The use of new antibacterial drugs against infections caused by multidrug-resistant Gram-negative bacteria: an Italian real-world evidence study in a Lombardy hospital.

Infections caused by multidrug-resistant (MDR) bacteria are typically associated with high morbidity and mortality, especially in vulnerable individuals such as patients with prolonged hospitalizations, immunocompromised individuals, and the elderly. This study aimed to provide post-marketing surveillance results concerning the prevalence of antibiotic resistance against Gram-negative bacteria through the collaboration of a multidisciplinary team. Patients involved have been treated with new antibacterial drugs, in particular ceftazidime/avibactam (C/A), meropenem/vaborbactam (M/V), cefiderocol, and ceftolozane/tazobactam (C/T). The most resistant bacterial species were Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter baumannii. Italian Drug Agency (AIFA) monitoring records for inpatients have been collected and analyzed, assessing the characteristics of the patients involved. Adverse drug reactions (ADRs) and drugs involved have been reported using a descriptive analytical approach. All data have been collected retrospectively from patient's medical records and entered into an electronic case report form (CRF). Among the 104 treated patients, Klebsiella spp. accounted for 50.1% of infections, Pseudomonas aeruginosa for 32.7%, Acinetobacter baumannii for 3%, and other bacterial species for 1.92% configuring polymicrobial infections. Regarding treatment outcomes, healing was achieved in 61 (58.6%) patients, 23 (22.1%) patients died, 8 (7.7%) patients discontinued empirical therapy, and 3 (2.9%) patients were lost to follow-up. Despite the introduction of new antibacterial drugs active against Gram-negative bacteria is improving the clinical scenario, it is crucial that the use of new antibacterial drugs be implemented by appropriate antimicrobial stewardship, surveillance programs, and monitoring efforts to prevent further spread of resistance. This study showed that the new antibiotics have good efficacy against MDR bacteria and cause negligible side effects.

Comparison and Analysis of Antibiotic Consumption in Two Italian Hospital Settings in Relation to the Fight of Antimicrobial Resistance.

Introduction: The emergence and spread of drug-resistant pathogens due to the improper use of antibiotics have become increasingly apparent in recent years. Objective: This retrospective comparative analysis aimed to assess and compare antibiotic prescription trends in Italy across two different regions based on geographic area and healthcare structure. One region represents a large hospital institution, while the other represents a populous local Italian health agency. The study also examined the impact of documented antibiotic stewardship programs and efforts to promote responsible antibiotic use at all levels, in alignment with international goals. Antibiotic consumption data were collected from the Umberto I Polyclinic Hospital and the ASL Napoli 3 South Local Health Agency. Methods: To compare consumption between regions, a standardized comparison using the Defined Daily Dose (DDD) was employed. The internal management system of each healthcare facility records all prescriptions and drug dispensations, and these data were extrapolated for this retrospective study. Results: A comparative assessment between the first half of 2022 and 2023 (January-June) highlighted a significant increase in beta-lactam antibiotic consumption, showing a twofold rise compared to the previous year's term. Regarding prescription averages, there was a noticeable increase of +29.00% in hospitalizations and +28.00% in hospital discharges within the ASL Napoli 3 South. Conversely, at Policlinico Umberto I, there was a marginal increase of +1.60% in hospitalizations and a decrease of -7.40% in hospital discharges. Conclusions: The study offers valuable insights into expenditure patterns and antibiotic consumption, underscoring the need for enhanced prescribing practices and awareness campaigns to address the issue of antibiotic resistance. The findings stress the importance of implementing international guidelines to combat the growing threat of antibiotic resistance and ensure the effective management of infectious diseases.

The Early Access and the Potential Cost Savings by the Compassionate Use of Onco-haematological Drugs: Results from the Italian Study Compass-O.

BACKGROUND: Compassionate drug use (CDU) provides early access to not yet authorised medicines and is funded by pharmaceutical companies. The observational retrospective study Compass-O monitored the CDU of onco-haematological drugs, managed by seven Italian units for cytotoxic drug preparations (Unità Farmaci Antiblastici [UFA]), between 1 January, 2016 and 31 December, 2021. OBJECTIVE: We aimed to evaluate the CDU of onco-haematological drugs managed by seven Italian UFA, between 2016 and 2021. METHODS: The seven UFA provided anonymised data concerning CDU approved in the study period. The early access and potential cost savings for the National Health System (Servizio Sanitario Nazionale [SSN]) were analysed for CDU concerning drug-therapeutic indication combinations with complete data and reimbursed by SSN up to December 2023 (date of study execution), according to the executive decision of the Italian Medicines Agency (Agenzia Italiana del Farmaco [AIFA]). Both analyses distinguished solid/liquid tumours and categorised the combinations as innovative (fully/conditionally) or non-innovative based on AIFA assessments. RESULTS: Compass-O collected 783 CDU authorisations, with 572 (73.1%) analysable in terms of early access and cost savings. On average, early access amounted to 514 days and the total cost savings was €376,115,801. Compassionate drug use approvals involved mainly solid tumours (93.7% vs 6.3% for liquid tumours), and the combination of trastuzumab emtansine-breast cancer was the most dispensed (n = 73; early access = 426 days; potential cost savings: €610,388). Out of 572 CDU approvals, 200 (35%) were innovative drug-therapeutic indication combinations, with 598 days of early access and a total potential saving of €113,124,069. CONCLUSIONS: The study Compass-O showed a significant economic burden of CDU and a relevant need for early access, particularly for innovative drugs. However, there is currently no structured monitoring of CDU in Italy, suggesting the need for a national observatory, of which Compass-O can be the pilot phase.

Effectiveness, Tolerability and Prescribing Choice of Antiviral Molecules Molnupiravir, Remdesivir and Nirmatrelvir/r: A Real-World Comparison in the First Ten Months of Use.

In 2022, three antiviral drugs-molnupiravir, remdesivir and nirmatrelvir/ritonavir-were introduced for treatment of mild-to-moderate COVID-19 in high-risk patients. The aim of this study is the evaluation of their effectiveness and tolerability in a real-life setting. A single-center observational study was set up, with the involvement of 1118 patients, with complete follow-up data, treated between the 5th of January and the 3rd of October 2022 at Santa Maria Goretti's hospital in Latina, Central Italy. A univariable and a multivariable analysis were performed on clinical and demographic data and composite outcome, the persistence of symptoms at 30 days and time to negativization, respectively. The three antivirals showed a similar effectiveness in containing the progression of the infection to severe COVID-19 and a good tolerability in the absence of serious adverse effects. Persistence of symptoms after 30 days was more common in females than males and less common in patients treated with molnupiravir and nirmatrelvir/r. The availability of different antiviral molecules is a strong tool and, if correctly prescribed, they can have a significant role in changing the natural history of infection for frail persons, in which vaccination could be not sufficient for the prevention of severe COVID-19.