Polymyxin B 10,000units/g / Trimethoprim 5mg/g eye ointment

The production of an L1 metallo-β-lactamase and an L2 serine active-site β-lactamase precludes the use of β-lactams for the treatment of Stenotrophomonas maltophilia infections. Preclinical data suggest that cefiderocol is the first approved β-lactam with reliable activity against S. maltophilia, but data on strains resistant to current first-line agents are limited, and no studies have assessed cefiderocol-based combinations. The objective of this study was to evaluate and compare the in vitro activity of cefiderocol alone and in combination with levofloxacin, minocycline, polymyxin B, or trimethoprim-sulfamethoxazole (TMP-SMZ) against a collection of highly resistant clinical S. maltophilia isolates. ABSTRACT The production of an L1 metallo-β-lactamase and an L2 serine active-site β-lactamase precludes the use of β-lactams for the treatment of Stenotrophomonas maltophilia infections. Preclinical data suggest that cefiderocol is the first approved β-lactam with reliable activity against S. maltophilia, but data on strains resistant to current first-line agents are limited, and no studies have assessed cefiderocol-based combinations. The objective of this study was to evaluate and compare the in vitro activity of cefiderocol alone and in combination with levofloxacin, minocycline, polymyxin B, or trimethoprim-sulfamethoxazole (TMP-SMZ) against a collection of highly resistant clinical S. maltophilia isolates. For this purpose, the MICs of cefiderocol, ceftazidime, levofloxacin, minocycline, polymyxin B, and TMP-SMZ for 37 S. maltophilia isolates not susceptible to levofloxacin and/or TMP-SMZ were determined. Nine strains with various cefiderocol MICs were then tested in time-kill experiments with cefiderocol alone and in combination with comparators. The only agents for which susceptibility rates exceeded 40% were cefiderocol (100%) and minocycline (97.3%). Cefiderocol displayed the lowest MIC50 and MIC90 values (0.125 and 0.5 mg/liter, respectively). In time-kill experiments, synergy was observed when cefiderocol was combined with levofloxacin, minocycline, polymyxin B, or TMP-SMZ against 4/9 (44.4%), 6/9 (66.7%), 5/9 (55.5%), and 6/9 (66.7%) isolates, respectively. These data suggest that cefiderocol displays potent in vitro activity against S. maltophilia, including strains resistant to currently preferred agents. Future dynamic and in vivo studies of cefiderocol alone and in combination are warranted to further define cefiderocol’s synergistic capabilities and its place in therapy for S. maltophilia infections.

Abstract licence: CC BY 4.0

BackgroundTo ameliorate the antibiotic resistance crisis, the drivers of resistance emergence and resistance spread must be better understood.MethodsWhole-genome sequencing and susceptibility testing were performed on clinical carbapenem-resistant Klebsiella pneumoniae isolates collected from August 2014 to July 2015 across 12 long-term acute care hospitals. Ancestral state reconstruction partitioned patients with resistant strains into those that likely acquired resistance via de novo evolution or cross-transmission. Logistic regression was used to evaluate the associations between patient characteristics/exposures and these 2 pathways: resistance due to predicted within-host emergence of resistance and resistance due to predicted cross-transmission. This framework is available in the user-friendly R package, phyloAMR (https://github.com/kylegontjes/phyloAMR).ResultsPhylogenetic analysis of 386 epidemic lineage carbapenem-resistant K. pneumoniae sequence type 258 isolates revealed differences in the relative contribution of de novo evolution and cross-transmission to the burden of resistance to 5 antibiotics. Clade-specific variations in rates of resistance emergence and their frequency and magnitude of spread were detected for each antibiotic. Phylogenetically informed regression modeling identified distinct clinical risk factors associated with each pathway. Exposure to the cognate antibiotic was an independent risk factor for resistance emergence (trimethoprim-sulfamethoxazole, colistin, and novel beta-lactam/beta-lactamase inhibitors) and resistance spread (trimethoprim-sulfamethoxazole, amikacin, and colistin). In addition to antibiotic exposures, comorbidities (eg, stage IV + decubitus ulcers) and indwelling medical devices (eg, gastrostomy tubes) were detected as unique risk factors for resistance spread.ConclusionsPhylogenetic contextualization generated insights and hypotheses into how bacterial genetic background, patient characteristics, and clinical practices influence the emergence and spread of antibiotic resistance.

Abstract licence: CC BY-NC-ND

ABSTRACT The genus Providencia includes species of ecological and clinical significance, with several members acting as opportunistic pathogens in hospital-acquired infections, particularly urinary tract infections (UTIs). However, overlapping phenotypic traits and genetic similarities among species pose challenges for accurate identification. In this study, we isolated strain PAZ2 from a urine sample of a hospitalized patient in Lanzhou, Gansu Province, China. While initial mass spectrometry analysis identified the strain as Providencia alcalifaciens, comprehensive genomic analysis revealed distinct characteristics suggesting a novel species. Comparative genomic analyses showed average nucleotide identity (ANI) values ranging from 79.92% to 94.73% and digital DNA-DNA hybridization (dDDH) values between 21.2% and 57.6% when compared with known Providencia species. The strain exhibited resistance to multiple antibiotics, including ampicillin, tetracycline, tigecycline, polymyxin B, colistin, trimethoprim-sulfamethoxazole, and ciprofloxacin. Biochemical characterization revealed distinct properties that differentiated PAZ2 from previously described species within the genus. Based on genomic and phenotypic evidence, we propose strain PAZ2 as the type strain of a novel species, Providencia lanzhouensis sp. nov. Geographic distribution analysis indicated P. lanzhouensis presence in five countries, with predominance in China. Notably, comparative genomic analysis revealed that P. lanzhouensis PAZ2 harbors an expanded repertoire of antimicrobial resistance genes compared to other Providencia strains with high ANI values. This discovery expands our understanding of Providencia taxonomy and highlights its clinical significance. Further studies investigating its pathogenicity mechanisms, antimicrobial resistance profiles, and epidemiological patterns will be crucial for developing effective treatment strategies. IMPORTANCE Accurate identification of bacterial pathogens is crucial for effective clinical treatment, yet current diagnostic methods sometimes fall short when encountering novel species. This study describes Providencia lanzhouensis, a new bacterial species isolated from a clinical setting in China, which was initially misidentified by conventional methods. Our discovery not only expands the known diversity of the Providencia genus but also reveals important insights about antimicrobial resistance in emerging pathogens. P. lanzhouensis carries multiple resistance genes, highlighting potential clinical challenges and the need for accurate identification in healthcare settings. This work demonstrates the importance of integrating multiple analytical approaches for bacterial identification and underscores the dynamic nature of bacterial evolution. These findings have significant implications for improving pathogen identification systems and developing effective treatment strategies in clinical practice. Accurate identification of bacterial pathogens is crucial for effective clinical treatment, yet current diagnostic methods sometimes fall short when encountering novel species. This study describes Providencia lanzhouensis, a new bacterial species isolated from a clinical setting in China, which was initially misidentified by conventional methods. Our discovery not only expands the known diversity of the Providencia genus but also reveals important insights about antimicrobial resistance in emerging pathogens. P. lanzhouensis carries multiple resistance genes, highlighting potential clinical challenges and the need for accurate identification in healthcare settings. This work demonstrates the importance of integrating multiple analytical approaches for bacterial identification and underscores the dynamic nature of bacterial evolution. These findings have significant implications for improving pathogen identification systems and developing effective treatment strategies in clinical practice.

Abstract licence: CC BY