Ceftazidime

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Ceftazidime
Ceftazidime.svg
Ceftazidime-from-xtal-3D-bs-17.png
Clinical data
Pronunciation /sɛfˈtæzɪdiːm/
sef-TAZ-i-deem
Trade names Fortaz, Tazicef, others [1]
AHFS/Drugs.com Monograph
MedlinePlus a686007
License data
Pregnancy
category
  • AU:B1
Routes of
administration 		Intravenous, intramuscular, inhalation
Drug class Third-generation cephalosporin
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 91% (IM)
Metabolism negligible
Elimination half-life 1.6–2 hours
Excretion 90–96% kidney
Identifiers
  • (6R,7R,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
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.069.720 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C22H22N6O7S2
Molar mass 546.57 g·mol−1
3D model (JSmol)
  • 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
  • InChI=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 Yes check.svgY
  • Key:ORFOPKXBNMVMKC-DWVKKRMSSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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. [1] [5] Specifically it is used for joint infections, meningitis, pneumonia, sepsis, urinary tract infections, malignant otitis externa, Pseudomonas aeruginosa infection, and vibrio infection. [1] It is given by injection into a vein, muscle, or eye. [1] [6]

Contents

Common side effects include nausea, allergic reactions, and pain at the site of injection. [1] Other side effects may include Clostridioides difficile diarrhea. [1] It is not recommended in people who have had previous anaphylaxis to a penicillin. [1] Its use is relatively safe during pregnancy and breastfeeding. [7] It is in the third-generation cephalosporin family of medications and works by interfering with the bacteria's cell wall. [1]

Ceftazidime was patented in 1978 and came into commercial use in 1984. [8] It is on the World Health Organization's List of Essential Medicines. [9] Ceftazidime is available as a generic medication. [1]

Medical uses

Ceftazidime is used to treat lower respiratory tract, skin, urinary tract, blood-stream, joint, and abdominal infections, and meningitis. [10]

Ceftazidime is the first-line treatment for the tropical infection, melioidosis, an important cause of sepsis in Asia and Australia. [11] [12]

Labeled indications include the treatment of patients with:

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. [14] However, ceftazidime is less effective for S. aureus than first and second generation cephalosporins. [15] Also, cephalosporins until fifth generation are not active against methicillin-resistant Staphylococcus aureus. [16]

Spectrum of activity

Clinically relevant organisms against which ceftazidime has activity include:

Ceftazidime generally has poor efficacy against anaerobes, such as Bacteroides spp. [10] [17]

The following represents MIC susceptibility data for a few clinically significant pathogens:

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. [10]

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%). [13]

Contraindications

Ceftazidime is contraindicated in people with a known allergy to ceftazidime or to any other cephalosporin antibiotic. [10]

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. [13] No dose adjustment is needed for those with liver disease.[ citation needed ]

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. [10]

Mechanism of action

Third-generation cephalosporins differ from earlier generations in the presence of a C=N-OCH3 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. [19]

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.[ citation needed ]

See also

Related Research Articles

<span class="mw-page-title-main">Beta-lactamase</span> Class of enzymes

Beta-lactamases (β-lactamases) are enzymes produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems (ertapenem), although carbapenems are relatively resistant to beta-lactamase. Beta-lactamase provides antibiotic resistance by breaking the antibiotics' structure. These antibiotics all have a common element in their molecular structure: a four-atom ring known as a beta-lactam (β-lactam) ring. Through hydrolysis, the enzyme lactamase breaks the β-lactam ring open, deactivating the molecule's antibacterial properties.

<span class="mw-page-title-main">Cephalosporin</span> Class of pharmaceutical drugs

The cephalosporins are a class of β-lactam antibiotics originally derived from the fungus Acremonium, which was previously known as Cephalosporium.

<span class="mw-page-title-main">Aztreonam</span> Chemical compound

Aztreonam, sold under the brand name Azactam among others, is an antibiotic used primarily to treat infections caused by gram-negative bacteria such as Pseudomonas aeruginosa. This may include bone infections, endometritis, intra abdominal infections, pneumonia, urinary tract infections, and sepsis. It is given by intravenous or intramuscular injection or by inhalation.

<span class="mw-page-title-main">Cefazolin</span> Antibiotic medication

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.

<span class="mw-page-title-main">Ceftriaxone</span> Antibiotic medication

Ceftriaxone, sold under the brand name Rocephin, is a third-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections. These include middle ear infections, endocarditis, meningitis, pneumonia, bone and joint infections, intra-abdominal infections, skin infections, urinary tract infections, gonorrhea, and pelvic inflammatory disease. It is also sometimes used before surgery and following a bite wound to try to prevent infection. Ceftriaxone can be given by injection into a vein or into a muscle.

<span class="mw-page-title-main">Amoxicillin/clavulanic acid</span> Combination antibiotic medication

Amoxicillin/clavulanic acid, also known as co-amoxiclav or amox-clav, sold under the brand name Augmentin, among others, is an antibiotic medication used for the treatment of a number of bacterial infections. It is a combination consisting of amoxicillin, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor. It is specifically used for otitis media, streptococcal pharyngitis, pneumonia, cellulitis, urinary tract infections, and animal bites. It is taken by mouth or by injection into a vein.

<span class="mw-page-title-main">Piperacillin</span> Antibiotic medication

Piperacillin is a broad-spectrum β-lactam antibiotic of the ureidopenicillin class. The chemical structure of piperacillin and other ureidopenicillins incorporates a polar side chain that enhances penetration into Gram-negative bacteria and reduces susceptibility to cleavage by Gram-negative beta lactamase enzymes. These properties confer activity against the important hospital pathogen Pseudomonas aeruginosa. Thus piperacillin is sometimes referred to as an "anti-pseudomonal penicillin".

<span class="mw-page-title-main">Carbapenem</span> Class of highly effective antibiotic agents

Carbapenems are a class of very effective antibiotic agents most commonly used for treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. Similar to penicillins and cephalosporins, carbapenems are members of the beta-lactam antibiotics drug class, which kill bacteria by binding to penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis. However, these agents individually exhibit a broader spectrum of activity compared to most cephalosporins and penicillins. Furthermore, carbapenems are typically unaffected by emerging antibiotic resistance, even to other beta-lactams.

<span class="mw-page-title-main">Cefepime</span> Fourth-generation Cephalosporin Antibiotic

Cefepime is a fourth-generation cephalosporin antibiotic. Cefepime has an extended spectrum of activity against Gram-positive and Gram-negative bacteria, with greater activity against both types of organism than third-generation agents. A 2007 meta-analysis suggested when data of trials were combined, mortality was increased in people treated with cefepime compared with other β-lactam antibiotics. In response, the U.S. Food and Drug Administration (FDA) performed their own meta-analysis which found no mortality difference.

<span class="mw-page-title-main">Cefotaxime</span> Chemical compound

Cefotaxime is an antibiotic used to treat several bacterial infections in humans, other animals, and plant tissue culture. Specifically in humans it is used to treat joint infections, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, sepsis, gonorrhea, and cellulitis. It is given either by injection into a vein or muscle.

Ampicillin/sulbactam is a fixed-dose combination medication of the common penicillin-derived antibiotic ampicillin and sulbactam, an inhibitor of bacterial beta-lactamase. Two different forms of the drug exist. The first, developed in 1987 and marketed in the United States under the brand name Unasyn, generic only outside the United States, is an intravenous antibiotic. The second, an oral form called sultamicillin, is marketed under the brand name Ampictam outside the United States, and generic only in the United States. Ampicillin/sulbactam is used to treat infections caused by bacteria resistant to beta-lactam antibiotics. Sulbactam blocks the enzyme which breaks down ampicillin and thereby allows ampicillin to attack and kill the bacteria.

<span class="mw-page-title-main">Cefoxitin</span> Chemical compound

Cefoxitin is a second-generation cephamycin antibiotic developed by Merck & Co., Inc. from Cephamycin C in the year following its discovery, 1972. It was synthesized in order to create an antibiotic with a broader spectrum. It is often grouped with the second-generation cephalosporins. Cefoxitin requires a prescription and as of 2010 is sold under the brand name Mefoxin by Bioniche Pharma, LLC. The generic version of cefoxitin is known as cefoxitin sodium.

β-Lactamase inhibitor Drugs that inhibit β-Lactamase enzymes

Beta-lactamases are a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. In bacterial resistance to beta-lactam antibiotics, the bacteria have beta-lactamase which degrade the beta-lactam rings, rendering the antibiotic ineffective. However, with beta-lactamase inhibitors, these enzymes on the bacteria are inhibited, thus allowing the antibiotic to take effect. Strategies for combating this form of resistance have included the development of new beta-lactam antibiotics that are more resistant to cleavage and the development of the class of enzyme inhibitors called beta-lactamase inhibitors. Although β-lactamase inhibitors have little antibiotic activity of their own, they prevent bacterial degradation of beta-lactam antibiotics and thus extend the range of bacteria the drugs are effective against.

<span class="mw-page-title-main">Cefodizime</span> Chemical compound

Cefodizime is a 3rd generation cephalosporin antibiotic with broad spectrum activity against aerobic gram positive and gram negative bacteria. Clinically, it has been shown to be effective against upper and lower respiratory tract infections, urinary tract infections, and gonorrhea. Cefodizime is a bactericidal antibiotic that targets penicillin-binding proteins (PBPs) 1A/B, 2, and 3 resulting in the eventual death of the bacterial cell. In vivo experimental models of infection showed that bacterial clearance by this drug is at least as effective compared with other 3rd generation cephalosporins. It has similar adverse effect profile to other 3rd generation cephalosporins as well, mainly being limited to gastrointestinal or dermatological side effects.

<span class="mw-page-title-main">Avibactam</span> Chemical compound

Avibactam is a non-β-lactam β-lactamase inhibitor developed by Actavis jointly with AstraZeneca. A new drug application for avibactam in combination with ceftazidime was approved by the FDA in 2015 for treating complicated urinary tract (cUTI) and complicated intra-abdominal infections (cIAI) caused by antibiotic-resistant pathogens, including those caused by multidrug resistant Gram-negative bacterial pathogens.

<span class="mw-page-title-main">Ceftolozane/tazobactam</span> Antibiotic

Ceftolozane/tazobactam, sold under the brand name Zerbaxa, (Merck) is a fixed-dose combination antibiotic medication used for the treatment of complicated urinary tract infections and complicated intra-abdominal infections in adults. Ceftolozane is a cephalosporin antibiotic, developed for the treatment of infections with gram-negative bacteria that are resistant to conventional antibiotics. It was studied for urinary tract infections, intra-abdominal infections and ventilator-associated bacterial pneumonia.

<span class="mw-page-title-main">Ceftazidime/avibactam</span> Combination antibiotic medication

Ceftazidime/avibactam, sold under the brand name Avycaz among others, is a fixed-dose combination medication composed of ceftazidime, a cephalosporin antibiotic, and avibactam, a β-lactamase inhibitor. It is used to treat complicated intra-abdominal infections, urinary tract infections, and pneumonia. It is only recommended when other options are not appropriate. It is given by infusion into a vein.

Meropenem/vaborbactam, sold under the brand name Vabomere among others, is a combination medication used to treat complicated urinary tract infections, complicated abdominal infections, and hospital-acquired pneumonia. It contains meropenem, a beta-lactam antibiotic, and vaborbactam, a beta-lactamase inhibitor. It is given by injection into a vein.

<span class="mw-page-title-main">Cefiderocol</span> Antibiotic

Cefiderocol, sold under the brand name Fetroja among others, is an antibiotic used to treat complicated urinary tract infections when no other options are available. It is indicated for the treatment of multi-drug-resistant Gram-negative bacteria including Pseudomonas aeruginosa. It is given by injection into a vein.

References

  1. 1 2 3 4 5 6 7 8 9 "Ceftazidime". The American Society of Health-System Pharmacists. Archived from the original on 20 December 2016. Retrieved 8 December 2016.
  2. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 Oct 2023.
  3. ↑ "Fortaz- ceftazidime injection, powder, for solution". DailyMed. U.S. National Library of Medicine. 28 July 2017. Archived from the original on 28 December 2021. Retrieved 12 June 2022.
  4. ↑ "Tazicef- ceftazidime injection, powder, for solution". DailyMed. U.S. National Library of Medicine. 24 March 2022. Archived from the original on 28 December 2021. Retrieved 12 June 2022.
  5. ↑ Katzung B (2019). Basic & Clinical Pharmacology (14th ed.). McGraw Hill. p. 803. ISBN   978-1-259-64115-2.
  6. ↑ Kamjoo S. "Intravitreal Injections". EyeWiki. American Academy of Ophthalmology. Archived from the original on 5 March 2021. Retrieved 12 January 2020.
  7. ↑ Hamilton R (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 87. ISBN   9781284057560.
  8. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 495. ISBN   9783527607495. Archived from the original on 2016-12-20.
  9. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  10. 1 2 3 4 5 Ceftazidime for Injection(R) [package insert]. Schaumburg, IL: Sagent; 2012. PDF of insert Archived 2014-04-23 at the Wayback Machine
  11. ↑ White NJ (May 2003). "Melioidosis". Lancet. 361 (9370): 1715–1722. doi:10.1016/S0140-6736(03)13374-0. PMID   12767750. S2CID   208790913.
  12. ↑ White NJ, Dance DA, Chaowagul W, Wattanagoon Y, Wuthiekanun V, Pitakwatchara N (September 1989). "Halving of mortality of severe melioidosis by ceftazidime". Lancet. 2 (8665): 697–701. doi:10.1016/S0140-6736(89)90768-X. PMID   2570956. S2CID   28919574.
  13. 1 2 3 "Ceftazidime". Lexicomp Online. Hudson, Ohio: Lexi-Drugs. April 2014. Archived from the original on 2014-04-23. Retrieved 2014-04-21.
  14. ↑ O'Callaghan H (1986). "Ceftazidime, a broad spectrum cephalosporin with activity against Ps. aeruginosa". Journal of Hygiene, Epidemiology, Microbiology, and Immunology. 30 (4): 449–453. PMID   3100612.
  15. ↑ Richards DM, Brogden RN (February 1985). "Ceftazidime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use". Drugs. 29 (2): 105–161. doi:10.2165/00003495-198529020-00002. PMID   3884319. S2CID   265707490.
  16. ↑ Bui T, Preuss CV (2023). "Cephalosporins". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID   31855361 . Retrieved 2023-04-13. However, what makes it unique from the rest of the cephalosporins is that it has coverage against methicillin-resistant Staphylococcus aureus (MRSA).
  17. ↑ Richards DM, Brogden RN (February 1985). "Ceftazidime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use". Drugs. 29 (2): 105–161. doi:10.2165/00003495-198529020-00002. PMID   3884319. S2CID   265707490.
  18. ↑ "Ceftazidime pentahydrate Susceptibility and Minimum Inhibitory Concentration (MIC) Data" (PDF). Toku-e. Archived from the original (PDF) on 2014-12-04.
  19. ↑ Sharma M, Pathak S, Srivastava P (October 2013). "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". J Clin Diagn Res. 7 (10): 2173–7. doi:10.7860/JCDR/2013/6460.3462. PMC   3843424 . PMID   24298468.
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