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| ==Overview== | | ==Overview== |
| | All patients with listeriosis require [[antibiotic therapy]]. [[Ampicillin]], with or without [[gentamicin]], is the [[antibiotic]] of choice for the treatment of listeriosis. Patients intolerant to [[penicillin]]s may be managed with [[TMP/SMZ|trimethoprim-sulfamethoxazole]]. Duration of therapy depends on the clinical syndrome and may range from several days in non-complicated gastroenteritis to 6 weeks in [[endocarditis]] or [[encephalitis]]. Listerial [[gastroenteritis]] is frequently self-limited among healthy adults, but a short course of oral [[ampicillin]] may be considered among [[immunocompromised]] or [[pregnant]] individuals or those who have ingested food implicated in outbreaks. Non-gastroenteritis listeriosis often require hospitalization and [[Intravenous|intravenous (IV)]] [[antibiotic]] therapy. |
| | ==Medical Therapy== |
| | * '''Either [[Ampicillin]], [[amoxicillin]], or [[penicillin G]] is effective for the treatment of listeriosis.''' |
| | *Addition of an [[aminoglycoside]], which confers [[synergistic]] [[bactericidal]] effects to [[ampicillin]], is recommended for the treatment of listerial [[bacteremia]], [[endocarditis]], [[brain abscess]], [[meningitis]], or [[encephalitis|rhombencephalitis]].<ref>{{Cite journal | issn = 0098-7484 | volume = 261 | issue = 9 | pages = 1313–1320 | last = Gellin | first = B. G. | coauthors = C. V. Broome | title = Listeriosis | journal = JAMA: the journal of the American Medical Association | date = 1989-03-03 | pmid = 2492614 }}</ref> |
| | *Alternatively, for patients unable to tolerate [[beta-lactam]]s, [[TMP/SMZ|trimethoprim-sulfamethoxazole]] may be administered. |
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| [[Ampicillin]], with or without [[gentamicin]], is considered the drug of choice for listeriosis. Patients intolerant of [[penicillin]]s may be managed with [[TMP/SMZ|trimethoprim-sulfamethoxazole]] alternatively. Suggested minimum duration of therapy depends on clinical manifestations: [[bacteremia]] for 2 weeks, [[meningitis]] for 3 weeks, [[endocarditis]] for 4 to 6 weeks, and [[brain abscess]] or rhombencephalitis for at least 6 weeks.
| | * The table below describes the recommended duration of therapy based upon the clinical syndrome:<ref>{{Cite journal | issn = 1058-4838 | volume = 24 | issue = 1 | pages = 1–9; quiz 10-11 | last = Lorber | first = B. | title = Listeriosis | journal = Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America | date = 1997-01 | pmid = 8994747 }}</ref><ref>{{Cite journal | issn = 0098-7484 | volume = 261 | issue = 9 | pages = 1313–1320 | last = Gellin | first = B. G. | coauthors = C. V. Broome | title = Listeriosis | journal = JAMA: the journal of the American Medical Association | date = 1989-03-03 | pmid = 2492614 }}</ref> |
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| ==Principles of Therapy==
| | {| style="border: 0px; font-size: 90%; margin: 0 18px;" |
| | | | style="background: #4479BA; font-weight: bold; font-style: italic; color: #FFFFFF; padding: 5px 5px;" align=center | Listeriosis Clinical Syndrome |
| * [[Ampicillin]], [[amoxicillin]], and [[penicillin G]] have been considered effective for listeriosis. For patients unable to tolerate [[beta-lactam]]s, [[TMP/SMZ|trimethoprim-sulfamethoxazole]] may be used alternatively. [[Chloramphenicol]] is not regarded as an acceptable option due to high treatment failure and relapse rates.<ref name="Stamm-">{{Cite journal | last1 = Stamm | first1 = AM. | last2 = Dismukes | first2 = WE. | last3 = Simmons | first3 = BP. | last4 = Cobbs | first4 = CG. | last5 = Elliott | first5 = A. | last6 = Budrich | first6 = P. | last7 = Harmon | first7 = J. | title = Listeriosis in renal transplant recipients: report of an outbreak and review of 102 cases. | journal = Rev Infect Dis | volume = 4 | issue = 3 | pages = 665-82 | month = | year = | doi = | PMID = 6750737 }}</ref>
| | | style="background: #4479BA; font-weight: bold; font-style: italic; color: #FFFFFF; padding: 5px 5px;" align=center | Duration of Antibiotic Therapy |
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| * Addition of an [[aminoglycoside]], which provides [[synergistic]] [[bactericidal]] effects to [[ampicillin]], is generally recommended for the treatment of listerial [[bacteremia]], [[endocarditis]], [[brain abscess]], [[meningitis]], or rhombencephalitis.<ref name="Gellin-1989">{{Cite journal | last1 = Gellin | first1 = BG. | last2 = Broome | first2 = CV. | title = Listeriosis. | journal = JAMA | volume = 261 | issue = 9 | pages = 1313-20 | month = Mar | year = 1989 | doi = | PMID = 2492614 }}</ref>
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| * [[Bacteremia]] should be treated for 2 weeks, [[meningitis]] for 3 weeks, [[endocarditis]] for 4 to 6 weeks, and [[brain abscess]] or rhombencephalitis for at least 6 weeks.
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| * [[Meningitis]] is the most common clinical manifestation, and antibiotics that penetrate well into the CSF should be chosen.
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| * [[Gastroenteritis]] caused by ''[[Listeria monocytogenes]]'' is usually self-limited and complete recovery typically occurs within 2 days. Persons who have ingested food implicated in outbreaks and who have a high risk of invasive illness may be treated with oral [[ampicillin]] or [[TMP/SMZ|trimethoprim-sulfamethoxazole]] for several days.<ref name="Lorber-1997">{{Cite journal | last1 = Lorber | first1 = B. | title = Listeriosis. | journal = Clin Infect Dis | volume = 24 | issue = 1 | pages = 1-9; quiz 10-1 | month = Jan | year = 1997 | doi = | PMID = 8994747 }}</ref>
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| ==Medical Therapy for ''Listeria monocytogenes'' <SMALL><SMALL><SMALL><SMALL><SMALL>Adapted from ''Clin Infect Dis. 1997;24(1):1-9.'',<ref name="Lorber-1997">{{Cite journal | last1 = Lorber | first1 = B. | title = Listeriosis. | journal = Clin Infect Dis | volume = 24 | issue = 1 | pages = 1-9; quiz 10-1 | month = Jan | year = 1997 | doi = | PMID = 8994747 }}</ref> ''Clin Infect Dis. 2005;40(9):1327-32.'',<ref name="Ooi-2005">{{Cite journal | last1 = Ooi | first1 = ST. | last2 = Lorber | first2 = B. | title = Gastroenteritis due to Listeria monocytogenes. | journal = Clin Infect Dis | volume = 40 | issue = 9 | pages = 1327-32 | month = May | year = 2005 | doi = 10.1086/429324 | PMID = 15825036 }}</ref> and ''Clin Infect Dis. 2004;39(9):1267-84.''<ref name="pmid15494903">Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15494903 Practice guidelines for the management of bacterial meningitis.] ''Clin Infect Dis'' 39 (9):1267-84. [http://dx.doi.org/10.1086/425368 DOI:10.1086/425368] PMID: [http://pubmed.gov/1549490315494903]</ref></SMALL></SMALL></SMALL></SMALL></SMALL>==
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| <SMALL><font color="#FF4C4C">'''▸ Click on the following categories to expand treatment regimens.'''</font></SMALL>
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| {|
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| <div style="border-radius: 5px 5px 0 0; border: solid 1px #20538D; border-bottom: 0px; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 225px; background: #A1BCDD; text-align: center;">
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| <font color="#FFF">
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| '''''L. monocytogenes''''' '''Infections'''
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| </font>
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| </div>
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| <div class="mw-customtoggle-table01" style="cursor: pointer; border-radius: 0 0 0 0; border: solid 1px #20538D; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 225px; background: #4479BA;">
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| <font color="#FFF">
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| ▸ '''Bacteremia'''
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| </font>
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| </div>
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| <div class="mw-customtoggle-table02" style="cursor: pointer; border-radius: 0 0 0 0; border: solid 1px #20538D; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 225px; background: #4479BA;">
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| <font color="#FFF">
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| ▸ '''Brain Abscess'''
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| </font>
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| </div>
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| <div class="mw-customtoggle-table03" style="cursor: pointer; border-radius: 0 0 0 0; border: solid 1px #20538D; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 225px; background: #4479BA;">
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| <font color="#FFF">
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| ▸ '''Endocarditis'''
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| </font>
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| </div>
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| <div class="mw-customtoggle-table04" style="cursor: pointer; border-radius: 0 0 0 0; border: solid 1px #20538D; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 225px; background: #4479BA;">
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| <font color="#FFF">
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| ▸ '''Gastroenteritis'''
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| </font>
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| </div>
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| <div class="mw-customtoggle-table05" style="cursor: pointer; border-radius: 0 0 0 0; border: solid 1px #20538D; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 225px; background: #4479BA;">
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| <font color="#FFF">
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| ▸ '''Meningitis'''
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| </font>
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| </div>
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| <div class="mw-customtoggle-table06" style="cursor: pointer; border-radius: 0 0 5px 5px; border: solid 1px #20538D; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 225px; background: #4479BA;">
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| <font color="#FFF">
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| ▸ '''Rhombencephalitis'''
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| </font>
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| </div>
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| {| class="mw-collapsible mw-collapsed" id="mw-customcollapsible-table01" style="background: #FFFFFF;"
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| {| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
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| ! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center | {{fontcolor|#FFF|''Listeria monocytogenes'', Bacteremia<sup>¶</sup>}}
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| |- | | |- |
| | style="padding: 0 5px; font-size: 90%; background: #F5F5F5" align=center | '''''Preferred Regimen''''' | | | style="background: #DCDCDC; padding: 5px 5px;" | Gastroenteritis, if indicated |
| | | style="background: #F0F0F0; padding: 5px 5px;" | Several days |
| |- | | |- |
| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Ampicillin]] 2 g IV q4h'''''<BR> OR <BR> ▸ '''''[[Penicillin G]] 4 MU IV q4h''''' | | | style="background: #DCDCDC; padding: 5px 5px;" | Listeriosis in pregnancy |
| | | style="background: #F0F0F0; padding: 5px 5px;" | 2 weeks |
| |- | | |- |
| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | PLUS | | | style="background: #DCDCDC; padding: 5px 5px;" | Listeriosis in neonates |
| | | style="background: #F0F0F0; padding: 5px 5px;" | 2 weeks |
| |- | | |- |
| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Gentamicin]] 2 mg/kg IV load, then 1.7 mg/kg IV q8h''''' | | | style="background: #DCDCDC; padding: 5px 5px;" | Meningitis |
| | | style="background: #F0F0F0; padding: 5px 5px;" | 2–3 weeks |
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| | style="padding: 0 5px; font-size: 90%; background: #F5F5F5" align=center | '''''Alternative Regimen''''' | | | style="background: #DCDCDC; padding: 5px 5px;" | Bacteremia |
| | | style="background: #F0F0F0; padding: 5px 5px;" | 2–4 weeks |
| |- | | |- |
| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[TMP/SMZ]] 10—20 mg/kg/day IV q6—12h''''' (TMP component)<BR> OR <BR> ▸ '''''[[Meropenem]] 2 g IV q8h''''' | | | style="background: #DCDCDC; padding: 5px 5px;" | Endocarditis |
| | | style="background: #F0F0F0; padding: 5px 5px;" | 4–6 weeks |
| |- | | |- |
| | style="padding: 0 5px; font-size: 90%; background: #F5F5F5" align=left | <sup>¶</sup><SMALL> '''Minimum duration of therapy: 2 weeks''' </SMALL> | | | style="background: #DCDCDC; padding: 5px 5px;" | Non-CNS listeriosis in immunocompromised hosts |
| | | style="background: #F0F0F0; padding: 5px 5px;" | 4–6 weeks |
| |- | | |- |
| | | style="background: #DCDCDC; padding: 5px 5px;" | Brain abscess or rhombencephalitis |
| | | style="background: #F0F0F0; padding: 5px 5px;" | 6 weeks |
| |} | | |} |
| |}
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| {| class="mw-collapsible mw-collapsed" id="mw-customcollapsible-table02" style="background: #FFFFFF;"
| | ===Antimicrobial Regimen=== |
| | valign=top |
| | *1. '''Meningitis''' <ref>{{cite book | last = Bartlett | first = John | title = Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases | publisher = Jones and Bartlett Learning | location = Burlington, MA | year = 2012 | isbn = 978-1449625580 }}</ref> |
| {| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
| | :* Preferred regimen: [[Ampicillin]] 2g IV q4-6h {{withorwithout}} [[Gentamicin]] 1.7 mg/kg IV q8h for more than 3 weeks |
| ! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center | {{fontcolor|#FFF|''Listeria monocytogenes'', Brain Abscess<sup>†</sup>}}
| | :* Alternative regimen: [[TMP-SMX]] 3-5 mg/kg (trimethoprim) IV q6h for more than 3 weeks |
| |- | | *2. '''Bacteremia''' |
| | style="padding: 0 5px; font-size: 90%; background: #F5F5F5" align=center | '''''Preferred Regimen''''' | | :* Preferred regimen: [[Ampicillin]] 2g IV q4-6h {{withorwithout}} [[Gentamicin]] 1.7 mg/kg IV q8h for 2 weeks |
| |- | | :* Alternative regimen: [[TMP-SMX]] 3-5 mg/kg (trimethoprim) q6h IV for 2 weeks |
| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Ampicillin]] 2 g IV q4h'''''<BR> OR <BR> ▸ '''''[[Penicillin G]] 4 MU IV q4h''''' | | *3. '''Brain abscess or rhomboencephalitis''' |
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| | :* Preferred regimen: [[Ampicillin]] 2g IV q4-6h {{withorwithout}} [[Gentamicin]] 1.7 mg/kg IV q8h for 4-6 weeks |
| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | PLUS
| | :* Alternative regimen: [[TMP-SMX]] 3-5 mg/kg (trimethoprim) q6h IV for 4-6 weeks |
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| | *4. '''Gastroenteritis''' |
| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Gentamicin]] 2 mg/kg IV load, then 1.7 mg/kg IV q8h'''''
| | :* Preferred regimen (1): [[Amoxicillin]] 2g IV q4-6h |
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| | :* Preferred regimen (2): [[TMP-SMX]] 3-5 mg/kg (trimethoprim) q6h IV for 7 days |
| | style="padding: 0 5px; font-size: 90%; background: #F5F5F5" align=center | '''''Alternative Regimen'''''
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| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[TMP/SMZ]] 10—20 mg/kg/day IV q6—12h''''' (TMP component)<BR> OR <BR> ▸ '''''[[Meropenem]] 2 g IV q8h'''''
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| | style="padding: 0 5px; font-size: 90%; background: #F5F5F5" align=left | <sup>†</sup><SMALL> '''Minimum duration of therapy: 6 weeks''' </SMALL>
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| ! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center | {{fontcolor|#FFF|''Listeria monocytogenes'', Endocarditis<sup>§</sup>}}
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| | style="padding: 0 5px; font-size: 90%; background: #F5F5F5" align=center | '''''Preferred Regimen'''''
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| |-
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| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Ampicillin]] 2 g IV q4h'''''<BR> OR <BR> ▸ '''''[[Penicillin G]] 4 MU IV q4h'''''
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| |-
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| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | PLUS
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| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Gentamicin]] 2 mg/kg IV load, then 1.7 mg/kg IV q8h'''''
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| |-
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| | style="padding: 0 5px; font-size: 90%; background: #F5F5F5" align=center | '''''Alternative Regimen'''''
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| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[TMP/SMZ]] 10—20 mg/kg/day IV q6—12h''''' (TMP component)<BR> OR <BR> ▸ '''''[[Meropenem]] 2 g IV q8h'''''
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| | style="padding: 0 5px; font-size: 90%; background: #F5F5F5" align=left | <sup>§</sup><SMALL> '''Minimum duration of therapy: 4—6 weeks''' </SMALL>
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| ! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center | {{fontcolor|#FFF|''Listeria monocytogenes'', Gastroenteritis}}
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| | style="padding: 0 5px; font-size: 90%; background: #F5F5F5" align=center | '''''Preferred Regimen'''''
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| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ Antimicrobial therapy is <u>'''not'''</u> warranted in most cases.
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| | style="padding: 0 5px; font-size: 90%; background: #F5F5F5" align=center | '''''Alternative Regimen''''' <BR> <SMALL> (For Outbreaks and Invasive Diseases) </SMALL>
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| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Ampicillin]] 500 mg PO q6h x 5 days'''''<BR> OR <BR> ▸ '''''[[TMP/SMZ]] 160/800 mg PO q12h x 5 days'''''
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| {| class="mw-collapsible mw-collapsed" id="mw-customcollapsible-table05" style="background: #FFFFFF;"
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| {| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
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| ! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center | {{fontcolor|#FFF|''Listeria monocytogenes'', Meningitis<sup>‡</sup>}}
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| | style="padding: 0 5px; font-size: 90%; background: #F5F5F5" align=center | '''''Preferred Regimen'''''
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| |-
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| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Ampicillin]] 2 g IV q4h'''''<BR> OR <BR> ▸ '''''[[Penicillin G]] 4 MU IV q4h'''''
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| |-
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| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | PLUS
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| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Gentamicin]] 2 mg/kg IV load, then 1.7 mg/kg IV q8h'''''
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| |-
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| | style="padding: 0 5px; font-size: 90%; background: #F5F5F5" align=center | '''''Alternative Regimen'''''
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| |-
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| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[TMP/SMZ]] 10—20 mg/kg/day IV q6—12h''''' (TMP component)<BR> OR <BR> ▸ '''''[[Meropenem]] 2 g IV q8h'''''
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| | style="padding: 0 5px; font-size: 90%; background: #F5F5F5" align=left | <sup>‡</sup><SMALL> '''Minimum duration of therapy: 3 weeks''' </SMALL>
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| ! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center | {{fontcolor|#FFF|''Listeria monocytogenes'', Rhombencephalitis<sup>†</sup>}}
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| |-
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| | style="padding: 0 5px; font-size: 90%; background: #F5F5F5" align=center | '''''Preferred Regimen'''''
| |
| |-
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| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Ampicillin]] 2 g IV q4h'''''<BR> OR <BR> ▸ '''''[[Penicillin G]] 4 MU IV q4h'''''
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| |-
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| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | PLUS
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| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[Gentamicin]] 2 mg/kg IV load, then 1.7 mg/kg IV q8h'''''
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| |-
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| | style="padding: 0 5px; font-size: 90%; background: #F5F5F5" align=center | '''''Alternative Regimen'''''
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| |-
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| | style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | ▸ '''''[[TMP/SMZ]] 10—20 mg/kg/day IV q6—12h''''' (TMP component)<BR> OR <BR> ▸ '''''[[Meropenem]] 2 g IV q8h'''''
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| | style="padding: 0 5px; font-size: 90%; background: #F5F5F5" align=left | <sup>†</sup><SMALL> '''Minimum duration of therapy: 6 weeks''' </SMALL>
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| ==References== | | ==References== |
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| {{reflist|2}} | | {{reflist|2}} |
|
| |
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| [[Category:Bacterial diseases]] | | {{WH}} |
| | {{WS}} |
| | |
| | [[Category:Emergency mdicine]] |
| [[Category:Disease]] | | [[Category:Disease]] |
| | [[Category:Up-To-Date]] |
| [[Category:Infectious disease]] | | [[Category:Infectious disease]] |
| [[Category:Wikifect]] | | [[Category:Neurology]] |
| | [[Category:Gastroenterology]] |