Cefazolin: Difference between revisions

{{Short description|Antibiotic medication}}

{{Redirect|Ancef|the similarly spelled trade name|Encef (disambiguation){{!}}Encef}}

{{Drugbox

| Watchedfields = changed

| verifiedrevid = 443508421

| drug_name =

| IUPAC_name = (6''R'',7''R'')-3-{[(5-methyl-1,3,4-thiadiazol-2-yl)thio]methyl}-8-oxo-7-[(1''H''-tetrazol-1-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

| image = Cefazolin.svg

| image2 = Cefazolinate-from-xtal-3D-bs-17.png

<!--Clinical data-->

| pronounce = {{IPAc-en|s|ə|ˈ|f|æ|z|ə|l|ə|n}}{{refn|{{MerriamWebsterDictionary|access-date=2016-01-21|Cefazolin}}}}

| tradename = Ancef, Cefacidal, other

| Drugs.com = {{drugs.com|monograph|cefazolin-sodium}}

| class = [[Cephalosporin|First-generation cephalosporin]]

| pregnancy_AU = B1

| pregnancy_US = B

| legal_status = Rx-only

| routes_of_administration = intravenous, intramuscular

<!--Pharmacokinetic data-->

| bioavailability = NA

| metabolism = ?

| elimination_half-life = 1.8 hours (given [[Intravenous therapy|IV]])<br>2 hours (given [[intramuscular injection|IM]])

| excretion = [[kidney]], unchanged

<!--Identifiers-->

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 25953-19-9

| ATC_prefix = J01

| ATC_suffix = DB04

| ATC_supplemental = {{ATCvet|J51|DB04}}

| PubChem = 33255

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB01327

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 30723

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D02299

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 474053

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 1435

<!--Chemical data-->

| C=14 | H=14 | N=8 | O=4 | S=3

| smiles = O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC(=O)Cn3nnnc3)CSc4nnc(s4)C)C(=O)O

| melting_point = 198

| melting_high = 200

| melting_notes = (decompose.)

<!-- Definition and medical uses -->

'''Cefazolin''', also known as '''cefazoline''' and '''cephazolin''', is a first-generation [[cephalosporin]] [[antibiotic]] used for the treatment of a number of [[bacterial infection]]s.<ref name=AHFS2016/> Specifically it is used to treat [[cellulitis]], [[urinary tract infections]], [[pneumonia]], [[endocarditis]], [[joint infection]], and [[biliary tract infections]].<ref name=AHFS2016/> It is also used to prevent [[group B streptococcal disease]] around the time of delivery and before surgery.<ref name=AHFS2016/> It is typically given by [[intramuscular injection|injection into a muscle]] or [[intravenous infusion|vein]].<ref name=AHFS2016>{{cite web|title=Cefazolin Sodium|url=https://www.drugs.com/monograph/cefazolin-sodium.html|publisher=The American Society of Health-System Pharmacists|access-date= 8 December 2016}}</ref>

<!-- Side effects and mechanism -->

Common side effects include [[diarrhea]], vomiting, [[yeast infections]], and [[allergic reactions]].<ref name=AHFS2016/> Historically, it was thought to be contraindicated in patients with allergies to penicillin, although several recent studies have refuted this and it is proven to be safe in almost all patients, including those with known penicillin allergies.<ref>{{Cite web |title=NEJM Journal Watch: Summaries of and commentary on original medical and scientific articles from key medical journals |url=https://www.jwatch.org/na53366/2021/03/23/cefazolin-use-patients-with-penicillin-allergy |access-date=2023-01-20 |website=www.jwatch.org}}</ref> It is relatively safe for use during [[pregnancy]] and [[breastfeeding]].<ref name=AHFS2016/><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=84}}</ref> Cefazolin is in the [[Cephalosporin|first-generation cephalosporin]] class of medication and works by interfering with the bacteria's [[cell wall]].<ref name=AHFS2016/>

<!-- History, society and culture -->

Cefazolin was patented in 1967 and came into commercial use in 1971.<ref>{{cite book| vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006|publisher=John Wiley & Sons|isbn=9783527607495|page=493|url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA493 |language=en |url-status=live |archive-url=https://web.archive.org/web/20170910171829/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA493 |archive-date=2017-09-10}}</ref><ref>{{cite patent |country=US |number=3516997 |status=patent |title=3,7-disubstituted cephalosporin compounds and preparation thereo |pubdate=1970-06-23 |gdate=1970-06-23 |fdate=1968-04-12 |pridate=1967-04-15 |inventor = Takano T, Kurita M, Nikaido H, Mera M, Konishi N, Nakagawa R |assign1=Fujisawa Pharmaceutical Co Ltd |url=https://worldwide.espacenet.com/publicationDetails/biblio?CC=US&NR=3516997&KC=&FT=E&locale=en_EP}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<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> It is available as a [[generic medication]].<ref name=AHFS2016/>

==Medical uses==

Cefazolin is used in a variety of infections provided that susceptible organisms are involved. It is indicated for use in the following infections:<ref name=":2">{{Cite web|title = DailyMed - CEFAZOLIN - cefazolin sodium injection, powder, for solution|url = http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=79afc719-8279-49f9-83b0-e0736c07eb5c|website = dailymed.nlm.nih.gov|access-date = 2015-11-05|url-status = live|archive-url = https://web.archive.org/web/20160306013731/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=79afc719-8279-49f9-83b0-e0736c07eb5c|archive-date = 2016-03-06}}</ref>

* [[Respiratory tract infection]]s

* [[Urinary tract infection]]s

* Skin infections

* Biliary tract infections

* Bone and joint infections

* Genital infections

* Blood infections ([[sepsis]])

* [[Endocarditis]]

It can also be used peri-operatively to prevent infections post-surgery, and is often the preferred drug for surgical prophylaxis.<ref name=":2" />

There is no penetration into the [[central nervous system]] and therefore cefazolin is not effective in treating [[meningitis]].<ref name=":0">{{cite book | vauthors = Trevor AJ, Katzung BG, Masters S |title = Basic & Clinical Pharmacology |publisher = McGraw Hill Education|year = 2015|isbn = 978-0-07-182505-4|location = New York|pages = 776–778}}</ref>

Cefazolin has been shown to be effective in treating methicillin-susceptible ''Staphylococcus aureus'' (MSSA) but does not work in cases of [[Methicillin-resistant Staphylococcus aureus|methicillin-resistant ''Staphylococcus aureus'']] (MRSA).<ref name=":2" /> In many instances of staphylococcal infections, such as bacteremia, cefazolin is an alternative to penicillin in patients who are allergic to penicillin.<ref name=":0" /> However, there is still potential for a reaction to occur with cefazolin and other cephalosporins in patients allergic to penicillin.<ref name=":2" /> Resistance to cefazolin is seen in several species of bacteria, such as ''[[Mycoplasma]]'' and ''[[Chlamydia (genus)|Chlamydia]]'', in which case different generations of cephalosporins may be more effective.<ref>{{cite web|title = Cefazolin (Injection Route)|publisher = Mayo Clinic|date = 1 July 2015|url = http://www.mayoclinic.org/drugs-supplements/cefazolin-injection-route/before-using/drg-20073267|url-status = live|archive-url = https://web.archive.org/web/20140419012252/http://www.mayoclinic.org/drugs-supplements/cefazolin-injection-route/before-using/drg-20073267|archive-date = 19 April 2014}}</ref> Cefazolin does not fight against ''[[Enterococcus]]'', anaerobic bacteria, or atypical bacteria, among others.<ref name=":0" />

=== Bacterial susceptibility ===

As a [[First generation cephalosporin|first-generation cephalosporin]] antibiotic, cefazolin and other first-generation antibiotics are very active against [[gram-positive bacteria]] and some [[gram-negative bacteria]].<ref name=":2" /> Their broad spectrum of activity can be attributed to their improved stability to many bacterial [[beta-lactamases]] compared to penicillins.<ref name=":0" />

=== Spectrum of activity ===

Gram-positive aerobes:<ref name=":2" /><ref name=":0" />

* ''[[Staphylococcus aureus]]'' (including beta-lactamase producing strains)

* ''[[Staphylococcus epidermidis]]''

* ''[[Streptococcus pyogenes]]'', ''[[Streptococcus agalactiae]]'', ''[[Streptococcus pneumoniae]]'' and other strains of streptococci

Gram-Negative Aerobes:<ref>{{Cite book | vauthors = Beauduy C, Winston L |publisher=McGraw Hill|url=https://accesspharmacy.mhmedical.com/content.aspx?bookid=2988&sectionid=250601638 |title=Basic & Clinical Pharmacology |year=2021 |edition=15}}</ref>

* ''[[Escherichia coli]]''

* ''[[Proteus mirabilis]]''

* ''[[Klebsiella pneumoniae]]''

=== Non susceptible===

The following are not susceptible:<ref name=":2" /><ref name=":0" />

* [[Methicillin-resistant Staphylococcus aureus|Methicillin-resistant ''staphylococcus aureus'']]

* ''[[Enterococcus]]''

* most strains of indole positive ''Proteus'' (''[[Proteus vulgaris]]'')

* ''[[Enterobacter|Enterobacter spp]]''.

* ''[[Morganella morganii]]''

* ''[[Providencia rettgeri]]''

* ''[[Serratia]] spp''.

* ''[[Pseudomonas]] spp''.

* ''[[Listeria]]''

==Special populations==

=== Pregnancy ===

Cefazolin is [[pregnancy category]] B, indicating general safety for use in pregnancy. Caution should be used in breastfeeding as a small amount of cefazolin enters the breast milk.<ref name=":2" /> Cefazolin can be used prophylactically against perinatal [[Group B streptococcal infection]] (GBS). Although [[penicillin]] and [[ampicillin]] are the standard of care for GBS prophylaxis, penicillin-allergic women with no history of [[anaphylaxis]] can be given cefazolin instead. These patients should be closely monitored as there is a small chance of an allergic reaction due to the similar structure of the antibiotics.<ref>{{Cite web|title = Prevention of Perinatal Group B Streptococcal Disease|url = https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5910a1.htm|website = www.cdc.gov|access-date = 2015-11-05|url-status = live|archive-url = https://web.archive.org/web/20151115063145/http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5910a1.htm|archive-date = 2015-11-15}}</ref>

=== Newborns ===

There has been no established safety and effectiveness for use in premature infants and neonates.<ref name=":2" />

=== Elderly ===

No overall differences in safety or effectiveness were observed in clinical trials comparing elderly and younger subjects, however the trials could not eliminate the possibility that some older individuals may have a higher level of sensitivity.<ref name=":2" />

===Additional considerations===

People with kidney disease and those on [[hemodialysis]] may need the dose adjusted.<ref name=":2" /> Cefazolin levels are not significantly affected by liver disease.

As with other antibiotics, cefazolin may [[drug interaction|interact]] with other medications being taken. Some important drugs that may interact with cefazolin such as [[probenecid]].<ref name=":0" />

==Side effects==

[[Adverse drug reaction|Side effect]]s associated with use of cefazolin therapy include:<ref name=":2" />

* Common (1–10%): diarrhea, stomach pain or upset stomach, vomiting, and rash.

* Uncommon (<1%): dizziness, headache, fatigue, itching, transient hepatitis.<ref>{{Cite web|url =http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/50461slr139_ancef_lbl.pdf|title =Cefazolin Prescribing Information|date =2004|publisher =FDA|url-status =live|archive-url =https://web.archive.org/web/20160304070705/http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/50461slr139_ancef_lbl.pdf|archive-date =2016-03-04}}</ref>

Patients with penicillin allergies could experience a potential reaction to cefazolin and other cephalosporins.<ref name=":2" /> As with other antibiotics, patients experiencing watery and/or bloody stools occurring up to three months following therapy should contact their prescriber.<ref name=":2" />

Like those of several other cephalosporins, the chemical structure of cefazolin contains an [[N-methylthiodiazole]] (NMTD or 1-MTD) side-chain. As the antibiotic is broken down in the body, it releases free NMTD, which can cause [[hypoprothrombinemia]] (likely due to inhibition of the enzyme [[vitamin K epoxide reductase]]) and a reaction with ethanol similar to that produced by disulfiram (Antabuse), due to inhibition of [[aldehyde dehydrogenase]].<ref>{{Cite book|title = Antibiotics, antifungals, and antivirals| vauthors = Stork CM|publisher =McGraw-Hill|year = 2006|location = New York|pages = 847}}</ref> Those with an allergy to [[side effects of penicillin|penicillin]] may develop a cross sensitivity to cefazolin.<ref>{{cite web |publisher =Vancouver Acute Pharmaceutical Sciences, Vancouver Hospital & Health Sciences Centre |date =2016 |access-date =May 19, 2017 |url =http://www.vhpharmsci.com/vhformulary/Tools/ANTIBIOTIC%20CROSS-SENSITIVITY%20CHART.pdf |title =Pharmaceutical Sciences CSU Parenteral Antibiotic Allergy cross-sensitivity chart |url-status =live |archive-url =https://web.archive.org/web/20160417213010/http://www.vhpharmsci.com/VHFormulary/Tools/ANTIBIOTIC%20CROSS-SENSITIVITY%20CHART.pdf |archive-date =April 17, 2016 }}</ref><ref name="Gonz2015">{{cite journal | vauthors = Gonzalez-Estrada A, Radojicic C | title = Penicillin allergy: A practical guide for clinicians | journal = Cleveland Clinic Journal of Medicine | volume = 82 | issue = 5 | pages = 295–300 | date = May 2015 | pmid = 25973877 | doi = 10.3949/ccjm.82a.14111 | s2cid = 6717270 | doi-access = free }}</ref>

== Mechanism of action ==

Cefazolin inhibits cell wall biosynthesis by binding [[penicillin-binding proteins]] which stops [[peptidoglycan]] synthesis. Penicillin-binding proteins are bacterial proteins that help to catalyze the last stages of peptidoglycan synthesis, which is needed to maintain the cell wall. They remove the D-[[alanine]] from the precursor of the peptidoglycan. The lack of synthesis causes the bacteria to lyse because they also continually break down their cell walls. Cefazolin is bactericidal, meaning it kills the bacteria rather than inhibiting their growth.<ref name=":0" />

==Cost==

Cefazolin is relatively inexpensive.<ref>{{cite book | vauthors = Cunha BA |title=Infectious Diseases in Critical Care Medicine |date=2009 |publisher=CRC Press |isbn=978-1-4200-9241-7 |page=506 |url=https://books.google.com/books?id=syasCQAAQBAJ&pg=PA506 |language=en}}</ref>

==Trade names==

It was initially marketed by [[GlaxoSmithKline]] under the trade name Nostof.<ref name=":3">{{Cite web|title = Cefazolin Sodium Injection | work = MedlinePlus Drug Information| publisher = U.S. National Library of Medicine | url = https://www.nlm.nih.gov/medlineplus/druginfo/meds/a682731.html |access-date = 2015-11-05|url-status = live|archive-url = https://web.archive.org/web/20151006090658/https://www.nlm.nih.gov/medlineplus/druginfo/meds/a682731.html|archive-date = 2015-10-06}}</ref>

Other trade names include: Cefacidal, Cefamezin, Cefrina, Elzogram, Faxilen, Gramaxin, Kefol, Kefzol, Kefzolan, Kezolin, Novaporin, Reflin, Zinol, and Zolicef.

== References ==

== External links ==

* [https://medlineplus.gov/druginfo/meds/a682731.html MedlinePlus Drug Information: Cefazolin Sodium Injection.]

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