What Do Surgeons Need to Know About Intra-Abdominal Infections? Guidance from the Surgical Infection Society

John Mazuski, MD, PhD

Intra-abdominal infections (IAIs) are defined as disease processes occurring in normally-sterile parts of the abdominal cavity and are generally treated mechanically, such as by surgery. IAIs are common and, despite the medical advances over the past decades, still pose a great risk to the patient, including the risk of death. Beginning in 1992, the Surgical Infection Society (SIS) has published a series of guidelines concerning the treatment of IAIs. The previous guideline was published jointly with the Infectious Diseases Society of America in 2010.

The latest solo version by the SIS, which included an in-depth literature review, was published this past January¹. The revision was planned with the intent of addressing the current challenges in treatment of IAIs. These challenges include the increasing prevalence of chronic diseases, which can impair the immune system and decrease the resiliency to infections, societal aging, and the rising global occurrence of bacterial antimicrobial resistance.

Specifics

What aspects of the latest IAI management guidelines should surgeons be aware of?

• Risk assessment stratifies patients according to factors including age, comorbidities, extent of infection, the possible presence of antibiotic-resistant bacteria, and signs of sepsis or septic shock as defined by the Surviving Sepsis Campaign² to guide treatment decisions and timing.
• Initiation of source control within 24 hours and even sooner in high-risk patients (eg, those with sepsis or septic shock), and use of the least invasive approach that achieves adequate source control.
• Consider the use of alternate or temporary source control in patients at higher risk of failure of usual source control measures, including abbreviated laparotomy and temporary abdominal closure in select at-risk patients or if second look laparotomy is planned.
• Use antimicrobials active against typical Gram-negative Enterobacteriaceae, Gram-positive cocci, and obligate anaerobes.
• Use of narrower-spectrum antibiotics for empiric therapy of lower-risk adults and children.
• Use of broader-spectrum antibiotics for higher-risk patients and those suspected of harboring resistant pathogens, for example, ceftolozane-tazobactam plus metronidazole for empiric therapy of adults suspected of infection with multiple drug-resistant strains of Pseudomonas aeruginosa.
• Begin antimicrobial therapy within 1 hour or as soon as possible after IAI diagnosis

“It’s not a revolutionary document, it’s an evolutionary document,” said John Mazuski, MD, PhD, Professor of Surgery at Washington University School of Medicine, Saint Louis, Missouri and lead author of the latest guidelines told Contagion^®. The general principles as to how treatment should be administered have not changed. “For surgeons, management principles of complicated IAI are part and parcel of our training. As surgeons, we are trained to know how to treat these infections. What the document strives to do is provide contemporary guidance on this subject,” said Dr. Mazuski.

The latest guidelines were revamped with 2 overarching goals. One was “to be absolutely transparent,” meaning that the evidence and the thinking underlying all the recommendations are presented. This was done to remove any debate over the reasoning behind the recommendations and quell any doubt about any influences behind the decisions made.

The other goal was to structure the text to create an algorithmic flow of information. The document, which Dr. Mazuski described as “nuanced,” was not intended to lay out hard-and-fast rules, but rather to guide the timely assessment of a patient’s condition and other factors that drive treatment decisions, including antibiotic selection, and what courses of action to take if treatment fails.

Efforts are underway to develop a software app that can be used in the examination room or at the bedside to help guide treatment.

Antimicrobial Stewardship

The algorithm approach emphasizes the principals of antimicrobial stewardship. “It’s been in every other guideline, but we wanted to make it more explicit here,” explained Dr. Mazuski.

Antimicrobial resistance is a global problem. The United States is not exempt. For example, the prevalence of fluoroquinolone resistance of Escherichia coli, one of the major IAI pathogens, is typically in the double digits in hospitals. In Dr. Mazuski’s institution, about 30% of all E. coli isolates are resistant to fluoroquinolone antibiotics. Resistance to beta-lactamase antibiotics like cephalosporins and penicillins due to the bacterial acquisition of extended-spectrum beta-lactamase enzymes which inactivate those antibiotics has grown from sporadic to extensive in the span of 2 decades.

The need for the rational use of antibiotics to curb the rise in antimicrobial resistance is not new. This has been recognized for over 30 years. But now, the problem has become a glaring and dangerous reality. “The difference between 30 years ago and now is that now we are seeing the consequences of our inappropriate use of antibiotics. We had a fabulous class of antibiotics—fluoroquinolones—which became available in the 1970s and 1980s, and we wasted them because we used them for every case of a sore throat or sinusitis. And now we’ve got widespread antibacterial resistance to fluoroquinolones. That explains the need for antimicrobial stewardship in a nutshell,” said Dr. Mazuski.

The document addresses the antimicrobial stewardship issue in several ways. One is the emphasis on risk assessment. A clear-eyed assessment of a patient will reveal cases where a broad-brush antibiotic strategy is the way to go, but also other cases where a more tailored approach is better. An otherwise healthy, 25-year-old with perforated appendicitis may not need an all-out antibiotic response. An antibiotic with a fairly narrow spectrum of activity could suffice as the first step. But, a 75-year-old patient with other medical issues who presents with a 3-4-day history of a perforated, gastric ulcer is a different situation.

Source Control

Another key element of the document is source control—identifying the origin of the infection and treating to eliminate that source. There can be a variety of potential organ sources, including perforated appendix, perforated gallbladder, perforated ulcer, abdominal abscess, the gastrointestinal tract (the overwhelming source of secondary peritonitis), and so on. Treatment may not be complicated, provided that it is correctly directed at the true source of the infection.

The revised guidelines make clear that using the least invasive approach to achieve adequate source control and tailoring the source control procedure to the individual patient is important. For instance, a damage-control strategy rather than a one-shot effort may be the best approach for an unstable critically-ill patient. One does what is most needed at the time to limit ongoing contamination and then returns a bit later, when the patient has stabilized, for completion of all surgical treatments that need to be done.

Intra-abdominal infections, like surgical skin/soft tissue infections, “are a different breed of animal” from pneumonia or bacteremia. This is because, for the former, there are mechanical means to treat them. The most effective antibiotic to treat an IAI, according to Dr. Mazuski, is the surgical scalpel. Excising the source of the infection rids the patient of the overwhelming majority of the infecting bacteria, with the remaining bacteria being mopped up by a targeted antibiotic or other therapy.

Source control is a facet of antimicrobial stewardship. “If you do appropriate source control and effective surgery, inevitably you will reduce your reliance on antimicrobials,” said Dr. Mazuski. The document makes the point that source control does not always mean doing the most invasive surgery. By intent, the guidelines do not discuss the nuts and bolts of how to address IAIs. Instead, the message is to use the least invasive approach that provides adequate source control, with suggestions regarding select patients, such as critically ill elderly patients.

Antimicrobial Recommendations

The bulk of the guideline recommendations concern the choice of antimicrobial agents, with the emphasis on the use of appropriate drugs at first before the final pathogens are known. The targets of treatment have been known for 50 years. These include Gram-negative Enterobacteriaceae, with Escherichia coli as the “main actor” and a plethora of anaerobic bacteria, in particular, Bacteroides fragilis. Treatment needs to cover these organisms and then can be nuanced in terms of the individualities of the patient.

The guidelines also make the point that not all situations in which the abdominal cavity is contaminated with these bacteria constitute an IAI. A patient who undergoes rapid surgical treatment of an abdominal gunshot wound does not have an IAI, although the patient is at risk for one, since the initial wound has created tissue damage and contamination that can drive the development of an IAI. However, attempting to treat the contamination with a prolonged antibiotic course does not prevent it from happening. When a case crosses the line from contamination to an established infection is uncertain. The guidelines recommend, for example, that patients with a lower gastrointestinal source treated greater than 12 hours after injury, or an upper gastrointestinal source like the stomach or duodenum treated 24 hours after injury be judged as having crossed the threshold between contamination and infection, and treated accordingly. The judgement is arbitrary; science lags behind physician experience on this one.

One Size Does Not Fit All

The development of bacterial resistance throughout the world has significantly impacted the antibiotic options available. In areas of the world where there is a high incidence of bacteria producing extended-spectrum beta-lactamases, carbapenems are still generally effective. However, heavy use is increasing resistance to these agents. Carbapenem-resistant Enterobacteriaceae (CRE) including E. coli and various species of Klebsiella, as well as other bacteria, such as Pseudomonas are being encountered more frequently. The widespread routine use of carbapenems will surely lead to a repeat of the glum history of increased resistance. For instance, hospitals in China are already facing the problem of widespread infections in their intensive care units due to Acinetobacter-resistant to carbapenems. Bacteria know no geographic boundaries. Without the implementation of stewardship practices like those outlined in the SIS revised guidelines, such resistant bacteria will become a US problem as well.

The recommendations address both the “garden variety” patient, like those with uncomplicated appendicitis or diverticulitis, as well as the more challenging cases. For patients who are sicker, such as those with signs of sepsis or septic shock, swift delivery of effective treatment is even more crucial. If the initial antibiotic selection does not hit the mark, the outcome can be death. For such urgent cases, the recommended antibiotic regimen is a broad approach from the get-go, with de-escalation of therapy to more “pathogen-directed therapy” once the pathogen is identified.

Patients who are already hospitalized have likely been treated with antibiotics. A different tactic is needed for these patients, since they could be predisposed to treatment failure or may already harbor antibiotic-resistance pathogens. The revised recommendations have recognized this in a nuanced way with the suggestion of a broader antimicrobial approach at first, but with awareness of the particular resistance problems in the particular hospital where the patient resides. There is no cookie-cutter approach. For institutions experiencing a problem of antibiotic resistance, the initial choice of “a more exotic antibiotic” like a carbapenem, aminoglycoside, or polymyxin drug could be prudent. For other institutions, this choice would be questionable. Patient risk factors also need to be considered; for example, some patients may be deemed more at risk of developing a fungal infection while others are not. “You have to know what you are dealing with,” explained Dr. Mazuski.

There’s no question, IAIs are a big deal. Nationally, there are about 500,000 cases of appendicitis each year, with hundreds of thousands of cases of cholecystitis. Not all are complicated, but the numbers add up. “In our institution, we see at least 1 patient a day with an intra-abdominal infection,” said Dr. Mazuski. IAIs and skin and soft tissue infections account for a large proportion of emergency general surgeries. The intention and hope of the revised guidelines is that the use of the step-by-step algorithmic approach will assist surgical practitioners in providing treatment of an IAI directed at patient and institutional individualities.

References

1. Mazuski JE, Tessier JM, May AK, et al. 2017 Surgical Infections 18:1-75.
2. Rhodes A, Evans LE, Alhazzani W, et al. 2017 Crit Care Med 45:486-55

Brian Hoyle, PhD, is a medical writer and editor from Halifax, Nova Scotia, Canada. He has been a full-time freelance writer/editor for over 15 years. Prior to that, he was a research microbiologist and lab manager. He can be reached at hoyle@square-rainbow.com.