MRSA in neonatal intensive care units (NICUs) and other units and increasing concern regarding the development of vancomycin resistance by S. aureus. Transfer of vanA‐mediated vancomycin resistance from VRE to MRSA has been demonstrated in vitro,3 and because clinical vancomycin‐resistant S. aureus (VRSA) isolates have been found to have the enterococcal vanA gene,4 intergeneric spread of resistance is the likely explanation. The objectives of this study were to determine the epidemiology of infection and colonization with VRE and identify the frequency of VRE‐MRSA cocolonization in children a nonoutbreak hospital setting.

Methods

 

The Children's National Medical Center (CNMC) is a full‐service pediatrics facility that houses 230 inpatient beds, including beds in 3 intensive care units. Laboratory surveillance data for VRE and MRSA infection and/or colonization from all units were analyzed. All S. aureus isolates were screened for vancomycin resistance according to the Centers for Disease Control and Prevention and Food and Drug Administration guidelines, since automated antimicrobial susceptibility test systems may not detect VRSA reliably.5

Active surveillance cultures (ASCs) are performed for detection VRE and MRSA in the NICU. During 2000‐2002, infants admitted to the NICU had ASCs of rectal swab specimens performed for detection of VRE on admission and weekly throughout their hospital stay. After the control of VRE was achieved, ASCs were performed at admission only, starting in 2003.6 ASCs of nasopharyngeal swab specimens for detection of MRSA were performed at admission and weekly thereafter during an outbreak of MRSA infection in 2004‐2005; ASCs were performed only on admission during the rest of the study period. Other units perform cultures for detection of VRE and MRSA when clinically relevant. Patients with VRE or MRSA infection or colonization are placed under contact isolation, regardless of the unit in which they are hospitalized.

VRE recovered from clinical specimens during 2005‐2006 were assessed by repetitive sequence–based polymerase chain reaction for genetic relatedness. Twenty‐five samples from 23 patients were analyzed by methods described elsewhere.7 The genetic relatedness of isolates was described as identical (similarity coefficient, ⩾0.97), similar (similarity coefficient, 0.95‐0.97), or unrelated (similarity coefficient, <0.95). Identical and similar isolates were considered to be part of genetically related clusters.

Results

 

VRE isolates collected from 23 patients from January 2005 through July 2006 were available for further analysis. Four clusters were detected by repetition polymerase chain reaction; VRE isolates from 4 patients were not part of these clusters. Cluster C1 had 3 patients (13%), C2 had 3 patients (13%), C3 had 11 patients (48%), and C4 had 2 patients (9%). Cluster C1 involved 2 patients with overlapping NICU stays, suggesting infant‐to‐infant spread; one had a culture positive for VRE within 1 day after admission, and the other had a culture positive for VRE 16 days after admission. Cluster C2 involved 2 patients with overlapping hospital stays, one in the NICU and the other in the cardiac intensive care unit (CICU), suggesting possible interunit transfer. Two genetically dissimilar isolates were collected from the patient in the CICU, for whom linezolid and a third‐generation cephalosporin were administered during the interval between performance of the 2 cultures.

In cluster C3, five patients from whom samples were obtained for ASC within 48 hours of NICU admission tested positive for VRE (Figure). These 5 patients were transferred to the CNMC from 4 hospitals in Washington, D.C., or Maryland. The cluster also included 2 patients with overlapping stays in the hematology care unit, consistent with patient‐to‐patient transmission. One of the hematology care unit patients had 2 VRE isolates recovered from cultures of rectal swab specimens obtained 56 days apart that had identical DNA fingerprints.

Figure.  Dendrogram of 23 vancomycin‐resistant enterococcus isolates. Genetically related samples are labeled clusters 1‐4. Isolates 1 and 2 are genetically distant.

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Throughout the study period, rates of VRE colonization in the NICU ranged from 0.3 to 2.9 cases per 1,000 patient‐days, and rates of MRSA colonization ranged from 0.1 to 3.4 cases per 1,000 patient‐days. The colonization‐infection ratio for VRE in the NICU was 1:20, representing 4 patients with meningitis or bloodstream infections and 82 with rectal colonization. For MRSA, the colonization‐infection ratio was nearly 1:1, with 75 bloodstream or soft tissue infections and 79 colonizations of the nasopharynx or endotracheal tube. For patients with multiple cultures positive for VRE, the median interval during which results of cultures were positive was 22 days, with a maximum interval of 328 days.

Eight patients in the NICU had cultures positive for both MRSA and VRE during the study period. Both organisms were detected within 6 weeks of each other for all 8 patients, and 1 patient had both MRSA and VRE recovered from the same foot ulcer. VRE was recovered only from a rectal swab for 7 of 8 patients, whereas MRSA was recovered from various body sites (Table). VRSA was not detected in these patients during the study period.

Table. 
Table.  Epidemiology of Vancomycin‐Resistant Enterococci (VRE) and Methicillin‐Resistant Staphylococcus aureus (MRSA) Cocolonization

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Discussion

 

In our study, findings of molecular epidemiological tools supported clinical evidence of interfacility and intrafacility transmission of VRE. Such transmission may occur via shared medical equipment or via the hands of personnel for whom patient contact occurred in more than 1 unit.6 Other major contributors to VRE transmission are admitted patients previously colonized with VRE.8 In our study, 9 of 12 NICU patients who had cultures positive for VRE were recognized within 1 day after admission. Of these 9 patients, 5 transferred from 4 different hospitals and had isolates from cluster C3, which may indicate the presence of a dominant VRE clone in the Washington, D.C., area. Alternatively, newly admitted patients may become colonized during the admission or transport process.

Patients may shed VRE intermittently for as long as 328 days, and 1 patient in our study remained colonized with the same strain for 56 days. This long‐term colonization likely led to ongoing transmission of VRE and possibility to VRE‐MRSA cocolonization.

Within the adult intensive care unit population, VRE‐MRSA coinfection and cocolonization have been investigated and have been shown to be risk factors for the development of intermediate resistance to vancomycin by S. aureus.9 In the CNMC NICU, outbreaks of MRSA infection and colonization have been difficult to control, leading to reservoirs of MRSA‐colonized infants.2 Additionally, coinfection and cocolonization with VRE and MRSA have occurred in the other units in the CNMC.10 During the study period, all patients with VRE‐MRSA cocolonization or coinfection were hospitalized in the NICU, where ASCs are performed for detection of both organisms. Seven of the 8 cocolonized patients had no clinical evidence of VRE infection. This finding indicates that many patients may have been cocolonized in other units but went undetected, because ASCs are only performed in the NICU at our hospital. In 1 patient, the simultaneous recovery of VRE and MRSA from the same body site represented an opportunity for transfer of vancomycin resistance between species. Consideration should be given for a “search and destroy” strategy, including rapid detection of resistant pathogens by means of ASCs, implementation of contact isolation, and improvement of adherence to infection control measures, such as hand hygiene.11

Acknowledgments

 

Financial support. Society for Pediatric Research (grant HD 007446 to L.B.).

Potential conflicts of interest. All authors report no conflicts of interest relevant to this article.

References

 
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