Comparative Pharmacology
Head-to-head clinical analysis: AVYCAZ versus CEFTRIAXONE SODIUM.
Peer-Reviewed Evidence
Head-to-head clinical analysis: AVYCAZ versus CEFTRIAXONE SODIUM.
AVYCAZ vs CEFTRIAXONE SODIUM
Head-to-head clinical comparison of therapeutic indices and safety profiles.
AVYCAZ is a combination of ceftazidime, a cephalosporin beta-lactam antibiotic, and avibactam, a non-beta-lactam beta-lactamase inhibitor. Ceftazidime inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to cell lysis. Avibactam protects ceftazidime from degradation by certain beta-lactamases, including Ambler class A, class C, and some class D enzymes.
Ceftriaxone inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), inhibiting transpeptidase activity, and disrupting peptidoglycan cross-linking.
Complicated intra-abdominal infections (cIAI) in combination with metronidazoleComplicated urinary tract infections (cUTI) including pyelonephritisHospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP)
Lower respiratory tract infectionsSkin and skin structure infectionsUrinary tract infectionsPelvic inflammatory diseaseBacterial septicemiaBone and joint infectionsIntra-abdominal infectionsMeningitisSurgical prophylaxisGonorrheaAcute otitis mediaLyme diseaseNeonatal sepsisCommunity-acquired pneumonia
1 vial (ceftazidime 2g and avibactam 0.5g) IV over 2 hours every 8 hours.
1-2 g IV/IM every 12-24 hours; maximum 4 g/day.
None Documented
None Documented
Ceftazidime: ~2.8 hours; avibactam: ~2.7 hours. Extended in renal impairment (e.g., CrCl <50 mL/min requires dose adjustment).
Terminal elimination half-life is 5.8-8.7 hours in adults with normal renal and hepatic function. In neonates, half-life is prolonged (up to 16 hours). In patients with renal impairment, half-life increases to 12-18 hours; in hepatic impairment, it may be 15-20 hours. Dose adjustment is not typically required unless both renal and hepatic impairment are present.
Ceftazidime is primarily excreted unchanged by the kidneys via glomerular filtration. Avibactam is also primarily eliminated renally and undergoes minimal metabolism. The metabolism of both components is not significantly mediated by cytochrome P450 enzymes.
Ceftriaxone is not extensively metabolized; it undergoes negligible hepatic metabolism. Approximately 33-67% is excreted unchanged in urine, and the remainder is excreted in feces via bile.
Ceftazidime: primarily renal (80-90% unchanged); avibactam: primarily renal (85-95% unchanged). Fecal excretion <1%.
Ceftriaxone is eliminated 33-67% unchanged in urine via glomerular filtration and tubular secretion, and the remainder is excreted in feces (primarily as microbiologically inactive metabolites) via biliary secretion. Biliary excretion accounts for approximately 35-45% of total clearance.
Ceftazidime: ~10% bound to albumin; avibactam: ~8% bound to human plasma proteins.
Ceftriaxone is 85-95% bound to plasma proteins, primarily albumin. Binding is saturable and concentration-dependent; free fraction increases at higher concentrations.
Ceftazidime: ~0.19 L/kg; avibactam: ~0.29 L/kg. Indicates extensive distribution into extracellular fluid.
Volume of distribution is 0.5-0.7 L/kg in adults, indicating extensive distribution into extracellular fluid and tissues. Vd is higher (0.8-1.0 L/kg) in neonates and decreased in elderly patients.
IV only; bioavailability is 100%.
IM: 100% bioavailable. Oral: not applicable (administered parenterally).
CrCl 31-50 mL/min: 1 vial IV q8h; CrCl 16-30 mL/min: 1 vial IV q12h; CrCl 6-15 mL/min: 1 vial IV q24h; CrCl ≤5 mL/min: 1 vial IV q48h.
For CrCl <10 mL/min: 2 g every 24 hours. No adjustment for CrCl >=10 mL/min.
No dosage adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C).
No adjustment required for Child-Pugh Class A or B. For Class C, use with caution; no specific dose adjustment defined.
Not approved for pediatric patients under 18 years of age.
50-75 mg/kg/day IV/IM divided every 12-24 hours; maximum 2 g/day.
Dose based on renal function, as per adult renal adjustment; no specific age-related adjustments.
No specific adjustment; monitor renal function and adjust based on CrCl as per renal guidelines.
No black box warning for AVYCAZ.
Do not use in neonates (≤28 days) if they are premature or have hyperbilirubinemia due to risk of bilirubin encephalopathy. Ceftriaxone displaces bilirubin from albumin, increasing risk of kernicterus. Calcium-containing solutions should not be administered within 48 hours of ceftriaxone use in neonates due to risk of fatal precipitation in lungs and kidneys.
["Hypersensitivity: Serious and occasionally fatal hypersensitivity reactions (anaphylaxis) have been reported in patients receiving beta-lactam antibiotics.","Clostridioides difficile-associated diarrhea (CDAD): Has been reported with nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis.","Direct Coombs test seroconversion: Positive direct Coombs test may develop during treatment, potentially interfering with crossmatching.","Central nervous system (CNS) adverse reactions: Including seizures, encephalopathy, and myoclonus have been reported, particularly in patients with renal impairment or higher doses.","Renal impairment: Dose adjustment required based on creatinine clearance.","Hepatotoxicity: Elevations of liver enzymes have been observed.","Nephrotoxicity: Concurrent use with nephrotoxic agents may increase risk."]
["Hypersensitivity reactions (anaphylaxis)","Clostridioides difficile-associated diarrhea","Risk of bilirubin encephalopathy in neonates with hyperbilirubinemia","Immune-mediated hemolytic anemia","Pancreatitis","Biliary sludge and pseudolithiasis","Seizures with high doses or renal impairment","Superinfection","Prolonged PT/INR (monitor in patients at risk)","Renal impairment: dose adjustment may be needed"]
["Known hypersensitivity to ceftazidime, avibactam, or other cephalosporins","Severe hypersensitivity (e.g., anaphylaxis) to any other beta-lactam antibacterial agents"]
["Hypersensitivity to ceftriaxone or any component","Hypersensitivity to cephalosporins","Premature neonates (≤41 weeks postmenstrual age)","Neonates (≤28 days) with hyperbilirubinemia","Neonates requiring calcium-containing IV solutions within 48 hours of ceftriaxone"]
Data Pending Review
Data Pending Review
No significant food interactions. However, alcohol should be avoided due to potential disulfiram-like reaction (nausea, vomiting, flushing, headache).
No significant food interactions. However, avoid alcohol (including in food/drink) during therapy and for 48 hours after last dose due to risk of disulfiram-like reaction (flushing, headache, nausea, vomiting).
AVYCAZ (ceftazidime-avibactam) is classified as FDA Pregnancy Category B. Animal reproduction studies in rats and rabbits at doses up to 1.6 times the human dose revealed no evidence of fetal harm. However, there are no adequate and well-controlled studies in pregnant women. Ceftazidime crosses the placenta. Risk cannot be ruled out; use only if clearly needed.
In animal studies, ceftriaxone sodium did not demonstrate teratogenicity. Human data are limited but do not indicate a significant risk of major birth defects. Use during the first trimester is generally considered safe, but caution is advised due to the bilirubin displacement potential in the third trimester, which may increase the risk of kernicterus in neonates.
Ceftazidime is excreted in human milk in low concentrations; avibactam excretion is unknown. The M/P ratio for ceftazidime is approximately 0.02. Caution is advised due to potential disruption of infant gut flora. Consider benefits of breastfeeding versus risk of infant exposure.
Ceftriaxone is excreted into breast milk in low amounts, with a milk-to-plasma (M/P) ratio of approximately 0.03. It is considered compatible with breastfeeding, but monitor the infant for potential gastrointestinal disturbances or allergic reactions.
No specific dose adjustments are recommended for pregnancy. Physiological changes in pregnancy (e.g., increased volume of distribution, enhanced renal clearance) may alter pharmacokinetics, but data are insufficient to recommend routine dose modification. Monitor clinical response and consider therapeutic drug monitoring if available.
Physiologic changes in pregnancy (e.g., increased volume of distribution, enhanced renal clearance) may require a dose increase to achieve therapeutic serum concentrations. Standard dosing is typically 1-2 g every 24 hours, but consider higher frequency (e.g., every 12 hours) in severe infections. Monitor clinical response and adjust accordingly.
Category C
Category C
AVYCAZ (ceftazidime-avibactam) is a beta-lactam/beta-lactamase inhibitor combination active against ESBLs, KPC, and OXA-48 carbapenemases. It is not active against metallo-beta-lactamases (e.g., NDM, VIM). Dose adjustment required for creatinine clearance <50 mL/min. Monitor for hypersensitivity reactions, including anaphylaxis. Can cause positive direct Coombs test without hemolysis.
Do not co-administer with calcium-containing IV solutions (including Ringer's lactate) due to risk of precipitation; avoid in neonates (<28 days) if requiring IV calcium. Administer IM deep intragluteal, not more than 1g per site. Crosses inflamed meninges; CSF levels 5-40% of serum. Highly protein-bound; displace bilirubin and may cause kernicterus in neonates. Monitor for biliary pseudolithiasis in prolonged use.
Take exactly as prescribed; complete full course even if feeling better.Inform your doctor if you have kidney disease; blood tests may be needed to adjust dose.Report any signs of allergic reaction (rash, hives, difficulty breathing, swelling).May cause diarrhea; tell your doctor if severe or persistent.Avoid alcohol during treatment and for 72 hours after last dose due to possible disulfiram-like reaction.
Complete the full course even if you feel better. Do not skip doses.Report any signs of allergy (rash, itching, swelling, difficulty breathing) immediately.May cause loose stools or diarrhea; notify your doctor if severe or persistent.Avoid alcohol during treatment and for 48 hours after last dose to prevent disulfiram-like reaction.If receiving this medication intravenously, inform staff if you are on calcium supplements or calcium-containing IV solutions.