The Surgical Infections Journal Club

Column Editor

Note From Column Editor, Philip S. Barie, MD, MBA

The mission of the Surgical Infection Society (www.sisna.org) is to educate healthcare providers and the public about infection in surgical patients and promote research in the understanding, prevention and management of surgical infections. The goals here are to educate and delight, to save you precious time, and to stimulate your interest in surgical infections. Surgical infections are not just those treated by surgery, but any infection that afflicts the surgical patient. The literature is disparate—important papers appear in surgical journals but may be published in infectious diseases, critical care, or general-interest medical literature. No matter the source, the focus is on high-quality data that improve patient care, emphasizing prospective trials and meta-analysis. Occasionally, momentous basic or translational science may be discussed if it changes the way we, as surgeons, think and act.

Duration of Antibiotic Therapy After Debridement of Diabetic Foot Infections

Pham T-T, Gariani K, Richard J-C, et al. Moderate to severe diabetic foot infections: A randomized, controlled pilot trial of post-debridement antibiotic treatment for 10 versus 20 days. Ann Surg. 2022;276(2):233-238

Summary: Sixty-six episodes of diabetic foot infection (DFI) of soft tissue only (excluding osteomyelitis) in 54 patients were treated by successful debridement followed by randomization (1:1) to either 10+2 or 20+2 days of antibiotic therapy. The primary end point was clinical remission at two months of follow-up. The most prevalent isolate was Staphylococcus aureus. Antibiotics were discretionary, and 28 regimens were prescribed; the most common prescription was amoxicillin-clavulanic acid. The median duration of parenteral therapy was one day, with the remainder given orally. In the intention-to-treat (ITT) population, clinical remission occurred in 27 patients (77%) in the 10-day arm compared with 22 (71%) in the 20-day arm (P=0.57) (noninferiority margin, –24% to 12%). Adverse events (P=0.71) and remission (P=0.32) were similar in both groups, and also noninferior. Overall, eight of 35 (23%) soft tissue DFIs in the 10-day arm and five of 31 (16%) cases in the 20-day arm recurred as new-onset osteomyelitis (P=0.53). By multivariable analysis, rates of remission and adverse events did not differ significantly between groups.

Commentary: DFI is a vexing constellation of dysregulated immunity, tissue ischemia, and poor wound healing. Add in that the portal of entry can sometimes be an occult foreign body, and that difficult-to-diagnose osteomyelitis can sometimes (not invariably) coexist, and it is little wonder that the failure rate for treatment with debridement and antibiotics can be 23% to 29%, as in this study. Guidance from the Infectious Diseases Society of America recommends two to three weeks of antimicrobial therapy in this circumstance, but that might be overtreatment, although the larger-scale study that is underway is needed for a definitive answer. The data suggest further that treatment failure may be unrelated to antibiotic duration. Recurrence as new-onset osteomyelitis, even after 20 days of antibiotic therapy, instead of only soft tissue infection suggests that adequacy of source control may be the major deficiency in caring for these patients; prolongation of antimicrobial therapy is no substitute. Almost without exception, when duration of antibiotic therapy for surgical infections is subjected to rigorous inquiry, the answer is that shorter is at least as good.

Timing of Antibiotics and Source Control in Sepsis, Septic Shock

Rüddel H, ThomasRüddel DO, Reinhart K, et al, and the MEDUSA Study Group. Adverse effects of delayed antimicrobial treatment and surgical source control in adults with sepsis: Results of a planned secondary analysis of a cluster randomized controlled trial. Crit Care. 2022;26(1):51

Summary: A planned secondary analysis was conducted of a cluster randomized trial of adult patients with sepsis treated in ICUs, to determine the effects of timing of antimicrobial therapy and delay of surgical source control during the first 48 hours after sepsis onset. The primary end point was 28-day mortality.

In the study, 4,792 patients received antimicrobial treatment and 1,595 patients underwent surgical source control. There was a linear relationship between timing of antimicrobial therapy and 28-day mortality, which increased significantly by 0.42% per hour of delay (odds ratio [OR], 1.019; 95% CI, 1.01-1.03; P=0.001). This effect was significant in patients with shock (OR, 1.018; 95% CI, 1.008-1.029]) and without shock (OR, 1.03; 95% CI, 1.01-1.04). Stratified by time interval, there were no differences when comparing antimicrobial treatment within one hour and one to three hours, or one hour and three to six hours. However, delays of more than six hours significantly increased mortality (OR, 1.41; 95% CI, 1.17-1.69), perhaps because the delays also increased the odds of progression to shock (OR per hour, 1.051; 95% CI, 1.022-1.081; P=0.001). Time to surgical source control was significantly associated with decreased odds of success (OR, 0.982; 95% CI, 0.971-0.994; P<0.01), but the odds of death increased only among patients with shock (adjusted OR, 1.013; 95% CI, 1.001-1.026; P=0.04).

The authors suggested that management of sepsis is time-critical, both for antimicrobial therapy and source control. Furthermore, for patients who are not yet in septic shock, early antiinfective treatment can prevent further deterioration.

Commentary: Two hypotheses underlie the premise of this planned post hoc analysis: First, timely antimicrobial therapy (the sooner, the better; ideally, within one hour) improves sepsis outcomes; and second, surgical source control, when indicated, must also be as timely as possible. For the former, the issue is nuanced; for the latter, data are surprisingly scant. These data help to prioritize care for seriously/critically ill patients with sepsis or septic shock. Regarding antimicrobial therapy, the important message is that delay of six hours or more increases the risk for development of shock and mortality. The more important finding here from the surgical perspective is that delayed source control (usually defined as successful surgical intervention for secondary peritonitis) decreases the odds of success, but that only patients with shock are at risk for death from delay.

Intraoperative Redosing of Antibiotic Prophylaxis

Wolfhagen N, Boldingh QJ, de Lange M, et al. Intraoperative redosing of surgical antibiotic prophylaxis in addition to preoperative prophylaxis versus single-dose prophylaxis for the prevention of surgical site infection: A meta-analysis and GRADE recommendation. Ann Surg. 2022;275(6):1050-1057

Summary: A meta-analysis was performed to determine the effect on the incidence of surgical site infections (ssI) of preoperative surgical antibiotic prophylaxis (pSAP) with additional intraoperative redosing (iSAP) compared with single-dose pSAP, after a systematic search of multiple publication databases (PROSPERO registration CRD42021229035 [an international database of prospectively registered systematic reviews with health-related outcomes]). Included studies compared the effectiveness of pSAP with iSAP on ssI incidence in patients undergoing multiple types of operations. A random effects model was used to estimate pooled odds ratios with 95% confidence intervals.

Two randomized controlled trials (RCTs) and eight cohort studies were included, with a total of 9,470 patients. Pooled ORs for ssI in patients receiving intraoperative redosing were 0.47 (95% CI, 0.19-1.16; I²=36% [low heterogeneity]) for RCTs and 0.55 (95% CI, 0.38-0.70; I²=56% [moderate heterogeneity]) for observational cohorts. There was considerable variation in antibiotics used and redosing protocols. The authors concluded that intraoperative redosing of SAP may reduce the incidence of ssI compared with single-dose pSAP, based on studies with considerable heterogeneity of antibiotic regimens and redosing protocols, and low certainty of evidence.

Commentary: Preoperative SAP is part of standard care for the prevention of ssI after contaminated cases, most clean-contaminated cases (but not elective laparoscopic cholecystectomy), and some clean procedures (e.g., insertion of a prosthesis). During “long” operations, intraoperative redosing of SAP is advisable, but there is great variation in redosing tactics and compliance. “Long” is a term of art because the half-life of the agent chosen for SAP also is crucial. Intraoperative redosing is optimal when short half-life agents are administered (e.g., cefazolin [1.2-2.2 hours], cefoxitin [0.7-1.1 hours]), but not for agents with a long half-life (e,g,, metronidazole [6-8 hours]. Ideal administration of SAP provides high tissue antibiotic concentrations at the time of incision and while the incision remains open (and thus vulnerable to inoculation by pathogens), but not after the incision is closed, and not to “cover” drains or catheters. Additional high-quality data are needed (only two RCTs included; inclusion of heterogeneous operation types that may have underpowered the estimate of the effect size), but this should serve as a reminder to redose intraoperatively when appropriate, based on case type, procedure duration, and agent chosen for SAP.

The First Surgical Operation? 31,000 Years Ago!

Maloney TR, Dilkes-Hall IE, Vlok M, et al. Surgical amputation of a limb 31,000 years ago in Borneo. Nature. 2022 Sep 7. doi:10.1038/s41586-022-05160-8

Summary: Late Pleistocene epoch remains of a human adolescent or young adult, possibly male, found in a cave in Borneo, show evidence of a healed left below-knee amputation. Radiocarbon dating of charcoal found at the burial site, and a combined uranium series and electron spin dating technique done on a sample from a left mandibular molar, combined with Bayesian modeling, yielded a combined age estimate of 31,201 to 30,714 years. Recovered left tibia and fibula shaft fragments showed unusual, remodeled bone growth covering the amputation sites, demonstrating healing and suggesting a deliberate surgical amputation, rather than comminuted, crushed fractures from an accident or animal attack, which are absent. Completely remodeled lamellar bone encased the distal fibula, indicating that the individual survived for a minimum of six to nine years after the procedure. There was no evidence of infection. Cortical thinning, more prominent on the left, suggested the “patient” was rarely ambulatory owing to the resultant incapacity.

Commentary: This finding changes history! In a remarkable feat of paleoanthropology and forensic pathology, convincing evidence has been presented that a formal surgical operation was performed more than 30,000 years ago, with long-term survival of the patient. Learned treatises on the history of surgery speculate that trepanations (craniotomy) some 5,000 to 10,000 years ago are the earliest operations performed on human beings, with survival commonplace. Scientific evidence exists of a partially healed forearm amputation some 7,000 years ago in skeletal remains of a Neolithic Era farmer unearthed in Buthiers-Boulancourt, France. This astonishing find extends the history of surgery 20 millennia into the past.

The circumstances can only be imagined. Was a traumatic amputation revised, or was surgery performed de novo for injury, a tumor, or deformity? Flaked chert (a hard, fine-grained sedimentary rock composed of micro- or cryptocrystalline quartz that can hold a fine, sharp edge) was found nearby, so the surgical instrument can be imagined. Lower extremity anatomy may have been known from the butchery of game. But what of hemostasis, infection control, or pain management? Considerable technology and expertise inform successful surgery. Was a tourniquet applied? Was the pharmacopeia of the primeval forest understood? Immobility must have been usually fatal to hunter-gatherers—what rehabilitation (or position in society) allowed survival for years? Much is written today of surgery in austere environments—there and then, technology and compassion combined for success in the most austere environment imaginable.