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1.
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
2.
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
3.
Dermatol Online J ; 24(4)2018 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-29906010

RESUMO

Fixed drug eruption (FDE) is an adverse drug reaction characterized by the development of well-circumscribed, round, dusky erythematous macules and plaques on cutaneous or mucosal surfaces. The reaction occurs on the same mucosal or cutaneous site with subsequent exposures to the offending drug. Although FDE usually manifests as a single lesion, in rare instances, more than one lesion may arise and this is referred to as a generalized eruption. Herein, we present a 31year-old man with history of cystic fibrosis who developed a generalized fixed drug eruption to piperacillin/tazobactam (Zosyn, Pfizer). We discuss our patient's course and review causes and outcomes of generalized fixed drug eruptions in the literature.


Assuntos
Antibacterianos/efeitos adversos , Erupção por Droga/etiologia , Ácido Penicilânico/análogos & derivados , Adulto , Anti-Inflamatórios/uso terapêutico , Erupção por Droga/tratamento farmacológico , Humanos , Masculino , Ácido Penicilânico/efeitos adversos , Piperacilina/efeitos adversos , Combinação Piperacilina e Tazobactam , Triancinolona/uso terapêutico
4.
Medicine (Baltimore) ; 97(25): e11168, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29924028

RESUMO

RATIONALE: Superior mesenteric venous thrombosis (SMVT) is a rare condition that carries high mortality. Very few cases have been reported of SMVT, complicating acute appendicitis. Early recognition requires a high index of suspicion and is crucial in successful treatment of such a life-threatening condition. PATIENT CONCERNS: A 33-year-old male presents with a 4-day history of right lower abdominal pain, nausea and subjective fever. CT scan showed acute appendicitis and a central filling defect in the superior mesenteric vein. DIAGNOSES: Acute appendicitis complicated by SMVT. INTERVENTIONS: Intravenous antibiotics, appendectomy, and anticoagulation. OUTCOMES: Repeat CT scan showed successful resolution of the SMVT at a 3-month follow up. LESSONS: Clinical awareness and high index of suspicion are essential to diagnose and manage SMVT, a serious complication of acute appendicitis.


Assuntos
Apendicectomia/métodos , Apendicite , Erros de Diagnóstico/prevenção & controle , Heparina de Baixo Peso Molecular/administração & dosagem , Oclusão Vascular Mesentérica , Veias Mesentéricas , Ácido Penicilânico/análogos & derivados , Piperacilina/administração & dosagem , Trombose Venosa , Adulto , Antibacterianos/administração & dosagem , Anticoagulantes/administração & dosagem , Apendicite/complicações , Apendicite/fisiopatologia , Apendicite/cirurgia , Intervenção Médica Precoce , Humanos , Masculino , Oclusão Vascular Mesentérica/diagnóstico , Oclusão Vascular Mesentérica/etiologia , Oclusão Vascular Mesentérica/fisiopatologia , Oclusão Vascular Mesentérica/terapia , Veias Mesentéricas/diagnóstico por imagem , Veias Mesentéricas/patologia , Ácido Penicilânico/administração & dosagem , Tazobactam , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Trombose Venosa/diagnóstico , Trombose Venosa/etiologia , Trombose Venosa/fisiopatologia , Trombose Venosa/terapia
5.
BMJ Case Rep ; 20182018 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-29880626

RESUMO

A 66-year-old woman presented with 2 days of fever and severe diarrhoea. She has a history of ulcerative colitis (UC), well controlled with medication. She also has a history of Ehlers-Danlos syndrome, infective endocarditis following aortic valve replacement and pulmonary embolism. She had complained of passing stool with traces of blood about 30 times per day. Stool testing for Clostridium difficile, routine culture and microscopy was done. She was started on ceftriaxone. CT scan revealed thick-walled colon consistent with UC flare. Flexible sigmoidoscopy showed active continuous colitis extending from the rectum to the proximal descending colon. Campylobacter jejuni was isolated from the stool and blood cultures yielded Pseudomonas aeruginosa. The antibiotic was transitioned to intravenous piperacillin/tazobactam and azithromycin followed by 2 weeks of intravenous cefepime. Her diarrhoea was controlled, and she was discharged for follow-up in 2 months.


Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Infecções por Campylobacter/fisiopatologia , Colite Ulcerativa/microbiologia , Fezes/microbiologia , Ácido Penicilânico/análogos & derivados , Infecções por Pseudomonas/fisiopatologia , Idoso , Infecções por Campylobacter/complicações , Infecções por Campylobacter/tratamento farmacológico , Coinfecção , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/fisiopatologia , Feminino , Febre , Humanos , Ácido Penicilânico/uso terapêutico , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/tratamento farmacológico , Sigmoidoscopia , Resultado do Tratamento
6.
Platelets ; 29(6): 628-631, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29863943

RESUMO

Pipercillin-tazobactam is a frequently used antibiotic that has a broad spectrum of antibacterial activity. The development of severe thrombocytopenia following the use of piperacillin-tazobactam is unusual. Several mechanisms have been proposed for the pathogenesis of thrombocytopenia in this setting which include immune and non-immune causes. Multiple case reports have shown the ability of piperacillin-tazobactam to cause drug-induced immune thrombocytopenia, likely through formation of antibodies that recognize platelets in the presence of soluble piperacillin. However, severe and rapid development of thrombocytopenia that occurs in association with reexposure to piperacillin-tazobactam has not been clearly demonstrated in the literature. We present two cases in whom severe and rapid development of thrombocytopenia has occurred subsequent to administration of piperacillin-tazobactam with a prior history of recent exposure to the drug. In both cases, thrombocytopenia improved immediately and dramatically following withdrawal of piperacillin-tazobactam with initiation of steroids and intravenous immunoglubulins, suggesting and immune related drug-induced thrombocytopenia.


Assuntos
Antibacterianos/efeitos adversos , Ácido Penicilânico/análogos & derivados , Trombocitopenia/etiologia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Humanos , Masculino , Ácido Penicilânico/efeitos adversos , Ácido Penicilânico/farmacologia , Piperacilina/efeitos adversos , Piperacilina/farmacologia , Combinação Piperacilina e Tazobactam , Trombocitopenia/patologia
7.
Diagn Microbiol Infect Dis ; 92(1): 75-77, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29884565

RESUMO

Ceftolozane/tazobactam is a combination intravenous antibiotic with potentially important activity against drug-resistant Gram-negative organisms. Ceftolozane/tazobactam's in vitro activity was evaluated in 30 samples collected from 23 adult cystic fibrosis patients with extended and pan-resistant Pseudomonas aeruginosa in 2015. Testing results demonstrated that 30% of the isolates were susceptible,13% were intermediate, and 57% were resistant. This suggests that ceftolozane/tazobactam may be a useful antibiotic in carefully selected, multidrug-resistant Pseudomonas isolates.


Assuntos
Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Fibrose Cística/microbiologia , Ácido Penicilânico/análogos & derivados , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Adulto , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana/métodos , Ácido Penicilânico/uso terapêutico , Escarro/microbiologia , Tazobactam
8.
Medicine (Baltimore) ; 97(19): e0688, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29742715

RESUMO

RATIONALE: Liver abscesses caused by Clostridium species infection are extremely rare. PATIENT CONCERNS: The authors report the first case of a liver abscess due to Clostridium haemolyticum, which occurred after transarterial chemoembolization (TACE) for hepatocellular carcinoma, in a 76-year-old woman who presented with right upper quadrant pain and fever. DIAGNOSES: Computed tomography of the abdomen after the second TACE showed an air-filled abscess around a compact, lipiodolized lesion in the right hepatic lobe. Pus culture showed the growth of C haemolyticum. INTERVENTIONS: Broad-spectrum antibiotics, including piperacillin/tazobactam and metronidazole, were administered, and a percutaneous 10-French pigtail catheter for pus drainage and culture was inserted in the liver abscess. OUTCOMES: Despite administering intensive treatments, she presented with rapid deterioration in mental status, liver function, and infection markers. She was transferred to the local hospital for palliative conservative treatment. LESSONS: Clostridia infections, including those involving C haemolyticum, are extremely rare, but should be considered as one of the causative organisms of liver abscess formation after TACE because of its rapid and fatal clinical course.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/efeitos adversos , Infecções por Clostridium/diagnóstico , Abscesso Hepático/diagnóstico , Abscesso Hepático/microbiologia , Neoplasias Hepáticas/terapia , Idoso , Antibacterianos/uso terapêutico , Infecções por Clostridium/tratamento farmacológico , Feminino , Humanos , Abscesso Hepático/tratamento farmacológico , Metronidazol/uso terapêutico , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/uso terapêutico , Piperacilina/uso terapêutico , Tazobactam
9.
BMJ Case Rep ; 20182018 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-29769193

RESUMO

Pericardial effusion can develop during any stage of pericarditis, and small effusions that appear rapidly can cause cardiac tamponade. Pyopericardium is a rare aetiology for tamponade. This is a case of an elderly diabetic lady, on steroid therapy for immune thrombocytopenia, who presented with fever and acute dyspnoea. She developed cardiac tamponade due to pyopericardium with Staphylococcus as the causative organism. Staphylococcus pyopericardium, in the absence of a primary focus of infection, progressing to tamponade is an uncommon scenario.


Assuntos
Tamponamento Cardíaco/etiologia , Derrame Pericárdico/complicações , Pericardite Constritiva/complicações , Doença Aguda , Idoso , Antibacterianos/administração & dosagem , Tamponamento Cardíaco/diagnóstico por imagem , Progressão da Doença , Drenagem , Feminino , Humanos , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/análogos & derivados , Derrame Pericárdico/diagnóstico por imagem , Pericardite Constritiva/tratamento farmacológico , Piperacilina/administração & dosagem , Combinação Piperacilina e Tazobactam , Púrpura Trombocitopênica Idiopática/complicações , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/isolamento & purificação , Tomografia Computadorizada por Raios X , Vancomicina/administração & dosagem
10.
PLoS One ; 13(5): e0197241, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29771929

RESUMO

Increasing evidence shows that active sites of proteins have non-trivial conformational dynamics. These dynamics include active site residues sampling different local conformations that allow for multiple, and possibly novel, inhibitor binding poses. Yet, active site dynamics garner only marginal attention in most inhibitor design efforts and exert little influence on synthesis strategies. This is partly because synthesis requires a level of atomic structural detail that is frequently missing in current characterizations of conformational dynamics. In particular, while the identity of the mobile protein residues may be clear, the specific conformations they sample remain obscure. Here, we show how an appropriate choice of ligand can significantly sharpen our abilities to describe the interconverting binding poses (conformations) of protein active sites. Specifically, we show how 2-(2'-carboxyphenyl)-benzoyl-6-aminopenicillanic acid (CBAP) exposes otherwise hidden dynamics of a protein active site that binds ß-lactam antibiotics. When CBAP acylates (binds) the active site serine of the ß-lactam sensor domain of BlaR1 (BlaRS), it shifts the time scale of the active site dynamics to the slow exchange regime. Slow exchange enables direct characterization of inter-converting protein and bound ligand conformations using NMR methods. These methods include chemical shift analysis, 2-d exchange spectroscopy, off-resonance ROESY of the bound ligand, and reduced spectral density mapping. The active site architecture of BlaRS is shared by many ß-lactamases of therapeutic interest, suggesting CBAP could expose functional motions in other ß-lactam binding proteins. More broadly, CBAP highlights the utility of identifying chemical probes common to structurally homologous proteins to better expose functional motions of active sites.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Metaloendopeptidases/metabolismo , Ácido Penicilânico/análogos & derivados , beta-Lactamases/metabolismo , Antibacterianos/química , Domínio Catalítico , Escherichia coli , Ligantes , Ressonância Magnética Nuclear Biomolecular , Ácido Penicilânico/química , Ácido Penicilânico/farmacologia , Conformação Proteica , Staphylococcus aureus
11.
Diagn Microbiol Infect Dis ; 92(1): 69-74, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29789189

RESUMO

A total of 18,656 Enterobacteriaceae and 4,175 Pseudomonas aeruginosa were consecutively collected from 85 US hospitals and tested for susceptibility by broth microdilution methods in a central monitoring laboratory (JMI Laboratories). The antimicrobial susceptibility and frequency of key resistance phenotypes were assessed and stratified by infection type as follows: bloodstream (BSI; 3,434 isolates; 15.0%), pneumonia (6,439; 28.2%), skin and skin structure (SSSI; 4,134; 18.1%), intra-abdominal (IAI; 951; 4.2%), and urinary tract (UTI; 7,873; 34.5%). Ceftazidime-avibactam was active against 99.9% to 100.0% of Enterobacteriaceae and 97.0% (pneumonia) to 99.4% (UTI) of P. aeruginosa isolates. Susceptibility rates were consistently lower for ß-lactams, such as ceftazidime (82.3% vs. 87.1-90.8%), piperacillin-tazobactam (87.5% vs. 90.2-95.6%), and meropenem (96.8% vs. 98.4-99.4%) among Enterobacteriaceae from pneumonia compared to other infection types. Susceptibility to gentamicin was also generally lower among isolates from pneumonia, whereas susceptibility to levofloxacin and colistin were lowest among BSI and SSSI isolates, respectively. The occurrence of multidrug-resistance (MDR; 8.2% overall), extensively drug-resistance (XDR; 1.1% overall), and carbapenem-resistant Enterobacteriaceae (CRE; 1.3% overall) phenotypes were markedly higher among isolates from patients with pneumonia compared to other infection types. Among P. aeruginosa, susceptibility rates for ceftazidime, piperacillin-tazobactam, and gentamicin were lowest among isolates from pneumonia, whereas susceptibility to meropenem was similar among isolates from BSI, pneumonia, and IAI (77.3-77.9%), and susceptibility to levofloxacin was markedly lower among UTI isolates (67.1%). The frequencies of P. aeruginosa isolates with MDR and XDR phenotypes were highest among isolates from patients with pneumonia.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/efeitos dos fármacos , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Compostos Azabicíclicos/uso terapêutico , Ceftazidima/uso terapêutico , Colistina/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Combinação de Medicamentos , Humanos , Meropeném , Testes de Sensibilidade Microbiana/métodos , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/uso terapêutico , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Tienamicinas/uso terapêutico , Estados Unidos
12.
Tohoku J Exp Med ; 245(1): 55-59, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29798969

RESUMO

Hemophagoytic lymphohistiocytosis (HLH) is a rare life-threatening disorder caused by overactivation of the immune system, associated with infections, autoimmune disorders, and malignancies. The pathological hallmark of HLH is phagocytosis of blood cells and platelets by activated macrophages and histiocytes. In this report, we describe the onset of HLH in three children, aged 2, 5 and 7 years old, during the treatment of acute focal bacterial nephritis (AFBN) with an antibiotic, piperacillin-tazobactam (PIPC-TAZ). AFBN is acute localized bacterial infection of the kidney without abscess formation. PIPC-TAZ was chosen for the treatment of AFBN, because it not only has indications for complicated urinary tract infections, but also covers most of the causative bacteria of urinary tract infections, including ß-lactamase-producing Escherichia coli. The clinical courses of the three patients were similar, and they were treated with PIPC-TAZ and amikacin (AMK) for AFBN. Fever went down 2 to 5 days later, and AMK was discontinued by day 6. However, fever recurred on 13 to 15 days after introduction of PIPC-TAZ therapy, even though all of the patients had no signs of recurrence of AFBN. The clinical features and laboratory tests of two patients fulfilled the criteria of HLH, whereas the other patient had initiated therapy before fulfilling the criteria. Cessation of PIPC-TAZ combined with corticosteroid therapy improved clinical symptoms. HLH of our patients was probably induced by PIPC-TAZ, as judged by the timing of the onset of HLH and the positivity of the drug-lymphocyte stimulation test. In conclusion, prolonged antibiotic therapy with PIPC-TAZ could be a cause of HLH.


Assuntos
Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Nefrite/microbiologia , Ácido Penicilânico/análogos & derivados , Doença Aguda , Medula Óssea/patologia , Criança , Pré-Escolar , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico por imagem , Masculino , Nefrite/diagnóstico por imagem , Ácido Penicilânico/uso terapêutico , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Tomografia Computadorizada por Raios X
13.
Indian J Med Microbiol ; 36(1): 32-36, 2018 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29735823

RESUMO

Background: The emergence of antibiotic resistance among bacterial pathogens in the hospital and community has increased the concern to the health-care providers due to the limited treatment options. Surveillance of antimicrobial resistance (AMR) in frequently isolated bacterial pathogens causing severe infections is of great importance. The data generated will be useful for the clinicians to decide empiric therapy on the local epidemiological resistance profile of the antimicrobial agents. This study aims to monitor the distribution of bacterial pathogen and their susceptibility pattern to the commonly used antimicrobial agents. Materials and Methods: This study includes Gram-negative bacilli collected from intra-abdominal, urinary tract and respiratory tract infections during 2014-2016. Isolates were collected from seven hospitals across India. All the study isolates were characterised up to species level, and minimum inhibitory concentration was determined for a wide range of antimicrobials included in the study panel. The test results were interpreted as per standard Clinical Laboratory Standards Institute guidelines. Results: A total of 2731 isolates of gram-negative bacteria were tested during study period. The most frequently isolated pathogens were 44% of Escherichia coli (n = 1205) followed by 25% of Klebsiella pneumoniae (n = 676) and 11% of Pseudomonas aeruginosa (n = 308). Among the antimicrobials tested, carbapenems were the most active, followed by amikacin and piperacillin/tazobactam. The rate of extended-spectrum beta-lactamase (ESBL)-positive isolates were ranged from 66%-77% in E. coli to 61%-72% in K. pneumoniae, respectively. Overall, colistin retains its activity in > 90% of the isolates tested and appear promising. Conclusion: Increasing rates of ESBL producers have been noted, which is alarming. Further, carbapenem resistance was also gradually increasing, which needs much attention. Overall, this study data show that carbapenems, amikacin and colistin continue to be the best agents available to treat drug-resistant infections. Thus continuous monitoring of susceptibility profile of the clinically important Gram-negative pathogens is of great importance to guide effective antimicrobial therapy.


Assuntos
Amicacina/uso terapêutico , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Escherichia coli/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Ácido Penicilânico/análogos & derivados , Pseudomonas aeruginosa/efeitos dos fármacos , Infecções Respiratórias/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/tratamento farmacológico , Humanos , Índia , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , Ácido Penicilânico/uso terapêutico , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/isolamento & purificação , Infecções Respiratórias/microbiologia , Infecções Urinárias/microbiologia , beta-Lactamases/isolamento & purificação
14.
Indian J Med Microbiol ; 36(1): 127-130, 2018 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29735843

RESUMO

Ceftolozane/tazobactam is a novel antimicrobial agent with activity against Pseudomonas aeruginosa and other common Gram-negative pathogens. In this study, we determined the antimicrobial susceptibility for a total of 149 clinical isolates of P. aeruginosa for the most commonly used antimicrobials including the new agent ceftolozane/tazobactam (C/T). Broth microdilution was performed to determine the minimum inhibitory concentration against various antimicrobials including C/T. Among the ß-lactam/ß-lactamase inhibitor, overall susceptibility was 67%, 55% and 51% for C/T, Piperacillin/Tazobactam (P/T) and Cefoperazone/Sulbactam, respectively. The variations in the susceptibility rates were noted among the three different ß-lactam/ß-lactamase inhibitors. Interestingly, 33% susceptibility was noted for C/T against isolates that were resistant to P/T, indicating the higher activity of C/T. This finding suggests about 33% of the P/T-resistant isolates can still be treated effectively with C/T. C/T could be a better alternative for the treatment of ESBL-producing organism, and thereby usage of higher antimicrobials can be minimised.


Assuntos
Antibacterianos/uso terapêutico , Cefoperazona/uso terapêutico , Cefalosporinas/uso terapêutico , Ácido Penicilânico/análogos & derivados , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Sulbactam/uso terapêutico , Inibidores de beta-Lactamases/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla , Humanos , Índia , Testes de Sensibilidade Microbiana , Ácido Penicilânico/uso terapêutico , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Tazobactam , Resultado do Tratamento
15.
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
Lesão Renal Aguda/induzido quimicamente , Quimioterapia Combinada/efeitos adversos , Rim/efeitos dos fármacos , Ácido Penicilânico/análogos & derivados , Tienamicinas/efeitos adversos , Vancomicina/efeitos adversos , Lesão Renal Aguda/sangue , Lesão 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
16.
Surg Today ; 48(9): 825-834, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29687153

RESUMO

PURPOSE: The development of surgical site infection (SSI) after biliary reconstruction is highly influenced by the presence of preoperative bacteria in the bile juice. We selected vancomycin and piperacillin/tazobactam (VCM + PIPC/TAZ) as perioperative prophylactic antibiotics for patients undergoing pancreaticoduodenectomy. This study aimed to retrospectively analyze the effectiveness of VCM + PIPC/TAZ compared to cefmetazole. METHODS: Seventy-two patients who underwent pancreaticoduodenectomy between April 2015 and March 2017 at our department were evaluated. Forty patients were administered cefmetazole as the perioperative prophylactic antibiotic, and 32 were administered VCM + PIPC/TAZ. The intraoperative VCM blood concentration (incision, biliary reconstruction, and wound closure) was measured during surgery to confirm the hemodynamics. RESULTS: The frequency of SSIs was significantly lower in the VCM + PIPC/TAZ group (8/32 patients) than in the cefmetazole group (20/40 patients, P = 0.031). Postoperatively, significantly fewer patients in the VCM + PIPC/TAZ group (4/32 patients) required ≥ 15 days of additional antibiotic administration compared to those in the cefmetazole group (14/40 patients, P = 0.033). Six of 32 patients in the VCM + PIPC/TAZ group showed redneck syndrome symptoms. There was no significant difference in the VCM blood concentration between patients with and without SSIs. CONCLUSIONS: The use of VCM + PIPC/TAZ can reduce the incidence of SSI after pancreaticoduodenectomy and also reduce the need for the additional administration of antibiotics for ≥ 15 days after surgery.


Assuntos
Antibioticoprofilaxia , Cefmetazol/administração & dosagem , Pancreaticoduodenectomia , Ácido Penicilânico/análogos & derivados , Piperacilina/administração & dosagem , Infecção da Ferida Cirúrgica/prevenção & controle , Vancomicina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Monitoramento de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Incidência , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Ácido Penicilânico/administração & dosagem , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/epidemiologia , Tazobactam , Fatores de Tempo , Vancomicina/sangue
17.
Pathology ; 50(4): 437-441, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29678480

RESUMO

Gram negative anaerobic organisms are important pathogens in a range of clinical infections, and susceptibility testing is not commonly performed in the microbiology laboratory. We performed anaerobic susceptibility testing on 70 clinically relevant Gram negative anaerobes isolated from routine cultures in a busy diagnostic laboratory which were identified by MALDI-TOF mass spectrometry (MALDI-TOF MS). The susceptibility testing was performed by two methods: Sensititre trays (ThermoFisher Scientific) against 15 different antibiotics, and Etests (bioMérieux) against five clinically relevant antibiotics (metronidazole, piperacillin-tazobactam, amoxicillin-clavulanate, meropenem and clindamycin). We found that all isolates were susceptible to metronidazole, and overall susceptibility to commonly used antibiotics such as piperacillin-tazobactam and amoxicillin-clavulanate was high (93-100% and 89-100%, respectively). Two isolates of Bacteroides fragilis were resistant to both broad spectrum ß-lactams and carbapenems. Comparing the two methods, using Sensititre broth microdilution as gold standard, there was high categorical agreement (92-100%). Antibiograms provide useful information for clinicians when choosing antimicrobials for infections caused by anaerobic organisms. This study has shown that in our area, use of metronidazole as a broad spectrum anti-anaerobic agent remains appropriate. Anaerobic susceptibility testing is also important to perform in individual clinical isolates, especially from sterile sites or in pure culture. The emergence of broad spectrum ß-lactam and carbapenem resistance in clinical isolates of Bacteroides fragilis is of concern and will require further monitoring. The Etest method was considered superior to Sensititre trays given that the higher inoculum used may allow demonstration of heteroresistance, anaerobiasis can be maintained during setup, lower failure rates, and the ability to select only the antibiotics required.


Assuntos
Antibacterianos/farmacologia , Infecções Bacterianas/microbiologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Farmacorresistência Bacteriana/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Carbapenêmicos/imunologia , Humanos , Testes de Sensibilidade Microbiana/métodos , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/farmacologia , Piperacilina/farmacologia , Combinação Piperacilina e Tazobactam
18.
Int J Antimicrob Agents ; 52(2): 293-296, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29678565

RESUMO

Acute appendicitis in children requires early surgery and short-course antibiotics active against Enterobacteriaceae and anaerobes. Although an aminoglycoside-containing three-drug regimen has been used successfully for decades, simpler regimens with similar efficacy are increasingly used. This study evaluated the impact of a switch from the combination of cefotaxime, metronidazole and gentamicin (regimen 1) to piperacillin/tazobactam (regimen 2) as first-line regimen for complicated acute appendicitis in children. In total, 171 children were enrolled [median (IQR) age, 10 (6-13) years], treated with regimen 1 (n = 80) or regimen 2 (n = 91) following surgery for complicated acute appendicitis. The two groups were comparable except for surgical approach (through laparoscopy in 46% vs. 88% for regimens 1 and 2, respectively; P < 0.001). Post-operative complications and duration of hospital stay were similar. Deviations from antibacterial treatment protocol decreased from 36% (29/80) to 14% (13/91) (P < 0.001), with a dramatic reduction in antibacterial treatment duration from median (IQR) of 15 (12-16) days to 5 (5-8) days (P < 0.001). Post-operative intra-abdominal abscess developed in 32 children (18.7%). Female sex (OR = 2.76, 95% CI 1.18-6.48; P = 0.02) and sepsis/septic shock on admission (OR = 4.72, 95% CI 1.12-19.97; P = 0.035) were independently associated with post-operative intra-abdominal abscess, but not antibacterial regimen. This study shows that simplification of first-line antibacterial regimen for complicated appendicitis in children was associated with reduced protocol deviation, reduced duration of antibiotics, and similar outcomes (post-operative complications and duration of hospital stay).


Assuntos
Antibacterianos/uso terapêutico , Apendicite/complicações , Fidelidade a Diretrizes/estatística & dados numéricos , Ácido Penicilânico/análogos & derivados , Peritonite/tratamento farmacológico , Complicações Pós-Operatórias/microbiologia , Adolescente , Apendicite/tratamento farmacológico , Apendicite/microbiologia , Apendicite/cirurgia , Cefotaxima/uso terapêutico , Criança , Quimioterapia Combinada , Feminino , Gentamicinas/uso terapêutico , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Metronidazol/uso terapêutico , Ácido Penicilânico/uso terapêutico , Peritonite/etiologia , Peritonite/microbiologia , Peritonite/patologia , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Complicações Pós-Operatórias/patologia , Guias de Prática Clínica como Assunto , Estudos Retrospectivos
19.
Bioanalysis ; 10(7): 461-473, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29633862

RESUMO

AIM: A simple, rapid, economical and sensitive HPLC-UV method was developed for the simultaneous quantification of ceftolozane and tazobactam in plasma samples. METHODOLOGY: After deproteinization followed by a liquid-liquid back-extraction, the compounds were separated on a C18 column (150 mm × 4.6 mm, 5 µm) with UV-visible detection at 220 nm. The mobile phase consisted of acetonitrile and potassium dihydrogenphosphate buffer at pH 3.0 (8:92, v/v), delivered isocratically at a flow rate of 1.0 ml/min and at a column oven temperature of 30°C. Cefepime was used as an internal standard. RESULTS: Linearity was achieved in the concentration range of 0.50-100.00 µg/ml for ceftolozane and 0.25-50.00 µg/ml for tazobactam. The intra- and interday precision showed good reproducibility with coefficients of variation of less than 9.26% for ceftolozane and 9.62% for tazobactam. CONCLUSION: The sample preparation procedure avoids expensive or time-consuming steps used by other previously published methods. The methodology was validated according to standard guidelines and was used for quantification of ceftolozane and tazobactam in plasma samples from critically ill patients.


Assuntos
Antibacterianos/sangue , Cefalosporinas/sangue , Cromatografia Líquida de Alta Pressão/métodos , Ácido Penicilânico/análogos & derivados , Plasma/química , Humanos , Ácido Penicilânico/sangue , Tazobactam
20.
N Biotechnol ; 47: 73-79, 2018 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-29614323

RESUMO

Aqueous two-phase systems (ATPSs) were screened for the production of 6-aminopenicillanic acid (6-APA) catalyzed by penicillin acylase, followed by the extractive separation of 6-APA from the reaction mixture. The key point of this study was to find an ATPS exhibiting a large difference in the partition coefficients of the biocatalyst and reaction products. Several ATPSs based on polyethylene glycol (PEG)/phosphate, PEG/citrate, and PEG/dextran were tested. We found that an ATPS consisting of 15 wt% of PEG 4000, 10 wt% of phosphates, 75 wt% of water (pH value 8.0 after dissolution) provided optimal separation of 6-APA from the enzyme. While the 6-APA was mainly found in the top PEG phase, the free enzyme favored the bottom salt-rich phase. This ATPS also fulfils other important requirements: (i) high buffering capacity, reducing an undesirable pH decrease due to the dissociation of phenylacetic acid (the side product of the reaction), (ii) a relatively low cost of the ATPS components, (iii) the possibility of electrophoretic transport of fine droplets as well as the reaction products for both the acceleration of phase separation and the enhancement of 6-APA concentration in the product stream. Extraction experiments in microcapillary and batch systems showed that the transport of 6-APA formed in the salt-rich phase to the corresponding PEG phase could occur within 30 s. The experimental results described form a base of knowledge for the development of continuously operating integrated microfluidic reactors-separators driven by an electric field for the efficient production of 6-APA.


Assuntos
Microfluídica/instrumentação , Ácido Penicilânico/análogos & derivados , Tampões (Química) , Dextranos/química , Peso Molecular , Ácido Penicilânico/síntese química , Fosfatos/química , Polietilenoglicóis/química , Viscosidade
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