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Dalbavancin is a novel, long-acting lipoglycopeptide characterized by a long elimination half-life coupled with excellent in vitro activity against multidrug-resistant Gram-positives. Although it is currently approved only for the treatment of acute bacterial skin and skin structure infections, an ever-growing amount of evidence supports the efficacy of dalbavancin as a long-term therapy in osteomyelitis, prosthetic joint infections, endocarditis, and bloodstream infections. This article provides a critical reappraisal of real-world use of dalbavancin for off-label indications. A search strategy using specific keywords (dalba-vancin, osteomyelitis, endocarditis, long-term suppressive therapy, bloodstream infection, pharmacokinetic/pharmacodynamic profile) until April 2021 was performed on the PubMed-MEDLINE database. As for other novel antibiotics, a conundrum between approved indications and potential innovative therapeutic uses has emerged for dalbavancin as well. The promising efficacy in challenging scenarios (i.e., osteomyelitis, endocarditis, prosthetic joint infections), coupled with the unique pharmacokinetic/pharmacodynamic properties, makes dalbavancin a valuable alternative to daily in-hospital intravenous or outpatient antimicrobial regimens in the treatment of long-term Gram-positive infections. This makes dalbavancin valuable in the current COVID-19 scenario, in which hospitalization and territorial medicine empowerment are unavoidable. Keywords: dalbavancin, osteomyelitis, endocarditis, long-term suppressive therapy, PK/PD properties, COVID-19

Here we describe a case of a methicillin-resistant coagulase-negative staphylococci prosthetic valve endocarditis in a patient considered not eligible for valve replacement due to high perioperative mortality risk and who did not tolerate oral antibiotic treatment. Under these circumstances, intravenous long-term chronic suppressive antibiotic therapy with dalbavancin, scheduling the doses using the serum bactericidal activity titers, proved to be safe and effective.

Discussion remains concerning the safety and tolerability of anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST) in older patients with aplastic anaemia (AA). Using data of 127 consecutive patients from the Dutch adult AA registry, we evaluated long-term treatment success of standard ATG-based IST as first-line treatment with a multi-state model. Only one death was potentially associated with ATG. Overall survival at 5 years was 79%. We defined Transplantation-, Treatment- and Disease-Free Survival (TT-DFS) as the ultimate success of this treatment. This means that a patient is alive, is currently transfusion-independent without having received an allogeneic stem cell transplantation, has not developed AML or MDS, and has stopped all medication for AA. The probability of TT-DFS was 42% at 5 years after start of IST. In patients younger than 40 years ( n  = 36) and in patients aged 60 or above ( n  = 53), this was 58% and 34%, respectively. Older age, more severe AA and absence of a PNH-clone of ≥ 1% all reduced the likelihood of reaching TT-DFS. These analyses on unselected nationwide data indicate that ATG-based IST is effective and safe also in older patients. They suggest that age, AA severity and presence of a PNH-clone should be taken into account when considering this treatment in older patients.

Background: Lifelong antibiotic therapy can be used as a strategy to manage chronic infections deemed incurable. While this may be beneficial in suppressing infections, its long-term consequences remain underexplored. Methods: Conducted at a tertiary healthcare network in Melbourne, Australia, this 10-year longitudinal observational study, starting in 2015, followed up an initial cohort of 29 patients prescribed suppressive long-term antibiotics. Data extracted from medical records included patient demographics, antibiotic use, adverse events, mortality, and Charlson Comorbidity Index scores. Outcomes were assessed using descriptive statistics. Results: Of the original cohort of 29 patients in 2015, 19 were still alive at the five-year follow-up, with 14 of those continuing antibiotic therapy. At the 10-year follow-up, an additional three patients had died (total 11/29; 38%), and one had ceased antibiotics (total 6/29; 21%). Notably, none of the patients who had previously ceased antibiotics resumed therapy. Four patients were lost to follow-up, and only two patients were seen by infectious disease specialists for their long-term antibiotic therapy. Ultimately, of the original 29 patients initially recruited, only seven patients were confirmed to remain on antimicrobials by the 10-year follow-up. Conclusions: This 10-year prospective study highlights the complexities of lifelong antibiotic therapy. While some patients may benefit from prolonged antibiotic therapy with prevention of relapsed infection, the high burden of comorbidities, therapy adjustments, and hospitalizations remains a challenge. Long-term care strategies and individualized treatment approaches are essential. Further research is needed to optimize outcomes and refine criteria for lifelong antibiotic use and its management.

Background Conflicting results has been reported regard osteoporosis and fractures in patients with Differentiated Thyroid Cancer (DTC). Our objective was to evaluate the long‐term effects of TSH suppression therapy with Levothyroxine (LT4) on trabecular bone score (TBS) and bone mineral density (BMD) in females with DTC after thyroidectomy. Methods About 145 women with resected DTC and receiving long‐term TSH therapy, were stratified according to the degree of TSH suppression. Mean duration of follow‐up was 12.3 ± 6.1 years. BMD and TBS, were assessed using dual‐energy X‐ray absorptiometry (DXA) and TBS iNsight (Med‐Imaps), at baseline (1‐3 months after surgery) and at the final study visit. Results In patients stratified by duration of TSH suppression therapy (Group I, 5‐10 years; Group II, >10 years), slight increases from baseline TSH levels were observed. Significant decreases in LS‐BMD and FN‐BMD were seen in patients after >10 years. TBS values were lower in Groups I (1.289 ± 0.122) and II (1.259 ± 0.129) compared with baseline values (P = .0001, both groups). Regarding the degree of TSH suppression, TBS was significantly reduced in those with TSH < 0.1 µU/mL (P = .0086), and not in patients with TSH suppression of 0.1.‐0.5 or >0.5 µU/mL. Conclusions We found deterioration of trabecular structure in patients with DTC and TSH suppression therapy below 0.1 µU/mL and after 5‐10 years of follow‐up. Significant changes in BMD according to TSH levels were not observed. Trabecular Bone Score is a useful technique for identifying thyroid cancer patients with risk of bone deterioration. There is a debate respect the effect of long‐term TSH suppression therapy in Thyroid Cancer. We have demonstrated according to the degree of suppression and duration (Group I, 5‐10 years; Group II, >10 years): TBS values were lower in Groups I (1.29 ± 0.12) and II (1.26 ± 0.13) compared with baseline values while decreases in L‐BMD and FN‐BMD were seen in patients after >10 years. Regarding the degree of TSH suppression, TBS was significantly reduced in those with TSH < 0.1 µU/mL (P = .0086), and not in patients with TSH suppression of 0.1.‐0.5 or >0.5 µU/mL. We described for the first time deterioration of trabecular structure in patients with DTC and TSH suppression therapy below 0.1 µU/mL and after 5‐10 years of follow‐up. Significant changes in BMD according to TSH levels were not observed. Therefore we support Trabecular Bone Score as a useful technique for identifying thyroid cancer patients with risk of bone fracture.

The aim was to describe the safety of indefinite administration of antibiotics, the so-called suppressive antibiotic therapy (SAT) and to provide insight into their impact on gut microbiota. 17 patients with SAT were recruited, providing a fecal sample. Bacterial composition was determined by 16S rDNA massive sequencing, and their viability was explored by PCR-DGGE with and without propidium monoazide. Presence of antibiotic multirresistant bacteria was explored through the culture of feces in selective media. High intra-individual variability in the genera distribution regardless of the antibiotic or antibiotic administration ingestion period, with few statistically significant differences detected by Bray-Curtis distance-based principle component analysis, permutational multivariate analysis of variance and linear discriminant analysis effect size analysis. However, the microbiota composition of patients treated with both beta-lactams and sulfonamides clustered by a heat map. Curiously, the detection of antibiotic resistant bacteria was almost anecdotic and CTX-M-15-producing E. coli were detected in two subjects. Our work demonstrates the overall clinical safety of SAT and the low rate of the selection of multidrug-resistant bacteria triggered by this therapy. We also describe the composition of intestinal microbiota under the indefinite use of antibiotics for the first time.