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1.
Artigo em Inglês | MEDLINE | ID: mdl-32667390

RESUMO

Capnocytophaga is a group of facultative anaerobic gram-negative bacteria present in the oral cavity of humans, dogs and cats, as part of their normal oral flora. Here, we described two cases of bloodstream infections (BSI) caused by Capnocytophaga in neutropenic autologous hematopoietic stem cell transplantation (auto-HSCT) patients with mucositis (Grade I and Grade III) identified by Maldi-Tof. They were successfully treated with ß-lactam (meropenem and piperacillin-tazobactam). The species C. sputigena was confirmed by 16S rRNA gene sequencing in one patient. The review of literature showed that C. ochraceae was the most frequent species causing BSI in auto-HSCT patients and that the patients usually presented mucositis and were neutropenic at the onset of the infection.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/diagnóstico , Capnocytophaga/isolamento & purificação , Infecções por Bactérias Gram-Negativas/diagnóstico , Transplante de Células-Tronco Hematopoéticas/métodos , Neutrófilos/imunologia , Adulto , Bacteriemia/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/imunologia , Humanos , Meropeném/uso terapêutico , Pessoa de Meia-Idade , Mucosite , Piperacilina/uso terapêutico , RNA Ribossômico 16S , Análise de Sequência de DNA , Tazobactam/uso terapêutico , Transplante Autólogo
3.
Brasília; s.n; 22 maio 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1097386

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 21 artigos e 13 protocolos.


Assuntos
Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Progressão da Doença , Betacoronavirus/efeitos dos fármacos , Piperacilina/uso terapêutico , Avaliação da Tecnologia Biomédica , Vacinas/provisão & distribução , Cloroquina/uso terapêutico , Ativador de Plasminogênio Tecidual/uso terapêutico , Corticosteroides/uso terapêutico , Ritonavir/uso terapêutico , Combinação de Medicamentos , Lopinavir/uso terapêutico , Cloridrato de Fingolimode/uso terapêutico , Tazobactam/uso terapêutico , Hidroxicloroquina/uso terapêutico , Insulina/uso terapêutico , Anticoagulantes/uso terapêutico
4.
Malawi Med J ; 31(3): 223-226, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31839893

RESUMO

Background: Necrotizing pneumonia and hyperleukocytosis, to the extent of that seen in leukaemia, is a rarely reported presentation. The commonest trigger of such a presentation is an inflammatory process caused by an overwhelming infection which leads to bone marrow irritation. However, the misdiagnosis of this clinical entity as leukaemia should be avoided at all costs so as to avoid the anxiety associated with a diagnosis of cancer, both to the patients and their families. Case presentation: Here, we report the case of a 22-month-old boy who was referred to our Pediatric Oncology Unit (POU). Owing to a high total leukocyte count (TLC) of 98,000 cells/µl, there was a strong suspicion of leukaemia. The boy had been reviewed at another hospital where he presented with fever and cough refractory to the commencement of tuberculosis medications as a result of chest radiography findings. Laboratory investigations performed on admission in the POU were negative for leukaemia and other myeloproliferative disorders. A chest computer tomography (CT) scan was performed to delineate opacification in the right middle lobe. This revealed multiple necrotic and emphysematous foci in line with a diagnosis of necrotizing pneumonia. Subsequently, the patient responded well to a course of piperacillin- tazobactam. The TLC normalized and the cough and fever resolved over a period of 2 weeks. Conclusion: Here, we describe a particularly rare case of leukaemoid reaction with a massive leukocyte count. Such patients can be easily misdiagnosed as having leukaemia or other myeloproliferative disorders, especially in settings with limited diagnostic availability. Such misdiagnosis can cause undue stress on the patient and their families. Thus, it is important that patients presenting with these symptoms should undergo a thorough review of history, physical examination and a structured workup.


Assuntos
Reação Leucemoide , Pulmão/diagnóstico por imagem , Pneumonia Necrosante/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Antibacterianos/uso terapêutico , Erros de Diagnóstico , Humanos , Lactente , Contagem de Leucócitos , Masculino , Piperacilina/uso terapêutico , Pneumonia Necrosante/tratamento farmacológico , Tazobactam/uso terapêutico , Resultado do Tratamento
5.
Int J Antimicrob Agents ; 54(6): 741-749, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31479741

RESUMO

The study aimed to evaluate saturation of piperacillin elimination in critically ill adult patients. Seventeen critically ill adult patients received continuous and intermittent infusion of piperacillin/tazobactam. Piperacillin plasma concentrations (n = 217) were analysed using population pharmacokinetic (PopPK) modelling. Post-hoc simulations were performed to evaluate the type I error rate associated with the study. Unseen data were used to validate the final model. The mean error (ME) and root mean square error (RMSE) were calculated as a measure of bias and imprecision, respectively. A PopPK model with parallel linear and non-linear elimination best fitted the data. The median and 95% confidence interval (CI) for the model parameters drug clearance (CL), volume of central compartment (V), volume of peripheral compartment (Vp) and intercompartmental clearance (Q) were 9 (7.69-11) L/h, 6.18 (4.93-11.2) L, 11.17 (7.26-12) L and 15.61 (12.66-23.8) L/h, respectively. The Michaelis-Menten constant (Km) and the maximum elimination rate for Michaelis-Menten elimination (Vmax) were estimated without population variability in the model to avoid overfitting and inflation of the type I error rate. The population estimates for Km and Vmax were 37.09 mg/L and 353.57 mg/h, respectively. The bias (ME) was -20.8 (95% CI -26.2 to -15.4) mg/L, whilst imprecision (RMSE) was 49.2 (95% CI 41.2-56) mg/L. In conclusion, piperacillin elimination is (partially) saturable. Moreover, the population estimate for Km lies within the therapeutic window and therefore saturation of elimination should be accounted for when defining optimum dosing regimens for piperacillin in critically ill patients.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Piperacilina/administração & dosagem , Piperacilina/farmacocinética , Idoso , Antibacterianos/sangue , Antibacterianos/uso terapêutico , Área Sob a Curva , Simulação por Computador , Estado Terminal , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piperacilina/sangue , Piperacilina/uso terapêutico
6.
Clin Lab ; 65(9)2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31532096

RESUMO

BACKGROUND: Therapeutic drug monitoring (TDM) of beta-lactam antibiotics has become a valuable tool to guide dosing in critically ill patients. The main goal of the study was to compare two routinely used techniques for beta-lactam TDM in intensive care unit (ICU) patient samples, namely isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) and high-performance liquid chromatography combined with ultra-violet detection (HPLC-UV). METHODS: A set of 80 sera/plasma samples from ICU patients receiving therapeutic meropenem or piperacillin dosage was investigated. Sample duplicates and quality assessment samples were assayed in parallel with an in-house LC-MS/MS and a commercially available IVD HPLC-UV kit. A pharmacokinetic and pharmacodynamic (PK/PD) target with ≥ 22.5 mg/L for piperacillin and ≥ 8.0 mg/L for meropenem was used for medical assessment of trough sample (n = 40) antibiotic concentrations. RESULTS: There was no difference between serum and Li-heparin plasmas. Concentration deviations were found for 4% of meropenem and 17% of piperacillin samples. Eliminating the influence of the systemic bias of approximately 10% for piperacillin, measurement discrepancies ≥ 25% between LC-MS/MS and HPLC-UV analyses were only observed for ≈ 4 - 6% of all samples. In the same way, identical PK/PD target attainment rates of 50 - 60% could be obtained. CONCLUSIONS: After correction of the analytical bias for piperacillin measurements, both methods showed comparable results, also with respect to clinical decision limits. HPLC-UV analysis is an adequate TDM methodology for testing of beta-lactam antibiotics in centers where no special knowledge in LC-MS/MS based TDM is present. However, potential matrix effects, interferences, and calibration issues for both methods must be taken into account.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Estado Terminal , Meropeném/uso terapêutico , Piperacilina/uso terapêutico , Espectrometria de Massas em Tandem/métodos , Antibacterianos/sangue , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Cromatografia Líquida de Alta Pressão/instrumentação , Cuidados Críticos/métodos , Monitoramento de Medicamentos/métodos , Humanos , Meropeném/sangue , Meropeném/farmacocinética , Piperacilina/sangue , Piperacilina/farmacocinética , Reprodutibilidade dos Testes , Raios Ultravioleta
7.
Lett Appl Microbiol ; 69(3): 198-203, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31236975

RESUMO

Pseudomonas aeruginosa is related to nosocomial infections, and it tends to become resistant during or after antimicrobial treatment. The ability to develop carbapenems resistance makes it difficult to treat. P. aeruginosa infections are often associated with high mortality, morbidity and treatment costs. A group of Chinese experts drafted a consensus for treatment of extensively drug-resistant Gram-negative bacilli (XDR-GNB) including extensively drug-resistant P. aeruginosa (XDR-PA). In this study, we studied the antibacterial activities of different antibiotic combinations against six carbapenems-resistant P. aeruginosa (CRPA) strains in vitro, and the results indicated that the combination of ceftazidime with cefoperazone-sulbatam was the best combination with excellent synergistic rate (100%). Besides, some combinations exhibited better effects than using antibiotics alone, reducing the MICs of both drugs significantly, such as ceftazidime/piperacillin-tazobactam and ceftazidime/aztreonam etc. However, there are also some combinations that showed no additional or synergistic effects, suggesting that not all combinations recommended by the guideline have the same effect against resistant P. aeruginosa. Our study screened out some effective combinations against six CRPA strains which might help to prevent the spread of antibiotic resistance through improving antibiotic effectiveness. SIGNIFICANCE AND IMPACT OF THE STUDY: This study measured the synergistic interactions between various antibiotics in vitro recommended by Chinese consensus statement against carbapenems-resistant Pseudomonas aeruginosa. The results of this study provide valuable evidence that some combinations may be a promising option for clinical treatment.


Assuntos
Antibacterianos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Aztreonam/uso terapêutico , Carbapenêmicos/uso terapêutico , Cefoperazona/uso terapêutico , Ceftazidima/uso terapêutico , China , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana , Quimioterapia Combinada , Humanos , Testes de Sensibilidade Microbiana , Piperacilina/uso terapêutico , Infecções por Pseudomonas/microbiologia , Tazobactam/uso terapêutico
8.
BMJ Case Rep ; 12(4)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30940665

RESUMO

A 74-year-old woman presented with dyspnoea and fever on a background of a large hepatic cyst thought to be stable in size. During her admission, she developed worsening shortness of breath. An echocardiogram revealed severely impaired cardiac output due to external compression by the hepatic cyst, which had grown rapidly. This was drained under ultrasound guidance and cultures of this fluid grew Pseudomonas aeruginosa: the organism responsible for the persistence of this giant hepatic cyst.


Assuntos
Baixo Débito Cardíaco/etiologia , Cistos/complicações , Hepatopatias/complicações , Infecções por Pseudomonas/complicações , Idoso , Antibacterianos/uso terapêutico , Cistos/diagnóstico por imagem , Drenagem , Dispneia/etiologia , Feminino , Humanos , Hepatopatias/diagnóstico por imagem , Metronidazol/uso terapêutico , Piperacilina/uso terapêutico , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/isolamento & purificação , Tazobactam/uso terapêutico , Tomografia Computadorizada por Raios X , Ultrassonografia de Intervenção
9.
J Pharmacokinet Pharmacodyn ; 46(3): 251-261, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30963365

RESUMO

This study aimed to characterize the population pharmacokinetics (PKs) of piperacillin and investigate probability of target attainment (PTA) and cumulative fraction of response (CFR) of various dosage regimens in critically ill patients during the early phase of sepsis. Forty-eight patients treated with piperacillin/tazobactam were recruited. Five blood samples were drawn before and during 0-0.5, 0.5-2, 2-4 and 4-6 or 8 h after administration. Population PKs was analyzed using NONMEM®. The PTA of 90%fT>MIC target and CFR were determined by Monte Carlo simulation. The two compartment model best described the data. Piperacillin clearance (CL) was 5.37 L/h, central volume of distribution (V1) was 9.35 L, and peripheral volume of distribution was 7.77 L. Creatinine clearance (CLCr) and mean arterial pressure had a significant effect on CL while adjusted body weight had a significant impact on V1. Subtherapeutic concentrations can occur during the early phase of sepsis in critically ill patients with normal renal function. The usual dosage regimen, 4 g of piperacillin infused over 0.5 h every 6 h, could not achieve the target for susceptible organisms with MIC 16 mg/L in patients with CLCr ≥ 60 mL/min. Our proposed regimen for the patients with CLCr 60-120 mL/min was an extended 2 h infusion of 4 g of piperacillin every 6 h. Most regimens provided CFR ≥ 90% for the E. coli infection while there was no dosage regimen achieved a CFR of 90% for the P. aeruginosa infection.


Assuntos
Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Piperacilina/farmacocinética , Piperacilina/uso terapêutico , Sepse/tratamento farmacológico , Sepse/metabolismo , Idoso , Estado Terminal , Escherichia coli/efeitos dos fármacos , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Método de Monte Carlo , Combinação Piperacilina e Tazobactam/farmacocinética , Combinação Piperacilina e Tazobactam/uso terapêutico , Estudos Prospectivos , Pseudomonas aeruginosa/efeitos dos fármacos
10.
Artigo em Inglês | MEDLINE | ID: mdl-30782987

RESUMO

Critically ill patients are frequently treated with empirical antibiotic therapy, including vancomycin and ß-lactams. Recent evidence suggests an increased risk of acute kidney injury (AKI) in patients who received a combination of vancomycin and piperacillin-tazobactam (VPT) compared with patients who received vancomycin alone or vancomycin in combination with cefepime (VC) or meropenem (VM), but most studies were conducted predominately in the non-critically ill population. A retrospective cohort study that included 2,492 patients was conducted in the intensive care units of a large university hospital with the primary outcome being the development of any AKI. The rates of any AKI, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, were 39.3% for VPT patients, 24.2% for VC patients, and 23.5% for VM patients (P < 0.0001 for both comparisons). Similarly, the incidences of stage 2 and stage 3 AKI were also significantly higher for VPT patients than for the patients in the other groups. The rates of stage 2 and stage 3 AKI, respectively, were 15% and 6.6% for VPT patients, 5.8% and 1.8% for VC patients, and 6.6% and 1.3% for VM patients (P < 0.0001 for both comparisons). In multivariate analysis, the use of vancomycin in combination with piperacillin-tazobactam was found to be an independent predictor of AKI (odds ratio [OR], 2.161; 95% confidence interval [CI], 1.620 to 2.883). In conclusion, critically ill patients receiving the combination of VPT had the highest incidence of AKI compared to critically ill patients receiving either VC or VM.


Assuntos
Lesão Renal Aguda/epidemiologia , Cefepima/uso terapêutico , Meropeném/uso terapêutico , Piperacilina/uso terapêutico , Tazobactam/uso terapêutico , Vancomicina/uso terapêutico , Idoso , Estado Terminal , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos
12.
Asian J Endosc Surg ; 12(4): 434-438, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30548102

RESUMO

INTRODUCTION: We conducted a prospective non-randomized comparison of children with uncomplicated appendicitis treated either by primary laparoscopic appendectomy (PLA) or by non-operative management (NOM) followed by interval laparoscopic appendectomy (ILA) if NOM was successful or emergency laparoscopic appendectomy (ELA) if NOM was unsuccessful. METHODS: Before 2015, all patients with uncomplicated appendicitis underwent PLA using a standard three-port technique. Postoperatively, piperacillin/tazobactam was administered until the white blood cell count was less than 10 000/µL and patients were afebrile. Since 2015, in cases of uncomplicated appendicitis, intravenous analgesia has been administered once after assessment, and then NOM has been immediately employed, with repeat doses of piperacillin/tazobactam administered every 8 h after admission. We have also used standard management cut-off criteria to determine when to perform laparoscopic appendectomy after NOM: if NOM fails, ELA is performed within 6 h, and if NOM is successful, ILA is planned. RESULTS: There were 103 eligible subjects for this study. Eleven cases of suspected complicated appendicitis were excluded, leaving 34 PLA cases and 58 NOM cases. After NOM, 27 patients were treated with ILA and 31 with ELA. There was one recurrence after successful NOM, and in two cases, patients' parents refused to consent to ILA after successful NOM. There were more perforations and significantly more residual abscesses in ELA than in PLA. Operative time and postoperative hospitalization were significantly longer among ELA patients than among PLA patients, and operative time was significantly shorter during ILA than in PLA. CONCLUSION: Further evaluation is required to confirm which patients will benefit most from NOM and what role PLA has in treating uncomplicated appendicitis.


Assuntos
Apendicite/tratamento farmacológico , Apendicite/cirurgia , Seleção de Pacientes , Tempo para o Tratamento , Antibacterianos/uso terapêutico , Apendicectomia/estatística & dados numéricos , Criança , Feminino , Humanos , Laparoscopia/estatística & dados numéricos , Masculino , Piperacilina/uso terapêutico , Estudos Prospectivos , Tazobactam/uso terapêutico
13.
World J Urol ; 37(5): 957-967, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30109484

RESUMO

BACKGROUND: Perioperative antibiotic prophylaxis (PAP) is an integral part of kidney transplantation to prevent surgical site infections (SSI). In July 2015, we changed our standard from a multiple-dose to a single-dose (SD) prophylaxis. Here, we report on results with both regimens and a related survey among Eurotransplant renal transplantation centers. METHODS: From July 2015, all kidney graft recipients of our center were scheduled to receive SD i.v. cefazolin (group SD, n = 107). They were compared to patients, transplanted since January 2014, receiving our previous standard (i.v. piperacillin/flucloxacillin) until postoperative day (POD) 7, plus oral sultamicillin until POD 10 (group MD, n = 105). The primary endpoint was the number of SSIs during a 3-month observational period. RESULTS: The frequency of SSI episodes was generally low (group SD vs. MD: 2 vs. 4, p = 0.40). Of note, urinary tract infections occurred in 40 SD vs. 36 MD patients, respectively (p = 0.60). Urinary tract infections were caused by Escherichia coli in 36.8%. Female gender was the only independent risk factor on multivariate analysis (p = 0.002). In addition, 12 episodes of urosepsis in both groups occurred. All-cause infection with multi-resistant bacteria occurred less frequently in SD vs. MD patients (3.7% vs. 8.6%, p = 0.16). A majority of Eurotransplant centers used i.v. single-dose cephalosporins (36.9%), although substances and duration varied remarkably. CONCLUSION: Single-dose cefazolin was equally effective and less expensive compared to our previous MD regimen. Based on these findings, we conclude that future prospective studies should be designed to confirm the non-inferiority of single-dose antibiotic regimens.


Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Transplante de Rim/métodos , Infecção da Ferida Cirúrgica/prevenção & controle , Adulto , Idoso , Ampicilina/uso terapêutico , Cefazolina/uso terapêutico , Infecções por Escherichia coli/epidemiologia , Europa (Continente) , Feminino , Floxacilina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Piperacilina/uso terapêutico , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Sepse/epidemiologia , Fatores Sexuais , Sulbactam/uso terapêutico , Inquéritos e Questionários , Infecções Urinárias/epidemiologia
14.
BMC Infect Dis ; 19(1): 1091, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31888581

RESUMO

BACKGROUND: This study investigated predominant microorganisms causing community-onset bacteraemia at the medical emergency department (ED) of a tertiary-care university hospital in Germany from 2013 to 2018 and their antimicrobial susceptibility patterns. METHODS: Antimicrobial resistance patterns in patients with positive blood cultures presenting to an internal medicine ED were retrospectively analysed. RESULTS: Blood cultures were obtained at 5191 of 66,879 ED encounters, with 1013 (19.5%) positive results, and true positive results at 740 encounters (diagnostic yield, 14.3%). The most frequently isolated relevant microorganisms were Enterobacterales (n = 439, 59.3%), Staphylococcus aureus (n = 92, 12.4%), Streptococcus pneumoniae (n = 34, 4.6%), Pseudomonas aeruginosa (n = 32, 4.3%), Streptococcus pyogenes (n = 16, 2.2%), Enterococcus faecalis (n = 18, 2.4%), and Enterococcus faecium (n = 12, 1.6%). Antimicrobial susceptibility testing revealed a high proportion of resistance against ampicillin-sulbactam in Enterobacterales (42.2%). The rate of methicillin-resistant Staphylococcus aureus was low (0.4%). Piperacillin-tazobactam therapy provided coverage for 83.2% of all relevant pathogens using conventional breakpoints. Application of the new European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations increased the percentage of susceptible isolates to high-dose piperacillin-tazobactam to 92.8% (p < 0.001). Broad-spectrum carbapenems would only cover an additional 4.8%. The addition of vancomycin or linezolid extended coverage by just 1.7%. CONCLUSIONS: Using an ureidopenicillin-beta-lactamase inhibitor combination at the high dose suggested by the new EUCAST recommendations provided nearly 93% coverage for relevant pathogens in patients with suspected bloodstream infection in our cohort. This might offer a safe option to reduce the empiric use of carbapenems. Our data support the absence of a general need for glycopeptides or oxazolidinones in empiric treatment.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Carbapenêmicos/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Piperacilina/uso terapêutico , Tazobactam/uso terapêutico , Antibacterianos/efeitos adversos , Carbapenêmicos/efeitos adversos , Serviço Hospitalar de Emergência , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/isolamento & purificação , Alemanha , Hospitais Universitários , Humanos , Testes de Sensibilidade Microbiana , Piperacilina/efeitos adversos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Estudos Retrospectivos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Tazobactam/efeitos adversos , Resultado do Tratamento
15.
Artigo em Inglês | MEDLINE | ID: mdl-30564307

RESUMO

Treating M. abscessus infection is challenging due to the potent ß-lactamase BlaMab (Beta-lactamase of M. abscessus ). Avibactam is a non-ß-lactam, ß-lactamase inhibitor shown to inhibit BlaMab. We tested whether avibactem can render piperacillin effective against M. Abscessus. In-vitro, avibactam enhanced the activity of piperacillin by 16-32 fold, with no significant effect on meropenem. In an in-vivo Galleria mellonella model, meropenem and piperacillin/avibactam significantly decreased infection burden compared to untreated controls. Neither piperacillin nor avibactam alone had a significant effect.


Assuntos
Compostos Azabicíclicos/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Mycobacterium abscessus/efeitos dos fármacos , Piperacilina/uso terapêutico , Inibidores de beta-Lactamases/uso terapêutico , Animais , Compostos Azabicíclicos/administração & dosagem , Compostos Azabicíclicos/farmacologia , Modelos Animais de Doenças , Combinação de Medicamentos , Sinergismo Farmacológico , Meropeném/uso terapêutico , Testes de Sensibilidade Microbiana , Mariposas , Piperacilina/administração & dosagem , Piperacilina/farmacologia , beta-Lactamases
16.
JAMA ; 320(10): 984-994, 2018 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-30208454

RESUMO

Importance: Extended-spectrum ß-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective "carbapenem-sparing" option to treat extended-spectrum ß-lactamase producers. Objectives: To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae. Design, Setting, and Participants: Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study. Interventions: Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician. Main Outcomes and Measures: The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used. Results: Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6% [1-sided 97.5% CI, -∞ to 14.5%]; P = .90 for noninferiority). Effects were consistent in an analysis of the per-protocol population. Nonfatal serious adverse events occurred in 5 of 188 patients (2.7%) in the piperacillin-tazobactam group and 3 of 191 (1.6%) in the meropenem group. Conclusions and relevance: Among patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality. These findings do not support use of piperacillin-tazobactam in this setting. Trial Registration: anzctr.org.au Identifiers: ACTRN12613000532707 and ACTRN12615000403538 and ClinicalTrials.gov Identifier: NCT02176122.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/mortalidade , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae , Ácido Penicilânico/análogos & derivados , Tienamicinas/uso terapêutico , Adulto , Idoso , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Bacteriemia/tratamento farmacológico , Causas de Morte , Ceftriaxona/farmacologia , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/mortalidade , Feminino , Humanos , Infecções por Klebsiella/mortalidade , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Meropeném , Pessoa de Meia-Idade , Ácido Penicilânico/efeitos adversos , Ácido Penicilânico/uso terapêutico , Piperacilina/efeitos adversos , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Tienamicinas/efeitos adversos
17.
J Infect Chemother ; 24(12): 954-957, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30193786

RESUMO

We aimed to clarify prophylactic antimicrobial effects of single-dose piperacillin (PIPC) for perioperative infections in the transurethral resection of bladder tumor (TURBT) in comparison with those of single-dose tazobactam/piperacillin (TAZ/PIPC) through a retrospective analysis. We analyzed data from 192 TURBT patients treated with single-dose (4 g) intravenous PIPC (P group) between April 2015 and April 2017. For comparison, we analyzed data from 50 TURBT patients treated with single-dose (4.5 g) intravenous TAZ/PIPC (T/P group) between June 2013 and April 2014. We compared the perioperative incidences of fever (≥38 °C) and bacteriuria in the two groups. The number of febrile patients was four (2.1%) in the P group and one (2.0%) in the T/P group, without significant difference (p = 0.970). Among these febrile patients, urine and blood samples of two patients in the P group tested positive for bacterial cultures of Citrobacter koseri and Enterococcus faecalis, respectively. None of the patients in the T/P group tested positive for urine culture, postoperatively. However, 22 patients (18.2%) in the P group tested positive for urine culture, and Staphylococcus epidermidis (six patients), E. faecalis (three patients), Escherichia coli (three patients), Streptococcus agalactiae (two patients), Staphylococcus aureus (two patients), and C. koseri (one patient) were isolated. There was no significant difference in the incidence of bacteriuria in these two groups (p = 0.055). Based on these results, single-dose PIPC administration for the prevention of perioperative infections in TURBT was as effective as TAZ/PIPC.


Assuntos
Antibioticoprofilaxia/métodos , Combinação Piperacilina e Tazobactam/administração & dosagem , Piperacilina/administração & dosagem , Período Pré-Operatório , Tazobactam/administração & dosagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravenosa , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Bacteriúria/sangue , Bacteriúria/microbiologia , Bacteriúria/urina , Feminino , Febre/sangue , Febre/microbiologia , Febre/urina , Humanos , Masculino , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam/uso terapêutico , Estudos Retrospectivos , Tazobactam/uso terapêutico , Neoplasias da Bexiga Urinária/cirurgia
18.
Praxis (Bern 1994) ; 107(19): 1007-1012, 2018 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-30227799

RESUMO

CME: Fusobacterium nucleatum/naviforme - a Rare but Serious Cause for Pyogenic Liver Abscesses Abstract. Pyogenic liver abscesses belong to the most common abdominal infections. Beside the most common pathogens, also rare forms like Fusobacteria, which can also be part of the natural oropharyngeal and enteral microbiome, may be considered to cause severe forms of abscesses of the liver. Since they may be more difficult to detect, they could become a challenge during diagnosis and therapy.


Assuntos
Infecções por Fusobacterium/diagnóstico , Fusobacterium nucleatum , Abscesso Hepático/diagnóstico , Adulto , Dor no Peito/etiologia , Terapia Combinada , Diagnóstico Diferencial , Drenagem , Quimioterapia Combinada , Infecções por Fusobacterium/terapia , Humanos , Infusões Intravenosas , Levofloxacino/uso terapêutico , Abscesso Hepático/microbiologia , Testes de Função Hepática , Imagem por Ressonância Magnética , Masculino , Metronidazol/uso terapêutico , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/uso terapêutico , Piperacilina/uso terapêutico , Tazobactam , Tomografia Computadorizada por Raios X
19.
Ital J Pediatr ; 44(1): 93, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30111350

RESUMO

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a serious life-treating condition characterized by skin eruption, fever, haematologic abnormalities, and multi-organ involvement that can be fatal if unrecognized, especially in patients with liver failure. Diagnosis may be difficult because it is rarely described in children and can mimic many different conditions. CASE PRESENTATION: We report two cases of DRESS syndrome due to prolonged antibiotic treatment in young children in whom recovery occurred following different therapeutic approaches. A previously healthy 5-year-old boy had been receiving intravenous vancomycin for right wrist and left elbow osteomyelitis and developed DRESS syndrome on day 30. The patient achieved a complete resolution of all symptoms with pulse methylprednisolone followed by oral prednisone. A 4-year-old girl with cystic fibrosis, pancreatic insufficiency, chronic pulmonary colonization by Gram-positive bacteria admitted for pulmonary exacerbation was treated with intravenous piperacillin-tazobactam and tobramycin. After 14 days of treatment, she developed DRESS syndrome: antibiotic treatment was therefore stopped, and without any further therapy, a progressive resolution of the patient's clinical features was observed within 7 days, while the normalization of laboratory abnormalities was achieved at 14 days. CONCLUSIONS: Our cases highlight that paediatricians should be aware of the clinical presentations of and therapeutic approaches for DRESS syndrome, especially in children receiving long-term antibiotic treatment. The removal of the offending drug is crucial and may be the only life-saving measure. In more aggressive cases, corticosteroid or other immunosuppressive drugs should be considered to achieve the best outcome.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos/etiologia , Eosinofilia/induzido quimicamente , Piperacilina/efeitos adversos , Tobramicina/efeitos adversos , Vancomicina/efeitos adversos , Pré-Escolar , Síndrome de Hipersensibilidade a Medicamentos/fisiopatologia , Quimioterapia Combinada , Diagnóstico Precoce , Eosinofilia/fisiopatologia , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Masculino , Osteomielite/tratamento farmacológico , Piperacilina/uso terapêutico , Pneumonia Bacteriana/tratamento farmacológico , Medição de Risco , Amostragem , Tobramicina/uso terapêutico , Vancomicina/uso terapêutico , Suspensão de Tratamento
20.
J Antimicrob Chemother ; 73(11): 3087-3094, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30137377

RESUMO

Objectives: To describe the achievement of unbound ß-lactam antibiotic concentration targets in a therapeutic drug monitoring (TDM) programme in critically ill patients, and the factors associated with failure to achieve a target concentration. Patients and methods: Plasma samples and clinical data were obtained for analysis from a single centre prospectively. Unbound concentrations of ceftriaxone, cefazolin, meropenem, ampicillin, benzylpenicillin, flucloxacillin and piperacillin were directly measured using ultracentrifugation. Factors associated with the achievement of pharmacokinetic/pharmacodynamic (PK/PD) targets or negative clinical outcomes were evaluated with binomial logistic regression. Results: TDM data from 330 patients, and 369 infection episodes, were included. The range of doses administered was 99.4% ± 45.1% relative to a standard daily dose. Dose increases were indicated in 33.1% and 63.4% of cases to achieve PK/PD targets of 100% fT>MIC and 100% fT>4×MIC, respectively. Dose reduction was indicated in 17.3% of cases for an upper PK/PD threshold of 100% fT>10×MIC. Higher protein bound ß-lactams (ceftriaxone and benzylpenicillin) had better therapeutic target attainment (P < 0.01), but were prone to excessive dosing. Augmented renal clearance (calculated CLCR >130 mL/min) increased the odds of failure to achieve 100% fT>MIC and 100% fT>4×MIC (OR 2.47 and 3.05, respectively; P < 0.01). Conclusions: Measuring unbound concentrations of ß-lactams as part of a routine TDM programme is feasible and demonstrates that a large number of critically ill patients do not achieve predefined PK/PD targets. The clinical significance of this finding is unknown due to the lack of correlation between PK/PD findings and clinical outcomes.


Assuntos
Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Monitoramento de Medicamentos , beta-Lactamas/farmacocinética , beta-Lactamas/uso terapêutico , Adulto , Idoso , Ceftriaxona/farmacocinética , Ceftriaxona/uso terapêutico , Estado Terminal/terapia , Feminino , Humanos , Modelos Logísticos , Masculino , Meropeném/farmacocinética , Meropeném/uso terapêutico , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Piperacilina/farmacocinética , Piperacilina/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento
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