Prevalence of genes encoding carbapenem-resistance in Klebsiella pneumoniae recovered from clinical samples in Africa: systematic review and meta-analysis

Abstract

Background: The potential of Klebsiella pneumoniae (K. pneumoniae) to acquire and spread carbapenem-resistant genes is the most concerning characteristic of the bacteria. In hospitals and other healthcare settings, multidrug-resistant K. pneumoniae can be prevalent and cause severe infections, posing significant challenges to patient management. Studying genetic variants and drug-resistant mutations in pathogenic bacteria of public health importance is essential. Therefore, this study aimed to assess the overall prevalence of carbapenemase-encoding genes in K. pneumoniae across Africa.

Methods: All studies published between January 2010, and December 2023, were retrieved from the electronic databases PubMed, Science Direct, and Scopus, as well as through the Google Scholar search engine. This systematic review and meta-analysis adhered strictly to the PRISMA guidelines. Data analysis was performed using STATA version 17. The quality of the included studies was critically evaluated using the "Joanna Briggs Institute" criteria. To evaluate heterogeneity among the studies, inverse variance (I2) tests were utilized. Subgroup analysis was conducted when heterogeneity exists among studies. To assess publication bias, we used a funnel plot and Egger's regression test. A random effects model was used to calculate the weighted pooled prevalence of genetic variants associated with carbapenem resistance in K. pneumoniae.

Results: A total of 49 potential studies were included in this systematic review and meta-analysis, encompassing 8,021 K. pneumoniae isolates. Among these isolates, 2,254 (28.1%) carbapenems-resistance-conferring genes were identified. The overall pooled prevalence of carbapenemase-encoding genes in K. pneumoniae isolated from clinical specimens across Africa was found to be 34.0% (95% CI: 26.01-41.98%). Furthermore, the pooled prevalence of the carbapenemase genes bla_OXA-48 and bla_NDM-1 was 16.96% (95% CI: 12.17-21.76%) and 15.08% (95% CI: 9.79-20.37%), respectively. The pooled prevalence of carbapenemase genes in K. pneumoniae isolates from clinical samples across Africa increased over time, reported as 20.4%(-0.7-41.4%) for 2010-2015, 34.5% (20.2-48.8%) for 2016-2020, and 35.2% (24.8-45.5%) for 2021-2023, with heterogeneity (I2) values of 36.5%, 96.7%, and 99.3%, respectively.

Conclusions: The emergence and spread of carbapenemase-encoding genes in K. pneumoniae pose a major threat to public health. Knowledge on the genetic mechanisms of carbapenem resistance is crucial for developing effective strategies to combat these multidrug-resistant infections and reduce their impact on healthcare systems. The carbapenemase genes bla_OXA-48 and bla_NDM-1 were the most prevalent and showed an increasing trend over time.

Keywords: Bla NDM-1; Bla OXA-48; K. pneumoniae; Carbapenemase-encoding genes; Clinical samples; Meta-analysis.

Fig. 1

PRISMA flow diagram showed the results of the search and reasons for exclusion of studies [24]

Fig. 2

Forest plot showing the pooled prevalence of carbapenemase gene variants in K. pneumoniae from a clinical sample in Africa

Fig. 3

Funnel plot showing publication biases of all carbapenemase gene variants in K. pneumoniae from clinical sample in Africa

Fig. 4

Forest plot showing the pooled prevalence of bla_OXA-48 genes in K. pneumoniae isolates from clinical samples in Africa

Fig. 5

Forest plot showing the pooled prevalence of bla_NDM-1 genes in K. pneumoniae isolates from clinical samples in Africa

Fig. 6

Forest plot showing pooled prevalence of bla_IMP, bla_VIM, and bla_KPC genes in K. pneumoniae isolates from clinical samples in Africa

Fig. 7

Forest plot showing the pooled prevalence of co-existence of genes (bla_NDM-1+OXA-48, bla_KPC+OXA-48, and blaI_MP+OXA-48) genes in K. pneumoniae isolates from clinical samples in Africa