Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Prenatal Intestinal Obstruction Affects the Myenteric Plexus and Causes Functional Bowel Impairment in Fetal Rat Experimental Model of Intestinal Atresia

<div><p>Background</p><p>Intestinal atresia is a rare congenital disorder with an incidence of 3/10 000 birth. About one-third of patients have severe intestinal dysfunction after surgical repair. We examined whether prenatal gastrointestinal obstruction might effect on the myenteric plexus and account for subsequent functional disorders.</p><p>Methodology/Principal Findings</p><p>We studied a rat model of surgically induced antenatal atresia, comparing intestinal samples from both sides of the obstruction and with healthy rat pups controls. Whole-mount preparations of the myenteric plexus were stained for choline acetyltransferase (ChAT) and nitric oxide synthase (nNOS). Quantitative reverse transcription PCR was used to analyze mRNAs for inflammatory markers. Functional motility and permeability analyses were performed in vitro. Phenotypic studies were also performed in 8 newborns with intestinal atresia. In the experimental model, the proportion of nNOS-immunoreactive neurons was similar in proximal and distal segments (6.7±4.6% vs 5.6±4.2%, p = 0.25), but proximal segments contained a higher proportion of ChAT-immunoreactive neurons (13.2±6.2% vs 7.5±4.3%, p = 0.005). Phenotypic changes were associated with a 100-fold lower concentration-dependent contractile response to carbachol and a 1.6-fold higher EFS-induced contractile response in proximal compared to distal segments. Transcellular (p = 0.002) but not paracellular permeability was increased. Comparison with controls showed that modifications involved not only proximal but also distal segments. Phenotypic studies in human atresia confirmed the changes in ChAT expression.</p><p>Conclusion</p><p>Experimental atresia in fetal rat induces differential myenteric plexus phenotypical as well as functional changes (motility and permeability) between the two sides of the obstruction. Delineating these changes might help to identify markers predictive of motility dysfunction and to define guidelines for post-surgical care.</p></div

Neurochemical plasticity of intestinal segments in human atresia.

<p>(<b>A,B</b>) The proportion of ChAT-IR myenteric neurons (normalized to the total number of Hu-IR neurons) was slightly but not significantly lower in distal segments than in proximal segments (n = 8; p = 0.31; two-tailed Wilcoxon test). (<b>A,C</b>) The proportion of nitric oxide synthase nNOS-IR neurons (normalized to the total number of Hu-IR neurons) was similar in proximal and distal segments (n = 8; p = 0,84; two-tailed Wilcoxon test). Magnifications 40X.</p

H&S histology of intestinal segments in human atresia.

<p>In proximal (<b>A</b>) and distal segments (<b>B</b>) of human atresia the mucosa had a normal aspect, with no alterations of the villi or crypts, but mild infiltration of the submucosa. Muscle hypertrophy was present in the proximal segments, predominating in the internal circular layer (<b>A</b>). Magnification ×25.</p

Neurally mediated contractile responses of ileal longitudinal muscle strips to electrical field stimulation (EFS) in experimental intestinal atresia.

<p>(<b>A</b>) Typical recording after EFS in proximal segment showing an increase in the contractile response. (<b>B</b>) Typical recording after EFS in distal segment from the same atresia as in (A) showing a lower contractile response than in proximal segment. (<b>C</b>) Neurally mediated contraction induced by EFS of longitudinal muscle was significantly higher in proximal than in distal segments (n = 12; *p<0.01; paired <i>t</i> test). Data are medians, 5–95th percentiles and range.</p

EFS-induced induced area under the curve (AUC) in absence or in presence of <i>N</i>-nitro-l-arginine methyl ester (l-NAME) and atropine in experimental intestinal atresia.

<p>Pre-treatment with N-nitro-L-arginine ester (L-NAME 50 µM) did not affect the EFS-induced contractile response of proximal segments (<b>A</b>) when compared to EFS-induced contractile response alone (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062292#pone-0062292-g004" target="_blank">figure 4A</a>), while atropine (1 µM) significantly reduced the EFS-induced contractile response of the same segments (<b>B</b>) when compared to EFS-induced contractile response alone (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062292#pone-0062292-g004" target="_blank">figure 4B</a>) (n = 12; *p = 0.002, two-tailed Wilcoxon test). Pre-treatment with L-Name (50 µM) (<b>C</b>) or atropine (1 µM) (<b>D</b>) did not affect the EFS-induced contractile response of distal segments (n = 12; p = 0.15, two-tailed Wilcoxon test). Data are individual values.</p

Histology of intestinal segments in experimental atresia.

<p>The external diameter of the gut was 1.5 to 2.2 times larger in the segment proximal to the atresia (<b>A</b>) than in the distal segment (<b>B</b>). Magnifications 5X. No difference in epithelial organization or inflammatory cell infiltration was observed between proximal (<b>C</b>) and distal (<b>D</b>) segments. Magnifications 25X. (<b>E</b>) For each experiment, proximal segments were taken 1 cm immediately above the atresia and distal segments 1 cm immediately below the atresia.</p

Neurochemical plasticity of the myenteric plexus in experimental intestinal atresia.

<p>The density of Hu-IR neurons was significantly higher in distal than in proximal segments whereas the density of SOX10-IR glial cells was similar in the two segments (<b>A</b>), resulting in a significantly higher glia/neurons ratio in the distal segment (n = 12; *p<0.05; two-tailed Wilcoxon test). (<b>B</b>). Magnification 40X.</p

Neuronal phenotype of the myenteric plexus in experimental intestinal atresia and controls.

<p>(<b>A</b>) In controls, the proportions of ChAT-IR myenteric neurons (normalized to the total number of Hu-IR neurons) was significantly higher in jejunal than in ileal segments (n = 10; *p<0.05; two-tailed Wilcoxon test). (<b>B</b>) The proportion of nNOS–IR myenteric neurons (normalized to the total number of Hu-IR neurons) was significantly higher in jejunal than in ileal segments (n = 10; *p<0.05; two-tailed Wilcoxon test). (<b>C</b>) In atresia, the proportion of ChAT-IR myenteric neurons (normalized to the total number of Hu-IR neurons) was significantly higher in proximal than in distal segments (n = 12; *p<0.05; two-tailed Wilcoxon test). (<b>D</b>) In contrast, the proportion of nNOS–IR myenteric neurons (normalized to the total number of Hu-IR neurons) was similar in proximal and distal segments (n = 12; two-tailed Wilcoxon test).</p