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This article focuses on the Mexico-United States border creation between 1821, year of the Mexican independence from Spain, and 1924, when the establishment of the Border Patrol shaped the current border control structure. This process will be analysed through the lens of smuggling, considering both the thread of union and separation that still determines the relations between the two countries. In particular, during the 50 years between the war against the United States (1846-1848) and the end of Porfírio Diaz’s regime in 1910, two simultaneous trends developed: on one side, the border crystallized, resulting in the consolidation of the flimsy “line of sand”, on the other side, a counter movement split the two national sovereignties , claiming their respective territories. Smuggling was the very first, fundamental human behaviour marking the border, paradoxically by challenging it.

Competing Interests: Conflict of interest: RC and PT are employes of Intexo Società Benefit. DP and PN have no conflict of interest to declare.

The new Cabotegravir + Rilpivirine long acting (CAB + RPV) is the injectable regimen for treatment-experienced people with HIV (PWH). Little data from real-world settings are available, particularly in more complex PWH. We aimed to investigate the effectiveness of CAB + RPV in our real-life cohort of experienced PWH. We conducted a prospective observational longitudinal study by enrolling PWH who switched to CAB + RPV. We recruited participants from our outpatient clinic and a lower percentage of complex PWH followed by our home-care assistance (HCA). We evaluated time to virological failure (VF) and time to treatment discontinuation (TD) for any cause using Cox regression analyses. In the subgroup followed by HCA we also analyzed the total HIV-DNA trend during the study period. We enrolled 62 participants: 52 were outpatients (83.9%) and 10 followed by HCA (16.1%). Mostly were males (66.1%), with a median age of 51 years (IQR 31-60). During a 31.5 person-years follow-up (PYFU), all participants maintained virological suppression (< 30cps/mL). We observed 9 discontinuations during follow-up, with a rate of discontinuation of 28.6 per 100 PYFU. The estimated probabilities of maintaining CAB + RPV at 24 and 48 weeks were 84.9% (SD: 0.5) and 79.2% (SD: 0.7), respectively. No significant predictors of discontinuations were found. In the subgroup, we found no significant changes in the HIV-DNA levels over time (p = 0.332). Our results confirm the efficacy of CAB + RPV as a switch strategy in virologically suppressed PWH and even in more complex individuals, encouraging its use in PWH in need, coupled with HCA home administration support., Competing Interests: Declarations. Conflict of Interest: A.C. received support for travel to meetings from ViiV Healthcare. A.B. received a speakers’ honoraria from ViiV Healthcare, and fees for attending advisory boards from Janssen-Cilag, S.D.G. was a paid consultant or member of the advisory boards for Gilead Sciences, ViiV Healthcare, Janssen-Cilag, Merck Sharp & Dohme and Bristol-Myers Squibb. None of the other authors have anything to declare. Ethical Approval: The study protocol and informed consent documents were reviewed and approved by our local Ethics Committee (Fondazione Policlinico Universitario A. Gemelli IRCCS) (7768/16). Consent to Participate: Individual consent was obtained before participation of the study., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Complicated urinary tract infections (cUTIs) represent a significant clinical challenge due to their association with sepsis, high morbidity and mortality, and an increased risk of recurrence and chronic infection. Effective management requires prompt, targeted interventions., Areas Covered: This review highlights the importance of early, targeted antibiotic therapy based on local resistance profiles, patient-specific factors, and pharmacokinetic/pharmacodynamic considerations. We examined emerging and existing antibiotics, including beta-lactams, fluoroquinolones, aminoglycosides, and beta-lactamase inhibitor combinations, which show potential against multidrug-resistant organisms (MDRO) linked to cUTI. Additionally, we propose revisiting the broad definition of cUTI to promote a more pragmatic approach that minimizes unnecessary antibiotic use and hospitalization., Expert Opinion: Current evidence underscores the need for antimicrobial stewardship, precise diagnostics, and innovative therapies to address cUTI while mitigating antimicrobial resistance. A targeted, patient-centered approach is essential to optimize outcomes and reduce the burden of resistant infections.

This is the first in a series of five papers that detail the role and substantial impact that external quality assessment (EQA) and their providers' services play in ensuring in-vitro diagnostic (IVD) performance quality. The aim is to give readers and users of EQA services an insight into the processes in EQA, explain to them what happens before EQA samples are delivered and after examination results are submitted to the provider, how they are assessed, what benefits participants can expect, but also who are stakeholders other than participants and what significance do EQA data and assessment results have for them. This first paper presents the history of EQA, insights into legal, financing and ethical matters, information technology used in EQA, structure and lifecycle of EQA programs, frequency and intensity of challenges, and unique requirements of extra-examination and educational EQA programs., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Tuberculous lymphadenitis is one of the most common extrapulmonary manifestation of tuberculosis. Lymphadenitis due to Listeria monocytogenes is rarely described. We present a case of a 59-year-old woman from Mexico presented to the Emergency Department with a 2-week history of erythematous and painful swelling in the right retromandibular area. An ultrasound-guided bedside needle aspiration of the lump was performed by an infectious diseases specialist and a diagnosis of Listeria monocytogenes and tuberculous coinfection was done. To our knowledge this is the first case of tuberculous and Listeria-associated lymphadenitis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Whole-slide imaging (WSI) has been adopted in many fields of pathology for education, quality assurance, and remote diagnostics. In 2021, the College of American Pathologists (CAP) updated guidelines to support pathology laboratories regarding the WSI systems validation process. However, the majority of published literature refers to histopathology rather than cytology. The aim of this study was to compare conventional light microscopy (CLM) and WSI in thin-layer cervical samples evaluation according to CAP guideline., Methods: A sample set of 64 thin-layer cervical specimens from women 25-64 years old who participated in cervical cancer screening programs in Tuscany was distributed among five cytologists at Institute for Cancer Research, Prevention and Clinical Network (Florence, Italy) for CLM analysis. After 2 weeks, the corresponding 64 digitally scanned slides were available at several magnifications for WSI evaluation., Results: Substantial/near perfect agreement between CLM and WSI evaluation (0.77 ≥ κ ≥1) was observed for the negative for intraepithelial lesion or malignancy (NILM) class with concordance rates from 83.3% to 100%.Variability in concordance was observed among all the cytologists: 50%-85.7% for low-grade squamous intraepithelial lesion (LSIL), 47.1%-100% for high-grade squamous intraepithelial lesion (HSIL), 50%-100% for atypical glandular cells (AGCs) favors adenocarcinoma (ADK) with moderate/near perfect agreement (0.47 ≥ κ ≥1). Concordance and agreement rates were also variable within the "borderline" cytological categories of atypical squamous cells of undetermined significance (ASC-US), atypical squamous cells cannot exclude an HSIL (ASC-H), and AGCs with lower or not computable kappa for some readers. The overall intralaboratory concordance between CLM and WSI was 92.9% with a near perfect agreement (κ = 0.84) for NILM. Substantial agreement (κ ≥0.65) was assessed for LSIL, HSIL/squamous cell carcinoma, AGCs, and ADK categories whereas the agreement was lower (κ ≤0.39) for ASC-US and ASC-H., Conclusions: This study showed an overall substantial/near perfect agreement between CLM and WSI for all the cytological categories except the "borderline" ASC-US and ASC-H. Further progress in cytology WSI systems are needed before introducing it in routine diagnostics., (© 2024 American Cancer Society.)

Background: Oxidative stress (OS) is the imbalance between oxidant and antioxidant molecules, in favour of oxidants, that has been associated with an increased risk of morbidity and mortality in ART-treated people living with HIV (PLWH). We aimed to assess factors associated with OS in virologically suppressed PLWH on long-term modern ART., Method: In this cross-sectional study we evaluated OS by measuring both the levels of derivatives-reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP). We also calculated the BAP/d-ROMs ratio, (OS index, OSi); a cut-off value < 7.3 indicated OS. Factors associated with OS markers were explored by linear regression model., Results: We enrolled 299 experienced PLWH with virological suppression (HIV-RNA < 50cps/mL). The mean of the d-ROMs levels was 409 UCARR (95%CI 394-422), whereas the mean of the BAP levels was 1.809 µmol/L (95%CI 1706-1851). The OSi mean value was 4.84, and 91.6% of the participants were below the cut-off value. By regression analysis, higher production of oxidants was associated with female sex (p < 0.001), current exposition to PIs (p = 0.030) and HCV co-infection (p = 0.006). Higher antioxidant capacity was correlated with higher HDL levels (p = 0.001). A lower OSi was associated with female sex (p = 0.003) and the current use of triple vs. dual regimen (p = 0.036). The OSi correlated negatively with cholesterol levels (p = 0.002) and positively with HDL (p < 0.001)., Conclusions: Virologically suppressed PLWH on long-term ART showed a marked OS. Female sex, the exposure to PIs, and HCV co-infection were associated with higher oxidants, while higher HDL levels were linked to better antioxidant capacity. Interestingly, dual therapy, especially INSTI-based regimens, was associated with lower oxidative stress compared to triple therapy., Competing Interests: Ethics declarations. Ethics approval and consent to participate: The study was conducted in accordance with the Good Clinical Practice and ethical principles of the Declaration of Helsinki. The protocol was reviewed and approved by our local Ethics Committees (ID4477 14/10/2021). Written informed consent was obtained from all participants. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

In glioblastoma, glioma-associated microglia/macrophages (GAMs) represent the major population of tumor infiltrating cells, with up to one half of the cells of the tumor mass. Recent studies have shown that microglia are involved in the maintenance of immunological homeostasis and protection against autoimmunity. However, despite the growing body of evidence on the topic, many aspects are yet to be clarified. In our study, 3 different situations emerged concerning the markers of microglial/macrophage-related and other cell types in GBM patients: i) most of the markers (IBA1, TMEM119, CD206 and CD86) show an ascending gradient from the tumor center to the non-tumor/healthy area of the brain; ii) one marker (CD204) shows a descending gradient, going from the center of the tumor to the non-tumor/healthy brain area; iii) two markers (CD163 and P2RY12) show no gradient. These observations support the idea that the magnitude of the diverted inflammation is a 'extensive' rather than a 'local' phenomenon and that could possibly play a role in disease resistance and relapse., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: BIC/FTC/TAF showed efficacy and tolerability in randomized trials as a switch strategy in virologically-suppressed people living with HIV. We evaluated its effectiveness in a real-life setting., Methods: A retrospective monocentric cohort including 431 virologically-suppressed (HIV-RNA <50 copies/ml) people switching to BIC/FTC/TAF in the period 2018-2022 was evaluated. Probabilities of virological failure (VF, i.e.2 consecutive HIV-RNA ≥50 copies/ml or a single HIV-RNA ≥200 copies/ml) and of treatment discontinuation (TD) were estimated by Kaplan-Meier, and predictors of both outcomes were identified through multivariable Cox regression. Analysis-of-variance for repeated measures was used to examine changes in CD4 count and CD4-to-CD8 ratio., Results: Overall, 16 VF occurred during 22 months of median follow-up time. Estimated probabilities of VF at 1, 2 and 3 years were 2.0% (95% CI 1.04.2%), 2.9% (95% CI 1.5%-5.6%) and 5.5% (95% CI 3.2%-9.2%), respectively. Caucasian ethnicity and a history of previous VF independently predicted VF. TD occurred in 42 cases, predominantly for simplification. One discontinuation due to VF was reported. No predictors of discontinuation were identified. An increase in CD4-to-CD8 ratio over 3 years was evidenced ( p < 0.001). Total cholesterol decreased over 3 years ( p < 0.001). Triglycerides did not significantly change ( p = 0.465)., Conclusions: BIC/FTC/TAF demonstrated high effectiveness, tolerability and safety., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.C. received support for travel to meetings from ViiV Healthcare, A.B. received speakers’ honoraria from ViiV Healthcare, and fees for attending advisory boards from Janssen-Cilag. SD.G. was a paid consultant or member of advisory boards for Gilead Sciences, ViiV Healthcare, Janssen-Cilag, Merck Sharp & Dohme and Bristol-Myers Squibb. All other authors: none to declare.

Introduction: This study aimed to present real-life data on the use, efficacy, and safety of administering antibiotic therapy through portable elastomeric pumps (pEP) in the outpatient setting., Methods: This retrospective observational cohort study was conducted from January 2020 to May 2023 in a large academic hospital in Rome, Italy. All patients receiving antibiotic therapy via pEP were included up to a follow-up period of 90 days after the end of antibiotic therapy. The primary outcome was the treatment response. Secondary endpoints were adverse events attributable to the drug administered, the vascular catheter, or the infection itself., Results: Of the 490 patients referred to our outpatient parenteral antibiotic therapy (OPAT) unit, 94 (19.2%) received antibiotic therapy via pEP and were included in the final analysis. The most frequently treated infections were those involving bone and prosthetics, including spondylodiscitis (n=27; 28.8%). Most infections were due to Pseudomonas aeruginosa (n=55; 48.3%). Cefepime (n=32; 34.0%), piperacillin/tazobactam (n=29; 30.9%), ceftolozane/tazobactam (n=7; 7.5%), and oxacillin (n=7; 7.5%) were the most frequently administered antibiotics. The infection cure rate reached 88.3% (n=83). 12 patients (12.8%) reported adverse events, of which half (6.4%) were drug-related and half (6.4%) were line-related., Conclusions: OPAT through portable elastomeric infusion pumps proved to be safe and effective. It also contributed to the reduction of healthcare costs, fully respecting the principles of personalized medicine. This strategy has emerged as a promising tool for antibiotic stewardship and infection control., (Copyright © 2024 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

Background : This study examined the impact of the COVID-19 lockdown on antiretroviral therapy (ART) prescriptions among persons living with HIV (PWH) in Italy. Methods : Data from the ICONA cohort included ART-naïve individuals who started ART between January 2019 and December 2022, and ART-experienced individuals who started new ART with HIV RNA ≤50 cps/mL from January 2016 to December 2022. The analysis focused on the proportion of PWH starting or switching to dual (2DR) versus triple (3DR) ART regimens. Comparisons were made using Chi-square and Kruskal-Wallis tests, with logistic regression (LR) to assess associations, adjusting for sex and age. Results : Among 2481 ART-naïve PWH, 17% were female, with a median age of 40. Using 2020 as the comparator (the lockdown year), the odds ratio (OR) from fitting a LR showed a reduced probability of prescribing 2DR both before and after 2020. The proportion of PWH starting 2DR was 9% in 2019, 18% in 2020, 13% in 2021, and 10% in 2022. Among 12,335 ART-experienced PWH, 20% were female, with a median age of 47. The proportion switching to 2DR rose from 24% in 2016 to 38% in 2020, 62% in 2021, and 65% in 2022, showing a >3-fold higher probability to be switched to 2DR instead of 3DR in recent years (2021-2022). Conclusions : For ART-naive PWH, 2DR initiation did not decrease during the 2020 lockdown but changed in the following years, possibly indicating shifts in clinical practice or resuming HIV services. For ART-experienced PWH, 2DR prescriptions increased significantly over time, especially for INSTI-based regimens.

Background: European countries have included healthcare workers (HCWs) among priority groups for COVID-19 vaccination. We established a multi-country hospital network to measure the SARS-CoV-2 incidence and effectiveness of COVID-19 vaccines among HCWs against laboratory-confirmed SARS-CoV-2 infection. Methods: HCWs from 19 hospitals in 10 countries participated in a dynamic prospective cohort study, providing samples for SARS-CoV-2 testing at enrolment and during weekly/fortnightly follow-up. We measured the incidence during pre-Delta (2 May-6 September 2021), Delta (7 September-14 December 2021), and Omicron (15 December 2021-2 May 2023) waves. Using Cox regression, we measured the relative vaccine effectiveness (rVE) of the first COVID-19 booster dose versus primary course alone during Delta and Omicron waves. Results: We included a total of 3015 HCWs. Participants were mostly female (2306; 79%), with a clinical role (2047; 68%), and had a median age of 44 years. The overall incidence of SARS-CoV-2 infection was 3.01/10,000 person-days during pre-Delta, 4.21/10,000 during Delta, and 23.20/10,000 during Omicron waves. rVE was 59% (95% CI: -25; 86) during Delta and 22% (1; 39) during Omicron waves. rVE was 51% (30; 65) 7-90 days after the first booster dose during the Omicron wave. Conclusions: The incidence of SARS-CoV-2 infection among HCWs was higher during the Omicron circulation period. The first COVID-19 vaccine booster provided additional protection against SARS-CoV-2 infection compared to primary course vaccination when recently vaccinated <90 days. This multi-country HCW cohort study addressing infection as the main outcome is crucial for informing public health interventions for HCWs.

Background: High incidence mpox rates suggest asymptomatic individuals may contribute to virus transmission. We undertook this study to assess the seroprevalence of IgG anti-MPXV in a cohort of asymptomatic PLWH, to analyze the size of the phenomenon of asymptomatic infections., Materials and Methods: From October 2022 to March 2023 we serially collected serum samples from PLWH attending our Clinic. IgG against MPXV have been assessed on stored cryopreserved samples with an ELISA. Only people with no previous reported vaccine against smallpox or mpox nor previous clinical manifestations consistent with a mpox diagnosis were included., Results: 285 PLWH were included. Twenty-one participants tested positive for IgG anti MPXV (7.37 %, 95 % CI 4.62-11.0). Seropositivity was predominant in male (15/285, 71.4) with a small fraction of female (6/285,28.6 %) and PWID (1/285,4.8 %)., Conclusions: Our findings suggest the possibility of an asymptomatic course of the mpox infection even in populations beyond traditional high-risk groups., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: This study aimed to present real-life data on the use, effectiveness, and safety of administering Ceftolozane/Tazobactam (C/T) through elastomeric pumps (EP) in the outpatient setting., Methods: This case series study was conducted from January 2022 to July 2023 in a large University Hospital in Rome, Italy. Patients receiving continuous infusion of C/T via EP were included up to a follow-up period of 90 days after the end of antibiotic therapy. The primary endpoint was the infection's clinical cure rate. Secondary endpoints were adverse events attributable to continuous home infusion of Ceftolozane/Tazobactam via elastomeric pumps., Results: Seven patients received C/T continuously infused via EP and were included in the final analysis. Three patients suffered from prosthetic joint infection ( n  = 3/7; 43%), two patients from osteomyelitis ( n  = 2/7; 29%), one patient from otomastoiditis ( n  = 1/7; 15%) and one from pneumonia ( n  = 1/7; 15%). All infection were sustained by P. aeruginosa. Five strains had MDR-type susceptibility profiles ( n  = 5/7; 71%) and two of these were DTR ( n  = 2/7; 29%). The infection cure rate reached 86% ( n  = 6/7). Two patients reported a complication related to the vascular catheter for drug infusion ( n  = 2/7; 29%)., Conclusions: Continuous infusion of Ceftolozane/Tazobactam by elastomeric pumps has been shown to be safe and effective in practice representing a viable option of intravenous treatment in outpatient setting for infection sustained by P. aeruginosa especially for multidrug-resistant strains.

Background: Colistin, administered as intravenous colistimethate (CMS), is still used in the critical care setting and current guidelines recommend high dosage CMS in patients undergoing continuous renal replacement therapy (CRRT). Due to the paucity of real-life data, we aimed to describe colistin pharmacokinetic/pharmacodynamic (PK/PD) profile in a cohort of critically ill patients with infections due to carbapenem-resistant (CR) bacteria undergoing CRRT., Results: All consecutive patients admitted to three Intensive Care Units (ICUs) of a large metropolitan University Hospital, treated with colistin for at least 48 h at the dosage of 6.75 MUI q12, after 9 MIU loading dose, and undergoing CRRT were included. After the seventh dose, patients underwent blood serial sampling during a time frame of 24 h. We included 20 patients, who had CR-Acinetobacter baumannii ventilator-associated pneumonia and were characterized by a median SAPS II and SOFA score of 41 [34.5-59.3] and 9 [6.7-11], respectively. Fifteen patients died during ICU stay and six recovered renal function. Median peak and trough colistin concentrations were 16.6 mcg/mL [14.8-20.6] and 3.9 mcg/mL [3.3-4.4], respectively. Median area under the time-concentration curve (AUC 0 - 24 ) and average steady-state concentration (C ss, avg ) were 193.9 mcg h/mL [170.6-208.6] and 8.07 mcg/mL [7.1-8.7]. Probability of target attainment of colistin pharmacodynamics according to the fAUC 0 - 24 /MIC target ≥ 12 was 100% for MIC ≤ 2 mcg/mL and 85% for MIC = 4 mcg/ML, although exceeding the toxicity limit of C ss, avg 3-4 mcg/mL., Conclusions: In critically ill patients with CR infections undergoing CRRT, recommended CMS dosage resulted in colistin plasmatic levels above bacterial MIC 90 , but exceeding the safety C ss, avg . limit., Trial Registration: This trial was registered in ClinicalTrials.gov on 23/07/2021 with the ID NCT04995133 (https//clinicaltrials.gov/study/NCT04995133)., (© 2024. The Author(s).)

Introduction: Dalbavancin is an antibiotic characterized by an extended half-life and efficacy against methicillin-resistant Staphylococci. Currently, there are only narrative reviews summarizing the evidence about the use of dalbavancin for infective endocarditis (IE), many of which are focused primarily on its use as consolidation therapy. For this reason, we conducted a systematic review to describe the clinical efficacy and the safety of dalbavancin in IE treatment., Methods: We searched for available evidence using the MEDLINE (PubMed), Embase, Scopus, Cochrane Library and Web of Science libraries, with no restrictions regarding the publication year. The risk of bias was performed using the Cochrane ROBINS-I tool for the comparative studies and the Newcastle-Ottawa Scale for descriptive studies., Results: Nine studies were included. All of them were observational. Native valve endocarditis was the most common kind of IE found in the studies' populations (128/263, 48.7%), followed by prosthetic valve endocarditis, and cardiovascular implantable electronic device-related endocarditis. Coagulase-negative Staphylococci were the most common pathogens isolated (83/269, 30.1%), followed by S. aureus, Enterococci spp and Streptococci spp. Five out of nine studies documented a clinical failure rate of less than 10%. Dalbavancin showed a favourable safety profile. Dalbavancin appears to be a promising option for the consolidation therapy of IE. However, further studies comparing dalbavancin with standard of care are needed., Prospero Registration Number: CRD42023430032., (© 2024. The Author(s).)

Background: To clarify whether next-generation sequencing (NGS) can be useful for resistance assessment in virologically suppressed highly treatment-experienced (HTE) individuals with MDR HIV., Methods: Ninety-one participants from the PRESTIGIO Registry were included. NGS was performed on HIV-DNA at 1%, 5% and 20% cut-offs; major drug resistance mutations (DRMs) were evaluated and compared with those detected in historical plasma genotypic resistance testing (h-GRT). APOBEC editing was also characterized., Results: Participants had a complex and long treatment history [median 23 (IQR 21-25) years of ART exposure) and had been virologically suppressed since a median of 3 (IQR 2-5) years. Among all major DRMs detected by HIV-DNA NGS and/or h-GRT, 30% were exclusively found through NGS. The highest detection rate of historical major DRMs was reached with NGS set at 1%, but unusual substitutions and extensive APOBEC hypermutations suggest technical issues and poor clinical relevance in the 1%-5% interval. At NGS set at 5%, 67.2% of historical major DRMs were detected. The number of major DRMs detected exclusively by DNA-NGS as minority variants (frequency 5%-20%) was significantly higher in individuals who later experienced virological rebound compared with those who maintained virological control [median 2 (IQR 1-3) versus 1 (0-2), P = 0.030] and positively correlated with viraemia levels at rebound (rho = 0.474, P = 0.030)., Conclusions: In non-viraemic people with an MDR virus, HIV-1 DNA NGS set at 5% is an acceptable technical cut-off that might help to reveal mutations with a potential clinical relevance. Moreover, the number of minority resistance mutations additionally detected by NGS might be associated with loss of virological control., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Novel beta-lactams show activity against many multidrug-resistant Gram-negative bacteria that cause severe lung infections. Understanding pharmacokinetic/pharmacodynamic characteristics of these agents may help optimise outcomes in the treatment of pneumonia., Objectives: To describe and appraise studies that report pulmonary pharmacokinetic and pharmacodynamic data of cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/cilastatin/relebactam and meropenem/vaborbactam., Methods: MEDLINE (PubMed), Embase, Web of Science and Scopus libraries were used for the literature search. Pulmonary population pharmacokinetic and pharmacokinetic/pharmacodynamic studies on adult patients receiving cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/cilastatin/relebactam, and meropenem/vaborbactam published in peer-reviewed journals were included. Two independent authors screened, reviewed and extracted data from included articles. A reporting guideline for clinical pharmacokinetic studies (ClinPK statement) was used for bias assessment. Relevant outcomes were included, such as population pharmacokinetic parameters and probability of target attainment of dosing regimens., Results: Twenty-four articles were included. There was heterogeneity in study methods and reporting of results, with diversity across studies in adhering to the ClinPK statement checklist. Ceftolozane/tazobactam was the most studied agent. Only two studies collected epithelial lining fluid samples from patients with pneumonia. All the other phase I studies enrolled healthy subjects. Significant population heterogeneity was evident among available population pharmacokinetic models. Probabilities of target attainment rates above 90% using current licensed dosing regiments were reported in most studies., Conclusions: Although lung pharmacokinetics was rarely described, this review observed high target attainment using plasma pharmacokinetic data for all novel beta-lactams. Future studies should describe lung pharmacokinetics in patient populations at risk of carbapenem-resistant pathogen infections., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Cefiderocol is a siderophore cephalosporin showing activity against various carbapenem-resistant Gram-negative bacteria (CR-GNB). No data currently exist about real-world use of cefiderocol in terms of types of therapy (e.g., empirical or targeted, monotherapy or combined regimens), indications, and patient characteristics., Methods: In this multicenter, prospective study, we aimed at describing the use of cefiderocol in terms of types of therapy, indications, and patient characteristics., Results: Cefiderocol was administered as empirical and targeted therapy in 27.5% (55/200) and 72.5% (145/200) of cases, respectively. Overall, it was administered as monotherapy in 101/200 cases (50.5%) and as part of a combined regimen for CR-GNB infections in the remaining 99/200 cases (49.5%). In multivariable analysis, previous isolation of carbapenem-resistant Acinetobacter baumannii odds ratio (OR) 2.56, with 95% confidence interval (95% CI) 1.01-6.46, p = 0.047] and previous hematopoietic stem cell transplantation (OR 8.73, 95% CI 1.05-72.54, p = 0.045) were associated with administration of cefiderocol as part of a combined regimen, whereas chronic kidney disease was associated with cefiderocol monotherapy (OR 0.38 for combined regimen, 95% CI 0.16-0.91, p = 0.029). Cumulative 30-day mortality was 19.8%, 45.0%, 20.7%, and 22.7% in patients receiving targeted cefiderocol for infections by Enterobacterales, A. baumannii, Pseudomonas aeruginosa, and any metallo-β-lactamase producers, respectively., Conclusions: Cefiderocol is mainly used for targeted treatment, although empirical therapies account for more than 25% of prescriptions, thus requiring dedicated standardization and guidance. The almost equal distribution of cefiderocol monotherapy and cefiderocol-based combination therapies underlines the need for further study to ascertain possible differences in efficacy between the two approaches., (© 2024. The Author(s).)

Clostridioides difficile (C. difficile) is a Gram-positive, spore-forming anaerobic bacterium emerged as a leading cause of diarrhea globally. CDI's ( Clostridioides difficile infection) impact on healthcare systems is concerning due to high treatment cost and increased hospitalisation time. The incidence of CDI has been influenced by hypervirulent strains such as the 027 ribotype, responsible for significant outbreaks in North America and Europe. CDI's epidemiology has evolved, showing increased community-acquired cases alongside traditional hospital-acquired infections. Mortality rates remain high, with recurrent infections further elevating the risk. Transmission of C. difficile primarily occurs via spores, which survive in healthcare settings and play a pivotal role in transmission. Not only health workers, but also the food chain could have a significant impact on the transmission of infection, although no confirmed foodborne cases have been documented. Pathogenicity of C. difficile involves spore germination and toxin production. Toxins A and B can cause cellular damage and inflammatory responses in the host, leading to colitis. Clinical picture can range from mild diarrhea to fulminant colitis with toxic megacolon, and bowel perforation. Risk factors for CDI include antibiotic exposure, advanced age, hospitalization, and use of proton pump inhibitors. Patients who experience abdominal surgery or patients with inflammatory bowel disease (IBD) are particularly susceptible due to their compromised gut microbiota. Management of CDI has evolved, with fidaxomicin emerging as a superior treatment option over vancomycin for initial and recurrent infections due to its reduction of recurrence rate. Faecal microbiota transplantation (FMT) is effective for recurrent CDI, restoring gut eubiosis. Bezlotoxumab, a monoclonal antibody against C. difficile toxin B, has shown promise in reducing recurrence rates. Severe cases of CDI may require surgical intervention, particularly in instances of toxic megacolon or bowel perforation. In conclusion, CDI remains a significant clinical entity. Further research are needed to improve patients' outcome and reduce the burden on healthcare systems.

Knowledge of Human Polyomavirus (HPyV) infection in the anal area and its association with sexually transmitted infections such as Human Papillomavirus (HPV) and Human Immunodeficiency Virus (HIV) remains limited. Therefore, anal specimens from 150 individuals of both sexes were analyzed for screening purposes. HPV DNA was found in 50.7% of cases, with a predominance of high-risk (HR) genotypes. HPyV DNA was found in 39.3% of samples, with Merkel Cell Polyomavirus (MCPyV) being the most common, with a higher viral load than JCPyV and BKPyV. In addition, MCPyV viral load increased in people living with HIV (PLWH) with HPV infection (p < 0.0001)., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: Severe infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) have been reported increasingly over the past few years. Many in-vivo and in-vitro studies have suggested a possible role of intravenous fosfomycin for the treatment of CRAB infections., Methods: This multi-centre, retrospective study included patients treated with intravenous fosfomycin for severe infections caused by CRAB admitted consecutively to four hospitals in Italy from December 2017 to December 2022. The primary goal of the study was to evaluate the risk factors associated with 30-day mortality in the study population. A propensity score matched analysis was added to the model., Results: One hundred and two patients with severe infections caused by CRAB treated with an intravenous fosfomycin-containing regimen were enrolled in this study. Ventilator-associated pneumonia (VAP) was diagnosed in 59% of patients, primary bacteraemia in 22% of patients, and central-venous-catheter-related infection in 16% of patients. All patients were treated with a regimen containing intravenous fosfomycin, mainly in combination with cefiderocol (n=54), colistin (n=48) or ampicillin/sulbactam (n=18). Forty-eight (47%) patients died within 30 days. Fifty-eight (57%) patients experienced clinical therapeutic failure. Cox regression analysis showed that diabetes, primary bacteraemia and a colistin-containing regimen were independently associated with 30-day mortality, whereas adequate source control of infection, early 24-h active in-vitro therapy, and a cefiderocol-containing regimen were associated with survival. A colistin-based regimen, A. baumannii colonization and primary bacteraemia were independently associated with clinical failure. Conversely, adequate source control of infection, a cefiderocol-containing regimen, and early 24-h active in-vitro therapy were associated with clinical success., Conclusions: Different antibiotic regimens containing fosfomycin in combination can be used for treatment of severe infections caused by CRAB., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

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.

Introduction: Sexually transmitted diseases (STDs) are a major cause of long-term disability. Urethral discharge syndrome (UDS), abnormal vaginal discharge (AVD) and genital ulcer disease (GUD) are very common in low-income and middle-income countries (LMICs), where, due to lack of resources, these infections are managed according to a syndromic approach. Although microbiological diagnosis using nuclear acid amplification tests (NAAT) is already a standard to prescribe targeted treatments in industrialised countries, no randomised clinical trials have been conducted to evaluate clinical usefulness and acceptability of NAAT in comparison with syndromic approach in LMICs. The results of this study could inform diagnostic guidelines since they may suggest an update of the current recommendation if microbiological diagnosis using NAAT in the management of STD is demonstrated to be both useful and acceptable in an LMIC context., Methods and Analysis: The primary objective of this randomised, open-label trial is to evaluate the clinical usefulness of a NAAT and its acceptability in comparison with a clinical syndromic approach and to explore whether this test could replace the syndromic approach in the management of STDs at a national referral hospital in Uganda. 220 patients presenting to the STD clinic at Mulago Hospital in Kampala, Uganda with AVD, UDS or GUD will be randomised to either standard of care (syndromic management) or NAAT-based treatment with a 1:1 ratio. All the patients will be asked to return after 2 or 3 weeks for a control visit. Primary outcome will be therapeutic appropriateness., Ethics and Dissemination: This trial was approved by the Mulago Hospital Research and Ethical Committee (MHREC2023-97) and the Uganda National Council for Science and Technology (HS31000ES). Patients will give informed consent to participate before taking part in the study. Results will be published in peer-reviewed journals in open-access formats and data made available in anonymised form., Trial Registration Number: NCT05994495., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This single-centre retrospective cohort study reports on the results of a descriptive (non-comparative) retrospective cohort study of early initiation of antivirals and combined monoclonal antibody therapy (mAbs) in 48 severely immunocompromised patients with COVID-19. The study assessed the outcomes and the duration of viral shedding. The patients started early combined therapy (ECT) a median of 2 days (interquartile range [IQR]: 1-3 days) after the diagnosis of SARS-CoV-2 infection. Except for 1 patient who died due COVID-19-related respiratory failure, patients had their first negative nasopharyngeal swab result after a median of 11 days (IQR: 6-17 days) after starting combined therapy. There were no reports of severe side effects. During a follow-up period of 512 days (interquartile range [IQR]: 413-575 days), 6 patients (12.5%) died and 16 (33.3%) were admitted to hospital. Moreover, 12 patients (25%) were diagnosed with SARS-CoV-2 reinfection a median of 245 days (IQR: 138-401 days) after starting combined treatment. No relapses were reported. Although there was no comparison group, these results compare favourably with the outcomes of severely immunocompromised patients with COVID-19 reported in the literature., (© 2024. The Author(s).)