What are the indications, adult dosing (including renal dose adjustments), contraindications, adverse effects, and monitoring recommendations for ceftazolin?

Ceftazolin: Clinical Overview

Ceftazolin is a first-generation cephalosporin with excellent activity against methicillin-susceptible Staphylococcus aureus (MSSA) and most Streptococcus species, but it lacks coverage of atypical respiratory pathogens, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA). 1

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Indications

Approved Uses

• Skin and soft tissue infections caused by MSSA, including necrotizing infections when combined with clindamycin for streptococcal coverage 1
• Surgical prophylaxis for clean and clean-contaminated procedures 1
• Bone and joint infections due to susceptible staphylococci 1
• Endocarditis caused by penicillin-susceptible streptococci or MSSA (when penicillin allergy precludes first-line agents) 2

Off-Label but Guideline-Supported Uses

• Animal bite prophylaxis when combined with an agent covering Pasteurella multocida (e.g., doxycycline or a fluoroquinolone), though amoxicillin-clavulanate is preferred 1
• Necrotizing soft tissue infections as part of combination therapy with clindamycin and penicillin for mixed aerobic-anaerobic flora 1

Key Limitations

• Does NOT cover Pseudomonas aeruginosa, MRSA, or atypical respiratory pathogens (Mycoplasma, Chlamydophila, Legionella) 1, 2
• Not appropriate for community-acquired pneumonia (CAP) because it lacks atypical coverage and is inferior to ceftriaxone for typical bacterial pathogens 1, 3
• Not recommended for hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) due to inadequate gram-negative and Pseudomonas coverage 1

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Adult Dosing

Standard Dosing (Normal Renal Function)

• Mild-to-moderate infections: 1 g IV every 8 hours 1, 2
• Severe infections (e.g., endocarditis, necrotizing fasciitis): 1–2 g IV every 6–8 hours 1, 2
• Surgical prophylaxis: 1–2 g IV as a single preoperative dose (repeat intraoperatively if procedure exceeds 3–4 hours) 1

Renal Dose Adjustments

Ceftazolin requires dose reduction in renal impairment because it is primarily eliminated via the kidneys (>90% urinary excretion) 2:

Creatinine Clearance (CrCl)	Recommended Dose
≥55 mL/min	Full dose: 1–2 g IV q6–8h
35–54 mL/min	1–2 g IV q8h or 500 mg–1 g IV q12h
11–34 mL/min	500 mg–1 g IV q12–24h
≤10 mL/min	500 mg IV q24–48h
Hemodialysis	500 mg–1 g IV after each dialysis session
Continuous renal replacement therapy (CRRT)	1–2 g IV q12h (adjust based on effluent rate)

Dosing adjustments are based on standard pharmacokinetic principles for renally cleared beta-lactams 2

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Contraindications

Absolute Contraindications

• Documented IgE-mediated (anaphylactic) hypersensitivity to cephalosporins 1
• History of severe immediate hypersensitivity (anaphylaxis, angioedema, Stevens-Johnson syndrome) to penicillins due to 1–10% cross-reactivity risk 1

Relative Contraindications (Use with Caution)

• Non-severe penicillin allergy (e.g., delayed rash): ceftazolin may be used cautiously if no alternative exists, but cephalosporins should generally be avoided unless penicillin allergy has been definitively excluded 1
• Severe renal impairment without dose adjustment: risk of drug accumulation, seizures, and neurotoxicity 2

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Adverse Effects

Common (≥1%)

• Pain at intramuscular injection site (minimal with IV administration) 2
• Gastrointestinal disturbances: nausea, diarrhea (less common than with broader-spectrum cephalosporins) 2
• Transient elevation of liver enzymes (AST, ALT) 2

Serious but Rare (<1%)

• Hypersensitivity reactions: rash, urticaria, anaphylaxis (1–10% cross-reactivity with penicillin-allergic patients) 1, 2
• Hematologic toxicity: eosinophilia, thrombocytopenia, positive direct Coombs test (rare; no cases reported in initial clinical trials) 2
• Nephrotoxicity: interstitial nephritis (rare; no renal toxicity observed in early studies) 2
• Clostridioides difficile infection: risk increases with prolonged use 1
• Seizures: rare, typically in patients with renal impairment receiving excessive doses 2

Drug Interactions

• Aminoglycosides: potential additive nephrotoxicity when used in combination (monitor renal function closely) 1
• Probenecid: decreases renal clearance of ceftazolin, prolonging half-life (may require dose adjustment) 2

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Monitoring Recommendations

Baseline Assessment

• Renal function (serum creatinine, estimated CrCl) to guide dosing 2
• Allergy history (specifically penicillin and cephalosporin hypersensitivity) 1
• Baseline complete blood count (CBC) and liver function tests (LFTs) in prolonged therapy 2

During Therapy

• Renal function: monitor serum creatinine every 2–3 days in patients with baseline renal impairment or receiving concomitant nephrotoxic agents 2
• Clinical response: assess fever resolution, wound healing, or infection control within 48–72 hours 1
• Signs of hypersensitivity: rash, pruritus, respiratory distress (discontinue immediately if anaphylaxis occurs) 1, 2
• CBC and LFTs: weekly monitoring in prolonged courses (>7–10 days) to detect hematologic or hepatic toxicity 2

Post-Therapy

• Follow-up cultures (if applicable) to confirm microbiologic eradication 1
• Assess for C. difficile infection if diarrhea develops during or after treatment 1

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Common Pitfalls and Caveats

Inappropriate Use in Pneumonia

• Never use ceftazolin for community-acquired pneumonia (CAP): it lacks atypical pathogen coverage (Mycoplasma, Chlamydophila, Legionella) and is inferior to ceftriaxone for typical bacterial pathogens 1, 3
• Not appropriate for hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP): inadequate gram-negative and Pseudomonas coverage 1

Inadequate Coverage for Resistant Organisms

• Does NOT cover MRSA: vancomycin or linezolid is required for suspected or confirmed MRSA infections 1
• Does NOT cover Pseudomonas aeruginosa: use antipseudomonal beta-lactams (piperacillin-tazobactam, cefepime, meropenem) when Pseudomonas is suspected 1
• Does NOT cover extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae: carbapenems or ceftolozane-tazobactam are required 4, 5, 6

Dosing Errors

• Failure to adjust dose in renal impairment: leads to drug accumulation, seizures, and neurotoxicity 2
• Underdosing in severe infections: use 2 g IV every 6–8 hours (not 1 g) for life-threatening infections such as endocarditis or necrotizing fasciitis 1, 2

Allergy Considerations

• Do NOT use ceftazolin in patients with documented IgE-mediated penicillin allergy unless penicillin allergy has been definitively excluded (1–10% cross-reactivity risk) 1
• Cephalosporins should be avoided in patients with severe immediate hypersensitivity to penicillins (anaphylaxis, angioedema, Stevens-Johnson syndrome) 1

Monotherapy Limitations

• Ceftazolin monotherapy is inadequate for necrotizing soft tissue infections: must be combined with clindamycin (for toxin suppression) and penicillin (for Clostridium species) 1
• Not appropriate for polymicrobial intra-abdominal infections: lacks anaerobic coverage (use ampicillin-sulbactam, piperacillin-tazobactam, or a carbapenem instead) 1

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Key Takeaways

• Ceftazolin is a narrow-spectrum first-generation cephalosporin with excellent MSSA and streptococcal coverage but lacks activity against MRSA, Pseudomonas, and atypical respiratory pathogens 1, 2
• Primary indications: skin/soft tissue infections, surgical prophylaxis, bone/joint infections, and endocarditis (when penicillin allergy precludes first-line agents) 1, 2
• Renal dose adjustment is mandatory: failure to adjust in renal impairment risks drug accumulation and neurotoxicity 2
• Never use for pneumonia (CAP, HAP, or VAP): inadequate spectrum for respiratory pathogens 1, 3
• Avoid in patients with severe penicillin allergy: 1–10% cross-reactivity risk 1