Cefazolin/ Cephazolin

Cefazolin belongs to the pharmacological class of first-generation cephalosporin antibiotics.

Cefazolin has been approved to relieve symptoms and also for the treatment and maintenance of endocarditis, bacterial, peritonitis, pneumonia, community-acquired pneumonia, S. aureus, methicillin-susceptible, skin and soft tissue infections, S. aureus, methicillin-susceptible and surgical prophylaxis

Cefazolin is not absorbed in the Gastrointestinal tract as it is administered parenterally. Cefazolin is not metabolized in the liver. Cefazolin is excreted unchanged in the urine. In 6 hours after the administered almost 60% of the drug gets excreted.

The common side effects involving the use of Cefazolin are nausea, vomiting, gas, weakness, tiredness, itching, diarrhea, headache , hypotension, heartburn, etc.

Cefazolin is available in the form of Intravenous Injection and Intramuscular injection.

Cefazolin is approved in the U.S., U.K., Germany, Japan, Malaysia, India, and China.

Cefazolin belongs to the pharmacological class of first-generation cephalosporin antibiotics.

Cefazolin is a cephalosporin antibiotic, a class of β-lactam antibiotics similar to penicillins, which binds to and inhibits penicillin-binding proteins (PBPs). Cefazolin binds to specific penicillin-binding proteins (PBPs) which are located inside the bacterial cell wall. Cefazolin inhibits the third and last stage of bacterial cell wall synthesis. Hence, the Cell lysis is then mediated by the bacterial cell wall autolytic enzymes such as autolysins.

Cefazolin has been approved to relieve symptoms and also for the treatment and maintenance of endocarditis, bacterial, peritonitis, pneumonia, community-acquired pneumonia, S. aureus, methicillin-susceptible, skin and soft tissue infections, S. aureus, methicillin-susceptible and surgical prophylaxis

Following a single 2 g dose of Cefazolin, the mean Tmax was found to be 0.25 hours and mean Cmax was found to be 280.9 mcg/mL.

The serum half-life for cefazolin is found to be approximately 1.8 hours following Intravenous administration and approximately 2 hours following Intramuscular administration.

Cefazolin is available in the form of Intravenous Injection and Intramuscular injection.

Cefazolin can be used in the following treatment:

• Endocarditis, bacterial

• Peritonitis
• Pneumonia, community-acquired pneumonia, S. aureus, methicillin-susceptible
• Skin and soft tissue infections, S. aureus, methicillin-susceptible
• Surgical prophylaxis

Cefazolin can help to relieve symptoms and also for the treatment and maintenance of endocarditis, bacterial, peritonitis, pneumonia, community-acquired pneumonia, S. aureus, methicillin susceptible, skin as well as soft tissue infections, S. aureus, methicillin susceptible and surgical prophylaxis.

Cefazolin is approved for use in the following clinical indications:

● Endocarditis, bacterial

● Peritonitis

● Pneumonia, community-acquired pneumonia, S. aureus, methicillin-susceptible

● Skin and soft tissue infections, S. aureus, methicillin-susceptible

● Surgical prophylaxis

Intravenous Injection: Administered intravenously by a registered medical practitioner.

Intramuscular Injection: Administered intramuscularly by a registered medical practitioner.

Endocarditis, bacterial

Prophylaxis for dental as well as the upper respiratory procedures: Infants, Children, or Adolescents: Intramuscular, Intravenous: 50 mg/kg 30 to 60 minutes before procedure; maximum dose of about 1,000 mg/dose.

Treatment: Children as well as Adolescents: IV: 100 mg/kg/day divided into doses every eight hours; usual adult dose: 2,000 mg/dose; maximum daily dose is 12 g/day.

Peritonitis

Prophylaxis: It is advised to touch contamination of PD line: Intraperitoneal: 125 mg per liter is advised

Invasive dental procedures: Intravenous: 25 mg/kg administered 30 to 60 minutes before procedure; maximum dose of about 1,000 mg/dose

Gastrointestinal or genitourinary procedures: Intravenous: 25 mg/kg administered 60 minutes before procedure; maximum dose of about 2,000 mg/dose

Treatment: Intraperitoneal:

Intermittent: 20 mg/kg for every 24 hours.

Continuous: Loading dose: 500 mg per liter of dialysate; maintenance of about 125 mg per liter of dialysate

Pneumonia, community-acquired pneumonia, S. aureus, methicillin-susceptible

Infants >3 months, Children, and Adolescents: Intravenous : 50 mg/kg/dose every 8 hours .

Skin and soft tissue infections, S. aureus, methicillin-susceptible

50 / 100 mg/kg/day divided every 8 hours.

Surgical prophylaxis

Infants, Children, and Adolescents: IV: 30 mg/kg within 60 minutes prior to procedure, might repeat in 4 hours for prolonged procedure or excessive blood loss (eg, >1,500 mL in adults).

500 mg/ vial, 1 gm/ vial

Intramuscular Injection and Intravenous Injection

• Dosage Adjustments in Kidney Patients:

The usual recommended dosing of 1 to 2 g IV every 8 hours.

• Dosage Adjustments in Pediatric Patients:

Infants, Children, and Adolescents: IM, IV:

Mild to moderate infections: 25 to 100 mg/kg/ day divided every 8 hours; maximum daily dose: 6 g/ day

Severe infections (eg, bone/joint infections): 100 to 150 mg/ kg/ day divided every 6 to 8 hours; maximum daily dose: 12 g/ day.

Avoid high acid foods like citrus fruits and juices like orange and grapefruit, soda and chocolates.

Alcohol intake might lead to nausea, vomiting and headache

Multivitamins and antacids contain minerals primarily magnesium calcium, aluminum, iron or zinc which binds to the antibiotic and refrain it from working. Spacing them at least for 2 hours after Cefazolin administration is recommended.

Cefazolin may be contraindicated under the following conditions:

• Patients with known hypersensitivity to cephalosporins.

The physician should closely monitor the patients and keep pharmacovigilance as follows:

• Hypersensitivity Reactions

Allergic reactions such as rash, urticaria, angioedema, anaphylaxis, erythema multiforme, Stevens-Johnson syndrome/ toxic epidermal necrolysis had been reported with the use of Cefadroxil. It is advised that before therapy with Cefadroxil is to be instituted, inquire whether the patient has a history of hypersensitivity reactions to Cefadroxil, cephalosporins, penicillin, or other drugs. Cross-hypersensitivity among beta-lactam antibacterial drugs might occur in up to 10% of patients having a history of penicillin allergy. If an allergic reaction to Cefadroxil occurs, it is advised to discontinue the drug and institute appropriate treatment.

• Clostridium difficile-Associated Diarrhea

Clostridium difficile-associated diarrhea (CDAD) had been reported with use of nearly all antibacterial agents, including Cefadroxil, and might range in severity from mild diarrhea to a fatal colitis. Treatment with antibacterial agents is said to alter the normal flora of the colon in turn leading to overgrowth of C. difficile. C. difficile also produces toxins A and B, which contribute to the development of Clostridium difficile-associated diarrhea Hyper Toxin-producing strains of C. difficile caused increased morbidity as well as mortality, as these infections can be refractory to antimicrobial therapy and might require colectomy. Clostridium difficile-associated diarrhea must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since Clostridium difficile-associated diarrhea had been reported to occur over two months after the administration of antibacterial agents.

• Risk of Development of Drug-resistant Bacteria

Prescribing cefazolin injection when used in the absence of proven or strongly suspected bacterial infection or as a prophylactic indication is unlikely to provide benefits to the patient as well as increases the risk of the development of drug-resistant bacteria. As with other antimicrobials, prolonged use of cefazolin injection might result in overgrowth of non-susceptible microorganisms.

• Drug/Laboratory Test Interactions Urinary Glucose

The administration of cefazolin might result in a false-positive reaction with glucose in the urine when using glucose tests based on Benedict's copper reduction reaction .This determines the amount of reducing substances like glucose in the urine. Hence, it is recommended that glucose tests based on enzymatic glucose oxidase be used. Coombs' Test Positive direct Coombs' tests had been reported during treatment with cefazolin.

• Patients with Overt or Known Subclinical Diabetes Mellitus/Carbohydrate Intolerance

As with other dextrose-containing solutions, cefazolin injection should be prescribed cautiously in patients with overt/ known subclinical diabetes mellitus/ carbohydrate intolerance for any reason.

Usage of alcohol should be avoided while on Cefazolin medication, as alcohol can worsen the effects of any underlying disease condition, including conditions such as dizziness, blurred vision, etc.

Very low concentrations of cefazolin are found in the milk of nursing mothers. Cefazolin sodium should be administered with caution to a nursing woman.

Category B:

The safety of the use of cefazolin sodium during pregnancy has not been established.

No sufficient scientific evidence is traceable regarding the use and safety of Cefazolin in concurrent use with any particular food.

The adverse reactions related to Cefazolin can be categorized as follows:

Common

• Injection site reactions
• Gas
• Rectal itching
• Fainting
• Lightheadedness
• Confusion
• Stomach pain
• Stomach cramps
• Nausea
• Vomiting
• Loss of appetite
• Skin rash or itching
• Hives
• White patches or sores inside the mouth or on the lips
• Vaginal itching or discharge
• Heartburn
• Weakness
• Tiredness
• Hypotension
• Drowsiness
• Headache
• Allergic reactions
• Diarrhea

Rare

• Pain
• Bluish color
• Changes in skin color
• Swelling of the foot or leg
• Tenderness

The clinically relevant drug interactions of Cefazolin is briefly summarized here:

The renal excretion of cefazolin is found to be inhibited by probenecid. Hence, co-administration of probenecid with cefazolin injection is not recommended.

The following are the side effects involving Cefazolin:

● Injection site reactions

● Gas

● Rectal itching

● Fainting

● Lightheadedness

● Confusion

● Stomach pain

● Stomach cramps

● Nausea

● Vomiting

● Loss of appetite

● Skin rash or itching

● Hives

● White patches or sores inside the mouth or on the lips

● Vaginal itching or discharge

● Heartburn

● Weakness

● Tiredness

● Hypotension

● Drowsiness

● Headache

● Allergic reactions

● Diarrhea

Pregnancy

The safety of the use of cefazolin sodium during pregnancy has not been established.

Lactation

Very low concentrations of cefazolin are found in the milk of nursing mothers. Cefazolin sodium

should be administered with caution to a nursing woman.

Pediatric

The safety of the use of cefazolin sodium in prematures and infants under one month of age has

not been established.

The safety as well as effectiveness of cefazolin injection for perioperative prophylaxis had not been established in pediatric patients who are younger than 10 years old.

Geriatric

No overall differences in safety as well as effectiveness had been observed between these subjects as well as the younger subjects. Other reported clinical experience had not identified differences in responses between the elderly as well as younger patients, but a greater sensitivity of some older individuals cannot be ruled out.

Physicians should be knowledgeable and vigilant about the treatment and identification of overdosage of Cefazolin.

Accidental overdose resulting in seizures might occur in patients with the renal impairment who receive doses greater than the recommended dosage of cefazolin. If seizures associated with accidental overdose occur, discontinue cefazolin injection and give supportive treatment.

Pharmacodynamics

Cefazolin (also known as cefazoline or cephazolin) is said to be a semi-synthetic first generation cephalosporin for the parenteral administration. Cefazolin is said to have a broad-spectrum antibiotic action due to inhibition of the bacterial cell wall synthesis. It attains high serum levels and is excreted quickly via the urine.

Pharmacokinetics

• Absorption

Not absorbed from the GI tract. It must be administered parenterally. Peak serum concentrations said to be attained 1-2 hours post intramuscular injection.

• Metabolism

Cefazolin is said to be not metabolized.

• Route of elimination

Cefazolin is said to be present at very low concentrations in the milk of nursing mothers. Cefazolin is found to be excreted unchanged in the urine. In the first 6 hours, approximately about 60% of the drug is found to be excreted in the urine, and this increases to 70%-80% within 24 hours.

1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/050779s013lbl.pdf
2. https://www.apotex.com/products/us/detail.asp?m=65050
3. https://www.drugs.com/dosage/cefazolin.html
4. https://www.empr.com/drug/cefazolin/
5. https://www.goodrx.com/cefazolin/what-is
6. https://medlineplus.gov/druginfo/meds/a682731.html
7. https://www.mayoclinic.org/drugs-supplements/cefazolin-injection-route/side-effects/drg-20073267?p=1