Cefizox Injection

Following IV administration of 1, 2, and 3 gram doses of Cefizox to normal volunteers, the following serum levels were obtained.

A serum half­life of approximately 1.7 hours was observed after IV administration.

Cefizox is 30% protein bound.

Cefizox is not metabolized, and is excreted virtually unchanged by the kidneys in 24 hours. This provides a high urinary concentration. Concentrations greater than 6000 μg/mL have been achieved in the urine by 2 hours after a 1 gram dose of Cefizox intravenously. Probenecid slows tubular secretion and produces even higher serum levels, increasing the duration of measurable serum concentrations.

Cefizox achieves therapeutic levels in various body fluids, e.g., cerebrospinal fluid (in patients with inflamed meninges), bile, surgical wound fluid, pleural fluid, aqueous humor, ascitic fluid, peritoneal fluid, prostatic fluid and saliva, and in the following body tissues: heart, gallbladder, bone, biliary, peritoneal, prostatic, and uterine.

In clinical experience to date, no disulfiram­like reactions have been reported with Cefizox.

Microbiology

The bactericidal action of ceftizoxime results from inhibition of cell­wall synthesis. Ceftizoxime is highly resistant to a broad spectrum of beta­lactamases (penicillinase and cephalosporinase), including Richmond types I, II, III, TEM, and IV, produced by both aerobic and anaerobic gram­positive and gram­negative organisms. Ceftizoxime has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections described in the INDICATIONS AND USAGE section:

Staphylococcus aureus (including penicillinase producing strains)

NOTE: Methicillin­resistant staphylococci are resistant to cephalosporins, including ceftizoxime.

Staphylococcus epidermidis (including penicillinase producing strains)

Streptococcus agalactiae

Streptococcus pneumoniae

Streptococcus pyogenes

NOTE: A streptococcal isolate that is susceptible to penicillin can be considered susceptible to ceftizoxime.4

NOTE: Ceftizoxime is usually inactive against most strains of Enterococcus faecalis.

Enterobacter spp.

Escherichia coli

Haemophilus influenzae (including ampicillin­resistant strains)

Klebsiella pneumoniae

Morganella morganii

Neisseria gonorrhoeae

Proteus mirabilis

Proteus vulgaris

Providencia rettgeri

Pseudomonas aeruginosa

Serratia marcescens

Bacteroides spp.

Peptococcus spp.

Peptostreptococcus spp.

The following in vitro data are available, but their clinical significance is unknown. At least 90% of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for ceftizoxime. However, the safety and effectiveness of ceftizoxime in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.

Aeromonas hydrophila

Citrobacter spp.

Moraxellacatarrhalis

Neisseria meningitis

Providencia stuartii

Susceptibility Testing Methods:

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method1 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of ceftizoxime powder. The MIC values should be interpreted according to the following criteria:

A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone, which prevents small-uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable, other therapy should be selected.

Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard ceftizoxime powder should provide the following MIC values:

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 30-μg ceftizoxime to test the susceptibility of microorganisms to ceftizoxime.

Reports from the laboratory providing results of the standard single-disk susceptibility test with a 30-μg ceftizoxime disk should be interpreted according to the following criteria:

Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for ceftizoxime.

As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 30-μg ceftizoxime disk should provide the following zone diameters in these laboratory test quality control strains:

For anaerobic bacteria, the susceptibility to ceftizoxime as MICs can be determined by standardized test methods. Agar dilution results can vary widely when using ceftizoxime. It is recommended that broth microdilution method be used when possible.3 The MIC values obtained should be interpreted according to following criteria:

Interpretation is identical to that described in Susceptibility Testing: Dilution Techniques.

As with other susceptibility techniques, the use of laboratory control microorganisms is required to control the technical aspects of the laboratory standardized procedures. Standardized ceftizoxime powder should provide the following MIC values:

Most strains of Pseudomonas aeruginosa are moderately susceptible to ceftizoxime.

Ceftizoxime achieves high levels in the urine (greater than 6000 μg/mL at 2 hours with 1 gram IV) and, therefore, the following zone sizes should be used when testing ceftizoxime for treatment of urinary tract infections caused by Pseudomonas aeruginosa.

Susceptible organisms produce zones of 20 mm or greater, indicating that the

test organism is likely to respond to therapy.

Organisms that produce zones of 11 to 19 mm are expected to be susceptible

when the infection is confined to the urinary tract (in which high antibiotic levels

are attained).

Resistant organisms produce zones of 10 mm or less, indicating that other

therapy should be selected.

Cefizox (ceftizoxime injection) is indicated in the treatment of infections due to susceptible strains of the microorganisms listed below.

Lower Respiratory Tract Infections caused by Klebsiella spp.; Proteus mirabilis; Escherichia coli; Haemophilus influenzae including ampicillin­resistant strains; Staphylococcus aureus (penicillinase­ and nonpenicillinase­producing); Serratia spp.; Enterobacter spp.; Bacteroides spp.; and Streptococcus spp. including S. pneumoniae, but excluding enterococci.

Urinary Tract Infections caused by Staphylococcus aureus (penicillinase­ and nonpenicillinase­producing); Escherichia coli; Pseudomonas spp. including P.aeruginosa; Proteus mirabilis; P. vulgaris; Providencia rettgeri (formerly Proteus rettgeri) and Morganella morganii (formerly Proteus morganii); Klebsiella spp.; Serratia spp. including S. marcescens; and Enterobacter spp.

Gonorrhea including uncomplicated cervical and urethral gonorrhea caused by Neisseria gonorrhoeae.

Pelvic Inflammatory Disease caused by Neisseria gonorrhoeae, Escherichia coli or Streptococcus agalactiae. NOTE: Ceftizoxime, like other cephalosporins, has no activity against Chlamydia trachomatis. Therefore, when cephalosporins are used in the treatment of patients with pelvic inflammatory disease and C. trachomatis is one of the suspected pathogens, appropriate anti­chlamydial coverage should be added.

Intra­Abdominal Infections caused by Escherichia coli; Staphylococcusepidermidis; Streptococcus spp. (excluding enterococci); Enterobacter spp.; Klebsiella spp.; Bacteroides spp. including B. fragilis; and anaerobic cocci, including Peptococcus spp. and Peptostreptococcus spp.

Septicemia caused by Streptococcus spp. including S. pneumoniae (but excluding enterococci); Staphylococcus aureus (penicillinase­ and nonpenicillinase­producing); Escherichia coli; Bacteroides spp. including B. fragilis; Klebsiella spp.; and Serratia spp.

Skin and Skin Structure Infections caused by Staphylococcus aureus (penicillinase­ and nonpenicillinase­producing); Staphylococcus epidermidis; Escherichia coli; Klebsiella spp.; Streptococcus spp. including Streptococcus pyogenes (but excluding enterococci); Proteus mirabilis; Serratia spp.; Enterobacter spp.; Bacteroides spp. including B. fragilis; and anaerobic cocci, including Peptococcus spp. and Peptostreptococcus spp.

Bone and Joint Infections caused by Staphylococcus aureus (penicillinase­ and nonpenicillinase­producing); Streptococcus spp. (excluding enterococci); Proteusmirabilis; Bacteroides spp.; and anaerobic cocci, including Peptococcus spp. and Peptostreptococcus spp.

Meningitis caused by Haemophilus influenzae. Cefizox has also been used successfully in the treatment of a limited number of pediatric and adult cases of meningitis caused by Streptococcus pneumoniae.

Cefizox has been effective in the treatment of seriously ill, compromised patients, including those who were debilitated, immunosuppressed, or neutropenic.

Infections caused by aerobic gram­negative and by mixtures of organisms resistant to other cephalosporins, aminoglycosides, or penicillins have responded to treatment with Cefizox.

Because of the serious nature of some urinary tract infections due to P. aeruginosa and because many strains of Pseudomonas species are only moderately susceptible to Cefizox, higher dosage is recommended. Other therapy should be instituted if the response is not prompt.

Susceptibility studies on specimens obtained prior to therapy should be used to determine the response of causative organisms to Cefizox. Therapy with Cefizox may be initiated pending results of the studies; however, treatment should be adjusted according to study findings. In serious infections, Cefizox has been used concomitantly with aminoglycosides (see PRECAUTIONS). Before using Cefizox concomitantly with other antibiotics, the prescribing information for those agents should be reviewed for contraindications, warnings, precautions, and adverse reactions. Renal function should be carefully monitored.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefizox and other antibacterial drugs, Cefizox 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.

Cefizox (ceftizoxime injection) is contraindicated in patients who have known allergy to the drug.

Cefizox® (ceftizoxime injection) is generally well tolerated. The most frequent adverse reactions (greater than 1% but less than 5%) are:

Hypersensitivity--Rash, pruritus, fever.

Hepatic--Transient elevation in AST (SGOT), ALT (SGPT), and alkaline phosphatase.

Hematologic--Transient eosinophilia, thrombocytosis. Some individuals have developed a positive Coombs test.

Local--Injection site--Burning, cellulitis, phlebitis with IV administration, pain, induration, tenderness, paresthesia.

The less frequent adverse reactions (less than 1%) are:

Hypersensitivity--Numbness and anaphylaxis have been reported rarely.

Hepatic--Elevation of bilirubin has been reported rarely.

Renal--Transient elevations of BUN and creatinine have been occasionally observed with Cefizox.

Hematologic--Anemia, including hemolytic anemia with occasional fatal outcome, leukopenia, neutropenia, and thrombocytopenia have been reported rarely.

Urogenital--Vaginitis has occurred rarely.

Gastrointestinal--Diarrhea; nausea and vomiting have been reported occasionally.

Symptoms of pseudomembranous colitis can appear during or after antibiotic treatment (see WARNINGS).

In addition to the adverse reactions listed above which have been observed in patients treated with ceftizoxime, the following adverse reactions and altered laboratory tests have been reported for cephalosporin­class antibiotics:

Stevens­Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, serum­sickness like reaction, toxic nephropathy, aplastic anemia, hemorrhage, prolonged prothrombin time, elevated LDH, pancytopenia, and agranulocytosis.

Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment, when the dosage was not reduced. (See DOSAGE AND ADMINISTRATION.) If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

Consult your pharmacist.

How to use Cefizox 10 Gram Solution For Injection

Consult your pharmacist.

Ceftizoxime has been assigned to pregnancy category B by the FDA. Animal data failed to reveal evidence of fetal harm. There are no controlled data in human pregnancy. Ceftizoxime should only be given during pregnancy when need has been clearly established.

Ceftizoxime is excreted into human milk in small amounts. Adverse effects in the nursing infant are unlikely. Other cephalosporins have been classified as compatible with breast-feeding by the American Academy of Pediatrics.

Substance Name

Ceftizoxime

CAS Registry Number

68401-81-0

Drug Class

Antiinfective Agents

Antibacterial Agents

Cephalosporins