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1.
BMJ Case Rep ; 14(9)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479885

RESUMO

Meropenem is a broad-spectrum carbapenem widely used to treat both Gram-positive and negative bacterial infections, including extended-spectrum beta-lactamase-producing microbes. We describe the occurrence of thrombocytopenia and hypersensitivity in a boy receiving intravenous meropenem for intra-abdominal sepsis secondary to perforated appendicitis. The patient developed a pruritic maculopapular rash with occasional petechiae, associated with severe thrombocytopenia, after 7 days of meropenem administration. Investigations for other causes of thrombocytopenia, including possible line sepsis, were unfruitful, and the thrombocytopenia did not resolve until cessation of meropenem. Drug-induced reactions should be considered in children receiving meropenem who present with a rash and thrombocytopenia.


Assuntos
Infecções Bacterianas , Trombocitopenia , Antibacterianos/efeitos adversos , Infecções Bacterianas/tratamento farmacológico , Criança , Humanos , Masculino , Meropeném/efeitos adversos , Tienamicinas/efeitos adversos , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico
3.
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
4.
Int J Antimicrob Agents ; 52(2): 180-184, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29649586

RESUMO

The combination of piperacillin/tazobactam (TZP) and vancomycin (VAN) provides a wide spectrum of activity against many pathogens acquired in healthcare settings. However, there have been reports of increased potential for nephrotoxicity with this combination. The aim of this study was to evaluate the nephrotoxic effect of TZP+VAN and to compare it with that of TZP and VAN monotherapies as well as VAN + meropenem (MEM), another broad-spectrum combination. A total of 402 patients receiving any of the antimicrobial regimens for >48 h were evaluated retrospectively over a 2-year period (2012-2013). Patients admitted to the intensive care unit, those with a baseline serum creatinine >2.0 mg/dL, patients on haemodialysis or peritoneal dialysis, pregnant women and those in septic shock were excluded. The presence and severity of acute kidney injury (AKI) was assessed according to the AKIN criteria. The incidence of AKI was significantly higher in the TZP+VAN group (41.3%) compared with the TZP (16.0%), VAN (15.7%) and VAN+MEM (10.1%) groups (P < 0.001). In the multivariate analysis, the risk of AKI increased 3.5-fold in patients treated with TZP+VAN and 1.7-fold in those who were receiving a potentially nephrotoxic drug when the antibiotic regimen was started compared with patients treated with VAN alone. Combined use of TZP+VAN carries a much higher risk of AKI than either antibiotic monotherapy regimen. Therefore, this broad-spectrum combination should be used cautiously in patients with a high likelihood of developing kidney injury.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Quimioterapia Combinada/efeitos adversos , Rim/efeitos dos fármacos , Ácido Penicilânico/análogos & derivados , Tienamicinas/efeitos adversos , Vancomicina/efeitos adversos , Injúria Renal Aguda/sangue , Injúria Renal Aguda/patologia , Adulto , Idoso , Creatinina/sangue , Feminino , Humanos , Rim/patologia , Modelos Logísticos , Masculino , Meropeném , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Pessoa de Meia-Idade , Ácido Penicilânico/efeitos adversos , Piperacilina/efeitos adversos , Combinação Piperacilina e Tazobactam , Infecções por Pseudomonas/sangue , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Estudos Retrospectivos , Infecções Estafilocócicas/sangue , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia
5.
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
6.
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
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.
Indian J Med Res ; 146(Supplement): S46-S52, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29205195

RESUMO

BACKGROUND & OBJECTIVES: The emergence and rapid spread of carbapenem resistance mediated by metallo-beta-lactamase (MBL) in Pseudomonas aeruginosa is of major concern due to limited therapeutic options. This study was aimed at detecting the presence of MBL and its association with integrons in imipenem-resistant P. aeruginosa isolates and to determine their genetic relatedness. METHODS: A total of 213 P. aeruginosa isolates were collected from two tertiary care centres and tested against anti-pseudomonal antibiotics by antimicrobial susceptibility testing, followed by the detection of MBL production by combined disk method. Minimum inhibitory concentration (MIC) of meropenem was determined by E-test. Multiplex polymerase chain reaction (PCR) was performed for the detection of blaSPM, blaIMP, blaVIM, blaNDM, blaGIM and blaSIM. PCR was carried out to characterize the variable region of class 1 integron. Transcongujation assay was carried out for the confirmation of plasmid-mediated resistance. Enterobacterial repetitive intergenic consensus sequence (ERIC)-PCR was performed for determining the genetic relatedness among P. aeruginosa isolates. RESULTS: Of the 213 P. aeruginosa isolates, 22 (10%) were found to be carbapenem resistant and these were from pus 18 (82%), urine 2 (9%), sputum 1 (5%) and tracheal wash 1 (5%). Among 22 isolates, 18 (81.8%) were found to be MBL producers by phenotypic method and MIC range of meropenem was 8 to >32 µg/ml. PCR amplification showed that 20 (91%) isolates carried any one of the MBL genes tested: blaVIM and blaNDM in seven (32%) and six (27%) isolates, respectively; blaVIM and blaNDMin three (14%); blaIMP and blaNDM in two (9%); blaVIM and blaIMP in one (5%) isolate. The blaVIM, blaIMP and blaNDM were found to co-exist in one isolate. None of the isolates were positive for blaSPM, blaSIM and blaGIM. All 22 isolates carried class I integron. Of the 20 MBL-positive isolates, transconjugants were obtained for 15 isolates. ERIC-PCR analysis showed all isolates to be clonally independent. INTERPRETATION & CONCLUSIONS: Our results showed 10.3 per cent of carbapenem resistance among P. aeruginosa isolates, and the coexistence of MBL-encoding genes among P. aeruginosa mediated by class I integron.


Assuntos
Farmacorresistência Bacteriana/genética , Integrons/genética , Pseudomonas aeruginosa/genética , beta-Lactamases/genética , Carbapenêmicos/efeitos adversos , Carbapenêmicos/uso terapêutico , Humanos , Meropeném , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/genética , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/patogenicidade , Centros de Atenção Terciária , Tienamicinas/efeitos adversos , Tienamicinas/uso terapêutico , beta-Lactamases/classificação , beta-Lactamases/isolamento & purificação
10.
Drugs Today (Barc) ; 53(10): 521-530, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29286054

RESUMO

On August 29, 2017, the United States Food and Drug Administration (FDA) approved meropenem/ vaborbactam fixed combination for the treatment of adults with complicated urinary tract infections (cUTI). The decision was based on substantial preclinical and clinical data, including two recent trials involving hundreds of adults with cUTI. Meropenem/ vaborbactam represents a powerful new treatment option to address antibiotic-resistant pathogens, including Klebsiella pneumoniae carbapenemase-producing bacteria. In this paper, we examine the work that led to FDA approval, with special emphasis on molecular pharmacology, pharmacokinetics, metabolism, efficacy and drug safety. We also look ahead, to explore how this promising new antimicrobial agent might be used in the near future to confront other drug-resistant infections..


Assuntos
Antibacterianos/uso terapêutico , Ácidos Borônicos/administração & dosagem , Compostos Heterocíclicos com 1 Anel/administração & dosagem , Tienamicinas/administração & dosagem , Infecções Urinárias/tratamento farmacológico , Ácidos Borônicos/efeitos adversos , Ácidos Borônicos/farmacocinética , Ácidos Borônicos/farmacologia , Ensaios Clínicos como Assunto , Interações Medicamentosas , Compostos Heterocíclicos com 1 Anel/efeitos adversos , Compostos Heterocíclicos com 1 Anel/farmacocinética , Compostos Heterocíclicos com 1 Anel/farmacologia , Humanos , Meropeném , Tienamicinas/efeitos adversos , Tienamicinas/farmacocinética , Tienamicinas/farmacologia
11.
J Antimicrob Chemother ; 72(10): 2891-2897, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29091190

RESUMO

Objectives: To determine the existence of concentration-toxicity relationships for common ß-lactam antibiotic adverse effects and define thresholds above which toxicity is more likely. Patients and methods: Retrospective review of consecutive patients treated with piperacillin, meropenem or flucloxacillin who underwent therapeutic drug monitoring (TDM) at St Vincent's Hospital (Sydney, Australia) between January 2013 and December 2015. Adverse events investigated included neurotoxicity, nephrotoxicity, hepatotoxicity and opportunistic Clostridium difficile infection. Toxicity was measured using observational grading criteria, clinical assessment and relevant serum biomarkers. These findings were correlated with trough TDM measurements at the time of toxicity presentation. Results: TDM results from 378 patients (piperacillin = 223, meropenem = 94 and flucloxacillin = 61) were investigated. There was no difference in baseline patient characteristics across antibiotic groups. A statistically significant elevation in mean serum trough concentrations (Cmin) was found in patients diagnosed with neurotoxicity (piperacillin, P < 0.01; meropenem, P = 0.04; flucloxacillin, P = 0.01) and those who developed nephrotoxicity whilst being treated with piperacillin (P < 0.01) or meropenem (P < 0.01). Incidence of hepatotoxicity and C. difficile was not related to Cmin. Threshold concentrations for which there is 50% risk of developing a neurotoxicity event (piperacillin, Cmin >361.4 mg/L; meropenem, Cmin >64.2 mg/L; flucloxacillin, Cmin >125.1 mg/L) or nephrotoxicity (piperacillin, Cmin >452.65 mg/L; meropenem, Cmin >44.45 mg/L) varied across antibiotics. Conclusions: Our data reveal an association between toxic concentrations for a number of ß-lactam agents and neurotoxic/nephrotoxic effects. We have defined threshold concentrations above which these toxicities become more likely. Clinicians should balance concerns for therapeutic efficacy with potential toxicity when considering aggressive therapy.


Assuntos
Antibacterianos/efeitos adversos , beta-Lactamas/efeitos adversos , Adulto , Idoso , Antibacterianos/sangue , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções por Clostridium/etiologia , Estudos de Coortes , Monitoramento de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Floxacilina/efeitos adversos , Floxacilina/sangue , Floxacilina/uso terapêutico , Humanos , Incidência , Masculino , Meropeném , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Síndromes Neurotóxicas/diagnóstico , Síndromes Neurotóxicas/etiologia , Piperacilina/efeitos adversos , Piperacilina/sangue , Piperacilina/uso terapêutico , Estudos Retrospectivos , Tienamicinas/efeitos adversos , Tienamicinas/sangue , Tienamicinas/uso terapêutico , beta-Lactamas/sangue , beta-Lactamas/uso terapêutico
12.
Prague Med Rep ; 118(2-3): 105-109, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28922108

RESUMO

We present two case reports of drug interaction between valproic acid and meropenem. In comparison with expected population-kinetic based serum levels, we observed 90.8 and 93.5% decrease in valproic acid serum levels during concomitant administration with meropenem. If carbapenems need to be administered to valproic acid treated patient, other anticonvulsant addition seems to be the appropriate as most probably the valproic acid dose escalation would not be sufficient to achieve therapeutic serum concentration.


Assuntos
Antibacterianos/efeitos adversos , Anticonvulsivantes/efeitos adversos , Tienamicinas/efeitos adversos , Ácido Valproico/efeitos adversos , Anticonvulsivantes/sangue , Interações Medicamentosas , Humanos , Masculino , Meropeném , Pessoa de Meia-Idade , Ácido Valproico/sangue
13.
Transfusion ; 57(11): 2715-2719, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28782250

RESUMO

BACKGROUND: Drug-induced immune thrombocytopenia (DITP) is a serious, life-threatening clinical syndrome, the diagnosis of which is consistently difficult. In this report, we present a case of DITP caused by meropenem that was confirmed by laboratory tests. CASE REPORT: A 59-year-old male patient developed severe thrombocytopenia 8 days after the administration of meropenem and cefoperazone-sulbactam. After other causes were ruled out, DITP was suspected. Drug-induced platelet (PLT) antibodies were detected by enzyme immunoassay, flow cytometry, and monoclonal antibody immobilization of PLT antigens (MAIPA). All these tests were performed in the presence and absence of the associated drugs. RESULTS: PLT antibodies were detected in the patient's serum only in the presence of meropenem. MAIPA experiments demonstrated that glycoprotein IIb/IIIa was the binding site of the meropenem-induced PLT antibodies. CONCLUSIONS: Drug-induced immune thrombocytopenia should be considered in cases of acute thrombocytopenia in patients undergoing meropenem treatment. Clinicians should be cognizant of DITP, and a definitive diagnosis should be pursued, if feasible.


Assuntos
Antibacterianos/efeitos adversos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/imunologia , Púrpura Trombocitopênica Idiopática/induzido quimicamente , Púrpura Trombocitopênica Idiopática/diagnóstico , Tienamicinas/efeitos adversos , Autoanticorpos/sangue , Sítios de Ligação , Plaquetas/imunologia , Técnicas de Laboratório Clínico/métodos , Humanos , Masculino , Meropeném , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/sangue
14.
Future Microbiol ; 12: 1001-1016, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28758800

RESUMO

Antibiotics are often used in neonates despite the absence of relevant dosing information in drug labels. For neonatal dosing, clinicians must extrapolate data from studies for adults and older children, who have strikingly different physiologies. As a result, dosing extrapolation can lead to increased toxicity or efficacy failures in neonates. Driven by these differences and recent legislation mandating the study of drugs in children and neonates, an increasing number of pharmacokinetic studies of antibiotics are being performed in neonates. These studies have led to new dosing recommendations with particular consideration for neonate body size and maturation. Herein, we highlight the available pharmacokinetic data for commonly used systemic antibiotics in neonates.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Recém-Nascido/fisiologia , Adulto , Aminoglicosídeos/administração & dosagem , Aminoglicosídeos/efeitos adversos , Aminoglicosídeos/farmacocinética , Antibacterianos/efeitos adversos , Peso ao Nascer/efeitos dos fármacos , Tamanho Corporal/efeitos dos fármacos , Cefalosporinas/administração & dosagem , Criança , Clindamicina/administração & dosagem , Clindamicina/efeitos adversos , Clindamicina/farmacocinética , Glicopeptídeos/administração & dosagem , Glicopeptídeos/efeitos adversos , Glicopeptídeos/farmacocinética , Humanos , Lactente , Reconciliação de Medicamentos , Meropeném , Metronidazol/administração & dosagem , Metronidazol/efeitos adversos , Metronidazol/farmacocinética , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/análogos & derivados , Piperacilina/administração & dosagem , Combinação Piperacilina e Tazobactam , Tienamicinas/administração & dosagem , Tienamicinas/efeitos adversos , Tienamicinas/farmacocinética , beta-Lactamas/administração & dosagem , beta-Lactamas/efeitos adversos , beta-Lactamas/farmacocinética
15.
Artigo em Inglês | MEDLINE | ID: mdl-28760891

RESUMO

Limited literature is available assessing nephrotoxicity with prolonged ß-lactam infusions. This study compared the incidence of acute kidney injury (AKI) associated with a prolonged ß-lactam infusion or an intermittent infusion. This was a retrospective, matched-cohort study at an academic medical center from July 2006 to September 2015. Adult patients who received piperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) for at least 48 h were evaluated. Patients were excluded for preexisting renal dysfunction or pregnancy. The primary outcome was difference in incidence of AKI evaluated using the RIFLE (risk, injury, failure, loss, and end-stage) criteria. Patients in the intermittent group were matched 3:1 to patients in the prolonged-infusion group based on the following: ß-lactam agent, age, gender, Charlson comorbidity index, baseline creatinine clearance, hypotension, receipt of vancomycin, and treatment in an intensive care unit. A total of 2,390 patients were included in the matched analysis, with 1,700 receiving intermittent infusions and 690 receiving prolonged infusion. The incidence of AKI was similar in the prolonged-infusion group to that in the intermittent-infusion group (21.6% versus 18.6%; P = 0.1). After multivariate regression, prolonged infusion was not associated with increased odds of AKI (odds ratio [OR], 1.07; 95% confidence interval [95% CI], 0.83 to 1.39). Independent predictors of AKI included TZP therapy, concomitant nephrotoxins, hypotension, and heart failure. Although AKIs were numerically more common in patients receiving prolonged ß-lactam infusions than those receiving intermittent infusions, prolonged infusion was not an independent risk factor for AKI.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Antibacterianos/efeitos adversos , Cefalosporinas/efeitos adversos , Ácido Penicilânico/análogos & derivados , Tienamicinas/efeitos adversos , Inibidores de beta-Lactamases/efeitos adversos , Injúria Renal Aguda/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Cefepima , Cefalosporinas/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Meropeném , Pessoa de Meia-Idade , Ácido Penicilânico/efeitos adversos , Ácido Penicilânico/uso terapêutico , Piperacilina/efeitos adversos , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Estudos Retrospectivos , Tienamicinas/uso terapêutico , Inibidores de beta-Lactamases/uso terapêutico
16.
Int J Antimicrob Agents ; 49(5): 579-588, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28363526

RESUMO

Ceftazidime/avibactam comprises the broad-spectrum cephalosporin ceftazidime and the non-ß-lactam ß-lactamase inhibitor avibactam. This phase 3, randomised, double-blind study (NCT01726023) assessed the efficacy and safety of ceftazidime/avibactam plus metronidazole compared with meropenem in patients with complicated intra-abdominal infection (cIAI) in Asian countries. Subjects aged 18-90 years and hospitalised with cIAI requiring surgical intervention were randomised 1:1 to receive every 8 h either: ceftazidime/avibactam (2000/500 mg, 2-h infusion) followed by metronidazole (500 mg, 60-min infusion); or meropenem (1000 mg, 30-min infusion). Non-inferiority of ceftazidime/avibactam plus metronidazole to meropenem was concluded if the lower limit of the 95% confidence interval (CI) for the between-group difference in clinical cure rate was greater than -12.5% at the test-of-cure (TOC) visit (28-35 days after randomisation) in the clinically evaluable (CE) population. Safety was also evaluated. Of 441 subjects randomised, 432 received at least one dose of study medication (ceftazidime/avibactam plus metronidazole, n = 215; meropenem, n = 217). In the CE population at the TOC visit, non-inferiority of ceftazidime/avibactam plus metronidazole to meropenem was demonstrated, with clinical cure reported for 93.8% (166/177) and 94.0% (173/184) of subjects, respectively (between-group difference, -0.2, 95% CI -5.53 to 4.97). The clinical cure rate with ceftazidime/avibactam plus metronidazole was comparable in subjects with ceftazidime-non-susceptible and ceftazidime-susceptible isolates (95.7% vs. 92.1%, respectively). Adverse events were similar between the study groups. Ceftazidime/avibactam plus metronidazole was non-inferior to meropenem in the treatment of cIAIs in Asian populations and was effective against ceftazidime-non-susceptible pathogens. No new safety concerns were identified.


Assuntos
Antibacterianos/uso terapêutico , Compostos Azabicíclicos/uso terapêutico , Ceftazidima/uso terapêutico , Infecções Intra-Abdominais/tratamento farmacológico , Metronidazol/uso terapêutico , Tienamicinas/uso terapêutico , Inibidores de beta-Lactamases/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ásia , Compostos Azabicíclicos/efeitos adversos , Ceftazidima/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla , Feminino , Hospitalização , Humanos , Infecções Intra-Abdominais/microbiologia , Masculino , Meropeném , Metronidazol/efeitos adversos , Pessoa de Meia-Idade , Tienamicinas/efeitos adversos , Resultado do Tratamento , Adulto Jovem , Inibidores de beta-Lactamases/efeitos adversos
17.
J Infect Public Health ; 10(6): 770-773, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28209320

RESUMO

The purpose of this study was to evaluate the observed incidence of acute kidney injury (AKI) in adult patients receiving either piperacillin-tazobactam (PT) and vancomycin or meropenem and vancomycin for at least 48h. In this retrospective cohort study, we included adult patients with no known renal dysfunction who received either the combination of PT-vancomycin or meropenem-vancomycin for at least 48h. The study's primary outcome was the incidence of acute kidney injury (AKI), defined by the Kidney Disease: Improving Global Outcomes (KDIGO) in patients with baseline normal renal function as an increase in serum creatinine (Scr) by ≥0.3mg/dl within 48h. A total of 183 patients were evaluated for AKI. The incidence of AKI was higher but not statistically different in the PT-vancomycin group (7.41%) compared with the meropenem-vancomycin group (5.33%). This study was not able to detect a statistically significant difference in AKI between the two treatment groups. A larger prospective study is warranted.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Antibacterianos/efeitos adversos , Ácido Penicilânico/análogos & derivados , Tienamicinas/efeitos adversos , Vancomicina/efeitos adversos , Inibidores de beta-Lactamases/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Meropeném , Pessoa de Meia-Idade , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/efeitos adversos , Piperacilina/administração & dosagem , Piperacilina/efeitos adversos , Combinação Piperacilina e Tazobactam , Estudos Retrospectivos , Tienamicinas/administração & dosagem , Vancomicina/administração & dosagem , Adulto Jovem , Inibidores de beta-Lactamases/administração & dosagem
18.
J Pharm Pract ; 30(2): 209-213, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26912532

RESUMO

PURPOSE: To prospectively evaluate the observed incidence of acute kidney injury (AKI) in adult patients receiving the combination of piperacillin-tazobactam and vancomycin versus the combination of cefepime or meropenem and vancomycin for greater than 72 hours. METHODS: This was a prospective, open-label cohort study at a community academic medical center involving adult patients over a 3-month time period who received either the combination of piperacillin-tazobactam and vancomycin or the combination of cefepime or meropenem and vancomycin for greater than 72 hours. The patients were evaluated for AKI, defined using specific criteria introduced by Kidney Disease: Improving global outcomes (KDIGO) acute kidney injury work group in 2012. RESULTS: A total of 85 patients receiving either antimicrobial combination were evaluated for AKI. The incidence of AKI was significantly higher in the piperacillin-tazobactam and vancomycin group (37.3%) compared with the cefepime or meropenem and vancomycin group (7.7%; χ2 = 7.80, P = .005). CONCLUSION: The result of this study suggests that the risk of developing AKI is increased in patients receiving the combination of piperacillin-tazobactam and vancomycin versus those receiving the combination of cefepime or meropenem and vancomycin.


Assuntos
Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/tratamento farmacológico , Cefalosporinas/efeitos adversos , Ácido Penicilânico/análogos & derivados , Tienamicinas/efeitos adversos , Vancomicina/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Cefepima , Cefalosporinas/administração & dosagem , Estudos de Coortes , Quimioterapia Combinada , Feminino , Humanos , Masculino , Meropeném , Pessoa de Meia-Idade , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/efeitos adversos , Piperacilina/administração & dosagem , Piperacilina/efeitos adversos , Combinação Piperacilina e Tazobactam , Estudos Prospectivos , Tienamicinas/administração & dosagem , Resultado do Tratamento , Vancomicina/administração & dosagem
19.
Ir J Med Sci ; 186(3): 729-732, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27686471

RESUMO

OBJECTIVE: Use of meropenem in our hospital has doubled in recent years. An audit in 2013 showed that although initiation of therapy with meropenem was generally appropriate, therapy was rarely subsequently reviewed and de-escalated where appropriate. Therefore, a structured stewardship initiative focussed on meropenem de-escalation was developed. METHODS: A local guideline for review and de-escalation of meropenem was developed and approved by the Antimicrobial Stewardship Team. The guideline outlined clinical and microbiological criteria which when met should lead to recommendation for meropenem de-escalation. Implementation of the guideline was piloted for a period of 4 weeks by a consultant microbiologist and an antimicrobial pharmacist. Days of meropenem use and crude mortality in those in whom de-escalation was implemented were compared with those where de-escalation was not recommended or was recommended but not implemented. RESULTS: Thirty-three patients were reviewed. Overall, a recommendation to de-escalate from meropenem to a specified alternative antibiotic was made for 18 (55 %) patients. This advice was followed for 12 (36 %) patients. The median days of meropenem use in patients where meropenem was de-escalated was 4.5 days (range 2-19) compared with 14 days (range 6-84) where de-escalation was not recommended or the recommendation was not implemented. There was no statistically significant difference in crude mortality between patients de-escalated from meropenem and those where meropenem was continued. CONCLUSION: This pilot study suggests that targeted carbapenem de-escalation stewardship activity based on pre-determined criteria, while labour intensive, can effectively and safely reduce meropenem use in the acute hospital setting.


Assuntos
Antibacterianos/efeitos adversos , Monitoramento de Medicamentos/métodos , Tienamicinas/efeitos adversos , Antibacterianos/farmacologia , Feminino , Humanos , Masculino , Meropeném , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Tienamicinas/farmacologia
20.
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
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