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1.
J Infect Dis ; 222(9): 1498-1504, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32914837

RESUMO

BACKGROUND: Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, in a rat model of foreign body osteomyelitis. METHODS: Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively. RESULTS: Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or vancomycin alone (4.64 log10 CFUs/g) (both P ≤ .02). The K-wires of animals receiving no treatment or vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group. CONCLUSIONS: Rifabutin or rifapentine with vancomycin were as active as rifampin with vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections.

2.
J Clin Microbiol ; 58(10)2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32727832

RESUMO

This study aimed to determine whether agar dilution, research-use-only disk diffusion (Mast Group Ltd., Bootle Merseyside, UK), Etest (bioMérieux, Inc., Durham, NC), and MIC test strip (MTS) (Liofilchem, Inc., Waltham, MA) methods yield equivalent results to those of broth microdilution (BMD) for imipenem-relebactam susceptibility testing using a collection of 297 Gram-negative bacilli, including members of the order Enterobacterales and Pseudomonas aeruginosa, enriched for drug resistance. MIC and disk diameter results were interpreted using United States Food and Drug Administration breakpoints. Overall, 76.8% of the isolates tested were susceptible to imipenem-relebactam by BMD. MIC values for agar dilution, Etest, and MTS were not significantly different from that for BMD, although they tended to be 1 to 2 dilutions higher. Essential agreement was 95.6% for agar dilution, 90.6% for Etest, and 85.2% for MTS. Categorical agreement was 98.0% for agar dilution, 73.1% for disk diffusion, 96.3% for Etest, and 96.6% for MTS. In conclusion, agar dilution and Etest yielded comparable results to BMD for imipenem-relebactam.

3.
Diagn Microbiol Infect Dis ; 97(3): 115040, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32354459

RESUMO

Staphylococci are the most common causes of periprosthetic joint infection (PJI). TNP-2092 is an investigational hybrid drug composed of rifamycin and quinolizinone pharmacophores conjugated via a covalent linker. We determined minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum biofilm bactericidal concentration (MBBC) values of TNP-2092 against 80 PJI-associated Staphylococcus aureus and Staphylococcus epidermidis isolates compared to ciprofloxacin and rifampin alone and in combination, alongside daptomycin and vancomycin. TNP-2092 exhibited the following activity against S. aureus: MIC50/MIC90, ≤0.0075/0.015 µg/mL; MBC50/MBC90, 0.5/4 µg/mL; and MBBC50/MBBC90, 0.5/2 µg/mL, and the following activity against S. epidermidis: MIC50/MIC90, ≤0.0075/0.015 µg/mL; MBC50/MBC90, 0.015/0.125 µg/mL; and MBBC50/MBBC90, 0.06/0.25 µg/mL. TNP-2092 MIC, MBC, and MBBC values were >8 µg/mL for 1 isolate, while MIC values were ≤0.25 µg/mL and MBC and MBBC values were ≤4 µg/mL for all other isolates. Results of this study show that TNP-2092 has promising in vitro activity against PJI-associated staphylococci.

4.
J Exp Appl Anim Sci ; 3(1): 7-14, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31404442

RESUMO

The most common organism-type causing orthopedic foreign body infection is the staphylococci, of which Staphylococcus aureus and Staphylococcus epidermidis are especially common. These organisms form biofilms on orthopedic foreign body surfaces, rendering such infections challenging and time consuming to treat. Our group evaluates novel therapeutics for orthopedic foreign body infection in animal models. A current limitation of most animal models is that that they only allow for the removal of one sample per animal, at the time of sacrifice. Herein, we describe a novel rat model of foreign body osteomyelitis that allows removal of foreign bodies at different time points, from the same infected animal. We demonstrate that this model can be used for both S. aureus and S. epidermidis orthopedic foreign body infection, with 3.56, 3.60 and 5.51 log10 cfu/cm2 S. aureus recovered at four, five and six weeks, respectively, after infection, and 2.08, 2.17 and 2.62 log10 cfu/cm2 S. epidermidis recovered at four, five and six weeks, respectively, after infection We evaluated the model with S. aureus infection treated with rifampin 25 mg/kg twice daily for 21 days. Using quantitative cultures, we were no longer able to detect bacteria as of the 14th day of treatment with bacteria becoming detectable again 7 days following die discontinuation of rifampin a period. This novel model allows monitoring of evolution of infection at the infection site in the same animal.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31358593

RESUMO

Bacteriophage-derived lysins are being developed as anti-infective agents. In an acute osteomyelitis methicillin-resistant Staphylococcus aureus (MRSA) model, rats receiving no treatment or treatment with daptomycin, exebacase (CF-301), or daptomycin plus exebacase had means of 5.13, 4.09, 4.65, and 3.57 log10 CFU/gram of bone, respectively. All treated animals had fewer bacteria than did untreated animals (P ≤ 0.0001), with daptomycin plus exebacase being more active than daptomycin (P = 0.0042) or exebacase (P < 0.001) alone.


Assuntos
Antibacterianos/uso terapêutico , Daptomicina/uso terapêutico , Endopeptidases/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Osteomielite/tratamento farmacológico , Animais , Antibacterianos/administração & dosagem , Daptomicina/administração & dosagem , Endopeptidases/administração & dosagem , Masculino , Osteomielite/microbiologia , Ratos , Ratos Sprague-Dawley , Vancomicina/uso terapêutico
6.
JBMR Plus ; 3(5): e10119, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31131342

RESUMO

We are developing electrical approaches to treat biofilm-associated orthopedic foreign-body infection. Although we have previously shown that such approaches have antibiofilm activity, the effects on bone have not been assessed. Herein, low-amperage 200 µA fixed direct current (DC) was compared with no current, in a rat femoral foreign-body infection model. In the infected group, a platinum implant seeded with S. epidermidis biofilm (105 CFU/cm2), plus 50 µL of a 109 CFU suspension of bacteria, were placed in the femoral medullary cavity of 71 rats. One week later, rats were assigned to one of four groups: infected with no current or DC, or uninfected with no current or DC. After 2 weeks, bones were removed and subjected to histopathology, micro-computed tomography (µCT), and strength testing. Histopathology showed no inflammation or bony changes/remodeling in the uninfected no current group, and some osteoid formation in the DC group; bones from the infected no current group had evidence of inflammation without bony changes/remodeling; along with inflammation, there was moderate osteoid present in the DC group. µCT showed more cortical bone volume and density, trabecular thickness, and cancellous bone volume in the DC group compared with the no current group, for both uninfected and infected bones (p < 0.05). There was no difference in torsional strength or stiffness between the no current versus DC groups, for both infected and uninfected bones (p > 0.05). © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

7.
J Orthop Surg Res ; 14(1): 43, 2019 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-30755223

RESUMO

BACKGROUND: Polymethylmethacrylate (PMMA) is used for local antimicrobial delivery in orthopedic infection. Oritavancin is a long half-life lipoglycopeptide with broad activity against Gram-positive bacteria. Herein, we addressed if 7.5% w/w oritavancin mixed into PMMA affects PMMA strength and whether it elutes from PMMA, compared to vancomycin. METHODS: Elution was assessed by placing an oritavancin- or vancomycin-loaded bead in a flow system with human plasma. Compressive strength of bland compared to oritavancin- or vancomycin-loaded PMMA was assessed after 0, 3, and 7 days of soaking in 1 ml of pooled normal human plasma at 37 °C, by testing to failure in axial compression using a servo-hydraulic testing machine. RESULTS: Median compressive strength on days 0, 3, and 7 for bland PMMA compared to oritavancin- or vancomycin-loaded PMMA was 80.1, 79.4, and 72.4 MPa, respectively; 93.3, 86.4, and 65.3 MPa, respectively; and 97.8, 82.7, and 65.9 MPa, respectively. Oritavancin reduced PMMA compressive strength after 3 and 7 days (P = 0.0250 and 0.0039, respectively), whereas vancomycin reduced the PMMA compressive strength after 0, 3, and 7 days (P = 0.0039, 0.0039, and 0.0062, respectively) as compared to bland PMMA. Oritavancin-loaded PMMA had higher compressive strength than vancomycin-loaded PMMA on days 3 and 7 (P = 0.0039 and 0.0062, respectively). Compressive elastic moduli were 1226, 1299, and 1394 MPa for bland PMMA; 1253, 1078, and 1245 MPa for oritavancin-loaded PMMA; and 986, 879, and 779 MPa for vancomycin-loaded PMMA on days 0, 3 and 7, respectively. Oritavancin-loaded PMMA had higher compressive elastic moduli than vancomycin-loaded PMMA on days 0 and 7 (P = 0.0250 and 0.0062, respectively). Following polymerization, 1.0% and 51.9% of the initial amount of oritavancin and vancomycin were detected, respectively. Cmax, Tmax, and AUC0-24 were 1.7 µg/ml, 2 h, and 11.4 µg/ml for oritavancin and 21.4 µg/ml, 2 h, and 163.9 µg/ml for vancomycin, respectively. CONCLUSIONS: Oritavancin-loaded PMMA had higher compressive strength than vancomycin-loaded PMMA on days 3 and 7 and higher compressive elastic moduli than vancomycin-loaded PMMA on days 0 and 7. However, proportionally less oritavancin than vancomycin eluted out of PMMA.


Assuntos
Antibacterianos/administração & dosagem , Lipoglicopeptídeos/administração & dosagem , Polimetil Metacrilato , Força Compressiva , Teste de Materiais
9.
Diagn Microbiol Infect Dis ; 93(2): 92-95, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30293677

RESUMO

Fixed DC was compared to ceftriaxone, ceftriaxone with 200 µA fixed DC, or no treatment in a rat model of methicillin-susceptible Staphylococcus aureus foreign-body osteomyelitis. After 3 weeks, fewer bacteria were present in bones of the ceftriaxone group (5.71 log10cfu/g [P = 0.0004]) and the ceftriaxone/DC group (3.53 log10cfu/g [P = 0.0002]) than untreated controls (6.70 log10cfu/g). Fewer bacteria were present in the ceftriaxone/DC group than in the ceftriaxone-alone and DC-alone groups (P = 0.0012 and 0.0008, respectively). There were also fewer bacteria on the implanted wires in the groups treated with ceftriaxone (5.47 log10cfu/cm2) or ceftriaxone/DC (2.82 log10cfu/cm2) than in the untreated controls (6.44 log10cfu/cm2 [P = 0.0003 and 0.0002, respectively]). There were fewer bacteria in the ceftriaxone/DC rats than in the ceftriaxone-alone- and fixed DC-alone-treated rats (P = 0.0017 and 0.0016, respectively). Fixed DC with an antibiotic may be useful for treating foreign-body infections caused by S. aureus.


Assuntos
Terapia por Estimulação Elétrica , Osteomielite/terapia , Infecções Relacionadas à Prótese/terapia , Infecções Estafilocócicas/terapia , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Modelos Animais de Doenças , Fêmur/cirurgia , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos da radiação , Ratos , Ratos Wistar
10.
Int J Antimicrob Agents ; 52(5): 692-696, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30075292

RESUMO

Clay is a substance historically utilized by indigenous cultures for the treatment of superficial wound infections. This study evaluated the effects of a recently identified clay - OMT Blue Clay - against staphylococci, streptococci, Enterobacteriaceae and non-fermenting Gram-negative bacilli. The clay and its aqueous leachate were evaluated against the bacteria in biofilm and planktonic states. Time-kill studies were used to assess planktonic activity. Biofilms on medical-grade Teflon discs were treated with a hydrated clay suspension or leachate. For the planktonic studies, clay and leachate exhibited bactericidal activity against all strains tested, with the exception of leachate against Staphylococcus aureus IDRL-6169 and USA300. All strains treated with clay suspension and leachate resulted in statistically significant biofilm population reductions compared with controls, except S. aureus IDRL-6169 and USA300 (P ≤ 0.05). OMT Blue Clay and its aqueous leachate exhibited bactericidal activity against a range of human pathogens in the planktonic and biofilm states.


Assuntos
Antibacterianos/farmacologia , Infecções Bacterianas/microbiologia , Argila , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Infecção dos Ferimentos/microbiologia , Antibacterianos/isolamento & purificação , Biofilmes/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Viabilidade Microbiana/efeitos dos fármacos
11.
Artigo em Inglês | MEDLINE | ID: mdl-29760145

RESUMO

Understanding which antimicrobial agents are likely to be active against Gram-negative bacilli can guide selection of antimicrobials for empirical therapy as mechanistic rapid diagnostics are adopted. In this study, we determined the MICs of a novel ß-lactam-ß-lactamase inhibitor combination, imipenem-relebactam, along with ceftolozane-tazobactam, imipenem, ertapenem, meropenem, ceftriaxone, and cefepime, against 282 drug-resistant isolates of Gram-negative bacilli. For isolates harboring blaKPC (n = 110), the addition of relebactam to imipenem lowered the MIC50/MIC90 from 16/>128 µg/ml for imipenem alone to 0.25/1 µg/ml. For isolates harboring blaCTX-M (n = 48), the MIC50/MIC90 of ceftolozane-tazobactam were 0.5/16 µg/ml (83% susceptible). For isolates harboring blaCMY-2 (n = 17), the MIC50/MIC90 of ceftolozane-tazobactam were 4/8 µg/ml (47% susceptible). Imipenem-relebactam was active against most KPC-producing (but not NDM- or IMP-producing) Enterobacteriaceae and is an encouraging addition to the present antibiotic repertoire.


Assuntos
Antibacterianos/farmacologia , Compostos Azabicíclicos/farmacologia , Cefalosporinas/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Imipenem/farmacologia , Tazobactam/farmacologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/metabolismo , Testes de Sensibilidade Microbiana
12.
Diagn Microbiol Infect Dis ; 90(1): 58-63, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29195766

RESUMO

We tested the in vitro activity of dalbavancin, vancomycin and daptomycin against 83 enterococcal isolates in planktonic and biofilm states. The MIC90 for vancomycin-susceptible Enterococcus faecalis was 0.125 and 4µg/mL for dalbavancin and daptomycin, respectively. For vancomycin-resistant Enterococcus faecium, the MIC90 was >16 and 2µg/mL for dalbavancin and daptomycin, respectively. Dalbavancin minimum biofilm inhibitory concentrations (MBICs) for vancomycin-susceptible and -resistant isolates were ≤0.25 and >16µg/mL, respectively. The daptomycin MBIC90 for all isolates was 4µg/mL. For E. faecalis and E. faecium, dalbavancin minimum biofilm bactericidal concentrations (MBBCs) for vancomycin-susceptible and -resistant isolates were ≤4 and >16µg/mL, respectively, whereas vancomycin MBBCs were >128µg/mL for all isolates, and daptomycin MBBC90 values for both species were 128µg/mL. In summary, dalbavancin exhibited in vitro activity against all tested isolates of vancomycin-susceptible, but not against vancomycin-resistant enterococci; activity was observed in both the planktonic and biofilm states.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Daptomicina/farmacologia , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecium/efeitos dos fármacos , Teicoplanina/análogos & derivados , Enterococos Resistentes à Vancomicina/efeitos dos fármacos , Vancomicina/farmacologia , Biofilmes/crescimento & desenvolvimento , Farmacorresistência Bacteriana Múltipla , Enterococcus faecalis/isolamento & purificação , Enterococcus faecium/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Teicoplanina/farmacologia , Enterococos Resistentes à Vancomicina/isolamento & purificação
13.
Artigo em Inglês | MEDLINE | ID: mdl-27821457

RESUMO

Foreign-body-associated infections are often difficult to treat, given that the associated microorganisms are in a biofilm state. Previously, we showed that a low-amperage direct electrical current (DC) reduces Propionibacterium acnes biofilms formed on implant-associated materials in vitro In this study, low-amperage DC was compared to ceftriaxone treatment or no treatment in a novel rat femur model of foreign-body osteomyelitis. A platinum implant seeded with a P. acnes biofilm (107 CFU/cm2) and 109 CFU of planktonic P. acnes was placed in the femoral medullary cavity. One week later, rats were assigned to one of three treatment groups: no treatment, ceftriaxone treatment, or 200-µA-DC treatment. After 2 weeks of treatment, there were fewer bacteria in the bones of the ceftriaxone group (3.06 log10 CFU/g of bone [P = 0.0209]) and the 200-µA-DC group (0.5 log10 CFU/g [P = 0.0015]) than in those of the control group (6.58 log10 CFU/g). The DC-exposed animals exhibited fewer bacteria than the ceftriaxone-treated animals (P = 0.0330). There were fewer bacteria on the implanted wires in the groups treated with ceftriaxone (0.1 log10 CFU/cm2) or a 200-µA DC (0.1 log10 CFU/cm2) than in the control group (2.53 log10 CFU/cm2 [P, 0.0003 for both comparisons]). Low-amperage DC may be useful for treating, or aiding in the treatment of, foreign-body infections caused by P. acnes.


Assuntos
Ceftriaxona/farmacocinética , Terapia por Estimulação Elétrica/métodos , Infecções por Bactérias Gram-Positivas/terapia , Osteomielite/terapia , Propionibacterium acnes , Animais , Fêmur , Corpos Estranhos/microbiologia , Humanos , Masculino , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Propionibacterium acnes/efeitos dos fármacos , Propionibacterium acnes/isolamento & purificação , Propionibacterium acnes/patogenicidade , Ratos Wistar
14.
Artigo em Inglês | MEDLINE | ID: mdl-27855064

RESUMO

Staphylococcal prosthetic joint infections (PJIs) are associated with biofilm formation, making them difficult to treat; if managed with debridement and implant retention, rifampin-based therapy is usually employed. Rifampin resistance potentially challenges PJI treatment. In investigating the effects of rifampin monotherapy on methicillin-resistant Staphylococcus aureus (MRSA) foreign-body osteomyelitis in rats, we previously demonstrated that rifampin resistance was selected but that it disappeared 14 days following rifampin monotherapy (1) and that rifampin resistance occurred less frequently following two rounds than following one round of rifampin monotherapy (2). Here, we compared rifampin monotherapy followed by rifampin-vancomycin combination therapy to rifampin-vancomycin combination therapy alone in experimental MRSA foreign-body osteomyelitis. Animals treated with rifampin monotherapy followed by rifampin-vancomycin combination therapy had decreased quantities of bacteria 14 days following treatment completion (P = 0.034) compared to those in animals treated with combination therapy alone. Additionally, some isolates recovered from animals treated with combination therapy alone, although still susceptible to rifampin, had higher MIC, minimum biofilm-inhibitory concentration (MBIC), and minimum biofilm-bactericidal concentration (MBBC) values than those of the inoculating strain. This suggests that rifampin may remain a feasible treatment option in foreign-body-associated orthopedic infections following the selection of rifampin resistance.


Assuntos
Osteomielite/tratamento farmacológico , Rifampina/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Animais , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Quimioterapia Combinada , Corpos Estranhos/microbiologia , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Osteomielite/microbiologia , Ratos Wistar , Infecções Estafilocócicas/microbiologia , Vancomicina/farmacologia
15.
PLoS One ; 11(12): e0168595, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27992529

RESUMO

Bacterial biofilms may form on indwelling medical devices such as prosthetic joints, heart valves and catheters, causing challenging-to-treat infections. We have previously described the 'electricidal effect', in which bacterial biofilms are decreased following exposure to direct electrical current. Herein, we sought to determine if the decreased bacterial quantities are due to detachment of biofilms or cell death and to investigate the role that reactive oxygen species (ROS) play in the observed effect. Using confocal and electron microscopy and flow cytometry, we found that direct current (DC) leads to cell death and changes in the architecture of biofilms formed by Gram-positive and Gram-negative bacteria. Reactive oxygen species (ROS) appear to play a role in DC-associated cell death, as there was an increase in ROS-production by Staphylococcus aureus and Staphylococcus epidermidis biofilms following exposure to DC. An increase in the production of ROS response enzymes catalase and superoxide dismutase (SOD) was observed for S. aureus, S. epidermidis and Pseudomonas aeruginosa biofilms following exposure to DC. Additionally, biofilms were protected from cell death when supplemented with antioxidants and oxidant scavengers, including catalase, mannitol and Tempol. Knocking out SOD (sodAB) in P. aeruginosa led to an enhanced DC effect. Microarray analysis of P. aeruginosa PAO1 showed transcriptional changes in genes related to the stress response and cell death. In conclusion, the electricidal effect results in death of bacteria in biofilms, mediated, at least in part, by production of ROS.


Assuntos
Biofilmes/crescimento & desenvolvimento , Eletricidade , Bactérias Gram-Negativas/fisiologia , Bactérias Gram-Positivas/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Técnicas de Silenciamento de Genes , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
16.
Diagn Microbiol Infect Dis ; 85(3): 356-359, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27130477

RESUMO

Pseudomonas aeruginosa causes a variety of life-threatening infections, some of which are associated with planktonic and others with biofilm states. Herein, we tested the combination of the novel cephalosporin, ceftolozane, with the ß-lactamase inhibitor, tazobactam, against planktonic and biofilm forms of 54 clinical isolates of P. aeruginosa, using cefepime as a comparator. MIC values were determined following Clinical and Laboratory Standards Institute (CLSI) guidelines. Minimum biofilm inhibitory concentration (MBIC) values were determined using biofilm-laden pegged lids incubated in antimicrobial challenge plates containing varying concentrations of ceftolozane/tazobactam. Pegged lids were then incubated in growth recovery plates containing cation-adjusted Mueller-Hinton broth to determine the minimum biofilm bactericidal concentration (MBBC). Ceftolozane/tazobactam was highly active against planktonic P. aeruginosa, with all 54 isolates studied testing susceptible (MIC ≤4/4µg/mL). On the other hand, 51/54 biofilm P. aeruginosa had MBICs ≥16/4µg/mL, and all 54 isolates had MBBCs >32µg/mL. Of the 54 isolates, 45 (83.3%) tested susceptible to cefepime, with the MIC50/MIC90 being 4/16µg/mL, respectively, and the MBIC90 and MBBC90 both being >256µg/mL. Although ceftolozane/tazobactam is a promising antimicrobial agent for the treatment of P. aeruginosa infections, it is not highly active against P. aeruginosa biofilms.


Assuntos
Anti-Infecciosos Urinários/farmacologia , Biofilmes/efeitos dos fármacos , Cefalosporinas/farmacologia , Ácido Penicilânico/análogos & derivados , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Inibidores de beta-Lactamases/farmacologia , Biofilmes/crescimento & desenvolvimento , Humanos , Testes de Sensibilidade Microbiana , Ácido Penicilânico/farmacologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Tazobactam
17.
Int J Bacteriol ; 2016: 9727810, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27073807

RESUMO

New strategies are needed for prevention of biofilm formation. We have previously shown that 24 hr of 2,000 µA of direct current (DC) reduces Staphylococcus epidermidis biofilm formation in vitro. Herein, we examined the effect of a lower amount of DC exposure on S. epidermidis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Propionibacterium acnes, and Candida albicans biofilm formation. 12 hr of 500 µA DC decreased S. epidermidis, S. aureus, E. coli, and P. aeruginosa biofilm formation on Teflon discs by 2, 1, 1, and 2 log10 cfu/cm(2), respectively (p < 0.05). Reductions in S. epidermidis, S. aureus, and E. coli biofilm formation were observed with as few as 12 hr of 200 µA DC (2, 2 and 0.4 log10 cfu/cm(2), resp.); a 1 log10 cfu/cm(2) reduction in P. aeruginosa biofilm formation was observed at 36 hr. 24 hr of 500 µA DC decreased C. albicans biofilm formation on Teflon discs by 2 log10 cfu/cm(2). No reduction in P. acnes biofilm formation was observed. 1 and 2 log10 cfu/cm(2) reductions in E. coli and S. epidermidis biofilm formation on titanium discs, respectively, were observed with 12 hr of exposure to 500 µA. Electrical current is a potential strategy to reduce biofilm formation on medical biomaterials.

18.
Diagn Microbiol Infect Dis ; 85(1): 77-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26906190

RESUMO

We determined the MIC and minimum biofilm bactericidal concentration (MBBC) of tedizolid and vancomycin against 97 isolates of Staphylococcus aureus and 74 isolates of Staphylococcus epidermidis associated with prosthetic joint infection. All isolates were vancomycin susceptible in the planktonic state; all staphylococci studied had a tedizolid MIC ≤0.5 µg/mL. The MBBC90 was >32 and >128 µg/mL for tedizolid and vancomycin, respectively.


Assuntos
Antibacterianos/farmacologia , Artrite Infecciosa/microbiologia , Testes de Sensibilidade Microbiana , Organofosfatos/farmacologia , Oxazóis/farmacologia , Infecções Relacionadas à Prótese/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Staphylococcus aureus Resistente à Meticilina , Staphylococcus/classificação , Staphylococcus/isolamento & purificação
19.
Antimicrob Agents Chemother ; 60(3): 1865-8, 2015 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-26666918

RESUMO

We examined the pharmacokinetic properties of vancomycin conjugated to a bone-targeting agent (BT) with high affinity for hydroxyapatite after systemic intravenous administration. The results confirm enhanced persistence of BT-vancomycin in plasma and enhanced accumulation in bone relative to vancomycin. This suggests that BT-vancomycin may be a potential carrier for the systemic targeted delivery of vancomycin in the treatment of bone infections, potentially reducing the reliance on surgical debridement to achieve the desired therapeutic outcome.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Portadores de Fármacos/uso terapêutico , Durapatita/metabolismo , Osteomielite/tratamento farmacológico , Vancomicina/administração & dosagem , Vancomicina/farmacocinética , Animais , Antibacterianos/farmacocinética , Osso e Ossos/metabolismo , Desbridamento , Modelos Animais de Doenças , Humanos , Osteomielite/microbiologia , Polietilenoglicóis/química , Ratos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/uso terapêutico
20.
Antimicrob Agents Chemother ; 60(3): 1476-80, 2015 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-26711752

RESUMO

Catheter-associated infections are difficult to treat with available antimicrobial agents because of their biofilm etiology. We examined the effect of low-amperage direct electrical current (DC) exposure on established bacterial and fungal biofilms in a novel experimental in vitro catheter model. Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida parapsilosis biofilms were grown on the inside surfaces of polyvinyl chloride (PVC) catheters, after which 0, 100, 200, or 500 µA of DC was delivered via intraluminally placed platinum electrodes. Catheter biofilms and intraluminal fluid were quantitatively cultured after 24 h and 4 days of DC exposure. Time- and dose-dependent biofilm killing was observed with all amperages and durations of DC administration. Twenty-four hours of 500 µA of DC sterilized the intraluminal fluid for all bacterial species studied; no viable bacteria were detected after treatment of S. epidermidis and S. aureus biofilms with 500 µA of DC for 4 days.


Assuntos
Infecções Relacionadas a Cateter/terapia , Cateteres/microbiologia , Terapia por Estimulação Elétrica/métodos , Biofilmes , Candida/patogenicidade , Candida/fisiologia , Infecções Relacionadas a Cateter/microbiologia , Eletrodos , Escherichia coli/patogenicidade , Escherichia coli/fisiologia , Pseudomonas aeruginosa/patogenicidade , Pseudomonas aeruginosa/fisiologia , Staphylococcus aureus/patogenicidade , Staphylococcus aureus/fisiologia , Staphylococcus epidermidis/patogenicidade , Staphylococcus epidermidis/fisiologia
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