Multidrug-Resistant ESKAPEEc Pathogens From Bloodstream Infections in South Africa: A Cross-Sectional Study Assessing Resistance to WHO AWaRe Antibiotics

Abstract

Background and aims: Multidrug-resistant (MDR) pathogens, particularly members of the ESKAPE group and Escherichia coli (collectively referred to as ESKAPEEc), are major contributors to bloodstream infections (BSIs) and pose significant treatment challenges. This study aimed to characterize the antimicrobial resistance (AMR) profiles of ESKAPEEc isolates from BSIs in public hospitals in the uMgungundlovu District, South Africa, and to assess their resistance to World Health Organization (WHO) Access, Watch, and Reserve (AWaRe) antibiotics.

Methods: Between November 2017 and December 2018, blood samples (n = 195) were collected from adult and paediatric patients with suspected BSIs. Isolates were identified using the VITEK 2 system and confirmed by polymerase chain reaction (PCR). Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method and interpreted according to EUCAST/CLSI guidelines. The multiple antibiotic resistance index (MARI) was calculated. One-way analysis of variance (ANOVA) was used to assess associations between MARI and clinical variables, including ward type and facility level.

Results: Out of 195 presumptive isolates, 159 were confirmed as ESKAPEEc. The most frequently identified pathogens were Klebsiella pneumoniae (28.9%) and Staphylococcus aureus (28.3%). High resistance rates were observed across WHO Access and Watch antibiotics, including ampicillin (76% in E. coli), gentamicin (67.4% in K. pneumoniae), and ciprofloxacin (≥ 60% in most species). Carbapenem resistance in Acinetobacter baumannii reached 90%. Overall, 94.9% of isolates were MDR, and 93.1% had MARI ≥ 0.2. Significant differences in MARI values were observed across ward groups and facility levels, with the highest values recorded in intensive care units (mean = 0.67, 95% CI: 0.62-0.72) and tertiary hospitals (mean = 0.64, 95% CI: 0.60-0.68), compared to regional hospitals (mean = 0.52, 95% CI: 0.47-0.57).

Conclusion: The findings reveal a high burden of MDR ESKAPEEc in BSIs and widespread resistance to WHO Watch antibiotics. Targeted antimicrobial stewardship and the implementation of microbiology-guided therapy are urgently needed to optimize patient outcomes and curb the spread of resistance.

Keywords: MAR index; WHO AWaRe; antimicrobial resistance; bloodstream infections; multidrug resistance; pathogens.

Figure 1

Distribution of ESKAPEEc Isolates by Species, Facility Level, Ward Group, and Ward Type. (A) Frequency distribution of ESKAPEEc species isolated from bloodstream infections (n = 159). Klebsiella pneumonia and Staphylococcus aureus were the most common species. (B) Isolate counts stratified by healthcare facility level, showing a predominance of isolates from regional hospitals compared to tertiary hospitals. (C) Isolate distribution across broader clinical categories (WardGroup), with Intensive Care Units (ICUs) and Outpatient/Clinic‐Based Services accounting for the highest numbers. (D) Detailed breakdown of isolate counts by specific hospital wards, with ICU, surgical, and pediatric wards contributing the highest proportions.

Figure 2

Heatmap showing the percentage of resistance to WHO AWaRe (Access, Watch, Reserve) antibiotics among ESKAPEE pathogens isolated from bloodstream infections. Resistance levels are color‐coded, with higher percentages indicated by warmer tones. Klebsiella pneumoniae and Acinetobacter baumannii exhibited the highest resistance to both Access and Watch category antibiotics, while Enterobacter cloacae had the highest resistance to Reserve antibiotics.

Figure 3

Distribution of Multiple Antibiotic Resistance Index (MARI) values by clinical setting. (A) Boxplot showing the distribution of MARI values across seven clinical ward groupings. The highest median MARI scores were observed in Intensive Care Units, Surgical Wards, and Specialist Wards, while Outpatient/Clinic‐Based Services had the lowest. (B) Boxplot comparing MARI values between facility levels. Tertiary hospitals showed significantly higher MARI values compared to regional hospitals (p < 0.001). The asterisk denotes a statistically significant difference.

Figure 4

Mean Multiple Antibiotic Resistance Index (MARI) with 95% confidence intervals by clinical setting. (A) Mean MARI values with 95% confidence intervals across seven ward group categories. Intensive Care Units, Surgical Wards, and Specialist Wards exhibited the highest mean MARI values. Sample sizes for each group are annotated above the error bars. (B) Mean MARI comparison between regional and tertiary hospitals, showing significantly higher resistance levels in tertiary facilities. Error bars represent 95% confidence intervals, with sample size (n) labeled above each mean point.