PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “aminoglycoside”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1977

Aminoglycoside nephrotoxicity. I. Effects of aminoglycoside antibiotics on iodohippurate accumulation in rabbit renal cortical slices.

The effects of aminoglycoside antibiotics on the accumulation of O-125I-hippurate (OIH) in rabbit renal cortical slices were assessed in an attempt to establish an in vitro model for aminoglycoside nephrotoxicity. Accumulation of OIH was measured after incubation of cortex slices in media containing aminoglycosides in different concentrations. All aminoglycosides depressed OIH accumulation in the following minimum concentrations: Dihydrostreptomycin and kanamycin, 2,000 microgram/ml (P less than 0.01); streptomycin and neomycin, 1,000 microgram/ml (P less than 0.05 and P less than 0.01); amikacin and tobramycin, 300 microgram/ml (P less than 0.05); gentamicin, 100 microgram/ml (P less than 0.05). A concentration of 2,000 microgram/ml caused the following reduction in OIH accumulation: Dihydrostreptomycin, 19.3%; streptomycin, 28.9%; kanamycin, 23.8%; neomycin, 62.5%; gentamicin, 68.0%; amikacin and tobramycin, 100%. Changes in pH of the incubation media after addition of aminoglycosides were only partially responsible for the observed depression of OIH accumulation and there was no evidence of substrate competition between aminoglycosides and OIH. The in vitro model described here appears to be inadequate as a sole predictor of aminoglycoside nephrotoxicity, but may provide a supplementary tool in the investigation of aminoglycoside proximal tubular cell toxicity.

Aminoglycosides↗
PubMed1979

Aminoglycoside-modifying enzymes among clinical isolates of Acinetobacter calcoaceticus subsp. anitratus (Herellea vaginicola): explanation for high-level aminoglycoside resistance.

Acinetobacter calcoaceticus subsp. anitratus (Herellea vaginicola) is an important cause of nosocomial infection in our hospital where A. calcoaceticus subsp. anitratus is the most frequently isolated gram-negative species resistant to one or more of the aminoglycoside antibiotics. Of 167 strains tested for susceptibility to aminoglycosides, only 6 strains were found that were resistant to >/=128 mug of kanamycin per ml; all others were susceptible to </=32 mug/ml. Five of these six strains were found to produce aminoglycoside-modifying enzymes. Two strains produced a phosphotransferase which mediates resistance to kanamycin and neomycin; three strains produced an acetyltransferase which mediates resistance to kanamycin, tobramycin, and amikacin (minimal inhibitory concentration >/= 128 mug/ml for each drug). No strain with lower level resistance to kanamycin, tobramycin, or amikacin had enzyme activity. Fourteen strains resistant to gentamicin failed to show significant enzymatic modification of that antibiotic. Although agarose gel electrophoresis of deoxyribonucleic acid preparations from the enzyme-producing strains showed plasmid bands in all, no transfer of aminoglycoside resistance could be achieved, nor was it cured by exposure to novobiocin, ethidium bromide, acridine orange, heat, or prolonged storage. Resistance to mercuric chloride, present in 2 of 60 strains, was lost by 1 strain after exposure to novobiocin, and the loss of resistance was associated with an apparent deletion of plasmid deoxyribonucleic acid.

Acinetobacter↗
PubMed1978

[Aminoglycoside-3'-phosphotransferase I from aminoglycoside-polyresistant strain E. coli 182].

An aminoglycoside-3'-phosphotransferase I catalyzing phosphorylation of some aminoglycoside antibiotics with the 3'-hydroxyl group has been purified from the cells of aminoglycoside resistant strain E. coli 182 by competitive affinity chromatography on neomycin-Sepharose and gel-filtration on Sephadex G-100. The product of enzymatic phosphorylation of kanamycin A was isolated and identified as kanamycin-3'-phosphate by NMR, thin-layer chromatography and chemical characterization. The kinetic properties of the enzyme were studied. The pH-optimum was between 7,8--8,0; the [S]0.5 values for kanamycin, neomycin and paromomycin were 2.10(-5) M, the energy of activation was 15,9 kcal/mol. The bivalent cations were required for activity of the enzyme, Mg2+ was the most effecient. The relative aminoglycoside antibiotics containing no 3'-hydroxyl group were competitive inhibitors of the enzyme activity with Ki values close to [S]0.5.

Aminoglycosides↗
PubMed1978

Cephalothin plus an aminoglycoside is more nephrotoxic than methicillin plus an aminoglycoside.

In a prospective, randomised, double-blind trial to determine if cephalothin plus an aminoglycoside is more nephrotoxic than methicillin plus an aminoglycoside, patients were assigned to one of four treatment groups: cephalothin and gentamicin (C.G.), cephalothin and tobramycin (C.T.), methicillin and gentamicin (M.G.), or methicillin and tobramycin (M.T.). The incidence of definite nephrotoxicity was: C.G., 7/23 (30.4%); C.T., 5/24 (20.8%); M.G., 2/20 (10%); and M.T., 1/23 (4.3%). There was no statistically significant difference in nephrotoxicity between the combined gentamicin groups (C.G. and M.G.) and the combined tobramycin groups (C.T. and M.T.). Definite nephrotoxicity developed in 12/47 (25.5%) of the combined cephalothin groups (C.G. and C.T.) and in only 3/43 (7%) of the combined methicilllin groups (M.G. and M.T.). The combination of cephalothin plus an aminoglycoside is therefore more nephrotoxic than the combination of methicillin plus an aminoglycoside.

Acute Kidney Injury↗
PubMed1978

1-N HAPA gentamicin B, a new aminoglycoside active against gentamicin resistant isolates--activity compared to other aminoglycosides.

1-N HAPA gentamicin B is a new aminoglycoside active against most Enterobacteriaceae, Pseudomonas aeruginosa and Staphylococcus aureus. Among 504 clinical isolates at a concentration of 12.5 microgram/ml all Staph. aureus, Escherichia coli, Klebsiella, Enterobacter, Proteus rettgeri, Providencia and 78% of Pseudomonas, 86% of Proteus morganii were inhibited. Like other aminoglycosides, the activity was greatest at an alkaline ph and reduced by high cations concentrations. 1-N HAPA gentamicin B was equal in activity to amikacin against both gentamicin-sensitive and resistant isolates. It inhibited bacteria containing many of the aminoglycoside inactivating enzymes. When combined with carbenicillin it inhibited in a synergistic manner many Gram-negative bacteria, particularly Pseudomonas and Serratia.

Aminoglycosides↗
PubMed1977

Effect of combinations of penicillin and aminoglycosides on Streptococcus faecalis: a comparative study of seven aminoglycoside antibiotics.

The 50% inhibitory concentrations (IC50) of benzylpenicillin, streptomycin, sisomicin, gentamicin, tobramycin, kanamycin, amikacin, and butirosin were determined for 58 clinical isolates of Streptococcus faecalis, 28 of which were recovered from cultures of blood samples from patients with endocarditis. The IC50 of streptomycin was less than 100 microng/ml for 42 strains, 192-10,000 microng/ml for eight, and larger than or equal to 10,000 micron/ml for eight. One isolate that was highly resistant to streptomycin was also highly resistant to kanamycin and butirosin. Extraordinarily high resistance to the other aminoglycosides was not observed. The bactericidal effects of combinations of penicillin and aminoglycosides were studied in 20 strains of S. faecalis that represented different levels of resistance to streptomycin. Significant enhancement of the effect of the combination of penicillin and streptomycin was found only in strains with an IC50 of smaller than or equal to 190 microng/ml. Combinations of penicillin and sisomicin, gentamicin, or tobramycin were effective even against strains that were highly resistant to streptomycin and kanamycin.

Amikacin↗
PubMed1978

Semisynthetic aminoglycoside antibacterials. 6. Synthesis of sisomicin, Antibiotic G-52, and novel 6'-substituted analogues of sisomicin from aminoglycoside 66-40C.

The discovery of aminoglycoside 66-40C, a novel dimeric, unsaturated imine produced by Micromonospora inyoensis, afforded a versatile intermediate for the synthesis of a variety of sisomicin analogues modified at the 6' position. The conversion of 66-40C into sisomicin, antibiotic G-52, and a series of novel 6'-substituted analogues of sisomicin is described, and the biological activity of the products is discussed.

Aminoglycosides↗
PubMed1977

Fortimicins A and B, new aminoglycoside antibiotics. IV. In vitro study of fortimicin A compared with other aminoglycosides.

The in vitro antimicrobial activity of fortimicin A, the most active member of the fortimicin complex, was compared with that of amikacin, gentamicin, sagamicin and tobramycin against 352 strains of Enterobacteriaceae and other medically significant organisms. Against most of these organisms fortimicin and amikacin had comparable levels of antimicrobial activity, generally slightly less than that of gentamicin, sagamicin or tobramycin. Fortimicin had relatively weak activity against Pseudomonas aeruginosa strains. Fortimicin shows many of the characteristics of other aminoglycoside antibiotics: (i) improved activity at alkaline pH, (ii) rapid, bactericidal action, (iii) reduced activity with increasing inoculum levels, and (iv) synergistic activity with penicillin against enterococci. The activity of fortimicin was compared to that of gentamicin, tobramycin and amikacin against a group of 95 naturally occurring, antibiotic-resistant Gram-negative bacilli other than Pseudomonas. The organisms were isolated from clinical sources and selected primarily for gentamicin resistance by the sensitivity disc test. Fortimicin showed excellent activity against this group of organisms. At a concentration of 6.2 mcg/ml, fortimicin inhibited the most strains (92.6%) followed by amikacin (90.5%), gentamicin (23.2%) and tobramycin (8.4%).

Aminoglycosides↗
PubMed1978

Enzymatic modification of aminoglycoside antibiotics: 3-N-acetyltransferase with broad specificity that determines resistance to the novel aminoglycoside apramycin.

Examination of a number of R-plasmid-containing bacterial isolates of animal origin has revealed the presence of a new aminoglycoside acetyltransferase (3-N) with a broad substrate range that includes all the disubstituted 2-deoxystreptamine antibiotics and also the novel monosubstituted antibiotic apramycin. Antibiotic derivatives acylated with hydroxyaminobutyric acid at the 1-amino position were not modified by the enzyme.

Acetyltransferases↗
PubMed2026

Comprehensive in silico genomics analysis of global trends and host-specific emergence of aminoglycoside resistance in Staphylococcus aureus: a One-Health perspective.

BACKGROUND: Aminoglycosides remain clinically valuable against Staphylococcus aureus. Aminoglycoside resistance in S. aureus represents a critical One Health concern and is primarily driven by aminoglycoside-modifying enzymes (AMEs), which are frequently plasmid-encoded. Although regional studies have provided valuable insights, the global epidemiology of aminoglycoside resistance determinants remains poorly characterized because comprehensive data integrating human, animal, and environmental reservoirs are still lacking. This study addresses this gap by analyzing over 110,000 S. aureus genomes (2000-2025) to map the global resistome, quantify temporal and host-specific trends, and assess the association between genetic determinants and phenotypic resistance. METHODS: We performed a retrospective One Health meta-analysis of 110,309 S. aureus genomes collected between 2000 and 2025 from 128 countries. Genomes were quality-filtered and aminoglycoside resistance determinants were identified using NCBI AMRFinderPlus (v4.0.23). Multilocus sequence typing and host-source harmonization (Human, Animal, Environment, Unknown) enabled clonal and reservoir stratification. Temporal trends in gene prevalence and resistance burden were modeled with robust regression. Geographic and host-associated structuring of key genes was assessed via &#x3c7;2 and enrichment tests. Machine-learning models (elastic-net, random forests, XGBoost) were benchmarked for minimum inhibitory concentration (MIC) prediction via nested cross-validation, with performance evaluated by mean absolute error, RMSE, and SHAP-based feature importance. All analyses were conducted in R and Python using publicly available, de-identified genomic data. RESULTS: Aminoglycoside resistance-associated genes were dominated by modifying enzyme determinants, with ant(6)-Ia, ant(9)-Ia, aph(3')-IIIa, sat4, aadD1, and aac(6')-Ie/aph(2'')-Ia occurring in 14-22% of isolates worldwide. Temporal analysis revealed significant declines in several major determinants, most notably ant(9)-Ia (-2.22 percentage points per year, p&#x2009;<&#x2009;0.001), whereas apmA exhibited a non-significant decreasing trend in animal isolates. Host structuring was marked: human clinical isolates concentrated common determinants, while animal and environmental isolates harbored rare alleles (apmA, spw, str, spd). Geographic mapping confirmed near-universal distribution of common genes but focal restriction of rare ones. Publicly available phenotypic data indicated strong activity of amikacin, whereas gentamicin showed a distinct resistant subpopulation that closely corresponded with AME gene carriage. Genotype-phenotype analyses demonstrated strong concordance, with gene-rich complements predicting resistant MIC strata and absence of determinants predicting susceptibility. Analysis across different gene classes revealed frequent co-occurrence of aminoglycoside resistance genes with determinants from other classes, such as mecA, blaZ, and MLS_B, embedding them within multidrug-resistant (MDR) genomic contexts. CONCLUSION: Over 25&#xa0;years, the prevalence of aminoglycoside resistance-associated genes in S. aureus has declined for several common determinants, while rare veterinary-linked alleles are emerging in animal isolates. Strong genotype-phenotype concordance supports genomic prediction for gentamicin and amikacin, where MIC data are available, although phenotypic confirmation remains essential. The frequent co-occurrence of aminoglycoside resistance genes with other antimicrobial resistance determinants indicates their integration within co-occurrence patterns of MDR genes, defined here as clusters of co-occurring resistance genes often carried on shared mobile genetic elements. These patterns highlight the need for integrated One Health surveillance combining clinical, veterinary, and environmental monitoring with plasmid-context resolution to anticipate emerging threats.

Aminoglycosides↗
PubMed1978

In vitro activity of 5-episisomicin in bacteria resistant to other aminoglycoside antibiotics.

Eighty-seven isolates of Pseudomonas, Enterobacteriaceae, and Staphylococcus, chosen because of their resistance to other aminoglycosides, were tested for susceptibility to 5-episisomicin. Tests were performed in Mueller-Hinton agar and also, with 38 of these isolates, in Mueller-Hinton broth. Of Enterobacteriaceae, 85 and 95.5% were inhibited by 5 and 10 mug of 5-episisomicin per ml, respectively. Amikacin inhibited 74 and 91% of the strains at 10 and 20 mug/ml, respectively. Fifty-four percent of P. aeruginosa were inhibited by 5-episisomicin and amikacin. Eighty-three percent of S. aureus were inhibited by netilmicin and amikacin, whereas only 50% were inhibited by 5-episisomicin. Isolates resistant to 5-episisomicin were most often resistant to the other aminoglycosides and occurred in gram-negative bacilli that did not carry aminoglycoside-modifying enzymes. Five of 23 isolates that carried a 6'-N-acetyltransferase (AAC-6') and one of two that carried an aminoglycoside 3-acetyltransferase were resistant to and acetylate 5-episisomicin. Strains carrying other aminoglycoside-modifying enzymes were inhibited by 5-episisomicin. Thus, 5-episisomicin is a promising aminoglycoside not attacked by most aminoglycoside-modifying enzymes. Resistance will probably most often be based upon nonenzymatic mechanisms which will also affect other aminoglycosides.

Drug Resistance, Microbial↗
PubMed2026

MT-RNR1 genotype testing for preventing aminoglycoside-mediated ototoxicity: A guideline developed by the UK Centre of Excellence in Regulatory Science and Innovation in Pharmacogenomics (CERSI-PGx).

Aminoglycosides are broad-spectrum antibiotics used in the management of severe infections. Aminoglycosides are associated with nephrotoxicity and ototoxicity. Although dosing strategies such as once-daily administration and therapeutic drug monitoring have reduced the incidence of nephrotoxicity, ototoxicity remains unpredictable and may occur at therapeutic concentrations. A strong association between specific mitochondrial DNA variants in MT-RNR1 (m.1555A&#x2009;>&#x2009;G, m.1494C&#x2009;>&#x2009;T and m.1095&#x2009;T&#x2009;>&#x2009;C) and aminoglycoside-induced hearing loss exists. These variants (frequency ~1 in 330 individuals across populations) predispose to irreversible, sensorineural hearing loss following aminoglycoside exposure, sometimes after a single dose. Avoidance of aminoglycosides is recommended at any detectable variant level. In England, laboratory-based MT-RNR1 testing is nationally commissioned, whereas point-of-care testing in time-critical settings like neonatal sepsis is delivered in some centres. Approximately 20% of aminoglycoside use is predictable providing opportunities for pre-emptive pharmacogenetic testing. Where MT-RNR1 testing results are unavailable and clinical urgency is high, aminoglycoside treatment should not be delayed. Early health economic evidence suggests that point-of-care testing in neonates may be cost-saving by preventing lifelong hearing loss. Regulatory and Health Technology Assessment bodies support targeted implementation of testing alongside further evidence generation. Overall, integration of MT-RNR1 pharmacogenetic testing offers a feasible and proportionate strategy to reduce harm while preserving access to life-saving antibiotic therapy. This guideline is grounded in the latest evidence in this field but cannot account for all individual factors relevant to patient care. Therefore, prescribers must conduct a thorough assessment of each patient's risk-benefit profile, ensuring that therapy is optimized to maximize benefits while minimizing potential harms.

Humans↗
PubMed1979

Relationship between aminoglycoside-induced nephrotoxicity and auditory toxicity.

We have reviewed our data from 391 patients entered into three prospective, double-blind studies of aminoglycosides and evaluated 127 cases to determine whether aminoglycoside-induced auditory toxicity and nephrotoxicity are independent events. The cases selected for evaluation included all patients treated for greater than 3 days (mean, 7.7 days) who had serial creatinine determinations and were able to cooperate with serial bedside audiograms (250 to 8,000 Hz). Patients received either gentamicin, tobramycin, or amikacin. Drug dosage was altered to keep serum levels 1 h after administration between 5 and 10 mug/ml (gentamicin or tobramycin) or 20 and 40 mug/ml (amikacin). The investigators evaluating auditory toxicity and nephrotoxicity were blind to the aminoglycoside being administered. The incidence of auditory toxicity in the nephrotoxic group (18.2%) was not significantly different from that in the nonnephrotoxic group (15.2%) (P = 0.75; Fisher exact test). There was no statistical difference between the nephrotoxic and auditory toxic groups in patient age, total dose of aminoglycoside, initial creatinine level, duration of therapy, or concurrent use of furosemide or cephalothin. We conclude that aminoglycoside-induced auditory toxicity and nephrotoxicity are independent events when the drug is administered for approximately 7 days and when aminoglycoside levels are maintained within a predefined range.

Amikacin↗
PubMed1979

Clinical isolation and characterization of aminoglycoside-resistant small colony variants of Enterobacter aerogenes.

Small colony variants of Enterobacter aerogenes, as well as the parental large colony type, grew in blood drawn for cultures on three separate days from a patient who had received suboptimal gentamicin therapy. Minimum inhibitory concentrations of four aminoglycoside antibiotics were eight to more than 16 times higher for small colony variants than for the normal large colony type. Small colony variants had defective catalase activity, which may have interfered with oxidative metabolism and aminoglycoside uptake. Small colony variants reverted readily to the parental type in vitro in the absence of aminoglycosides. Clinically isolated small colony variants appeared similar to those selected in the presence of gentamicin in vitro, with respect to colony morphology, aminoglycoside resistance and catalase deficiency. The isolation of small colony variants during gentamicin therapy in vivo suggests that such variants may be a cause of treatment failure in patients receiving aminoglycosides.

Aminoglycosides↗
PubMed1976

In vitro activity of amikacin and ten other aminoglycoside antibiotics against gentamicin-resistant bacterial strains.

Sixty-nine strains of gentamicin-resistant gram-negative bacilli obtained from different geographical sources were tested for susceptibility to 11 aminoglycoside antibiotics. From the results of determinations of minimal inhibitory concentrations, patterns of resistance were established for 45 strains of Enterobacteriaceae and 24 strains of Pseudomonas aeruginosa. Overall, 81% of the strains were sensitive to amikacin and 33% of the strains were sensitive to butirosin, the next most active compound. Results indicated that 54% of the P. aeruginosa strains were sensitive to amikacin and 33% were sensitive to tobramycin. From resistance patterns, enzymes responsible for inactivation of the antibiotics were deduced. The most common enzyme was aminoglycoside nucleotidyltransferase(2''), either alone or combined with either aminoglycoside phosphotransferase(3')-I or aminoglycoside phosphotransferase(3')-II. Aminoglycoside acetyltransferase(2) was identified exclusively in strains of Providencia stuartii. Specific enzymes could not be identified for 30 strains, 21 of which were P. aeruginosa.

Amikacin↗