From the Guidelines
For the treatment of infections caused by KPC-producing carbapenem-resistant Enterobacterales (CRE), including K. pneumoniae, ceftazidime/avibactam and meropenem/vaborbactam are recommended as first-line treatment options. This recommendation is based on the most recent and highest quality evidence available, which suggests that these novel β-lactam agents have improved clinical outcomes in patients with CRE infections compared to traditional antibiotic regimens 1. The use of ceftazidime/avibactam has been supported by several observational studies, which have shown a higher rate of 30-day clinical success and lower 28-day mortality compared to other treatment regimens 1. Meropenem/vaborbactam has also been shown to be effective in the treatment of CRE infections, with a higher clinical cure rate and reduced nephrotoxicity compared to the best available therapy 1.
Key Considerations
- The site of infection should be considered when choosing between ceftazidime/avibactam and meropenem/vaborbactam, with meropenem/vaborbactam potentially being preferred for infections such as pneumonia due to its improved intrapulmonary penetration 1.
- Local epidemiology and the emergence of resistance to ceftazidime/avibactam should also be taken into account when selecting a treatment regimen 1.
- Imipenem/relebactam and cefiderocol may be considered as alternative treatment options, although clinical studies on their efficacy in KPC-producing CRE infections are limited 1.
Treatment Approach
- Empiric therapy for suspected K. pneumoniae infections should include a carbapenem or a combination of piperacillin-tazobactam with an aminoglycoside, with treatment guided by susceptibility testing once available 1.
- Treatment duration should be optimized to minimize further resistance development while ensuring clinical cure, typically ranging from 7-14 days depending on the infection site and severity.
- Infection control measures, including hand hygiene, contact precautions, and antimicrobial stewardship, are essential to prevent the spread of AMR in K. pneumoniae 1.
From the FDA Drug Label
Vaborbactam does not have any antibacterial activity. Vaborbactam does not decrease the activity of meropenem against meropenem-susceptible organisms Resistance Mechanisms of beta-lactam resistance may include the production of beta-lactamases, modification of PBPs by gene acquisition or target alteration, up-regulation of efflux pumps, and loss of outer membrane porin. VABOMERE demonstrated in vitro activity against Enterobacteriaceae in the presence of some beta-lactamases and extended-spectrum beta-lactamases (ESBLs) of the following groups: KPC, SME, TEM, SHV, CTX-M, CMY, and ACT. In the Phase 3 cUTI trial with VABOMERE, some isolates of E. coli, K. pneumoniae, E. cloacae, C. freundii, P. mirabilis, P. stuartii that produced beta-lactamases, were susceptible to VABOMERE (minimum inhibitory concentration ≤4 mcg /mL). Some beta-lactamases were also produced by an isolate of K. pneumoniae that was not susceptible to VABOMERE (minimum inhibitory concentration ≥32 mcg/mL).
Antimicrobial Resistance (AMR) in K. pneumoniae: VABOMERE has demonstrated in vitro activity against K. pneumoniae that produce certain beta-lactamases, including KPC. However, some isolates of K. pneumoniae may not be susceptible to VABOMERE, particularly those that produce metallo-beta-lactamases or oxacillinases with carbapenemase activity.
- Key points:
- VABOMERE is active against K. pneumoniae that produce certain beta-lactamases, including KPC.
- Some isolates of K. pneumoniae may not be susceptible to VABOMERE.
- The efficacy of VABOMERE in treating clinical infections due to K. pneumoniae has been established in adequate and well-controlled clinical trials 2.
From the Research
Antimicrobial Resistance in K. Pneumoniae
- Antimicrobial resistance in K. pneumoniae is a growing concern, with increasing reports of carbapenem-resistant strains 3, 4, 5.
- The emergence of resistance to newer agents like ceftazidime-avibactam further complicates treatment options 5, 6.
- Combination therapy with ceftazidime-avibactam and other antimicrobials, such as aztreonam, colistin, or meropenem, may be effective against multidrug-resistant K. pneumoniae strains 3, 6.
Treatment Options for Carbapenem-Resistant K. Pneumoniae
- Colistin, tigecycline, and ceftazidime-avibactam are potential treatment options for carbapenem-resistant K. pneumoniae infections 3, 4, 5.
- Aztreonam, in combination with meropenem-vaborbactam or ceftazidime-avibactam, may also be effective against these strains 3, 6, 7.
- Cefiderocol, a newer antibiotic, has shown promise in treating complicated hospital-acquired K. pneumoniae infections, including those with NDM and OXA-48 resistance mechanisms 7.
Importance of Infection Control Measures
- Infection control measures are crucial in limiting the spread of multidrug-resistant organisms, particularly in cases where treatment options are limited 4.
- Implementing infection control measures, such as proper hygiene and isolation protocols, can help prevent the transmission of resistant strains and reduce the risk of outbreaks 4.