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 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 are often beneficial but others can cause infectious diseases. The number of t ...

. 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 Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity ...

sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

urinary tract infections A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidney ...

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. 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 nutrie ...

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. Common side effects include nausea,

allergic reactions Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...

, 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 Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follow ...

to a

penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...

. Its use is relatively safe during

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

and

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...

. 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 antibiotics ...

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 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 ...

. 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 Toxic epidermal necrolysis (TEN) 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 flu-like symptoms. A few days later th ...

Stevens–Johnson syndrome Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN), it forms a spectrum of disease, with SJS being less severe. Erythema ...

, and

erythema multiforme Erythema multiforme (EM) is a skin condition that appears with red patches evolving into target lesions, typically on both hands. It is a type of erythema possibly mediated by deposition of immune complexes (mostly IgM-bound complexes) in the s ...

, 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 (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...

(8%), increased lactate dehydrogenase (6%), increased gamma-glutamyl transferase (5%), positive direct

Coombs test A Coombs test, also known as antiglobulin test (AGT), is either of two blood tests used in immunohematology. They are the direct and indirect Coombs tests. The direct Coombs test detects antibodies that are stuck to the surface of the red blood ce ...

(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 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 infe ...

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

* {{CephalosporinAntiBiotics Cephalosporin antibiotics Thiadiazoles Thiazoles ...

also bear this

functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the rest ...

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 carbapenems ...

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 In organic chemistry, an imine ( or ) is a functional group or organic compound containing a carbon–nitrogen double bond (). The nitrogen atom can be attached to a hydrogen or an organic group (R). The carbon atom has two additional single bon ...

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

, 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 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 carbapenems ...

enzymes produced by many

Gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...

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 oft ...

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 abdominal ...

, a

monobactam Monobactams are monocyclic and bacterially-produced β-lactam antibiotics. The β-lactam ring is not fused to another ring, in contrast to most other β-lactams. Monobactams are effective only against aerobic Gram-negative bacteria (e.g., ''Nei ...

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