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1.
Eur J Clin Pharmacol ; 77(2): 197-205, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32975650

RESUMO

PURPOSE: Tigecycline is one of few antibiotics active against multidrug-resistant bacteria; however, the assessment of dosing strategies to optimize its activity is needed. The purpose was to use Monte Carlo Simulation (MCS) to determine if safe tigecycline dosing options attaining breakpoints for pharmacokinetic/pharmacodynamic (PK-PD) targets in non-critically ill adults could be identified. METHODS: Publications that evaluated tigecycline dosing regimens and provided mean PK variables of interest (minimum 2 of: elimination rate constant or half-life and volume of distribution or clearance), with SDs, were included. Weighted mean (±SDs) for each PK parameter were determined. Food and Drug Administration minimum inhibitory concentration (MIC) tigecycline breakpoints for susceptible (MIC ≤ 2 µg/mL), intermediate (MIC 4 µg/mL), and resistant (MIC ≥ 8 µg/mL) Enterobacteriaceae were used. MCS probability distributions for PK-PD target attainment of AUC for total tigecycline plasma concentration from 0 to 24 h following an intravenous dose (AUCtotal, 0-24h) to MIC ratios of ≥ 18, 7, and 4.5 were generated, with success defined as ≥ 80% probability of target attainment at a given MIC. RESULTS: Ten studies (n = 442) were eligible. Tigecycline 150 mg IV q12h for ward patients with resistant bacteria up to a MIC of 0.48, 1, and 2 µg/mL for an AUCtotal, 0-24h/MIC target attainment of 18, 7, and 4.5, respectively, may be appropriate. CONCLUSION: Bacterial infections with tigecycline MICs ≥ 0.48-2 µg/mL, depending on AUCtotal, 0-24h/MIC target, may require treatment with alternate antibiotics due to target attainment failure.


Assuntos
Antibacterianos/administração & dosagem , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/efeitos dos fármacos , Tigeciclina/administração & dosagem , Adulto , Antibacterianos/farmacocinética , Área Sob a Curva , Simulação por Computador , Conjuntos de Dados como Assunto , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana Múltipla , Enterobacteriaceae/isolamento & purificação , Enterobacteriaceae/fisiologia , Infecções por Enterobacteriaceae/sangue , Infecções por Enterobacteriaceae/microbiologia , Meia-Vida , Humanos , Infusões Intravenosas , Testes de Sensibilidade Microbiana , Método de Monte Carlo , Tigeciclina/farmacocinética
2.
J Clin Lab Anal ; 35(9): e23915, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34331328

RESUMO

BACKGROUND: Carbapenem-resistant K. pneumoniae (CRKP) bloodstream infections (BSI) must be rapidly identified to improve patient survival rates. This study investigated a new mass spectrometry-based method for improving the identification of CRKP BSI and explored potential biomarkers that could differentiate CRKP BSI from sensitive. METHODS: Mouse models of BSI were first established. MALDI-TOF MS was then used to profile serum peptides in CRKP BSI versus normal samples before applying BioExplorer software to establish a diagnostic model to distinguish CRKP from normal. The diagnostic value of the model was then tested against 32 clinical CRKP BSI and 27 healthy serum samples. Finally, the identities of the polypeptides used to establish the diagnostic model were determined by secondary mass spectrometry. RESULTS: 107 peptide peaks were shared between the CRKP and normal groups, with 18 peaks found to be differentially expressed. Five highly expressed peptides in the CRKP group (m/z 1349.8, 2091.3, 2908.2, 4102.1, and 8129.5) were chosen to establish a diagnostic model. The accuracy, specificity and sensitivity of the model were determined as 79.66%, 81.48%, and 78.12%, respectively. Secondary mass spectrometry identified the Fibrinogen alpha chain (FGA), Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and Serum amyloid A-2 protein (SAA2) as the source of the 5 serum peptides. CONCLUSIONS: We successfully established a serum peptide-based diagnostic model that distinguished clinical CRKP BSI samples from normal healthy controls. The application of MALDI-TOF MS to measure serum peptides, therefore, represents a promising approach for early BSI diagnosis of BSI, especially for multidrug-resistant bacteria where identification is urgent.


Assuntos
Antibacterianos/farmacologia , Biomarcadores/sangue , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Infecções por Enterobacteriaceae/diagnóstico , Espectrometria de Massas/métodos , Fragmentos de Peptídeos/sangue , Sepse/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana Múltipla , Diagnóstico Precoce , Infecções por Enterobacteriaceae/sangue , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Pessoa de Meia-Idade , Sepse/sangue , Sepse/tratamento farmacológico , Sepse/microbiologia , Adulto Jovem
3.
Artigo em Inglês | MEDLINE | ID: mdl-31844001

RESUMO

Benapenem is a novel carbapenem. The objective of this study was to determine the pharmacokinetic (PK)/pharmacodynamic (PD) cutoff values and evaluate the optimal administration regimens of benapenem for the treatment of bacterial infections via PK/PD modeling and simulation. Ertapenem was used as a control. Infected mice received an intravenous (i.v.) injection of benapenem or ertapenem of 14.6, 58.4, or 233.6 mg/kg of body weight, and the PK/PD profiles were evaluated. The MICs were determined by using a 2-fold agar dilution method. Mathematical models were developed to characterize the pharmacokinetic profile of benapenem in humans and mice. Monte Carlo simulations were employed to determine the cutoff values and the appropriate benapenem dosing regimens for the treatment of infections caused by clinical isolates of Enterobacteriaceae Two 2-compartment models were developed to describe the PK profiles of benapenem in humans and mice. A two-site binding model was applied to fit the protein binding in mouse plasma. Through correlation analysis, the percentage of the time that the free drug concentration remains above the MIC (%fT>MIC) was determined to be the indicator of efficacy. Results from the simulation showed that the probability of target attainment (PTA) against the tested isolates was over 90% with the dosing regimens studied. The PK/PD cutoff value of benapenem was 1 mg/liter at a %fT>MIC of 60% when given at a dose of 1,000 mg/day by i.v. drip for 0.5 h. The established model provides a better understanding of the pharmacological properties of benapenem for the treatment of Enterobacteriaceae infections. The proposed PK/PD cutoff value suggests that benapenem is a promising antibacterial against the Enterobacteriaceae The cutoff value of 1 mg/liter may be a useful guide for the clinical use of benapenem and for surveillance for benapenem resistance.


Assuntos
Antibacterianos/farmacocinética , Carbapenêmicos/farmacocinética , Desenvolvimento de Medicamentos , Infecções por Enterobacteriaceae/tratamento farmacológico , Modelos Estatísticos , Adulto , Animais , Antibacterianos/sangue , Antibacterianos/farmacologia , Área Sob a Curva , Carbapenêmicos/sangue , Carbapenêmicos/farmacologia , Enterobacter cloacae/efeitos dos fármacos , Enterobacter cloacae/crescimento & desenvolvimento , Infecções por Enterobacteriaceae/sangue , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/patologia , Ertapenem/sangue , Ertapenem/farmacocinética , Ertapenem/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Feminino , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/crescimento & desenvolvimento , Masculino , Camundongos , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , Método de Monte Carlo
4.
Infection ; 48(6): 955-958, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32880846

RESUMO

We report a case of catheter associated bloodstream infection due to Enterobacter ludwigii with a massive aggregation on the outside surface of a central venous catheter (CVC). The 57 years old patient with a history of spondylodiscitis and Staphylococcus aureus-associated endocarditis was admitted to the intensive care unit for acute cerebral infarction. The patient developed signs of infections and the CVC was removed 11 days after placement. The infectious agent was identified by standard diagnostics to the genus level as belonging to the Enterobacter cloacae complex, and additional molecular testing determined the species as E. ludwigii. The catheter was selected for a study aiming to identify the influence of blood components on the formation of central venous catheter-associated biofilms. In this course a massive biofilm was recognized and is presented here.


Assuntos
Infecções Relacionadas a Cateter/diagnóstico , Cateteres Venosos Centrais/microbiologia , Enterobacter/isolamento & purificação , Infecções por Enterobacteriaceae/diagnóstico , Sepse/diagnóstico , Biofilmes , Infecções Relacionadas a Cateter/sangue , Infecções Relacionadas a Cateter/microbiologia , Enterobacter/fisiologia , Infecções por Enterobacteriaceae/sangue , Infecções por Enterobacteriaceae/microbiologia , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Sepse/sangue , Sepse/microbiologia
5.
Fish Shellfish Immunol ; 97: 531-539, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31794844

RESUMO

Yellow catfish (Pelteobagrus fulvidraco) has been an economically important freshwater species in China because of its good meat quality. In present, the high-density breeding industry has suffered great damage from bacterial infections, in especial, the rapid illness and death of fish caused by bacterial septicemia leads to huge economic losses. Therefore, it is urgent and important to identify pathogenic bacteria and study its pathogenicity. In this study, we isolated a bacterial strain from the yellow catfish with typical septicemia and named it E. 719, then, by morphological observations, regression infection, biochemical identification, 16S rDNA sequence analysis and triple PCR identification, E. 719 was determined to be Edwardsiella ictaluri. Further, we infected yellow catfish with E. ictaluri to study its effects on mortality rate, hematological, histopathological disturbances and expression of immune genes. The mortality results showed that E. ictaluri was highly pathogenic, all infected fish died after 14 days post injection, and the distribution of bacteria in body kidney, spleen, liver, head kidney and brain of fish was continuously detected by measuring the amount of bacteria in the tissues. In addition, the number of red blood cells decreased significantly with the time of infection, while the number of white blood cells and thrombocytes increased. In particular, the number of monocytes and neutrophils increased significantly in the differential leucocyte count (DLC). Histopathologic changes observed by HE staining showed similar results, gill, intestine, spleen and head kidney showed obvious inflammation, bleeding and necrosis. Besides, checking by real time quantitative RT-PCR assays, in both spleen and head kidney tissues which were the major immune organs, mRNA expressions of immune gene IL-1ß, TNF-α, and MR significantly increased in the early and middle stages of infection, which suggested that the infection of E. ictaluri caused a strong immune response in yellow catfish. This study provides a preliminary basis for the diagnosis and treatment of pathophysiology septicemia in yellow catfish induced by E. ictaluri.


Assuntos
Peixes-Gato , Edwardsiella ictaluri/fisiologia , Infecções por Enterobacteriaceae/veterinária , Doenças dos Peixes/imunologia , Sepse/veterinária , Animais , Infecções por Enterobacteriaceae/sangue , Infecções por Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/imunologia , Doenças dos Peixes/sangue , Doenças dos Peixes/genética , Sepse/sangue , Sepse/genética , Sepse/imunologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-30275092

RESUMO

Plazomicin is an FDA-approved aminoglycoside for the treatment of complicated urinary tract infections. In this open-label study, 24 adults with normal renal function or mild, moderate, or severe renal impairment (n = 6 per group) received a single 7.5-mg/kg of body weight dose of plazomicin as a 30-min intravenous infusion. Total clearance declined with renal impairment, resulting in 1.98-fold and 4.42-fold higher plazomicin exposures, as measured by the area under the concentration-time curve from 0 h to infinity, in subjects with moderate and severe impairment, respectively, than in subjects with normal renal function. (This study has been registered at ClinicalTrials.gov under identifier NCT01462136.).


Assuntos
Antibacterianos/farmacocinética , Infecções por Enterobacteriaceae/tratamento farmacológico , Insuficiência Renal/tratamento farmacológico , Sisomicina/análogos & derivados , Infecções Urinárias/tratamento farmacológico , Idoso , Antibacterianos/sangue , Antibacterianos/farmacologia , Área Sob a Curva , Esquema de Medicação , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/patogenicidade , Enterobacteriaceae/fisiologia , Infecções por Enterobacteriaceae/sangue , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/fisiopatologia , Feminino , Humanos , Infusões Intravenosas , Rim/efeitos dos fármacos , Rim/microbiologia , Rim/fisiopatologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/sangue , Insuficiência Renal/microbiologia , Insuficiência Renal/fisiopatologia , Índice de Gravidade de Doença , Sisomicina/sangue , Sisomicina/farmacocinética , Sisomicina/farmacologia , Infecções Urinárias/sangue , Infecções Urinárias/microbiologia , Infecções Urinárias/fisiopatologia
7.
J Antimicrob Chemother ; 73(11): 3176-3180, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30099554

RESUMO

Objectives: Carbapenems are widely recommended for the treatment of infections caused by ESBL producers however, non-carbapenem ß-lactams such as ß-lactam/ß-lactamase inhibitor combinations (BLBLIs) deserve consideration for the treatment of ESBL infections. Cefoperazone/sulbactam is one of the most commonly used BLBLIs in China; however, few outcome studies have been reported. In this study, we evaluated and compared the clinical efficacy of cefoperazone/sulbactam with that of a carbapenem in the treatment of bloodstream infections (BSIs) caused by ESBL-producing Enterobacteriaceae. Methods: Patients with monomicrobial ESBL-producing Enterobacteriaceae BSIs empirically treated with cefoperazone/sulbactam or a carbapenem were included. Outcomes of interest were clinical response and 14 day mortality. To make a comparison of the efficacy of cefoperazone/sulbactam and a carbapenem more accurate, propensity score analysis was performed. Results: No statistically significant differences in success rates or 14 day mortality were found between the cefoperazone/sulbactam (n = 17) and carbapenem (n = 46) groups. In the propensity score analysis with 17 case-control pairs, the success rate in the cefoperazone/sulbactam group (70.6%, 12/17) was lower than that in the carbapenem group (94.1%, 16/17), but the difference was not significant (P = 0.175). Sepsis-related mortality and 14 day mortality rates did not significantly differ either (P = 1.000 for both). In the cefoperazone/sulbactam group, 66.7% (2/3) of the patients with a Pitt bacteraemia score ≥5 died within 14 days, whereas none (0/14) of the patients with a Pitt bacteraemia score <5 died within 14 days (P = 0.022). Conclusions: This study showed that cefoperazone/sulbactam had a lower success rate and a higher 14 day mortality rate compared with carbapenems, although the differences were not statistically significant because of the small patient numbers. Further evaluation of cefoperazone/sulbactam is needed.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Carbapenêmicos/uso terapêutico , Cefoperazona/uso terapêutico , Infecções por Enterobacteriaceae/tratamento farmacológico , Sulbactam/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , China , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/enzimologia , Infecções por Enterobacteriaceae/sangue , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Inibidores de beta-Lactamases/uso terapêutico , beta-Lactamases , beta-Lactamas/uso terapêutico
8.
Transpl Infect Dis ; 20(1)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29151282

RESUMO

BACKGROUND: Bloodstream infection (BSI) represents an important source of morbidity and mortality, as well as an increasing therapeutic challenge, among solid organ transplant recipients. Understanding the epidemiological and microbiological characteristics of BSI following renal transplantation is paramount to the implementation of appropriate preventative and therapeutic measures. METHODS: We conducted a retrospective review of all BSI episodes occurring between July 2009 and April 2016 in adult patients, who received a renal transplant at Royal Free London hospital. RESULTS: A total of 116 episodes of BSI occurred in 87 patients, 43 (49.4%) of them men. The mean age at BSI was 54.37 ± 12.81 years. Late-onset BSI (>12 months post transplant) represented 55.2%, with the median time to BSI being 16.28 month. Sixty-seven patients had single BSI and 20 had recurrent episodes. Enterobacteriaceae were responsible for 73.7% of BSI, with Escherichia coli the commonest causative organism (46.6%). The urinary tract was the most frequent source of infection in 56.9%. Among the E. coli infections, 100% of the tested isolates were sensitive to meropenem, ertapenem, tigecycline, and fosfomycin, and >90% were sensitive to piperacillin-tazobactam, amikacin, and colistin. Lower susceptibility rates were encountered for ceftriaxone (70.6%), amoxicillin-clavulanic acid (48.1%), cotrimoxazole (40.4%), trimethoprim (37.3%), and amoxicillin (21.6%). During BSI, the median serum creatinine increased from a reference of 131 µmol/L to a peak of 219 µmol/L. Acute kidney injury (AKI) complicated 75/116 BSI episodes (64.7%)-stage 1: 34, stage 2: 31, and stage 3 AKI: 10 episodes. After 3 months, the median creatinine remained elevated at 146 µmol/L. The 3-month mortality rate was 8% (7/87), and the death-censored graft loss was 6.9% (6/87). No significant difference was seen between BSI of urinary and non-urinary sources in the incidence of AKI (χ2  = 0.24, P = .6) or the percentage of creatinine change between baseline and peak and 3-month creatinines (P = .2 and .7 respectively). CONCLUSIONS: Urinary tract infection remains the commonest source of systemic infection among kidney transplant recipients and resistance to commonly used frontline antibiotics is common; thus, prevention and early detection are paramount. The appropriate choice of initial empirical antibiotic is vital to improve the outcome. Each unit needs to understand the epidemiology of organisms causing BSI in their transplant patients and their antibiotic susceptibilities.


Assuntos
Bacteriemia/complicações , Bacteriemia/epidemiologia , Transplante de Rim/efeitos adversos , Transplantados , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/microbiologia , Adulto , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Infecções Relacionadas a Cateter/sangue , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/sangue , Infecções por Enterobacteriaceae/microbiologia , Infecções por Escherichia coli/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sepse , Infecções Urinárias/sangue
9.
Ann Clin Microbiol Antimicrob ; 17(1): 19, 2018 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-29728100

RESUMO

BACKGROUND: Raoultella planticola, a Gram-negative, aerobic bacillus commonly isolated from soil and water, rarely causes invasive infections in humans. Septic shock from R. planticola after burn injury has not been previously reported. CASE PRESENTATION: A 79-year-old male was admitted to the emergency intensive care unit after extensive flame burn injury. He accidently caught fire while burning trash and plunged into a nearby tank filled with contaminated rainwater to extinguish the fire. The patient developed septic shock on day 10. The blood culture detected R. planticola, which was identified using the VITEK-2 biochemical identification system. Although appropriate antibiotic treatment was continued, the patient died on day 12. CONCLUSIONS: Clinicians should be aware of fatal infections in patients with burn injury complicated by exposure to contaminated water.


Assuntos
Bacteriemia/etiologia , Bacteriemia/microbiologia , Queimaduras/complicações , Queimaduras/microbiologia , Enterobacteriaceae/patogenicidade , Choque Séptico/etiologia , Choque Séptico/microbiologia , Idoso , Antibacterianos/farmacologia , Hemocultura , Queimaduras/fisiopatologia , Enterobacteriaceae/classificação , Enterobacteriaceae/efeitos dos fármacos , Infecções por Enterobacteriaceae/sangue , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , Humanos , Unidades de Terapia Intensiva , Masculino , Testes de Sensibilidade Microbiana , Infecção dos Ferimentos/complicações , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia
10.
J Fish Dis ; 41(9): 1453-1458, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29882594

RESUMO

This report describes a case of systemic bacterial infection caused by Edwardsiella tarda in a Western African lungfish (Protopterus annectens) exposed to poor environmental and husbandry conditions. The fish presented with a large, external ulcerative lesion and died 2 weeks after developing anorexia. Histological evaluation revealed multifocal areas of necrosis and heterophilic and histiocytic inflammation throughout multiple tissues. Gram stain identified small numbers of intra- and extracellular monomorphic Gram-negative 1 to 2 µm rod-shaped bacilli. Cytology of lung granuloma, kidney and testes imprints identified heterophilic inflammation with phagocytosis of small monomorphic bacilli and some heterophils exhibiting cytoplasmic projections indicative of heterophil extracellular traps (HETs). Initial phenotypic analysis of isolates from coelomic fluid cultures identified E. tarda. Subsequent molecular analysis of spleen, liver and intestine DNA using an E. tarda-specific endpoint PCR assay targeting the bacterial fimbrial subunit yielded a 115 bp band. Sequencing and BLASTN search revealed the sequence was identical (76/76) to E. tarda strain FL95-01 (GenBank acc. CP011359) and displayed 93% sequence identity (66/71) to Edwardsiella hoshinae strain ATCC 35051 (GenBank acc. CP011359). This is the first report of systemic edwardsiellosis in a lungfish with concurrent cytologically identified structures suggestive of HETs.


Assuntos
Edwardsiella tarda/isolamento & purificação , Infecções por Enterobacteriaceae/veterinária , Doenças dos Peixes/sangue , Peixes/microbiologia , Animais , Anorexia , Técnicas Citológicas , DNA Bacteriano/genética , Edwardsiella tarda/genética , Edwardsiella tarda/imunologia , Edwardsiella tarda/fisiologia , Infecções por Enterobacteriaceae/sangue , Infecções por Enterobacteriaceae/microbiologia , Armadilhas Extracelulares/imunologia , Doenças dos Peixes/microbiologia , Granulócitos/ultraestrutura , Rim/citologia , Rim/microbiologia , Rim/patologia , Pulmão/citologia , Pulmão/microbiologia , Pulmão/patologia , Pulmão/ultraestrutura , Masculino , Filogenia , Reação em Cadeia da Polimerase , Sepse/microbiologia , Testículo/citologia , Testículo/microbiologia , Testículo/patologia
11.
Clin Infect Dis ; 64(3): 257-264, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28013264

RESUMO

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) are associated with considerable mortality. As mechanisms of carbapenem resistance are heterogeneous, it is unclear if mortality differs based on resistance mechanisms. We sought to determine whether CRE resistance mechanism determination is prognostically informative. METHODS: We conducted an observational study comparing 14-day mortality between patients with carbapenemase-producing (CP)-CRE compared with non-CP-CRE bacteremia. Clinical data were collected on all patients. A comprehensive DNA microarray-based assay was performed on all isolates to identify ß-lactamase-encoding genes. RESULTS: There were 83 unique episodes of monomicrobial CRE bacteremia during the study period: 37 (45%) CP-CRE and 46 (55%) non-CP-CRE. The majority of CP-CRE isolates were bla KPC (92%), followed by bla NDM (5%) and bla OXA-48-type (3%). CP-CRE isolates were more likely to have meropenem minimum inhibitory concentrations (MICs) ≥16 µg/mL, while non-CP-CRE isolates were more likely to have meropenem MICs ≤1 µg/mL (P value < .001). A total of 18 (22%) patients died within 14 days, including 12 (32%) in the CP-CRE group and 6 (13%) in the non-CP-CRE group. Adjusting for severity of illness on day 1 of bacteremia, underlying medical conditions, and differences in antibiotic treatment administered, the odds of dying within 14 days were more than 4 times greater for CP-CRE compared with non-CP-CRE bacteremic patients (adjusted odds ratio, 4.92; 95% confidence interval, 1.01-24.81). CONCLUSION: Our findings suggest that CP-CRE may be more virulent than non-CP-CRE and are associated with poorer outcomes. This underscores the added importance of delineating underlying resistance mechanisms of CRE to direct antibiotic treatment decisions.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/mortalidade , Proteínas de Bactérias/metabolismo , Carbapenêmicos/uso terapêutico , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/mortalidade , Enterobacteriaceae/enzimologia , Resistência beta-Lactâmica , beta-Lactamases/metabolismo , Adulto , Idoso , Antibacterianos/farmacologia , Bacteriemia/sangue , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Estudos de Coortes , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/patogenicidade , Infecções por Enterobacteriaceae/sangue , Feminino , Humanos , Masculino , Meropeném , Pessoa de Meia-Idade , Estudos Retrospectivos , Tienamicinas/farmacologia , Tienamicinas/uso terapêutico , Resultado do Tratamento , beta-Lactamases/genética
12.
Jpn J Vet Res ; 65(1): 29-37, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29791118

RESUMO

The aim of the present study was to examine the applicability of the direct determination of trace and major element concentrations in serum samples collected from Holstein dairy cattle with acute coliform mastitis (n = 53) compared with a healthy control group (n = 39). Twenty-eight elements (Na, Mg, Al, Si, S, Cl, K, Ca, Ti, V, Cr, Mn, Fe, Ce, Ni, Cu, Zn, Ga, As, Se, Br, Rb, Sr, Y, Zr, Nb, Mo, and Pb) were detected by particle-induced X-ray emission (PIXE). Significant differences were observed in serum K, Fe, Zn, and Br concentrations, but not in those of the remaining twenty-four elements. Furthermore, serum Fe concentrations (0.751 ± 0.583 µg/ml, n = 18) were significantly lower in dairy cattle with a poor prognosis than in those with a good prognosis (0.945 ± 0.393 µg/ml, n = 35, P < 0.05) and healthy controls (1.458 ± 0.391 µg/ml, n = 39, P < 0.01). We proposed a diagnostic cut-off point for serum Fe concentrations of <0.82 µg/ml based on receiver operating characteristic (ROC) curves in order to identify cattle with a poor prognosis. The results of the present study indicated that assessing the elemental composition of serum, particularly iron, is a promising prognostic tool for determining the outcomes of cattle with severe acute coliform mastitis.


Assuntos
Infecções por Enterobacteriaceae/veterinária , Enterobacteriaceae , Mastite Bovina/sangue , Metais/sangue , Espectrometria por Raios X , Doença Aguda , Animais , Bovinos , Infecções por Enterobacteriaceae/sangue , Feminino
13.
Antimicrob Agents Chemother ; 60(1): 522-31, 2016 01.
Artigo em Inglês | MEDLINE | ID: mdl-26552978

RESUMO

The study objective was to evaluate the population pharmacokinetics and pharmacodynamics of extended-infusion piperacillin-tazobactam in children hospitalized in an intensive care unit. Seventy-two serum samples were collected at steady state from 12 patients who received piperacillin-tazobactam at 100/12.5 mg/kg of body weight every 8 h infused over 4 h. Population pharmacokinetic analyses were performed using NONMEM, and Monte Carlo simulations were performed to estimate the piperacillin pharmacokinetic profiles for dosing regimens of 80 to 100 mg/kg of the piperacillin component given every 6 to 8 h and infused over 0.5, 3, or 4 h. The probability of target attainment (PTA) for a cumulative percentage of the dosing interval that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (TMIC) of ≥50% was calculated at MICs ranging from 0.25 to 64 mg/liter. The mean ± standard deviation (SD) age, weight, and estimated glomerular filtration rate were 5 ± 3 years, 17 ± 6.2 kg, and 118 ± 41 ml/min/1.73 m(2), respectively. A one-compartment model with zero-order input and first-order elimination best fit the pharmacokinetic data for both drugs. Weight was significantly associated with piperacillin clearance, and weight and sex were significantly associated with tazobactam clearance. Pharmacokinetic parameters (mean ± SD) for piperacillin and tazobactam were as follows: clearance, 0.22 ± 0.07 and 0.19 ± 0.07 liter/h/kg, respectively; volume of distribution, 0.43 ± 0.16 and 0.37 ± 0.14 liter/kg, respectively. All extended-infusion regimens achieved PTAs of >90% at MICs of ≤16 mg/liter. Only the 3-h infusion regimens given every 6 h achieved PTAs of >90% at an MIC of 32 mg/liter. For susceptible bacterial pathogens, piperacillin-tazobactam doses of ≥80/10 mg/kg given every 8 h and infused over 4 h achieve adequate pharmacodynamic exposures in critically ill children.


Assuntos
Antibacterianos/farmacocinética , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/efeitos dos fármacos , Ácido Penicilânico/análogos & derivados , Fatores Etários , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Área Sob a Curva , Criança , Pré-Escolar , Simulação por Computador , Estado Terminal , Esquema de Medicação , Enterobacteriaceae/crescimento & desenvolvimento , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/sangue , Infecções por Enterobacteriaceae/microbiologia , Feminino , Taxa de Filtração Glomerular , Meia-Vida , Humanos , Lactente , Unidades de Terapia Intensiva , Masculino , Testes de Sensibilidade Microbiana , Método de Monte Carlo , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/sangue , Ácido Penicilânico/farmacocinética , Piperacilina/administração & dosagem , Piperacilina/sangue , Piperacilina/farmacocinética , Combinação Piperacilina e Tazobactam , Fatores Sexuais
14.
Antimicrob Agents Chemother ; 60(4): 2150-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26810655

RESUMO

The Clinical and Laboratory Standards Institute (CLSI) revised cefepime (CFP) breakpoints forEnterobacteriaceaein 2014, and MICs of 4 and 8 µg/ml were reclassified as susceptible-dose dependent (SDD). Pediatric dosing to provide therapeutic concentrations against SDD organisms has not been defined. CFP pharmacokinetics (PK) data from published pediatric studies were analyzed. Population PK parameters were determined using NONMEM, and Monte Carlo simulation was performed to determine an appropriate CFP dosage regimen for SDD organisms in children. A total of 664 CFP plasma concentrations from 91 neonates, infants, and children were included in this analysis. The median patient age was 1.0 month (interquartile range [IQR], 0.2 to 11.2 months). Serum creatinine (SCR) and postmenstrual age (PMA) were covariates in the final PK model. Simulations indicated that CFP dosing at 50 mg/kg every 8 h (q8h) (as 0.5-h intravenous [i.v.] infusions) will maintain free-CFP concentrations in serum of >4 and 8 µg/ml for >60% of the dose interval in 87.1% and 68.6% of pediatric patients (age, ≥30 days), respectively, and extending the i.v. infusion duration to 3 h results in 92.3% of patients with free-CFP levels above 8 µg/ml for >60% of the dose interval. CFP clearance (CL) is significantly correlated with PMA and SCR. A dose of 50 mg/kg of CFP every 8 to 12 h does not achieve adequate serum exposure for older children with serious infections caused by Gram-negative bacilli with a MIC of 8 µg/ml. Prolonged i.v. infusions may be useful for this population.


Assuntos
Antibacterianos/farmacocinética , Cefalosporinas/farmacocinética , Infecções por Enterobacteriaceae/tratamento farmacológico , Modelos Estatísticos , Infecções por Pseudomonas/tratamento farmacológico , Antibacterianos/sangue , Antibacterianos/uso terapêutico , Cefepima , Cefalosporinas/sangue , Cefalosporinas/uso terapêutico , Simulação por Computador , Creatinina/sangue , Cálculos da Dosagem de Medicamento , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/crescimento & desenvolvimento , Infecções por Enterobacteriaceae/sangue , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Lactente , Recém-Nascido , Infusões Intravenosas , Masculino , Testes de Sensibilidade Microbiana , Método de Monte Carlo , Infecções por Pseudomonas/sangue , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento
15.
Transpl Infect Dis ; 17(6): 921-5, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26436411

RESUMO

Infections with Cronobacter sakazakii are mainly described among neonates and infants, with contaminated powdered infant formulas most often incriminated as the cause. We describe here a case of C. sakazakii bacteremia secondary to a suspected cyst infection in a heart-and-kidney transplant patient with polycystic kidney disease.


Assuntos
Bacteriemia/microbiologia , Cronobacter sakazakii/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Transplante de Coração/efeitos adversos , Doenças Renais Policísticas/patologia , Infecções por Enterobacteriaceae/sangue , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade
16.
Ceylon Med J ; 60(1): 10-2, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25804911

RESUMO

INTRODUCTION: Although dengue management guidelines do not advice on use of antibiotics in dengue shock syndrome, unrecognised bactraemia is likely to contribute to morbidity and mortality. OBJECTIVES: To assess the occurance of secondary bacteraemia in adult patients with prolonged dengue fever. METHODS: A prospective study was conducted recruiting patients with confirmed acute dengue infection who had prolonged fever (>5 days). Two sets of blood cultures were taken in such patients prior to institution of antibiotic therapy. Demographic, clinical, haematological and biochemical parameters were recorded. Development of ascites and pleural effusions were detected using ultrasonography. RESULTS: Fourty patients (52.5% males) with a mean age of 29.8 years (SD 13.6) were studied. The average duration of fever was 7.9 days (SD 1.8). Ten patients (25%) had bacterial isolates in their blood cultures; Staphylococcus aureus (n=2), coliforms (n=3), pseudomonas (n=1) and 4 had mixed growths. The culture positive group had severe body aches at admission and higher fever, third space fluid accumulation, a significant drop in platelets and a higher CRP. CONCLUSIONS: A quarter of dengue patients with prolonged fever had a bacterial isolate. Culture positive patients appeared more ill with body aches and had higher degrees of fever during the latter part of the illness. Increased vascular permeability may predispose to bacterial seepage into blood. Although white cell count is not helpful in detecting bacteraemia, low platelet count and elevation of CRP seem to be helpful.


Assuntos
Bacteriemia/epidemiologia , Coinfecção/epidemiologia , Dengue/epidemiologia , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Pseudomonas/epidemiologia , Infecções Estafilocócicas/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Bacteriemia/sangue , Proteína C-Reativa/metabolismo , Coinfecção/sangue , Dengue/sangue , Progressão da Doença , Infecções por Enterobacteriaceae/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Prospectivos , Infecções por Pseudomonas/sangue , Distribuição por Sexo , Sri Lanka/epidemiologia , Infecções Estafilocócicas/sangue , Adulto Jovem
17.
J Clin Lab Anal ; 27(2): 113-20, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23349061

RESUMO

We collected and analyzed the time to detection (TTD) of blood cultures in the BacT/Alert automated system from 2002 to 2007. Among the 10,893 monomicrobial isolates from a total of 133,735 blood culture sets, the recoveries of aerobic bottles were compared with those of anaerobic bottles in this study. Significantly more Gram-positive cocci (except Staphylococcus aureus and enterococci), glucose nonfermentative Gram-negative bacteria, and yeast were recovered from aerobic bottles than from anaerobic bottles. The average TTD was 19.0 hr and 20.1 hr for the aerobic and anaerobic bottles, respectively, and 96.8% of the microorganisms were detected within the first 72 hr. Of the 5,489 microorganisms recovered from both of the blood culture bottle pair, microbial growth was significantly more often detected first in the anaerobic bottles than the aerobic bottles for Enterobacteriaceae except Serratia marcescens, while S. aureus, coagulase-negative staphylococci and Pseudomonas aeruginosa were more often detected first in the aerobic bottles. According to these data, we conclude that the earlier positivity of anaerobic bottles is a useful marker for rapid presumptive identification of Enterobacteriaceae infection.


Assuntos
Bacteriemia/microbiologia , Técnicas Bacteriológicas/instrumentação , Técnicas Bacteriológicas/métodos , Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/isolamento & purificação , Anaerobiose , Bacteriemia/sangue , Bacteriemia/diagnóstico , Infecções por Enterobacteriaceae/sangue , Infecções por Enterobacteriaceae/diagnóstico , Humanos , Estudos Retrospectivos , Fatores de Tempo
19.
Transfus Med ; 22(6): 450-1, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23035958

RESUMO

BACKGROUND: Citrobacter koseri has not been associated to infection caused by blood component transfusions. CASE REPORT: A 46-year-old female patient presented sudden chills, dyspnoea, and tachycardia during a transfusion from a unit of packed red blood cells. Citrobacter koseri was isolated in the two sample collected from the patient and from the content of the packed red blood cells. RESULTS: We report a case of bacteraemia due to a transfusion of contaminated red blood cells. CONCLUSION: C. koseri should be taken into account in bacteraemias caused by transfusion of blood components.


Assuntos
Bacteriemia/etiologia , Citrobacter koseri/isolamento & purificação , Infecções por Enterobacteriaceae/etiologia , Transfusão de Eritrócitos/efeitos adversos , Eritrócitos/microbiologia , Bacteriemia/sangue , Infecções por Enterobacteriaceae/sangue , Feminino , Humanos , Pessoa de Meia-Idade
20.
Infection ; 39(5): 485-8, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21706224

RESUMO

Yokenella regensburgei belongs to the Enterobacteriaceae and shares some biochemical characteristics with Hafnia alvei. A few case reports have suggested that it is an opportunistic pathogen, but there is no strong evidence to support its clinical importance. Until recently, it was difficult to accurately differentiate between Y. regensburgei and H. alvei by use of routine identification techniques. Here, we present a case of soft tissue infection and bacteremia caused by Y. regensburgei, which was successfully treated by intravenous administration of ceftriaxone for three weeks, and review the previous literature.


Assuntos
Bacteriemia/tratamento farmacológico , Infecções por Enterobacteriaceae/diagnóstico , Hospedeiro Imunocomprometido , Infecções Oportunistas/diagnóstico , Infecções dos Tecidos Moles/tratamento farmacológico , Adulto , Antibacterianos/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Ceftriaxona/uso terapêutico , Diagnóstico Diferencial , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/sangue , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/patologia , Hafnia alvei , Humanos , Infusões Intravenosas , Perna (Membro)/microbiologia , Perna (Membro)/patologia , Masculino , Infecções Oportunistas/sangue , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/patologia , Infecções dos Tecidos Moles/diagnóstico , Infecções dos Tecidos Moles/microbiologia , Infecções dos Tecidos Moles/patologia , Taiwan , Resultado do Tratamento
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