Screening for β-lactam resistance by penicillin G in the Streptococcus anginosus group challenged by rare strains with altered PBPs

Abstract

Background Streptococcus anginosus group (SAG) strains are common pathogens causing abscesses and bacteraemia. They are generally susceptible to β-lactams, which constitute first-line treatment. EUCAST recommends testing penicillin G susceptibility to screen for β-lactam resistance. Isolates categorized as susceptible (negative screening) can be reported as susceptible to aminopenicillins and third-generation cephalosporins. Objectives To assess the reliability of penicillin G resistance screening in predicting β-lactam resistance in SAG blood culture isolates, and to investigate isolates for which this test would be unreliable. Methods We determined the susceptibility to penicillin G, amoxicillin and ceftriaxone of 90 SAG blood culture isolates, all with negative penicillin G resistance screening. β-Lactam-resistant strains were sequenced and compared with susceptible reference SAG strains. Results We detected two isolates displaying β-lactam resistance, especially to third-generation cephalosporins, despite negative screening for penicillin G resistance. For these isolates, amino acid substitutions were identified next to the essential PBP motifs SxxK, SxN and/or KS/TGS/T. Changes in these motifs have been previously linked to β-lactam resistance in Streptococcus pneumoniae. Conclusions Our study suggests that aminopenicillin and third-generation cephalosporin susceptibility should be determined for SAG strains in the event of severe infection as screening for penicillin G resistance might not be sufficient to detect resistance mechanisms that predominantly affect cephalosporins. The PBP sequencing of resistant SAG strains allowed us to detect amino acid changes potentially linked to β-lactam resistance.

Streptococcus suis serotype 9 in Italy: genomic insights into high-risk clones with emerging resistance to penicillin

“…In S. pneumoniae , the origin of sequences encoding PBPs with a low affinity for β-lactams has been traced back to interspecies recombination with commensal species belonging to the same genus, Streptococcus mitis or Streptococcus oralis . 9 , 10 , 14 The presence of large blocks of mutations in our isolates suggests a similar mechanism might have occurred in S. suis .…”

“…β-Lactams covalently bind to the active domains of the PBPs, transpeptidase or carboxypeptidase, which harbour the active motifs SXXK, (S/Y)XN and (K/H)(D/T)G. Such binding prevents the peptide crosslinking of the glycan strains, a crucial step in the synthesis of peptidoglycan. 9 , 10 Resistance has been extensively studied in Streptococcus pneumoniae , in which the main resistance mechanisms are mutations in the active sites of the PBP sequences, which reduce β-lactam binding affinity. 9 , 11–15 S. suis is traditionally considered susceptible to β-lactams.…”

Brain abscess caused by Streptococcus anginosus group: Three case reports

“…The penicillin-mediated and penicillin resistance rates of the Streptococcus pharyngis group are less than 2%[ 2 ]. Ceftriaxone-resistant strains are rare, and resistance to the drug is not routinely tested[ 3 ]. One hundred and twenty isolates of Streptococcus pharyngis were tested in vitro, with minimal inhibit concentrations (MICs) of 0.5 mg/L for vancomycin[ 4 ] and 2 μg/mL for linezolid MIC 90 [ 5 ], thus indicating that the bacteria are sensitive to both the antibiotics.…”

Microbiological Epidemiology of Invasive Infections Due to Non-Beta-Hemolytic Streptococci, France, 2021

“…As in Streptococcus pneumoniae , the loss of susceptibility results from mutations in the genes encoding the penicillin-binding proteins which alter their affinity for one or more beta-lactam molecules. Resistance rates greatly vary between streptococcal groups with penicillin nonsusceptible isolates reaching rates as high as 35% in the S. mitis and S. sanguinis groups while remaining extremely rare in the S. anginosus group ( 19 – 21 ). Thus, resistance to beta-lactam antibiotics is very common in certain streptococcal species and frequently complexifies the therapeutic management of difficult-to-treat infections such as bone and joint infections or infective endocarditis.…”