6. CONCLUSÕES
Os isolados de E. aerogenes apresentaram-se mais resistentes a amicacina e mais susceptíveis a gentamicina, enquanto que os isolados de K. pneumoniae apresentaram- se mais resistentes a gentamicina e mais susceptíveis a amicacina.
Nos isolados de K. pneumoniae o gene mais detectado foi o ant(2”)-Ia, seguido de aac(3)-IIa, aph(3’)-VI e aac(6’)-Ib.
Os isolados de E. aerogenes não apresentaram o gene aac(6’)-Ib, nesta espécie o aph(3’)-VI foi o gene mais detectado, seguido de aac(3)-IIa e ant(2”)-Ia.
Os genes codificadores de metiltransferases 16S rRNA (armA, rmtB e rmtD) e a acetiltransferase AAC(3)-Ia não foram detectados nos isolados estudados.
A concordância entre fenótipo e genótipo de resistência foi abaixo de 50% em ambas espécies, sugerindo a não expressão dos genes e a presença de outros mecanismos de resistência não pesquisados.
A maioria dos isolados de K. pneumoniae e E. aerogenes analisados, selecionados por serem resistentes a aminoglicosídeos e portadores do gene blaKPC-2, estavam
colonizando os pacientes. A presença desses isolados carreando genes para EMAs e KPC, principalmente colonizando pacientes, é alarmante, visto que essas bactérias podem atuar na disseminação de mecanismos de resistência dentro da unidade hospitalar.
Genes codificadores de EMAs estavam disseminados em isolados de K. pneumoniae e E. aerogenes provenientes dos quatro hospitais de Recife-PE. O acúmulo de determinantes de resistência pelos isolados podem limitar as opções terapêuticas disponíveis para o tratamento de infecções por essas bactérias, podendo explicar muitos episódios de insucesso na tentativa de controle das infecções hospitalares.
REFERÊNCIAS
ALEKSHUN, M. N.; LEVY, S. B. Molecular mechanisms of antibacterial multidrug resistance. Cell. v. 128, p. 1037–1050, 2007.
ALMAGHRABI, R.; CLANCY, C. J.; DOI, Y. Carbapenem-Resistant Klebsiella pneumoniae Strains Exhibit Diversity in Aminoglycoside-Modifying Enzymes, Which Exert Differing Effects on Plazomicin and Other Agents. Antimicrobial Agents and Chemotherapy. v. 58, p. 4443-51, 2014.
ALMEIDA, A. C. S. et al. First description of KPC-2-producing Pseudomonas putida in Brazil. Antimicrobial Agents and Chemotherapy. v. 56, p. 2205-2206, 2012a.
AL SHEIKH, Y. A.; MARIE, M. A.; JOHN, J. Prevalence of 16S rRNA methylase genes among β-lactamase-producing Enterobacteriaceae clinical isolates in Saudi Arabia. Libyan Journal of Medicine. v. 7; 9, p. 24432, 2014.
ANDERSON, K. F.; LONSWAY, D. R.; RASHEED, J. K.; BIDDLE, J.; JENSEN, B.; MCDOUGAL, L. K.; CAREY, R. B.; THOMPSON, A.; STOCKER, S.; LIMBAGO, B.; PATEL, J. B. Evaluation of methods to identify the Klebsiella pneumoniae carbapenemase in Enterobacteriaceae. Journal of Clinical Microbiology. v.45, p.2723- 2725, 2007.
ANDRADE, L. N. et al. Dissemination of blaKPC-2 by the spread of Klebsiella pneumoniae clonal complex 258 clones (ST258, ST11, ST437) and plasmids (IncFII, IncN, IncL/M) among Enterobacteriaceae species in Brazil. Antimicrobial Agents and Chemotherapy. v. 55, p. 3579-3583, 2011.
ANDRADE, L. N.; VITALI, L.; GASPAR, G. G. et al. Expansion and evolution of a virulent, extensively drugresistant (polymyxin B-resistant), QnrS1-, CTX-M-2-, and KPC-2-producing Klebsiella pneumoniae ST11 international high-risk clone. Journal of Clinical Microbiology. v. 52, p. 2530-5, 2014.
ANVISA - Agência Nacional de Vigilância Sanitária. Nota técnica nº 01/2013. Medidas de prevenção e controle de infecções por enterobactérias multirresistentes. 2013.
ANVISA - Agência Nacional de Vigilância Sanitária. Boletim Informativo nº07/2014. Segurança do Paciente e Qualidade em Serviços de Saúde. 2014.
AVENT, M. L. et al. Current use of aminoglycosides: indications, pharmacokinetics and monitoring for toxicity. Internal Medicine Journal. v. 41, n. 6, p. 441-449, 2011.
BEAUCLERK, A. A.; CUNDLIFFE, E. Sites of action of two ribosomal RNA methylases responsible for resistance to aminoglycosides. Journal of Molecular Biology. v.193, p. 661– 671, 1987.
BECKER, B.; COOPER, M.A. Aminoglycoside Antibiotics in the 21st Century. ACS Chemical Biology. v. 8, p. 105−115, 2013.
BIENDO, M.; CANARELLI, B.; THOMAS, D. et al. Successive Emergence of Extended- Spectrum β -Lactamase-Producing and Carbapenemase-Producing Enterobacter aerogenes Isolates in a University Hospital. Journal of Clinical Microbiology. v. 46, n. 3, p. 1037– 1044, 2008.
BOGAERTS, P.; GALIMAND, M.; BAURAING, C. et al. Emergence of ArmA and RmtB aminoglycoside resistance 16S rRNA methylases in Belgium. Journal of Antimicrobial Chemotherapy. v. 59, n. 3, p. 459-64, 2007.
BOGAERTS, P.; BOUCHAHROUF, W.; DE CASTRO, R. R. et al. Emergence of NDM-1- producing Enterobacteriaceae in Belgium. Antimicrobial Agents and Chemotherapy. v. 55(6), p. 3036-8, 2011.
BRATU, S.; LANDMAN, D.; ALAM, M. et al. Detection of KPC carbapenem-hydrolyzing enzymes in Enterobacter spp. from Brooklyn, New York. Antimicrobial Agents and Chemotherapy. v. 49(2), p. 776-778, 2005c.
BREMMER, D. N.; CLANCY, C. J.; PRESS, E. G. et al. KPC-Producing Klebsiella pneumoniae Strains That Harbor AAC(6’)-Ib Exhibit Intermediate Resistance to Amikacin. Antimicrobial Agents and Chemotherapy. v. 58, n.12, p. 7597–7600, 2014.
BROLUND, A.; EDQUIST, P. J.; MÄKITALO, B. et al. Epidemiology of extended-spectrum β-lactamase producing Escherichia coli in Sweden 2007-2011. Clinical Microbiology Infect. 20(6), p. 344-52, 2014.
BUENO, M. F. C.; FRANCISCO, G. R.; O´HARA, J. A. et al. Coproduction of 16S rRNA methyltransferase RmtD or RmtG with KPC-2 and CTX-M group extended-spectrum β- lactamases in Klebsiella pneumoniae. Antimicrobial Agents and Chemotherapy. v. 57, n. 5, p. 2397–2400, 2013.
CABRAL e LOPES. Klebsiella pneumoniae: mecanismos de resistência aos beta-lactâmicos. Novas Edições Acadêmicas. c.10, p. 63, 2014.
CABRAL, A. B.; MELO, R. C. A.; MACIEL, M. A. V.; LOPES, A. C. S. Multidrug resistance genes, including blaKPC and blaCTX-M-2, among Klebsiella pneumoniae isolated in Recife, Brazil. Revista da Sociedade Brasileira de Medicina Tropical, v. 45, p.572-578, 2012.
CALDWELL, A. S. J.; BERGHUISA, A. M. Small-angle x-ray scattering analysis of the bifunctional antibiotic resistance enzyme aminoglycoside (6’) acetyltransferase-Ie aminoglycoside (2’) phosphotransferase-Ia reveals a rigid solution structure. Antimicrobial Agents and Chemotherapy. p. 1899 –1906, 2012.
CARVALHAES, C. G.; CAYÔ, R.; GALES, A. C. Klebsiella pneumoniae carbapenemase- producing Klebsiella pneumoniae in the intensive care unit: a real challenge to physicians, scientific community, and society. Shock. 39 p. 32-7, 2013.
CHAMBERS, H. F.; SANDE, M. A.; Fármacos antimicrobianos: Os aminoglicosídeos. In: GOODMAN & GILMAN, (eds). As Bases Farmacológicas da Terapêutica, 9.ed, Rio de Janeiro-RJ, McGrawHill, cap. 46, p. 812-25, 1996.
CHANG, M. R.; BIBERG, C. A.; LOPES, F. A. et al. The first report of infection with Klebsiella pneumoniae carrying the bla(kpc) gene in State of Mato Grosso do Sul, Brazil. Revista da Sociedade Brasileira de Medicina Tropical. v. 46, p. 114-5, 2013.
CHEN, L. F.; ANDERSON, D. J.; PATERSON, D. L. Overview of the epidemiology and the threat of Klebsiella pneumoniae carbapenemases (KPC) resistance. Infection and Drug Resistance. v. 5, p. 133-141, 2012.
CHEVALIER, J., PAGÈS, J. M., AND MALLÉA, M. In vivo modification of porin activity conferring antibiotic resistance to Enterobacter aerogenes. Biochemical and Biophysical Research Communications. 266, p. 248–251, 1999.
CLINICAL AND LABORATORY STANDARDS INSTITUTE. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fourth Informational Supplement, CLSI M100- S24 Wayne, USA, 2014.
CUNDLIFFE E. How antibiotic-producing organisms avoid suicide. Annual Review Microbiology. v. 43, 207–33, 1989.
CUZON, G. et al. Worldwide diversity of Klebsiella pneumoniae that produce beta-lactamase blaKPC-2 gene. Emerging Infectious Diseases. v. 16, n. 9, p. 1349-1356, 2010.
DEL PELOSO, P. F.; BARROS, M. F. L.; SANTOS, F. A. Sepse por Serratia marcescens KPC. Jornal Brasileiro de Patologia e Medicina Laboratorial. v. 46, p. 365-367, 2010.
DEMYDCHUK, J.; OLIYNYK, Z.; FEDORENKO, V. Analysis of a kanamycin resis-tance gene (kmr) from Streptomyces kanamyceticus and a mutant with increased aminoglycoside resistance. Journal of Basic Microbiology. v. 38, p. 231–239, 1998.
DIAS-GOLÇALVES, V.; LENGRUBER, F.; FONSECA, B. et al. Detection and characterization of multidrug-resistant enterobacteria bearing aminoglycoside-modifying gene in a university hospital at Rio de Janeiro, Brazil, along three decades. Biomédica. v. 35, p. 117-24, 2015.
DIENE, S. M.; MERHEJ, V.; HENRY, M. et al. Ther hizome of the multidrug-resistant Enterobacteraerogenes genome reveals hownew “killerbugs” are created because of asympatric life style. Molecular Biology and Evolution. v. 30, p. 369–383, 2013.
DOI, Y.; J. WACHINO, K.; YAMANE, N. et al. Spread of novel aminoglycoside resistance gene aac(6′)-Iad among Acinetobacter clinical isolates in Japan. Antimicrobial Agents and Chemotherapy. v. 48, p. 2075-2080, 2004.
DOI, Y.; ARAKAWA, Y. 16S Ribosomal RNA Methylation: Emerging Resistance Mechanismo against Aminoglycosides. Clinical Infections Diseases. v.45, p. 88-94, 2007.
DOI, Y., D. DE OLIVEIRA GARCIA, J. ADAMS, AND D. L. PATERSON. Coproduction of novel 16S rRNA methylase RmtD and metallo-β-lactamase SPM-1 in a panresistant Pseudomonas aeruginosa isolate from Brazil. Antimicrobial Agents and Chemotherapy. v.51, p. 852-856, 2007.
DRAWZ, S. M.; BONOMO, R. A. Three decades of beta-lactamase inhibitors. Clinical microbiology reviews. v. 23, n. 1, p. 160-201, 2010.
DU, J.; LI, P.; LIU, H. Phenotypic and molecular characterization of multidrug resistant Klebsiella pneumoniae isolated from a university teaching hospital, China. PLoS One. v. 16;9(4), p. e95181, 2014.
DURANTE-MANGONI, E.; GRAMMATIKOS, A.; UTILI, R. et al. Do we still need the aminoglycosides¿ International Journal of Antimicrobial Agents. v.33, p. 201-2015, 2009.
ENDIMIANI, A.; CARIAS, L. L.; HUJER, A. M. et al. Presence of plasmid-mediated quinolone resistance in Klebsiella pneumoniae isolates possessing blaKPC in the United States. Antimicrobial Agents and Chemotherapy. v. 52, p. 2680-2, 2008.
FARMER, J. J. III, DAVIS, B. R., HICKMAN-BRENNER, F. W. et al. Biochemical identification of new species and biogroups of Enterobacteriaceae isolated from clinical specimens. Journal Clinical.Microbiology. v. 21, p. 46–76, 1985.
FEHLBERG, L. C.; CARVALHO, A. M.; CAMPANA, E. H. et al. Emergence of Klebsiella pneumoniae - producing KPC-2 carbapenemase in Paraíba, Northeastern Brazil. Brazilian Journal of Infectious Diseases. v. 16, p. 577-80, 2012.
FOLSTER, J. P.; RICKERT, R.; BARZILAY, E. J. et al. Identification of the aminoglycoside resistance determinants armA and rmtC among non-Typhi Salmonella isolates from humans in the United States. Antimicrobial Agents and Chemotherapy. v. 53, p. 4563–4564, 2009.
FRITSCHE, T. R.; CASTANHEIRA, M.; MILLER, G. H. et al. Detection of methyltransferases conferring high-level resistance to aminoglycosides in enterobacteriaceae from Europe, North America, and Latin America. Antimicrobial Agents and Chemotherapy. v. 52, p.1843–1845, 2008.
GALES, A. C.; CASTANHEIRA, M.; JONES, R. N. et al. Antimicrobial resistance among Gram-negative bacilli isolated from Latin America: results from SENTRY Antimicrobial Surveillance Program (Latin America, 2008-2010). Diagnostic Microbiology and Infectious Disease. v. 73, n. 4, p. 354–360, 2012.
GALIMAND, M.; COURVALIN, P.; LAMBERT, T. Plasmid-mediated high-level resistance to aminoglycosides in Enterobacteriaceae due to 16S rRNA methylation. Antimicrobial Agents and Chemotherapy. v. 47(8), p. 2565-71, 2003.
GALIMAND, M.; SABTCHEVA, S.; COURVALIN, P.; LAMBERT, T. Worldwide disseminated armA aminoglycoside resistance methylase gene is borne by composite transposon Tn1548. Antimicrobial Agents and Chemotherapy, v.49, p. 2949–2953, 2005.
GALIMAND, M.; COURVALIN, P.; LAMBERT, T. RmtF, a new member of the aminoglycoside resistance 16S rRNA N7 G1405 methyltransferase family. Antimicrobial Agents and Chemotherapy. v. 56, p. 3960-2, 2012.
GARBATI, M. A.; AL GODHAIR, A. I. The growing resistance of Klebsiella pneumoniae; the need to expand our antibiogram: case report and review of the literature. African Journal of Infectious Diseases. v. 7, p. 8-10, 2013.
GOLEBIEWSKI, M., KERN-ZDANOWICZ, I., ZIENKIEWICZ, M. et al. Complete nucleotide sequence of the pCTX-M3 plasmid and its involvement in spread of the extended- spectrum β-lactamase gene blaCTX-M-3. Antimicrobial Agents and Chemotherapy. v. 51, p. 3789–3795, 2007.
HABEEB, M. A.; HAQUE, A.; IVERSEN, A. et al. Occurrence of virulence genes, 16S rRNA methylases, and plasmid-mediated quinolone resistance genes in CTX-M-producing Escherichia coli from Pakistan. European Journal of Clinical Microbiology Infectious Diseases. v. 33, p. 399-409, 2014.
HARYANI, Y.; NOORZALEHA, A. S.; FATIMAH, A. B. et al. Incidence of Klebsiella pneumonia in street foods sold in Malaysia and their characterization by antibiotic resistance, plasmid profiling, and RAPD–PCR analysis. Food Control. v. 18, p. 847–853, 2007.
HIDALGO, L.; HOPKINS, K. L.; GUTIERREZ, B. et al. Association of the novel aminoglycoside resistance determinant RmtF with NDM carbapenemase in Enterobacteriaceae isolated in India and the UK. Journal Antimicrobial Chemotherapy. v. 68, p. 1543-50, 2013.
HIRSCH, E. B.; TAM, V. H. Detection and treatment options for Klebsiella pneumoniae carbapenemase (KPCs): an emerging cause of multidrug-resistant infection. Journal Antimicrobial Chemotherapy. v.65, p. 1119-25, 2010.
HOPKINS, K. L.; ESCUDERO, J. A.; HIDALGO, L.; GONZALEZ-ZORN, B. 16S rRNA methyl-transferase RmtC in Salmonella enterica serovar Virchow. Emerging Infectious Diseases.v. 16, p. 712–715, 2010.
HOUGHTON, J. L.; GREEN, K. D.; CHEN, W. et al. The future of aminoglycosides: the end or renaissance? Chembiochem. v. 11, p. 880–902, 2010.
HU, X.; XU, B.; YANG, Y. et al. A high throughput multiplex PCR assay for simultaneous detection of seven aminoglycoside-resistance genes in Enterobacteriaceae. BMC Microbiology. v.14; p.13:58, 2013.
HUANG, J., YE, M., JIA, X., YU, F., WANG, M. Coexistence of armA and genes encoding aminoglycoside-modifying enzymes in Acinetobacter baumannii. African Journal of Microbiology Research. v. 6, p. 5325-533, 2012.
JÁCOME, P. R.; ALVES, L. R.; CABRAL, A. B.; LOPES, A. C.; MACIEL, M. A. First report of KPC-producing Pseudomonas aeruginosa in Brazil. Antimicrobial Agents and Chemotherapy. v. 56, p. 4990, 2012.
JANDA, J. M.; ABBOTT, S. L. The Enterobacteria, 2nd ed. Washington D.C.: ASM press, 411p, 2006.
JIANG, Y.; YU, D.; WEI, Z. et al. Complete nucleotide sequence of Klebsiella pneumoniae multidrug resistance plasmid pKP048, carry-ing blaKPC-2, blaDHA-1, qnrB4, and armA. Antimicrobial Agents and Chemotherapy. v. 54, p. 3967–3969, 2010.
KANG, H.Y.; KIM, K.Y.; KIM, J. et al. Distribution of conjugative-plasmid-mediated 16S rRNA methylase genes among amikacin-resistant Enterobacteriaceae isolates collected in 1995 to 1998 and 2001 to 2006 at a university hospital in South Korea and identification of conjugative plasmids mediating dissemination of 16S rRNA methylase. Journal of Clinical Microbiology. v. 46, p. 700–706, 2008.
KIM, E. S.; JEONG, J. Y.; CHOI, S. H. et al. Plasmid-mediated fluoroquinolone efflux pump gene, qepA, in Escherichia coli clinical isolates in Korea. Diagnostic Microbiology and Infectious Disease. v. 65(3), p. 335–338, 2009.
KONEMAN, E.W.; ALLEN, S.D.; JANDRA, W.M.; SCHRECKENBERGER, P.C.; WINN, W.C. Diagnóstico Microbiológico: Texto e Atlas Colorido. 6. ed. Rio de Janeiro: MEDSI Editora Médica e Científica, 2008.
LANDELLE, C.; PAGANI, L.; HARBARTH, S. Is patient isolation the single must important measure to prevent the spread of multidrug-resistant pathogens? Virulence. v.4, n.2, p.163- 71, 2013.
LEE, C. C.; LEE, N. Y.; YAN, J. J. et al. Bacteremia due to Extended-Spectrum-β- Lactamaseproducing Enterobacter cloacae: Role of Carbapenem Therapy. Antimicrobial Agents and Chemotherapy. v. 54 (9), p. 3551–3556, 2010.
LIANG, C.; XING, B.; YANG, X. et al. Molecular epidemiology of aminoglycosides resistance on Klebsiella pneumonia in a hospital in China. International Journal of Clinical and Expeimenteal Medicines. v. 8, p. 1381-1385, 2015.
LIVERMORE, D. M., MUSHTAQ, S., WARNER, M. et al. Activity of aminoglycosides, including ACHN-490, against carbapenem resistant Enterobacteriaceae isolates. Journal Antimicrobial Chemotherapy. v. 66, p. 48–53, 2011.
LOPES, A. C. S.; CABRAL, A. B.; MACIEL, M. A. V. et al. Relação entre a presença do gene blaKPC e perfil de resistência aos carbapenêmicos e em isolados de Enterobacter
aerogenes e Enterobacter cloacae provenientes de Recife-PE, Brasil. In: XXII CONGRESSO LATINOAMERICANO DE MICROBIOLOGIA - ALAM, Cartagena, 2014. Medellín: Universidad de Antioquia, 2014. v.5. p. 47.
MAGNET, S.; BLANCHARD, J. S. Molecular insights into aminoglycoside action and resistance. Chemical Reviews. v. 105, p. 477–98, 2005.
MARCHAIM, D.; NAVON-VENEZIA, S.; SCHWABER, M. J. et al. Isolation of imipenem- resistant Enterobacter species: emergence of KPC-2 carbapenemase, molecular characterization, epidemiology, and outcomes. Antimicrobial Agents and Chemotherapy. v. 52, n. 4, p.1413-1418, 2008.
MARRA, A. R.; CAMARGO, L. F.; PIGNATARI, A. C. et al. The Brazilian SCOPE Study Group Nosocomial Bloodstream Infections in Brazilian Hospitals: Analysis of 2,563 Cases from a Prospective Nationwide Surveillance Study. Journal of Clinical Microbiology. v. 49, n. 5, p.1866–1871, 2011.
MARTÍNEZ, J.; MARTÍNEZ, L.; ROSENBLUETH, M. et al. How are gene sequence analyses modifying bacterial taxonomy? The case of Klebsiella. International Microbiology. 7(4), p. 261-8, 2004.
MELO, R. C. A.; BARROS, E. M. R.; LOUREIRO, N. G. et al. Presence of fimH, mrkD and irp2 virulence genes in KPC-2-producing Klebsiella pneumoniae isolates in Recife-PE, Brazil. Current Microbiology, 2014.
MEZZATESTA, M. L., GONA, F., AND STEFANI, S. Enterobacter cloacae complex: clinical impact and emerging antibiotic resistance. Future Microbiology. v. 7, p. 887–902, 2012.
MEZZATESTA, M. L.; GONA, F.; CAIO, C. et al. Emergence of an extensively drug- resistant ArmA- and KPC-2-producing ST101 Klebsiella pneumoniae clone in Italy. Journal of Antimicrobial Chemotherapy. v. 68(8), p. 1932-4, 2013.
MIRIAGOU, V.; TZOUVELEKIS, L. S.; ROSSITER, S. et al. Imipenem Resistance in a Salmonella Clinical Strain Due to Plasmid-Mediated Class A Carbapenemase KPC-2. Antimicrobial Agents and Chemotherapy. v. 47, p. 1297-1300, 2003.
MIRÓ, E.; GRÜNBAUM, F.; GÓMEZ, L. et al. Characterization of aminoglycoside- modifying enzymes in enterobacteriaceae clinical strains and characterization of the plasmids implicated in their diffusion. Microbial Drug Resistance. v. 19(2), p. 94-9, 2013.
MITSCHER, L. A. Antibiotics and antimicrobial agents. In: FOYE, W. O. et. All. (eds.) Principles of Medicinal Chemistry, 5. ed, Baltimore, Willians e Wilkins, cap. 34, p. 788-791, 2002.
MONTEIRO, J.; SANTOS, A. F.; ASENSI, M. D. et al. First report of KPC-2-producing Klebsiella pneumoniae strains in Brazil. Antimicrobial Agents and Chemotherapy. v.53, n.1, p. 333-334, 2009.
NAAS, T. et al. Genetic structures at the origin of acquisition of the beta-lactamase bla KPC gene. Antimicrobial agents and chemotherapy. v. 52, n. 4, p. 1257-1263, 2008.
NAVON-VENEZIA, S.; CHMELNITSKY, I.; LEAVITT, A. et al. Plasmid-mediated imipenem-hydrolyzing enzyme KPC-2 among multiple carbapenem-resistant Escherichia coli clones in Israel. Antimicrobial Agents and Chemotherapy. v.50, n. 9, p. 3098-3101, 2005.
NORDMANN, P; POIREL, L. Emerging carbapenemases in Gram-negative aerobes. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. v. 8, n. 6, p. 321-331, Jun 2002.
NORDMANN, P.; CUZON, G.; NAAS, T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. The Lancet Infectious Diseases. v. 9, n. 4, p. 228–36, 2009.
OERTEL, R., NEUMEISTER, V. & KIRCH, W. Hydrophilic Interaction Chromatography Combined with Tandem-Mass Spectrometry to Determine Six Aminoglycosides in Serum. Journal of Chromatography A 1058, p. 197-201, 2004.
O'HARA, J. A.; MC GANN, P.; SNESRUD, E. C. et al. Novel 16S rRNA methyltransferase RmtH produced by Klebsiella pneumoniae associated with war-related trauma. Antimicrobial Agents and Chemotherapy. v. 57(5), p. 2413-6, 2013.
OHTA, T., HASEGAWA, M. Analysis of the nucleotide sequence of fmrT encod-ing the self- defense gene of the istamycin producer, Streptomyces tenjimariensis ATCC 31602; comparison with the squences of kamB of Streptomyces tenebrarius NCIB 11028 and kamC of Saccharopolyspora hirsuta CL102. Journal of Antibiotics. v. 46, p. 511–517, 1993a.
OLIVEIRA, J.F.P.; CIPULLO, J.P.; BURDMANN, E. A. Nefrotoxicidade dos aminoglicosídeos. Brazilian Journal Cardiovascular Surgery. v. 21, p. 444-452, 2006.
PAPP-WALLACE K. M.; BETHEL C. R.; DISTLER, A. M. Inhibitor resistance in the KPC- 2 betalactamase, a preeminent property of this class A beta-lactamase. Antimicrobial Agents and Chemotherapy. v. 54(2), p. 890-7, 2010.
PARK, C. H.; ROBICSEK, A.; JACOBY, G. A. et al. Prevalence in the United States of aac(6’)-Ib-cr encoding a ciprofloxacin-modifying enzyme. Antimicrobial Agents and Chemotherapy. v. 50, p. 3953–5, 2006.
PATEL, G.; BONOMO, R. A. Status report on carbapenemases: challenges and prospects. Expert Review of Anti-Infective Therapy. v. 9(5), p. 555-70, 2011.
PATEL, J. B.; RASHEED, J. K.; BRANDON KITCHEL, M. S. Carbapenemases in Enterobacteriaceae: activity, epidemiology and laboratory detection. Clinical Microbiology News. v. 31, p. 55-62, 2009.
PATERSON, D. L.; BONOMO, R. A. Extended-spectrum beta-lactamases: a clinical update. Clinical Microbiology Reviews. v.18, p.657-686, 2005.
PATERSON, D. L. Resistance in gram-negative bacteria: Enterobacteriaceae. American Journal of Infection Control. v. 34, n. 5 Suppl 1, p. S20-8; discussion S64-73, 2006.
PAVEZ, M.; MAMIZUKA, E. M.; LINCOPAN, N. Early dissemination of KPC-2-producing Klebsiella pneumoniae strains in Brazil. Antimicrobial Agents and Chemotherapy. v.53, n. 6, p. 2702, 2009.
PAWAR, M.; MEHTA, Y.; KHURANA, P.; CHAUDHARY, A.; KULKARNI, V.; TREHAN, N. Ventilator-associated pneumonia: incidence, risk factors, outcome, and microbiology. Journal of Cardiothoracic and Vascular Anesthesia. v. 17, p. 22–28. 2003.
PEIRANO, G.; SEKI, L.; PASSOS, V. L. V. et al. Carbapenem-hydrolysing beta-lactamase KPC-2 in Klebsiella pneumoniae isolated in Rio de Janeiro, Brazil. The Journal of Antimicrobial Chemotherapy. v.63, n.2, p.265-268, 2009.
PEREIRA, P. S.; BORGHI, M.; ALBANO, R. M. et al. Coproduction of NDM-1 and KPC-2 in Enterobacter hormaechei from Brazil. Microbial Drug Resistance. Dec 4, 2014.
PEREZ, A., et al. Involvement of the AcrAB-TolC efflux pump in the resistance, fitness, and virulence of Enterobacter cloacae. Antimicrobial Agents and Chemotherapy. v. 56, n. 4, p. 2084-2090, 2012.
PETRELLA, S.; ZIENTAL-GELUS, N.; MAYER, C. et al. Genetic and structural insights into the dissemination potential of the extremely-broad-spectrum class A beta-lactamase (ESBL) KPC-2 identified in two strains of Escherichia coli and Enterobacter cloacae isolated
from the same patient in France. Antimicrobial Agents and Chemotherapy. v. 52, p. 3725– 3736, 2008.
PINSETA, F.R. Síntese e relação estrutura-toxicidade de derivados aminoglicosídeos como potenciais protótipos na busca de um fármaco seguro para o tratamento da Doença de Ménière, 2010. Dissertação (Mestrado) - Universidade de São Paulo, 2010.
PODSCHUM, R.; ULLMANN, U. Klebsiella spp. As nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clinical Microbiology Reviews. v.11, n.4, p.589-603, 1998.
POIREL, L., LAGRUTTA, E., TAYLOR, P. et al. Emergence of metallo- β-lactamase NDM- 1-producing multidrug-resistant Escherichia coli in Australia. Antimicrobial Agents and Chemotherapy. v. 54, p. 4914–4916, 2010.
POIREL, L., DORTET, L., BERNABEU, S., NORDMANN, P. Genetic features of blaNDM- 1-positive Enterobacteriaceae. Antimicrobial Agents and Chemotherapy.v. 55, p. 5403– 5407, 2011c.
POIREL, L., REVATHI, G., BERNABEU, S. et al. Detection of NDM- 1-producing Klebsiella pneumoniae in Kenya. Antimicrobial Agents and Chemotherapy. v. 55, p. 934– 936, 2011d.
POIREL, L.; LABARCA, J.; BELLO, H. et al. Emergence of the 16S rRNA methylase RmtG in an extendedspectrum- β-lactamase-producing and colistin-resistant Klebsiella pneumoniae isolate in Chile. Antimicrobial Agents and Chemotherapy. v. 58(1), p. 618-9, 2014.
QUEENAN, A. M.; BUSH, K. Carbapenemases: the versatile beta-lactamases. Clinical Microbiology Reviews. v. 20, n. 3, p. 440-458, Jul 2007.
RAMIREZ, M. S.; TOLMASKY, M. E. Aminoglycoside modifying enzymes. Drug Resistance Updates. v, 13(6), p. 151–171, 2010.
RIBEIRO, V. B.; ANDRADE, L. N.; LINHARES, A. R. et al. Molecular characterization of Klebsiella pneumoniae carbapenemase-producing isolates in southern Brazil. Journal of Medical Microbiology. 62 (Pt 11), p. 1721-7, 2013.
RIZI, K. S.; PEERAYEH, S. N.; BAKHSHI, B. et al. Prevalence of integrons and Antimicrobial Resistance Genes Among Clinical Isolates of Enterobacter spp. From Hospitals of Tehran. International Journal of Enteric Pathogens. 3(1): e22531, 2015.
ROBLEDO, I. E.; AQUINO, E. E.; VÁZQUEZ, G. J. Detection of the KPC Gene in Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii during a PCR-Based Nosocomial Surveillance. Study in Puerto Rico. Antimicrobial Agents and Chemotherapy. v. 55, p. 2968-70, 2011.
RODRÍGUEZ, E.; BAUTISTA, A.; BARRERO, L. First report of a Salmonella enterica serovar typhimurium isolate with carbapenemase (KPC-2) in Colombia. Antimicrobial Agents and Chemotherapy. v. 58(2), p.1263-4, 2014.
ROSSI, F.; ANDREAZZI, D. B. Resistência Bacteriana: interpretando o antibiograma – Editora Atheneu, São Paulo, 2005.
SCHJØRRING, S.; STRUVE, C.; KROGFELT, K. A. Transfer of antimicrobial resistance plasmids from Klebsiella pneumoniae to Escherichia coli in the mouse intestine. Journal of Antimicrobial Chemotherapy. v. 62, p. 1086–1093, 2008.
SETNY, P.; TRULSKY, J. Search for Novel Aminoglycosides by Combining Fragment- Based Virtual Screening and and 3D-QSAR Scoring. Journal of Chemical Information and Modeling. v.49, p. 390-400, 2009.
SHAW, K. J.; RATHER,P. N.; HARE, R. S. et al. Molecular Genetics of Aminoglycoside Resistance Genes and Familial Relationships of the Aminoglycoside-Modifying Enzymes. Microbiological Reviews. v. 57, p. 138-163, 1993.
SHANMUGAM, P.; MEENAKSHISUNDARAM, J.; JAYARAMAN, P. blaKPC gene Detection in Clinical Isolates of Carbapenem Resistant Enterobacteriaceae in a Tertiary Care Hospital. Journal of Clinical and Diagnostic Research. v. 7(12), p. 2736-8, 2013.
SHEN, P.; WEI, Z.; JIANG, y. et al. Novel genetic environment of the carbapenem- hydrolyzing beta-lactamase KPC-2 among Enterobacteriaceae in China. Antimicrobial Agents and Chemotherapy. v. 53, n. 10, p. 4333-4338, 2009.
SHENG, J-F.; LI, J-J.; TU, S. et al. blaKPC and rmtB on a single plasmid in Enterobacter
amnigenus and Klebsiella pneumoniae isolates from the same patient. European Jounal of Clinical of Microbiology e Infectious Diseases. v. 31, p. 1585–1591, 2012.
SIEVERT, D. M., RICKS, P., EDWARDS, J. R. et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009–2010. Infection Control Hospital Epidemiology. v, 34(1), p.1-14, 2013.
SNYDER, G. M. ; O’FALLON, E.; D’AGATA, E. M. C. Co-colonization with multiple different species of multidrug-resistant Gram negative bacteria. Am. J. Infect. Control. p.1- 5, 2011.
SPANU, T.; DE ANGELIS, G.; CIPRIANI, M. et al. In vivo emergence of tigecycline resistance in multidrugresistant Klebsiella pneumoniae and Escherichia coli. Antimicrobial Agents Chemotherary. v. 56(8), p. 4516-8, 2012.
SOUZA LOPES, A. C.; RODRIGUES, J. F.; MORAIS JÚNIOR, M. A. Molecular typing of Klebsiella pneumoniae isolates from public hospitals in Recife, Brazil. Microbiological Research. v.160, n.1, p.37-46, 2005.
TAMMA, P. D.; COSGROVE, S. E.; MARAGAKIS, L. L. Combination Therapy for Treatment of Infections with Gram-Negative Bacteria. Clinical Microbiology Reviews. v. 25, p. 450-470, 2012.
THIOLAS, A., BOLLET, C., LASCOLA, B. et al. Successive emergence of Enterobacter aerogenes strains resistant to imipenem and colistinina patient. Antimicrobial Agents Chemotherapy. v. 49, p.1354–1358, 2005.
TIAN, G. B.; RIVERA, J. I.; PARK, Y. S. et al. Sequence type ST405 Escherichia coli isolate producing QepA1, CTX-M-15, and RmtB from Detroit, Michigan. Antimicrobial Agents Chemotherapy. v. 55(8), p. 3966-7, 2011.
TIJET, N.; ANDRES, P.; CHUNG, C. et al. rmtD2, a new allele of a 16S rRNA methylase gene, has been present in Enterobacteriaceae isolates from Argentina for more than a decade. Antimicrobial Agents and Chemotherapy. v. 55, p. 904 –909, 2011.
TRABULSI, L. R.; ALTERTHUM, F. Microbiologia. 5ª ed. São Paulo: Atheneu, 2008.
TSAI, M. H.; CHU, S. M.; HSU, J. F., et al. Risk Factors and Outcomes for Multidrug- Resistant Gram-Negative Bacteremia in the NICU. Pediatrics, 2014.