Staphylococcus massiliensis isolated from human blood cultures, Germany, 2017–2020

Coagulase-negative staphylococci (CoNS) are abundant inhabitants of the human skin and the mucosa with limited pathogenicity [1, 2], as opposed to Staphylococcus aureus [3] and other members of the S. aureus complex [4, 5]. Device-related infections are one of the most common manifestations of CoNS infections, causing high morbidity and mortality [6, 7]. With the advent of modern tools in routine microbiological diagnostics such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), pathogen detection has experienced a remarkable refinement within the past decade [8, 9]. However, reliable species identification by MALDI-TOF MS relies greatly on the quality and accuracy of the employed database. Over the past years, the species identification and differentiation of clinical CoNS isolates have improved significantly, leading to the identification of novel or “rare” species in clinical specimens [10]. Indeed, the “true” clinical relevance of many CoNS species is frequently underappreciated. Staphylococcus massiliensis is a recently described CoNS first reported in 2010 from a cerebral abscess [11], and later from healthy human skin [12]. In 2012, Zong postulated to conceptualize S. massiliensis as part of the normal human skin microflora [13]. Until today, data pertaining to the pathogenic potential of this microorganism and possible treatment approaches is scarce. Here, we report the challenges and limitations in the identification of S. massiliensis in blood cultures from three patients at a university hospital in southwest Germany.

We describe here the incongruency of bacterial species identification for S. massiliensis using three different methods, namely sequencing of the 16S rRNA coding gene, MALDI-TOF MS, and WGS. While Sanger sequencing of the 16S rRNA coding gene correctly identified S. massiliensis, both mass spectrometry and next-generation sequencing were unable to clearly distinguish S. massiliensis from closely related staphylococcal species. Indeed, Zong previously reported the misidentification as Staphylococcus simulans by the MicroScan Walkaway 96 system [13]. Our results demonstrate that even modern and high-resolution identification techniques, such as MALDI-TOF MS and WGS, are dependent on the quality and currentness of the database. Although WGS is frequently regarded as a new gold standard for the molecular characterization of bacteria, the used databases are not necessarily reliable for newly described species and non-model organisms. The clinical relevance of S. massiliensis is still unclear. In all three patients, we detected S. massiliensis in the blood culture. Despite clear clinical signs of infection and inflammatory processes, the interpretation of blood culture positivity for S. massiliensis remains difficult. In both, patients 1 and 2, other clinically relevant pathogens were detected, and COVID-19 was diagnosed in patient 3, thus rendering a causative role of S. massiliensis uncertain. In addition, only one blood culture pair was taken for patients 1 and 2, and the time to positivity for all blood culture bottles was rather long (> 16 h) for all three patients, so that contamination cannot be completely ruled out. Thus, no definitive statement can be made regarding the clinical relevance of the S. massiliensis findings in our patients. Nonetheless, the accuracy of species identification is essential for further investigations on the clinical relevance of S. massiliensis as a potential pathogen. While the detection of CoNS in blood cultures is frequently considered contamination, specific CoNS species, such as Staphylococcus epidermidis and Staphylococcus capitis, may well be clinically relevant, in particular if indwelling devices are present [16]. The first description of S. massiliensis dates back to 2010, when Al Malsalma and colleagues reported the detection of this staphylococcal species from clinical specimen of a 52-year-old male patient (from 2005) with a brain tumor [11]. He developed a cerebral abscess after neurosurgery, which was drained and sent for microbiological diagnostics. Indeed, CoNS can cause post-surgical intracranial infections, rendering the findings of Al Malsalma et al. plausible. However, S. massiliensis has also been suggested as commensal of the human skin as it has been found in the skin of a fresh wound and healthy human skin [12, 13]. On a different note, consistent with the findings of Zong et al. of the presence of a mobile staphylococcal cassette chromosome mec in S. massiliensis [17], we detected the presence of multiple resistance genes in one of our isolates. The presence of clinically relevant antimicrobial resistance genes in skin commensals may pose therapeutic challenges and may be relevant for the acquisition of antibiotic resistances in facultative pathogens [18], such as members of the S. aureus complex, which warrants further investigations.

In conclusion, our data add to the scarce body of evidence that S. massiliensis may be detected in clinical samples for routine microbiological diagnostics. Thus far, the clinical relevance is still unclear and further clinical and experimental studies are needed to elucidate the pathogenic properties and virulence of S. massiliensis. The technical advancement in microbiological diagnostics will introduce new depths in species identification and specification of novel organisms within the next years.