Ceftolozane/tazobactam

Ceftolozane/tazobactam
Clinical data
Trade names	Zerbaxa (with tazobactam)
Routes of; administration	Intravenous
ATC code	J01DI54 (WHO) (combination with β-lactamase inhibitor);
Legal status
Legal status	Approved US January 2015;
Identifiers
	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;
CAS Number	689293-68-3 ;
PubChem CID	53234134;
ChemSpider	25999973;
CompTox Dashboard (EPA)	DTXSID901031217 ;
Chemical and physical data
Formula	C23H30N12O8S2
Molar mass	666.689 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC(C)(C(=O)O)O/N=C(/c1nc(sn1)N)\C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C[n+]4cc(c(n4C)N)NC(=O)NCCN)C(=O)[O-];
	InChI InChI=1S/C23H30N12O8S2/c1-23(2,20(40)41)43-31-11(15-30-21(26)45-32-15)16(36)29-12-17(37)35-13(19(38)39)9(8-44-18(12)35)6-34-7-10(14(25)33(34)3)28-22(42)27-5-4-24/h7,12,18,25H,4-6,8,24H2,1-3H3,(H7,26,27,28,29,30,32,36,38,39,40,41,42)/b31-11-/t12-,18-/m1/s1; Key:JHFNIHVVXRKLEF-DCZLAGFPSA-N;

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

^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.{{cite journal}}: CS1 maint: numeric names: authors list (link)
^ http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427534.htm
^ "www.accessdata.fda.gov" (PDF).

[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.{{cite journal}}: CS1 maint: numeric names: authors list (link)

[7] ttp://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427534.htm

[8] "www.accessdata.fda.gov" (PDF).

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