Essentials for Selecting Antimicrobial Therapy for Intra-Abdominal Infections

Abstract

Intra-abdominal infection (IAI) is a complex disease entity in which different aspects must be balanced in order to select the proper antimicrobial regimen and determine duration of therapy. A current classification indicates different faces of peritonitis. Primary peritonitis implies an intact gastrointestinal tract without overt barrier disruption. Secondary peritonitis refers to localized or diffuse peritoneal inflammation and abscess formation due to disruption of the anatomical barrier. Tertiary peritonitis includes cases that cannot be solved by a single or even sequential surgical intervention, often in combination with sequential courses of antimicrobial therapy. The most frequently used classification distinguishes ‘uncomplicated’ and ‘complicated’ IAI. In uncomplicated IAI, the infectious process is contained within a single organ, without anatomical disruption. In complicated IAI, disease is extended, with either localized or generalized peritonitis. However, there exists more than a single dimension of complexity in IAI, including severity of disease expression through systemic inflammation. As the currently used classifications of IAI often incite confusion by mixing elements of anatomical barrier disruption, severity of disease expression and (the likelihood of) resistance involvement, we propose an alternative for the current widely accepted classification. We suggest abandoning the terms ‘uncomplicated’ and ‘complicated’ IAI, as they merely confuse the issue. Furthermore, the term ‘tertiary peritonitis’ should likewise be discarded, as this simply refers to treatment failure of secondary peritonitis resulting in a state of persistent infection and/or inflammation. Hence, anatomical disruption and disease severity should be separated into different phenotypes for the same disease in combination with either presence or absence of risk factors for involvement of pathogens that are not routinely covered in first-line antimicrobial regimens (Pseudomonas aeruginosa, enterococci, Candida species and resistant pathogens). Generally, these risk factors can be brought back to recent exposure to antimicrobial agents and substantial length of stay in healthcare settings (5–7 days). As such, we developed a grid based on the different components of the classification: (i) anatomical disruption; (ii) severity of disease expression; and (iii) either community-acquired/early-onset healthcare-associated origin or healthcare-associated origin and/or recent antimicrobial exposure. The grid allows physicians to define the index case of IAI in a more unequivocal way and to select the most convenient empirical antimicrobial regimens. The grid advises on the necessity of covering nosocomial Gram-negative bacteria (including P. aeruginosa), enterococci and yeasts. The basis of antimicrobial therapy for IAI is that both Gram-negative and anaerobic bacteria should always be covered.In recent years, some newer agents such as doripenem, moxifloxacin and tigecycline have been added to the antimicrobial armamentarium for IAI. For patients in whom the source can be adequately controlled, antimicrobial therapy should be restricted to a short course (e.g. 3–7 days in peritonitis).