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The Journal of Antibiotics Jul 1982Synergistic effects of the cell wall-affecting antibiotics, dibekacin (DKB) and fosfomycin (FOM) and a macrolide antibiotic, midecamycin (MDM) or its derivative...
Synergistic effects of a macrolide and a cell wall-affecting antibiotic on Pseudomonas aeruginosa in vitro and in vivo. 2. Combined effects of a macrolide with a fosfomycin and an aminoglycoside antibiotic.
Synergistic effects of the cell wall-affecting antibiotics, dibekacin (DKB) and fosfomycin (FOM) and a macrolide antibiotic, midecamycin (MDM) or its derivative 9,3"-di-O-acetylmidecamycin (MOM) against Pseudomonas aeruginosa were investigated in vitro and in vivo. Synergistic effects were evaluated by estimating the number of viable bacteria at varying intervals after the two kinds of antibiotics were added to the logarithmic phase of the bacterial solution. Six hours after addition of antibiotic, the viable bacterial count of the culture treated with FOM and MOM underwent 2 log reduction compared to that which treated with FOM alone. Thus synergistic effect was significant. The number of viable bacteria treated with DKB and MDM showed slight reduction at 3 hours after addition of the two antibiotics and a marked reduction was noted after 20 hours compared with the control. Synergistic action was also demonstrated in in vivo experiments using mice. Three experimental mouse infection models, intraperitoneal infection, subcutaneous infection with carrageenan solution and burn infection were used. FOM was administered subcutaneously. DKB was administered intramuscularly. MDM or MOM was administered by the oral route. In all three experiments the survival rate of infected mice treated with FOM and MOM increased significantly compared to control mice. Similar synergistic effect was also obtained with DKB and MDM.
Topics: Animals; Anti-Bacterial Agents; Cell Wall; Depression, Chemical; Dibekacin; Drug Synergism; Drug Therapy, Combination; Female; Fosfomycin; Kanamycin; Leucomycins; Mice; Pseudomonas Infections; Pseudomonas aeruginosa
PubMed: 6816781
DOI: 10.7164/antibiotics.35.858 -
Clinical Ophthalmology (Auckland, N.Z.) Sep 2010Epithelial disorders after eye surgery can result in visual deterioration and patient discomfort. Such disorders may be caused by drug toxicity. In the present study, we...
PURPOSE
Epithelial disorders after eye surgery can result in visual deterioration and patient discomfort. Such disorders may be caused by drug toxicity. In the present study, we evaluated the toxicity of ophthalmic solutions, with or without benzalkonium chloride (BAK) as the preservative, used for postoperative care.
METHODS
A range of commercially available antibiotic and anti-inflammatory ophthalmic solutions used postoperatively (ie, levofloxacin, moxifloxacin, gatifloxacin, norfloxacin, tosufloxacin, dibekacin, cefmenoxime, diclofenac, bromfenac, pranoprofen, betamethasone, and fluoromethorone) were assessed in three corneal cell lines and one conjunctival cell line. All antibiotic solutions were BAK free. Cell viability was determined with the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay after cells had been exposed to the drugs for 48 h. The effects of preservatives on cell viability were also determined. Toxicity was compared using the cell viability score (CVS).
RESULTS
Based on results of the MTT assay and CVS, the order of cell viability after exposure to the antibiotic solutions was cefmenoxime ≥ tosufloxicin ≥ dibekacin ≥ levofloxacin ≥ norfloxacin = gatifloxacin = moxifloxacin. For the anti-inflammatory solutions, the order of cell viability was betamethasone ≥ betamethasone + fradiomycin > preservative-free diclofenac ≥ preservative-free bromfenac >> 0.02% fluoromethorone ≥ 0.1% fluoromethorone = diclofenac + preservative = bromfenac + preservative = pranoprofen. The anti-inflammatory drugs were more toxic than the antibiotics. The toxicity of antibiotic drugs against ocular surface cells was dependent on the pharmaceutical components of the solution, whereas that of the anti-inflammatory drugs was dependent on both the pharmaceutical components and the preservatives.
CONCLUSION
Postoperative drug-induced epitheliopathy may be caused primarily by anti-inflammatory drugs. CVS is useful in comparing the cytotoxicity of different drugs.
PubMed: 20922036
DOI: 10.2147/opth.s12452 -
Antimicrobial Agents and Chemotherapy Oct 2014Stenotrophomonas maltophilia IOMTU250 has a novel 6'-N-aminoglycoside acetyltransferase-encoding gene, aac(6')-Iak. The encoded protein, AAC(6')-Iak, consists of 153...
Stenotrophomonas maltophilia IOMTU250 has a novel 6'-N-aminoglycoside acetyltransferase-encoding gene, aac(6')-Iak. The encoded protein, AAC(6')-Iak, consists of 153 amino acids and has 86.3% identity to AAC(6')-Iz. Escherichia coli transformed with a plasmid containing aac(6')-Iak exhibited decreased susceptibility to arbekacin, dibekacin, neomycin, netilmicin, sisomicin, and tobramycin. Thin-layer chromatography showed that AAC(6')-Iak acetylated amikacin, arbekacin, dibekacin, isepamicin, kanamycin, neomycin, netilmicin, sisomicin, and tobramycin but not apramycin, gentamicin, or lividomycin.
Topics: Acetyltransferases; Anti-Bacterial Agents; Dibekacin; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Neomycin; Netilmicin; Sisomicin; Stenotrophomonas maltophilia; Tobramycin
PubMed: 25092711
DOI: 10.1128/AAC.03354-14 -
Antimicrobial Agents and Chemotherapy Aug 1983We have developed a homogeneous substrate-labeled fluorescent immunoassay for the measurement of dibekacin concentrations in serum and plasma. The fluorogenic enzyme...
We have developed a homogeneous substrate-labeled fluorescent immunoassay for the measurement of dibekacin concentrations in serum and plasma. The fluorogenic enzyme substrate beta-galactosyl-umbelliferone was covalently attached to tobramycin, an aminoglycoside structurally similar to dibekacin, to prepare a fluorogenic drug reagent (FDR). The FDR is nonfluorescent under assay conditions, but fluoresces upon hydrolysis by beta-galactosidase. However, binding of the FDR by antiserum to the cross-reactive drug kanamycin prevents enzyme hydrolysis. The fixed level of FDR competes with dibekacin within the sample for the limiting number of antibody-binding sites in the reaction mixture. Unbound FDR is hydrolyzed by beta-galactosidase to release a fluorescent product that is proportional to the dibekacin concentration in the sample. The assay exhibits good precision, standard curve reproducibility, recovery, sensitivity, and correlation with a comparative method. Additionally, the substrate-labeled fluorescent immunoassay is rapid and easy to perform.
Topics: Binding Sites, Antibody; Dibekacin; Fluorescent Antibody Technique; Humans; Kanamycin
PubMed: 6357071
DOI: 10.1128/AAC.24.2.240 -
The Journal of Antibiotics Nov 1975The aminoglycoside phosphotransferase of Pseudomonas aeruginosa 21-75 was purified by affinity chromatography using dibekacin-Sephadex 4B or lividomycin A-Sepharose 4B...
The aminoglycoside phosphotransferase of Pseudomonas aeruginosa 21-75 was purified by affinity chromatography using dibekacin-Sephadex 4B or lividomycin A-Sepharose 4B followed by DEAE Sephadex A-50 chromatography. It had activities of both the known aminoglycoside 3'-phosphotransferases I and II, and transferred phosphate from ATP to the 3'-hydroxyl group of kanamycin A, ribostamycin and butirosin A and 5-hydroxyl group of lividomycin A. This enzyme was designated aminoglycoside 3'-phosphotransferase III. It showed strong substrate inhibition by kanamycin A and ribostamycin when their concentration exceeded 6 muM. Purification and characterization of this enzyme are reported.
Topics: Aminoglycosides; Butirosin Sulfate; Kanamycin; Paromomycin; Phosphotransferases; Pseudomonas aeruginosa; Ribostamycin
PubMed: 53228
DOI: 10.7164/antibiotics.28.845 -
Interactive Cardiovascular and Thoracic... Sep 2012Empyema is a well-known complication following lung resection. In particular, empyema caused by methicillin-resistant Staphylococcus aureus (MRSA) is difficult to treat.... (Comparative Study)
Comparative Study
OBJECTIVES
Empyema is a well-known complication following lung resection. In particular, empyema caused by methicillin-resistant Staphylococcus aureus (MRSA) is difficult to treat. Here, we present our experience of MRSA empyema treated with local irrigation using arbekacin.
METHODS
Six patients consisted of 4 males and 2 females with an average age of 65.7 years. They developed MRSA empyema following lung resection and were treated at our institution between 2007 and 2011. Cases comprised four primary and one metastatic lung cancer, and 1 patient was a living lung transplantation donor. The surgical procedure consisted of four lobectomies, one segmentectomy and one wedge resection. After diagnosis of MRSA empyema, anti-MRSA drugs were administered intravenously in all cases. In addition, arbekacin irrigation at a dose of 100 mg dissolved in saline was performed after irrigation with saline only.
RESULTS
The average number of postoperative days for the diagnosis of MRSA empyema was 13 (range 4-19). The period of irrigation ranged from 6 to 46 days. Arbekacin irrigation did not induce nephrotoxicity or other complications, and no bacteria resistant to arbekacin was detected in the thoracic cavity. We re-operated on 1 case because he had pulmonary fistula and severe wound infection. At the time of removing the thoracic catheter, MRSA in the pleural effusion disappeared completely in 3 patients. The period until MRSA concentration in the pleural effusion became negative after starting arbekacin irrigation ranged from 4 to 9 days. In the remaining cases, in which MRSA did not disappear, the catheter was removed because of no inflammatory reaction after stopping irrigation and clamping the catheters. All patients were discharged from our institution without thoracic catheterization and no patients had relapsed during the follow-up period ranging from 6 to 44 months.
CONCLUSIONS
Irrigation of the thoracic cavity with arbekacin proved to be an effective, safe and readily available method for treating MRSA empyema following lung resection.
Topics: Aged; Aged, 80 and over; Anti-Infective Agents; Dibekacin; Empyema, Pleural; Female; Follow-Up Studies; Humans; Male; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Pneumonectomy; Postoperative Complications; Retrospective Studies; Staphylococcal Infections; Therapeutic Irrigation; Thoracic Cavity; Treatment Outcome
PubMed: 22718464
DOI: 10.1093/icvts/ivs285 -
The Journal of Antibiotics May 1996Aminoglycoside antibiotics (AGs) with a free 2'-amino group were subjected to enzymatic N-acetylation using a cell free extract that contained an aminoglycoside... (Comparative Study)
Comparative Study
Aminoglycoside antibiotics (AGs) with a free 2'-amino group were subjected to enzymatic N-acetylation using a cell free extract that contained an aminoglycoside 2'-N-acetyltransferase, AAC (2'), derived from a kasugamycin-producing strain of Streptomyces kasugaensis. TLC and antibiotic assay of the incubated reaction mixtures revealed that a modified compound retaining substantial antibiotic activity was formed from arbekacin (ABK), while modification of the other AGs resulted in the marked decrease in antibiotic activity. Structure determination following isolation from a large scale reaction mixture showed the modified ABK to be 2'-N-acetyl ABK. In addition, 2',6'-di-N-acetyl ABK was formed as a minor product. The same conversion also occurred with dibekacin (DKB) resulting in the formation of 2'-N-acetyl DKB and 2',6'-di-N-acetyl DKB. MIC determination showed antibacterial activity (1.56 approximately 3.13 micrograms/ml) of 2'-N-acetyl ABK against a variety of organisms. By contrast, 2'-N-acetyl DKB showed no substantial antibiotic activity. We believe 2'-N-acetyl ABK has the highest and broadest antibacterial activity, compared with known N-acetylated AGs.
Topics: Acetylation; Acetyltransferases; Acylation; Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Microbial Sensitivity Tests; Molecular Structure; Streptomyces; Structure-Activity Relationship
PubMed: 8682723
DOI: 10.7164/antibiotics.49.458 -
Microbiology Spectrum Aug 2022Seven drug-resistant strains of Stenotrophomonas maltophilia were isolated from patients at two university hospitals in Nepal. S. maltophilia JUNP497 was found to encode...
Stenotrophomonas maltophilia from Nepal Producing Two Novel Antibiotic Inactivating Enzymes, a Class A β-Lactamase KBL-1 and an Aminoglycoside 6'--Acetyltransferase AAC(6')-Iap.
Seven drug-resistant strains of Stenotrophomonas maltophilia were isolated from patients at two university hospitals in Nepal. S. maltophilia JUNP497 was found to encode a novel class A β-lactamase, KBL-1 (Kathmandu β-lactamase), consisting of 286 amino acids with 52.98% identity to PSV-1. Escherichia coli transformants expressing were less susceptible to penicillins. The recombinant KBL-1 protein efficiently hydrolyzed penicillins. The genomic environment surrounding was a unique structure, with the upstream region derived from strains in China and the downstream region from strains in India. S. maltophilia JUNP350 was found to encode a novel 6'-N-aminoglycoside acetyltransferase, AAC(6')-Iap, consisting of 155 amino acids with 85.0% identity to AAC(6')-Iz. E. coli transformants expressing were less susceptible to arbekacin, amikacin, dibekacin, isepamicin, neomycin, netilmicin, sisomicin and tobramycin. The recombinant AAC(6')-Iap protein acetylated all aminoglycosides tested, except for apramycin and paromomycin. The genomic environment surrounding was 90.99% identical to that of S. maltophilia JV3 obtained from a rhizosphere in Brazil. Phylogenetic analysis based on whole genome sequences showed that most S. maltophilia isolates in Nepal were similar to those isolates in European countries, including Germany and Spain. The emergence of drug-resistant S. maltophilia has become a serious problem in medical settings worldwide. The present study demonstrated that drug-resistant S. maltophilia strains in Nepal harbored novel genes encoding a class A β-lactamase, KBL-1, or a 6'-N-aminoglycoside acetyltransferase, AAC(6')-Iap. Genetic backgrounds of most S. maltophilia strains in Nepal were similar to those in European countries. Surveillance of drug-resistant S. maltophilia in medical settings in Nepal is necessary.
Topics: Acetyltransferases; Amino Acids; Anti-Bacterial Agents; Escherichia coli; Humans; Microbial Sensitivity Tests; Nepal; Penicillins; Phylogeny; Stenotrophomonas maltophilia; beta-Lactamases
PubMed: 35862995
DOI: 10.1128/spectrum.01143-22 -
The Journal of Antibiotics Dec 1980Cross resistance of kanamycin-resistant mutants of E. coli Q13 to other aminoglycosides (streptomycin, neomycin, gentamicin and dibekacin) was demonstrated in vivo...
Cross resistance of kanamycin-resistant mutants of E. coli Q13 to other aminoglycosides (streptomycin, neomycin, gentamicin and dibekacin) was demonstrated in vivo (growth) and in vitro (polyphenylalanine synthesis, codon misreading and translocation on the ribosomes). Kanamycin-resistant mutants, R1-4, R2-1, R2-2, R3-3 and R3-5 showed various degrees of cross-resistance to streptomycin, gentamicin, neomycin and dibekacin in vivo. In vitro, polyphenylalanine synthesis was more resistant to kanamycin, streptomycin, neomycin and gentamicin on the ribosomes of the kanamycin-resistant mutants than on those of the parental strain. In the presence of kanamycin, neomycin or gentamicin, less degrees of [14C]isoleucine uptake with poly[U] (codon misreading) were observed on the ribosomes obtained from the resistant mutants than on the sensitive cell ribosomes. The N-acetyl-[14C]phenylalanyl-puromycin synthesis enhanced by an elongation factor, EF-G and GTP (translocation) was more resistant to kanamycin and dibekacin on the mutant ribosomes than on the parental ribosomes. The results indicate that the cross-resistance to other aminoglycoside antibiotics, as well as the kanamycin resistance, are attributed to mutational alterations of the ribosomes in these mutants.
Topics: Aminoglycosides; Anti-Bacterial Agents; Codon; Cross Reactions; Drug Resistance, Microbial; Escherichia coli; Kanamycin; Mutation; Peptide Biosynthesis; Peptides; Peptidyl Transferases; RNA, Transfer; Ribosomes
PubMed: 7019176
DOI: 10.7164/antibiotics.33.1527 -
Emerging Infectious Diseases Apr 2007To investigate the exact isolation frequency of 16S rRNA methylase-producing, gram-negative pathogenic bacteria, we tested 87,626 clinical isolates from 169 hospitals....
To investigate the exact isolation frequency of 16S rRNA methylase-producing, gram-negative pathogenic bacteria, we tested 87,626 clinical isolates from 169 hospitals. Twenty-six strains from 16 hospitals harbored 16S rRNA methylase genes, which suggests sparse but diffuse spread of pan-aminoglycoside-resistant microbes in Japan.
Topics: Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Japan; Methyltransferases; Microbial Sensitivity Tests; RNA, Ribosomal, 16S
PubMed: 17553289
DOI: 10.3201/eid1304.060501