Abstract
The worldwide propagation of antimicrobial resistance represents one of the biggest threats to global health and development. Multi-drug-resistant organisms (MDROs), including carbapenem-resistant non-fermenting Gram-negatives and Enterobacterales, present a heterogeneous and mutating spread. Infections by MDRO are often associated with an unfavorable outcome, especially among critically ill populations. The polymyxins represented the backbone of antibiotic regimens for Gram-negative MDROs in recent decades, but their use presents multiple pitfalls. Luckily, new agents with potent activity against MDROs have become available in recent times and more are yet to come. Now, we have the duty to make the best use of these new therapeutic tools in order not to prematurely compromise their effectiveness and at the same time improve patients’ outcomes. We reviewed the current literature on ceftazidime/avibactam, meropenem/vaborbactam and cefiderocol, focusing on antimicrobial spectrum, on the prevalence and mechanisms of resistance development and on the main in vitro and clinical experiences available so far. Subsequently, we performed a step-by-step construction of a speculative algorithm for a reasoned prescription of these new antibiotics, contemplating both empirical and targeted use. Attention was specifically posed on patients with life-risk conditions and in settings with elevated prevalence of MDRO.
Highlights
In 2020, WHO outlined multi-drug-resistant organisms (MDROs) as one of the biggest threats to global health, development, and food security; this phenomenon is accelerated by misuse of antibiotics and produces longer hospital stays, higher medical costs and increased mortality [1]
Among mechanically ventilated patients with life-threatening infections caused by CR Enterobacterales (CRE), mostly with septic shock and multiorgan failure, a CZA-containing regimen was an independent predictor of survival and clinical cure [23]
Karaiskos et al found a significantly lower mortality in subjects with Klebsiella pneumoniae carbapenemase (KPC)-Kp bloodstream infections (BSIs) treated with a CZA-containing regimen with respect to those treated with “classic” agents, mainly colistin and tigecycline (18.3% vs. 40.8%) [24]
Summary
In 2020, WHO outlined multi-drug-resistant organisms (MDROs) as one of the biggest threats to global health, development, and food security; this phenomenon is accelerated by misuse of antibiotics and produces longer hospital stays, higher medical costs and increased mortality [1]. The risk of the sudden introduction of a new MDRO into regions of non-endemicity via cross-border patient transfers or returning travelers is on the prowl, as witnessed by the two distinct outbreaks of New Delhi MBL (NDM) producing K. pneumoniae infections that occurred in Tuscany and Western Pomerania in 2019 [2,3]. Even considering its ageing population, one third of MDRO-related deaths of the EEA occur in Italy, heavily affecting infants and older people. This burden is mostly healthcare-associated and comparable to the cumulative effect of influenza, tuberculosis and HIV [4]. We focused our attention on CZA, MVB and CFDC rather than other new antibiotics in the pipeline as they have been available for longer and benefit from a wider available literature and real-life clinical experience
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