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. 2023 Mar 31;13:1117160. doi: 10.3389/fcimb.2023.1117160

Table 1.

Reports of reduced susceptibility to β-lactams amongst group A Streptococcus isolates and the associated amino acid substitutions identified.

Country
(study period)
Sample source Number OR Rates β-lactam antibiotics Antibiotic resistance test MIC Breakpoint standards Mutations identified References
PBP2x PBP2a PBP2b PBP1a PBP1b
Mexico
2001
Pharyngotonsillitis 10(5%) Penicillin G E-test 0.25–0.75 μg/ml NCCLS (Amábile-Cuevas et al., 2001)
India
2002-2003
Acute pharyngotonsillitis 7(20.6%) Penicillin E-test 0.19-0.25μg/ml CLSI (Capoor et al., 2006)
Japan
2006-2008
Pharyngitis 2/93 Penicillin G Broth microdilution >2.0μg/ml CLSI 2007 (Ogawa et al., 2011)
India
2016-2017
Upper respiratory tract infections 4(8%), 2(4.2%),
2(5.3%)
Ampicillin
cefotaxime
ceftriaxone
MALDI-TOF Mass Spectrometry (VITEK MS, bioMerieux) MIC, 0.12-8μg/ml CLSI (Berwal et al., 2018)
Australia
2020
4/9667 NC NC NC NC STMK to SAMK
STMK to STIK
(Hayes et al., 2020a)
USA
2017-2018
Blood and wound isolates 2/282 ampicillin & cefotaxime Broth Microdilution & E-test Ampicillin 8-fold higher, cefotaxime 3-fold higher CLSI T553K substitution (Vannice et al., 2020)
USA
2020
Mouse Model of Necrotizing Myositis Pro601Leu amino acid replacement in PBP2X (Olsen et al., 2020)
Iceland
1995-2006
emm12 strains, 332/1575 A 2-fold increased penicillin G and ampicillin MIC Disk diffusion method CLSI, EUCAST Met593Thr
Ile502Val
Pro676Ser
Lys708Glu
(Southon et al., 2020)
Japan
2015-2016
Skin, Pus, Tonsil 3 Agar dilution method CLSI M593T, A397V T459A (Ikeda et al., 2021)
2022 Identified 464 pbp2x alleles 564 pbp2a alleles 389 pbp1a alleles 427 pbp1b alleles (Beres et al., 2022)
USA
2015-2021
55/13727 None isolates exhibited nonsusceptibility to b-lactams emm43.4/PBP2x-T553K variant, two isolates ampicillin MIC 0.25 mg/ml, 129/340 (37.9%) of isolates with elevated β-lactam MICs (Chochua et al., 2022)
USA
2022
An isogenic mutant strain was generated and virulence assessed in a mouse model of necrotizing myositis Strains with the chimeric SDSE-like PBP2X had reduced susceptibility in vitro to nine β-lactam antibiotics (Olsen et al., 2022)

NCCLS (National Committee for Clinical Laboratory Standards) is the predecessor of Clinical and Laboratory Standards Institute (CLSI) ; WGS, Whole-genome sequencing; MALDI-TOF, Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry; —, No data OR No clear.