Antimicrobial resistance (AR) is an urgent global public health threat. In the U.S., more than 2.8 million antimicrobial-resistant infections occur each year. CDC is concerned about the emergence and spread of new forms of resistance and rising resistant infections in the community (outside hospitals). Community infections can put more people at risk, make spread more difficult to identify and contain and threaten the progress made to protect patients in hospitals. In July 2024, CDC published Antimicrobial Resistance Threats in the United States, 2021-2022, highlighting that new data show that six bacterial antimicrobial-resistant hospital-onset infections increased by a combined 20% during the COVID-19 pandemic compared to the pre-pandemic period, peaking in 2021, and remaining above pre-pandemic levels in 2022. In addition, the number of reported clinical cases of Candida auris (C. auris) – a type of yeast that can spread in healthcare facilities, is often resistant to antifungal medications, and can cause severe illness – increased nearly five-fold from 2019 to 2022.
This retrospective cohort study evaluated antimicrobial susceptibility of bacteria isolated from adults (aged ≥18 years) with and without cancer seeking care in 198 outpatient health-care settings in the USA. 53 006 (3.2%) of 1 655 594 pathogens identified were from 27 421 patients with cancer and 1 602 588 (96.8%) were from 928 128 patients without cancer. For Pseudomonas aeruginosa, carbapenem non-susceptibility was higher in pathogen isolates from patients with cancer (816 [14.4%] of 5683) than patients without cancer (10 709 [11.3%] 94 419; OR 1.22 [95% CI 1.13-1.32]). For Enterobacterales, fluoroquinolone non-susceptibility was higher in pathogen isolates from patients with cancer (8662 [28.0%] of 30 867) than patients without cancer (238 479 [21.8%] of 1 095 996; OR 1.44 [1.40-1.47]), as was carbapenem non-susceptibility (472 [1.5%] of 30 867 vs 9165 [0.8%] of 1 095 996; OR 1.89 [1.72-2.07]), multidrug-resistant pathogens (2672 [8.7%] of 30 867 vs 48 962 [4.5%] of 1 095 996; OR 2.03 [1.95-2.11]), and extended-spectrum β-lactamase producers (4343 [16.5%] of 26 327 vs 93 977 [9.4%] of 996 853; OR 1.96 [1.90-2.03]). For Staphylococcus aureus, methicillin resistance was higher in pathogen isolates from patients with cancer (4747 [53.0%] of 8959) than patients without cancer (129 291 [48.3%] of 267 520; OR 1.20 [1.15-1.25]). For Enterococcus spp, vancomycin resistance was higher in pathogen isolates from patients with cancer (1329 [18.6%] of 7145) than patients without cancer (12 333 [9.1%] of 135 772]; ORR 2.20 [2.06-2.34). The rates and corresponding IRRs of AMR pathogens per 1000 isolates was also higher in patients with cancer compared with patients without cancer, particularly for carbapenem non-susceptible P aeruginosa (IRR 2.06 [1.91-2.21]) and vancomycin-resistant enterococci (IRR 3.06 [2.89-3.24]). For all comparisons, p<0.0001. AMR proportions and IRRs for most key pathogens were up to three-times higher in isolates from outpatients with cancer than those without cancer, highlighting the need for enhanced surveillance, infection prevention, and timely diagnostic stewardship to improve antibiotic prescribing in this population.
Antimicrobial resistance (AMR) is a substantial global health threat. Patients with haematological malignancies have an increased risk of AMR infection due to disease-related and treatment-related immunosuppression. The prevalence of AMR bacterial infections from seven WHO priority pathogens in patients with haematological malignancies was 35% (95% CI 30-40; I2 99.4%). The most frequent AMR infections reported were bloodstream infections, with the highest reported AMR pathogens in third-generation cephalosporin-resistant Enterobacterales (pooled prevalence rate 44% [95% CI 23-64; I2 99.8%]), methicillin-resistant Staphylococcus aureus (43% [31-54; I2 95.9%]), and vancomycin-resistant enterococci (41% [26-56; I2 96.2%]). 53 (65%) of the 81 studies that reported mortality showed higher mortality rates associated with AMR infections. 168 (61%) studies were conducted in high-income countries, with no studies published from the WHO Africa region, revealing a substantial data gap from low-income and middle-income regions.
Innovative diagnostic solutions for the infections associated multi-drug-resistant pathogens, are crucial for identifying and understanding these pathogens, initiating efficient treatment regimens, and curtailing their spread. While next-generation sequencing has proven invaluable in diagnosis over the years, the most glaring drawbacks must be addressed quickly. Many promising pathogen-associated and host biomarkers hold promise, but their sensitivity and specificity remain questionable. In this review, authors discuss current and emerging diagnostic approaches, pinpointing the limitations and challenges associated with each technique and their potential to help address drug-resistant bacterial threats. They further critically delve into the need for accelerated diagnosis in low- and middle-income countries, which harbour more infectious disease threats. Overall, this review provides an up-to-date overview of the diagnostic approaches needed for a prompt response to imminent or possible bacterial infectious disease outbreaks.
Antibiotics that target multiple cellular functions are anticipated to be less prone to bacterial resistance. In this study, authors hypothesize that while dual targeting is crucial, it is not sufficient in preventing resistance. Only those antibiotics that simultaneously target membrane integrity and block another cellular pathway display reduced resistance development. Authors show that resistance evolution against these antibiotics is limited in ESKAPE pathogens, including E. coli, K. pneumoniae, A. baumannii and P. aeruginosa, while dual-target topoisomerase antibiotics are prone to resistance. They discover several mechanisms restricting resistance. Finally, the authors detect rapid eradication of bacterial populations upon toxic exposure to membrane targeting antibiotics.. This work provides guidelines for the future development of antibiotics.
Multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-hvKP) combines high pathogenicity with multidrug resistance to become a new superbug. MDR-hvKP reports continue to emerge, shattering the perception that hypervirulent K. pneumoniae (hvKP) strains are antibiotic sensitive. Patients infected with MDR-hvKP strains have been reported in Asia, particularly China. Although hvKP can acquire drug resistance genes, MDR-hvKP seems to be more easily transformed from classical K. pneumoniae (cKP), which has a strong gene uptake ability. To better understand the biology of MDR-hvKP, this review discusses the virulence factors, resistance mechanisms, formation pathways, and identification of MDR-hvKP. Given their destructive and transmissible potential, continued surveillance of these organisms and enhanced control measures should be prioritized.
The emergence of difficult-to-treat resistant (DTR) P. aeruginosa has significant implications for the selection of empiric therapies. This study aimed to compare antimicrobial resistance of P. aeruginosa from ICU and non-ICU patients and discuss empiric treatment options. N.309 P. aeruginosa strains isolated from hospitalized patients in 2023 were included, of which 30% were isolated from ICU patients, while 70% were isolated from non-ICU patients. Antimicrobial susceptibility results for six classes with potential activity against P. aeruginosa were collected, resistance between ICU and non-ICU isolates comparing. Ciprofloxacin resistance was significantly higher in non-ICU patients than in ICU patients; piperacillin-tazobactam resistance was higher in ICU patients than in non-ICU patients. The prevalence of DTR P. aeruginosa was similar between the two groups and joint resistance to imipenem and ceftazidime was more prevalent in ICU patients. Additionally, carbapenemase-producing strains were more common in ICU patients. Ceftolozane-tazobactam, whose efficacy against P. aeruginosa DTR remains preserved, as empiric treatment would improve its appropriateness by 21% in patients in intensive care and by 19% in patients not admitted to intensive care, compared to the currently recommended first-line treatments.
Multidrug-resistant bacterial infections are a rising threat to human health and currently account for 1.3 million deaths annually and 70% of these deaths are due to gram-negative pathogens, and no new classes of gram-negative-active antibiotics have been approved by the US Food and Drug Administration in the past 55 years. The challenges of converting compounds with in vitro biochemical activity to whole cell gram-negative antibacterial activity are significant, as the outer membrane and promiscuous efflux pumps thwart the potential of most antibiotic candidates. Significant strides have been made toward understanding compound penetration and accumulation in gram-negative bacteria, but efflux remains a major obstacle for antibiotic drug discovery. Recent advances in machine learning (ML) algorithms and increased accessibility of code and programs for the nonexpert suggest artificial intelligence could help address the efflux problem. The authors discuss work toward understanding efflux and cast a vision for how ML can be utilized to address compound efflux from gram-negative bacteria.
A total of 425 patients undergoing treatment for odontogenic infectious diseases of the facial area during 2019–2023 were involved in the study. The object of the study was 106 clinical isolates of S. aureus that were isolated and identified from patients. Prediction of the development of antimicrobial resistance of S. aureus to various antibiotics was carried out on the basis of the received sensitivity data of the studied isolates in 2019–2023 using the exponential smoothing method. The antimicrobial resistance of S. aureus isolates to various antibiotics changed annually during 2019–2023. The level of resistance of S. aureus isolates to benzylpenicillin wavered between 40%–50% from 2019 to 2023 with the trend of an 18.0% increase over the next five years. A uniform plateau of antimicrobial resistance of S. aureus to cefoxitin is predicted at the level of 32.0% during 2024–2028. Authors recorded the highest portions of S. aureus resistant to norfloxacin (33.3%) and ciprofloxacin (16.7%) in 2023 with prediction of its increasing in the next five years within the range of 20.0%. It was established that S. aureus may reach 100.0% resistance to gentamicin in 2027. According to exponential smoothing, the level of S. aureus resistance to amikacin will increase by 22.7% over the next five-year period. Moreover, representatives of this species of bacteria can develop complete (100.0%) resistance to tetracycline as early as 2027.Mathematical prediction of the development of antimicrobial sensitivity of S. aureus isolates showed a high probability of its development to antibiotics of all groups in the next five years.