What alternative antibiotics can be used if a patient is resistant to ceftazidime (Ceftazidime)-avibactam (Avibactam)?

From the Guidelines

If a patient is resistant to ceftazidime-avibactam, the most appropriate alternative antibiotic to consider is meropenem-vaborbactam, as suggested by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines 1. When considering alternative antibiotics for a patient resistant to ceftazidime-avibactam, several factors such as the type of infection, severity, and resistance patterns must be taken into account.

Key Considerations

• The patient's specific infection and resistance patterns should guide the choice of alternative antibiotics.
• For severe infections due to carbapenem-resistant Enterobacterales (CRE), meropenem-vaborbactam or ceftazidime-avibactam (if active in vitro) are suggested by the ESCMID guidelines 1.
• In cases where the infection is caused by CRE carrying metallo-b-lactamases and/or resistant to all other antibiotics, including ceftazidime-avibactam and meropenem-vaborbactam, treatment with cefiderocol may be conditionally recommended 1.

Alternative Antibiotics

• Meropenem-vaborbactam (4g IV every 8 hours) is a newer agent specifically designed for resistant gram-negative bacteria.
• Cefiderocol (2g IV every 8 hours) offers a novel mechanism of action and may be considered for severe infections due to CRE.
• For non-severe infections due to CRE, under the consideration of antibiotic stewardship, the use of an old antibiotic chosen from among the in vitro active ones on an individual basis and according to the source of infection may be considered good clinical practice 1.

Important Notes

• The choice of antibiotic should be guided by susceptibility testing, as resistance to ceftazidime-avibactam often indicates complex resistance mechanisms.
• Combination therapy may be required in severe infections, and dosing adjustments are necessary for patients with renal impairment.
• Infectious disease consultation is recommended to optimize therapy against resistant pathogens.

From the Research

Alternative Antibiotics for Ceftazidime-Avibactam Resistance

If a patient is resistant to ceftazidime-avibactam, several alternative antibiotics can be considered:

• For urinary tract infections (UTIs) due to AmpC-β-lactamase-producing Enterobacteriales, options include:
  • Nitrofurantoin
  • Fosfomycin
  • Pivmecillinam
  • Fluoroquinolones
  • Cefepime
  • Piperacillin-tazobactam
  • Carbapenems 2
• For UTIs due to ESBL-E coli, options include:
  • Nitrofurantoin
  • Fosfomycin
  • Pivmecillinam
  • Amoxicillin-clavulanate
  • Finafloxacin
  • Sitafloxacin 2
• For UTIs due to ESBL-Klebsiella pneumoniae, options include:
  • Pivmecillinam
  • Fosfomycin
  • Finafloxacin
  • Sitafloxacin 2
• For UTIs due to carbapenem-resistant Enterobacteriales (CRE), options include:
  • Ceftazidime-avibactam
  • Meropenem/vaborbactam
  • Imipenem/cilastatin-relebactam
  • Colistin
  • Fosfomycin
  • Aztreonam
  • Amoxicillin-clavulanate
  • Aminoglycosides including plazomicin
  • Cefiderocol
  • Tigecycline 2
• For infections due to multidrug-resistant (MDR) Pseudomonas spp., options include:
  • Fluoroquinolones
  • Ceftazidime
  • Cefepime
  • Piperacillin-tazobactam
  • Carbapenems including imipenem-cilastatin/relebactam
  • Meropenem
  • Fosfomycin
  • Ceftolozane-tazobactam
  • Ceftazidime-avibactam
  • Aminoglycosides including plazomicin
  • Aztreonam
  • Cefiderocol
  • Colistin 2

Mechanisms of Resistance

Resistance to ceftazidime-avibactam can occur through various mechanisms, including:

• AmpC β-lactamase production 3
• ESBL production 4
• Carbapenemase production 5

Activity of Alternative Antibiotics

The activity of alternative antibiotics against ceftazidime-avibactam-resistant isolates varies:

• Cefiderocol, ceftazidime-avibactam, and eravacycline exhibit high activity against carbapenem-resistant E. coli isolates 5
• Ceftazidime-avibactam is active against fluoroquinolone-resistant Enterobacteriaceae and Pseudomonas aeruginosa 4