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Vancomycin-resistant Enterococcus spp isolated from community acquired infections and colonizations in Querétaro City, Mexico

      To the Editor:
      Members of the genus Enterococcus are part of the human microbiota. They are found mainly in the gastrointestinal tract, but can also be detected colonizing the upper airways, the oral cavity, the skin, the vagina, and the urethra. Since the 1990s, enterococci have emerged as nosocomial pathogen, nowadays ranking as the third to fourth most common nosocomial agent worldwide; however, prevalence in Latin America has remained low. Enterococci have developed multidrug resistance (MDR) profiles, particularly to vancomycin (ie, that have become vancomycin-resistant enterococci [VRE]), that make them a global public health concern.
      • Arias C.A.
      • Murray B.E.
      The rise of the Enterococcus: beyond vancomycin resistance.
      • Rubinstein E.
      • Keynan Y.
      Vancomycin-resistant Enterococci.
      There have been reports of community-acquired (CA) infections and colonizations due to VRE.
      • Stevenson K.B.
      • Searle K.
      • Stoddard G.J.
      • Samore M.
      Methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci in rural communities, western United States.
      • Padiglione A.A.
      • Grabsch E.A.
      • Olden D.
      • Hellard M.
      • Sinclair M.I.
      • Fairley C.K.
      • et al.
      Fecal colonization with vancomycin-resistant enterococci in Australia.
      • Endtz H.P.
      • van den Braak N.
      • van Belkum A.
      • Kluytmans J.A.
      • Koeleman J.G.
      • Spanjaard L.
      • et al.
      Fecal carriage of vancomycin-resistant enterococci in hospitalized patients and those living in the community in The Netherlands.
      • Wendt C.
      • Krause C.
      • Xander L.U.
      • Loffler D.
      • Floss H.
      Prevalence of colonization with vancomycin-resistant enterococci in various population groups in Berlin.
      The mechanism of spread in these cases is still unclear. It has been suggested that patients colonized while hospitalized could be the source of transmission.
      • Stevenson K.B.
      • Searle K.
      • Stoddard G.J.
      • Samore M.
      Methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci in rural communities, western United States.
      Enterococci surveillance and monitoring studies have been scarce in México and have mainly focused on its nosocomial presence. Yet the studies that have been conducted have shown a significant increase in the rate of enterococcal nosocomial infections—and up to 26% frequency of VRE.
      • Cornejo-Juarez P.
      • Velásquez-Acosta C.
      • Díaz-Gonzalez A.
      • Volkow-Fernandez P.
      Trend of antimicrobial drug-susceptibility of blood isolates at an oncological center (1998-2003).
      • Jones R.N.
      • Guzman-Blanco M.
      • Gales A.C.
      • Gallegos B.
      • Castro A.L.
      • Martino M.D.
      • et al.
      Susceptibility rates in Latin American nations: report from a regional resistance surveillance program (2011).
      Moreover, a retrospective study held in Querétaro city
      • Leo-Amador G.E.
      • Borbolla-Ramos A.
      • Morales-Lara J.A.
      • Pérez-González H.A.
      • Hernandez-Montiel H.L.
      • Solis-S J.C.
      Infection or colonization and antimicrobial susceptibility of Enterococcus spp at a regional hospital in Queretaro, Mexico.
      reported that 35% (Enterococcus faecalis) and 60% (Enterococcus faecium) of infecting enterococci strains were resistant to vancomycin, suggesting an incremental spread of VRE strains in this Mexican region. Thus, the aim of our study was to assess the frequency of CA VRE in Querétaro City, Mexico.
      An observational study of enterococci-positive cultures identified in outpatients by 6 private clinical laboratories (authorized and certified by Mexican authorities) in Querétaro city, México, between August 2004 and November 2011 was carried out. For further analysis, samples classified as CA urinary tract infection (CUTI) (urine samples with a bacterial colony count ≥100,000 cfu/mL) and CA colonization (CAC) (from semen, female genital tract samples, and urethral discharge samples [none of the latter was part of segmented urine cultures]) were included. Enterococcal isolates were identified by conventional microbiologic testing. Antibiotic susceptibility tests were done using either the Kirby-Bauer disk diffusion method or the automated MicroScan system (Siemens Healthcare Diagnostics, Deerfield, IL). Resistance to vancomycin was analyzed, as was resistance to ampicillin, penicillin, linezolid, high-level resistance (HLR) to gentamicin (500 μg), HLR to streptomycin (1,000 μg), erythromycin, rifampicin, ciprofloxacin, levofloxacin, and nitrofurantoin (tested only in urine cultures), based on Clinical and Laboratory Standards Institute (CSLI) references. MDR was determined based on the recently standardized international terminology recommended by the European Centre for Disease Prevention and Control and the Centers for Disease Control and Prevention.
      • Magiorakos A.P.
      • Srinivasan A.
      • Carey R.B.
      • Carmeli Y.
      • Falagas M.E.
      • Giske C.G.
      • et al.
      Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance.
      Statistical analysis to determine differences between proportions was performed with the Fisher exact test; a P value ≤ .05 was considered significant.
      Data from a total of 312 enterococci isolates were included for analysis. Twenty-one VRE isolates (6.7%) were found. This frequency is higher than the up to 2% reported previously in the few studies assessing CA VRE.
      • Stevenson K.B.
      • Searle K.
      • Stoddard G.J.
      • Samore M.
      Methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci in rural communities, western United States.
      • Padiglione A.A.
      • Grabsch E.A.
      • Olden D.
      • Hellard M.
      • Sinclair M.I.
      • Fairley C.K.
      • et al.
      Fecal colonization with vancomycin-resistant enterococci in Australia.
      • Endtz H.P.
      • van den Braak N.
      • van Belkum A.
      • Kluytmans J.A.
      • Koeleman J.G.
      • Spanjaard L.
      • et al.
      Fecal carriage of vancomycin-resistant enterococci in hospitalized patients and those living in the community in The Netherlands.
      • Wendt C.
      • Krause C.
      • Xander L.U.
      • Loffler D.
      • Floss H.
      Prevalence of colonization with vancomycin-resistant enterococci in various population groups in Berlin.
      Regarding Latin America, only a previous 2005 Mexican study had assessed community enterococci, finding no VRE isolates from urine specimens at that time.
      • Cornejo-Juarez P.
      • Velásquez-Acosta C.
      • Díaz-Gonzalez A.
      • Volkow-Fernandez P.
      Trend of antimicrobial drug-susceptibility of blood isolates at an oncological center (1998-2003).
      This suggests that the appearance of VRE at the community level has recently emerged in this country. As for the type of sample source, urine (59.6%) was the prevailing source, although no statistical differences were found between the proportions by sample source between CUTI (6.4%) and CAC (7.1%). This suggests that these colonizing VRE, under certain host and/or environment conditions, could be causing infection. As for distribution by species, consistent with reports from different countries,
      • Arias C.A.
      • Murray B.E.
      The rise of the Enterococcus: beyond vancomycin resistance.
      • Rubinstein E.
      • Keynan Y.
      Vancomycin-resistant Enterococci.
      as well as a previous work in México that analyzed outpatient samples,
      • Cornejo-Juarez P.
      • Velásquez-Acosta C.
      • Díaz-Gonzalez A.
      • Volkow-Fernandez P.
      Trend of antimicrobial drug-susceptibility of blood isolates at an oncological center (1998-2003).
      E faecalis were the predominant (96.8%) specie. In contrast, a very low prevalence of E faecium strains (2.2%) was observed. Despite its lower presence in the community, previous reports of CA VRE have showed that E faecium is the main enterococci species that displays resistance to vancomycin.
      • Stevenson K.B.
      • Searle K.
      • Stoddard G.J.
      • Samore M.
      Methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci in rural communities, western United States.
      • Padiglione A.A.
      • Grabsch E.A.
      • Olden D.
      • Hellard M.
      • Sinclair M.I.
      • Fairley C.K.
      • et al.
      Fecal colonization with vancomycin-resistant enterococci in Australia.
      • Endtz H.P.
      • van den Braak N.
      • van Belkum A.
      • Kluytmans J.A.
      • Koeleman J.G.
      • Spanjaard L.
      • et al.
      Fecal carriage of vancomycin-resistant enterococci in hospitalized patients and those living in the community in The Netherlands.
      This is not consistent with what we observed in our work, because no statistically significant difference between species was found, suggesting that in our population, E faecalis is capable of developing resistance to vancomycin to a similar a degree as E faecium. Also, this species distribution strongly suggests that nosocomial strains could not be the main source of CA VRE in our work, because VRE E faecium is the most common nosocomial agent within the Enterococcus genus, both worldwide
      • Arias C.A.
      • Murray B.E.
      The rise of the Enterococcus: beyond vancomycin resistance.
      • Rubinstein E.
      • Keynan Y.
      Vancomycin-resistant Enterococci.
      and specifically in Querétaro City.
      • Leo-Amador G.E.
      • Borbolla-Ramos A.
      • Morales-Lara J.A.
      • Pérez-González H.A.
      • Hernandez-Montiel H.L.
      • Solis-S J.C.
      Infection or colonization and antimicrobial susceptibility of Enterococcus spp at a regional hospital in Queretaro, Mexico.
      Thus, a plausible explanation for the presence of VRE in the community could be antibiotic misuse, which was identified in 2010 and that resulted in Mexican authorities establishing new guidelines to regulate the sale and dispensing of antibiotics.

      DOF. [Agreement that establishes the guidelines that shall be followed to sale and dispense antibiotics. Ministry of Health. Official Journal of the Federation. Mexico. May 27th, 2010]. Available from: http://dof.gob.mx/nota_detalle.php?codigo=5144336&fecha=27/05/2010. Accessed February 8, 2014.

      It has previously been suggested that a predictor of VRE isolates in CA infections could be the use of antibiotics such as cephalosporins and fluoroquinolones within 3 months before their identification.
      • Endtz H.P.
      • van den Braak N.
      • van Belkum A.
      • Kluytmans J.A.
      • Koeleman J.G.
      • Spanjaard L.
      • et al.
      Fecal carriage of vancomycin-resistant enterococci in hospitalized patients and those living in the community in The Netherlands.
      The resistance profiles to the antimicrobials considered by the CSLI were compared between enterococcal CUTI and CAC. No statistical differences between proportions were observed in the resistance to each antibiotic, with the exception of HLR gentamicin (CUTI 41.5% vs CAC 26.8%; P ≤ .05). Based on its therapeutic usefulness, antimicrobials were considered acceptable if ≤30% of the isolates were resistant to each. Nitrofurantoin (2.7%), linezolid (11.3%), and ampicillin (15%) met this criteria. The antibiotics with >30% resistant isolates were rifampicin (34.2%), ciprofloxacin (34.6%), HLR gentamicin (35.4%), levofloxacin (36.6%), HLR streptomycin (48.3%), and erythromycin (83.5%). Regarding ampicillin, resistance observed in our study was comparable to the 13% described in CA urinary infections in a previous Mexican work.
      • Cornejo-Juarez P.
      • Velásquez-Acosta C.
      • Díaz-Gonzalez A.
      • Volkow-Fernandez P.
      Trend of antimicrobial drug-susceptibility of blood isolates at an oncological center (1998-2003).
      The resistance to β-lactam antibiotics observed can be considered still low. This is important because the use of this type of antibiotic, in synergistic combination with aminoglycosides, remains the first choice of treatment for severe enterococcal infections.
      • Rubinstein E.
      • Keynan Y.
      Vancomycin-resistant Enterococci.
      However, it is of concern that there was a lower sensibility to high doses of aminoglycosides. The effect of fewer therapeutic options derived from this trend toward increased resistance to HLR aminoglycosides has been pointed out by other researchers.
      • Arias C.A.
      • Murray B.E.
      The rise of the Enterococcus: beyond vancomycin resistance.
      • Rubinstein E.
      • Keynan Y.
      Vancomycin-resistant Enterococci.
      A total of 134 isolates met the criteria for the MDR analysis, of which 128 (95.5%) were E faecalis. Twelve isolates (8.9%) were MDR (resistant to 3 or more antimicrobial categories). Resistance to 5 antimicrobial categories was the highest level of resistance. Within these MDR isolates, 5 (42%) were VRE and all belonged to the E faecalis species. As for the type of isolate, CUTI prevailed (9 isolates, 75%), although no statistical difference between proportions of CUTI and CAC was found. The proportion of VRE observed increased in relation to the resistance to a greater number of antimicrobial categories (16%, 33%, and 100% of the isolates resistant to 3, 4, and 5 antimicrobial categories were VRE, respectively).
      It is important to emphasize that the presence of vancomycin resistance—together with resistance to other clinically useful antibiotics in CA enterococci strains—lessens the therapeutic options in case of infection.
      Ours is the first report of VRE isolated from community samples in Latin America, and we showed a 6.7% frequency and up to 42% association to MDR, with E faecalis being the predominant species found. Our work suggests that the mechanisms for the selection of resistance to vancomycin are present in the community. This could be the result of antibiotic misuse in the country. Further epidemiologic studies regarding emergence of VRE at the community level should be done to identify risk factors and establish appropriate strategies of prevention, control, and eradication.

      Acknowledgments

      We gratefully acknowledge A. Vázquez-Mellado, N. Pacheco-Hernández, S. Arteaga-Rodríguez, J.M. Ruiz-Acosta, A. Martínez-Quiroz, and L. Esparza-Silva for facilitating access to the data collected.

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      1. DOF. [Agreement that establishes the guidelines that shall be followed to sale and dispense antibiotics. Ministry of Health. Official Journal of the Federation. Mexico. May 27th, 2010]. Available from: http://dof.gob.mx/nota_detalle.php?codigo=5144336&fecha=27/05/2010. Accessed February 8, 2014.