Felice Valzano

A 65-year-old man without identifiable risk factors for multidrug-resistant pathogens was admitted with peritonitis, isolating NDM-producing Escherichia coli from a rectal swab and intraoperative samples. After surgery, ceftazidime-avibactam/aztreonam was administered. Due to poor clinical response, he was switched to imipenem-relebactam/aztreonam, resulting in a successful outcome. Whole-genome sequencing detected bla _NDM-5 and bla _CMY-148 β-lactamases, PBP3 YRIN insertion, and mutated cirA gene. This case illustrates the importance of considering different mechanisms of resistance when choosing combination therapy.

Purpose: Bloodstream infections (BSIs) pose a significant health threat, requiring effective diagnostic processes to ensure appropriate treatment. Monitoring the quality of blood cultures (BCs) process (the cornerstone of BSIs etiological diagnosis) is critical. This study aimed to describe an automated tool, BD DREAM™ (Digital Remote Extraction Analysis & Monitoring), designed for monitoring key performance indicators (KPIs) in the BCs process. Methods: A multicenter study was conducted across six Italian hospitals, analyzing 234,978 BC bottles, associated with 55,819 episodes. The system monitored KPIs related to mean blood volume per bottle, rates of solitary episodes, rate of BCs from central venous catheter (CVC) unpaired with concomitant BCs from peripheral vein, and contamination rates. Results: The findings highlighted significant variability in BC practices among centers and hospital services, with mean blood volume per bottle below recommended standards (6.45 mL vs. ≥ 8.0 mL), with 21.8% (range 3.2–62.9%) of episodes classified as solitary. The rate of BCs from CVC unpaired with concomitant BCs from peripheral vein was 14.9% (range 10.2–39.0%). Overall, contamination rates ranged from 4.2 to 4.7%, depending on the criteria adopted for definition. The setting with the more critical values was medical area. Conclusion: The tool was useful for immediate visualization and identification of hospital services with critical performance. These results suggest that integrating BC digital monitoring tools into clinical microbiology workflows is possible. Further studies will be needed to demonstrate that the implementation of BD DREAM™ can lead to enhancement of diagnostic accuracy, optimization of resources allocation, and improvement of patient outcomes.

New β-lactam–β-lactamase inhibitor combinations represent last-resort antibiotics to treat infections caused by multidrug-resistant Pseudomonas aeruginosa . Carbapenemase gene acquisition can limit their spectrum of activity, and reports of resistance toward these new molecules are increasing. In this multi-center study, we evaluated the prevalence of resistance to ceftazidime–avibactam (CZA) and comparators among P. aeruginosa clinical isolates from bloodstream infections, hospital-acquired or ventilator-associated pneumonia, and urinary tract infections, circulating in Southern Italy. We also investigated the clonality and content of relevant β-lactam resistance mechanisms of CZA-resistant (CZA ^R ) isolates. A total of 120 P . aeruginosa isolates were collected. CZA was among the most active β-lactams, retaining susceptibility in the 81.7% of cases, preceded by cefiderocol (95.8%) and followed by ceftolozane–tazobactam (79.2%), meropenem–vaborbactam (76.1%), imipenem–relebactam (75%), and aztreonam (69.6%). Among non-β-lactams, colistin and amikacin were active against 100% and 85.8% of isolates respectively. In CZA ^R strains subjected to whole-genome sequencing ( n = 18), resistance was mainly due to the expression of metallo-β-lactamases (66.6% VIM-type and 5.5% FIM-1), followed by PER-1 (16.6%) and GES-1 (5.5%) extended-spectrum β-lactamases, mostly carried by international high-risk clones (ST111 and ST235). Of note, two strains producing the PER-1 enzyme were resistant to all β-lactams, including cefiderocol. In conclusion, the CZA resistance rate among P. aeruginosa clinical isolates in Southern Italy remained low. CZA ^R isolates were mostly metallo-β-lactamases producers and belonging to ST111 and ST253 epidemic clones. It is important to implement robust surveillance systems to monitor emergence of new resistance mechanisms and to limit the spread of P. aeruginosa high-risk clones. IMPORTANCE: Multidrug-resistant Pseudomonas aeruginosa infections are a growing threat due to the limited therapeutic options available. Ceftazidime–avibactam (CZA) is among the last-resort antibiotics for the treatment of difficult-to-treat P. aeruginosa infections, although resistance due to the acquisition of transferable β-lactamase genes is increasing. With this work, we report that CZA represents a highly active antipseudomonal β-lactam compound (after cefiderocol), and that metallo-β-lactamases (VIM-type) and extended-spectrum β-lactamases (GES and PER-type) production is the major factor underlying CZA resistance in isolates from Southern Italian hospitals. In addition, we reported that such resistance mechanisms were mainly carried by the international high-risk clones ST111 and ST235.

Antimicrobial resistance (AMR) poses several issues concerning the management of hospital-acquired infections, leading to increasing morbidity and mortality rates and higher costs of care. Multidrug-resistant (MDR) bacteria can spread in the healthcare setting by different ways. The most important are direct contact transmission occurring when an individual comes into physical contact with an infected or colonized patient (which can involve healthcare workers, patients, or visitors) and indirect contact transmission occurring when a person touches contaminated objects or surfaces in the hospital environment. Furthermore, in recent years, toilets in hospital settings have been increasingly recognised as a hidden source of MDR bacteria. Different sites in restrooms, from toilets and hoppers to drains and siphons, can become contaminated with MDR bacteria that can persist there for long time periods. Therefore, shared toilets may play an important role in the transmission of nosocomial infections since they could represent a reservoir for MDR bacteria. Such pathogens can be further disseminated by bioaerosol and/or droplets potentially produced during toilet use or flushing and be transmitted by inhalation and contact with contaminated fomites. In this review, we summarize available evidence regarding the molecular features of MDR bacteria contaminating toilets of healthcare environments, with a particular focus on plumbing components and sanitary installation. The presence of bacteria with specific molecular traits in different toilet sites should be considered when adopting effective managing and containing interventions against nosocomial infections potentially due to environmental contamination. Finally, here we provide an overview of traditional and new approaches to reduce the spreading of such infections.