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 Pathogenic bacteria are bacteria that can cause disease. This article focuses on the bacteria that are pathogenic to humans. Most species of bacteria are harmless and many are beneficial but others can cause infectious diseases. The number of t ...

. Specifically it is used for

joint infections Acute septic arthritis, infectious arthritis, suppurative arthritis, pyogenic arthritis, osteomyelitis, or joint infection is the invasion of a joint by an infectious agent resulting in joint inflammation. Generally speaking, symptoms typicall ...

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 A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra ( urethritis) while upper urinary tract infections affect the kidney (pye ...

malignant otitis externa Otitis externa, also called swimmer's ear, is inflammation of the ear canal. It often presents with ear pain, swelling of the ear canal, and occasionally decreased hearing. Typically there is pain with movement of the outer ear. A high fever i ...

, ''Pseudomonas aeruginosa'' infection, and

vibrio infection ''Vibrio'' is a genus of Gram-negative bacteria, which have a characteristic curved-rod (comma) shape, several species of which can cause foodborne infection or soft-tissue infection called Vibriosis. Infection is commonly associated with eati ...

. It is given by

injection into a vein Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

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 An eye is a sensory organ that allows an organism to perceive visual information. It detects light and converts it into electro-chemical impulses in neurons (neurones). It is part of an organism's visual system. In higher organisms, the ey ...

. Common side effects include nausea,

allergic reactions Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermatitis, alle ...

, 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 The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus '' Acremonium'', which was previously known as ''Cephalosporium''. Together with cephamycins, they constitute a subgroup of β-lactam antibiot ...

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 The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. 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, but complications can range from fever and skin changes to pneumon ...

, 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 Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and #Classification, Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN) overlap, they are considered febrile mucocutaneous d ...

, and

erythema multiforme Erythema multiforme (EM) is an immune-mediated inflammatory skin condition associated with several viral infections, that appears with red patches evolving into target lesions, typically on both hands. It is typically associated with infection ...

, 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 Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along wi ...

(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 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, mathem ...

(7%), increased

AST AST, Ast, or ast may refer to: Science and technology * Attention schema theory, of consciousness or subjective awareness Computing * Abstract syntax tree, a finite, labeled, directed tree used in computer science * Anamorphic stretch transform, ...

(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 Cefuroxime, sold under the brand name Zinacef among others, is a second-generation cephalosporin antibiotic used to treat and prevent a number of bacterial infections. These include pneumonia, meningitis, otitis media, sepsis, urinary tract inf ...

& 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 Beta-lactamases (β-lactamases) are enzymes () produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems ( ertapenem), although carbapene ...

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 In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated as ...

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 Pyridinium refers to the cation . It is the conjugate acid of pyridine. Many related cations are known involving substituted pyridines, e.g. picolines, lutidines, collidines. They are prepared by treating pyridine with acids. As pyridine is often ...

moiety increases water-solubility. Ceftazidime shares the same variable R-group side chain with

aztreonam Aztreonam, sold under the brand name Azactam among others, is an antibiotic used primarily to treat infections caused by gram-negative bacteria such as ''Pseudomonas aeruginosa''. This may include bone infections, endometritis, intra abdomi ...

, a

monobactam Monobactams are bacterially-produced monocyclic β-lactam antibiotics. The β-lactam ring is not fused to another ring, in contrast to most other β-lactams. Monobactams are narrow-spectrum antibiotics effective only against (strictly or fa ...

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