Ceftolozane

Ceftolozane
Systematic (IUPAC) name
(6R,7R)-3-([3-Amino-4-(2-aminoethylcarbamoylamino)-2-methylpyrazol-1-ium-1-yl]methyl)-7-([(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(2-carboxypropan-2-yloxyimino)acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
Clinical data
Trade names Zerbaxa (with tazobactam)
Routes of
administration		 Intravenous
Legal status
Legal status
  • Approved US January 2015
Identifiers
CAS Number 689293-68-3 YesY
ATC code J01DI54 (WHO) (combination with β-lactamase inhibitor)
PubChem CID 53234134
ChemSpider 25999973
Chemical data
Formula C23H30N12O8S2
Molar mass 666.689 g/mol

Ceftolozane is a 5th generation cephalosporin antibiotic, developed for the treatment of infections with gram-negative bacteria that have become resistant to conventional antibiotics.[1] It was studied for urinary tract infections, intra-abdominal infections and ventilator-associated bacterial pneumonia. Ceftolozane is combined with the β-lactamase inhibitor tazobactam, which protects ceftolozane from degradation.[2][3][4][5][6] Ceftolozane-tazobactam (trade name Zerbaxa) is indicated for the treatment of complicated urinary tract infections and complicated intra abdominal infections.[7]

Spectrum of activity

The in vitro activity of ceftolozane–tazobactam has been examined in five surveillance studies of isolates from Europe and North America.[8] In these studies, ceftolozane–tazobactam was notable for its activity against Pseudomonas aeruginosa, a moderately common cause of hospital-acquired infections that is commonly multi-drug resistant. Ninety percent of P. aeruginosa isolates were inhibited by a ceftolozane–tazobactam at a concentration of 4 μg/mL (MIC90), making it the most potent anti-pseudomonal antibiotic in clinical use.

In these same studies, ceftolozane–tazobactam exhibited MIC90 values of <1 μg/mL for Escherichia coli, Citrobacter koseri, Morganella morganii, Proteus mirabilis, Salmonella species, and Serratia marcescens. Somewhat poorer activity is observed for the Klebsiella and Enterobacter species, with the MIC90 for extended spectrum beta lactamase (ESBL) expressing Klebsiella pnueumonia being >32 μg/mL.

References

  1. ↑ Long, T. E.; Williams, J. T. (2014). "Cephalosporins currently in early clinical trials for the treatment of bacterial infections". Expert Opinion on Investigational Drugs 23 (10): 1375. doi:10.1517/13543784.2014.930127.
  2. ↑ Takeda, S; Nakai, T; Wakai, Y; Ikeda, F; Hatano, K (2007). "In vitro and in vivo activities of a new cephalosporin, FR264205, against Pseudomonas aeruginosa". Antimicrobial Agents and Chemotherapy 51 (3): 826–30. doi:10.1128/AAC.00860-06. PMC: 1803152. PMID 17145788.
  3. ↑ Toda, A; Ohki, H; Yamanaka, T; Murano, K; Okuda, S; Kawabata, K; Hatano, K; Matsuda, K; Misumi, K; Itoh, K; Satoh, K; Inoue, S (2008). "Synthesis and SAR of novel parenteral anti-pseudomonal cephalosporins: Discovery of FR264205". Bioorganic & Medicinal Chemistry Letters 18 (17): 4849–52. doi:10.1016/j.bmcl.2008.07.085. PMID 18701284.
  4. ↑ Sader, H. S.; Rhomberg, P. R.; Farrell, D. J.; Jones, R. N. (2011). "Antimicrobial activity of CXA-101, a novel cephalosporin tested in combination with tazobactam against Enterobacteriaceae, Pseudomonas aeruginosa, and Bacteroides fragilis strains having various resistance phenotypes". Antimicrobial Agents and Chemotherapy 55 (5): 2390–4. doi:10.1128/AAC.01737-10. PMC: 3088243. PMID 21321149.
  5. ↑ Craig, W. A.; Andes, D. R. (2013). "In vivo activities of ceftolozane, a new cephalosporin, with and without tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae, including strains with extended-spectrum β-lactamases, in the thighs of neutropenic mice". Antimicrobial Agents and Chemotherapy 57 (4): 1577–82. doi:10.1128/AAC.01590-12. PMC: 3623364. PMID 23274659.
  6. ↑ Zhanel, G. G.; Chung, P; Adam, H; Zelenitsky, S; Denisuik, A; Schweizer, F; Lagacé-Wiens, P. R.; Rubinstein, E; Gin, A. S.; Walkty, A; Hoban, D. J.; Lynch Jp, 3rd; Karlowsky, J. A. (2014). "Ceftolozane/tazobactam: A novel cephalosporin/β-lactamase inhibitor combination with activity against multidrug-resistant gram-negative bacilli". Drugs 74 (1): 31–51. doi:10.1007/s40265-013-0168-2. PMID 24352909.
  7. ↑ http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427534.htm
  8. ↑ "www.accessdata.fda.gov" (PDF).
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