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Erschienen in: Wiener klinische Wochenschrift 11-12/2016

01.06.2016 | original article

Emergence of multidrug-resistant Proteus mirabilis in a long-term care facility in Croatia

verfasst von: Branka Bedenić, Nataša Firis, Vesna Elveđi-Gašparović, Marija Krilanović, Krešimir Matanović, Iva Štimac, Josefa Luxner, Jasmina Vraneš, Tomislav Meštrović, Gernot Zarfel, Andrea Grisold

Erschienen in: Wiener klinische Wochenschrift | Ausgabe 11-12/2016

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Summary

Background

An increased frequency of Proteus mirabilis isolates resistant to expanded-spectrum cephalosporins was observed recently in a long-term care facility in Zagreb (Godan). The aim of this study was the molecular characterization of resistance mechanisms to new cephalosporins in P. mirabilis isolates from this nursing home.

Methods

Thirty-eight isolates collected from 2013–2015 showing reduced susceptibility to ceftazidime were investigated. Antibiotic susceptibilities were determined by broth microdilution method. Inhibitor-based tests were performed to detect extended-spectrum (ESBLs) and AmpC β-lactamases. AmpC β-lactamases were characterized by polymerase chain reaction (PCR) followed by sequencing of bla ampC genes. Quinolone resistance determinants (qnr genes) were characterized by PCR. Genotyping of the isolates was performed by repetitive element sequence (rep)-PCR and pulsed-field gel electrophoresis (PFGE).

Results

Presence of an AmpC β-lactamase was confirmed in all isolates by combined-disk test with phenylboronic acid. All isolates were resistant to amoxicillin alone and combined with clavulanate, cefotaxime, ceftriaxone, cefoxitin, and ciprofloxacin; but susceptible to cefepime, imipenem, and meropenem. PCR followed by sequencing using primers targeting bla ampc genes revealed CMY-16 β-lactamase in all but one strain. Bla cmy-16 was carried by a non-conjugative plasmid which did not belong to any known plasmid-based replicon typing (PBRT) group. Rep-PCR identified one large clone consisting of 15 isolates, three pairs or related isolates, one triplet, and four singletons. PFGE confirmed the clonality of the isolates.

Conclusions

This is the first report of multidrug resistant P. mirabilis in a nursing home in Croatia. Cephalosporin resistance was due to plasmid-mediated AmpC β-lactamase CMY-16.
Literatur
1.
Zurück zum Zitat Grover CN, Sahni BAK, Bhattacharya CS. Therapeutic challenges of ESBLs and AmpC β-lactamase producers in a tertiary care center. Med J Armed Forces. 2013;69:4–10.CrossRef Grover CN, Sahni BAK, Bhattacharya CS. Therapeutic challenges of ESBLs and AmpC β-lactamase producers in a tertiary care center. Med J Armed Forces. 2013;69:4–10.CrossRef
2.
Zurück zum Zitat Bush K. Is it important to identify extended-spectrum β-lactamase-producing isolates? Eur J Clin Microbiol Infect Dis. 1996;15:361–4.CrossRefPubMed Bush K. Is it important to identify extended-spectrum β-lactamase-producing isolates? Eur J Clin Microbiol Infect Dis. 1996;15:361–4.CrossRefPubMed
3.
Zurück zum Zitat Phillipon A, Arlet G, Lagrange H. Origin and impact of plasmid-mediated extended-spectrum β-lactamases. Eur J Clin Microbiol Infect Dis. 1994;13(Suppl 1):17–29.CrossRef Phillipon A, Arlet G, Lagrange H. Origin and impact of plasmid-mediated extended-spectrum β-lactamases. Eur J Clin Microbiol Infect Dis. 1994;13(Suppl 1):17–29.CrossRef
4.
Zurück zum Zitat Tan TJ, Yong NG, Koh TK, Hsu LY. Evaluation of screening methods to detect plasmid-mediated AmpC in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis. Antimicrob Agents Chemother. 2009;53:146–9.CrossRefPubMed Tan TJ, Yong NG, Koh TK, Hsu LY. Evaluation of screening methods to detect plasmid-mediated AmpC in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis. Antimicrob Agents Chemother. 2009;53:146–9.CrossRefPubMed
5.
Zurück zum Zitat Datta P, Gupta V, Arora S, Garg S, Chander J. Epidemiology of extended-spectrum β-lactamase, AmpC, and carbapenemase production in Proteus mirabilis. Jpn J Infect Dis. 2014;67:44–6.CrossRefPubMed Datta P, Gupta V, Arora S, Garg S, Chander J. Epidemiology of extended-spectrum β-lactamase, AmpC, and carbapenemase production in Proteus mirabilis. Jpn J Infect Dis. 2014;67:44–6.CrossRefPubMed
7.
Zurück zum Zitat Sardelić S, Bedenić B, Šijak D, Colinon C, Kalenić S. Emergence of Proteus mirabilis isolates producing TEM-52 β-lactamase in Croatia. Chemotherapy. 2010;56:208–13.CrossRefPubMed Sardelić S, Bedenić B, Šijak D, Colinon C, Kalenić S. Emergence of Proteus mirabilis isolates producing TEM-52 β-lactamase in Croatia. Chemotherapy. 2010;56:208–13.CrossRefPubMed
8.
Zurück zum Zitat Tonkic M, Mohar B, Sisko-Kraljević K, Mesko-Meglic K, Goić-Barisić I, Novak A, Kovacić A, Punda-Polić V. High prevalence and molecular characterization of extended-spectrum β-lactamase-producing Proteus mirabilis isolates in southern Croatia. J Med Microbiol. 2010;59:1185–90.CrossRefPubMed Tonkic M, Mohar B, Sisko-Kraljević K, Mesko-Meglic K, Goić-Barisić I, Novak A, Kovacić A, Punda-Polić V. High prevalence and molecular characterization of extended-spectrum β-lactamase-producing Proteus mirabilis isolates in southern Croatia. J Med Microbiol. 2010;59:1185–90.CrossRefPubMed
9.
Zurück zum Zitat CLSI. Clinical and Laboratory Standards Institute Performance Standards for Antimicrobial Susceptibility Testing. 21st informational supplement. Wayne, PA: CLSI; 2011, pp. M100–21. CLSI. Clinical and Laboratory Standards Institute Performance Standards for Antimicrobial Susceptibility Testing. 21st informational supplement. Wayne, PA: CLSI; 2011, pp. M100–21.
10.
Zurück zum Zitat Jarlier V, Nicolas MH, Fournier G, Philippon A. Extended broad-spectrum β-lactamases conferring transferable resistance to newer β-lactam agents in Enterobacteriaceae: hospital prevalence and susceptibility patterns. Rev Infect Dis. 1998;10:867–78.CrossRef Jarlier V, Nicolas MH, Fournier G, Philippon A. Extended broad-spectrum β-lactamases conferring transferable resistance to newer β-lactam agents in Enterobacteriaceae: hospital prevalence and susceptibility patterns. Rev Infect Dis. 1998;10:867–78.CrossRef
11.
Zurück zum Zitat Coudron PE. Inhibitor-based methods for detection of plasmid-mediated AmpC β-lactamases in Klebsiella spp., Escherichia coli and Proteus mirabilis. J Clin Microbiol. 2005;43:4163–7.CrossRefPubMedPubMedCentral Coudron PE. Inhibitor-based methods for detection of plasmid-mediated AmpC β-lactamases in Klebsiella spp., Escherichia coli and Proteus mirabilis. J Clin Microbiol. 2005;43:4163–7.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Elwell S, Falkow LP. The characterization of R plasmids and the detection of plasmid-specified genes. In: Lorian V, editor. Antibiotics in Laboratory Medicine, 2nd edn. Baltimore: Williams and Wilkins; 1986. pp. 683–721. Elwell S, Falkow LP. The characterization of R plasmids and the detection of plasmid-specified genes. In: Lorian V, editor. Antibiotics in Laboratory Medicine, 2nd edn. Baltimore: Williams and Wilkins; 1986. pp. 683–721.
13.
Zurück zum Zitat Nüesch-Inderbinen MT, Haechler H, Kayser FH. Detection of genes coding for extended-spectrum SHV β-lactamases in clinical isolates by a molecular genetic method, and comparison with the E test. Eur J Clin Microbiol Infect Dis. 1996;15:398–402.CrossRefPubMed Nüesch-Inderbinen MT, Haechler H, Kayser FH. Detection of genes coding for extended-spectrum SHV β-lactamases in clinical isolates by a molecular genetic method, and comparison with the E test. Eur J Clin Microbiol Infect Dis. 1996;15:398–402.CrossRefPubMed
14.
Zurück zum Zitat Arlet G, Brami D, Decre D, Flippo A, Gaillot O, Lagrange PH, Philippon A. Molecular characterization by PCR restriction fragment polymorphism of TEM β-lactamases. FEMS Microbiol Lett. 1995;134:203–8.PubMed Arlet G, Brami D, Decre D, Flippo A, Gaillot O, Lagrange PH, Philippon A. Molecular characterization by PCR restriction fragment polymorphism of TEM β-lactamases. FEMS Microbiol Lett. 1995;134:203–8.PubMed
15.
Zurück zum Zitat Woodford N, Ward ME, Kaufmann ME, Turton J, Fagan EJ, James D, Johnson AP, Pike R, Warner M, Cheasty T, Pearson A, Harry S, Leach JB, Loughrey A, Lowes JA, Warren RE, Livermore DM. Community and hospital spread of Escherichia coli producing CTX-M extended-spectrum β-lactamases in the UK. J Antimicrob Chemother. 2004;54:735–43.CrossRefPubMed Woodford N, Ward ME, Kaufmann ME, Turton J, Fagan EJ, James D, Johnson AP, Pike R, Warner M, Cheasty T, Pearson A, Harry S, Leach JB, Loughrey A, Lowes JA, Warren RE, Livermore DM. Community and hospital spread of Escherichia coli producing CTX-M extended-spectrum β-lactamases in the UK. J Antimicrob Chemother. 2004;54:735–43.CrossRefPubMed
16.
Zurück zum Zitat Pagani L, Mantengoli E, Migliavacca R, Nucleo E, Pollini S, Spalla M, Daturi R, Romero E, Rossolini GM. Multifocal detection of multidrug-resistant Pseudomonas aeruginosa producing PER-1 extended-spectrum β-lactamase in Northern Italy. J Clin microbiol. 2004;42:2523–9.CrossRefPubMedPubMedCentral Pagani L, Mantengoli E, Migliavacca R, Nucleo E, Pollini S, Spalla M, Daturi R, Romero E, Rossolini GM. Multifocal detection of multidrug-resistant Pseudomonas aeruginosa producing PER-1 extended-spectrum β-lactamase in Northern Italy. J Clin microbiol. 2004;42:2523–9.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Perez-Perez FJ, Hanson ND. Detection of plasmid-mediated AmpC β-lactamase genes in clinical isolates by using multiplex PCR. J Clin Microbiol. 2002;40:2153–62.CrossRefPubMedPubMedCentral Perez-Perez FJ, Hanson ND. Detection of plasmid-mediated AmpC β-lactamase genes in clinical isolates by using multiplex PCR. J Clin Microbiol. 2002;40:2153–62.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Hanson ND, Moland ES, Hossain A, Neville SA, Gosbell IB, Unusual TKS. Salmonella enterica serotype typhimurium isolate producing CMY-7, SHV-9 and OXA-30 β-lactamases. J Antimicrob Chemother. 2002;49(6):1011–4.CrossRefPubMed Hanson ND, Moland ES, Hossain A, Neville SA, Gosbell IB, Unusual TKS. Salmonella enterica serotype typhimurium isolate producing CMY-7, SHV-9 and OXA-30 β-lactamases. J Antimicrob Chemother. 2002;49(6):1011–4.CrossRefPubMed
19.
Zurück zum Zitat Saladin M, Cao VY, Lambert T. Diversity of CTX-M beta-lactamases and their promoter regions from Enterobacteriaceae isolated in three Parisian hospitals. FEMS Microbiol Lett. 2002;209:161–8.PubMed Saladin M, Cao VY, Lambert T. Diversity of CTX-M beta-lactamases and their promoter regions from Enterobacteriaceae isolated in three Parisian hospitals. FEMS Microbiol Lett. 2002;209:161–8.PubMed
20.
Zurück zum Zitat Robischek A, Jacoby GA, Hooper DC. The worldwide emergence of plasmid-mediated quinolone resistance. Lancet Infect Dis. 2006;6:629–40.CrossRef Robischek A, Jacoby GA, Hooper DC. The worldwide emergence of plasmid-mediated quinolone resistance. Lancet Infect Dis. 2006;6:629–40.CrossRef
21.
Zurück zum Zitat Carattoli A, Bertini L, Villa L, Falbo V, Hopkins KL, Threfall EJ. Identification of plasmids by PCR-based replicon typing. J Microbiol Methods. 2005;63:219.CrossRefPubMed Carattoli A, Bertini L, Villa L, Falbo V, Hopkins KL, Threfall EJ. Identification of plasmids by PCR-based replicon typing. J Microbiol Methods. 2005;63:219.CrossRefPubMed
22.
Zurück zum Zitat Overdevest S, Willemsen C, Elberts M, Verhulsts P, Rijnsburger J, Savelkoulnd A, Kluytmans JW. Evaluation of the DiversiLab Typing Method in a Multicenter Study. Assessing Horizontal Spread of Highly Resistant Gram-Negative Rods. J Clin Microbiol. 2011;49:3551–54.CrossRefPubMedPubMedCentral Overdevest S, Willemsen C, Elberts M, Verhulsts P, Rijnsburger J, Savelkoulnd A, Kluytmans JW. Evaluation of the DiversiLab Typing Method in a Multicenter Study. Assessing Horizontal Spread of Highly Resistant Gram-Negative Rods. J Clin Microbiol. 2011;49:3551–54.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Kaufman ME. Pulsed-Field Gel Electrophoresis. In: Woodford N, Johnsons A, editors. Molecular bacteriology. Protocols and clinical applications, 1st edn. New York: Humana Press Inc.; 1998. pp. 33–51. Kaufman ME. Pulsed-Field Gel Electrophoresis. In: Woodford N, Johnsons A, editors. Molecular bacteriology. Protocols and clinical applications, 1st edn. New York: Humana Press Inc.; 1998. pp. 33–51.
24.
Zurück zum Zitat Tenover F, Arbeit R, Goering RV, Mickelsen PA, Murray BE, Persing DH, Swaminthan B. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol. 1995;33:2233–9.PubMedPubMedCentral Tenover F, Arbeit R, Goering RV, Mickelsen PA, Murray BE, Persing DH, Swaminthan B. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol. 1995;33:2233–9.PubMedPubMedCentral
25.
Zurück zum Zitat Black JA, Moland ES, Thomson KA. AmpC disk test for identification of plasmid-mediated-AmpC β-lactamases in Enterobacteriaceae lacking chromosomal AmpC β-lactamase. J Clin Microbiol. 2005;43:3110–3.CrossRefPubMedPubMedCentral Black JA, Moland ES, Thomson KA. AmpC disk test for identification of plasmid-mediated-AmpC β-lactamases in Enterobacteriaceae lacking chromosomal AmpC β-lactamase. J Clin Microbiol. 2005;43:3110–3.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat D’Andrea MM, Literacka E, Zioga A, Giani T, Baraniak A, Fiett J, Sadowi E, Tassios T, Rossolini GM, Gniadkowski M, Miriagou V. Evolution and spread of multidrug-resistant Proteus mirabilis clone with chromosomal AmpC β-lactamase in Europe. Antimicrob Agents Chemother. 2011;55:2735–42.CrossRefPubMedPubMedCentral D’Andrea MM, Literacka E, Zioga A, Giani T, Baraniak A, Fiett J, Sadowi E, Tassios T, Rossolini GM, Gniadkowski M, Miriagou V. Evolution and spread of multidrug-resistant Proteus mirabilis clone with chromosomal AmpC β-lactamase in Europe. Antimicrob Agents Chemother. 2011;55:2735–42.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Giakoupi P, Tambić-Andrašević A, Vourli S, Škrlin J, Šestan-Crnek S, Tzouvelekis LS, Vatoupoulos AC. Transferable DHA-1 cephalosporinase in Escherichia coli. Int J Antimicrob Agents. 2006;27:77–80.CrossRef Giakoupi P, Tambić-Andrašević A, Vourli S, Škrlin J, Šestan-Crnek S, Tzouvelekis LS, Vatoupoulos AC. Transferable DHA-1 cephalosporinase in Escherichia coli. Int J Antimicrob Agents. 2006;27:77–80.CrossRef
28.
Zurück zum Zitat Rubić Ž, Soprek S, Jelić M, Radić M, Novak A, GoićBarišić I, Tonkić M, Tambić-Andrašević A. The first detection of plasmid-mediated AmpC β-lactamase in multidrug-resistant Proteus mirabilis isolates from University Hospital Split, Croatia 24th European congress of clinical Microbiology and Infectios Diseases, Barcelona, Spain. 2014. Rubić Ž, Soprek S, Jelić M, Radić M, Novak A, GoićBarišić I, Tonkić M, Tambić-Andrašević A. The first detection of plasmid-mediated AmpC β-lactamase in multidrug-resistant Proteus mirabilis isolates from University Hospital Split, Croatia 24th European congress of clinical Microbiology and Infectios Diseases, Barcelona, Spain. 2014.
29.
Zurück zum Zitat Bedenić B, Matanović K, Mekić S, Varda-Brkić D, Šeol-Martinac B. Coproduction of CTX-M-15 and CMY-2 in animal Escherichia coli isolate from Croatia 24th European congress of clinical Microbiology and Infectios Diseases, Barcelona, Spain. 2014. Bedenić B, Matanović K, Mekić S, Varda-Brkić D, Šeol-Martinac B. Coproduction of CTX-M-15 and CMY-2 in animal Escherichia coli isolate from Croatia 24th European congress of clinical Microbiology and Infectios Diseases, Barcelona, Spain. 2014.
30.
Zurück zum Zitat Zujić-Atalić V, Bedenić B, Kocsis E, Mazzariol A, Sardelić S, Barišić M, Plečko V, Bošnjak Z, Mijač M, Jajić I, Vranić-Ladavac M, Cornaglia G. Diversity of carbapenemases in clinical isolates of Enterobacteriaceae in Croatia-the results of the multicenter study. Clin Microbiol Infect. 2004;20:894–903.CrossRef Zujić-Atalić V, Bedenić B, Kocsis E, Mazzariol A, Sardelić S, Barišić M, Plečko V, Bošnjak Z, Mijač M, Jajić I, Vranić-Ladavac M, Cornaglia G. Diversity of carbapenemases in clinical isolates of Enterobacteriaceae in Croatia-the results of the multicenter study. Clin Microbiol Infect. 2004;20:894–903.CrossRef
31.
Zurück zum Zitat Literacka E, Empel J, Baraniak A, Sadowy E, Hryniewic W, Gniadkowski M. Four variants of the Citrobacter freundii AmpC type cephalosporinase including tow novel enzymes, CMY-14 and CMY-15 in a Proteus mirabilis clone widespread in Poland. Antimicrob Agents Chemother. 2004;48:4136–43.CrossRefPubMedPubMedCentral Literacka E, Empel J, Baraniak A, Sadowy E, Hryniewic W, Gniadkowski M. Four variants of the Citrobacter freundii AmpC type cephalosporinase including tow novel enzymes, CMY-14 and CMY-15 in a Proteus mirabilis clone widespread in Poland. Antimicrob Agents Chemother. 2004;48:4136–43.CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Migliavacca R, Migliavacca A, Nucleo E, Ciaponi A, Spalla M, Luca C De, Pagani L. Molecular epidemiology of ESBL producing Proteus miraiblis isolates from a long-term care and rehabilitation facility in Italy. New Microbiol. 2007;30:362–366.PubMed Migliavacca R, Migliavacca A, Nucleo E, Ciaponi A, Spalla M, Luca C De, Pagani L. Molecular epidemiology of ESBL producing Proteus miraiblis isolates from a long-term care and rehabilitation facility in Italy. New Microbiol. 2007;30:362–366.PubMed
33.
Zurück zum Zitat Tenover F, Emery SL, Spiegel CA. Identification of plasmid-mediated AmpC β-lactamases in Escherichia coli, Klebsiella spp and Proteus mirabilis can potentially improve reporting of cephalosporin susceptibility testing results. J Clin Microbiol. 2009;47:294–299.CrossRefPubMed Tenover F, Emery SL, Spiegel CA. Identification of plasmid-mediated AmpC β-lactamases in Escherichia coli, Klebsiella spp and Proteus mirabilis can potentially improve reporting of cephalosporin susceptibility testing results. J Clin Microbiol. 2009;47:294–299.CrossRefPubMed
34.
Zurück zum Zitat Luzzaro F. Spread of multidrug-resistant Proteus mirabilis isolates producing an AmpC-type β-lactamase:epidemiology and clinical management. Int J Antimicrob Agents. 2009;33:328–333.CrossRefPubMed Luzzaro F. Spread of multidrug-resistant Proteus mirabilis isolates producing an AmpC-type β-lactamase:epidemiology and clinical management. Int J Antimicrob Agents. 2009;33:328–333.CrossRefPubMed
Metadaten
Titel
Emergence of multidrug-resistant Proteus mirabilis in a long-term care facility in Croatia
verfasst von
Branka Bedenić
Nataša Firis
Vesna Elveđi-Gašparović
Marija Krilanović
Krešimir Matanović
Iva Štimac
Josefa Luxner
Jasmina Vraneš
Tomislav Meštrović
Gernot Zarfel
Andrea Grisold
Publikationsdatum
01.06.2016
Verlag
Springer Vienna
Erschienen in
Wiener klinische Wochenschrift / Ausgabe 11-12/2016
Print ISSN: 0043-5325
Elektronische ISSN: 1613-7671
DOI
https://doi.org/10.1007/s00508-016-1005-x

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