1.Molecular Epidemiologic Analysis of Nosocomial Escherichia coli Isolates.
Sung Yong SEOL ; Dong Taek CHO ; Yoo Chul LEE ; Je Chul LEE ; Haeng Seop SHIN ; Hee Kyung CHANG ; Jeong Min KIM ; Kyung Sook KIM
Journal of the Korean Society for Microbiology 1997;32(1):1-14
One hundred and eighteen strains of Escherichia coli isolated from clinical specimens were epidemiologically analyzed for antimicrobial resistance, EcoRI restriction endonuclease analysis, southern hybridization with TEM and SHV probe of conjugative R plasmids. 1. Sixty-two to 73% of E. coli isolates were resistant to ampicillin, carbenicillin, sulfisomidine, and tetracycline, and 20-27% to kanamycin, gentamicin, tobramycin, and nalidixic acid. However more than 93% were susceptible to cephalosporins and all strains were highly susceptible to cefotetan, imipenem, aztreonam, and amikacin. 2. Twelve strains were susceptible to all drugs tested and the multiple resistant strains showed 65 resistance pattern types. 3. Thirty-six resistant strains(34%) transferred R plasmids to E. coli RG488 or RG176 by mixed culture. Fifty-six plasmids with 31 different resistant phenotype were obtained from them. 4. Some of 15 plasmids derived from 10 strains showed identical or similar EcoRI restriction endonuclease digestion patterns, hybridized fragment patterns with TEM probe by southern hybridization, and resistance levels of j3-lactams and aminoglycosides. These results indicate that the epidemic strains or plasmids were present in this hospital and molecular genetic analysis of R plasmids can be used to discriminate clinical isolates of multi- resistant E. coli.
Amikacin
;
Aminoglycosides
;
Ampicillin
;
Aztreonam
;
Carbenicillin
;
Cefotetan
;
Cephalosporins
;
Digestion
;
DNA Restriction Enzymes
;
Escherichia coli*
;
Escherichia*
;
Gentamicins
;
Imipenem
;
Kanamycin
;
Molecular Biology
;
Nalidixic Acid
;
Phenotype
;
Plasmids
;
R Factors
;
Sulfisomidine
;
Tetracycline
;
Tobramycin
2.Pharmacokinetics of amikacin in plasma of healthy goats after intravenous injection once daily for three days.
Sania NASEEM ; Mudasir SULTANA ; Rajinder RAINA ; Nrip Kishore PANKAJ ; Pawan Kumar VERMA ; Nasir Ahmad NASIR ; Azad Ahmad AHANGER ; Shafiqur RAHMAN ; Shahid PRAWEZ
Korean Journal of Veterinary Research 2011;51(4):253-257
Amikacin is a semisynthetic derivative of kanamycin and primarily active against aerobic Gram-negative-pathogens with limited activity against Gram-positive bacteria. Meager study was reported on pharmacokinetic data on multi-days administration of amikacin. Hence, pharmacokinetics study was done in five clinically healthy goats (n = 5), after intravenous bolus injection of amikacin sulfate at the dose rate of 10 mg/kg body weight daily for three consecutive days. The amikacin concentrations in plasma and pharmacokinetics-parameters were analyzed by using microbiological assay technique and noncompartmental open-model, respectively. The mean peak plasma concentrations (Mean +/- SD) of amikacin at time zero (Cp0) was 114.19 +/- 20.78 and 128.67 +/- 14.37 microg/mL, on day 1st and 3rd, respectively. The mean elimination half-life (t(1/2)ke) was 1.00 +/- 0.28 h on day 1st and 1.22 +/- 0.29 h on day 3rd. Mean of area under concentration-time curve (AUC(0-->infinity)) was 158.26 +/- 60.10 and 159.70 +/- 22.74 microg.h/mL, on day 1st and 3rd respectively. The total body clearance (ClB) and volume of distribution at steady state (Vdss) on day 1st and 3rd were ClB = 0.07 +/- 0.02 and 0.06 +/- 0.01 L/h.kg and Vdss = 0.10 +/- 0.03 and 0.11 +/- 0.05 L/kg, respectively. No-significant difference was noted in both drug-plasma concentration and pharmacokinetics-parameters, respectively. Amikacin concentration in plasma was found higher up-to 4 h and 6 h onward on down-ward trends favour to reduce toxicity. Which also support the pharmacokinetic-pharmacodynamic way of dosing of aminoglycosides and hence, amikacin may be administered 10 mg/kg intravenously daily to treat principally Gram-negative pathogens and limitedly Gram-positive-pathogens.
Amikacin
;
Aminoglycosides
;
Body Weight
;
Goats
;
Gram-Positive Bacteria
;
Half-Life
;
Injections, Intravenous
;
Kanamycin
;
Plasma
3.Evaluating Home-made Disks for the Detection of the Aminoglycoside High-Level Resistance of Enterococci.
Sung Ryul KIM ; Joseph JEONG ; Jeong Hwan SHIN ; Hyung Hoi KIM ; Seon Ho LEE ; Chulhun L CHANG ; Han Chul SON
Korean Journal of Clinical Pathology 2000;20(4):379-383
BACKGROUND: High-level gentamicin and streptomycin disks are not easily available, despite their critical role in detection of high-level resistance to aminoglycosides in enterococci. Therefore, the possibility of applicating home-made disks to test high-level resistance of enterococci to aminoglycosides was evaluated. METHODS: The disk diffusion method using home-made disks was compared with minimal inhibitory concentrations(MIC) in 53 clinical isolates of enterococci, and, the stability of the disks were also evaluated by disk diffusion testing, biweekly, for 14 weeks. RESULTS: The high-level resistance rates to gentamicin(GM) and streptomycin(SM) were 60% and 43%, respectively. Thirty eight % of the enterococci were highly resistant in both GM and SM. The results of the disk diffusion method were consistent with the MIC until 10 weeks after production of the disks. After 12 weeks, the inhibition zones of GM- or SM-susceptible strains decreased by 2.9-3.9 mm, and the discrepancy rates were 5-24% between the results of the MIC and disk diffusion method. The storage temperature of -20degrees C versus -70degrees C showed no difference in the inhibition zone. CONCLUSION: It has been demonstrated that home-made high-level GM and SM disks are stable at -20degrees C for 10 weeks, and the results of disk diffusion method on the disks show they are applicable for the test of susceptibility of aminoglycosides to enterococci.
Aminoglycosides
;
Diffusion
;
Enterococcus
;
Gentamicins
;
Streptomycin
4.Pharmacokinetics of Gentamicin and Amikacin in Korean Children with Normal Renal Function.
Jin Young PARK ; Kyung Bae KWON ; Mee Ran KIM ; Hoan Jong LEE ; Jin Q KIM ; Wan Gyoon SHIN ; Kyoung Ho PARK ; Hae Lim CHUNG
Journal of the Korean Pediatric Society 1994;37(2):185-192
We analysed retrospectively pharmacokinetic parameters of gentamicin and amikacin in 44 and 58 Korean pediatric patients, respectively, with normal renal function. Pharmacokinetic parameters were calculated from two concentrations in serum by method of Sawchuck. There was wide individual variation in peak serum concentrations of gentamicin and amikacin, Administration of the usually recommended doses yielded subtherapeutic concentrations in 47% and 82%, respectevely, of patients in the peak concentrations of gentamicin and amikacin. The volumes of distribution of gentamicin and amikacin in children of over 1 year of age were 0.37+/-0.13L/kg and 0.41+/-0.13L/kg which are greater than those reported from the western countries. We conclude that the wide individual variation and high frequency of subtherapeutic levels in the peak concentrations of gentamicin and amikacin obtained by usually recommended dosage as well as the narrow safety margin of these drugs necessitate monitoring of serum concentration and adjustment of individual dosage regimen early in the course of treatment with aminoglycosides.
Amikacin*
;
Aminoglycosides
;
Child*
;
Gentamicins*
;
Humans
;
Pharmacokinetics*
;
Retrospective Studies
5.Frequency of Resistance to Aminog lycoside Antibiotics in Staphy lococcus aureus Isolated from Tertiary Hospitals.
Hong Bin KIM ; Thoma KIM ; Bo Bin LEE ; Ui Seok KIM ; Sang Won PARK ; Jong Wook SHIN ; Myoung Don OH ; Eui Chong KIM ; Yeong Seon LEE ; Bong Su KIM ; Kang Won CHOE
Korean Journal of Infectious Diseases 2002;34(1):39-46
BACKGROUND: Staphylococcus aureus is one of the most important pathogens, causing severe morbidity and fatal infections. To date rapid evolution of antibiotic resistance in S. aureus, including recent emergence of vancomycin-resistant S. aureus (VRSA), has been a serious concern and an obstacle to the effective treatment. The purpose of this study is to update the resistance patterns against aminoglycoside antibiotics which play an important role in the therapy of serious staphylococcal infections. METHODS: Clinical isolates were collected from 8 university-affiliated hospitals during the period of June 1999 to January 2001. Susceptibility tests against 9 antibiotics were performed by disk diffusion method. Minimum inhibitory concentrations (MICs) of arbekacin against non-susceptible strains were determined by microbroth dilution method RESULTS: Among total 682 isolates exclusive of consecutive ones from the same patients, 199 (29%) were from pus, 152 (22%) from respiratory specimens, 137 (20%) from blood, 38 (6%) from urine. Of 682 isolates, 588 (87%) isolates were resistant to at least one of the aminoglycosides tested. Overall prevalence of MRSA was 64% (439/682), and resistance rates of MRSA were summarized as follows; kanamycin (KM) 98%, tobramycin (TOB) 98%, gentamicin (GM) 95%, amikacin (AMK) 90%, neomycin (NEO) 63%, streptomycin (SM) 31%, netilmicin (NET) 18%, arbekacin (ABK) 13%. MRSA isolates were resistant to multiple aminoglycosides, and 88% of them were resistant to all four aminoglycosides of KM, TOB, GM, and AMK. MICs of ABK against 58 non-susceptible strains ranged from 2 to 128 microgram/mL. CONCLUSION: More than 90% of MRSA isolates were resistant against kanamycin, tobramycin, gentamicin, and amikacin. Moreover, most of MRSA isolates were multi-drug resistant to all these four aminoglycosides. Resistance rates against arbekacin and netilmicin were less than 20%. Arbekacin was the most susceptible antibiotic of the aminoglycosides tested.
Amikacin
;
Aminoglycosides
;
Anti-Bacterial Agents*
;
Diffusion
;
Drug Resistance, Microbial
;
Gentamicins
;
Humans
;
Kanamycin
;
Methicillin-Resistant Staphylococcus aureus
;
Microbial Sensitivity Tests
;
Neomycin
;
Netilmicin
;
Prevalence
;
Staphylococcal Infections
;
Staphylococcus aureus
;
Streptomycin
;
Suppuration
;
Tertiary Care Centers*
;
Tobramycin
6.Aminoglycoside gentamicin research: fundamental progress and new application prospects.
Xinyun JIAN ; Zixin DENG ; Yuhui SUN
Chinese Journal of Biotechnology 2015;31(6):829-844
As an important aminoglycosides antibiotic, gentamicin has been used clinically over decades. With the development in modern biological technology, the mechanisms of gentamicin action and resistance, its biosynthesis and structural modification were studied in great depth. Meanwhile, its emerging novel bioactivities and potential applications are also under extensive exploration. Here we summarize the latest progresses and prospects towards the future development of gentamicin for more efficient and effective uses.
Aminoglycosides
;
biosynthesis
;
chemistry
;
Gentamicins
;
biosynthesis
;
chemistry
7.Effects of Aminoglycoside Antibiotics on Acetylcholine-induced Potassium Currents in Guinea-pig Outer Hair Cell.
Joon Kyoo LEE ; Hyong Ho CHO ; Seok Jin MOON ; Jung Ho KOOK ; Myung Joo JANG ; Han Seong JEONG ; Yong Bum CHO ; Jong Seong PARK
Korean Journal of Otolaryngology - Head and Neck Surgery 2005;48(11):1329-1335
BACKGROUND AND OBJECTIVES: Aminoglycoside antibiotics are widely used for the treatment of infection caused by Gram-negative bacilli, but prolonged exposure to it can cause permanent hearing loss since are reported to interrupt the function of medial olivocochlear bundle. This study was designed to explore the effects of several aminoglycoside antibiotics on acetylcholine, the neurotransmitter of medial olivocochlear bundle, and how it affects potassium currents of the guinea pig outer hair cells. MATERIALS AND METHOD: Using extracted outer hair cells from Guinea pigs, potassium currents induced by acetylcholine were recorded using the whole-cell patch clamp technique. The effects of different aminoglycoside antibiotics on the potassium current were also studied. RESULTS: Acetylcholine increased the potassium currents of outer hair cells. All of aminoglycoside antibiotics tested such as neomycin, streptomycin, gentamicin, and amikacin decreased the acetylcholine-induced potassium current. CONCLUSION: These experimental results suggest that aminoglycoside antibiotics have effects on the membrane potential of outer hair cells regulated by acetylcholine, which is thought to be one of the mechanisms of aminoglycoside ototoxicity.
Acetylcholine
;
Amikacin
;
Aminoglycosides
;
Animals
;
Anti-Bacterial Agents*
;
Gentamicins
;
Guinea Pigs
;
Hair*
;
Hearing Loss
;
Membrane Potentials
;
Neomycin
;
Neurotransmitter Agents
;
Potassium*
;
Streptomycin
8.Evaluation of aminoglycoside resistance phenotypes and genotyping of acetyltransferase in Escherichia coli.
Hai-shen KONG ; Xue-fen LI ; Ju-fang WANG ; Min-jin WU ; Xiao CHEN ; Qing YANG
Journal of Zhejiang University. Medical sciences 2006;35(1):83-86
<b>OBJECTIVEb>To investigate the prevalence of aminoglycoside resistance and genotyping of acetyltransferase in Escherichia coli.
<b>METHODSb>Resistance phenotypes to 12 antibiotics of 44 Escherichia coli isolates were analyzed using agar dilution method and 3 aminoglycoside resistance genes aac(3)-I, II and aac(6')-I were determined by PCR method.
<b>RESULTSb>In 44 clinical isolates, the occurrence of ESBLs was 45.45%, resistance rates were discrepant for amikacin (18.18%), gentamicin (56.82%) and tobramycin (61.36%), the prevalence of phenotype TG (tobramycin and gentamicin) indicative of aac(3)-II production and TGA (tobramycin, gentamicin and amikacin) indicative of aac(6')-I production were 36.36% and 18.18%, respectively. The most common aminoglycoside resistance genotype of acetyltransferase was aac(3)-II (52.27%) and aac(6')-I was lower (29.55%), but no aac(3)-I was detected.
<b>CONCLUSIONb>At least 2 acetyltransferase genes exist in this area i.e. aac(3)-II and aac(6')-I.
Acyltransferases ; genetics ; Amikacin ; pharmacology ; Aminoglycosides ; pharmacology ; Drug Resistance, Bacterial ; genetics ; Escherichia coli ; enzymology ; genetics ; Genotype ; Gentamicins ; pharmacology ; Phenotype ; Tobramycin ; pharmacology
9.Characterization of Acinetobacter baumannii Co-producing Carbapenemases OXA-23 and OXA-66, and armA 16S Ribosomal RNA Methylase at a University Hospital in South Korea.
Hye Won JEONG ; Bo Ra SON ; Dong Ick SHIN ; Donghee RYU ; Seung Bok HONG ; Kyudong HAN ; Kyeong Seob SHIN
Korean Journal of Clinical Microbiology 2011;14(2):67-73
BACKGROUND: In the present study, the resistance mechanisms against carbapenems and aminoglycosides for 23 strains of multi-drug-resistant Acinetobacter baumannii isolated at a university hospital were investigated. METHODS: The minimal inhibitory concentrations (MICs) were determined via broth microdilution or Etest. The genes encoding OXA-type carbapenemases and 16S rRNA methylase were identified using multiplex PCR, and the amplified products were sequenced. Conjugation experiments were conducted, and an epidemiologic study was performed using enterobacterial repetitive intergenic consensus (ERIC)-PCR. RESULTS: In the isolates, the MICs of the tested aminoglycosides, including arbekacin, were >1024 microg/mL; the MICs of aztreonam, cefepime, ceftazidime, and ciprofloxacin ranged from 64 to 128 microg/mL; and the MICs of carbapenem ranged from 32 to 64 microg/mL, as determined through the broth microdilution test. According to the E-test, the MICs of ampicillin/sulbactam and colistin were 8 and 0.25 to 0.38 microg/mL, respectively. Sequence analysis confirmed that all of the isolates expressed carbapenemases OXA-23 and OXA-66, as well as armA 16S rRNA methylase. In addition, ISAba1 was identified upstream of the gene encoding OXA-23. OXA-23 and armA were not transferred to Escherichia coli J53 cells in the transconjugation experiments. ERIC-PCR molecular fingerprinting produced a single pattern in all cases. CONCLUSION: The co-production of OXA-23 and armA 16S rRNA methylase may be attributed to the multidrug resistance of the A. baumannii isolates in the present study. Stricter surveillance and more rapid detection are necessary to prevent the spread of this type of resistance in the future.
Acinetobacter
;
Acinetobacter baumannii
;
Aminoglycosides
;
Aztreonam
;
Carbapenems
;
Ceftazidime
;
Cephalosporins
;
Ciprofloxacin
;
Colistin
;
Consensus
;
Dermatoglyphics
;
Dibekacin
;
Drug Resistance, Multiple
;
Epidemiologic Studies
;
Escherichia coli
;
Methyltransferases
;
Multiplex Polymerase Chain Reaction
;
Republic of Korea
;
RNA, Ribosomal, 16S
;
Sequence Analysis
10.Combining microbial and chemical syntheses for the production of complex natural products.
Chinese Journal of Natural Medicines (English Ed.) 2022;20(10):729-736
Nature, a rich source of bioactive natural products, serves as a massive pool of drug candidates for the pharmaceutical industry. However, the supply of these structurally complex chemicals is costly as most of the natural products are scarce in nature, thus requiring de novo synthesis. The supply chain issue hinders the development of novel therapeutic agents from natural products. Microbial synthesis, based on the expression of biosynthetic genes in a suitable microbial host to produce certain chemicals, is a sustainable strategy to produce complex natural products. However, this strategy requires gaining insights into the biosynthesis of target molecules. Most natural products are biosynthetically unknown or not fully elucidated; thus, the sole application of microbial synthesis strategy to produce a given molecule is challenging. In this review, we highlight a strategy that combines microbial and chemical syntheses to tackle the supply chain issue in developing drugs from natural products. We believe this strategy can revive the drug development pipeline for natural products.
Biological Products/chemistry*
;
Aminoglycosides