Clinical and Microbiological Characteristics of Hospital-Acquired Methicillin-Resistant Staphylococcus aureus Bacteremia Caused by a Community-Associated PVL-Negative Strain.

BACKGROUND: ST72-SCCmecIV, a community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain in Korea, originated in the community and has been spreading in health care settings. Herein, we describe the clinical and microbiological characteristics of patients with hospital-acquired MRSA bacteremia (MRSAB) caused by community-associated strains.
METHODS: We analyzed hospital-acquired MRSAB cases caused by ST72-SCCmecIV using a prospective cohort of patients with SAB in a tertiary hospital in Korea from July 2008 to December 2018. We compared the clinical and microbiological characteristics of ST72-SCCmecIV with ST5-SCCmecII, a representative hospital-associated genotype strain.
RESULTS: Of the 1782 S. aureus bacteremia (SAB) cases, 628 (35.2%) were hospital-acquired MRSAB. Of the 628 isolates, 431 (68.6%) were ST5-SCCmecII and 152 (24.2%) were ST72-SCCmecIV. Patients with ST72-SCCmecIV were younger than those with ST5-SCCmecII and less likely to have a history of recent surgery, antibiotic treatment, nasal MRSA colonization, and central venous catheter placement. Compared with ST5-SCCmecII, ST72-SCCmecIV isolates were more likely to have vancomycin MICs ≤1.0 mg/L (P < .001). Osteoarticular infection as the site of infection (7.2% [11/152] vs 1.4% [6/431]) was more common in patients with ST72-SCCmecIV. There were no significant differences in the rate of recurrence (≤90 days), persistent bacteremia (≥7 days), or 30- and 90-day mortality rates between the 2 groups.
CONCLUSIONS: Osteoarticular infections were more prevalent in ST72-SCCmecIV MRSAB. Mortality rates between the ST72-SCCmecIV and ST5-SCCmecII groups were not significantly different.

Methicillin-resistant Staphylococcus aureus (MRSA) exhibits enhanced virulence and causes a wide range of infections from mild to life-threatening conditions in both hospital and community settings. Historically, MRSA infections have primarily occurred among hospitalized patients. However, a growing number of community-associated MRSA (CA-MRSA) infections have recently emerged worldwide [1, 2], and new MRSA strains, often called CA-MRSA strains, have been isolated. As such, their virulence factors have not yet been completely established. CA-MRSA strains present different characteristics from those of the traditional hospital-associated MRSA (HA-MRSA) strains [3].

S. aureus can evade the host innate immunity [4] and may secrete toxins such as Panton-Valentine leukocidin (PVL), which is lytic to human neutrophils and has pro-inflammatory effects [5]. The distribution and prevalence of dominant CA-MRSA clones and PVL gene status vary among countries [3]. In the United States, CA-MRSA isolates are mostly attributed to the single-clone sequence type (ST) 8 (pulsotype USA 300) possessing PVL [6, 7]. In South Korea, ST72-SCCmecIV is the major CA-MRSA clone [8, 9] and is distinct from other clones in Asia and around the world [10]. Particularly, unlike the PVL-positive CA-MRSA isolates from Western countries, ST72-SCCmecIV isolates do not carry the PVL gene. This PVL-negative ST72-SCCmecIV CA-MRSA strain first emerged in the community and has been spreading in health care settings [11-13]. However, there have only been a few reports on hospital-acquired MRSA bacteremia (MRSAB) caused by ST72-SCCmecIV [14-16].

We thus evaluated the clinical and microbiological characteristics and outcomes of Korean patients with MRSAB caused by ST72-SCCmecIV and compared them with those caused by ST5-SCCmecII, a representative HA-MRSA genomic strain in Korea.

METHODS

Study Design and Patients

This prospective cohort study was conducted at the Asan Medical Center (Seoul, Republic of Korea) from July 2008 through December 2018. This 2700-bed institution is a university-affiliated teaching hospital that provides both primary and tertiary care. All adult patients with S. aureus bacteremia (SAB) were prospectively enrolled and observed for 90 days. SAB cases were reviewed by infectious disease (ID) experts within 2 or 3 days after the identification of S. aureus on blood culture tests. ID experts recommended the following routine as protocol. Follow-up blood cultures were performed every 2 to 3 days until the patient tested negative. Echocardiography and fundoscopic examination were recommended to detect cardiac vegetation and endophthalmitis, respectively. It was also recommended that vancomycin trough concentrations be monitored and maintained at 15–20 mg/L in patients with SAB. Patients were excluded from the analysis if they had polymicrobial bacteremia, had been discharged before obtaining positive blood culture results, or had SAB within the previous 3 months. Demographic characteristics, underlying diseases or conditions and their severity, severity of bacteremia, place of infection, initial source of SAB, presence of a central venous catheter (CVC) or other prosthetic devices, patient management, and clinical outcomes were recorded. The Charlson Comorbidity Index (CCI) was used to measure the composite score of severity of preexisting comorbidities [17]. A positive culture from a patient who had been hospitalized for ≥48 hours was defined as hospital-acquired bloodstream infection [18]. Within this SAB cohort, hospital-acquired MRSAB cases caused by ST72-SCCmecIV and ST5-SCCmecII strains were selected and analyzed.

Patient Consent

The protocol of this study was approved by the Institutional Review Board of Asan Medical Center (IRB No. 2013-0234), which waived the requirement for written or verbal consent from the patients based on the observational nature of the study.

Laboratory and Microbiological Data

All S. aureus isolates were identified using the standard methods. The first blood isolate obtained from the patient was used for microbiological and molecular assessments. The minimum inhibitory concentration (MIC) of vancomycin was determined using the broth microdilution method. All isolates underwent vancomycin susceptibility testing according to the Clinical and Laboratory Standards Institute (CLSI) guidelines with the inclusion of 1.5-mg/L dilution [19-21]. Antimicrobial susceptibilities were determined using the MicroScan system (Dade Behring, West Sacramento, CA, USA) and the standard criteria of the CSLI. Polymerase chain reaction of the mecA gene was performed to confirm methicillin resistance. δ-hemolysin activity was used to determine agr functionality as described previously [22]. PVL genes, the staphylococcal cassette chromosome mec (SCCmec) type, and the multilocus sequence type (MLST) were identified as previously described [23-27]. MLST allele names and STs were derived from the MLST database (http://www.mlst.net).

Data Collection and Information on Variables

Data on the following variables were obtained from all patients: age, sex, underlying diseases or conditions, recent surgery history, history of immunosuppressive therapy, presence or absence of medical devices, primary site of infection, metastatic infection, antibiogram results, patient management, and clinical outcome. The site of infection was determined based on clinical, radiological, and bacteriological investigations performed at the time of initial blood culture. Infective endocarditis was defined according to the modified Duke criteria [28]. We classified bacteremia without an identifiable site of infection as primary bacteremia. Metastatic infection was defined as the development of a new sterile site infection if it was neither clinically apparent at the time of initial blood culture nor detected in the initial diagnostic tests. Infection foci were evaluated for focus removal and categorized as eradicable and noneradicable foci. Eradicable foci were subdivided into eradicated and not eradicated; eradicable foci included surgically removable infections or drainable abscesses and indwelling foreign bodies such as intravenous catheters. Noneradicable foci included pneumonia, endocarditis, primary bacteremia, and osteomyelitis or arthritis. Prosthetic devices included orthopedic devices, cardiovascular electronic devices, prosthetic valves, and vascular grafts. Septic shock was defined as sepsis with persistent hypotension that requires vasopressors to maintain mean arterial pressure ≥65 mmHg and lactate level ≥2 mmol/L despite adequate fluid resuscitation [29]. Recurrent bacteremia was defined as SAB occurrence within 90 days of resolution of the first episode, whereas persistent bacteremia was defined as SAB lasting at least 7 days.

Statistical Analysis

Pearson’s χ-square test or the Fisher exact test was used to analyze the categorical variables, whereas the Student t test and Mann-Whitney U test were used to analyze normally and non–normally distributed continuous variables, respectively. Univariable and multivariable analyses using logistic regression models were performed to identify the independent risk factors for crude mortality. Age, sex, MRSA genotype, and variables with P < .05 in the univariable analysis were included in the multivariable logistic regression model. Odds ratios and their 95% CIs were calculated. All P values were 2-tailed, and P values <.05 were considered statistically significant. Data were analyzed using SPSS, version 21.0 (IBM Co., Armonk, NY, USA).

RESULTS

Study Population

We found 1782 SAB cases, comprising 924 (51.9%) MRSA and 628 (35.2%) hospital-acquired MRSA bacteremia. Of the 628 isolates, 431 (68.6%) were ST5-SCCmecIV and 152 (24.2%) were ST72-SCCmecII. Therefore, we analyzed 583 hospital-acquired MRSAB cases. Excluded 45 (7.2% of the total hospital-acquired MRSAB) isolates that belonged to the 14 MLST types other than ST72-SCCmecII or ST5-SCCmecIV (Supplementary Table 1).

Patient Characteristics

The clinical characteristics of 583 patients with hospital-acquired MRSAB caused by ST72-SCCmecIV and ST5-SCCmecII strains are summarized in Table 1. Patients with ST72-SCCmecIV were younger than those with ST5-SCCmecII (median age, 63 vs 65 years; P = .013) and had hematologic malignancy more frequently (13.8% [21/152] vs 4.6% [20/431]). There were no significant differences in the frequency of other underlying diseases and CCI between the 2 groups. Meanwhile, patients with ST72-SCCmecIV were less likely to have a history of recent surgery (27% [41/152] vs 39.9% [172/431]; P = .004), prior antibiotic treatment (within 1 month; 41.4% [63/152] vs 86.5% [373/431]; P < .001), nasal MRSA colonization (16.4% [25/152] vs 45.2% [195/431]; P < .001), and central venous catheter placement (17.7% [68/152] vs 73.5% [317/431]; P = .001). The ST72-SCCmecIV strain caused more frequent osteoarticular infections than ST5-SCCmecII (7.2% [11/152] vs 1.4% [6/431]; P = .001). Intravascular catheter–related infections were more common in the ST5-SCCmecII group (43.4% [66/152] vs 52.9% [228/431]; P = .044). There were no significant differences in the frequency of metastatic infections or vancomycin use as definitive antibiotic therapy between the 2 groups. In univariable and multivariable logistic regression analyses to identify clinical factors associated with infections with ST72-SCCmecIV, end-stage renal disease, prior antibiotic treatment, and agr dysfunction were significantly associated with ST72-SCCmecIV MRSAB (Supplementary Table 2). An association between the osteoarticular infection for primary infection foci and ST72-SCCmecIV MRSAB showed borderline significance (P = .052). Considering the rarity of hospital-onset bone and joint infections excluding postoperative infection, we further reviewed the cases of osteoarticular infections (Supplementary Table 3). Symptoms in all patients with osteoarticular infections, with exception of 3 patients for whom symptom onset could not be confirmed from the medical record, began before admission (median [range], 4 [1-20] days).

Table 1.

Clinical Characteristics of Adult Patients With Hospital-Acquired MRSAB (n = 583)

Characteristics	ST5 (n = 431)	ST72 (n = 152)	P
Age, median (IQR), y	65 (55–73)	63 (50–71)	.013
Male	285 (66.1)	87 (57.2)	.050
Underlying diseases
Solid cancer	199 (46.2)	65 (42.8)	.468
Hematologic malignancy	20 (4.6)	21 (13.8)	<.001
Diabetes mellitus	131 (30.4)	47 (30.9)	.904
Liver cirrhosis	64 (14.8)	26 (17.1)	.508
End-stage renal disease	33 (7.7)	14 (9.2)	.545
Chronic pulmonary diseasea	18 (4.2)	3 (1.3)	.096
Heart failure	22 (5.1)	8 (5.3)	.939
Hypertension	171 (39.7)	56 (36.8)	.538
Solid organ transplantation	40 (9.3)	10 (6.6)	.306
CCI, median (IQR)	3 (2–5)	2 (2–5)	.821
CCI >4	114 (26.5)	38 (25.0)	.726
Predisposing condition
Recent surgeryb	172 (39.9)	41 (27.0)	.004
Prior antibiotic treatment b	373 (86.5)	63 (41.4)	<.001
Nasal MRSA colonizationc	195 (45.2)	25 (16.4)	<.001
Immunosuppressive treatmentb	136 (31.6)	52 (34.2)	.547
Central venous catheter	317 (73.5)	68 (44.7)	<.001
Noncatheter prosthetic devicesd	58 (13.5)	22 (14.5)	.754
Septic shocke	62 (14.4)	22 (14.5)	.979
Primary site of infection
Intravascular catheter–related	228 (52.9)	66 (43.4)	.044
Pneumonia	47 (10.9)	13 (8.6)	.412
Surgical site infection	36 (8.4)	13 (8.6)	.939
Osteoarticular infection	6 (1.4)	11 (7.2)	<.001
Skin and soft tissue infection	12 (2.8)	5 (3.3)	.750
Infective endocarditis	4 (0.9)	4 (2.6)	.121
Other	45 (10.4)	12 (7.9)	.363
Unknown (primary bacteremia)	51 (11.8)	23 (15.1)	.294
Metastatic infection	55 (12.8)	21 (13.8)	.740
Source control			.003
Eradicated	255 (59.2)	72 (47.4)
Not eradicated	16 (3.7)	15 (9.9)
Noneradicable foci	160 (37.1)	65 (42.8)
Definitive antibiotic treatment
Vancomycin	352 (81.7)	122 (80.3)	.702
Teicoplanin	108 (25.1)	41 (27.0)	.642
Initial vancomycin trough level, median (IQR), mg/L	18.3 (10.0–23.3)	17.0 (10.2–22.4)	.100

Data are presented as No. (%), unless otherwise indicated.

Abbreviations: CCI, Charlson Comorbidity Index; IQR, interquartile range; MRSA, methicillin-resistant Staphylococcus aureus; MRSAB, hospital-acquired methicillin-resistant Staphylococcus aureus bacteremia.

aIncludes chronic pulmonary obstructive lung disease and bronchiectasis.

bWithin a month before MRSA bacteremia.

cPositive result of the nasal swab test performed within 48 hours after confirmation of positive blood culture.

dIncludes pacemaker/implantable cardioverter-defibrillator (8 patients), prosthetic heart valves (20 patients), orthopedic devices (21 patients), and vascular grafts (27 patients).

eSepsis with persistent hypotension that requires vasopressors to maintain mean arterial pressure ≥65 mmHg and lactate level ≥2 mmol/L despite adequate fluid resuscitation.

Microbiological Characteristics

The microbiological characteristics and antibiotic susceptibilities of MRSA strains are summarized in Table 2. Most of the ST5-SCCmecII isolates (96.1%) had agr dysfunction, whereas most of the ST72-SCCmecIV isolates (90.1%) possessed agr function. ST72-SCCmecIV isolates exhibited lower vancomycin MIC distribution and were less likely to be resistant to various classes of antibiotics, including clindamycin, ciprofloxacin, erythromycin, fusidic acid, gentamicin, and rifampicin, than ST5-SCCmecII isolates (Table 2).

Table 2.

Microbiologic Characteristics of 583 MRSA Isolates Causing Bloodstream Infections

Characteristic	ST5 (n = 431)	ST72 (n = 152)	P
agr dysfunction	414 (96.1)	15 (9.9)	<.001
Vancomycin MIC by BMD
≤1.0 mg/L	302 (70.1)	136 (89.5)	<.001
1.5 mg/L	117 (27.1)	15 (9.9)	<.001
≥2.0 mg/L	12 (2.8)	1 (0.7)	.127
Resistance to:
Clindamycin	422 (97.9)	33 (21.7)	<.001
Ciprofloxacin	427 (99.1)	13 (8.6)	<.001
Erythromycin	426 (98.8)	39 (25.7)	<.001
Fusidic acid	372 (86.3)	2 (1.3)	<.001
Gentamicin	339 (78.7)	14 (9.2)	<.001
Rifampin	41 (9.5)	2 (1.3)	.001
Trimethoprim/sulfamethoxazole	9 (2.1)	1 (0.7)	.243

Abbreviations: BMD, broth microdilution method; MIC, minimum inhibitory concentration; MRSA, methicillin-resistant Staphylococcus aureus.

Treatment Outcomes

Table 3 compares the treatment outcomes of patients with ST72-SCCmecIV vs ST5-SCCmecII isolates. Those with ST5-SCCmecII isolates were more likely to receive medical care in the intensive care unit (35.7% [154/431] vs 12.5% [19/152]; P < .001). However, there were no significant differences in terms of 30- and 90-day mortality or persistent (≥7 days) and recurrent bacteremia between the 2 groups. Univariable and multivariable logistic regression analyses were performed to identify independent risk factors for mortality (Table 4).

Table 3.

Clinical Outcomes of 583 Adult Patients With Hospital-Acquired MRSAB

Outcome	ST5 (n = 431)	ST72 (n = 152)	P
ICU	154 (35.7)	19 (12.5)	<.001
Mortality (within 30 d)	91 (21.1)	24 (15.8)	.156
Mortality (within 90 d)	147 (34.1)	41 (27.0)	.106
Persistent bacteremia ≥7 d	75/429 (17.5)	18/145 (12.4)	.152
Recurrent bacteremia within 90 d	20 (4.6)	4 (2.6)	.284

Abbreviations: ICU, intensive care unit; MRSAB, hospital-acquired methicillin-resistant Staphylococcus aureus bacteremia.

Table 4.

Univariable and Multivariable Analysis of Risk Factors Associated With 30-Day Mortality in 583 Adult Patients With Hospital-Acquired MRSAB

Risk Factor	Univariable Analysis		Multivariable Analysisa
	OR (95% CI)	P	OR (95% CI)	P
Age ≥65 y	1.04 (0.69–1.57)	.836	1.35 (0.86–2.13)	.197
Male	0.94 (0.62–1.43)	.765	0.86 (0.55–1.35)	.523
Underlying solid cancer	1.35 (0.90–2.03)	.148
Hematologic malignancy	1.34 (0.64–2.83)	.438
Diabetes mellitus	0.81 (0.51–1.27)	.353
Liver cirrhosis	1.60 (0.96–2.70)	.074
End-stage renal disease	0.69 (0.30–1.59)	.388
Chronic pulmonary diseaseb	1.37 (0.49–3.86)	.548
Heart failure	1.02 (0.41–2.55)	.969
Hypertension	0.49 (0.31–0.77)	.002	0.40 (0.24–0.66)	<.001
Solid organ transplantation	0.64 (0.28–1.46)	.291
CCI >4	2.63 (1.71–4.04)	<.001	2.80 (1.79–4.40)	<.001
Intravascular catheter–related	0.84 (0.56–1.27)	.406
Pneumonia	3.44 (1.96–6.02)	<.001	3.64 (1.84–7.20)	<.001
Surgical site infection	0.44 (0.17–1.13)	.088
Osteoarticular infection	0.25 (0.03–1.89)	.178
Skin and soft tissue infection	0.25 (0.03–1.89)	.178
Infective endocarditis	1.36 (0.27–6.84)	.707
Unknown (primary bacteremia)	0.94 (0.51–1.75)	.852
Metastatic infection	1.43 (0.81–2.51)	.217
Source control
Eradicated	1	NA	1	NA
Not eradicated	2.12 (0.92–4.85)	.077	2.43 (1.02–5.82)	.046
Noneradicable foci	1.59 (1.04–2.44)	.032	1.10 (0.66–1.86)	.692
MRSA genotype
ST5-SCCmec II	1	NA	1	NA
ST72-SCCmec IV	0.70 (0.43–1.15)	.158	0.65 (0.39–1.10)	.116
agr dysfunction	1.56 (0.94–2.56)	.083
Vancomycin MIC by BMD
≤1.0 mg/L	1	NA
1.5 mg/L	0.93 (0.57–1.52)	.771
≥2.0 mg/L	0.72 (0.16–3.22)	.677

Abbreviations: BMD, broth microdilution; CCI, Charlson Comorbidity Index; MIC, minimal inhibitory concentration; MRSA, methicillin-resistant Staphylococcus aureus; MRSAB, hospital-acquired methicillin-resistant Staphylococcus aureus bacteremia; NA, not applicable; OR, odds ratio; SCC, staphylococcal cassette chromosome; ST, sequence type.

aMultivariable analysis included age, sex, MRSA genotype, and variables showing significant differences (P < 0.05) in the univariable analysis.

bIncludes chronic pulmonary obstructive lung disease and bronchiectasis.

In univariable analyses, high CCI (>4), pneumonia as the site of infection, and noneradicated foci were significantly associated with 30-day mortality, whereas underlying hypertension was negatively correlated with 30-day mortality. Vancomycin MICs were not associated with 30-day mortality. In addition, the ST72-SCCmecIV strain had no significant effect on mortality.

In multivariable analyses, after controlling for several confounders and including other significant variables, there was no significant difference in 30-day mortality between the ST72-SCCmecIV and ST5-SCCmecII groups. CCI >4 (adjusted odds ratio [aOR], 2.80; 95% CI, 1.79–4.40), pneumonia as the site of infection (aOR, 3.64; 95% CI, 1.84–7.20), noneradicated foci (aOR, 2.43; 95% CI, 1.02–5.82), and underlying hypertension (aOR, 0.40; 95% CI, 0.24–0.66) were independently associated with 30-day mortality. After stratification by strain type, hypertension (aOR, 0.38; 95% CI, 0.21–0.37), CCI >4 (aOR, 2.11; 95% CI, 1.26–3.52), pneumonia (aOR, 3.46; 95% CI, 1.60–7.47), and noneradicated foci (aOR, 3.21; 95% CI, 1.06–9.69) were independently associated with 30-day mortality in the ST5-SCCmecII group. In the ST72-SCCmecIV group, CCI >4 (aOR, 6.95; 95% CI, 2.22–21.76) and pneumonia (aOR, 5.75; 95% CI, 1.18–28.01) showed significance (Supplementary Table 4). There were no significant differences in 30-day mortality in the ST72-SCCmecIV group compared with hospital-associated MRSA strains including ST5-SCCmecII and others (Supplementary Table 5). We performed a sensitivity analysis after excluding patients with osteoarticular infections, but mortality was not associated with any specific sequence type (Supplementary Table 6).

DISCUSSION

In this study, we evaluated the clinical characteristics and outcomes of patients with hospital-acquired MRSAB caused by ST72-SCCmecIV, a representative PVL-negative CA-MRSA strain in Korea, by comparing with the clinical characteristics and outcomes of patients with ST5-SCCmecII, a representative HA-MRSA strain in Korea. Osteoarticular infections were more frequently observed in ST72-SCCmecIV MRSAB, and ST72-SCCmecIV isolates were more likely to have vancomycin MICs ≤1.0 mg/L than ST5-SCCmecII. Mortality and recurrence rates were not significantly different between the 2 groups.

Osteoarticular infections were more prevalent in ST72-SCCmecIV MRSAB in our study cohort. According to Lee et al., who analyzed CA-MRSA bacteremia cases and compared them with CA-MSSA, bone and joint infections were independent risk factors for CA-MRSA caused by ST72-SCCmecIV [30]. In another study on MRSAB, ST72-SCCmecIV isolates caused osteoarticular infection more frequently than ST5-SCCmecII [13]. Therefore, ST72-SCCmecIV is suggested to play a role in the predominance of osteoarticular infections in patients with CA-MRSA bacteremia. However, the association between osteoarticular infections and ST72-SCCmecIV observed in our study should be interpreted cautiously. Although the prevalence of osteoarticular infection was higher in the ST72-SCCmecIV MRSAB group than in the ST5-SCCmecII MRSAB group, the proportion was low (7%) relative to other infection sources. Given that most osteoarticluar infection cases in the ST72 group had symptoms before admission, they may have been misclassified as having hospital-acquired infection.

Furthermore, we found that ST72-SCCmecIV isolates were more likely to have vancomycin MICs ≤1.0 mg/L than ST5-SCCmecII isolates. MIC values of CA-MRSA clones are usually lower than those of HA-MRSA clones [31]. Because only hospital infections were analyzed, this study was consistent with previous studies. Several studies have shown that a high vancomycin MIC is associated with worse clinical outcomes [32-34]. In our study, however, increased vancomycin MICs were not associated with mortality.

Whether there are differences in mortality associated with infections caused by CA-MRSA and HA-MRSA strains remains controversial [2, 35–38]. Previous studies have found that the mortality rate associated with infections caused by ST72-SCCmecIV was similar to or lower than that of infections caused by ST5-SCCmecII or other comparative HA-MRSA strains [13, 16]. In this study, we controlled the potential confounding factors and included only hospital-acquired SAB for a more accurate comparison. As a result, mortality was not significantly different between the 2 groups. Although ST72-SCCmecIV may be more virulent in theory, the real-world outcome is complex. The exact reasons have not been elucidated; however, we attribute this to 3 factors. First, a previous study revealed that strain-specific virulence factors such as staphylococcal superantigen genes, including sel, sec, and tst, which are less commonly found in ST72-SCCmecIV isolates, might contribute to higher mortality in ST5-SCCmecII infections [13]. Second, because vancomycin MICs in the ST5-SCCmecII group were higher, its bactericidal activity is reduced. Lastly, the percentage of patients with recent surgery or CVC presence was higher in the ST5-SCCmecII group than in the ST72-SCCmecIV group, suggesting that ST72-SCCmecIV can invade the host bloodstream without those portals of entry. However, given the readily removable nature of vascular catheters such as central-line catheters, the higher rate of indwelling CVC may be conversely responsible for the lower mortality. Overall, the ST72-SCCmecIV strain might be more virulent itself, as it caused bacteremia in the absence of these prerequisites. Given this, mortality may be more related to the patient’s comorbidities and site of acquisition rather than the strain itself.

Our study had some limitations. First, patients included those only from a single hospital; therefore, our findings may not be entirely representative of CA-MRSA strains in Korea. Second, because our comparative analysis only included hospital-acquired infections and excluded community-acquired infections, our findings cannot be generalized to all ST72-SCCmecIV strains. Third, we did not perform high-resolution methods such as whole-genome sequencing, which could provide information on resistance and virulence as well as genotype [39]. Therefore, further studies with whole-genome sequencing analysis are needed. Lastly, distinguishing infection foci and metastatic infection could be challenging, as we did not routinely perform tests that are highly sensitive to detect early infections such as positron emission tomography scans.

In conclusion, osteoarticular infection was more frequently observed in hospital-acquired MRSAB caused by ST72-SCCmecIV than in hospital-acquired MRSAB caused by ST5-SCCmecII. The ST72-SCCmecIV strain was not associated with worse clinical outcomes, including 30-day mortality, 90-day mortality, persistent bacteremia, and recurrence, when compared with ST5-SCCmecII.

Supplementary Data

Supplementary materials are available at Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.

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