2025/04/29 by Carlo Pallotto, M Benvenuto, Daniela Francisci · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Antibiotic Resistance in Bacteria #Antibiotics Pharmacokinetics and Efficacy #Orthopedic Infections and Treatments
paper · pdf · doi:10.1093/jacamr/dlaf087
openalex publication_date 2025/04/29 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30
Carbapenem-resistant Acinetobacter baumannii (CRAB) is a significant cause of hospital-acquired infections and has a high mortality rate.1 Acinetobacter spp. are a rare cause of shoulder prosthetic joint infection (PJI); its incidence ranges from 0.6% to 1.2%.2 Even Pseudomonas aeruginosa (PA) is rarely isolated from PJI (3%–5%).3 Limited treatment options are currently available for CRAB, such as cefiderocol, ampicillin/sulbactam, fosfomycin and minocycline, in monotherapy or combination.4 Fosfomycin is a broad-spectrum bactericidal antibiotic that inhibits the synthesis of the bacterial cell wall of both Gram-negative and Gram-positive bacteria.5 In combination with other antibiotics (e.g. cefiderocol) fosfomycin has been used in the treatment of CRAB infections,1 and increasing evidence is available about its use as outpatient parenteral antibiotic treatment (OPAT).6 We describe a case of shoulder PJI due to WT carbapenem-susceptible PA and CRAB that was successfully treated using a two-step surgical procedure and antibiotic therapy with ciprofloxacin by mouth (PO), minocycline PO, and fosfomycin administered by an elastomeric pump as OPAT. An 85-year-old man underwent a right shoulder prosthesis implantation because of a humerus fracture in June 2023. After 9 weeks, a fistula on the right shoulder was detected and rare colonies of WT PA were isolated by a fistula swab. At Week 13, the patient was evaluated by an infectious diseases specialist for the first time. The patient was afebrile; blood tests showed a slight increase in C-reactive protein (CRP) (2.1 mg/dL). As a consequence of the diagnosis of PJI and of microbiological data, surgery was recommended as primary treatment, but the patient categorically refused. Therefore, chronic suppressive antibiotic therapy with ciprofloxacin 750 mg twice daily was recommended. After 8 weeks the patient stopped the treatment of his own accord, but at Week 34 the fistula, which had healed during ciprofloxacin administration, reappeared and the patient asked for a new evaluation. The prosthesis was removed, and a spacer was placed at Week 37. WT PA (ciprofloxacin MIC 0.25 mg/L) and CRAB (minocycline MIC ≤4 mg/L) were isolated from sonicated prosthesis material (all the different components) and the single intraoperative bone and soft tissues samples. As a consequence, a new antibiotic regimen was started with ciprofloxacin 750 mg twice daily orally and minocycline 200 mg twice daily orally due to the unwillingness of the patient to be hospitalized. In addition, continuous-infusion fosfomycin (20 g every 24 h) was administered using an elastomeric pump after the insertion of a peripherally implanted central catheter. Renal function was in the range of normality (estimated glomerular filtration rate 86 mL/min). Fosfomycin was chosen due to its synergistic potential both against PA in combination with ciprofloxacin and against CRAB with minocycline and its potential administration as OPAT.7,8 Over the 14 week course of this treatment, the patient was regularly monitored by periodic blood tests. Due to the treatment with fosfomycin, the following adverse effects were detected: mild hypokalaemia corrected with potassium oral supplementation, and oral cavity candidiasis, treated with nystatin. After treatment initiation, the surgical wound rapidly healed. Blood tests, including neutrophil leucocyte count and CRP count, were normal. The second step of the surgical treatment was performed only 29 weeks after the placement of the spacer to remove it and implant a new prosthesis on the right shoulder. From Week 14 to Week 29 fosfomycin was discontinued while ciprofloxacin and minocycline were still administered. Spacer intraoperative samples were negative on culture as well as the sonicated material. Ciprofloxacin and minocycline were stopped on Day 15 after last implantation. In the postoperative period, the patient underwent a clinical, radiological and biochemical follow-up. The surgical wound rapidly healed. After about 5 months, no signs nor symptoms of infection were detected. The available data regarding the use of fosfomycin for the treatment of CRAB infections are limited. Different studies suggest a possible role for combination therapy with fosfomycin and cefiderocol for the treatment of severe CRAB infections.1 Minocycline is also a treatment option for CRAB infections when used as a component of a combination regimen due to a high susceptibility rate.4 Regarding the use of fosfomycin in combination with minocycline, their synergistic bactericidal effect was demonstrated in vitro.8 In the setting of PJI when a fully oral regimen is not adequate to guarantee the eradication of the infection, OPAT can be used.9 Due to its stability for at least 5 days at a storage temperature between 4°C and 34°C, fosfomycin is eligible in a continuous infusion in the context of OPAT.10 This work has several limitations as a single case report. Moreover, synergistic tests between the administered antibiotics were not performed. On the other hand, in our case report, the use of an OPAT regimen with IV fosfomycin administered by an elastomeric pump in combination with ciprofloxacin and minocycline was effective—together with surgery—in the treatment of polymicrobial PJI due to CRAB and PA. A combination therapy involving fosfomycin administered as OPAT can also be a possible option for difficult-to-treat Gram-negative PJI; it could provide the possibility of a shorter hospital stay thereby improving the quality of life of patients. Further studies are needed to better explore this treatment strategy. This study was carried out as part of our routine work. The authors have no conflicts of interests to declare.