Emerging treatment options for acute bacterial skin and skin structure infections: focus on intravenous delafloxacin

Infection and Drug Resistance Dovepress open access to scientific and medical research REVIEW Infection and Drug Resistance downloaded from https://www.dovepress.com/ by 213.32.48.132 on 12-Jul-2018 For personal use only. Open Access Full Text Article Emerging treatment options for acute bacterial skin and skin structure infections: focus on intravenous delafloxacin This article was published in the following Dove Press journal: Infection and Drug Resistance Elda Righi Alessia Carnelutti Antonio Vena Matteo Bassetti Infectious Diseases Division, Santa Maria della Misericordia University Hospital, Udine, Italy Current scenario of complicated skin and soft tissue infections Correspondence: Elda Righi Infectious Diseases Division, Santa Maria della Misericordia University Hospital, 50, Colugna Street, Udine 33100, Italy Tel +39 0432 55 9355 Fax +39 0432 55 9371 Email The clinical spectrum of skin infections is highly variable and ranges from mild forms to life-threatening diseases.1 Among these, acute bacterial skin and skin structure infections (ABSSSI), formerly referred to as complicated skin and soft tissue infections, represent a frequent reason for hospital admission and a common cause of morbidity in the community.2,3 A nearly 3-fold increase in ABSSSI visit rates had been documented among patients presenting to the emergency departments with skin abscesses and cellulitis in the USA.2,4 Staphylococcus aureus represents the most common cause of ABSSSI, and methicillin-resistant S. aureus (MRSA) is often the most frequently isolated pathogen in complicated forms.3,5 In Europe, despite a high variability in prevalence, MRSA isolation can reach up to 25% in ABSSSI, especially in those areas where antimicrobial resistance represents a concern (e.g., Italy, Greece, and Eastern Europe).6,7 In the USA, community-acquired (CA) MRSA strains are endemic and frequently associated with skin infections and purulent skin abscesses, with reported outbreaks in military 479 submit your manuscript | www.dovepress.com Infection and Drug Resistance 2018:11 479–488 Dovepress © 2018 Righi et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://dx.doi.org/10.2147/IDR.S142140 Powered by TCPDF (www.tcpdf.org) Abstract: The increase in hospitalization due to acute bacterial skin and skin structure infections (ABSSSI) caused by resistant pathogens supports the need for new treatment options. Antimicrobial options for ABSSSI that provide broad-spectrum coverage, including gram-negative pathogens and multidrug-resistant gram-positive bacteria, such as methicillinresistant Staphylococcus aureus (MRSA), are limited. Delafloxacin is a novel fluoroquinolone available as intravenous and oral formulations and is characterized by an increased efficacy in acidic environments and activity on bacterial biofilm. Delafloxacin displays enhanced in vitro activity against MRSA, and enterococci, while maintaining efficacy against gram-negative pathogens and anaerobes. Delafloxacin has been studied for the treatment of ABSSSI and respiratory infections. Phase III studies have demonstrated noninferiority of delafloxacin compared to vancomycin, linezolid, tigecycline, and the combination of vancomycin plus aztreonam in the treatment of ABSSSI. Due to its favorable pharmacokinetic characteristics, the wide spectrum of action, and the potential for sequential therapy, delafloxacin represents a promising option in the empirical and targeted treatment of ABSSSI, both in hospital- and in community-based care. Keywords: bacterial skin and skin structure infections, multidrug-resistant bacteria, methicillinresistant Staphylococcus aureus, delafloxacin Dovepress Infection and Drug Resistance downloaded from https://www.dovepress.com/ by 213.32.48.132 on 12-Jul-2018 For personal use only. Righi et al recruits, athletes, and prisoners.8,9 MRSA prevalence among patients with ABSSSI undergoing microbiological cultures was reported as high as 75%–80% in the USA.3,10,11 The increase in hospital admissions required to treat ABSSSI with intravenous (IV) antibiotics along with the spread of multidrug-resistant (MDR) bacteria have caused a considerable impact on hospital stay and patient’s morbidity, reinforcing the need for new treatment options.12 New therapeutic options for the treatment of ABSSSI have recently become available and offer advantages such as MRSA coverage as well as the possibility for outpatient treatment (e.g., IV to oral switch and/or infrequent administration).13 New therapeutic options for complicated skin and soft tissue infections Antimicrobials that are commonly used in the treatment of ABSSSI due to methicillin-susceptible S. aureus (MSSA) include beta-lactams, especially oxacillin and flucloxacillin, fluoroquinolones (e.g., moxifloxacin and levofloxacin), and clindamycin.1 MRSA is suspected in the presence of several risk factors, including nosocomial or health care-associated infection, previous MRSA infection or colonization, recent exposure to antimicrobial agents, and abscesses.14,15 Vancomycin has been considered for decades as the drug of choice for ABSSSI caused by MRSA. In two European surveys documenting the choices of antibiotics for the treatment of ABSSSI, vancomycin was found to be the most used antimicrobial in both 2010 and 2015.16,17 Various studies, however, have now highlighted that vancomycin presents several limitations in the treatment of MRSA. First, a progressive increase in vancomycin minimum inhibitory concentrations (MICs) over the years was observed in S. aureus and was associated with less favorable clinical outcomes compared to isolates with MIC below 1 mg/L.18 Second, a decreased efficacy of vancomycin has been documented in severe infections caused by MSSA compared to MRSA.19,20 Third, in order to achieve adequate plasmatic concentrations, therapeutic drug monitoring is needed to minimize the risk of nephrotoxicity.21 Finally, vancomycin requires twice-daily IV administration, limiting the possibility for outpatient parenteral antibiotic therapy. Several novel therapeutic options have become available for the treatment of ABSSSI caused by MDR bacteria, including strains with increased vancomycin MICs (Table 1).13 Data on the efficacy of new agents for ABSSSI are mainly derived from noninferiority trials and do not directly c ompare the efficacy of newer compounds. Neverthe (...truncated)