Cefotaxime is an

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 ...

used to treat several bacterial infections in humans, other animals, and plant tissue culture. Specifically in humans it is used to treat joint infections, pelvic inflammatory disease,

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, urinary tract infections,

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 ...

, gonorrhea, and cellulitis. It is given either by injection into a vein or

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 ...

. Common side effects include nausea, allergic reactions, and inflammation at the site of injection. Another side effect may include ''Clostridioides difficile'' diarrhea. It is not recommended in people who have had previous anaphylaxis 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 ...

. It is relatively safe for use 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. Cefotaxime was discovered in 1976 and came into commercial use in 1980. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication.

Medical uses

It is a broad-spectrum antibiotic with activity against numerous

gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. The Gram stain is ...

and

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

. Given its broad spectrum of activity, cefotaxime is used for a variety of infections, including: * Lower respiratory tract infections – e.g. pneumonia (most commonly caused by ''S. pneumoniae'') * Genitourinary system infections – urinary tract infections (e.g. ''E. coli'', ''S. epidermidis'', ''P. mirabilis'') and cervical/urethral gonorrhea * Gynecologic infections – e.g. pelvic inflammatory disease, endometritis, and pelvic cellulitis *

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 ...

– secondary to ''Streptococcus'' spp., ''S. aureus'', ''E. coli'', and ''Klebsiella'' spp. * Intra-abdominal infections – e.g. peritonitis * Bone and joint infections – ''S. aureus'', ''Streptococcus'' spp. * CNS infections – e.g. meningitis/ ventriculitis secondary to ''N. meningitidis'', ''H. influenzae'', ''S. pneumoniae'' Although cefotaxime has demonstrated efficacy in these infections, it is not necessarily considered to be the first-line agent. In meningitis, cefotaxime crosses the blood–brain barrier better than cefuroxime. Cefotaxima

Spectrum of activity

As a β-lactam antibiotic in the third-generation class of cephalosporins, cefotaxime is active against numerous Gram-positive and Gram-negative bacteria, including several with resistance to classic β-lactams such as penicillin. These bacteria often manifest as infections of the lower respiratory tract, skin, central nervous system, bone, and intra-abdominal cavity. While regional susceptibilities must always be considered, cefotaxime typically is effective against these organisms (in addition to many others): * ''Staphylococcus aureus'' (not including MRSA) and ''S. epidermidis'' * ''Streptococcus pneumoniae'' and ''S. pyogenes'' * ''Escherichia coli'' * ''Haemophilus influenzae'' * ''Neisseria gonorrhoeae'' and ''N. meningitidis'' * ''Klebsiella'' spp. * ''Burkholderia cepacia'' * ''Proteus mirabilis'' and ''P. vulgaris'' * ''Enterobacter'' spp. * ''Bacteroides'' spp. * ''Fusobacterium'' spp. Notable organisms against which cefotaxime is not active include '' Pseudomonas'' and '' Enterococcus''. As listed, it has modest activity against the anaerobic '' Bacteroides fragilis''. The following represents MIC susceptibility data for a few medically significant microorganisms: * ''H. influenzae'': ≤0.007 – 0.5 μg/mL * ''S. aureus'': 0.781 – 172 μg/mL * ''S. pneumoniae'': ≤0.007 – 8 μg/mL Historically, cefotaxime has been considered to be comparable to ceftriaxone (another third-generation cephalosporin) in safety and efficacy for the treatment of bacterial meningitis, lower respiratory tract infections, skin and soft tissue infections, genitourinary tract infections, and bloodstream infections, as well as prophylaxis for abdominal surgery. The majority of these infections are caused by organisms traditionally sensitive to both cephalosporins. However, ceftriaxone has the advantage of once-daily dosing, whereas the shorter half-life of cefotaxime necessitates two or three daily doses for efficacy. Changing patterns in microbial resistance suggest cefotaxime may be suffering greater resistance than ceftriaxone, whereas the two were previously considered comparable. Considering regional microbial sensitivities is also important when choosing any antimicrobial agent for the treatment of infection.

Adverse reactions

Cefotaxime is contraindicated in patients with a known hypersensitivity to cefotaxime or other cephalosporins. Caution should be used and risks weighed against potential benefits in patients with an allergy to penicillin, due to cross-reactivity between the classes. The most common adverse reactions experienced are: * Pain and inflammation at the site of injection/infusion (4.3%) * Rash, pruritus, or fever (2.4%) * Colitis, diarrhea, nausea, vomiting (1.4%)

Mechanism of action

Cefotaxime is a β-lactam antibiotic (which refers to the structural components of the drug molecule itself). As a class, β-lactams inhibit bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs). This inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) in the absence of cell wall assembly. Due to the mechanism of their attack on bacterial cell wall synthesis, β-lactams are considered to be

bactericidal A bactericide or bacteriocide, sometimes abbreviated Bcidal, is a substance which kills bacteria. Bactericides are disinfectants, antiseptics, or antibiotics. However, material surfaces can also have bactericidal properties based solely on their p ...

. Unlike β-lactams such as penicillin and amoxicillin, which are highly susceptible to degradation by β-lactamase enzymes (produced, for example, nearly universally by ''S. aureus''), cefotaxime boasts the additional benefit of resistance to β-lactamase degradation due to the structural configuration of the cefotaxime molecule. The ''syn''-configuration of the methoxy imino moiety confers stability against

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

s. Consequently, the spectrum of activity is broadened to include several β-lactamase-producing organisms (which would otherwise be resistant to β-lactam antibiotics), as outlined below. Cefotaxime, like other β-lactam antibiotics, does not only block the division of bacteria, including

cyanobacteria Cyanobacteria ( ) are a group of autotrophic gram-negative bacteria that can obtain biological energy via oxygenic photosynthesis. The name "cyanobacteria" () refers to their bluish green (cyan) color, which forms the basis of cyanobacteri ...

, but also the division of cyanelles, the

photosynthetic Photosynthesis ( ) is a Biological system, system of biological processes by which Photoautotrophism, photosynthetic organisms, such as most plants, algae, and cyanobacteria, convert light energy, typically from sunlight, into the chemical ener ...

organelle In cell biology, an organelle is a specialized subunit, usually within a cell (biology), cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as Organ (anatomy), organs are to th ...

s of the glaucophytes, and the division of

chloroplast A chloroplast () is a type of membrane-bound organelle, organelle known as a plastid that conducts photosynthesis mostly in plant cell, plant and algae, algal cells. Chloroplasts have a high concentration of chlorophyll pigments which captur ...

s of

bryophyte Bryophytes () are a group of embryophyte, land plants (embryophytes), sometimes treated as a taxonomic Division (taxonomy), division referred to as Bryophyta ''Sensu#Common qualifiers, sensu lato'', that contains three groups of non-vascular pla ...

s. In contrast, it has no effect on the plastids of the vascular plants. This supports the endosymbiotic theory and indicates an

evolution Evolution is the change in the heritable Phenotypic trait, characteristics of biological populations over successive generations. It occurs when evolutionary processes such as natural selection and genetic drift act on genetic variation, re ...

of plastid division in land plants.

Administration

Cefotaxime is administered by intramuscular injection or intravenous infusion. As cefotaxime is metabolized to both active and inactive metabolites by the liver and largely excreted in the urine, dose adjustments may be appropriate in people with renal or hepatic impairment.

Plant tissue culture

Cefotaxime is the only cephalosporin which has very low toxicity in plants, even at higher concentration (up to 500 mg/L). It is widely used to treat plant tissue infections with Gram-negative bacteria, while vancomycin is used to treat the plant tissue infections with Gram-positive bacteria.

References

External links

* {{portal bar, Medicine Cephalosporin antibiotics Thiazoles Acetate esters World Health Organization essential medicines Wikipedia medicine articles ready to translate Sanofi Ketoxime ethers