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Revision as of 20:52, 10 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank', 'ChEMBL').← Previous edit Latest revision as of 15:00, 14 December 2024 edit undoAleovas (talk | contribs)7 edits →Medical uses: As per linked reference, activity against MRSA is found in fifth generation cephalosporins, not the fourthTag: Visual edit 
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{{cs1 config|name-list-style=vanc}}
{{Drugbox
{{Short description|Antibiotic medication}}
| verifiedrevid = 443510449
{{Infobox drug
| IUPAC_name = (6''R'',7''R'',''Z'')-7-(2-(2-aminothiazol-4-yl)-<br />2-(2-carboxypropan-2-yloxyimino)acetamido)-8-oxo-<br />3-(pyridinium-1-ylmethyl)-5-thia-1-aza-bicyclo<br />oct-2-ene-2-carboxylate
| Verifiedfields = changed
| image = Ceftazidime.svg
| Watchedfields = changed
| width = 300px
| verifiedrevid = 460024696
| image = Ceftazidime.svg
| width = 300
| alt =
| image2 = Ceftazidime-from-xtal-3D-bs-17.png
| alt2 = <!-- Clinical data -->
| pronounce = {{IPAc-en|s|ɛ|f|ˈ|t|æ|z|ᵻ|d|iː|m}}<br />{{respell|sef|TAZ|i|deem}}
| tradename = Fortaz, Tazicef, others<ref name=AHFS2016/>
| Drugs.com = {{drugs.com|monograph|ceftazidime}}
| MedlinePlus = a686007
| licence_EU = yes
| DailyMedID = Ceftazidime
| pregnancy_AU = B1
| pregnancy_AU_comment =
| pregnancy_category =
| routes_of_administration = ], ], ]
| class = ]
| ATCvet =
| ATC_prefix = J01
| ATC_suffix = DD02
| ATC_supplemental = <!-- Legal status -->
| legal_AU = S4
| legal_AU_comment =
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment =
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment =
| legal_US = Rx-only
| legal_US_comment = <ref>{{cite web | title=Fortaz- ceftazidime injection, powder, for solution | work = DailyMed | publisher = U.S. National Library of Medicine | date=28 July 2017 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=78982c98-7866-49f1-989f-a289c4242358 | access-date=12 June 2022 | archive-date=28 December 2021 | archive-url=https://web.archive.org/web/20211228201711/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=78982c98-7866-49f1-989f-a289c4242358 | url-status=live }}</ref><ref>{{cite web | title=Tazicef- ceftazidime injection, powder, for solution | work = DailyMed | publisher = U.S. National Library of Medicine | date=24 March 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=40d48c5d-650e-461b-a67b-7e65772d1b92 | access-date=12 June 2022 | archive-date=28 December 2021 | archive-url=https://web.archive.org/web/20211228200954/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=40d48c5d-650e-461b-a67b-7e65772d1b92 | url-status=live }}</ref>
| legal_EU =
| legal_EU_comment =
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = <!-- For countries not listed above -->


<!-- Pharmacokinetic data -->| bioavailability = 91% (])
<!--Clinical data-->
| protein_bound =
| tradename = Fortaz, Tazicef
| metabolism = negligible
| Drugs.com = {{drugs.com|monograph|ceftazidime}}
| metabolites =
| MedlinePlus = a686007
| onset =
| pregnancy_AU = B1
| pregnancy_US = B
| legal_AU = S4
| routes_of_administration = ], intramuscular

<!--Pharmacokinetic data-->
| bioavailability = 91% (])
| metabolism = negligible
| elimination_half-life = 1.6–2 hours | elimination_half-life = 1.6–2 hours
| duration_of_action =
| excretion = 90–96% ]
| excretion = 90–96% ]


<!--Identifiers--> <!-- Identifiers -->| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 72558-82-8
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_supplemental =
| CAS_number = 72558-82-8
| PubChem = 5481173
| ATC_prefix = J01
| IUPHAR_ligand =
| ATC_suffix = DD02
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| PubChem = 5481173
| DrugBank = DB00438
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| DrugBank = DB00438
| ChemSpiderID = 4587145
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| UNII_Ref = {{fdacite|correct|FDA}}
| ChemSpiderID = 4587145
| UNII = DZR1ENT301
| UNII_Ref = {{fdacite|correct|FDA}}
| KEGG =
| UNII = DZR1ENT301
| ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 3508 | ChEBI = 3508
| ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = <!-- blanked - oldvalue: 201 --> | ChEMBL = 44354
| C=22 | H=22 | N=6 | O=7 | S=2 | NIAID_ChemDB =
| PDB_ligand =
| molecular_weight = 546.58 ]/]
| synonyms = <!-- Chemical and physical data -->
| smiles = O=C2N1/C(=C(\CS12NC(=O)C(=NOC(C(=O)O)(C)C)c3nc(sc3)N)C4ccccc4)C()=O
| IUPAC_name = (6''R'',7''R'',''Z'')-7-(2-(2-aminothiazol-4-yl)-2-(2-carboxypropan-2-yloxyimino)acetamido)-8-oxo-3-(pyridinium-1-ylmethyl)-5-thia-1-aza-bicyclooct-2-ene-2-carboxylate
| InChI = 1/C22H22N6O7S2/c1-22(2,20(33)34)35-26-13(12-10-37-21(23)24-12)16(29)25-14-17(30)28-15(19(31)32)11(9-36-18(14)28)8-27-6-4-3-5-7-27/h3-7,10,14,18H,8-9H2,1-2H3,(H4-,23,24,25,29,31,32,33,34)/t14-,18-/m1/s1
| C = 22
| InChIKey = ORFOPKXBNMVMKC-RDTXWAMCBJ
| H = 22
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| N = 6
| StdInChI = 1S/C22H22N6O7S2/c1-22(2,20(33)34)35-26-13(12-10-37-21(23)24-12)16(29)25-14-17(30)28-15(19(31)32)11(9-36-18(14)28)8-27-6-4-3-5-7-27/h3-7,10,14,18H,8-9H2,1-2H3,(H4-,23,24,25,29,31,32,33,34)/b26-13-/t14-,18-/m1/s1
| O = 7
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| S = 2
| StdInChIKey = ORFOPKXBNMVMKC-DWVKKRMSSA-N
| SMILES = O=C2N1/C(=C(\CS12NC(=O)C(=NOC(C(=O)O)(C)C)c3nc(sc3)N)C4ccccc4)C()=O
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C22H22N6O7S2/c1-22(2,20(33)34)35-26-13(12-10-37-21(23)24-12)16(29)25-14-17(30)28-15(19(31)32)11(9-36-18(14)28)8-27-6-4-3-5-7-27/h3-7,10,14,18H,8-9H2,1-2H3,(H4-,23,24,25,29,31,32,33,34)/b26-13-/t14-,18-/m1/s1
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = ORFOPKXBNMVMKC-DWVKKRMSSA-N
| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}} }}


<!-- Definition and medical uses -->
'''Ceftazidime''' (]) ({{IPAc-en|icon|s|ɛ|f|ˈ|t|æ|z|ɨ|d|iː|m}}) is a third-generation ] ]. Like other third-generation cephalosporins, it has broad spectrum activity against ] and ] ]. Unlike most third-generation agents, it is active against '']'', however it has weaker activity against Gram-positive microorganisms and is not used for such infections. '''Ceftazidime pentahydrate''' is marketed under various trade names including '''Cefzim''' (]), '''Fortum''' (]), and '''Fortaz'''.
'''Ceftazidime''', sold under the brand name '''Fortaz''' among others, is a third-generation cephalosporin ] useful for the treatment of a number of ].<ref name=AHFS2016/><ref>{{Cite book| vauthors = Katzung B |title=Basic & Clinical Pharmacology | edition = 14th|publisher=McGraw Hill|year=2019|pages=803 | isbn = 978-1-259-64115-2 }}</ref> Specifically it is used for ], ], ], ], ], ], ], and ].<ref name=AHFS2016/> It is given by ], ], or ].<ref name=AHFS2016>{{cite web |title=Ceftazidime |url=https://www.drugs.com/monograph/ceftazidime.html |publisher=The American Society of Health-System Pharmacists |access-date=8 December 2016 |url-status=live|archive-url=https://web.archive.org/web/20161220230855/https://www.drugs.com/monograph/ceftazidime.html|archive-date=20 December 2016}}</ref><ref>{{cite web | vauthors = Kamjoo S |title=Intravitreal Injections | work = EyeWiki | publisher = American Academy of Ophthalmology |url=https://eyewiki.aao.org/Intravitreal_Injections |access-date=12 January 2020 |archive-date=5 March 2021 |archive-url=https://web.archive.org/web/20210305065813/https://eyewiki.aao.org/Intravitreal_Injections |url-status=live }}</ref>


<!-- Side effects and mechanism -->
==Clinical use==
Common side effects include nausea, ], and pain at the site of injection.<ref name=AHFS2016/> Other side effects may include ].<ref name=AHFS2016/> It is not recommended in people who have had previous ] to a ].<ref name=AHFS2016/> Its use is relatively safe during ] and ].<ref name=Ric2015>{{cite book| vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=9781284057560|page=87}}</ref> It is in the ] family of medications and works by interfering with the bacteria's ].<ref name=AHFS2016/>
{{main|Cephalosporin}}


<!-- Society and culture -->
Ceftazidime is usually reserved for the treatment of infections caused by ''Pseudomonas aeruginosa''. It is also used in the ] therapy of ] ], in combination with other antibiotics. It is usually given ] or ] every 8–12 hours (2 - 3 times a day), with dosage varying by the indication, infection severity, and/or renal function of the recipient.
Ceftazidime was patented in 1978 and came into commercial use in 1984.<ref>{{cite book| vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery|date=2006|publisher=John Wiley & Sons|isbn=9783527607495|page=495|url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA495|url-status=live|archive-url=https://web.archive.org/web/20161220085422/https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA495|archive-date=2016-12-20}}</ref> It is on the ].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> Ceftazidime is available as a ].<ref name=AHFS2016/>


==Medical uses==
Ceftazidine is first line treatment for the rare tropical infection, ].<ref>{{cite journal |author=White NJ |title=Melioidosis |journal=Lancet |year=2003| volume=361| pages=1715–722| pmid=12767750 |doi=10.1016/S0140-6736(03)13374-0 |issue=9370}}</ref>
Ceftazidime is used to treat lower respiratory tract, skin, urinary tract, blood-stream, joint, and abdominal infections, and meningitis.<ref name="Sagent"/>

Ceftazidime is the first-line treatment for the tropical infection, ], an important cause of sepsis in Asia and Australia.<ref>{{cite journal | vauthors = White NJ | title = Melioidosis | journal = Lancet | volume = 361 | issue = 9370 | pages = 1715–1722 | date = May 2003 | pmid = 12767750 | doi = 10.1016/S0140-6736(03)13374-0 | s2cid = 208790913 }}</ref><ref>{{cite journal | vauthors = White NJ, Dance DA, Chaowagul W, Wattanagoon Y, Wuthiekanun V, Pitakwatchara N | title = Halving of mortality of severe melioidosis by ceftazidime | journal = Lancet | volume = 2 | issue = 8665 | pages = 697–701 | date = September 1989 | pmid = 2570956 | doi = 10.1016/S0140-6736(89)90768-X | s2cid = 28919574 }}</ref>

Labeled indications include the treatment of patients with:
* ''Pseudomonas aeruginosa'' infections
* other Gram-negative, aerobic infections
* neutropenic fever<ref name="Lexi"/>

As a class, cephalosporins have activity against Gram-positive and Gram-negative bacteria. The balance of activity tips toward Gram-positive organisms for earlier generations; later generations of cephalosporins have more Gram-negative coverage. Ceftazidime is one of the few in this class with activity against ''Pseudomonas aeruginosa''.<ref>{{cite journal | vauthors = O'Callaghan H | title = Ceftazidime, a broad spectrum cephalosporin with activity against Ps. aeruginosa | journal = Journal of Hygiene, Epidemiology, Microbiology, and Immunology | volume = 30 | issue = 4 | pages = 449–453 | date = 1986 | pmid = 3100612 | url = https://pubmed.ncbi.nlm.nih.gov/3100612/ }}</ref> However, ceftazidime is less effective for ''S. aureus'' than first and second generation cephalosporins.<ref>{{cite journal | vauthors = Richards DM, Brogden RN | title = Ceftazidime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use | journal = Drugs | volume = 29 | issue = 2 | pages = 105–161 | date = February 1985 | pmid = 3884319 | doi = 10.2165/00003495-198529020-00002 | s2cid = 265707490 }}</ref> Also, cephalosporins until fifth generation are not active against methicillin-resistant ''Staphylococcus aureus''.<ref>{{cite book | vauthors = Bui T, Preuss CV | chapter = Cephalosporins |date=2023 |chapter-url = http://www.ncbi.nlm.nih.gov/books/NBK551517/ | title = StatPearls |access-date=2023-04-13 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=31855361 |quote=However, what makes it unique from the rest of the cephalosporins is that it has coverage against methicillin-resistant Staphylococcus aureus (MRSA). }}</ref>

=== Spectrum of activity ===
Clinically relevant organisms against which ceftazidime has activity include:
* '''Gram-negative aerobes''' such as ''Enterobacter'', ''Escherichia coli'', ''Haemophilus influenzae'', ''Klebsiella spp.'', ''Proteus spp.'', ''Pseudomonas aeruginosa'', and ''Neisseria meningitidis''
* '''Gram-positive aerobes''', such as group B streptococci, ''Streptococcus pneumoniae'', and ''Streptococcus pyogenes''
Ceftazidime generally has poor efficacy against anaerobes, such as ''Bacteroides'' spp.<ref name="Sagent"/><ref>{{cite journal | vauthors = Richards DM, Brogden RN | title = Ceftazidime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use | journal = Drugs | volume = 29 | issue = 2 | pages = 105–161 | date = February 1985 | pmid = 3884319 | doi = 10.2165/00003495-198529020-00002 | s2cid = 265707490 }}</ref>

The following represents MIC susceptibility data for a few clinically significant pathogens:
* ''Escherichia coli'': 0.015–512&nbsp;μg/mL
* ''Pseudomonas aeruginosa'': ≤0.03–1024&nbsp;μg/mL <ref>{{cite web |url=http://www.toku-e.com/Assets/MIC/Ceftazidime%20pentahydrate.pdf |title=Ceftazidime pentahydrate Susceptibility and Minimum Inhibitory Concentration (MIC) Data | work = Toku-e |archive-url=https://web.archive.org/web/20141204114533/http://www.toku-e.com/Assets/MIC/Ceftazidime%20pentahydrate.pdf |archive-date=2014-12-04}}</ref>

== Side effects ==
Ceftazidime is generally well tolerated. When side effects occur, they are most commonly local effects from the intravenous line site, allergic reactions, and gastrointestinal symptoms. According to one manufacturer, in clinical trials, allergic reactions including itching, rash, and fever, happened in fewer than 2% of patients. Rare but more serious allergic reactions, such as ], ], and ], have been reported with this class of antibiotics, including ceftazidime. Gastrointestinal symptoms, including diarrhea, nausea, vomiting, and abdominal pain, were reported in fewer than 2% of patients.<ref name="Sagent"/>

Another source reported, in addition, blood tests of patients may show increased ] (8%), increased lactate dehydrogenase (6%), increased gamma-glutamyl transferase (5%), positive direct ] (4%), increased ] (thrombocythemia) (2%), increased ] (7%), increased ] (6%), or increased alkaline phosphatase (4%).<ref name="Lexi">{{cite web | work = Lexicomp Online | publisher = Lexi-Drugs | location = Hudson, Ohio | date = April 2014 | url=http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6560 |title=Ceftazidime |access-date=2014-04-21 |url-status=live |archive-url=https://web.archive.org/web/20140423041750/http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6560 |archive-date=2014-04-23 }}</ref>

=== Contraindications ===
Ceftazidime is contraindicated in people with a known allergy to ceftazidime or to any other cephalosporin antibiotic.<ref name="Sagent"/>

=== Precautions ===
Ceftazidime is mainly eliminated by the kidneys into the urine. As such, drug levels in the blood may build up in persons with kidney injury or kidney disease. This includes those on dialysis. In these cases of renal impairment, the drug is dosed less frequently.<ref name="Lexi"/> No dose adjustment is needed for those with liver disease.{{cn|date=March 2023}}

=== Pregnancy ===
According to the manufacturer, research studies in mice and rats showed no evidence of harm to the fetus, even at up to 40 times the human dose of ceftazidime. Importantly, though, no high-quality research studies of the effects of the drug in pregnant women were conducted.<ref name="Sagent">Ceftazidime for Injection(R) . Schaumburg, IL: Sagent; 2012. {{webarchive|url=https://web.archive.org/web/20140423022408/http://www.sagentpharma.com/Products/Ceftazidime/Catalog/Ceftazidime_PI1.pdf |date=2014-04-23 }}</ref>

==Mechanism of action==
Third-generation cephalosporins differ from earlier generations in the presence of a C=N-OCH<sub>3</sub> group in their chemical structure (] & ] also bear this ] but are only listed as class II). This group provides improved stability against certain ] enzymes produced by Gram-negative bacteria. These bacterial enzymes rapidly destroy earlier-generation cephalosporins by breaking open the drug's beta-lactam chemical ring, leading to antibiotic resistance. Though initially active against these bacteria, with widespread use of third-generation cephalosporins, some Gram-negative bacteria that produce extended-spectrum beta-lactamases (ESBLs) are even able to inactivate the third-generation cephalosporins. Infections caused by ESBL-producing Gram-negative bacteria are of particular concern in hospitals and other healthcare facilities.<ref>{{cite journal |vauthors=Sharma M, Pathak S, Srivastava P |title=Prevalence and antibiogram of Extended Spectrum β-Lactamase (ESBL) producing Gram negative bacilli and further molecular characterization of ESBL producing Escherichia coli and Klebsiella spp |journal=J Clin Diagn Res |volume=7 |issue=10 |pages=2173–7 |date=October 2013 |pmid=24298468 |pmc=3843424 |doi=10.7860/JCDR/2013/6460.3462 }}</ref>


==Chemistry== ==Chemistry==
In addition to the ''syn''-configuration of the ] ], compared to other third-generation cephalosporins, the more complex moiety (containing two ] and a ] group) confers extra stability to ] enzymes produced by many ] bacteria. The extra stability to β-lactamases increases the activity of ceftazidime against otherwise resistant Gram-negative organisms including ''Pseudomonas aeruginosa''. The charged ] moiety increases water-solubility. In addition to the ''syn''-configuration of the ] ], compared to other third-generation cephalosporins, the more complex moiety (containing two ] and a ] group) confers extra stability to beta-lactamase enzymes produced by many ] bacteria. The extra stability to β-lactamases increases the activity of ceftazidime against otherwise resistant Gram-negative organisms including ''Pseudomonas aeruginosa''. The charged ] moiety increases water-solubility. Ceftazidime shares the same variable R-group side chain with ], a ] antibiotic; the two drugs share a similar spectrum of activity, including activity against ''Pseudomonas aeruginosa''.{{cn|date=March 2023}}

==See also==
* ]


==References== ==References==
{{reflist}} {{reflist}}

== External links ==
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/ceftazidime | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Ceftazidime }}


{{CephalosporinAntiBiotics}} {{CephalosporinAntiBiotics}}
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