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Alene Geteneh, Sirak Biset, Melese Abate Reta, Emerging β-lactam non-susceptibility in Group A Streptococcus: implications for Ethiopia’s healthcare system, JAC-Antimicrobial Resistance, Volume 7, Issue 1, February 2025, dlaf020, https://doi.org/10.1093/jacamr/dlaf020
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Abstract
The emergence of β-lactam non-susceptibility in Group A Streptococcus (GAS) or Streptococcus pyogenes represents a major challenge for the global public health, particularly in resource-limited settings like Ethiopia. GAS, a primary cause of pharyngitis and invasive infections, is conventionally treated with β-lactam antibiotics such as penicillin. However, the recent evidence raises concerns about the treatment efficacy with reduced susceptibility, the diagnostic limitations, and the potential for complications such as acute rheumatic fever. This commentary calls for attention to the antimicrobial resistance trends in Ethiopian GAS isolates, underscoring the need for routine susceptibility testing, advanced molecular diagnostics, and strengthened laboratory capacities to guide effective treatment strategies and mitigate the antibiotic resistance-associated risks.
Introduction
The effective treatment of Group A Streptococcus (GAS) pharyngitis is crucial for the prevention of acute rheumatic fever and its complications. β-lactam antibiotics, particularly penicillin, have been the standard choice. Despite this, treatment failures remain a significant problem, possibly due to the intracellular persistence of Streptococcus pyogenes, biofilm formation, protection by β-lactamase-producing bacteria, alteration of the commensal microbiota, or inadequate tissue penetration by penicillin. While the Kirby–Bauer disc diffusion test is widely used in resource-limited settings like Ethiopia due to its simplicity and cost-effectiveness, caution is needed when interpreting results, as zone size discrepancies may not always reflect clinical outcomes.1,2
To this review, non-susceptibility refers both resistant (R) and intermediate (I) categories; where the ‘I’ indicates an increased exposure implying that higher doses of penicillin V/G or amoxicillin can be effective. The non-susceptibility of S. pyogenes to β-lactams is still extremely uncommon. The current CLSI guidelines recommend confirmation of unusual resistance patterns through advanced testing and public health laboratory verification.3 Yet, such practices are limited in Ethiopia, in which we solely depend on the Kirby–Bauer disc diffusion approach, raising concerns about its detection power. Resistance trends reported from countries like India, China, and Mexico suggest rising penicillin minimum inhibitory concentrations in some isolates.4–6 The relevance of these findings to Ethiopia warrants further exploration given the methodological constraints of the local studies.7–11
Antibiotic resistance trends in Ethiopia
A summary of GAS resistance patterns from 2015 to 2023 is presented in Table 1. The table reflects variability across studies and resistance to key antibiotics. Resistance to penicillin remains rare, but alarming rates of non-susceptibility to alternative therapies such as macrolides, lincosamides, and even third- and fourth-generation cephalosporins raise a red flag for the public.
Antibiotic resistance trends of GAS isolates from tonsilo-pharyngeal infections in Ethiopia (2015–23)
| Author . | Penicillin % (n/N) . | Vancomycin % (n/N) . | Chloramphenicol % (n/N) . | Clindamycin % (n/N) . | Azithromycin % (n/N) . | Erythromycin % (n/N) . | Tetracycline % (n/N) . | Amoxicillin % (n/N) . | Ampicillin % (n/N) . | Ciprofloxacin % (n/N) . | Trimethoprim–sulphamethazole % (n/N) . | Gentamicin % (n/N) . | Ceftriaxone % (n/N) . | Cefotaxime % (n/N) . | Cefepime % (n/N) . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Tesfaw et al.7 | 0 | NA | 0 | 0 | NA | 0 | 52.5 (21/40) | 0 | NA | NA | NA | NA | 0 | NA | NA |
| Zelelie et al.8 | NA | NA | 47.1 (8/17) | NA | NA | 41.2 (7/17) | 35.3 (6/17) | 41.2 (7/17) | 29.4 (5/17) | 23.5 (4/17) | 35.3 (6/17) | 35.3 (6/17) | 35.3 (6/17) | NA | NA |
| Kebede et al.9 | NA | 35.7 (5/14) | 21.4 (3/14) | 57.1 (8/14) | NA | 35.7 (5/14) | 28.6 (4/14) | NA | NA | NA | NA | NA | 35.7 (5/14) | 21.4 (3/14) | 14.3 (2/14) |
| Fenta et al.10 | 0 | 0 | 46.7 (7/15) | 0 | NA | 33.3 (5/15) | 66.7 (10/15) | 13.3 (2/15) | NA | NA | NA | NA | 20 (3/15) | NA | NA |
| Tadesse et al.11 | 0 | 4.4 (1/23) | 4.4 (1/23) | 8.7 (2/23) | 30 (7/23) | 39.1 (9/23) | 56.5 (13/23) | NA | NA | NA | NA | NA | 13.0 (3/23) | NA | NA |
| Author . | Penicillin % (n/N) . | Vancomycin % (n/N) . | Chloramphenicol % (n/N) . | Clindamycin % (n/N) . | Azithromycin % (n/N) . | Erythromycin % (n/N) . | Tetracycline % (n/N) . | Amoxicillin % (n/N) . | Ampicillin % (n/N) . | Ciprofloxacin % (n/N) . | Trimethoprim–sulphamethazole % (n/N) . | Gentamicin % (n/N) . | Ceftriaxone % (n/N) . | Cefotaxime % (n/N) . | Cefepime % (n/N) . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Tesfaw et al.7 | 0 | NA | 0 | 0 | NA | 0 | 52.5 (21/40) | 0 | NA | NA | NA | NA | 0 | NA | NA |
| Zelelie et al.8 | NA | NA | 47.1 (8/17) | NA | NA | 41.2 (7/17) | 35.3 (6/17) | 41.2 (7/17) | 29.4 (5/17) | 23.5 (4/17) | 35.3 (6/17) | 35.3 (6/17) | 35.3 (6/17) | NA | NA |
| Kebede et al.9 | NA | 35.7 (5/14) | 21.4 (3/14) | 57.1 (8/14) | NA | 35.7 (5/14) | 28.6 (4/14) | NA | NA | NA | NA | NA | 35.7 (5/14) | 21.4 (3/14) | 14.3 (2/14) |
| Fenta et al.10 | 0 | 0 | 46.7 (7/15) | 0 | NA | 33.3 (5/15) | 66.7 (10/15) | 13.3 (2/15) | NA | NA | NA | NA | 20 (3/15) | NA | NA |
| Tadesse et al.11 | 0 | 4.4 (1/23) | 4.4 (1/23) | 8.7 (2/23) | 30 (7/23) | 39.1 (9/23) | 56.5 (13/23) | NA | NA | NA | NA | NA | 13.0 (3/23) | NA | NA |
NA, not applicable.
Antibiotic resistance trends of GAS isolates from tonsilo-pharyngeal infections in Ethiopia (2015–23)
| Author . | Penicillin % (n/N) . | Vancomycin % (n/N) . | Chloramphenicol % (n/N) . | Clindamycin % (n/N) . | Azithromycin % (n/N) . | Erythromycin % (n/N) . | Tetracycline % (n/N) . | Amoxicillin % (n/N) . | Ampicillin % (n/N) . | Ciprofloxacin % (n/N) . | Trimethoprim–sulphamethazole % (n/N) . | Gentamicin % (n/N) . | Ceftriaxone % (n/N) . | Cefotaxime % (n/N) . | Cefepime % (n/N) . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Tesfaw et al.7 | 0 | NA | 0 | 0 | NA | 0 | 52.5 (21/40) | 0 | NA | NA | NA | NA | 0 | NA | NA |
| Zelelie et al.8 | NA | NA | 47.1 (8/17) | NA | NA | 41.2 (7/17) | 35.3 (6/17) | 41.2 (7/17) | 29.4 (5/17) | 23.5 (4/17) | 35.3 (6/17) | 35.3 (6/17) | 35.3 (6/17) | NA | NA |
| Kebede et al.9 | NA | 35.7 (5/14) | 21.4 (3/14) | 57.1 (8/14) | NA | 35.7 (5/14) | 28.6 (4/14) | NA | NA | NA | NA | NA | 35.7 (5/14) | 21.4 (3/14) | 14.3 (2/14) |
| Fenta et al.10 | 0 | 0 | 46.7 (7/15) | 0 | NA | 33.3 (5/15) | 66.7 (10/15) | 13.3 (2/15) | NA | NA | NA | NA | 20 (3/15) | NA | NA |
| Tadesse et al.11 | 0 | 4.4 (1/23) | 4.4 (1/23) | 8.7 (2/23) | 30 (7/23) | 39.1 (9/23) | 56.5 (13/23) | NA | NA | NA | NA | NA | 13.0 (3/23) | NA | NA |
| Author . | Penicillin % (n/N) . | Vancomycin % (n/N) . | Chloramphenicol % (n/N) . | Clindamycin % (n/N) . | Azithromycin % (n/N) . | Erythromycin % (n/N) . | Tetracycline % (n/N) . | Amoxicillin % (n/N) . | Ampicillin % (n/N) . | Ciprofloxacin % (n/N) . | Trimethoprim–sulphamethazole % (n/N) . | Gentamicin % (n/N) . | Ceftriaxone % (n/N) . | Cefotaxime % (n/N) . | Cefepime % (n/N) . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Tesfaw et al.7 | 0 | NA | 0 | 0 | NA | 0 | 52.5 (21/40) | 0 | NA | NA | NA | NA | 0 | NA | NA |
| Zelelie et al.8 | NA | NA | 47.1 (8/17) | NA | NA | 41.2 (7/17) | 35.3 (6/17) | 41.2 (7/17) | 29.4 (5/17) | 23.5 (4/17) | 35.3 (6/17) | 35.3 (6/17) | 35.3 (6/17) | NA | NA |
| Kebede et al.9 | NA | 35.7 (5/14) | 21.4 (3/14) | 57.1 (8/14) | NA | 35.7 (5/14) | 28.6 (4/14) | NA | NA | NA | NA | NA | 35.7 (5/14) | 21.4 (3/14) | 14.3 (2/14) |
| Fenta et al.10 | 0 | 0 | 46.7 (7/15) | 0 | NA | 33.3 (5/15) | 66.7 (10/15) | 13.3 (2/15) | NA | NA | NA | NA | 20 (3/15) | NA | NA |
| Tadesse et al.11 | 0 | 4.4 (1/23) | 4.4 (1/23) | 8.7 (2/23) | 30 (7/23) | 39.1 (9/23) | 56.5 (13/23) | NA | NA | NA | NA | NA | 13.0 (3/23) | NA | NA |
NA, not applicable.
Implications for alternative treatments
Penicillin-allergic patients often rely on macrolides and lincosamides, yet resistance rates in Ethiopia reach up to 41.2%8–11 and 57.1%,9 respectively. This review also noted that azithromycin was less resistant than erythromycin, and this could be due to its chemical stability, better tissue penetration, and the differences in prescribing practices. About one-third of isolates resistant to erythromycin were susceptible to clindamycin in Arba Minch,10 and in Gondar, 39.1% of erythromycin-resistant isolates had reduced resistance to clindamycin.11 This could indicate the possibility of high inducible clindamycin resistance in Ethiopia, a phenomenon known as macrolide–lincosamide–streptogramin B (MLSB) resistance, as was reported by Gambia.12 The higher level of resistance to macrolides and lincosamides limits their utility as alternative treatments, necessitating the exploration of other therapeutic options and stricter antimicrobial stewardship policies in Ethiopia.
Amoxicillin has replaced penicillin as the preferred treatment for paediatrics when penicillin is unavailable, a situation occasionally observed in some Ethiopian healthcare facilities. Its adoption is also favoured due to the convenience of once-daily dosing, which enhances treatment adherence.13 However, studies from Ethiopia report that resistance to amoxicillin among GAS isolates can be as high as 41.2%.8,10 This high level of resistance in paediatric populations is probably driven by factors such as overuse, misuse, and the dissemination of strains resistant through mechanisms like β-lactamase production and horizontal gene transfer.
The non-susceptibility of third- and fourth-generation cephalosporins, such as ceftriaxone, cefotaxime, and cefepime, key β-lactam antibiotics used in the treatment of penicillin-resistant streptococcal infections, shows non-susceptibility rates of 14.3%–35.7% in the Amhara region of Ethiopia.8,9,11 Most remarkably, vancomycin, though not conventionally used for GAS management, exhibits significant resistance of as high as 35.7% in Ethiopian isolates, underscoring the urgency for action.9,11 This concerning trend could emanate either from the general empiric administration of antibiotics or from the local circulation of resistant bacterial strains. The trend we observed underscores the critical need for strict performance of either antimicrobial stewardship or exploration of new therapeutic options.
Conclusions
The variability in antimicrobial resistance patterns among GAS isolates in Ethiopia underscores the importance of standardized diagnostic practices and routine susceptibility testing. Public health laboratories must prioritize confirmation of resistance trends to inform evidence-based treatment guidelines. Enhanced laboratory capacity, combined with molecular investigations of resistance mechanisms, is vital for mitigating the public health burden of GAS infections in Ethiopia.
Funding
This study was carried out as part of our routine work.
Transparency declarations
None to declare.
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