Antimicrobial Drugs- Cephalosporins 1st Generation

First-generation cephalosporins are broad-spectrum, bactericidal antibiotics primarily effective against gram-positive bacteria, commonly used to treat skin, bone, urinary, and respiratory infections with low toxicity and reliable efficacy

Name of the Cephalosporins 1st Generation

• Ampicillin
• Cefadroxil
• Cephalexin
• Cephalothin
• Cephapirin
• Cephradine

1.Ampicillin

Mechanism of Action

 Inhibits bacterial cell wall synthesis. The rigid, cross-linked cell wall is assembled in several steps. Ampicillin exerts its effects on susceptible bacteria in the final stage of the cross-linking process by binding with and inactivating penicillin-binding proteins (enzymes responsible for linking the cell wall strands). This action causes bacterial cell lysis and death.

Pharmacokinetics

• Peak plasma time: 1-2 hr (oral)
• Bioavailability: 30-40%
• Protein bound: 15-25%
• Blister and tissue fluids, bile, and CSF with inflamed meninges
• Metabolism: Liver
• Half-life: 1-1.8 hr (normal renal function); 7-20 hr (anuria/end-stage renal disease)
• Excretion: Urine (90% within 24 hr)

Contraindications

Hypersensitivity to any penicillin, infection caused by penicillinase-producing organism

Adverse Reactions

• CNS: Chills, fatigue, fever, headache, malaise
• CV: Chest pain, edema, thrombophlebitis
• EENT: Epistaxis, glossitis, laryngeal stridor, mucocutaneous candidiasis, stomatitis, throat tightness
• GI: Abdominal distention, diarrhea, diarrhea related to Clostridium difficile, enterocolitis, flatulence, gastritis, nausea, pseudomembranous colitis, vomiting GU: Dysuria, urine retention, vaginal candidiasis
• HEME: Agranulocytosis, anemia, eosinophilia, leukopenia, thrombocytopenia, thrombocytopenic purpura
• SKIN: Erythema multiforme; erythematous, mildly pruritic maculopapular rash or other types of rash; exfoliative dermatitis; pruritus; urticaria
• Other: Anaphylaxis, facial edema, injection site pain

Nursing Considerations

• Avoid giving ampicillin to patients with non-nucleosis because of increased risk of rash.
• Expect to give ampicillin for 48 to 72 hours after patient becomes asymptomatic. For streptococcal infection, expect to give ampicillin for at least 10 days after cultures show streptococcal eradication to reduce risk of rheumatic fever or glomerulonephritis.
• To dilute ampicillin for I.M. use, add (depending on manufacturer) 1.2 ml of sterile water or bacteriostatic water for injection to each 125-mg vial, 1 ml of diluent to each 250-mg vial, 1.8 ml of diluent to each 500-mg vial, 3.5 ml of diluent to each 1-g vial, or 6.8 ml of diluent to each 2-g vial.
• To dilute ampicillin for intermittent infusion, add 5 ml of sterile water or bacteriostatic water for injection to each 125-, 250-, or 500-mg vial or 7.4 to 10 ml of diluent to each 1- or 2-g vial. Infuse in suitable diluent at less than 30 mg/ml.
• Monitor patient closely for anaphylaxis, which may be life-threatening. Patients at greatest risk are those with a history of multiple allergies, hypersensitivity to cephalosporins, or a history of asthma, hay fever, or urticaria.
• Notify prescriber if patient has evidence of superinfection; expect to stop drug and provide appropriate treatment.
• If long-term or high-dose ampicillin therapy is required, closely monitor results of renal and liver function tests and CBCs.  Monitor patient closely for diarrhea, which may be pseudomembranous colitis caused by Clostridium difficile. If diarrhea occurs, notify prescriber and expect to withhold ampicillin and administer fluids, electrolytes, protein, and an antibiotic effective against C. difficile.

Patient Teaching

• Stress the importance of taking the full course of ampicillin exactly as prescribed.
• Tell patient to take dose with 8 oz of water 30 minutes before or 2 hours after meals.
• Instruct patient to shake suspension well before each use, keep bottle tightly closed between uses, and discard unused portion after 14 days if refrigerated or 7 days if stored at room temperature.
• Review signs of allergic reaction; if they occur, tell patient to hold next ampicillin dose and contact prescriber immediately.
• Urge patient to tell prescriber about diarrhea that’s severe or lasts longer than 3 days. Remind patient that watery or bloody stools may occur 2 or more months after antibiotic therapy and may be serious, requiring prompt treatment.

2.Cefadroxil

Mechanism of Action

Interferes with bacterial cell wall synthesis by inhibiting the final step in the crosslinking of peptidoglycan strands. Peptidoglycan makes cell membranes rigid and protective. Without it, bacterial cells rupture and die

rsensitivity to cephalosporins or their components

Adverse Reactions

• CNS: Chills, fever, headache, seizures
• CV: Edema E
• ENT: Hearing loss
• GI: Abdominal cramps, diarrhea, elevated liver function test results, hepatic failure, hepatomegaly, nausea, oral candidiasis, pseudomembranous colitis, vomiting
• GU: Elevated BUN level, nephrotoxicity, renal failure, vaginal candidiasis
• HEME: Eosinophilia, hemolytic anemia, hypoprothrombinemia, neutropenia, thrombocytopenia, unusual bleeding
• MS: Arthralgia
• RESP: Dyspnea
• SKIN: Ecchymosis, erythema, erythema multiforme, pruritus, rash, Stevens-Johnson syndrome
• Other: Anaphylaxis, superinfection

Pharmacokinetics

• Half-Life: 1-2 hr; 20-24 hr in renal failure
• Peak Plasma Time: 70-90 min
• Protein Bound: 20%
• Absorption: rapid & well absorbed orally
• Distribution: crosses placenta
• Vd: 0.31 L/kg
• Metabolism: hepatic minimal
• Elimination: urine 90% unchanged

Contraindications

 Hypersensitivity to cephalosporins or penicillin

Nursing Considerations

• Use cefadroxil cautiously in patients with impaired renal function or a history of GI disease, particularly colitis. Also use drug cautiously in patients who are hypersensitive to penicillin because cross-sensitivity has occurred in about 10% of such patients. 
• If possible, obtain culture and sensitivity test results, as ordered, before giving drug.
• Be aware that an allergic reaction may occur a few days after therapy starts.
• Monitor BUN and serum creatinine levels for early signs of nephrotoxicity. Also monitor fluid intake and output; decreasing urine output may indicate nephrotoxicity.
• Assess bowel pattern daily; severe diarrhea may indicate pseudomembranous colitis.
• Assess for signs of superinfection, such as perineal itching, fever, malaise, redness, pain, swelling, drainage, rash, diarrhea, and cough or sputum changes.

Patient Teaching

• Instruct patient to complete the prescribed course of therapy.
• Tell patient to shake oral suspension before measuring and to use a liquidmeasuring device to ensure accurate doses.
• Tell patient to refrigerate oral suspension and to discard the unused portion after 14 days.
• Urge patient to report watery, bloody stools to prescriber immediately, even up to 2 months after drug therapy has ended.
• Inform patient that yogurt and buttermilk can help maintain intestinal flora and decrease diarrhea.
• Teach patient to recognize and report evidence of superinfection, such as furry tongue, perineal itching, and loose, foul-smelling stools.

3.Cephalexin

Mechanism of Action

Like all cephalosporins, cephalexin interferes with bacterial cell wall synthesis by inhibiting the final step in the crosslinking of peptidoglycan strands. Peptidoglycan makes the cell membrane rigid and protective. Without it, bacterial cells rupture and die. This mechanism of action is most effective against bacteria that divide rapidly, including many gram-positive and gram-negative bacteria.

Pharmacokinetics

• Bioavailability: 90%; absorption delayed in young children
• Peak serum time: 1 hr
• Peak plasma concentration: 10-18 mcg/mL (500-mg dose)
• Protein bound: 6-15%
• Minimally metabolized in liver
• Half-life: 0.5-1.2 hr
• Excretion: Urine (80-100% as unchanged drug)

Administration

• Give with or without food.
• Refrigerate oral suspension

Contraindications

Hypersensitivity to cephalosporins or penicillin

Precautions:

•   renal impairment, phenylketonuria
•  history of GI disease
• debilitated or emaciated patients
• elderly patients
• pregnant or breastfeeding patients.

Adverse reactions

• CNS: fever, headache, lethargy, paresthesia, syncope,seizures
• CV: edema, hypotension, vasodilation, palpitations, chest pain
• EENT: hearing loss
• GI: nausea, vomiting, diarrhea, abdominal cramps, oral candidiasis, pseudomembranous colitis
• GU: vaginal candidiasis, nephrotoxicity
• Hematologic: lymphocytosis, eosinophilia, bleeding tendency, hemolytic anemia, neutropenia, thrombocytopenia, agranulocytosis, bone marrow depression
• Musculoskeletal: joint pain Respiratory: dyspnea
• Skin: rash, maculopapular and erythematous urticaria
• Other: superinfection, chills, pain, allergic reaction, hypersensitivity reactions including anaphylaxis, serum sickness

Patient monitoring

• Assess for signs and symptoms of serious adverse reactions, including hypersensitivity, severe diarrhea, and bleeding.
• During long-term therapy, monitor CBC and liver and kidney function test results.

 Patient teaching

• Instruct patient to stop taking drug and contact prescriber immediately if he develops rash or difficulty breathing.
•  Tell patient to take drug with full glass of water.
•   Advise patient to report severe diarrhea.
•   As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

Nursing Considerations

• Use cephalexin cautiously in patients hypersensitive to penicillin because crosssensitivity occurs in about 10% of them. If possible, obtain culture and sensitivity test results, as ordered, before giving drug.
• Monitor patient’s BUN and serum creatinine levels to detect early signs of nephrotoxicity. Also monitor fluid intake and output; decreasing urine output may indicate nephrotoxicity.
• Monitor for allergic reactions a few days after therapy starts.
• Assess CBC, hematocrit, and serum AST, ALT, bilirubin, LD, and alkaline phosphatase levels during long-term therapy.
• Assess patient’s bowel pattern daily; severe diarrhea may indicate pseudomembranous colitis caused by Clostridium difficile. If diarrhea occurs, notify prescriber and expect to withhold cefotaxime and treat with fluids, electrolytes, protein, and an antibiotic effective against C. difficile.
• Assess patient for pharyngitis, ecchymosis, bleeding, and arthralgia; they may indicate a blood dyscrasia.

4.Cephapirin

Mechanism of Action

 Interferes with bacterial cell wall synthesis by inhibiting the final step in the crosslinking of peptidoglycan strands. Peptidoglycan makes the cell membrane rigid and protective. Without it, bacterial cells rupture and die.

Contraindications

Hypersensitivity to cephalosporins or their components

Adverse Reactions

• CNS: Chills, fever, headache, seizures
• CV: Edema
• EENT: Hearing loss
• GI: Abdominal cramps, diarrhea, elevated liver function test results, hepatic failure, hepatomegaly, nausea, oral candidiasis, pseudomembranous colitis, vomiting
• GU: Elevated BUN level, nephrotoxicity, renal failure, vaginal candidiasis
• HEME: Eosinophilia, hemolytic anemia, hypoprothrombinemia, neutropenia, thrombocytopenia, unusual bleeding MS: Arthralgia
• RESP: Dyspnea
• SKIN: Ecchymosis, erythema, erythema multiforme, pruritus, rash, Stevens-Johnson syndrome
• Other: Anaphylaxis; injection site pain, redness, and swelling; superinfection

Nursing Considerations

• Use cephapirin cautiously in patients hypersensitive to penicillins because crosssensitivity has occurred in about 10% of such patients.
• If possible, obtain culture and sensitivity test results, as ordered, before giving drug.
• For I.V. injection, reconstitute 1 g with 10 ml or more of appropriate diluent, such as sterile water for injection. Administer I.V. injection slowly over 3 to 5 minutes through tubing of a flowing compatible I.V. fluid.  For I.V. infusion, dilute further in 50 ml of D5W or normal saline solution and infuse over 15 to 30 minutes. Stop primary I.V. solution during cephapirin delivery
• For I.M. injection, reconstitute 1-g vial with 2 ml sterile water for injection or bacteriostatic water for injection. Inject deep into large muscle mass, such as the gluteus maximus.
• Store reconstituted drug up to 24 hours at room temperature or 10 days refrigerated.
• Don’t give cloudy solution.
• Assess I.V. site for extravasation and phlebitis.
• Monitor BUN and serum creatinine levels to detect early signs of nephrotoxicity. Also, monitor fluid intake and output; decreasing urine output may indicate nephrotoxicity.
• Monitor patient for allergic reactions a few days after therapy starts.
• Assess CBC, hematocrit, and serum AST, ALT, bilirubin, LD, and alkaline phosphatase levels during long-term therapy.
• Assess patient’s bowel pattern daily; severe diarrhea may indicate pseudomembranous colitis.
• Assess patient for pharyngitis, ecchymosis, bleeding, and arthralgia; they may indicate a blood dyscrasia.
•   Assess patient for furry tongue, perineal itching, and loose, foul-smelling stool; they may indicate superinfection.

Patient Teaching

Instruct patient to immediately report severe diarrhea or evidence of blood dyscrasia or superinfection to prescriber.

Caution

penicillin allergy, renal dysfunction, antibiotic-associated colitis, seizure disorder, concomitant use of nephrotoxic drugs

5.Cephradine

Mechanism of Action

 Interferes with bacterial cell wall synthesis by inhibiting the final step in the crosslinking of peptidoglycan strands. Peptidoglycan makes the cell membrane rigid and protective. Without it, bacterial cells rupture and die.

Contraindications

 Hypersensitivity to cephalosporins or their components

Adverse Reactions

• CNS: Chills, fever, headache, seizures
• CV: Edema
• EENT: Hearing loss, oral candidiasis
• GI: Abdominal cramps, diarrhea, elevated liver function test results, hepatic failure, hepatomegaly, nausea, pseudomembranous colitis, vomiting
• GU: Elevated BUN level, nephrotoxicity, renal failure, vaginal candidiasis
• HEME: Eosinophilia, hemolytic anemia, hypoprothrombinemia, neutropenia, thrombocytopenia, unusual bleeding
• MS: Arthralgia
• RESP: Dyspnea
• SKIN: Ecchymosis, erythema, erythema multiforme, pruritus, rash, Stevens-Johnson syndrome
• Other: Anaphylaxis, superinfection

Nursing Considerations

• If possible, obtain culture and sensitivity test results, as ordered, before giving drug.
• Monitor patients hypersensitive to penicillin for evidence of hypersensitivity reaction because cross-sensitivity has occurred in about 10% of such patients.
• Store oral suspension for 7 days at room temperature or for 14 days if refrigerated.
• Monitor BUN and serum creatinine levels to detect early signs of nephrotoxicity. Also monitor fluid intake and output; decreasing urine output may indicate nephrotoxicity.
• Monitor patient for allergic reactions a few days after therapy starts. If hypersensitivity develops, be prepared to stop drug and administer antihistamines, corticosteroids, and vasopressors, as ordered. Also prepare to administer oxygen, maintain an open airway, and assist with endotracheal intubation, as appropriate.
• Assess CBC, hematocrit, and serum AST, ALT, bilirubin, LD, and alkaline phosphatase levels during long-term therapy.
• Assess patient’s bowel pattern daily; severe diarrhea may indicate pseudomembranous colitis. Obtain a stool specimen to test for Clostridium difficile. Keep in mind that this serious adverse reaction can occur during therapy or up to several weeks after therapy ends. Also avoid giving antiperistaltic antidiarrheals, such as atropine and diphenoxylate or loperamide, because they may delay elimination of toxins from the bowel and damage the colon from toxin retention. Mild cases may respond after cephradine is discontinued. For moderate or severe cases, be prepared to administer fluids, electrolytes, and protein replacement as ordered.
• If patient has a history of GI disease, especially ulcerative colitis, regional enteritis, or antibiotic-associated colitis, assess him often for diarrhea because he is at risk for pseudomembranous colitis.
• Assess patient for pharyngitis, ecchymosis, bleeding, and arthralgia; these may indicate a blood dyscrasia.
• If patient has a seizure, notify prescriber immediately and expect to discontinue drug. Institute seizure precautions according to facility policy.

Patient Teaching

• If patient develops GI distress, advise him to take cephradine with food.
• Advise patient to complete prescribed course of therapy.
• Urge patient to avoid missing doses and to take the drug at evenly spaced intervals. If patient misses a dose, instruct him to take it as soon as possible unless it’s almost time for the next dose. Emphasize that he shouldn’t double the dose.
• Tell patient that yogurt and buttermilk help maintain intestinal flora and can decrease diarrhea during therapy.
• Instruct patient to immediately report to prescriber severe diarrhea or evidence of blood dyscrasia or superinfection. Warn patient not to take any OTC antidiarrheals before consulting prescriber.
• Tell patient to notify prescriber if symptoms don’t improve within a few days.

Oral administration

Adults:

• Urinary tract infections: 500mg four times daily or 1g twice daily. Infections which are severe or chronic may necessitate the administration of higher doses. Where complications arise including prostatitis and epididymitis continued intensive treatment is required.
• Respiratory tract infections: 250 to 500mg four times daily or 500mg to 1g twice daily, dependent on the site and severity of the infection.
• Skin and soft tissue infections: 250 to 500mg four times daily or 500mg to 1g twice daily, again dependent on the site and severity of the infection.

Children:

• Total daily dose of 25 to 50mg/kg given in two or four equally divided doses.
• Otitis media: Total daily dose of 75 to 100mg/kg given in divided doses 6 to 12 hourly.
• Maximum daily dosage: 4 gm

Elderly:

The normal adult dose is appropriate. Patients with impaired renal or hepatic function should be monitored during treatment.

For injectable administration:

• Adult: The usual dose is 2-4 gm daily in four equally divided doses up to 8 gm daily. For prophylaxis a single preoperative dose of 1-2 gm intramuscularly or intravenously is given.
• Children: The dose is 50-100 mg/kg daily in four equally divided doses, up to 300 mg/kg daily in severe infection.

Side Effects

• Blood and lymphatic system disorders- Unknown: blood disorders (including thrombocytopenia, leucopenia, agranulocytosis, aplastic anaemia and haemolytic anaemia)
• Immune system disorders- Unknown: Fever, serum sickness like reactions, anaphylaxis
• Psychiatric disorders- Unknown: Confusion, sleep disturbances
• Nervous system disorders- Unknown: hyperactivity, hypertonia, dizziness, nervousness; Rarely: Headache
• Hepatobiliary disorders- Frequency unknown: Liver, enzyme disturbances, transient hepatitis, cholestatic jaundice
• Renal and urinary disorders- Unknown: Reversible interstitial nephritis
• Investigations- Unknown: Elevation of blood urea nitrogen, serum creatinine, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase.

Precautions & Warnings

• Prolonged use of an anti-infective may result in the development of superinfection due to the emergence of resistant organisms.
• Cephradine should be administered with care to patients hypersensitive to penicillins because of the risk of cross-sensitivity between beta-lactam antibiotics.
• Cephalosporin antibiotics may cause a positive result in Coombs’ testing. When Coombs testing is performed on neonates whose mothers received cephalosporins prior to labour, it should be noted that a positive result may be due to the drug.
• Cephradine may cause a false positive urine glucose result when Benedict’s or Fehling’s solutions or tablets such as Clinitest are used in the testing. This does not occur with enzyme-based tests (e.g. Clinistix, Diastix).
• Dosage adjustment is necessary in renal impairment.
• This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Monitoring Requirements:

Therapeutic:  Culture and sensitivities, serum levels, signs and symptoms of infection (e.g. fever, WBC)

REFERENCES

1. Robert Kizior, Keith Hodgson, Saunders Nursing Drug handbook,1st edition 2024, Elsevier Publications. ISBN-9780443116070
2. McGraw Hill- Drug Handbook, Seventh Edition, 2013, McGraw Hill Education Publications,9780071799430.
3. April Hazard, Cynthia Sanoski, Davi’s Drug Guide for Nurses -Sixteenth Edition 2019, FA Davis Company Publications,9780803669451.
4. Jones and Bartlet, Pharmacology for Nurses, Second Edition, 2020, Jones and Bartlet Learning Publications, ISBN 9781284141986.
5. Nursebro.com, Search – Nursebro

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