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

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. METHODS: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. FINDINGS: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2-11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75-1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58-1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91-1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70-1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11-0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50-0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38-0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45-0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. INTERPRETATION: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. FUNDING: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Performance Evaluation of the Verigene Gram-Positive and Gram-Negative Blood Culture Test for Direct Identification of Bacteria and Their Resistance Determinants from Positive Blood Cultures in Hong Kong.

A multicenter study was conducted to evaluate the diagnostic performance and the time to identifcation of the Verigene Blood Culture Test, the BC-GP and BC-GN assays, to identify both Gram-positive and Gram-negative bacteria and their drug resistance determinants directly from positive blood cultures collected in Hong Kong.A total of 364 blood cultures were prospectively collected from four public hospitals, in which 114 and 250 cultures yielded Gram-positive and Gram-negative bacteria, and were tested with the BC-GP and BC-GN assay respectively. The overall identification agreement for Gram-positive and Gram-negative bacteria were 89.6% and 90.5% in monomicrobial cultures and 62.5% and 53.6% in polymicrobial cultures, respectively. The sensitivities for most genus/species achieved at least 80% except Enterococcus spp. (60%), K.oxytoca (0%), K.pneumoniae (69.2%), whereas the specificities for all targets ranged from 98.9% to 100%. Of note, 50% (7/14) cultures containing K.pneumoniae that were missed by the BC-GN assay were subsequently identified as K.variicola. Approximately 5.5% (20/364) cultures contained non-target organisms, of which Aeromonas spp. accounted for 25% and are of particular concern. For drug resistance determination, the Verigene test showed 100% sensitivity for identification of MRSA, VRE and carbapenem resistant Acinetobacter, and 84.4% for ESBL-producing Enterobacteriaceae based on the positive detection of mecA, vanA, blaOXA and blaCTXM respectively.Overall, the Verigene test provided acceptable accuracy for identification of bacteria and resistance markers with a range of turnaround time 40.5 to 99.2 h faster than conventional methods in our region

Difference in time to result between conventional culture-based method and the Verigene Test.

<p>^a Difference in time between BC-GP or BC-GN result and final culture-based identification and drug susceptibility test results</p><p>^b Only the isolates with concordant results from cultured-based method and the Verigene test were included for the time to result assessment.</p><p>Difference in time to result between conventional culture-based method and the Verigene Test.</p

Resistance gene profile in Gram negative organisms collected in this study.

<p>^a species identified by 16s Sequencing</p><p>Resistance gene profile in Gram negative organisms collected in this study.</p

Performance of BC-GP for identification of Gram positive organisms.

<p>^<i>a</i><i>95% confidence interval was calculated using Adjusted Wald Method (</i><a href="http://www.measuringu.com/wald.htm" target="_blank"><i>http</i>:<i>//www</i>.<i>measuringu</i>.<i>com/wald</i>.<i>htm</i></a>)</p><p>^b Misidentifed as <i>S</i>. <i>pneumoniae</i></p><p>Performance of BC-GP for identification of Gram positive organisms.</p

The overall concordance in bacterial identification between Verigene test and culture-based method in different study sites.

<p>QMH: Queen Mary Hospital; PMH: Princess Margaret Hospital; UCH: United Christian Hospital; PYNEH: Pamela Youde Nethersole Eastern Hospital; 95%CI: 95% confidence interval</p><p>^a 95% confidence interval was calculated using Adjusted Wald Method (<a href="http://www.measuringu.com/wald.htm" target="_blank">http://www.measuringu.com/wald.htm</a>)</p><p>The overall concordance in bacterial identification between Verigene test and culture-based method in different study sites.</p

Performance of Verigene Test in detection of drug resistant organisms.

<p>MRSA: Methicillin resistant <i>Staphylococcus aureus</i>; MRSE: Methicillin resistant <i>Staphylococcus epidermidis;</i> VRE: Vancomycin resistant Enterococcus; ESBL: Extended spectrum beta-lactamase; MDR <i>Acinetobacter</i>: Multidrug resisant <i>Acinetobacter</i></p><p>^a 95% confidence interval was calculated using Adjusted Wald Method (<a href="http://www.measuringu.com/wald.htm" target="_blank">http://www.measuringu.com/wald.htm</a>)</p><p>Performance of Verigene Test in detection of drug resistant organisms.</p

The identities of bacteria in cultures with discordant results reported by culture-based method and the Verigene Test.

<p>^a Organisms are not included in the Verigene Test identification panel</p><p>The identities of bacteria in cultures with discordant results reported by culture-based method and the Verigene Test.</p

Performance of BC-GN for idenifcation of Gram negative organisms.

<p>^a95% confidence interval was calculated using Adjusted Wald Method (<a href="http://www.measuringu.com/wald.htm" target="_blank">http://www.measuringu.com/wald.htm</a>)</p><p>^b Species were confirmed by 16s rRNA sequencing</p><p>^c Misidentified as <i>Enterobacter spp</i>. by BC-GN</p><p>^d Seven isolates were confirmed to be <i>K</i>. <i>variicola</i> instead of <i>K</i>. <i>pneumoniae</i>by 16s rRNA and yGGEsequencing. After the discrepancy resolution, the sensitivity for <i>K</i>. <i>pneumoniae</i> was raised to 80% (36/45).</p><p>^e One was misidentified as mixed culture of <i>K</i>. <i>pneumoniae</i> and <i>K</i>. <i>oxytoca</i> whereas the other one was misidentified as mixed cultured of <i>K</i>. <i>pneumoniae</i> and <i>Enterobacter</i></p><p>^f Misidentified as <i>K</i>. <i>oxytoca</i></p><p>Performance of BC-GN for idenifcation of Gram negative organisms.</p