Ceftazidime

{{cs1 config|name-list-style=vanc}} {{Short description|Antibiotic medication}} {{Infobox drug | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 460024696 | image = Ceftazidime.svg | image_class = skin-invert-image | width = 300 | alt = | image2 = Ceftazidime-from-xtal-3D-bs-17.png | image_class2 = bg-transparent | alt2 =  | 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 = Intravenous, intramuscular, inhalation | class = Third-generation cephalosporin | ATCvet = | ATC_prefix = J01 | ATC_suffix = DD02 | ATC_supplemental =  | legal_AU = S4 | legal_AU_comment = | legal_BR =  | legal_BR_comment = | legal_CA =  | legal_CA_comment = | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK =  | 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 =  | legal_UN_comment = | legal_status =

| CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 72558-82-8 | CAS_supplemental = | PubChem = 5481173 | IUPHAR_ligand = | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00438 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 4587145 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = DZR1ENT301 | KEGG = | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 3508 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 44354 | NIAID_ChemDB = | PDB_ligand = | synonyms =  | 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-bicyclo[4.2.0]oct-2-ene-2-carboxylate | C = 22 | H = 22 | N = 6 | O = 7 | S = 2 | SMILES = O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC(=O)C(=NOC(C(=O)O)(C)C)c3nc(sc3)N)C[n+]4ccccc4)C([O-])=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 = }}

'''Ceftazidime''', sold under the brand name '''Fortaz''' among others, is a third-generation cephalosporin antibiotic useful for the treatment of a number of bacterial infections.<ref name=AHFS2016/><ref>{{Cite book| vauthors = Katzung B |title=Basic & Clinical Pharmacology | edition = 14th|publisher=McGraw Hill|year=2019|page=803 | isbn = 978-1-259-64115-2 }}</ref> Specifically it is used for joint infections, meningitis, pneumonia, sepsis, urinary tract infections, malignant otitis externa, ''Pseudomonas aeruginosa'' infection, and vibrio infection.<ref name=AHFS2016/> It is given by injection into a vein, muscle, or eye.<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>

Common side effects include nausea, allergic reactions, and pain at the site of injection.<ref name=AHFS2016/> Other side effects may include ''Clostridioides difficile'' diarrhea.<ref name=AHFS2016/> It is not recommended in people who have had previous anaphylaxis to a penicillin.<ref name=AHFS2016/> Its use is relatively safe during pregnancy and breastfeeding.<ref name=Ric2015>{{cite book| vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=978-1-284-05756-0|page=87}}</ref> It is in the third-generation cephalosporin family of medications and works by interfering with the bacteria's cell wall.<ref name=AHFS2016/>

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=978-3-527-60749-5|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 World Health Organization's List of Essential Medicines.<ref name="WHO21st">{{cite book | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06 | hdl-access=free }}</ref> Ceftazidime is available as a generic medication.<ref name=AHFS2016/>

==Medical uses== 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, melioidosis, 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 }}</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 = https://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 μg/mL * ''Pseudomonas aeruginosa'': ≤0.03–1024 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 toxic epidermal necrolysis, Stevens–Johnson syndrome, and erythema multiforme, 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 eosinophils (8%), increased lactate dehydrogenase (6%), increased gamma-glutamyl transferase (5%), positive direct Coombs test (4%), increased platelets (thrombocythemia) (2%), increased ALT (7%), increased AST (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) [package insert]. Schaumburg, IL: Sagent; 2012. [http://www.sagentpharma.com/Products/Ceftazidime/Catalog/Ceftazidime_PI1.pdf PDF of insert] {{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 (cefuroxime & cefuzonam also bear this functional group but are only listed as class II). This group provides improved stability against certain beta-lactamase 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== In addition to the ''syn''-configuration of the imino side chain, compared to other third-generation cephalosporins, the more complex moiety (containing two methyl and a carboxylic acid group) confers extra stability to beta-lactamase enzymes produced by many Gram-negative bacteria. The extra stability to β-lactamases increases the activity of ceftazidime against otherwise resistant Gram-negative organisms including ''Pseudomonas aeruginosa''. The charged pyridinium moiety increases water-solubility. Ceftazidime shares the same variable R-group side chain with aztreonam, a monobactam antibiotic; the two drugs share a similar spectrum of activity, including activity against ''Pseudomonas aeruginosa''.{{cn|date=March 2023}}

==See also== * Ceftazidime/avibactam

==References== {{reflist}}

== External links == {{Commons}} * {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/ceftazidime | archive-url = https://web.archive.org/web/20170123232345/https://druginfo.nlm.nih.gov/drugportal/name/Ceftazidime | archive-date = January 23, 2017 | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Ceftazidime }}

Category:Cephalosporin antibiotics Category:Thiazoles Category:Pyridinium compounds Category:Zwitterions Category:World Health Organization essential medicines Category:Wikipedia medicine articles ready to translate Category:Ketoxime ethers