Marco Falcone

Infections caused by multidrug-resistant Gram-negative (MDR-GN) bacteria, particularly carbapenem-resistant organisms (CROs), constitute a significant burden in critically ill patients (CIPs). A multidisciplinary, collaborative approach is essential for responsible antibiotic use in CIPs, balancing the necessity for effective treatment with mitigation of antimicrobial resistance (AMR). While the efficacy of existing antibiotics against CROs is increasingly limited due to resistance development and suboptimal pharmacokinetic/pharmacodynamic properties, several barriers impede the widespread adoption of new agents, including selective susceptibility testing, limited availability, high costs, and concerns regarding the fostering of resistance. Antimicrobial stewardship (AMS) strategies aim to optimize antibiotic use; however, there is an ongoing debate between restrictive and enabling approaches for new antibiotics in CIPs with CRO infections. While restrictive strategies focus on limiting antibiotic use to mitigate resistance, they may delay necessary treatment and negatively impact professional culture. Enablement strategies promote informed decision-making and accessibility when needed but require substantial workforce and expertise. In this narrative review and expert opinion, we propose an algorithm supporting a coordinated AMS approach in CIPs, emphasizing the importance of early diagnosis and appropriate therapy. We advocate for an enablement strategy for new antibiotics in CIPs with MDR-GN infections, aiming to reduce mortality and toxicity associated with older agents. This strategy should be integrated into local AMS programmes under the guidance of experienced clinicians.

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are major causes of respiratory tract infections across different age groups. Although primarily regarded as respiratory pathogens, both viruses have been associated with cardiac complications, whose clinical spectrum remains incompletely characterized. We systematically reviewed published cases of RSV- and hMPV-associated cardiac involvement and compared their clinical characteristics and outcomes. PubMed, Scopus, and EMBASE were systematically searched for reports describing cardiac complications associated with laboratory-confirmed RSV or hMPV infection. Individual patient data were pooled and analyzed using descriptive and univariate analyses. Multivariable logistic regression was used to identify characteristics associated with hMPV versus RSV diagnosis, while multiple correspondence analysis (MCA) was performed to explore multivariate patterns of clinical presentation. Age-stratified sensitivity analyses were additionally performed. Overall, 102 cases were included, comprising 71 RSV (69.6%) and 31 hMPV (30.4%). hMPV cases were significantly older than RSV cases (41.5 years, interquartile range 3.5–63.0 vs. 1.5 years, interquartile range 0.2–31.0; p < 0.001) and had a higher burden of comorbidities. Myocarditis was the most frequently reported cardiac complication in both groups (87.1% hMPV vs. 74.6% RSV), followed by heart failure and pericarditis. ICU admission was more frequent among hMPV cases (96.8% vs. 77.5%; p = 0.034), whereas overall clinical outcomes did not significantly differ between groups. In exploratory multivariable analyses, dyspnea (aOR 16.280, 95% CI 1.370–193.475) and cough (aOR 6.059, 95% CI 1.062–34.552) were associated with hMPV diagnosis, whereas rhinorrhea (aOR 0.031, 95% CI 0.003–0.286) and lethargy/altered mental status (aOR 0.103, 95% CI 0.015–0.712) were associated with RSV diagnosis. ICU admission was also associated with hMPV diagnosis (aOR 11.033, 95% CI 1.125–108.173). These estimates were characterized by wide confidence intervals and should be interpreted cautiously. MCA showed substantial overlap between RSV and hMPV cases, without clear separation of their overall clinical presentation, while most between-group differences were attenuated in age-stratified analyses. In conclusion, both RSV and hMPV can be associated with a broad spectrum of potentially severe cardiac complications, with myocarditis representing the predominant reported manifestation. Despite some differences in demographic and clinical characteristics, their overall cardiac and clinical phenotypes substantially overlap. These findings support greater awareness of potential cardiac involvement during severe RSV and hMPV infections, while highlighting the need for prospective, systematically investigated cohorts to establish the incidence, mechanisms, and long-term outcomes of these complications.

Cefepime/enmetazobactam (FEP/META) is a novel β-lactam/β-lactamase inhibitor combination with activity against Enterobacterales, including extended-spectrum β-lactamase-producing isolates, but real-world clinical data outside randomized trials remain limited. We conducted a retrospective multicenter descriptive study across 13 Italian hospitals. Eligible patients had infections caused by Enterobacterales and received ≥72 h of cefepime/enmetazobactam therapy (alone or in combination with other antimicrobials) under a compassionate-use program. Thirty-two patients were included. The most frequently isolated pathogens were Escherichia coli (16/32, 50.0%) and Klebsiella pneumoniae (13/32, 40.6%). Extended-spectrum β-lactamase production was documented in 29/32 isolates (90.6%), while β-lactam/β-lactamase inhibitor resistance and fluoroquinolone resistance were each observed in 18/32 isolates (56.2%). Four isolates were ertapenem-resistant but remained susceptible to imipenem and meropenem; no carbapenemase production was confirmed. FEP/META was safely administered as targeted therapy in most cases and was used both as monotherapy and in combination regimens, according to clinical severity and source of infection. Clinical cure was achieved in all patients, and microbiological eradication was documented in 25/32 cases (78.1%). No in-hospital deaths were recorded. Despite the inherent limitations of retrospective real-world studies, our findings suggest that cefepime/enmetazobactam may be a well-tolerated component of carbapenem-sparing treatment strategies for selected documented Enterobacterales infections. In 32 real-world documented Enterobacterales infections, cefepime/enmetazobactam achieved 100% clinical cure and 78.1% microbiological eradication, with favorable tolerability. IMPORTANCE: Antibiotic-resistant infections are an increasing challenge, and clinicians need effective treatments that can reduce reliance on carbapenems, which are often considered last-line antibiotics. Cefepime/enmetazobactam is a new antibiotic combination with activity against resistant Enterobacterales, particularly ESBL-producing bacteria, but real-world clinical data remain limited. This multicenter Italian study describes its use in 32 patients with Enterobacterales infections, including urinary tract, bloodstream, and respiratory infections. Clinical cure was achieved in all patients, microbiological eradication was documented in most cases, and no in-hospital deaths occurred. These findings suggest that cefepime/enmetazobactam may be a useful and well-tolerated carbapenem-sparing option for selected resistant gram-negative infections, while emphasizing the need for larger studies to confirm its role in routine clinical practice.

Background: Workplace-related outbreaks of invasive pneumococcal disease (IPD) have been increasingly reported among shipyard workers, yet their epidemiological and clinical features remain incompletely characterized. This systematic review and meta-analysis aimed to synthesize available evidence on IPD outbreaks in shipyard settings. Methods: A systematic search of PubMed/MEDLINE, Scopus, EMBASE, and medRxiv was conducted up to March 2026. Observational studies reporting IPD outbreaks in shipyards were included. Pooled incidence rates and clinical outcomes were estimated using random-effects models, with heterogeneity assessed by I² statistics. Risk of bias was evaluated using the Newcastle–Ottawa Scale. Results: Eight studies describing six outbreaks across four European countries (France, Norway, Northern Ireland, Finland; 2015–2025) were included, encompassing 131 cases among 35,623 workers. The pooled incidence was 368.9 cases per 100,000 workers with an attack rate of 2.36 per 1000 person-months for total cases, compared to 200.49 cases per 100,000 workers (95%CI 103.54–387.85) and 1.10 cases per 1000 person-months (95% CI 0.17–2.03) for laboratory confirmed cases, with considerable heterogeneity across studies. Most cases occurred in men (97.7%), with the median age ranging from 39 to 48 years. Hospitalizations occurred in 79.1% of cases, intensive care unit admission in 13.7%, and the case fatality ratio was 0.8%. Serotype 4 accounted for 67.2% of characterized isolates. Occupational exposures and shared accommodation may have contributed to transmission, although this could not be formally assessed. Conclusions: IPD outbreaks in shipyard settings are characterized by high incidence but relatively favorable outcomes, likely reflecting workforce demographics. However, considerable heterogeneity and methodological limitations across studies constrain the interpretation of pooled estimates. Preventive strategies, including vaccination and workplace-targeted interventions, should be considered as plausible public health measures, with a proactive role for occupational health services.

Lamivudine/dolutegravir (3TC/DTG) is an effective and well-tolerated antiretroviral regimen for most people with HIV (PWH) who are virologically suppressed; however, specific clinical characteristics, such as prior hepatitis B virus (HBV) exposure or archived resistance-associated mutations (RAMs), may influence the risk of virological failure (VF). We conducted a retrospective, monocentric cohort study to evaluate the incidence and predictors of VF among PWH who switched to 3TC/DTG after achieving virological suppression (HIV-RNA < 50 copies/mL). A total of 188 PWH were included. Over 5082 patient-years of follow-up (PYFU), 8 individuals (4.3%) experienced VF, corresponding to an incidence rate of 1.45 per 1000 PYFU. The cumulative probabilities of VF at 1, 2, 3, 4, and 5 years were 0.6%, 2.7%, 2.7%, 4.2%, and 22.3%, respectively. In exploratory multivariable analyses, anti-HBc positivity was associated with an increased risk of VF (adjusted hazard ratio [aHR] 4.80, 95% CI 1.03–22.43; p = 0.046). After adjustment for age and sex, individuals with anti-HBc positivity who had switched from a tenofovir-containing regimen showed the highest risk of VF compared with anti-HBc-negative individuals without prior tenofovir exposure (aHR 15.06, 95% CI 1.40–161.38; p = 0.025). Given the limited number of virological events, these findings should be interpreted with caution. Nevertheless, they suggest that prior HBV exposure, particularly in the context of tenofovir discontinuation, may represent a clinically relevant factor when considering simplification to 3TC/DTG.

Background and objectives: Metallo-β-lactamase (MBL)-producing Enterobacterales infections are an urgent global healthcare problem with limited treatment options. To obtain greater understanding of international perspectives on optimal management of serious infections due to MBL-producing Enterobacterales, we used a modified Delphi process to elicit experts’ opinion and establish consensus. Methods: A Delphi panel comprising 10 expert physicians experienced in antimicrobial-resistant bacterial infection management were surveyed on epidemiology, disease, testing and management of MBL-producing Enterobacterales infections. Consensus statements were based on survey responses and reviewed by the panel for endorsement or revisions to achieve consensus during a virtual meeting. Results: All panellists acknowledged MBL-producing Enterobacterales as a key source of antimicrobial resistance and infection in most countries. All agreed these infections have high morbidity and mortality, leading to the need for critical-level care, longer hospital stays and significant healthcare costs. The negative clinical and economic consequences of MBL-producing Enterobacterales are compounded by inappropriate use of multidrug antimicrobial regimens. Therefore, a specific MBL-targeting agent is considered desirable. When aztreonam-avibactam and cefiderocol are available, the preferred first-line treatment is aztreonam-avibactam, per in vitro data showing aztreonam-avibactam activity against >90% of New Delhi MBL-producing Enterobacterales. If aztreonam-avibactam or cefiderocol are unavailable, treatment options are limited to co-administration of antimicrobials. Regional differences made it difficult to achieve unanimous consensus across all survey questions due to differences in patient factors, local epidemiology and testing availability. Conclusions: The Delphi panel reached consensus on optimal management of MBL-producing Enterobacterales, confirming need for targeted MBL treatment, with monotherapy preferred where available.

Background: Among MDR bacteria, carbapenem-resistant Acinetobacter baumannii (CRAB) is a major concern due to the limited therapeutic options. Objectives: To identify predictors to aid in the clinical management of critically ill patients. Methods: We conducted a multicentre prospective study in Italy, enrolling patients with CRAB colonization who were admitted to ICUs between 2020 and 2023. Multivariable logistic regression analysis was performed to identify potential risk factors for CRAB infection. To account for competing risks, we used the cumulative incidence function (CIF) and Fine–Gray regression analysis, providing an accurate assessment of the risk of CRAB infection. Additionally, a logistic regression model was performed to estimate the impact of different types of critically ill patients on the risk of infection. Results: We included 564 colonized patients, and 381 (67.5%) developed a CRAB infection in the ICU. In the logistic regression model, multisite colonization (OR 2.78; 95% CI: 1.90–4.08; P < 0.001), Charlson comorbidity index (CCI) ≥3 (OR 1.59; 95% CI: 1.00–2.50; P = 0.047), mechanical ventilation (OR 1.48; 95% CI: 1.00–2.18; P = 0.048), male gender (OR 2.06; 95% CI: 1.38–3.10; P < 0.001), and time from ICU admission to colonization ≤12 days (OR 2.00; 95% CI: 1.36–2.94; P < 0.001) were independent predictors of CRAB infection. Findings were confirmed in the Fine–Gray model. In a secondary model, COVID-19 (OR 2.31; 95% CI: 1.30–4.10; P = 0.004) and burn patients (OR 4.84; 95% CI: 1.65–14.17; P = 0.004) were risk factors for CRAB infection. Conclusions: Early colonization from ICU admission, multisite colonization, CCI, mechanical ventilation and male gender are key risk factors for CRAB infection. These factors support clinicians in the management of critically ill patients with prior CRAB colonization.

Background: Pre-exposure passive immune prophylaxis (PrEP) might contribute to improve hematologic malignancy (HM) outcomes; however, there are currently no specific guidelines to inform patient selection. Methods: A literature review and a Delphi consensus process were used to identify COVID-19 risk factors, critical COVID-19 outcomes, and efficacy of PrEP against SARS-CoV-2 in HMs. An analytic hierarchy process was used to assign a priority score to candidate outcomes and to determine the PrEP indications. For these decisions, the experts assumed adequate compliance with anti-COVID-19 vaccination and acknowledged the effectiveness of PrEP in reducing SARS-CoV-2-related mortality and hospital admissions. Results: Based on the literature review, the expert panel identified 80 risk categories among patients with HM and prioritized eight clinical outcomes related to SARS-CoV-2 PrEP. The highest mean priority scores were observed for HM-related mortality (7.0), intensive care unit admission (6.7), and delays in anti-HM treatment (6.6). Based on such a framework, the experts deemed that if there was a variant-specific PrEP promptly available, it would be considered mandatory for all candidates receiving allogeneic hematopoietic cell transplantation, CAR-T therapy, or bispecific antibodies, regardless of local viral epidemiology. During epidemiological waves, variant-specific PrEP would also be recommended for patients with HMs at high risk of unfavorable COVID-19 clinical outcomes. Conclusions: This study identified PrEP indications for patients with HM receiving appropriate active immunization against COVID-19.