Browsing by Subject "Antimicrobial resistance"
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Item 322. Evaluation of the BioFire® Bone and Joint Infection (BJI) Panel for the Detection of Microorganisms and Antimicrobial Resistance Genes in Synovial Fluid Specimens(Oxford University Press, 2020-12) Graue, Corrin; Schmitt, Bryan H.; Waggoner, Amy; Laurent, Frederic; Abad, Lelia; Bauer, Thomas; Mazariegos, Irving; Balada-Llasat, Joan-Miquel; Horn, Jarid; Wolk, Donna; Jefferis, Alexa; Hermans, Mirjam; Verhoofstad, Irma; Butler-Wu, Susan; Umali-Wilcox, Minette; Murphy, Caitlin N.; Cabrera, Barbara J.; Esteban, Jaime; Macias-Valcayo, Alicia; Craft, David; von Bredow, Benjamin; Leber, Amy; Everhart, Kathy; Dien Bard, Jennifer; Mestas, Jvier; Daly, Judy; Barr, Rebecca; Kensinger, Bart; Pons, Benedicte; Jay, Corinne; Pathology and Laboratory Medicine, School of MedicineBackground Bone and Joint Infections (BJIs) present with non-specific symptoms that may include pain, swelling, and fever and are associated with high morbidity and significant risk of mortality. BJIs can be caused by a variety of bacteria and fungi, including anaerobes and microorganisms that can be challenging to culture or identify by traditional microbiological methods. Clinicians primarily rely on culture to identify the pathogen(s) responsible for infection. The BioFire® Bone and Joint Infection (BJI) Panel (BioFire Diagnostics, Salt Lake City, UT) is designed to detect 15 gram-positive bacteria (including seven anaerobes), 14 gram-negative bacteria (including one anaerobe), two yeast, and eight antimicrobial resistance (AMR) genes from synovial fluid specimens in about an hour. The objective of this study was to evaluate the performance of an Investigational Use Only (IUO) version of the BioFire BJI Panel compared to various reference methods. Methods Remnant synovial fluid specimens, which were collected for routine clinical care at 13 study sites in the US and Europe, underwent testing using an IUO version of the BioFire BJI Panel. Performance of this test was determined by comparison to Standard of Care (SoC) consisting of bacterial culture performed at each study site according to their routine procedures. Results A total of 1544 synovial fluid specimens were collected and tested with the BioFire BJI Panel. The majority of specimens were from knee joints (77.9%) and arthrocentesis (79.4%) was the most common collection method. Compared to SoC culture, overall sensitivity was 90.2% and specificity was 99.8%. The BioFire BJI Panel yielded a total of 268 Detected results, whereas SoC yielded a total of 215 positive results for on-panel analytes. Conclusion The BioFire BJI Panel is a sensitive, specific, and robust test for rapid detection of a wide range of analytes in synovial fluid specimens. The number of microorganisms and resistance genes included in the BioFire BJI Panel, together with a reduced time-to-result and increased diagnostic yield compared to culture, is expected to aid in the timely diagnosis and appropriate management of BJIs.Item Antibiotics in the pipeline: a literature review (2017–2020)(Springer, 2021-10-04) Al-Tawfiq, Jaffar A.; Momattin, Hisham; Al-Ali, Anfal Y.; Eljaaly, Khalid; Tirupathi, Raghavendra; Haradwala, Mohamed Bilal; Areti, Swetha; Alhumaid, Saad; Rabaan, Ali A.; Al Mutair, Abbas; Schlagenhauf, Patricia; Medicine, School of MedicineIntroduction Antimicrobial resistance (AMR) is an emerging global threat. It increases mortality and morbidity and strains healthcare systems. Health care professionals can counter the rising AMR by promoting antibiotic stewardship and facilitating new drug development. Even with the economic and scientific challenges, it is reassuring that new agents continue to be developed. Methods This review addresses new antibiotics in the pipeline. We conducted a review of the literature including Medline, Clinicaltrials.org, and relevant pharmaceutical companies for approved and in pipeline antibiotics in phase 3 or new drug application (NDA). Results We found a number of new antibiotics and reviewed their current development status, mode of action, spectra of activity, and indications for which they have been approved. The included studies from phase 3 clinical trials were mainly utilized for the treatment of acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, and pneumonia acquired in the healthcare settings. The number of these agents is limited against high priority organisms. The identified antibiotics were based mainly on previously known molecules or pre-existing antimicrobial agents. Conclusion There are a limited number of antibiotics against high priority organisms such as multi-drug-resistant Pseudomonas aeruginosa, and carbapenem-resistant Enterobacteriaceae. New antimicrobial agents directed against the top priority organisms as classified by the World Health Organization are urgently needed.Item Carbapenem use correlates with percentage of patients with COVID-19 in intensive care units(Springer, 2023) AlBahrani, Salma; Almogbel, Feras; Alanazi, Wafa; Almutairi, Saleh Hamdi; Alanazi, Mohammed; Maximos, Sameh; Azaiez, Faten; Osman, Assim; Almuthen, Sharifah; Jebakumar, Arulanantham Zechariah; Al‑Tawfiq, Jaffar A.; Medicine, School of MedicineBackground: The first wave of COVID-19 pandemic may have significantly impacted antimicrobial consumption in hospitals. The objective of this study was to assess the evolution of carbapenem consumption and describe the implemented measures during the first year of the COVID-19 pandemic. Methods: We calculated carbapenem consumption for all the hospital and for intensive care units (ICU) for three periods: baseline (before COVID-19 cases, January 2019-February 2020), and the period of COVID-19 cases as a pre-intervention (March-August 2020) and a post-intervention phase (September 2020-December 2021). Results: During the study period, the percentage of admitted COVID-19 patients increased in the months of April-August of 2020 (pre-intervention period) from 5 to 26% of total admitted patients. The consumption of carbapenems (DDD/1000 patient days) increased from a mean of 67.1 at baseline to 142.9 pre-intervention. In ICUS, there was an increase in the mean from 125.7 to 240.8 DDD/1000 patient days. After interventions, the DDD/1000 patient days decreased by 49.5% overall the hospital and by 36% in ICUs. For the post-intervention period, there was a correlation between COVID-19 cases and carbapenem usage in the ICU but not the overall hospital. Conclusion: An increase in the antimicrobial consumption during the first wave of COVID-19 pandemic was noticed, especially in the ICU. Antimicrobial stewardship programs are essential to reduce consumption rate.Item Five-year resistance trends in pathogens causing healthcare-associated infections at a multi-hospital healthcare system in Saudi Arabia, 2015-2019(Elsevier, 2021) Al Mutair, Abbas; Alhumaid, Saad; Al Alawi, Zainab; Zaidi, Abdul Rehman Z.; Alzahrani, Ahmed J.; Al-Tawfiq, Jaffar A.; Al-Shammari, Haifa; Rabaan, Ali A.; Khojah, Osamah; Al-Omari, Awad; Medicine, School of MedicineObjectives: Awareness of antimicrobial resistance (AMR) patterns in a given healthcare setting is important to inform the selection of appropriate antimicrobial therapy to reduce the further rise and spread of AMR as well as the rate of healthcare-associated infections (HAIs) and multidrug-resistant (MDR) organisms. We aimed to describe resistance patterns to several antimicrobial agents in pathogens causing HAIs isolated from patients using data gathered at three private tertiary-care hospitals in Saudi Arabia. Methods: Data on trends in AMR among bacteria causing HAIs and MDR events in children and adults at three private hospitals were collected retrospectively (2015-2019) using surveillance data. Results: Over the 5-year period, 29 393 pathogens caused 17 539 HAIs in 15 259 patients. Approximately 57.3% of patients were female and the mean age was 38.4 ± 16.8 years (81.4% adults, 18.6% children). Gram-negative pathogens were four times more likely to cause HAIs compared with Gram-positive bacteria (79.3% vs. 20.7%). Ranking of causative pathogens in decreasing order was Escherichia coli (42.2%), Klebsiella spp. (16.8%) and Staphylococcus aureus (13.9%). Acinetobacter spp. were the only pathogens to decrease significantly (7% reduction; P = 0.033). The most common resistant pathogens were extended-spectrum cephalosporin-resistant E. coli (37.1%), extended-spectrum cephalosporin-resistant Klebsiella (27.8%), carbapenem-non-susceptible Acinetobacter spp. (19.5%), carbapenem-non-susceptible Pseudomonas aeruginosa (19.2%) and methicillin-resistant S. aureus (18.6%). Conclusion: National collaboration is required by prompt feedback to local authorities to tackle regional differences in AMR. This can help plan timely containment interventions to stop and contain microbial threats and swiftly assess their impact.Item Global emerging resistance in pediatric infections with TB, HIV, and gram-negative pathogens(Taylor & Francis, 2021-02) Enane, Leslie A.; Christenson, John C.; Pediatrics, School of MedicineInfants, children and adolescents are at risk of life-threatening, antimicrobial-resistant infections. Global burdens of drug-resistant TB, HIV and gram-negative pathogens have a particular impact on paediatric age groups, necessitating a paediatric-focused agenda to address emerging resistance. Dedicated approaches are needed to find, successfully treat and prevent resistant infections in paediatric populations worldwide. Challenges include the diagnosis and identification of resistant infections, limited access to novel antimicrobials or to paediatric-friendly formulations, limited access to research and clinical trials and implementation challenges related to prevention and successful completion of treatment. In this review, the particular complexities of emerging resistance in TB, HIV and gram-negative pathogens in children, with attention to both clinical and public health challenges, are highlighted. Key principles of a paediatric-focused agenda to address antimicrobial resistance are outlined. They include quality of care, increasing equitable access to key diagnostics, expanding antimicrobial stewardship and infection prevention across global settings, and health system strengthening. Increased access to research studies, including clinical trials, is needed. Further study and implementation of care models and strategies for child- or adolescent-centred management of infections such as HIV and TB can critically improve outcome and avoid development of resistance. As the current global pandemic of a novel coronavirus, SARS-CoV-2, threatens to disrupt health systems and services for vulnerable populations, this is a critical time to mitigate against a potential surge in the incidence of resistant infections.Item Induction of β-Lactamase Activity and Decreased β-Lactam Susceptibility by CO2 in Clinical Bacterial Isolates(American Society for Microbiology, 2017-07-19) Mullen, Nathan; Raposo, Hugo; Gudis, Polyxeni; Barker, Linsey; Humphries, Romney M.; Schmitt, Bryan H.; Relich, Ryan F.; May, Meghan; Pathology and Laboratory Medicine, School of MedicineAntimicrobial susceptibility testing of clinical isolates is a crucial step toward appropriate treatment of infectious diseases. The clinical isolate Francisella philomiragia 14IUHPL001, recently isolated from a 63-year-old woman with atypical pneumonia, featured decreased susceptibility to β-lactam antibiotics when cultivated in 5% CO2. Quantitative β-lactamase assays demonstrated a significant (P < 0.0001) increase in enzymatic activity between bacteria cultivated in 5% CO2 over those incubated in ambient air. The presence of β-lactamase genes blaTEM and blaSHV was detected in the clinical isolate F. philomiragia 14IUHPL001 by PCR, and the genes were positively identified by nucleotide sequencing. Expression of blaTEM and blaSHV was detected by reverse transcription-PCR during growth at 5% CO2 but not during growth in ambient air. A statistically significant alkaline shift was observed following cultivation of F. philomiragia 14IUHPL001 in both ambient air and 5% CO2, allowing desegregation of the previously reported effects of acidic pH from the currently reported effect of 5% CO2 on blaTEM and blaSHV β-lactamases. To ensure that the observed phenomenon was not unique to F. philomiragia, we evaluated a clinical isolate of blaTEM-carrying Haemophilus influenzae and found parallel induction of blaTEM gene expression and β-lactamase activity at 5% CO2 relative to ambient air. IMPORTANCE β-Lactamase induction and concurrent β-lactam resistance in respiratory tract pathogens as a consequence of growth in a physiologically relevant level of CO2 are of clinical significance, particularly given the ubiquity of TEM and SHV β-lactamase genes in diverse bacterial pathogens. This is the first report of β-lactamase induction by 5% CO2.Item Preventing Antimicrobial Resistance Together: Reflections on AMR Week 2023(Springer, 2024) Al‑Tawfiq, Jaffar A.; Ebrahim, Shahul H.; Memis, Ziad A.; Medicine, School of MedicineItem Quantitative Evaluation of the Economic Impact of Antimicrobial Resistance on the Treatment of Community-Acquired Acute Pyelonephritis in Korea(Korean Society of Infectious Diseases, 2022) Cheong, Taul; Ahn, Jungmo; Kim, Yun Seop; Pai, Hyunjoo; Kim, Bongyoung; Economics, School of Liberal ArtsBackground: The proportion of antimicrobial-resistant Enterobacteriales as a causative pathogen of community-acquired acute pyelonephritis (APN) has been increasing. The aim of this study was to quantitatively evaluate the impact of antimicrobial resistance on medical costs and length of hospital stay for the treatment of APN. Materials and methods: A single-center retrospective cohort study was conducted between January 2018 and December 2019. All hospitalized patients aged ≥19 years who were diagnosed with community-acquired APN were recruited, and those diagnosed with Enterobacteriales as a causative pathogen were included. Log-linear regression analysis was performed to determine the risk factors for medical costs and length of hospital stay. Results: A total of 241 patients participated in this study. Of these, 75 (31.1%) and 87 (36.1%) had extended-spectrum beta-lactamase (ESBL)-producing pathogens and ciprofloxacin-resistant pathogens as the causative pathogen, respectively. Based on the log-linear regression model, ESBL-producing Enterobacteriales is a causative pathogen that is, on average, 27.0%, or United States Dollar (USD) 1,211 (P = 0.026) more expensive than non-ESBL-producing Enterobacteriales. A patient who is a year older would incur USD 23 (P = 0.040) more, those having any structural problems in the urinary tract would incur USD 1,231 (P = 0.015) more, and those with a unit increase in the Pitt bacteremia score would incur USD 767 (P <0.001) more, with all other variables constant. Having a case in which ESBL-producing Enterobacteriales is a causative pathogen would explain staying 22.0% longer or 2 more days (P = 0.050) in the hospital than non-ESBL-producing Enterobacteriales. A patient who is 10 years older would, on average, would have to stay for half a day longer (P = 0.045). Any structural problems in the urinary tract explain a longer stay (2.4 days longer; P = 0.032), and moving from 0 to 5 on the Pitt bacteremia score would explain four more days (P = 0.038) in the hospital. Conclusion: Patients with community-acquired APN with ESBL-producing Enterobacteriale as the causative pathogen would incur, on average, 27.0% higher medical costs and 22.0% longer hospitalization days than patients detected with non-ESBL-producing pathogens.Item Targeting Mannitol Metabolism as an Alternative Antimicrobial Strategy Based on the Structure-Function Study of Mannitol-1-Phosphate Dehydrogenase in Staphylococcus aureus(American Society for Microbiology, 2019-07-09) Nguyen, Thanh; Kim, Truc; Ta, Hai Minh; Yeo, Won Sik; Choi, Jongkeun; Mizar, Pushpak; Lee, Seung Seo; Bae, Taeok; Chaurasia, Akhilesh Kumar; Kim, Kyeong Kyu; Microbiology & Immunology, IU School of MedicineMannitol-1-phosphate dehydrogenase (M1PDH) is a key enzyme in Staphylococcus aureus mannitol metabolism, but its roles in pathophysiological settings have not been established. We performed comprehensive structure-function analysis of M1PDH from S. aureus USA300, a strain of community-associated methicillin-resistant S. aureus, to evaluate its roles in cell viability and virulence under pathophysiological conditions. On the basis of our results, we propose M1PDH as a potential antibacterial target. In vitro cell viability assessment of ΔmtlD knockout and complemented strains confirmed that M1PDH is essential to endure pH, high-salt, and oxidative stress and thus that M1PDH is required for preventing osmotic burst by regulating pressure potential imposed by mannitol. The mouse infection model also verified that M1PDH is essential for bacterial survival during infection. To further support the use of M1PDH as an antibacterial target, we identified dihydrocelastrol (DHCL) as a competitive inhibitor of S. aureus M1PDH (SaM1PDH) and confirmed that DHCL effectively reduces bacterial cell viability during host infection. To explain physiological functions of SaM1PDH at the atomic level, the crystal structure of SaM1PDH was determined at 1.7-Å resolution. Structure-based mutation analyses and DHCL molecular docking to the SaM1PDH active site followed by functional assay identified key residues in the active site and provided the action mechanism of DHCL. Collectively, we propose SaM1PDH as a target for antibiotic development based on its physiological roles with the goals of expanding the repertory of antibiotic targets to fight antimicrobial resistance and providing essential knowledge for developing potent inhibitors of SaM1PDH based on structure-function studies.IMPORTANCE Due to the shortage of effective antibiotics against drug-resistant Staphylococcus aureus, new targets are urgently required to develop next-generation antibiotics. We investigated mannitol-1-phosphate dehydrogenase of S. aureus USA300 (SaM1PDH), a key enzyme regulating intracellular mannitol levels, and explored the possibility of using SaM1PDH as a target for developing antibiotic. Since mannitol is necessary for maintaining the cellular redox and osmotic potential, the homeostatic imbalance caused by treatment with a SaM1PDH inhibitor or knockout of the gene encoding SaM1PDH results in bacterial cell death through oxidative and/or mannitol-dependent cytolysis. We elucidated the molecular mechanism of SaM1PDH and the structural basis of substrate and inhibitor recognition by enzymatic and structural analyses of SaM1PDH. Our results strongly support the concept that targeting of SaM1PDH represents an alternative strategy for developing a new class of antibiotics that cause bacterial cell death not by blocking key cellular machinery but by inducing cytolysis and reducing stress tolerance through inhibition of the mannitol pathway.Item What does the dust in your home mean for your health?(The Conversation US, Inc., 2019-06-17) Filippelli, Gabriel; Earth and Environmental Sciences, School of Science