Emerging threat of WHO priority pathogens in ICU-associated CLABSI and CAUTI: an integrated analysis of resistance patterns, epidemiological trends, and stewardship strategies

Contemporary emergence of multidrug resistance (MDR) urges regular updates on circulating pathogens and their antimicrobial resistance profiles. We aimed to identify the burden of MDR and World Health Organization (WHO) priority Gram negative pathogens among patients admitted with febrile illness to Abbassia Fever Hospital, a major Public Fever Hospital in Egypt. The carbapenemase- and extended spectrum beta-lactamases (ESBLs)-encoding genes carried by the isolates were also identified. A total of 9602 clinical specimens were collected from febrile patients during 2018 and 2019. The recovered bacterial isolates were examined for antimicrobial susceptibility using disk diffusion test. Susceptibility to colistin was tested using E-test. ESBLs production was phenotypically and genotypically analyzed. A total of 790 bacterial isolates (612 Gram negative and 178 Gram positive) were recovered. A percentage of 77.6%, and 62.9% of the Gram negative and positive isolates showed MDR phenotype, respectively. WHO priority pathogens were abundant, including carbapenem-resistant (CR) Enterobacterales (105/187; 56.1%) and CR glucose non-fermenters (82/187; 43.8%) such as: A. baumannii (55; 29.4%), P. aeruginosa (27; 14.4%). Carbapenemase- and ESBLs-encoding genes were detected in 56.1% and 30.8% of Enterobacterales and in 43.8% and 46.3% of glucose non-fermenters, respectively. Antimicrobials such as fosfomycin and chloramphenicol retained good activities against MDR Gram negative pathogens. This study highlights the regional burden of MDR and priority Gram negative pathogens. The obtained data are of relevant medical importance for implementation of evidence-based antimicrobial stewardship programs and for tailoring the existing empirical treatment guidelines.

The Centers for Disease Control and Prevention STRIVE Initiative: Construction of a National Program to Reduce Health Care-Associated Infections at the Local Level.

ABSTRACTObjectives.To assess antibiotic susceptibility of World Health Organization (WHO) priority bacteria (Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Salmonella spp., Staphylococcus aureus, and Streptococcus pneumoniae) in blood cultures at the Orinoquía regional hospital in Colombia.Methods.This was cross-sectional study using routine laboratory data for the period 2019–2021. Data on blood samples from patients suspected of a bloodstream infection were examined. We determined: the total number of blood cultures done and the proportion with culture yield; the characteristics of patients with priority bacteria; and the type of bacteria isolated and antibiotic resistance patterns.Results.Of 25 469 blood cultures done, 1628 (6%) yielded bacteria; 774 (48%) of these bacteria were WHO priority pathogens. Most of the priority bacteria isolated (558; 72%) were gram-negative and 216 (28%) were gram-positive organisms. Most patients with priority bacteria (666; 86%) were hospitalized in wards other than the intensive care unit, 427 (55%) were male, and 321 (42%) were ≥ 60 years of age. Of the 216 gram-positive bacteria isolated, 205 (95%) were Staphylococcus aureus. Of the 558 gram-negative priority bacteria isolated, the three most common were Escherichia coli (34%), Klebsiella pneumoniae (28%), and Acinetobacter baumannii (20%). The highest resistance of Staphylococcus aureus was to oxacillin (41%). For gram-negative bacteria, resistance to antibiotics ranged from 4% (amikacin) to 72% (ampicillin).Conclusions.Bacterial yield from blood cultures was low and could be improved. WHO priority bacteria were found in all hospital wards. This calls for rigorous infection prevention and control standards and continued surveillance of antibiotic resistance.

Structural insights into the inhibition of bacterial RecA by naphthalene polysulfonated compounds.

Background: Central-line–associated bloodstream infection (CLABSI) and catheter-associated urinary tract infection (CAUTI) definitions continue to be refined to ensure accuracy. As facilities decrease CLABSI and CAUTI, and as midline catheters become more widely utilized, we sought to understand our non–central-line bloodstream infections (NCLBSI) and non–catheter-associated urinary tract infections (NCAUTI). Total healthcare-associated bloodstream infections (HABSIs) and urinary tract infections (HAUTIs) may provide more objective measures. Methods: The CHOC Children’s Hospital is a 334-bed quaternary-care hospital in Orange, California, with 146 intensive care unit (ICU) beds. We retrospectively reviewed all HABSIs (CLABSIs + NCLBSIs) and HAUTIs (CAUTIs + NCAUTIs) from July 1, 2016, to June 30, 2019, for demographic and microbiologic data. Both HABSI and HAUTI were defined as healthcare-associated infection when the date of event occurs on or after the third calendar day of admission. CLABSI and CAUTI were both defined using CDC-NHSN criteria. Mucosal barrier injury laboratory-confirmed bloodstream infections were excluded. Results: In a 3-year period, there were 100 HABSIs, of which 26 (26%) were NCLBSIs. The mean age for HABSI was 81 months. Enteric gram-negative infections (42%) and Staphylococcus aureus (35%) were the most common etiology for NCLBSI. The most common etiologies for CLABSI were coagulase-negative staphylococci (23%), Staphylococcus aureus (22%), and enteric gram-negatives (22%). Pseudomonas aeruginosa accounted for 16% of CLABSIs, but no NCLBSIs (Fig. 1). There was 1 midline catheter NCLBSI. There were 49 HAUTIs, of which 39 (80%) were NCAUTIs. One asymptomatic bacteremic urinary tract infection was included with the CAUTIs. The mean age for HAUTI was 55 months. The most common etiology of CAUTI was Pseudomonas aeruginosa (50%), whereas for NCAUTI the most common etiology was enteric gram-negative organisms (69%) (Fig. 2). In total, 11 HAUTIs (22%) resulted in secondary sepsis. Most HABSIs and HAUTIs occurred in the ICU setting. There were 6 deaths (6%) among HABSI patients and 3 deaths (8%) among HAUTI patients within 2 weeks of infection (Fig. 3). Conclusions: A preponderance of HABSIs were CLABSIs, but most HAUTIs were NCAUTIs. Although patient demographic and microbiologic differences exist in CLABSIs and NCLBSIs as well as CAUTIs and NCAUTIs, S. aureus and P. aeruginosa are important pathogens, particularly in device-associated infections. Trending total numbers of HABSIs and HAUTIs may be less subjective and may avert the shifting of categories seen with increased use of midline catheters. In addition, non–device-associated infections are potential causes of morbidity and mortality.Funding: NoneDisclosures: None

Background: Central line-associated bloodstream infections (CLABSIs) and catheter-associated urinary tract infections (CAUTIs) cause significant morbidity and mortality among hospitalized patients. Over the last 10 to 20 years, hospital accountability for the prevention of device-associated infections increased at the state and national levels. For example, the Centers for Medicare & Medicaid Services implemented the Hospital Inpatient Quality Reporting Program in 2015. The objective of this study was to assess the impact of increased federal attention on infection prevention using longitudinal data from the National Healthcare Safety Network (NHSN). We hypothesize that there was a significant decrease in statewide standardized infection ratios (SIRs) for CLABSI and CAUTI over the last 8 years. Methods: We collected SIRs for CLABSI and CAUTI in acute care hospitals for all 50 states and Washington D.C. from the NHSN database from 2015 to 2022. For CLABSI, we performed unique analyses for critical care units, wards, and neonatal intensive care (NICU) locations. For CAUTI, we stratified by critical care units and wards. We included all states with more than 5 hospitals reporting data. Those with fewer than 5 were excluded by listwise deletion in the corresponding analysis. We tested trends over time using linear mixed effect models with year as fixed effect and state as random effect. We also included an indicator variable representing the influence of SARS-CoV-2 (Covid-19) on healthcare-associated infections (HAIs). We elected an alpha of 0.05 as the threshold for statistical significance. Results: Overall, CLABSI and CAUTI SIRs exhibited significant negative slopes (Figures 1-5) after controlling for the influence of Covid-19. Each analysis revealed progressively lower SIRs compared to the previous year except for the 2019-2020 interval. Interestingly, the linear trend resumed after 2020 with subsequently lower SIRs in 2021 and 2022. Covid-19 had a greater influence on CLABSI SIRs in critical care settings compared to ward or NICU locations. The slope of CAUTI SIRs were impacted less by Covid-19 in wards compared to critical care settings. Conclusion: The results of the analysis demonstrate that CLABSI and CAUTI are trending in the desired direction despite the HAI spike during Covid-19. Government and hospital stakeholders in the United States should be encouraged by the reported trends and continue to prioritize the funding and use of resources for evidence-based device-associated infection prevention.

After issuing the "Global action plan on antimicrobial resistance" in 2015, the World Health Organization (WHO) established a priority pathogens list for supporting research and development of novel antimicrobials. We conducted a comprehensive analysis of the WHO priority organisms in a Japanese tertiary hospital to apprehend the local AMR epidemiology. Data were obtained from electrical medical records in Osaka University Hospital between January 2010 and March 2021. The critical, high, and medium "priority pathogens list" categories of the WHO were used to compare results between the early (2010-2015) and late (2016-2021) phases. Out of 52,130 culture-positive specimens, a total of 9,872 (18.9%) contained WHO priority isolates. In comparison to early phases, late phases were likely to have higher rates of carbapenem resistance in Pseudomonas aeruginosa (15.7% vs 25.0%, P<0.001), 3rd generation cephalosporin resistance in Escherichia coli (11.5% vs 17.8%, P<0.001) as well as Klebsiella pneumoniae (1.6% vs 4.4%, P<0.001), and ampicillin resistance in Haemophilus influenzae (2.4% vs 3.9%, P<0.001). After 2015, however, the proportion of methicillin-resistant and vancomycin-intermediate Staphylococcus aureus was low. In this study, in-hospital mortality was comparable among patients with resistance to the three WHO priority pathogen types: critical (5.9%), high (3.9%), and medium (3.8%), and no significant change was observed between two phases in each category. However, significant interactions for in-hospital mortality were observed in subgroup analyses between "critical priority" AMR and the presence of comorbid conditions, such as chronic kidney disease or diabetes mellitus. To implement better antimicrobial stewardship policies and practices, local priority pathogens and "high-risk" patients for in-hospital death need to be acknowledged and evaluated periodically.

Internal Validation Process of Health Care-associated Infections (HAI) Data in a Group of Private Hospitals from Brazil

Bacterial resistance towards clinically used antibiotics continues to emerge and represents an increasing threat to human health. To address growing antibiotics resistance globally, the World Health Organization (WHO) has published a list of antibiotic-resistant priority pathogens. The major objective of publishing this list is to guide and promote research and development (R&D) for treating these priority pathogens. The suggested long-term solution by WHO is to explore new classes of antibiotics with novel modes of action. This thesis describes the results of a research program aimed at investigating novel scaffolds acting against WHO priority antibiotic-resistant bacteria. The work that forms the major part of the research described in the first part (Chapters 2 to 4) of the thesis, was directed towards development of simplified analogues of nucleoside antibiotics; a class of bacterial derived natural products acting against novel target, the MraY enzyme (translocase I). Due to their promising antibacterial activity against a broad spectrum of Gram-positive as well as Gram-negative bacteria, nucleoside antibiotics have been considered as promising lead structures for the development of novel antibacterial agents. Based on their structural characteristics, nucleoside antibiotics have been classified into four classes: i) uridylpeptides, ii) ribosamino-uridines, iii) tunicamycins and iv) capuramycins. In this work, three nucleoside antibiotics including mureidomycin (uridylpeptide class), muraymycins (ribosamino-uridine class) and caprazamycins (ribosamino-uridine class) were selected for investigating their simplified analogues. Chapter 2 describes development towards mureidomycin nucleoside antibiotics. The chapter begins with uridine scaffold optimisation study by increasing hydrophobicity on to its C-5 position. By using the established solid-phase Suzuki-Miyaura cross-coupling reaction, we have rapidly synthesised a library of 20 different C-5 substituted uridine analogues. Following to that, through preliminary biological screening of the C-5 substituted uridine analogues, we have been able to generate our proof of concept that increasing hydrophobicity on to the C-5 position of uridine leads to increase antibacterial activity. At this stage, this optimised synthetic protocol is ready to extrapolate further for late stage modification of mureidomycin after having linked with the peptidyl western zone. Chapter 3 outlines our systematic approach towards the synthesis of simplified analogues of muraymycin nucleoside antibiotic. Several methodologies are reported for synthesis of the core glycyluridine structure of muraymycins. It appears from the review of literature that gaining access to this core glycyluridine is not as straightforward as envisaged. Therefore, in this work, we designed simplified muraymycin analogues by replacing the complex glycyluridine with a simplified serine template. This chapter reports our detailed SAR study for minimum structural requirement of the simplified serine template with the outcome of three active hit compounds against WHO priority antibiotic-resistant bacteria. Detailed investigation of simplified caprazamycin analogues is the theme in Chapter 4. This work was initiated with our published review of literature, carried out to reveal the essential pharmacophores present in caprazamycin nucleoside antibiotics. The SAR analysis suggested that a simplified cyclic ring in place of the complex diazepanone ring, linked with key pharmacophores would engender a potent simplified caprazamycin analogue. Based on the SAR analysis, we designed 1,3,5-trisubstituted pyrazoles as a simplified cyclic core to hold key pharmacophores similar to the caprazamycin natural product. This chapter comprises of a detailed discussion of our attempts to synthesise 1,3,5-trisubstituted pyrazoles for reducing complexity of caprazamycin natural products. The second area of research in this thesis, described in Chapter 5, was based on investigating small molecules active against WHO priority pathogens. The present work was focused on building pyrazole linked phenylthiazole analogues. A library of total 24 novel pyrazole linked phenylthiazole compounds were synthesised to explore structure-activity relationships. Chapter 5 finishes with a detailed discussion of the antibacterial activity observed against methicillin-resistant Staphylococcus aureus (MRSA).

To assess the in vitro antimicrobial performance of a non-medicated hydro-responsive wound dressing (HRWD) on the sequestration and killing of wound relevant microorganisms found on the World Health Organization (WHO) priority pathogens list. Suspensions of Pseudomonas aeruginosa, Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA) were placed on petri dishes. Dressings were each placed on top, incubated for 30 minutes and then removed from the inoculated petri dish. The surface of the dressings previously in contact with the bacterial suspensions were placed directly onto a tryptone soy agar (TSA) plate and incubated for 24 hours. Dressings were then removed from the TSA plate and the level of bacterial growth on the plates was assessed. Sequestered microorganism viability was assessed using LIVE/DEAD viability kits and visualisation by epifluorescence. Our results indicated that HRWDs sequester and retain Pseudomonas aeruginosa, Acinetobacter baumannii and MRSA within the dressing. Non-medicated HRWDs containing bound PHMB (polyhexamethylene biguanide, HRWD+PHMB) killed the microorganisms sequestered within the dressing matrix. These data suggest that non-medicated HRWD+PHMB is an effective against WHO priority pathogens and promoting goal of antimicrobial stewardship in wound care.

BackgroundThe world health organization (WHO) priority lifesaving medicines are medicines recommended for the prevention and treatment of leading causes of under-five morbidity and mortality. They should be available in all health systems and at all times. However, the availability of these medicines and its determinants is not well studied in Ethiopia in general and in primary public health facilities Amhara region in particular.ObjectiveThe study aimed to assess the availability and challenges of the WHO-recommended priority lifesaving medicines for under-five children in primary public health facilities of the Amhara region.MethodsA cross-sectional study design was conducted from February to December 2020 in 98 health centers and 22 primary hospitals in the Amhara region, Ethiopia. Facilities were selected with a simple random sampling technique. The data were collected through a pretested and structured questionnaire. Binary logistic regression was used to identify predictors associated with availability of WHO-recommended priority lifesaving medicines for under-five children.ResultsThe availability of oral rehydration salt was high (82.5%) and the availability of vitamin A (47.5%), morphine tablet (13.3%), and artesunate rectal suppository (7.5%) were within low and very low WHO range respectively. Budget adequacy (AOR = 12.9 CI= (2.1–78.2)), periodic review of stock level ((AOR = 13.4,CI=(1.9–92.0)), training on integrated pharmaceutical logistic system ((AOR = 4.5,CI=(1.0-20.5)), inclusion of WHO priority under five children facility specific medicine list (AOR = 12.4,CI=(2.3–66.4)), lead time for EPSA(Ethiopia Pharmaceutical Supply Agency) procurement (AOR = 7.9,CI=(1.3–44.8)) were significantly associated with availability of all WHO priority lifesaving medicines for under- five children.ConclusionThe average availability of WHO-recommended priority lifesaving medicines for under-five children was low. The habit of updating bincard and adoption of the life-saving medicine list were the independent predictors of medication availability.

Surveillance of device-associated infections at a tertiary care hospital of Punjab

Risk factors for device-associated infection related to organisational characteristics of intensive care units: findings from the Korean Nosocomial Infections Surveillance System

Purpose: In the present study, an attempt is made to understand the pattern of HAIs (Healthcare Associated Infections) [device associated infections such as Catheter Associated Urinary Tract Infection (CAUTI), Ventilator Associated Event (VAE), Central Line-Associated Bloodstream Infection (CLABSI) &amp; Surgical Site Infection (SSI) by analyzing statistical tool of quality indicators] and to establish a bench mark for HAIs in a single hospital for a period of 5 years. Methods: The Microbiologist &amp; ICN’s conduct rounds in ICU’s &amp; wards and collect data for active surveillance. The details of culture positive samples are collected by Microbiologist from the laboratory for passive surveillance. The surveillance forms (active &amp; passive) capture details of individual patients. The data collection forms are prepared and updated as per Centers for Disease Control and Prevention (CDC), National Healthcare Safety Network (NHSN) guidelines. The data is analyzed and presented in the meeting of Hospital Infection Control Committee meeting &amp; discussed with clinicians. Results: The cumulative (5 years) CAUTI rate is 0.45, VAE is 2.42, CLABSI is 1.35 &amp; SSI is 0.21. HAI rates were highest for VAE (2.42/1000 ventilator days), the next was CLABSI (1.35/1000 central line days), followed by CAUTI (0.45/1000 urinary catheter days). SSI rate was 0.21/ 100 surgeries. Conclusions: Before the study was started, the benchmark were 2 for CAUTI, 5.5 for VAE, 3 for CLABSI and 2 for SSI. We could able to reduce the baseline benchmark and established our new benchmark as 1 for CAUTI, 3 for VAE, 2 for CLABSI and 1 for SSI that can be used in developing HAI prevention policies by the institution.

Select health care–associated infections are declining