CEPHALOTHIN: WHAT IT IS FOR, MECHANISM OF ACTION, DOSE - MEDICINE - 2025

The cefalotina is an antibacterial of the cephalosporin, whose effect is similar to that of penicillins. The predominant spectrum of action is on gram positive and some gram negative bacteria. It is the first cephalosporin marketed in 1964.

Cephalosporins are a group of antibiotics developed in the middle of the last century. Its name derives from the name of a fungus -Cephalosporium acremonium-, from which a compound with bactericidal properties was obtained. This discovery, which occurred in 1948, was the starting point for the development of a new class of antimicrobials.

Source: pxhere.com

Cephalosporin antibiotics evolved over time according to changes in their spectrum of bactericidal action. This change has allowed its classification in five generations, cephalothin belonging to the first generation.

The bactericidal activity of the antibiotic, like other 1st generation cephalosporins, is on gram-positive germs. However, some gram-negative bacteria are also susceptible to its use.

Cephalothin administration is exclusively parenteral, both intravenously and intramuscularly. However, intramuscular administration is rare due to local effects of the drug, including pain.

Intravenously, the antibiotic reaches therapeutic levels quickly and is highly protein bound. Its half-life is relatively short, 45 minutes to an hour. It can easily spread to any tissue except the nervous system, as it does not penetrate the blood-brain barrier. Just over 30% is inactivated in the liver and its elimination is through the urine.

Cephalothin is an affordable, effective, safe, and very well-tolerated drug. Currently the drug is used in many countries to treat infections by susceptible germs. In the United States, the FDA has discontinued the use of cephalothin, due to the existence of more effective cephalosporins.

What is it for?

The usefulness of cephalothin is based on the spectrum of bactericidal action it possesses. The term bactericidal spectrum refers to the sensitivity of different groups of bacteria to an antibiotic. In the case of a 1st generation cephalosporin, its effect is on gram-positive and some gram-negative bacteria.

Cephalosporins were developed as an alternative to the use of penicillins, with a similar effect but a superior spectrum of action.

Sensitive bacteria

Gram-positive bacteria, such as Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus epidermidis, and S. auereus. It also has action against the gram-negative bacteria Klebsiella sp, Proteus mirabilis and Escherichia coli. It is possible its use in case of infections by Shigella sp. and Salmonella sp.

The effect on Haemophilus influenza is limited, and requires the association with another antibiotic. Enterococci are resistant to almost all cephalosporins, including cephalothin.

Clinical uses

The bacterial sensitivity to the antibiotic allows its use in infections where these bacteria participate. Treatment of both superficial and deep infections is common. In addition, the distribution characteristics of cephalothin make it useful in soft tissues, as well as in bones and joints.

Infections where cephalothin is commonly used are:

- Pyodermatitis or skin infections. Common skin germs can cause soft tissue infection under certain circumstances. The germs involved are Staphylococcus aureus or Streptococcus epidermidis.

- Skin infections secondary to burns. Skin burns cause the loss of the protective barrier and exposure of the deep planes. One consequence of these injuries is bacterial invasion and infection of both the dermis and the subcutaneous tissue, and even the muscle.

- Otitis externa and media. One of the causative agents of external otitis is Staphylococcus aureus. Bacteria such as Streptococcus pneumoniae, Group A Streptococcus, and Haemophillus influenzae can cause otitis media.

- Pharyngitis and other upper respiratory infections, especially those caused by Streptococcus pyogenes.

- Pneumonia caused by sensitive germs, such as Streptococcus pneumoniae.

- Bacterial endocarditis. In cases where the infection is due to Streptococcus viridans or Staphylococcus susceptible to methicillin.

- Urinary tract infections, such as those caused by Escherichia coli.

- Acute cholecystitis. Inflammation of the gallbladder, with or without stones, can lead to bacterial infection.

- Osteomyelitis.

- Septic arthritis.

- Septicemia.

Additionally, prior to surgeries, cephalothin is used as an option for infection prevention.

Mechanism of action

Cephalosporins are β-lactam antibiotics, whose activity prevents the synthesis of the cell wall of bacteria. This is due to the inhibition of the transpeptidase enzymes necessary for the synthesis of the protective barrier. Consequently, bacterial death occurs.

The bacterial cell wall is made up of protein molecules associated with a carbohydrate, called peptidoglycans. These molecules give stability and resistance to the bacterial cell membrane, allowing it to grow and replicate.

Transpeptidases are the enzymes responsible for the synthesis of peptidoglycan. These enzymes are called penicillin-binding proteins (PFPs), since β-lactam antibiotic molecules can be attached to their structure.

The effect of antibiotics such as cephalothin requires binding to PFPs to prevent them from performing their synthetic function. Consequently, peptidoglycans will not be able to bind to the bacterial cell wall due to the inhibition of transpeptidases.

Loss of configuration, increased permeability, and cell wall lesions ultimately lead to the death - lysis - of the bacteria.

Adult and pediatric dosage

The effectiveness of antibiotics, particularly cephalosporins, depends on their permanence in plasma at adequate concentrations. The dose calculated on the basis of weight and the interval between doses guarantees the antimicrobial effect against a specific bacteria.

Cephalothin is presented in ampoules containing lyophilized powder. Administration is parenterally, preferably intravenously, after reconstitution and dilution.

Adults

Depending on the severity of the infection, the daily dose in adults ranges between 75 and 150 mg / kg / day. Generally, 1 to 2 grams can be given intravenously at 4, 6, or 8 hour intervals, not to exceed 12 grams per day. This dosing scheme ensures that therapeutic doses are maintained in the plasma to fight infection.

For severe infections, such as osteomyelitis or sepsis, use of the maximum dose in a short dose interval is considered.

At the liver level, about 35% of cephalothin is transformed into a metabolite with reduced activity. 65 to 70% of the antibiotic is eliminated in the urine, which implies a dose adjustment in cases of kidney failure. The dose taking into account the glomerular filtration rate -expressed in milliliters per minute- is:

- From 30 to 50 ml / min, 1 gram is used every 6 hours.

- Between 10 and 30 ml / min, 1 gram every 8 hours.

- Less than 10 ml / min, 1 gram every 12 hours or 500 mg every 6 hours

- In the cases of hemodialysis and peritoneal dialysis, the dose reduction will be between 20 and 50%.

Pediatric

Due to the immaturity of the renal system in neonates and young infants, its administration should be with caution. A dose of cephalothin of 50 mg / kg / day in an interval not less than 8 hours can be used safely.

In infants, pre-school and school children, the effective dose ranges from 80 to 160 mg / kg / day, at intervals of 6 to 8 hours.

Side effects

Despite being a safe and well-tolerated drug, it is possible to observe some reactions - rare - with the use of cephalothin.

Renal

There are three factors that trigger kidney effects from the use of cephalothin:

- Simultaneous use of nephrotoxic drugs, such as amikacin.

- Pre-existing kidney failure, which can be aggravated by the use of the antibiotic.

- The hypersensitivity reaction can lead to the deposition of immune complexes, inducing renal failure.

With proper administration, and in the absence of drug hypersensitivity, cephalothin rarely affects kidney function.

Allergic or hypersensitivity reactions

They are uncommon and can be seen in 10-15% of patients receiving cephalothin. They include both skin reactions and respiratory symptoms. Systemic effects can lead to peripheral vasodilation and shock.

Hypersensitivity is mediated by a hapten-antibody reaction, due to previous exposure to the drug.

Reactions can be skin rash, local or generalized rash, and itching. Nasal congestion, runny nose, sneezing, and bronchial hyperresponsiveness are the most frequent respiratory symptoms. In severe cases, angioedema, glottis edema, and anaphylactic shock are possible.

Although rare, hypersensitivity can induce immune-related kidney failure.

Digestive system

Despite being a well-tolerated drug, it is possible to observe gastrointestinal effects, such as nausea, vomiting and drug diarrhea. Pseudomembranous colitis is due to the replication of Clostridium difficile, caused by a decrease in the intestinal bacterial flora.

Hematological

Hematological side effects are very rare and hemolytic anemia, decreased platelets, or a decrease in all blood cells - pancytopenia - may be observed, the mechanism of which is not yet clear.

Liver

The effect of cephalothin at the hepatic level is uncommon, and includes a transient increase in bilirubin and liver enzymes.

Nervous system

Cephalothin does not cross the blood-brain barrier, so neurological symptoms are practically non-existent. Symptoms such as dizziness or headache during treatment are not usually associated with the use of cephalothin, however it is possible to observe transient confusion.

Local effects

Both intramuscular and intravenous injection can trigger local inflammatory reactions. The intramuscular route is not recommended due to local pain and irritation after drug placement. Phlebitis is a complication associated with intravenous use.

Contraindications

In some circumstances, the use of cephalothin or cephalosporins is prohibited or restricted. Contraindications to the use of the drug can be absolute or relative, depending on the implicit risk to health.

Absolute

The absolute contraindication for the use of cephalothin is demonstrated hypersensitivity or allergy to its component. In penicillin anaphylaxis, the use of any cephalosporin is also contraindicated. This is due to the similarity of the components of the molecules, which can induce severe hypersensitivity cross reactions.

Relative

- Hypersensitivity to penicillin that does not imply anaphylaxis.

- Pregnancy. Cephalothin is a class B risk medicine, without teratogenic effects on the fetus in animals. Its use in pregnant women should be supervised.

- Liver failure.

- Digestive system disorders, especially chronic colopathies.

- Renal insufficiency.

- Hematological alterations.

- Hypoproteinemia.

- Simultaneous use with aminoglycosides, probenecid or anticoagulants.

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