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Organic Letters May 2020The clinical aminoglycoside antibiotic gentamicin is a mixture of several difficult-to-separate major and minor components. The relative inaccessibility of the minor...
The clinical aminoglycoside antibiotic gentamicin is a mixture of several difficult-to-separate major and minor components. The relative inaccessibility of the minor components in particular complicates efforts to separate antibacterial activity from nephro- and/or ototoxicity and to clarify the origin of the potentially therapeutically important read-through activity. With a view to facilitating such studies, the synthesis of a fully and selectively protected garamine-based acceptor has been developed from readily available sisomicin. Glycosylation of this acceptor with a 6-azido-6,7-dideoxy-d-glycero-d-glucoheptopyranosyl donor affords gentamicin B1 after deprotection, whereas employment of a 2-azido-2-deoxy-d-glucopyranosyl donor under ,-dimethylformamide-directed glycosylation conditions affords gentamicin X2 after deprotection.
Topics: Aminoglycosides; Anti-Bacterial Agents; Disaccharides; Gentamicins; Glycosylation; Humans; Molecular Structure
PubMed: 32343899
DOI: 10.1021/acs.orglett.0c01107 -
Journal of Orthopaedic Surgery and... May 2021To investigate the clinical effect of gastrocnemius muscle flaps combined with vancomycin/gentamicin-calcium sulfate combined and autologous iliac bone graft in the...
Gastrocnemius muscle flap with vancomycin/gentamicin-calcium sulfate and autogenous iliac bone graft for the phase I treatment of localized osteomyelitis after tibial plateau fracture surgery.
PURPOSE
To investigate the clinical effect of gastrocnemius muscle flaps combined with vancomycin/gentamicin-calcium sulfate combined and autologous iliac bone graft in the phase I treatment of traumatic focal osteomyelitis (Cierny-Mader type III) after tibial plateau fracture surgery.
METHODS
From July 2009 to January 2018, 35 patients with localized osteomyelitis (Cierny-Mader type III) who met the inclusion criteria were followed up and treated. All patients were infected after undergoing internal fracture fixation surgery. Among them, 18 cases were plate-exposed, 14 cases were due to sinus tracts, two were due to skin necrosis, and one was bone-exposed. We treated patients with several measures. All cases were then followed up. The follow-up indicators included Hospital for Special Surgery knee scores (HSS), the time of laying drainage pipe, bone healing time, infection control rate, and the incidence of nonunion and other complications.
RESULTS
All patients were followed up for 24-60 months. None of them underwent amputation. For repairing soft tissue defects, 17 cases were covered with a muscle flap using the medial head of gastrocnemius alone, 15 cases were treated with the lateral head of gastrocnemius muscle, and three cases were covered with the combination of the two heads. Compared to the preoperative score, we found that the average HSS improved at the 1-year and 2-year follow-up (54 vs. 86 vs. 87).
CONCLUSION
Using a gastrocnemius muscle flap combined with vancomycin/gentamicin-calcium sulfate and autogenous iliac bone was an effective method for the phase I treatment of osteomyelitis (Cierny-Mader type III) after tibial plateau fracture surgery. In the primary treatment of focal traumatic osteomyelitis, it can decrease the treatment time, number of surgeries, pain of patients, time of bone healing, postoperative exudation, and infection recurrence rate and increase the healing bone's strength.
Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bone Transplantation; Calcium Sulfate; Combined Modality Therapy; Female; Fracture Fixation, Internal; Gentamicins; Humans; Ilium; Male; Middle Aged; Muscle, Skeletal; Osteomyelitis; Postoperative Complications; Surgical Flaps; Tibial Fractures; Vancomycin
PubMed: 34044871
DOI: 10.1186/s13018-021-02496-1 -
Journal of Veterinary Internal Medicine May 2018Therapeutic drug monitoring and minimum inhibitory concentration (MIC) data allow more informed use of gentamicin.
BACKGROUND
Therapeutic drug monitoring and minimum inhibitory concentration (MIC) data allow more informed use of gentamicin.
HYPOTHESIS/OBJECTIVES
To measure peak and trough serum gentamicin concentrations in horses after a 6.6 mg/kg dose of gentamicin given IV and the MIC of gentamicin of bacteria for which gentamicin might be selected.
METHODS
Retrospective analysis of hospital records. Peak and trough plasma gentamicin concentrations were measured after 6.6 mg/kg gentamicin IV in 339 hospitalized horses. The MIC of gentamicin was measured for 503 isolates from ambulatory practice and 33 from hospital practice. The distribution of gentamicin concentrations and MIC results were compared to current recommendations for MIC breakpoints.
RESULTS
The median serum gentamicin concentration at 60 minutes after administration (C ) was 21.4 μg/mL with a distribution indicating that bacteria with MIC ≥2 μg/mL were unlikely to be exposed to sufficient gentamicin for effective killing. Approximately 90% of isolates from ambulatory practice and 36% of hospital isolates had MICs at or below breakpoints for susceptibility with most of the remainder unlikely to be responsive, even to higher IV doses.
CONCLUSIONS AND CLINICAL IMPORTANCE
Gentamicin at a dosage of 6.6 mg/kg IV is likely to be effective against the majority of infections encountered in ambulatory practice, but less effective in an equine hospital. Because there was a dichotomy of most bacteria as being clearly susceptible or clearly resistant to gentamicin, it appears unlikely that higher doses would have been more efficacious, especially in the hospitalized population in our study.
Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Gentamicins; Horse Diseases; Horses; Microbial Sensitivity Tests; Retrospective Studies
PubMed: 29575239
DOI: 10.1111/jvim.15078 -
Clinical Obstetrics and Gynecology Sep 2008Gentamicin, an aminoglycoside with broad antimicrobial activity, is commonly used in both obstetrics and gynecology. Traditional dosing regimens for gentamicin have... (Review)
Review
Gentamicin, an aminoglycoside with broad antimicrobial activity, is commonly used in both obstetrics and gynecology. Traditional dosing regimens for gentamicin have called for 3 times daily dosing, but recent insights into the pharmacodynamics of the drug have led to multiple studies of once-daily dosing regimens. Many studies have demonstrated efficacy, safety, and economy of the 24-hour dosing interval, resulting in recommendations that this become the standard for aminoglycoside administration. However, because of the unique considerations for drug administration in pregnant and postpartum women, the once-daily dosing regimens have not been widely adopted. Additional studies in pregnant and postpartum women have demonstrated therapeutic noninferiority, no increase in adverse events, and significant cost savings with once-daily dosing versus 3 times daily dosing of gentamicin. We review the literature and present rationale based on multiple controlled studies supporting single-daily dosing of gentamicin, 5 mg/kg/d actual body weight, for many common obstetrics-gynecology infections.
Topics: Adult; Anti-Bacterial Agents; Chorioamnionitis; Dose-Response Relationship, Drug; Drug Administration Schedule; Endometritis; Female; Gentamicins; Humans; Postpartum Period; Pregnancy; Pregnancy Complications, Infectious; Puerperal Disorders; Safety; Treatment Outcome
PubMed: 18677142
DOI: 10.1097/GRF.0b013e31818091cd -
Journal of Orthopaedic Surgery and... Feb 2022Present work was aimed to gather accessible evidence on the eradication rates and related postoperative complications of antibiotic-loaded calcium sulfate (CS) as an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Present work was aimed to gather accessible evidence on the eradication rates and related postoperative complications of antibiotic-loaded calcium sulfate (CS) as an implant in the treatment of chronic osteomyelitis (COM).
METHODS
Databases including PubMed, EMBASE, Medline, Ovid and Cochrane library were searched from their dates of initiation until November 2021. Two independent authors scrutinized the relevant studies based on the effectiveness of radical debridement combined with antibiotic-loaded CS for COM; data extraction and quality assessment of the Methodological Index for Non-Randomized Studies (MINORS) criteria were also performed by the authors. In addition, clinical efficacy mainly depended on the evaluation of eradication rates and complications, and all the extracted data are pooled and analyzed by STATA 16.0.
RESULTS
A total of 16 studies with 917 patients (920 locations) were recruited, with an overall eradication rate of 92%. Moreover, the overall reoperation rate, overall refracture rate, overall delayed wound healing rate, and the rate of aseptic wound leakage were 9.0%, 2.0%, 20.0%, and 12.0%, respectively. Moreover, the choice of tobramycin-loaded CS or vancomycin combined with gentamicin-loaded CS did not affect the eradication rate, and the incidence of postoperative complications in COM patients (all [Formula: see text]). The general quality of the included studies was fair.
CONCLUSIONS
Our meta-analysis indicated that the overall eradication rate of COM treated with antibiotic-loaded CS was 92%. Delayed healing is the most common postoperative complication. The choice of tobramycin-loaded CS or vancomycin combined with gentamicin-loaded CS did not affect the eradication rate and the incidence of postoperative complications in COM patients.
Topics: Anti-Bacterial Agents; Calcium Sulfate; Gentamicins; Humans; Incidence; Osteomyelitis; Postoperative Complications; Tobramycin; Vancomycin
PubMed: 35183215
DOI: 10.1186/s13018-022-02980-2 -
Systematic Reviews Sep 2014A high level of resistance in Neisseria gonorrhoeae has developed against penicillins, sulphonamides, tetracyclines and quinolones, and recent surveillance data have... (Review)
Review
BACKGROUND
A high level of resistance in Neisseria gonorrhoeae has developed against penicillins, sulphonamides, tetracyclines and quinolones, and recent surveillance data have shown a gradual reduction in sensitivity to current first-line agents with an upward drift in the minimum inhibitory concentration of ceftriaxone. Laboratory sensitivity testing suggests that gentamicin, an aminoglycoside, may be an effective treatment option for gonorrhoea infection when used as a single intramuscular dose.
METHODS
A search of electronic reference databases and grey literature was used to identify randomised trials and well-conducted prospective studies with concurrent controls evaluating single-dose gentamicin against placebo or a comparator regimen in the treatment of uncomplicated gonorrhoea infection in men and women aged 16 years and over. The primary outcome was microbiological cure of N. gonorrhoeae.
RESULTS
Eight hundred and thirty-nine studies were identified, of which five (1,063 total participants) were included. All five studies administered single-dose gentamicin via intramuscular injection to men with uncomplicated gonococcal urethritis. Three studies were randomised trials, one was quasi-randomised and one was non-randomised but included a comparator arm. Comparator antibiotics included an alternative aminoglycoside or antibiotic used in the syndromic management of male urethritis. Methodology was poorly described in all five included studies. The high risk of bias within studies and clinical heterogeneity between studies meant that it was inappropriate to pool data for meta-analysis. Cure rates of 62% to 98% were reported with gentamicin treatment. The relative risk of cure was comparable between gentamicin and comparator antibiotics.
CONCLUSIONS
The studies identified provide insufficient data to support or refute the efficacy and safety of single-dose intramuscular gentamicin in the treatment of uncomplicated gonorrhoea infection. Additional randomised trials to evaluate gentamicin for this indication are therefore required.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42012002490.
Topics: Anti-Bacterial Agents; Gentamicins; Gonorrhea; Humans; Injections, Intramuscular; Neisseria gonorrhoeae; Treatment Outcome
PubMed: 25239090
DOI: 10.1186/2046-4053-3-104 -
Proceedings of the National Academy of... Dec 2020Gentamicin is a potent broad-spectrum aminoglycoside antibiotic whose use is hampered by ototoxic side-effects. Hospital gentamicin is a mixture of five gentamicin...
Gentamicin is a potent broad-spectrum aminoglycoside antibiotic whose use is hampered by ototoxic side-effects. Hospital gentamicin is a mixture of five gentamicin C-subtypes and several impurities of various ranges of nonexact concentrations. We developed a purification strategy enabling assaying of individual C-subtypes and impurities for ototoxicity and antimicrobial activity. We found that C-subtypes displayed broad and potent in vitro antimicrobial activities comparable to the hospital gentamicin mixture. In contrast, they showed different degrees of ototoxicity in cochlear explants, with gentamicin C2b being the least and gentamicin C2 the most ototoxic. Structure-activity relationships identified sites in the C4'-C6' region on ring I that reduced ototoxicity while preserving antimicrobial activity, thus identifying targets for future drug design and mechanisms for hair cell toxicity. Structure-activity relationship data suggested and electrophysiological data showed that the C-subtypes both bind and permeate the hair cell mechanotransducer channel, with the stronger the binding the less ototoxic the compound. Finally, both individual and reformulated mixtures of C-subtypes demonstrated decreased ototoxicity while maintaining antimicrobial activity, thereby serving as a proof-of-concept of drug reformulation to minimizing ototoxicity of gentamicin in patients.
Topics: Animals; Anti-Bacterial Agents; Cochlea; Drug Contamination; Gentamicins; Hair Cells, Auditory; Hospitals; Ion Channels; Mechanotransduction, Cellular; Microbial Sensitivity Tests; Rats, Sprague-Dawley; Sisomicin; Structure-Activity Relationship
PubMed: 33288712
DOI: 10.1073/pnas.2013065117 -
International Journal of Nanomedicine 2017We investigated the efficacy of liposomal gentamicin formulations of different surface charges against and . The liposomal gentamicin formulations were prepared by the...
We investigated the efficacy of liposomal gentamicin formulations of different surface charges against and . The liposomal gentamicin formulations were prepared by the dehydration-rehydration method, and their sizes and zeta potential were measured. Gentamicin encapsulation efficiency inside the liposomal formulations was determined by microbiologic assay, and stability of the formulations in biologic fluid was evaluated for a period of 48 h. The minimum inhibitory concentration and the minimum bactericidal concentration were determined, and the in vitro time kill studies of the free form of gentamicin and liposomal gentamicin formulations were performed. The activities of liposomal gentamicin in preventing and reducing biofilm-forming and were compared to those of free antibiotic. The sizes of the liposomal formulations ranged from 625 to 806.6 nm in diameter, with the zeta potential ranging from -0.22 to -31.7 mV. Gentamicin encapsulation efficiency inside the liposomal formulation ranged from 1.8% to 43.6%. The liposomes retained >60% of their gentamicin content during the 48 h time period. The minimum inhibitory concentration of neutral formulation was lower than that of free gentamicin (0.25 versus 1 mg/L for and 0.5 versus 1 mg/L for ). The negatively charged formulation exhibited the same bacteriostatic concentration as that of free gentamicin. The minimum bactericidal concentration of neutral liposomes on planktonic bacterial culture was twofold lower than that of free gentamicin, whereas the negatively charged formulations were comparable to free gentamicin. The killing time curve values for the neutral negatively charged formulation against planktonic and were better than those of free gentamicin. Furthermore, liposomal formulations prevent the biofilm-formation ability of these strains better than free gentamicin. In summary, liposomal formulations could be an effective lipid nanoparticle to combat acute infections where planktonic bacteria are predominant.
Topics: Animals; Anti-Bacterial Agents; Biofilms; Gentamicins; Humans; Klebsiella oxytoca; Liposomes; Male; Microbial Sensitivity Tests; Nanoparticles; Particle Size; Plankton; Pseudomonas aeruginosa; Rats
PubMed: 29075113
DOI: 10.2147/IJN.S141709 -
Journal of Veterinary Internal Medicine Sep 2021Irreversible sensorineural auditory loss has been reported in humans treated with aminoglycosides but not in horses.
BACKGROUND
Irreversible sensorineural auditory loss has been reported in humans treated with aminoglycosides but not in horses.
OBJECTIVE
Investigate if auditory loss occurs in horses treated using the recommended IV daily dosage of gentamicin for 7 consecutive days.
ANIMALS
Ten healthy adult horses (7-15 years; females and males, 5 each).
METHODS
Prospective study. Physical and neurological examinations and renal function tests were performed. Gentamicin sulfate was administered at a dosage of 6.6 mg/kg via the jugular vein on alternating sides for 7 days. Gentamicin peak and trough concentrations were measured. Horses were sedated using detomidine hydrochloride IV to perform brainstem auditory evoked responses (BAER) before the first dose, immediately after the last dose, and 30 days after the last dose. Peaks latencies, amplitudes, and amplitude ratios were recorded. Data from the second and last BAER were compared to results at baseline. Bone conduction was performed to rule out conduction disorders.
RESULTS
Seven horses had auditory loss: complete bilateral (N = 1), complete unilateral (N = 2), and partial unilateral (N = 4). Based on physical examination and BAER results, sensorineural auditory loss was suspected. Absent bone conduction ruled out a conduction disorder and further supported sensorineural auditory loss in horses with completely absent BAER. Auditory dysfunction was reversible in 4 of 7 horses.
CONCLUSIONS AND CLINICAL IMPORTANCE
Gentamicin at recommended doses may cause sensorineural auditory loss in horses that might be irreversible. Follow-up studies are needed to investigate if other dosing protocols present a similar risk.
Topics: Animals; Anti-Bacterial Agents; Evoked Potentials, Auditory, Brain Stem; Female; Follow-Up Studies; Gentamicins; Horses; Male; Prospective Studies
PubMed: 34322916
DOI: 10.1111/jvim.16221 -
British Medical Journal Jan 1967
Topics: Bacteria; Gentamicins; Humans; Urinary Tract Infections
PubMed: 6015651
DOI: No ID Found