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1.
Clin Infect Dis ; 70(4): 704-709, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-31328228

RESUMO

Plazomicin (ACHN-490) is a novel parenteral aminoglycoside developed to target multidrug-resistant Enterobacteriaceae. It has recently been approved by the Food and Drug Administration for the management of complicated urinary tract infections and pyelonephritis caused by susceptible organisms. When compared with meropenem, plazomicin was not inferior. The adverse-event profile for plazomicin was comparable to meropenem except for an increased additional rise in serum creatinine in the plazomicin arm compared with the meropenem arm. This review focuses on the mode of action, antimicrobial activity, pharmacokinetics, clinical indications, and safety profile of this drug. Considerations for formulary addition and its place in therapy are also discussed.


Assuntos
Aminoglicosídeos , Farmacorresistência Bacteriana Múltipla , Aminoglicosídeos/efeitos adversos , Antibacterianos/efeitos adversos , Humanos , Sisomicina/efeitos adversos , Sisomicina/análogos & derivados
2.
Clin Infect Dis ; 68(6): 1058-1062, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30060092

RESUMO

Delafloxacin (ABT 492) is a new fluoroquinolone available in both oral and parenteral formulations. It has recently been approved by the Food and Drug Administration for the management of acute bacterial skin and skin structure infections. When compared to combination therapy of vancomycin and aztreonam, delafloxacin was not inferior and had a favorable adverse event profile. Furthermore, its anti-methicillin-resistant Staphylococcus aureus (MRSA) activity and favorable clinical response in MRSA infections distinguishes it from other fluoroquinolones. This review focuses on the mode of action, antimicrobial activity, pharmacokinetics and pharmacodynamics, clinical indications, and safety profile of this drug. Considerations for formulary addition and its place in therapy are also discussed.


Assuntos
Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Fluoroquinolonas/química , Humanos , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , Resultado do Tratamento
3.
Clin Infect Dis ; 61(4): 627-32, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-25900171

RESUMO

Oritavancin is a lipoglycopeptide antibiotic that has been shown to be effective for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). This antibiotic has multiple mechanisms of action including inhibiting peptidoglycan cell wall synthesis and disrupting bacterial cell membrane, leading to cell death. Oritavancin is highly active against common gram-positive pathogens including methicillin-resistant Staphylococcus aureus, vancomycin-intermediate S. aureus, vancomycin-resistant S. aureus, and vancomycin-resistant enterococci. The drug is administered as a single intravenous dose of 1200 mg over 3 hours in adult patients, and because of its terminal half-life of 393 hours, repeat dosing is not required in the treatment of ABSSIs. There is a very slow elimination from tissue sites, and no dosing adjustments are required for renal or hepatic insufficiency. Two clinical trials have demonstrated noninferiority compared with vancomycin in the treatment of ABSSSIs. Other than liver enzyme elevation and the occurrence of osteomyelitis, oritavancin has been associated with adverse events similar to those of vancomycin in follow-up for up to 60 days. Patients should be monitored for osteomyelitis and alternate therapy given in the case of confirmed or suspected osteomyelitis. Although oritavancin is an attractive antibiotic to consider in the outpatient area, its efficacy and safety in the treatment of other sites of infection are yet to be established.


Assuntos
Antibacterianos/farmacologia , Antibacterianos/farmacocinética , Glicopeptídeos/farmacologia , Glicopeptídeos/farmacocinética , Administração Intravenosa , Antibacterianos/uso terapêutico , Ensaios Clínicos como Assunto , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Enzimas/sangue , Glicopeptídeos/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Meia-Vida , Humanos , Lipoglicopeptídeos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Osteomielite/induzido quimicamente , Dermatopatias Bacterianas/tratamento farmacológico , Infecções dos Tecidos Moles/tratamento farmacológico
4.
Crit Care ; 18(3): R118, 2014 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-24916853

RESUMO

INTRODUCTION: Controversy exists regarding optimal treatment for ventilator-associated pneumonia (VAP) due to methicillin-resistant Staphylococcus aureus (MRSA). The primary objective of this study was to compare clinical success of linezolid versus vancomycin for the treatment of patients with MRSA VAP. METHODS: This was a multicenter, retrospective, observational study of patients with VAP (defined according to Centers for Disease Control and Prevention criteria) due to MRSA who were treated with linezolid or vancomycin. MRSA VAP was considered when MRSA was isolated from a tracheal aspirate or bronchoalveolar lavage. Clinical success was evaluated by assessing improvement or resolution of signs and symptoms of VAP by day 14. After matching on confounding factors, logistic regression models were used to determine if an association existed between treatment arm and clinical success. RESULTS: A total of 188 patients were evaluated (101 treated with linezolid and 87 with vancomycin). The mean ± standard deviation Acute Physiology and Chronic Health Evaluation (APACHE) II score was 21 ± 11 for linezolid- and 19 ± 9 for vancomycin-treated patients (P = 0.041). Clinical success occurred in 85% of linezolid-treated patients compared with 69% of vancomycin-treated patients (P = 0.009). After adjusting for confounding factors, linezolid-treated patients were 24% more likely to experience clinical success than vancomycin-treated patients (P = 0.018). CONCLUSIONS: This study adds to the evidence indicating that patients with MRSA VAP who are treated with linezolid are more likely to respond favorably compared with patients treated with vancomycin.


Assuntos
Acetamidas/uso terapêutico , Antibacterianos/uso terapêutico , Staphylococcus aureus Resistente à Meticilina , Oxazolidinonas/uso terapêutico , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Vancomicina/uso terapêutico , APACHE , Acetamidas/efeitos adversos , Adulto , Anemia/induzido quimicamente , Antibacterianos/efeitos adversos , Feminino , Humanos , Nefropatias/induzido quimicamente , Linezolida , Masculino , Oxazolidinonas/efeitos adversos , Pneumonia Associada à Ventilação Mecânica/microbiologia , Pneumonia Associada à Ventilação Mecânica/mortalidade , Estudos Retrospectivos , Trombocitopenia/induzido quimicamente , Resultado do Tratamento , Vancomicina/efeitos adversos
5.
J Antimicrob Chemother ; 68(12): 2852-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23873647

RESUMO

OBJECTIVES: The purpose of this study was to conduct a pharmacokinetic and pharmacodynamic evaluation of high (320/1600 mg) and standard (160/800 mg) doses of trimethoprim/sulfamethoxazole and linezolid in outpatients with mild diabetic foot infections (DFIs). METHODS: Both viable skin/soft tissue from the infection site and serum were obtained at various times after antibiotic administration from 18 patients (6 per study group) being treated with linezolid, standard doses of trimethoprim/sulfamethoxazole or high doses of trimethoprim/sulfamethoxazole during a follow-up clinic visit. These samples were assayed for drug concentrations by liquid chromatography in tandem with mass spectrometry. Patient sera were also utilized in time-kill assays against two strains of Staphylococcus aureus and three strains of ß-haemolytic streptococci. RESULTS: The mean tissue/serum ratio for linezolid was 0.46 (range, 0.18-0.71). The mean tissue/serum ratio for trimethoprim was 1.2 (range, 0.3-4.5) for both standard and high doses, and 0.23 (range, 0.1-0.46) and 0.36 (range, 0.14-1.28) for standard and high doses of sulfamethoxazole, respectively. Linezolid exhibited inhibitory activity in time-kill assays against strains of S. aureus (0.45 ± 0.5 log10 cfu/mL) and ß-haemolytic streptococci (2.2 ± 0.6 log10 cfu/mL), while trimethoprim/sulfamethoxazole exhibited bactericidal (>3 log kill) activity against all of these isolates. These findings were consistent for each sampling time and for high as well as standard doses of trimethoprim/sulfamethoxazole. CONCLUSIONS: This pharmacokinetic/pharmacodynamic study found that trimethoprim/sulfamethoxazole exhibits good skin/soft tissue penetration in patients with DFIs as well as bactericidal activity in serum against strains of S. aureus and ß-haemolytic streptococci.


Assuntos
Acetamidas/farmacocinética , Antibacterianos/farmacocinética , Infecções Bacterianas/tratamento farmacológico , Pé Diabético/complicações , Oxazolidinonas/farmacocinética , Combinação Trimetoprima e Sulfametoxazol/farmacocinética , Acetamidas/administração & dosagem , Acetamidas/farmacologia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Cromatografia Líquida , Feminino , Humanos , Linezolida , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Oxazolidinonas/administração & dosagem , Oxazolidinonas/farmacologia , Soro/química , Pele/química , Staphylococcus aureus/efeitos dos fármacos , Streptococcus/efeitos dos fármacos , Espectrometria de Massas em Tandem , Fatores de Tempo , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/farmacologia
6.
Clin Infect Dis ; 55 Suppl 3: S173-80, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22903949

RESUMO

In October 2010, the new cephalosporin, ceftaroline fosamil, was approved by the US Food and Drug Administration for therapy of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSIs). The active metabolite, ceftaroline, demonstrates in vitro activity against typical bacterial pathogens most often associated with CABP or ABSSSIs, including resistant Gram-positive pathogens such as multidrug-resistant Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus. The efficacy and safety of ceftaroline fosamil was assessed in 2 large phase 3 programs of randomized, double-blind, clinical trials for CABP and ABSSSIs. For both indications, therapy with ceftaroline fosamil was observed to be noninferior to the comparator agents (ceftriaxone for CABP and vancomycin plus aztreonam for ABSSSIs) at both a standard test of cure assessment time (8-15 days after discontinuation of study drug) and an early assessment time point (day 3 or 4 of study). In the integrated analysis of the trials for CABP (FOCUS 1 and 2), clinical cure rates for the ceftaroline group were numerically higher than those for the ceftriaxone group (for the clinically evaluable population 84.3% vs 77.7%; difference: 6.6%; 95% confidence interval, 1.6%-11.8%). Among patients with CABP caused by S. pneumoniae, clinical cure rates were markedly higher in the ceftaroline treatment group than in the ceftriaxone treatment group (59 of 69 [85.5%] vs 48 of 70 [68.6%], respectively). For the ABSSSI studies (CANVAS 1 and 2), microbiologically evaluable (ME) success rates were similar between the treatment groups. Notably, the clinical cure rates in ME patients with methicillin-resistant S. aureus ABSSSIs were 142 of 152 (93.4%) and 115 of 122 (94.3%), for ceftaroline and vancomycin plus aztreonam, respectively, and did not differ from those achieved in infections due to methicillin-susceptible S. aureus (93.0%-94.5%). Ceftaroline fosamil was well tolerated, with a safety profile similar to the comparator agents used in these phase 3 trials.


Assuntos
Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Antibacterianos/efeitos adversos , Cefalosporinas/efeitos adversos , Ensaios Clínicos como Assunto , Humanos , Pneumonia Bacteriana/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Ceftarolina
7.
Ann Pharmacother ; 46(10): 1281-6, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23012385

RESUMO

BACKGROUND: Doripenem is a group 2 carbapenem with enhanced in vitro activity against gram-negative bacteria including Pseudomonas aeruginosa. There is a paucity of pharmacokinetic/pharmacodynamic data on doripenem in patients with febrile neutropenia. OBJECTIVE: To conduct a pharmacokinetic evaluation of 2 doses of doripenem in patients with febrile neutropenia and provide probability estimates of attaining effective drug exposure against common gram-negative pathogens. METHODS: We obtained multiple blood samples from 12 adults with febrile neutropenia who were receiving either 500 mg or 1000 mg of intravenous doripenem over 4 hours every 8 hours. Following at least 2 doses, serum concentrations were measured in each subject at 1, 4, 6, and 8 hours after initiation of a dose by a validated high-performance liquid chromatography assay. The derived pharmacokinetic parameters from these serum levels were used to perform a 5000-patient Monte Carlo simulation against bacteria with minimal inhibitory concentrations (MICs) of 0.008-64 mg/L to determine probability estimates of the time in which unbound drug concentrations remain above the MIC (fT(>MIC)). RESULTS: The mean pharmacokinetic parameters in these patients were a volume of distribution of 43.9 L, an elimination rate constant of 0.37 h(-1), a total clearance of 14.4 L/h, and an area under the concentration-time curve of 57.6 mg•h/L. An optimal probability of target attainment (40% fT(>MIC)) of 90% was obtained against bacteria with MICs ≤2 mg/L and ≤4 mg/L with 500-mg and 1000-mg doses, respectively. Adverse events associated with doripenem were not observed. CONCLUSIONS: The findings from this analysis of doripenem suggest that higher doses, as well as prolonged infusions, may be necessary to optimally treat selected gram-negative bacteria (eg, P. aeruginosa) in patients with febrile neutropenia.


Assuntos
Antibacterianos/administração & dosagem , Carbapenêmicos/administração & dosagem , Bactérias Gram-Negativas/efeitos dos fármacos , Neutropenia/tratamento farmacológico , Adulto , Idoso , Antibacterianos/sangue , Antibacterianos/farmacocinética , Carbapenêmicos/sangue , Carbapenêmicos/farmacocinética , Doripenem , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Método de Monte Carlo , Neutropenia/metabolismo , Adulto Jovem
8.
Clin Infect Dis ; 52(9): 1156-63, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21467022

RESUMO

Ceftaroline (PPI 0903, formerly TAK-599), the active metabolite of a N-phosphono prodrug, ceftaroline fosamil, has been approved by the US Food and Drug Administration for the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. This antimicrobial agent binds to penicillin binding proteins (PBP) inhibiting cell wall synthesis and has a high affinity for PBP2a, which is associated with methicillin resistance. Ceftaroline is consistently active against multidrug-resistant Streptococcus pneumoniae and Staphylococcus aureus, including methicillin-resistant, vancomycin-intermediate, linezolid-resistant, and daptomycin-nonsusceptible strains. It possesses variable activity against Enterobacteriaceae and good activity against oral anaerobes. The drug is usually administrated intravenously at 600 mg every 12 h. Ceftaroline has low protein binding and is excreted by the kidneys and thus requires dose adjustments in individuals with renal failure. Clinical trials have demonstrated noninferiority when compared with vancomycin in the treatment of acute bacterial skin and skin structure infections and noninferiority when compared with ceftriaxone in the treatment of community-acquired bacterial pneumonia. Ceftaroline demonstrated a safety profile similar to that of comparator drugs in clinical trials.


Assuntos
Antibacterianos/farmacologia , Cefalosporinas/classificação , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Adulto , Animais , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Cefalosporinas/química , Cefalosporinas/farmacocinética , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Ensaios Clínicos como Assunto , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Coelhos , Streptococcus pneumoniae/efeitos dos fármacos , Ceftarolina
9.
Surg Infect (Larchmt) ; 22(8): 771-779, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33835882

RESUMO

Background: The long-acting lipoglycopeptides dalbavancin and oritavancin possess excellent microbiologic activity against gram-positive bacteria and provide prolonged tissue exposure at sites of infection. Moreover, these antibiotics are well tolerated and do not require therapeutic drug monitoring. Methods: Pharmacokinetic/pharmacodynamic experiments ascertained that one to two doses of these long-acting agents can provide an extended period (≥6 weeks) of antimicrobial therapy. Results: Clinical studies subsequently found that microbiologic and clinical response rates with these agents were comparable to standard antibiotic agents used in the treatment of bone and joint infections. In addition, pharmacoeconomic analyses have discovered cost savings with the use of these antimicrobial agents in the treatment of serious deep-seated bacterial infections. Conclusions: Thus, these long-acting lipoglycopeptides offer potential for cost-effective outpatient parenteral antibiotic therapy of difficult to treat infections, such as osteomyelitis.


Assuntos
Antibacterianos , Osteomielite , Antibacterianos/uso terapêutico , Bactérias Gram-Positivas , Humanos , Lipoglicopeptídeos , Osteomielite/tratamento farmacológico
10.
J Clin Pharmacol ; 60(2): 172-180, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31423601

RESUMO

Monte Carlo simulations (MCSs) are used in antibiotic development to predict the probability of pharmacodynamic target attainment (PTA) for a dosing regimen. However, for ß-lactam/ß-lactamase inhibitor combinations (BL-BLICs), methods for linking simulated concentration profiles of the ß-lactam (BL) and ß-lactamase inhibitor (BLI) components are rarely described. Using a previously defined pharmacokinetic model of ceftazidime/avibactam from critically ill patients, we performed four 5000-patient MCSs using different methods of increasing complexity to couple the BL and BLI components and compared PTA for ceftazidime and avibactam targets of >70% fT>MIC and >70% fT>1 mg/L, respectively, at MICs from 1 to 128 mg/L. Method A ignored all covariates and correlations, whereas methods B, C, and D enhanced associations by adding (B) pharmacokinetic parameter correlation within each drug only; (C) pharmacokinetic parameter correlation within each drug and creatinine clearance (CRCL); and (D) pharmacokinetic parameter correlation within each drug, CRCL, and pharmacokinetic parameter correlation between drugs. Method D produced a simulated patient population that best recapitulated the observed relationships between pharmacokinetic parameters in actual patients. Ceftazidime/avibactam PTA at MIC 8 mg/L (the susceptibility break point) and 16 mg/L ranged from 92.4% to 98.3% and 80.2% to 88.4%, respectively. PTA was lowest with method A, whereas PTA estimates were similar for all other methods. Compared with ignoring all pharmacokinetic parameter associations, the inclusion of covariate relationships and parameter correlation between both components of ceftazidime/avibactam leads to fewer patients with discordant pharmacokinetic parameters and results in higher PTA. Consideration of these methodologies should guide future MCS analyses for BL-BLIC.


Assuntos
Compostos Azabicíclicos/administração & dosagem , Compostos Azabicíclicos/farmacocinética , Ceftazidima/administração & dosagem , Ceftazidima/farmacocinética , Método de Monte Carlo , Inibidores de beta-Lactamases/administração & dosagem , Inibidores de beta-Lactamases/farmacocinética , beta-Lactamas/administração & dosagem , beta-Lactamas/farmacocinética , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Compostos Azabicíclicos/uso terapêutico , Ceftazidima/uso terapêutico , Simulação por Computador , Esquema de Medicação , Combinação de Medicamentos , Humanos , Testes de Sensibilidade Microbiana , Modelos Biológicos , Modelos Estatísticos , Inibidores de beta-Lactamases/uso terapêutico , beta-Lactamas/uso terapêutico
11.
Clin Infect Dis ; 49(12): 1908-14, 2009 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-19911938

RESUMO

Telavancin, a derivative of vancomycin, is a lipoglycopeptide antibiotic that has been shown to be effective for the treatment of complicated skin and skin-structure infections. It has also been effective in the treatment of gram-positive pneumonia. This antibiotic has a dual mechanism of action by inhibiting peptidoglycan synthesis and causing membrane depolarization. Telavancin is consistently active against Staphylococcus aureus, including methicillin-resistant S. aureus, vancomycin-intermediate S. aureus, linezolid-resistant S. aureus, and daptomycin-nonsusceptible strains. The drug is usually administrated intravenously at 10 mg/kg every 24 h. Telavancin is excreted by the kidneys, and thus, dosage adjustments are required in cases of renal failure. Clinical trials have demonstrated non-inferiority, compared with vancomycin, in the treatment of complicated skin and skin-structure infections and pneumonia. Telavancin is associated with higher rates of renal events, altered taste, nausea, and vomiting but lesser rates of pruritus and infusion-related events, compared with vancomycin.


Assuntos
Aminoglicosídeos/farmacologia , Antibacterianos/farmacologia , Aminoglicosídeos/efeitos adversos , Aminoglicosídeos/farmacocinética , Aminoglicosídeos/uso terapêutico , Química Farmacêutica , Humanos , Lipoglicopeptídeos
12.
Surg Infect (Larchmt) ; 20(1): 55-61, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30351195

RESUMO

BACKGROUND: The pharmacokinetics, especially the volume of distribution (Vd), of ß-lactam antibiotics can be altered in critically ill patients. This can lead to decreased serum concentrations and a reduction in clinical cures. Ceftazidime/avibactam (CZA) is a new antimicrobial agent utilized in critically ill patients although its pharmacokinetics has not been well defined in these patients. PATIENTS AND METHODS: In this study, the serum concentrations of CZA from adult patients treated in an intensive care unit (ICU) with standard dosing regimens were measured and both pharmacokinetic and pharmacodynamic parameters were computed. The pharmacodynamic analyses included Monte Carlo simulations to determine the probability of target attainment (PTA: free ceftazidime concentrations exceed the minimum inhibitory concentration [MIC] for 50% of the dosing interval; free avibactam concentrations exceed 1 mg/L over the dosing interval) and serum time-kill curves against multi-drug-resistant Enterobacteriaceae susceptible to CZA. Serum concentrations were measured in 10 critically ill patients at two, four, six, and eight hours after multiple doses (infused over two hours) of CZA. RESULTS: A significant linear relation between creatinine clearance and total body clearance was identified for both ceftazidime (R = 0.91) and avibactam (R = 0.88). The mean clearance, volume of distribution, and half-life for ceftazidime were 6.1 ± 3.8 L/h, 35 ± 10.5 L, and 4.8 ± 2.15 h, respectively. For avibactam, these values were 11.1 ± 6.8 L/h, 50.8 ± 14.3 L, and 4.1 ± 2.1 h, respectively. Ceftazidime/avibactam achieved optimal PTA for bacteria with MICs of 16 mg/L or less. Furthermore, time-kill experiments revealed that serum concentrations of CZA, at each collection time, exhibited bactericidal (≥ 3 log10 CFU/mL reduction) activity against each of the study isolates. CONCLUSION: In conclusion, our study results suggest that the current dosing regimens of CZA can provide effective antimicrobial activity in ICU patients against CZA-susceptible (MIC ≤8 mg/L) isolates.


Assuntos
Antibacterianos/farmacologia , Antibacterianos/farmacocinética , Compostos Azabicíclicos/farmacologia , Compostos Azabicíclicos/farmacocinética , Ceftazidima/farmacologia , Ceftazidima/farmacocinética , Estado Terminal , Inibidores de beta-Lactamases/farmacologia , Inibidores de beta-Lactamases/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Compostos Azabicíclicos/administração & dosagem , Ceftazidima/administração & dosagem , Combinação de Medicamentos , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/fisiologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Pessoa de Meia-Idade , Método de Monte Carlo , Estudos Prospectivos , Soro/química , Fatores de Tempo , Inibidores de beta-Lactamases/administração & dosagem
13.
Int J Antimicrob Agents ; 32(4): 320-5, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18715762

RESUMO

Increasing resistance to fluoroquinolones in uropathogens has become a clinical concern. The purpose of this study was to analyse the urinary bactericidal activity (UBA) of levofloxacin against fluoroquinolone-resistant strains of Escherichia coli. Ten healthy adult subjects (aged 23-60 years) received single doses of levofloxacin (250, 500, 750 and 1000 mg) and then blood and urine samples were collected in intervals (0-1.5, 1.5-4, 4-8, 8-12 and 12-24h) over 24h. Both serum and urine concentrations were measured by a validated high-performance liquid chromatography assay. Bactericidal titres in urine were determined against E. coli isolates with minimum inhibitory concentrations of 0.125, 4, 8, 16, 32 and 64microg/mL for levofloxacin. The mean serum pharmacokinetic parameters for these doses of levofloxacin were similar to previously published values. The mean peak urinary concentrations (0-1.5h) were 210, 347, 620 and 536microg/mL for the 250, 500, 750 and 1000 mg dose, respectively. Each dose of levofloxacin exhibited early (0-1.5h time period) bactericidal activity in urine in virtually all subjects against E. coli strains with MICs

Assuntos
Antibacterianos/farmacologia , Antibacterianos/urina , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Fluoroquinolonas/farmacologia , Levofloxacino , Ofloxacino/farmacologia , Ofloxacino/urina , Administração Oral , Adulto , Antibacterianos/administração & dosagem , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Ofloxacino/administração & dosagem , Adulto Jovem
14.
Int J Antimicrob Agents ; 29(1): 39-43, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17189093

RESUMO

Telithromycin is a new ketolide antimicrobial with a good in vitro activity against both aerobic and anaerobic respiratory pathogens. In this study, we evaluated the antibacterial activity over time of telithromycin (800mg), azithromycin (500mg), and amoxicillin/clavulanate (875/125mg) in serum following single oral doses of these agents to 10 healthy subjects. Inhibitory and bactericidal titers were determined at 2, 6, 12, and 24h after each dose and the median titer was used to determine antibacterial activity. Against two azithromycin-resistant strains of Streptococcus pneumoniae, both telithromycin (MIC=0.25 and 0.5 microg/mL) and amoxicillin/clavulanate exhibited inhibitory and cidal activity for at least 6h. All three antibiotics provided prolonged (>or=12h) inhibitory activity against strains of Hemophilus influenzae (telithromycin MIC=4.0 microg/ml). Both telithromycin and amoxicillin/clavulanate exhibited rapid and prolonged inhibitory activity (>or=12h) against each of the anaerobes studied (Finegoldia [Peptostreptococcus] magna Peptostreptococcus micros, Prevotella bivia, and Prevotella melaninogenica). Moreover, both agents provided bactericidal activity against both Prevotella species. In this ex vivo pharmacodynamic study, we found that telithromycin provided rapid and prolonged antibacterial activity in serum against macrolide-resistant strains of S. pneumoniae, beta-lactamase-positive and -negative strains of H. influenzae, and common respiratory anaerobic pathogens. These findings suggest that telithromycin could have clinical utility in the treatment of community-acquired mixed aerobic-anaerobic respiratory tract infections, including chronic sinusitis and aspiration pneumonia.


Assuntos
Combinação Amoxicilina e Clavulanato de Potássio/farmacologia , Azitromicina/farmacologia , Bactérias/efeitos dos fármacos , Cetolídeos/farmacologia , Teste Bactericida do Soro , Administração Oral , Adulto , Combinação Amoxicilina e Clavulanato de Potássio/administração & dosagem , Combinação Amoxicilina e Clavulanato de Potássio/sangue , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Antibacterianos/farmacologia , Azitromicina/administração & dosagem , Azitromicina/sangue , Bactérias Aeróbias/efeitos dos fármacos , Bactérias Anaeróbias/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Haemophilus influenzae/efeitos dos fármacos , Humanos , Cetolídeos/administração & dosagem , Cetolídeos/sangue , Masculino , Pessoa de Meia-Idade , Peptostreptococcus/efeitos dos fármacos , Prevotella/efeitos dos fármacos , Prevotella melaninogenica/efeitos dos fármacos , Streptococcus pneumoniae/efeitos dos fármacos , Fatores de Tempo
15.
Clin Infect Dis ; 43(4): 518-24, 2006 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-16838243

RESUMO

Tigecycline (GAR-936) is the first glycylcycline antibiotic to be approved by the US Food and Drug Administration (FDA). The drug overcomes the 2 major resistance mechansisms of tetracycline: drug-specific efflux pump acquisition and ribosomal protection. Tigecycline is active against many gram-positive and -negative organisms, including methicillin-resistant Staphylococcus aureus, vancomycin-intermediate and -resistant enterococci, and extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae. It is also active against many anaerobic bacteria, as well as atypical pathogens, including rapidly growing, nontuberculous mycobacteria. Tigecycline is concentrated in cells and is eliminated primarily via biliary excretion. Diminished renal function does not significantly alter its systemic clearance. Furthermore, tigecycline does not interfere with common cytochrome P450 enzymes, making pharmacokinetic drug interactions uncommon. It provides parenteral therapy for complicated skin/skin-structure and intra-abdominal infections. The only prominent adverse effects are associated with tolerability, most notably nausea and vomiting. Tigecycline will be most useful as empirical therapy for polymicrobial infections, especially in cases in which deep tissue penetration is needed or in which multidrug-resistant pathogens are suspected.


Assuntos
Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Minociclina/análogos & derivados , Antibacterianos/economia , Humanos , Testes de Sensibilidade Microbiana , Minociclina/economia , Minociclina/farmacologia , Minociclina/uso terapêutico , Tigeciclina
16.
Clin Infect Dis ; 42(11): 1598-607, 2006 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-16652318

RESUMO

The usefulness of fluoroquinolones for the treatment of mixed aerobic and anaerobic infections has been investigated since these agents started being used in clinical practice. Newer compounds have increased in vitro activity against anaerobes, but clinically relevant susceptibility breakpoints for these bacteria have not been established. Pharmacodynamic analyses and corroboration by new data from clinical trials have enhanced our knowledge concerning the use of fluoroquinolones to treat selective anaerobic pathogens. These studies suggest that newer agents could be useful in the treatment of several types of mixed aerobic and anaerobic infections, including skin and soft-tissue, intra-abdominal, and respiratory infections. The major concerns with expanding the use of fluoroquinolones to treat anaerobic infections have been reports of increasing resistance in Bacteroides group isolates and the impact of these antibiotics on the incidence of Clostridium difficile-associated disease.


Assuntos
Antibacterianos/farmacologia , Bactérias Anaeróbias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Fluoroquinolonas/farmacologia , Humanos
17.
Clin Vaccine Immunol ; 23(11): 884-887, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27581438

RESUMO

Patients with end-stage renal disease (ESRD) and on dialysis are at increased risk of pneumococcal disease. We evaluated the immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) in this population. Eligible patients with ESRD and on dialysis were given a single dose of PCV13. The concentrations of serum antibodies against 13 pneumococcal capsular polysaccharides were measured at the baseline and at 2 and 12 months postvaccination. A response to the vaccine was defined as a ≥2-fold increase in antibody concentration from that at the baseline and an absolute postvaccination value of at least 1 µg/ml. Seventeen patients completed the study. Increases in the concentrations of antibodies to the vaccine serotype were demonstrated 2 months after vaccination. The geometric mean antibody concentrations at 12 months postvaccination declined by 38% to 72% compared to those measured at 2 months postvaccination. A response to at least 1 serotype in the vaccine was seen in all patients at both 2 and 12 months postvaccination. The overall rate of the response to each individual vaccine serotype varied between 23.5% and 94.1% at 2 months postvaccination and 23.5% and 65% at 12 months postvaccination. Pain at the injection site was the most common local reaction. Vaccination with PCV13 induces antibody responses to vaccine serotypes in patients with ESRD and on dialysis at 2 months postvaccination. However, the decline in antibody concentrations at 12 months postvaccination with a conjugate pneumococcal vaccine requires further study. (This study has been registered at ClinicalTrials.gov under registration no. NCT01974817.).


Assuntos
Anticorpos Antibacterianos/sangue , Imunogenicidade da Vacina , Falência Renal Crônica/imunologia , Vacinas Pneumocócicas/imunologia , Polissacarídeos Bacterianos/imunologia , Streptococcus pneumoniae/imunologia , Idoso , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/imunologia , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/efeitos adversos , Diálise Renal
18.
Clin Infect Dis ; 41 Suppl 5: S293-302, 2005 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-16080068

RESUMO

Several parenteral antimicrobials have been introduced into clinical practice over the course of the last decade. Some of these agents (e.g., linezolid, daptomycin, and tigecycline) are prototypes of new classes of compounds. In comparative clinical trials, these newer anti-infectives have been shown to be safe and to have low rates of discontinuation by patients. However, long-term use has revealed unique toxicities associated with the use of some of these drugs. The adverse events and potential drug interactions associated with the use of these antibiotics are variable and require familiarity with the safety profile of each drug. It is especially important that clinicians be able to recognize serious adverse events associated with the use of specific drugs, because most of the adverse events can be readily reversed by cessation of therapy.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Interações Medicamentosas , Humanos
19.
Pharmacotherapy ; 25(10 Pt 2): 44S-54S, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16178675

RESUMO

The growing threat posed by antibiotic-resistant pathogens is a major challenge for infectious disease practitioners and public health officials. In recent years, the prevalence of resistance among key bacterial pathogens, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Streptococcus pneumoniae, and Enterococcus sp, has increased at an alarming rate. The impact of antimicrobial resistance is manifold and can ultimately lead to treatment failure and increased morbidity and mortality. To control the spread of resistance and subsequent impact, a multifaceted approach is warranted. Awareness and surveillance of antimicrobial resistance, prudent use of antibiotics, and compliance with infection control techniques may help contain the emergence and spread of resistant organisms.


Assuntos
Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/prevenção & controle , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/prevenção & controle , Farmacorresistência Bacteriana , Controle de Infecções/métodos , Controle de Infecções/tendências , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/prevenção & controle , Infecções Bacterianas/microbiologia , Infecção Hospitalar/microbiologia , Humanos
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