ceftazidime
Regulatory sources consulted
Approved indications
- Serious infections due to susceptible gram-negative organisms, including hospital-acquired pneumonia, cystic fibrosis, meningitis, urinary, skin, intra-abdominal, and osteoarticular infections, dialysis-associated peritonitis, bacteremia, and febrile neutropenia.
Contraindications
Absolute
- Hypersensitivity to ceftazidime or cephalosporins, or a history of a severe immediate reaction to another beta-lactam.
Clinical warnings
- Major warning · It may cause severe hypersensitivity or anaphylaxis. Review any history of immediate beta-lactam reactions before use and discontinue if an allergic reaction occurs. — CIMA/AEMPS, ficha técnica 67007
- Major warning · It may cause Clostridioides difficile-associated diarrhea during or after treatment; assess significant diarrhea and avoid antiperistaltic drugs if colitis is suspected. — CIMA/AEMPS, ficha técnica 67007
- Major warning · Renal accumulation may cause encephalopathy, seizures, nonconvulsive status epilepticus, myoclonus, or coma; adjust strictly by CrCl and monitor neurologic status. — CIMA/AEMPS, ficha técnica 67007
Drug interactions
- HighNephrotoxic drugs and potent diuretics
Mechanism: Concomitant high doses may worsen renal function.
Recommendation: Closely monitor renal function.
CIMA/AEMPS, ficha técnica 67007
- ModerateChloramphenicol
Mechanism: In vitro antagonism with ceftazidime has been observed.
Recommendation: Avoid the combination when bactericidal activity is required.
CIMA/AEMPS, ficha técnica 67007
Adverse events
Common (≥1%)
Nausea, diarrhea, and rash
Rare but serious
Anaphylaxis, C. difficile colitis, and severe cytopenias
Pregnancy and lactation
Use during pregnancy only when clearly indicated. Small amounts pass into milk; monitor the infant for diarrhea, candidiasis, or sensitization and assess continuation according to the product.
Recent literature (PubMed)
Klebsiella pneumoniae carbapenemase (KPC) variants, which refer to the substitution, insertion, or deletion of amino acid sequence compared to wild blaKPC type, have reduced utility of ceftazidime-avibactam (CZA), a pioneer antimicrobial agent in treating carbapenem-resistant Enterobacterales infections. So far, more than 150 blaKPC variants have been reported worldwide, and most of the new variants were discovered in the past 3 years, which calls for public alarm. The KPC variant protein enhances the affinity to ceftazidime and weakens the affinity to avibactam by changing the KPC structure, thereby mediating bacterial resistance to CZA. At present, there are still no guidelines or expert consensus to make recommendations for the diagnosis and treatment of infections caused by KPC variants. In addition, meropenem-vaborbactam, imipenem-relebactam, and other new β-lactam-β-lactamase inhibitor combinations have little discussion on KPC variants. This review aims to discuss the clinical characteristics, risk factors, epidemiological characteristics, antimicrobial susceptibility profiles, methods for detecting blaKPC variants, treatment options, and future perspectives of blaKPC variants worldwide to alert this new great public health threat. Limited information indicates that ceftazidime produces low levels in milk that are not expected to cause adverse effects in breastfed infants. Occasionally disruption of the infant's gastrointestinal flora, resulting in diarrhea or thrush have been reported with cephalosporins, but these effects have not been adequately evaluated. Ceftazidime and is acceptable in nursing mothers.
The Infectious Diseases Society of America (IDSA) publishes annual guidance on the treatment of antimicrobial-resistant (AMR) gram-negative infections. Within the AMR guidance, suggested dosages of antibiotics for adults infected with AMR pathogens are provided. This document serves as a companion document to the IDSA guidance to assist pediatric specialists with dosing β-lactam agents for the treatment of AMR infections in children. A panel of 13 pediatric infectious diseases specialists, including 11 pharmacists and 2 physicians, reviewed existing pharmacokinetic/pharmacodynamic, animal, and clinical data for newer β-lactam agents that are available in the United States and suggested for the treatment of AMR infections (ie, cefiderocol, ceftazidime-avibactam, ceftazidime-avibactam and aztreonam, ceftolozane-tazobactam, imipenem-cilastatin-relebactam, meropenem-vaborbactam, sulbactam-durlobactam). Suggested dosing for ampicillin-sulbactam is also provided, given complexities in dosing for carbapenem-resistant Acinetobacter baumannii infections. Consensus-based suggested dosing for β-lactam agents used to treat AMR infections in neonates, infants, children, and adolescents and relevant supporting evidence are provided. Content is up to date as of December 1, 2024. Gaps and limitations to existing data are discussed. Optimizing antibiotic dosing is critical to improving the outcomes of children with AMR infections.
Infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), including carbapenem-resistant (CR) Enterobacterales (CRE; harboring mainly blaKPC, blaNDM, and blaOXA-48-like genes), CR- or MDR/XDR-Pseudomonas aeruginosa (production of VIM, IMP, or NDM carbapenemases combined with porin alteration), and Acinetobacter baumannii complex (producing mainly OXA-23, OXA-58-like carbapenemases), have gradually worsened and become a major challenge to public health because of limited antibiotic choice and high case-fatality rates. Diverse MDR/XDR-GNB isolates have been predominantly cultured from inpatients and hospital equipment/settings, but CRE has also been identified in community settings and long-term care facilities. Several CRE outbreaks cost hospitals and healthcare institutions huge economic burdens for disinfection and containment of their disseminations. Parenteral polymyxin B/E has been observed to have a poor pharmacokinetic profile for the treatment of CR- and XDR-GNB. It has been determined that tigecycline is suitable for the treatment of bloodstream infections owing to GNB, with a minimum inhibitory concentration of ≤ 0.5 mg/L. Ceftazidime-avibactam is a last-resort antibiotic against GNB of Ambler class A/C/D enzyme-producers and a majority of CR-P. aeruginosa isolates. Furthermore, ceftolozane-tazobactam is shown to exhibit excellent in vitro activity against CR- and XDR-P. aeruginosa isolates. Several pharmaceuticals have devoted to exploring novel antibiotics to combat these troublesome XDR-GNBs. Nevertheless, only few antibiotics are shown to be effective in vitro against CR/XDR-A. baumannii complex isolates. In this era of antibiotic pipelines, strict implementation of antibiotic stewardship is as important as in-time isolation cohorts in limiting the spread of CR/XDR-GNB and alleviating the worsening trends of resistance.
Pneumonia is frequently encountered in clinical practice, and Gram-negative bacilli constitute a significant proportion of its aetiology, especially when it is acquired in a hospital setting. With the alarming global rise in multidrug resistance in Gram-negative bacilli, antibiotic therapy for treating patients with pneumonia is challenging and must be guided by in vitro susceptibility results. In this review, we provide an overview of antibiotics newly approved for the treatment of pneumonia caused by Gram-negative bacilli. Ceftazidime-avibactam, imipenem-relebactam and meropenem-vaborbactam have potent activity against some of the carbapenem-resistant Enterobacterales, especially Klebsiella pneumoniae carbapenemase producers. Several novel antibiotics have potent activity against multidrug-resistant Pseudomonas aeruginosa, such as ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relabactam and cefiderocol. Cefiderocol may also play an important role in the management of pneumonia caused by Acinetobacter baumannii, along with plazomicin and eravacycline.