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Surgical site infection (SSI) rates in low- and middle-income countries (LMICs) range from 8 to 30% of procedures, making them the most frequent healthcare-acquired infection (HAI) with substantial morbidity, mortality, and economic impacts. Presented here is an approach to surgical site infection prevention based on surveillance and focused on five critical areas identified by international experts. These five areas include 1. Collecting valid, high-quality data; 2. Linking HAIs to economic incapacity, underscoring the need to prioritize infection prevention activities; 3. Implementing SSI surveillance within infection prevention and control (IPC) programs to enact structural changes, develop procedural skills, and alter healthcare worker behaviors; 4. Prioritizing IPC training for healthcare workers in LMICs to conduct broad-based surveillance and to develop and implement locally applicable IPC programs; and 5. Developing a highly accurate and objective international system for defining SSIs, which can be translated globally in a straightforward manner. Finally, we present a clear, unambiguous framework for successful SSI guideline implementation that supports developing sustainable IPC programs in LMICs. This entails 1. Identifying index operations for targeted surveillance; 2. Identifying IPC "champions" and empowering healthcare workers; 3. Using multimodal improvement measures; 4. Positioning hand hygiene programs as the basis for IPC initiatives; 5. Use of telecommunication devices for surveillance and healthcare outcome follow-ups. Additionally, special considerations for pediatric SSIs, antimicrobial resistance development, and antibiotic stewardship programs are addressed.

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BACKGROUND: Antibiotic prophylaxis is frequently continued for 1 day or more after surgery to prevent surgical site infection. Continuing antibiotic prophylaxis after an operation might have no advantage compared with its immediate discontinuation, and it unnecessarily exposes patients to risks associated with antibiotic use. In 2016, WHO recommended discontinuation of antibiotic prophylaxis after surgery. We aimed to update the evidence that formed the basis for that recommendation. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, CINAHL, CENTRAL, and WHO regional medical databases for randomised controlled trials (RCTs) on postoperative antibiotic prophylaxis that were published from Jan 1, 1990, to July 24, 2018. RCTs comparing the effect of postoperative continuation versus discontinuation of antibiotic prophylaxis on the incidence of surgical site infection in patients undergoing any surgical procedure with an indication for antibiotic prophylaxis were eligible. The primary outcome was the effect of postoperative surgical antibiotic prophylaxis continuation versus its immediate discontinuation on the occurrence of surgical site infection, with a prespecified subgroup analysis for studies that did and did not adhere to current best practice standards for surgical antibiotic prophylaxis. We calculated summary relative risks (RRs) with corresponding 95% CIs using a random effects model (DerSimonian and Laird). We evaluated heterogeneity with the χ2 test, I2, and τ2, and visually assesed publication bias with a contour-enhanced funnel plot. This study is registered with PROSPERO, CRD42017060829. FINDINGS: We identified 83 relevant RCTs, of which 52 RCTs with 19 273 participants were included in the primary meta-analysis. The pooled RR of surgical site infection with postoperative continuation of antibiotic prophylaxis versus its immediate discontinuation was 0·89 (95% CI 0·79-1·00), with low heterogeneity in effect size between studies (τ2=0·001, χ2 p=0·46, I2=0·7%). Our prespecified subgroup analysis showed a significant association between the effect estimate and adherence to best practice standards of surgical antibiotic prophylaxis: the RR of surgical site infection was reduced with continued antibiotic prophylaxis after surgery compared with its immediate discontinuation in trials that did not meet best practice standards (0·79 [95% CI 0·67-0·94]) but not in trials that did (1·04 [0·85-1·27]; p=0·048). Whether studies adhered to best practice standards explained all variance in the pooled estimate from the primary meta-analysis. INTERPRETATION: Overall, we identified no conclusive evidence for a benefit of postoperative continuation of antibiotic prophylaxis over its discontinuation. When best practice standards were followed, postoperative continuation of antibiotic prophylaxis did not yield any additional benefit in reducing the incidence of surgical site infection. These findings support WHO recommendations against this practice. FUNDING: None.

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Background: Sepsis is the leading cause of maternal death in sub-Saharan Africa (SSA), a region that sees some of the highest rates of maternal death and morbidity in the world. As one of the most commonly performed surgical procedures in SSA and a proved risk factor for surgical site infection (SSI), cesarean section (CS) is an important operation to target because of its massive impact on maternal and neonatal health. There is currently insufficient published data available on the patient and facility-based context around SSI after CS to establish a true and clear understanding of this infectious category. The objective of this study was to collect accurate and valid data on the incidence of SSI after CS and the circumstances around SSI in two Kenyan hospitals. Hypothesis: Our primary analysis focused on the consequences of timing of peri-operative antimicrobial prophylaxis. We hypothesized that patients who were given antibiotics pre-operatively would show lower SSI rates than those given the agents post-operatively. Methods: This was an Institutional Review Board-approved observational study of 609 women who had CS operations at two Kenyan hospitals from September to December 2015. Thika provided antimicrobial prophylaxis prior to incision for all patients, and Kiambu provided only post-operative prophylaxis. It should be noted that this difference was the result of a previous intervention at Thika and not a part of this observational study. Results: Patients at the two hospitals had similar pre-operative characteristics indicating a relatively healthy population. The median age was 26 ± 6 years (range 18-43) at Thika and 26 ± 5 (18-44) at Kiambu. Median parity was 1 ± 1 (range 0-7) at Thika and 1 ± 1 (0-10). Patients also went through a comparable number of antenatal care visits (median 4 ± 1 at both hospitals). The number of patients with prolonged rupture of the membranes was 103 (34.4%) at Thika and 99 (32.9%) at Kiambu. There was a slightly higher number of patients with meconium-stained liquor at Kiambu Hospital (115) than at Thika (74). The SSI rate was 4.0% (12/299; 11 superficial, 1 deep) at Thika and 9.3% (28/301; 18 superficial, 7 deep, 3 organ/space) at Kiambu. Conclusions: The data show a striking difference between SSI rates in patients who were given properly timed pre-operative antibiotics and patients who were given only post-operative antibiotics. Administration of post-operative antibiotics is currently the norm in much of SSA, and there is strong evidence that many of the infectious problems encountered in this population would be reduced by the provision of antibiotic prophylaxis prior to the incision.

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Aim: Recently approved for use in complicated intra-abdominal infection, eravacycline is a novel fluorocycline with broad spectrum of activity against resistant Gram-negative pathogens. This manuscript is a pooled analysis of two Phase III trials. Clinical efficacy: Clinical cure rates were 86.8% for eravacycline versus 87.6% for ertapenem, and 90.8% for eravacycline versus 91.2% for meropenem in the Intent to Treat (micro-ITT) populations, and 87.0% for eravacycline versus 88.8% ertapenem, and 92.4 versus 91.6% for meropenem in the Modified Intent to Treat (MITT) populations. Safety: Eravacycline is well tolerated, with lower rates of nausea, vomiting and diarrhea than other tetracyclines. Conclusion: Eravacycline is an effective new option for use in complicated intra-abdominal infections, and in particular, for the treatment of extended-spectrum ß-lactamase- and carbapenem-resistant Enterobacteriaceae-expressing organisms.

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Cesarean section (CS) is the most common operative procedure performed in sub-Saharan Africa (SSA), accounting for as much as 80% of the surgical workload. In contrast to CSs performed in high-income countries, CSs performed in SSA are accompanied by high morbidity and mortality rates. This operation is the most important known variable associated with an increased probability of postpartum bacterial infection. The objective of this review was to assess surgical outcomes related to CS in SSA. PubMed (including Medline), CINAHL, Embase, and the World Health Organization's Global Health Library were searched without date or language restrictions. A total of 26 studies reporting surgical site-infection rates after CS were identified, representing 14,063 women from 14 countries. The vast majority (76.7%) of CSs performed were emergency operations. The overall CS rate for women included in this review was 12.4% (range: 1.0%-41.9%). Only 17 of 26 total studies reported a significant proportion of women receiving antimicrobials of any kind. The surgical site-infection rate was 15.6% and the wound-infection rate 10.3%.

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In Gram-negative bacterial sepsis, production of excess pro-inflammatory cytokines results in hyperinflammation and tissue injury. Anti-inflammatory cytokines such as IL-10 inhibit inflammation and enhance tissue healing. Here, we report a novel approach to treat septicemia associated with intra-abdominal infection in a murine model by delicately balancing pro- and anti-inflammatory cytokines. A novel oligosaccharide compound AVR-25 selectively binds to the TLR4 protein (IC50 = 0.15 µM) in human peripheral blood monocytes and stimulates IL-10 production. Following the cecal ligation and puncture (CLP) procedure, intravenous dosing of AVR-25 (10 mg/kg, 6-12 h post-CLP) alone and in combination with antibiotic imipenem protected both young adult (10-12 week old) and aged (16-18 month old) mice against polymicrobial infection, organ dysfunction, and death. Proinflammatory cytokines (TNF-α, MIP-1, i-NOS) were decreased significantly and restoration of tissue damage was observed in all organs. A decrease in serum C-reactive protein (CRP) and bacterial colony forming unit (CFU) confirmed improved bacterial clearance. Together, these findings demonstrate the therapeutic ability of AVR-25 to mitigate the storm of inflammation and minimize tissue injury with high potential for adjunctive therapy in intra-abdominal sepsis.

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BACKGROUND: Evidence-based guidelines from the World Health Organization (WHO) have recommended a high (80%) fraction of inspired oxygen (FiO2) to reduce surgical site infection in adult surgical patients undergoing general anaesthesia with tracheal intubation. However, there is ongoing debate over the safety of high FiO2. We performed a systematic review to define the relative risk of clinically relevant adverse events (AE) associated with high FiO2. METHODS: We reviewed potentially relevant articles from the WHO review supporting the recommendation, including an updated (July 2018) search of EMBASE and PubMed for randomised and non-randomised controlled studies reporting AE in surgical patients receiving 80% FiO2 compared with 30-35% FiO2. We assessed study quality and performed meta-analyses of risk ratios (RR) comparing 80% FiO2 against 30-35% for major complications, mortality, and intensive care admission. RESULTS: We included 17 moderate-good quality trials and two non-randomised studies with serious-critical risk of bias. No evidence of harm with high FiO2 was found for major AE in the meta-analysis of randomised trials: atelectasis RR 0.91 [95% confidence interval (CI) 0.59-1.42); cardiovascular events RR 0.90 (95% CI 0.32-2.54); intensive care admission RR 0.93 (95% CI 0.7-1.12); and death during the trial RR 0.49 (95% CI 0.17-1.37). One non-randomised study reported that high FiO2 was associated with major respiratory AE [RR 1.99 (95% CI 1.72-2.31)]. CONCLUSIONS: No definite signal of harm with 80% FiO2 in adult surgical patients undergoing general anaesthesia was demonstrated and there is little evidence on safety-related issues to discourage its use in this population.

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BACKGROUND: In 2016, the World Health Organization (WHO) strongly recommended the use of a high fraction of inspired oxygen (FiO2) in adult patients undergoing general anaesthesia to reduce the risk of surgical site infection (SSI). Since then, further trials have been published, trials included previously have come under scrutiny, and one article was retracted. We updated the systematic review on which the recommendation was based. METHODS: We performed a systematic literature search from January 1990 to April 2018 for RCTs comparing the effect of high (80%) vs standard (30-35%) FiO2 on the incidence of SSI. Studies retracted or under investigation were excluded. A random effects model was used for meta-analyses; the sources of heterogeneity were explored using meta-regression. RESULTS: Of 21 RCTs included, six were newly identified since the publication of the WHO guideline review; 17 could be included in the final analyses. Overall, no evidence for a reduction of SSI after the use of high FiO2 was found [relative risk (RR): 0.89; 95% confidence interval (CI): 0.73-1.07]. There was evidence that high FiO2 was beneficial in intubated patients [RR: 0.80 (95% CI: 0.64-0.99)], but not in non-intubated patients [RR: 1.20 (95% CI: 0.91-1.58); test of interaction; P=0.048]. CONCLUSIONS: The WHO updated analyses did not show definite beneficial effect of the use of high perioperative FiO2, overall, but there was evidence of effect of reducing the SSI risk in surgical patients under general anaesthesia with tracheal intubation. However, the evidence for this beneficial effect has become weaker and the strength of the recommendation needs to be reconsidered.

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BACKGROUND: Increasing antimicrobial resistance among pathogens that cause complicated intraabdominal infections (cIAIs) supports the development of new antimicrobials. Eravacycline, a novel member of the fluorocycline family, is active against multidrug-resistant bacteria including extended-spectrum ß-lactamase (ESBL) and carbapenem-resistant Enterobacteriaceae. METHODS: IGNITE4 was a prospective, randomized, double-blind trial. Hospitalized patients with cIAI received either eravacycline 1 mg/kg every 12 hours or meropenem 1 g every 8 hours intravenously for 4-14 days. The primary objective was to demonstrate statistical noninferiority (NI) in clinical cure rates at the test-of-cure visit (25-31 days from start of therapy) in the microbiological intent-to-treat population using a NI margin of 12.5%. Microbiological outcomes and safety were also evaluated. RESULTS: Eravacycline was noninferior to meropenem in the primary endpoint (177/195 [90.8%] vs 187/205 [91.2%]; difference, -0.5%; 95% confidence interval [CI], -6.3 to 5.3), exceeding the prespecified margin. Secondary endpoints included clinical cure rates in the modified ITT population (231/250 [92.4%] vs 228/249 [91.6%]; difference, 0.8; 95% CI, -4.1, 5.8) and the clinically evaluable population (218/225 [96.9%] vs 222/231 [96.1%]; (difference, 0.8; 95% CI -2.9, 4.5). In patients with ESBL-producing Enterobacteriaceae, clinical cure rates were 87.5% (14/16) and 84.6% (11/13) in the eravacycline and meropenem groups, respectively. Eravacycline had relatively low rates of adverse events for a drug of this class, with less than 5%, 4%, and 3% of patients experiencing nausea, vomiting, and diarrhea, respectively. CONCLUSIONS: Treatment with eravacycline was noninferior to meropenem in adult patients with cIAI, including infections caused by resistant pathogens. CLINICAL TRIALS REGISTRATION: NCT01844856.

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OBJECTIVE: Rising antibiotic resistance could reduce the effectiveness of antibiotics in preventing postoperative infections. We investigated trends in the efficacy of antibiotic prophylaxis regimens for 3 commonly performed surgical procedures-appendectomy, cesarean section, and colorectal surgery-and 1 invasive diagnostic procedure, transrectal prostate biopsy (TRPB). DESIGN: Systematic review and meta-analysis. METHODS: We searched PubMed and Cochrane databases (through October 31, 2017) for randomized control trials (RCTs) that measured the efficacy of antibiotic prophylaxis for 4 index procedures in preventing postoperative infections (surgical site infections [SSIs] following the 3 surgical procedures and a combination of urinary tract infections [UTIs] and sepsis following TRPB). RESULTS: Of 399 RCTs, 74 studies (9 appendectomy, 11 cesarean section, 39 colorectal surgery, and 15 TRPB) were included. Multilevel logistic regression models with random intercepts for each study showed no statistically significant increase in SSIs over time for appendectomy (adjusted odds ratio [aOR] per year, 1.03; 95% confidence interval [CI], 0.92-1.16; P=.57), cesarean section (aOR per year, 1.01; 95% CI, 0.96-1.05; P=.80), and TRPB (aOR per year, 0.95; 95% CI, 0.77-1.18; P=.67). However, there was a significant increase in SSIs proportion following colorectal surgery (aOR per year, 1.049; 95% CI, 1.03-1.07; P<.001). CONCLUSION: The efficacy of antibiotic prophylaxis agents in preventing SSIs following colorectal surgery has declined. Small number of RCTs and low infections rates limited our ability to assess true effect for simple appendectomy, cesarean section, or TRPB.

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INTRODUCTION: Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) infections are limited and CRE infections remain associated with high clinical failure and mortality rates, particularly in vulnerable patient populations. A Phase 3, multinational, open-label, randomized controlled trial (TANGO II) was conducted from 2014 to 2017 to evaluate the efficacy/safety of meropenem-vaborbactam monotherapy versus best available therapy (BAT) for CRE. METHODS: A total of 77 patients with confirmed/suspected CRE infection (bacteremia, hospital-acquired/ventilator-associated bacterial pneumonia, complicated intra-abdominal infection, complicated urinary tract infection/acute pyelonephritis) were randomized, and 47 with confirmed CRE infection formed the primary analysis population (microbiologic-CRE-modified intent-to-treat, mCRE-MITT). Eligible patients were randomized 2:1 to meropenem-vaborbactam (2 g/2 g over 3 h, q8h for 7-14 days) or BAT (mono/combination therapy with polymyxins, carbapenems, aminoglycosides, tigecycline; or ceftazidime-avibactam alone). Efficacy endpoints included clinical cure, Day-28 all-cause mortality, microbiologic cure, and overall success (clinical cure + microbiologic eradication). Safety endpoints included adverse events (AEs) and laboratory findings. RESULTS: Within the mCRE-MITT population, cure rates were 65.6% (21/32) and 33.3% (5/15) [95% confidence interval (CI) of difference, 3.3% to 61.3%; P = 0.03)] at End of Treatment and 59.4% (19/32) and 26.7% (4/15) (95% CI of difference, 4.6% to 60.8%; P = 0.02) at Test of Cure;.Day-28 all-cause mortality was 15.6% (5/32) and 33.3% (5/15) (95% CI of difference, - 44.7% to 9.3%) for meropenem-vaborbactam versus BAT, respectively. Treatment-related AEs and renal-related AEs were 24.0% (12/50) and 4.0% (2/50) for meropenem-vaborbactam versus 44.0% (11/25) and 24.0% (6/25) for BAT. Exploratory risk-benefit analyses of composite clinical failure or nephrotoxicity favored meropenem-vaborbactam versus BAT (31.3% [10/32] versus 80.0% [12/15]; 95% CI of difference, - 74.6% to - 22.9%; P < 0.001). CONCLUSIONS: Monotherapy with meropenem-vaborbactam for CRE infection was associated with increased clinical cure, decreased mortality, and reduced nephrotoxicity compared with BAT. CLINICAL TRIALS REGISTRATION: NCT02168946. FUNDING: The Medicines Company.

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Surgical site infections remain an important topic of concern for surgeons in all specialties and are currently the focus of global health agencies for prevention. Because patients have numerous co-morbidities that increase the risks of surgical site infections, and because of the emergence of more resistant pathogens, it is necessary to revise and update guidelines to assist surgeons in the prevention of these infections. This article will summarize the most recent WHO Global Guidelines for the prevention of Surgical Site Infection that will have applicability for surgeons in all countries.

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The initial management of patients with suspected acute biliary infection starts with the measurement of vital signs to assess whether or not the situation is urgent. If the case is judged to be urgent, initial medical treatment should be started immediately including respiratory/circulatory management if required, without waiting for a definitive diagnosis. The patient's medical history is then taken; an abdominal examination is performed; blood tests, urinalysis, and diagnostic imaging are carried out; and a diagnosis is made using the diagnostic criteria for cholangitis/cholecystitis. Once the diagnosis has been confirmed, initial medical treatment should be started immediately, severity should be assessed according to the severity grading criteria for acute cholangitis/cholecystitis, and the patient's general status should be evaluated. For mild acute cholangitis, in most cases initial treatment including antibiotics is sufficient, and most patients do not require biliary drainage. However, biliary drainage should be considered if a patient does not respond to initial treatment. For moderate acute cholangitis, early endoscopic or percutaneous transhepatic biliary drainage is indicated. If the underlying etiology requires treatment, this should be provided after the patient's general condition has improved; endoscopic sphincterotomy and subsequent choledocholithotomy may be performed together with biliary drainage. For severe acute cholangitis, appropriate respiratory/circulatory management is required. Biliary drainage should be performed as soon as possible after the patient's general condition has been improved by initial treatment and respiratory/circulatory management. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

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Antimicrobial therapy is a mainstay of the management for patients with acute cholangitis and/or cholecystitis. The Tokyo Guidelines 2018 (TG18) provides recommendations for the appropriate use of antimicrobials for community-acquired and healthcare-associated infections. The listed agents are for empirical therapy provided before the infecting isolates are identified. Antimicrobial agents are listed by class-definitions and TG18 severity grade I, II, and III subcategorized by clinical settings. In the era of emerging and increasing antimicrobial resistance, monitoring and updating local antibiograms is underscored. Prudent antimicrobial usage and early de-escalation or termination of antimicrobial therapy are now important parts of decision-making. What is new in TG18 is that the duration of antimicrobial therapy for both acute cholangitis and cholecystitis is systematically reviewed. Prophylactic antimicrobial usage for elective endoscopic retrograde cholangiopancreatography is no longer recommended and the section was deleted in TG18. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

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Management bundles that define items or procedures strongly recommended in clinical practice have been used in many guidelines in recent years. Application of these bundles facilitates the adaptation of guidelines and helps improve the prognosis of target diseases. In Tokyo Guidelines 2013 (TG13), we proposed management bundles for acute cholangitis and cholecystitis. Here, in Tokyo Guidelines 2018 (TG18), we redefine the management bundles for acute cholangitis and cholecystitis. Critical parts of the bundles in TG18 include the diagnostic process, severity assessment, transfer of patients if necessary, and therapeutic approach at each time point. Observance of these items and procedures should improve the prognosis of acute cholangitis and cholecystitis. Studies are now needed to evaluate the dissemination of these TG18 bundles and their effectiveness. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

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BACKGROUND: The prevalence of antimicrobial resistance among gram-negative pathogens in complicated intra-abdominal infections (cIAIs) has increased. In the absence of timely information on the infecting pathogens and their susceptibilities, local or regional epidemiology may guide initial empirical therapy and reduce treatment failure, length of stay and mortality. The objective of this study was to assess the cost-effectiveness of ceftolozane/tazobactam + metronidazole compared with piperacillin/tazobactam in the treatment of hospitalized US patients with cIAI at risk of infection with resistant pathogens. METHODS: We used a decision-analytic Monte Carlo simulation model to compare the costs and quality-adjusted life years (QALYs) of persons infected with nosocomial gram-negative cIAI treated empirically with either ceftolozane/tazobactam + metronidazole or piperacillin/tazobactam. Pathogen isolates were randomly drawn from the Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS) database, a surveillance database of non-duplicate bacterial isolates collected from patients with cIAIs in medical centers in the USA from 2011 to 2013. Susceptibility to initial therapy was based on the measured susceptibilities reported in the PACTS database determined using standard broth micro-dilution methods as described by the Clinical and Laboratory Standards Institute (CLSI). RESULTS: Our model results, with baseline resistance levels from the PACTS database, indicated that ceftolozane/tazobactam + metronidazole dominated piperacillin/tazobactam, with lower costs ($44,226/patient vs. $44,811/patient respectively) and higher QALYs (12.85/patient vs. 12.70/patient, respectively). Ceftolozane/tazobactam + metronidazole remained the dominant choice in one-way and probabilistic sensitivity analyses. CONCLUSIONS: Based on surveillance data, ceftolozane/tazobactam is more likely to be an appropriate empiric therapy for cIAI in the US. Results from a decision-analytic simulation model indicate that use of ceftolozane/tazobactam + metronidazole would result in cost savings and improves QALYs, compared with piperacillin/tazobactam.

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