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1.
J Glob Antimicrob Resist ; 33: 120-129, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36948495

RESUMO

OBJECTIVE: Generic medications are widely used because of their low cost. However, some generic medications show lower quality and clinical efficacy compared with brand-name medications, especially for antimicrobial drugs. Levofloxacin is a fluoroquinolone antimicrobial drug with excellent antimicrobial activity and wide antimicrobial spectrum, while it is susceptible to drug resistance. Our study aims to evaluate the bioequivalence of generic and brand-name levofloxacin. METHODS: The pharmacokinetic (PK) parameters (Cmax, AUC0∼24, Tmax, and t1/2), pharmacodynamic (PD) parameters (in vitro antibacterial activity and the inhibition of resistant mutation), and PK/PD analysis (the probability of target attainment; the cumulative fraction of response) calculated by Monte Carlo simulation were investigated. RESULTS: Our results demonstrated that compared with generics, brand-name levofloxacin not only had higher drug content, it also showed higher antimicrobial susceptibility, higher resistance to mutation ability, and higher percentage of each dosage interval wherein plasma concentration of antimicrobial agents exceeded the MPC90 (mutant prevention concentration to prevent the mutation of 90% strains) against various clinical isolates. Although the differences in AUC0∼24 between brand-name levofloxacin and generics were not statistically significant (P > 0.05, F test), Monte Carlo simulation results showed cumulative fraction of response values for PK/PD of brand-name medications were higher than generics. CONCLUSION: Our results indicated that PK or PD equivalence did not imply therapeutic equivalence; thus, we suggest including PK/PD analysis in the bioequivalence evaluation system, which benefits prediction of clinical outcome with high application value.


Assuntos
Anti-Infecciosos , Levofloxacino , Levofloxacino/farmacologia , Método de Monte Carlo , Antibacterianos , Fluoroquinolonas/farmacologia
2.
J Ayub Med Coll Abbottabad ; 35(Suppl 1)(4): S746-S751, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38406904

RESUMO

Background: Helicobacter pylori (H. pylori) is a gram-negative bacterium which usually resides in the mucoid lining of the stomach and may cause different gastric pathologies e.g., Gastritis, peptic ulcer disease, adenocarcinoma of the gastric system and mucoid associated lymphoma (MALT). The Objective was to compare the effect of 7-days Vonoprazan based triple therapy and 14-days Esomeprazole based triple therapy on eradication rate, compliance and cost effectiveness in Helicobacter pylori infected patients. Methods: This clinical trial was performed in the Department of Pharmacology Army Medical College, National University of Medical Sciences (NUMS) in collaboration with the Gastroenterology Department, Pak Emirates Military Hospital (PEMH) Rawalpindi from December 2022 to March 2023. A total of one hundred and twenty-two patients with dyspepsia symptoms and yielding lab results positive for Helicobacter pylori by stool antigen test were enrolled in the study. They were randomly allocated into two groups. The Esomeprazole group received 14 days of triple therapy orally with Esomeprazole 20 mg twice a day; Amoxicillin 1000 mg twice a day; and Levofloxacin 500 mg one time a day. The comparative Vonoprazan group was given 7-days triple therapy orally with Vonoprazan 20 mg twice a day; Amoxicillin 1000 mg twice a day; and Levofloxacin 500 mg one time a day. Eradication success was evaluated by stool antigen test four weeks later, as counted from the start of treatment. compliance and cost-effectiveness of both therapies were also assessed. Results: The eradication rate was (95.1%) in the Vonoprazan group with 58 out of 61 patients negative for H. pylori and (93.1%) in Esomeprazole group with 54 patients out of 58 yielding a negative result demonstrating p-value of 0.64. Compliance was 95.0% in the Esomeprazole group with p-value of 0.07. Cost effective ratio for Vonoprazan triple therapy was lower (731.8PKR) than the Esomeprazole group. Conclusion: One two-week Vonoprazan regimen demonstrated improved eradication rate, good compliance, and better tolerability in patients with less cost and a half duration of treatment in comparison with two weeks Esomeprazole regimen, attesting that one week Vonoprazan therapy is more cost efficacious in producing better results.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Pirróis , Sulfonamidas , Humanos , Amoxicilina/uso terapêutico , Amoxicilina/farmacologia , Antibacterianos/farmacologia , Análise Custo-Benefício , Análise de Custo-Efetividade , Quimioterapia Combinada , Esomeprazol/uso terapêutico , Esomeprazol/farmacologia , Infecções por Helicobacter/tratamento farmacológico , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Paquistão , Resultado do Tratamento
3.
Diagn Microbiol Infect Dis ; 103(1): 115662, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35321800

RESUMO

Although early transition from intravenous to oral antimicrobials can reduce hospitalization duration, susceptibility breakpoints have not been established for many oral antimicrobials against Escherichia coli and Klebsiella pneumoniae bacteremia. Thus, we used population pharmacokinetic models, pharmacokinetic/pharmacodynamic indices, and Monte Carlo simulations to evaluate the probability of target attainment (PTA) for common oral antimicrobial dosages against E. coli and K. pneumoniae. The oral antimicrobial agents evaluated included cephalexin, cefaclor, cefditoren, amoxicillin/clavulanic acid, faropenem, and levofloxacin. For E. coli, the percentage of isolates with minimum inhibitory concentrations for which a PTA >90% was achieved was 53% and less than 20% for levofloxacin and the ß-lactams, respectively. For K. pneumoniae, the percentages of isolates for which a PTA >90% was achieved were comparatively higher (cephalexin, 73%; amoxicillin/clavulanic acid, 83%; levofloxacin, 96%). Our results suggest clinicians should check if pharmacokinetic/pharmacodynamic indices are achieved in individual patients before transitioning to oral antimicrobial therapy.


Assuntos
Anti-Infecciosos , Infecções por Escherichia coli , Amoxicilina , Antibacterianos/uso terapêutico , Cefalexina , Ácido Clavulânico , Escherichia coli , Infecções por Escherichia coli/tratamento farmacológico , Humanos , Klebsiella pneumoniae , Levofloxacino/farmacologia , Testes de Sensibilidade Microbiana , Método de Monte Carlo , Probabilidade
4.
J Antimicrob Chemother ; 77(5): 1344-1352, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35178577

RESUMO

OBJECTIVES: This study aimed at characterizing the pharmacokinetics (PK) of oral levofloxacin in adult patients in order to optimize dosing scheme and explore the PK/pharmacodynamics (PD) of levofloxacin in bone and joint infections (BJIs). METHODS: From November 2015 to December 2019, all patients hospitalized in Cochin Hospital, treated with levofloxacin and who had at least one dosage for therapeutic drug monitoring were included. PK was described using non-linear mixed-effect modelling. In a subgroup of patients with BJIs, the association between PK, MIC for the isolated pathogen and clinical outcome was investigated. Monte Carlo simulations investigated dosing regimens to achieve the PK/PD target (AUC/MIC ratio >100). RESULTS: One hundred and two patients were included (199 measurements), including 32 treated for BJI. A one-compartment model with first-order absorption and elimination best described the data. Effects of estimated creatinine clearance (eCLCR) and age were significant on levofloxacin clearance. In BJI patients, no significant association was found between levofloxacin PK/microbiological parameters and either clinical outcome or adverse events. Based on our model, we proposed optimized oral levofloxacin dosing regimens according to renal function, to reach the PK/PD target AUC/MIC ratio >100 for three frequent causative pathogens (Staphylococcus aureus, Enterobacterales and Pseudomonas aeruginosa). CONCLUSIONS: Our results reinforce the need of determining the MIC and using therapeutic drug monitoring in complex infections caused by P. aeruginosa.


Assuntos
Doenças Transmissíveis , Levofloxacino , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Área Sob a Curva , Humanos , Levofloxacino/farmacologia , Testes de Sensibilidade Microbiana , Método de Monte Carlo , Pseudomonas aeruginosa , Staphylococcus aureus
5.
Artigo em Inglês | MEDLINE | ID: mdl-34801729

RESUMO

Aeromonas hydrophila is an opportunistic bacteria with an overwhelming impact on fish farming industry especially with upraising of drug resistant mutants. This study aimed to evaluate and compare the therapeutic and side effects of levofloxacin (LEV), chitosan-nanoparticles (CNPs), and fructooligosaccharides (FOS) in control of this infection in tilapia. A total of 160 Nile-tilapia divided into 8-groups; G1: negative-control, G2: infected-control, G3: non-infected-(levofloxacin (LEV) 10 mg/kg bwt), G4: non-infected-(chitosan-nanoparticles (CNPs) 1 g/kg ration), G5: non-infected-(fructooligosaccharides (FOS) 20 g/kg ration), G6: infected-LEV, G7: infected-CNPs and G8: infected-FOS for 7 days. MICs were (0.125 µg/ml and 1.25 mg/ml) for LEV and CNPs respectively. No mortalities or significant adverse effects were recorded in non-infected treated-groups while infected were (20%) LEV, (30%) CNPs, (40%) FOS and (70%) G2. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) decreased by LEV and CNPs than FOS while all increased total protein (TP) and albumin than G2. Malondialdehyde (MDA) significantly decreased and superoxide dismutase (SOD) and reduced glutathione (GSH) increased in all infected-treated groups than G2 in various degrees. Urea and creatinine descending order were FOS, LEV then CNPs decreased significantly than G2. LEV musculature residues, using HPLC, decreased gradually till the 5th day; 621.00 ± 0.66, 270.00 ± 0.48 then 64.00 ± 0.40, and 471.00 ± 0.79, 175.00 ± 0.52 ppb then not detected at 1st, 3rd, and 5th days of withdrawal in non-infected and infected groups respectively. Finally, LEV and CNPs were superior as bactericidal, decreasing mortalities and enzyme activities while CNPs and FOS increased performance, non-specific immunity, and antioxidant biomarkers.


Assuntos
Aeromonas hydrophila/efeitos dos fármacos , Antibacterianos/farmacologia , Doenças dos Peixes/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Nanopartículas/química , Ração Animal , Animais , Antibacterianos/análise , Antioxidantes/metabolismo , Aquicultura , Quitosana/química , Quitosana/farmacologia , Ciclídeos/crescimento & desenvolvimento , Ciclídeos/microbiologia , Doenças dos Peixes/microbiologia , Doenças dos Peixes/mortalidade , Doenças dos Peixes/patologia , Infecções por Bactérias Gram-Negativas/mortalidade , Infecções por Bactérias Gram-Negativas/patologia , Infecções por Bactérias Gram-Negativas/veterinária , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Levofloxacino/análise , Levofloxacino/farmacologia , Testes de Sensibilidade Microbiana , Oligossacarídeos/farmacologia , Prebióticos , Taxa de Sobrevida
6.
Braz J Microbiol ; 52(2): 597-606, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33483896

RESUMO

BACKGROUND AND AIM: Extensively drug-resistant (XDR) Klebsiella pneumoniae represent a major threat in intensive care units. The aim of the current study was to formulate a niosomal form of azithromycin (AZM) and to evaluate its in vitro effect on XDR K. pneumoniae as a single agent or in combination with levofloxacin. MATERIAL AND METHODS: Forty XDR K. pneumoniae isolates (23 colistin-sensitive and 17 colistin-resistant) were included in the study. Formulation and characterization of AZM niosomes were performed. The in vitro effect of AZM solution/niosomes alone and in combination (with levofloxacin) was investigated using the checkerboard assay, confirmed with time-kill assay and post-antibiotic effect (PAE). RESULTS: The AZM niosome mean minimal inhibitory concentration (MIC) (187.4 ± 209.1 µg/mL) was significantly lower than that of the AZM solution (342.5 ± 343.4 µg/mL). AZM niosomes/levofloxacin revealed a 40% synergistic effect compared to 20% with AZM solution/levofloxacin. No antagonistic effect was detected. The mean MIC values of both AZM niosomes and AZM solution were lower in the colistin-resistant group than in the colistin-sensitive group. The mean PAE time of AZM niosomes (2.3 ± 1.09 h) was statistically significantly longer than that of the AZM solution (1.37 ± 0.5 h) (p = 0.023). CONCLUSION: AZM niosomes were proved to be more effective than AZM solution against XDR K. pneumoniae, even colistin-resistant isolates.


Assuntos
Antibacterianos/farmacologia , Azitromicina/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Levofloxacino/farmacologia , Antibacterianos/química , Azitromicina/química , Composição de Medicamentos , Farmacorresistência Bacteriana Múltipla , Sinergismo Farmacológico , Klebsiella pneumoniae/crescimento & desenvolvimento , Lipossomos/química , Lipossomos/farmacologia , Testes de Sensibilidade Microbiana
7.
Molecules ; 27(1)2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-35011255

RESUMO

Helicobacter pylori is one of the most frequent human pathogens and a leading etiological agent of various gastric diseases. As stringent response, coordinated by a SpoT protein, seems to be crucial for the survivability of H. pylori, the main goal of this article was to use in silico computational studies to find phytochemical compounds capable of binding to the active site of SpoT from H. pylori and confirm the ability of the most active candidates to interfere with the virulence of this bacterium through in vitro experiments. From 791 natural substances submitted for the virtual screening procedure, 10 were chosen and followed for further in vitro examinations. Among these, dioscin showed the most interesting parameters (the lowest MIC, the highest anti-biofilm activity in static conditions, and a relatively low stimulation of morphological transition into coccoids). Therefore, in the last part, we extended the research with a number of further experiments and observed the ability of dioscin to significantly reduce the formation of H. pylori biofilm under Bioflux-generated flow conditions and its capacity for additive enhancement of the antibacterial activity of all three commonly used antibiotics (clarithromycin, metronidazole, and levofloxacin). Based on these results, we suggest that dioscin may be an interesting candidate for new therapies targeting H. pylori survivability and virulence.


Assuntos
Antibacterianos/química , Produtos Biológicos/química , Diosgenina/análogos & derivados , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Pirofosfatases/química , Virulência/efeitos dos fármacos , Sequência de Aminoácidos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Domínio Catalítico , Claritromicina/farmacologia , Diosgenina/química , Diosgenina/farmacologia , Avaliação Pré-Clínica de Medicamentos , Humanos , Levofloxacino/farmacologia , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Ligação Proteica , Conformação Proteica
8.
Artigo em Inglês | MEDLINE | ID: mdl-32482677

RESUMO

We isolated spontaneous levofloxacin-resistant strains of Mycobacterium aurum to study the fitness cost and compensatory evolution of fluoroquinolone resistance in mycobacteria. Five of six mutant strains with substantial growth defects showed restored fitness after being serially passaged for 18 growth cycles, along with increased cellular ATP level. Whole-genome sequencing identified putative compensatory mutations in the glgC gene that restored the fitness of the resistant strains, presumably by altering the bacterial energy metabolism.


Assuntos
Mycobacterium tuberculosis , Farmacorresistência Bacteriana/genética , Levofloxacino/farmacologia , Mutação , Mycobacteriaceae
9.
Am J Health Syst Pharm ; 76(2): 108-113, 2019 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31408091

RESUMO

PURPOSE: The stages of development of a health system-wide antimicrobial stewardship program (ASP) using existing personnel and technology are described. SUMMARY: Small hospitals with limited resources may struggle to meet ASP requirements, particularly facilities without onsite infectious disease physicians and/or experienced infectious disease pharmacists. Strategies for ASP development employed by Avera Health, a 33-hospital health system in the Midwest, included identifying relevant drug utilization and resistance patterns, education and pathway development, and implementation of Web-based conferencing to provide pharmacists throughout the system with access to infectious disease expertise on a daily basis. These efforts resulted in an evolving single-system ASP that has leveraged existing resources to overcome some system barriers. Program outcomes to date include a reduction in the use of a targeted agent, improved pathogen susceptibility trends, and rates of hospital-associated Clostridium difficile infection below national benchmarks. CONCLUSION: The Avera Health ASP grew from a collaborative project targeting levofloxacin overuse and resistance among key bacteria to a formal, health system-wide ASP in a rural setting. This program used existing personnel to provide standardized processes, educational campaigns, and antimicrobial expertise through the use of technology. This ASP program may provide helpful examples of ASP strategies for other rural health systems with similar resources.


Assuntos
Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/organização & administração , Infecções por Clostridium/tratamento farmacológico , Hospitais Rurais/organização & administração , Desenvolvimento de Programas , Antibacterianos/farmacologia , Gestão de Antimicrobianos/economia , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/isolamento & purificação , Clostridioides difficile/fisiologia , Infecções por Clostridium/microbiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Uso de Medicamentos , Hospitais Rurais/economia , Humanos , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Testes de Sensibilidade Microbiana , Farmacêuticos/organização & administração , Serviço de Farmácia Hospitalar/economia , Serviço de Farmácia Hospitalar/organização & administração , Papel Profissional , Avaliação de Programas e Projetos de Saúde , Serviços de Saúde Rural/economia , Serviços de Saúde Rural/organização & administração
10.
Microb Pathog ; 135: 103625, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31325570

RESUMO

This study was design to evaluate the physiological properties of bacteriophage-insensitive Klebsiella pneumoniae (BIKP) mutants in association with the antibiotic cross-resistance, ß-lactamase activity, and gene expression. Klebsiella pneumoniae ATCC 23357(KPWT), ciprofloxacin-induced antibiotic-resistant K. pneumoniae ATCC 23357 (KPCIP), and clinically isolated antibiotic-resistant K. pneumoniae 10263 (KPCLI) were used to isolate BIKP mutants against KPB1, PBKP02, PBKP21, PBKP29, PBKP33, and PBKP35. PBKP35-induced mutants, including bacteriophage-insensitive K. pneumoniae ATCC 23357 (BIKPWT), ciprofloxacin-induced K. pneumoniae ATCC 23357 (BIKPCIP), and clinically isolated antibiotic-resistant K. pneumoniae CCARM 10263 (BIKPCLI). BIKPWT, BIKPCIP, and BIKPCLI were resistant to Klebsiella bacteriophages, KPB1, PBKP02, PBKP21, PBKP29, and PBKP33. The antibiotic cross-resistance to cefotaxime, cephalothin, chloramphenicol, ciprofloxacin, erythromycin, kanamycin, levofloxacin, and nalidixic acid was observed in BIKPWT. The relative expression levels of vagC was increased by more than 8-folds in BIKPWT, corresponding to the increased ß-lactamase activity. The aac(6')-Ib-cr was overexpressed in BIKP mutants, responsible for aminoglycoside and quinolone resistance. The phage-resistant mutants decreased the antibiotic susceptibilities in association with ß-lactamase activity and antibiotic resistance-related gene expression. The results pointed out the cross-resistance of BIKP mutants to antibiotics, which might be considered when applying for the therapeutic use of bacteriophage.


Assuntos
Antibacterianos/farmacologia , Bacteriófagos/fisiologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/virologia , Aminoglicosídeos/genética , Cefotaxima/farmacologia , Cefalotina/farmacologia , Cloranfenicol/farmacologia , Ciprofloxacina/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Regulação Bacteriana da Expressão Gênica , Humanos , Levofloxacino/farmacologia , Terapia por Fagos , Quinolonas/farmacologia , beta-Lactamases/genética
11.
J Ocul Pharmacol Ther ; 35(6): 366-371, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31066613

RESUMO

Purpose: Patients with open globe injuries routinely receive fluoroquinolone (FQ) prophylaxis to prevent bacterial infectious endophthalmitis. Owing to the rarity of this infection, there is an absence of clinical trials evaluating optimal prophylactic FQ dosing. To address this knowledge gap, we conducted a Monte Carlo simulation (MCS)-based study to identify the FQ dosing option(s) that optimize pharmacokinetic-pharmacodynamic FQ target attainment against common bacterial pathogens implicated in post-traumatic bacterial infectious endophthalmitis (PTBIE). Methods: Weighted mean pharmacokinetic parameters and standard deviations for ciprofloxacin, levofloxacin, and moxifloxacin were calculated from published studies in healthy volunteers. The incidence and FQ susceptibility profiles for the most common bacteria causing PTBIE were extracted from the literature. MCS was used to determine the cumulative fraction of response (CFR) for 5 FQ dosing options to determine the probability of attaining pathogen-specific target 24-hour area under the curve to minimum inhibitory concentration ratios in the vitreous humor of the eye against the 4 most common causative bacteria seen in PTBIE. Results: Moxifloxacin 400 mg po daily (M400) achieved the highest CFR (72%). Levofloxacin dosing options achieved CFRs between 54% and 63%. Ciprofloxacin dosing options achieved CFRs between 28% and 35%. Conclusion: M400 optimized the likelihood of prophylactic success in the prevention of PTBIE, and based on the study findings, M400 is predicted to optimize the probability of success compared with ciprofloxacin and levofloxacin dosing options currently endorsed by expert opinion.


Assuntos
Antibacterianos/administração & dosagem , Antibioticoprofilaxia/métodos , Endoftalmite/prevenção & controle , Infecções Oculares Bacterianas/prevenção & controle , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Ciprofloxacina/administração & dosagem , Ciprofloxacina/farmacocinética , Ciprofloxacina/farmacologia , Bases de Dados Factuais , Relação Dose-Resposta a Droga , Endoftalmite/microbiologia , Infecções Oculares Bacterianas/microbiologia , Ferimentos Oculares Penetrantes/complicações , Ferimentos Oculares Penetrantes/tratamento farmacológico , Humanos , Levofloxacino/administração & dosagem , Levofloxacino/farmacocinética , Levofloxacino/farmacologia , Testes de Sensibilidade Microbiana , Modelos Biológicos , Método de Monte Carlo , Moxifloxacina/administração & dosagem , Moxifloxacina/farmacocinética , Moxifloxacina/farmacologia , Probabilidade
12.
Artigo em Inglês | MEDLINE | ID: mdl-29876099

RESUMO

Background: A high level of antibiotic consumption in France means antimicrobial resistance requires rigorous monitoring. The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) is a global surveillance study that monitors the in vitro activities of tigecycline and a panel of marketed antimicrobials against clinically important Gram-positive and Gram-negative isolates. Methods: Annually clinically relevant strains were prospectively included in the survey through a national network of hospital-based laboratories. MICs were determined locally by broth microdilution using CLSI guidelines. Antimicrobial susceptibility was assessed using European Committee on Antimicrobial Susceptibility Testing breakpoints. Results: Thirty-three centres in France collected 26,486 isolates between 2004 and 2016. Enterococcus species were highly susceptible (≥94.4%) to linezolid, tigecycline and vancomycin. Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), were susceptible (≥99.9%) to tigecycline, vancomycin and linezolid. Between 2004 and 2016, 27.7% of S. aureus isolates were MRSA, decreasing from 28.0% in 2013 to 23.5% in 2016. Susceptibility of Streptococcus pneumoniae isolates was 100% to vancomycin, and > 99.0% to levofloxacin, linezolid and meropenem; 3.0% were penicillin-resistant S. pneumoniae (100% susceptibility to vancomycin and linezolid). Escherichia coli isolates were highly susceptible (> 98.0%) to meropenem, tigecycline and amikacin. The rate of extended-spectrum ß-lactamase (ESBL) positive E. coli increased from 2004 (3.0%), but was stable from 2012 (23.1%) to 2016 (19.8%). Susceptibility of Klebsiella pneumoniae isolates was 99.4% to meropenem and 96.5% to amikacin. The proportion of ESBL-positive K. pneumoniae isolates increased from 2004 (7.5%) to 2012 (33.3%) and was highest in 2016 (43.6%). A. baumannii was susceptible to meropenem (81.0%) and amikacin (74.9%); none of the 6.2% of isolates identified as multidrug-resistant (MDR) was susceptible to any agents with breakpoints. P. aeruginosa isolates were most susceptible to amikacin (88.5%), and MDR rates were 13.6% in 2013 to 4.0% in 2016; susceptibility of MDR isolates was no higher than 31.4% to amikacin. Conclusions: Rates of MRSA decreased slowly, while rates of ESBL-positive E. coli and K. pneumoniae increased from 2004 to 2016. Susceptibility of Gram-positive isolates to vancomycin, tigecycline, meropenem and linezolid was well conserved, as was susceptibility of Gram-negative isolates to tigecycline and meropenem. The spread of MDR non-fermentative isolates must be carefully monitored.


Assuntos
Farmacorresistência Bacteriana Múltipla/fisiologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/isolamento & purificação , Amicacina/farmacologia , Enterococcus/efeitos dos fármacos , Enterococcus/isolamento & purificação , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , França , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Levofloxacino/farmacologia , Linezolida/farmacologia , Meropeném/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificação , Tigeciclina/farmacologia , Vancomicina/farmacologia
13.
Ann Clin Microbiol Antimicrob ; 15(1): 60, 2016 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-27938381

RESUMO

BACKGROUND: Bacteria treated with different classes of antibiotics exhibit changes in susceptibility to successive antibiotic treatments. This study was designed to evaluate the influence of sequential antibiotic treatments on the development of antibiotic resistance in Klebsiella pneumoniae associated with ß-lactamase and efflux pump activities. METHODS: The antibiotic susceptibility, ß-lactamase activity, and efflux activity were determined in K. pneumoniae grown at 37 °C by adding initial (0 h) and second antibiotics (8 or 12 h). Treatments include control (CON; no first and second antibiotic addition), no initial antibiotic addition followed by 1 MIC ciprofloxacin addition (CON-CIP), no initial antibiotic addition followed by 1 MIC meropenem addition (CON-MER), initial 1/4 MIC ciprofloxacin addition followed by no antibiotic addition (1/4CIP-CON), initial 1/4 MIC ciprofloxacin addition followed by 1 MIC ciprofloxacin addition (1/4CIP-CIP), and initial 1/4 MIC ciprofloxacin addition followed by 1 MIC meropenem addition (1/4CIP-MER). RESULTS: Compared to the CON, the initial addition of 1/4 MIC ciprofloxacin inhibited the growth of K. pneumoniae throughout the incubation period. The ciprofloxacin treatments (CON-CIP and 1/4CIP-CIP) showed significant reduction in the number of K. pneumoniae cells compared to meropenem (CON-MER and 1/4CIP-MER). The 1/4CIP-CIP achieved a further 1 log reduction of K. pneumoniae, when compared to the 1/4CIP-CON and 1/CIP-MER. The increase in sensitivity of K. pneumoniae to cefotaxime, kanamycin, levofloxacin, nalidixic acid was observed for CON-CIP. Noticeable cross-resistance pattern was observed at the 1/4CIP-CIP, showing the increased resistance of K. pneumoniae to chloramphenicol, ciprofloxacin, kanamycin, levofloxacin, nalidixic acid norfloxacin, sulphamethoxazole/trimethoprim, and tetracycline. The levels of ß-lactamase activities were estimated to be 8.4 µmol/min/ml for CON, 7.7 µmol/min/ml for 1/4CIP-CON and as low as 2.9 µmol/min/ml for CON-CIP. Compared to the absence of phenylalanine-arginine-ß-naphthylamide (PAßN), the fluorescence intensity of EtBr was increased in K. pneumoniae cells treated at the CON, CON-CIP, and CON-MER in the presence of PAßN. However, the efflux pump activity remained in K. pneumoniae cells treated at the 1/CIP, 1/CIP-CIP, and 1/CIP-MER in the presence of PAßN. CONCLUSION: The results suggest that the pre-exposed antibiotic history, treatment order, and concentrations influenced the development of multiple antibiotic resistant associated with ß-lactamase and efflux pump activities. This study highlights the importance of antibiotic treatment conditions, which would be taken into consideration when new antibiotic strategy is designed to prevent antibiotic resistance.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Klebsiella pneumoniae/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Ciprofloxacina/farmacologia , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/genética , Levofloxacino/farmacologia , Testes de Sensibilidade Microbiana , beta-Lactamases/metabolismo
14.
Infect Dis (Lond) ; 47(12): 846-51, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26167850

RESUMO

BACKGROUND: Stenotrophomonas maltophilia has emerged as an important opportunistic pathogen in recent years. Increasing antimicrobial resistance and other contraindications have greatly compromised trimethoprim/sulfamethoxazole (SXT) as the first-line therapeutic option. The objective of this study was to explore other options for treating hospital-acquired pneumonia (HAP) caused by S. maltophilia. METHODS: A total of 102 strains of S. maltophilia were isolated from sputum and bronchoalveolar lavage (BAL) specimens of patients with HAP in our institution. The minimum inhibitory concentration (MIC) values of minocycline, tigecycline, moxifloxacin, and levofloxacin were determined by the agar dilution method. Based on the MICs and the population pharmacokinetic parameters of the investigated antimicrobials, a Monte Carlo simulation was performed to simulate the pharmacokinetic/pharmacodynamic (PK/PD) indices of different regimens. The probability of target attainment (PTA) was estimated at each MIC value and the cumulative fraction of response (CFR) was calculated to evaluate the efficacy of these regimens. RESULTS: The susceptibility rates to minocycline, tigecycline, moxifloxacin, and levofloxacin were 96.1%, 80.4%, 74.5%, and 69.6%, respectively. The estimated CFRs were 96.2% for minocycline 100 mg twice daily; 50.8%/67.1%/75.4% for tigecycline 50/75/100 mg twice daily; 34.3%/48.0%/56.6% for levofloxacin 500/750/1000 mg once daily; and 45.7% for moxifloxacin 400 mg once daily. CONCLUSIONS: The simulation results suggest that minocycline may be a proper choice for treatment of HAP caused by S. maltophilia, while tigecycline, moxifloxacin, and levofloxacin may not be optimal as monotherapy.


Assuntos
Antibacterianos/farmacologia , Antibacterianos/farmacocinética , Infecção Hospitalar/tratamento farmacológico , Método de Monte Carlo , Pneumonia/tratamento farmacológico , Stenotrophomonas maltophilia/efeitos dos fármacos , Stenotrophomonas maltophilia/patogenicidade , Adulto , Líquido da Lavagem Broncoalveolar/microbiologia , Infecção Hospitalar/microbiologia , Feminino , Fluoroquinolonas/farmacocinética , Fluoroquinolonas/farmacologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Levofloxacino/farmacocinética , Levofloxacino/farmacologia , Masculino , Testes de Sensibilidade Microbiana , Minociclina/análogos & derivados , Minociclina/farmacocinética , Minociclina/farmacologia , Moxifloxacina , Pneumonia/microbiologia , Escarro/microbiologia , Stenotrophomonas maltophilia/isolamento & purificação , Tigeciclina
15.
Chemosphere ; 119: 282-288, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25036942

RESUMO

The characteristics of the oxidative transformation of the antibiotic levofloxacin (abbreviated as LEV) by manganese oxide were investigated. Up to 91% of LEV were removed with an equivalent of 200 units (abbreviated as equiv) of manganese oxide within a 35-day treatment period. A total of ten transformation products were identified, and five of them were newly reported. A tentative transformation pathway of LEV in the manganese oxide system involving oxidation and dealkylation was proposed. In addition, the variation in the genotoxicity and antibacterial activity along with the treatment by manganese oxide were traced using a SOS/umu assay and Escherichia coli growth inhibition assay, respectively. The results indicated that the genotoxicity significantly decreased in response to treatment with manganese oxide, while the antibacterial activity was not markedly affected until 160-equiv of δ-MnO2 were added. This study suggests that the oxidative degradation of LEV by manganese oxide can play an important role in the natural attenuation of LEV in sediment or soil matrices. The transformation reaction may be further optimized for removing quinolone antibiotics from wastewater or other environmental matrices to reduce the potential risk.


Assuntos
Antibacterianos/química , Levofloxacino/química , Compostos de Manganês/química , Óxidos/química , Antibacterianos/farmacologia , Antibacterianos/toxicidade , Poluentes Ambientais/química , Poluentes Ambientais/toxicidade , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Levofloxacino/farmacologia , Levofloxacino/toxicidade , Testes de Mutagenicidade , Oxirredução , Salmonella typhimurium/efeitos dos fármacos
16.
Int J Clin Pharm ; 36(5): 995-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25097067

RESUMO

BACKGROUND: Medicinal leech therapy is effective in establishing venous outflow in congested flaps and replants. However, its use is also associated with infections, especially from Aeromonas species. To prevent this nosocomial infection, levofloxacin has been established as prophylaxis during leech therapy in our hospital. OBJECTIVES: To study the implementation rate of a guideline, to study the effect of levofloxacin on possible Aeromonas infections, and to evaluate the financial impact of this preventive measure. SETTING: A retrospective analysis on all patients treated with Hirudo medicinalis between July 2007 and March 2011 was performed at the Ghent University Hospital, Belgium. METHOD: A list of patients treated with leeches was retrieved from the pharmacy database. Patient characteristics, date of start and stop of leech therapy were collected. Data on routine diagnostic cultures during leech therapy, date and type of clinical sample, while cultivated micro-organism with antibiotic susceptibility were obtained from the laboratory database. MAIN OUTCOME MEASURE: percentage implementation rate of a guideline, presence of Aeromonas infections, financial impact of levofloxacin prophylaxis. RESULTS: Fifty-one patients were treated with leeches. Forty-six (90.2 %) patients were treated according the guideline. Fourteen out of 51 patients (27.5 %) were suspected for postoperative wound infections. From them, 60 clinical samples were sent for microbiological analysis. These included exudates (26.7 %), peroperative samples (5.0 %), puncture fluid (1.7 %), blood cultures (3.3 %) or smears from burns (63.3 %). No Aeromonas species were cultivated. Comparison between period before and after implementation of levofloxacin prophylaxis revealed that levofloxacin prevents colonization or infection with Aeromonas species in relation to leech therapy. The direct cost for levofloxacin prophylaxis in the current study was 2,570 euro. Based on data obtained in a previous study, we presume that a minimum cost-saving of 20,500 euro was realised during the current study period by implementation of antimicrobial prophylaxis. CONCLUSIONS: This study demonstrates successful implementation of a guideline for levofloxacin prophylaxis during leech therapy. Following its introduction, no Aeromonas species related to the use of leeches were isolated as compared to 8.5 % in the baseline period.


Assuntos
Aeromonas/efeitos dos fármacos , Antibacterianos/farmacologia , Antibioticoprofilaxia , Infecções por Bactérias Gram-Negativas/prevenção & controle , Aplicação de Sanguessugas/efeitos adversos , Levofloxacino/farmacologia , Adolescente , Adulto , Antibacterianos/economia , Antibioticoprofilaxia/economia , Antibioticoprofilaxia/estatística & dados numéricos , Criança , Análise Custo-Benefício , Feminino , Infecções por Bactérias Gram-Negativas/economia , Fidelidade a Diretrizes/economia , Humanos , Levofloxacino/economia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
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