Antibiotic resistance is one of the greatest growing public health threats and a worldwide priority. According to the WHO, drug-resistant diseases may cause 10 million deaths a year by 2050 and have a substantial impact on the global economy, driving up to 24 million people into poverty. The ongoing COVID-19 pandemic has exposed the fallacies and vulnerability of healthcare systems worldwide, displacing resources from existing programs and reducing funding for antimicrobial resistance (AMR) fighting efforts. Moreover, as already seen for other respiratory viruses, such as flu, COVID-19 is often associated with superinfections, prolonged hospital stays, and increased ICU admissions, further aggravating healthcare disruption. These events are accompanied by widespread antibiotic use, misuse, and inappropriate compliance with standard procedures with a potential long-term impact on AMR. Still, COVID-19-related measures such as increasing personal and environmental hygiene, social distancing, and decreasing hospital admissions could theoretically help the AMR cause. However, several reports have shown increased antimicrobial resistance during the COVID-19 pandemic. This narrative review focuses on this “twindemic”, assessing the current knowledge of antimicrobial resistance in the COVID-19 era with a focus on bloodstream infections and provides insights into the lessons learned in the COVID-19 field that could be applied to antimicrobial stewardship initiatives.

Background: Periprosthetic joint infection (PJI) is a devastating complication that develops after total joint arthroplasty (TJA), whose incidence is expected to increase over the years. Traditionally, surgical treatment of PJI has been based on algorithms, where early infections are preferably treated with debridement, antibiotics, and implant retention (DAIR) and late infections with two-stage revision surgery. Two-stage revision is considered the “gold standard” for treatment of chronic prosthetic joint infection (PJI) as it enables local delivery of antibiotics, maintenance of limb-length and mobility, and easier reimplantation. Many studies have attempted to identify potential predicting factors for early diagnosis of PJI, but its management remains challenging. In this observational retrospective study, we investigated the potential role of inflammatory blood markers (neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory index (SII), systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation (AISI)) as prognostic factors in two-stage exchange arthroplasty for PJI. Methods: A single-center retrospective analysis was conducted, collecting clinical data and laboratory parameters from patients submitted to prosthetic explantation (EP) for chronic PJI. Laboratory parameters (PCR, NLR, MLR, PLR, SIRI, SII, and AISI) were evaluated at the explantation time; at 4, 6, and 8 weeks after surgery; and at reimplantation time. The correlation between laboratory parameters and surgery success was evaluated and defined as infection absence/resolution at the last follow-up. Results: A total of 57 patients with PJI were evaluated (62% males; average age 70 years, SD 12.14). Fifty-three patients with chronic PJI were included. Nine patients underwent DAIR revision surgery and chronic suppressive therapy; two patients died. Nineteen patients completed the two-stage revision process (prosthetic removal, spacer placement, and subsequent replanting). Among them, none showed signs of reinfection or persistence of infection at the last available follow-up. The other twenty-three patients did not replant due to persistent infection: among them, some (the most) underwent spacer retention; others (fewer in number) were submitted to resection arthroplasty and arthrodesis (Girdlestone technique) or chronic suppressive antibiotic therapy; the remaining were, over time, lost to follow-up. Of the patients who concluded the two-stage revision, the ones with high SIRI values (mean 3.08 SD 1.7 and p-value 0.04) and MLR values (mean 0.4 SD 0.2 and p-value 0.02) at the explantation time were associated with a higher probability of infection resolution. Moreover, higher variation in the SIRI and PCR, also defined, respectively, as delta-SIRI (mean −2.3 SD 1.8 and p-value 0.03) and delta-PCR (mean −46 SD 35.7 and p-value 0.03), were associated with favorable outcomes. Conclusions: The results of our study suggest that, in patients with PJI undergoing EP, the SIRI and MLR values and delta-SIRI and delta-PCR values could be predictive of a favorable outcome. The evaluation of these laboratory indices, especially their determination at 4 weeks after removal, could therefore help to determine which patients could be successfully replanted and to identify the best time to replant. More studies analyzing a wider cohort of patients with chronic PJI are needed to validate the promising results of this study.

In the face of the rapid evolution of the COVID-19 pandemic, healthcare professionals on the frontline are in urgent need of frequent updates in the accomplishment of their practice. Hence, clinicians started to search for prompt, valid information on sources that are parallel to academic journals. Aim of this work is to investigate the extent of this phenomenon. We administered an anonymous online cross-sectional survey to 645 Italian clinicians. Target of the survey were all medical figures potentially involved in the management of COVID-19 cases. 369 questionnaires were returned. 19.5% (n = 72) of respondents were younger than 30 years-old; 49,3% (n = 182) worked in Infectious Diseases, Internal Medicine or Respiratory Medicine departments, 11.5% (n = 42) in Intensive Care Unit and 7.4% (n = 27) were general practitioner. 70% (n = 261) of respondents reported that their use of social media to seek medical information increased during the pandemic. 39.3% (n = 145) consistently consulted Facebook groups and 53.1% (n = 196) Whatsapp chats. 47% (n = 174) of respondents reported that information shared on social media had a consistent impact on their daily practice. In the present study, we found no difference in social media usage between age groups or medical specialties. Given the urgent need for scientific update during the present pandemic, these findings may help understanding how clinicians access new evidences and implement them in their daily practice.

Background: Italian oral pre-exposure prophylaxis (PrEP) implementation faced challenges until the drug reimbursement approval in 2023. National real-life data on effectiveness are lacking. This study aimed to report incidence rates (IR) of HIV and other sexually transmitted infections (STIs), along with probabilities and predictors of poor adherence and PrEP discontinuation. Methods: Prospective national cohort study (ItaPrEP) on oral PrEP users (PrUs) in eight Italian centers (September 2017–November 2023) that could partially provide free drug supplies. IRs of HIV and STIs, and Kaplan–Meier estimated probabilities of poor adherence and discontinuation were evaluated. Mixed-effect logistic models with random intercept on the center were used to explore the association between risk factors and poor adherence and discontinuation. Results: About 1758 PrUs were included, 98% MSM; five HIV seroconversions were observed with an IR 0.187/100 person-year follow-up (PYFU; 95% CI: 0.061–0.436). IR/100 PYFU were 13.1 (95%CI:11.7–14.5) for syphilis, 23.8 (95% CI: 22–25.7) for chlamydia, and 24.2 (95% CI: 22.4–26.1) for gonorrhea. The 2-year probability of poor adherence and discontinuation was 57.9% (95% CI: 54.8–61.0) and 37.1% (95% CI: 34.3–40.1), respectively. Chemsex and switching schedule were associated with poor adherence, unlike a high educational level. Age >40 years, free drug supplies, and laboratory monitoring were associated with a lower risk of discontinuation, while chemsex was associated with a higher risk. Conclusions: In this Italian oral PrEP program, the HIV incidence was lower than that observed in pivotal clinical trials in high-risk populations and close to that of observational real-life studies. Identifying fragile groups (youngest, low educational level, and chemsex users) and addressing barriers (free drugs and monitoring) are key to targeting strategies to improve oral PrEP implementation.

The increasing emergence of bacterial strains with new resistance determinants has become a threat to current antibiotic therapies in recent years. This has prompted research for innovative options with improved efficacy and safety profiles: long-acting glycopeptides, such as dalbavancin and oritavancin, are currently approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI). Their efficacy, microbiological profile, and ease of administration may provide an answer to this challenge, as well as reducing length of stay and hospital costs. This narrative review aims to explore the current evidence on the real-word use of dalbavancin and oritavancin, in labelled and off-label indications in clinical practice. A PubMed library database search with no time limits was performed using the following terms: long-acting antibiotics, dalbavancin, oritavancin. Registration studies confirmed non-inferiority of long-acting glycopeptides to standard of care in ABSSSI (dalbavancin DISCOVER 1 and 2: 79.7% clinical success in the dalbavancin group and 79.8% in the vancomycin-linezolid group; oritavancin SOLO I: 82,3% clinical success in the oritavancin group versus 78,9% for the vancomycin group; SOLO II: 80,1% clinical success versus 82,9%). Large cohorts have confirmed similar success rates in ABSSSI treatment in real-world practice. Evidence for off-label indications is still rather scarce but promising, especially in bone and joint infections therapy for both dalbavancin and oritavancin, and infective endocarditis for dalbavancin. Moreover, these drugs may have their place in non-adherent patients, in setting of addition or difficult access to healthcare. Another potential use of these drugs is in patients with oral intake impairment or reduced gastro-intestinal absorption. However, the low penetration in cerebrospinal fluid of dalbavancin and the unfavourable outcomes in the only case report of oritavancin treatment in human meningitis despite encouraging animal models would seem to make these molecules unsuitable for central nervous system infection therapy. Most of the available evidence is based on small retrospective cohorts, so robust prospective studies investigating off-label indications are needed.

Background: Megaprostheses were first employed in oncological orthopedic surgery, but more recently, additional applications have arisen. These implants are not without any risks and device failure is quite frequent. The most feared complication is undoubtedly the implants’ infection; however, the exact incidence is still unknown. This systematic review aims to estimate in the current literature the overall incidence of megaprosthesis infections and to investigate possible risk/protective factors. Methods: We conducted a systematic search for studies published from July 1971 to December 2023 using specific keywords. To be included, studies needed to report either the megaprosthesis anatomical site, and/or whether the megaprosthesis was coated, and/or the surgical indication as oncological or non-oncological reasons. Results: The initial literature search resulted in 1281 studies. We evaluated 10,456 patients and the overall infection rate was 12%. In cancer patients, the infection rate was 22%, while in non-oncological patients, this was 16% (trauma 12%, mechanical failure 17%, prosthetic joint infections 26%). The overall infection rates comparing coated and uncoated implants were 10% and 12.5%, respectively. Conclusions: The number of megaprosthesis implants is increasing considerably. In traumatological patients, the infection rate is lower compared to all the other subgroups, while the infection rate remains higher in the cancer patient group. As these devices become more common, focused studies exploring epidemiological data, clinical outcomes, and long-term complications are needed to address the uncertainties in prevention and management.