Bactericidal activity of daptomycin, vancomycin, teicoplanin and linezolid against Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium using human peak free serum drug concentrations

2007 ◽  
Vol 29 (3) ◽  
pp. 322-325 ◽  
Author(s):  
J. Brauers ◽  
M. Kresken ◽  
A. Menke ◽  
A. Orland ◽  
H. Weiher ◽  
...  
2016 ◽  
Vol 11 (31) ◽  
pp. 113-122
Author(s):  
Carla Franco Porto Belmont Souza ◽  
Luiz Eduardo Souza da Silva Irineu ◽  
Renan Silva De Souza ◽  
Renato da Silva Teixeira ◽  
Ivina Sanches Pereira ◽  
...  

A resistência microbiana tem se mostrado um problema de proporções mundiais, causando estado de morbidade e mortalidade em diversos pacientes. Em vista disso, tem crescido a busca por métodos alternativos naturais de profilaxia. A investigação clínica sugere que o Extrato de Cranberry está entre as melhores propostas de prevenção natural. O Cranberry (Vaccinium macrocarpon) é um fruto que tem crescido comercialmente pelo sabor e propriedades benéficas à saúde. Dentre as formas comercializadas estão: o suco, o chá e as cápsulas contendo o extrato seco. A ação desta planta está relacionada ao tratamento de doenças do trato urinário, por possuir substâncias que inibem a adesão bacteriana ao epitélio do trato urinário, dificultando sua proliferação e reprodução. Dentre todas as infecções relacionadas à assistência a saúde, a Infecção do Trato Urinário é a mais frequentemente associada a procedimentos invasivos. Se não for tratada, pode resultar em complicações como pielonefrite aguda, bacteremia e pionefrose. Portanto, cranberry pode ser uma nova alternativa para o combate das infecções uroepiteliais, por ser um produto natural de preço acessível, e com formas de comercialização diversificada, ao contrário dos antimicrobianos convencionais, que por sua vez são caros e podem acabar causando resistência nos micro-organismos. Este trabalho teve como objetivo avaliar in vitro a atividade antimicrobiana do extrato de Cranberry, adquirido em farmácia de manipulação, sobre 8 micro-organismos isolados de infecções urinárias. As cepas utilizadas, adquiridas da coleção da FIOCRUZ, foram: Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, Serratia marscecens, Staphylococcus aureus, Enterococcus faecalis e Enterococcus faecium. No estudo, foram utilizados o caldo Mueller Hinton (MH), Extrato de Cranberry e as bactérias patogênicas. O ensaio foi realizado em triplicata, com o uso de um controle de crescimento dos micro-organismos e o experimento para avaliação do crescimento bacteriano na presença do extrato. A turbidez foi medida com o auxílio de um espectrofotômetro, no comprimento de onda de 600 nm, antes e após 24 horas de incubação à 37 ºC. O procedimento forneceu a Densidade Ótica, do qual possibilitou a identificação da inibição microbiana. Para análise estatística foi utilizado o Teste t de Student. O Extrato de Cranberry apresentou atividade antimicrobiana sobre as bactérias Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Serratia marscecens e Enterococcus faecalis (p < 0,05), confirmando seu efeito benéfico em infecções urinárias. No entanto, não teve efeito inibitório significativo sobre Pseudomonas aeruginosa, Proteus mirabilis e Enterococcus faecium (p > 0,05).


2004 ◽  
Vol 48 (8) ◽  
pp. 2871-2875 ◽  
Author(s):  
Kenneth H. Rand ◽  
Herbert J. Houck

ABSTRACT We previously observed marked synergy between daptomycin and both rifampin and ampicillin against vancomycin-resistant enterococci (VRE). Because the synergy between daptomycin and ampicillin was observed for 100% of VRE strains with high-level ampicillin resistance (ampicillin MIC of ≥128 μg/ml), we looked for synergy between daptomycin and other β-lactams against 18 strains of methicillin-resistant Staphylococcus aureus (MRSA) by employing a time-kill method using Mueller-Hinton broth supplemented to 50 mg of Ca2+/liter. All strains were resistant to oxacillin (16 of 18 strains were resistant at drug concentrations of ≥256 μg/ml), and all strains were susceptible to daptomycin (the MIC at which 90% of the tested isolates were inhibited was 1 μg/ml). Daptomycin was tested at concentrations of 2, 1, 0.5, 0.25, 0.125, and 0.0625 μg/ml alone or in combination with oxacillin at a fixed concentration of 32 μg/ml. Synergy was found for all 18 strains with daptomycin at one-half the MIC in combination with 32 μg of oxacillin/ml, and synergy was found for 11 of 18 strains (61%) with daptomycin at one-fourth the MIC or less in combination with oxacillin. At 24 h, the daptomycin-oxacillin combination with daptomycin at one-half the MIC showed bactericidal activity against all 18 strains, and the combination with one-fourth the daptomycin MIC showed bactericidal activity against 9 of 18 strains. We also used a novel screening method to look for synergy between daptomycin and other β-lactams. In this approach, daptomycin was incorporated into Ca2+-supplemented Mueller-Hinton agar at subinhibitory concentrations, and synergy was screened by comparing test antibiotic Kirby-Bauer disks on agar with and without daptomycin. By this method, daptomycin with ampicillin-sulbactam, ticarcillin-clavulanate, or piperacillin-tazobactam showed synergy comparable to or greater than daptomycin with oxacillin. For seven of the eight strains tested, time-kill studies confirmed synergy between daptomycin and ampicillin-sulbactam with ampicillin in the range of 2 to 8 μg/ml. The combination of daptomycin and β-lactams may be useful for the treatment of MRSA infection, but further studies are needed to elucidate the mechanisms and to determine the in vivo efficacy of the combination.


2014 ◽  
Vol 58 (7) ◽  
pp. 3976-3982 ◽  
Author(s):  
Carmela T. M. Mascio ◽  
Laurent Chesnel ◽  
Grace Thorne ◽  
Jared A. Silverman

ABSTRACTSurotomycin (CB-183,315) is an orally administered, minimally absorbed, selective bactericidal cyclic lipopeptide in phase 3 development for the treatment ofClostridium difficile-associated diarrhea. The aim of this study was to evaluate the emergence of resistance inC. difficile(ATCC 700057 and three recent clinical isolates from the restriction endonuclease analysis groups BI, BK, and K), vancomycin-susceptible (VS)Enterococcus faecalis(ATCC 49452), vancomycin-resistant (VR)E. faecalis(ATCC 700802), VSEnterococcus faecium(ATCC 6569), and VRE. faecium(ATCC 51559) under anaerobic conditions. The rate of spontaneous resistance was below the limit of detection (<10−8to <10−9) for surotomycin at 16 and 32× the MIC for all isolates tested. Under selective pressure by serial passage,C. difficilegrew in a maximum of 4 μg/ml surotomycin (final MICs of 2 to 8 μg/ml [4- to 16-fold higher than those of the naive control]) at day 15, with the exception of theC. difficileBK strain, which grew in 16 to 32 μg/ml (final MICs of 8 to 32 μg/ml [16- to 64-fold higher than those of the naive control]). Enterococci remained relatively unchanged over 15 days, growing in a maximum of 8 μg/ml surotomycin (final MICs of 2 to 16 μg/ml [8- to 64-fold higher than those of the naive control]). Of the isolates tested, no cross-resistance to vancomycin, rifampin, ampicillin, metronidazole, or moxifloxacin was observed. Surotomycin at 20× MIC demonstrated equally rapid bactericidal activity (≥3-log-unit reduction in CFU/ml in ≤8 h) against naive and reduced-susceptibility isolates ofC. difficile, VSEnterococcus(VSE), and VREnterococcus(VRE), except forC. difficileBK (2.6-log-unit reductions for both). These results suggest that emergence of resistance to surotomycin againstC. difficile,E. faecalis, andE. faeciumis likely to be rare.


2002 ◽  
Vol 46 (6) ◽  
pp. 1845-1850 ◽  
Author(s):  
Kavindra V. Singh ◽  
George M. Weinstock ◽  
Barbara E. Murray

ABSTRACT Enterococcus faecalis isolates are resistant to clindamycin (CLI) and quinupristin-dalfopristin (Q-D), and this is thought to be a species characteristic. Disruption of a gene (abc-23, now designated lsa, for “lincosamide and streptogramin A resistance”) of E. faecalis was associated with a ≥40-fold decrease in MICs of Q-D (to 0.75 μg/ml), CLI (to 0.12 to 0.5 μg/ml), and dalfopristin (DAL) (to 4 to 8 μg/ml) for the wild-type E. faecalis parental strain (Q-D MIC, 32 μg/ml; CLI MIC, 32 to 48 μg/ml; DAL MIC, 512 μg/ml). Complementation of the disruption mutant with lsa on a shuttle plasmid resulted in restoration of the MICs of CLI, Q-D, and DAL to wild-type levels. Under high-stringency conditions, lsa was found in 180 of 180 isolates of E. faecalis but in none of 189 other enterococci. Among 19 erm(B)-lacking Enterococcus faecium strains, 9 (47%) were highly susceptible to CLI (MIC, 0.06 to 0.25 μg/ml) and had DAL MICs of 4 to 16 μg/ml; for the remaining erm(B)-lacking E. faecium strains, the CLI and DAL MICs were 4 to >256 and 2 to >128 μg/ml, respectively. In contrast, none of 32 erm(B)-lacking E. faecalis strains were susceptible (CLI MIC range, 16 to 32 μg/ml; DAL MIC range, ≥32 μg/ml). When lsa was introduced into an E. faecium strain initially susceptible to CLI, the MICs of CLI and DAL increased ≥60-fold and that of Q-D increased 6-fold (to 3 to 6 μg/ml). Introduction of lsa into two DAL-resistant (MICs, >128 μg/ml), Q-D-susceptible (MICs, 0.5 and 1.5 μg/ml) E. faecium strains (CLI MICs, 12 and >256 μg/ml) resulted in an increase in the Q-D MICs from 3- to 10-fold (to 8 and >32 μg/ml), respectively. Although efflux was not studied, the similarity (41 to 64%) of the predicted Lsa protein to ABC proteins such as Vga(A), Vga(B), and Msr(A) of Staphylococcus aureus and YjcA of Lactococcus lactis and the presence of Walker A and B ATP-binding motifs suggest that this resistance may be related to efflux of these antibiotics. In conclusion, lsa appears to be an intrinsic gene of E. faecalis that explains the characteristic resistance of this species to CLI and Q-D.


1998 ◽  
Vol 42 (3) ◽  
pp. 721-724 ◽  
Author(s):  
Michael J. Rybak ◽  
Diane M. Cappelletty ◽  
Tabitha Moldovan ◽  
Jeffrey R. Aeschlimann ◽  
Glenn W. Kaatz

ABSTRACT The activities of the oxazolidinone antibacterial agents eperezolid (PNU-100592) and linezolid (PNU-100766) were compared with that of vancomycin against clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus (n = 200), coagulase-negative staphylococci (n = 100), and vancomycin-susceptible and -resistant Enterococcus faecalisand Enterococcus faecium (n = 50). Eperezolid and linezolid demonstrated good in vitro inhibitory activity, regardless of methicillin susceptibility for staphylococci (MIC at which 90% of the isolates are inhibited [MIC90] range, 1 to 4 μg/ml) or vancomycin susceptibility for enterococci (MIC90 range, 1 to 4 μg/ml). In time-kill studies, eperezolid and linezolid were bacteriostatic in action. A postantibiotic effect of 0.8 ± 0.5 h was demonstrated for both eperezolid and linezolid against S. aureus, S. epidermidis, E. faecalis, and E. faecium.


2009 ◽  
Vol 53 (5) ◽  
pp. 2171-2175 ◽  
Author(s):  
Helio S. Sader ◽  
Thomas R. Fritsche ◽  
Ronald N. Jones

ABSTRACT The in vitro activity of iclaprim, a novel diaminopyrimidine derivative, was evaluated against 5,937 recent gram-positive clinical isolates collected in the United States and Europe. Iclaprim demonstrated potent activity against Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA]), beta-hemolytic Streptococcus spp., and Enterococcus faecalis strains tested. In addition, iclaprim exhibited bactericidal activity against all S. aureus strains tested, including MRSA.


2014 ◽  
Vol 63 (2) ◽  
pp. 210-217 ◽  
Author(s):  
Markus Woegerbauer ◽  
Josef Zeinzinger ◽  
Burkhard Springer ◽  
Peter Hufnagl ◽  
Alexander Indra ◽  
...  

The aminoglycoside phosphotransferase aph(3′)-IIa primarily inactivates kanamycin and neomycin, whilst aph(3′)-IIIa also inactivates amikacin. The aim of this study was to determine the frequency of both resistance genes in major human pathogens to obtain their baseline prevalence in the gene pool of these bacterial populations in Austria. In total, 10 541 Escherichia coli, Enterococcus faecalis, Enterococcus faecium, Pseudomonas aeruginosa, Salmonella enterica subsp. enterica and Staphylococcus aureus isolates were collected representatively without selection bias between 2008 and 2011. Isolates were analysed by aph(3′)-IIIa/nptIII- and aph(3′)-IIa/nptII-specific TaqMan real-time PCR. For positive strains, MICs using Etests were performed and resistance gene sequences were determined. The overall prevalence of aph(3′)-IIIa/nptIII was 1.62 % (95 % confidence interval: 1.38–1.88 %). In Escherichia coli, enterococci, Staphylococcus aureus, P. aeruginosa and Salmonella spp., the aph(3′)-IIIa/nptIII prevalence was 0.47 % (0–1.47 %), 37.53 % (32.84–42.40 %), 2.90 % (1.51–5.02 %), 0 % (0–0.32 %) and 0 % (0–0.037 %), respectively. Eleven of a total of 169 carriers showed single-nucleotide polymorphisms in the resistance allele. The overall prevalence of aph(3′)-IIa/nptII was 0.0096 % (0–0.046 %). Escherichia coli (0–0.70 %), enterococci (0–0.75 %), Staphylococcus aureus (0–0.73 %) and P. aeruginosa (0–0.32 %) did not carry aph(3′)-IIa. A single Salmonella isolate was positive, resulting in an aph(3′)-IIa prevalence of 0.013 % (0–0.058 %). aph(3′)-IIIa/nptIII carriers were moderately prevalent in the strains tested except for in enterococci, which appeared to be an important reservoir for aph(3′)-IIIa. aph(3′)-IIa/nptII genes were detected at clinically irrelevant frequencies and played no significant role in the aminoglycoside resistance gene pool during the observation period.


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