Bacteriophage therapy has recently attracted increased interest, particularly in difficult-to-treat infections. Although it is not a novel concept, standardized treatment guidelines are currently lacking. We present the first steps towards the establishment of a “multidisciplinary phage task force” (MPTF) and a standardized treatment pathway, based on our experience of four patients with severe musculoskeletal infections. After review of their medical history and current clinical status, a multidisciplinary team found four patients with musculoskeletal infections eligible for bacteriophage therapy within the scope of Article 37 of the Declaration of Helsinki. Treatment protocols were set up in collaboration with phage scientists and specialists. Based on the isolated pathogens, phage cocktails were selected and applied intraoperatively. A draining system allowed postoperative administration for a maximum of 10 days, 3 times per day. All patients received concomitant antibiotics and their clinical status was followed daily during phage therapy. No severe side-effects related to the phage application protocol were noted. After a single course of phage therapy with concomitant antibiotics, no recurrence of infection with the causative strains occurred, with follow-up periods ranging from 8 to 16 months. This study presents the successful outcome of bacteriophage therapy using a standardized treatment pathway for patients with severe musculoskeletal infection. A multidisciplinary team approach in the form of an MPTF is paramount in this process.

In times where only a few novel antibiotics are to be expected, antimicrobial resistance remains an expanding global health threat. In case of chronic infections caused by therapy-resistant pathogens, physicians have limited therapeutic options, which are often associated with detrimental consequences for the patient. This has resulted in a renewed interest in alternative strategies, such as bacteriophage (phage) therapy. However, there are still important hurdles that currently impede the more widespread implementation of phage therapy in clinical practice. First, the limited number of good-quality case series and clinical trials have failed to show the optimal application protocol in terms of route of administration, frequency of administration, treatment duration and phage titer. Second, there is limited information on the systemic effects of phage therapy. Finally, in the past, phage therapy has been applied intuitively in terms of the selection of phages and their combination as parts of phage cocktails. This has led to an enormous heterogeneity in previously published studies, resulting in a lack of reliable safety and efficacy data for phage therapy. We hereby present a study protocol that addresses these scientific hurdles using a multidisciplinary approach, bringing together the experience of clinical, pharmaceutical and molecular microbiology experts.

Vancomycin is commonly used in outpatient parenteral antimicrobial therapy (OPAT) of Gram-positive infections. Therapeutic drug monitoring and adverse event monitoring pose a challenge. Outcome data of vancomycin in OPAT (vOPAT) are limited. The study aim was to report the safety and efficacy of a structured vOPAT program implemented in the University Hospitals Leuven. The program provides continuous elastomeric infusion of vancomycin at home with biweekly follow-up at the outpatient clinic. Demographics, clinical, biochemical and treatment parameters, target attainment parameters and clinical outcomes were recorded. An e-survey was conducted to assess patient satisfaction. Thirty-five vOPAT episodes in 32 patients were included. During 206 follow-up consultations, 203 plasma concentration measurements were registered with a median vancomycin plasma concentration of 22.5 mg/L (range 6.6–32.0). The majority of concentrations (68.5%) were within the therapeutic range (20.0–25.0 mg/L). Adverse event rates, including drug- (5.7%) and catheter-related (5.7%) events, were low. For 32 vOPAT episodes, a clinical cure rate of 100% was observed. All patients who completed the e-survey were satisfied with their vOPAT course. These findings show that a structured vOPAT program with rigorous follow-up provides safe and effective ambulatory treatment of patients with vancomycin in continuous infusion.

Aspergillus fracture-related infection (FRI) is a rare, but severe complication in trauma surgery. The optimal antifungal treatment for Aspergillus osteomyelitis, including FRI, has not been established yet, as only cases have been documented and data on bone penetration of antifungal drugs are scarce. We describe a patient with Aspergillus fumigatus FRI of the tibia who was treated with isavuconazole after developing liver function disturbances during voriconazole therapy. Isavuconazole, the active moiety formed after hydrolysis of the prodrug isavuconazonium sulfate by plasma esterases, was administered in a maintenance dose of 200 mg q24 h, followed by 150 mg q24 h. The patient completed a six-month antifungal treatment course. Although fracture union was not achieved during six months of follow-up after therapy cessation, no confirmatory signs of FRI were observed. Additionally, two literature searches were conducted to review available data on antifungal treatment of Aspergillus osteomyelitis and bone penetration of antifungals. One hundred and eight cases of Aspergillus osteomyelitis, including six (5.6%) FRI cases, were identified. Voriconazole and (lipid formulations of) amphotericin B were the most commonly used antifungals. In three (2.8%) cases isavuconazole was prescribed as salvage therapy. Data on antifungal bone penetration were reported for itraconazole, voriconazole, amphotericin B, anidulafungin and 5-fluorocytosin. Isavuconazole might be a promising alternative for the treatment of Aspergillus osteomyelitis. However, standardized case documentation is needed to evaluate the efficacy of isavuconazole and other antifungals in the treatment of Aspergillus osteomyelitis, including FRI.

The National Reference Center for Hantavirus in Belgium is currently using the Hantavirus IgM/IgG ELISA Progen kit (Heidelberg, Germany) for the detection of the most prevalent Hantavirus in Western Europe, Puumala virus (PUUV). Two commercially available PUUV kits were compared: Progen and RIDASCREEN^® Hantavirus Puumala IgM/IgG ELISA assay (Darmstadt, Germany). Methods: The sensitivity was evaluated with a panel of 68 samples from patients with an acute infection (n = 44) or a past infection (n = 24). Specificity was evaluated with a panel of 62 samples from patients with potentially false borderline results (n = 7) (no seroconversion), seronegative samples (n = 25) and potentially cross reacting samples (n = 30). Discordances were resolved by immunoblot. Substantial agreement was calculated using Cohen kappa coefficient. Results: The RIDASCREEN^® kit showed a higher specificity (IgM: 94.3%; IgG: 94.4%) than the Progen kit (IgM: 77.0% IgG: 93.0%). The sensitivity for IgM ELISA was 100% for both assays. IgG sensitivity was, respectively, 98.3% and 100% for Progen and RIDASCREEN^®. A Cohen kappa coefficient of 0.76 and 0.90 was found between Puumala IgM and IgG, respectively. Conclusions: This study showed a higher specificity for the RIDASCREEN^® kit than the Progen kit, while the sensitivity was as good as for the Progen kit.