Systematic review of multidrug-resistant Klebsiella pneumoniae in the Arabian Peninsula: molecular epidemiology and resistance patterns

Abstract

Background: The rapid emergence of multidrug-resistant Klebsiella pneumoniae (MDR K. pneumoniae) is a major public health and economic burden worldwide. Various resistance mechanisms complicate treatment, leading to increased morbidity and mortality. Despite numerous studies conducted in Gulf Health Council (GHC) countries, the molecular epidemiology of MDR K. pneumoniae remains not clearly defined. This systematic review aims to analyze the emergence of antimicrobial resistance genes in MDR K. pneumoniae across GHC countries.

Methods: A systematic search was conducted using PubMed, ScienceDirect, and OpenMD for articles published up to March 15, 2023. The search strategy focused on the bacterial name, drug-resistance genotypes, and GHC countries. The review followed PRISMA guidelines, with two independent reviewers assessing the risk of bias using NIH Study Quality Assessment tools.

Results: The primary search yielded 1,663 studies, of which 67 met the inclusion criteria. Saudi Arabia contributed the most studies, with 41 (61.1%), followed by Kuwait with 7 (10.4%), and the UAE with 6 (9%) studies. Oman and Qatar each contributed 4 studies (6%), and Bahrain contributed three studies (4.5%). The remaining 4 studies (4.4%) were from multiple GHC countries. The studies exhibited considerable heterogeneity in detection methods, target genes, and resistance mechanisms. Notably, only one environmental study was conducted in the UAE, and one community-based study in Kuwait, while the remaining studies focused on clinical samples. Various resistance mechanisms and patterns were observed between countries and across different years within the same country. The review highlighted the widespread prevalence of ESBL genes, particularly bla _TEM and bla _CTX-M-15, and the emergence of carbapenemase genes such as bla _OXA-48 and bla _NDM-1 and bla _KPC-2. Additionally, colistin resistance through the mcr-1 gene and mgrB mutations was reported in Saudi Arabia and the UAE, posing a significant public health challenge.

Conclusion: Data from GHC countries shows significant gaps, particularly in community and environmental and molecular epidemiology studies. Limited molecular and genome-based investigations hinder comprehensive AMR surveillance. Implementing standardized methodologies and fostering molecular and genome-based AMR surveillance programs at both national and regional levels within the GHC are essential for effectively combating the spread of MDR K. pneumoniae and improving public health outcomes in the region.

Keywords: Arabian Peninsula; MDR Klebsiella pneumoniae; antimicrobial resistance gene; carbapenem-resistant Klebsiella pneumoniae; molecular epidemiology; the GHC countries.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flow-chart describes the results of molecular epidemiological studies of MDR K. pneumoniae in the GHC countries. The flow chart was downloaded from http://www.prisma-statement.org/.

Figure 2

A timeline of K. pneumoniae studies conducted in the GHC countries, illustrating the samples collection year of each study. The label “GHC” indicates studies that involved samples collected from different GHC countries.

Figure 3

Distribution of sample types from which K. pneumoniae isolates were obtained. (A) Sterile samples: collected through invasive procedures (e.g., blood, CSF), often associated with life-threatening infections. (B) Non-sterile samples: obtained through non-invasive methods (e.g., urine, sputum), typically linked to less severe infections.

Figure 4

The genotypic methods used for the detection of antimicrobial resistance genes and identification of different sequence types in MDR K. pneumoniae were reported in studies conducted in the GHC countries. The label “GHC” reflects the studies conducted on samples obtained from different GHC countries.”

Figure 5

Distribution of most prevalent ESBL and carbapenemase genes in the GHC Countries. The map figure was licensed from Shutterstock (https://www.shutterstock.com) and modified using PowerPoint to express the prevalence of ARGs in each country of GHC.

Figure 6

The distribution of K. pneumoniae sequence types in the GHC countries shows the variety of K. pneumoniae sequence types in different geographical regions.