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1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
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
8.
J Med Case Rep ; 11(1): 278, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28964265

RESUMO

BACKGROUND: Cystic fibrosis is an autosomal recessive disorder characterized by chronic progressive multisystem involvement. AH1N1 virus infections caused classic influenza symptoms in the majority of cystic fibrosis patients while others experienced severe outcomes. CASE PRESENTATION: We report a case of late incidental cystic fibrosis diagnosis in a young Caucasian man suffering from respiratory failure following infection due to AH1N1 influenza virus. The patient was admitted to our department with fever, cough, and dyspnea at rest unresponsive to antibiotics CONCLUSIONS: Late diagnosis of cystic fibrosis in uncommon. This report highlights the importance of early cystic fibrosis diagnosis to minimize risk of occurrence of potential life-threatening complications.


Assuntos
Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Diagnóstico Tardio , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/complicações , Influenza Humana/virologia , Pneumonia/complicações , Antibacterianos/administração & dosagem , Ceftazidima/administração & dosagem , Colistina/administração & dosagem , Fibrose Cística/reabilitação , Fibrose Cística/terapia , Drenagem Postural , Testes Genéticos , Humanos , Achados Incidentais , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/tratamento farmacológico , Masculino , Meropeném , Pneumonia/diagnóstico por imagem , Pneumonia/tratamento farmacológico , Pneumonia/virologia , Encaminhamento e Consulta , Suor , Tienamicinas/administração & dosagem , Tomografia Computadorizada por Raios X , Adulto Jovem
9.
Adv Chronic Kidney Dis ; 24(4): 219-227, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28778361

RESUMO

Appropriate antibiotic dosing is critical to improve outcomes in critically ill patients with sepsis. The addition of continuous renal replacement therapy makes achieving appropriate antibiotic dosing more difficult. The lack of continuous renal replacement therapy standardization results in treatment variability between patients and may influence whether appropriate antibiotic exposure is achieved. The aim of this study was to determine if continuous renal replacement therapy effluent flow rate impacts attaining appropriate antibiotic concentrations when conventional continuous renal replacement therapy antibiotic doses were used. This study used Monte Carlo simulations to evaluate the effect of effluent flow rate variance on pharmacodynamic target attainment for cefepime, ceftazidime, levofloxacin, meropenem, piperacillin, and tazobactam. Published demographic and pharmacokinetic parameters for each antibiotic were used to develop a pharmacokinetic model. Monte Carlo simulations of 5000 patients were evaluated for each antibiotic dosing regimen at the extremes of Kidney Disease: Improving Global Outcomes guidelines recommended effluent flow rates (20 and 35 mL/kg/h). The probability of target attainment was calculated using antibiotic-specific pharmacodynamic targets assessed over the first 72 hours of therapy. Most conventional published antibiotic dosing recommendations, except for levofloxacin, reach acceptable probability of target attainment rates when effluent rates of 20 or 35 mL/kg/h are used.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Terapia de Substituição Renal/métodos , Sepse/tratamento farmacológico , Antibacterianos/sangue , Cefepima , Ceftazidima/administração & dosagem , Ceftazidima/sangue , Ceftazidima/farmacocinética , Cefalosporinas/administração & dosagem , Cefalosporinas/sangue , Cefalosporinas/farmacocinética , Simulação por Computador , Estado Terminal/terapia , Humanos , Levofloxacino/administração & dosagem , Levofloxacino/sangue , Levofloxacino/farmacocinética , Meropeném , Testes de Sensibilidade Microbiana , Método de Monte Carlo , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/sangue , Ácido Penicilânico/farmacocinética , Piperacilina/administração & dosagem , Piperacilina/sangue , Piperacilina/farmacocinética , Tazobactam , Tienamicinas/administração & dosagem , Tienamicinas/sangue , Tienamicinas/farmacocinética
10.
BMJ Case Rep ; 20172017 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-28751433

RESUMO

A 55-year-old man undergoing chemotherapy for recurrent multiple myeloma presented with a 2-day history of bilateral lower leg rash with pain and oedema. On examination, there were numerous non-palpable retiform pruritic patches over both lower legs. Skin pnch biopsy demonstrated a diffuse interstitial neutrophilic infiltrate with necrosis. Peripheral blood and skin tissue cultures both isolated Citrobacterfreundii, consistent with a rare form of ecthyma gangrenosum. The patient responded with appropriate antibiotic therapy and removal of medical port. He made a full recovery from this infectious complication of his underlying immunosuppression.


Assuntos
Antibacterianos/administração & dosagem , Citrobacter freundii/efeitos dos fármacos , Ectima/microbiologia , Infecções por Enterobacteriaceae/microbiologia , Extremidade Inferior/microbiologia , Mieloma Múltiplo/tratamento farmacológico , Tienamicinas/administração & dosagem , Desbridamento , Ectima/tratamento farmacológico , Ectima/imunologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Humanos , Hospedeiro Imunocomprometido , Masculino , Meropeném , Pessoa de Meia-Idade , Mieloma Múltiplo/imunologia , Doenças Raras , Resultado do Tratamento
11.
Pharmacotherapy ; 37(10): e96-e102, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28699652

RESUMO

Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) are becoming increasingly common worldwide. Although CPE infections can be fatal, few reports in the literature have described effective and successful treatments for infectious diseases caused by several types of IMP CPE, and, to our knowledge, no reports have described the successful treatment of IMP-6 CPE infections. We describe two patients who developed bacteremia caused by IMP-6 CPE after surgery for cancer who were successfully treated with amikacin plus high-dose prolonged-infusion meropenem. Both patients were treated over a 2-week period using amikacin 15 mg/kg at various intervals based on therapeutic drug monitoring and meropenem 2000 mg infused over 3 hours every 12 hours. The dosages of amikacin and meropenem were determined based on the creatinine clearance of each patient. Both patients were cured of their bacteremia and did not experience any antibiotic-related adverse effects. Based on the outcomes of these patients, it appears that amikacin plus high-dose prolonged-infusion meropenem may be safe and effective for the treatment of bacteremia caused by IMP-6 CPE.


Assuntos
Amicacina/uso terapêutico , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Enterobacteriáceas Resistentes a Carbapenêmicos/enzimologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Tienamicinas/uso terapêutico , Idoso , Amicacina/administração & dosagem , Antibacterianos/administração & dosagem , Bacteriemia/microbiologia , Proteínas de Bactérias/biossíntese , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Quimioterapia Combinada , Infecções por Enterobacteriaceae/microbiologia , Humanos , Masculino , Meropeném , Testes de Sensibilidade Microbiana , Tienamicinas/administração & dosagem , Resultado do Tratamento , beta-Lactamases/biossíntese
12.
J Med Case Rep ; 11(1): 48, 2017 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-28219414

RESUMO

BACKGROUND: Skull base osteomyelitis is an uncommon disease that usually complicates a malignant external otitis with temporal bone involvement. It affects predominantly diabetic and immunocompromised males and has a high mortality rate. Pseudomonas aeruginosa is the most common causative organism. Currently, there is no consensus about the best therapeutic option. Here we describe a case of severe skull base osteomyelitis caused by Pseudomonas aeruginosa with progressive palsy of cranial nerves that was successfully managed with prolonged outpatient continuous infusion of ceftazidime plus oral ciprofloxacin. CASE PRESENTATION: A 69-year-old Caucasian man presented with dysphagia, headache, and weight loss. He complained of left earache and purulent otorrhea. Over the following weeks he developed progressive palsy of IX, X, VI, and XII cranial nerves and papilledema. A petrous bone computed tomography scan showed a mass in the left jugular foramen with a strong lytic component that expanded to the cavum. A biopsy was then performed and microbiological cultures grew Pseudomonas aeruginosa. After 6 weeks of parenteral antibiotic treatment, our patient was discharged and treatment was continued with a domiciliary continuous infusion of a beta-lactam through a peripherally inserted central catheter, along with an oral fluoroquinolone for 10 months. Both radiological and clinical responses were excellent. CONCLUSIONS: Skull base osteomyelitis is a life-threating condition; clinical suspicion and correct microbiological identification are key to achieve an accurate and timely diagnosis. Due to the poor outcome of Pseudomonas aeruginosa skull base osteomyelitis, prolonged outpatient parenteral antibiotic therapy administered by continuous infusion could be a valuable option for these patients.


Assuntos
Antibacterianos/administração & dosagem , Ceftazidima/administração & dosagem , Ciprofloxacina/administração & dosagem , Osteomielite/tratamento farmacológico , Infecções por Pseudomonas , Pseudomonas aeruginosa , Idoso , Erros de Diagnóstico , Quimioterapia Combinada , Humanos , Masculino , Meropeném , Osteomielite/diagnóstico , Osteomielite/microbiologia , Tomografia por Emissão de Pósitrons , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Base do Crânio/diagnóstico por imagem , Tienamicinas/administração & dosagem , Tomografia Computadorizada por Raios X
13.
Eur J Clin Pharmacol ; 73(3): 333-342, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27966034

RESUMO

OBJECTIVES: The aim of this study was to evaluate different dosage regimens of meropenem in elderly patients in relation with renal function using a population pharmacokinetic (popPK) model. METHODS: The data of 178 elderly patients treated with meropenem was collected from different sources. A popPK model was developed by using NONMEM® and the influence of different covariates on meropenem CL and V1 was observed. Monte Carlo dosing simulations were performed at steady state to observe the % T > MIC for targets of 40, 60 and 80% of dosage intervals at different levels of creatinine clearance (CLCR). RESULTS: The data was described by a two-compartment model and the values of parameter estimates for CL, V1, Q and V2 were 5.27 L/h, 17.2 L, 9.92 L/h and 10.6 L, respectively. The CLCR, body weight and centre had a significant influence on meropenem CL while no direct influence of age was observed. Extended infusions had pharmacokinetic and pharmacodynamic (PK/PD) breakpoint one dilution greater than corresponding short infusion regimens for each target of % T > MIC. CONCLUSION: Meropenem CL was significantly lower in the elderly compared to CL reported in younger patients due to the reduced renal function. An extended infusion of 1000 mg q8h can be considered for empirical treatment of infections in elderly patients when CLCR is ≤ 50 mL/min. A continuous infusion of 3000 mg daily dose is preferred if CLCR > 50 mL/min. However, a higher daily dose of meropenem would be required for resistant strains (MIC >8 mg/L) of bacteria if CLCR is >100 mL/min.


Assuntos
Antibacterianos/farmacocinética , Testes de Função Renal , Tienamicinas/farmacocinética , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Feminino , Humanos , Masculino , Meropeném , Método de Monte Carlo , Tienamicinas/administração & dosagem , Tienamicinas/sangue
14.
Pediatr Blood Cancer ; 64(6)2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27873451

RESUMO

BACKGROUND: This randomized prospective study was designed to assess whether piperacillin/tazobactam (PIPC/TAZ) is as effective as meropenem (MEPM) as a first-line antibiotic treatment for febrile neutropenia (FN). PROCEDURE: FN episodes were randomly assigned to receive either PIPC/TAZ (337.5 mg/kg per day in three doses, 1-hr DIV, maximum 13.5 g per day) or MEPM (120 mg/kg per day in three doses, 1-hr DIV, maximum 3 g per day). Clinical responses were evaluated 120 hr after the DIV. RESULTS: A total of 434 febrile episodes in 105 patients (42 females and 63 males) with a median age of 8 years (range 0-25) were included in this trial. Blood cultures were positive in 47 out of the 434 episodes (10.8%). Regarding responses to the treatment, success rates between the PIPC/TAZ and MEPM groups were similar (62.4 vs. 65.9%, P = 0.484), even if patients were restricted to those with bacteremia (26.1 vs 37.5%, P = 0.534). Mortality rates did not significantly differ between the two groups (0.8 vs. 0%, P = 0.500). CONCLUSION: Both PIPC/TAZ and MEPM appeared to be equally efficacious and safe. Carbapenems are now broadly used to treat FN; however, this may increase the prevalence of drug-resistant bacteria. In this regard, the treatment using PIPC/TAZ for FN is more beneficial.


Assuntos
Antibacterianos/administração & dosagem , Neutropenia Febril Induzida por Quimioterapia/tratamento farmacológico , Neoplasias Hematológicas/tratamento farmacológico , Ácido Penicilânico/análogos & derivados , Tienamicinas/administração & dosagem , Adolescente , Adulto , 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
15.
Clin Microbiol Infect ; 23(3): 179-187, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27793737

RESUMO

OBJECTIVES: In Norway, initial treatment of febrile neutropenia (FN) has traditionally been benzylpenicillin plus an aminoglycoside. Internationally, FN is often treated with a broad-spectrum ß-lactam antibiotic. We aimed to compare these two regimens in a prospective, randomized, trial in patients with lymphoma or leukaemia with an expected period of neutropenia ≥7 days, and a suspected bacterial infection. METHODS: Adult neutropenic patients with lymphoma or leukaemia, and a suspected bacterial infection, were randomized for treatment with benzylpenicillin plus an aminoglycoside or meropenem. The primary endpoint was clinical success, defined as no modification of antibiotics and clinical stability 72 h after randomization. RESULTS: Among 322 randomized patients, 297 proved evaluable for analyses. Fifty-nine per cent (95% CI 51%-66%), (87/148) of the patients given benzylpenicillin plus an aminoglycoside were clinically stable, and had no antibiotic modifications 72 h after randomization, compared with 82% (95% CI 75%-87%), (122/149) of the patients given meropenem (p <0.001). When the antibiotic therapy was stopped, 24% (95% CI 18%-32%), (36/148) of the patients given benzylpenicillin plus an aminoglycoside, compared with 52% (95% CI 44%-60%), (78/149) of the patients given meropenem, had no modifications of their regimens (p <0.001). In the benzylpenicillin plus an aminoglycoside arm, the all-cause fatality within 30 days of randomization was 3.4% (95% CI 1.2%-7.9%), (5/148) of the patients, compared with 0% (95% CI 0.0%-3.0%), (0/149) of the patients in the meropenem arm (p 0.03). CONCLUSION: Clinical success was more common in FN patients randomized to meropenem compared with the patients randomized to benzylpenicillin plus an aminoglycoside. The all-cause fatality was higher among the patients given benzylpenicillin plus an aminoglycoside.


Assuntos
Aminoglicosídeos/administração & dosagem , Antibacterianos/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Leucemia/complicações , Linfoma/complicações , Penicilina G/administração & dosagem , Tienamicinas/administração & dosagem , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Meropeném , Pessoa de Meia-Idade , Mortalidade , Neutropenia/complicações , Noruega , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
16.
Crit Care ; 20(1): 343, 2016 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-27776537

RESUMO

BACKGROUND: Ventriculitis is a complication of temporary intraventricular drains. The limited penetration of meropenem into the cerebrospinal fluid (CSF) is well known. However, ventricular CSF pharmacokinetic data in patients with ventriculitis are lacking. The aim of this study was to evaluate meropenem pharmacokinetics in the serum and CSF of neurocritical care patients with proven or suspected ventriculitis. METHODS: We conducted an observational pharmacokinetic study of neurocritical care patients with proven or suspected ventriculitis receiving meropenem. Multiple blood and CSF samples were taken and were described using nonparametric pharmacokinetic modelling with Pmetrics. RESULTS: In total, 21 patients (median age 52 years, median weight 76 kg) were included. The median (range) of peak and trough concentrations in serum were 20.16 (4.40-69.00) mg/L and 2.54 (0.00-31.40) mg/L, respectively. The corresponding peak and trough concentrations in CSF were 1.20 (0.00-6.20) mg/L and 1.28 (0.00-4.10) mg/L, respectively, with a median CSF/serum ratio (range) of 0.09 (0.03-0.16). Median creatinine clearance ranged from 60.7 to 217.6 ml/minute (median 122.5 ml/minute). A three-compartment linear population pharmacokinetic model was most appropriate. No covariate relationships could be supported for any of the model parameters. Meropenem demonstrated poor penetration into CSF, with a median CSF/serum ratio of 9 % and high interindividual pharmacokinetic variability. CONCLUSIONS: Administration of higher-than-standard doses of meropenem and therapeutic drug monitoring in both serum and CSF should be considered to individualise meropenem dosing in neurocritical care patients with ventriculitis.


Assuntos
Antibacterianos/líquido cefalorraquidiano , Ventriculite Cerebral/líquido cefalorraquidiano , Ventriculite Cerebral/tratamento farmacológico , Cuidados Críticos/métodos , Tienamicinas/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Masculino , Meropeném , Pessoa de Meia-Idade , Estudos Prospectivos , Tienamicinas/administração & dosagem
17.
Acta Anaesthesiol Scand ; 60(10): 1425-1436, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27655029

RESUMO

BACKGROUND: Controversies remain regarding optimal dosing and the need for plasma concentration measurements when treating intensive care patients with beta-lactam antibiotics. METHODS: We studied ICU patients treated with either antibiotic, excluding patients on renal replacement therapy. Antibiotic concentrations were measured at the mid and end of the dosing interval, and repeated after 2-3 days when feasible. Glomerular filtration rate (GFR) was estimated from plasma creatinine and cystatin C, GFR calculated from cystatin C (eGFR) and measured creatinine clearance (CrCl). Measured concentrations were compared to the clinical susceptible breakpoints for Pseudomonas aeruginosa, 16 and 2 mg/l for piperacillin and meropenem respectively. RESULTS: We analysed 33 and 31 paired samples from 20 and 19 patients treated with piperacillin-tazobactam and meropenem respectively. Antibiotic concentrations at the mid and end of the dosing interval were for piperacillin, 27.0 (14.7-52.9) and 8.6 (2.7-30.3); and for meropenem, 7.5 (4.7-10.2) and 2.4 (1.0-3.5). All values median (interquartile range) and concentrations in mg/l. The percentage of measured concentrations below the breakpoint at the mid and end of the dosing interval were for piperacillin, 27% and 61%; and for meropenem, 6% and 48%. Lower estimates of GFR were associated with higher concentrations but concentrations varied greatly between patients with similar GFR. The correlation with terminal concentration half-life was similar for eGFR and CrCl. CONCLUSIONS: With standard doses of meropenem and piperacillin-tazobactam, plasma concentrations in ICU patients vary > 10-fold and are suboptimal in a significant percentage of patients. The variation is large also between patients with similar renal function.


Assuntos
Antibacterianos/administração & dosagem , Unidades de Terapia Intensiva , Ácido Penicilânico/análogos & derivados , Tienamicinas/administração & dosagem , Idoso , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Meropeném , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/sangue , Piperacilina/administração & dosagem , Piperacilina/sangue , Combinação Piperacilina e Tazobactam , Estudos Prospectivos , Tienamicinas/sangue
18.
Int J Low Extrem Wounds ; 15(2): 161-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27079487

RESUMO

Serratia marcescens is a Gram-negative bacillus belonging to the Enterobacteriaceae family. Cutaneous infection with Serratia is rare, and usually occurs in immunocompromised individuals. Primary cutaneous infections are uncommon, but they are typically severe and are associated with significant morbidity and mortality. The pathogenetic factors leading to S. marcescens infection are not fully understood, but contributing virulence factors include proteases, secreted exotoxins, and the formation of biofilm. We report a case of cellulitis occurring in a splenectomized patient, which led to multiple wound debridements and a transmetatarsal amputation. This dramatic case led us to review the published literature on soft tissue infections caused by S. marcescens.


Assuntos
Amputação Cirúrgica/métodos , Celulite (Flegmão) , Ciprofloxacina/administração & dosagem , Fasciite Necrosante , Dermatoses do Pé , Infecções por Serratia , Serratia marcescens/isolamento & purificação , Esplenectomia/efeitos adversos , Tienamicinas/administração & dosagem , Idoso , Antibacterianos/administração & dosagem , Biópsia/métodos , Celulite (Flegmão)/etiologia , Celulite (Flegmão)/patologia , Celulite (Flegmão)/fisiopatologia , Celulite (Flegmão)/terapia , Desbridamento/métodos , Fasciite Necrosante/etiologia , Fasciite Necrosante/patologia , Fasciite Necrosante/fisiopatologia , Fasciite Necrosante/terapia , Dermatoses do Pé/etiologia , Dermatoses do Pé/patologia , Dermatoses do Pé/fisiopatologia , Dermatoses do Pé/terapia , Humanos , Masculino , Meropeném , Infecções por Serratia/etiologia , Infecções por Serratia/patologia , Infecções por Serratia/fisiopatologia , Infecções por Serratia/terapia , Dermatopatias Vesiculobolhosas/etiologia , Dermatopatias Vesiculobolhosas/patologia , Dermatopatias Vesiculobolhosas/fisiopatologia , Dermatopatias Vesiculobolhosas/terapia , Resultado do Tratamento
19.
World J Urol ; 34(11): 1555-1559, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26951136

RESUMO

PURPOSE: To evaluate the efficacy of meropenem single dose before transrectal prostate biopsy, instead of ciprofloxacin in the era of fluoroquinolones resistance. METHODS: This prospective study included patients with indications for prostatic biopsy from January to December 2014. Those with known resistance in fluoroquinolones or meropenem or with decreased creatinine clearance were excluded. Patients were randomized into two groups, and statistical analysis was carried out. Group A received a 3-day course of ciprofloxacin 500 bid per os starting the day before biopsy. Group B received 1 g meropenem intravenously 1 h prior to the procedure. Patients were followed up for 15 days, and those with lower urinary tract symptoms (LUTS) and fever were called for hospitalization. Urine and blood cultures were obtained. RESULTS: A total of 110 patients, 52-75 years old (mean 67.5, median 66) participated in the study, allocated in Groups A and B. After the procedure, 18 patients (32.7 %) of Group A reported macroscopic hematuria, while 10 (18.2 %) reported rectal blood loss. Nine patients (16.3 %) presented because of fever and LUTS. One of them developed septic shock and died in the ICU. Cultures revealed multi-resistant E. coli with high sensitivity to meropenem, and patients were treated accordingly. In Group B, 20 (36.3 %) patients presented with macroscopic hematuria and 9 (16.3 %) with rectal blood loss. One patient returned to hospital with LUTS and fever. Cultures revealed Klebsiella pneumoniae sensitive to colimycine. CONCLUSIONS: A single dose of meropenem prior to prostate biopsy is a safe and effective way to avoid the possible infectious complications in high-risk patients.


Assuntos
Antibioticoprofilaxia/métodos , Biópsia por Agulha/efeitos adversos , Ciprofloxacina/administração & dosagem , Endossonografia/métodos , Infecções por Escherichia coli/prevenção & controle , Biópsia Guiada por Imagem/efeitos adversos , Tienamicinas/administração & dosagem , Idoso , Antibacterianos/administração & dosagem , Relação Dose-Resposta a Droga , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/etiologia , Infecções por Escherichia coli/microbiologia , Seguimentos , Humanos , Masculino , Meropeném , Pessoa de Meia-Idade , Estudos Prospectivos , Doenças Prostáticas/diagnóstico , Reto , Fatores de Tempo
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