Pharm D
Cephalosporins are a large group of antibacterial drugs initially derived from the mold Acremonium (previously called Cephalosporium). They have bactericidal actions and work similarly to beta-lactams by binding to block the activity of enzymes responsible for making peptidoglycan, an essential part of the bacterial cell wall.
Cephalosporins were discovered in 1945. However, structural improvements were made to make it more effective against a broader range of bacteria, and with each new structure emerged a new cephalosporin generation. Cephalosporins are called broad-spectrum antibiotics, as they are active against many bacteria. Most cephalosporin drugs have the prefix cef, ceph, or kef.
Cephalosporins are grouped into generations according to their effectiveness against different organisms, their characteristics, and their development:
Penicillin and cephalosporins are chemically similar, containing the beta-lactam molecular structure. Cross-sensitivity occurs in some patients and indicates that someone who has had an anaphylaxis reaction with penicillin is at risk of having the same with cephalosporins, too. Therefore, you must be cautious while administering cephalosporins to patients sensitive to the beta-lactam ring.
Most cephalosporins are administered parenterally because they are not absorbed from the gastrointestinal tract. Some are absorbed from the gastrointestinal tract and can be administered orally, but food hinders the absorption rate, although not the amount absorbed. Two cephalosporins, oral cefuroxime and cefpodoxime, have been shown to increase absorption when given with food.
After absorption, cephalosporins are widely distributed, although most are not distributed in the central nervous system. Cefuroxime from second and third-generation drugs, such as cefotaxime, ceftizoxime, ceftriaxone, and ceftazidime, crosses the blood-brain barrier. Cefepime from the fourth generation also crosses the blood-brain barrier, but the extent to which it does is not known.
Many cephalosporins are not metabolized at all. Cefotaxime is metabolized to the non-acetyl form, which provides less antibacterial activity than the parent compound. To a small extent, ceftriaxone is metabolized in the intestines to inactive metabolites, which are excreted via the biliary system.
Primarily, all cephalosporins are excreted unchanged by the kidneys except cefoperazone and ceftriaxone, which are excreted in feces through bile.
Cephalosporins’ mechanism of action is similar to penicillin’s. They work by inhibiting cell wall synthesis by binding to the bacterial penicillin-binding protein on the cell membrane. After the drug damages the bacterial cell wall by binding to the penicillin-binding proteins, the body’s natural defense mechanism is to eliminate the bacterial load.
Generally, cephalosporins are indicated for the treatment of:
Each cephalosporin generation has different therapeutic uses. First-generation cephalosporins act primarily against gram-positive organisms. However, depending on the patient’s sensitivity to penicillin, they can be used as alternative therapy in an allergic patient.
First-generation cephalosporins are also used to treat staphylococcal and streptococcal infections, including pneumonia, cellulitis, and osteomyelitis.
Second-generation cephalosporins act against gram-positive bacteria. Cefoxitin and cefotetan are the only second-generation cephalosporins effective against anaerobes.
Third-generation cephalosporins are effective against gram-negative organisms and are the drugs of choice for infections caused by Enterobacter, P. aeruginosa, and anaerobic organisms.
Fourth-generation cephalosporins are structurally related to third-generation cephalosporins. However, they have an extra ammonium group that makes them rapidly penetrable through the other membranes of gram-negative bacteria, enhancing their activity. Moreover, they are active against β-lactamase producing Enterobacteriaceae, which may inactivate third-generation cephalosporins.
Some fourth-generation cephalosporins have excellent activity against gram-positive bacteria, such as methicillin-susceptible staphylococci, penicillin-resistant pneumococci, and viridans group streptococci. Cefepime is the only fourth-generation cephalosporin available in the United States. Fourth-generation cephalosporins are active against a wide range of gram-positive and gram-negative bacteria. Therefore, they are called broad-spectrum antibiotics and are used for severe infections that are often antibiotic-resistant.
Fifth-generation cephalosporins are active against methicillin-resistant Staphylococcus aureus (MRSA) and gram-positive bacteria. The only currently used fifth-generation cephalosporin in the USA is ceftaroline. It is effective against susceptible gram-negative bacteria and retains the activity of the later-generation cephalosporins.
Cephalosporins are generally well tolerated. However, sometimes, they can cause adverse effects such as confusion, seizures, nausea, bleeding, vomiting, and diarrhea.
Cefoperazone, cefotetan, and ceftriaxone specifically can decrease the prothrombin time and partial thromboplastin time, leading to increased chances of bleeding, especially in the population in which dose adjustment is required, such as elderly, debilitated, malnourished, and immunocompromised patients and those with renal impairment, hepatic disease, or impaired vitamin K synthesis or storage.
Before starting cephalosporin therapy, take a detailed medical and drug history of the patient to rule out if they are allergic to penicillin or cephalosporins. Often, patients mix gastrointestinal upset with allergy. Therefore, it is essential to rule out if it was a GI disturbance previously or an anaphylaxis reaction.
Before administering the first dose, obtain a culture and sensitivity specimen; therapy may begin once the pending test results arrive. Periodically check test results to assess the drug’s effectiveness. Continuously evaluate the patient for possible hypersensitivity reactions or other adverse effects.
Administer cephalosporins at least one hour before bacteriostatic antibacterial drugs, such as tetracyclines, erythromycins, and chloramphenicol, which can decrease the cephalosporin uptake by bacterial cell walls; the antibacterial drugs inhibit bacterial cell growth.
Refrigerate oral suspensions. They are stable for 14 days and should not be consumed after that. Shake well before administering and ensure the dose is correct. For reconstitution, dilution, and storage of drugs, follow the manufacturer’s guidelines and check expiration dates.
To administer an IM dose, use the gluteal or mid-lateral muscle, which can be given into the large muscle; rotate sites to minimize tissue injury, pain, and inflammation. Do not mix cephalosporin IV infusion with other drugs, especially with aminoglycosides, as they can inactivate cephalosporins. If another drug has to be given intravenously, temporarily stop the injection of the primary drug.
Ensure the IV dilution is adequate and rotate injection sites for intravenous administration every 48 hours to minimize local vein irritation or thrombophlebitis. Using a small-gauge needle in a more prominent available vein may be helpful.
Cephalosporin drug therapy monitors renal functions, and the dose is adjusted in severe renal impairment patients. In patients with decreased renal function, monitor renal function, blood urea nitrogen, serum creatinine, and urine output for significant changes. Also, monitor prothrombin time and platelet counts. Assess the patient for signs of hypoprothrombinemia, which may occur with or without bleeding, especially during therapy with cefoperazone, cefotetan, or ceftriaxone.
Patients with long-term cephalosporin therapy are at risk of developing possible fungal and bacterial superinfection, especially elderly and debilitated patients and those receiving immunosuppressants or radiation therapy. Therefore, monitor them for any signs and symptoms of superinfection, such as fever, malaise, muscle aches and pains, and oral ulcerations, and treat them appropriately.
Sodium salts of cephalosporins can retain water and cause swelling and high blood pressure. Therefore, monitor the patient’s blood pressure and watch for possible fluid retention, especially in hypertensive patients.
When cephalosporins are prescribed, it is essential to educate patients and their caregivers. The following points should be noted for patient teaching, and the patient should be asked to follow the guidelines.
Cephalosporins remain essential drugs for treating various infections, from mild to severe. However, they should be used only when desperately required. Too often, the usage of broad-spectrum antibiotics leads to antibiotic resistance. Therefore, a culture and sensitivity specimen should be obtained, and cephalosporin therapy should be started when needed.
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