Cefazolin - Dosage, Indications, and Side Effects

Overview

Cefazolin is a broad-spectrum antibiotic used in the treatment of various bacterial infections. It belongs to a class of medications called cephalosporins. It is also known as Cefazoline or Cephazolin. It is a first-generation antibiotic used to treat pneumonia (lung infection), joint infections, urinary tract infections, endocarditis, and biliary tract infections. It can also be administered to prevent infections before and after surgery. Cefazolin was granted initial approval by the United States Food and Drug Administration (US FDA) in 1973, and the Cefazolin injection was approved on March 18, 1998.

How Does Cefazolin Work?

Cefazolin is used in the treatment of a wide variety of bacterial infections. However, this medication may not be helpful for common colds, flu, or viral infections. It must be used only to treat or prevent bacterial infections that are proven or strongly suspected to reduce the development of drug-resistant bacteria. It is effective against gram-positive and some gram-negative bacteria and interferes with the bacterial cell wall, thus destroying or preventing bacterial growth.

Indications of Cefazolin

• Cefazolin is indicated in treating adults and pediatric patients with infections of the respiratory tract caused by Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae; skin infections caused by Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus agalactiae; urinary tract infections caused by Escherichia coli and Proteus mirabilis; and infections of the bone and joints, biliary tract, and genital areas.

• It is also used in treating adults and pediatric patients with endocarditis (inflammation of the heart valve lining) due to Staphylococcus aureus and Streptococcus pyogenes and septicemia (bloodstream infection) caused by Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli, and Proteus mirabilis.

• Cefazolin can also be used as a perioperative prophylaxis (before surgery) in adults.

Contraindications of Cefazolin

• Cefazolin is contraindicated in patients with a history of immediate hypersensitivity reactions (severe allergic reactions) to the drug, its components, or other Cephalosporins, penicillins, or other beta-lactam drugs.

• Cefazolin is not recommended for pregnant and lactating women and infants younger than one month.

Available Doses and Dose Forms

Cefazolin is available in powder form for reconstitution and as a premixed solution. In powdered form, it is available in doses of 500 mg (milligrams), one gm, two gm, 10 g, 20 g, 100 g, and 300 g. As a premixed intravenous (IV) solution, it is available in doses of one g/50 mL (gram per milliliter) and two gm/100 mL. Cefazolin is administered intravenously for approximately 30 minutes. If the dose required does not equal one gm or two gm, Cefazolin is not recommended, and in such cases, an alternative formulation must be considered.

The dosage of Cefazolin for adults depends on the type of infection and severity, as follows:

• Moderate to severe infections - 500 mg to one gm, every six to eight hours.

• Mild infections caused by gram-positive cocci - 250 - 500 mg every eight hours.

• Acute urinary tract infections - one gm every 12 hours.

• Pneumococcal pneumonia - 500 mg every 12 hours

• Severe life-threatening infections - one to 1.5 gm every six hours.

The recommended dose of Cefazolin injection for pediatric patients with creatinine clearance of 70 mL/min (milliliter per minute) or greater is as follows:

• Mild to moderate infections - 25 mg/kg (milligram per kilogram) to 50 mg/kg, divided into three or four equal doses.

• Severe infections - The dose may be increased to 100 mg/kg, divided into three or four equal doses.

The recommended dose for perioperative prophylaxis in adults with creatinine clearance equal to 55 mL/min or greater is one or two gm of Cefazolin administered half an hour to one hour before surgery, and an additional dose of 500 mg to one g for lengthy surgical procedures (more than two hours). The recommended dose for 24 hours post-surgery is 500 mg to one g every six to eight hours.

Warnings and Precautions

• Hypersensitivity: Beta-lactam antibacterial drugs, including Cefazolin, can cause hypersensitivity reactions in some patients. Therefore, before prescribing Cefazolin, medical history must be taken carefully to inquire about any previous hypersensitivity to medications. Hypersensitivity can also occur in some patients due to the high concentrations of corn-derived dextrose solution in Cefazolin injections. Therefore, it must be prescribed with caution in patients with a known case of carbohydrate intolerance or subclinical diabetes mellitus (a condition in which blood sugar levels are increased).

• Diarrhea: Antibacterial agents usually alter the normal flora in the intestine, resulting in the overgrowth of Clostridium difficile microorganisms. Cefazolin can cause Clostridium difficile-associated diarrhea (CDAD) in some patients. Therefore, medical history must be taken carefully, as CDAD can occur over two months following the administration of antibacterial drugs. Cefazolin must be discontinued if CDAD is suspected or confirmed, and appropriate fluid management, treatment for Clostridium difficile, protein supplements, and surgical evaluation must be considered depending on the clinical presentation.

• Seizures: Cefazolin can cause seizures (uncontrolled body movements), especially in patients with renal disorders, when the dose is not modified appropriately. Cefazolin injections must be discontinued in such patients, and anticonvulsant therapy must be considered in patients with a known history of seizures.

• Drug Resistance: If Cefazolin is prescribed in the absence of proven or strongly suspected bacteria or for a prophylactic indication, it may not provide the desired benefit to the patient. It also increases the risk of developing drug-resistant bacteria. Prolonged use of Cefazolin can also result in the overgrowth of nonsusceptible microbes. Therefore, repeated evaluation of patients is necessary during the treatment.

• Laboratory Test Interactions: Cefazolin administration can cause false-positive reactions when Benedict’s copper reduction reaction is conducted to determine glucose in the urine. Therefore, the use of enzymatic glucose oxidase is recommended in glucose tests.

Adverse Effects of Cefazolin

Some of the adverse effects of Cefazolin include:

• Hypersensitivity.

• Nausea and vomiting.

• Diarrhea (loose, watery stools).

• Urticaria (itchy, red bumps on the skin).

• Mouth ulcers.

• Fever.

• Stomach cramps.

• Anorexia (an eating disorder characterized by fear of weight gain).

• Injection site reactions.

• Pruritus (itching).

• Headache.

• Confusion.

• Dizziness.

• Fatigue.

• Increased liver enzymes and creatinine levels.

For Patients

What Are Bacterial Infections?

Infections or illnesses caused by single-celled microorganisms called bacteria are called bacterial infections. They multiply and release toxins in the respiratory tract, skin, urinary tract, genital areas, and various other parts of the body. They spread through direct or indirect contact, cough or sneeze droplets, insect bites, contaminated food and water, etc. Bacteria can cause different types of infections, depending on the infected part of the body.

Some of the common symptoms of bacterial infection include:

• Fever.

• Fatigue.

• Headache.

• Chills.

• Nausea and vomiting.

• Swelling of lymph nodes.

Antibiotic medications can successfully treat bacterial infections, as they are highly effective and support the immune system in fighting these infections. However, if left untreated, it can increase the severity and lead to further complications.

What Is Cefazolin?

Cefazolin is a prescription medicine used to treat bacterial infections of the skin, respiratory tract, urinary tract, genital areas, bones, and joints. It belongs to a class of medications called cephalosporins. It acts by destroying bacterial organisms or by preventing their growth. It is also administered before or after certain surgical procedures to prevent infections.

However, Cefazolin is ineffective for common cold, flu, or viral infections. The duration of treatment mainly depends on the type of infection and the patient’s response to the medication. Patients must not take antibiotics unnecessarily or without proper diagnosis to prevent the development of drug-resistant bacteria.

How Effective Is Cefazolin?

Cefazolin is a first-generation, broad-spectrum antibiotic used for a wide range of bacterial infections. It is very active against gram-positive and some gram-negative bacteria. Various studies have demonstrated it to be effective and associated with minimal side effects compared to penicillins.

Recent research also suggests that Cefazolin can be an alternative to antistaphylococcal penicillins (ASPs) in treating methicillin-susceptible Staphylococcus aureus infective endocarditis. The drug is overall safe and well-tolerated by many patients, as they start feeling better within a few days of treatment with Cefazolin.

How Should Cefazolin Be Taken?

Cefazolin is available as a powder to be mixed with liquid or as a premixed solution to be administered intravenously (into a vein) for over 30 minutes. It can also be given intramuscularly (into a muscle). A healthcare professional must administer Cefazolin in a clinic or hospital. It is usually injected once every six, eight, or 12 hours, depending on the type and severity of the infection.

What Are the Side Effects of Cefazolin?

The side effects of Cefazolin include:

• Nausea and vomiting.

• Headache.

• Diarrhea.

• Confusion.

• Weakness.

• Drowsiness.

• Dizziness.

• Tiredness.

• Genital itching.

• White patches in the mouth.

• Loss of appetite.

• Pain, swelling, or redness at the injection site.

• Stomach pain.

• Black or tarry stools.

• Cloudy or dark urine.

What Must the Patient Inform the Doctor Before Taking Cefazolin?

• Before starting the treatment, patients must tell the doctor if they are allergic to Cefazolin, its components, other Cephalosporins, or any other medications.

• Before starting treatment with Cefazolin, patients must tell the doctor if they have a history of or suffer from stomach or intestinal diseases, kidney diseases, or other medical conditions.

• Before administering Cefazolin, patients must inform the doctor if they take herbal medicines, vitamins, nutritional supplements, over-the-counter (OTC) drugs, or any other medications.

• Female patients must inform the doctor if they are pregnant, suspecting pregnancy, planning to become pregnant, or breastfeeding before taking Cefazolin.

What Are the Precautionary Measures to Be Followed While Taking Cefazolin?

• Severe allergic reactions can occur in some patients during the treatment with Cefazolin; therefore, patients must inform the doctor in such situations, following which the treatment is discontinued.

• Antibacterial medications, including Cefazolin, can cause diarrhea in some patients; however, it stops after treatment. Patients must consult the doctor if they experience watery or bloody stools, even after two or more months since the last dose of Cefazolin.

• The doctor must be informed if the patients experience seizures after a Cefazolin injection, as the dose needs to be modified, or the drug may be discontinued.

• Cefazolin is used to treat only bacterial infections but is ineffective for viral or other infections. Skipping the dose or not taking the complete course can reduce the effectiveness of treatment or increase the development of drug-resistant bacteria.

Dietary Considerations

A normal diet can be followed during the treatment with Cefazolin unless instructed otherwise by the prescribing doctor.

Missed Dose

The missed dose must be taken immediately, as soon as it is remembered. However, if it is almost time for the next dose, it can be skipped, and the regular dosing schedule must be followed.

Storage

Cefazolin must be stored in a freezer in its original container at a temperature of -20 degrees Celcius (-4 degrees Fahrenheit) or below. It must be handled carefully, as the containers can be fragile in their frozen state.

For Doctors

Pharmacological Aspects of Cefazolin

Mechanism of Action

Cefazolin is a broad-spectrum cephalosporin antibiotic that acts by inhibiting bacterial septum and bacterial cell wall synthesis by binding to the specific penicillin-binding proteins (PBPs) present inside the bacterial cell wall. Bacterial cell lysis is mediated by autolytic enzymes such as autolysins, which prevent cross-linkage of peptidoglycan chains responsible for bacterial wall strength and rigidity.

Pharmacodynamics

Cephazolin's exact pharmacokinetic/pharmacodynamic relationship has not been determined in patients. Cefazolin is a first-generation, semi-synthetic cephalosporin developed for parenteral administration. It has a broad spectrum of antibiotic action against gram-positive and some gram-negative bacteria. Cefazolin inhibits bacterial cell wall synthesis, attains high serum levels, and is excreted mainly via urine.

Pharmacokinetics

Studies have demonstrated that after an intravenous administration of Cefazolin in normal subjects, the mean serum concentration was around 185 mcg/mL (micrograms per milliliter). It was around 4 mcg/mL at eight hours for a 1g dose of Cefazolin. At constant intravenous infusion with doses of 3.5 mg/kg for one hour and 1.5 mg/kg for the next two hours, the serum concentration was around 28 mcg/mL. The half-life of Cefazolin following an intravenous administration is approximately 1.8 hours. Studies conducted in infected patients indicated that Cefazolin produces approximately equivalent peak serum concentration as healthy volunteers. Cefazolin was excreted unchanged in urine; during the first six hours, approximately 60 percent of Cefazolin was excreted in urine, which increased up to 70 to 80 percent within 24 hours of administration.

Drug Interactions

Administration of Probenecid with Cefazolin is not recommended, as Probenecid can inhibit the renal excretion of Cefazolin.

Clinical Studies

The activity of Cefazolin against gram-negative enteric bacteria and gram-positive cocci isolated from patients was evaluated using an agar dilution method involving trypticase soy agar. Approximately 108 organisms from overnight culture in one calibrated loop were streaked onto the agar plates that contained Cefazolin in a two-fold dilution. The minimum inhibitory concentration (MIC) after incubation was 37 degrees for 18 hours. The results demonstrated the in-vitro activity of Cefazolin against various strains of Escherichia coli (E.coli), Proteus mirabilis, and Klebsiella. Eighty percent of strains of E. coli were susceptible to a Cefazolin concentration of 1.6 mcg (micrograms) or less, whereas 100 percent were susceptible to a concentration of 3.1 mcg.

The clinical efficacy of Cefazolin was determined in 105 patients suffering from endocarditis, pneumonia, and infections of the urinary tract or soft tissues by administering Cefazolin in a dose ranging from 250 to 1000 mg as an intramuscular injection four times a day for 5 to 42 days. Cefazolin provided significant improvement in the clinical state of all patients.

A comparison of Cefazolin for its clinical and bacteriological cure with intramuscular Cephaloridine demonstrated no treatment failures in pneumococcal pneumonia patients. The results also demonstrated Cefazolin as the more potent anti-pneumococcal agent that achieved higher serum levels with lower doses. Cefazolin was equivalent to Cephaloridine in treating pneumococcal pneumonia, soft tissue, and urinary tract infections. It also demonstrated that Cefazolin was equivalent to Cephaloridine regarding tolerance and acceptability.

Nonclinical Toxicology

Long-term carcinogenicity and mutagenicity studies have not been performed with Cefazolin injection. No significant changes in mating or fertility were observed in the fertility studies conducted in rats at 2000 mg/kg/day (milligram per kilogram per day), approximately three times higher than the maximum recommended dose in humans.

Specific Considerations

• Pregnancy: Cefazolin can cross the placenta; however, data collected from various studies over several decades have not established any drug-associated risk, miscarriage, major birth defects, or adverse outcomes in pregnant women.

• Lactation: Adequate data is not available to determine the effects of Cefazolin on milk production, or the breastfed child. Therefore, the benefits of breastfeeding and any adverse effects of Cefazolin must be considered, along with the requirement of the drug for the breastfeeding mother.

• Pediatric Use: Cefazolin injections can be administered to pediatric patients for whom the appropriate dosage formulation can be determined. However, the safety and effectiveness of the drug are not established in premature infants and neonates.

• Geriatric Use: No significant difference in response was observed with Cefazolin between the younger and elderly individuals. However, elderly patients must be frequently monitored during the treatment.

• Renal Impairment: A lower dose or dose modification is required in adult and pediatric patients with low urinary output or other renal conditions.