Volume 33, Issue 3, 2025
Review
The burden of infections caused by Metallo-Beta-Lactamase-Producing Enterobacterales in Italy: epidemiology, outcomes, and management
Tiseo Giusy,
Stefani Stefania,
Fasano Francesca Romana,
Falcone Marco
Metallo-β-lactamase (MBL)-producing Enterobacterales represent a growing public health threat due to their intrinsic resistance to several antibiotics. In Italy, the burden of infections caused by these organisms has been steadily increasing. In recent years, MBL-producing Klebsiella pneumoniae, particularly those carrying New Delhi metallo-β-lactamase (NDM) enzyme, have emerged across multiple Italian regions, frequently associated with high-risk clones such as ST147. These infections are associated with high morbidity, mortality, and healthcare costs. While advances in diagnostic techniques have improved the detection of MBLs, underreporting and heterogeneous practices are common. Therapeutic options remain limited.
The rising incidence and clinical complexity of MBL-producing Enterobacterales in Italy underscores the urgent need for coordinated actions to improve surveillance, diagnostics, infection control, and optimize antimicrobial stewardship. The development of novel therapeutic agents and the implementation of strategies for managing MBLs are crucial to reduce their clinical and public health impact. This review aims to provide a comprehensive overview of the current epidemiology, clinical outcomes, and management challenges of infections caused by MBL-producing Enterobacterales in Italy.
Managing Multidrug-Resistant Pandoraea spp.: current evidence and knowledge gaps
Geremia Nicholas,
Di Bella Stefano
Pandoraea species are emerging Gram-negative non-fermenting pathogens increasingly associated with human infections, particularly in patients with cystic fibrosis, immunocompromised hosts, and critically ill individuals. These bacteria exhibit intrinsic multi-drug resistance (MDR), complicating treatment and management. A comprehensive literature search was conducted to identify relevant studies concerning Pandoraea infections on PubMed/MEDLINE/Google Scholar and books written by experts in microbiology and infectious diseases. Pandoraea isolates frequently demonstrate resistance to the most common antimicrobials, such as β-lactams, aminoglycosides, fluoroquinolones, and polymyxins. Interestingly, many strains retain susceptibility to imipenem (IMP) despite resistance to meropenem due to the production of specific oxacillinase-type β-lactamases (OXA) called OXA-1152. Although robust clinical data are lacking, IMP and trimethoprim-sulfamethoxazole (SXT) are the most active agents and may be considered for empirical or combination therapy. Data on the efficacy of newer antibiotics against Pandoraea spp. are extremely limited and often inconsistent. This lack of strong evidence highlights a significant knowledge gap. A few antibiotic options are appropriate for treating Pandoraea spp. with IMP and SXT, which remains the treatment of choice, as well as in combination in the case of severe infections. This review focuses on a niche topic to support clinicians in selecting appropriate therapeutic decisions without precise evidence-based medicine.
Extending follow-up visits in people with HIV (PLWH) receiving bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) therapy: an expert opinion
Di Perri Giovanni,
Bonora Stefano
Our confidence on the efficacy of antiretroviral therapy has steadily increased in the last decade thanks to the continuous improvement of drugs, strategies and the ability to cope with the increase in life expectancy of patients living with HIV (PLHIV). Nevertheless antiretroviral therapy keeps on being a lifelong commitment and the current clinical research on anti-HIV treatment also points on the possibility to mitigate a series of remaining difficulties like patients’ adherence, stigma and the logistic burden associated to periodical monitoring and drug refills. The newly developed long-acting injectables drugs made it possible to reduce the frequency of administration and improved adherence, but at present the recipients of these new solutions are asked to join the outpatient HIV services at least every two months to receive their injections and undergo immunovirological monitoring. This also because these newly developed options consist of two (2DR) instead of three drugs and such close monitoring might be necessary due to the lesser genetic barrier and forgiveness. The patients who instead are under stable oral antiretroviral therapy with persistent virologic suppression may benefit from extension of the time between consecutive controls. This particularly applies when 2nd generation integrase inhibitors (INSTIs)-based three-drug regimens (3DR) are considered. Properties like intrinsic potency, genetic barrier, forgiveness, tolerability and safety make such regimens well suitable for less frequent immunovirological monitoring. The case of the single-tablet regimen consisting of Bictegravir/Emtricitabine/Tenofovir alafenamide (BIC/FTC/TAF) is unique, as in a single pill with a total net weight of 275 we actually find all the necessary ingredients to ensure the success of such initiative. Such powerful option looks as the most promising treatment to successfully increase the time between consultations and thus providing the resulting advantages.
Risk of autochthonous human Schistosomiasis transmission in Italy
De Vito Andrea,
Colpani Agnese,
Moi Giulia,
Moné Hélène,
Mouahid Gabriel,
Fusco Daniela,
Marchese Valentina,
Madeddu Giordano,
Richter Joachim
Introduction. Schistosoma (S.) haematobium is a widespread tropical helminthic zoonosis. Schistosomiasis was endemic in some foci in Southern Europe until the sixties of the last century. Autochthonous transmission of human schistosomiasis was first reported in the French island of Corsica in 2014, and the schistosome responsible for this emergence was also linked to partial hybridisation between S. haematobium and the bovine schistosome species S. bovis. Transmission has recently been retrospectively confirmed in southern Spain as well.
Risk of introduction of schistosomiasis to Italy. The distance between southern Corsica and northern Sardinia is 12 km. The freshwater snail Bulinus (B.) truncatus, one of the intermediate mollusc hosts of S. haematobium, is known to be endemic in some regions of southern Europe, including Corsica, Spain, and Portugal, where it transmits the zoonotic S. bovis. B. truncatus appears still to be endemic in Sardinia and possibly also in Sicily. Furthermore, schistosomiasis of ungulates caused by S. bovis, transmitted by the same vector snail, also appears to be endemic in Sardinia. Migrant populations and returnees to Italy have been found to be infested with schistosomes, and tourism to local freshwater bodies is increasing.
Discussion and conclusions. There is a considerable potential risk of autochthonous schistosomiasis being introduced to Italy. Therefore, surveillance has to be intensified to prevent the establishment of an autochthonous transmission cycle of human schistosomiasis in Italy. Systematic screening strategies for individuals who have been possibly exposed to endemic areas need to be established. Curative treatment of identified cases is mandatory. Praziquantel, the drug of choice, needs to be readily available throughout Italy.
Malacological surveillance of snail populations focusing on potential transmission sites is recommended. A one-health approach is recommended to verify the actual epidemiological situation of autochthonous S. bovis infestation and, thereby, to investigate the risk of establishing a zoonotic reservoir. Clinicians should be aware that, in some circumstances, schistosomiasis may occur in individuals who have never travelled to known endemic areas before.
Original article
Attitudes towards antibiotic use in end-of-life care: a nationwide Italian physician survey
Moroni Matteo,
Antonione Raffaella,
Taddei Eleonora,
Patil Luigi,
Fantoni Massimo
Background. Many patients receive antibiotics at the end of their lives: prudent use in this setting is essential to limit side effects and selective pressure. Evaluating benefits and harms of antibiotics in this context is complex, with many factors influencing final decisions, including transition to end-of-life care and diagnosis of impending death. We aimed to investigate attitudes towards antibiotic prescription among key specialists involved in end-of-life care, also as part of a consensus on antibiotic prescription at the end of life.
Materials and Methods. An anonymous ten-question survey was conducted in January 2025, over a one-month period, on the websites of the Italian Society of Infectious and Tropical Diseases (SIMIT), the Italian Society of Palliative Care (SICP), the Italian Society of General Practitioners (SIMG), and the Italian Federation of Associations of Internal Medicine Physicians (FADOI), with a denominator of 9224 potential respondents. Specialists were invited to respond questions about usual practice with both end-stage oncological and non-oncological patients. A descriptive analysis of the aggregated data was performed.
Results. 880 physicians (9.5% of the denominator) participated (59.2% female), most working in hospitals (56.7%) and internal medicine departments (39.9%). A plurality (40.8%) had less than 10 years of work experience. Attitudes towards infection management and antibiotic prescription varied widely. More than half of the respondents reported treating infections differently in oncological versus non-oncological patients. Only a minority used antibiotics to treat respiratory secretions. Most could not rely on institutional guidelines for antibiotic prescription in terminally ill patients.
Conclusion. The attitude towards antibiotic prescription at the end of life is influenced by many factors, including the physician’s background and setting. Case-by-case decision-making and advanced care planning could be significantly supported by guidelines based on studies that provide real-life data and effectively stratify patients and scenarios.
Impact of blood culture positivity on clinical outcomes in sepsis: a prospective observational study
Meena Durga Shankar,
Talkar Manish Anant,
Kumar Deepak,
Midha Naresh,
Bohra Gopal Krishana,
Tak Vibhor
Background. Bacteremia is usually considered a marker for severe infection, yet the correlation between blood culture positivity and mortality in sepsis remains uncertain. This study aimed to evaluate whether blood culture positivity is associated with adverse clinical outcomes in patients with sepsis.
Methods. This prospective observational study included adult patients with sepsis admitted to a tertiary care hospital. Patients were classified into culture-positive and culture-negative groups based on blood culture results. Clinical outcomes including 30-day mortality, length of hospital stay, and vasopressor requirement were compared. Multivariable logistic and Cox regression models were used to assess the independent association of bacteremia with mortality, adjusting for age, and comorbidities.
Results. Of 633 patients, 41.9% (n=265) were blood culture-positive. Although culture-positive patients had higher SOFA, SAPS II scores, and procalcitonin levels, 30-day mortality was similar between groups (20.8% vs. 26.1%; p = 0.12). Length of hospital stay was comparable (median 14 vs. 16 days; p=0.374), as was ICU stay duration (p=0.693). On multivariable analysis, bacteremia was not independently associated with 30-day mortality (adjusted OR 0.62, 95% CI:0.28-1.37, p=0.236). Kaplan-Meier analysis showed a non-significant trend toward higher survival in the culture-positive group (HR 1.30, 95% CI: 0.80-2.10, p=0.293).
Conclusions. Although blood culture-positive sepsis was associated with higher disease severity at presentation, it did not result in increased 30-day mortality. These findings suggest that bacteremia alone does not determine sepsis outcomes, and culture-negative sepsis should be managed with equal clinical urgency.
Validation of a clinical scoring system to differentiate mycobacterial and bacterial causes of spondylodiscitis: a retrospective cohort study from Kerala, India
Niyas Vettakkara Kandy Muhammed,
Ananthanarayanan Rajalakshmi,
Zunimol Mohamed Puthiyaveettil,
Mohan Dheeraj,
Malla Sundeep,
Van Den Broucke Steven,
Vlieghe Erika,
Bottieau Emmanuel,
Gupta Nitin
Background: Mycobacterial and bacterial spondylodiscitis require distinct therapeutic approaches. However, microbiological diagnosis is often delayed or unavailable in resource-limited settings. This study aimed to validate a clinical scoring system developed in a prior retrospective cohort study in Karnataka (India) to differentiate these aetiologies.
Methods: We conducted a retrospective cohort study of patients with microbiologically confirmed spondylodiscitis admitted between January 2017 and August 2024 in a tertiary care centre in Kerala, India. Demographic, clinical, laboratory, imaging, and treatment data were compared between the two groups, and the scoring system's diagnostic performance was assessed.
Results: Of 151 patients with infectious spondylodiscitis, 73 patients with community-acquired microbiologically confirmed infection were included. Of these, 32 (44%) had mycobacterial, and 41 (56%) had bacterial spondylodiscitis [Staphylococcus aureus (37%), Escherichia coli (11%), Klebsiella pneumoniae (11%), Streptococcus spp (4.1%), Salmonella spp (1.4%)]. The scoring system demonstrated good diagnostic accuracy for bacterial aetiology (AUC: 0.78; 95% CI: 0.67–0.88). Mycobacterial cases were younger, had longer symptom duration, lower C-reactive protein and leukocyte counts, and more frequent vertebral height loss on imaging. The rate of clinical improvement was similar between groups.
Conclusions: The validated clinical scoring system reliably distinguishes mycobacterial from bacterial spondylodiscitis and may guide empirical management in settings where timely microbiological diagnosis is not feasible.
Back to normality? Respiratory viruses, Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Bordetella pertussis trends: local epidemiological update after the COVID-19 storm
Avolio Manuela,
Reffo Ingrid,
Rigo Silvia,
del Fabro Giovanni,
Garlatti Costa Elena,
Marson Gloria,
Grazioli Silvia,
Nascimben Fabiana,
Arcidiacono Domenico,
De Santi Laura,
Bianco Luca,
Pellis Tommaso,
Nadalin Gabriella,
Crapis Massimo,
Basaglia Giancarlo,
Venturini Sergio
Background: The COVID-19 pandemic deeply impacted the epidemiology of respiratory viruses and bacteria, including Mycoplasma pneumoniae (MP), Chlamydophila pneumoniae (CP), and Bordetella pertussis (BP). We have retrospectively examined the circulation patterns of major non-culturable respiratory pathogens that cause acute respiratory infections (ARIs) over four years (2021-2024), encompassing both the pandemic and post-pandemic phases.
Methods: The study was conducted in the five hospitals of the Friuli Venezia Giulia region, in northeastern Italy from January 2021 to December 2024. A total of 11,208 respiratory samples from adult and pediatric patients displaying symptoms of ARIs, but negative for SARS-CoV-2, in accordance with our testing protocols, were tested for the following pathogens: influenza A and B (FLU A-B), adenovirus (ADV), coronaviruses (COV) 229E, NL63, OC43, bocavirus (BOV), enterovirus (EV), metapneumovirus (MPV), rhinovirus (RV), parainfluenza types 1–4 (PIV 1–4), respiratory syncytial virus A and B (RSV A/B), MP, CP, BP, and B. parapertussis (BPP).
Results: The number of tests increased from 1,076 in 2021 to 4,377 in 2024. Overall positivity rates rose as follows: 27.4% (295/1,076) in 2021, 33.6% (714/2,125) in 2022, 41.3% (1,500/3,631) in 2023, and 47.2% (2,067/4,377) in 2024. RV, ADV, BOV, COV, PIV 1-4, MPV, and RSV A/B gradually returned to pre-pandemic circulation levels. FLU A-B, not detected in 2021, re-emerged in 2022. MP, BP, and CP, nearly absent in 2021 and 2022, reappeared in 2023.
Conclusion: This retrospective study assessed the circulation of respiratory viruses, MP, Co and BP in our geographical area, observing their gradual and asynchronous re-emergence following the COVID-19 pandemic. Strengthening advanced molecular microbiological diagnostics within clinical and epidemiological settings is crucial for supporting new surveillance models and promoting the judicious use of antibiotics.
Impact of the COVID-19 pandemic on tuberculosis services in a rural area of Senegal
Menotti Giulia,
Giglia Maddalena,
Riccardi Niccolò,
Diop YacineMar,
Ndiaye Mamadou,
Gning Lamin,
Diaw Mama Moussa,
Fumagalli Giovanni,
Saderi Laura,
Sotgiu Giovanni,
Besozzi Giorgio,
Tadolini Marina
Background: The Coronavirus disease (COVID-19) pandemic significantly impacted on tuberculosis (TB) services in both high and low TB burden countries. Objectives: This study aimed to investigate the impact of COVID-19 on TB outpatient services in terms of new TB case notifications and treatment outcomes in a rural area of Senegal.
Methods: A retrospective observational study was conducted at the Health Care Centre of Diofior (HCD) in the Fimela district, Fatick Region (Senegal), covering the period from January 1st, 2018, to December 31st, 2022. Data were divided into pre-COVID-19 (until March 31st, 2020) and during-COVID-19 (from April 1st, 2020) periods for analysis.
Results: Among the 246 TB cases included (63.4% male, median age 38.4 years), 94 (38.2%) had been diagnosed in the pre-COVID-19 period and 152 (61.8%) in the during-COVID-19 period. In 2020, TB case notifications dropped by 24.4% compared to 2019, followed by an increase of 70.6% in 2021 and 91.2% in 2022. The TB treatment success rate decreased from 85.1% before COVID-19 to 77.6% in during-COVID-19 period. Moreover, mortality increased from 2.1% to 5.3%, and the lost-to-follow-up rate rose from 8.5% to 14.5% between the pre- and during-COVID-19 periods.
Conclusions: Although the number of COVID-19 cases reported in Senegal was relatively low in the study period compared to other settings, our study indicates that the pandemic had a significant impact on TB services in this rural area of Senegal.
Case report
A destruent case of recurrent primary naso-pharyngeal tuberculosis in a migrant
Sarassi Andrea Sergio,
Riccardi Niccolò,
Fumagalli Giovanni,
Pelosi Alessandra,
Repossi Alice Claudia,
Ferrarese Maurizio,
Mantero Marco,
Blasi Francesco Bruno Arturo,
Ruffo Codecasa Luigi
A 24-year-old Ukrainian man with post-natal developmental disability was treated for presumptive facial cutaneous TB in 2018 in his home country. After moving to Italy, his nostril lesion recurred in 2021, expanding to the upper lip, but he was lost to follow-up before a diagnosis was made. In 2023, when symptoms worsened, a biopsy was performed showing chronic inflammation and negative microbiological molecular tests and culture. By 2024, the lesion spread to the eyelids with worsening ulcerations. After surgical resection, histology revealed a vegetative, haemorrhagic mucosa with necrotic granulomatous inflammation and rifampin-susceptible Mycobacterium tuberculosis (Mtb) was detected at molecular testing. Diagnosis of recurrent primary cutaneous TB without pulmonary involvement was made and treatment for drug susceptible TB was initiated, leading to complete remission of the facial lesions.
Primary cutaneous TB without pulmonary involvement is rare, presenting as nodules, plaques, papules, or ulcers. Diagnosis requires systemic evaluation, imaging, infection screening and expert consultation. Cutaneous TB (CTB) is uncommon in Ukraine and accounts for less than 2% of extrapulmonary TB cases with frequent association with immunosuppression and delayed presentation. Although infrequent, CTB mirrors the wider TB scenario, that is also characterized by MDR-TB in 27% of new and 45% of retreatment cases, and XDR-TB in 13% of MDR-TB cases. In individuals coming from TB endemic areas with strong clinical suspicion, empirical TB diagnosis should always be considered despite negative microbiology to enable timely treatment and prevent progression. A multidisciplinary approach is essential for accurate diagnosis and optimal management.
Late-Onset Combined Immunodeficiency presenting with Progressive Multifocal Leukoencephalopathy and associated Immune Reconstitution Inflammatory Syndrome
Mezzadri Luca,
Borghesi Maria Lucia,
Comoli Patrizia,
Pozzi Maria Rosa,
Lapadula Giuseppe,
Rossi Marianna,
Bonfanti Paolo
Progressive multifocal leukoencephalopathy (PML) can rarely occur in individuals with occult immunosuppression. Here, we describe the case of an adult man who presented with PML, in whom CD4+ lymphocytopenia and hypogammaglobulinemia were subsequently identified, leading to a diagnosis of late-onset combined immunodeficiency. Intravenous immunoglobulin replacement therapy was initiated. His clinical course, though complicated by immune reconstitution inflammatory syndrome, was favorable.
The Infections in the History of Medicine
The contribution of Philippe Ricord (1800-1889) in the diagnosis and treatment of gonorrhea
Tsaraklis Athanasios,
Michaleas Spyros N.,
Dimitriadis Ioannis,
Pantos Constantinos,
Tzavellas Elias,
Karamanou Marianna
Philippe Ricord was a French physician who made significant contributions to the field of venereal diseases, particularly syphilis and gonorrhea, during the 19th century. He is known for his work in distinguishing between the two diseases, which were often confused due to their similar symptoms. Although his opinion on the etiology of gonorrhea turned out to be wrong, his contribution to its treatment was significant. The humorous way he conveyed his instructions, as well as its treatment, was challenging. Nevertheless, his work laid the foundations for the discovery of its cause and the appropriate treatment of gonorrhea in the future.
Diphtheria: a serious asphyctic disease that reappears occasionally. Description of the disease in Northeastern Italy from the 16th century onwards.
Contini Carlo,
Simonetti Omar,
Alvino Matteo,
Manfredini Stefano,
Vicentini Chiara Beatrice
Diphtheria is a serious and potentially fatal infection caused by Corynebacterium diphtheriae, which, before the introduction of universal vaccination, was the leading cause of illness and death among children and young adults, but which now causes sporadic but worrying outbreaks worldwide and not only among unvaccinated people.
We narrate the first descriptions of the disease until the introduction of seroprophylaxis and vaccination as well as the spread, clinical expression and treatment of diphtheria in Ferrara, and in North-Eastern Upper Adriatic Sea. We also deal with the dramatic resurgence of disease in particular categories of people and in certain countries.
The sources consulted were the Academy of Sciences of Ferrara, the Ariostea Municipal Library, periodicals of Trieste and literature books.
In the period analyzed (1869-1898), 2794 people died in Ferrara, with a maximum of 44.24 per 10,000 inhabitants in 1883 and a minimum of 0.32 in 1898. Deaths from diphtheria were highly prevalent in the countryside compared to the cities (36% vs 23%, respectively); the female gender was most affected due the prolonged contact with sick people and unhealthy environments. Mortality was very high in those patients aged from 5 to 10 years and from 3 to 5 years, with a much lower percentage in the age groups between 1 to 3 and 10 to 15 years. Cauterization of tonsil plaques, brushing with hydrochloric acid, mucilaginous gargles, cinchona, astringent substances, were among the main remedies proposed by some distinguished academics of the time before the advent of serotherapy. Some authors were the first to describe the effects of post-diphtheria paralysis including phonation disorders. The academic Baldassari connected diphtheria trends to weather variations. In the Eastern Upper Adriatic region, diphtheria was such a threat in the last thirty years of the 19th century that it surpassed cholera and typhus in terms of mortality. The disease was more common in the coastal region than on the mainland. Istria, Koper, Poreč and Pula were the cities with the highest number of cases in 1871 and 1872. The disease hit hard between October 1894 and the first months of 1895. Prophylactic measures to combat the disease included closing schools, isolating the infected patients, and publishing recommendations text on school hygiene
Diphtheria, although almost completely eradicated in most industrialized countries thanks to mass vaccination campaigns, remains endemic where inadequate vaccination policies, low socioeconomic status, inaccessibility to public health care, wars, displacement, migratory movements are present.
