cefoperazone

Action and Spectrum

Actions and spectrum: 

Actions: 

• Bactericidal: cefoperazone exerts its antimicrobial effects by inhibiting cell wall synthesis, leading to cell lysis and death of the bacteria. 

Spectrum of Activity: 

• Gram-positive Bacteria: cefoperazone is effective against certain gram-positive bacteria, including Staphylococcus aureus and Streptococcus species. 
• Gram-negative Bacteria: cefoperazone has a broad spectrum of activity against many gram-negative bacteria, including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, and Haemophilus influenzae. 
• Anaerobic Bacteria: cefoperazone also exhibits activity against some anaerobic bacteria, such as Bacteroides species. 

Drug Interaction

Adverse Reaction

Frequency not defined 

• Black, tarry, stools 
• chills 
• dark urine 
• fast heartbeat 
• pain or swelling at injection site 
• pale skin 
• sore throat 
• tenderness 
• unusual bleeding or bruising 
• upper right stomach pain 
• watery or bloody diarrhea 
• bluish color of the skin 
• cough 
• difficulty in breathing or swallowing 
• fever 
• light-colored stools 
• nausea 
• painful or difficult urination 
• skin itching, redness, or rash 
• stomach cramps 
• swelling of the leg or foot 
• vomiting 
• yellow eyes and skin 

Black Box Warning

Black Box Warning: 

cefoperazone does not have a black box warning. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: cefoperazone should not be administered to patients with a known hypersensitivity or allergy to cephalosporins or other beta-lactam antibiotics. 
• Previous Severe Allergic Reactions: Individuals who have experienced severe allergic reactions, such as anaphylaxis, to cephalosporins or penicillins in the past should avoid using cefoperazone. 
• History of Cholestatic Jaundice or Hepatic Dysfunction: cefoperazone should be avoided in patients with a history of cholestatic jaundice or hepatic dysfunction associated with the use of cephalosporins. 
• Severe Renal Impairment: severe renal impairment should not receive cefoperazone due to the risk of accumulation and increased toxicity. 
• Concurrent Use with Disulfiram: The combination of cefoperazone and disulfiram (a medication used to treat alcohol dependence) may lead to a disulfiram-like reaction, characterized by nausea, vomiting, and flushing, and should be avoided. 
• Neonates with Hyperbilirubinemia: cefoperazone use is contraindicated in neonates with hyperbilirubinemia or other risk factors for increased bilirubin levels due to its potential to displace bilirubin from protein-binding sites and increase the risk of bilirubin encephalopathy (kernicterus).

Caution: 

• Gastrointestinal Disorders: cefoperazone can disrupt the normal gut flora, potentially leading to overgrowth of Clostridium difficile, causing severe diarrhoea and colitis. Patients with a history of gastrointestinal disorders should be monitored closely for signs of colitis during treatment. 
• Central Nervous System Effects: Some patients may experience central nervous system (CNS) side effects, including headache, dizziness, and confusion. Caution should be exercised in patients with a history of CNS disorders or those taking other medications that may have CNS effects. 
• Impaired Liver Function: Patients with hepatic impairment may experience delayed elimination of cefoperazone, leading to increased drug levels in the body. Dose adjustments may be necessary in these individuals. 
• Renal Impairment: cefoperazone is primarily excreted by the kidneys, and patients with renal impairment may require dosage adjustments to prevent drug accumulation and potential toxicity. 
• Pregnancy and Lactation: The safety of cefoperazone in pregnancy and lactation has not been well-established, and the potential benefits should be weighed against the risks before use in pregnant or nursing women. 
• Use in Pediatrics and Geriatrics: Special caution should be exercised when prescribing cefoperazone to pediatric and geriatric patients, as they may have specific susceptibility to adverse effects or require dose adjustments based on age and medical condition.

Comorbidities: 

• Immunocompromised Conditions: Patients with immunocompromised conditions, such as HIV/AIDS, cancer, or organ transplant recipients, may be more susceptible to severe bacterial infections and may require special considerations and monitoring when using cefoperazone. 
• Diabetes: Patients with diabetes may be at higher risk of developing bacterial infections, and proper glycemic control is essential for effective treatment and prevention of complications. 
• Cardiovascular Diseases: Patients with certain cardiovascular conditions, such as heart failure or valvular disease, may be at increased risk of developing infective endocarditis, which could require antibiotic treatment with agents like cefoperazone. 
• Chronic Respiratory Conditions: Patients with chronic respiratory conditions, like chronic obstructive pulmonary disease, may be prone to bacterial respiratory infections that may be treated with cefoperazone. 

Pregnancy / Lactation

Pregnancy consideration: pregnancy category: B 

Lactation: excreted into human milk: yes  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

cefoperazone is a broad-spectrum cephalosporin antibiotic that belongs to the third generation of cephalosporins. It exerts its antibacterial activity by inhibiting bacterial cell wall synthesis, essential for the structural integrity of bacteria. 

Mechanism of Action: cefoperazone acts by binding to specific penicillin-binding proteins (PBPs) located on the bacterial cell wall. This binding inhibits the cross-linking of peptidoglycan chains, an essential step in bacterial cell wall synthesis. As a result, the bacterial cell wall weakens and becomes more susceptible to osmotic pressure, leading to cell lysis and bacterial death.  

Pharmacodynamics: 

• Bactericidal Activity: cefoperazone is a bactericidal antibiotic, meaning it kills bacteria rather than just inhibiting their growth. It achieves this by interfering with the synthesis of the bacterial cell wall. 
• Inhibition of Cell Wall Synthesis: cefoperazone, like other cephalosporins, binds to specific penicillin-binding proteins (PBPs) located on the bacterial cell wall. This binding inhibits the transpeptidation step of peptidoglycan synthesis, which is essential for the structural integrity of bacterial cell walls. 
• Lysis of Bacterial Cells: By inhibiting cell wall synthesis, cefoperazone weakens the bacterial cell wall, making it more susceptible to osmotic pressure. As a result, the bacterial cells undergo lysis (rupture) when they try to expand, leading to bacterial death. 
• Time-Dependent Killing: cefoperazone exhibits time-dependent killing, which means its bactericidal effect is dependent on the duration of time the drug concentration remains above the minimum inhibitory concentration (MIC) for the targeted bacteria. 
• Post-Antibiotic Effect: After the drug is removed, cefoperazone can continue to inhibit bacterial growth for a period known as the post-antibiotic effect. This effect allows for less frequent dosing and helps maintain therapeutic efficacy.

Pharmacokinetics: 

Absorption 

cefoperazone is administered intravenously (IV) or intramuscularly (IM). IV administration ensures rapid and complete absorption into the bloodstream, while IM administration provides slower absorption. The drug is not available for oral use. 

Distribution 

Once absorbed, cefoperazone distributes throughout the body fluids and tissues, including the lungs, skin, bone, and cerebrospinal fluid. It has a high volume of distribution, indicating its wide distribution into tissues. 

Metabolism 

cefoperazone undergoes minimal metabolism in the liver. The majority of the drug is excreted unchanged in the urine. 

Elimination and excretion 

The primary route of elimination for cefoperazone is via the kidneys through renal excretion. Only a small amount is excreted in the bile and feces. The elimination half-life of cefoperazone is relatively long, allowing for extended dosing intervals. 

Adminstartion

Administration: 

Intravenous (IV) Administration: 

• cefoperazone is typically administered as an intravenous infusion directly into the vein. 
• It should be reconstituted and diluted as per the manufacturer’s instructions or the healthcare provider’s recommendation. 
• The healthcare provider will determine the appropriate dosage and infusion rate based on the patient’s age, renal function, weight, and the severity of the infection. 

Intramuscular (IM) Administration: 

• Some formulations of cefoperazone are suitable for intramuscular injection. 
• The healthcare provider will choose the appropriate injection site, usually in the upper arm, thigh, or buttocks. 
• Proper aseptic techniques should be followed during the injection to minimize the risk of infection. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: cefoperazone 

Pronounced: ( sef-oh-PER-a-zone)  

Why do we use cefoperazone? 

• Intra-abdominal Infections: cefoperazone is used to treat infections in the abdominal cavity, such as peritonitis, caused by bacteria like Escherichia coli, Klebsiella spp., and Streptococcus spp. 
• Respiratory Tract Infections: the respiratory infections, including pneumonia, bronchitis, and lung abscess, caused by pathogens like Haemophilus influenzae and Streptococcus pneumoniae. 
• Skin and Soft Tissue Infections: cefoperazone can be used to treat soft tissue or skin infections like cellulitis and impetigo, caused by susceptible bacteria. 
• Urinary Tract Infections: It is caused by Escherichia coli, Proteus mirabilis, and other susceptible organisms. 
• Septicemia and Bacteremia: cefoperazone may be used in severe systemic infections like septicemia and bacteremia caused by susceptible bacteria. 
• Gynecological Infections: It is sometimes prescribed for the treatment of gynecological infections, such as pelvic inflammatory disease (PID) caused by susceptible pathogens.