What it's for (Indications)
- Ceftazidime/avibactam is indicated for the treatment of various serious infections caused by susceptible Gram-negative microorganisms.
- Specifically, it is approved for complicated intra-abdominal infections (cIAI) in combination with metronidazole, complicated urinary tract infections (cUTI) including pyelonephritis, and hospital-acquired bacterial pneumonia (HABP) including ventilator-associated bacterial pneumonia (VABP).
- Furthermore, it is indicated for the treatment of infections due to aerobic Gram-negative organisms in adult patients who have limited treatment options.
- This includes infections caused by carbapenemase-producing Enterobacteriaceae (CPE) and other multidrug-resistant pathogens where alternative therapies may be ineffective or unavailable.
- The efficacy of ceftazidime/avibactam in these scenarios is attributed to its ability to overcome resistance mechanisms mediated by certain beta-lactamases, significantly expanding treatment possibilities for challenging infections.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | The recommended dosage of ceftazidime/avibactam for adult patients with a creatinine clearance (CrCl) greater than 50 mL/min is 2 grams of ceftazidime and 0.5 grams of avibactam administered every 8 hours by intravenous infusion over 2 hours. The duration of treatment depends on the type and severity of the infection, and the patient's clinical and microbiological response, typically ranging from 7 to 14 days. Dose adjustment is crucial for patients with renal impairment. For instance, in patients with CrCl 31 to 50 mL/min, the dose is reduced to 1 gram ceftazidime and 0.25 grams avibactam every 8 hours. For CrCl 16 to 30 mL/min, it is 0.5 grams ceftazidime and 0.125 grams avibactam every 8 hours. Patients with end-stage renal disease (CrCl ≤ 15 mL/min) requiring hemodialysis should receive 0.5 grams ceftazidime and 0.125 grams avibactam every 24 hours after hemodialysis on dialysis days. Proper reconstitution and dilution of the powder for concentrate are essential prior to administration to ensure safe and effective delivery. |
Safety & Warnings
Common Side Effects
- Ceftazidime/avibactam, while generally well-tolerated, can cause a range of side effects.
- Common adverse reactions reported in clinical trials include gastrointestinal disturbances such as nausea, vomiting, diarrhea, and abdominal pain.
- Headache, dizziness, and rash are also frequently observed.
- Infusion site reactions, including phlebitis or inflammation, may occur.
- Less common but notable side effects include transient elevations in liver enzymes (AST, ALT, alkaline phosphatase) and changes in renal function tests (e.
- g.
- , increased creatinine).
- More serious adverse events, though rare, can include severe hypersensitivity reactions (e.
- g.
- , anaphylaxis, Stevens-Johnson syndrome), *Clostridioides difficile*-associated diarrhea (CDAD), seizures, especially in patients with pre-existing renal impairment where dosage adjustments are not adequately made, and other central nervous system effects.
- Patients should be monitored for these potential adverse effects throughout treatment, and any concerning symptoms should be promptly evaluated.
Serious Warnings
- Black Box Warning: Ceftazidime/avibactam does not carry a formal FDA-mandated Black Box Warning. However, it is crucial for healthcare professionals and patients to be aware of several serious warnings and precautions associated with its use, which are often highlighted prominently in prescribing information. These serious warnings include the potential for severe hypersensitivity reactions, ranging from rash to life-threatening anaphylaxis, which necessitate immediate discontinuation of the drug and appropriate medical management. Another significant concern is the risk of *Clostridioides difficile*-associated diarrhea (CDAD), which can manifest as mild diarrhea to severe, potentially fatal colitis, and requires careful consideration in any patient presenting with diarrhea post-antibiotic treatment. Furthermore, central nervous system adverse reactions, such as seizures, encephalopathy, tremor, and myoclonus, have been reported, particularly in patients with renal impairment where dosage adjustments were not appropriate, underscoring the importance of renal function monitoring and precise dose modification. These serious risks, while not requiring a "Black Box," demand vigilant patient monitoring and judicious prescribing practices to ensure optimal patient outcomes and safety.
- Several important warnings are associated with the use of ceftazidime/avibactam.
- Patients should be carefully assessed for a history of hypersensitivity reactions to cephalosporins, penicillins, or other beta-lactam antibiotics, as cross-reactivity can occur, potentially leading to severe and even fatal anaphylactic reactions.
- If an allergic reaction occurs, the drug should be immediately discontinued.
- Like all broad-spectrum antibiotics, ceftazidime/avibactam can alter the normal gastrointestinal flora, leading to the overgrowth of *Clostridioides difficile* and subsequent *Clostridioides difficile*-associated diarrhea (CDAD), which can range in severity from mild diarrhea to fatal colitis.
- Careful diagnosis is required in patients presenting with diarrhea post-antibiotic use.
- Central nervous system adverse reactions, including seizures, encephalopathy, tremor, and myoclonus, have been reported, particularly in patients with renal impairment who did not receive appropriate dosage adjustments.
- Renal function should be monitored, and doses adjusted accordingly.
- Development of drug-resistant bacteria is a constant concern with antibiotic use, thus ceftazidime/avibactam should only be used for infections proven or strongly suspected to be caused by susceptible bacteria to preserve its effectiveness and minimize resistance.
How it Works (Mechanism of Action)
Ceftazidime/avibactam exerts its bactericidal activity through a dual mechanism. Ceftazidime, a third-generation cephalosporin, acts by inhibiting bacterial cell wall synthesis. It covalently binds to and inactivates penicillin-binding proteins (PBPs) located on the inner bacterial cytoplasmic membrane, thereby disrupting peptidoglycan synthesis, which is essential for cell wall integrity. This disruption leads to osmotic instability and subsequent bacterial cell lysis and death. Avibactam is a novel non-beta-lactam beta-lactamase inhibitor that restores the activity of ceftazidime against many Gram-negative bacteria that produce beta-lactamase enzymes. Avibactam forms a stable, covalent adduct with beta-lactamases, including Ambler Class A (e.g., KPC, CTX-M, SHV, TEM), Class C (AmpC), and some Class D (e.g., OXA-48-like) enzymes, effectively preventing them from hydrolyzing ceftazidime. This synergistic action allows ceftazidime to reach and bind to its PBP targets, thereby overcoming resistance mediated by these enzymes and expanding the spectrum of activity to cover multidrug-resistant pathogens, rendering the combination highly effective against difficult-to-treat infections.
Commercial Brands (Alternatives)
No other brands found for this formula.