Choosing the appropriate antibiotics to treat bacterial infections has grown more challenging as a result of the emergence of antibiotic-resistant bacteria.Aminoglycosides,as broad-spectrum antibiotics,are increasingl...Choosing the appropriate antibiotics to treat bacterial infections has grown more challenging as a result of the emergence of antibiotic-resistant bacteria.Aminoglycosides,as broad-spectrum antibiotics,are increasingly being used clinically;however,for most effective employment of aminoglycosides,a comprehensive understanding of aminoglycoside resistance genes’prevalence and dissemination is required.Therefore,to better understand the global resistance status of aminoglycoside antibiotics and the prevalence of antibiotic-resistance genes(ARGs)in various bacterial species,this systematic review gathered relevant data from multiple studies.Two primary resistance mechanisms-aminoglycoside enzymatic modification and 16S rRNA methylation-were assessed,and the prevalence of the corresponding ARGs was described.The coexistence of aminoglycoside ARGs with other ARGs was also demonstrated,as was the relationship between aminoglycoside ARGs and resistant phenotypes.The lack of effective therapeutic agents to combat resistant pathogens presents a real threat to public health.The combination of aminoglycosides with other antibiotics may provide a novel treatment strategy.展开更多
The objective of this study was to investigate the genetic basis of high level aminoglycoside resistance in Acinetobacter baumannii clinical isolates from Beijing,China.173 A.baumannii clinical isolates from hospitals...The objective of this study was to investigate the genetic basis of high level aminoglycoside resistance in Acinetobacter baumannii clinical isolates from Beijing,China.173 A.baumannii clinical isolates from hospitals in Beijing from 2006 to 2009 were first subjected to high level aminoglycoside resistance(HLAR,MIC to gentamicin and amikacin>512 mg/mL)phenotype selection by broth microdilution method.The strains were then subjected to genetic basis analysis by PCR detection of the aminoglycoside modifying enzyme genes(aac(3)-Ⅰ,aac(3)-Ⅱc,aac(60)-Ⅰb,aac(60)-Ⅱ,aph(4)-Ⅰa,aph(30)-Ⅰ,aph(30)-Ⅱb,aph(30)-Ⅲa,aph(30)-Ⅵa,aph(2″)-Ⅰb,aph(2″)-Ⅰc,aph(2″)-Ⅰd,ant(2″)-Ⅰa,ant(3″)-Ⅰand ant(40)-Ⅰa)and the 16S rRNA methylase genes(armA,rmtB and rmtC).Correlation analysis between the presence of aminoglycoside resistance gene and HLAR phenotype were performed by SPSS.Totally 102(58.96%)HLAR isolates were selected.The HLAR rates for year 2006,2007,2008 and 2009 were 52.63%,65.22%,51.11%and 70.83%,respectively.Five modifying enzyme genes(aac(3)-Ⅰ,detection rate of 65.69%;aac(60)-Ⅰb,detection rate of 45.10%;aph(30)-Ⅰ,detection rate of 47.06%;aph(30)-Ⅱb,detection rate of 0.98%;ant(3″)-Ⅰ,detection rate of 95.10%)and one methylase gene(armA,detection rate of 98.04%)were detected in the 102 A.baumannii with aac(3)-Ⅰ+aac(60)-Ⅰ+þant(3″)-Ⅰ+armA(detection rate of 25.49%),aac(3)-Ⅰ+aph(30)-Ⅰ+ant(3″)-Ⅰ+armA(detection rate of 21.57%)and ant(3″)-Ⅰ+armA(detection rate of 12.75%)being the most prevalent gene profiles.The values of chi-square tests showed correlation of armA,ant(3″)-Ⅰ,aac(3)-Ⅰ,aph(30)-Ⅰand aac(60)-Ⅰb with HLAR.armA had significant correlation(contingency coefficient 0.685)and good contingency with HLAR(kappa 0.940).The high rates of HLAR may cause a serious problem for combination therapy of aminoglycoside with β-lactams against A.baumannii infections.As armA was reported to be able to cause high level aminoglycoside resistance to most of the clinical impo展开更多
Klebsiella pneumoniae （ K. pneumoniae） is one of the main gmn-negative bacilli in clinical practice. Nosocomial infections caused by K. pneumoniae producing extended-spectrum β-lactamases （ESBLs） are very difficu...Klebsiella pneumoniae （ K. pneumoniae） is one of the main gmn-negative bacilli in clinical practice. Nosocomial infections caused by K. pneumoniae producing extended-spectrum β-lactamases （ESBLs） are very difficult to treat. This paper investigated the resistant characteristics of K. pneumoniae producing ESBLs and their aminoglycoside-modifying enzyme gene expressions including Nacetyltransferases and O-adenyltransferases. Bacteria identification and ESBLs confirmatory tests were performed by Phoenix^TM-100 system. And minimum inhibitory concentrations （MICs） of gentamicin, amikacin, kanamycin, tobranycin, netilmicin and neomycin in 53 K. pneumoniae isolates were detected by agar dilution. In addition, six aminoglycoside-modifying enzyme genes were amplified by polymerase chain reaction （PCR） and verified by DNA sequencer. It was found that imipenem and meropenem against 120 K. pneumoniae isolates produced powerful antimicrobial activities. The resistant rates of gentamicin and amikacin were 55.0% and 46.7%, respectively. Except neomycin, MIC50 and MIC90 of gentamicin, amikacin, kanamycin, tobramycin and netilmicin in 53 K. pneumoniae were all 〉 128 μg/ml, and the resistant rates were 83.0%, 52.3%, 75.5%, 81.1% and 69.8%, respectively. However, neomycin was only 39.6%. In addition, five modifying enzyme genes, including aac（3）-Ⅰ, aac（3）-Ⅱ, aac（6＇）-Ⅰb, ant（3＂）-Ⅰ, ant（2＂）-Ⅰ genes, were found in 53 isoaltes except aac （6＇）-Ⅱ, and their positive rates were 11.3%, 67.9%, 47.2%, 1.9% and 39.6%, respectively. It was also confirmed by nucleotide sequence analysis that the above resistant genes shared nearly 100% identities with GenBank published genes. The results obtained in the present study indicated that K. pneumoniae producing ESBLs strains are rapidly spreading in our hospital, and their resistance to aminoglycosides may be associated with aminoglycoside-modifying enzyme gene expressions.展开更多
Background Acinetobacter baumannii is one of the main gramnegative bacilli in clinical practice Nosocomial infections caused by multidrug resistance Acinetobacter baumannii is very difficult to treat This study was de...Background Acinetobacter baumannii is one of the main gramnegative bacilli in clinical practice Nosocomial infections caused by multidrug resistance Acinetobacter baumannii is very difficult to treat This study was designed to investigate the antimicrobial resistance characteristics and four resistant gene expressions of aminoglycosidemodifying enzymes including Nacetyltransferases and Ophosphotransferases in Acinetobacter baumannii Methods Bacterial identification and antimicrobial susceptibility test were performed by PhoenixTM system in 247 strains of Acinetobacter baumannii Minimal inhibitory concentrations (MICs) of seven aminoglycosides including gentamicin, amikacin, kanamycin, tobramycin, netilmicin, neomycin and streptomycin in 15 strains of multidrug resistant Acinetobacter baumannii were detected by agar dilution Four aminoglycosidemodifying enzyme genes were amplified by polymerase chain reaction (PCR) and verified by DNA sequencerResults The resistance rates of 247 strains of Acinetobacter baumannii against cefotaxime, levofloxacin, piperacillin, aztreonam, tetracycline, ciprofloxacin and chloramphenicol were more than 50% Imipenem and meropenem showed high antibacterial activities with resistance rates of 32% and 41% MIC50 and MIC90 of gentamicin, amikacin, streptomycin and kanamycin in 15 strains of multidrug resistant Acinetobacter baumanii were all more than 1024 mg/L, and the resistance rates were 100%, 100%, 100% and 933%, respectively But their resistance rates to tobramycin, netilmicin and neomycin were 867%, 933% and 467%, respectively Three modifying enzyme genes, including aacC1, aacC2 and aacA4 genes, were found in 15 strains, but aphA6 had not been detected Their positive rates were 933%, 200% and 200%, respectively These three genes existed simultaneously in No19 strain Nucleotide sequences of aacC1, aacC2 and aacA4 genes shared 100%, 979% and 997% identities with GenBank genes (AY307113, S68058 and AY307114)Conclusion Multidrug resistant Acinetobacter baumannii strains展开更多
基金the National Key Research and Development Program of China(2020YFE0205700,2022YFC2303900)the major projects of the National Natural Science Foundation of China(22193064)+2 种基金the Research Foundation for Youth Scholars of Beijing Technology and Business University(19008022271)the National Science and Technology Major Project(2018ZX10714002)the Science Foundation(2022SKLID303)of the State Key Laboratory of Infectious Disease Prevention and Control,China.
文摘Choosing the appropriate antibiotics to treat bacterial infections has grown more challenging as a result of the emergence of antibiotic-resistant bacteria.Aminoglycosides,as broad-spectrum antibiotics,are increasingly being used clinically;however,for most effective employment of aminoglycosides,a comprehensive understanding of aminoglycoside resistance genes’prevalence and dissemination is required.Therefore,to better understand the global resistance status of aminoglycoside antibiotics and the prevalence of antibiotic-resistance genes(ARGs)in various bacterial species,this systematic review gathered relevant data from multiple studies.Two primary resistance mechanisms-aminoglycoside enzymatic modification and 16S rRNA methylation-were assessed,and the prevalence of the corresponding ARGs was described.The coexistence of aminoglycoside ARGs with other ARGs was also demonstrated,as was the relationship between aminoglycoside ARGs and resistant phenotypes.The lack of effective therapeutic agents to combat resistant pathogens presents a real threat to public health.The combination of aminoglycosides with other antibiotics may provide a novel treatment strategy.
基金This study was supported by the National Natural Science Foundation of China(Nos.81321004 and 81361138020)the National Mega-project for Innovative Drugs(Nos.2012ZX09301002-001,2012ZX09301002-005 and 2014ZX09507009).
文摘The objective of this study was to investigate the genetic basis of high level aminoglycoside resistance in Acinetobacter baumannii clinical isolates from Beijing,China.173 A.baumannii clinical isolates from hospitals in Beijing from 2006 to 2009 were first subjected to high level aminoglycoside resistance(HLAR,MIC to gentamicin and amikacin>512 mg/mL)phenotype selection by broth microdilution method.The strains were then subjected to genetic basis analysis by PCR detection of the aminoglycoside modifying enzyme genes(aac(3)-Ⅰ,aac(3)-Ⅱc,aac(60)-Ⅰb,aac(60)-Ⅱ,aph(4)-Ⅰa,aph(30)-Ⅰ,aph(30)-Ⅱb,aph(30)-Ⅲa,aph(30)-Ⅵa,aph(2″)-Ⅰb,aph(2″)-Ⅰc,aph(2″)-Ⅰd,ant(2″)-Ⅰa,ant(3″)-Ⅰand ant(40)-Ⅰa)and the 16S rRNA methylase genes(armA,rmtB and rmtC).Correlation analysis between the presence of aminoglycoside resistance gene and HLAR phenotype were performed by SPSS.Totally 102(58.96%)HLAR isolates were selected.The HLAR rates for year 2006,2007,2008 and 2009 were 52.63%,65.22%,51.11%and 70.83%,respectively.Five modifying enzyme genes(aac(3)-Ⅰ,detection rate of 65.69%;aac(60)-Ⅰb,detection rate of 45.10%;aph(30)-Ⅰ,detection rate of 47.06%;aph(30)-Ⅱb,detection rate of 0.98%;ant(3″)-Ⅰ,detection rate of 95.10%)and one methylase gene(armA,detection rate of 98.04%)were detected in the 102 A.baumannii with aac(3)-Ⅰ+aac(60)-Ⅰ+þant(3″)-Ⅰ+armA(detection rate of 25.49%),aac(3)-Ⅰ+aph(30)-Ⅰ+ant(3″)-Ⅰ+armA(detection rate of 21.57%)and ant(3″)-Ⅰ+armA(detection rate of 12.75%)being the most prevalent gene profiles.The values of chi-square tests showed correlation of armA,ant(3″)-Ⅰ,aac(3)-Ⅰ,aph(30)-Ⅰand aac(60)-Ⅰb with HLAR.armA had significant correlation(contingency coefficient 0.685)and good contingency with HLAR(kappa 0.940).The high rates of HLAR may cause a serious problem for combination therapy of aminoglycoside with β-lactams against A.baumannii infections.As armA was reported to be able to cause high level aminoglycoside resistance to most of the clinical impo
文摘Klebsiella pneumoniae （ K. pneumoniae） is one of the main gmn-negative bacilli in clinical practice. Nosocomial infections caused by K. pneumoniae producing extended-spectrum β-lactamases （ESBLs） are very difficult to treat. This paper investigated the resistant characteristics of K. pneumoniae producing ESBLs and their aminoglycoside-modifying enzyme gene expressions including Nacetyltransferases and O-adenyltransferases. Bacteria identification and ESBLs confirmatory tests were performed by Phoenix^TM-100 system. And minimum inhibitory concentrations （MICs） of gentamicin, amikacin, kanamycin, tobranycin, netilmicin and neomycin in 53 K. pneumoniae isolates were detected by agar dilution. In addition, six aminoglycoside-modifying enzyme genes were amplified by polymerase chain reaction （PCR） and verified by DNA sequencer. It was found that imipenem and meropenem against 120 K. pneumoniae isolates produced powerful antimicrobial activities. The resistant rates of gentamicin and amikacin were 55.0% and 46.7%, respectively. Except neomycin, MIC50 and MIC90 of gentamicin, amikacin, kanamycin, tobramycin and netilmicin in 53 K. pneumoniae were all 〉 128 μg/ml, and the resistant rates were 83.0%, 52.3%, 75.5%, 81.1% and 69.8%, respectively. However, neomycin was only 39.6%. In addition, five modifying enzyme genes, including aac（3）-Ⅰ, aac（3）-Ⅱ, aac（6＇）-Ⅰb, ant（3＂）-Ⅰ, ant（2＂）-Ⅰ genes, were found in 53 isoaltes except aac （6＇）-Ⅱ, and their positive rates were 11.3%, 67.9%, 47.2%, 1.9% and 39.6%, respectively. It was also confirmed by nucleotide sequence analysis that the above resistant genes shared nearly 100% identities with GenBank published genes. The results obtained in the present study indicated that K. pneumoniae producing ESBLs strains are rapidly spreading in our hospital, and their resistance to aminoglycosides may be associated with aminoglycoside-modifying enzyme gene expressions.
文摘Background Acinetobacter baumannii is one of the main gramnegative bacilli in clinical practice Nosocomial infections caused by multidrug resistance Acinetobacter baumannii is very difficult to treat This study was designed to investigate the antimicrobial resistance characteristics and four resistant gene expressions of aminoglycosidemodifying enzymes including Nacetyltransferases and Ophosphotransferases in Acinetobacter baumannii Methods Bacterial identification and antimicrobial susceptibility test were performed by PhoenixTM system in 247 strains of Acinetobacter baumannii Minimal inhibitory concentrations (MICs) of seven aminoglycosides including gentamicin, amikacin, kanamycin, tobramycin, netilmicin, neomycin and streptomycin in 15 strains of multidrug resistant Acinetobacter baumannii were detected by agar dilution Four aminoglycosidemodifying enzyme genes were amplified by polymerase chain reaction (PCR) and verified by DNA sequencerResults The resistance rates of 247 strains of Acinetobacter baumannii against cefotaxime, levofloxacin, piperacillin, aztreonam, tetracycline, ciprofloxacin and chloramphenicol were more than 50% Imipenem and meropenem showed high antibacterial activities with resistance rates of 32% and 41% MIC50 and MIC90 of gentamicin, amikacin, streptomycin and kanamycin in 15 strains of multidrug resistant Acinetobacter baumanii were all more than 1024 mg/L, and the resistance rates were 100%, 100%, 100% and 933%, respectively But their resistance rates to tobramycin, netilmicin and neomycin were 867%, 933% and 467%, respectively Three modifying enzyme genes, including aacC1, aacC2 and aacA4 genes, were found in 15 strains, but aphA6 had not been detected Their positive rates were 933%, 200% and 200%, respectively These three genes existed simultaneously in No19 strain Nucleotide sequences of aacC1, aacC2 and aacA4 genes shared 100%, 979% and 997% identities with GenBank genes (AY307113, S68058 and AY307114)Conclusion Multidrug resistant Acinetobacter baumannii strains
