Sir,

Infections caused by carbapenem-resistant Acinetobacter baumannii are often responsible for severe hospital-acquired infections, such as ventilator-associated pneumonia and bloodstream infections, and are associated with high morbidity and mortality among critically ill or immunocompromised patients, while therapeutic options remain extremely limited [1]. An expert consensus highlighted the role and appropriate use of cefiderocol in infections caused by carbapenem-resistant non-fermenting Gram-negative bacilli, supporting its effectiveness in A. baumannii infections, and suggesting lower mortality and markedly reduced nephrotoxicity compared with colistin-based regimens [1].

Cefiderocol (FDC) is a crucial salvage treatment for multidrug-resistant (MDR) Gram-negative bacteria infections (GNBIs) [2]. FDC (Fetroja^®) is approved for treating serious GNBIs in adults, specifically complicated Urinary Tract Infections (cUTIs), including pyelonephritis, and hospital-acquired bacterial pneumonia (HABP)/ventilator-associated bacterial pneumonia (VABP), especially when other treatments are not effective [3]. FDC is reserved for patients with limited or no other treatment options due to its role as a last-resort antibiotic [3]. It’s effective against resistant bacteria, including those producing Extended-Spectrum β-Lactamases (ESBLs) and carbapenemases [3-4].

A comprehensive study confirmed the importance of FDC as a last-resort option for patients with GNBIs [2]. A recent large multicentre retrospective study, the CEFI-BAC study, described the distribution of anatomical sites of infections in 239 patients with MDR GNBIs treated with FDC as monotherapy or combination therapy in a real-world setting; however, the study did not include patients with infective endocarditis (IE) [4].

The objective of our study is to report what we believe to be the first case described in the literature of native-valve IE caused by MDR A.baumannii treated with FDC in combination with tigecycline (TGC) and colistin (COL).

A 50-year-old woman patient with end-stage renal disease undergoing intermittent haemodialysis was admitted to our hospital in July 2025 with septic shock. On admission, the patient was febrile, and her blood pressure was 90/60 mmHg. A chestcomputed tomography scan documented multiple embolic pulmonary abscesses. A transthoracic echocardiogram (TTE) showed multiple motile vegetations, the largest measuring 14 x 6 mm, adhered to the tricuspid valve, as well as a motile vegetation measuring 8 x 4 mm in the right atrium. Multiple blood cultures were positive for A.baumannii. The minimum inhibitory concentration (MICs, mg/L) and antimicrobial susceptibility (S: susceptible and R: resistant) of the A. baumannii strain, according to EUCAST criteria, were as follows: gentamycin >8 mg/L (R); ciprofloxacin >2 mg/L (R); amikacin >32 (R): meropenem >8 (R); colistin <=0.5 (S); cotrimoxazole >160/40 (R); and cefiderocol <1 mm (S).

Based on the modified Duke criteria, clinical signs and symptoms of the patient fulfil the criteria for tricuspid and right atrial IE. The arteriovenous fistula was not considered the source of bacteraemia. Arterial catheter-drawn blood cultures were negative, while venipuncture-drawn blood cultures resulted positive. The blood test showed an elevated white blood cell count of 32,340/mm³ with neutrophilia of 91.6% and a platelet count of 42,000/mm³; C-reactive protein was 345 mg/L and procalcitonin was 14.092 ng/mL. Inotropic support was begun, with empirical antibiotic therapy including linezolid and piperacillin–tazobactam, subsequently changed to FDC 750 mg 2 times per day by 6-hour extended infusion, after a 2 g loading dose, TGC, 50 mg 2 times per day after a 100 mg loading dose, and COL, 1.15 MIU 2 times per day on non-dialysis days, 1.5 MIU 2 times per day after dialysis. The dosages of FDC and COL were adjusted according to the modality of extracorporeal renal support. The interval between the first positive blood cultures and the initiation of targeted antimicrobial therapy was three days. The patient remained on intermittent haemodialysis, through the arteriovenous fistula. Blood cultures became negative after just 3 days of targeted antibiotic therapy, remaining negative at 7, 14 and 21 days. Surgical management of IE was considered, but an excessive surgical risk existed. A TEE was repeated every ten days, showing a gradual improvement in the endocarditic vegetation. On the 40th day of therapy, the tricuspid and right atrium vegetations disappeared on TEE, and blood cultures resulted negative. However, while waiting to complete six to eight weeks of antibiotic therapy, on the 43rd day a fulminant episode of congestive heart failure during haemodialysis occurred, resulting in the patient’s death.

Including the present report, the analysis of the current literature through PubMed, Scopus and the Cochrane Library, revealed seven cases of endocarditis treated with FDC (Table 1): three cases due to XDR Acinetobacter, two cases caused by MDR Pseudomonas aeruginosa, and two further cases caused by MDR Achromobacter xylosoxidans [5-10].

The cohort comprised four men and three women with a mean age of 67.57 years; there were two deaths and five recoveries. The aortic valve was affected in five cases and the tricuspid valve in one, while one patient had ICD-associated infective endocarditis [7]. FDC was administered as monotherapy in a single patient [6], whereas in the remaining cases, it was used in various combinations with other antibiotics. Of note is the recent use of FDC in combination with eravacycline [9-10]. Two patients also required surgery, and one patient required ICD replacement. All patients, except for two, one from the present report and a second described by Salvati A et al. [10], recovered.

To the best of our knowledge, there are no reported cases of MDR A. baumannii native valve IE treated with FDC [5-10]. This reported case adds to the limited clinical experience supporting FDC-based regimens in selected cases of multidrug-resistant A. baumannii IE.

Clinicians should exercise caution and obtain susceptibility testing especially when considering FDC monotherapy [11-12]. Determining whether monotherapy or combination therapy is more appropriate for MDR-induced GNBIs remains a matter of debate. Although no overall benefit from combination therapy appears to exist in real-world settings [12], it has been associated with improved 28-day survival in selected high-risk patients.

Lou L et al. [9] reported that eravacycline combined with cefiderocol may represent a novel and effective treatment option for refractory IE caused by carbapenem-resistant A.baumannii.

In the literature there is evidence of 29 cases of native valve IE and of 17 cases of prosthetic valve IE [14]. Regarding native valve endocarditis, the cases involved 20 males and 2 females, while demographic information was unavailable for two cases; specifically, two patients absconded from the hospital, and no further information about them was obtained.

The mean age was 35.33 years; excluding the single 8-year-old paediatric patient, the mean age was 36.38 years. The aortic valve was affected in 14 cases, the mitral valve in another 14, the tricuspid valve in three, and the pulmonary valve in one.

Involvement of multiple valves was identified in 4 cases: aortic and mitral in one case, aortic and tricuspid in one case, and aortic, mitral, and tricuspid in one patient. A thrombus-like mass was detected in two patients: one case involved the right atrium, while the other involved the left ventricle. Survival was observed in 18 patients, whereas 12 patients died.

Regarding the 17 cases of prosthetic valve endocarditis, the aortic valve was involved in 11 cases, the mitral valve in 6, and the tricuspid valve in one patient; finally, involvement of both the aortic and mitral valves occurred in 2 patients. Of the 17 patients, 12 were male and 5 were female, with a mean age of 60.58 years. A favourable outcome was observed in 10 patients, while 7 patients unfortunately died. There was evidence of 5 cases of endocarditis caused by MDR strains: 4 involved native valves (2 deaths, 2 survivors) and 1 involved a prosthetic valve and resulted in death. There was also evidence of 11 cases of XDR Acinetobacter endocarditis, with 7 deaths and 4 favourable outcomes; 5 cases involved native valves and another 5 involved prosthetic valves. Finally, 1 case of infection caused by an XDR strain resulted in CIED-related endocarditis in an 82-year-old Italian woman who died.

Author contributions

Conceptualización: AM, SG. Investigación: AM, SG. Análisis formal: AM. Metodología: AM. Validación: AM. Supervisión: AM, SG. Redacción – borrador original: AM. Redacción – revisión y edición: AM, SG. All authors have read and approved the final version of the manuscript.

Conflict of interest

The authors declare that there are no conflicts of interest.

References

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