Infections caused by Acinetobacter baumannii (A. baumannii) bacteria are increasingly recognized as a serious health threat, especially in healthcare facilities, and are associated with increased morbidity, mortality and duration of hospital stay, as well as with high healthcare costs (Giamarellou et al. Acinetobacter baumannii: a universal threat to public health? Int. J. Antimicrob. Agents, 2008, 32(2), 106-9; Howard et al. Acinetobacter baumannii. An emerging opportunistic pathogen. Virulence 2012, 3(3), 243-250).
A. baumannii is a rod-shaped Gram-negative bacillus that is aerobic, and non-motile. It behaves as an opportunistic pathogen mainly affecting immunocompromised subjects, for example those having an underlying disease, such as chronic lung disease or diabetes, and those hospitalized for long periods and subjected to multiple invasive procedures.
A. baumannii is often implicated in nosocomial infections, so it has a high incidence among patients experiencing prolonged hospital stay, and is a particularly relevant source of infections in hospital intensive care units (ICUs). Among the main risk factors for acquiring A. baumannii is the use of artificial devices commonly employed in hospital settings, such as dialysis, mechanical ventilation, sutures or catheters, due to the notorious ability of A. baumannii to survive for extended periods on environmental surfaces.
A. baumannii can cause infections in virtually every organ system of the human body, including pneumonia, surgical site infections, skin and soft tissue infections, urinary tract infections, post-operative meningitis and catheter-related infections.
Hospital-acquired pneumonia is the most common life-threatening hospital-acquired infection, and is mainly associated with the use of mechanical ventilation, known as ventilator associated pneumonia (VAP). VAP infections caused by Acinetobacter are between 8% and 35% of total VAP cases.
Bloodstream infections (BSI) are also common nosocomial infections, which are also associated with increased morbidity, mortality and duration of hospital stay. Infections caused by Acinetobacter correspond to 2% of the total BSI cases, with a particular high incidence in ICU-acquired BSI.
Other reported hospital-acquired infections associated with A. baumannii are, for example, surgical site infections (SSI) and urinary tract infections, such as catheter-associated urinary tract infections (CAUTI) or hospitalized community-acquired urinary tract infections.
A. baumannii infections are currently treated with different broad- or semi-broad spectrum antibiotics or combinations, including, for example, the carbapenems imipenem, meropenem and doripenem, which are first choice drugs. However, treatment of A. baumannii infections is challenging since it has emerged as a highly drug-resistant pathogen, especially carbapenem-resistant, and therefore other alternative broad-spectrum antibacterials are also used in therapy, such as polymyxins (colistin, polymyxin E and polymyxin B), tigecycline, tetracyclines (minocycline and doxycycline) or aminoglycosides (amikacin and tobramycin). None of the currently used treatments are specific for A. baumannii. 
The use of such broad-spectrum antibacterials entails important drawbacks, since they have a substantial impact on the normal flora, potentially diminishing the immunologic function of microbiota and potentially generating treatment-induced co-infections caused by resistant strains, as disclosed for example in Jernberg et al. Long-term impacts of antibiotic exposure on the human intestinal microbiota, Microbiology, 2010, 156(Pt 11), 3216-3223.
Moreover, in a retrospective study performed with 26,107 patients, it was concluded that the use of broad-spectrum antibiotics may have a relationship with the development of irritable bowel syndrome (IBS), as disclosed in Villarreal et al. Use of broad-spectrum antibiotics and the development of irritable bowel syndrome, WMJ, 2012, 111(1), 17-20.
In contrast, treatments using pathogen-specific antibacterials that kill exclusively the infecting bacteria would minimize the impact on normal flora and would avoid the selection of resistant strains of non-infecting bacteria of microbiota, thus minimizing any treatment-induced co-morbidities.
To date, the only pathogen-specific compound that has been described in prior art is a synthetic cyclo-peptide known by the laboratory code POL7080, that is currently under clinical development. It has been reported that POL7080 has antimicrobial activity exclusively against Pseudomonas bacteria but, conversely, shows no activity against Acinetobacter bacteria.
Therefore, there is still a need to develop new antibacterial agents that are effective for treating the life-threatening infections caused by Acinetobacter bacteria and that also show a selective antimicrobial pattern to avoid the disadvantages associated to the non-selective broad-spectrum antibiotics currently used in therapy.
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USPTO Backgrounds