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blaOXA-23: A serious obstacle to controlling the spread and treatment of Acinetobacter baumannii strains
ARTICLE IN PRESS American Journal of Infection Control ■■ (2015) ■■–■■
Contents lists available at ScienceDirect
American Journal of Infection Control
American Journal of Infection Control
j o u r n a l h o m e p a g e : w w w. a j i c j o u r n a l . o r g
Brief reports
ISAba1/blaOXA-23: A serious obstacle to controlling the spread and treatment of Acinetobacter baumannii strains Giselle Fukita Viana MSc a, Maisa Cristina Barreto Zago PharmD a, Rafael Renato Brondani Moreira MSc a, Mirian Nicéa Zarpellon PhD b, Thatiany Cevallos Menegucci MSc a, Celso Luiz Cardoso PhD a, Maria Cristina Bronharo Tognim PhD a,* a b
Departamento de Ciências Básica da Saúde, Universidade Estadual de Maringá, PR, Brazil Hospital Universitário de Maringá, Universidade Estadual de Maringá, PR, Brazil
Key Words: Acinetobacter baumannii insertion sequence blaOXA-23 gene resistance carbapenems
This study demonstrated a direct correlation between Acinetobacter baumannii clusters carrying the ISAba1/blaOXA-23 gene and increased minimal inhibitory concentrations for carbapenems and greater clonal diversity. Our findings showed that clusters carrying ISAba1 are widely distributed in our hospital, further complicating the treatment and control of infections caused by A baumannii. © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
The increase in the number of multidrug-resistant strains of Acinetobacter baumannii that produce class D carbapenemases, mainly OXA-23, drastically limits the available therapeutic options.1 The dissemination of OXA-23–producing A baumannii has been reported worldwide, including in Brazil. Although this enzyme only weakly hydrolyzes carbapenems, insertion of a sequence such as ISAba1 may enhance the expression of the blaOXA-23 gene, conferring high resistance. Another important aspect of the insertion of this sequence is the capacity to transfer resistance genes among the strains.1-3 A previous study by our research group showed that in our region, multidrug-resistant strains of A baumannii have become a serious problem because of their high resistance to carbapenems and their endemic situation.4 This study investigated the presence of ISAba1 associated with the blaOXA-23 gene and its role in the resistance and dissemination of clinical isolates of A baumannii during a 5-year period. METHODS The Microbiology Laboratory of the State University of Maringá, Paraná, Brazil, is responsible for monitoring the more prevalent
* Address correspondence to Maria Cristina Bronharo Tognim, PhD, Laboratório de Microbiologia, Departamento de Ciências Básica da Saúde, Universidade Estadual de Maringá, Avenida Colombo 5790. CEP 87020-900 Maringá, Paraná, Brazil. E-mail address: [email protected] (M.C.B. Tognim). Funding/Support: Supported by the Coordenação de Aperfeiçoamento do Pessoal de Ensino Superior. Conflicts of Interest: None to report.
pathogens and antimicrobial resistance patterns. It conducts research on the principal genes involved in the production of enzymes that confer resistance, such as carbapenemases, in the University of Maringá Hospital, which serves the city of Maringá and the surrounding region. The university hospital has 123 beds and provides general and advanced medical and diagnostic services and public health care for the population of 754,570 residing in the Maringá Metropolitan Region and numerous surrounding towns. The adult intensive care unit (ICU) has 8 beds located in individual rooms with handwashing facilities. Gloves and gowns are required for patient contact, and chlorhexidine and alcohol-based hand gel are used for hand hygiene. Among the multidrug-resistant pathogens monitored, A baumannii has been the main cause of nosocomial infections in the ICU, with a total of 472 isolates collected from January 2009-December 2013. For this study, the first isolate from each patient admitted to the ICU (n = 133) was typed by enterobacterial repetitive intergenic consensus–polymerase chain reaction, as previously described,5 and analyzed using BioNumerics version 6.5 (Applied Maths, Sint-Martens-Latem, Belgium). Isolates were judged to have the same cluster if the Dice correlation coefficient was ≥0.93. Sixty-eight distinct clusters of A baumannii were included in this study. The identification and analysis of the antimicrobial susceptibility profile were carried out in the laboratory using Phoenix (BD Diagnostics, Sparks Glencoe, MD). The minimal inhibitory concentrations (MICs) of meropenem, imipenem, and polymyxin B were confirmed by the agar dilution method.6
0196-6553/© 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajic.2015.11.020
ARTICLE IN PRESS G.F. Viana et al. / American Journal of Infection Control ■■ (2015) ■■–■■
2
DISCUSSION
Multiplex polymerase chain reaction analyses were performed to detect blaKPC gene and metallo-β-lactamase (blaIMP, blaVIM, blaGIM, blaSPM, blaSIM, and blaNDM)7 and oxacillinase genes (blaOXA-23, blaOXA-24, blaOXA-51, blaOXA-58, and blaOXA-143).8 ISAba1 was detected using the primers ISAba1F and ISAba1R in combination with the primers OXA-23 (R and F).3
This study showed that not only the presence of the blaOXA-23 gene, but also its association with ISAba1, had a key role in increasing the MICs of carbapenems to treat A baumannii and also on increasing the genetic variability of the bacterium. A baumannii clusters (n = 68) showed high rates of resistance to almost all of the antimicrobial agents tested, including carbapenems (85% were resistant isolates), similar to findings elsewhere in Latin America.1 The presence of the ISAba1/blaOXA-23 gene was the main resistance mechanism found in the A baumannii isolates. The dissemination of the ISAba1/blaOXA-23 gene has also been reported in other Brazilian states and worldwide.1-3 However, to our knowledge, this is the first study to demonstrate the increase of ISAba1/blaOXA-23 over time. We observed a significant increase in the number of isolates carrying the ISAba1/blaOXA-23 gene and a direct correlation with high MICs for carbapenems (ie, A baumanii clusters carrying only blaOXA-23 showed MIC50 = 8 μg/mL, whereas A baumanii clusters carrying ISAba1/blaOXA-23 showed MIC50 = 32 μg/mL). The location of ISAba1 upstream of the blaOXA-23 gene might explain the overexpression of this gene. Higher MICs decrease the chances of therapeutic success, even with the use of pharmacokinetic-pharmacodynamic strategies, such as prolonged infusion of meropenem and increases in the dose.9 The clonal variability increased in the same period as the increase in the rates of ISAba1/blaOXA-23-producing A baumannii isolates. Between 2004 and 2009, an endemic clone of A baumannii was detected in our hospital,4 and the blaOXA-23 gene was detected in this cluster. Monitoring this endemic clone in our hospital revealed that the clonal variability increased beginning in 2010, the same year as an increase in A baumannii carrying ISAba1/blaOXA-23. Another study demonstrated a correlation between an increase in clonal variability and the presence of mobile elements, such as IMP-1.10 Likewise, a study verified the presence of various A baumannii clusters cocirculating in an ICU and a possible relationship to ISAba1.11
RESULTS Different clones of A baumannii proved to be resistant to most of the antimicrobial classes tested. Cephalosporins, fluoroquinolones, tetracyclines, and aminoglycosides, including carbapenems, showed low in vitro activity against A baumannii isolates (85% of the isolates were carbapenem resistant). The annual distribution of resistance rates to carbapenems are presented in Table 1. A high susceptibility rate was observed only for polymyxin B (100% of the isolates were susceptible). All 68 A baumannii isolates possessed the blaOXA-51 gene. The isolates were negative for the genes blaOXA-24, blaOXA-58, blaOXA-143, blaVIM, blaSPM, blaSIM, blaGIM, blaIMP, blaNDM, and blaKPC. Forty-eight isolates (71%) possessed the blaOXA-23 gene, and only 3 of them were susceptible to carbapenems. The association ISAba1 upstream of the blaOXA-23 gene was detected in 39 (81%) of the carbapenem-resistant A baumannii isolates, and 3 of these also showed ISAba1 downstream of the gene. Four of the isolates carrying only blaOXA-51 also had ISAba1 upstream of this gene. All were resistant to carbapenems. The determinations of MICs and their association with carbapenemases are described in Table 2. Both the minimum inhibitory concentration capable of inhibiting 50% of the isolates tested (MIC50) and MIC capable of inhibiting 90% of the isolates tested for polymyxin B were 2 μg/mL, independently of the presence or absence of the blaOXA-23 gene and its association with ISAba1. Carbapenem-resistant A baumannii isolates carrying the ISAba1-blaOXA-23 combination increased markedly, from 22% in 2009 to 73% in 2013. The genetic variability of these isolates also increased. In 2009, 34 A baumannii isolates were collected, and 9 clones were detected. In 2013, 18 A baumannii isolates were collected, and 11 clones were detected (Table 1).
Table 1 Annual distribution of clonality and resistance to carbapenems and carbapenemases of Acinetobacter baumannii clusters Year of isolation Distribution of clonality
2009
2010
2011
2012
2013
Isolates/clusters (N = 133/N = 68), n % Resistance (clusters) Cluster blaOXA-51 gene alone Cluster blaOXA-51 + blaOXA-23 gene Cluster blaOXA-51 gene + ISAba1 Cluster blaOXA-51 blaOXA-23 gene + ISAba1
34/9 80 2 (22) 4 (44) 1 (12) 2 (22)
41/19 82 6 (31) 2 (11) 2 (11) 9 (47)
18/14 94 3 (21) 1 (8) — 10 (71)
22/15 87 3 (20) 1 (7) 1 (7) 10 (66)
18/11 82 2 (18) 1 (9) — 8 (73)
NOTE. Values are n (%) or as otherwise indicated. Pearson correlation: resistance and clonality/year: 0.88.
Table 2 Minimal inhibitory concentration to carbapenems of 68 Acinetobacter baumannii clusters, according to their mechanism of resistance No. of clusters and cumulative percentage inhibited at MIC (μg ml−1) Mechanism resistance (no. of clusters) Negative for blaOXA-23 gene (n = 20) Positive for blaOXA-23 gene and negative for ISAba1 (n = 9) Positive for blaOXA-23 gene and positive for ISAba1 (n = 39) Total of clusters (n = 68)
0.5
1
2
4
8
16
32
64
MIC50
MIC90
2 (10) 1 (11) 0 (0) 3 (4)
5 (35) 1 (22) 0 (0) 7 (15)
2 (45) 0 (0) 0 (0) 2 (18)
1 (50) 0 (0) 0 (0) 1 (19)
5 (75) 3 (56) 1 (3) 9 (32)
3 (90) 1 (67) 10 (28) 14 (53)
2 (100) 2 (89) 23 (87) 27 (93)
0 (0) 1 (100) 4 (100) 5 (100)
4 8 32 16
16 64 64 32
NOTE. Values are n (%). MIC, minimum inhibitory concentration; MIC50, minimum inhibitory concentration capable of inhibiting 50% of the isolates tested; MIC90, minimum inhibitory concentration capable of inhibiting 90% of the isolates tested.
ARTICLE IN PRESS G.F. Viana et al. / American Journal of Infection Control ■■ (2015) ■■–■■
Our study suggests that the presence of the association ISAba1-blaOXA-23 was directly correlated with the increases in the MIC levels for carbapenems and in the clonal variability. These findings illustrate the difficulty of controlling this microorganism and emphasize the need for effective surveillance and the rational use of carbapenems.
Acknowledgment We thank Dr. Janet W. Reid (JWR Associates) for reviewing and editing the English language of our text.
References 1. Zarrilli R, Giannouli M, Tomasone F, Triassi M, Tsarikis A. Carbapenem resistance in Acinetobacter baumannii: the molecular epidemic features of an emerging problem in health care facilities. J Infect Dev Ctries 2009;3:335-41. 2. Chagas TPG, Carvalho KR, Santos ICO, Carvalho-Assef APD, Asensi MD. Characterization of carbapenem-resistant Acinetobacter baumannii in Brazil (2008–2011): countrywide spread of OXA-23–producing clones (CC15 and CC79). Diagn Microbiol Infect Dis 2014;79:468-72.
3
3. Turton JF, Ward ME, Woodford N, Kaufmann ME, Pike R, Livermore DM, et al. The role of ISAba1in expression of OXA carbapenemase genes in Acinetobacter baumannii. FEMS Microbiol Lett 2006;258:72-7. 4. Saalfeld SMS, Viana GF, Siqueira VLD, Cardoso CL, Garcia LB, Bronharo Tognim MC. Endemic carbapenem-resistant Acinetobacter baumannii in a Brazilian intensive care unit. J Hosp Infect 2009;72:365-8. 5. Silbert S, Pfaller MA, Hollis RJ, Barth AL, Sader HS. Evaluation of three molecular typing techniques for nonfermentative Gram-negative bacilli. Infect Control Hosp Epidemiol 2004;25:847-51. 6. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; twenty-fourth informational supplement. Document M100-S24. Wayne (PA): Clinical and Laboratory Standards Institute; 2014. 7. Poirel L, Walsh TR, Cuvillier V, Nordmann P. Multiplex PCR for detection of acquired carbapenemase genes. Diagn Microbiol Infect Dis 2011;70:119-23. 8. Higgins PG, Lehmann M, Seifert H. Inclusion of OXA-143 primers in a multiplex polymerase chain reaction (PCR) for genes encoding prevalent OXA carbapenemases in Acinetobacter spp. Int J Antimicrob Agents 2010;35:305. 9. Lomaestro BM, Drusano GL. Pharmacodynamic evaluation of extending the administration time of meropenem using a Monte Carlo simulation. Antimicrob Agents Chemother 2005;49:461-3. 10. Tognim MCB, Gales AC, Penteado AP, Silbert S, Sader HS. Dissemination of IMP-1 metallo-β-lactamase–producing Acinetobacter species in a Brazilian teaching hospital. Infect Control Hosp Epidemiol 2006;27:742-7. 11. Valenzuela JK, Thomas L, Partridge SR, van der Reijden T, Dijkshoorn L, Iredell J. Horizontal gene transfer in a polyclonal outbreak of carbapenem-resistant Acinetobacter baumannii. J Clin Microbiol 2007;45:453-60.
Contents lists available at ScienceDirect
American Journal of Infection Control
American Journal of Infection Control
j o u r n a l h o m e p a g e : w w w. a j i c j o u r n a l . o r g
Brief reports
ISAba1/blaOXA-23: A serious obstacle to controlling the spread and treatment of Acinetobacter baumannii strains Giselle Fukita Viana MSc a, Maisa Cristina Barreto Zago PharmD a, Rafael Renato Brondani Moreira MSc a, Mirian Nicéa Zarpellon PhD b, Thatiany Cevallos Menegucci MSc a, Celso Luiz Cardoso PhD a, Maria Cristina Bronharo Tognim PhD a,* a b
Departamento de Ciências Básica da Saúde, Universidade Estadual de Maringá, PR, Brazil Hospital Universitário de Maringá, Universidade Estadual de Maringá, PR, Brazil
Key Words: Acinetobacter baumannii insertion sequence blaOXA-23 gene resistance carbapenems
This study demonstrated a direct correlation between Acinetobacter baumannii clusters carrying the ISAba1/blaOXA-23 gene and increased minimal inhibitory concentrations for carbapenems and greater clonal diversity. Our findings showed that clusters carrying ISAba1 are widely distributed in our hospital, further complicating the treatment and control of infections caused by A baumannii. © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
The increase in the number of multidrug-resistant strains of Acinetobacter baumannii that produce class D carbapenemases, mainly OXA-23, drastically limits the available therapeutic options.1 The dissemination of OXA-23–producing A baumannii has been reported worldwide, including in Brazil. Although this enzyme only weakly hydrolyzes carbapenems, insertion of a sequence such as ISAba1 may enhance the expression of the blaOXA-23 gene, conferring high resistance. Another important aspect of the insertion of this sequence is the capacity to transfer resistance genes among the strains.1-3 A previous study by our research group showed that in our region, multidrug-resistant strains of A baumannii have become a serious problem because of their high resistance to carbapenems and their endemic situation.4 This study investigated the presence of ISAba1 associated with the blaOXA-23 gene and its role in the resistance and dissemination of clinical isolates of A baumannii during a 5-year period. METHODS The Microbiology Laboratory of the State University of Maringá, Paraná, Brazil, is responsible for monitoring the more prevalent
* Address correspondence to Maria Cristina Bronharo Tognim, PhD, Laboratório de Microbiologia, Departamento de Ciências Básica da Saúde, Universidade Estadual de Maringá, Avenida Colombo 5790. CEP 87020-900 Maringá, Paraná, Brazil. E-mail address: [email protected] (M.C.B. Tognim). Funding/Support: Supported by the Coordenação de Aperfeiçoamento do Pessoal de Ensino Superior. Conflicts of Interest: None to report.
pathogens and antimicrobial resistance patterns. It conducts research on the principal genes involved in the production of enzymes that confer resistance, such as carbapenemases, in the University of Maringá Hospital, which serves the city of Maringá and the surrounding region. The university hospital has 123 beds and provides general and advanced medical and diagnostic services and public health care for the population of 754,570 residing in the Maringá Metropolitan Region and numerous surrounding towns. The adult intensive care unit (ICU) has 8 beds located in individual rooms with handwashing facilities. Gloves and gowns are required for patient contact, and chlorhexidine and alcohol-based hand gel are used for hand hygiene. Among the multidrug-resistant pathogens monitored, A baumannii has been the main cause of nosocomial infections in the ICU, with a total of 472 isolates collected from January 2009-December 2013. For this study, the first isolate from each patient admitted to the ICU (n = 133) was typed by enterobacterial repetitive intergenic consensus–polymerase chain reaction, as previously described,5 and analyzed using BioNumerics version 6.5 (Applied Maths, Sint-Martens-Latem, Belgium). Isolates were judged to have the same cluster if the Dice correlation coefficient was ≥0.93. Sixty-eight distinct clusters of A baumannii were included in this study. The identification and analysis of the antimicrobial susceptibility profile were carried out in the laboratory using Phoenix (BD Diagnostics, Sparks Glencoe, MD). The minimal inhibitory concentrations (MICs) of meropenem, imipenem, and polymyxin B were confirmed by the agar dilution method.6
0196-6553/© 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajic.2015.11.020
ARTICLE IN PRESS G.F. Viana et al. / American Journal of Infection Control ■■ (2015) ■■–■■
2
DISCUSSION
Multiplex polymerase chain reaction analyses were performed to detect blaKPC gene and metallo-β-lactamase (blaIMP, blaVIM, blaGIM, blaSPM, blaSIM, and blaNDM)7 and oxacillinase genes (blaOXA-23, blaOXA-24, blaOXA-51, blaOXA-58, and blaOXA-143).8 ISAba1 was detected using the primers ISAba1F and ISAba1R in combination with the primers OXA-23 (R and F).3
This study showed that not only the presence of the blaOXA-23 gene, but also its association with ISAba1, had a key role in increasing the MICs of carbapenems to treat A baumannii and also on increasing the genetic variability of the bacterium. A baumannii clusters (n = 68) showed high rates of resistance to almost all of the antimicrobial agents tested, including carbapenems (85% were resistant isolates), similar to findings elsewhere in Latin America.1 The presence of the ISAba1/blaOXA-23 gene was the main resistance mechanism found in the A baumannii isolates. The dissemination of the ISAba1/blaOXA-23 gene has also been reported in other Brazilian states and worldwide.1-3 However, to our knowledge, this is the first study to demonstrate the increase of ISAba1/blaOXA-23 over time. We observed a significant increase in the number of isolates carrying the ISAba1/blaOXA-23 gene and a direct correlation with high MICs for carbapenems (ie, A baumanii clusters carrying only blaOXA-23 showed MIC50 = 8 μg/mL, whereas A baumanii clusters carrying ISAba1/blaOXA-23 showed MIC50 = 32 μg/mL). The location of ISAba1 upstream of the blaOXA-23 gene might explain the overexpression of this gene. Higher MICs decrease the chances of therapeutic success, even with the use of pharmacokinetic-pharmacodynamic strategies, such as prolonged infusion of meropenem and increases in the dose.9 The clonal variability increased in the same period as the increase in the rates of ISAba1/blaOXA-23-producing A baumannii isolates. Between 2004 and 2009, an endemic clone of A baumannii was detected in our hospital,4 and the blaOXA-23 gene was detected in this cluster. Monitoring this endemic clone in our hospital revealed that the clonal variability increased beginning in 2010, the same year as an increase in A baumannii carrying ISAba1/blaOXA-23. Another study demonstrated a correlation between an increase in clonal variability and the presence of mobile elements, such as IMP-1.10 Likewise, a study verified the presence of various A baumannii clusters cocirculating in an ICU and a possible relationship to ISAba1.11
RESULTS Different clones of A baumannii proved to be resistant to most of the antimicrobial classes tested. Cephalosporins, fluoroquinolones, tetracyclines, and aminoglycosides, including carbapenems, showed low in vitro activity against A baumannii isolates (85% of the isolates were carbapenem resistant). The annual distribution of resistance rates to carbapenems are presented in Table 1. A high susceptibility rate was observed only for polymyxin B (100% of the isolates were susceptible). All 68 A baumannii isolates possessed the blaOXA-51 gene. The isolates were negative for the genes blaOXA-24, blaOXA-58, blaOXA-143, blaVIM, blaSPM, blaSIM, blaGIM, blaIMP, blaNDM, and blaKPC. Forty-eight isolates (71%) possessed the blaOXA-23 gene, and only 3 of them were susceptible to carbapenems. The association ISAba1 upstream of the blaOXA-23 gene was detected in 39 (81%) of the carbapenem-resistant A baumannii isolates, and 3 of these also showed ISAba1 downstream of the gene. Four of the isolates carrying only blaOXA-51 also had ISAba1 upstream of this gene. All were resistant to carbapenems. The determinations of MICs and their association with carbapenemases are described in Table 2. Both the minimum inhibitory concentration capable of inhibiting 50% of the isolates tested (MIC50) and MIC capable of inhibiting 90% of the isolates tested for polymyxin B were 2 μg/mL, independently of the presence or absence of the blaOXA-23 gene and its association with ISAba1. Carbapenem-resistant A baumannii isolates carrying the ISAba1-blaOXA-23 combination increased markedly, from 22% in 2009 to 73% in 2013. The genetic variability of these isolates also increased. In 2009, 34 A baumannii isolates were collected, and 9 clones were detected. In 2013, 18 A baumannii isolates were collected, and 11 clones were detected (Table 1).
Table 1 Annual distribution of clonality and resistance to carbapenems and carbapenemases of Acinetobacter baumannii clusters Year of isolation Distribution of clonality
2009
2010
2011
2012
2013
Isolates/clusters (N = 133/N = 68), n % Resistance (clusters) Cluster blaOXA-51 gene alone Cluster blaOXA-51 + blaOXA-23 gene Cluster blaOXA-51 gene + ISAba1 Cluster blaOXA-51 blaOXA-23 gene + ISAba1
34/9 80 2 (22) 4 (44) 1 (12) 2 (22)
41/19 82 6 (31) 2 (11) 2 (11) 9 (47)
18/14 94 3 (21) 1 (8) — 10 (71)
22/15 87 3 (20) 1 (7) 1 (7) 10 (66)
18/11 82 2 (18) 1 (9) — 8 (73)
NOTE. Values are n (%) or as otherwise indicated. Pearson correlation: resistance and clonality/year: 0.88.
Table 2 Minimal inhibitory concentration to carbapenems of 68 Acinetobacter baumannii clusters, according to their mechanism of resistance No. of clusters and cumulative percentage inhibited at MIC (μg ml−1) Mechanism resistance (no. of clusters) Negative for blaOXA-23 gene (n = 20) Positive for blaOXA-23 gene and negative for ISAba1 (n = 9) Positive for blaOXA-23 gene and positive for ISAba1 (n = 39) Total of clusters (n = 68)
0.5
1
2
4
8
16
32
64
MIC50
MIC90
2 (10) 1 (11) 0 (0) 3 (4)
5 (35) 1 (22) 0 (0) 7 (15)
2 (45) 0 (0) 0 (0) 2 (18)
1 (50) 0 (0) 0 (0) 1 (19)
5 (75) 3 (56) 1 (3) 9 (32)
3 (90) 1 (67) 10 (28) 14 (53)
2 (100) 2 (89) 23 (87) 27 (93)
0 (0) 1 (100) 4 (100) 5 (100)
4 8 32 16
16 64 64 32
NOTE. Values are n (%). MIC, minimum inhibitory concentration; MIC50, minimum inhibitory concentration capable of inhibiting 50% of the isolates tested; MIC90, minimum inhibitory concentration capable of inhibiting 90% of the isolates tested.
ARTICLE IN PRESS G.F. Viana et al. / American Journal of Infection Control ■■ (2015) ■■–■■
Our study suggests that the presence of the association ISAba1-blaOXA-23 was directly correlated with the increases in the MIC levels for carbapenems and in the clonal variability. These findings illustrate the difficulty of controlling this microorganism and emphasize the need for effective surveillance and the rational use of carbapenems.
Acknowledgment We thank Dr. Janet W. Reid (JWR Associates) for reviewing and editing the English language of our text.
References 1. Zarrilli R, Giannouli M, Tomasone F, Triassi M, Tsarikis A. Carbapenem resistance in Acinetobacter baumannii: the molecular epidemic features of an emerging problem in health care facilities. J Infect Dev Ctries 2009;3:335-41. 2. Chagas TPG, Carvalho KR, Santos ICO, Carvalho-Assef APD, Asensi MD. Characterization of carbapenem-resistant Acinetobacter baumannii in Brazil (2008–2011): countrywide spread of OXA-23–producing clones (CC15 and CC79). Diagn Microbiol Infect Dis 2014;79:468-72.
3
3. Turton JF, Ward ME, Woodford N, Kaufmann ME, Pike R, Livermore DM, et al. The role of ISAba1in expression of OXA carbapenemase genes in Acinetobacter baumannii. FEMS Microbiol Lett 2006;258:72-7. 4. Saalfeld SMS, Viana GF, Siqueira VLD, Cardoso CL, Garcia LB, Bronharo Tognim MC. Endemic carbapenem-resistant Acinetobacter baumannii in a Brazilian intensive care unit. J Hosp Infect 2009;72:365-8. 5. Silbert S, Pfaller MA, Hollis RJ, Barth AL, Sader HS. Evaluation of three molecular typing techniques for nonfermentative Gram-negative bacilli. Infect Control Hosp Epidemiol 2004;25:847-51. 6. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; twenty-fourth informational supplement. Document M100-S24. Wayne (PA): Clinical and Laboratory Standards Institute; 2014. 7. Poirel L, Walsh TR, Cuvillier V, Nordmann P. Multiplex PCR for detection of acquired carbapenemase genes. Diagn Microbiol Infect Dis 2011;70:119-23. 8. Higgins PG, Lehmann M, Seifert H. Inclusion of OXA-143 primers in a multiplex polymerase chain reaction (PCR) for genes encoding prevalent OXA carbapenemases in Acinetobacter spp. Int J Antimicrob Agents 2010;35:305. 9. Lomaestro BM, Drusano GL. Pharmacodynamic evaluation of extending the administration time of meropenem using a Monte Carlo simulation. Antimicrob Agents Chemother 2005;49:461-3. 10. Tognim MCB, Gales AC, Penteado AP, Silbert S, Sader HS. Dissemination of IMP-1 metallo-β-lactamase–producing Acinetobacter species in a Brazilian teaching hospital. Infect Control Hosp Epidemiol 2006;27:742-7. 11. Valenzuela JK, Thomas L, Partridge SR, van der Reijden T, Dijkshoorn L, Iredell J. Horizontal gene transfer in a polyclonal outbreak of carbapenem-resistant Acinetobacter baumannii. J Clin Microbiol 2007;45:453-60.