Editor's note: With the increase in multi-drug resistant Gram-negative bacterial infections (MDR-GNB) worldwide, the use strategy of carbapenems as key drugs for the treatment of such infections has received widespread attention. However, the problem of drug resistance caused by the overuse of carbapenems is becoming increasingly serious, which not only challenges the ability of clinical treatment of serious infections, but also forces experts and scholars in the field of infectious diseases worldwide to seek more effective antibacterial drug use solutions. At the just-concluded 34th European Congress of Clinical Microbiology and Infectious Diseases (ESCMID Global 2024), Dr. Pranita Tamma from the Johns Hopkins University School of Medicine and Dr. Heiman Wertheim from the Radboud University Medical Center held a wonderful debate on the use of carbapenems in the treatment of MDR-GNB infections. At the conference, "Infectious Disease Frontier" specially invited two experts to share their profound insights and valuable experiences on this topic.Infectious Disease Frontier: Could you share the unique advantages of Carbapenem antibiotics in treating multi-drug resistant Gram-negative infections, and do these advantages justify their use as a first-line treatment?
Dr. Tamma: Carbapenems, such as Meropenem, Imipenem, and Ertapenem, have significant roles due to their broad-spectrum activity. Notably, Meropenem and Imipenem are effective against Pseudomonas, a capability Ertapenem lacks. This distinction is crucial when choosing an initial treatment, especially for critically ill patients who might be infected with Pseudomonas. The decision to use carbapenems early in the treatment process is influenced by the prevalence of resistant organisms in a particular region. For instance, in the United States, a smaller percentage of E. coli are ESBL-producers compared to other parts of the world like India and potentially China. In settings with high ESBL prevalence, initiating treatment with a carbapenem in intensive care units might be prudent, followed by a rapid switch to a narrower-spectrum antibiotic once specific pathogens are identified.
Infectious Disease Frontier: In your view, what are the potential risks associated with the use of carbapenem antibiotics? Are you concerned that these risks may outweigh the potential benefits in treating multidrug-resistant Gram-negative infections?
Dr. Wertheim: Globally, Carbapenems have been overused, leading to significant resistance, particularly in the Mediterranean and parts of Asia. This misuse largely arises from a lack of precise diagnostics, which would allow for more targeted treatments. Now, we face widespread Carbapenem resistance, diminishing these drugs’ effectiveness. In places like the Netherlands, Sweden, and Norway, where antibiotic resistance rates remain low, it’s crucial to not repeat these errors and to use antibiotics more judiciously. Carbapenems are no longer as successful due to this resistance, necessitating a search for alternative strategies.
Infectious Disease Frontier: How do you suggest managing and preventing the potential emergence of carbapenem resistance? Do you believe that current resistance monitoring and management strategies are adequate?
Dr. Tamma: Managing carbapenem resistance involves careful consideration of antibiotic necessity and rapid discontinuation or de-escalation once an infection is ruled out or identified as caused by a non-resistant organism. Effective infection control practices are essential, especially meticulous hand hygiene and environmental cleaning to prevent the spread of carbapenemase-producing organisms like KPC, NDM, and OXA-48. Unfortunately, in regions where carbapenemase prevalence is high, our hand is often forced to use broad-spectrum drugs empirically. However, improving infection control and judicious use of antibiotics remain our best strategies in combating resistance.
Infectious Disease Frontier: What alternative or complementary treatment options do you suggest for addressing the current challenges in treating multidrug-resistant Gram-negative infections?
Dr. Wertheim: This is a complex area. There are several old and new antibiotics available, including Aminoglycosides and Fluoroquinolones, though resistance issues also affect these. Newer compounds are being developed as Carbapenem-sparing strategies, which is promising. Understanding the specific pathogens, their resistance mechanisms, and the most effective antibiotics for each case is essential. Local epidemiology should guide empirical and directed therapy choices, highlighting the importance of comprehensive national guidelines for antibiotic use. It is vital for healthcare providers to know all available antibiotics, their mechanisms of action, and when they become ineffective due to resistance. Developing national recommendations based on local data is crucial for devising effective treatment strategies.
