🧬 INTRODUCTION
Klebsiella pneumoniae carbapenemases (KPCs) represent a significant class A β-lactamase threat among Gram-negative bacteria, known for their capacity to hydrolyze a wide spectrum of β-lactams, including carbapenems—the last line of defense in treating multidrug-resistant infections. This study aimed to systematically evaluate the global distribution, prevalence, and resistance patterns of KPC-producing Gram-negative bacterial clinical isolates. The comprehensive analysis incorporated data from 119 eligible studies out of 1993 screened articles, covering all major continents and offering a critical snapshot of KPC's global burden. These organisms, especially Klebsiella pneumoniae and Escherichia coli, are increasingly implicated in nosocomial outbreaks and community infections that pose severe challenges to current antibiotic therapies. This research reinforces the urgency to adopt robust infection control protocols and antimicrobial stewardship measures on a global scale.
🌍 GLOBAL DISTRIBUTION OF KPC-PRODUCING BACTERIA
The review confirms the widespread global distribution of KPC-producing Gram-negative pathogens. Asia led the published data with 49 studies, followed by Europe (29), North America (14), South America (11), and Africa (3), with an additional 13 studies spanning multiple continents. This wide geographic representation underscores the critical reality that no region remains unaffected. While high-income countries have reported relatively advanced detection and surveillance systems, resource-limited nations may underreport due to infrastructure constraints. The global reach of these resistant pathogens calls for international collaboration in monitoring and response mechanisms. Mobility of populations, international trade, and travel play key roles in the dissemination, making KPCs a true global public health concern.
🔬 MOLECULAR CHARACTERISTICS AND GENE DETECTION
The genetic characterization of the KPC-producing isolates revealed a dominant presence of the blaKPC-2 and blaKPC-3 genes. Among the studies evaluating specific genes, 91% (52/57) identified blaKPC-2, while 46% (26/57) reported blaKPC-3, indicating the prevalence of these two alleles in global outbreaks. These genes are frequently located on transferable plasmids, enhancing their potential for interspecies transmission. The molecular epidemiology of KPCs is essential not only for diagnostics but also for tracking the emergence of new resistant clones. Genetic surveillance helps in understanding local versus imported cases, guiding infection control policies. Continued research in this area is vital for early detection and tailored therapeutic strategies.
🦠 DIVERSITY OF BACTERIAL SPECIES PRODUCING KPC
While Klebsiella pneumoniae remains the most common KPC-producer (96 studies), the enzyme's presence in multiple other species indicates widespread gene dissemination. These include Escherichia coli (52), Enterobacter cloacae (31), Citrobacter spp. (24), and even less common isolates like Raoultella spp. and Morganella spp. This species diversity increases the difficulty of detection and treatment, especially in settings where laboratory capacity is limited. The evolution of resistance across a broad spectrum of clinically significant bacteria suggests that resistance is no longer restricted to a single genus but is rather an ecosystem-level threat. This highlights the need for comprehensive species-specific surveillance to understand the complete clinical burden.
💊 RESISTANCE PATTERNS AND TREATMENT CHALLENGES
One of the critical observations from the analysis is the resistance patterns displayed by these organisms. Resistance to ceftazidime–avibactam remained low (0–4%), making it one of the most promising therapeutic agents. However, resistance to other agents like polymyxins (4–80%), tigecycline (0–73%), and trimethoprim–sulfamethoxazole (5.6–100%) was more variable and often alarmingly high. These findings reflect the shrinking therapeutic arsenal available to clinicians. Multidrug resistance among KPC-producing isolates not only leads to limited treatment options but also results in increased morbidity, mortality, and healthcare costs. These resistance patterns call for the urgent development of novel antimicrobials and optimization of combination therapies.
🛡️ RECOMMENDATIONS AND GLOBAL IMPLICATIONS
The global rise in KPC-producing organisms necessitates immediate action through comprehensive infection control strategies, including enhanced hand hygiene, contact precautions, and environmental decontamination. Equally important are antimicrobial stewardship programs to curb the inappropriate use of broad-spectrum antibiotics. International guidelines should support the integration of rapid molecular diagnostic tools and real-time data-sharing platforms. Given the ability of KPC genes to rapidly disseminate across species and continents, a “One Health” approach that encompasses human, animal, and environmental health is required. Without a coordinated global response, KPCs could escalate into an untreatable pandemic-level antimicrobial resistance crisis.
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