Changes in Antimicrobial Resistance of Staphylococci Isolated from Bloodstream Infection and the Impact of COVID-19

doi:10.21203/rs.3.rs-8396245/v1

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Research Article

Changes in Antimicrobial Resistance of Staphylococci Isolated from Bloodstream Infection and the Impact of COVID-19

https://doi.org/10.21203/rs.3.rs-8396245/v1

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Objective

To analyze the changes in antimicrobial resistance of Staphylococcus aureus (S. aureus) and coagulase-negative staphylococci (CoNS) in bloodstream infections (BSIs) bloodstream infections (BSIs) between 2018 and 2024, and to assess the impact of the COVID-19 pandemic on these trends.

Methods

A total of 575 S. aureus and 1,014 CoNS isolates were retrospectively reviewed. Demographic characteristics and resistance rates to 16 antimicrobial agents were compared. Statistical analyses included the chi-square (χ²) test and Mann-Kendall trend analysis.

Results

CoNS infections were more common in minors and the elderly, while S. aureus predominated in young and middle-aged adults. CoNS exhibited higher resistance rates to most antimicrobials compared to S. aureus, with Methicillin-Resistant CoNS (MRCNS) detection rates exceeding 70%. An increasing trend in resistance was observed for penicillin G in S. aureus and for fluoroquinolones in CoNS. Following the COVID-19 pandemic, resistance rates to several agents—such as penicillin G, clindamycin, and ciprofloxacin—further increased in both groups. No resistance to linezolid, vancomycin, or tigecycline was detected.

Conclusion

The resistance profile of staphylococci in bloodstream infections has intensified, with the COVID-19 pandemic contributing to increased resistance rates for certain antimicrobials. Continuous surveillance is essential to guide appropriate antimicrobial therapy.

Bloodstream infection

Staphylococcus aureus

Coagulase-negative staphylococci

Antimicrobial resistance

COVID-19

Trend analysis

Bloodstream infections (BSIs) are common and severe infectious diseases in clinical practice [1, 2]. Staphylococci are frequent pathogens in both healthcare-associated and community-acquired infections. Among them, Staphylococcus aureus (S. aureus) and Coagulase-Negative Staphylococci (CoNS) are the two most commonly isolated species in clinical settings and represent major causative agents of BSIs [3]. With the widespread use of antimicrobial agents, drug resistance in staphylococci has become an increasingly serious problem. The emergence of methicillin-resistant strains, specifically Methicillin-Resistant S. aureus (MRSA) and Methicillin-Resistant CoNS (MRCNS), has significantly increased treatment difficulties and poses a major challenge to clinical management [4, 5]. This study aims to analyze the resistance data of S. aureus and CoNS isolates from BSIs to 16 commonly used antimicrobial agents between 2018 and 2024. The objective is to elucidate the temporal trends in antimicrobial resistance of these two staphylococcal groups and to assess the impact of the COVID-19 pandemic on their resistance profiles.

1. Study Subjects

Clinical isolates were collected from a tertiary hospital in the Northwest Sichuan Regional Medical Center between January 2018 and December 2024. The isolates included S. aureus and CoNS obtained from positive blood cultures. After excluding repeated isolates from the same patient, a total of 575 S. aureus and 1,014 CoNS isolates were included in the study. The study to analyse routinely collected data was approved by the Ethics Committee Office of Mianyang Central Hospital, Mianyang City, Sichuan Province, China (Approval No. 2S202403146-01). The study adhered to the principles of the Helsinki Declaration. Since the data analyzed were anonymized and routinely collected, the Ethics Committee of Mianyang Central Hospital waived the requirement for informed consent. The detailed study flow is presented in Fig. 1.

2. Methods

2.1 Bacterial Culture

Blood cultures were performed using the Bact/Alert 3D system (BioMérieux, Marcy l Etoile, France) and the BacT/ALERT® TIRTUO™ automated microbial culture system (BioMérieux, Marcy l Etoile, France). When a positive signal was detected, the positive bottles were unloaded, and the broth was aseptically aspirated and inoculated onto both blood agar and chocolate agar plates. The plates were then incubated at 35 ℃ in a CO₂ incubator for 18 to 24 hours.

2.2 Bacterial Identification and Antimicrobial Susceptibility Testing

Colonies from the subcultured plates were selected for identification and antimicrobial susceptibility testing. Bacterial identification and antibiotic susceptibility profiles were determined using the VITEK 2 Compact automated system (BioMérieux, Marcy l Etoile, France) with appropriate identification and susceptibility cards. Alternatively, bacterial identification was also performed using the VITEK® MS MALDI-TOF mass spectrometry system (BioMérieux, Marcy l'Etoile, France), which was introduced into the laboratory in 2019.

2.3 Interpretation Criteria

Antimicrobial susceptibility testing results were interpreted and reported in accordance with the standards recommended by the CLSI guidelines of the respective year.

2.4 Statistical Analysis

Analysis of annual resistance rates was performed using WHONET 5.6 software. Comparative data analysis was conducted with SPSS 26.0 (SPSS Inc., Chicago, USA). The overall resistance rates between S. aureus and CoNS were compared using the chi-square (χ²) test. Similarly, the χ² test was applied to analyze changes in resistance rates across the pre-pandemic, pandemic, and post-pandemic periods. In addition, the non-parametric Mann-Kendall trend test was employed to assess the annual trend in resistance rates for each antimicrobial agent from 2018 to 2024. A P-value < 0.05 was considered statistically significant.

1. Patient Baseline Characteristics

As shown in Table 1, this study included 575 patients with S. aureus infections and 1,014 patients with CoNS infections. The two groups exhibited distinct demographic profiles in terms of sex and age distribution. No statistically significant difference was observed in sex distribution between the two groups (χ² = 1.430, p = 0.232). In the S. aureus group, males accounted for 61.7% and females for 38.3%, while in the CoNS group, 58.7% were male and 41.3% were female, indicating a similar sex composition. In contrast, a significant difference was found in age distribution (χ² = 120.679, p < 0.001). S. aureus infections were predominantly identified in young and middle-aged adults aged 18–65 years (51.8%), followed by older adults aged 66–79 years (28.2%). In comparison, CoNS infections were more common in minors aged 0–17 years (31.3%) and individuals aged ≥ 80 years (13.7%). This distribution pattern suggests that CoNS infections contribute to a relatively higher burden among pediatric and very elderly populations, whereas S. aureus infections are more frequently observed among young and middle-aged adult patients. Age may be an important factor influencing the epidemiological characteristics of these two types of staphylococcal infections.

Table 1

Gender and age distribution of the included patients.
Characteristics	S. Aureus (N = 575)	CoNS (N = 1,014)	χ²	P
Gender,N(%)			1.430	0.232
Male	355(61.7%)	595(58.7%)
Female	220(38.3%)	419(41.3%)
Age distribution, N(%)			120.679	< 0.001**
0–17 years	80(13.9%)	317(31.3%)
18–65 years	298(51.8%)	284(28.0%)
66–79 years	162(28.2%)	274(27.0%)
≥ 80 years	35(6.1%)	139(13.7%)
Comparison between S. aureus and CoNS. P-value ≤ 0.05 was statistically significant. ** for p < 0.01.

2. Strains changes by year

As shown in Fig. 2, from 2018 to 2024, the detection of pathogens causing bloodstream infections showed dynamic changes. The number of S. aureus isolates peaked during the COVID-19 pandemic (2020–2022) and subsequently declined. The detection trend of MRSA was similar. However, notably, its proportion among S. aureus isolates has remained consistently high since 2023. The number of CoNS isolates gradually increased from 2020, reaching a peak in 2023 (202 isolates), with a slight decrease in 2024. Overall, from 2018 to 2024, the detection of CoNS showed a linear upward trend. Furthermore, the proportion of MRCNS among total CoNS remained at a very high level throughout the study period (generally > 70%), indicating that methicillin-resistant strains have long dominated among CoNS, with their epidemiological pattern remaining stable.

3. Comparison of the overall drug resistance between and CoNS

3. Comparison of the overall drug resistance between S. aureus and CoNS

According to the data presented in Table 2, a comparative analysis of drug resistance rates was conducted between 575 isolates of S. aureus and 1,014 isolates of CoNS from 2018 to 2024. Significant differences in resistance to various antimicrobial agents were observed between the two groups. CoNS exhibited markedly higher resistance rates than S. aureus to the following agents: Oxacillin (75.2% vs. 30.5%), rifampicin (6.9% vs. 0.4%), fluoroquinolones—ciprofloxacin (42.8% vs. 17.5%), levofloxacin (46.5% vs. 17.4%), Cotrimoxazole (57.0% vs. 10.8%), and erythromycin (82.2% vs. 56.1%). No resistant strains were detected for linezolid, vancomycin, or tigecycline against either bacterial group, demonstrating excellent antibacterial activity. Nitrofurantoin and quinupristin/dalfopristin showed no resistance in S. aureus, while only minimal resistance was observed in CoNS (0.5%). Overall, CoNS exhibited higher resistance rates to the majority of tested antimicrobial agents compared to S. aureus, with particularly pronounced differences observed for fluoroquinolones, macrolides, and folate pathway inhibitors.

Table 2

Resistance percentages of different antibiotics between 2018and 2024 among *S. aureus* and CoNS isolates.
Antimicrobial Agent	S. Aureus (N = 575)		CoNS (N = 1,014)		χ²	P
Antimicrobial Agent	Numbers	Rates, %	Numbers	Rates, %	χ²	P
Penicillin G	532	92.5%	978	96.4%	1.451	0.228
Oxacillin	175	30.5%	763	75.2%	40.092	< 0.01**
Gentamicin	21	3.7%	101	10.0%	3.110	0.078
Rifampicin	2	0.4%	70	6.9%	6.007	0.014*
Ciprofloxacin	101	17.5%	434	42.8%	15.197	< 0.01**
Levofloxacin	100	17.4%	472	46.5%	19.474	< 0.01**
Moxifloxacin	91	15.8%	272	26.8%	3.609	0.057
Cotrimoxazole	62	10.8%	578	57.0%	47.627	< 0.01**
Clindamycin	169	29.4%	323	31.9%	0.147	0.701
Erythromycin	322	56.1%	834	82.2%	15.966	< 0.01**
Nitrofurantoin	0	0%	5	0.5%	0.522	0.470
Linezolid	0	0%	0	0%	/	/
Vancomycin	0	0%	0	0%	/	/
Quinupristin/dalfopristin	0	0%	5	0.5%	0.522	0.470
Tetracycline	110	19.1%	201	19.8%	0.016	0.901
Tigecycline	0	0%	0	0%	/	/
Chi-square test was conducted between the resistance rates for the S. aureus and CoNS isolates. P-value ≤ 0.05 was statistically significant. * for p < 0.05. ** for p < 0.01.

4. Annual drug resistance trends

This study also employed the Mann-Kendall trend test to examine the annual trends in drug resistance for S. aureus and CoNS.

As shown in Table 3, the resistance rates of S. aureus to 16 antimicrobial agents exhibited varying degrees of change between 2018 and 2024. Notably, the resistance rate to penicillin (Penicillin-G) increased from 87.1% in 2018 to 100% in 2024. The Mann-Kendall trend test confirmed a statistically significant upward trend (Z = 1.652, p < 0.05). The resistance rate to oxacillin showed an overall increase amid fluctuations, rising from 8.6% to 39.1%, although this trend did not reach statistical significance. Resistance rates to clindamycin and erythromycin also displayed considerable inter-annual variation without a clear, statistically significant overall trend. It is important to note that resistance rates for several other agents, including gentamicin, rifampicin, ciprofloxacin, levofloxacin, moxifloxacin, cotrimoxazole, and tetracycline, fluctuated across the study years but did not demonstrate a statistically significant upward or downward trend. Furthermore, no resistant strains were detected throughout the entire study period for nitrofurantoin, linezolid, vancomycin, quinupristin/dalfopristin, or tigecycline, resulting in sustained resistance rates of 0%.

Table 3

Changing resistance rates of *S. aureus* to 16 antimicrobial agents, 2018 to 2024.
Antimicrobial agent	2018 N = 79	2019 N = 58	2020 N = 107	2021 N = 117	2022 N = 122	2023 N = 45	2024 N = 47	Z	P
Penicillin G	87.1	86.4	94.2	93.1	91.6	100	100	1.652	< 0.05*
Oxacillin	8.6	20.3	44.2	41.6	27.7	36.4	39.1	0.901	NS^#
Gentamicin	5.4	10.2	5.8	0	5.9	0	6.5	0	NS^#
Rifampicin	0	5.1	3.8	0	1.7	0	0	-0.901	NS^#
Ciprofloxacin	17.2	27.1	7.7	24.8	23.5	11.4	17.4	-0.300	NS^#
Levofloxacin	17.2	27.1	7.7	24.8	23.5	9.1	17.4	-0.300	NS^#
Moxifloxacin	17.2	25.4	7.7	24.8	20.2	4.5	10.9	-0.901	NS^#
Cotrimoxazole	11.0	13.8	14.4	16.8	13.4	4.5	8.7	-0.601	NS^#
Clindamycin	15.1	23.7	42.3	51.5	16.0	22.7	34.8	0.601	NS^#
Erythromycin	41.9	50.8	67.3	71.3	52.9	59.1	52.2	0.601	NS^#
Nitrofurantoin	0	0	0	0	0	0	0	0	NS^#
Linezolid	0	0	0	0	0	0	0	0	NS^#
Vancomycin	0	0	0	0	0	0	0	0	NS^#
Quinupristin/dalfopristin	0	0	0	0	0	0	0	0	NS^#
Tetracycline	19.4	30.5	14.4	24.8	25.2	15.9	23.9	0	NS^#
Tigecycline	0	0	0	0	0	0	0	0	NS^#
Manner-Kendall test was conducted to show linear trends for16 antimicrobial agents of S. aureus from 2018 to 2024. Data are presented as % unless otherwise specified. P-value ≤ 0.05 was statistically significant. * for p < 0.05. ^# NS, not significant.

As presented in Table 4, the resistance rates of CoNS to 16 antimicrobial agents exhibited distinct trends from 2018 to 2024. A statistically significant increasing trend was observed for the following agents: ciprofloxacin (rising from 33.3% to 46.7%; Z = 1.952, p < 0.05), levofloxacin (from 39.8% to 48.7%; Z = 1.802, p < 0.05), and quinupristin/dalfopristin (from 0% to 0.7%; Z = 2.103, p < 0.05). In contrast, a statistically significant decreasing trend was noted for gentamicin (declining from 17.1% to 8.7%; Z = -1.652, p < 0.05). It is noteworthy that the resistance rates for penicillin G and oxacillin remained consistently high (Penicillin G > 95%, Oxacillin > 69%) throughout the study period, though their trends were not statistically significant. Similarly, the resistance rate to erythromycin persisted at a high level (ranging from 77.8% to 84.3%). No resistant strains were detected for linezolid, vancomycin, or tigecycline during the entire study, demonstrating their sustained and favorable antibacterial activity. In summary, CoNS exhibited a significant rise in resistance to fluoroquinolones, while a decline was observed for gentamicin. For the majority of the remaining antimicrobials, the changes in resistance rates were not statistically significant.

Table 4

Changing resistance rates of CoNS to 16 antimicrobial agents, 2018 to 2024.
Antimicrobial agent	2018 (N = 101)	2019 (N = 71)	2020 (N = 142)	2021 (N = 174)	2022 (N = 171)	2023 (N = 202)	2024 (N = 153)	Z	P
Penicillin G	95.9	95.1	95.7	97.4	95.6	97.0	98.0	1.202	NS^#
Oxacillin	70.7	69.9	77.8	77.3	76.4	74.0	76.7	0.300	NS^#
Gentamicin	17.1	8.7	12.4	10.3	8.9	7.1	8.7	-1.652	< 0.05*
Rifampicin	8.9	7.6	9.7	9.0	3.6	7.6	3.3	-1.352	NS^#
Ciprofloxacin	33.3	37.5	45.4	42.1	41.8	46.7	46.7	1.952	< 0.05*
Levofloxacin	39.8	39.7	47.6	44.6	47.1	50.3	48.7	1.802	< 0.05*
Moxifloxacin	22.0	25.0	30.8	20.2	26.7	30.5	29.3	0.901	NS^#
Cotrimoxazole	59.3	58.0	60.5	56.2	54.7	58.9	52.0	-1.502	NS^#
Clindamycin	31.1	31.5	31.9	32.2	21.8	41.1	32.0	1.201	NS^#
Erythromycin	82.9	78.8	84.3	84.1	77.8	82.2	84.0	0	NS^#
Nitrofurantoin	0	0	0	0.4	1.3	1.0	0	0.901	NS^#
Linezolid	0	0	0	0	0	0	0	0	NS^#
Vancomycin	0	0	0	0	0	0	0	0	NS*
Quinupristin/dalfopristin	0	0	0	0.4	0.4	1.0	0.7	2.103	< 0.05*
Tetracycline	18.7	26.1	18.9	16.3	22.7	18.3	20.7	0	NS^#
Tigecycline	0	0	0	0	0	0	0	0	NS^#
Manner-Kendall test was conducted to show linear trends for16 antimicrobial agents of CoNS from 2018 to 2024. Data are presented as % unless otherwise specified. P-value ≤ 0.05 was statistically significant. * for p < 0.05. ^# NS, not significant.

5. Drug resistance changes before, during and after the COVID-19 pandemic

As illustrated in Table 5, this study analyzed changes in the resistance of S. aureus across three periods: pre-pandemic (2018–2019), during the pandemic (2020–2022), and post-pandemic (2023–2024). The results revealed significant changes in resistance rates for multiple antimicrobial agents over these phases. Notably, the resistance rate to penicillin G increased from 86.9% in the pre-pandemic period to 92.7% during the pandemic, reaching 100% in the post-pandemic phase, with a highly statistically significant difference (P = 0.000). Similarly, resistance to oxacillin showed a significant rise from 13.9% to 37.0% and subsequently to 37.4% (P = 0.000). Resistance rates for clindamycin and erythromycin also increased significantly, from 19.0% and 46.0% to 36.1% and 63.6%, respectively, and remained elevated thereafter (P = 0.001 and P = 0.002, respectively). In contrast, the resistance rate to moxifloxacin demonstrated a statistically significant decline to 7.6% in the post-pandemic period (P = 0.012). For other agents, including gentamicin, rifampicin, ciprofloxacin, levofloxacin, cotrimoxazole, and tetracycline, resistance rates fluctuated across the periods without exhibiting a statistically significant trend. In summary, the COVID-19 pandemic was associated with a significant increase in resistance rates of S. aureus to several antimicrobials, such as penicillin G, oxacillin, clindamycin, and erythromycin. This suggests that the pandemic may have influenced the epidemiological landscape of antimicrobial resistance.

Table 5

Changes in resistance of *S. aureus* before, during, and after the COVID-19 pandemic.
Antimicrobial agent	2018–2019 (N = 137)		2020–2022 (N = 346)		2023–2024 (N = 92)		χ²	P
Antimicrobial agent	Numbers	Rates, %	Numbers	Rates, %	Numbers	Rates, %	χ²	P
Penicillin G	119	86.9%	322	92.7%	92	100.0%	19.690	0.000**
Oxacillin	19	13.9%	130	37.6%	34	37.4%	29.818	0.000**
Gentamicin	10	7.3%	13	3.8%	3	3.3%	2.949	0.229
Rifampicin	3	2.2%	6	1.7%	0	0.0%	3.273	0.195
Ciprofloxacin	30	21.9%	65	18.8%	13	14.3%	2.238	0.327
Levofloxacin	30	21.9%	65	18.8%	12	13.1%	2.999	0.223
Moxifloxacin	29	21.2%	62	17.9%	7	7.6%	8.827	0.012*
Cotrimoxazole	17	12.4%	51	14.7%	6	6.5%	5.003	0.082
Clindamycin	26	19.0%	125	36.1%	26	28.5%	14.592	0.001**
Erythromycin	63	46.0%	220	63.6%	51	55.0%	12.727	0.002*
Nitrofurantoin	0	0.0%	0	0.0%	0	0.0%	/	/
Linezolid	0	0.0%	0	0.0%	0	0.0%	/	/
Vancomycin	0	0.0%	0	0.0%	0	0.0%	/	/
Quinupristin/dalfopristin	0	0.0%	0	0.0%	0	0.0%	/	/
Tetracycline	33	24.1%	75	21.7%	18	19.7%	0.686	0.710
Tigecycline	0	0.0%	0	0.0%	0	0.0%	/	/
The resistance rates of S. aureus were compared across the pre- (2018–2019), peri- (2020–2022), and post- (2023–2024)COVID-19 periods using a χ2 test. P-value ≤ 0.05 was statistically significant. P ≤ 0.05, *P ≤ 0.01.

As shown in Table 6, this study analyzed the changes in antimicrobial resistance of CoNS across three periods: pre-pandemic (2018–2019), during the pandemic (2020–2022), and post-pandemic (2023–2024). The results indicate that for the majority of tested antimicrobial agents, no statistically significant differences in resistance rates were observed among the three periods. However, two notable exceptions were identified. The resistance rate to ciprofloxacin increased from 35.5% in the pre-pandemic period to 42.7% during the pandemic and further rose to 46.5% in the post-pandemic period, a trend that was statistically significant (P = 0.049). Additionally, the resistance rate to clindamycin showed a significant increase to 37.2% in the post-pandemic period, compared to 30.8% and 28.3% in the pre-pandemic and pandemic periods, respectively (P = 0.025). Resistance rates to other agents exhibited some degree of fluctuation but did not reach statistical significance. In summary, the COVID-19 pandemic was associated with a significant increase in resistance rates of CoNS to ciprofloxacin and clindamycin. These findings highlight the importance of monitoring resistance trends for these antimicrobial agents in the context of a pandemic.

Table 6

Changes in resistance of CoNS before, during, and after the COVID-19 pandemic.
Antimicrobial agent	2018–2019 (N = 172)		2020–2022 (N = 487)		2023–2024 (N = 355)		χ²	P
Antimicrobial agent	Numbers	Rates, %	Numbers	Rates, %	Numbers	Rates, %	χ²	P
Penicillin G	165	95.9%	468	96.1%	346	97.5%	1.454	0.483
Oxacillin	121	70.3%	376	77.2%	266	74.9%	3.170	0.205
Gentamicin	23	13.4%	51	10.5%	27	7.6%	4.549	0.103
Rifampicin	14	8.1%	36	7.4%	20	5.6%	1.512	0.470
Ciprofloxacin)	61	35.5%	208	42.7%	165	46.5%	6.046	0.049*
Levofloxacin	68	39.5%	227	46.6%	177	49.9%	4.995	0.082
Moxifloxacin	40	23.3%	125	25.7%	107	30.1%	3.426	0.180
Cotrimoxazole	101	58.7%	278	57.1%	199	56.1%	0.339	0.844
Clindamycin	53	30.8%	138	28.3%	132	37.2%	7.414	0.025*
Erythromycin	140	81.4%	399	81.9%	295	83.1%	0.296	0.862
Nitrofurantoin	0	0.0%	3	0.6%	2	0.6%	1.874	0.392
Linezolid	0	0.0%	0	0.0%	0	0.0%	/	/
Vancomycin	0	0.0%	0	0.0%	0	0.0%	/	/
Quinupristin/dalfopristin	0	0.0%	2	0.4%	3	0.8%	2.510	0.285
Tetracycline	38	22.1%	94	19.3%	69	19.4%	0.660	0.719
Tigecycline	0	0.0%	0	0.0%	0	0.0%	/	/
The resistance rates of CoNS were compared across the pre- (2018–2019), peri- (2020–2022), and post- (2023–2024)COVID-19 periods using a χ2 test. P-value ≤ 0.05 was statistically significant. *P ≤ 0.05.

This study systematically analyzed the clinical distribution and antimicrobial resistance trends of S. aureus and CoNS in bloodstream infections from 2018 to 2024. The findings reveal significant differences between the two groups in terms of population distribution, resistance profiles, and temporal dynamics, particularly regarding the evolving patterns observed before, during, and after the COVID-19 pandemic.

First, in terms of population distribution, this study indicates that S. aureus infections are more frequently observed among young and middle‑aged patients (18–65 years), whereas CoNS infections are proportionally higher in pediatric patients (0–17 years) and individuals aged ≥ 80 years. Previous research confirms that CoNS are the predominant pathogens in extreme age groups such as newborns, particularly among preterm and low‑birth‑weight infants.[6] Although prospective data specifically for patients aged ≥ 80 years are still evolving, recent multicenter retrospective studies focusing on Staphylococcus aureus bacteremia in the oldest old (≥ 85 years) and in frail nursing home residents (mean age > 80 years) have provided strong supportive evidence regarding its unique epidemiology, high mortality, and the critical impact of functional status beyond chronological age alone.[7, 8] That study reported a high burden of MRSA colonization or infection in patients aged ≥ 70 years in both ICU and non‑ICU settings, reinforcing the view that advanced age is an important risk factor for staphylococcal infections, especially those caused by resistant strains. These differences are likely associated with host immune status, underlying comorbidities, and healthcare exposures—such as invasive procedures (e.g., indwelling catheters) that are more common in elderly and pediatric populations, among whom CoNS are significant nosocomial pathogens [9]. Age therefore stands out as one of the factors distinguishing the epidemiological profiles of these two staphylococcal infections.

Second, one of the most prominent findings of this study is that CoNS isolated from bloodstream infections exhibited significantly higher overall resistance rates to most tested antimicrobial agents than S. aureus, particularly to fluoroquinolones, macrolides (erythromycin), and folate pathway inhibitors (cotrimoxazole). This may be attributed to the fact that, as commensals of the skin, CoNS have more opportunities to acquire and carry resistance genes. Moreover, in clinical practice, CoNS infections are often regarded as contamination or colonization, leading to delays in standardized susceptibility testing and targeted treatment, which may indirectly select for and retain resistant strains.[9–11] Fortunately, linezolid, vancomycin, and tigecycline remained 100% susceptible against both bacterial groups. Quinupristin/dalfopristin and nitrofurantoin also showed complete activity against S. aureus. These agents currently represent reliable last-line options for the treatment of multidrug-resistant staphylococcal infections, especially those caused by MRSA and MRCNS.

Annual trend analysis revealed a dynamically changing resistance landscape. S. aureus exhibited a significant and consistent upward trend in resistance to penicillin G, ultimately reaching 100%, which aligns with the highly prevalent production of penicillinase in this species [12, 13]. In contrast, resistance trends in CoNS were more complex. A significant increase in resistance to fluoroquinolones (e.g., ciprofloxacin, levofloxacin) was observed, likely driven by selective pressure from the extensive clinical use of these agents [14, 15]. Although historical data have shown that CoNS resistance to gentamicin was historically maintained above 20% and continued to rise [16–18], our study demonstrated a significant decreasing trend. This shift may be related to adjustments in clinical usage strategies for aminoglycosides or changes in the stability of associated resistance genes. It suggests that gentamicin may still be considered an alternative option in some cases for treating actual CoNS infections, but its use must be guided by susceptibility testing results. Particularly noteworthy is the emergence of low-level resistance to quinupristin/dalfopristin in CoNS, which increased from zero to a minimal rate. While the current incidence remains very low, this signals an early warning of developing resistance to reserve antimicrobial agents.

The COVID-19 pandemic undoubtedly served as a major disruptive event, significantly altering the epidemiology of bacterial resistance [19–22]. Our data demonstrate that during and after the pandemic period, S. aureus exhibited significant increases in resistance rates to penicillin G, oxacillin, clindamycin, and erythromycin. This trend may be attributed to the widespread empirical use of antibiotics, heightened cross‑transmission pressure due to the concentrated treatment of critically ill patients, and the potential weakening of routine infection control measures during the pandemic. For CoNS, the pandemic was similarly associated with a significant rise in resistance to ciprofloxacin and clindamycin. These strongly suggest that global public health crises can exert a profound impact on antimicrobial resistance, potentially accelerating the dissemination and dominance of certain resistant clones.

The annual distribution of bacterial isolates provides further evidence of the pandemic's impact. The isolation rates of S. aureus and MRSA from bloodstream infections peaked during 2020–2022 and subsequently declined. However, the proportion of MRSA among all S. aureus isolates remained persistently high from 2023 onward, indicating that the prevalence pressure of MRSA has not diminished despite the overall decrease in total detections. Concurrently, CoNS exhibited a linear upward trend in total isolate numbers, accompanied by consistently high proportions of MRCNS exceeding 70%. This underscores that CoNS constitute a substantial and highly resistant reservoir of pathogens in current clinical practice, with their associated disease burden and control challenges continuously escalating.

the antimicrobial resistance profile of staphylococci isolated from bloodstream infections remains serious, with the COVID-19 pandemic having accelerated the increase in resistance rates to certain agents. Therefore, individualized risk assessment and empirical antibiotic selection in clinical practice should be based on both the pathogen species and patient age characteristics. It is imperative to strengthen ongoing microbiological surveillance, remain vigilant regarding the escalating resistance of CoNS to fluoroquinolones, and implement rigorous antimicrobial stewardship—particularly in the post-pandemic era—to curb the further dissemination of resistant strains.

S. Aureus Staphylococcus aureus

CoNS coagulase-negative staphylococci

χ² chi-square test.

BSIs bloodstream infections

MRCNS Methicillin-Resistant CoNS

MRSA Methicillin-Resistant S. aureus

NS not significant

Acknowledgements

Not applicable.

Author contributions

Yan Wu collected and assembled the data and drafted the original manuscript. Mengjun Zhou was responsible for data analysis and revised the original manuscript. Both the authors endorsed the final manuscript.

Funding

This research received no external funding.

Data availability

The raw data supporting the findings of this study are available from Mianyang Central Hospital. But restrictions apply to the availability of these data, which were used under licence for the current study and so are not publicly available. The raw data are, however, available upon request and with the permission of Mianyang Central Hospital.

Ethics approval and consent to participate

The study to analyse routinely collected data was approved by the Ethics Committee Office of Mianyang Central Hospital, Mianyang City, Sichuan Province, China (Approval No. 2S202403146-01). The study adhered to the principles of the Helsinki Declaration. Since the data analyzed were anonymized and routinely collected, the Ethics Committee of Mianyang Central Hospital waived the requirement for informed consent.

Consent for publication

All authors have agreed to the submitted version of the manuscript.

Competing interests

The authors declare no competing interests.

Author details

¹ Department of Clinical Laboratory, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, China.

² Epidemiology and Health Statistics, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, China.

^*Corresponding author

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Changes in Antimicrobial Resistance of Staphylococci Isolated from Bloodstream Infection and the Impact of COVID-19

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Abstract

Objective

Methods

Results

Conclusion

Figures

Introduction

Subjects and Methods

1. Study Subjects

2. Methods

2.1 Bacterial Culture

2.2 Bacterial Identification and Antimicrobial Susceptibility Testing

2.3 Interpretation Criteria

2.4 Statistical Analysis

Results

1. Patient Baseline Characteristics

2. Strains changes by year

3. Comparison of the overall drug resistance between and CoNS

4. Annual drug resistance trends

5. Drug resistance changes before, during and after the COVID-19 pandemic

Discussion

Conclusion

Abbreviations

Declarations

References

Additional Declarations

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