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Infections of cardiac implantable electronic devices (CIEDs) and vascular grafts are some of the most dreaded complications of these otherwise life-saving devices. Many of these infections are not responsive to conventional treatment, such as systemic antibiotics and surgical irrigation and debridement. Therefore, innovative strategies to prevent and manage these conditions are warranted. Among these, there is an increasing interest in phages as a therapeutical option. In this review, we aim to collect the available evidence for the clinical application of phage therapy for CIED and vascular graft infections through literature research. We found 17 studies for a total of 34 patients. Most of the indications were left ventricular assist device (LVAD) (n = 20) and vascular graft infections (n = 7). The bacteria most often encountered were Staphylococcus aureus (n = 18) and Pseudomonas aeruginosa (n = 16). Clinical improvements were observed in 21/34 (61.8%) patients, with microbiological eradication in 18/21 (85.7%) of them. In eight cases, an adverse event related to phage therapy was reported. Phage therapy is a promising option for difficult-to-treat CIED and vascular graft infections by means of an individualized approach. Clinical trials and expanded access programs for compassionate use are needed to further unveil the role of phage therapy in clinical application. [ABSTRACT FROM AUTHOR]

Background Native vertebral osteomyelitis (NVO) caused by Staphylococcus aureus is associated with high risk of treatment failure and increased morbidity. The role of rifampin-based therapy for the treatment of this condition is controversial. The goal of this systematic review and meta-analysis is to explore the efficacy and safety of rifampin-based therapy for the treatment of S. aureus NVO. Methods We searched Cochrane, Embase, Medline, Scopus, and Web of Science databases for studies published up to May 2023, focusing on adults with NVO treated with or without rifampin-containing regimens. A random-effects model meta-analysis estimated relative risks and risk difference with 95% confidence intervals (CI). Results Thirteen studies (2 randomized controlled trials and 11 comparative cohort studies), comprising 244 patients with S. aureus NVO who received rifampin and 435 who did not, were analyzed. Meta-analysis showed that rifampin-based regimens were associated with lower risk of clinical failure (risk difference, −14%; 95% CI, −19% to −8%; P <.001; I 2 = 0%; relative risk, 0.58; 95% CI,.37–.92, P =.02, I 2 = 21%). Only 1 study reported on adverse events. All studies had a high or uncertain risk of bias, and the certainty of evidence was rated as very low. Conclusions Adjunctive rifampin therapy might be associated with lower risk of S. aureus NVO treatment failure; however, the low certainty of evidence precludes drawing definitive conclusions that would alter clinical practice. A randomized trial is necessary to corroborate these findings. [ABSTRACT FROM AUTHOR]

Dalbavancin is a long-acting lipoglycopeptide that is registered for the treatment of acute bacterial skin and skin structure infections, and it is also increasingly used for infections that require prolonged antibiotic treatment. Here, we present the results from the first 2 years of a service set up in December 2021 for the therapeutic drug monitoring (TDM) of dalbavancin in clinical settings. In particular, we compared the trough concentration (Cmin) to maximum concentration (Cmax) in patients with osteoarticular infections receiving prolonged treatment with dalbavancin. Log-linear regression models were used to estimate the timing of dalbavancin administration with the goal of maintaining Cmin concentrations of >8 mg/L in the two TDM-based strategies. From December 2021 to November 2023, 366 TDMs of dalbavancin from 81 patients were performed. The Cmin and Cmax concentrations of dalbavancin ranged from 4.1 to 70.5 mg/L and from 74.9 to 995.6 mg/L, respectively. With log-linear regression models, we estimated that each injection should be administered every 42–48 days to maintain the Cmin concentrations. Out of the 81 patients, 37 received at least three doses of dalbavancin for the treatment of osteoarticular infections. Despite there being no significant differences in the days of dalbavancin treatment (130 ± 97 versus 106 ± 102 days), the patients in the Cmax-based TDM group received a significantly lower number of dalbavancin injections (5.2 ± 1.8 versus 7.3 ± 2.6 injections, p = 0.005), and they were administered over a longer period of time (40 ± 10 versus 29 ± 14 days, p = 0.013) than in the Cmin-based TDM group. In conclusion, Cmax-based TDM was associated with a significant reduction in the inter-individual variability of dalbavancin concentrations and lower drug dosing frequency than those of Cmin-based TDM. This approach could, therefore, favor a more rational and targeted use of dalbavancin in patients requiring prolonged treatment. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is the most common sexually transmitted infection, linked to several types of lesions. HPV, specifically HPV 16, accounts for most of anal cancer cases. In this study, we evaluated the proportion of samples tested positive for HPV and characterized genotypes distribution in anal specimens collected from individuals at risk of anal HPV infection attending from 2018 to 2022 a large Infectious Diseases Department in Italy. The presence of HPV DNA was investigated through a commercial kit detecting 12 HR‐HPV, 8 probable/possible HR‐HPV, and 8 LR‐HPV genotypes. Among 1514 samples, 84% (1266/1514) resulted positive for any type of HPV. The prevalence of high‐risk HPV types remained high during all the years of the study period, from 2018 to 2022, ranging from 65% to 73%. Most of HR‐HPV, LR‐HPV and HPV 16 positive samples were collected from men >45 years. HPV 16 was also the most frequent type in men and women. We did not observe significant variations between years in detection of HR‐HPV, instead of LR‐HPV, that significantly decreased. In conclusion, the high prevalence of oncogenic HPV genotypes underlines the necessity of clear anal HPV screening guidelines and, along with frequent HR‐HPV coinfections, reinforces the urge to intensify the anti‐HPV vaccination campaign. [ABSTRACT FROM AUTHOR]

Cystoisospora belli causes intestinal infection in immunocompromised hosts, including human immunodeficiency viruses (HIV)-positive patients, especially from tropical and sub-tropical areas, with watery and recurrent diarrhea, leading in advanced cases to malabsorption and death. Microbiological diagnosis is limited by intermittent or low shedding of oocysts in stool; therefore, endoscopy may be necessary to identify the pathogen in histological samples. Trimethoprim-sulfamethoxazole (TMP-SMX) represents the treatment of choice, and alternative agents are used in recurrences, but limited efficacy is described. Here, we present recently observed case of severe and fatal infection due to C. belli in a HIV-positive 40-year-old man from Brazil, revealing several limitations in diagnosis and therapy, which need to be investigated further. In particular, it is still not clear how the infection persisted over time leading to malabsorption, kidney injury, and subsequent death, even if a reasonable immune reconstitution was demonstrated. Additionally, we investigated what mechanisms might cause, whether failure of recovery of the immune response specifically to C. belli, drug malabsorption, resistance to TMP-SMX, sequestration into lymphoid tissue, or co-presence of visceral untreated Kaposi sarcoma. Also, the appropriate dosage and way of administration of the best therapeutic regimen were examined, since there is a lack of literature on these issues. Globalization and wider use of immunosuppressive therapies underline the importance of maintaining adequate awareness, also in HIV-negative and non-immigrant populations. [ABSTRACT FROM AUTHOR]

In recent years, there has been a notable increase in research output on native vertebral osteomyelitis (NVO), coinciding with a rise in its incidence. However, clinical outcomes remain poor, due to frequent relapse and long-term sequelae. Additionally, the lack of a standardized definition and the use of various synonyms to describe this condition further complicate the clinical understanding and management of NVO. We propose a new framework to integrate the primary diagnostic tools at our disposal. These collectively fall into three main domains: clinical, radiological, and direct evidence. Moreover, they and can be divided into seven main categories: (a) clinical features, (b) inflammatory biomarkers, (c) imaging techniques, microbiologic evidence from (d) blood cultures and (e) invasive techniques, (f) histopathology, and (g) empirical evidence of improvement following the initiation of antimicrobial therapy. We provide a review on the evolution of these techniques, explaining why no single method is intrinsically sufficient to formulate an NVO diagnosis. Therefore, we argue for a consensus-driven, multi-domain approach to establish a comprehensive and universally accepted definition of NVO to enhance research comparability, reproducibility, and epidemiological tracking. Ongoing research effort is needed to refine these criteria further, emphasizing collaboration among experts through a Delphi method to achieve a standardized definition. This effort aims to streamline research, expedite accurate diagnoses, optimize diagnostic tools, and guide patient care effectively., Competing Interests: At least one of the (co-)authors is a member of the editorial board of Journal of Bone and Joint Infection. The peer-review process was guided by an independent editor, and the authors also have no other competing interests to declare., (Copyright: © 2024 Francesco Petri et al.)

Background: Recent advances in shotgun metagenomic sequencing (sMGS) for detecting microbial cell-free DNA (mcfDNA) in peripheral blood have shown promise across various patient populations. This study evaluates the application of sMGS for diagnosing osteoarticular infections (OAIs), a condition with significant diagnostic challenges., Methods: We conducted a retrospective analysis on 73 patients suspected of OAIs at the Mayo Clinic from 2019 to 2023, incorporating mcfDNA sMGS (Karius test [KT]) into their diagnostic evaluation. We categorized the clinical impact of KT on OAI diagnoses and management into 4 distinct outcomes. (1) KT was able to confirm an established diagnosis, (2) KT supported noninfectious diseases diagnosis, (3) KT established an unsuspected diagnosis, (4) KT did not add relevant information., Results: In our cohort, KT was performed in 73 patients. Among the infected individuals, KT yielded positive results in 22 of 43 (51.2%) cases. Of these 22 cases, 11 (50%) showed agreement with conventional diagnostic workup, whereas in 5 (22.7%) cases, the KT established an unsuspected diagnosis. Native vertebral osteomyelitis diagnosis ( P < .001) or OAIs with concomitant presence of endocarditis or endovascular infection ( P = .005) were statistically associated with a definite, probable, or possible diagnostic certainty of KT result., Conclusions: In complex OAIs, KT enhanced diagnostic accuracy by 11.6%, proving especially beneficial in diagnosing native vertebral osteomyelitis and infections with concurrent endocarditis or endovascular complications. Our findings underscore the utility of KT in the diagnostic workflow for challenging OAI cases, potentially altering clinical management for a significant subset of patients., Competing Interests: Potential conflicts of interest. All authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Native vertebral osteomyelitis (NVO) caused by Staphylococcus aureus is associated with high risk of treatment failure and increased morbidity. The role of rifampin-based therapy for the treatment of this condition is controversial. The goal of this systematic review and meta-analysis is to explore the efficacy and safety of rifampin-based therapy for the treatment of S. aureus NVO., Methods: We searched Cochrane, Embase, Medline, Scopus, and Web of Science databases for studies published up to May 2023, focusing on adults with NVO treated with or without rifampin-containing regimens. A random-effects model meta-analysis estimated relative risks and risk difference with 95% confidence intervals (CI)., Results: Thirteen studies (2 randomized controlled trials and 11 comparative cohort studies), comprising 244 patients with S. aureus NVO who received rifampin and 435 who did not, were analyzed. Meta-analysis showed that rifampin-based regimens were associated with lower risk of clinical failure (risk difference, -14%; 95% CI, -19% to -8%; P < .001; I2 = 0%; relative risk, 0.58; 95% CI, .37-.92, P = .02, I2 = 21%). Only 1 study reported on adverse events. All studies had a high or uncertain risk of bias, and the certainty of evidence was rated as very low., Conclusions: Adjunctive rifampin therapy might be associated with lower risk of S. aureus NVO treatment failure; however, the low certainty of evidence precludes drawing definitive conclusions that would alter clinical practice. A randomized trial is necessary to corroborate these findings., Competing Interests: Potential conflicts of interest. S. E. Z, E. F. B. , M. P., F. P., J. M., M. H. M., P. S., and A. J. T. declare no competing interests. A. J. T. reports honoraria for medical writing from UpToDate; a role as unpaid executive board member for Musculoskeletal Infection Society. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)