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1.
Clin Infect Dis ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38306487

RESUMO

Gram-negative antibiotic resistance continues to grow as a global problem due to the evolution and spread of ß-lactamases. The early ß-lactamase inhibitors (BLIs) are characterized by spectra limited to class A ß-lactamases and ineffective against carbapenemases and most extended spectrum ß-lactamases. In order to address this therapeutic need, newer BLIs were developed with the goal of treating carbapenemase producing, carbapenem resistant organisms (CRO), specifically targeting the Klebsiella pneumoniae carbapenemase (KPC). These BL/BLI combination drugs, ceftazidime/avibactam, meropenem/vaborbactam, and imipenem/relebactam, have proven to be indispensable tools in this effort. However, non-KPC mechanisms of resistance are rising in prevalence and increasingly challenging to treat. It is critical for clinicians to understand the unique spectra of these BL/BLIs with respect to non-KPC CRO. In Part 1of this two-part series, we describe the non-KPC attributes of the newer BL/BLIs with a focus on utility against Enterobacterales and Pseudomonas aeruginosa.

2.
Antimicrob Agents Chemother ; 66(3): e0216721, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35007135

RESUMO

Trimethoprim/sulfamethoxazole (TMP/SMZ) is considered the treatment of choice for infections caused by Stenotrophomonas maltophilia, but limited pharmacodynamic data are available to support current susceptibility breakpoints or guide optimal dosing. Time-kill studies using a TMP/SMZ concentration of 4/40 µg/mL were conducted to compare 4 S. maltophilia with 4 Escherichia coli isolates having the same MICs (0.25/4.75 to 4/76 µg/mL) in cation-adjusted Mueller-Hinton broth (CAMHB) and ISO-Sensitest broth (ISO broth). With the exception of the resistant isolates (4/76 µg/mL), which resulted in regrowth approaching the growth of the control, TMP/SMZ displayed significantly greater killing for E. coli than for S. maltophilia at each MIC. Against E. coli, the mean changes at 24 h were -4.49, -1.73, -1.59, and +1.83 log10 CFU for isolates with MICs of 0.25/4.75, 1/19, 2/39, and 4/74 µg/mL, respectively. The area under the concentration-time curve for the free, unbound fraction of the drug (fAUC)/MIC ratio required for stasis and 1-log10 and 2-log10 CFU reductions were 40.7, 59.5, and 86.3, respectively. In contrast, TMP/SMZ displayed no stasis or CFU reductions against any S. maltophilia isolate regardless of the MIC, and no pharmacodynamic thresholds were quantifiable. Observations were consistent in both CAMHB and ISO broth. These data add increasing evidence that current TMP/SMZ susceptibility breakpoints against S. maltophilia should be reassessed.


Assuntos
Stenotrophomonas maltophilia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cátions , Escherichia coli , Testes de Sensibilidade Microbiana , Combinação Trimetoprima e Sulfametoxazol/farmacologia
3.
ACS Nano ; 9(11): 10909-15, 2015 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-26426746

RESUMO

We demonstrate the use of "holey" graphene as a mask against molecular adsorption. Prepared porous graphene is transferred onto a Au{111} substrate, annealed, and then exposed to dilute solutions of 1-adamantanethiol. In the pores of the graphene lattice, we find islands of organized, self-assembled molecules. The bare Au in the pores can be regenerated by postdeposition annealing, and new molecules can be self-assembled in the exposed Au region. Graphene can serve as a robust, patternable mask against the deposition of self-assembled monolayers.

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