BMC Infectious Diseases | |
Genetic relatedness and risk factor analysis of ampicillin-resistant and high-level gentamicin-resistant enterococci causing bloodstream infections in Tanzanian children | |
Bjørn Blomberg2  Nina Langeland2  Roland Jureen3  Rob Willems5  Karim P Manji1  Samuel Maselle4  Stein Christian Mohn2  Håvard Aamodt2  | |
[1] Department of Pediatrics and Child Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania;Center for Tropical Infectious Diseases, Department of Medicine, Haukeland University Hospital, Bergen, Norway;National University Health System, Singapore City, Singapore;Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania;Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands | |
关键词: Africa; Tanzania; Multilocus sequence typing; Pulsed-field gel electrophoresis; Bacteremia; Sepsis; Microbial drug resistance; Enterococcus faecium; Enterococcus faecalis; Enterococcus; | |
Others : 1135651 DOI : 10.1186/s12879-015-0845-8 |
|
received in 2014-09-30, accepted in 2015-02-19, 发布年份 2015 | |
【 摘 要 】
Background
While enterococci resistant to multiple antimicrobials are spreading in hospitals worldwide, causing urinary tract, wound and bloodstream infections, there is little published data on these infections from Africa.
Methods
We assessed the prevalence, susceptibility patterns, clinical outcome and genetic relatedness of enterococcal isolates causing bloodstream infections in children in a tertiary hospital in Tanzania, as part of a prospective cohort study of bloodstream infections among 1828 febrile children admitted consecutively from August 2001 to August 2002.
Results
Enterococcal bacteraemia was identified in 2.1% (39/1828) of admissions, and in 15.3% (39/255) of cases of culture-confirmed bloodstream infections. The case-fatality rate in children with Enterococcus faecalis septicaemia (28.6%, 4/14) was not significantly different from those with Enterococcus faecium septicaemia (6.7%, 1/15, p = 0.12). E. faecium isolates commonly had combined ampicillin-resistance and high-level gentamicin resistance (HLGR), (9/17), while E. faecalis frequently displayed HLGR (6/15), but were ampicillin susceptible. None of the tested enterococcal isolates displayed vancomycin resistance by Etest or PCR for vanA and vanB genes. Multi-locus sequence-typing (MLST) showed that the majority of E. faecium (7/12) belonged to the hospital associated Bayesian Analysis of Population Structure (BAPS) group 3–3. Pulsed-field gel electrophoresis (PFGE) indicated close genetic relationship particularly among E. faecium isolates, but also among E. faecalis isolates. There was also correlation between BAPS group and PFGE results. Risk factors for enterococcal bloodstream infection in univariate analysis were hospital-acquired infection and clinical diagnosis of sepsis with unknown focus. In multivariate analysis, neonates in general were relatively protected from enterococcal infection, while both prematurity and clinical sepsis were risk factors. Malnutrition was a risk factor for enterococcal bloodstream infection among HIV negative children.
Conclusion
This is the first study to describe bloodstream infections caused by ampicillin-resistant HLGR E. faecium and HLGR E. faecalis in Tanzania. The isolates of E. faecium and E. faecalis, respectively, showed high degrees of relatedness by genotyping using PFGE. The commonly used treatment regimens at the hospital are insufficient for infections caused by these microbes. The study results call for increased access to microbiological diagnostics to guide rational antibiotic use in Tanzania.
【 授权许可】
2015 Aamodt et al.; licensee BioMed Central.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150311020440120.pdf | 781KB | download | |
Figure 1. | 106KB | Image | download |
【 图 表 】
Figure 1.
【 参考文献 】
- [1]Sghir A, Gramet G, Suau A, Rochet V, Pochart P, Dore J: Quantification of bacterial groups within human fecal flora by oligonucleotide probe hybridization. Appl Environ Microbiol 2000, 66(5):2263-6.
- [2]Damborg P, Top J, Hendrickx AP, Dawson S, Willems RJ, Guardabassi L: Dogs are a reservoir of ampicillin-resistant Enterococcus faecium lineages associated with human infections. Appl Environ Microbiol 2009, 75(8):2360-5.
- [3]Witte W, Wirth R, Klare I: Enterococci. Chemotherapy 1999, 45(2):135-45.
- [4]Low DE, Keller N, Barth A, Jones RN: Clinical prevalence, antimicrobial susceptibility, and geographic resistance patterns of enterococci: results from the SENTRY Antimicrobial Surveillance Program, 1997–1999. Clin Infect Dis 2001, 32(Suppl 2):S133-45.
- [5]Treitman AN, Yarnold PR, Warren J, Noskin GA: Emerging incidence of Enterococcus faecium among hospital isolates (1993 to 2002). J Clin Microbiol 2005, 43(1):462-3.
- [6]Bonten MJ, Willems RJ: [Vancomycin-resistant enterococcus–chronicle of a foretold problem]. Nederlands Tijdschrift Voor Geneeskunde 2012, 156(38):A5233.
- [7]Oppenheim BA: The changing pattern of infection in neutropenic patients. J Antimicrob Chemother 1998, 41 Suppl D:7-11.
- [8]Pedro-Botet ML, Modol JM, Valles X, Romeu J, Sopena N, Gimenez M, et al.: Changes in bloodstream infections in HIV-positive patients in a university hospital in Spain (1995–1997). Int J Infect Dis 2002, 6(1):17-22.
- [9]Kristich CJ, Little JL, Hall CL, Hoff JS: Reciprocal regulation of cephalosporin resistance in Enterococcus faecalis. mBio 2011, 2(6):e00199-00111.
- [10]Kristich CJ, Little JL: Mutations in the beta subunit of RNA polymerase alter intrinsic cephalosporin resistance in Enterococci. Antimicrob Agents Chemother 2012, 56(4):2022-7.
- [11]Georgopapadakou NH, Liu FY: Binding of beta-lactam antibiotics to penicillin-binding proteins of Staphylococcus aureus and Streptococcus faecalis: relation to antibacterial activity. Antimicrob Agents Chemother 1980, 18(5):834-6.
- [12]Moellering RC Jr, Weinberg AN: Studies on antibiotic syngerism against enterococci. II. Effect of various antibiotics on the uptake of 14 C-labeled streptomycin by enterococci. J Clin Invest 1971, 50(12):2580-4.
- [13]Paterson DL: “Collateral damage” from cephalosporin or quinolone antibiotic therapy. Clin Infect Dis 2004, 38(Suppl 4):S341-5.
- [14]Pallares R, Pujol M, Pena C, Ariza J, Martin R, Gudiol F: Cephalosporins as risk factor for nosocomial Enterococcus faecalis bacteremia. A matched case–control study. Arch Intern Med 1993, 153(13):1581-6.
- [15]Dahms RA, Johnson EM, Statz CL, Lee JT, Dunn DL, Beilman GJ: Third-generation cephalosporins and vancomycin as risk factors for postoperative vancomycin-resistant enterococcus infection. Arch Surg 1998, 133(12):1343-6.
- [16]Willems RJ, Top J, van Santen M, Robinson DA, Coque TM, Baquero F, et al.: Global spread of vancomycin-resistant Enterococcus faecium from distinct nosocomial genetic complex. Emerg Infect Dis 2005, 11(6):821-8.
- [17]Cattoir V, Leclercq R: Twenty-five years of shared life with vancomycin-resistant enterococci: is it time to divorce? J Antimicrob Chemother 2013, 68(4):731-42.
- [18]Huycke MM, Sahm DF, Gilmore MS: Multiple-drug resistant enterococci: the nature of the problem and an agenda for the future. Emerg Infect Dis 1998, 4(2):239-49.
- [19]McCracken M, Wong A, Mitchell R, Gravel D, Conly J, Embil J, et al.: Molecular epidemiology of vancomycin-resistant enterococcal bacteraemia: results from the Canadian Nosocomial Infection Surveillance Program, 1999–2009. J Antimicrob Chemother 2013, 68(7):1505-9.
- [20]Hsieh YC, Lee WS, Ou TY, Hsueh PR: Clonal spread of CC17 vancomycin-resistant Enterococcus faecium with multilocus sequence type 78 (ST78) and a novel ST444 in Taiwan. Eur J Clin Microbiol Infect Dis 2010, 29(1):25-30.
- [21]Laverde Gomez JA, van Schaik W, Freitas AR, Coque TM, Weaver KE, Francia MV, et al.: A multiresistance megaplasmid pLG1 bearing a hylEfm genomic island in hospital Enterococcus faecium isolates. Int J Med Microbiol 2011, 301(2):165-75.
- [22]Top J, Willems R, Blok H, de Regt M, Jalink K, Troelstra A, et al.: Ecological replacement of Enterococcus faecalis by multiresistant clonal complex 17 Enterococcus faecium. Clin Microbiol Infect 2007, 13(3):316-9.
- [23]Willems RJ, Top J, van Schaik W, Leavis H, Bonten M, Siren J, et al.: Restricted gene flow among hospital subpopulations of Enterococcus faecium. mBio 2012, 3(4):e00151-00112.
- [24]Lebreton F, van Schaik W, McGuire AM, Godfrey P, Griggs A, Mazumdar V, et al.: Emergence of epidemic multidrug-resistant Enterococcus faecium from animal and commensal strains. mBio 2013, 4(4):e00534-13.
- [25]Patterson JE, Barry M, Gallant J, Mangine LS, Farrel P, Latif A: Epidemiology of high-level gentamicin resistant enterococcal isolates from Zimbabwe. Am J Trop Med Hyg 1990, 43(4):397-9.
- [26]Keddy KH, Klugman KP, Liebowitz LD: Incidence of high-level gentamicin resistance in enterococci at Johannesburg Hospital. S Afr Med J 1996, 86(10):1273-6.
- [27]McCarthy KM, Van Nierop W, Duse A, Von Gottberg A, Kassel M, Perovic O, et al.: Control of an outbreak of vancomycin-resistant Enterococcus faecium in an oncology ward in South Africa: effective use of limited resources. J Hosp Infect 2000, 44(4):294-300.
- [28]Chingwaru W, Mpuchane SF, Gashe BA: Enterococcus faecalis and Enterococcus faecium isolates from milk, beef, and chicken and their antibiotic resistance. J Food Prot 2003, 66(6):931-6.
- [29]Blomberg B, Manji KP, Urassa WK, Tamim BS, Mwakagile DS, Jureen R, et al.: Antimicrobial resistance predicts death in Tanzanian children with bloodstream infections: a prospective cohort study. BMC Infect Dis 2007, 7:43. BioMed Central Full Text
- [30]IMCI Integrated Management of Childhood Illness. Model Chapter for Textbooks. Document no. WHO/FCH/CAH/01.01. Accessible from http://whqlibdoc.who.int/hq/2001/WHO_FCH_CAH_01.01.pdf. Geneva: World Health Organization; 2001.
- [31]Collee JG, Marmion BP, Irvine R, Fraser AG, Simmons A: Mackie & McCartney Practical Medical Microbiology. 14th edition. Churchill Livingstone, New York; 1996.
- [32]Angeletti S, Lorino G, Gherardi G, Battistoni F, De Cesaris M, Dicuonzo G: Routine molecular identification of enterococci by gene-specific PCR and 16S ribosomal DNA sequencing. J Clin Microbiol 2001, 39(2):794-7.
- [33]NCCLS. Performance standards for antimicrobial disk susceptibility tests. Approved standard M2-M7. Wayne, Pa, USA 1997 (7th edition).
- [34]Murray BE, Singh KV, Heath JD, Sharma BR, Weinstock GM: Comparison of genomic DNAs of different enterococcal isolates using restriction endonucleases with infrequent recognition sites. J Clin Microbiol 1990, 28(9):2059-63.
- [35]Dahl KH, Simonsen GS, Olsvik O, Sundsfjord A: Heterogeneity in the vanB gene cluster of genomically diverse clinical strains of vancomycin-resistant enterococci. Antimicrob Agents Chemother 1999, 43(5):1105-10.
- [36]Homan WL, Tribe D, Poznanski S, Li M, Hogg G, Spalburg E, et al.: Multilocus sequence typing scheme for Enterococcus faecium. J Clin Microbiol 2002, 40(6):1963-71.
- [37]Siegman-Igra Y, Fourer B, Orni-Wasserlauf R, Golan Y, Noy A, Schwartz D, et al.: Reappraisal of community-acquired bacteremia: a proposal of a new classification for the spectrum of acquisition of bacteremia. Clin Infect Dis 2002, 34(11):1431-9.
- [38]Masinde A, Gumodoka B, Kilonzo A, Mshana SE: Prevalence of urinary tract infection among pregnant women at Bugando Medical Centre, Mwanza, Tanzania. Tanzan J Health Res 2009, 11(3):154-9.
- [39]Moyo SJ, Aboud S, Kasubi M, Maselle SY: Bacterial isolates and drug susceptibility patterns of urinary tract infection among pregnant women at Muhimbili National Hospital in Tanzania. Tanzan J Health Res 2010, 12(4):236-40.
- [40]Iwen PC, Kelly DM, Linder J, Hinrichs SH, Dominguez EA, Rupp ME, et al.: Change in prevalence and antibiotic resistance of Enterococcus species isolated from blood cultures over an 8-year period. Antimicrob Agents Chemother 1997, 41(2):494-5.