TY - JOUR. T1 - Aminoglycoside-Induced Hair Cell Death of Inner Ear Organs Causes Functional Deficits in Adult Zebrafish (Danio rerio). AU - Uribe, Phillip M.. AU - Sun, Huifang. AU - Wang, Kevin. AU - Asuncion, James D.. AU - Wang, Qi. AU - Chen, Chien Wei. AU - Steyger, Peter S.. AU - Smith, Michael E.. AU - Matsui, Jonathan I.. PY - 2013/3/22. Y1 - 2013/3/22. N2 - Aminoglycoside antibiotics, like gentamicin, kill inner ear sensory hair cells in a variety of species including chickens, mice, and humans. The zebrafish (Danio rerio) has been used to study hair cell cytotoxicity in the lateral line organs of larval and adult animals. Little is known about whether aminoglycosides kill the hair cells within the inner ear of adult zebrafish. We report here the ototoxic effects of gentamicin on hair cells in the saccule, the putative hearing organ, and utricle of zebrafish. First, adult zebrafish received a single 30 mg/kg intraperitoneal injection of fluorescently-tagged gentamicin (GTTR) to ...
The three classes of enzymes which inactivate aminoglycosides and lead to bacterial resistance are reviewed. DNA hybridization studies have shown that different genes can encode aminoglycoside-modifying enzymes with identical resistance profiles. Comparisons of the amino acid sequences of 49 aminoglycoside-modifying enzymes have revealed new insights into the evolution and relatedness of these proteins. A preliminary assessment of the amino acids which may be important in binding aminoglycosides was obtained from these data and from the results of mutational analysis of several of the genes encoding aminoglycoside-modifying enzymes. Recent studies have demonstrated that aminoglycoside resistance can emerge as a result of alterations in the regulation of normally quiescent cellular genes or as a result of acquiring genes which may have originated from aminoglycoside-producing organisms or from other resistant organisms. Dissemination of these genes is aided by a variety of genetic elements ...
TY - CONF. T1 - The Role of Gemtuzumab Ozogamicin in Elderly AML Patients in Complete Remission. AU - Siragusa, Sergio. PY - 2007. Y1 - 2007. N2 - The majority of patients (pts) with acute myeloid leukemia (AML) are diagnosed in their 6th and 7th decade of life. AML in elderly pts is associated with poor response to conventional chemotherapy and limited long-term survival, reflecting a higher incidence multidrug resistance mechanisms, a low bone marrow reserve which may prevent/delay the recovery of hematopoiesis after treatment, and the occurrence of co-morbidities. Gemtuzumab ozogamicin (GO) is an immunoconjugate with a humanized anti-CD33 that after internalization, releases a cytotoxic drug, calicheamicin; ≥80% of AML pts have myeloid blast cells that express the CD33 surface antigen. GO as a single agent has low antileukemic activity (Sievers et al, J Clin Oncol 2001;19:3244-54). However, GO is being used at lower doses in combined chemotherapy regimens as induction or postremission ...
TY - JOUR. T1 - Diversity of high-level aminoglycoside resistance mechanisms among Gram-negative nosocomial pathogens in Brazil. AU - Ballaben, Anelise S.. AU - Andrade, Leonardo N.. AU - Galetti, Renata. AU - Ferreira, Joseane C.. AU - McElheny, Christi L.. AU - Mettus, Roberta T.. AU - da Silva, Paulo. AU - de Oliveira Garcia, Doroti. AU - Darini, Ana Lucia C.. AU - Doib, Yohei. PY - 2018/11. Y1 - 2018/11. UR - http://www.scopus.com/inward/record.url?scp=85055604011&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=85055604011&partnerID=8YFLogxK. U2 - 10.1128/AAC.01550-18. DO - 10.1128/AAC.01550-18. M3 - Letter. C2 - 30150471. AN - SCOPUS:85055604011. VL - 62. JO - Antimicrobial Agents and Chemotherapy. JF - Antimicrobial Agents and Chemotherapy. SN - 0066-4804. IS - 11. M1 - e01550-18. ER - ...
Agarwal, J., Kalyan, R. and Singh, M. (2009) High-Level Aminoglycoside Resistance and Beta-Lactamase Production in Enterococci at a Tertiary Care Hospital in India. Japanese Journal of Infectious Diseases, 62, 158-159.
PRIMARY OBJECTIVES:. I. To test whether outcomes of patients of age 60 or older with previously untreated non-M3 acute myeloid leukemia treated with azacitidine plus gemtuzumab ozogamicin are sufficient to warrant phase III investigation.. II. To estimate the frequency and severity of toxicities of this regimen in the good- and poor-risk groups of patients.. III. To investigate in a preliminary manner the disease-free survival of patients who achieve complete remission and receive post-remission therapy on this study.. IV. To investigate in a preliminary manner the cytogenetic response rates of patients treated with this regimen.. V. To investigate in a preliminary manner the effects of cytogenetic abnormalities, promoter and global methylation changes, and multidrug resistance on overall survival and response to azacitidine plus gemtuzumab ozogamicin therapy.. OUTLINE: Patients are stratified according to risk status (good [60-69 years of age OR Zubrod performance status [PS] 0-1] vs poor [,= ...
PRIMARY OBJECTIVES:. I. To test whether outcomes of patients of age 60 or older with previously untreated non-M3 acute myeloid leukemia treated with azacitidine plus gemtuzumab ozogamicin are sufficient to warrant phase III investigation.. II. To estimate the frequency and severity of toxicities of this regimen in the good- and poor-risk groups of patients.. III. To investigate in a preliminary manner the disease-free survival of patients who achieve complete remission and receive post-remission therapy on this study.. IV. To investigate in a preliminary manner the cytogenetic response rates of patients treated with this regimen.. V. To investigate in a preliminary manner the effects of cytogenetic abnormalities, promoter and global methylation changes, and multidrug resistance on overall survival and response to azacitidine plus gemtuzumab ozogamicin therapy.. OUTLINE: Patients are stratified according to risk status (good [60-69 years of age OR Zubrod performance status [PS] 0-1] vs poor [,= ...
2. 19 Aminoglycoside Antibiotics 34. Li, X. , L. Zhang, G. A. McKay, and K. Poole. 2003. Role of the acetyltransferase AAC(6p)-Iz modifying enzyme in aminoglycoside resistance in Stenotrophomonas maltophilia. J. Antimicrob. Chemother. 51:803-811. 35. , M. Tod, Y. Cohen, and O. Petitjean. 1995. Aminoglycosides. Med. Clin. N. Am. 79:761-87. 36. , T. A. Smith, R. J. Zheng, P. Nordmann, and J. S. Blanchard. 2003. Aminoglycoside resistance resulting from tight drug binding to an altered aminoglycoside acetyltransferase. 1999. Semisynthetic aminoglycoside antibiotics: development and enzymatic modifications. J. Infect. Chemother. 5:1-9. Kotra, L. , J. Haddad, and S. Mobashery. 2000. Aminoglycosides perspectives on mechanisms of action and resistance and strategies to counter resistance. Antimicrob. Agents Chemother. 44:3249-3256. 2. 19 Aminoglycoside Antibiotics 34. Li, X. , L. Zhang, G. A. McKay, and K. Poole. 2003. Role of the acetyltransferase AAC(6p)-Iz modifying enzyme in aminoglycoside ...
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Neomycin is an aminoglycoside antibiotic. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses ...
Neomycin is an aminoglycoside antibiotic. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses ...
Since the introduction into clinical practice of the aminoglycoside class of antibiotics, a number of other antimicrobial agents with improved safety profile have entered the market. Studies have failed to demonstrate the superiority of aminoglycoside-containing regimens in a number of infection settings. This has raised doubts regarding the actual clinical utility of aminoglycosides. However, the recent emergence of infections due to Gram-negative bacterial strains with advanced patterns of antimicrobial resistance has prompted physicians to reconsider these old antibacterial agents. This revived interest in the use of aminoglycosides has brought back to light the debate on the two major issues related to these compounds, namely the spectrum of antimicrobial susceptibility and toxicity. Although some of the aminoglycosides retain activity against the majority of Gram-negative clinical bacterial isolates in many parts of the world, the relatively frequent occurrence of nephrotoxicity and ...
Staphylococcus aureus is a notorious pathogen which often causes nosocomial and community attained infections. These infections steadily increased after evolving the resistance due to indecorous practice of antibiotics and now become a serious health issue. Ouabain is a Na+/K+-ATPase inhibitor that leads to increase the heart contraction in patients with congestive heart failure. In the present study, in vitro antimicrobial effect of ouabain together with aminoglycosides was determined against clinical and non-clinical S. aureus strains. Using checkerboard, Gentamycin uptake and biofilm assays, we analysed he interactions of ouabain with aminoglycosides. Ouabain induced the staphylocidal potency of aminoglycosides by remarkably reducing the MIC of gentamycin (GEN) by 16 (0.25 μg/mL), 8 folds (0.5 μg/mL) amikacin (AMK); and 16 folds (1.0 μg/mL) with kanamycin (KAN), compared to their individual doses. OBN severely reduced cell viability within 60 min with GEN (1 μg/mL), KAN (2 μg/mL) and 90 min with
Bacterial infections are common in the neonates and are a major cause of morbidity and mortality. Sixty percent of preterm infants admitted to neonatal intensive care units received at least one antibiotic during the first week of life. Penicillins, aminoglycosides and cephalosporins comprised 53, 43 and 16%, respectively. Kinetic parameters such as the half-life (t1/2), clearance (Cl), and volume of distribution (Vd) change with development, so the kinetics of penicillins, cephalosporins and aminoglycosides need to be studied in order to optimise therapy with these drugs. The aim of this study is to review the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate in a single article in order to provide a critical analysis of the literature and thus provide a useful tool in the hands of physicians. The bibliographic search was performed electronically using PubMed, as the search engine, until February 2nd, 2010. Medline search terms were as follows: pharmacokinetics AND
Prospective, multicenter, uncontrolled cohort study to analyze the efficacy of a risk adapted treatment strategy, including gemtuzumab ozogamicin (GO) d
The effects of aminoglycoside antibiotics on cellular functions of the LLC-PK1 kidney epithelial cell line were studied as a model system for aminoglycoside nephrotoxicity. The treatment with aminoglycoside antibiotics for 3 days caused a decrease in the dome number in the confluent LLC-PK1 cells and an increase in the floating cells in the culture medium. The inhibition of dome formation was dose-dependent and the rank-order of the degree of inhibition was compatible with the rank-order of in vivo nephrotoxicity. Aminoglycosides also decreased the intracellular content of cyclic AMP, with a correlation between the alteration of dome formation and cyclic AMP content. The specific activities of N-acetyl-beta-D-glucosaminidase (marker for lysosomes), aminopeptidase and alkaline phosphatase (marker for apical membranes) and (Na++K+)-adenosine triphosphatase (marker for basolateral membranes) in the homogenate were decreased by gentamicin treatment. Lysosomal and apical membrane enzymes released ...
Aminoglycosides are highly potent, antibiotics with several properties for the treatment of life-threatening infections. Aminoglycosides have concentration
The tirandamycins are a small group of natural products that contain a bicyclic ketal system and a tetramic acid moiety, the latter of which is found in different natural products from a variety of sources and which is characterized by a 2,4-pyrrolidinedione ring system. Members of this structural family have shown a wide range of biological activities like in antiparasitic, antifungal and anti-HIV evaluations, and furthermore, have shown potential usefulness because of their potent antibacterial properties. Streptolydigin, an analogue of the tirandamycins, is known to function as an antibacterial agent through inhibiting the chain initiation and elongation steps RNA polymerase transcription. The structural diversity in the tirandamycin family originates from the different oxidation patterns observed in the bicycic ketal system, and these modifications are determinant features for the bioactivity associated with these molecules. In the first study that looked at the gene cluster for tirandamycin ...
Aminoglycoside Antibiotic Joel Jimenez Ms. R. Bolton October 30 2014 Aminoglycosides Antibiotic In my research paper I will be talking about the important of...
Hepatotoxicity, Including Veno-occlusive Liver Disease (VOD). Inform patients that liver problems, including severe, life-threatening, or fatal VOD may develop during MYLOTARG treatment. Prior to receiving MYLOTARG, inform patients who previously received, or will receive an HSCT that they may be at increased risk for developing VOD. Inform patients that the risk of developing VOD after an allogeneic HSCT is increased after receiving treatment with MYLOTARG. Inform patients that signs or symptoms of liver toxicity, including rapid weight gain, right upper quadrant pain and tenderness, hepatomegaly, and ascites should be monitored regularly during treatment, but these symptoms may not identify all patients at risk or prevent the complications of liver toxicity. Inform patients that liver problems may require dosing interruption or permanent discontinuation of MYLOTARG [see Warnings and Precautions (5.1)].. ...
A quick and simple procedure is presented for the extraction of aminoglycoside antibiotics from bovine meat and milk. A single operator can easily analyze 20 samples per day.
DISCUSSION. Although the ototoxic effects of aminoglycosides were first described in the 1940s, the underlying mechanisms remain unclear. Hearing damage associated with aminoglycoside use can include permanent hearing loss and tinnitus secondary to the degradation of sensorineural hair cells of the cochlea and/or vestibule. Damage to cochlear hair cells is thought to be mediated by oxidative stress, starting at the base where high-frequency sounds are decoded and advancing to the apex6,8,13,14,15. In the present study, we identified hearing complaints after aminoglycoside use in 27% of medical records analyzed, similar to what has been described in the literature (27.8%)11. Higher frequencies of TB and hearing complaints among male subjects in our study were also consistent with previous reports. This finding may be related to the increased tendency for ototoxicity risk factor exposure in men compared to women4,11,13.. In this study, we examined the relationship between hearing complaints and ...
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Startseite » Publications » A culture medium for screening pandrug- resistance to aminoglycosides in Gram-negative bacteria. ...
This phase II trial studies the how well fractionated gemtuzumab ozogamicin works in treating measurable residual disease in participants with acute myeloid leukemia. Immunotherapy with monoclonal antibodies, such as gemtuzumab ozogamicin, may help the bodys immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. ...
Aminoglycosides are mainly distributed in the extracellular fluid, so when they are given to neonates who have a large amount of extracellular fluid, their distribution is increased. In our data, the volume of distribution (Vd) of Arbekacin in the neonates was twice that of the adults, 0.54 l/kg. Therefore, the dose per weight of aminoglycosides to the neonates should be increased more than to the adults. In the renal function of the neonates, differentiation of the nephron is completed within 36 weeks after conception, but it is functionally immature ...
Specifically dimethylates two adjacent adenosines in the loop of a conserved hairpin near the 3-end of 16S rRNA in the 30S particle. Its inactivation leads to kasugamycin resistance ...
Specifically dimethylates two adjacent adenosines in the loop of a conserved hairpin near the 3-end of 16S rRNA in the 30S particle. Its inactivation leads to kasugamycin resistance ...
Methods for determining proteins and protein-bound compounds comprising enzymatic modification - diagram, schematic, and image 04 ...
4AQY: Dissociation of Antibacterial Activity and Aminoglycoside Ototoxicity in the 4-Monosubstituted 2-Deoxystreptamine Apramycin.
3,4-α-Epoxyneamine and its related aminoglycosidic antibiotic derivatives containing 3,4-α-epoxyneamine moiety in the molecule thereof are now provided, which may be in the form of their amino-protected and partially hydroxyl-protected product and which are useful as intermediates for use in the synthetic production of therapeutically valuable 3-deoxy derivatives of aminoglycosidic antibiotics.
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
The global systemic antibiotics market was respected at $39.6 billion in 2013 and is expected to reach $41.2 billion by 2020, at a CAGR of 0.8%. Antibiotics present in the marketplace such as aminoglycoside antibiotics and it covers about 79% of the global demand. Furthermore, the other antibiotics such as penicillin have 8%, tetracycline 4%, erythromycin 7%, streptomycin 1% and chloramphenicol has 1 % market ...
Advances that open new avenues in developing aminoglycosideantibiotics During the last twenty years, there have been numerous advances inthe understanding of the chemistry, biochemistry, and recognitionof aminoglycosides.
The Food and Drug Administration said Monday Pfizer Inc. is withdrawing its cancer drug Mylotarg from the U.S. market after a clinical study showed the drug wasnt effective and had...
2003 ஆம் ஆண்டு வாக்கில், இப்படி நான் எழுதிய கடிதம் ஒரு காவலூழியருக்கு போய்சேர, அந்த அரை கிறுக்கனோ, நானே போலீசு எனக்கு தெரியாம என் மீது எப்படி வழக்கு வரும் என என்னை கேட்க, ஒன்னு பத்திரிகையை பாரு; இல்லேன்ன கோர்டுல போய் பார்த்துட்டு பேசு என பதில் சொன்னதும், கோர்டுல பார்த்துட்டு, பின்னர் மன்னிப்பு கேட்டு நன்றியும் தெரிவித்தார் ...
Exposure to aminoglycoside antibiotics can lead to the generation of toxic levels of reactive oxygen species (ROS) within mechanosensory hair cells of the inner ear that have been implicated in hearing and balance disorders. Better understanding of the origin of aminoglycoside-induced ROS could focus the development of therapies aimed at preventing this event. In this work, we used the zebrafish lateral line system to monitor the dynamic behavior of mitochondrial and cytoplasmic oxidation occurring within the same dying hair cell following exposure to aminoglycosides. The increased oxidation observed in both mitochondria and cytoplasm of dying hair cells was highly correlated with mitochondrial calcium uptake. Application of the mitochondrial uniporter inhibitor Ru360 reduced mitochondrial and cytoplasmic oxidation, suggesting that mitochondrial calcium drives ROS generation during aminoglycoside-induced hair cell death. Furthermore, targeting mitochondria with free radical scavengers conferred ...
Background & objective: Multidrug-resistant Acinetobacter baumannii (MDR-AB) is an important nosocomial pathogen which is associated with significant morbidity and mortality, particularly in high-risk populations. Aminoglycoside-modifying enzymes (AMEs) and 16S ribosomal RNA (16S rRNA) methylation are two important mechanisms of resistance to aminoglycosides. The aim of this study was to determine the prevalence of 16S rRNA methylase (armA, rmtA, rmtB, rmtC, and rmtD), and the AME genes [aac(6′)-Ib, aac(3)-I, ant(3′′)-I, aph(3′)-I and aac(6)-Id], among clinical isolates of A. baumannii in Tehran, Iran. Methods: Between November 2015 to July 2016, a total of 110 clinical strains of A. baumannii were isolated from patients in two teaching hospitals in Tehran, Iran. Antimicrobial susceptibility testing was performed according to Clinical and Laboratory Standards Institute guidelines. The presence of genes encoding the AMEs and16S rRNA methylases responsible for resis-tance was investigated by
TY - JOUR. T1 - Selective inactivation of aminoglycosides by newer beta-lactam antibiotics. AU - Jorgensen, J. H.. AU - Crawford, S. A.. PY - 1982/1/1. Y1 - 1982/1/1. N2 - Combinations of aminoglycoside and beta-lactam antibiotics may act synergistically against certain microorganisms. However, aminoglycosides have been shown to interact chemically with certain beta-lactam antibiotics resulting in diminished activity of the aminoglycoside. Two beta-lactam antiotics, moxalactam and cefotaxime, as well as several other beta-lactams in current use, were studied for possible inactivation of gentamicin, tobramycin and amikacin. Aqueous mixtures of each of the three aminoglycosides plus a beta-lactam antibiotic (moxalactam, cefotaxime, cephalothin, carbenicillin, ticarcillin or penicillin) were prepared in ratios of 10:1 and 50:1 (beta-lactam: aminoglycoside). Gentamicin and tobramycin were markedly inactivated by carbenicillin and ticarcillin, and to a lesser degree by penicillin (only at the 50:1 ...
TY - JOUR. T1 - Aminoglycoside Resistance. T2 - The Emergence of Acquired 16S Ribosomal RNA Methyltransferases. AU - Doi, Yohei. AU - Wachino, Jun ichi. AU - Arakawa, Yoshichika. PY - 2016/6/1. Y1 - 2016/6/1. N2 - Aminoglycoside-producing Actinobacteria are known to protect themselves from their own aminoglycoside metabolites by producing 16S ribosomal RNA methyltransferase (16S-RMTase), which prevents them from binding to the 16S rRNA targets. Ten acquired 16S-RMTases have been reported from gram-negative pathogens. Most of them posttranscriptionally methylate residue G1405 of 16S rRNA resulting in high-level resistance to gentamicin, tobramycin, amikacin, and plazomicin. Strains that produce 16S-RMTase are frequently multidrug-resistant or even extensively drug-resistant. Although the direct clinical impact of high-level aminoglycoside resistance resulting from production of 16S-RMTase is yet to be determined, ongoing spread of this mechanism will further limit treatment options for ...
Unexpected. If there is a term that sums up life it could very well be: unexpected. Life is full of unexpected moments. Some of these moments can be full of unexpected blessings while others may be full of unexpected obstacles. However, sometimes the unexpected can be both an obstacle and blessing at the same time; you just need someone to help you see both sides. The Greenwood Genetic Center is a place that helps shed some light on the ...
Summary The polymerase chain reaction (PCR) was used to identify the aacA-aphD, aphA3 and aadC genes, encoding the aminoglycoside-modifying enzymes AAC(6′)-APH(2′), APH(3′)III and ANT(4′ 4
Looking for online definition of fidaxomicin in the Medical Dictionary? fidaxomicin explanation free. What is fidaxomicin? Meaning of fidaxomicin medical term. What does fidaxomicin mean?
Amikacin sulfate, a active ingredient of samu AMIKACIN injection, is a semi-synthetic aminoglycosides antibiotics derived from Kanamycin. Amikacin, like other aminoglycoside antibiotics, is a bactericidal agent that exerts its action at the level of bacterial ribosome. Amikacin has been shown to be effective against Gram-positive and Gram-negative bacteria, and many aminoglycoside-resistant strains due to its ability to resist degradation by aminoglycoside inactivating enzymes known to affect Gentamicin, Tobramycin and Kanamycin. Amikacin is a broad spectrum bactericidal antibiotic agent well absorbed following intravenous, subcutaneous or intramuscular injection and rapidly transmitted to skin and soft tissue, so it maintains a high therapeutic blood level. Amikacin has few side effects such as nephrotoxicity and ototoxicity ...
The US Food and Drug Administration recently approved gemtuzumab ozogamicin (Mylotarg) for the treatment of patients 60 years of age and older who are in first relapse with CD33-positive acute myeloid leukemia (AML) and are not considered 1
Stress stimuli can lead to remodeling of the actin cytoskeleton and subsequent alteration of cell adhesion and permeation as well as cell functions and cell fate. We investigated redox-dependent Rho GTPase-linked pathways controlling the actin cytoskeleton in the inner ear of the CBA mouse, by using aminoglycoside antibiotics as a noxious stimulus that causes loss of sensory cells via the formation of reactive oxygen species. Kanamycin treatment in vivo interfered with the formation of F-actin, disturbed the arrangement of β-actin in the stereocilia of outer hair cells, and altered the intermittent adherens junction/tight junction complexes between outer hair cells and supporting cells. The drug treatment also activated Rac1 and promoted the formation of the complex of Rac1 and p67phox while decreasing the activity of RhoA and reducing the formation of the RhoA/p140mDia complex. In inner-ear-derived cell lines, expression of mutated Rac1 changed the structural arrangement of F-actin and ...
Aminoglycosides are very important antibiotics in cystic fibrosis patients because of their efficacy against Ps aeruginosa. They are usually combined with a β lactam antibiotic in cases of pulmonary exacerbation caused by chronic colonisation with Ps aeruginosa.2-4 Several studies in severely ill patients have shown that once daily administration of aminoglycosides is as effective and probably less toxic than conventional thrice daily administration. For these antibiotics, efficacy is closely correlated with serum peak concentration and the ratio of serum peak to minimum inhibitory concentration of the bacteria, whereas toxicity depends on the trough serum level.7 16 17 Furthermore, the postantibiotic effect of aminoglycosides on Gram negative bacteria seems to be partly related to the serum peak value.8Administration once daily allows a high peak concentrations to be reached and enables the trough concentration to be as low as possible.. These conditions were clearly demonstrated in our study. ...
There is no established dosing schedule for once-daily aminoglycoside dosing regimens, and accepted guidelines for monitoring therapy are lacking. We derived a simplified schedule from the Hull and Sarubbi (J. H. Hull and F. A. Sarubbi, Ann. Intern. Med. 85:183-189, 1976) nomogram, for which efficacy and safety in a once-daily dosing regimen were previously demonstrated, and prospectively followed serum aminoglycoside levels in patients. The standard treatment was gentamicin or tobramycin at 4 mg/kg of body weight given intravenously once daily. When the renal function was decreased, the daily dose was reduced, as follows: for an estimated creatinine clearance of between 50 and 80 ml/min, the daily dose was 3.25 mg/kg, for an estimated creatinine clearance of between 30 and 50 ml/min, the daily dose was 2.5 mg/kg, and for an estimated creatinine clearance of below 30 ml/min, the daily dose was 2 mg/kg. A total of 221 patients were studied (184 received gentamicin and 37 received tobramycin). First
Sekar, R., Srivani, R., Vignesh, R., Kownhar, H. and Shankar, E.M. (2008) Low Recovery Rates of High-Level Aminoglycoside-Resistant Enterococci Could be Attributable to Restricted Usage of Aminoglycosides in Indian Settings. Journal of Medical Microbiology, 57, 397-398.