Ceftazidime, sold under the brand name Fortaz among others, is a third-generation cephalosporin

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

useful for the treatment of a number of bacterial infections. Specifically it is used for joint infections,

meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...

, pneumonia, sepsis, urinary tract infections, malignant otitis externa, ''Pseudomonas aeruginosa'' infection, and

vibrio infection ''Vibrio'' is a genus of Gram-negative bacteria, possessing a curved-rod (comma) shape, several species of which can cause foodborne infection, usually associated with eating undercooked seafood. Being highly salt tolerant and unable to surviv ...

. It is given by injection into a vein,

muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

, or

eye Eyes are organs of the visual system. They provide living organisms with vision, the ability to receive and process visual detail, as well as enabling several photo response functions that are independent of vision. Eyes detect light and conv ...

. Common side effects include nausea, allergic reactions, and pain at the site of injection. Other side effects may include ''Clostridium difficile'' diarrhea. It is not recommended in people who have had previous anaphylaxis to a

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. Its use is relatively safe during pregnancy and breastfeeding. It is in the third-generation cephalosporin family of medications and works by interfering with the bacteria's

cell wall A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough, flexible, and sometimes rigid. It provides the cell with both structural support and protection, and also acts as a filtering mech ...

. Ceftazidime was patented in 1978 and came into commercial use in 1984. It is on the World Health Organization's List of Essential Medicines. Ceftazidime is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

Medical uses

Ceftazidime is used to treat lower respiratory tract, skin, urinary tract, blood-stream, joint, and abdominal infections, and meningitis. Ceftazidime is the first-line treatment for the tropical infection,

melioidosis Melioidosis is an infectious disease caused by a gram-negative bacterium called ''Burkholderia pseudomallei''. Most people exposed to ''B. pseudomallei'' experience no symptoms; however, those who do experience symptoms have signs and symptoms t ...

, an important cause of sepsis in Asia and Australia. Labeled indications include the treatment of patients with: * ''Pseudomonas aeruginosa'' infections * other Gram-negative, aerobic infections * neutropenic fever As a class, cephalosporins have activity against Gram-positive and Gram-negative bacteria. The balance of activity tips toward Gram-positive organisms for earlier generations; later generations of cephalosporins have more Gram-negative coverage. Ceftazidime is one of the few in this class with activity against ''Pseudomonas aeruginosa''. It is not active against methicillin-resistant ''Staphylococcus aureus''.

Spectrum of activity

Clinically relevant organisms against which ceftazidime has activity include: * Gram-negative aerobes such as ''Enterobacter'', ''Escherichia coli'', ''Haemophilus influenzae'', ''Klebsiella spp.'', ''Proteus spp.'', ''Pseudomonas aeruginosa'', and ''Neisseria meningitidis'' * Gram-positive aerobes, such as group B streptococci, ''Streptococcus pneumoniae'', and ''Streptococcus pyogenes'' Ceftazidime generally has poor efficacy against anaerobes, such as ''Bacteroides'' spp. The following represents MIC susceptibility data for a few clinically significant pathogens: * ''Escherichia coli'' – 0.015 μg/mL – 512 μg/mL * ''Pseudomonas aeruginosa'' – ≤0.03 μg/mL – 1024 μg/mL

Side effects

Ceftazidime is generally well tolerated. When side effects 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. Another source reported, in addition, blood tests of patients may show increased eosinophils (8%), increased lactate dehydrogenase (6%), increased gamma-glutamyl transferase (5%), positive direct Coombs test (4%), increased

platelets Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...

(thrombocythemia) (2%), increased

ALT Alt or ALT may refer to: Abbreviations for words * Alt account, an alternative online identity also known as a sock puppet account * Alternate character, in online gaming * Alternate route, type of highway designation * Alternating group, mathema ...

(7%), increased AST (6%), or increased alkaline phosphatase (4%).Lexicomp Online, Lexi-Drugs, Hudson, Ohio: Lexi-Comp, Inc.; 2014; April 20, 2014.

Contraindications

Ceftazidime is contraindicated in people with a known allergy to ceftazidime or to any other cephalosporin antibiotic.

Precautions

Ceftazidime is mainly eliminated by the kidneys into the urine. As such, drug levels in the blood may build up in persons with kidney injury or kidney disease. This includes those on dialysis. In these cases of renal impairment, the drug is dosed less frequently. No dose adjustment is needed for those with liver disease.

Pregnancy

According to the manufacturer, research studies in mice and rats showed no evidence of harm to the fetus, even at up to 40 times the human dose of ceftazidime. Importantly, though, no high-quality research studies of the effects of the drug in pregnant women were conducted.Ceftazidime for Injection(R) ackage insert Schaumburg, IL: Sagent; 2012
PDF of insert

Mechanism of action

Third-generation cephalosporins differ from earlier generations in the presence of a C=N-OCH₃ group in their chemical structure ( cefuroxime &

cefuzonam Cefuzonam (International Nonproprietary Name, INN) is a second-generation cephalosporin antibiotic. References

* {{CephalosporinAntiBiotics Cephalosporin antibiotics Thiadiazoles Thiazoles ...

also bear this functional group but are only listed as class II). This group provides improved stability against certain beta-lactamase enzymes produced by Gram-negative bacteria. These bacterial enzymes rapidly destroy earlier-generation cephalosporins by breaking open the drug's beta-lactam chemical ring, leading to antibiotic resistance. Though initially active against these bacteria, with widespread use of third-generation cephalosporins, some Gram-negative bacteria that produce extended-spectrum beta-lactamases (ESBLs) are even able to inactivate the third-generation cephalosporins. Infections caused by ESBL-producing Gram-negative bacteria are of particular concern in hospitals and other healthcare facilities.

Chemistry

In addition to the ''syn''-configuration of the imino side chain, compared to other third-generation cephalosporins, the more complex moiety (containing two

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in many ...

and a

carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...

group) confers extra stability to β-lactamase enzymes produced by many Gram-negative bacteria. The extra stability to β-lactamases increases the activity of ceftazidime against otherwise resistant Gram-negative organisms including ''Pseudomonas aeruginosa''. The charged pyridinium moiety increases water-solubility. Ceftazidime shares the same variable R-group side chain with aztreonam, a monobactam antibiotic; the two drugs share a similar spectrum of activity, including activity against ''Pseudomonas aeruginosa''.

References

External links

* {{Portal bar , Medicine Cephalosporin antibiotics Thiazoles Pyridinium compounds Zwitterions World Health Organization essential medicines Wikipedia medicine articles ready to translate