From the Guidelines
The recommended treatment approach for Klebsiella pneumoniae infections producing OXA-48 and NDM carbapenemases in India is ceftazidime/avibactam plus aztreonam, as this combination has shown in vitro synergy and significantly lower 30-day mortality rates compared to other antibiotics active in vitro 1. This approach is based on the strongest and most recent evidence, which prioritizes the reduction of morbidity, mortality, and improvement of quality of life. The use of ceftazidime/avibactam plus aztreonam is recommended due to its effectiveness against MBL-producing Enterobacterales, which are endemic in the Indian subcontinent 1. Some key points to consider in the treatment of these infections include:
- The combination of ceftazidime/avibactam and aztreonam has been shown to be effective in reducing mortality rates in patients with MBL-producing CRE infections 1.
- Cefiderocol may also be considered as an alternative option for the treatment of MBL-producing CRE infections, although the strength of recommendation is conditional and the certainty of evidence is low 1.
- The treatment approach should be guided by antimicrobial susceptibility testing whenever possible, as resistance patterns can vary 1.
- Source control through drainage of abscesses or removal of infected devices is crucial for successful treatment 1. It is essential to note that the treatment of Klebsiella pneumoniae infections producing OXA-48 and NDM carbapenemases is challenging due to the extensive resistance created by the dual carbapenemase production, resulting in high mortality rates 1. Therefore, combination therapy and infection control measures are critical to prevent the spread of these resistant organisms. While other studies may provide additional information on the treatment of these infections, the most recent and highest-quality study recommends the use of ceftazidime/avibactam plus aztreonam as the preferred treatment approach 1.
From the Research
Treatment Approach for Klebsiella pneumoniae Infections Producing OXA-48 and NDM Carbapenemases in India
The treatment of Klebsiella pneumoniae infections producing OXA-48 and NDM carbapenemases is a challenging task due to the limited availability of effective antibiotic options.
- The best available treatment option for OXA-48 producers is ceftazidime-avibactam, where available and when the price permits its use 2.
- Colistin remains as the second-line option if in vitro susceptibility is demonstrated with an appropriate method 2.
- For NDM producers, ceftazidime-avibactam and aztreonam combination or cefiderocol can be used, where available 2, 3.
- Higher cefiderocol MICs against NDM producers is concerning, and aztreonam-avibactam provides hope for the treatment of NDM producers 2.
- Combination therapy with fosfomycin and other agents such as imipenem, meropenem, or tigecycline may also be effective against OXA-48 producing K. pneumoniae strains 4.
- Targeted treatment with antibiotics such as tigecycline, meropenem, amikacin, ceftazidime-avibactam, imipenem, and colistin may be useful in treating OXA-48-related infections 5.
Key Considerations
- The choice of antibiotic therapy should be guided by susceptibility testing and clinical experience 2, 5.
- Combination therapy may not always confer additional benefit, and the use of definitive therapy including at least one active agent and source control may be protective 6.
- The global mortality rate at 30 days for OXA-48-related infections can be significant, highlighting the need for effective treatment strategies 5.