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 pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

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, intense headache, vomiting and neck stiffness and occasion ...

pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...

sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...

, urinary tract infections, malignant otitis externa, ''Pseudomonas aeruginosa'' infection, and vibrio infection. It is given by injection into a vein,

muscle Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...

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

anaphylaxis Anaphylaxis (Greek: 'up' + 'guarding') is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of the use of emergency medication on site. It typicall ...

to a

penicillin Penicillins (P, PCN or PEN) are a group of beta-lactam antibiotic, β-lactam antibiotics originally obtained from ''Penicillium'' Mold (fungus), moulds, principally ''Penicillium chrysogenum, P. chrysogenum'' and ''Penicillium rubens, P. ru ...

. Its use is relatively safe during

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

and

breastfeeding Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...

. 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 that surrounds some Cell type, cell types, found immediately outside the cell membrane. It can be tough, flexible, and sometimes rigid. Primarily, it provides the cell with structural support, shape, protection, ...

. 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, 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''. However, ceftazidime is less effective for ''S. aureus'' than first and second generation cephalosporins. Also, cephalosporins until fifth generation are 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'': 0.015–512 μg/mL * ''Pseudomonas aeruginosa'': ≤0.03–1024 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 Toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, is a type of severe skin reaction. Together with Stevens–Johnson syndrome (SJS) it forms a spectrum of disease, with TEN being more severe. Early symptoms include fever and f ...

, 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 The direct and indirect Coombs tests, also known as antiglobulin test (AGT), are blood tests used in immunohematology. The direct Coombs test detects antibodies that are stuck to the surface of the red blood cells. Since these antibodies sometimes ...

(4%), increased

platelets Platelets or thrombocytes () are a part of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a blood clot. Platelets have no cell nucleus; they are fragments of cyto ...

(thrombocythemia) (2%), increased ALT (7%), increased AST (6%), or increased alkaline phosphatase (4%).

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 also bear this

functional group In organic chemistry, a functional group is any substituent or moiety (chemistry), moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions r ...

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 In organic chemistry and biochemistry, a side chain is a substituent, chemical group that is attached to a core part of the molecule called the "main chain" or backbone chain, backbone. The side chain is a hydrocarbon branching element of a mo ...

, compared to other third-generation cephalosporins, the more complex moiety (containing two methyl and a

carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...

group) confers extra stability to beta-lactamase enzymes produced by many

Gram-negative Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists ...

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 Ketoxime ethers