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Article

Use of Daptomycin for the Treatment of Infective Endocarditis Due to Methicillin-Susceptible Staphylococcus aureus (MSSA): A Multicenter Retrospective Study

by
Andrea Tommasi
1,†,
Cesare Bolla
2,
Laura Curci
1,
Serena Penpa
3,
Giovanni Genga
1,
Cristina Sarda
2,
Elisabetta Svizzeretto
1,
Andrea Salvaderi
4,
Giorgia Piceni
3,
Giuseppe Vittorio De Socio
1,
Daniela Francisci
1,‡ on behalf of the LEIOT Study Group,
Antonio Maconi
3,
Guido Chichino
2 and
Carlo Pallotto
1,*,†
1
Infectious Diseases Clinic, Santa Maria della Misericordia Hospital, University of Perugia, 06100 Perugia, Italy
2
Infectious Diseases, Department of Internal Medicine, Azienda Ospedaliera-Universitaria SS. Antonio e Biagio e Cesare Arrigo, 15100 Alessandria, Italy
3
Research Training Innovation Infrastructure, Research and Innovation Department, Azienda Ospedaliera-Universitaria SS. Antonio e Biagio e Cesare Arrigo, 15100 Alessandria, Italy
4
Infectious Diseases Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
Membership of the Group Name is provided in the Acknowledgments.
Microbiol. Res. 2026, 17(2), 29; https://doi.org/10.3390/microbiolres17020029
Submission received: 15 November 2025 / Revised: 9 January 2026 / Accepted: 20 January 2026 / Published: 23 January 2026
Versions Notes

Abstract

Infective endocarditis (IE) due to methicillin-susceptible Staphylococcus aureus (MSSA) still represents a clinical and therapeutic issue. Discrepancies between guidelines, clinical studies and clinical practice have already been highlighted, especially regarding daptomycin use in MSSA cases. The aim of this study was to evaluate daptomycin’s impact on outcomes in this setting. This was a retrospective observational study. We enrolled all patients with MSSA IE admitted from 2015 to 2023. Patients were divided into two groups according to daptomycin administration. We enrolled 76 patients, with 49 in group A (standard treatment) and 27 in group B (treated with daptomycin). The in-hospital crude mortality was 14.3% and 29.6% in group A and B, respectively (p = 0.191). Only heart failure was significantly associated with negative outcome in the univariate and multivariate analyses (OR 6.424, 95% CI, 1.680–24.559; p = 0.007). In this study population, daptomycin treatment for IE due to MSSA was not associated with a reduced mortality rate. Heart failure was the only independent risk factor associated with in-hospital mortality.

1. Introduction

Infective endocarditis (IE) is a clinical condition characterized by the invasion of the cardiac valve apparatus, the parietal endocardium, and/or the septa by bacteria, leading to damage of the underlying cardiac tissues [1]. In the United States, Staphylococcus aureus is the most frequent etiologic agent of IE [2], and it is also associated with the highest number of deaths in healthcare-associated endocarditis cases [3]. These findings were also reported in our setting over a 40-year period [4]. The 2023 European Society of Cardiology (ESC) guidelines [1] proposed different treatment regimens for this condition, considering the antibiotic resistance profile (methicillin-resistant Staphylococcus aureus (MRSA) vs. methicillin-sensitive Staphylococcus aureus (MSSA)) and allergies that potentially reduce therapeutic options, as well as the type of endocarditis (native valve vs. prosthetic valve). The recommended therapy for native valve IE (NVE) due to MSSA consists of cloxacillin or cefazolin for 4–6 weeks. In case of prosthetic valve endocarditis (PVE), the total treatment duration should be at least 6 weeks. Moreover, the treatment regimen should be intensified by adding gentamicin for 2 weeks and rifampicin for the whole treatment duration (administration of rifampicin should be delayed for 3–5 days after treatment initiation). This regimen has remained unchanged compared to the previous edition (2015) of the ESC guidelines [5]. Nevertheless, in clinical practice, different therapeutic regimens are often used. Tissot-Dupont and colleagues highlighted how even the authors of the guidelines did not respect their own treatment indications, especially for staphylococcal and blood culture negative IE [6]. In a previously published study as part of the LEIOT Study Group, we confirmed loose adherence to the treatment guidelines and showed that a greater percentage of patients received daptomycin even when it was not strictly indicated [7]. This finding was not surprising because daptomycin is also largely used for IE in non-staphylococcal settings [8,9,10,11]. In the present context, where other treatment options for staphylococcal endocarditis such as fifth-generation cephalosporins or long-acting antibiotics are available [12,13,14], deviations from guidelines could increase even further.
The reason why deviations from guidelines are described more commonly in staphylococcal cases may rest on their increased severity [6,7]. Notoriously, S. aureus is an intrinsically virulent pathogen; it possesses multiple virulence factors with different mechanisms of action that allow it to interfere with neutrophil chemotaxis, migration and phagocytosis, the complement pathway, oxidative burst, and leukocyte lysis. Notably, Panton–Valentine leukocydin (PVL) production is associated with skin and skin structure infection, necrotizing pneumonia, and increased mortality [15]. Moreover, S. aureus resistance to methicillin represents another source of concern, especially due to its presence all over the world, both in healthcare settings and in the community [15,16]. In addition to this, S. aureus also shows reduced susceptibility with different patterns such as heteroresistance, MIC creep, and tolerance; these phenomena are explained by tolerance to glycopeptides, which has still not been associated with possible clinical implications [15,16,17].
The aim of the present study was to evaluate the use of daptomycin for IE due to MSSA in our centers and its impact on patients’ outcomes.

2. Materials and Methods

2.1. Study Design and Population

This was a retrospective observational multicenter study evaluating patients with infective endocarditis caused by MSSA, hospitalized at the Infectious Disease Clinic, “Santa Maria della Misericordia” Hospital, Perugia, Italy, and at the Azienda Ospedaliera-Universitaria “SS. Antonio e Biagio e Cesare Arrigo”, Alessandria, Italy, between 1 January 2015 and 31 December 2023. Inclusion criteria were (i) diagnosis of “definite” or “probable/possible” IE according to the ESC guidelines available at the moment of admission, and (ii) written informed consent for retrospective studies. A total of 76 patients were enrolled and then divided into two groups: group A consisted of patients receiving anti-staphylococcal beta-lactams such as cefazolin and oxacillin, while group B consisted of patients receiving daptomycin in mono- or combination therapy. Only targeted therapy was considered for group assignment.
We recorded clinical, epidemiological, and microbiological data at baseline for each patient. These data were extracted from their medical records and collected in an ad hoc electronic case report form.

2.2. Statistical Analysis

The statistical analysis was performed using IBM SPSS Statistics version 26. Continuous non-Gaussian variables were represented as median and interquartile range (IQR), while categorical variables were represented as frequency and percentage. Comparison between groups was performed with a two-tailed Mann–Whitney test or a chi-squared test (with Yates’ correction when appropriate), depending on variable distribution. A value of p less than 0.05 was considered statistically significant. Risk factors for in-hospital mortality (negative outcome) were evaluated by logistic regression and univariate and multivariate analysis and expressed as an odds ratio with 95% confidential interval.

2.3. Ethical Considerations

All the patients had previously provided written informed consent for retrospective studies in agreement with local Ethics Committees. The entire study was conducted in compliance with the principles of good clinical practice and consistently with the Declaration of Helsinki.

3. Results

A total of 76 patients were enrolled, with 49 (64.5%) in group A and 27 (35.5%) in group B. In group B, daptomycin was administered as a monotherapy in 3/27 (11.1%) cases, in combination with a beta-lactam other than ASP or cefazolin in 18/27 (66.7%) cases, and in combination with antibiotics of other classes in 6/27 (22.2%) cases. Table 1 summarizes the baseline characteristics of the study population and each group’s clinical and outcome findings. The groups were similar in terms of the patients’ sex, number of patients with prosthetic valves and pacemakers/intracardiac devices, risk factors, and comorbidities. A slightly and not statistically significant difference was reported for the type of valve involved: aortic IE tended to be more frequent in group B while mitral valve IE was more common in group B (p = 0.055). Patients in group B were significantly younger (median age 57 year, IQR 41–70 years vs. 71, IQR 53–81 years in group A, p = 0.023) and had a slightly lower Charlson comorbidity index (CCI) (median CCI was 5, IQR 2–6 and 3, IQR 1–5 in group A and group B, respectively, p = 0.063). The clinical characteristics at admission, incidence of global embolic events, surgical treatment, and length of hospital stay were similar in the two groups. On the other hand, spleen embolization occurred in 2/49 (4.1%) patients in group A and 6/27 (22.2%) patients in group B (p = 0.038). In group A, perivalvular abscess was detected in 4/49 (8.2%) patients, while in group B, it was detected in 8/27 (59.6%) patients (p = 0.033). The primary outcome was in-hospital mortality. Notably, in group B—comprising patients treated with daptomycin—mortality was higher (29.6% vs. 14.3%), although this difference did not reach the threshold for statistical significance (p = 0.191). A survival analysis confirmed this finding (Figure S1 in Supplementary Files).
Table 2 shows the results of the univariate and multivariate analyses for risk factors for in-hospital mortality. Heart failure was the only variable significantly associated with in-hospital mortality in the univariate analysis (OR 5.80, 95% CI 1.65–20.39; p = 0.006); having a prosthetic valve increased the risk for negative outcomes without reaching the threshold for statistical significance (OR 3.00, 95% CI 0.89–10.28; p = 0.076). Both of these variables were evaluated in the multivariate analysis, in which only “heart failure” confirmed the statistically significant association with mortality (OR 6.42, 95% CI, 1.68–24.56; p = 0.007).
Table 3. Summary of recent literature on MSSA endocarditis.
Table 3. Summary of recent literature on MSSA endocarditis.
Author, YearStudy DesignTotal Number of PatientsAntibioticsEtiologyOutcomesComments
Jean B. et al., 2024 [18]Retrospective multicenter study216ASP 139 (64.4%) or cefazolin 77 (35.6%)MSSANo difference in 30-day mortalityBlaZ and inoculum effect independently associated with 30-day mortality
Calderón-Parra J. et al., 2024 [19]Retrospective multicenter study42094 (22.4%) ASP or cefazolin and 326 (77.6%) combination therapyMSSANo difference in in-hospital and one-year mortalityNo differences for relapses and persistent bacteremias; more frequent drug-related adverse events in the combination therapy group
Destrem AL. et al., 2024 [20]Retrospective multicenter study19294 (48.9%) cefazolin, 98 (51%) cloxacillin175 S. aureus cases (91.1%); 17 coagulase-negative staphylococci cases (8.9%)Primary composite outcome was not statistically differentPrimary composite endpoint defined as 90-day mortality + embolic event + relapse < 90 days after end of treatment
Lecomte R. et al., 2024 [21]Post hoc analysis of a prospective cohort single-center study208101 (48.6%) ASP or cefazolin, 107 (52.4%) otherMSSAEmpirical treatment with ASP/cefazolin was associated with a shorter duration of bacteremiaNative valve endocarditis (p = 0.01) and intracardiac abscess were associated with a longer duration of bacteremia
Karan A. et al., 2023 [22]Mini case series2Nafcillin plus ertapenemMSSA
Herrera-Hidalgo L. et al., 2023 [23]Prospective multicenter cohort study with a retrospective analysis631Cloxacillin 537 (85%), cefazolin 57 (9%), both 37 (6%)MSSANo difference in one-year IE-related mortality and rate of relapses
Lefèvre B. et al., 2021 [24]Single-center retrospective study7335 (48%) ASPs, 38 (52%) cefazolinMSSANo difference in 90-day all-cause mortality and or incident renal or liver toxicity events
Lecomte R. et al., 2021 [25]Retrospective multicenter study21053 (25.2%) cefazolin, 157 (74.8%) ASPsMSSANo difference in 90-day mortalityCCI, CNS embolism, and ICU admission were associated with higher mortality
Le Bot A. et al., 2021 [26]Retrospective multicenter study180Association with rifampin 101 (56.1%), no rifampin 79 (43.9%)S. aureus 114 (63.3%), coagulase-negative staphylococci 66 (36.7%)No difference in one-year mortality and relapse ratesRifampin associated with longer hospital stay; CNS embolism and MRSA were associated with higher 1-year mortality
Pericàs JM. et al., 2017 [27]Prospective multicenter cohort study62Anti-staphylococcal β-lactam antibiotics (vancomycin MIC was lower than <1.5 mg/L in 28 cases (45%) and higher in 34 cases (55%))MSSANo difference in in-hospital and 1-year mortality
Abbreviations: ASP, anti-staphylococcal penicillins; IE, infective endocarditis; MSSA, methicillin-susceptible Staphylococcus aureus; CCI, Charlson comorbidity index; CNS, central nervous system; ICU, intensive care unit.

4. Discussion

In the 2023 ESC guidelines, the recommendations for IE due to MSSA confirmed the effectiveness of well-established anti-staphylococcal beta-lactam-based therapeutic regimens that have been in use for years. This finding appears to be supported by the available literature (Table 3): five out of eleven studies evaluated outcomes based on the use of cefazolin vs. anti-staphylococcal penicillins, reporting no significant differences in clinical outcomes between the two antibiotic classes [18,20,23,24,25]. Several of these studies also assessed adverse events, with no substantial differences according to the antibiotic administered. Cefazolin and anti-staphylococcal penicillins also appeared to be equivalent when used as empiric therapy for MSSA infective endocarditis, and both were associated with a shorter duration of bacteraemia compared to other treatments, regardless of the possible addition of an aminoglycoside [21]. Some studies described a possible better outcome in cefazolin-treated cases compared to ones receiving anti-staphylococcal penicillins [28] but these findings need to be clarified further.
However, for nearly all etiologies of endocarditis, the scientific literature has long described cases of the use of different antibiotic regimens, as highlighted in the study by Tissot-Dupont [6] and in a recent European survey [8], with a discordance with the 2015 ESC guidelines of over 50%. The reasons for this choice, in our opinion and in our clinical practice, often depend primarily on the beta-lactam dose required, with multiple daily doses often difficult to manage at home, thus necessitating an extended hospital stay of at least 4–6 weeks, leading to higher hospitalization costs and patient discomfort. For this reason, daptomycin is often introduced directly during the hospital stay. The same issue of multiple daily doses was raised also for vancomycin administration, which the guidelines reserve for MRSA cases and patients with allergies, while daptomycin, traditionally administered at a dose of 10 mg/kg every 24 h, does not have this problem. This was also confirmed by a 2022 survey promoted by SITA GIOVANI (Young Investigators Group of the Italian Society of Anti-Infective Therapy). Using a cross-sectional, internet-based questionnaire, the survey collected responses from 55 clinicians across twelve Italian regions. Daptomycin was reported as the first-line treatment choice in 31.48% of cases. The rationale for this preference was its use as empiric therapy for both native and prosthetic valve infections, allowing for an aminoglycoside-sparing combination regimen with high bactericidal activity and favorable clinical efficacy [9].
In the context of deviations from current guidelines, combination antibiotic therapy is also frequently discussed. The combination of daptomycin and beta-lactams has been frequently described in the literature for treatment of MRSA endocarditis, whereas data on MSSA endocarditis remain limited. In regard to MSSA infection, in a recent animal model, daptomycin combined with beta-lactams demonstrated significantly greater efficacy than any monotherapy in sterilizing valve vegetations and preventing the development of daptomycin non-susceptibility [29]. However, the literature has also described a lack of enhanced efficacy of daptomycin and beta-lactam combination therapy, likely due to the high bactericidal potency of beta-lactams when used as the backbone of the treatment of MSSA infections [30]. Thus, daptomycin/beta-lactam combination therapy should be reserved only for cases where there is a need to reach sites where daptomycin does not guarantee therapeutic efficacy, such as the lungs. A recent multicenter retrospective study by Calderón-Parra and colleagues evaluated the outcome of native valve MSSA infective endocarditis treated with standard monotherapy vs. combination therapy. The rates of relapses and persistent bacteremia were comparable between groups, while drug-related adverse events were more frequently observed in patients receiving combination therapy [19]. There is also a small case series involving two patients with MSSA endocarditis in which the combination of ertapenem and cefazolin was successfully used as salvage therapy for patients for whom blood cultures had failed to clear with beta-lactam therapy alone [22]. Given the limited evidence and the absence of a larger case series, this findings should be considered as a suggestion for a potential direction for future research.
According to ESC guidelines [1], rifampicin is recommended for the treatment of prosthetic valve endocarditis (PVE) caused by Staphylococcus aureus (both MSSA and MRSA), due to its antibiofilm properties. However, recent evidence has shown no significant differences in clinical outcomes between patients with PVE treated with rifampicin and those treated without it [26]. Vancomycin is included in current guidelines as a possible therapeutic option for MSSA infective endocarditis in patients with beta-lactam allergy. However, its use should be limited to cases with no easy alternatives because both cloxacillin monotherapy and the cloxacillin–gentamicin combination have demonstrated superior efficacy compared to either teicoplanin or vancomycin [31]. Moreover, the MIC phenotype of vancomycin was not associated with patient demographics, clinical outcome or virulence gene repertoire in patients with IE due to MSSA treated with anti-staphylococcal beta-lactams [27].
The main finding in the above mentioned literature seems to be the discrepancy between studies—even if defined as real-world studies—and the daily practice of physicians. Daptomycin seemed to be administered in a relevant number of cases of IE due to MSSA in the real life but only a few studies addressed this subject [7,9], and, as a consequence, evidence in this field is still lacking.
A preliminary multicenter study by our research group had already found that in both the Infectious Disease unit of Perugia and Alessandria (Italy), deviation from the guidelines was quantitatively significant especially for Staphylococcus aureus IE, with overprescription of daptomycin [7].
In an attempt to contribute to clarify this subject, we designed the current study to investigate whether the use of anti-staphylococcal beta-lactam therapy compared to daptomycin (alone or in combination with other drugs) has an impact on in-hospital mortality. Analyzing the baseline characteristics of the two groups, we found a significantly higher median age in patients receiving beta-lactam therapy (median age was 66 and 71 years in group A and group B, respectively; p = 0.023). It should be mentioned that in our study, the patients receiving a combination of daptomycin and beta-lactam/other antibiotics or daptomycin alone were all included in group B, due to the small sample size.
A more detailed examination suggests that the patients in group B presented a more severe clinical profile at onset. Specifically, among thromboembolic complications such as perivalvular abscesses, splenic embolization was significantly more frequent in group B. These findings, as well as the greater number of cases complicated by valve perforation present in group B, could suggest a more severe clinical situation although this difference was not statistically significant. As a consequence, we can hypothesize that the choice of a non-beta-lactam therapeutic regimen, such as daptomycin, may have been driven by the clinician’s perception of a severe clinical presentation at diagnosis, conducive to a deviation from standard first-line treatment indications. Consistently with our findings, severe and/or complicated clinical presentations have already been associated with antibiotic treatments different from the ones suggested by international guidelines [6] such as daptomycin for MSSA IE. As part of this reasoning, vegetations larger than 10 mm were observed in 48.1% of the patients in group B compared to 30.6% in group A (p = 0.205). The “Italian Study on Endocarditis” (SEI) identified vegetation size >10 mm as well as Staphylococcus aureus etiology, prosthetic valve endocarditis and right-sided localization as risk factors for embolization [32]. In this regard, although without reaching statistical significance, a higher proportion of patients in group B had a prosthetic valve (group A 16.3% vs. group B 33.3%, p = 0.157), also suggesting that the choice of daptomycin was influenced by antibiofilm activity and the aim of avoiding prescription of rifampicin, especially when contraindicated due to interactions with warfarin in patients with mechanical valves.
In-hospital mortality was higher in subjects with daptomycin treatment regimens, although this did not reach statistical significance (group A 14.3% vs. group B 29.6%, p = 0.191). In our opinion, this finding is attributable to the major baseline severity of the patients in group B. A similar trend was observed in the univariate analysis, assessing risk factors related to in-hospital mortality in the two groups. Only heart failure reached statistical significance (OR 5.797, 95% CI 1.648–20.389; p = 0.006), confirmed in the multivariate analysis, where heart failure was confirmed as an independent predictor of in-hospital mortality (OR 6.424, 95% CI 1.68–24.559; p = 0.007). Daptomycin administration did not impact mortality (OR 2.526, 95% CI 0.8–7.979, p = 0.114). These results are comparable to those in the literature. We have previously described how adherence to a treatment’s guidelines did not positively impact IE outcomes [7]. In this study, the authors reported that the great part of cases without adherence to guidelines were due to daptomycin use for MSSA IE. Rodriguez Esteban and colleagues, in a Spanish study on 162 IE cases, reached similar conclusions [33].
These findings suggest that IE due to S. aureus still represents a clinical and therapeutic challenge for clinicians. New treatment strategies or new antibiotic molecules directed toward different targets such as metallophores could represent an option to be considered in future studies [34].
Our study has some limitations that must be discussed. It is a retrospective study with a cohort of patients from only two Infectious Disease units. Furthermore, both hospitals are tertiary-level institutions, which also include a Cardiovascular Surgery unit, allowing for rapid initial surgical evaluation and ongoing reassessments, and potentially leading to early cardiac surgery interventions where indicated. In contrast, many hospitals in Italy lack this capability and this could represent a selection bias. The time frame analyzed encompassed the years of the SARS-CoV-2 pandemic, a period during which the Infectious Disease units across Italy primarily admitted patients with this infection. It is therefore plausible to hypothesize that this factor may have negatively impacted the enrollment of IE cases from March 2020 onwards. The main limitation of the study, however, is related to the small sample size, particularly in group B, which made it impossible to further differentiate patients on monotherapy with daptomycin from those on combination therapy with daptomycin and other antibiotics. Moreover, the relatively elevated percentage of cases of prosthetic valve IE could have also influenced the outcome. In addition to this, some data were missing, especially on follow-up blood culture and treatment side effects. Finally, the small sample size made our findings difficult to generalize. Further multicenter studies with a larger sample size, including hospitals with different characteristics, are needed.
In conclusion, in our experience, daptomycin administration in IE due to MSSA does not improve clinical outcome but, notably, this group of patients were found to have a more severe clinical presentation at admission; only heart failure emerged as an independent predictor of mortality in both univariate and multivariate analyses. Data from the literature support the clinical equivalence between anti-staphylococcal penicillins and cephalosporins in the treatment of MSSA IE, while data regarding the combined use of daptomycin and beta-lactams were not sufficient to provide a robust rationale for its clinical application. Finally, a discrepancy between clinical studies and daily practice was evidenced and could represent an interesting field of analysis for future studies.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/microbiolres17020029/s1, Figure S1: Survival analysis.

Author Contributions

Conceptualization, A.T., C.P., C.B., D.F. and G.V.D.S.; methodology, A.T. and C.P.; data curation, A.T., C.B., L.C., C.P., S.P., C.S., G.G., E.S., A.S., G.P. and LEIOT Study Group; data analysis, C.P.; writing—original draft preparation, A.T. and C.P.; writing—review and editing, A.T., C.P., L.C., C.B., S.P., C.S., G.G., E.S., A.S., G.P., A.M., G.C., G.V.D.S. and D.F.; supervision, C.P. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

This study was conducted according to the principles of good clinical practice and the Declaration of Helsinki. It is approved by the Ethics Committee of the enrolling centers (Azienda Ospedaliera Universitaria Nazionale SS Antonio e Biagio e Cesare Arrigo, protocol number ASO.mInf.22.03; date of approval 3 May 2022) This is an observational retrospective study. According to Local Ethics Committee recommendations, patients provided a signed consent form for retrospective studies.

Informed Consent Statement

Informed consent for retrospective studies was obtained from all subjects involved in the study.

Data Availability Statement

The datasets analyzed in the current study are not publicly available due to privacy protection reasons but are available from the corresponding author on reasonable request.

Acknowledgments

LEIOT Study Group: Andrea Tommasi, Laura Curci, Giovanni Genga, Elisabetta Svizzeretto, Carlo Pallotto, Giuseppe Vittorio De Socio, Daniela Francisci, Elisa Stolaj, Chiara Papalini, Francesco Paciosi, Sara Benedetti (Perugia), Cesare Bolla, Serena Penpa, Cristina Sarda, Andrea Salvaderi, Giorgia Piceni, Antonio Maconi and Guido Chichino (Alessandria).

Conflicts of Interest

D.F. has received funds for speaking at symposia on behalf of Gilead, Janssen, MSD, ViiV Healthcare and Abbvie, and for participation in an advisory board on behalf of Janseen. C.P. received funds for speaking at symposia on behalf of Insmed and travel support for attending meetings on behalf of Gilead, Pfizer, Advanz Pharma, Tillots, Mundipharma and NordicPharma. G.V.D.L. has received funds for speaking at symposia on behalf of Gilead and ViiV Healthcare. The other authors declare no conflict of interests.

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Table 1. Characteristics of the study population, treatment, and outcomes.
Table 1. Characteristics of the study population, treatment, and outcomes.
Study Population
n = 76		Group A
n = 49		Group B
n = 27		p
Males, n (%)45 (59.2)28 (57.1)17 (63.0)0.802
Age, year, median (IQR)66 (46.8–78.8)71 (53–81)57 (41–70)0.023
Valve involved, n (%) a 0.055
-
Aortic
22 (30.1)10 (20.8)12 (48.0)
-
Mitral
28 (38.4)23 (47.9)5 (20.0)
-
Tricuspid
12 (16.4)9 (18.8)3 (12.0)
-
Multiple localizations
8 (11.0)5 (10.4)3 (12.0)
-
Other
3 (4.1)1 (2.1)2 (8.0)
Prosthetic valve, n (%)17 (22.4)8 (16.3)9 (33.3)0.157
PMK/ICD, n (%)8 (10.5)5 (10.2)3 (11.1)0.789
Risk factors and comorbidities, n (%)
-
Previous IE
11 (14.5)8 (16.3)3 (11.1)0.781
-
Predisposing heart condition
43 (56.6)26 (53.1)17 (62.9)0.554
-
Previous cardiosurgical intervention
26 (34.2)15 (30.6)11 (40.7)0.523
-
Chronic renal insufficiency
17 (22.4)11 (22.4)6 (22.2)0.791
-
Hemodialysis
2 (2.6)1 (2.0)1 (3.7)0.753
-
Intravenous drug use
15 (19.7)11 (22.4)4 (14.8)0.618
-
Diabetes mellitus
15 (19.7)11 (22.4)4 (14.8)0.618
Charlson Comorbidity Index, median (IQR)4 (2–6)5 (2–6)3 (1–5)0.063
Characteristics at admission, n (%)
-
Fever
61 (80.3)38 (77.6)23 (85.2)0.618
-
TIA/stroke
10 (13.2)6 (12.2)4 (14.8)0.97
-
Other embolization
26 (34.2)17 (34.7)9 (33.3)0.894
Vegetation size > 10 mm, n (%)28 (36.8)15 (30.6)13 (48.1)0.205
Embolic complications, n (%)
Pt with ≥1 embolic event46 (60.5)29 (59.2)17 (63.0)0.938
Total embolic events895534
Embolic events, median (IQR)1 (0–2)1 (0–1)1 (0–2)0.407
Embolic localization:
-
Central nervous system
16 (21.1)10 (20.4)6 (22.2)0.914
-
Spleen
8 (10.5)2 (4.1)6 (22.2)0.038
-
Skin and skin structures
14 (18.4)9 (18.4)5 (18.5)0.77
-
Spondylodiscitis
12 (15.8)9 (18.4)3 (11.1)0.616
-
Liver
2 (2.6)1 (2.0)1 (3.7)0.753
-
Kidney
7 (9.2)3 (6.1)4 (14.8)0.401
-
Lung
17 (22.4)12 (24.5)5 (18.5)0.756
-
Other
13 (17.1)9 (18.4)4 (14.8)0.94
Other complications, n (%)
-
Valvular perforation
10 (13.2)4 (8.2)6 (22.2)0.167
-
Perivalvular abscess
12 (15.8)4 (8.2)8 (29.6)0.033
-
Dehiscence of the prosthesis
1 (1.3)01 (3.7)>0.1
-
Acute renal failure
12 (15.8)7 (14.3)5 (18.5)0.876
-
Heart failure
15 (19.7)8 (16.3)7 (25.9)0.481
Surgical treatment, n (%)28 (37.1)15 (28.9)13 (52.0)0.205
In-hospital mortality, n (%)15 (19.7)7 (14.3)8 (29.6)0.191
Length of hospital stay, days, median (IQR)39 (20.8–53.8)39 (23–52)41 (15.5–59.5)0.912
Note: a, n = 73, n = 48, n = 25 in study population, group A, and group B, respectively.
Table 2. Risk factors for in-hospital mortality in univariate and multivariate analyses.
Table 2. Risk factors for in-hospital mortality in univariate and multivariate analyses.
Positive Outcome
n = 61		Negative Outcome * n = 15Univariate Analysis (OR, 95% CI)pMultivariate Analysis (OR, 95% CI)p
Females, n (%)23 (37.7)8 (53.3)1.89 (0.61–5.90)0.274
Age, median (IQR)66 (46–77)64 (53–85)1.02 (0.98–1.05)0.353
Prosthetic valve, n (%)11 (18.0)6 (40.0)3.00 (0.89–10.28)0.0763.59 (0.93–13.86)0.063
Previous infective endocarditis7 (11.5)4 (26.7)2.81 (0.70–11.25)0.146
Predisposing heart conditions, n (%)32 (52.5)11 (73.3)2.58 (0.74–8.98)0.137
Chronic renal failure, n (%)13 (21.3)4 (26.7)1.34 (0.37–4.92)0.656
Intravenous drug use, n (%)10 (16.4)5 (33.3)2.55 (0.72–9.08)0.148
Diabetes mellitus, n (%)12 (19.7)3 (20.0)1.02 (0.25–4.20)0.977
Charlson comorbidity index, n (%)4 (2–6)5 (2.5–7)1.19 (0.95–1.50)0.136
Vegetation size > 10 mm, n (%)22 (36.1)6 (40.0)1.18 (0.37–3.76)0.777
Fever at admission, n (%)49 (80.3)12 (80.0)0.98 (0.24–4.03)0.977
TIA/stroke at admission, n (%)8 (13.1)2 (13.3)1.02 (0.19–5.38)0.982
Patients with ≥1 embolic event, n (%)39 (63.9)7 (46.7)0.494 (0.16–1.55)0.225
Central nervous system embolic event, n (%)13 (21.3)3 (20.0)0.92 (0.23–3.77)0.911
Lung embolic event, n (%)13 (21.3)4 (26.7)1.34 (0.37–4.92)0.656
Valvular perforation, n (%)9 (14.8)1 (6.7)0.41 (0.05–3.54)0.42
Perivalvular abscess, n (%)10 (16.4)2 (13.3)0.79 (0.15–4.03)0.771
Acute renal failure, n (%)8 (13.1)4 (26.7)2.41 (0.62–9.43)0.207
Heart failure, n (%)8 (13.1)7 (46.7)5.80 (1.65–20.39)0.0066.42 (1.68–24.56)0.007
Surgical treatment, n (%)23 (37.7)5 (33.3)0.83 (0.25–2.72)0.753
Daptomycin administration, n (%)19 (30.6)8 (53.3)2.53 (0.80–7.98)0.114
Note: *, negative outcome was defined as in-hospital mortality.
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Tommasi, A.; Bolla, C.; Curci, L.; Penpa, S.; Genga, G.; Sarda, C.; Svizzeretto, E.; Salvaderi, A.; Piceni, G.; De Socio, G.V.; et al. Use of Daptomycin for the Treatment of Infective Endocarditis Due to Methicillin-Susceptible Staphylococcus aureus (MSSA): A Multicenter Retrospective Study. Microbiol. Res. 2026, 17, 29. https://doi.org/10.3390/microbiolres17020029

AMA Style

Tommasi A, Bolla C, Curci L, Penpa S, Genga G, Sarda C, Svizzeretto E, Salvaderi A, Piceni G, De Socio GV, et al. Use of Daptomycin for the Treatment of Infective Endocarditis Due to Methicillin-Susceptible Staphylococcus aureus (MSSA): A Multicenter Retrospective Study. Microbiology Research. 2026; 17(2):29. https://doi.org/10.3390/microbiolres17020029

Chicago/Turabian Style

Tommasi, Andrea, Cesare Bolla, Laura Curci, Serena Penpa, Giovanni Genga, Cristina Sarda, Elisabetta Svizzeretto, Andrea Salvaderi, Giorgia Piceni, Giuseppe Vittorio De Socio, and et al. 2026. "Use of Daptomycin for the Treatment of Infective Endocarditis Due to Methicillin-Susceptible Staphylococcus aureus (MSSA): A Multicenter Retrospective Study" Microbiology Research 17, no. 2: 29. https://doi.org/10.3390/microbiolres17020029

APA Style

Tommasi, A., Bolla, C., Curci, L., Penpa, S., Genga, G., Sarda, C., Svizzeretto, E., Salvaderi, A., Piceni, G., De Socio, G. V., Francisci, D., on behalf of the LEIOT Study Group, Maconi, A., Chichino, G., & Pallotto, C. (2026). Use of Daptomycin for the Treatment of Infective Endocarditis Due to Methicillin-Susceptible Staphylococcus aureus (MSSA): A Multicenter Retrospective Study. Microbiology Research, 17(2), 29. https://doi.org/10.3390/microbiolres17020029

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