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1.
Assist Inferm Ric ; 43(2): 83-90, 2024.
Artigo em Italiano | MEDLINE | ID: mdl-38873717

RESUMO

. The overlap Stevens-Johnson syndrome due to meropenem administration. Clinical case and nursing care. A case of overlap Stevens-Johnson syndrome caused by meropenem administration is described. It is a rare cutaneous reaction due to delayed hypersensitivity to drugs characterised by the destruction and separation of the skin epithelium and mucous membranes, affecting between 10% and 29% of the body surface area. The clinical description of the case and a detailed description of nursing management and interventions based on the available literature are reported.


Assuntos
Antibacterianos , Meropeném , Síndrome de Stevens-Johnson , Síndrome de Stevens-Johnson/enfermagem , Síndrome de Stevens-Johnson/etiologia , Humanos , Meropeném/administração & dosagem , Meropeném/efeitos adversos , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Feminino , Masculino , Tienamicinas/administração & dosagem , Tienamicinas/efeitos adversos
2.
Expert Opin Drug Metab Toxicol ; 14(10): 1007-1021, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30106599

RESUMO

INTRODUCTION: Meropenem/vaborbactam (M/V) represents the first carbapenem and ß-lactamase inhibitor combination approved for treatment of complicated urinary tract infections (cUTIs), including pyelonephritis. Vaborbactam is a novel boronic acid, ß-lactamase inhibitor with a high affinity for serine ß-lactamases, including Klebsiella pneumoniae carbapenemase (KPC). This combination, Vabomere™, was approved in August 2017 by the United States Food and Drug Administration for the treatment of cUTIs in patients 18 years or older, including pyelonephritis, caused by the following susceptible microorganisms: Escherichia coli, K. pneumoniae, and Enterobacter cloacae species complex. Areas covered: Relevant literature regarding microbiology, pharmacokinetics, pharmacodynamics, and clinical trials evaluating efficacy, safety, and tolerability will be discussed. Expert opinion: Current treatment options for KPC-producing infections such as aminoglycosides, polymyxins, fosfomycin, and tigecycline are associated with concerns regarding efficacy, toxicities, optimal dosing, and/or development of resistance. Additionally, resistance to the new combination product of ceftazidime/avibactam has also emerged. Current clinical evidence supporting the use of M/V for KPC-producing infections is limited to an open-label, randomized, phase III study in a small number of patients with serious infections due to carbapenem-resistant Enterobacteriaceae. Although M/V is not approved for KPC-producing infections, we believe that M/V will become a preferred agent for KPC-producing Enterobacteriaceae infections.


Assuntos
Antibacterianos/administração & dosagem , Ácidos Borônicos/administração & dosagem , Tienamicinas/administração & dosagem , Infecções Urinárias/tratamento farmacológico , Animais , Antibacterianos/farmacocinética , Ácidos Borônicos/farmacocinética , Combinação de Medicamentos , Farmacorresistência Bacteriana , Humanos , Meropeném , Ensaios Clínicos Controlados Aleatórios como Assunto , Tienamicinas/farmacocinética
3.
Expert Opin Pharmacother ; 19(13): 1495-1502, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30160990

RESUMO

INTRODUCTION: Meropenem-vaborbactam is a new beta-lactam/beta-lactamase inhibitor combination that combines a carbapenem antibiotic with a first-in-class, boronic acid pharmacophore, serine beta-lactamase inhibitor which has potent inhibitory activity against class A carbapenemases, especially Klebsiella pneumoniae carbapenemases (KPC), in addition to other class A and class C beta-lactamases. The US Food and Drug Administration has recently approved meropenem-vaborbactam for the treatment of adult patients with complicated urinary tract infections including acute pyelonephritis. Areas covered: A PubMed search was performed to gather the most current and relevant articles regarding meropenem-vaborbactam. In this review the authors discuss the chemistry, mechanism of action, pharmacokinetics, pharmacodynamics, antimicrobial spectrum, and efficacy and safety of meropenem-vaborbactam for the treatment of complicated urinary tract infections including acute pyelonephritis Expert opinion: Although meropenem-vaborbactam is approved for treatment for complicated urinary tract infections including acute pyelonephritis, it is unlikely, at this point, to be utilized widely beyond cases that are caused by KPC-producing Enterobacteriaceae. It may also be a potential treatment option for complicated urinary tract infections caused by KPC-producing Enterobacteriaceae that are resistant to ceftazidime-avibactam. Long-term safety data with this novel beta-lactamase inhibitor is still needed although early data suggests that it will be safe and well tolerated.


Assuntos
Ácidos Borônicos/administração & dosagem , Tienamicinas/administração & dosagem , Infecções Urinárias/tratamento farmacológico , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Compostos Azabicíclicos/administração & dosagem , Ceftazidima/administração & dosagem , Combinação de Medicamentos , Enterobacteriaceae/efeitos dos fármacos , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Meropeném , Pielonefrite/tratamento farmacológico
4.
Int J Pharm ; 548(1): 443-453, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30008433

RESUMO

Antibiotic combination therapy is promising for the treatment of lower respiratory tract infections caused by multi-drug resistant Gram-negative pathogens. Inhaled antibiotic therapy offers the advantage of direct delivery of the drugs to the site of infection, as compared to the parenteral administrations. In this study, we developed composite particle formulations of colistin and meropenem. The formulations were characterized for particle size, morphology, specific surface area, surface chemical composition, in-vitro aerosolization performance and in-vitro antibacterial activity. The combinations demonstrated enhanced antibacterial activity against clinical isolates of Acinetobacter baumannii N16870 and Pseudomonas aeruginosa 19147, when compared with antibiotic monotherapy. Spray-dried meropenem alone showed a poor aerosolization performance as indicated by a low fine particle fraction (FPF) of 32.5 ±â€¯3.3%. Co-spraying with colistin improved the aerosolization of meropenem with up to a two-fold increase in the FPF. Such improvements in aerosolization can be attributed to the enrichment of colistin on the surface of composite particles as indicated by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS), and the increases in particle porosity. Intermolecular interactions between colistin and meropenem were observed for the combination formulations as measured by FT-IR. In conclusion, our results show that co-spray drying with colistin improves the antibacterial activity and aerosol performance of meropenem and produces a formulation with synergistic bacterial killing.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/administração & dosagem , Colistina/administração & dosagem , Pseudomonas aeruginosa/efeitos dos fármacos , Tienamicinas/administração & dosagem , Acinetobacter baumannii/crescimento & desenvolvimento , Administração por Inalação , Aerossóis , Antibacterianos/química , Colistina/química , Sinergismo Farmacológico , Meropeném , Tamanho da Partícula , Porosidade , Pseudomonas aeruginosa/crescimento & desenvolvimento , Propriedades de Superfície , Tienamicinas/química
5.
BMJ Case Rep ; 20182018 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-30021738

RESUMO

Microbial keratitis is a common corneal condition, with many known risk factors. We present a case of an 88-year-old female patient with a multidrug-resistant Achromobacter xylosoxidans corneal ulcer in a previously failed second penetrating keratoplasty, successfully managed with topical meropenem drops administered hourly around the clock, for five days preceding and then hourly day only, for five days following a repeat third penetrating keratoplasty. Topical meropenem 50 mg/mL was prepared by mixing a 500 mg vial of meropenem with 10 mL of sterile water with pharmacy advice that administration should be within an hour. To the best of our knowledge, this is the first report of the use of topical meropenem in the management of A.xylosoxidans keratitis. This case highlights the importance of the mean inhibitory concentrations for antibiotics when considering sensitivities. Topical meropenem may be a useful treatment option for multidrug-resistant bacterial corneal ulcers that are resistant to conventional therapy.


Assuntos
Achromobacter denitrificans , Antibacterianos/administração & dosagem , Úlcera da Córnea/tratamento farmacológico , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Tienamicinas/administração & dosagem , Achromobacter denitrificans/efeitos dos fármacos , Administração Oftálmica , Idoso de 80 Anos ou mais , Úlcera da Córnea/microbiologia , Úlcera da Córnea/cirurgia , Resistência a Múltiplos Medicamentos , Farmacorresistência Bacteriana Múltipla , Infecções Oculares Bacterianas/microbiologia , Feminino , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Ceratoplastia Penetrante , Meropeném , Cuidados Pré-Operatórios/métodos
6.
Medicine (Baltimore) ; 97(25): e11200, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29924043

RESUMO

RATIONALE: Acute calculous cholecystitis is a prevalent disease whose diagnosis and management still face significant debate. Although the overall incidence of gallstone disease is 18.8% in European women aged 30 to 69 years, there is little data and experience in managing acute calculous cholecystitis in populations over 80 years old. The incidence of acute cholecystitis among the elderly is probably increasing. For the reason, we here highlight the advantages and disadvantage of various treatment and management opens based on a 96-year-old patient. PATIENT CONCERNS: We present a rare case in which a 96-year-old woman suffered from abdominal pain, nausea, and lack of appetite for over a month. DIAGNOSES: She was diagnosed with acute calculous cholecystitis and pancreatitis. INTERVENTIONS: She was successfully treated without surgery, regaining her physical health after 5 months. OUTCOMES: The question of how to manage acute calculous cholecystitis is extremely difficult in many aspects. The patient of very advanced age presented in this paper, not very well diagnosed and with a life-threating condition, survived because of careful treatment and reasonable decision-making. LESSONS: The take-away from this case is that, in a high-risk senile patient, strict conservative therapy of cholecystitis may be successful, as it can avoid the complications of surgery and leave the patient with a good quality of life.


Assuntos
Colecistite Aguda/complicações , Colecistite Aguda/tratamento farmacológico , Tratamento Conservador/métodos , Pancreatite/complicações , Pancreatite/tratamento farmacológico , Administração Intravenosa , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Colecistite Aguda/diagnóstico , Tomada de Decisão Clínica/métodos , Confiabilidade dos Dados , Feminino , Humanos , Meropeném , Tienamicinas/administração & dosagem , Tienamicinas/uso terapêutico , Resultado do Tratamento
7.
BMJ Case Rep ; 20182018 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-29643137

RESUMO

Empyema secondary to foreign body aspiration is rare in adults. We present a case of empyema in a 77-year-old male patient related to a remote aspiration event during a dental procedure. A CT of the chest and bronchoscopy confirmed that a metallic foreign body was located within the right lower lobe bronchus. His pleural fluid culture revealed Sphingomonas paucimobilis which is a low-virulent opportunistic gram-negative bacilli and rarely causes infection. The patient received meropenem followed by levofloxacin and recovered uneventfully. The attempt of foreign body removal was failed due to chronic inflammation, and the patient refused further surgical management.


Assuntos
Antibacterianos/administração & dosagem , Corpos Estranhos/diagnóstico por imagem , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Levofloxacino/administração & dosagem , Sphingomonas , Tienamicinas/administração & dosagem , Idoso , Broncoscopia , Empiema Pleural/etiologia , Infecções por Bactérias Gram-Negativas/diagnóstico , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Meropeném , Aspiração Respiratória , Sphingomonas/isolamento & purificação , Tomografia Computadorizada por Raios X
8.
Medicine (Baltimore) ; 97(15): e0305, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29642157

RESUMO

RATIONALE: Necrotizing fasciitis (NF) is defined as a rare, rapidly progressive, and highly lethal skin infection characterized by necrosis of the fascia and subcutaneous tissue. PATIENT CONCERNS: The present study aims to discuss the case of a 35-year-old man who developed NF following a routine sterile right distal radius bone plate removal surgery. DIAGNOSES: The patient was suspected of NF based on his clinical manifestations, laboratory tests, and imaging results. The diagnosis of NF was confirmed by histological examinations. INTERVENTIONS: Serial prompt and extensive debridement was performed during the rapid and aggressive extension of the skin infection, together with antibiotics and supportive treatments. OUTCOMES: The condition of the patient finally improved on the sixth day of disease progression. Skin grafting of his right forearm wound was performed successfully 2 months after the admission. LESSONS: NF can occur during the perioperative period for routine clean radius plate removal operation in patients with no risk factor for NF. The objective is to remind the physicians to stay aware of this disease, especially its early clinical signs and symptoms. Urgent subsequent treatment, including surgical debridement, antibiotic therapy, and supporting management, is the key to ensure the survival and better prognosis of patients.


Assuntos
Placas Ósseas , Cefonicida/administração & dosagem , Desbridamento/métodos , Descompressão Cirúrgica/métodos , Remoção de Dispositivo/efeitos adversos , Fasciite Necrosante , Antebraço , Reoperação/efeitos adversos , Streptococcus pyogenes/isolamento & purificação , Tienamicinas/administração & dosagem , Vancomicina/administração & dosagem , Adulto , Antibacterianos/administração & dosagem , Remoção de Dispositivo/métodos , Progressão da Doença , Fasciite Necrosante/diagnóstico , Fasciite Necrosante/etiologia , Fasciite Necrosante/fisiopatologia , Antebraço/diagnóstico por imagem , Antebraço/patologia , Fixação de Fratura/instrumentação , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Meropeném , Fraturas do Rádio/cirurgia , Reoperação/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
9.
Diagn Microbiol Infect Dis ; 91(3): 294-297, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29661528

RESUMO

Meropenem exposures from 15 children (8-17 years old) with cystic fibrosis (CF) acute pulmonary exacerbation were analyzed to define the pharmacodynamic threshold required for a positive response. The primary endpoint was the relative increase in forced expiratory volume in 1 s (↑FEV1) between pre- and posttreatment. Meropenem pharmacodynamic indices (fT > MIC, fAUC/MIC, fCmin/MIC) over the first 24 h were estimated for each participant based on their individual parameter estimates and the isolated pathogen with the highest meropenem MIC. Pseudomonas aeruginosa was the most common pathogen (n = 11/15). The mean ± SD ↑FEV1 was 18.8% ± 11.3% posttreatment. The mean (range) fT > MIC exposure was 63% (0-100%). An Emax model determined a significant relationship between fT > MIC and ↑FEV1 (r2 = 0.8, P < 0.0004). 65% fT > MIC was a significant predictor of response; the median (25th, 75th %) ↑FEV1 was 28.5% (22.2%, 31.7%) in those patients who achieved above 65% fT > MIC and 7.8% (1.1%, 12.6%) in those at or below 65% fT > MIC (P = 0.001). This is the first study in CF children to link meropenem exposure with a positive response as measured by ↑FEV1. Larger studies are required to confirm this exposure threshold.


Assuntos
Antibacterianos/administração & dosagem , Fibrose Cística/complicações , Pneumonia Bacteriana/epidemiologia , Tienamicinas/administração & dosagem , Adolescente , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Criança , Feminino , Humanos , Masculino , Meropeném , Testes de Sensibilidade Microbiana , Pneumonia Bacteriana/patologia , Pseudomonas aeruginosa/isolamento & purificação , Tienamicinas/farmacocinética , Tienamicinas/farmacologia , Fatores de Tempo , Resultado do Tratamento
10.
Intern Med J ; 48(4): 461-465, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29623994

RESUMO

Six cases of cutaneous melioidosis from southwestern Australia, a non-endemic region occurred as a result of Burkholderia pseudomallei contamination of normal saline that was used for irrigating superficial wounds. Treatment with parenteral meropenem, given by continuous infusion for 2 weeks, followed by oral antibiotics was successful in all cases.


Assuntos
Burkholderia pseudomallei , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/epidemiologia , Surtos de Doenças , Melioidose/diagnóstico , Melioidose/epidemiologia , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Burkholderia pseudomallei/isolamento & purificação , Infecção Hospitalar/tratamento farmacológico , Feminino , Humanos , Infusões Intravenosas , Masculino , Meropeném , Pessoa de Meia-Idade , Tienamicinas/administração & dosagem , Resultado do Tratamento , Austrália Ocidental/epidemiologia
11.
JAMA ; 319(8): 788-799, 2018 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-29486041

RESUMO

Importance: Meropenem-vaborbactam is a combination carbapenem/beta-lactamase inhibitor and a potential treatment for severe drug-resistant gram-negative infections. Objective: To evaluate efficacy and adverse events of meropenem-vaborbactam in complicated urinary tract infection (UTI), including acute pyelonephritis. Design, Setting, and Participants: Phase 3, multicenter, multinational, randomized clinical trial (TANGO I) conducted November 2014 to April 2016 and enrolling patients (≥18 years) with complicated UTI, stratified by infection type and geographic region. Interventions: Eligible patients were randomized 1:1 to receive meropenem-vaborbactam (2g/2g over 3 hours; n = 274) or piperacillin-tazobactam (4g/0.5g over 30 minutes; n = 276) every 8 hours. After 15 or more doses, patients could be switched to oral levofloxacin if they met prespecified criteria for improvement, to complete 10 days of total treatment. Main Outcomes and Measures: Primary end point for FDA criteria was overall success (clinical cure or improvement and microbial eradication composite) at end of intravenous treatment in the microbiologic modified intent-to-treat (ITT) population. Primary end point for European Medicines Agency (EMA) criteria was microbial eradication at test-of-cure visit in the microbiologic modified ITT and microbiologic evaluable populations. Prespecified noninferiority margin was -15%. Because the protocol prespecified superiority testing in the event of noninferiority, 2-sided 95% CIs were calculated. Results: Among 550 patients randomized, 545 received study drug (mean age, 52.8 years; 361 [66.2%] women; 374 [68.6%] in the microbiologic modified ITT population; 347 [63.7%] in the microbiologic evaluable population; 508 [93.2%] completed the trial). For the FDA primary end point, overall success occurred in 189 of 192 (98.4%) with meropenem-vaborbactam vs 171 of 182 (94.0%) with piperacillin-tazobactam (difference, 4.5% [95% CI, 0.7% to 9.1%]; P < .001 for noninferiority). For the EMA primary end point, microbial eradication in the microbiologic modified ITT population occurred in 128 of 192 (66.7%) with meropenem-vaborbactam vs 105 of 182 (57.7%) with piperacillin-tazobactam (difference, 9.0% [95% CI, -0.9% to 18.7%]; P < .001 for noninferiority); microbial eradication in the microbiologic evaluable population occurred in 118 of 178 (66.3%) vs 102 of 169 (60.4%) (difference, 5.9% [95% CI, -4.2% to 16.0%]; P < .001 for noninferiority). Adverse events were reported in 106 of 272 (39.0%) with meropenem-vaborbactam vs 97 of 273 (35.5%) with piperacillin-tazobactam. Conclusions and Relevance: Among patients with complicated UTI, including acute pyelonephritis and growth of a baseline pathogen, meropenem-vaborbactam vs piperacillin-tazobactam resulted in a composite outcome of complete resolution or improvement of symptoms along with microbial eradication that met the noninferiority criterion. Further research is needed to understand the spectrum of patients in whom meropenem-vaborbactam offers a clinical advantage. Trial Registration: clinicaltrials.gov Identifier: NCT02166476.


Assuntos
Antibacterianos/administração & dosagem , Ácidos Borônicos/administração & dosagem , Ácido Penicilânico/análogos & derivados , Pielonefrite/tratamento farmacológico , Tienamicinas/administração & dosagem , Infecções Urinárias/tratamento farmacológico , Doença Aguda , Adulto , Idoso , Antibacterianos/efeitos adversos , Ácidos Borônicos/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Meropeném , Pessoa de Meia-Idade , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/efeitos adversos , Piperacilina/administração & dosagem , Piperacilina/efeitos adversos , Combinação Piperacilina e Tazobactam , Guias de Prática Clínica como Assunto , Tienamicinas/efeitos adversos , Urina/microbiologia
12.
Medicine (Baltimore) ; 97(6): e9620, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29419663

RESUMO

RATIONALE: Infective endocarditis (IE) is a life-threatening disease, mostly caused by gram-positive bacteria. Gram-negative bacteria were identified as a causative organism in relatively small number of cases. Although, antibiotic-resistant Escherichia coli is common cause of gram-negative endocarditis, AmpC beta-lactamase (BL)-harboring E coli is very rare cause of IE. Furthermore, emphysematous endocarditis is also a very rare manifestation of E coli infection. PATIENT CONCERNS: We report a case of 80-year-old female patient presenting with dizziness, fever, and altered mental status, who was finally diagnosed with emphysematous endocarditis caused by E coli harboring an AmpC BL gene. DIAGNOSIS: Her chest computed tomography revealed air bubbles surrounding the annulus of a mitral valve and a transesophageal echocardiogram revealed a hyperechogenic mass fixed on the posteromedial side of the mitral annulus with 2 eccentric mitral regurgitation jets. Blood cultures grew E coli which harbored the DHA-type AmpC BL. The organism belonged to a B2 phylogenic group, and multilocus sequence typing analyses revealed that the strains were of ST-95. INTERVENTIONS: She was treated with meropenem following the resistant profiles, and surgery was recommended by the healthcare professional, but denied by the patient's guardians. She was transferred to another hospital due to a refusal for further treatment. LESSONS: Emphysematous endocarditis is an uncommon complication of E coli bacteremia. Certain phylogenetic groups may be associated with development of E coli endocarditis.


Assuntos
Proteínas de Bactérias/metabolismo , Enfisema , Endocardite Bacteriana , Escherichia coli , Tienamicinas , beta-Lactamases/metabolismo , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Técnicas de Tipagem Bacteriana/métodos , Ecocardiografia Transesofagiana/métodos , Enfisema/diagnóstico , Enfisema/etiologia , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/fisiopatologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Escherichia coli/fisiologia , Proteínas de Escherichia coli/metabolismo , Feminino , Humanos , Meropeném , Testes de Sensibilidade Microbiana/métodos , Administração dos Cuidados ao Paciente/métodos , Tienamicinas/administração & dosagem , Tienamicinas/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
13.
New Microbiol ; 41(1): 47-51, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29313863

RESUMO

This case series explored the pharmacokinetic/pharmacodynamic (PK/PD) characteristics of meropenem (MEM) in adult cystic fibrosis (CF) patients hospitalized for a pulmonary exacerbation. From January 2015 to June 2016, all adult patients with cystic fibrosis (CF) and chronic pulmonary infection due to meropenem (MEM)-susceptible/intermediate Pseudomonas aeruginosa who received at least 48 h of MEM as an extended 3-hour infusion for treating a pulmonary exacerbation were enrolled. MEM plasma concentrations were determined by high-performance liquid chromatography. Six adult CF patients with a median age of 47 years were included in the study. MEM showed a high Vd (mean 45.98 L, standard deviation [SD] ±34.45). A minimal PK/PD target of 40% T > minimum inhibitory concentration (MIC) with respect to the MEM MIC of P. aeruginosa strains isolated from sputum during exacerbation was achieved in 5/6 patients (83%). MEM failed to achieve this target only in one patient, whose strain showed the highest MEM MIC in our cohort (8 mg/L). In all patients, MEM was well tolerated, and no adverse events were reported. In conclusion, high-dose, extended-infusion MEM during pulmonary exacerbation showed a high Vd in six adult CF patients with high median age, and was well tolerated.


Assuntos
Fibrose Cística/tratamento farmacológico , Infecções por Pseudomonas/tratamento farmacológico , Tienamicinas/farmacocinética , Tienamicinas/uso terapêutico , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Farmacorresistência Bacteriana , Feminino , Humanos , Masculino , Meropeném , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Infecções por Pseudomonas/sangue , Pseudomonas aeruginosa/efeitos dos fármacos , Tienamicinas/administração & dosagem , Tienamicinas/sangue
14.
J Antimicrob Chemother ; 73(1): 191-198, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28961812

RESUMO

OBJECTIVES: To use a population pharmacokinetic approach to define maximally effective meropenem dosing recommendations for treatment of Acinetobacter baumannii and Pseudomonas aeruginosa infections in a large cohort of patients with septic shock. METHODS: Adult patients with septic shock and conserved renal function, treated with meropenem, were eligible for inclusion. Seven blood samples were collected during a single dosing interval and meropenem concentrations were measured by a validated HPLC-MS/MS method. Monte Carlo simulations were employed to define optimum dosing regimens for treatment of empirical or targeted therapy of A. baumannii and P. aeruginosa. EudraCT-no. 2014-002555-26 and NCT02240277. RESULTS: Fifty patients were included, 26 male and 24 female, with a median age of 64 years with an all-cause 90 day mortality of 34%. A two-compartment linear model including creatinine clearance (CLCR) as a covariate best described meropenem pharmacokinetics. For empirical treatment of A. baumannii, 2000 mg/6 h was required by intermittent (30 min) or prolonged (3 h) infusion, whereas 6000 mg/day was required with continuous infusion. For P. aeruginosa, 2000 mg/8 h or 1000 mg/6 h was required for both empirical and targeted treatment. In patients with a CLCR of ≤ 100 mL/min, successful concentration targets could be reached with intermittent dosing of 1000 mg/8 h. CONCLUSIONS: In patients with septic shock and possible augmented renal clearance, doses should be increased and/or administration should be performed by prolonged or continuous infusion to increase the likelihood of achieving therapeutic drug concentrations. In patients with normal renal function, however, standard dosing seems to be sufficient.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/administração & dosagem , Infecções por Pseudomonas/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Tienamicinas/administração & dosagem , Acinetobacter baumannii/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacocinética , Cromatografia Líquida de Alta Pressão , Creatinina/sangue , Feminino , Humanos , Masculino , Meropeném , Taxa de Depuração Metabólica/fisiologia , Pessoa de Meia-Idade , Modelos Teóricos , Estudos Prospectivos , Pseudomonas aeruginosa/efeitos dos fármacos , Choque Séptico/microbiologia , Espectrometria de Massas em Tandem , Tienamicinas/farmacocinética , Adulto Jovem
15.
J Infect Chemother ; 24(2): 92-98, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29054458

RESUMO

The purpose of this study was to estimate the in vivo pharmacokinetics of meropenem during intermittent-infusion hemodiafiltration (I-HDF) and clarify its optimal dosage and dosing interval in patients receiving I-HDF. The clearance of meropenem by online hemodiafiltration (OL-HDF) and I-HDF was predicted using an in vitro system and assessed to establish whether the results obtained are applicable to clinical cases. In the in vivo study, the mean volume of distribution (Vd), non-I-HDF clearance (CLnon-I-HDF), and I-HDF clearance (CLI-HDF) were 15.80 ± 3.59 l, 1.05 ± 0.27 l/h, and 5.78 ± 1.03 l/h. Dosing regimens of 0.25 g once daily for a MIC of 8 µg/ml and of 0.5 g once daily for a MIC of 16 µg/ml achieved 40% T > MIC. In the in vitro and in vivo studies, observed CLHDF was similar to predictive CLHDF (= Cf/Cp × (QD + QSUB)). In conclusion, adjustments to the dose and interval of meropenem were developed based on the presumed susceptibility of pathogens to meropenem in patients receiving I-HDF. We suggest 0.5 g once daily as an appropriate regimen for empirical treatment.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Hemodiafiltração , Tienamicinas/administração & dosagem , Tienamicinas/farmacocinética , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Meropeném , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Fatores de Tempo
16.
J Infect Chemother ; 24(5): 393-397, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29249641

RESUMO

A 73-year-old woman was admitted with consciousness disturbance following a fever. Abdominal computed tomography revealed a large liver abscess with which the presence of Desulfovibrio desulfuricans and Escherichia coli was confirmed by thorough blood and abscess content culture. Empiric meropenem treatment was switched to cefoperazone/sulbactam, followed by ampicillin/sulbactam based on susceptibility testing. Desulfovibrio desulfuricans is a common bacterium that rarely causes liver abscess and may be overlooked during co-infection due to overgrowth of the accompanying bacteria. Clinicians should bear Desulfovibrio desulfuricans in mind and select the appropriate antibiotics according to susceptibility testing when anaerobic bacteria are detected in a liver abscess.


Assuntos
Coinfecção/microbiologia , Desulfovibrio desulfuricans/isolamento & purificação , Infecções por Desulfovibrionaceae/microbiologia , Infecções por Escherichia coli/microbiologia , Escherichia coli/isolamento & purificação , Abscesso Hepático/microbiologia , Idoso , Ampicilina/administração & dosagem , Cefoperazona/administração & dosagem , Coinfecção/sangue , Coinfecção/tratamento farmacológico , Desulfovibrio desulfuricans/efeitos dos fármacos , Infecções por Desulfovibrionaceae/sangue , Infecções por Desulfovibrionaceae/tratamento farmacológico , Quimioterapia Combinada , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/sangue , Infecções por Escherichia coli/tratamento farmacológico , Feminino , Humanos , Abscesso Hepático/diagnóstico por imagem , Abscesso Hepático/tratamento farmacológico , Meropeném , Tienamicinas/administração & dosagem
17.
Eur J Drug Metab Pharmacokinet ; 43(1): 45-53, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28616823

RESUMO

BACKGROUND AND OBJECTIVE: For patients with intracranial infection, local intrathecal administration of meropenem may be a useful method to obtain a sufficient drug concentration in the cerebral spinal fluid (CSF). However, a large inter-individual variability may pose treatment efficacy at risk. This study aimed to identify factors affecting drug concentration in the CSF using population pharmacokinetics method. METHODS: After craniotomy, aneurysm patients with an indwelling lumbar cistern drainage tube who received a combined intravenous and intrathecal administration of meropenem for the treatment of suspected intracranial infection were enrolled. Venous blood and CSF specimens were collected for determining meropenem concentrations. Nonlinear mixed-effects modeling method was used to fit blood and CSF concentrations simultaneously and to develop the population pharmacokinetic model. The proposed model was applied to simulate dosage regimens. RESULTS: A three-compartmental model was established to describe meropenem in vivo behavior. Lumbar CSF drainage resulted in a drug loss, and drug clearance in CSF (CLCSF) was employed to describe this. The covariate analysis found that the drainage volume (mL/day) was strongly associated with CLCSF, and the effect of creatinine clearance was significant on the clearance of meropenem in blood (CL). Visual predictive check suggested that the proposed pharmacokinetic model agreed well with the observations. Simulation showed that both intravenous and intrathecal doses should be increased with the increases of minimum inhibitory concentration and daily CSF drainage volume. CONCLUSION: This model incorporates covariates of the creatinine clearance and the drainage volume, and a simple to use dosage regimen table was created to guide clinicians with meropenem dosing.


Assuntos
Aneurisma/complicações , Infecções do Sistema Nervoso Central/tratamento farmacológico , Craniotomia/efeitos adversos , Tienamicinas/administração & dosagem , Tienamicinas/farmacocinética , Administração Intravenosa , Adulto , Idoso , Aneurisma/sangue , Aneurisma/líquido cefalorraquidiano , Aneurisma/cirurgia , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Antibacterianos/líquido cefalorraquidiano , Antibacterianos/farmacocinética , Infecções do Sistema Nervoso Central/sangue , Infecções do Sistema Nervoso Central/líquido cefalorraquidiano , Infecções do Sistema Nervoso Central/complicações , Feminino , Humanos , Injeções Espinhais , Masculino , Meropeném , Pessoa de Meia-Idade , Modelos Biológicos , Tienamicinas/sangue , Tienamicinas/líquido cefalorraquidiano , Adulto Jovem
18.
Int J Antimicrob Agents ; 51(3): 484-487, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28709989

RESUMO

This study was conducted to identify optimal dosage regimens and estimate pharmacokinetic/pharmacodynamic (PK/PD) characteristics of short-infusion (SI) versus extended-infusion (EI) biapenem against Pseudomonas aeruginosa infections in Chinese intensive care unit (ICU) patients. A total of 85 strains of P. aeruginosa were collected, and the minimum inhibitory concentration (MIC) of biapenem was measured by the serial two-fold agar dilution method. We designed four frequently used clinical regimens: biapenem 300 mg I.V. q12h, q8h, and q6h, and 600 mg q12h. The Monte Carlo Simulation (MCS) was performed using previously published pharmacokinetic data to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of these regimens as an SI (0.5 h) and an EI (1 h, 2 h, 3 h, and 4 h). For a target of 40%fT>MIC (serum drug concentration remains above the MIC for a dosing period), none of the regimens achieved any CFRs>90% for P. aeruginosa, multidrug-resistant P. aeruginosa (MDR-PA) and even non-MDR-PA. The traditional biapenem SI regimens most commonly seen in clinical practice were insufficient in treating both MDR and non-MDR P. aeruginosa in ICU patients. However, biapenem 600 mg q12h over 2-4 h EI regimens could achieve CFR>90% with 20%fT>MIC. Clinical trials should aim to validate the potentially greater PK/PD index with higher, more frequent doses and longer extended infusions.


Assuntos
Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/farmacocinética , Infecções por Pseudomonas/tratamento farmacológico , Tienamicinas/administração & dosagem , Tienamicinas/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos/farmacologia , China , Feminino , Humanos , Infusões Intravenosas/métodos , Unidades de Terapia Intensiva , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Método de Monte Carlo , Estudos Prospectivos , Tienamicinas/farmacologia , Fatores de Tempo , Adulto Jovem
19.
J Microbiol Immunol Infect ; 51(4): 473-477, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28690028

RESUMO

BACKGROUND: Although survival of children with hematological diseases and cancer has increased dramatically, life-threatening complications due to bacterial infections occur in 5-10% of febrile episodes in pediatric cancer patients. A prospective randomized study was performed to clarify the usefulness of meropenem (MEPM) and piperacillin/tazobactam (PIPC/TAZ) with or without intravenous immunoglobulin (IVIG) as second-line therapy for pediatric patients with febrile neutropenia (FN). PROCEDURE: As first-line therapy for FN, 105 patients with 434 episodes were randomly assigned to receive MEPM or PIPC/TAZ. A total of 71 pediatric patients and 144 episodes were judged as failures and enrolled for second-line treatment. In second-line treatment, patients were randomized to a group of MEPM and PIPC/TAZ with or without IVIG. MEPM was given to patients who received PIPC/TAZ as first-line treatment, and PIPC/TAZ was given to patients who received MEPM as first-line treatment. RESULTS: The total success rate of second-line therapy was 49.3%. MEPM with or without IVIG was effective in 44.3% of cases, and PIPC/TAZ with or without IVIG was effective in 55.3%; this difference was not significant. The success rate in patients with serum IgG under 1000 mg/dl was 41.3% in the MEPM or PIPC/TAZ group and 64.3% in the MEPM + IVIG or PIPC/TAZ + IVIG group (p = 0.028). CONCLUSIONS: The present results suggest that PIPC/TAZ is as effective as MEPM and safe for second-line treatment of FN in pediatric patients. Furthermore, IVIG appears very effective for patients with low serum IgG levels.


Assuntos
Antibacterianos/administração & dosagem , Neutropenia Febril/tratamento farmacológico , Imunoglobulinas Intravenosas/administração & dosagem , Ácido Penicilânico/análogos & derivados , Tienamicinas/administração & dosagem , Inibidores de beta-Lactamases/administração & dosagem , Adolescente , Antibacterianos/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Meropeném , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/efeitos adversos , Piperacilina/administração & dosagem , Piperacilina/efeitos adversos , Combinação Piperacilina e Tazobactam , Estudos Prospectivos , Tienamicinas/efeitos adversos , Resultado do Tratamento , Adulto Jovem
20.
J Infect Public Health ; 11(4): 486-490, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29153444

RESUMO

BACKGROUND: The appropriate use of broad-spectrum antibiotics, including appropriate de-escalation, is essential to reduce the emergence of antibiotic resistance. In surgical floors antibiotics are prescribed for prophylaxis (mostly, single dose), empirical treatment (started if infection is suspected till bacteria are identified with its sensitivity to antibiotics), or treatment of well-defined infection of previously isolated bacteria with its sensitivity to antibiotics. In this study, we aimed to evaluate the use of broad-spectrum antibiotics based on requests for cultures and de-escalation based on sensitivity results of culture tests at tertiary care hospital. METHOD: A retrospective cohort study was conducted to evaluate the utilization of broad-spectrum antibiotics on surgical floors at a tertiary care center in Jeddah, Saudi Arabia. Patients who are admitted to surgical floors were included if they received any of three broad-spectrum antibiotics (piperacillin-tazobactam, imipenem-cilastatin or meropenem) from 1 June 2014 to 31 August 2014. Data were collected on whether culture and sensitivity test requests were made within 24h of starting antibiotics, the duration of antibiotic therapy and the number of days to de-escalation after receiving culture and sensitivity results. RESULTS: Of the 163 patients who received broad-spectrum antibiotics, culture tests were requested in 112. Before receiving culture results, one patient was discharged and one died. The results of culture tests justified continuation of broad-spectrum antibiotics in only 22 patients, whereas 24 showed no microbial growth in any culture. De-escalation was delayed >24h after culture results became available in 33 out of 64 eligible patients. On the other hand, 51 patients continued receiving broad spectrum antibiotics without any culture test during the whole treatment course. CONCLUSION: The use of broad-spectrum antibiotics in surgical floors at a tertiary care hospital in Saudi Arabia was largely unjustified by culture-test result. Interventions are needed to enforce culture and sensitivity test requests within 24h of starting the broad spectrum antibiotics therapy with further follow up to ensure appropriate de-escalation and discontinuation whenever indicated.


Assuntos
Antibacterianos/administração & dosagem , Cilastatina/administração & dosagem , Uso de Medicamentos/estatística & dados numéricos , Imipenem/administração & dosagem , Ácido Penicilânico/análogos & derivados , Infecção da Ferida Cirúrgica/prevenção & controle , Centros de Atenção Terciária , Adulto , Idoso , Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/métodos , Cilastatina/uso terapêutico , Combinação Imipenem e Cilastatina , Estudos de Coortes , Contagem de Colônia Microbiana , Combinação de Medicamentos , Feminino , Humanos , Imipenem/uso terapêutico , Masculino , Meropeném , Pessoa de Meia-Idade , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/uso terapêutico , Piperacilina/administração & dosagem , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Uso Indevido de Medicamentos sob Prescrição/estatística & dados numéricos , Estudos Retrospectivos , Arábia Saudita , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/microbiologia , Tienamicinas/administração & dosagem , Tienamicinas/uso terapêutico
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