International Nosocomial Infection Control Consortium (INICC) report of health care-associated infections, data summary of 25 countries for 2014 to 2023, Surgical Site Infections Module.

BACKGROUND: Surgical site infection (SSI) rates are higher in low-resource countries (LRC) than in high-income counterparts. METHODS: Prospective cohort study using the INICC Surveillance Online System, from 116 hospitals in 75 cities across 25 Latin-American, Asian, Eastern-European, and Middle-Eastern countries: Argentina, Bahrain, Brazil, Colombia, Costa Rica, Dominican Republic, Ecuador, Egypt, Honduras, India, Kosovo, Kuwait, Lebanon, Mexico, Mongolia, Pakistan, Papua New Guinea, Philippines, Poland, Romania, Saudi Arabia, Thailand, Turkey, Venezuela, Vietnam. CDC/NHSN definitions were applied. Surgical procedures (SPs) were categorized according to the International Classification of Diseases criteria. RESULTS: From 2014 to 2023, we collected data on 1,251 SSIs associated with 56,617 SPs. SSI rates were significantly higher in SPs of INICC compared to CDC/NHSN data: hip prosthesis (3.68% vs 0.67%, relative risk [RR]=5.46, 95% confidence interval [CI]=3.71-8.03, P<.001), knee prosthesis (2.02% vs 0.58%, RR=3.49, 95% CI=1.87-6.49, P<.001), coronary artery bypass (4.16% vs 1.37%, RR=3.03, 95% CI=2.35-3.91, P<.001), peripheral vascular bypass (15.69% vs 2.93%, RR=5.35, 95% CI=2.30-12.48, P<.001), abdominal aortic aneurysm repair (8.51% vs 2.12%, RR=4.02, 95% CI=2.11-7.65, P<.001), spinal fusion (6.47% vs 0.70%, RR=9.27, 95% CI=6.21-13.84, P<.001), laminectomy (2.68% vs 0.72%, RR=3.75, 95% CI=2.36-5.95, P<.001), among others. CONCLUSIONS: Elevated SSI rates in LRCs emphasize the need for effective interventions.

Incidence and risk factors for catheter-associated urinary tract infection in 623 intensive care units throughout 37 Asian, African, Eastern European, Latin American, and Middle Eastern nations: A multinational prospective research of INICC.

OBJECTIVE: To identify urinary catheter (UC)-associated urinary tract infection (CAUTI) incidence and risk factors. DESIGN: A prospective cohort study. SETTING: The study was conducted across 623 ICUs of 224 hospitals in 114 cities in 37 African, Asian, Eastern European, Latin American, and Middle Eastern countries. PARTICIPANTS: The study included 169,036 patients, hospitalized for 1,166,593 patient days. METHODS: Data collection took place from January 1, 2014, to February 12, 2022. We identified CAUTI rates per 1,000 UC days and UC device utilization (DU) ratios stratified by country, by ICU type, by facility ownership type, by World Bank country classification by income level, and by UC type. To estimate CAUTI risk factors, we analyzed 11 variables using multiple logistic regression. RESULTS: Participant patients acquired 2,010 CAUTIs. The pooled CAUTI rate was 2.83 per 1,000 UC days. The highest CAUTI rate was associated with the use of suprapubic catheters (3.93 CAUTIs per 1,000 UC days); with patients hospitalized in Eastern Europe (14.03) and in Asia (6.28); with patients hospitalized in trauma (7.97), neurologic (6.28), and neurosurgical ICUs (4.95); with patients hospitalized in lower-middle-income countries (3.05); and with patients in public hospitals (5.89).The following variables were independently associated with CAUTI: Age (adjusted odds ratio [aOR], 1.01; P < .0001), female sex (aOR, 1.39; P < .0001), length of stay (LOS) before CAUTI-acquisition (aOR, 1.05; P < .0001), UC DU ratio (aOR, 1.09; P < .0001), public facilities (aOR, 2.24; P < .0001), and neurologic ICUs (aOR, 11.49; P < .0001). CONCLUSIONS: CAUTI rates are higher in patients with suprapubic catheters, in middle-income countries, in public hospitals, in trauma and neurologic ICUs, and in Eastern European and Asian facilities.Based on findings regarding risk factors for CAUTI, focus on reducing LOS and UC utilization is warranted, as well as implementing evidence-based CAUTI-prevention recommendations.

International Nosocomial Infection Control Consortium (INICC) report of health care associated infections, data summary of 45 countries for 2015 to 2020, adult and pediatric units, device-associated module.

BACKGROUND: Reporting on the International Nosocomial Infection Control Consortium study results from 2015 to 2020, conducted in 630 intensive care units across 123 cities in 45 countries spanning Africa, Asia, Eastern Europe, Latin America, and the Middle East. METHODS: Prospective intensive care unit patient data collected via International Nosocomial Infection Control Consortium Surveillance Online System. Centers for Disease Control and Prevention/National Health Care Safety Network definitions applied for device-associated health care-associated infections (DA-HAI). RESULTS: We gathered data from 204,770 patients, 1,480,620 patient days, 936,976 central line (CL)-days, 637,850 mechanical ventilators (MV)-days, and 1,005,589 urinary catheter (UC)-days. Our results showed 4,270 CL-associated bloodstream infections, 7,635 ventilator-associated pneumonia, and 3,005 UC-associated urinary tract infections. The combined rates of DA-HAIs were 7.28%, and 10.07 DA-HAIs per 1,000 patient days. CL-associated bloodstream infections occurred at 4.55 per 1,000 CL-days, ventilator-associated pneumonias at 11.96 per 1,000 MV-days, and UC-associated urinary tract infections at 2.91 per 1,000 UC days. In terms of resistance, Pseudomonas aeruginosa showed 50.73% resistance to imipenem, 44.99% to ceftazidime, 37.95% to ciprofloxacin, and 34.05% to amikacin. Meanwhile, Klebsiella spp had resistance rates of 48.29% to imipenem, 72.03% to ceftazidime, 61.78% to ciprofloxacin, and 40.32% to amikacin. Coagulase-negative Staphylococci and Staphylococcus aureus displayed oxacillin resistance in 81.33% and 53.83% of cases, respectively. CONCLUSIONS: The high rates of DA-HAI and bacterial resistance emphasize the ongoing need for continued efforts to control them.

An international prospective study of INICC analyzing the incidence and risk factors for catheter-associated urinary tract infections in 235 ICUs across 8 Asian Countries.

BACKGROUND: Identify urinary catheter (UC)-associated urinary tract infections (CAUTI) incidence and risk factors (RF) in 235 ICUs in 8 Asian countries: India, Malaysia, Mongolia, Nepal, Pakistan, the Philippines, Thailand, and Vietnam. METHODS: From January 1, 2014, to February 12, 2022, we conducted a prospective cohort study. To estimate CAUTI incidence, the number of UC days was the denominator, and CAUTI was the numerator. To estimate CAUTI RFs, we analyzed 11 variables using multiple logistic regression. RESULTS: 84,920 patients hospitalized for 499,272 patient days acquired 869 CAUTIs. The pooled CAUTI rate per 1,000 UC-days was 3.08; for those using suprapubic-catheters (4.11); indwelling-catheters (2.65); trauma-ICU (10.55), neurologic-ICU (7.17), neurosurgical-ICU (5.28); in lower-middle-income countries (3.05); in upper-middle-income countries (1.71); at public-hospitals (5.98), at private-hospitals (3.09), at teaching-hospitals (2.04). The following variables were identified as CAUTI RFs: Age (adjusted odds ratio [aOR] = 1.01; 95% CI = 1.01-1.02; P < .0001); female sex (aOR = 1.39; 95% CI = 1.21-1.59; P < .0001); using suprapubic-catheter (aOR = 4.72; 95% CI = 1.69-13.21; P < .0001); length of stay before CAUTI acquisition (aOR = 1.04; 95% CI = 1.04-1.05; P < .0001); UC and device utilization-ratio (aOR = 1.07; 95% CI = 1.01-1.13; P = .02); hospitalized at trauma-ICU (aOR = 14.12; 95% CI = 4.68-42.67; P < .0001), neurologic-ICU (aOR = 14.13; 95% CI = 6.63-30.11; P < .0001), neurosurgical-ICU (aOR = 13.79; 95% CI = 6.88-27.64; P < .0001); public-facilities (aOR = 3.23; 95% CI = 2.34-4.46; P < .0001). DISCUSSION: CAUTI rate and risk are higher for older patients, women, hospitalized at trauma-ICU, neurologic-ICU, neurosurgical-ICU, and public facilities. All of them are unlikely to change. CONCLUSIONS: It is suggested to focus on reducing the length of stay and the Urinary catheter device utilization ratio, avoiding suprapubic catheters, and implementing evidence-based CAUTI prevention recommendations.

Decreasing central line-associated bloodstream infections rates in intensive care units in 30 low- and middle-income countries: An INICC approach.

BACKGROUND: Central line (CL)-associated bloodstream infections (CLABSIs) occurring in the intensive care unit (ICU) are common and associated with a high burden. METHODS: We implemented a multidimensional approach, incorporating an 11-element bundle, education, surveillance of CLABSI rates and clinical outcomes, monitoring compliance with bundle components, feedback of CLABSI rates and clinical outcomes, and performance feedback in 316 ICUs across 30 low- and middle-income countries. Our dependent variables were CLABSI per 1,000-CL-days and in-ICU all-cause mortality rates. These variables were measured at baseline and during the intervention, specifically during the second month, third month, 4 to 16 months, and 17 to 29 months. Comparisons were conducted using a two-sample t test. To explore the exposure-outcome relationship, we used a generalized linear mixed model with a Poisson distribution to model the number of CLABSIs. RESULTS: During 1,837,750 patient-days, 283,087 patients, used 1,218,882 CL-days. CLABSI per 1,000 CL-days rates decreased from 15.34 at the baseline period to 7.97 in the 2nd month (relative risk (RR) = 0.52; 95% confidence interval [CI] = 0.48-0.56; P < .001), 5.34 in the 3rd month (RR = 0.35; 95% CI = 0.32-0.38; P < .001), and 2.23 in the 17 to 29 months (RR = 0.15; 95% CI = 0.13-0.17; P < .001). In-ICU all-cause mortality rate decreased from 16.17% at baseline to 13.68% (RR = 0.84; P = .0013) at 17 to 29 months. CONCLUSIONS: The implemented approach was effective, and a similar intervention could be applied in other ICUs of low- and middle-income countries to reduce CLABSI and in-ICU all-cause mortality rates.

Assessing the impact of a multidimensional approach and an 8-component bundle in reducing incidences of ventilator-associated pneumonia across 35 countries in Latin America, Asia, the Middle East, and Eastern Europe.

BACKGROUND: Ventilator associated pneumonia (VAP) occurring in the intensive care unit (ICU) are common, costly, and potentially lethal. METHODS: We implemented a multidimensional approach and an 8-component bundle in 374 ICUs across 35 low and middle-income countries (LMICs) from Latin-America, Asia, Eastern-Europe, and the Middle-East, to reduce VAP rates in ICUs. The VAP rate per 1000 mechanical ventilator (MV)-days was measured at baseline and during intervention at the 2nd month, 3rd month, 4-15 month, 16-27 month, and 28-39 month periods. RESULTS: 174,987 patients, during 1,201,592 patient-days, used 463,592 MV-days. VAP per 1000 MV-days rates decreased from 28.46 at baseline to 17.58 at the 2nd month (RR = 0.61; 95% CI = 0.58-0.65; P < 0.001); 13.97 at the 3rd month (RR = 0.49; 95% CI = 0.46-0.52; P < 0.001); 14.44 at the 4-15 month (RR = 0.51; 95% CI = 0.48-0.53; P < 0.001); 11.40 at the 16-27 month (RR = 0.41; 95% CI = 0.38-0.42; P < 0.001), and to 9.68 at the 28-39 month (RR = 0.34; 95% CI = 0.32-0.36; P < 0.001). The multilevel Poisson regression model showed a continuous significant decrease in incidence rate ratios, reaching 0.39 (p < 0.0001) during the 28th to 39th months after implementation of the intervention. CONCLUSIONS: This intervention resulted in a significant VAP rate reduction by 66% that was maintained throughout the 39-month period.

Plug-and-Play Regularization Using Linear Solvers.

There has been tremendous research on the design of image regularizers over the years, from simple Tikhonov and Laplacian to sophisticated sparsity and CNN-based regularizers. Coupled with a model-based loss function, these are typically used for image reconstruction within an optimization framework. The technical challenge is to develop a regularizer that can accurately model realistic images and be optimized efficiently along with the loss function. Motivated by the recent plug-and-play paradigm for image regularization, we construct a quadratic regularizer whose reconstruction capability is competitive with state-of-the-art regularizers. The novelty of the regularizer is that, unlike classical regularizers, the quadratic objective function is derived from the observed data. Since the regularizer is quadratic, we can reduce the optimization to solving a linear system for applications such as superresolution, deblurring, inpainting, etc. In particular, we show that using iterative Krylov solvers, we can converge to the solution in few iterations, where each iteration requires an application of the forward operator and a linear denoiser. The surprising finding is that we can get close to deep learning methods in terms of reconstruction quality. To the best of our knowledge, the possibility of achieving near state-of-the-art performance using a linear solver is novel.

A review of bridging clinical studies between different presentations of biological products approved by the United States Food and Drug Administration (US FDA).

INTRODUCTION: There is growing interest in the development of multiple presentations for biological products for subcutaneous (SC) injection for life cycle management and product differentiation. Bridging clinical studies are required to extrapolate the existing data package to new presentations. AREAS COVERED: This review compiles information of bridging clinical studies conducted for biological products administered by the SC route and approved in more than one presentation by the United States Food and Drug Administration's Center for Drug Evaluation and Research up until 31 December 2021. Information regarding indication(s), presentation(s), approval pathways, approval timelines, and various aspects of bridging clinical studies was collected from published documents. EXPERT OPINION: The type of bridging clinical study can depend on the extent of differences between presentations, existing data packages, and the stage of the product development. Design of a bridging clinical study should be based on the characteristics of a biological product and should be aimed at detecting the relevant differences between presentations. Single-dose comparative pharmacokinetics in normal healthy volunteers is the most common bridging clinical study design. Covariates like body weight and injection site should be considered during the design of these studies. The impact of the different user interfaces of presentations should also be considered.

Device Development for Biosimilars: Human Factor Engineering for a Teriparatide Pen.

BACKGROUND: A thorough Human Factors Engineering (HFE) process was implemented to develop a new Teriparatide Pen for the treatment of osteoporosis. The pen provides a cost-effective treatment alternative to branded teriparatide pens. The HFE process ensured that the pen was safe and effective to use and fulfilled the regulatory requirements. RESEARCH DESIGN AND METHODS: The HFE process utilized a risk-based approach that included understanding the users and other use characteristics, preliminary analyses including a thorough risk assessment, a formative and two validation studies. The studies were carried out with intended users - patients, caregivers and healthcare professionals (HCPs) - in the form of simulated use assessments. RESULTS: The preliminary analyses supported the design of the pen's user interface, including its Instructions for Use (IFU). The formative study helped to optimize the user interface. The validation study results were largely favorable but indicated a minor scope for improvement. The IFU was therefore further improved, and a bridging validation study assessed the revised IFU and found it to be effective in supporting the correct use of the pen. CONCLUSIONS: The HFE process ensured and demonstrated that the Teriparatide Pen was safe and effective for its intended use.

International Nosocomial Infection Control Consortium (INICC) report, data summary of 45 countries for 2013-2018, Adult and Pediatric Units, Device-associated Module.

BACKGROUND: We report the results of INICC surveillance study from 2013 to 2018, in 664 intensive care units (ICUs) in 133 cities, of 45 countries, from Latin-America, Europe, Africa, Eastern-Mediterranean, Southeast-Asia, and Western-Pacific. METHODS: Prospective data from patients hospitalized in ICUs were collected through INICC Surveillance Online System. CDC-NHSN definitions for device-associated healthcare-associated infection (DA-HAI) were applied. RESULTS: We collected data from 428,847 patients, for an aggregate of 2,815,402 bed-days, 1,468,216 central line (CL)-days, 1,053,330 mechanical ventilator (MV)-days, 1,740,776 urinary catheter (UC)-days. We found 7,785 CL-associated bloodstream infections (CLAB), 12,085 ventilator-associated events (VAE), and 5,509 UC-associated urinary tract infections (CAUTI). Pooled DA-HAI rates were 5.91% and 9.01 DA-HAIs/1,000 bed-days. Pooled CLAB rate was 5.30/1,000 CL-days; VAE rate was 11.47/1,000 MV-days, and CAUTI rate was 3.16/1,000 UC-days. P aeruginosa was non-susceptible (NS) to imipenem in 52.72% of cases; to colistin in 10.38%; to ceftazidime in 50%; to ciprofloxacin in 40.28%; and to amikacin in 34.05%. Klebsiella spp was NS to imipenem in 49.16%; to ceftazidime in 78.01%; to ciprofloxacin in 66.26%; and to amikacin in 42.45%. coagulase-negative Staphylococci and S aureus were NS to oxacillin in 91.44% and 56.03%, respectively. Enterococcus spp was NS to vancomycin in 42.31% of the cases. CONCLUSIONS: DA-HAI rates and bacterial resistance are high and continuous efforts are needed to reduce them.

Six-year study on peripheral venous catheter-associated BSI rates in 262 ICUs in eight countries of South-East Asia: International Nosocomial Infection Control Consortium findings.

BACKGROUND: Short-term peripheral venous catheter-associated bloodstream infection rates have not been systematically studied in Asian countries, and data on peripheral venous catheter-associated bloodstream infections incidence by number of short-term peripheral venous catheter days are not available. METHODS: Prospective, surveillance study on peripheral venous catheter-associated bloodstream infections conducted from 1 September 2013 to 31 May 2019 in 262 intensive care units, members of the International Nosocomial Infection Control Consortium, from 78 hospitals in 32 cities of 8 countries in the South-East Asia Region: China, India, Malaysia, Mongolia, Nepal, Philippines, Thailand, and Vietnam. For this research, we applied definition and criteria of the CDC NHSN, methodology of the INICC, and software named INICC Surveillance Online System. RESULTS: We followed 83,295 intensive care unit patients for 369,371 bed-days and 376,492 peripheral venous catheter-days. We identified 999 peripheral venous catheter-associated bloodstream infections, amounting to a rate of 2.65/1000 peripheral venous catheter-days. Mortality in patients with peripheral venous catheter but without peripheral venous catheter-associated bloodstream infections was 4.53% and 12.21% in patients with peripheral venous catheter-associated bloodstream infections. The mean length of stay in patients with peripheral venous catheter but without peripheral venous catheter-associated bloodstream infections was 4.40 days and 7.11 days in patients with peripheral venous catheter and peripheral venous catheter-associated bloodstream infections. The microorganism profile showed 67.1% were Gram-negative bacteria: Escherichia coli (22.9%), Klebsiella spp (10.7%), Pseudomonas aeruginosa (5.3%), Enterobacter spp. (4.5%), and others (23.7%). The predominant Gram-positive bacteria were Staphylococcus aureus (11.4%). CONCLUSIONS: Infection prevention programs must be implemented to reduce the incidence of peripheral venous catheter-associated bloodstream infections.

Six-year multicenter study on short-term peripheral venous catheters-related bloodstream infection rates in 204 intensive care units of 57 hospitals in 19 cities of India: International Nosocomial Infection Control Consortium (INICC) findings.

BACKGROUND: Short-term peripheral venous catheters-related bloodstream infections (PVCR-BSIs) rates have not been systematically studied in developing countries, and data on their incidence by number of device-days are not available. METHODS: Prospective, surveillance study on PVCR-BSI conducted from September 1, 2013 to May 31, 2019 in 204 intensive care units (ICUs), members of the International Nosocomial Infection Control Consortium (INICC), from 57 hospitals in 19 cities of India. We applied US INICC definition criteria and reported methods using the INICC Surveillance Online System. RESULTS: We followed 7,513 ICU patients for 296,893 bed-days and 295,795 short term peripheral venous catheter (PVC)-days. We identified 863 PVCR-BSIs, amounting to a rate of 2.91/1,000 PVC-days. Mortality in patients with PVC but without PVCR-BSI was 4.14%, and 11.59% in patients with PVCR-BSI. The length of stay in patients with PVC but without PVCR-BSI was 4.13 days, and 5.9 days in patients with PVCR-BSI. The micro-organism profile showed 68% of gram negative bacteria: Escherichia coli (23%), Klebsiella spp (15%), Pseudomonas aeruginosa (5%), and others. The predominant gram-positive bacteria were Staphylococcus aureus (10%). CONCLUSIONS: PVCR-BSI rates found in our ICUs were much higher than rates published from industrialized countries. Infection prevention programs must be implemented to reduce the incidence of PVCR-BSIs.

Fast High-Dimensional Bilateral and Nonlocal Means Filtering.

Existing fast algorithms for bilateral and nonlocal means filtering mostly work with grayscale images. They cannot easily be extended to high-dimensional data such as color and hyperspectral images, patch-based data, flow-fields, etc. In this paper, we propose a fast algorithm for high-dimensional bilateral and nonlocal means filtering. Unlike existing approaches, where the focus is on approximating the data (using quantization) or the filter kernel (via analytic expansions), we locally approximate the kernel using weighted and shifted copies of a Gaussian, where the weights and shifts are inferred from the data. The algorithm emerging from the proposed approximation essentially involves clustering and fast convolutions, and is easy to implement. Moreover, a variant of our algorithm comes with a guarantee (bound) on the approximation error, which is not enjoyed by existing algorithms.We present some results for high-dimensional bilateral and nonlocal means filtering to demonstrate the speed and accuracy of our proposal. Moreover, we also show that our algorithm can outperform state-of-the-art fast approximations in terms of accuracy and timing.

Device-Associated Infection Rates in 20 Cities of India, Data Summary for 2004-2013: Findings of the International Nosocomial Infection Control Consortium.

OBJECTIVE: To report the International Nosocomial Infection Control Consortium surveillance data from 40 hospitals (20 cities) in India 2004-2013. METHODS: Surveillance using US National Healthcare Safety Network's criteria and definitions, and International Nosocomial Infection Control Consortium methodology. RESULTS: We collected data from 236,700 ICU patients for 970,713 bed-days Pooled device-associated healthcare-associated infection rates for adult and pediatric ICUs were 5.1 central line-associated bloodstream infections (CLABSIs)/1,000 central line-days, 9.4 cases of ventilator-associated pneumonia (VAPs)/1,000 mechanical ventilator-days, and 2.1 catheter-associated urinary tract infections/1,000 urinary catheter-days In neonatal ICUs (NICUs) pooled rates were 36.2 CLABSIs/1,000 central line-days and 1.9 VAPs/1,000 mechanical ventilator-days Extra length of stay in adult and pediatric ICUs was 9.5 for CLABSI, 9.1 for VAP, and 10.0 for catheter-associated urinary tract infections. Extra length of stay in NICUs was 14.7 for CLABSI and 38.7 for VAP Crude extra mortality was 16.3% for CLABSI, 22.7% for VAP, and 6.6% for catheter-associated urinary tract infections in adult and pediatric ICUs, and 1.2% for CLABSI and 8.3% for VAP in NICUs Pooled device use ratios were 0.21 for mechanical ventilator, 0.39 for central line, and 0.53 for urinary catheter in adult and pediatric ICUs; and 0.07 for mechanical ventilator and 0.06 for central line in NICUs. CONCLUSIONS: Despite a lower device use ratio in our ICUs, our device-associated healthcare-associated infection rates are higher than National Healthcare Safety Network, but lower than International Nosocomial Infection Control Consortium Report.

Challenges in the Laboratory Diagnosis and Management of Dengue Infections.

Dengue fever is considered the most important arthropod-borne viral diseases in terms of morbidity and mortality. An accurate and efficient diagnosis of dengue plays an important role in case confirmation. The virus may be isolated during the viremic phase (within day 5 of illness), from serum, plasma and peripheral blood mononuclear cells. Enzyme linked immunoassay (ELISA) has demonstrated the presence of high levels of dengue NS1 antigen and tests may be performed by enzyme-immunoassays (EIAs) or immune-chromatographic (ICT) methods. These assays are specific with respect to different flaviviruses. Conventional and real time RT PCR, nested PCR, multiplex PCR and Nucleic acid sequence based amplification (NASBA) have been described as sensitive and relatively rapid method of detecting the virus during the early viremic phase. Other tests used include assay of anti-dengue specific IgM and IgG ELISA. Currently no curative treatment in terms of anti-viral drugs is available for dengue and patients are managed with rest and aggressive supportive therapy. Management may be done at home or in the hospital depending on the severity of the illness. Hospital management includes fluid therapy, blood component transfusion and other modalities of treatments like steroids, recombinant factor VII and management of complications. Various vaccines are in trial stages and may become available in the near future.

Surgical site infection rates in six cities of India: findings of the International Nosocomial Infection Control Consortium (INICC).

BACKGROUND: Surgical site infections are a threat to patient safety. However, in India, data on their rates stratified by surgical procedure are not available. METHODS: From January 2005 to December 2011, the International Nosocomial Infection Control Consortium (INICC) conducted a cohort prospective surveillance study on surgical site infections in 10 hospitals in 6 Indian cities. CDC National Healthcare Safety Network (CDC-NHSN) methods were applied and surgical procedures were classified into 11 types, according to the ninth edition of the International Classification of Diseases. RESULTS: We documented 1189 surgical site infections, associated with 28 340 surgical procedures (4.2%; 95% CI: 4.0-4.4). Surgical site infections rates were compared with INICC and CDC-NHSN reports, respectively: 4.3% for coronary bypass with chest and donor incision (4.5% vs 2.9%); 8.3% for breast surgery (1.7% vs 2.3%); 6.5% for cardiac surgery (5.6% vs 1.3%); 6.0% for exploratory abdominal surgery (4.1% vs 2.0%), among others. CONCLUSIONS: In most types of surgical procedures, surgical site infections rates were higher than those reported by the CDC-NHSN, but similar to INICC. This study is an important advancement towards the knowledge of surgical site infections epidemiology in the participating Indian hospitals that will allow us to introduce targeted interventions.

The adenylyltransferase domain of bacterial Pnkp defines a unique RNA ligase family.

Pnkp is the end-healing and end-sealing component of an RNA repair system present in diverse bacteria from ten different phyla. To gain insight to the mechanism and evolution of this repair system, we determined the crystal structures of the ligase domain of Clostridium thermocellum Pnkp in three functional states along the reaction pathway: apoenzyme, ligase • ATP substrate complex, and covalent ligase-AMP intermediate. The tertiary structure is composed of a classical ligase nucleotidyltransferase module that is embellished by a unique α-helical insert module and a unique C-terminal α-helical module. Structure-guided mutational analysis identified active site residues essential for ligase adenylylation. Pnkp defines a new RNA ligase family with signature structural and functional properties.

Solution structure and DNA-binding properties of the phosphoesterase domain of DNA ligase D.

The phosphoesterase (PE) domain of the bacterial DNA repair enzyme LigD possesses distinctive manganese-dependent 3'-phosphomonoesterase and 3'-phosphodiesterase activities. PE exemplifies a new family of DNA end-healing enzymes found in all phylogenetic domains. Here, we determined the structure of the PE domain of Pseudomonas aeruginosa LigD (PaePE) using solution NMR methodology. PaePE has a disordered N-terminus and a well-folded core that differs in instructive ways from the crystal structure of a PaePE•Mn(2+)• sulfate complex, especially at the active site that is found to be conformationally dynamic. Chemical shift perturbations in the presence of primer-template duplexes with 3'-deoxynucleotide, 3'-deoxynucleotide 3'-phosphate, or 3' ribonucleotide termini reveal the surface used by PaePE to bind substrate DNA and suggest a more efficient engagement in the presence of a 3'-ribonucleotide. Spectral perturbations measured in the presence of weakly catalytic (Cd(2+)) and inhibitory (Zn(2+)) metals provide evidence for significant conformational changes at and near the active site, compared to the relatively modest changes elicited by Mn(2+).

Structures and activities of archaeal members of the LigD 3'-phosphoesterase DNA repair enzyme superfamily.

LigD 3'-phosphoesterase (PE) is a component of the bacterial NHEJ apparatus that performs 3'-end-healing reactions at DNA breaks. The tertiary structure, active site and substrate specificity of bacterial PE are unique vis-à-vis other end-healing enzymes. PE homologs are present in archaea, but their properties are uncharted. Here, we demonstrate the end-healing activities of two archaeal PEs--Candidatus Korarchaeum cryptofilum PE (CkoPE; 117 amino acids) and Methanosarcina barkeri PE (MbaPE; 151 amino acids)--and we report their atomic structures at 1.1 and 2.1 Å, respectively. Archaeal PEs are minimized versions of bacterial PE, consisting of an eight-stranded ß barrel and a 3(10) helix. Their active sites are located in a crescent-shaped groove on the barrel's outer surface, wherein two histidines and an aspartate coordinate manganese in an octahedral complex that includes two waters and a phosphate anion. The phosphate is in turn coordinated by arginine and histidine side chains. The conservation of active site architecture in bacterial and archaeal PEs, and the concordant effects of active site mutations, underscore a common catalytic mechanism, entailing transition state stabilization by manganese and the phosphate-binding arginine and histidine. Our results fortify the proposal that PEs comprise a DNA repair superfamily distributed widely among taxa.

Sequence-specific 1H, 13C and 15N assignments of the phosphoesterase (PE) domain of Pseudomonas aeruginosa DNA ligase D (LigD).

DNA ligase D (LigD), consisting of polymerase, ligase and phosphoesterase domains, is the essential catalyst of the bacterial non-homologous end-joining pathway of DNA double-strand break repair. The phosphoesterase (PE) module performs manganese-dependent 3'-phosphomonoesterase and 3'-ribonucleoside resection reactions that heal broken ends in preparation for sealing. LigD PE exemplifies a structurally and mechanistically unique class of DNA end-processing enzymes. Here, we present the resonance assignments of the PE domain of Pseudomonas aeruginosa LigD comprising the N-terminal 177 residues.