From the Guidelines
For the treatment of Klebsiella pneumoniae infections caused by KPC-producing carbapenem-resistant Enterobacterales (CRE), ceftazidime/avibactam and meropenem/vaborbactam are the recommended first-line treatment options. These novel β-lactam agents have shown improved clinical outcomes and reduced mortality compared to traditional antibiotic regimens 1. The choice between ceftazidime/avibactam and meropenem/vaborbactam may depend on the site of infection, with meropenem/vaborbactam potentially being preferred for pneumonia due to its high epithelial lining fluid (ELF) concentrations 1.
Key Considerations
- Ceftazidime/avibactam and meropenem/vaborbactam have been shown to be effective in treating KPC-producing CRE infections, with a significant reduction in 28-day mortality 1.
- Imipenem/relebactam and cefiderocol may also be considered as potential alternatives, although clinical studies on their efficacy in KPC-producing CRE infections are limited 1.
- Local epidemiology and the emergence of resistance to ceftazidime/avibactam should be taken into account when selecting a treatment option 1.
Treatment Options
- Ceftazidime/avibactam: recommended as a first-line treatment option for KPC-producing CRE infections 1.
- Meropenem/vaborbactam: recommended as a first-line treatment option for KPC-producing CRE infections, potentially preferred for pneumonia 1.
- Imipenem/relebactam and cefiderocol: may be considered as alternative treatment options, although more evidence is needed to support their use 1.
From the FDA Drug Label
2 Complicated Urinary Tract Infections (cUTI), including Pyelonephritis AVYCAZ (ceftazidime and avibactam) is indicated for the treatment of complicated urinary tract infections (cUTI) including pyelonephritis in adult and pediatric patients (at least 31 weeks gestational age) caused by the following susceptible gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii complex, Proteus mirabilis, and Pseudomonas aeruginosa.
3 Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP) AVYCAZ (ceftazidime and avibactam) is indicated for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adult and pediatric patients (at least 31 weeks gestational age) caused by the following susceptible gram-negative microorganisms: Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae.
Klebsiella Pneumoniae is listed as one of the susceptible gram-negative microorganisms for the treatment of Complicated Urinary Tract Infections (cUTI) and Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP) with AVYCAZ (ceftazidime and avibactam) 2.
Additionally, Klebsiella pneumoniae is also listed as a susceptible microorganism for the treatment of Nosocomial Pneumonia with piperacillin and tazobactam for injection 3.
- Key points:
- AVYCAZ is indicated for the treatment of cUTI and HABP/VABP caused by Klebsiella pneumoniae.
- Piperacillin and tazobactam for injection is indicated for the treatment of nosocomial pneumonia caused by Klebsiella pneumoniae.
From the Research
Klebsiella Pneumoniae Infections
- Klebsiella pneumoniae (Kp) is an opportunistic pathogen and a leading cause of healthcare-associated infections, mostly affecting individuals with compromised immune systems or suffering from concurrent bacterial infections 4.
- The dramatic increase in hypervirulent strains and the emergence of new multidrug-resistant clones have resulted in Kp occurrence among previously healthy people and increased morbidity and mortality 4.
Treatment of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) Infections
- Many antibiotics, including the carbapenem group, fail to treat Klebsiella pneumoniae infections effectively, and the definitive treatment for CRKP infections is still uncertain 5.
- Ceftazidime-avibactam (CZA), meropenem-vaborbactam, and imipenem/cilastatin-relebactam are novel antimicrobial agents that have shown considerable improvement in safety and efficacy compared to traditional polymyxin-based combination therapy for the treatment of KPC infections 6.
- CZA and meropenem-vaborbactam combinations have high potential for synergism against CRKP isolates, with synergy detected against 97.6% of the isolates in the checkerboard test 5.
Resistance to Ceftazidime-Avibactam
- CZA-resistant strains have been reported increasingly, especially with pneumonia or prior suboptimal blood exposure to C/A treatment 7.
- A retrospective study found that 17 patients had colonization or invasive infection due to Klebsiella pneumoniae with resistance to C/A and susceptibility to meropenem, with the blaKPC genotype detected in all isolates revealing a D179Y mutation in the blaKPC-2 gene 7.
Comparative In Vitro Activity of Novel β-Lactam/β-Lactamase Inhibitor Combinations
- Imipenem-relebactam (IRL) demonstrated excellent activity against CRKP and CRPA with susceptibility rates at 95.8% and 91.7%, respectively 8.
- CZA and meropenem-vaborbactam showed comparable susceptibility to IRL against CRKP, but susceptibility of CRPA to CZA was modest at 79.2%, whereas most CRPA strains were resistant to meropenem-vaborbactam 8.