Cefiderocol for the Treatment of Nosocomial Bloodstream Infections Caused by Stenotrophomonas maltophilia: A Case Series and Literature Review

Abstract

Introduction

The treatment of Stenotrophomonas maltophilia bloodstream infections (BSI) remains challenging due to the organism's intrinsic multidrug resistance and the potential side effects of commonly used first-line antibiotics.

Methods

Here, we describe four cases of S. maltophilia BSI treated with cefiderocol (≥ 72 h) in different Italian hospitals. Additionally, we conducted a PubMed search to identify other studies reporting cases of S. maltophilia BSI managed with cefiderocol.

Results

We reviewed a total of 8 cases of S. maltophilia BSI [median age 52.5 years (Q1–Q3 27.5–61.0), 50% males] treated with cefiderocol, including ours. BSI sources were mainly central venous catheters (62.5%) and the lower respiratory tract (25.0%). Cefiderocol was used as first-line therapy in 87.5% of patients (7/8), with a median treatment duration of 14 days (IQR 6.2–16.0). Combination therapy was administered in 62.5% of cases. Infection source control was required in 75.0% and achieved in 40.0%. Clinical success was observed in 62.5% of patients, with microbiological eradication in 87.5%. In-hospital mortality occurred in 37.5% of cases, with one death directly attributable to S. maltophilia. No significant differences were observed in terms of outcomes between cefiderocol monotherapy and combination therapy.

Conclusions

Based on our findings and a review of the literature, cefiderocol-based regimens show promise as an effective treatment option for S. maltophilia BSI, warranting further investigation in larger studies.

Key Summary Points

We reviewed 8 cases of S. maltophilia bloodstream infections, including 4 new cases treated with cefiderocol.

Central venous catheters (62.5%) and lower respiratory tract (25.0%) were primary infection sources; source control was achieved in 40.0%.

Cefiderocol was used as first-line therapy in 87.5%, achieving clinical success in 62.5% and microbiological eradication in 87.5%.

In-hospital mortality was 37.5%, with no outcome differences between monotherapy and combination therapy.

Cefiderocol shows promise as an effective treatment option for S. maltophilia BSI.

Introduction

Stenotrophomonas maltophilia is an opportunistic pathogen that predominantly causes nosocomial bloodstream infections (BSI) and pneumonia [1, 2] in critically ill and immunocompromised patients [3–5]. Over the last decade, it has been reported as a leading cause of carbapenem-resistant Gram-negative BSI in the USA [6], with a mortality rate of around 20%, reaching as high as 69% in some studies [3, 7].

Due to the presence of both intrinsic and acquired antibiotic resistance mechanisms [8–13], therapeutic options for S. maltophilia BSI are mainly limited to trimethoprim–sulfamethoxazole (TMP-SMX) [14], fluoroquinolones, tetracyclines, and glycylcyclines. However, these agents are not without drawbacks, including high rates of allergy [15], resistance [16, 17], side effects [18–20], and challenges in achieving pharmacodynamic targets [21]. Recently, cefiderocol, a novel siderophore cephalosporin, was approved by the Food and Drug Administration (FDA) for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria, including S. maltophilia [22]. However, this approval was based on randomized clinical trials that included only six patients with S. maltophilia infections [23, 24], none of whom had BSI.

To date, very few published observational case reports have provided data on the efficacy of cefiderocol in treating S. maltophilia BSI with promising results [25–27]. Nevertheless, experience in using cefiderocol for these infections remains limited. Therefore, clinical data to guide and support the use of this novel antibiotic in S. maltophilia BSI are urgently needed. The purpose of this study is to present a series of four consecutive patients treated with cefiderocol for S. maltophilia BSI and to review published studies involving patients with S. maltophilia BSI.

Methods

In the present report, we focus on four patients who had BSI caused by S. maltophilia and were treated (≥ 72 h) with cefiderocol. These patients are a part of a retrospective cohort study conducted from 1 January 2021 to 31 December 2022 across 14 hospitals in Italy. The study aimed to assess the impact of current Infectious Disease Society of America (IDSA) guidelines recommendations on the clinical outcome of patients with S. maltophilia BSI [28]. Detailed analysis of the complete cohort results is currently underway.

Bibliographic Research

To identify clinical reports of patients with S. maltophilia BSI receiving cefiderocol treatment beyond the setting of clinical trials, we searched Embase and Medline for all English written reports published up to 18 March 2024, using the search terms “cefiderocol” or “S-649266” AND “Stenotrophomonas maltophilia”. This study only included reports detailing patients aged 18 years and above who were treated with cefiderocol for a minimum of 72 h due to BSI caused by S. maltophilia.

Definitions

Patient outcomes were classified as either clinical success or failure at the end of the follow-up period. This period began on the index date and concluded on the date of death or the last documented clinical visit up to October 2024 for our four patients. For cases sourced from the medical literature, follow-up ended as per the clinical details provided in the respective reports.

A successful clinical outcome was defined as the complete resolution of signs and symptoms attributable to S. maltophilia infection, without the need for additional antibiotic therapy targeting S. maltophilia during the follow-up period, except when de-escalation therapy was required. Microbiological resolution was evaluated only for patients with a follow-up blood culture and was defined as obtaining negative follow-up cultures during cefiderocol therapy. Clinical failure was defined as an absence of clinical response, recurrence, and/or all-cause in-hospital mortality.

Microbiological Procedures

The identification of S. maltophilia and in vitro antibiotic susceptibility testing were performed at participating hospitals using local routine methods. Susceptibility patterns were reported according to the 2023 EUCAST recommendations or, for antibiotics without EUCAST recommendations (e.g., levofloxacin, chloramphenicol), the 2023 CLSI Performance Standards.

Cefiderocol Administration

Cefiderocol was administered according to the prescribing information at a dosage of 2 g intravenous over 3 h repeated every 8 h. Dose adjustments were required only for patients with moderate to severe renal dysfunction [creatinine clearance (CLCr) < 60 mL/min] or for those with augmented renal clearance (CLCr ≥ 120 mL/min).

Ethics

The study was approved by the institutional review board of the coordinating center (Comitato Etico interaziendale, City of Health and Sciences, Turin, pratica no. 202/2023, PROT.N. 0066633) and was conducted in accordance with the Declaration of Helsinki. Informed consent was deemed unnecessary due to the retrospective nature of the study. STROBE recommendations were followed.

Results

Clinical Cases of S. maltophilia BSI Treated with Cefiderocol

Case 1. A 47-year-old female with no significant medical history was admitted to the intensive care unit (ICU) due to viral myocarditis complicated by cardiogenic shock and hemophagocytic lymphohistiocytosis. She received immunosuppressive therapy with high-dose steroids, etoposide, and cyclosporine. On the 60th day of hospitalization, she developed central venous catheter (CVC)-related BSI caused by S. maltophilia. She was treated with cefiderocol plus levofloxacin for 3 days, and her CVC was also removed. Empirical antibiotic therapy was switched to TMP-SMX, which was administered for additional 14 days. No significant adverse events were reported during treatment, and negativization of the blood cultures was achieved after the first 2 days of antimicrobial therapy with cefiderocol plus levofloxacin. The patient was discharged after 215 days with no reported infection relapse.

Case 2. An 82-year-old female patient presented to the emergency department with complaints of melena and rectal bleeding. Her medical history revealed a diagnosis of acute lymphoblastic leukemia undergoing treatment with imatinib, previous breast cancer treated with chemotherapy, and severe aortic stenosis. Following a nearly month-long hospitalization in the medical unit, she was diagnosed with a CVC-related BSI caused by S. maltophilia. Initially, she received empirical treatment with piperacillin/tazobactam for 3 days, which was subsequently switched to cefiderocol for 7 days based on microbiological identification. Follow-up blood cultures were negative for S. maltophilia after 3 days of cefiderocol therapy. Her hospital stay lasted a total of 43 days. At the time of discharge, there were no clinical signs of recurrent infection, and blood cultures remained negative.

Case 3. A 21-year-old man was admitted to the hospital due to extensive burns covering 90% of his body surface. On the 70th day of hospitalization, he developed sepsis, and blood cultures revealed the presence of S. maltophilia. He received a 14-day course of combination therapy with cefiderocol and TMP-SMX. Additionally, he underwent multiple surgical debridements to excise infected necrotic tissue. Microbiological eradication was successfully achieved after 7 days of antibiotic treatment, and no infection relapses were reported. Unfortunately, he succumbed to his critical condition on the 91st day of admission.

Case 4. An 18-year-old man was admitted to the hospital for an allogeneic hematopoietic stem cell transplant due to refractory T-cell lymphoblastic lymphoma. On the 47th day of his hospitalization, while in a neutropenic phase, he developed a CVC-related BSI caused by S. maltophilia. Initial treatment with cefiderocol monotherapy was initiated, but removal of the vascular catheter was not feasible. Unfortunately, the patient passed away on the 4th day of treatment. Follow-up blood cultures were not performed.

Cumulative Summary of Our Cases and Published Cases in the Medical Literature

A systematic PubMed search identified five cases of S. maltophilia BSI treated with cefiderocol [25–27, 29]. However, one case was excluded due to the patient being a newborn (5 weeks old) [25]. This resulted in a total of eight cases reviewed, including the four cases from our cohort. The clinical characteristics of the study population are summarized in Table 1.

Table 1.

Baseline characteristics and clinical outcomes of the study population following treatment with cefiderocol

	Study population (n = 8; n/N)
Median age, (Q1–Q3)a	52.5 (27.5–61.0)
Male gendera	3/6 (50.0%)
Hospital ward admissiona
Intensive care unit	3/6 (50.0%)
Internal medicine	1/6 (16.7%)
Onco-haematology unit	1/6 (16.7%)
Other	1/6 (16.7%)
Underlying disease
Cardiovascular diseasea	4/6 (66.7%)
Onco-hematologic disease	4/8 (50.0%)
Chronic kidney diseasea	3/6 (50.0%)
Hematopoietic stem cell transplantation	1/8 (12.5%)
Solid organ transplant	1/8 (12.5%)
Diabetesa	1/6 (16.7%)
Neurological diseasea	1/6 (16.7%)
Gastrointestinal diseasea	1/6 (16.7%)
Median Charlson Comorbidity Index, (Q1–Q3)a	3.5 (0.5–5.8)
Predisposing conditions
Central venous catheter	7/8 (87.5%)
Urinary bladder catheter	6/8 (75.0%)
Continuous renal replacement therapy	2/8 (25.0%)
Intermittent hemodialysis	1/8 (12.5%)
Surgery, within previous month	1/8 (12.5%)
Source of infection
CVC-related BSI	5/8 (62.5%)
HAP/VAP	2/8 (25.0%)
Burn infection	1/8 (12.5%)
Presentation with sepsis/septic shocka	4/6 (66.7%)
Cefiderocol treatment
First line therapyb	7/8 (87.5%)
Combination therapy	5/8 (62.5%)
Length of treatment, days (median, interquartile range)	14 (6.2–16.0)
Need for ICU admission for S. maltophilia infectionc	0/3 (0%)
Successful clinical outcome	5/8 (62.5%)
Clinical failured	3/8 (37.5%)
Microbiological failure	0/7 (0%)
Length of hospital stay (days), median (range)	96 (30–215)

BSI Bloodstream Infection, CVC Central Venous Catheter, HAP Hospital-associated pneumonia, VAP ventilator-associated pneumonia

^aInformation available in 6 out of 8 patients

^bOnly molecules with activity against S. maltophilia were considered

^cInformation was available for six patients, three of whom were already in the ICU at the time they developed S. maltophilia bloodstream infections

^dClinical failures were due to deaths in all cases; however, only 1 out of 3 deaths was attributable to S. maltophilia

Patient Demographics

Patients' age ranged from 18 to 82 years (median 52.5 years; Q1–Q3 27.5–61.0), with 50.0% being male. Cardiovascular disease was the most common underlying condition (66.7%, 4 out of 6 patients for whom information was available), followed by onco-hematological disease (50.0%, 4 out of 8). Multiple underlying conditions were present in 50.0% of the cases, and the median Charlson comorbidity index, calculated for 6 out of 8 cases, was 3.5 (Q1–Q3 0.5–5.8). At the onset of S. maltophilia BSI, 87.5% of patients (7 out of 8) had a CVC in place, and 75.0% (6 out of 8) had a urinary bladder catheter (Table 1).

Infection Sources and Pathogen Profile

The most frequent infection sources were the CVC (5/8; 62.5%) and the lower respiratory tract (2/8; 25.0%). The remaining patient had a BSI secondary to a burn wound infection (Table 1). Notably, 66.7% of the patients presented with sepsis or septic shock, while two patients (25.0%) had polymicrobial BSI, with one involving extended-spectrum beta-lactamase (ESBL)-producing E. coli and the other an unspecified pathogen. In all cases, appropriate treatment was administered based on the judgment of the attending physicians.

As for antibiotic susceptibility profiles, approximately 90.0% of S. maltophilia isolates (7/8) were susceptible to TMP-SMX at elevated dosages according to EUCAST criteria, while only 37.5% were reported to be susceptible to levofloxacin per CLSI guidelines (3/8). Susceptibility data for other antibiotics with established CLSI clinical breakpoints (minocycline, ceftazidime and ticarcillin–clavulanic acid) were unavailable for our cases and in the published literature. Cefiderocol susceptibility was reported in 6 out of 8 cases; in five of these, broth microdilution was performed, whereas disk diffusion testing was used in the remaining case. Regardless of the methodology used, cefiderocol demonstrated in vitro activity against all tested isolates.

Therapeutic Approaches and Source Control

Seven of the eight patients (87.5%) received cefiderocol as first-line therapy, while one patient (12.5%) was treated with cefiderocol as a second-line option. In this case, prior antibiotic therapy included levofloxacin administered for 9 days (Table 2).

Table 2.

Clinical presentations, antibiotic treatment, clinical course

Patient, ref	Age (year)	Type of infection	Polymicrobial infection	Antibiotic treatment before cefiderocol	Cefiderocol susceptibility	Cefiderocol treatment	Treatment after cefiderocol	Source control potentially achievable/achieved	Microbiological eradication	In-hospital mortality	SM infection relapse
Case 1	47	CVC- BSI	No	No	Microdilution method MIC = 0.016 mg/L	Cefiderocol + levofloxacin for 3 days	TMP-SMX for 15 days	Yes (CVC removal, performed)	Yes	No	No
Case 2	82	CVC-BSI	No	Piperacillin/ tazobactam for 3 days	Microdilution method MIC = 0.016 mg/L	Cefiderocol for 7 days	No	Yes (CVC removal, not performed)	Yes	No	No
Case 3	21	Wound infection  in a severely burned patient	No	No	Microdilution method MIC ≤ 2 mg/L	Cefiderocol + TMP-SMX for 14 days	No	Yes, multiple surgical debridement performed	Yes	Yes	No
Case 4	18	CVC-BSI	No	No	Microdilution method MIC = 0.062 mg/L	Cefiderocol for 4 days	No	Yes (CVC removal, not performed)	Unknown	Yes	No
Case 5, Medioli et al. [27]	62	CVC-BSI complicated with septic thrombosis	No	Piperacillin/ tazobactam + daptomycin for 2 days; levofloxacin for 9 days	Disk diffusion method MIC = 25 mm	Cefiderocol + levofloxacin for 22 days + intra-lock therapy with TMP-SMX for 14 days	Minocycline plus the lock therapy with TMP-SMX as a chronic suppressive therapy	Yes (CVC removal, not performed)	Yes	No	No
Case 6, Fratoni et al. [29]	58	Bacteriemic VAP	Yes; SM + ESBL-producing E.coli	No	Microdilution method MIC = 0.125 mg/L	Cefiderocol for 14 days + tigecycline for 10 days	No	No	Yes	Yes	No
Case 7, Lupia et al. [26]	NA	Bacteriemic HAP	No	No	Disk diffusion method, but MIC not reported	Cefiderocol for 22 days	No	No	Yes	No	No
Case 8, Lupia et al. [26]	NA	CVC-BSI	Yes; SM + isolated pathogen not specified	No	Disk diffusion method, but MIC not reported	Cefiderocol + TMP-SMX for 14 days	No	Yes (Unknown)	Yes	No	No

BSI blood stream infection, CVC central venous catheter, CVC-BSI central venous catheter reated BSI, MIC minimum inhibitory concentration, NA not available, SM S. maltophilia, SSssTI,  TMP-SMX trimethoprim- sulfamethoxazole, VAP ventilator-associated pneumonia

The mean duration of cefiderocol therapy was 14 days (Q1–Q3 6.2–16.0 days). Combination antibiotic therapy was given in five out of eight patients (62.5%), with TMP-SMX and levofloxacin each used in two cases (25.0%), and tigecycline in one (12.5%). Lock therapy with TMP-SMX was combined with systemic cefiderocol treatment in a single case (Table 2). Infection source control was deemed necessary in 6 patients (75.0%). Information regarding adequate source control was available in 5 out of 6 patients and it was achieved in 2 out of 5 cases (40.0%).

Clinical Outcomes Overall

Five patients (62.5%) achieved a successful clinical outcome at the end of treatment (Table 1). Follow-up blood cultures were performed in 7 of 8 patients (87.5%), with microbiological eradication achieved in all of these cases. Clinical failure occurred in three patients (37.5%) and was due to death in all cases, of which only one was attributable to S. maltophilia infection. There was no statistically significant difference in clinical success between those receiving cefiderocol as monotherapy versus combination therapy [66.7% (2/3) vs. 60.0% (3/5); P = 1.0] or as primary versus second-line therapy [57.1% (4/7) vs. 100% (1/1); P = 1.0].

Discussion

To the best of our knowledge, this study represents the largest real-world case series investigating the use of cefiderocol for the treatment of S. maltophilia BSI. A notable strength of our study is that it addresses a critical gap in the literature, as patients with S. maltophilia BSI are often underrepresented in randomized clinical trials.

In recent years, the incidence of S. maltophilia BSI has been increasing, largely driven by the growing population of at-risk patients [3, 30–33]. This trend is likely attributable to advancements in cancer therapies, the increased use of invasive medical devices, and the widespread administration of broad-spectrum antibiotics [30, 31, 34]. Notably, S. maltophilia has emerged as the leading cause of carbapenem-resistant Gram-negative BSI in the United States, with approximately 45% of cases originating in the community [6].

In this context, therapeutic options for managing S. maltophilia BSI are limited to a few antibiotics, including levofloxacin, TMP-SMX, minocycline, and tigecycline [35]. However, these agents present significant limitations, including a high risk of toxicity and side effects, increasing rates of both in vitro and in vivo resistance development, and challenges in achieving optimal pharmacokinetic/pharmacodynamic targets [14–21]. Furthermore, despite multiple studies comparing various therapeutic regimens, no clinical evidence currently supports any single antibiotic as the definitive treatment for S. maltophilia BSI [36–41].

Cefiderocol, a catechol-substituted siderophore cephalosporin approved for the treatment of severe infections caused by Gram-negative bacilli with limited or no therapeutic options [22], has demonstrated high in vitro efficacy against S. maltophilia, with susceptibility rates exceeding 95–98% of isolates tested [42, 43]. Despite these promising in vitro findings, clinical experience with cefiderocol for S. maltophilia infections, particularly BSI, remains limited [26, 27].

In the APEKS-NP trial, among cefiderocol-treated patients, there was a single case of non-bacteremic pneumonia caused by S. maltophilia that achieved both clinical cure and microbiological eradication [24]. Conversely, in the CREDIBLE-CR trial, five patients with S. maltophilia infections (none of whom had bacteremia) were treated with cefiderocol, but none achieved clinical cure or microbiological eradication [23]. In the present study, which included a population of patients with multiple comorbidities, we observed significantly higher cure rates compared to the pooled results from clinical trials (1 out of 6 patients; 16%). Specifically, we achieved a clinical success rate of 70%, aligning with real-world outcomes observed for other non-fermenting microorganisms treated with cefiderocol [44–46].

In the CREDIBLE trial, all patients with S. maltophilia infections treated with cefiderocol had nosocomial pneumonia, and 60% of them exhibited a fourfold increase in MIC values during treatment [23]. In contrast, in our study, which exclusively included patients with BSI, no increase in cefiderocol MICs was observed as all patients with available follow-up blood cultures (7 out of 8) demonstrated microbiological clearance following cefiderocol administration. While directly comparing our findings with clinical trial data is challenging, it is important to consider that, in the context of HAP-VAP, the development of in vivo resistance could reflect exposure to subtherapeutic concentrations of cefiderocol at the pulmonary level, potentially facilitating MIC increases [47]. However, further studies are needed to explore this hypothesis in greater detail.

In our study, all clinical failures were associated with all-cause in-hospital mortality, with no evident benefit observed for combination therapy over monotherapy or for first-line therapy compared to subsequent treatments. Notably, even when applying a broader mortality criterion (in-hospital mortality) that included patients who died more than 3 months after the diagnosis of bacteremia, the mortality rate in our cohort remained lower than the approximately 60% reported in the literature [3, 30–33]. However, accurately attributing mortality directly to S. maltophilia BSI is challenging, as these infections may act more as an indicator of patient severity rather than a primary cause of death [3, 30–33]. This hypothesis is further supported by the clinical profiles of the three patients who died in our study, all of whom had critical underlying conditions, including severe burn injuries, terminal-stage oncohematologic diseases, and prolonged intensive care unit stays.

In our study, cefiderocol was administered for a duration of up to 22 days. Although we did not specifically address safety issues, none of the patients required treatment discontinuation due to adverse events, confirming the drug's good tolerability, consistent with findings from previous studies [23, 24].

This study has several limitations. The most significant is the small sample size, as we were able to include only eight patients, which limits the generalizability of our conclusions. Second, the decision to initiate cefiderocol therapy, the use of concomitant antibiotics, and the duration of treatment were determined by the treating physicians rather than predefined criteria. This lack of uniformity may complicate the interpretation of cefiderocol’s role in the treatment of BSI. Third, although four patients were derived from a large retrospective database, the remaining four were included from previously published studies, introducing the potential for publication bias. Additionally, the retrospective nature of the data collection and the reliance on case reports from existing literature result in significant gaps in information, including details of patients’ medical histories and susceptibility profiles of the isolates. For example, MIC values were not reported for most cases. Lastly, the follow-up duration was inconsistent and limited to only a few days after cefiderocol withdrawal, which may have hindered the detection of recurrences or the evaluation of the long-term effects of treatment in this population.

Conclusions

The results of our analysis support the use of cefiderocol as an effective therapeutic option for managing BSI caused by multidrug-resistant S. maltophilia, including in frail, critically ill, or medically unstable patients. However, larger studies addressing the role of combination therapy are needed.

Author Contributions

Conceptualization: Antonio Vena, Matteo Bassetti; Methodology: Antonio Vena, Laura Mezzogori, Nadia Castaldo, Silvia Corcione, Renato Pascale; formal analysis: Antonio Vena, Laura Mezzogori, Nadia Castaldo, Silvia Corcione, Renato Pascale; Data curation: Antonio Vena, Laura Mezzogori, Nadia Castaldo, Silvia Corcione, Renato Pascale, Maddalena Giannella, Simone Mornese Pinna, Daniele Roberto Giacobbe, Davide Fiore Bavaro, Vincenzo Scaglione, Benedetta Fumarola, Gabriele Pagani, Francesco Giuseppe De Rosa, Michele Bartoletti, Matteo Bassetti Curation: Antonio Vena, Laura Mezzogori, Nadia Castaldo, Silvia Corcione, Renato Pascale, Maddalena Giannella, Simone Mornese Pinna, Daniele Roberto Giacobbe, Davide Fiore Bavaro, Vincenzo Scaglione, Benedetta Fumarola, Gabriele Pagani, Francesco Giuseppe De Rosa, Michele Bartoletti, Matteo Bassetti; Writing—original draft preparation: Antonio Vena, Laura Mezzogori, Nadia Castaldo, Silvia Corcione; Writing—review and editing: Antonio Vena, Laura Mezzogori, Nadia Castaldo, Silvia Corcione, Renato Pascale, Maddalena Giannella, Simone Mornese Pinna, Daniele Roberto Giacobbe, Davide Fiore Bavaro, Vincenzo Scaglione, Benedetta Fumarola, Gabriele Pagani, Francesco Giuseppe De Rosa, Michele Bartoletti, Matteo Bassetti.

Funding

This study was supported by an independent medical grant from Pfizer, Shionogi & Co., Ltd and Tillotts Pharma, AG. The funders have no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The funds required for the publication of the study will be drawn from the budget of our affiliated universities and hospitals, specifically allocated for this type of expense.

Data Availability

The data presented in this study will be available from the corresponding author on reasonable request and provided all regulatory and privacy requirements are fulfilled.

Declarations

Conflict of Interest

Outside the submitted work, Antonio Vena reports research grants and/or personal fees for advisor/consultant and/or speaker/chairman from Gilead, Menarini, MSD, Pfizer, Astella and Shionogi. Outside the submitted work, Matteo Bassetti reports research grants and/or personal fees for advisor/consultant and/or speaker/chairman from BioMérieux, Cidara, Gilead, Menarini, MSD, Pfizer and Shionogi. Outside the submitted work, Daniele Roberto Giacobbe reports investigator-initiated grants from Pfizer Inc., Shionogi, BioMérieux and Gilead Italia, and personal fees for advisor/speaker from Pfizer Inc., Menarini and Tillotts Pharma. Laura Mezzogori, Nadia Castaldo, Silvia Corcione, Renato Pascale, Maddalena Giannella, Simone Mornese Pinna, Davide Fiore Bavaro, Vincenzo Scaglione, Benedetta Fumarola, Gabriele Pagani, Francesco Giuseppe De Rosa and Michele Bartoletti have nothing to declare. Matteo Bassetti and Daniele Roberto Giacobbe are Editorial Board members of Infectious Diseases and Therapy. Matteo Bassetti and Daniele Roberto Giacobbe were not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions.

Ethical Approval

The study was approved by the institutional review board of the coordinating centre (Comitato Etico interaziendale, City of Health and Sciences, Turin, pratica no. 202/2023, PROT.N. 0066633) and was in accordance with the declaration of Helsinki. Informed consent was deemed unnecessary due to the retrospective nature of the study. STROBE recommendations were followed.