Cefoperazone Dihydrate

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H27N9O8S2.2H2O
Molecular Weight	681.698
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.O.[H][C@]12SCC(CSC3=NN=NN3C)=C(N1C(=O)[C@H]2NC(=O)[C@H](NC(=O)N4CCN(CC)C(=O)C4=O)C5=CC=C(O)C=C5)C(O)=O

InChI

InChIKey=OMYIZCZQILAOGB-BYLXUVCXSA-N

InChI=1S/C25H27N9O8S2.2H2O/c1-3-32-8-9-33(21(39)20(32)38)24(42)27-15(12-4-6-14(35)7-5-12)18(36)26-16-19(37)34-17(23(40)41)13(10-43-22(16)34)11-44-25-28-29-30-31(25)2;;/h4-7,15-16,22,35H,3,8-11H2,1-2H3,(H,26,36)(H,27,42)(H,40,41);2*1H2/t15-,16-,22-;;/m1../s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050551s043lbl.pdf
Curator's Comment: description was created based on several sources, including: http://www.rxlist.com/cefobid-drug.htm

Cefoperazone (marketed under the name Cefobid) is a third-generation cephalosporin antibiotic. Cefoperazone has a broad spectrum of activity: Respiratory Tract Infections caused by S. pneumoniae, H. influenzae, S. aureus (penicillinase and non-penicillinase producing strains), S. pyogenes (Group A beta-hemolytic streptococci), P. aeruginosa, Klebsiella pneumoniae, E. coli, Proteus mirabilis, and Enterobacter species. Peritonitis and Other Intra-abdominal Infections caused by E. coli, P. aeruginosa, and anaerobic gram-negative bacilli (including Bacteroides fragilis). Bacterial Septicemia caused by S. pneumoniae, S. agalactiae, S. aureus, Pseudomonas aeruginosa, E. coli, Klebsiella spp., Klebsiella pneumoniae, Proteus species (indole-positive and indole-negative), Clostridium spp. and anaerobic gram-positive cocci. Infections of the Skin and Skin Structures caused by S. aureus (penicillinase and non-penicillinase producing strains), S. pyogenes, and P. aeruginosa. Pelvic Inflammatory Disease, Endometritis, and Other Infections of the Female Genital Tract caused by N. gonorrhoeae, S. epidermidis, S. agalactiae, E. coli, Clostridium spp., Bacteroides species (including Bacteroides fragilis), and anaerobic gram-positive cocci. Cefobid has no activity against Chlamydia trachomatis. Therefore, when Cefobid is used in the treatment of patients with pelvic inflammatory disease and C. trachomatis is one of the suspected pathogens, appropriate anti-chlamydial coverage should be added. Urinary Tract Infections caused by Escherichia coli and Pseudomonas aeruginosa. Cefoperazone, a third-generation cephalosporin, interferes with cell wall synthesis by binding to the penicillin-binding proteins (PBPs), thus preventing cross-linking of nascent peptidoglycan. Cefoperazone is stable to penicillinases and has a high degree of stability to many beta-lactamases produced by gram-negative bacteria. When tested in vitro, cefoperazone has demonstrated synergistic interactions with aminoglycosides against gram-negative bacilli. As with all cephalosporins, hypersensitivity manifested by skin reactions or drug fever. Reversible neutropenia may occur with prolonged administration. Diarrhea or loose stools has been reported also.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bacterial penicillin-binding protein 233 Target ID: CHEMBL2354204 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6448021	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Respiratory tract infections 85 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050551s043lbl.pdf	Curative	Approved 8429	CEFOBID Approved Use Respiratory Tract Infections caused by S. pneumoniae, H. influenzae, S. aureus (penicillinase and non-penicillinase producing strains), S. pyogenes* (Group A beta-hemolytic streptococci), P. aeruginosa, Klebsiella pneumoniae, E. coli, Proteus mirabilis, and Enterobacter species. Launch Date 1982
Peritonitis and other intra-abdominal infections 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050551s043lbl.pdf	Curative	Approved 8429	CEFOBID Approved Use Peritonitis and Other Intra-abdominal Infections caused by E. coli, P. aeruginosa,* and anaerobic gram-negative bacilli (including Bacteroides fragilis). Launch Date 1982
Sepsis 71 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050551s043lbl.pdf	Curative	Approved 8429	CEFOBID Approved Use Bacterial Septicemia caused by S. pneumoniae, S. agalactiae, S. aureus, Pseudomonas aeruginosa, E. coli, Klebsiella spp., Klebsiella pneumoniae, Proteus species (indole-positive and indole-negative), Clostridium spp. and anaerobic gram-positive cocci. Launch Date 1982
Skin and skin structure infections 80 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050551s043lbl.pdf	Curative	Approved 8429	CEFOBID Approved Use Infections of the Skin and Skin Structures caused by S. aureus (penicillinase and non-penicillinase producing strains), S. pyogenes,* and P. aeruginosa. Launch Date 1982
Pelvic inflammatory disease 12 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050551s043lbl.pdf	Curative	Approved 8429	CEFOBID Approved Use Pelvic Inflammatory Disease, Endometritis, and Other Infections of the Female Genital Tract caused by N. gonorrhoeae, S. epidermidis, S. agalactiae, E. coli, Clostridium spp., Bacteroides species (including Bacteroides fragilis), and anaerobic gram-positive cocci. Launch Date 1982
Urinary tract infections 205 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050551s043lbl.pdf	Curative	Approved 8429	CEFOBID Approved Use Urinary Tract Infections caused by Escherichia coli and Pseudomonas aeruginosa. Launch Date 1982

C_max

Value	Dose	Co-administered	Analyte	Population
154.9 mg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3619425	1 g single, intravenous dose: 1 g route of administration: Intravenous experiment type: SINGLE co-administered:		CEFOPERAZONE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
221.8 mg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3619425	2 g single, intravenous dose: 2 g route of administration: Intravenous experiment type: SINGLE co-administered:		CEFOPERAZONE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
211.62 mg × h/L per 1.73 m² EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3619425	1 g single, intravenous dose: 1 g route of administration: Intravenous experiment type: SINGLE co-administered:	CEFOPERAZONE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
421.63 mg × h/L per 1.73 m² EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3619425	2 g single, intravenous dose: 2 g route of administration: Intravenous experiment type: SINGLE co-administered:	CEFOPERAZONE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1147.5 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6644441	100 mg/kg 3 times / day multiple, intravenous dose: 100 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	CEFOPERAZONE serum	Homo sapiens population: UNHEALTHY age: NEWBORN sex: UNKNOWN food status: UNKNOWN
541.2 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6644441	50 mg/kg 3 times / day multiple, intravenous dose: 50 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	CEFOPERAZONE serum	Homo sapiens population: UNHEALTHY age: NEWBORN sex: UNKNOWN food status: UNKNOWN
761.7 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6644441	100 mg/kg single, intravenous dose: 100 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	CEFOPERAZONE serum	Homo sapiens population: UNHEALTHY age: NEWBORN sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
1.649 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3619425	1 g single, intravenous dose: 1 g route of administration: Intravenous experiment type: SINGLE co-administered:	CEFOPERAZONE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.044 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3619425	2 g single, intravenous dose: 2 g route of administration: Intravenous experiment type: SINGLE co-administered:	CEFOPERAZONE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.063 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6644441	100 mg/kg 3 times / day multiple, intravenous dose: 100 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	CEFOPERAZONE serum	Homo sapiens population: UNHEALTHY age: NEWBORN sex: UNKNOWN food status: UNKNOWN
0.185 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6644441	50 mg/kg 3 times / day multiple, intravenous dose: 50 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	CEFOPERAZONE serum	Homo sapiens population: UNHEALTHY age: NEWBORN sex: UNKNOWN food status: UNKNOWN
0.063 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6644441	100 mg/kg single, intravenous dose: 100 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	CEFOPERAZONE serum	Homo sapiens population: UNHEALTHY age: NEWBORN sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT4 146 OAT1 599 OAT2 145 OAT3 642	P-gp 1537 OATP1B3 350 BCRP 561

Drug as perpetrator

Target	Modality	Activity
OAT2 147	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [IC50 1330 uM]
OAT3 644	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [Ki 1890 uM]
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [Ki 210 uM]
OAT4 146	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [Ki 2800 uM]

Drug as victim

Target	Modality	Activity
BCRP 561	substrate 3367 Sources: https://link.springer.com/article/10.1007/s11095-015-1641-2 Page: 5.0	yes
OATP1B3 350	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21372390/	yes
P-gp 1537	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679430/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3493	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3493
ChemicalBook	CB4752040	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4752040
MolPort	MolPort-006-069-122	https://www.molport.com/shop/molecule-link/MolPort-006-069-122
Selleck Chemicals	cefoperazone-cefobid	http://www.selleckchem.com/products/cefoperazone-cefobid.html
ZINC	ZINC000003830432	http://zinc15.docking.org/substances/ZINC000003830432
eMolecules	3715751	https://www.emolecules.com/cgi-bin/more?vid=3715751

PubMed

Title	Date	PubMed
[The clinical investigation of bacteriology of chronic suppurative otitis media].	2001 Dec	12541726
[Determination of unbound concentration of drug in drug-human serum albumin mixture by high performance frontal analysis].	2001 Jul	12545492
[Characterization of cefoperazone resistance gene on plasmid pFC in E. coli HX88108].	2001 Mar	12733347
Rat renal organic anion transporter rOAT1 mediates transport of urinary-excreted cephalosporins, but not of biliary-excreted cefoperazone.	2002	15618660
[Complex detoxication therapy in obstructive jaundice of tumor genesis].	2002	12669551
The importance of pets as reservoirs of resistant Enterococcus strains, with special reference to vancomycin.	2002 Aug	12241027
[A control study on bacterial resistance and clinical features of lower respiratory tract infection with Pseudomonas aeruginosa in medical intensive care unit and general ward].	2002 Dec	12654234
First occurrence of transferable extended-spectrum beta-lactamase hydrolyzing cefoperazone in multiresistant nosocomial strains of Klebsiella pneumoniae from two hospitals in Czech and Slovak Republics.	2002 Oct	12462425
Antimicrobial susceptibility of major pathogens of orofacial odontogenic infections to 11 beta-lactam antibiotics.	2002 Oct	12354209
[Efficacy and safety of cefoperazone/sulbactam in the treatment of children with mucoviscidosis during exacerbation of the bronchopulmonary process].	2003	15176099
[Comparative clinical and epidemiological evaluation of beta-lactam antibiotics in the treatment of intraabdominal infections].	2003	12914120
[Yearly changes in antibacterial activities of cefozopran against various clinical isolates between 1996 and 2001--II. Gram-negative bacteria].	2003 Aug	14567255
Carbapenem-resistant Pseudomonas aeruginosa-carrying VIM-2 metallo-beta-lactamase determinants, Croatia.	2003 Aug	12971373
The status of drug resistance and ampC gene expression in Enterobacter cloacae.	2003 Aug	12935420
[Surveillance of susceptibility of clinical isolates to cefmetazole between 2000 and 2002].	2003 Dec	15007873
[Current data on antibiotic resistance of the most important bovine mastitis pathogens in Switzerland].	2003 Dec	14725183
Detection limits of antimicrobials in ewe milk by delvotest photometric measurements.	2003 Feb	12647952
[Comparative analysis of the effectiveness and costs of azithromycin and cefoperazone treatment of patients during COPD exacerbation].	2003 Jan	12712826
Current status of drug resistance among gram-negative bacilli isolated from admitted cases in a tertiary care centre.	2003 Jan	12693450
Specific determination of unbound oxacillin in protein solution with cefoperazone by high-performance frontal analysis with chemiluminescence detection.	2003 Jan	12583007
[Activity of fourth generation cephalosporins against clinical isolates of Enterobacteriaceae].	2003 Jul-Sep	14756068
Emergence of ceftriaxone-resistant Salmonella isolates and rapid spread of plasmid-encoded CMY-2-like cephalosporinase, Taiwan.	2003 Mar	12643826
[Changes of antimicrobial resistance among nonfermenting gram-negative bacilli isolated from intensive care units from 1994 to 2001 in China].	2003 Mar 10	12820914
Interaction of human and rat organic anion transporter 2 with various cephalosporin antibiotics.	2003 Mar 28	12650826
Retrospective analysis of antibiotic susceptibility patterns of respiratory isolates of Pseudomonas aeruginosa in a Turkish University Hospital.	2003 Mar 7	12665428
[Assay of Acinetobacter SPP drug-resistance by Kirby-Bauer and Etest method].	2003 May	12754133
Preoperative antimicrobial administration for prevention of postoperative infection in patients with laparoscopic cholecystectomy.	2003 Oct	14627340
The susceptibility of non-fermentative Gram-negative bacilli to cefperazone and sulbactam compared with other antibacterial agents.	2003 Oct	14522108
Square-wave voltammetric determination of cefoperazone in a bacterial culture, pharmaceutical drug, milk, and urine.	2003 Sep	12898110
[Clinical and bacteriological substantiation of the use of cefoperazone/sulbactam in complex therapy of patients with pyo-destructive forms of lower respiratory tract infection (LRTI)].	2004	15628799
Double-disk synergy test positivity in Stenotrophomonas maltophilia clinical strains.	2004	15114869
[Changes in plasma levels of LPS, TNFalpha and IL-6 in burn patients with severe infection treated with Imipenem or Cefoperazone].	2004 Apr	15312472
Pacemaker lead endocarditis caused by Achromobacter xylosoxidans.	2004 Apr	15082906
Flies and Campylobacter infection of broiler flocks.	2004 Aug	15496257
External decontamination of wild leeches with hypochloric acid.	2004 Aug 25	15329153
Effective antibiotic regime for postoperative acute cholangitis in biliary atresia--an evolving scene.	2004 Dec	15616934
Amebic liver abscess, Mirizzi syndrome, and acute hepatic failure.	2004 Feb	15104375
Isolation and characterisation of Arcobacter butzleri from meat.	2004 Feb 15	14967558
[Study of resistance mechanism on cefotaxime resistant Proteus mirabilis isolated from clinical specimens and its clinical background].	2004 Jan	15103887
Separation of cefoperazone enantiomers using beta-cyclodextrin as chiral additive by capillary zone electrophoresis.	2004 Jan	14628298
Comparison in a rat thigh abscess model of imipenem, meropenem and cefoperazone-sulbactam against Acinetobacter baumannii strains in terms of bactericidal efficacy and resistance selection.	2004 Jan 8	14713318
Antibiotic susceptibility of coagulase-negative staphylococci isolated from goats' milk.	2004 Jun	15194138
In vitro activities of beta-lactam antibiotics alone and in combination with sulbactam against Gram-negative bacteria.	2004 Jun	15194130
In vitro activity of cefepime and cefpirome compared to other third-generation cephem antibiotics against gram-negative nosocomial pathogens.	2004 Nov	15587586
[Comparison of efficacy between ceftriaxone and cefoperazone plus sulbactam in peri-operative treatment of acute suppurative cholangitis].	2004 Nov 17	15631798
Pharmacokinetics of quinacrine in the treatment of prion disease.	2004 Nov 29	15569390
Arcobacter species in humans.	2004 Oct	15504280
Acute interstitial nephritis due to cefoperazone.	2004 Sep	15213314
[Survey of the utilization and adverse effects of antibacterial drugs in patients admitted for respiratory diseases].	2005 Feb	15699017
[Distribution and drug-resistance of 3 500 gram-negative bacteria in Guangzhou].	2005 Feb	15698988

Patents

Sample Use Guides

In Vivo Use Guide

The usual adult daily dose is 2 to 4 grams per day administered in equally divided doses every 12 hours. In severe infections or infections caused by less sensitive organisms, the total daily dose and/or frequency may be increased. Patients have been successfully treated with a total daily dosage of 6–12 grams divided into 2, 3 or 4 administrations ranging from 1.5 to 4 grams per dose. When treating infections caused by Streptococcus pyogenes, therapy should be continued for at least 10 days.

Route of Administration: Other

In Vitro Use Guide

MIC90 of cefoperazone against S. marcescens, E. cloacae, ESBL-K. pneumoniae and A. baumannii were >128 mg/L.

Name

Type

Language

Cefoperazone Dihydrate

Common Name

English

(6R,7R)-7-[(R)-2-(4-Ethyl-2,3-dioxo-1-piperazinecarboxamido)-2-(4-hydroxyphenyl)acetamido]-3-{[(1-methyl-1H-tetrazol-5-yl)thio]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid dihydrate

Systematic Name

English

5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[[(2R)-2-[[(4-ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino]-2-(4-hydroxyphenyl)acetyl]amino]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-8-oxo-, hydrate (1:2), (6R,7R)-

Systematic Name

English

5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[[[[(4-ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino](4-hydroxyphenyl)acetyl]amino]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-8-oxo-, dihydrate, [6R-[6α,7β(R*)]]-

Systematic Name

English

Code System Code Type Description

RS_ITEM_NUM

1097705