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CLINICAL SCIENCE
The prevalence of aminoglycoside-modifying enzyme genes (aac (6′)-I, aac (6′)-II, ant (2″)-I, aph (3′)-VI) in Pseudomonas aeruginosa
Farzam Vaziri, Shahin Najar Peerayeh
Corresponding author
najarp_s@modares.ac.ir

/ Tel.: 00 98 021 82883870
, Qorban Behzadian Nejad, Abbas Farhadian
Department of Bacteriology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
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    "titulo" => "The prevalence of aminoglycoside-modifying enzyme genes <span class="elsevierStyleItalic">&#40;aac &#40;6&#8242;&#41;-I&#44; aac &#40;6&#8242;&#41;-II&#44; ant &#40;2&#8243;&#41;-I&#44; aph &#40;3&#8242;&#41;-VI&#41;</span> in <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>"
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          "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">Lane 1&#44; 1000 bp DNA size marker&#59; Lane 2&#44; <span class="elsevierStyleItalic">aac</span>&#40;6&#8242;&#41;-II &#40;125 bp&#41;&#59; Lane 5&#44; <span class="elsevierStyleItalic">aph</span>&#40;3&#8242;&#41;-VI &#40;800 bp&#41;&#59; Lane 7&#44; <span class="elsevierStyleItalic">ant</span>&#40;2<span class="elsevierStyleItalic">&#8243;</span>&#41;-I &#40;524 bp&#41;&#59; Lanes 8 and 9&#44; <span class="elsevierStyleItalic">aac</span>&#40;6&#8242;&#41;-I &#40;392 bp&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle70">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> &#40;<span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#41; is one of the primary opportunistic pathogens responsible for nosocomial infections&#46; The most important problem in the eradication of <span class="elsevierStyleItalic">P&#46; aeruginosa</span> is the frequently observed multi-drug resistance of the species&#46;<a class="elsevierStyleCrossRef" href="#bib1">1</a> In addition&#44; <span class="elsevierStyleItalic">P&#46; aeruginosa</span> can also acquire resistance to various antimicrobial agents&#44; such as aminoglycosides&#44; &#946;-lactams<a class="elsevierStyleCrossRef" href="#bib2">2</a> and fluoroquinolones&#46;<a class="elsevierStyleCrossRef" href="#bib3">3</a> Aminoglycosides are an important component of antipseudomonal chemotherapy&#44;<a class="elsevierStyleCrossRef" href="#bib4">4</a> and they exhibit synergy with &#946;-lactams&#46;<a class="elsevierStyleCrossRef" href="#bib5">5</a> Resistance to aminoglycosides occurs via enzymatic modification&#44; impermeability&#44; the activity of efflux pumps &#40;MexXY-OprM&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib6">6</a> the PhoP-PhoQ system&#44;<a class="elsevierStyleCrossRef" href="#bib7">7</a> ndvB-dependent biofilm formation&#44;<a class="elsevierStyleCrossRef" href="#bib8">8</a> and the activity of 16s rRNA methylases&#46;<a class="elsevierStyleCrossRef" href="#bib9">9</a> Among these mechanisms&#44; the inactivation of drugs by plasmid- or chromosome-encoded modifying enzymes is the most common&#46; These modifying enzymes include aminoglycoside phosphoryl transferase &#40;<span class="elsevierStyleItalic">aph</span>&#41;&#44; aminoglycoside acetyltransferase &#40;<span class="elsevierStyleItalic">aac</span>&#41;&#44; and aminoglycoside nucleotidyl transferase &#40;<span class="elsevierStyleItalic">ant</span>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib10">10&#8211;12</a> Four of these enzymes&#44; encoded by <span class="elsevierStyleItalic">aac &#40;6&#8242;&#41;-I&#44; aac &#40;6&#8242;&#41;-II&#44; ant &#40;2&#8243;&#41;-I&#44;</span> and <span class="elsevierStyleItalic">aph &#40;3&#8242;&#41;-VI</span>&#44; are of particular significance because they are among the most common modifying enzymes present in <span class="elsevierStyleItalic">P&#46; aeruginosa&#44;</span> and their substrates are the most important antipseudomonal aminoglycosides&#46; <span class="elsevierStyleItalic">aac</span> &#40;6&#8242;&#41;-I confers resistance to tobramycin and amikacin&#44; <span class="elsevierStyleItalic">aac</span> &#40;6&#8242;&#41;-II and <span class="elsevierStyleItalic">ant</span> &#40;2<span class="elsevierStyleItalic">&#8243;</span>&#41;-I inactivate tobramycin and gentamicin&#44; and amikacin is the substrate of <span class="elsevierStyleItalic">aph</span> &#40;3&#8242;&#41;-VI&#46;<a class="elsevierStyleCrossRefs" href="#bib13">13&#44;14</a></p><p id="para20" class="elsevierStylePara elsevierViewall">The aim of the present nationwide study was to investigate the occurrence of aminoglycoside resistance and the prevalence of the resistance-modifying enzyme genes&#44; <span class="elsevierStyleItalic">aac &#40;6&#8242;&#41;-I&#44; aac &#40;6&#8242;&#41;-II&#44; ant &#40;2&#8243;&#41;-I</span> and <span class="elsevierStyleItalic">aph &#40;3&#8242;&#41;-VI&#44;</span> in <span class="elsevierStyleItalic">P&#46; aeruginosa</span> isolated from several hospitals in seven Iranian cities&#46;</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle80">METHODS AND MATERIALS</span><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle90">Collection of bacterial isolates</span><p id="para30" class="elsevierStylePara elsevierViewall">A total of 250 non-duplicate&#44; clinical isolates of <span class="elsevierStyleItalic">P&#46; aeruginosa</span> were collected from a nationwide distribution of several hospitals in seven cities in Iran &#40;Tehran&#44; Shiraz&#44; Zahedan&#44; Tabriz&#44; Sannandaj&#44; Sari&#44; and Ahvaz&#41; between May 2007 and January 2008&#46; Strain data and the demographic and clinical data for each patient were regularly forwarded to our laboratory&#46; The study population was 62&#37; male and 38&#37; female&#46; The specimens were isolated from urine &#40;38&#37;&#41;&#44; wounds &#40;18&#37;&#41;&#44; the trachea &#40;18&#37;&#41;&#44; blood &#40;10&#37;&#41;&#44; sputum &#40;9&#37;&#41;&#44; and other sources &#40;7&#37;&#41;&#46; Isolate confirmations were conducted using conventional biochemical tests&#44; and then the isolates were stored at &#8211;76&#176;C in glycerol skim milk broth&#46;</p></span><span id="cesec40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle100">Antimicrobial susceptibility testing</span><p id="para40" class="elsevierStylePara elsevierViewall">Antimicrobial susceptibility tests were performed using the disk diffusion method according to Clinical and Laboratory Standards Institute &#40;CLSI&#41; guidelines<a class="elsevierStyleCrossRef" href="#bib15">15</a> for three aminoglycosides &#91;gentamicin &#40;10 &#956;g&#41;&#44; amikacin &#40;30 &#956;g&#41;&#44; and tobramycin &#40;10 &#956;g&#41;&#93; and for five other antibiotics &#91;imipenem &#40;10 &#956;g&#41;&#44; piperacillin &#40;100 &#956;g&#41;&#44; ticarcillin &#40;75 &#956;g&#41;&#44; ceftazidime &#40;30 &#956;g&#41;&#44; and ciprofloxacin &#40;5 &#956;g&#41;&#93;&#46; All drugs were obtained from Mast laboratories &#40;Merseyside&#44; United Kingdom&#41;&#46; For all 250 isolates&#44; the minimum inhibitory concentrations &#40;MIC&#41; of amikacin&#44; gentamicin&#44; and tobramycin were determined using the E-test &#40;Biodisk&#44; Dalvagen&#44; Sweden&#41; according to CLSI guidelines&#46; <span class="elsevierStyleItalic">P&#46; aeruginosa</span> &#40;ATCC 27853&#41; served as a control for the disk diffusion and E-tests&#46;</p></span><span id="cesec50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle110">Polymerase chain reaction amplification</span><p id="para50" class="elsevierStylePara elsevierViewall">Polymerase chain reaction &#40;PCR&#41; was used to screen all 250 isolates for the presence of the modifying enzyme genes&#44; <span class="elsevierStyleItalic">aac &#40;6&#8242;&#41;-I&#44; aac &#40;6&#8242;&#41;-II&#44; ant &#40;2&#8243;&#41;-I</span> and <span class="elsevierStyleItalic">aph &#40;3&#8242;&#41;-VI</span>&#46; The total template DNA for the PCR amplification was extracted from the supernatant of a mixture of <span class="elsevierStyleItalic">P&#46; aeruginosa</span> cells produced by the boiling method&#46; PCR amplification was performed using 2&#46;5 &#956;L of the template DNA&#44; 1 &#956;L of each primer&#44;<a class="elsevierStyleCrossRef" href="#bib16">16</a> 19&#46;5 &#956;L master mix&#44; and 1 &#956;L of Taq DNA polymerase &#40;CinnaGen&#41; in a total volume of 25 &#956;L&#46; A thermocycler &#40;Mastercycler gradient&#59; Eppendorf&#44; Hamburg&#44; Germany&#41; was programmed with the appropriate conditions&#46; Then&#44; 5 &#956;l of each PCR product was analyzed by electrophoresis on a 1&#37; &#40;w&#47;v&#41; TAE agarose gel &#40;Fermentas UAB&#44; Vilnius&#44; Lithuania&#41; containing 0&#46;1 &#956;l&#47;ml ethidium bromide&#46; The amplicons were then visualized on a UV transilluminator and photographed &#40;BioDoc-Analyse&#59; Biometra&#44; Goettingen&#44; Germany&#41;&#46;</p></span><span id="cesec60" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle120">Statistical analysis</span><p id="para60" class="elsevierStylePara elsevierViewall">All statistical analyses were performed using Statistical Package for Social Sciences &#40;SPSS&#41; software &#40;version 11&#46;5&#41; for Windows &#40;&#967;<span class="elsevierStyleSup">2</span>-test and Fisher&#39;s exact test&#41;&#46; <span class="elsevierStyleItalic">P-</span>values of &#60;0&#46;05 were considered significant&#46;</p></span></span><span id="cesec70" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle130">RESULTS AND DISCUSSION</span><p id="para70" class="elsevierStylePara elsevierViewall">The resistance rates as determined using the disk diffusion method are presented in <a class="elsevierStyleCrossRef" href="#fig1">Figure 1</a>&#46; According to the disk diffusion method&#44; 135 isolates were resistant to aminoglycosides&#46; The resistance rates according to the E-test &#40;base on MICs&#41; were as follows&#58; gentamicin 40&#37;&#44; tobramycin 36&#37;&#44; and amikacin 21&#37;&#46; The aminoglycoside susceptibility profiles according to the disk diffusion and E-test results for the 250 isolates are listed in <a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a>&#46;</p><elsevierMultimedia ident="fig1"></elsevierMultimedia><elsevierMultimedia ident="tbl1"></elsevierMultimedia><p id="para80" class="elsevierStylePara elsevierViewall">PCR analysis revealed the absence of resistance genes in susceptible isolates&#46; The prevalence of aminoglycoside resistance genes in the 135 resistant isolates &#40;as determined by the disk diffusion method&#41; was as follows&#58; <span class="elsevierStyleItalic">aac &#40;6&#8242;&#41;-II</span> was detected in 36&#37; of the resistant isolates&#44; <span class="elsevierStyleItalic">ant &#40;2&#8243;&#41;-I</span> was detected in 28&#37;&#44; <span class="elsevierStyleItalic">aph &#40;3&#8242;&#41;-VI</span> in 11&#37;&#44; and <span class="elsevierStyleItalic">aac &#40;6&#8242;&#41;-I</span> was found in 7&#37; of the resistant isolates &#40;<a class="elsevierStyleCrossRef" href="#fig2">Figure 2</a>&#41;&#46; Interestingly&#44; individual aminoglycoside-resistant isolates carried multiple &#40;two to four&#41; modifying enzyme genes&#46; Six isolates harbored <span class="elsevierStyleItalic">ant&#40;2&#8243;&#41;-I</span> and <span class="elsevierStyleItalic">aac</span>&#40;6&#8242;&#41;-II&#59; three harbored <span class="elsevierStyleItalic">aph&#40;3&#8242;&#41;-VI</span> and <span class="elsevierStyleItalic">ant&#40;2&#8243;&#41;-I</span>&#59; two harbored <span class="elsevierStyleItalic">ant&#40;2&#8243;&#41;-I</span> and <span class="elsevierStyleItalic">aac&#40;6&#8242;&#41;-I&#59;</span> and three isolates harbored <span class="elsevierStyleItalic">ant&#40;2&#8243;&#41;-I</span>&#44; <span class="elsevierStyleItalic">aac&#40;6&#8242;&#41;-II</span> and <span class="elsevierStyleItalic">aph&#40;3&#8242;&#41;-VI&#46;</span> Only one isolate harbored all four genes&#46;</p><elsevierMultimedia ident="fig2"></elsevierMultimedia><p id="para90" class="elsevierStylePara elsevierViewall">Several previous studies have examined the occurrence of aminoglycoside resistance mechanisms in <span class="elsevierStyleItalic">P&#46; aeruginosa</span> isolated from different countries&#46; The overall incidence of aminoglycoside resistance found in our study &#40;according to the disk diffusion test and the E-test&#41; was much higher than the incidence that has been reported previously in different countries worldwide&#46;<a class="elsevierStyleCrossRefs" href="#bib14">14&#44;16&#44;17</a> However&#44; Estahbanati and co-workers reported that 53&#46;3&#37; of clinical isolates from Iranian burn patients were resistant to amikacin&#44; and 90&#46;7&#37; were resistant to gentamicin&#44; a result that reveals a high level of aminoglycoside resistance in their study&#46;<a class="elsevierStyleCrossRef" href="#bib18">18</a></p><p id="para100" class="elsevierStylePara elsevierViewall">The aminoglycoside resistance rate was almost as high in our isolates&#44; and most of the resistant isolates harbored modifying enzyme genes&#46; In addition&#44; none of the susceptible isolates harbored these resistance genes&#46; These results highlight the importance of aminoglycoside-modification-related mechanisms in aminoglycoside resistance in <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#46; Two genes&#44; <span class="elsevierStyleItalic">aac &#40;6&#8242;&#41;-II</span> and <span class="elsevierStyleItalic">ant &#40;2&#8243;&#41;-I&#44;</span> were the most frequent resistance genes observed in these isolates&#46; These results are similar to what has been observed in different studies in other countries&#46;<a class="elsevierStyleCrossRefs" href="#bib19">19&#8211;21</a> All isolates harboring the <span class="elsevierStyleItalic">aac &#40;6&#8242;&#41;-II</span> gene were resistant to gentamicin and tobramycin &#40;100&#37; concordance&#41;&#44; which indicates that <span class="elsevierStyleItalic">aac</span> &#40;6&#8242;&#41;-II is a significant determinant of gentamicin and tobramycin resistance in <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#46; It is important to mention that we encountered an unexpected phenotype in some isolates &#40;<a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a>&#41;&#46; For example&#44; when an isolate harbored only the <span class="elsevierStyleItalic">aph &#40;3&#8242;&#41;-VI</span> gene&#44; which has amikacin as a substrate&#44; resistance to gentamicin&#44; tobramycin&#44; and amikacin was observed&#46; We presume that the reason for this phenomenon might be the action of other resistance mechanisms&#44; such as impermeability&#44; efflux pumps&#44; or other types of modifying enzymes&#46; On the other hand&#44; we detected 15 isolates which co-harbored two&#44; three&#44; or four aminoglycoside-modifying enzyme genes simultaneously&#44; which is in contrast to several studies conducted in the USA and Europe&#44; which reported that the majority of isolates exhibit only a single aminoglycoside modifying gene&#46;<a class="elsevierStyleCrossRef" href="#bib22">22</a></p><elsevierMultimedia ident="tbl2"></elsevierMultimedia><p id="para110" class="elsevierStylePara elsevierViewall">Miller et al&#46; brought together the results of several studies of aminoglycoside resistance in <span class="elsevierStyleItalic">P&#46; aeruginosa</span> carried out worldwide&#46;<a class="elsevierStyleCrossRef" href="#bib22">22</a> Their results indicated that in Europe&#44; <span class="elsevierStyleItalic">aac&#40;6&#8242;&#41;-II</span> was the most prevalent resistance gene &#40;32&#46;5&#37;&#41;&#44; followed by <span class="elsevierStyleItalic">ant&#40;2&#8243;&#41;-I</span> &#40;16&#46;9&#37;&#41;&#46; These results are in concordance with our study&#46; In contrast to our results&#44; a Korean nationwide study of 250 isolates of <span class="elsevierStyleItalic">P&#46; aeruginosa</span> reported that <span class="elsevierStyleItalic">aph&#40;3&#8242;&#41;-VI</span>&#44; <span class="elsevierStyleItalic">ant&#40;2&#8243;&#41;-I</span>&#44; and <span class="elsevierStyleItalic">aac&#40;6&#8242;&#41;-I</span> were all prevalent&#44; but none harbored <span class="elsevierStyleItalic">aac&#40;6&#8242;&#41;-II</span>&#46;<a class="elsevierStyleCrossRef" href="#bib16">16</a> The difference in the distribution of modifying enzymes may derive from differences in aminoglycoside prescription patterns&#44; the selection of bacterial population or geographical differences in the occurrence of aminoglycoside resistance genes&#46;</p></span><span id="cesec80" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle140">CONCLUSIONS</span><p id="para120" class="elsevierStylePara elsevierViewall">In conclusion&#44; although aminoglycosides remain useful antipseudomonal agents&#44; resistance to these drugs continues to be a major issue&#44; especially in Iran&#46; Because these aminoglycoside resistance genes are usually located on mobile genetic elements &#40;i&#46;e&#46;&#44; plasmid&#44; transposon&#44; or integrons&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib23">23&#44;24</a> there is a growing concern that they could easily spread and be disseminated among other bacteria&#46; Integrons that carry gene cassettes encoding both <span class="elsevierStyleItalic">aac</span>s and carbapenemases will only exacerbate this problem&#46;<a class="elsevierStyleCrossRef" href="#bib25">25</a> The design of novel aminoglycosides with stronger affinity for their targets and resistance to these modifying enzymes is inevitable&#44;<a class="elsevierStyleCrossRef" href="#bib26">26</a> and the new generation of anti-<span class="elsevierStyleItalic">Pseudomonas</span> therapy is forthcoming&#46;<a class="elsevierStyleCrossRef" href="#bib27">27</a> Aminoglycoside resistance among clinical isolates of <span class="elsevierStyleItalic">P&#46; aeruginosa</span> promises to become a major clinical concern in the future&#44; and continuous local surveillance of aminoglycoside resistance is crucial&#46;</p></span></span>"
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          "identificador" => "cesec10"
          "titulo" => "INTRODUCTION"
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        2 => array:3 [
          "identificador" => "cesec20"
          "titulo" => "METHODS AND MATERIALS"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "cesec30"
              "titulo" => "Collection of bacterial isolates"
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            1 => array:2 [
              "identificador" => "cesec40"
              "titulo" => "Antimicrobial susceptibility testing"
            ]
            2 => array:2 [
              "identificador" => "cesec50"
              "titulo" => "Polymerase chain reaction amplification"
            ]
            3 => array:2 [
              "identificador" => "cesec60"
              "titulo" => "Statistical analysis"
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        3 => array:2 [
          "identificador" => "cesec70"
          "titulo" => "RESULTS AND DISCUSSION"
        ]
        4 => array:2 [
          "identificador" => "cesec80"
          "titulo" => "CONCLUSIONS"
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        5 => array:2 [
          "identificador" => "xack639490"
          "titulo" => "ACKNOWLEDGEMENTS"
        ]
        6 => array:1 [
          "titulo" => "REFERENCES"
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      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2011-02-01"
    "fechaAceptado" => "2011-05-16"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "KEYWORDS"
          "identificador" => "xpalclavsec1582733"
          "palabras" => array:5 [
            0 => "<span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>"
            1 => "Antibiotic"
            2 => "Resistance"
            3 => "<span class="elsevierStyleItalic">aac &#40;6&#8242;&#41;-II</span>"
            4 => "<span class="elsevierStyleItalic">ant &#40;2&#8243;&#41;-I</span>"
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    "resumen" => array:1 [
      "en" => array:2 [
        "resumen" => "<span id="ceabs10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle10">INTRODUCTION&#58;</span><p id="spara50" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> &#40;<span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#41; is one of the primary opportunistic pathogens responsible for nosocomial infections&#46; Aminoglycosides are an important component of antipseudomonal chemotherapy&#46; The inactivation of drugs by modifying enzymes is the most common mechanism of aminoglycoside resistance&#46;</p></span> <span id="ceabs20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">OBJECTIVES&#58;</span><p id="spara60" class="elsevierStyleSimplePara elsevierViewall">The inactivation of aminoglycosides by modifying enzymes is the primary resistance mechanism employed by <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#46; The aim of the present study was to investigate the occurrence of aminoglycoside resistance and the prevalence of four important modifying enzyme genes &#40;<span class="elsevierStyleItalic">aac &#40;6&#8242;&#41;-I&#44; aac &#40;6&#8242;&#41;-II&#44; ant &#40;2&#8243;&#41;-I&#44; aph &#40;3&#8242;&#41;-VI</span>&#41; in <span class="elsevierStyleItalic">P&#46; aeruginosa</span> in Iran&#46;</p></span> <span id="ceabs30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">METHODS&#58;</span><p id="spara70" class="elsevierStyleSimplePara elsevierViewall">A total of 250 clinical isolates of <span class="elsevierStyleItalic">P&#46; aeruginosa</span> were collected from several hospitals in seven cities in Iran&#46; Antimicrobial susceptibility tests &#40;using the disk diffusion method and E-tests&#41; were performed for all 250 isolates&#46; In addition&#44; all isolates were screened for the presence of modifying enzyme genes by polymerase chain reaction&#46;</p></span> <span id="ceabs40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle40">RESULTS&#58;</span><p id="spara80" class="elsevierStyleSimplePara elsevierViewall">The resistance rates&#44; as determined by the disk diffusion method&#44; were as follows&#58; gentamicin 43&#37;&#44; tobramycin 38&#37;&#44; and amikacin 24&#37;&#46; Of the genes examined&#44; <span class="elsevierStyleItalic">aac &#40;6&#8242;&#41;-II</span> &#40;36&#37;&#41; was the most frequently identified gene in phenotypic resistant isolates&#44; followed by <span class="elsevierStyleItalic">ant &#40;2&#8243;&#41;-I&#44; aph &#40;3&#8242;&#41;-VI&#44;</span> and <span class="elsevierStyleItalic">aac &#40;6&#8242;&#41;-I</span>&#46;</p></span> <span id="ceabs50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle50">CONCLUSIONS&#58;</span><p id="spara90" class="elsevierStyleSimplePara elsevierViewall">Aminoglycoside resistance in <span class="elsevierStyleItalic">P&#46; aeruginosa</span> remains a significant problem in Iran&#46; Therefore&#44; there is considerable local surveillance of aminoglycoside resistance&#46;</p></span>"
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          "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">The antimicrobial resistance rate of 250 <span class="elsevierStyleItalic">P&#46; aeruginosa</span> isolates as determined by the disk diffusion method AMI&#58; amikacin&#44; GEN&#58; gentamicin&#44; TOB&#58; tobramycin&#44; IMI&#58; imipenem&#44; PIP&#58; piperacillin&#44; TIC&#58; ticarcillin&#44; CAZ&#58; ceftazidime&#44; CIP&#58; ciprofloxacin&#46;</p>"
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          "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">Lane 1&#44; 1000 bp DNA size marker&#59; Lane 2&#44; <span class="elsevierStyleItalic">aac</span>&#40;6&#8242;&#41;-II &#40;125 bp&#41;&#59; Lane 5&#44; <span class="elsevierStyleItalic">aph</span>&#40;3&#8242;&#41;-VI &#40;800 bp&#41;&#59; Lane 7&#44; <span class="elsevierStyleItalic">ant</span>&#40;2<span class="elsevierStyleItalic">&#8243;</span>&#41;-I &#40;524 bp&#41;&#59; Lanes 8 and 9&#44; <span class="elsevierStyleItalic">aac</span>&#40;6&#8242;&#41;-I &#40;392 bp&#41;&#46;</p>"
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                  \t\t\t\t  " align="center" valign="top" scope="col">Resistant&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Gentamicin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">108&#40;43&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">8&#40;3&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">134&#40;53&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Tobramycin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">95&#40;38&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">7&#40;2&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">148&#40;59&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">103&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
            1 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">MIC&#40;&#956;g&#47;ml&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">MIC&#40;&#956;g&#47;ml&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">MIC&#40;&#956;g&#47;ml&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">MIC 50&#37; &#40;ug&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">MIC 90&#37; &#40;ug&#47;mL&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">&#62;256&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">&#8211;256128&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">64&#8211;128&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">4&#8211;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">&#60;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top" style="border-bottom: 2px solid black">Amikacin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">59&#40;23&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">7&#40;2&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">184&#40;73&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">134&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">128&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tfn1"
              "etiqueta" => "1&#46;"
              "nota" => "<p class="elsevierStyleNotepara" id="cenpara10">Zone diameter &#40;mm&#41; for gentamicin and tobramycin&#44; R&#58;&#60;12&#44; I&#58;13-14&#44; S&#58;&#62;15&#59; for amikacin&#44; R&#58;&#60;14&#44; I&#58;15-16&#44; S&#58;&#62;17&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tfn2"
              "etiqueta" => "2&#46;"
              "nota" => "<p class="elsevierStyleNotepara" id="cenpara20">MIC breakpoint&#40;&#956;g&#47;ml&#41; for gentamicin and tobramycin&#44; R&#58;&#62;16&#44; I&#58;8&#59; S&#58;&#60;4&#59; for amikacin&#44; R&#58;&#62;64&#44; I&#58;32&#44; S&#58;&#60;16&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">Aminoglycoside susceptibility profiles according to the disk diffusion method and MIC results &#40;E-test&#41; for 250 <span class="elsevierStyleItalic">P&#46; aeruginosa</span> isolates &#40;according to CLSI guidelines&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib15">15</a></p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl2"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="top" scope="col">Gene&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">no&#46; of isolates &#40;&#37;&#41;<a class="elsevierStyleCrossRef" href="#tfn3">1</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">Expected resistance<a class="elsevierStyleCrossRef" href="#tfn4">2</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">Observed resistance phenotypes &#40;no&#46; of isolates&#41;<a class="elsevierStyleCrossRef" href="#tfn5">3</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">aac&#40;6&#8242;&#41;-I</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">9&#40;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">TOB&#44;AMI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">Unexpected resistance to GEN&#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">aac&#40;6&#8242;&#41;-II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">49&#40;36&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">GEN&#44;TOB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">Unexpected resistance to AMI&#40;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">ant&#40;2&#8243;&#41;-I</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">38&#40;28&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">GEN&#44;TOB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">As expected&#40;38&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">aph&#40;3&#8242;&#41;-VI</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&#40;11&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">AMI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">Unexpected resistance to GEN and TOB&#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">aac&#40;6&#8242;&#41;-II&#43; ant&#40;2&#8243;&#41;-I</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">6&#40;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">GEN&#44;TOB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">As expected&#40;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">ant&#40;2&#8243;&#41;-I&#43; aph&#40;3&#8242;&#41;-VI</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">3&#40;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">AMI&#44;GEN&#44;TOB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">As expected&#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">aac&#40;6&#8242;&#41;-I&#43; ant&#40;2&#8243;&#41;-I</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2&#40;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">AMI&#44;GEN&#44;TOB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">As expected&#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">ant&#40;2&#8243;&#41;-I</span> &#43; <span class="elsevierStyleItalic">aac&#40;6&#8242;&#41;-II</span> &#43;<span class="elsevierStyleItalic">aph&#40;3&#8242;&#41;-VI</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">3&#40;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">AMI&#44;GEN&#44;TOB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">As expected&#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">aac</span>&#40;6&#8242;&#41;-II <span class="elsevierStyleItalic">ant</span>&#40;2&#8243;&#41;-I&#43; &#43; <span class="elsevierStyleItalic">aph</span>&#40;3&#8242;&#41;-VI &#43; <span class="elsevierStyleItalic">aac</span>&#40;6&#8242;&#41;-I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">1&#40;&#8764;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">AMI&#44;GEN&#44;TOB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">As expected&#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
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          "notaPie" => array:3 [
            0 => array:3 [
              "identificador" => "tfn3"
              "etiqueta" => "1&#46;"
              "nota" => "<p class="elsevierStyleNotepara" id="cenpara30">According to the disk diffusion method&#44; a total of 135 resistant isolates were identified&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tfn4"
              "etiqueta" => "2&#46;"
              "nota" => "<p class="elsevierStyleNotepara" id="cenpara40">AMI&#58; amikacin&#44; GEN&#58; gentamicin&#44; TOB&#58; tobramycin&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tfn5"
              "etiqueta" => "3&#46;"
              "nota" => "<p class="elsevierStyleNotepara" id="cenpara50">Described in greater detail in the text&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara40" class="elsevierStyleSimplePara elsevierViewall">Prevalence of aminoglycoside modifying enzymes genes and the correlation between these genes and phenotypic patterns in aminoglycoside resistant <span class="elsevierStyleItalic">P&#46; aeruginosa</span> isolates&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "REFERENCES"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "cebibsec10"
          "bibliografiaReferencia" => array:27 [
            0 => array:3 [
              "identificador" => "bib1"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mechanisms of antibiotic resistance in Pseudomonas aeruginosa"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              PA Lambert \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "J R Soc Med"
                        "fecha" => "2002"
                        "volumen" => "95"
                        "numero" => "suppl 41"
                        "paginaInicial" => "22"
                        "paginaFinal" => "26"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12216271"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib2"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence of Ambler class A and D &#946;-lactamases among clinical isolates of Pseudomonas aeruginosa in Korea"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              YJ Park \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1093/jac/dki160"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Antimicrob Chemother"
                        "fecha" => "2005"
                        "volumen" => "56"
                        "paginaInicial" => "122"
                        "paginaFinal" => "127"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15890715"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1093/jac/dki160"
                      "WWW" => array:1 [
                        "link" => "10&#46;1093&#47;jac&#47;dki160"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib3"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              S Jalal \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              O Ciofu \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              N H&#8856;iby \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              N Gotoh \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              patients Wretlind B&#46; Molecular mechanisms of fluoroquinolone resistance in Pseudomonas aeruginosa isolates from cystic fibrosis \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/AAC.44.3.710-712.2000"
                      "Revista" => array:6 [
                        "tituloSerie" => "Antimicrob Agents Chemother"
                        "fecha" => "2000"
                        "volumen" => "44"
                        "paginaInicial" => "710"
                        "paginaFinal" => "712"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10681343"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib4"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Therapeutic guidelines for Pseudomonas aeruginosa infections"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              H Giamarellou \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Int J antimicrob Agen"
                        "fecha" => "2000"
                        "volumen" => "16"
                        "paginaInicial" => "103"
                        "paginaFinal" => "106"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "10&#46;1016&#47;S0924-8579&#40;00&#41;00212-0"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib5"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "&#946;-lactam and aminoglycoside resistance rates and mechanisms among Pseudomonas aeruginosa in French general practice &#40;community and private healthcare centres&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              V Dubois \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              C Arpin \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              V Dupart \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              A Scavelli \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              L Coulange \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              C Andre \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1093/jac/dkn174"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Antimicrob Chemother"
                        "fecha" => "2008"
                        "volumen" => "62"
                        "paginaInicial" => "316"
                        "paginaFinal" => "323"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18467306"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1093/jac/dkn174"
                      "WWW" => array:1 [
                        "link" => "10&#46;1093&#47;jac&#47;dkn174"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib6"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chromosomal mechanisms of aminoglycoside resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              S Islam \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              H Oh \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              S Jalal \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              F Karpati \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              O Ciofu \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              N H&#8856;iby \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1469-0691.2009.02999.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Microbiol Infect"
                        "fecha" => "2009"
                        "volumen" => "15"
                        "paginaInicial" => "60"
                        "paginaFinal" => "66"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19754760"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1111/j.1469-0691.2009.02999.x"
                      "WWW" => array:1 [
                        "link" => "10&#46;1111&#47;j&#46;1469-0691&#46;2008&#46;02097&#46;x"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib7"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Role of Pseudomonas aeruginosa PhoP-PhoQ in resistance to antimicrobial cationic peptides and aminoglycosides"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              E Macfarlane \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              A Kwasnicka \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              R Hancock \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Microbiol"
                        "fecha" => "2000"
                        "volumen" => "146"
                        "paginaInicial" => "2543"
                        "paginaFinal" => "2554"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib8"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High-level antibiotic resistance in Pseudomonas aeruginosa biofilm&#58; the ndvB gene is involved in the production of highly glycerol-phosphorylated &#946;-&#40;1&#8594;3&#41;-glucans&#44; which bind aminoglycosides"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
                              I Sadovskaya \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              E Vinogradov \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              J Li \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              A Hachani \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              K Kowalska \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              A Filloux \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Glycobiol"
                        "fecha" => "2010"
                        "volumen" => "20"
                        "paginaInicial" => "895"
                        "paginaFinal" => "904"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "10&#46;1093&#47;glycob&#47;cwq047"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib9"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High prevalence of metallo- &#946;-lactamase and 16S rRNA methylase coproduction among imipenem- resistant Pseudomonas aeruginosa isolates in Brazil"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => """
                              Y Doi \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              AC Ghilardi \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              J Adams \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              GD de Oliveira \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              DL Paterson \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1128/AAC.00443-07"
                      "Revista" => array:6 [
                        "tituloSerie" => "Antimicrob Agents Chemother"
                        "fecha" => "2007"
                        "volumen" => "51"
                        "paginaInicial" => "3388"
                        "paginaFinal" => "3390"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17576840"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                    1 => array:2 [
                      "doi" => "10.1128/AAC.00443-07"
                      "WWW" => array:1 [
                        "link" => "10&#46;1128&#47;AAC&#46;00443-07"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib10"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              KJ Shaw \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              PN Rather \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              RS Hare \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              GH Miller \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/mr.57.1.138-163.1993"
                      "Revista" => array:6 [
                        "tituloSerie" => "Microbiol Rev"
                        "fecha" => "1993"
                        "volumen" => "57"
                        "paginaInicial" => "138"
                        "paginaFinal" => "163"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8385262"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib11"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Aminoglycoside antibiotic resistance by enzymatic deactivation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
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Article information
ISSN: 18075932
Original language: English
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

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Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos