Over the last decade the proliferation of antibiotic-resistant pathogens has been a growing problem, especially in some geographic areas, making useless most of the classical antibiotic therapies. The rapid emergence of resistant bacteria is the result of different factors as the intrinsic microbial complexity, the growing attitude to travel of humans, animals and goods, the use of antibiotics outside hospitals, and the lack of precise therapeutic chooses for high risk group of patients. The antibiotic-resistance becomes certainly a serious problem when a resistant pathogen, and often multi-resistant today, is present in an infective site. In fact in a recent estimate of the Centre for Disease Control and Prevention (CDC) about 90.000 deaths per year in the USA are attributable to bacterial infections and in particular to resistant pathogens. It appears clear that the clinic relevance of this problem is the decimation of the sensible germs of the normal flora that leads to the upper hand of the only resistant bacteria. The antibiotic therapy, in fact, select the resistance and each bacteria has developed a particular strategy to survive: mutations of the genetic content or acquisition of resistance genes from the external. Among the Gram positive bacteria, besides methicillin resistant Staphyloccocus aureus, there are other pathogens such as coagulase-negative staphylococci (CoNS), Enterococcus faecium and Enterococcus faecalis, some species of streptococci and multiresistant Corynebacterium. The CoNS, eg. S. epidermidis, S. hominis and S. haemolyticus, are recognized as new important nosocomial pathogens and are not only responsible of invasive infections but have become in few years resistant to oxacillin (›60%) and multiresistant. The unsuspected fragility of glycopeptides, which for 40 years have been the most important treatment against infections due to Gram-positive bacteria, has posed the need for new antimicrobial molecules. Among the therapeutic possible options there are linezolid, tygecyline and daptomycin, but new other molecules are appearing in the clinical use like ceftobiprole and dalbavancin.

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Epidemiology of infectious endocarditis has changed in last decades, endocarditis associated to hospital practices, sustained by multiresistant pathogens being highly increased. In particular, methicillin-resistant staphylococci (MRSA), almost resistant to a number of other antimicrobial classes, often exhibit a reduced susceptibility to vancomycin (h-VISA) with MICs'values >1 mg/l, leading to suppose a reduced therapeutic efficacy of this drug. Thirty-one percent of MRSA strains in the ICE study, which prospectively collected more than 5000 endocarditis, were h-VISA. Daptomycin shows a rapid bactericidal activity against both methicillin-susceptible staphylococcci (MSSA) and MRSA, included those strains with reduced susceptibility to vancomycin. Daptomycin shows a good therapeutic efficacy in staphylococcal endocarditis: MRSA 71%, MSSA 75%. These data suggest the use of daptomycin as initial therapy for treatment of staphylococcal endocarditis, independently from methcillin susceptibility. Some experimental data showed that daptomycin efficacy can diminish, if it is used as a rescue therapy after vancomycin failure. The thickness of bacterial cell-wall recognized in h-VISA strains can represent a physical and electrical barrier to reach both the vancomycin and daptomycin target site. However, the reduced efficacy of daptomycin following vancomycin exposure is an extremely rare event in the clinical practice. It is preferrable to use daptomycin as first line therapy, at a proper dosage. As far as endocarditis is concerned, recent data proved the excellent daptomycin tolerability, with dosages up to 8-10 mg/kg/die. During the treatment, CPK values must be always monitored. For endocarditis sustained by vancomycin-resistant enterococci, therapeutic choices are based on linezolid or ampicillin-ceftriaxone combination therapy. Daptomycin alone, or in association with gentamycin and rifampin, can represent a promising therapeutic alternative.

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Infections in immunocompromised host are increasing worldwide. Definition of immunocompromised host encompasses a number of different pathologies, such as immune-haematological, oncological, intensivist, in addition to all patients being treated with different monoclonal antibodies and TNF-α inhibitors. Daptomycin is a novel lipopeptide antimicrobial drug, its activity against Gram-positive bacteria being rapidly cidal, without phenomenon related to bacterial lysis. Daptmomycin received approval for treatment of complicated skin and skin structures infections, sepsis, and right side endocarditis sustained by S. aureus. This article will focus the role of this new drug in the treatment of severe infections in the immunocompromised host. Clinical cases observed recently will be also presented.

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