Resistant Pathogen-associated Skin and Skin-structure Infections: Antibiotic Options

Daniel Curcio


Expert Rev Anti Infect Ther. 2010;8(9):1019-1036. 

In This Article

Expert Commentary & Five-year View

Although uncomplicated SSSIs can usually be treated using oral antibiotics on an outpatient basis,[174] most cSSSIs involve deep soft tissues or have complicating factors and, therefore, initial hospitalization is often required to perform surgery and administer systemic antimicrobial therapy.[174]

Appropriate antibiotic management of these cases remains a challenge because of emerging resistance among pathogens such as MRSA, VRE and certain Gram-negative bacilli (i.e., ESBL-producing Enterobacteriaceae and MDR P. aeruginosa, among others).

The initial selection of antimicrobial therapy for treatment of cSSSI is extremely important because an association has been shown between inappropriate empiric antimicrobial therapy and delayed clinical resolution, increased length of hospital stay and an increased risk of mortality. Kollef stated "Initial empirical therapy with broad-spectrum antimicrobials attempts to address this dilemma by getting it right up front".[175] The goal is to provide treatment active against the most likely pathogens until culture/susceptibility test results are obtained. Based on this concept, the cornerstone in cSSSI is to identify those patients who have risk factors for MDR pathogens. A practical approach that includes these parameters is proposed in Figure 2.

Figure 2.

Patients in which complicated skin and skin-structure infection due to multidrug-resistant pathogens should be suspected.
3GC: Third-generation cephalosporins; CA-MRSA: Community-acquired methicillin-resistant Staphylococcus aureus; cSSSI: Complicated skin and skin-structure infection. MDR: Multidrug resistant.

Infection caused by MRSA is one of the greatest – if not the greatest – challenge related to cSSSI, not only in hospital-acquired infection but increasingly in a community setting. Vancomycin has very much been seen as the mainstay of treatment worldwide but its MIC creep is undermining its perceived utility. Furthermore, an increasing number of new agents are being introduced, many of which have advantages over vancomycin, and these will be used as alternatives (i.e., linezolid, daptomycin and tigecycline). Among the investigational agents, the newer cephalosporins, which have marked anti-MRSA activity, such as ceftobiprole and ceftaroline, again look promising as bactericidal and safe drugs, but their impact on the hospital environment, particularly in relation to the selection of ESBL and AmpC Enterobacteriaceae, may well prove to be a substantial problem.

Carbapenems are stable against hydrolyzing activity of ESBLs and are regarded as the drug of choice for the treatment of cSSSIs caused by ESBL-producing Enterobacteriaceae. However, its overuse/misuse is related to the selection and emergence of carbapenem-resistant A. baumannii and P. aeruginosa. The optimization of carbepenem pharmacodynamic parameters (i.e., extended infusion), as well as the therapeutic substitition by other agents with the same spectrum and minor potential for collateral damage (i.e., tigecycline), could be an excellent option in these cases.

Related to the development of antimicrobial agents, there are currently 16 compounds in the late stages of development and eight of them have activity only against Gram-positive microorganisms; none are active against carbapenemase-producing bacteria. In this context, physicians should take into account that, in the coming years, few antibiotics will be available to treat severe infections due to Gram-negative MDR pathogens.[176]

In summary, the appropriateness of administration, based on local resistance patterns, is the most important determinant to optimize the the antimicrobial treatment, but dosing intervals and dose probably play similarly important roles in outcomes. However, in most of the studies, the primary reason for administration of inappropiate antimicrobial therapy was the presence of MDR Gram-negative and Gram-positive bacteria that were not susceptible to the prescribed antibiotic regimen, therefore it is mandatory to take into account in each patient their individual risk factors for MDR pathogens in order to select the better antibiotic and improve the clinical outcomes. In addition to systemic antibacterial therapy, adequate surgery of devitalized tissues, or drainage of abscesses or fluid collections, is an integral part of the appropriate management of cSSSI. The timing of surgical intervention may also be critical; for necrotizing infections, early surgery can be life-saving.


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