Response to “Re-Thinking the Definition of Complicated Intra-Abdominal Infection”

To the Editor:

We thank Dr. Zhang and colleagues for their comments regarding “The Surgical Infection Society Revised Guidelines on the Management of Intra-Abdominal Infection” [1]. They appropriately point out the difficulties inherent in defining a complicated intra-abdominal infection (IAI). They also note that death and other adverse outcomes are not necessarily dependent on whether or not a patient has an uncomplicated versus a complicated IAI, but rather on the host's physiologic response to that infection, regardless of the exact nature of the IAI.

It was precisely for these reasons that an attempt was made to avoid using the term complicated IAI within the guideline as much as possible, even though much of the guideline material relates to disease processes usually characterized as complicated IAI. The problem is the word complicated. The origin of the term complicated IAI is somewhat obscure, but it was most likely coined to describe an infection in which a person with a localized infection, such as acute appendicitis or acute diverticulitis, sustained a complication such as perforation. Thus, the term complicated IAI implies an infection spreading beyond the organ of origin, generally necessitating a source control procedure for control.

For many clinicians unfamiliar with this specific terminology, however, complicated implies a disease process of greater complexity and severity, which is presumably more difficult to manage and associated with a higher mortality rate. As Dr. Zhang and colleagues note, however, treating a severely ill patient with biliary tract disease, which technically could be called an uncomplicated IAI, may be a much greater challenge than treating a patient with a straightforward complicated IAI, such as perforated appendicitis.

Unfortunately, the definition of complicated IAI used in this and previous guidelines is the one used by regulatory agencies, such as the United States Food and Drug Administration. In the United States, the only evaluable patients in clinical registration trials of anti-infective agents for IAI are those who have positive cultures, essentially limiting subjects to those who have undergone source control procedures for a complicated IAI. Pharmaceutical companies must adhere to this definition when promoting their products in the United States and elsewhere. Thus, it is not practical to dispense with this term and use an alternative definition at this time.

Nonetheless, throughout the guideline, many recommendations were characterized as applying to patients with a lower or higher risk of an adverse outcome, irrespective of the nature of their infections. In effect, this mimics the proposal of Zhang et al. without changing the definition of a complicated IAI. This approach was outlined in Section I of the guideline. Key components of that stratification include markers of physiologic dysfunction, such as sepsis or septic shock, elevated Acute Physiology and Chronic Health Evaluation II scores, and other evidence of organ system dysfunction. In agreement with Dr. Zhang and colleagues, these are the primary drivers of morbidity and death with IAI. Certain characteristics of the infection itself, however, such as a diffuse nature with a minimal host response localizing the infection, or the presence of resistant bacteria, may also adversely affect outcomes.

Finally, despite the extensive nature of this guideline, its scope had to be limited. Not all infections arising in the abdominal region could be addressed. The primary focus was on those infections generally described as complicated IAI; recommendations on the management of other abdominal infections, such as cholangitis and Clostridium difficile colitis, were not made. Other guidelines are available that focus more specifically on these pathologic processes [2–4].