Antibacterial activity of trospectomycin (U-63366F) and initial evaluations of disk diffusion susceptibility tests

Barry, Arthur L.; Jones, Ronald N.; Thornsberry, Clyde

doi:10.1128/aac.33.4.569

Cited by 15 publications

(10 citation statements)

References 6 publications

(6 reference statements)

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“…Um exemplo é o que foi observado em relação ao novo aminociclitol testado, a trospectomicina. Essa droga, o mais potente derivado da espectinomicina, é inativada pelas mesmas enzimas que destroem a estreptomicina e a gentamicina e, portanto, o resultado obtido in vitro (94% de sensibilidade) deve representar falsa sensibilidade 10 . Cloranfenicol e tetraciclina são antimicrobianos para os quais é comum observar-se sensibilidade dos enterococos, mesmo para cepas resistentes a todos os outros antimicrobianos.…”

Section: Discussionunclassified

“…Todos os 87 isolados foram também testados contra dez drogas alternativas potencialmente úteis no tratamento de infecções enterocócicas. As drogas avaliadas foram: ciprofloxacina, clinafloxacina 9 , esparfloxacina, doxiciclina, eritromicina, espectinomicina, trospectomicina 10 , cloranfenicol, trimetoprim-sulfametoxazol e novobiocina. Essas drogas foram avaliadas pelas técnicas de E test e/ou difusão em disco.…”

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Avaliação da sensibilidade a antimicrobianos de 87 amostras clínicas de enterococos resistentes à vancomicina

Saraiva¹,

Jones²,

Erwin³

et al. 1997

Rev. Assoc. Med. Bras.

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INTRODUÇÃOEmbora, normalmente, colonizantes do trato gastrointestinal e genital feminino, os enterococos têm-se destacado, nos últimos anos, como pató-genos importantes em infecção hospitalar. Dados norte-americanos já os apontam como segunda causa mais comum de infecção nosocomial nos Estados Unidos, estando particularmente associados a infecções do trato urinário, infecções de ferida cirúr-gica e bacteremias 1 . Paralelamente ao aumento da incidência, tem-se observado rápido aumento na freqüência de cepas resistentes aos antimicrobianos de uso corrente, mesmo aos glicopeptídeos 2 . Análise de dados enviados ao Center for Disease Control (CDC)

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Section: Discussionunclassified

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Avaliação da sensibilidade a antimicrobianos de 87 amostras clínicas de enterococos resistentes à vancomicina

Saraiva¹,

Jones²,

Erwin³

et al. 1997

Rev. Assoc. Med. Bras.

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“…During the late 1980s, there were many attempts to make spectinomycin variants for treatment of bacterial infections (39,40), but none of these drugs are in clinical use.…”

Section: Conclusion and Future Outlookmentioning

confidence: 99%

Structural recognition of spectinomycin by resistance enzyme ANT(9) fromEnterococcus faecalis

Selmer²

2020

Preprint

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Spectinomycin is a ribosome-binding antibiotic that blocks the translocation step of translation. A prevalent resistance mechanism is the modification of the drug by aminoglycoside nucleotidyl transferase (ANT) enzymes of the spectinomycin-specific ANT(9) family or by the dual-specificity ANT(3")(9) family that also acts on streptomycin. We previously reported the structural mechanism of streptomycin modification by the ANT(3")(9) AadA from Salmonella enterica. ANT(9) from Enterococcus faecalis adenylates the 9-hydroxyl of spectinomycin. We here present the first structures of spectinomycin bound to an ANT enzyme. Structures were solved for ANT(9) in apo form, in complex with ATP, spectinomycin and magnesium or in complex with only spectinomycin. ANT (9) shows similar overall structure as AadA with an N-terminal nucleotidyltransferase domain and a C-terminal α-helical domain. Spectinomycin binds close to the entrance of the interdomain cleft, while ATP is buried at the bottom. Upon drug binding, the C-terminal domain rotates by 14 degrees to close the cleft, allowing contacts of both domains with the drug.Comparison with AadA shows that spectinomycin specificity is explained by a straight α5 helix and a shorter α5-α6 loop that would clash with the larger streptomycin substrate. In the active site, we observe two magnesium ions, one of them in a previously un-observed position that may activate the 9-hydroxyl for deprotonation by the catalytic base Glu-86. The observed binding mode for spectinomycin suggests that also spectinamides and aminomethyl spectinomycins, recent spectinomycin analogues with expansions in position 4 of the C ring, will be subjected to modification by ANT(9) and ANT(3")(9) enzymes.

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“…The following MIC ranges are proposed for the NCCLS HTM method QC guidelines (percent of results in proposed range): cefdinir, 0.5 to 4 p.g/ml (100%); cefepime, 0.5 to 2 ,ug/ml (100%); cefetamet, 0.5 to 2 ,ug/ml (97.3%); cefpirome, 0.25 to 1 ,ug/ml (100%); ceftibuten, 0.25 to 1 p.g/ml (100%); fleroxacin, 0.03 to 0.12 ,ug/ml (100%); temafloxacin, 0.008 to 0.03 ,ug/ml (100%); clarithromycin, 4 to 16 ,ug/ml (100%); RP59500, 4 to 16 pg/ml (100%); trospectomycin, 0.5 to 2 p.g/ml (100%). The 10 new and investigational compounds evaluated in this study have all been shown to have significant activity against H. influenzae (1,2,(4)(5)(6)(7)(8)(9)(10)16). The MIC QC data summarized should expand the number of drugs which can be reliably tested in HTM broth against Haemophilus spp.…”

mentioning

confidence: 93%

“…To expand the number of therapeutic agents that can be tested against Haemophilus spp. isolates, we report MIC quality control (QC) guidelines for 10 drugs having significant activity (1,2,(4)(5)(6)(7)(8)(9)(10)16).…”

mentioning

confidence: 99%

MIC quality control guidelines for Haemophilus susceptibility tests using cefdinir (FK482), cefepime, cefetamet, cefpirome, ceftibuten, fleroxacin, temafloxacin, clarithromycin, RP59500, and trospectomycin

et al. 1992

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A multilaboratory study was performed to establish broth microdilution MIC quality control (QC) guidelines for 10 investigational drugs which previously demonstrated significant activity against Haemophilus influenzae. MIC QC ranges for H. influenzae ATCC 49247 with Haemophilus test medium were determined by using multiple contemporary lots of Haemophilus test medium and the National Committee for Clinical Laboratory Standards' recommended numbers of replicate tests. On the basis of these results, QC ranges (generally modal MIC + one log2 dilution) are proposed for cefdinir, cefepime, cefetamet, cefpirome, ceftibuten, fleroxacin, temafloxacin, clarithromycin, RP59500, and trospectomycin. The proposed QC guidelines for clarithromycin and temafloxacin were recently accepted by the National Committee for Clinical Laboratory Standards.

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Antibacterial activity of trospectomycin (U-63366F) and initial evaluations of disk diffusion susceptibility tests

Cited by 15 publications

References 6 publications

Avaliação da sensibilidade a antimicrobianos de 87 amostras clínicas de enterococos resistentes à vancomicina

Avaliação da sensibilidade a antimicrobianos de 87 amostras clínicas de enterococos resistentes à vancomicina

Structural recognition of spectinomycin by resistance enzyme ANT(9) fromEnterococcus faecalis

MIC quality control guidelines for Haemophilus susceptibility tests using cefdinir (FK482), cefepime, cefetamet, cefpirome, ceftibuten, fleroxacin, temafloxacin, clarithromycin, RP59500, and trospectomycin

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