CEFTAZIDIME DIHYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H21N6O7S2.2ClH.H
Molecular Weight	619.498
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure of CEFTAZIDIME DIHYDROCHLORIDE

Structure Search

SMILES

[H+].Cl.Cl.[H][C@]12SCC(C[N+]3=CC=CC=C3)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC(C)(C)C([O-])=O)\C4=CSC(N)=N4)C([O-])=O

InChI

InChIKey=JLZLIGALAZXURA-ZYMGEXDGSA-N

InChI=1S/C22H22N6O7S2.2ClH/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);2*1H/b26-13-;;/t14-,18-;;/m1../s1

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050578s055,050634s023lbledt.pdf

Ceftazidime is a semisynthetic, broad-spectrum, beta-lactam antibiotic, used especially for Pseudomonas and other gram-negative infections in debilitated patients. Ceftazidime is used to treat lower respiratory tract, skin, urinary tract, blood-stream, joint, and abdominal infections, and meningitis. The drug is given intravenously (IV) or intramuscularly (IM) every 8–12 hours (two or three times a day), with dose and frequency varying by the type of infection, severity, and/or renal function of the patient. Injectable formulations of ceftazidime are currently nebulized "off-label" to manage Cystic Fibrosis, non-Cystic Fibrosis bronchiectasis, drug-resistant nontuberculous mycobacterial infections, ventilator-associated pneumonia, and post-transplant airway infections. Ceftazidime is generally well-tolerated. When side effects do 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Penicillin-binding protein 1 5 Target ID: CHEMBL4268 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17470659	Inhibitor 8297
Penicillin-binding protein 1A 45 Target ID: CHEMBL1813 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8308866	Inhibitor 8297
Penicillin-binding protein 1B 22 Target ID: CHEMBL1814 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8308866	Inhibitor 8297
Penicillin-binding protein 3 7 Target ID: CHEMBL4269 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17470659	Inhibitor 8297
Penicillin-binding protein 4 5 Target ID: CHEMBL2549 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17470659	Inhibitor 8297
Penicillin-binding protein 2 24 Target ID: CHEMBL5539 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17470659	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Lower respiratory tract infections 51 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050578s055,050634s023lbledt.pdf	Curative	Approved 8429	FORTAZ Approved Use Ceftazidime for injection, USP is indicated for the treatment of patients with infections caused by susceptible strains of the designated organisms in the following diseases: Lower Respiratory Tract Infections, including pneumonia, caused by Pseudomonas aeruginosa and other Pseudomonas spp.; Haemophilus influenzae, including ampicillin-resistant strains; Klebsiella spp.; Enterobacter spp.; Proteus mirabilis; Escherichia coli; Serratia spp.; Citrobacter spp.; Streptococcus pneumoniae; and Staphylococcus aureus (methicillin-susceptible strains). Skin and Skin-Structure Infections caused by Pseudomonas aeruginosa; Klebsiella spp.; Escherichia coli; Proteus spp., including Proteus mirabilis and indole-positive Proteus; Enterobacter spp.; Serratia spp.; Staphylococcus aureus (methicillin-susceptible strains); and Streptococcus pyogenes (group A beta-hemolytic streptococci). Urinary Tract Infections, both complicated and uncomplicated, caused by Pseudomonas aeruginosa; Enterobacter spp.; Proteus spp., including Proteus mirabilis and indole-positive Proteus; Klebsiella spp.; and Escherichia coli. Bacterial Septicemia caused by Pseudomonas aeruginosa, Klebsiella spp., Haemophilus influenzae, Escherichia coli, Serratia spp., Streptococcus pneumoniae, and Staphylococcus aureus (methicillin-susceptible strains). Bone and Joint Infections caused by Pseudomonas aeruginosa, Klebsiella spp., Enterobacter spp., and Staphylococcus aureus (methicillin-susceptible strains). Gynecologic Infections, including endometritis, pelvic cellulitis, and other infections of the female genital tract caused by Escherichia coli. Intra-abdominal Infections, including peritonitis caused by Escherichia coli, Klebsiella spp., and Staphylococcus aureus (methicillin-susceptible strains) and polymicrobial infections caused by aerobic and anaerobic organisms and Bacteroides spp. (many strains of Bacteroides fragilis are resistant). Central Nervous System Infections, including meningitis, caused by Haemophilus influenzae and Neisseria meningitidis. Ceftazidime for injection, USP has also been used successfully in a limited number of cases of meningitis due to Pseudomonas aeruginosa and Streptococcus pneumoniae. Ceftazidime for injection, USP may be used alone in cases of confirmed or suspected sepsis. Ceftazidime for injection, USP has been used successfully in clinical trials as empiric therapy in cases where various concomitant therapies with other antibiotics have been used. Ceftazidime for injection, USP may also be used concomitantly with other antibiotics, such as aminoglycosides, vancomycin, and clindamycin; in severe and life-threatening infections; and in the immunocompromised patient. When such concomitant treatment is appropriate, prescribing information in the labeling for the other antibiotics should be followed. The dose depends on the severity of the infection and the patient's condition. To reduce the development of drug-resistant bacteria and maintain the effectiveness of ceftazidime for injection, USP and other antibacterial drugs, ceftazidime for injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Launch Date 1985
Skin and skin structure infections 80 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050578s055,050634s023lbledt.pdf	Curative	Approved 8429	FORTAZ Approved Use Ceftazidime for injection, USP is indicated for the treatment of patients with infections caused by susceptible strains of the designated organisms in the following diseases: Lower Respiratory Tract Infections, including pneumonia, caused by Pseudomonas aeruginosa and other Pseudomonas spp.; Haemophilus influenzae, including ampicillin-resistant strains; Klebsiella spp.; Enterobacter spp.; Proteus mirabilis; Escherichia coli; Serratia spp.; Citrobacter spp.; Streptococcus pneumoniae; and Staphylococcus aureus (methicillin-susceptible strains). Skin and Skin-Structure Infections caused by Pseudomonas aeruginosa; Klebsiella spp.; Escherichia coli; Proteus spp., including Proteus mirabilis and indole-positive Proteus; Enterobacter spp.; Serratia spp.; Staphylococcus aureus (methicillin-susceptible strains); and Streptococcus pyogenes (group A beta-hemolytic streptococci). Urinary Tract Infections, both complicated and uncomplicated, caused by Pseudomonas aeruginosa; Enterobacter spp.; Proteus spp., including Proteus mirabilis and indole-positive Proteus; Klebsiella spp.; and Escherichia coli. Bacterial Septicemia caused by Pseudomonas aeruginosa, Klebsiella spp., Haemophilus influenzae, Escherichia coli, Serratia spp., Streptococcus pneumoniae, and Staphylococcus aureus (methicillin-susceptible strains). Bone and Joint Infections caused by Pseudomonas aeruginosa, Klebsiella spp., Enterobacter spp., and Staphylococcus aureus (methicillin-susceptible strains). Gynecologic Infections, including endometritis, pelvic cellulitis, and other infections of the female genital tract caused by Escherichia coli. Intra-abdominal Infections, including peritonitis caused by Escherichia coli, Klebsiella spp., and Staphylococcus aureus (methicillin-susceptible strains) and polymicrobial infections caused by aerobic and anaerobic organisms and Bacteroides spp. (many strains of Bacteroides fragilis are resistant). Central Nervous System Infections, including meningitis, caused by Haemophilus influenzae and Neisseria meningitidis. Ceftazidime for injection, USP has also been used successfully in a limited number of cases of meningitis due to Pseudomonas aeruginosa and Streptococcus pneumoniae. Ceftazidime for injection, USP may be used alone in cases of confirmed or suspected sepsis. Ceftazidime for injection, USP has been used successfully in clinical trials as empiric therapy in cases where various concomitant therapies with other antibiotics have been used. Ceftazidime for injection, USP may also be used concomitantly with other antibiotics, such as aminoglycosides, vancomycin, and clindamycin; in severe and life-threatening infections; and in the immunocompromised patient. When such concomitant treatment is appropriate, prescribing information in the labeling for the other antibiotics should be followed. The dose depends on the severity of the infection and the patient's condition. To reduce the development of drug-resistant bacteria and maintain the effectiveness of ceftazidime for injection, USP and other antibacterial drugs, ceftazidime for injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Launch Date 1985
Urinary tract infections 205 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050578s055,050634s023lbledt.pdf	Curative	Approved 8429	FORTAZ Approved Use Ceftazidime for injection, USP is indicated for the treatment of patients with infections caused by susceptible strains of the designated organisms in the following diseases: Lower Respiratory Tract Infections, including pneumonia, caused by Pseudomonas aeruginosa and other Pseudomonas spp.; Haemophilus influenzae, including ampicillin-resistant strains; Klebsiella spp.; Enterobacter spp.; Proteus mirabilis; Escherichia coli; Serratia spp.; Citrobacter spp.; Streptococcus pneumoniae; and Staphylococcus aureus (methicillin-susceptible strains). Skin and Skin-Structure Infections caused by Pseudomonas aeruginosa; Klebsiella spp.; Escherichia coli; Proteus spp., including Proteus mirabilis and indole-positive Proteus; Enterobacter spp.; Serratia spp.; Staphylococcus aureus (methicillin-susceptible strains); and Streptococcus pyogenes (group A beta-hemolytic streptococci). Urinary Tract Infections, both complicated and uncomplicated, caused by Pseudomonas aeruginosa; Enterobacter spp.; Proteus spp., including Proteus mirabilis and indole-positive Proteus; Klebsiella spp.; and Escherichia coli. Bacterial Septicemia caused by Pseudomonas aeruginosa, Klebsiella spp., Haemophilus influenzae, Escherichia coli, Serratia spp., Streptococcus pneumoniae, and Staphylococcus aureus (methicillin-susceptible strains). Bone and Joint Infections caused by Pseudomonas aeruginosa, Klebsiella spp., Enterobacter spp., and Staphylococcus aureus (methicillin-susceptible strains). Gynecologic Infections, including endometritis, pelvic cellulitis, and other infections of the female genital tract caused by Escherichia coli. Intra-abdominal Infections, including peritonitis caused by Escherichia coli, Klebsiella spp., and Staphylococcus aureus (methicillin-susceptible strains) and polymicrobial infections caused by aerobic and anaerobic organisms and Bacteroides spp. (many strains of Bacteroides fragilis are resistant). Central Nervous System Infections, including meningitis, caused by Haemophilus influenzae and Neisseria meningitidis. Ceftazidime for injection, USP has also been used successfully in a limited number of cases of meningitis due to Pseudomonas aeruginosa and Streptococcus pneumoniae. Ceftazidime for injection, USP may be used alone in cases of confirmed or suspected sepsis. Ceftazidime for injection, USP has been used successfully in clinical trials as empiric therapy in cases where various concomitant therapies with other antibiotics have been used. Ceftazidime for injection, USP may also be used concomitantly with other antibiotics, such as aminoglycosides, vancomycin, and clindamycin; in severe and life-threatening infections; and in the immunocompromised patient. When such concomitant treatment is appropriate, prescribing information in the labeling for the other antibiotics should be followed. The dose depends on the severity of the infection and the patient's condition. To reduce the development of drug-resistant bacteria and maintain the effectiveness of ceftazidime for injection, USP and other antibacterial drugs, ceftazidime for injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Launch Date 1985
Cystic fibrosis 120 Sources: https://clinicaltrials.gov/ct2/show/NCT02504827	Primary	Phase IV 63	FORTAZ Approved Use Ceftazidime for injection, USP is indicated for the treatment of patients with infections caused by susceptible strains of the designated organisms in the following diseases: Lower Respiratory Tract Infections, including pneumonia, caused by Pseudomonas aeruginosa and other Pseudomonas spp.; Haemophilus influenzae, including ampicillin-resistant strains; Klebsiella spp.; Enterobacter spp.; Proteus mirabilis; Escherichia coli; Serratia spp.; Citrobacter spp.; Streptococcus pneumoniae; and Staphylococcus aureus (methicillin-susceptible strains). Skin and Skin-Structure Infections caused by Pseudomonas aeruginosa; Klebsiella spp.; Escherichia coli; Proteus spp., including Proteus mirabilis and indole-positive Proteus; Enterobacter spp.; Serratia spp.; Staphylococcus aureus (methicillin-susceptible strains); and Streptococcus pyogenes (group A beta-hemolytic streptococci). Urinary Tract Infections, both complicated and uncomplicated, caused by Pseudomonas aeruginosa; Enterobacter spp.; Proteus spp., including Proteus mirabilis and indole-positive Proteus; Klebsiella spp.; and Escherichia coli. Bacterial Septicemia caused by Pseudomonas aeruginosa, Klebsiella spp., Haemophilus influenzae, Escherichia coli, Serratia spp., Streptococcus pneumoniae, and Staphylococcus aureus (methicillin-susceptible strains). Bone and Joint Infections caused by Pseudomonas aeruginosa, Klebsiella spp., Enterobacter spp., and Staphylococcus aureus (methicillin-susceptible strains). Gynecologic Infections, including endometritis, pelvic cellulitis, and other infections of the female genital tract caused by Escherichia coli. Intra-abdominal Infections, including peritonitis caused by Escherichia coli, Klebsiella spp., and Staphylococcus aureus (methicillin-susceptible strains) and polymicrobial infections caused by aerobic and anaerobic organisms and Bacteroides spp. (many strains of Bacteroides fragilis are resistant). Central Nervous System Infections, including meningitis, caused by Haemophilus influenzae and Neisseria meningitidis. Ceftazidime for injection, USP has also been used successfully in a limited number of cases of meningitis due to Pseudomonas aeruginosa and Streptococcus pneumoniae. Ceftazidime for injection, USP may be used alone in cases of confirmed or suspected sepsis. Ceftazidime for injection, USP has been used successfully in clinical trials as empiric therapy in cases where various concomitant therapies with other antibiotics have been used. Ceftazidime for injection, USP may also be used concomitantly with other antibiotics, such as aminoglycosides, vancomycin, and clindamycin; in severe and life-threatening infections; and in the immunocompromised patient. When such concomitant treatment is appropriate, prescribing information in the labeling for the other antibiotics should be followed. The dose depends on the severity of the infection and the patient's condition. To reduce the development of drug-resistant bacteria and maintain the effectiveness of ceftazidime for injection, USP and other antibacterial drugs, ceftazidime for injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Launch Date 1985

AUC

Value	Dose	Analyte	Population
21.3 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2088186	75 mg/kg other, intravenous dose: 75 mg/kg route of administration: Intravenous experiment type: OTHER co-administered:	CEFTAZIDIME serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
18 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2088186	75 mg/kg 1 times / day other, intravenous dose: 75 mg/kg route of administration: Intravenous experiment type: OTHER co-administered:	CEFTAZIDIME unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
285 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2088186	25 mg/kg 3 times / day multiple, intravenous dose: 25 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	CEFTAZIDIME serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
9.6 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2088186	25 mg/kg 3 times / day multiple, intravenous dose: 25 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:		CEFTAZIDIME serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
1 g 3 times / day multiple, intravenous Highest studied dose Dose: 1 g, 3 times / day Route: intravenous Route: multiple Dose: 1 g, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/050578s061,050634s028lbl.pdf	unhealthy, adult n = 1 Health Status: unhealthy Condition: pneumonia Age Group: adult Sex: unknown Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/050578s061,050634s028lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/050578s061,050634s028lbl.pdf
300 mg/kg 14 times / day multiple, intravenous Highest studied dose Dose: 300 mg/kg, 14 times / day Route: intravenous Route: multiple Dose: 300 mg/kg, 14 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8821302/	unhealthy, children n = 15 Health Status: unhealthy Condition: cystic fibrosis Age Group: children Sex: unknown Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/8821302/	Other AEs: Urticaria, Itchy rash... Other AEs: Urticaria (3 patients) Itchy rash (4 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/8821302/

AEs

AE	Significance	Dose	Population
Urticaria	3 patients	300 mg/kg 14 times / day multiple, intravenous Highest studied dose Dose: 300 mg/kg, 14 times / day Route: intravenous Route: multiple Dose: 300 mg/kg, 14 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8821302/	unhealthy, children n = 15 Health Status: unhealthy Condition: cystic fibrosis Age Group: children Sex: unknown Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/8821302/
Itchy rash	4 patients	300 mg/kg 14 times / day multiple, intravenous Highest studied dose Dose: 300 mg/kg, 14 times / day Route: intravenous Route: multiple Dose: 300 mg/kg, 14 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8821302/	unhealthy, children n = 15 Health Status: unhealthy Condition: cystic fibrosis Age Group: children Sex: unknown Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/8821302/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	inhibitor 1767		inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 BCRP 699 OATP1B1 788 OATP1B3 706 OCT1 512 OCT2 647 OAT1 599 OAT3 642 MRP3 157 BSEP 402	CYP1A2 1054 CYP2B6 664 UGT1A1 418 P-gp 1537 BCRP 561 OATP1B1 406 OATP1B3 350 OCT1 327 OCT2 355 OAT1 326 OAT3 339 MRP3 50 BSEP 52	CYP 76

Drug as perpetrator

Target	Modality	Activity
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	no
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	no
CYP 147	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000CllinPharmR.pdf Page: 38.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 14.0	no
MRP3 207	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	no
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	no
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	no

Drug as victim

Target	Modality	Activity
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	inconclusive
BSEP 52	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	inconclusive
MRP3 50	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	inconclusive
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	inconclusive
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	inconclusive
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	inconclusive
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	inconclusive
OCT1 327	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	inconclusive
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	inconclusive
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	inconclusive
UGT1A1 418	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	inconclusive
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	no
CYP2B6 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	no
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 15.0	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf Page: 18.0

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00IKZD
A2B Chem	AI66201
AK Scientific	9619AJ
AK Scientific	E115
AK Scientific	G174
AbovChem LLC	HY-B0593
Alfa Chemistry	223351
Alfa Chemistry	ACM73547703
Angene	AGN-PC-0WHB0Y
ApexBio Technology	B3539
AstaTech	42417
AstaTech	42446
AstaTech	C16303
BOC Sciences	72558-82-8
BOC Sciences	78439-06-2
Bide Pharmatech	BD120321
BioSynth	Q-200813
Bosche Scientific	C2791
Cayman Chemical	14828
Chem Scene	CS-2810
Chem-Impex International	2879
Compound Cloud	5481173
Compound Cloud	6321415
Compound Cloud	6536864
Hairui	HR126019
Hairui	HR127562
Hairui	HR131790
Hangzhou APIChem Technology	AC-18971
Hangzhou APIChem Technology	AC-18972
Hangzhou Yuhao Chemical Technology	LT7093
KeyOrganics	AS-75297
Lab Network	249
MedChem Express	HY-B0593
MolPort	MolPort-003-698-286
MolPort	MolPort-006-137-763
MolPort	MolPort-020-001-272
MolPort	MolPort-044-183-269
MolPort	MolPort-046-588-802
Molnova	M15778
PI Chemicals	PI-10779
PI Chemicals	PI-38675
Ryan Scientific	Iohexol
Sigma Aldrich	A6987
Sigma Aldrich	A6987\|SIGMA
Sigma Aldrich	C3809
Sigma Aldrich	C3809\|SIGMA
Sigma Aldrich	CDS020667
TargetMol	T1305
Tetrahedron	TS75058
Toronto Research Chemicals	C244100
Toronto Research Chemicals	C244128
Vitas-M Laboratory	STK047059
W&J PharmaChem	100160
Wonderchem	WC-009UYU
ZINC	ZINC000003871960	http://zinc15.docking.org/substances/ZINC000003871960
ZINC	ZINC000008035456	http://zinc15.docking.org/substances/ZINC000008035456
ZINC	ZINC000008582317	http://zinc15.docking.org/substances/ZINC000008582317
ZINC	ZINC000254846637	http://zinc15.docking.org/substances/ZINC000254846637
ZINC	ZINC000254846639	http://zinc15.docking.org/substances/ZINC000254846639
eMolecules	193065907
eMolecules	301160656
eMolecules	313121473
eMolecules	48600981
eMolecules	50241616
mcule	MCULE-1860404300
mcule	MCULE-5264603916
mcule	MCULE-9068634681

PubMed

Title	Date	PubMed
Renal tolerance of ceftazidime in animals.	1981 Sep	19802993
Pharmacokinetics and therapeutic efficacy of imipenem, ceftazidime, and ceftriaxone in experimental meningitis due to an ampicillin- and chloramphenicol-resistant strain of Haemophilus influenzae type b.	1984 Jan	6322679
Efficacy of ciprofloxacin in animal models of infection: endocarditis, meningitis, and pneumonia.	1987 Apr 27	3578331
Hallucinations in association with ceftazidime.	1988 Oct 1	3140957
Ceftazidime-induced encephalopathy in a patient with renal impairment.	1988 Sep	3046579
Neurotoxicity associated with ceftazidime therapy in geriatric patients with renal dysfunction.	1991	1923920
Ceftazidime-induced hemolysis in a patient with drug-dependent antibodies reactive by immune complex and drug adsorption mechanisms.	1991 Mar	1996549
Animal models as predictors of outcome of therapy with broad spectrum cephalosporins.	1992 Apr	1601755
Ceftazidime encephalopathy: absence status and toxic hallucinations.	1992 Apr	1583528
Relative efficacies of broad-spectrum cephalosporins for treatment of methicillin-susceptible Staphylococcus aureus experimental infective endocarditis.	1993 Mar	8460924
Efficacy of cefepime in a Staphylococcus aureus endocarditis rat model.	1993 Nov	8150772
Neurotoxicity associated with intraperitoneal ceftazidime therapy in a CAPD patient.	1994	7827199
Ceftazidime-related nonconvulsive status epilepticus.	1994 Mar 14	8122952
[Convulsions associated with the administration of excessive dose of ceftazidime in patients with renal failure].	1994 Sep-Oct	7855759
[Acute interstitial nephritis. Role of ceftazidime].	1996	9033764
Mania due to clarithromycin therapy in a patient who was not infected with human immunodeficiency virus.	1996 Mar	8853002
[Analysis of the etiologic structure of urinary tract infection and antibiotic-resistance of its pathogens].	1997	9412416
QT prolongation and Torsades de Pointes associated with clarithromycin.	1998 Apr	9576415
[Basic and clinical studies on tazobactam/piperacillin in pediatric field].	1998 Jun	9755831
[Fatal encephalopathy induced by ceftazidime].	1998 Nov-Dec	10070247
Nonconvulsive status epilepticus associated with cephalosporins in patients with renal failure.	2001 Aug	11498064
Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients.	2001 Nov	11792017
Meningitis caused by Enterococcus gallinarum in patients with ventriculoperitoneal shunts.	2003 Dec	14691658
Acute renal failure and cystic fibrosis.	2003 Jul	12818927
Retrospective review of neurotoxicity induced by cefepime and ceftazidime.	2003 Mar	12627936
Correlation between candiduria and departmental antibiotic use.	2003 Mar	12623318
Creutzfeldt-Jakob-like EEG in a patient with end-stage renal failure.	2004 Jan	14671069
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
CR5/20--Acute renal failure in a child with cystic fibrosis awaiting lung transplantation--a good outcome after all.	2006	17036408
Disseminated invasive aspergillosis in a patient with acute leukaemia.	2006	16918060
Cephalosporin-induced myoclonus.	2006 Mar 28	16567688
Antibiotics modulate the stimulated cytokine response to endotoxin in a human ex vivo, in vitro model.	2006 Oct	16939481
One center's experience: the serology and drugs associated with drug-induced immune hemolytic anemia--a new paradigm.	2007 Apr	17381629
Multichannel liquid chromatography-tandem mass spectrometry cocktail method for comprehensive substrate characterization of multidrug resistance-associated protein 4 transporter.	2007 Dec	17939016
Encephalopathy with myoclonic jerks resulting from ceftazidime therapy: an under-recognized potential side-effect when treating febrile neutropenia.	2007 Feb	17325906
Ceftazidime-associated biliary sludge in neonatal sepsis: a first report.	2009 Dec	20071298
Adverse drug reactions in medical intensive care unit of a tertiary care hospital.	2009 Jul	19421963
Sonographic assessment of ceftriaxone-associated biliary pseudolithiasis in Chinese children.	2010	21227004
Investigation of the effects of some drugs and phenolic compounds on human dihydrofolate reductase activity.	2015 Mar	25418905
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.	2015 May 18	25811541

Patents

Sample Use Guides

In Vivo Use Guide

The usual adult dosage is 1 gram administered intravenously or intramuscularly every 8 to 12 hours. The dosage and route should be determined by the susceptibility of the causative organisms, the severity of infection, and the condition and renal function of the patient.

Route of Administration: Other

In Vitro Use Guide

Ceftazidime–avibactam and comparator antibacterial agents were tested by reference broth microdilution against 417non-repetitive Gram-negative bacilli (387 unselected, plus 30selected blaKPC-positive, meropenem – nonsusceptible, Kleb-siella pneumoniae) collected prospectively from medical centersat Hospital das Clínicas da Faculdade de Medicina da Uni-versidade de São Paulo, Brazil, in 2014 and 2015. Minimum inhibitory concentrations (MICs), one per isolate, were determined by reference Clinical and Laboratory Standards Institute (CLSI) broth microdilution methods using frozen microtiter plates pre-loaded with antibiotic-containing growth medium. MICs ofceftazidime–avibactam were measured by varying the concen-tration of ceftazidime in twofold increments with avibactamat a fixed concentration of 4 mg/L. Addition of avibactam at 4 mg/L decreased MICs of cef-tazidime against unselected Enterobacteriaceae, especially K.pneumoniae, Citrobacter freundii, and Enterobacter cloacae, among which MIC90values decreased from 128 to >128 mg/L to0.5–4 mg/L. Among the unselected isolates of these three species 37–73% were susceptible to ceftazidime, whereas 100%were susceptible to ceftazidime–avibactam.

Name

Type

Language

CEFTAZIDIME DIHYDROCHLORIDE

Common Name

English

1-(((6R,7R)-7-(((2Z)-(2-AMINO-4-THIAZOLYL)((1-CARBOXY-1-METHYLETHOXY)IMINO)ACETYL)AMINO)-2-CARBOXY-8-OXO-5-THIA-1-AZABICYCLO(4.2.0)OCT-2-EN-3-YL)METHYL)PYRIDINIUM CHLORIDE MONOHYDROCHLORIDE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C357