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<meta name="keywords" content="CN184225, cidomycin response, garamycin response, gentamicin response, gentamicin sulfate response, mt-ts1, septopal response, sign or symptom, trmu, autosomal dominant, autosomal recessive, birth defects, chromosomal disease, chromosome, clinical features, clinical findings, clinical genetics, clinical recommendations, clinvar, congenital chromosomal disease, consumer genetic resources, cytogenetic location, disease characteristics, disease definitions, disease descriptions, disease ontology, disease synonyms, disease vocabulary, dysmorphology, entrez, familial disease, gene, gene-disease relationship, genereviews, genetic disease, genetic disorder, genetic terminology, genetic testing registry, genetics home reference, genomic disease, gtr, hereditary disease, heritable disease, hpo, human phenotype ontology, inherited disease, management guidelines, maternal inheritance, medgen, medical genetics, medical subject headings, mesh, mitochondrial inheritance, mode of inheritance, national center for biotechnology information, national institutes of health, national library of medicine, ncbi, nih, nlm, omim, ordo, orphanet, paternal inheritance, phenome, position statements, professional practice guidelines, rare disease, reference sequence, refseq, snomed ct, syndrome, undiagnosed diseases, x-linked recessive" /><meta name="description" content="Aminoglycosides are widely used antibiotics which inhibit protein synthesis in bacteria by binding to bacterial 16S ribosomal subunits. Aminoglycosides are associated with a number of adverse events, including nephrotoxicity and ototoxicity. The risk of aminoglycoside-induced ototoxicity is increased in patients who carry certain variants in the MT-RNR1 gene. MT-RNR1 is found in the mitochondrial genome and encodes the 12S ribosomal subunit. Some MT-RNR1 variants cause the 12S subunit to more closely resemble the bacterial 16S subunit, which can lead to aminoglycoside molecules binding to the ribosome. This ultimately results in hearing loss due to cell death in the cochlea. The Clinical Pharmacogenetics Implementation Consortium (CPIC) have published recommendations on aminoglycoside use in patients carrying MT-RNR1 variants in the journal Clinical Pharmacology and Therapeutics. These recommendations are also available on the CPIC and PharmGKB websites." /><meta name="robots" content="index,nofollow,noarchive" />
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<!--
UID=776533
ConceptID=CN184225
-->
<!--imgCountBooks = 0--><h1 class="medgenTitle"><div class="MedGenTitleText">Gentamicin response</div></h1><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>776533</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier assigned by MedGen (starting with CN) for terms&#10;that cannot be identified in NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">CN184225</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Sign or Symptom</dd></dl></div></div><table class="medgenTable"><tbody><tr><td>Synonyms:</td>
<td>Cidomycin response; Garamycin response; Gentamicin sulfate response; Septopal response</td></tr>
<tr><td>Drug:</td>
<td>
<div class="divPopper rprt" id="drug_108181"><div><strong>Gentamicin</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>108181</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS)&#10;Click for more information.">C0546866</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Antibiotic</dd></dl></div></div></div>
<div class="spaceAbove">The sulfate salt form of gentamycin, a broad-spectrum aminoglycoside antibiotic complex produced by the fermentation of Micromonospora purpurea or M. echinospora, with antibacterial activity. Gentamicin is a thermostable complex containing the gentamicins C1, C1a, C2, C2a and C2b. [from NCI]</div></div>
<div class="hangingIndent"><a title="click for more information" class="jig-ncbipopper" href="#drug_108181" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">Gentamicin</a></div></td></tr>
<tr><td colspan="2" class="small"> </td></tr><tr><td><a class="help jig-ncbi-popper" data-jig="ncbipopper" href="#target-gene-loc">Genes (locations):<img class="pulldown" src="//static.pubmed.gov/portal/portal3rc.fcgi/4223267/img/4204968" /></a><div class="display-none" id="target-gene-loc">
Gene(s) directly associated with<br />
this condition or phenotype.</div></td>
<td><a target="_blank" title="MT-TS1 - ID: 4574 - NCBI Gene" href="/gene/4574" class="medgenPMinfo">MT-TS1</a>; <a target="_blank" title="TRMU - ID: 55687 - NCBI Gene" href="/gene/55687" class="medgenPMinfo">TRMU</a> (22q13.31)</td></tr>
</tbody></table></div><div class="rprt-body jig-ncbiinpagenav" data-jigconfig="smoothScroll: false, gotoTopLink: true, gotoTopLinkText: '', gotoTopLinkAttrs: {'title': 'Go to the top of the page'},allHeadingLevels: ['h1'], topOfPageTOC: true, tocId: 'my-toc'"><div id="rprt-tabs-1" class="rprt-tab"><div id="tb-termsProp-1"><div class="leftCol mgCol"><div>
<div class="portlet mgSection" id="ID_100">
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Definition">Definition</h1><a sid="100" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
<div class="portlet_content ln">Aminoglycosides are widely used antibiotics which inhibit protein synthesis in bacteria by binding to bacterial 16S ribosomal subunits. Aminoglycosides are associated with a number of adverse events, including nephrotoxicity and ototoxicity. The risk of aminoglycoside-induced ototoxicity is increased in patients who carry certain variants in the MT-RNR1 gene. MT-RNR1 is found in the mitochondrial genome and encodes the 12S ribosomal subunit. Some MT-RNR1 variants cause the 12S subunit to more closely resemble the bacterial 16S subunit, which can lead to aminoglycoside molecules binding to the ribosome. This ultimately results in hearing loss due to cell death in the cochlea. The Clinical Pharmacogenetics Implementation Consortium (CPIC) have published recommendations on aminoglycoside use in patients carrying MT-RNR1 variants in the journal Clinical Pharmacology and Therapeutics. These recommendations are also available on the CPIC and PharmGKB websites. [from <a title="The Pharmacogenomics Knowledge Base" href="http://www.pharmgkb.org" class="defSource" target="_blank">PharmGKB</a>]</div>
</div>
<div class="portlet mgSection" id="ID_117">
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Additional_descriptions">Additional descriptions</h1><a sid="117" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
<div class="portlet_content ln"><div class="mgSection"><strong>From Medical Genetics Summaries</strong><br />Gentamicin is an aminoglycoside antibiotic that is used to treat sepsis. Gentamicin is administered by injection to treat serious infections caused by gram-negative bacteria (for example, Pseudomonas aeruginosa, Proteus species, Escherichia coli, Klebsiella-Enterobacter-Serratia species, and Citrobacter species). Additionally, gentamicin is used as an adjuvant treatment for infections caused by gram-positive bacteria (such as Staphylococcus species). Gentamicin may also be used topically to treat ophthalmic and dermatological infections.&#13;
In most individuals, prolonged exposure to high gentamicin levels will cause ototoxicity (damage to the inner ear). However, among individuals who have specific variants in the mitochondrial gene MT-RNR1, a single dose of gentamicin can result in hearing loss (cochleotoxicity). This toxicity occurs in genetically susceptible individuals, despite serum drug concentrations within the normal therapeutic range. This hearing loss can be triggered not only by gentamicin, but by other aminoglycoside antibiotics and is referred to as aminoglycoside-induced hearing loss (AIHL).&#13;
Substantial literature has reported that a high proportion of individuals with the MT-RNR1 m.1555A&gt;G variant (NC_012920.1:m.1555A&gt;G) develop hearing loss after receiving aminoglycoside therapy. The onset of hearing loss among these individuals varies, but once it occurs, it is usually moderate to profound, bilateral, and irreversible. Additional MT-RNR1 genotypes associated with increased risk of AIHL include m.1095T&gt;C and m.1494C&gt;T.&#13;
The FDA-approved drug label for gentamicin does not include a statement regarding MT-RNR1; however, the Clinical Pharmacogenetics Implementation Consortium (CPIC) has published guidelines for administration of aminoglycosides, including gentamicin, with respect to variants in the MT-RNR1 gene. These guidelines recommend avoiding the use of aminoglycoside antibiotics, such as gentamicin unless there are no satisfactory alternatives, by individuals who have a MT-RNR1 genotype that puts them at high risk for AIHL. The CPIC guideline further advises that individuals with normal-risk alleles or uncertain-risk alleles at the MT-RNR1 locus should all use aminoglycosides at standard doses for the shortest feasible course, with regular evaluation for hearing loss. This extends the 2014 American College of Medical Genetics and Genomics guideline with the following recommendation: “Single-gene testing may be warranted in cases in which the medical or family history, or presentation of the hearing loss, suggests a specific etiology. For example, testing for mitochondrial DNA variants associated with aminoglycoside ototoxicity may be considered for individuals with a history of use of aminoglycoside antibiotics.”  <a target="_blank" href="https://www.ncbi.nlm.nih.gov/books/NBK285956">https://www.ncbi.nlm.nih.gov/books/NBK285956</a></div><div class="mgSection"><strong>From GeneReviews</strong><br />Mitochondrial nonsyndromic hearing loss and deafness is characterized by sensorineural hearing loss (SNHL) of variable onset and severity. Pathogenic variants in MT-RNR1 can be associated with predisposition to aminoglycoside ototoxicity and/or late-onset SNHL. Hearing loss associated with aminoglycoside ototoxicity is bilateral and severe to profound, occurring within a few days to weeks after administration of any amount (even a single dose) of an aminoglycoside antibiotic such as gentamycin, tobramycin, amikacin, kanamycin, or streptomycin. Pathogenic variants in MT-TS1 are usually associated with childhood onset of SNHL that is generally nonsyndromic – although the MT-TS1 substitution m.7445A&gt;G has been found in some families who also have palmoplantar keratoderma (scaling, hyperkeratosis, and honeycomb appearance of the skin of the palms, soles, and heels).</div></div>
</div>
<div class="portlet mgSection" id="ID_118">
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Term_Hierarchy">Term Hierarchy</h1><a sid="118" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
<div class="portlet_content ln HierarchyGTR"><div class="jig-ncbitabs"><ul><li><a href="#tabGTR">GTR</a></li><li><a href="#tabMGEN">MeSH</a></li></ul><div id="tabGTR"><div class="search_result"><div class="rprts"><div class="chiclet_legend"><span class="chiclet_list" style="position:static;"><span title="Clinical test" class="chiclet Ccolor round">C</span><span>Clinical test,  </span><span title="Research test" class="chiclet Rcolor round">R</span><span>Research test,  </span><span title="OMIM" class="chiclet Ocolor ">O</span><span>OMIM,  </span><span title="GeneReview" class="chiclet Gcolor">G</span><span><em>GeneReviews</em>,  </span><span title="ClinVar" class="chiclet Vcolor">V</span><span>ClinVar  </span></span></div><div id="hierarchy" class="margin_t1"><div class="ds_tree"><ul><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=CN184091[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=776458">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet unavailable" title="OMIM">O</span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1422/" ref="ncbi_uid=776458">G</a></span><span class="chiclet unavailable" title="ClinVar">V</span></span><span class="TLline"><a href="/medgen/776458" ref="tree=GTR&amp;ncbi_uid=776458&amp;link_uid=776458" title="View MedGen record for 'Aminoglycoside antibacterials response'">Aminoglycoside antibacterials response</a></span><ul><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=CN184546[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=776649">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet unavailable" title="OMIM">O</span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1422/" ref="ncbi_uid=776649">G</a></span><span class="chiclet unavailable" title="ClinVar">V</span></span><span class="TLline"><a href="/medgen/776649" ref="tree=GTR&amp;ncbi_uid=776649&amp;link_uid=776649" title="View MedGen record for 'Amikacin response'">Amikacin response</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=C1838854[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=374074">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet Ocolor" title="OMIM"><a ref="ncbi_uid=374074" target="_blank" href="/omim/516030">O</a></span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/?term=(NBK1422%20OR%20NBK1434)%20AND%20gene%5Bbook%5D&amp;showtype=onebook" ref="ncbi_uid=374074">G</a></span><span class="chiclet Vcolor" title="ClinVar"><a target="_blank" href="/clinvar?LinkName=medgen_clinvar&amp;from_uid=374074" ref="ncbi_uid=374074">V</a></span></span><span class="TLline"><a href="/medgen/374074" ref="tree=GTR&amp;ncbi_uid=374074&amp;link_uid=374074" title="View MedGen record for 'Aminoglycoside-induced deafness'">Aminoglycoside-induced deafness</a></span></li><li class="matched_ds"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=CN184225[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=776533">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet unavailable" title="OMIM">O</span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1422/" ref="ncbi_uid=776533">G</a></span><span class="chiclet Vcolor" title="ClinVar"><a target="_blank" href="/clinvar?LinkName=medgen_clinvar&amp;from_uid=776533" ref="ncbi_uid=776533">V</a></span></span><span class="TLline">Gentamicin response</span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=CN184547[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=776650">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet unavailable" title="OMIM">O</span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1422/" ref="ncbi_uid=776650">G</a></span><span class="chiclet unavailable" title="ClinVar">V</span></span><span class="TLline"><a href="/medgen/776650" ref="tree=GTR&amp;ncbi_uid=776650&amp;link_uid=776650" title="View MedGen record for 'Kanamycin response'">Kanamycin response</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=C1154708[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=776646">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet unavailable" title="OMIM">O</span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1422/" ref="ncbi_uid=776646">G</a></span><span class="chiclet unavailable" title="ClinVar">V</span></span><span class="TLline"><a href="/medgen/776646" ref="tree=GTR&amp;ncbi_uid=776646&amp;link_uid=776646" title="View MedGen record for 'Streptomycin response'">Streptomycin response</a></span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=CN184545[DISCUI]&amp;test_type=Clinical" ref="ncbi_uid=776648">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet unavailable" title="OMIM">O</span><span class="chiclet Gcolor" title="GeneReviews"><a target="_blank" href="/books/NBK1422/" ref="ncbi_uid=776648">G</a></span><span class="chiclet unavailable" title="ClinVar">V</span></span><span class="TLline"><a href="/medgen/776648" ref="tree=GTR&amp;ncbi_uid=776648&amp;link_uid=776648" title="View MedGen record for 'Tobramycin response'">Tobramycin response</a></span></li></ul></li></ul></div></div></div></div></div><div id="tabMGEN"><div class="ds_tree"><ul><li><span class="TLline"><a href="/medgen/776458" ref="tree=MeSH" title="MedGen record for Aminoglycoside antibacterials response">Aminoglycoside antibacterials response</a></span><ul><li><span class="matched_ds">Gentamicin response</span></li></ul></li></ul></div></div></div></div>
</div>
<div class="portlet mgSection" id="ID_105">
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Professional_guidelines">Professional guidelines</h1><a sid="105" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
<div class="portlet_content ln"><h3 class="subhead">PubMed<a class="help jig-ncbi-popper" data-jig="ncbipopper" href="#guidelinesHelpPM"><img class="pulldown" src="//static.pubmed.gov/portal/portal3rc.fcgi/4223267/img/4204968" /></a></h3>
<div class="nl"><a target="_blank" href="/pubmed/38233317">Clinical chorioamnionitis at term: definition, pathogenesis, microbiology, diagnosis, and treatment.</a></div>
<div class="portlet_content ln"><span class="medgenPMauthor">Jung E,
Romero R,
Suksai M,
Gotsch F,
Chaemsaithong P,
Erez O,
Conde-Agudelo A,
Gomez-Lopez N,
Berry SM,
Meyyazhagan A,
Yoon BH</span><br />
<span class="medgenPMjournal">Am J Obstet Gynecol</span>
2024 Mar;230(3S):S807-S840.
Epub 2023 Mar 21
doi: 10.1016/j.ajog.2023.02.002.
<span class="bold">PMID: </span><a href="/pubmed/38233317" target="_blank">38233317</a><a href="/pmc/articles/PMC11288098" target="_blank" class="PubMedFree">Free PMC Article</a></div>
<div class="nl"><a target="_blank" href="/pubmed/6912860">Treatment of gentamicin-resistant Klebsiella urinary tract infections with cephradine, augmentin, cefuroxime and amikacin.</a></div>
<div class="portlet_content ln"><span class="medgenPMauthor">Hart CA,
Desmond AD,
Percival A</span><br />
<span class="medgenPMjournal">J Antimicrob Chemother</span>
1981 Sep;8(3):231-7.
doi: 10.1093/jac/8.3.231.
<span class="bold">PMID: </span><a href="/pubmed/6912860" target="_blank">6912860</a></div>
<div class="nl"><a target="_blank" href="/pubmed/901720">Factors influencing the therapeutic response to gentamicin treatment in children [proceedings].</a></div>
<div class="portlet_content ln"><span class="medgenPMauthor">Ashurst A,
Houston IB,
Mawer GE,
Sambo-Donga L</span><br />
<span class="medgenPMjournal">Br J Clin Pharmacol</span>
1977 Jun;4(3):394P-395P.
doi: 10.1111/j.1365-2125.1977.tb00742.x.
<span class="bold">PMID: </span><a href="/pubmed/901720" target="_blank">901720</a></div>
<div><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=(gentamicin%20response)%20AND%20(%22english%20and%20humans%22%5BFilter%5D)%20AND%20(%20(%22practice%20guideline%22%5BFilter%5D)%20OR%20(practice*%5Btitl%5D%20AND%20(guideline%5Btitl%5D%20OR%20parameter%5Btitl%5D%20OR%20resource%5Btitl%5D%20OR%20bulletin%5Btitl%5D%20OR%20best%5Btitl%5D))%20OR%20(genetic*%5Btitl%5D%20AND%20(evaluation%5Btitl%5D%20OR%20counseling%5Btitl%5D%20OR%20screening%5Btitl%5D%20OR%20test*%5Btitl%5D))%20OR%20(clinical%5Btitl%5D%20AND%20((expert%5Btitl%5D%20AND%20consensus%5Btitl%5D)%20OR%20utility%5Btitl%5D%20OR%20guideline*%5Btitl%5D))%20OR%20(management%5Btitl%5D%20AND%20(clinical%5Btitl%5D%20OR%20diagnos*%5Btitl%5D%20OR%20recommendation%5Btitl%5D%20OR%20pain%5Btitl%5D%20OR%20surveillance%5Btitl%5D%20OR%20emergency%5Btitl%5D%20OR%20guideline*%5Btitl%5D%20OR%20therap*))%20OR%20(treatment%5Btitl%5D%20AND%20((evaluation%5Btitl%5D%20AND%20diagnosis%5Btitl%5D)%20OR%20(assessment%5Btitl%5D%20AND%20prevention%5Btitl%5D)%20OR%20therap*))%20OR%20(Diagnos*%5Btitl%5D%20AND%20(prenatal%5Btitl%5D%20OR%20treatment%5Btitl%5D%20OR%20follow-up%5Btitl%5D%20OR%20statement%5Btitl%5D%20OR%20criteria%5Btitl%5D%20OR%20newborn%5Btitl%5D%20OR%20differential%5Btitl%5D%20OR%20neonatal%5Btitl%5D%20OR%20neonate%5Btitl%5D))%20OR%20(guideline*%5Btitl%5D%20AND%20(pharmacogenetic*%5Btitl%5D%20OR%20recommendation%5Btitl%5D%20OR%20therap*%5Btitl%5D%20OR%20evidence-based%5Btitl%5D%20OR%20consensus%5Btitl%5D%20OR%20(technical%5Btitl%5D%20AND%20standard*%5Btitl%5D)%20OR%20(molecular%5Btitl%5D%20AND%20testing%5Btitl%5D)))%20OR%20(risk%5Btitl%5D%20AND%20assessment%5Btitl%5D)%20OR%20(recommendation*%5Btitl%5D%20AND%20(statement%5Btitl%5D%20OR%20Evidence-based%5Btitl%5D%20OR%20Consensus%5Btitl%5D))%20OR%20(care%20AND%20((Patient%5Btitl%5D%20AND%20standard*%5Btitl%5D)%20OR%20primary%5Btitl%5D%20OR%20psychosocial%5Btitl%5D))%20OR%20(Health%5Btitl%5D%20AND%20supervision%5Btitl%5D)%20OR%20(statement%5Btitl%5D%20AND%20(policy%5Btitl%5D%20OR%20position%5Btitl%5D%20OR%20Consensus%5Btitl%5D))%20OR%20(pharmacogenetics%5Btitl%5D%20AND%20(Dosing%5Btitl%5D%20OR%20therap*%5Btitl%5D%20OR%20genotype*%5Btitl%5D%20OR%20drug*%5Btitl%5D))%20OR%20(Chemotherapy%5Btitl%5D%20AND%20decision*%5Btitl%5D)%20OR%20(screening%5Btitl%5D%20AND%20(newborn%5Btitl%5D%20OR%20neonat*%5Btitl%5D%20OR%20detection%5Btitl%5D%20OR%20diagnos*%5Btitl%5D))%20OR%20(criteria%5Btitl%5D%20OR%20genotype*%5Btitl%5D)%20)%20NOT%20(%22Case%20reports%22%5BPublication%20type%5D%20OR%20%22clinical%20study%22%5BPublication%20Type%5D%20OR%20%22randomized%20controlled%20trial%22%5BPublication%20Type%5D)" title="PubMed search">See all (114)</a></div><h3 class="subhead">Curated<a class="help jig-ncbi-popper" data-jig="ncbipopper" href="#guidelinesHelpCurated"><img class="pulldown" src="//static.pubmed.gov/portal/portal3rc.fcgi/4223267/img/4204968" /></a></h3><h3 class="nl vspace"><a href="https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=877ab1fd-6c0e-42f6-9522-f5efaa96018d" target="_blank">DailyMed Drug Label, gentamicin, 2022</a></h3>
<h3 class="nl vspace"><a href="https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a73a5453-c091-43fd-aae2-d992152363b1" target="_blank">DailyMed Drug Label, GENTAMICIN, 2012</a></h3>
</div>
</div>
<div class="display-none help-popup" id="guidelinesHelpPM">These guidelines are articles in PubMed that match specific search criteria developed by MedGen to capture the most relevant practice guidelines. This list may not be comprehensive and may include broader topics as well. See the <a href="/medgen/docs/faq/" title="Frequently asked questions" target="_blank">FAQ</a> for details.</div><div class="display-none help-popup" id="guidelinesHelpCurated">These guidelines are manually curated by the MedGen team
to supplement articles available in PubMed. See the <a href="/medgen/docs/faq/" title="Frequently asked questions" target="_blank">FAQ</a> for details.</div>
<div class="portlet mgSection" id="ID_120">
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Therapeutic_recommendations">Therapeutic recommendations</h1><a sid="120" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
<div class="portlet_content ln" id="therapeutic"><strong>From <a href="https://www.ncbi.nlm.nih.gov/books/NBK285956" target="_blank">Medical Genetics Summaries</a></strong><br /><div id="TheraputicContent"><div class="divPopper rprt" id="gentamicin_REF_4" style="display: none;">4. McDermott J.H., Wolf J., Hoshitsuki K., Huddart R., et al. Clinical Pharmacogenetics Implementation Consortium Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype. Clin Pharmacol Ther. 2021.</div><div class="divPopper rprt" id="gentamicin_REF_6" style="display: none;">6. Alford R.L., Arnos K.S., Fox M., Lin J.W., et al. American College of Medical Genetics and Genomics guideline for the clinical evaluation and etiologic diagnosis of hearing loss. Genet Med. 2014;16(4):347–55.</div><p><b>Excerpt from the CPIC guidelines for Aminoglycosides and MT-RNR1 variants</b>
.</p><p>The critical pharmacogenetics recommendation for a person with an <i>MT-RNR1</i> variant which predisposes to AIHL is that aminoglycoside antibiotics are relatively contraindicated, meaning that aminoglycosides should be avoided unless the increased risk of hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies. There is insufficient evidence to suggest that the adverse drug reaction may be more profound with some members of the aminoglycoside class than others. As such, this guidance covers all aminoglycoside antibiotics irrespective of class. We provide a strong recommendation that carriers of <i>MT-RNR1</i> variants that predispose to AIHL should avoid aminoglycosides unless the increased risk of permanent hearing loss is outweighed by the risk of infection without safe or effective alternative therapies… If no effective alternative to an aminoglycoside is thought to be available, we advise use for the shortest possible time, consultation with an infectious disease expert for alternative approaches, therapeutic drug monitoring and frequent assessment for hearing loss, both during and after therapy, in consultation with an audiovestibular physician.</p><p>An individual with no detectable <i>MT-RNR1</i> variant or carrying <i>MT-RNR1</i> variants not considered to be predisposing to AIHL (normal risk), including the m.827A&gt;G variant, should still be considered at risk of AIHL. In addition to <i>MT-RNR1</i>, AIHL is often associated with other risk factors such as prematurity, renal impairment, severe inflammatory response syndrome, prolonged therapy regimens, and supratherapeutic plasma concentrations. As such, irrespective of the presence of an <i>MT-RNR1</i> variant which predisposes to AIHL, precautions such as renal monitoring, therapeutic drug monitoring, and utilizing the lowest effective dose should be applied. Finally, if an individual with an actionable <i>MT-RNR1</i> variant has previously received aminoglycosides and not developed AIHL, this does not preclude them from developing AIHL with subsequent doses.</p><p><i>Considerations for aminoglycoside use in patients at increased risk of AIHL</i>. For the purposes of this guideline, appropriateness for use of aminoglycoside antibiotics can be considered for three scenarios: First, an equally or more effective agent is available for the condition; second, there is reason to believe that an aminoglycoside might lead to superior outcomes, but evidence is poor, the effect-size is small, or the outcome is not clinically meaningful; and third, there is good evidence for significantly superior efficacy of an aminoglycoside-containing treatment regimen for a clinically meaningful outcome.</p><p>[….]</p><p>In all cases, an aminoglycoside used in patients at increased risk of AIHL due to the presence of an <i>MT-RNR1</i> variant should be administered for the shortest possible period, under expert supervision, with therapeutic drug and ototoxicity monitoring, and with clinical audiovestibular assessment performed during and after treatment. Irrespective of whether an individual carries a pathogenic <i>MT-RNR1</i> variant, all patients who receive aminoglycoside antibiotics, especially those prescribed prolonged courses, should be monitored for ototoxicity in line with existing local and international guidelines.</p><p>[….]</p><p>Based on the available literature, at present there is not sufficient evidence to define a level of heteroplasmy where aminoglycoside administration becomes safe, especially as the mutational load may differ from tissue to tissue and be dependent upon the genotyping technique utilized. As such, we have not tailored this guideline based on the level of heteroplasmy. Rather, we recommend that if a relevant <i>MT-RNR1</i> variant is detected, the guidance should be followed as set out for a homoplasmic variant.</p><p><b>Please review the complete CPIC therapeutic recommendations that are located here: (</b>
<b>4</b>
<b>).</b>
</p><p><b>Excerpt from the American College of Medical Genetics and Genomics (ACMG) Guideline for the Clinical Evaluation and Etiologic Diagnosis of Hearing Loss:</b>
</p><p>For individuals lacking physical findings suggestive of a known syndrome and having medical and birth histories that do not suggest an environmental cause of hearing loss, a tiered diagnostic approach should be implemented.</p><p>Pretest genetic counseling should be provided, and, with patient’s informed consent, genetic testing should be ordered.</p><p>Single-gene testing may be warranted in cases in which the medical or family history, or presentation of the hearing loss, suggests a specific etiology. For example, testing for mitochondrial DNA mutations associated with aminoglycoside ototoxicity may be considered for individuals with a history of use of aminoglycoside antibiotics.</p><p><b>Please review the complete ACMG therapeutic recommendations that are located here: (</b>
<b>6</b>
<b>).</b>
</p></div></div>
</div>
</div></div></div></div></div></div></div>
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<h2 class="offscreen_noflow">Supplemental Content</h2>
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<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Table_of_contents">Table of contents</h1><a sid="113" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
<div class="portlet_content ln"><ul id="my-toc"></ul></div>
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<div class="portlet_content ln"><ul><li><a href="/gtr/tests?term=CN184225%5bDISCUI%5d&amp;filter=method%3A2%5F7" target="_blank">Sequence analysis of the entire coding region (1)</a></li>
<li><a href="/gtr/tests?term=CN184225%5bDISCUI%5d&amp;filter=method%3A2%5F19" target="_blank">Targeted variant analysis (2)</a></li>
<li class="portletSeeAll portletSeeAllPad"><total><a href="/gtr/tests?term=CN184225%5bDISCUI%5d" target="_blank">See all (3)</a></total></li>
</ul></div>
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<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Clinical_resources">Clinical resources</h1><a sid="119" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
<div class="portlet_content ln"><ul><li><a href="https://www.pharmgkb.org/chemical/PA449753" target="_blank">PharmGKB</a></li><li><a href="https://www.pharmgkb.org/chemical/PA452167" target="_blank">PharmGKB</a></li><li><a href="https://clinicaltrials.gov/search?cond=Gentamicin%20response" target="_blank">ClinicalTrials.gov</a></li></ul></div>
</div>
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<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Practice_guidelines">Practice guidelines</h1><a sid="121" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
<div class="portlet_content ln"><ul class="a_poppers"><li><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=(gentamicin%20response)%20AND%20(%22english%20and%20humans%22%5BFilter%5D)%20AND%20(%20(%22practice%20guideline%22%5BFilter%5D)%20OR%20(practice*%5Btitl%5D%20AND%20(guideline%5Btitl%5D%20OR%20parameter%5Btitl%5D%20OR%20resource%5Btitl%5D%20OR%20bulletin%5Btitl%5D%20OR%20best%5Btitl%5D))%20OR%20(genetic*%5Btitl%5D%20AND%20(evaluation%5Btitl%5D%20OR%20counseling%5Btitl%5D%20OR%20screening%5Btitl%5D%20OR%20test*%5Btitl%5D))%20OR%20(clinical%5Btitl%5D%20AND%20((expert%5Btitl%5D%20AND%20consensus%5Btitl%5D)%20OR%20utility%5Btitl%5D%20OR%20guideline*%5Btitl%5D))%20OR%20(management%5Btitl%5D%20AND%20(clinical%5Btitl%5D%20OR%20diagnos*%5Btitl%5D%20OR%20recommendation%5Btitl%5D%20OR%20pain%5Btitl%5D%20OR%20surveillance%5Btitl%5D%20OR%20emergency%5Btitl%5D%20OR%20guideline*%5Btitl%5D%20OR%20therap*))%20OR%20(treatment%5Btitl%5D%20AND%20((evaluation%5Btitl%5D%20AND%20diagnosis%5Btitl%5D)%20OR%20(assessment%5Btitl%5D%20AND%20prevention%5Btitl%5D)%20OR%20therap*))%20OR%20(Diagnos*%5Btitl%5D%20AND%20(prenatal%5Btitl%5D%20OR%20treatment%5Btitl%5D%20OR%20follow-up%5Btitl%5D%20OR%20statement%5Btitl%5D%20OR%20criteria%5Btitl%5D%20OR%20newborn%5Btitl%5D%20OR%20differential%5Btitl%5D%20OR%20neonatal%5Btitl%5D%20OR%20neonate%5Btitl%5D))%20OR%20(guideline*%5Btitl%5D%20AND%20(pharmacogenetic*%5Btitl%5D%20OR%20recommendation%5Btitl%5D%20OR%20therap*%5Btitl%5D%20OR%20evidence-based%5Btitl%5D%20OR%20consensus%5Btitl%5D%20OR%20(technical%5Btitl%5D%20AND%20standard*%5Btitl%5D)%20OR%20(molecular%5Btitl%5D%20AND%20testing%5Btitl%5D)))%20OR%20(risk%5Btitl%5D%20AND%20assessment%5Btitl%5D)%20OR%20(recommendation*%5Btitl%5D%20AND%20(statement%5Btitl%5D%20OR%20Evidence-based%5Btitl%5D%20OR%20Consensus%5Btitl%5D))%20OR%20(care%20AND%20((Patient%5Btitl%5D%20AND%20standard*%5Btitl%5D)%20OR%20primary%5Btitl%5D%20OR%20psychosocial%5Btitl%5D))%20OR%20(Health%5Btitl%5D%20AND%20supervision%5Btitl%5D)%20OR%20(statement%5Btitl%5D%20AND%20(policy%5Btitl%5D%20OR%20position%5Btitl%5D%20OR%20Consensus%5Btitl%5D))%20OR%20(pharmacogenetics%5Btitl%5D%20AND%20(Dosing%5Btitl%5D%20OR%20therap*%5Btitl%5D%20OR%20genotype*%5Btitl%5D%20OR%20drug*%5Btitl%5D))%20OR%20(Chemotherapy%5Btitl%5D%20AND%20decision*%5Btitl%5D)%20OR%20(screening%5Btitl%5D%20AND%20(newborn%5Btitl%5D%20OR%20neonat*%5Btitl%5D%20OR%20detection%5Btitl%5D%20OR%20diagnos*%5Btitl%5D))%20OR%20(criteria%5Btitl%5D%20OR%20genotype*%5Btitl%5D)%20)%20NOT%20(%22Case%20reports%22%5BPublication%20type%5D%20OR%20%22clinical%20study%22%5BPublication%20Type%5D%20OR%20%22randomized%20controlled%20trial%22%5BPublication%20Type%5D)" title="PubMed search">PubMed</a><div class="help-popup">See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the <a href="/medgen/docs/faq/" title="Frequently asked questions" target="_blank">FAQ</a> for details.</div></li></ul><h3 class="subhead">Curated</h3><ul class="a_poppers"><li><a target="_blank" href="https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=877ab1fd-6c0e-42f6-9522-f5efaa96018d">DailyMed Drug Label, 2022</a><div>DailyMed Drug Label, gentamicin, 2022</div></li><li><a target="_blank" href="https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a73a5453-c091-43fd-aae2-d992152363b1">DailyMed Drug Label, 2012</a><div>DailyMed Drug Label, GENTAMICIN, 2012</div></li></ul></div>
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<div class="portlet_content ln"><ul><li><a href="http://www.omim.org/search?index=entry&amp;start=1&amp;limit=10&amp;sort=score%20desc&amp;field=number&amp;search=590080%20610230" target="_blank">OMIM</a></li><li><a href="/clinvar/?term=4574[geneid]" target="_blank">View MT-TS1 variations in ClinVar</a></li><li><a href="/clinvar/?term=55687[geneid]" target="_blank">View TRMU variations in ClinVar</a></li><li><a href="/nuccore/237874202" target="_blank">RefSeqGene</a></li></ul></div>
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<div class="portlet_content ln"><ul><li><a href="https://vsearch.nlm.nih.gov/vivisimo/cgi-bin/query-meta?v:project=medlineplus&amp;query=Gentamicin%20response" target="_blank">MedlinePlus</a></li></ul></div>
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<li>
<a href="/books/NBK285956" ref="ncbi_uid=&amp;discoId=gtr_reviews&amp;linkpos=2&amp;linkpostotal=4" target="_blank">Medical Genetics Summaries</a>
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<li>
<a href="/pubmed/clinical?term=Gentamicin%20response" ref="ncbi_uid=&amp;discoId=gtr_reviews&amp;linkpos=3&amp;linkpostotal=4" target="_blank">PubMed Clinical Queries</a>
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<a href="/pubmed?term=Gentamicin%20response%20AND%20humans[mesh]%20AND%20review[publication%20type]" ref="ncbi_uid=&amp;discoId=gtr_reviews&amp;linkpos=4&amp;linkpostotal=4" target="_blank">Reviews in PubMed</a>
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<div class="brieflinkpop offscreen_noflow">Related medical variations</div>
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<a class="brieflinkpopperctrl" href="/gene?LinkName=medgen_gene_diseases&amp;from_uid=776533" ref="log$=recordlinks">Gene</a>
<div class="brieflinkpop offscreen_noflow">Related information in NCBI Gene</div>
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<a class="brieflinkpopperctrl" href="/gtr/tests?term=CN184225[DISCUI]" ref="log$=recordlinks">GTR</a>
<div class="brieflinkpop offscreen_noflow">Related information in GTR</div>
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<a class="brieflinkpopperctrl" href="/gtr/tests?term=CN184225[DISCUI]&amp;test_type=Clinical" ref="log$=recordlinks">GTR(Clinical)</a>
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<a class="brieflinkpopperctrl" href="/omim?LinkName=medgen_omim_gene&amp;from_uid=776533" ref="log$=recordlinks">OMIM(Genes)</a>
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<a class="brieflinkpopperctrl" href="/pmc?LinkName=medgen_pmc&amp;from_uid=776533" ref="log$=recordlinks">PMC Articles</a>
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