Cefazolin Explained

Cefazolin, also known as cefazoline and cephazolin, is a first-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections. Specifically it is used to treat cellulitis, urinary tract infections, pneumonia, endocarditis, joint infection, and biliary tract infections. It is also used to prevent group B streptococcal disease around the time of delivery and before surgery. It is typically given by injection into a muscle or vein.[1]

Common side effects include diarrhea, vomiting, yeast infections, and allergic reactions.[1] 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.[2] It is relatively safe for use during pregnancy and breastfeeding.[1] [3] Cefazolin is in the first-generation cephalosporin class of medication and works by interfering with the bacteria's cell wall.[1]

Cefazolin was patented in 1967 and came into commercial use in 1971.[4] [5] It is on the World Health Organization's List of Essential Medicines.[6] It is available as a generic medication.[1]

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:[7]

It can also be used peri-operatively to prevent infections post-surgery, and is often the preferred drug for surgical prophylaxis.

There is no penetration into the central nervous system and therefore cefazolin is not effective in treating meningitis.[8]

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 (MRSA). In many instances of staphylococcal infections, such as bacteremia, cefazolin is an alternative to penicillin in patients who are allergic to penicillin. However, there is still potential for a reaction to occur with cefazolin and other cephalosporins in patients allergic to penicillin. Resistance to cefazolin is seen in several species of bacteria, such as Mycoplasma and Chlamydia, in which case different generations of cephalosporins may be more effective.[9] Cefazolin does not fight against Enterococcus, anaerobic bacteria, or atypical bacteria, among others.

Bacterial susceptibility

As a first-generation cephalosporin antibiotic, cefazolin and other first-generation antibiotics are very active against gram-positive bacteria and some gram-negative bacteria. Their broad spectrum of activity can be attributed to their improved stability to many bacterial beta-lactamases compared to penicillins.

Spectrum of activity

Gram-positive aerobes:

Gram-Negative Aerobes:[10]

Non susceptible

The following are not susceptible:

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. 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.[11]

Newborns

There has been no established safety and effectiveness for use in premature infants and neonates.

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.

Additional considerations

People with kidney disease and those on hemodialysis may need the dose adjusted. Cefazolin levels are not significantly affected by liver disease.

As with other antibiotics, cefazolin may interact with other medications being taken. Some important drugs that may interact with cefazolin such as probenecid.

Side effects

Side effects associated with use of cefazolin therapy include:

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

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.[13] Those with an allergy to penicillin may develop a cross sensitivity to cefazolin.[14] [15]

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.

Cost

Cefazolin is relatively inexpensive.[16]

Trade names

It was initially marketed by GlaxoSmithKline under the trade name Nostof.[17]

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

External links

Notes and References

  1. Web site: Cefazolin Sodium. The American Society of Health-System Pharmacists. 8 December 2016.
  2. Web site: NEJM Journal Watch: Summaries of and commentary on original medical and scientific articles from key medical journals . 2023-01-20 . www.jwatch.org.
  3. Book: Hamilton R . Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. 2015. Jones & Bartlett Learning. 9781284057560. 84.
  4. Book: Fischer J, Ganellin CR . Analogue-based Drug Discovery . 2006. John Wiley & Sons. 9783527607495. 493. en . live . https://web.archive.org/web/20170910171829/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA493 . 2017-09-10.
  5. US . 3516997 . patent . 3,7-disubstituted cephalosporin compounds and preparation thereo . 1970-06-23 . 1970-06-23 . 1968-04-12 . 1967-04-15 . Takano T, Kurita M, Nikaido H, Mera M, Konishi N, Nakagawa R . Fujisawa Pharmaceutical Co Ltd .
  6. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 21st list 2019 . 2019 . 10665/325771 . World Health Organization . World Health Organization . Geneva . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO . free .
  7. Web site: DailyMed - CEFAZOLIN - cefazolin sodium injection, powder, for solution. dailymed.nlm.nih.gov. 2015-11-05. live. https://web.archive.org/web/20160306013731/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=79afc719-8279-49f9-83b0-e0736c07eb5c. 2016-03-06.
  8. Book: Trevor AJ, Katzung BG, Masters S . Basic & Clinical Pharmacology . McGraw Hill Education. 2015. 978-0-07-182505-4. New York. 776–778.
  9. Web site: Cefazolin (Injection Route). Mayo Clinic. 1 July 2015. live. https://web.archive.org/web/20140419012252/http://www.mayoclinic.org/drugs-supplements/cefazolin-injection-route/before-using/drg-20073267. 19 April 2014.
  10. Book: Beauduy C, Winston L . McGraw Hill. Basic & Clinical Pharmacology . 2021 . 15.
  11. Web site: Prevention of Perinatal Group B Streptococcal Disease. www.cdc.gov. 2015-11-05. live. https://web.archive.org/web/20151115063145/http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5910a1.htm. 2015-11-15.
  12. Web site: Cefazolin Prescribing Information. 2004. FDA. live. https://web.archive.org/web/20160304070705/http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/50461slr139_ancef_lbl.pdf. 2016-03-04.
  13. Book: Antibiotics, antifungals, and antivirals. Stork CM. McGraw-Hill. 2006. New York. 847.
  14. Web site: Vancouver Acute Pharmaceutical Sciences, Vancouver Hospital & Health Sciences Centre . 2016 . May 19, 2017 . Pharmaceutical Sciences CSU Parenteral Antibiotic Allergy cross-sensitivity chart . live . https://web.archive.org/web/20160417213010/http://www.vhpharmsci.com/VHFormulary/Tools/ANTIBIOTIC%20CROSS-SENSITIVITY%20CHART.pdf . April 17, 2016 .
  15. Gonzalez-Estrada A, Radojicic C . Penicillin allergy: A practical guide for clinicians . Cleveland Clinic Journal of Medicine . 82 . 5 . 295–300 . May 2015 . 25973877 . 10.3949/ccjm.82a.14111 . 6717270 . free .
  16. Book: Cunha BA . Infectious Diseases in Critical Care Medicine . 2009 . CRC Press . 978-1-4200-9241-7 . 506 . en.
  17. Web site: Cefazolin Sodium Injection . MedlinePlus Drug Information. U.S. National Library of Medicine . 2015-11-05. live. https://web.archive.org/web/20151006090658/https://www.nlm.nih.gov/medlineplus/druginfo/meds/a682731.html. 2015-10-06.