In search of the best method to detect carriage of carbapenem-resistant Pseudomonas aeruginosa in humans: a systematic review.

BACKGROUND: Detection of carbapenem-resistant Pseudomonas aeruginosa (CR-PA) in humans is important to prevent transmission. However, the most optimal culture method to detect CR-PA is unknown. This systematic review aims to determine which culture method is most sensitive and which culture methods are used to detect CR-PA in humans. Second, to establish the most feasible culture method taking into account the turnaround time (TAT), and third, to provide an overview of the sampling sites used to detect carriage. METHODS: We systematically searched the electronic databases Embase, Medline Ovid, Cochrane, Scopus, CINAHL, and Web of Science until January 27, 2023. All diagnostic accuracy studies comparing two or more culture methods to detect CR-PA and recent outbreak or surveillance reports on CR-PA carriage or infection in humans, which describe culture methods and their results, were eligible for inclusion. We used QUADAS-2 guideline for diagnostic accuracy studies and the STROBE or ORION guideline for outbreak-surveillance studies to assess the risk of bias. RESULTS: Six diagnostic accuracy studies were included. An enrichment broth was found to increase the detection of CR-PA. Using an enrichment broth extended the TAT by 18-24 h, yet selective media could reduce the TAT by 24 h compared to routine media. In total, 124 outbreak-surveillance studies were included, of which 17 studies with surveillance samples and 116 studies with clinical samples. In outbreak-surveillance studies with surveillance samples, perianal, rectal swabs or stools were the most common sampling site/specimen (13/17, 76%). A large variety was observed in whether and which kind of enrichment broth and selective media were used. CONCLUSIONS: We found a benefit of using an enrichment step prior to inoculation of the material onto selective media for the detection of CR-PA. More research is needed to determine the most sensitive sampling site and culture method. TRAIL REGISTRATION: This study was registered in the PROSPERO International prospective register of systematic reviews (registration number: CRD42020207390, http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42020207390 ).

Clinical impact of multidrug-resistant bacterial infections in patients with cirrhosis.

Aim: Recently, the emergency of multidrug-resistant organisms (MDRO) has complicated the management of bacterial infections (BI) in cirrhosis. We aimed to assess their clinical impact on patients with decompensated cirrhosis. Methods: A retrospective study included consecutive cirrhotic patients hospitalized for acute decompensation (AD) between January 2010 and December 2019. Results: A total of 518 AD admissions in 219 patients were included, with 260 BI episodes (50.2%). MDRO prevalence was 38.2% of the total isolates. Recent antibiotic use (OR = 4.91), nosocomial infection (OR = 2.95), and healthcare-associated infection (OR = 3.45) were their main risk factors. MDROs were associated with empiric treatment failure (OR = 23.42), a higher prevalence of sepsis (OR = 4.93), ACLF (OR = 3.42) and mortality. Conclusion: The clinical impact of MDROs was pejorative, with an increased risk of empiric treatment failure, organ failure and death.

In recent years, an increasing spread of multidrug-resistant bacteria had been observed worldwide. The emergence of these strains could represent a major problem in fragile patients such as cirrhotic patients. Over 10 years, our study analyzed the bacteriological profile of cirrhotic patient infections. The multidrug-resistant bacteria prevalence was 38.2%. Exposure to healthcare facilities and recent antibiotic use, were their main risk factors. These strains had a negative impact with an increased risk of treatment failure and death.

New Study Alert! Significant prevalence and negative clinical impact of multidrug-resistant organism (MDRO) infections in patients with cirrhosis. Main risk factors: recent antibiotic use and exposure to healthcare facilities. #cirrhosis #bacterialinfection #antibiotherapy #resistance.

Refractoriness to anti-Helicobacter pylori treatment attributed to phenotypic resistance patterns in patients with gastroduodenopathy in Guayaquil-Ecuador.

BACKGROUND: Treatment of Helicobacter pylori gastric infection is complex and associated with increased rates of therapeutic failure. This research aimed to characterize the H. pylori infection status, strain resistance to antimicrobial agents, and the predominant lesion pattern in the gastroduodenal mucosa of patients with clinical suspicion of refractoriness to first- and second-line treatment who were diagnosed and treated in a health center in Guayaquil, Ecuador. METHODS: A total of 374 patients with upper gastrointestinal symptoms and H. pylori infection were preselected and prescribed one of three triple therapy regimens for primary infection, as judged by the treating physician. Subsequently, 121 patients who returned to the follow-up visit with persistent symptoms after treatment were studied. RESULTS: All patients had H. pylori infection. Histopathological examination diagnosed chronic active gastritis in 91.7% of cases; premalignant lesions were observed in 15.8%. The three triple therapy schemes applied showed suboptimal efficacy (between 47.6% and 77.2%), with the best performance corresponding to the scheme consisting of a proton pump inhibitor + amoxicillin + levofloxacin. Bacterial strains showed very high phenotypic resistance to all five antimicrobials tested: clarithromycin, 82.9%; metronidazole, 69.7%; amoxicillin and levofloxacin, almost 50%; tetracycline, 38.2%. Concurrent resistance to clarithromycin-amoxicillin was 43.4%, to tetracycline-metronidazole 30.3%, to amoxicillin-levofloxacin 27.6%, and to clarithromycin-metronidazole 59.2%. CONCLUSIONS: In vitro testing revealed resistance to all five antibiotics, indicating that H. pylori exhibited resistance phenotypes to these antibiotics. Consequently, the effectiveness of triple treatments may be compromised, and further studies are needed to assess refractoriness in quadruple and concomitant therapies.

Epidemiologic analysis of antimicrobial resistance in hospital departments in China from 2022 to 2023.

Bacterial drug resistance monitoring in hospitals is a crucial aspect of healthcare management and a growing concern worldwide. In this study, we analysed the bacterial drug resistance surveillance in our hospital from 2022 Q1 to 2023 Q2. The main sampling sources were respiratory, blood, and urine-based, and the main clinical infections were respiratory and genitourinary in nature. Specimens were inoculated and cultured; bacterial strains were isolated using a VITEK® 2 Compact 60-card automatic microorganism identifier (bioMerieux, Paris, France) and their matching identification cards were identified, and manual tests were supplemented for strain identification. The most common Gram-positive bacteria detected were Staphylococcus aureus, followed by Enterococcus faecalis (E. faecalis), Staphylococcus epidermidis (S. epidermidis), and Staphylococcus haemolyticus (S. haemolyticus). The most common Gram-negative bacteria detected were Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The most prevalent multidrug-resistant bacteria were those producing extended-spectrum beta-lactamases, followed by methicillin-resistant Staphylococcus aureus, followed by carbapenem-resistant Enterobacterales. This study suggests that the prevention and control of infections in the respiratory and genitourinary systems should be the focus of anti-infective work and that the use of antimicrobials should be reduced and regulated to prevent the emergence and spread of resistant bacteria.

Microbial isolates and antibiotic sensitivity in patients hospitalized with odontogenic infections at a tertiary center over 10 years.

Objectives: This study investigated causative strains and their antibiotic sensitivity in patients who were hospitalized for maxillofacial odontogenic infections at a tertiary center in South Korea over the past 10 years with the aim of providing guidelines for the selection of appropriate empirical antibiotics. Materials and Methods: Patients with head and neck fascial space abscesses due to odontogenic infections who underwent incision and drainage surgery with pus culture tests between 2013 and 2022 at the Department of Oral and Maxillofacial Surgery, Dankook University Hospital were included. The bacterial isolates and antibiotic sensitivity of each strain were analyzed for 2013-2022, 2013-2017, and 2018-2022. The affected fascial spaces were classified into primary, secondary, and deep neck spaces. Results: In the 192 patients included in this study, 302 strains were detected. Viridans streptococcus had the highest frequency (51.7%), followed by Prevotella spp. (16.9%), Staphylococcus spp. (5.6%), and Klebsiella pneumoniae (4.6%). The identification rate of viridans streptococcus significantly increased from 41.8% in 2013-2017 to 60.9% in 2018-2022. Viridans streptococcus showed an antibiotic sensitivity of 80.5% to ampicillin; the sensitivity to penicillin antibiotics decreased over the study period. Antibiotic susceptibility was approximately 94% for third-generation cephalosporins. K. pneumoniae, which was identified at a high percentage in patients with deep neck space infection, showed increasing antibiotic resistance to most antibiotics over the study period. Conclusion: Viridans streptococcus was identified in head and neck fascial space abscesses with the highest frequency. Empirical antibiotics should be effective against this strain; penicillin antibiotics are considered inappropriate. For effective treatment of deep neck space abscesses, bacterial culture and antibiotic sensitivity tests performed as soon as possible are essential.

Review of knockout technology approaches in bacterial drug resistance research.

Gene knockout is a widely used method in biology for investigating gene function. Several technologies are available for gene knockout, including zinc-finger nuclease technology (ZFN), suicide plasmid vector systems, transcription activator-like effector protein nuclease technology (TALEN), Red homologous recombination technology, CRISPR/Cas, and others. Of these, Red homologous recombination technology, CRISPR/Cas9 technology, and suicide plasmid vector systems have been the most extensively used for knocking out bacterial drug resistance genes. These three technologies have been shown to yield significant results in researching bacterial gene functions in numerous studies. This study provides an overview of current gene knockout methods that are effective for genetic drug resistance testing in bacteria. The study aims to serve as a reference for selecting appropriate techniques.

[New antibiotics for the treatment of urinary tract infections]. / Neue Antibiotika in der Behandlung von Harnwegsinfektionen.

Urinary tract infections (UTIs) are among the most common bacterial infections. The clinical phenotypes of UTIs are heterogeneous, ranging from rather benign uncomplicated infections to complicated UTIs and pyelonephritis to severe urosepsis. Antibiotics have become indispensable in modern medicine, but the development of resistance is threatening clinical effectiveness. Antimicrobial resistance rates are locally high in UTIs, however can vary significantly depending on the population studied and the type of study. In addition, between 1990 and 2010, there was a discovery void in the development of new antibiotics that is still having an impact today. In recent years, UTIs have emerged as an infection model for research into novel antibiotics. In the last 10 years, novel gram-negative active drugs have been explored in these groups. On the one hand, novel beta-lactam/beta-lactamase inhibitor combinations were investigated, and there has also been further development of cephalosporins and aminoglycosides.

Outbreak investigations after identifying carbapenem-resistant Pseudomonas aeruginosa: a systematic review.

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) are a serious cause of healthcare-associated infections. Part of the infection prevention and control measures are outbreak investigations (OI) of patients, healthcare workers (HCW), and the environment after identifying a CRPA in order to identify carriers and environmental reservoirs, so that targeted actions can be taken to prevent further transmission. However, little is known on when and how to perform such OI. Therefore, this systematic review aims to summarize OI performed after detection of CRPA in the endemic and epidemic hospital setting. MAIN TEXT: Articles related to our research question were identified through a literature research in multiple databases (Embase, Medline Ovid, Cochrane, Scopus, Cinahl, Web of Science, and Google Scholar) until January 12, 2022 (Prospero registration number CRD42020194165). Hundred-twenty-six studies were included. In both the endemic and the epidemic setting, a median number of two out of seven predefined components of OI were identified. In the endemic setting, the most frequent component of OI was screening of the environment (28 studies, 62.2%). In the epidemic setting, screening of the environment (72 studies, 88.9%), and screening of patients during hospitalization (30 studies, 37%) were most frequently performed. Only 19 out of 126 studies (15.1%) reported screening of contact patients, and 37 studies reported screening of healthcare workers (HCW, 29.4%). CONCLUSION: Due to probable underreporting of OI in the literature, the available evidence for the usefulness of the individual components of OI is scarce. This could lead to inhomogeneous performance of OI after detection of CRPA in the healthcare setting, and with this, potential under- or overscreening. While we could show evidence for the usefulness for environmental screening in order to identify the mode of transmission, evidence for HCW screening is scarce and might not lead to the identification of modes of transmission. Further studies are needed to better understand CI in different settings and, finally, develop guidance on when and how to best perform OI.

Study on Virulence Genes, Drug Resistance and Molecular Epidemiology of Klebsiella pneumoniae with High Virulence in Inner Mongolia, China.

Objective: The purpose of this study was to analyse the clinical, microbiological and molecular epidemiological characteristics of patients with pyogenic liver abscess (PLA) caused by Klebsiella pneumoniae (KPN) in Inner Mongolia, China. Methods: The KPN isolates from 78 KPN-PLA cases admitted to a tertiary teaching hospital in Baotou, Inner Mongolia, from 2016 to 2019 were studied systematically and described comprehensively. The virulence factors, drug resistance and sequence types of KPN in different samples were identified by a wire-drawing test, polymerase chain reaction, a drug susceptibility test and multi-site sequence typing. Results: There were more male than female KPN-PLA patients (P<0.05). The mortality rate was 2.5%, and KPN-PLA was significantly associated with diabetes mellitus (P<0.05). Most of the KPN isolates in the puncture fluid of patients with KPN-PLA were hypervirulent KPN (HvKP). The positive rate of the KPN-PLA specimens was higher than that of the blood and urine specimens. The KPN isolates of the urine specimens had higher drug resistance than the other two (P<0.05). The hypermucoviscous KPN, aerobic actin (aero) (+), K1 and K2 serotypes accounted for 80.8%, 89.7%, 56.4% and 26.9%, respectively. In addition to ironB (3.8%), the detection rates of virulence factors rmpA, irp2, entB, iucD, aero, wcaG, iutA, kfu, ybtA, iron, fimH and mrkD were higher (69.2%-100.0%). The positive rate of KPN isolates of the KPN-PLA puncture fluid was higher than that of the blood and urine samples (P<0.05). In addition, ST23 was found to be the dominant ST (32.1%) of KPN-PLA in the Baotou region. Conclusion: In the KPN-PLA specimens, the KPN isolates were more virulent than those in the blood and urine specimens, and a carbapenem-resistant HvKP strain emerged. This research will help improve the understanding of HvKP and provide useful suggestions for KPN-PLA treatments.

The Clinical Evaluation of Third-generation Cephalosporins As Definitive Therapy for Enterobacter spp. and Klebsiella aerogenes Bacteremia.

Objective Third-generation cephalosporins (3GCs) may be susceptible in vitro to Enterobacter spp. and Klebsiella aerogenes. However, treatment with mainly fourth-generation cephalosporins or carbapenems is currently recommended. Diversification of antimicrobial agents in therapy is required to avoid the selection pressure of resistant organisms by broad-spectrum antimicrobial agents. This study investigated the clinical efficacy of 3GC therapy for Enterobacter spp. and Klebsiella aerogenes bacteremia in a multicenter, retrospective, observational study. Methods Patients with Enterobacter spp. or Klebsiella aerogenes detected in blood cultures and treated with a susceptible antimicrobial agent were included in the study. Propensity score matching was performed to align patient background bases, and clinical outcomes between the 3GC and non-3GC groups were compared. Treatment success was defined as having no need for treatment escalation or the addition of other antimicrobial agents, no recurrence, or no death within 30 days. Results The study included 188 cases, of which 57 and 131 were included in the 3GC and non-3GC treatment groups, respectively; 53 patients in each group were matched by propensity score matching. There were no significant differences between groups in rates of switching to a susceptible antimicrobial or adding another agent, relapse within 30 days, or death within 30 days. In the 3GC group, source control was associated with favorable clinical outcomes. Conclusion Definitive 3GC therapy for susceptible Enterobacter spp. and Klebsiella aerogenes bacteremia is as clinically effective and valuable a targeted therapy as non-3GC therapy and can be implemented under conditions in which infection source control measures are in place.

Virulence associated characteristics and drug resistance of Klebsiella pneumoniae isolated from patients living in Zhongjiang county of Sichuan province / 中国基层医药

Objective:To investigate the distribution characteristics of virulence-related phenotypes/genotype, capsular serotype, drug resistance phenotypes, and sequence typing (ST) of Klebsiella pneumoniae in patients living in Zhongjiang county, improve clinical understanding, and provide evidence for the prevention and control of bacterial drug resistance and clinical rational drug use. Methods:The data of 135 strains of Klebsiella pneumoniae isolated from patients who received treatment in Zhongjiang County People's Hospital from July to December 2019 were retrospectively analyzed. Bacterial identification and drug sensitivity testing were performed using the WalkAway-40Plus automated microbiology system. Strains with a high viscosity phenotype were identified using wire drawing experiments. Hypervirulence-associated capsular serotype and virulence genes were verified by polymerase chain reaction. ST of Klebsiella pneumoniae strain was identified using multilocus sequence typing. Results:Strains with a high viscosity phenotype were identified in 50.4% of the 135 strains. 54.1%, 54.8%, and 54.1% of the strains were positive for virulence genes iucA, iroN, rmpA. The proportion of strains with capsular Serotype K1 or K2 was 11.9% and 15.6%, respectively. A total of 65 kinds of ST were identified, with ST23 and ST37 being the most common, accounting for 11.1% and 6.7%, respectively. The resistance rate of the strains to 16 kinds of antibiotics was 0.0%-25.2%, and the resistance rate to Carbapenem antibiotics, Amikacin, and Tigecycline was less than 1%. The positive rate of virulence gene of strains with a high viscosity phenotype was significantly higher than that of strains without a high viscosity phenotype ( P < 0.001), and its resistance rate to Cephalosporin was significantly lower in strains with a high viscosity phenotype than that in strains without a high viscosity phenotype ( P < 0.001). Conclusion:Klebsiella pneumoniae in Zhongjiang County is characterized by "high virulence and low drug resistance". It is necessary to continuously monitor the changes in the virulence and drug resistance of Klebsiella pneumoniae in Zhongjiang County, Sichuan Province, and be alert to the rapid dissemination of highly virulent strains.

The characteristics and changes of bacterial infection and drug resistance in pediatric intensive care unit from 2016 to 2020 / 中国小儿急救医学

Objective:To investigate the characteristics and changes of bacterial infection and drug resistance in PICU at Children′s Hospital of Fudan University from 2016 to 2020.Methods:All the strains were collected at Children′s Hospital of Fudan University from January 1 st, 2016 to December 31 st, 2020.Antimicrobial susceptibility test was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were analyzed according to CLSI 2020 breakpoints. Results:(1)Bacterial distribution: 2 551 bacteria were monitored from 2016 to 2020 in our center.The top 3 bacteria were all gram-negative bacteria.Among them, Burkholderia cepacian showed a tortuous downward trend(13.45% to 1.18%), and Klebsiella pneumoniae showed an upward trend(6.05% to 10.61%).The most common infected site was respiratory tract, although the strains in the respiratory tract decreased year by year.Baumanii was the most common bacteria in respiratory infections.Staphylococcus epidermidis was the most common bacteria from 2016 to 2017 in blood infections, but Achromobacter xylosoxidans were became the most common bacteria from 2018 to 2020.Enterococcus faecium was the most common bacteria in urinary infections.(2) Drug resistance: Baumanii had a high drug resistance rate to amikacin, gentamicin, cefepime, and cefitadine, with no obvious changes over the years, which had a gradually decreasing drus resistance rate to cefoperazone sulbactam, showing a tortuous upward trend to imipenem and meropenem.Baumanii and Pseudomonas aeruginosa had a low drug resistance to levofloxacin over the years, but with high resistance rates in 2020.Escherichia coliand and Klebsiella pneumoniae still had high resistance rates to beta-lactam antibiotics, and their resistance rates to levofloxacin were decreasing.Escherichia coli and Klebsiella pneumoniae showed decreasing resistance rates to imipenem and increased resistance rates to meropenem.The resistance rate of Enterococcus faecium to levofloxacin decreased and always showed a high susceptibility rate to polypeptide antibiotics.Neither Staphylococcus epidermidis nor Staphylococcus aureus were currently resistant to tetracycline antibiotics, and the resistance rates of aminoglycoside antibiotics, such as gentamicin, was also declining.Conclusion:The bacterial infection in PICU shows as the main characteristics of respiratory infection and gram-negative bacteria infection.Carbapenem-resistant Enterobacteriaceae bacteria, Enterococci and Staphylococcus species are becoming increasingly more resistant.

Benefits and Challenges of the Use of Two Novel vB_Efa29212_2e and vB_Efa29212_3e Bacteriophages in Biocontrol of the Root Canal Enterococcus faecalis Infections.

Bacteriophage therapy has emerged as a strategy supplementing traditional disinfection protocols to fight biofilms. The aim of the study was to isolate the phages against E. faecalis and to characterize its biological features, morphology, and lytic activity in a formed biofilm model. METHODS: E. faecalis ATCC 29212 strain was used for the trial. Two novel vB_Efa29212_2e and vB_Efa29212_3e virulent phages were isolated from urban wastewater and characterized. The E. faecalis biofilm was established in 15 bovine teeth for 21 days. Transmission (TEM) and scanning electron (SEM) microscopes with the colony-forming unit (CFU) counting were used for assessment. RESULTS: Isolated phages differed in morphology. Taxonomy for vB_Efa29212_2e (Siphoviridae, Efquatovirus) and for vB_Efa29212_3e (Herelleviridae, Kochikohdavirus) was confirmed. Both phages were stable at a temperature range of 4-50 °C and showed a different tolerance to chemicals: 15% EDTA, 1-3% sodium hypochlorite, and chlorhexidine. SEM analysis showed distortion of bacteria cells after phage inoculation, which proved the lytic activity against E. faecalis. A 54.6% reduction in the E. faecalis biofilm confirmed bacteriophage efficacy against isolates in the ex vivo model. CONCLUSIONS: Results strongly support the concept that phage therapy has a real therapeutic potential for the prevention and treatment of E. faecalis-associated infections.

The Mechanism of Bacterial Resistance and Potential Bacteriostatic Strategies.

Bacterial drug resistance is rapidly developing as one of the greatest threats to human health. Bacteria will adopt corresponding strategies to crack the inhibitory effect of antibiotics according to the antibacterial mechanism of antibiotics, involving the mutation of drug target, secreting hydrolase, and discharging antibiotics out of cells through an efflux pump, etc. In recent years, bacteria are found to constantly evolve new resistance mechanisms to antibiotics, including target protective protein, changes in cell morphology, and so on, endowing them with multiple defense systems against antibiotics, leading to the emergence of multi-drug resistant (MDR) bacteria and the unavailability of drugs in clinics. Correspondingly, researchers attempt to uncover the mystery of bacterial resistance to develop more convenient and effective antibacterial strategies. Although traditional antibiotics still play a significant role in the treatment of diseases caused by sensitive pathogenic bacteria, they gradually lose efficacy in the MDR bacteria. Therefore, highly effective antibacterial compounds, such as phage therapy and CRISPER-Cas precision therapy, are gaining an increasing amount of attention, and are considered to be the treatments with the moist potential with regard to resistance against MDR in the future. In this review, nine identified drug resistance mechanisms are summarized, which enhance the retention rate of bacteria under the action of antibiotics and promote the distribution of drug-resistant bacteria (DRB) in the population. Afterwards, three kinds of potential antibacterial methods are introduced, in which new antibacterial compounds exhibit broad application prospects with different action mechanisms, the phage therapy has been successfully applied to infectious diseases caused by super bacteria, and the CRISPER-Cas precision therapy as a new technology can edit drug-resistant genes in pathogenic bacteria at the gene level, with high accuracy and flexibility. These antibacterial methods will provide more options for clinical treatment, and will greatly alleviate the current drug-resistant crisis.

Epidemiology and Outcomes of Bacterial Coinfection in Hospitalized Children With Respiratory Viral Infections: A Single Center Retrospective Chart Review.

OBJECTIVE: Children with viral respiratory illness are often suspected of having bacterial coinfection. This study was designed to determine the impact of bacterial coinfection on hospital course and outcomes and the rate of antimicrobial misuse. METHODS: Single-center retrospective chart review, including all hospitalized children who had a respiratory viral panel sent within 48 hours of admission from January 2015 to December 2019. Patients who had a positive respiratory, urine, blood culture within 24 hours of admission were identified. Demographics, resource utilization, and outcomes were compared between the 2 groups. RESULTS: This study included 2192 patients. Of those, 269 patients had positive bacterial cultures. Out of these cultures from 192 patients were identified as contaminants. True bacterial coinfection was 3.5% (77/2192). Almost 1/3 of admitted patients were prescribed empiric antimicrobials. Children with bacterial coinfection tended to be younger (median age 8.4 months vs 16.3 months, p < 0.01) and had higher proportion of prematurity (23.3% vs 12.1%, p < 0.01). Children with bacterial coinfection were more likely to require ICU admission (37.6% vs 23.9%, p < 0.01) and intubation (28.5% vs 5.3 %, p < 0.01). They had higher ICU (5.7 days vs 1.9 days, p < 0.01) and hospital length of stay (4.0 days vs 2.0 days, p < 0.01), higher mortality (2.6% vs 0.2%, p = 0.02), and a higher median cost of hospital care ($3774.44 vs $2424.49.90, p < 0.01). CONCLUSIONS: The rate of bacterial coinfection in hospitalized children with viral infections is very low, which contradicts the routine administration of empiric antimicrobials. Patients with coinfection require more hospital resources and have worse clinical outcomes.

Eurasian griffon vultures carry widespread antimicrobial resistant Salmonella and Campylobacter of public health concern.

The global emergence of antimicrobial-resistant (AMR) strains of Salmonella and Campylobacter is a serious public health concern. Both bacteria are leading causes of human gastrointestinal foodborne infections and the two most reported zoonoses in the European Union. By feeding on livestock carcasses, especially from intensive farming, as well as on landfill sites, obligate avian scavengers can become infected with zoonotic pathogens and AMR strains, and can be considered large-scale sentinels of the environmental burden. In this study, we assessed the occurrence and AMR of Salmonella spp. and Campylobacter spp. in 218 Eurasian griffon vultures (Gyps fulvus) captured in north-eastern Spain. We isolated Salmonella from 8.1 % of individuals and Campylobacter lari from 4.7 %. Among the 10 different Salmonella serovars found, monophasic S. Typhimurium was the most frequent. Genotyping analysis revealed same strains of monophasic S. Typhimurium shared by gulls, livestock and humans. Isolates from both bacterial species presented AMR to important antimicrobials (tetracyclines, fluoroquinolones and ß-lactams). In conclusion, this study shows that Eurasian griffon vultures in north-eastern Spain are carriers of widespread AMR zoonotic Salmonella and Campylobacter. More comprehensive analyses are still needed to understand the potential risk of spill-over from those wild birds to humans.

A Retrospective, Longitudinal External Study of the robustness and reproducibility of National Antibacterial Prescribing Survey Data.

BACKGROUND: Point prevalence surveys are used internationally to audit antibacterial use as well as the impact of interventions on improving prescribing and resistance rates. The annual National Antibacterial Prescribing Survey provides data on the appropriateness of antibacterial agent prescribing in Australian hospitals. Assessing the survey's robustness and result reproducibility is essential to its role in improving antibacterial prescribing practice. AIM: To evaluate the reproducibility of internal assessments of antibacterial agent prescribing of both guideline compliance and appropriateness from a Western Australian hospital. METHOD: Census data of 1051 prescriptions from 2013 to 2017 surveys were independently assessed for compliance based on Australian Therapeutic Guidelines - Antibiotics, and appropriateness, based on agent selection, therapy duration and microbiological test results. Concordance of these findings with internal hospital assessments was analysed. RESULTS: This external study did not reproduce internal hospital audit results for compliance with guideline parameters. Non-compliant prescribing rate was significantly (p < 0.001) higher externally at 50.7% (533/1051) than internal assessment at 34.9% (367/1051). External analysis also found a significantly smaller proportion of prescriptions to be appropriate (551/1051, 52.4%) compared to internal analysis (745/1051, 70.9%) p < 0.001. Cohen's Kappa analysis found a moderate agreement for compliance (0.49) and appropriateness (0.50) between the external and internal evaluations. CONCLUSION: The lack of adequate reproducibility of compliance and appropriateness assessments may limit the generalisability of the audit's results. Validating point prevalence surveys that assess antibacterial agent prescribing can increase confidence and improve reproducibility of their findings; as they provide important data for antimicrobial stewardship programs.

GLO1 Contributes to the Drug Resistance of Escherichia coli Through Inducing PER Type of Extended-Spectrum ß-Lactamases.

Background: Escherichia coli-associated antimicrobial resistance (AMR) issue so far needs urgent considerations. This study aims to screen the potent genes associated with extended-spectrum ß-lactamases (ESBLs) in drug-resistant Escherichia coli and elucidate the specific drug-resistant mechanism. Methods: Clinical ESBLs-EC samples were obtained based on the microbial identification, and the whole genome was sequenced. In combination with the significantly enriched pathways, several differently expressed genes were screened and verified by RT-PCR. Furthermore, through knocking out glyoxalase 1 (GLO1) gene and transfecting overexpressed plasmids, the potential relationship between GLO1 and ESBLs was then investigated. Lastly, the concentrations of ß-lactamases in bacteria and supernatant from different groups were examined by enzyme-linked immunosorbent assay (ELISA). Results: After successful isolation and identification of ESBLs-EC, the whole genome and eighteen differential metabolic pathways were analyzed to select differently expressed genes, including add, deoD, guaD, speG, GLO1, VNN1, etc. RT-PCR results showed that there were no differences in these genes between the standard bacteria and susceptible Escherichia coli. Remarkably, the relative levels of four genes including speG, Hdac10, GLO1 and Ppcdc were significantly increased in ESBLs-EC in comparison with susceptible strains, whereas other gene expression was decreased. Further experiments utilizing gene knockout and overexpression strains confirmed the role of GLO1. At last, a total of 10 subtypes of ß-lactamases were studied using ELISA, including BES-, CTX-M1-, CTX-M2-, OXA1-, OXA2-, OXA10-, PER-, SHV-, TEM-, and VEB-ESBLs, and results demonstrated that GLO1 gene expression only affected PER-ß-lactamases but had no effects on other ß-lactamases. Conclusion: SpeG, Hdac10, GLO1 and Ppcdc might be associated with the drug-resistant mechanism of Escherichia coli. Of note, this study firstly addressed the role of GLO1 in the drug resistance of ESBLs-EC, and this effect may be mediated by increasing PER-ß-lactamases.

Antibiotic resistance among bacteria isolated from war-wounded patients at the Weapon Traumatology Training Center of the International Committee of the Red Cross from 2016 to 2019: a secondary analysis of WHONET surveillance data.

BACKGROUND: A substantial body of evidence has recently emphasized the risks associated with antibiotic resistance (ABR) in conflicts in the Middle East. War-related, and more specifically weapon-related wounds can be an important breeding ground for multidrug resistant (MDR) organisms. However, the majority of available evidence comes from the military literature focused on risks and patterns of ABR in infections from combat-related injuries among military personnel. The overall aim of this study is to contribute to the scarce existing evidence on the burden of ABR among patients, including civilians with war-related wounds in the Middle East, in order to help inform the revision of empirical antibiotic prophylaxis and treatment protocols adopted in these settings. The primary objectives of this study are to: 1) describe the microbiology and the corresponding resistance profiles of the clinically relevant bacteria most commonly isolated from skin, soft tissue and bone biopsies in patients admitted to the WTTC; and 2) describe the association of the identified bacteria and corresponding resistance profiles with sociodemographic and specimen characteristics. METHODS: We retrospectively evaluated the antibiograms of all consecutive, non-duplicate isolates from samples taken from patients admitted to the ICRC WTTC between 2016 and 2019, limited to skin and soft tissue samples and bone biopsies. We collected data on socio-demographic characteristics from patient files and data on specimens from the WHONET database. We ran univariate and multivariable logistic regression models to test the association between bacterial and resistance profiles with sociodemographic and specimen characteristics. RESULTS: Patients who were admitted with war-related trauma to the ICRC reconstructive surgical project in Tripoli, Lebanon, from 2016 to 2019, presented with high proportion of MDR in the samples taken from skin and soft tissues and bones, particularly Enterobacterales (44.6%), MRSA (44.6%) and P. aeruginosa (7.6%). The multivariable analysis shows that the odds of MDR isolates were higher in Iraqi patients (compared to Syrian patients) and in Enterobacterales isolates (compared to S. aureus isolates). CONCLUSIONS: Our findings stress the importance of regularly screening patients who present with complex war-related injuries for colonization with MDR bacteria, and of ensuring an antibiotic-sensitivity testing-guided antimicrobial therapeutic approach.