Penicillin susceptibility among invasive MSSA infections: a multicentre study in 16 Spanish hospitals

Abstract

Objectives To determine the prevalence of penicillin susceptibility among MSSA causing bloodstream infections (BSIs) in 16 Spanish hospitals and to characterize the penicillin-susceptible MSSA (MSSA-PENS) isolates. Methods A total of 1011 Staphylococcus aureus isolates were collected from blood cultures in 16 Spanish hospitals during 2018–19 (6–12 months) and their susceptibility to 18 antimicrobials was determined. The MSSA-PENS isolates were selected and examined by PCR to determine the presence of the blaZ gene, other resistance genes and the genes lukF/lukS-PV, eta, etb and tst. The immune evasion cluster (IEC) type was also analysed. All the MSSA-PENS isolates were submitted to S. aureus protein A (spa) typing and the clonal complexes (CCs) were assigned according to their spa type. Results The prevalence of MSSA was 74.6% (754/1011) and 14.9% (151/1011) were MSSA-PENS-blaZnegative. MSSA-PENS-blaZnegative isolates (n = 151) were ascribed to 88 spa types and 11 CCs. The most frequent CCs were CC5 (35/151) and CC398 (25/151), with t002-CC5 and t571-CC398 being the most common lineages. Pan-susceptibility was identified in 117 of the 151 MSSA-PENS-blaZnegative isolates (77.5%). In the remaining isolates, erythromycin and clindamycin resistance was the most frequent resistance found, although tobramycin, ciprofloxacin, fusidic acid, mupirocin and/or tetracycline resistance was also detected. Thirty-eight MSSA-PENS-blaZnegative isolates were IEC negative and four isolates were Panton–Valentine leucocidin (‘PVL’) positive. Conclusions A high penicillin susceptibility rate was detected among MSSA, opening therapeutic opportunities for BSIs. The emergence of new successful MSSA-PENS clones could be responsible for these data. The detection among MSSA-PENS-blaZnegative isolates of the clonal lineage CC398 or the absence of an IEC raises questions about their possible animal origin, requiring further analysis.

Shared antibiotic resistance and virulence genes in Staphylococcus aureus from diverse animal hosts

“…Also notable is that 43 out of 114 genomes from six STs presented blaZ . For comparison, high penicillin susceptibility rate has been reported in MSSA from bloodstream infections in humans, primarily from CCs 5 and 398 46 . Penicillin may be considered a therapeutic option in the treatment of animal infections, but ST identity should be carefully considered as blaZ appears to be more phylogenetically widespread in animal-associated S. aureus .…”

Genomic epidemiology and characterisation of penicillin-sensitive Staphylococcus aureus isolates from invasive bloodstream infections in China: an increasing prevalence and higher diversity in genetic typing be revealed

“…CC5 is one of the most dominant clones among both MRSA and MSSA in China [ 27 ]. In addition, CC5 has also been demonstrated as one of the most prevalent clones among MSSA-PEN S strains in other studies [ 32 , 41 ].…”

“…Several additional amino acid changes were detected among these isolates (Figure S2). For instance, the mutations in isolates SKLX44218, SKLX56709 and SKLX61252 introduced a frameshift (c.92delA) introducing a premature stop codon at codon 43 (L43*); the G223 T substitution in isolate SKLX62838 resulted in a premature stop codon at codon 75 (E75*); and the nonsynonymous amino acid substitutions occurring in the other isolates comprised those previously reported in the CC5-t002 isolate X1953 [ 32 ]. We also examined the mutations in the blaI gene for these 11 isolates and found that there were no changes in the sequences of the blaI gene in isolates SKLX56709 and SKLX61252, whereas isolate SKLX62838 exhibited a change in codon 21 (p.D21G), and the other isolates showed changes in codon 2 (p.A2 T).…”

“…Cefazolin inoculum effect (CzIE) is a phenomenon mediated by staphylococcal β-lactamases[ 20 ], which has been demonstrated to be associated with therapeutic failures and increased mortality[ 43 ]. Interestingly, we found that in addition to some nonsynonymous amino acid substitutions occurring in the blaZ gene reported early [ 32 ], a single-nucleotide deletion (c.92delA) was detected in three isolates, introducing a frameshift and premature stop codon predicted to induce expression of truncated blaZ . Similarly, we also found a single-nucleotide deletion within the blaR1 gene (c.466delA) in seven isolates that introduced a premature stop codon and suppressed blaR1 expression.…”

“…While scientists have paid increasing attention to more-resistant strains, and studies have often underestimated the significance of methicillin-sensitive S. aureus strains for years, penicillin-sensitive S. aureus strains appear to have crept back in “under the radar”. In some developed countries, such as the USA, Spain, France and Canada, researchers have reported that the proportion of penicillin-susceptible S. aureus is approximately 15–45% [ 11 , 15 , 25 , 32 ]. Penicillin is a narrow-spectrum agent that offers several advantages, such as lower average MIC and treatment cost and better theoretical pharmacokinetic and pharmacodynamic profiles compared with the usual first-line treatments.…”