Skip to main content
Download PDF

Pandemic clone USA300 in a Brazilian hospital: detection of an emergent lineage among methicillin-resistant Staphylococcus aureus isolates from bloodstream infections

Antimicrobial Resistance & Infection Control volume 11, Article number: 114 (2022) Cite this article

Abstract

Background

Staphylococcus aureus is one of the leading causes of bloodstream infections (BSI) worldwide. In Brazil, the hospital-acquired methicillin-resistant S. aureus USA100/SCCmecII lineage replaced the previously well-established clones. However, the emergence of community-associated (CA) MRSA lineages among hospitalized patients is an increasing issue.

Methods

Consecutive S. aureus isolates recovered from BSI episodes of patients admitted between January 2016 and December 2018 in a Brazilian teaching hospital were tested for antimicrobial resistance, their genotypic features were characterized, and the clinical characteristics of the patients were evaluated.

Results

A total of 123 S. aureus isolates were recovered from 113 patients. All isolates were susceptible to linezolid, teicoplanin and vancomycin and 13.8% were not susceptible to daptomycin. Vancomycin MIC50 and MIC90 of 2 mg/L were found for both MRSA and MSSA isolates. The MRSA isolation rate was 30.1% (37/123), and 51.4% of them carried the SCCmec type II, followed by SCCmecIV (40.5%). Among the 37 MRSA isolates, the main lineages found were USA100/SCCmecII/ST5 and ST105 (53.7%) and USA800/ST5/SCCmecIV (18.9%). Surprisingly, six (16%) CA-MRSA isolates, belonging to USA300/ST8/SCCmecIVa that carried PVL genes and the ACME cassette type I, were detected. These six patients with USA300 BSI had severe comorbidities, including cancer, and most had a Charlson score ≥ 5; furthermore, they were in wards attended by the same health professionals. MRSA isolates were associated with hospital acquired infections (p = 0.02) in more elderly patients (p = 0.03) and those diagnosed with hematologic cancer (p = 0.04). Among patients diagnosed with MRSA BSI, 19 (54.3%) died.

Conclusions

The pandemic MRSA USA300 was detected for the first time in the Brazilian teaching hospital under study, and its cross-transmission most probably occurred between patients with BSI. This lineage may already be circulating among other Brazilian hospitals, which highlights the importance of carrying out surveillance programs to fight multidrug resistant and hypervirulent isolates.

Background

Staphylococcus aureus is one of the most common causes of bloodstream infections (BSI) worldwide [1, 2]. The presence of an indwelling device or a skin and soft tissue infection (SSTI) associated to hospital (HA) or community (CA) BSI are the most common sources of this pathogen [3]. S. aureus BSIs, especially those caused by MRSA, cause higher rates of morbidity and mortality and the costs associated to such infections are burdensome, especially in middle and low-income countries [4]. In addition, the presence of methicillin-resistant S. aureus (MRSA) as the cause of BSI represents a therapeutic challenge in health care institutions [5]. However, there has been a reduction in the number of MRSA isolated from BSI worldwide [1, 6]. Diekema and coworkers [1] showed that S. aureus was the main Gram-positive bacteria isolated from BSI in a 20-year surveillance period, between 1997 and 2016, involving 45 nations, including those in Latin America. The authors showed that there was a decline in the number of MRSA isolates over these years and that daptomycin resistance among S. aureus isolates remained rare (< 0.1%); furthermore, during that period there was no trend toward an increase in the vancomycin MIC.

Over recent years, the substitution of well-established MRSA lineages has been described in hospital environments [7, 8]. In Brazilian hospitals, the previously predominant MRSA lineage, known as the Brazilian Endemic Clone (BEC/ST239) has been fully replaced by the New York/Japan lineage among BSI isolates (USA100/ST5 or ST105) [9,10,11]. Lately, our group also detected the emergence of USA1100/ST30, a CA-MRSA lineage in Brazilian hospital settings [8, 10]. Curiously, in Brazil, the pandemic clone USA300/ST8/SCCmecIVa and the USA300-Latin American Variant (LV)/SCCmecIVc-e lineages have remained rare [11]. These related lineages present different SCCmec subtypes and the USA300-LV lacks the operon ACME [12]. However, these lineages could carry the Panton-Valentine leukocidin genes and are considered hypervirulent, since once they are present in the environment; they can spread easily, leading to infections with high mortality rates [13].

Molecular studies have helped the epidemiological surveillance of S. aureus BSI, highlighting the constant clonal change that has been taking place in health institutions and the dissemination of MRSA clones that can lead to higher rates of morbidity and mortality [14]. Moreover, constant monitoring of S. aureus BSI can also help surveillance programs in containing the spread of their resistance and virulence. In recent years, our group conducted a surveillance of S. aureus BSI in a University Hospital of Rio de Janeiro, Brazil, to identify the emergence of new clones or new resistance traits that may alter the epidemiology and treatment of these infections. This study aims to continue this surveillance through the characterization of S. aureus isolates from BSI over a three-year period in relation to antimicrobial resistance and virulence associated with different clones and correlate these results with clinical data of the patients.

Methods

Clinical isolates and setting

This prospective cohort study evaluated the phenotypic and molecular profiles of S. aureus isolates recovered from consecutive episodes of BSI occurring in adult patients (> 18 years old), who were admitted to the Hospital Universitário Clementino Fraga Filho (HUCFF) between January 2016 and December 2018. HUCFF is a tertiary public teaching hospital in Rio de Janeiro, Brazil, which currently has 300 active beds.

The first isolate of an episode of S. aureus BSI were analyzed, with subsequent documentation of blood cultures, clinical improvement, and anti-staphylococcal therapy. Demographic data, classification of the BSI episode [15], treatment and length of stay were collected from each patient.

All blood cultures were processed using the BacT/ALERT system (BioMerieux, Durham, NC, USA). Bacterial identification was performed by the automated VITEK2® system (BioMerieux) and confirmed by MALDI-TOF MS (Matrix Assisted Laser Desorption Ionization/ Time of Flight Mass Spectrometry) (Bruker Daltonics, Billerica, MA, USA) [16].

Antimicrobial susceptibility tests and SCCmec typing

Susceptibility to methicillin and trimethoprim-sulfamethoxazole (TMP/STX) was determined using the disk-diffusion test method (Oxoid, Cambrigde, UK) according to the CLSI guidelines [17]. Minimum inhibitory concentrations (MICs) for daptomycin, linezolid, oxacillin, teicoplanin and vancomycin (Sigma-Aldrich Chemical Company, St Louis, MO, USA) were determined by the broth microdilution (BMD) method, using fresh cation-adjusted Muller-Hinton broth (CAMHB). Daptomycin received a supplement of calcium (50 μg/mL) [17]. The ceftaroline MICs were determined by the gradient diffusion method (Etest®, BioMérieux) for all MRSA isolates. S. aureus ATCC 25923 and ATCC 29213 were used as controls for the disk-diffusion and BMD tests, respectively.

The SCCmec typing [18] and subtyping [19] for isolates resistant to oxacillin by the disk-diffusion method were assessed by multiplex polymerase chain reaction (PCR), using bacterial DNA obtained using the QIAamp DNA Mini Kit (QIAGEN, Hilden, Germany). The Staphylococcus strains used as positive controls are described in Salgueiro et al. [20].

Phenotypic tests for screening of hVISA isolates

All isolates presenting a MIC ≥ 2 mg/L for vancomycin were screened for the hVISA (heteroresistant vancomycin-intermediate S. aureus) phenotype [21, 22]. Plates with BHI agar (Becton Dickson, Franklin Lakes, NJ, USA), containing 3 and 4 mg/L of vancomycin were swabbed with 0.5 McFarland standard suspension (108 CFU/mL) of S. aureus and incubated at 35 to 37 °C for 24 h. Reduced susceptibility to vancomycin was defined as the growth of one or more colony-forming units (CFU) at either of the two concentrations. BHI agar plates with 4 mg/L of vancomycin and supplemented with 16 g/L of pancreatic casein digestion (Merck), were also inoculated with four 10μL spots from a 0.5 McFarland inoculum [22]. An isolate was considered to have reduced susceptibility to vancomycin if at least one spot had two or more CFUs. S. aureus ATCC 29,213 (MSSA) and Mu3 (hVISA) were used as controls [23].

Genotypic profile of MRSA isolates

All MRSA isolates were typed by pulsed-field gel electrophoresis (PFGE) after digestion of whole cell DNA with SmaI in a CHEF-DRIII system (Bio-Rad, Richmond, CA, USA), as previously described [24]. The PFGE fingerprints were compared by the unweighted pair-group method with arithmetic mean clustering analysis, applying the Dice correlation coefficient. Isolates with four or fewer bands of difference or minimum of 80% similarity were classified as belonging to the same genotype [25]. The clonal lineages were defined by comparison with national [10] and international clones [26]. Representative isolates from each genotype, identified in PFGE, underwent Multilocus Sequence Typing (MLST) [27].

Detection of virulence genes

The detection of PVL genes was carried out in all MRSA isolates using PCR [28]. Isolates belonging to the USA300/ST8/SCCmecIV lineage also underwent ACME typing [29]. The Staphylococcus strains used as positive controls are described in Schuenck et al. [28].

Statistical analysis

Categorical variables were compared using the chi-square or Fisher exact tests, and continuous variables were compared using the Wilcoxon test. A p value < 0.05 was considered to be statistically significant. All analyses were performed using SPSS 21.0 for Windows (SPSS, Inc).

Results

Baseline characteristics of patients presenting S. aureus BSI

During the study period, 113 patients developed S. aureus BSI. Ten of them presented two BSI episodes. Thus, a total of 123 S. aureus isolates were recovered. Most of the patients (53.1%; 60/113), who were men, presented at least one comorbidity (89.4%) and developed central line-associated BSI (55.8%) or secondary bacteremia due to SSTI (24.8%). MRSA was associated to more elderly patients (p = 0.03), hematologic cancer (p = 0.04) and hospital-associated BSI (p = 0.02). A total of 50 (44.2%) patients died, and among those diagnosed with MRSA BSI, 54.3% died (Table 1).

Table 1 Baseline characteristics of 113 patients presenting methicillin-resistant Staphylococcus aureus bloodstream infections
Full size table

Antimicrobial susceptibility, hVISA screening and SCCmec typing

According to the disk-diffusion method, 30.1% (37/123) of S. aureus isolates were resistant to cefoxitin and were characterized as MRSA. Overall, 51.4% (19/37) of these isolates carried the SCCmecII lineage, followed by SCCmecIV (15/37; 40.5%), SCCmecIII (2/37; 5.4%) and SCCmecV (1/37; 2.7%). Among the SCCmecIV isolates those that were subtyped as SCCmecIVa belonged to USA300 lineage. Only the SCCmecIII isolates were resistant to TMP/STX.

Table 2 shows the MIC results. Both MRSA and MSSA isolates presented MIC50 and MIC90 = 2 mg/L for vancomycin. This MIC value was found in 90% of the SCCmecII isolates and in 53.3% of those that carried the SCCmecIV. The ceftaroline MICs in the MRSA isolates ranged from 0.25 to 0.75 mg/L. The oxacillin MICs, MIC50 and MIC90, were 256 and ≥ 256 mg/L, respectively in the MRSA isolates, and 1 and 2 mg/L among the MSSA isolates. All isolates were susceptible to linezolid, teicoplanin and vancomycin. Seventeen (13.8%) S. aureus isolates were non-susceptible to daptomycin, and among them, five (29.4%) were MRSA isolates.

Table 2 Minimal inhibitory concentration of different antimicrobials against 123 Staphylococcus aureus isolates from bloodstream infections
Full size table

All the 72 (58.5%) isolates that presented a vancomycin MIC = 2 mg/L were screened for the hVISA phenotype. However, no hVISA phenotype was found.

Genotypic profiles and virulence genes in MRSA isolates

The PFGE patterns and general characteristics of 37 MRSA isolates recovered from BSI are presented in Fig. 1. The isolates were clustered among specific lineages: USA100/SCCmecII of ST5 (3 isolates; 8.1%) and ST105 (16; 43.2%), a single-locus variant (SLV) of ST5; USA800/ST5/SCCmecIV (7; 18.9%); USA300/ST8/SCCmecIVa (6; 16.2%); USA1100/ST30/SCCmecIV (2; 5.4%) and BEC/ST239/SCCmecIII (2; 5.4%). One isolate carrying the SCCmec type V lineage and related to ST1 was also found. The PVL genes were found in all isolates of the USA300/ST8 and USA1100/ST30 lineages.

Fig. 1
figure 1

Dendrogram of the PFGE patterns and characteristics related to the genetic background of 37 MRSA isolates recovered from bloodstream infections. Isolates showing a similarity coefficient ≥ 80% were considered genetically related. *PVL genes positive isolates; ST, Sequence type; SCCmec, Staphylococcal cassette chromosome mec; MIC, Minimum inhibitory concentration; OXA, oxacillin; VAN, vancomycin; DAP, daptomycin; MM, Month; DD, Day; YY, Year; Hem, Hematology; Neph, Nephrology; Vas Surg, Vascular Surgery; Emer, Emergence; Gen Surg, General Surgery; Int Med, Internal Medicine; Hep, Hepatology; Psyc, Psychiatry; Derm, Dermatology; ICU, Intensive Care Unit; Card, Cardiology; Ger, Geriatrics; Inf Dis, Infectious Disease; CCU, Coronary Care Unit; HA, Hospital-associated; HCA, Healthcare-associated; CA, Community-associated; BEC, Brazilian endemic clone; ND, not determined

Full size image

Characteristics of the USA300 isolates

All the USA300/ST8/SCCmecIVa isolates (1963, 1967, 1982, 1988, 2013, and 2020) carried both PVL virulence genes and ACME cassette type I (Table 3). These isolates were recovered from different patients, who had developed hospital or healthcare-associated BSIs. All these individuals had severe comorbidities and all, but one patient (isolate number 2020), had a central line in situ when diagnosed with BSI. Four patients presented a Charlson score ≥ 5. Most of these patients were undergoing cancer treatment, although not at the same unit. Figure 2 shows the timeline distribution of the six patients with BSI caused by the USA300 according to their hospital ward. A direct nosocomial transmission could not be clearly established, although some patients were admitted to the hospital only a few days apart, and there was a ≥ 90% similarity between the isolates (Fig. 1). However, the wards occupied by these patients are physically close to each other (along the same corridor), and the same healthcare workers and cleaning staff attended these wards.

Table 3 Clinical and microbiological characteristics related to six patients that presented bloodstream infections caused by the pandemic MRSA USA300/ST8/SCCmecIVa lineage
Full size table
Fig. 2
figure 2

Timeline distribution of the six patients who presented bloodstream infections caused by USA300/ST8/SCCmecIVa isolates according to hospital ward. BC—Blood culture positive for MRSA USA300; †Death as outcome

Full size image

Discussion

In this study, we characterized consecutive S. aureus isolates from BSI in a teaching hospital in Rio de Janeiro for three years and the emergence of the pandemic CA-MRSA USA300/ST8/SCCmecIVa lineage was detected for the first time in this hospital. The patients with USA300 BSI were in wards that were attended by the same health professionals and, therefore, we hypothesized a cross-transmission of these isolates occurred in the hospital. Although other hospitals may not have the same epidemiological situation seen here, these results may reflect a picture of the circulating strains of S. aureus that cause BSI in Brazil.

Although the CA-MRSA lineages are classically related to SSTI, they have also been widely implicated in HA-BSI [30, 31]. According to Kourtis et al. [32] CA-MRSA infections provide a reservoir that contributes to the incidence of healthcare-associated diseases and fuels transmission both within and outside healthcare settings. Our group has been carrying out a surveillance of S. aureus BSI in this hospital (HUCFF) for years and, although we have described the presence of community S. aureus lineages in this hospital since 2009 [8, 10, 33,34,35] we had not yet seen the presence and spread of USA300/ST8/SCCmecIVa. Some Brazilian studies have shown the presence of CA-MRSA isolates in hospitals recovered from different clinical sources, including occasionally USA300/ST8/SCCmecIV isolates [36,37,38,39]. However, these studies did not characterize the isolates of this lineage accurately. Furthermore, different from what has been described in Latin American countries about the occurrence of the USA300-LV lineage [11], here, the isolates that belonged to USA300/ST8 carried the PVL genes, the SCCmec type IVa, as well as the ACME-I cassette, and were characterized as the USA300/ST8 North American lineage. Patients with USA300 BSI presented severe comorbidities and most had a Charlson score ≥ 5 and cancer. Curiously, among the patients with MRSA BSI this pathology was most frequently associated to those presenting USA300 (p < 0.05) (data not shown). Although we were not able to demonstrate a time–space relationship among all of them, a close genetic similarity of the isolates leads us to suggest a possible horizontal transmission associated with this clonal lineage. Furthermore, even if all the patients involved did not occupy the same ward at the same time, there would be a possible sharing of unscreened patients, which may be the focus of the outbreak, pointing out the need for constant surveillance of this pandemic clonal lineage within this hospital.

The present study shows a great diversity of MRSA clonal lineages causing BSI which was also observed in previous studies by our group in this teaching hospital [8, 9]. Here, the USA100 lineage is the main MRSA clone (51.4%). These data confirm the replacement of the prior prevalent BEC clone, which now represents only 5.4% of MRSA isolates found. Bride et al. [38], in a study conducted in a hospital in the southeast of Brazil characterized S. aureus isolates from various clinical sources and the USA100/ST5 lineage was prevalent among HA-infections. However, in our study, most of the USA100 isolates belonged to ST105 (84.2%), a SLV from ST5. Although this is the first report of this lineage in our hospital, it has already been detected in S. aureus isolates from BSI in other Brazilian hospitals [8, 9]. Viana and coworkers recently evaluated MRSA isolates from different hospitals in Rio de Janeiro, between 2014 and 2017 and observed the emergence of this SCCmecII/ST105 lineage, which has presented multidrug resistance characteristics and seems to be associated with increased evasion when exposed to monocytic cells [40].

The successful spread of S. aureus isolates is commonly attributed to their antimicrobial resistance profile, but virulence may also play a crucial role in colonization and infection [41]. In the present study, the presence of PVL genes was evaluated in all MRSA isolates and only the CA-MRSA lineages related to USA300/ST8 and USA1100/ST30 were positive. Besides, USA300 presented the two virulence determinants investigated, PVL genes and ACME-I. Some authors have reported an association between virulence and mortality among patients with S. aureus BSI, indicating that the transmission of a virulent pathogen to an already debilitated patient can worsen his clinical condition [7]. However, more studies are needed to better understand the relevance of virulence determinants in S. aureus bloodstream infections.

Among Latin American countries, the MRSA isolates accounted for almost half of the S. aureus BSI described over the last few years [1, 11]. In Brazil, the MRSA isolation rates vary according to the region. For example, a study conducted at a tertiary oncology care center in Rio de Janeiro detected 26.3% of methicillin resistance among S. aureus isolates recovered from BSI [42]. On the other hand, Primo and coworkers [4] showed a MRSA isolation rate of 58.3% among S. aureus BSI in a teaching hospital located in the central-west region of Brazil. The MRSA isolation rate in HUCFF in Rio de Janeiro has remained around 30% in BSI caused by S. aureus, since 2011, as previously described by our group [10], similarly to the findings of the present study, which reinforces the need for constant surveillance directed towards this pathogen.

A structured management in diagnosis and treatment of S. aureus BSI, which differs accordingly to methicillin-resistance, is crucial for an optimal outcome [43]. Vancomycin is the first-line treatment for MRSA BSI worldwide [5], although non-susceptible vancomycin isolates have been already reported [21, 44]. In the present study, no hVISA/VISA (Vancomycin-intermediate S. aureus) or VRSA (vancomycin-resistant S. aureus) isolates were detected. However, 58.5% of the isolates presented a high vancomycin MIC, and 76% (28/37) of them were MRSA isolates. The clinical efficacy of this antimicrobial can be critically affected by a MIC = 2 mg/L [21]. Thus, daptomycin has become an important alternative to treat MRSA BSI [45]. However, 13.5% of MRSA isolates in the present study were characterized as non-susceptible to daptomycin. Although daptomycin resistance among S. aureus remains rare worldwide (< 0.1%) [1], Silva et al. [46] also found isolates non-susceptible to daptomycin (4.7%) in a Brazilian study involving 128 clinical S. aureus isolates. We have already described BSI caused by non-susceptible daptomycin S. aureus isolates (MIC of 2 and 4 mg/L) among MRSA-VISA isolates in the hospital of the present study [2]. This data is of great concern because of its impact on the patient’s outcome.

In a previous study, da Silva et al. suggested that comorbidities can contribute to a greater susceptibility for acquiring bacterial infections, such as MRSA BSI [47], in elderly patients. We also verified that MRSA BSI was associated with older patients (p = 0.03). In fact, in our study most patients (101/113; 89.4%) presented at least one comorbidity, which may indicate a close relationship with age. Although the global prevalence of MRSA BSI in patients with cancer is relatively low [48], in this study this pathogen was detected in 46% of the patients under study. Even though this study demonstrated that elderly and cancer patients were the most affected, we concluded that the high mortality rates found may not be due to MRSA infection, but to the severe health condition of the patients evaluated.

Some limitations of this study include a lack of national epidemiological data on S. aureus BSI, which could make comparative analyses in relation to clinical and microbiological aspects related to this type of infection difficult. Furthermore, we only characterized BSI S. aureus isolates, and we did not assess the colonized patients to confirm the hospital spread of USA300/ST8. Although we found S aureus isolates from other lineages disseminated in the hospital that seemed to be endemic, such as the USA100 lineage, the unusual presence of the pandemic and hypervirulent USA300/ST8 clone must be highlighted. This is because of its ability to establish itself in hospital settings as has been well described in North American studies; highlighting the fact that this lineage could also become endemic in Brazilian hospitals.

Conclusions

The emergence of MRSA isolates of the USA300/ST8/SCCmecIVa lineage was reported in the Brazilian teaching hospital under study. This possibly occurred due to an in-hospital spread among patients with BSI. Therefore, we conclude that this pandemic and hypervirulent lineage may already be circulating among Brazilian hospitals and could be associated to future hospital outbreaks.

Availability of data and materials

The data sets generated and analyzed during the current study, such as the PFGE and MLST are not publicly available as there is no public database to deposit PFGE results and no new ST was found in the present study. However, these data are available from the corresponding author on request.

Abbreviations

BSI:

Bloodstream infections

SSTI:

Skin and soft tissue infection

HA and CA:

Hospital and community-associated

MSSA:

Methicillin-susceptible S. aureus

MRSA:

Methicillin-resistant S. aureus

BEC:

Brazilian endemic clone

CA-MRSA:

Community-associated MRSA

BMD:

Broth microdilution

MIC:

Minimum inhibitory concentration

CAMHB:

Cation-adjusted Muller-Hinton broth

PVL:

Panton-Valentine leucocidin

ACME:

Arginine Catabolic Mobile Element

SCCmec :

Staphylococcal cassette chromosome mec

PFGE:

Pulsed-field gel electrophoresis

MLST:

Multilocus Sequence Type

HUCFF:

Hospital Universitário Clementino Fraga Filho

ATCC:

American type culture collection

LV:

Latin American variant

TMP/STX:

Trimethoprim/sulfamethoxazole

CLSI:

Clinical and Laboratory Standards Institute VISA: vancomycin-intermediate S. aureus

hVISA:

Heteroresistant vancomycin-intermediate S. aureus

CFU:

Colony-forming unit

BHI:

Brain heart infusion

SLV:

Single-locus variant

PCR:

Polymerase chain reaction

References

  1. Diekema DJ, Hsueh P-R, Mendes RE, Pfaller MA, Rolston KV, Sader HS, et al. The microbiology of bloodstream infection: 20-year trends from the SENTRY antimicrobial surveillance program. Antimicrob Agents Chemother. 2019;63(7):e00355-e419.

    Article  CAS  Google Scholar 

  2. Kern WV, Rieg S. Burden of bacterial bloodstream infection-a brief update on epidemiology and significance of multidrug-resistant pathogens. Clin Microbiol Infect. 2020;26(2):151–7.

    Article  CAS  Google Scholar 

  3. Kwiecinski JM, Horswill AR. Staphylococcus aureus bloodstream infections: pathogenesis and regulatory mechanisms. Curr Opin Microbiol. 2020;53:51–60.

    Article  CAS  Google Scholar 

  4. Primo MGB, Guilarde AO, Martelli CMT, Batista LJ de A, Turchi MD. Healthcare-associated Staphylococcus aureus bloodstream infection: length of stay, attributable mortality, and additional direct costs. Braz J Infect Dis. 2012;16(6):503–9.

  5. Turner NA, Sharma-Kuinkel BK, Maskarinec SA, Eichenberger EM, Shah PP, Carugati M, et al. Methicillin-resistant Staphylococcus aureus: an overview of basic and clinical research. Nat Rev Microbiol. 2019;17(4):203–18.

    Article  CAS  Google Scholar 

  6. Gagliotti C, Högberg LD, Billström H, Eckmanns T, Giske CG, Heuer OE, et al. Staphylococcus aureus bloodstream infections: diverging trends of methicillin-resistant and methicillin-susceptible isolates, EU/EEA, 2005 to 2018. Euro Surveill. 2021;26(46).

  7. Park K-H, Chong YP, Kim S-H, Lee S-O, Choi S-H, Lee MS, et al. Community-associated MRSA strain ST72-SCCmecIV causing bloodstream infections: clinical outcomes and bacterial virulence factors. J Antimicrob Chemother. 2015;70(4):1185–92.

    Article  CAS  Google Scholar 

  8. Chamon RC, Ribeiro S da S, da Costa TM, Nouér SA, Dos Santos KRN. Complete substitution of the Brazilian endemic clone by other methicillin-resistant Staphylococcus aureus lineages in two public hospitals in Rio de Janeiro, Brazil. Braz J Infect Dis. 2017;21(2):185–9.

  9. Caiaffa-Filho HH, Trindade PA, Gabriela da Cunha P, Alencar CS, Prado GVB, Rossi F, et al. Methicillin-resistant Staphylococcus aureus carrying SCCmec type II was more frequent than the Brazilian endemic clone as a cause of nosocomial bacteremia. Diagn Microbiol Infect Dis. 2013;76(4):518–20.

  10. Damasco AP, da Costa TM, Morgado PGM, Guimarães LC, Cavalcante FS, Nouér SA, et al. Daptomycin and vancomycin non-susceptible methicillin-resistant Staphylococcus aureus clonal lineages from bloodstream infection in a Brazilian teaching hospital. Braz J Infect Dis. 2019;23(2):139–42.

    Article  Google Scholar 

  11. Arias CA, Reyes J, Carvajal LP, Rincon S, Diaz L, Panesso D, et al. A prospective cohort multicenter study of molecular epidemiology and phylogenomics of Staphylococcus aureus bacteremia in Nine Latin American countries. Antimicrob Agents Chemother. 2017;61(10):e00816-e817.

    Article  Google Scholar 

  12. Reyes J, Rincón S, Díaz L, Panesso D, Contreras GA, Zurita J, et al. Dissemination of methicillin-resistant Staphylococcus aureus USA300 sequence type 8 lineage in Latin America. Clin Infect Dis. 2009;49(12):1861–7.

    Article  CAS  Google Scholar 

  13. Kempker RR, Farley MM, Ladson JL, Satola S, Ray SM. Association of methicillin-resistant Staphylococcus aureus (MRSA) USA300 genotype with mortality in MRSA bacteremia. J Infect. 2010;61(5):372–81.

    Article  Google Scholar 

  14. Smith JT, Eckhardt EM, Hansel NB, Eliato TR, Martin IW, Andam CP. Genomic epidemiology of methicillin-resistant and -susceptible Staphylococcus aureus from bloodstream infections. BMC Infect Dis. 2021;21(1):589.

    Article  CAS  Google Scholar 

  15. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008;36(5):309–32.

    Article  Google Scholar 

  16. Patel R. MALDI-TOF MS for the diagnosis of infectious diseases. Clin Chem. 2015;61(1):100–11.

    Article  CAS  Google Scholar 

  17. Clinical and Laboratory Standards Institute, editor. Performance standards for antimicrobial susceptibility testing. Wayne (PA), USA; 2021.

  18. Milheiriço C, Oliveira DC, de Lencastre H. Update to the multiplex PCR strategy for assignment of mec element types in Staphylococcus aureus. Antimicrob Agents Chemother. 2007;51(9):3374–7.

    Article  Google Scholar 

  19. Zhang K, McClure J-A, Elsayed S, Louie T, Conly JM. Novel multiplex PCR assay for characterization and concomitant subtyping of staphylococcal cassette chromosome mec types I to V in methicillin-resistant Staphylococcus aureus. J Clin Microbiol. 2005;43(10):5026–33.

    Article  CAS  Google Scholar 

  20. Salgueiro VC, Seixas MDL, Guimarães LC, Ferreira D de C, Da Cunha DC, Nouér SA, et al. High rate of neonates colonized by methicillin-resistant Staphylococcus species in an Intensive Care Unit. J Infect Dev Ctries. 2019;13(9):810–6.

  21. da Costa TM, Morgado PGM, Cavalcante FS, Damasco AP, Nouér SA, Dos Santos KRN. Clinical and microbiological characteristics of heteroresistant and vancomycin-intermediate Staphylococcus aureus from bloodstream infections in a Brazilian teaching hospital. PLoS ONE. 2016;11(8):e0160506.

    Article  Google Scholar 

  22. Satola SW, Farley MM, Anderson KF, Patel JB. Comparison of detection methods for heteroresistant vancomycin-intermediate Staphylococcus aureus, with the population analysis profile method as the reference method. J Clin Microbiol. 2011;49(1):177–83.

    Article  Google Scholar 

  23. Hiramatsu K, Aritaka N, Hanaki H, Kawasaki S, Hosoda Y, Hori S, et al. Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin. Lancet. 1997;350(9092):1670–3.

    Article  CAS  Google Scholar 

  24. Vivoni AM, Diep BA, de Gouveia Magalhães AC, Santos KRN, Riley LW, Sensabaugh GF, et al. Clonal composition of Staphylococcus aureus isolates at a Brazilian university hospital: identification of international circulating lineages. J Clin Microbiol. 2006;44(5):1686–91.

    Article  CAS  Google Scholar 

  25. van Belkum A, Tassios PT, Dijkshoorn L, Haeggman S, Cookson B, Fry NK, et al. Guidelines for the validation and application of typing methods for use in bacterial epidemiology. Clin Microbiol Infect. 2007;13(Suppl 3):1–46.

    Article  Google Scholar 

  26. McDougal LK, Steward CD, Killgore GE, Chaitram JM, McAllister SK, Tenover FC. Pulsed-field gel electrophoresis typing of oxacillin-resistant Staphylococcus aureus isolates from the United States: establishing a national database. J Clin Microbiol. 2003;41(11):5113–20.

    Article  CAS  Google Scholar 

  27. Enright MC, Day NP, Davies CE, Peacock SJ, Spratt BG. Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus. J Clin Microbiol. 2000;38(3):1008–15.

    Article  CAS  Google Scholar 

  28. Schuenck RP, Cavalcante FS, Emery E, Giambiagi-de Marval M, dos Santos KRN. Staphylococcus aureus isolates belonging to different multilocus sequence types present specific virulence gene profiles. FEMS Immunol Med Microbiol. 2012;65(3):501–4.

    Article  CAS  Google Scholar 

  29. Diep BA, Stone GG, Basuino L, Graber CJ, Miller A, des Etages S-A, et al. The arginine catabolic mobile element and staphylococcal chromosomal cassette mec linkage: convergence of virulence and resistance in the USA300 clone of methicillin-resistant Staphylococcus aureus. J Infect Dis. 2008;197(11):1523–30.

    Article  CAS  Google Scholar 

  30. Otter JA, French GL. Community-associated methicillin-resistant Staphylococcus aureus strains as a cause of healthcare-associated infection. J Hosp Infect. 2011;79(3):189–93.

    Article  CAS  Google Scholar 

  31. Diekema DJ, Richter SS, Heilmann KP, Dohrn CL, Riahi F, Tendolkar S, et al. Continued emergence of USA300 methicillin-resistant Staphylococcus aureus in the United States: results from a nationwide surveillance study. Infect Control Hosp Epidemiol. 2014;35(3):285–92.

    Article  Google Scholar 

  32. Kourtis AP, Hatfield K, Baggs J, Mu Y, See I, Epson E, et al. Vital signs: epidemiology and recent trends in methicillin-resistant and in methicillin-susceptible Staphylococcus aureus bloodstream infections—United States. MMWR Morb Mortal Wkly Rep. 2019;68(9):214–9.

    Article  Google Scholar 

  33. Polyclonal presence of non-multiresistant methicillin-resistant Staphylococcus aureus isolates carrying SCCmec IV in health care-associated infections in a hospital in Rio de Janeiro, Brazil. Diagn Microbiol Infect Dis. 2009;64(4):434–41.

  34. Caboclo RMF, Cavalcante FS, Iorio NLP, Schuenck RP, Olendzki AN, Felix MJ, et al. Methicillin-resistant Staphylococcus aureus in Rio de Janeiro hospitals: dissemination of the USA400/ST1 and USA800/ST5 SCCmec type IV and USA100/ST5 SCCmec type II lineages in a public institution and polyclonal presence in a private one. Am J Infect Control. 2013;41(3):e21-26.

    Article  CAS  Google Scholar 

  35. Cavalcante FS, Schuenck RP, Ferreira DC, da Costa CR, Nouér SA, dos Santos KRN. Methicillin-resistant Staphylococcus aureus: spread of specific lineages among patients in different wards at a Brazilian teaching hospital. J Hosp Infect. 2014;86(2):151–4.

    Article  CAS  Google Scholar 

  36. Rossi F, Diaz L, Wollam A, Panesso D, Zhou Y, Rincon S, et al. Transferable vancomycin resistance in a community-associated MRSA lineage. N Engl J Med. 2014;370(16):1524–31.

    Article  CAS  Google Scholar 

  37. Zuma AVP, Lima DF, Assef APDC, Marques EA, Leão RS. Molecular characterization of methicillin-resistant Staphylococcus aureus isolated from blood in Rio de Janeiro displaying susceptibility profiles to non-β-lactam antibiotics. Braz J Microbiol. 2017;48(2):237–41.

    Article  CAS  Google Scholar 

  38. Bride L de L, Pereira MF, Barbosa MC, Silva NC, Klein NM, Nascimento TC, et al. Differences in resistance profiles and virulence genes among methicillin-resistant and methicillin-susceptible Staphylococcus aureus of different lineages at a public tertiary hospital. Rev Soc Bras Med Trop. 2019;52:e20190095.

  39. Veloso JO, Lamaro-Cardoso J, Neves LS, Borges LFA, Pires CH, Lamaro L, et al. Methicillin-resistant and vancomycin-intermediate Staphylococcus aureus colonizing patients and intensive care unit environment: virulence profile and genetic variability. APMIS. 2019;127(11):717–26.

    Article  CAS  Google Scholar 

  40. Viana AS, Nunes Botelho AM, Moustafa AM, Boge CLK, Pires Ferreira AL, da Silva Carvalho MC, et al. Multidrug-resistant methicillin-resistant Staphylococcus aureus associated with bacteremia and monocyte evasion, Rio de Janeiro. Brazil Emerg Infect Dis. 2021;27(11):2825–35.

    Article  CAS  Google Scholar 

  41. Kim HJ, Choi Q, Kwon GC, Koo SH. Molecular epidemiology and virulence factors of methicillin-resistant Staphylococcus aureus isolated from patients with bacteremia. J Clin Lab Anal. 2020;34(3):e23077.

    Article  Google Scholar 

  42. Velasco E, Thuler LC, Martins CA, Nucci M, Dias LM, Gonçalves VM. Epidemiology of bloodstream infections at a cancer center. Sao Paulo Med J. 2000;118(5):131–8.

    Article  CAS  Google Scholar 

  43. Kimmig A, Hagel S, Weis S, Bahrs C, Löffler B, Pletz MW. Management of Staphylococcus aureus Bloodstream infections. Front Med (Lausanne). 2020;7:616524.

    Article  Google Scholar 

  44. Rossato AM, Primon-Barros M, Dias CAG, d’Azevedo PA. Vancomycin MIC and agr dysfunction in invasive MRSA infections in southern Brazil. Braz J Microbiol. 2020;51(4):1819–23.

    Article  CAS  Google Scholar 

  45. Jorgensen SCJ, Zasowski EJ, Trinh TD, Lagnf AM, Bhatia S, Sabagha N, et al. Daptomycin plus β-lactam combination therapy for methicillin-resistant Staphylococcus aureus bloodstream infections: a retrospective, comparative cohort study. Clin Infect Dis. 2020;71(1):1–10.

    Article  CAS  Google Scholar 

  46. Silva DM, Menezes EMN, Silva EV, Lamounier TAC. Prevalence and antimicrobial susceptibility profile of ESKAPE pathogens from the Federal District. Brazil J Bras Patol Med Lab. 2017;53:240–5.

    CAS  Google Scholar 

  47. da Silva NCZ, da Rocha JA, do Valle FM, Silva ASDN, Ehrlich S, Martins IS. The impact of ageing on the incidence and mortality rate of bloodstream infection: A hospital-based case-cohort study in a tertiary public hospital of Brazil. Trop Med Int Health. 2021;26(10):1276–84.

  48. Li Z, Zhuang H, Wang G, Wang H, Dong Y. Prevalence, predictors, and mortality of bloodstream infections due to methicillin-resistant Staphylococcus aureus in patients with malignancy: systemic review and meta-analysis. BMC Infect Dis. 2021;21(1):74.

    Article  Google Scholar 

Download references

Acknowledgements

Infection Control Group HUCFF/UFRJ: Ana Pereira Rangel, Anna Carla Castiñeiras, Christiany Moçali Gonçalez, Joana Freire, Luiz Felipe Guimarães and Raquel Batista.

Funding

This study was supported by Brazilian grants from Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ, grants #E-26/202.592/2019, #E-26/010.000172/2016, #E-26/010.001463/2019, #E-26/211.554/2019; #E-26/201.071/2020 and #E-26/211.284/2021), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, grants #307594/2021-1 and 11423381/2018-0), and Coordenação de Aperfeiçoamento Pessoal de Nível Superior – Brasil (CAPES)– Finance Code 001.

Author information

Author notes

  1. Mariana Fernandes Augusto, Débora Cristina da Silva Fernandes and Tamara Lopes Rocha have contributed equally to this work

Authors and Affiliations

  1. Laboratório de Infecção Hospitalar, Departamento de Microbiologia Médica, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, CCS, Bloco I, Sala I2-010 - Cidade Universitária, Rio de Janeiro, RJ, CEP 21941-590, Brazil

    Mariana Fernandes Augusto, Tamara Lopes Rocha de Oliveira & Kátia Regina Netto dos Santos

  2. Departamento de Microbiologia, Imunologia e Parasitologia, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil

    Débora Cristina da Silva Fernandes

  3. Centro Multidisciplinar de Macaé, Universidade Federal do Rio de Janeiro, Macaé, Brazil

    Fernanda Sampaio Cavalcante

  4. Departamento de Patologia, Faculdade de Medicina, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil

    Raiane Cardoso Chamon

  5. Serviço de Patologia Clínica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Adriana Lúcia Pires Ferreira

  6. Faculdade de Medicina, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Simone Aranha Nouér

Authors
  1. Mariana Fernandes Augusto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Débora Cristina da Silva Fernandes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tamara Lopes Rocha de Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fernanda Sampaio Cavalcante
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Raiane Cardoso Chamon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Adriana Lúcia Pires Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Simone Aranha Nouér
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kátia Regina Netto dos Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

Infection Control Group HUCFF/UFRJ

  • Ana Pereira Rangel
  • , Anna Carla Castiñeiras
  • , Christiany Moçali Gonçalez
  • , Joana Freire
  • , Luiz Felipe Guimarães
  •  & Raquel Batista

Contributions

ALPF received the blood cultures and processed them while DCSF was responsible for the collection and storage of the S. aureus isolates identified. MFA, TLRO and DCSF analyzed the S. aureus isolates and conducted the experiments described in the “Methods” section. SAN was responsible for the clinical evaluation of the patients, and for gathering their clinical characteristics, as well as for the final statistical analysis. DCSF gathered the data. MFA and TLRO drafted the manuscript. KRNS, FSC and RCC supervised and critically reviewed the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Kátia Regina Netto dos Santos.

Ethics declarations

Ethics approval and consent to participate

The Human Research Ethics Committee of Hospital Universitário Clementino Fraga Filho approved the present study under number CAAE40652714.0.0000.5257.

Consent for publication

The Human Research Ethics Committee of the Hospital Universitário Clementino Fraga Filho waived the written informed consent for the present study.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Augusto, M.F., da Silva Fernandes, D.C., de Oliveira, T.L.R. et al. Pandemic clone USA300 in a Brazilian hospital: detection of an emergent lineage among methicillin-resistant Staphylococcus aureus isolates from bloodstream infections. Antimicrob Resist Infect Control 11, 114 (2022). https://0-doi-org.brum.beds.ac.uk/10.1186/s13756-022-01154-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://0-doi-org.brum.beds.ac.uk/10.1186/s13756-022-01154-3

Keywords

Antimicrobial Resistance & Infection Control

ISSN: 2047-2994

Contact us