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Antibiotics | Retrospective Analysis of the Evolution of Multidrug-Resistant Gram-Negative Bacterial Infections in Tunisia from 1999 to 2019

Antibiotics | Retrospective Analysis of the Evolution of Multidrug-Resistant Gram-Negative Bacterial Infections in Tunisia from 1999 to 2019
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This study systematically analyzed the evolutionary trends of multidrug-resistant Gram-negative bacteria over 20 years (1999-2019) using nationwide data from 11 hospitals in Tunisia. The article reveals the severe situation of antibiotic misuse and resistance dissemination in common pathogens such as E. coli, K. pneumoniae, A. baumannii, and P. aeruginosa. These findings are critical for understanding resistance mechanisms, optimizing empirical treatment strategies, and promoting rational antimicrobial use.

 

Literature Overview
This article, 'Historical Overview of the Evolution of Multidrug-Resistant Gram-Negative Infections in Tunisia from 1999 to 2019', published in the journal Antibiotics, reviews and summarizes the resistance patterns of Gram-negative bacteria in Tunisia. By analyzing antimicrobial resistance profiles of over 213,434 isolates across 11 hospitals, the study systematically evaluates temporal changes in resistance rates for four major pathogens (E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii) and provides detailed longitudinal resistance data while highlighting Tunisia's critical challenges with antibiotic overuse and resistant strain dissemination.

Background Knowledge
Multidrug-resistant Gram-negative bacteria (MDR-GNB) represent significant global public health threats due to their complex cell wall structures and robust acquired resistance mechanisms, which severely limit therapeutic options. These pathogens primarily cause healthcare-associated and community-acquired infections, including urinary tract infections, bloodstream infections, respiratory infections, and intra-abdominal infections. In Tunisia, excessive antibiotic use and inadequate regulation have led to widespread dissemination of resistant strains (e.g., ESBL- and carbapenemase-producing organisms), particularly in hospital settings. Based on long-term data from Tunisia's antimicrobial resistance surveillance program (LART), this study assesses temporal resistance trends to inform empirical treatment strategies and future antimicrobial stewardship policies.

 

 

Research Methods and Experiments
The study collected 213,434 Gram-negative bacterial isolates (including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii) from 11 Tunisian hospitals between 1999 and 2019. Antimicrobial susceptibility testing employed EUCAST-recommended disk diffusion methods to evaluate resistance patterns against multiple antibiotics (including third-generation cephalosporins, carbapenems, fluoroquinolones, and aminoglycosides). The research further assessed resistance variations across different sample sources (urine, blood, respiratory specimens) and applied statistical analyses (Spearman correlation) to determine temporal resistance trends.

Key Conclusions and Perspectives

  • Escherichia coli resistance to third-generation cephalosporins increased from 5.4% to 16.5% between 1999 and 2019, indicating continuous escalation of resistance.
  • Klebsiella pneumoniae resistance to imipenem rose from 1% to 18.6%, though amikacin maintained relatively high sensitivity.
  • Pseudomonas aeruginosa showed no significant increase in imipenem resistance, while Acinetobacter baumannii demonstrated a dramatic rise in carbapenem resistance from 34.5% to 84.2%, with generally low sensitivity to multiple antibiotics.
  • The high incidence of carbapenem-resistant K. pneumoniae (CRKP) and A. baumannii (CRAB) underscores the urgent need for enhanced resistance control measures in Tunisia.
  • While amikacin and polymyxins still showed activity against resistant strains, increasing resistance rates after 2017 highlight emerging challenges with second-line agent efficacy.

Research Significance and Prospects
This study provides national-level evidence for antimicrobial resistance trends in Tunisia, offering critical insights for empirical treatment strategies and antimicrobial stewardship policies. Future research should investigate molecular resistance mechanisms and explore novel antimicrobial agents or combination therapies to address escalating resistance challenges. Enhanced surveillance of resistance genes in environmental and food chain reservoirs is also essential to prevent zoonotic transmission of resistance from animal and agricultural sources.

 

 

Conclusion
This study systematically documents the evolutionary patterns of multidrug-resistant Gram-negative bacteria in Tunisia from 1999 to 2019. Findings reveal significant increases in resistance rates for E. coli and K. pneumoniae, with rapid escalation of carbapenem resistance in A. baumannii, while P. aeruginosa maintains relative stability. The data emphasize urgent requirements for antimicrobial stewardship programs, particularly in hospital environments. This work provides foundational reference for optimizing antibiotic use policies, implementing resistance control strategies, and advancing development of novel antimicrobial agents in Tunisia.

 

Reference:
Lamia Kanzari, Sana Ferjani, Basma Mnif, Adnene Hammami, and Ilhem Boutiba-Ben Boubaker. Historical Overview of the Evolution of Multidrug-Resistant Gram-Negative Infections in Tunisia from 1999 to 2019. Antibiotics.