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1.
J Infect Chemother ; 28(1): 87-90, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34535403

RESUMO

We describe a case of a 48 years old male with left sided endocarditis and septic emboli secondary to a Pseudomonas aeruginosa strain that developed resistance to other ß-lactam antibiotics during therapy resulting in prolonged bacteremia. Blood cultures sterilized within 1 day of initiating ceftolozane/tazobactam 3 g every 8 hours in combination with ciprofloxacin. Steady state free ceftolozane plasma Cmax and Cmin concentrations were calculated to be 122.2µg/mL and 24.3µg/mL, respectively. The multidrug-resistant strain harbored chromosomal ß-lactamases OXA-486 and PDC-3, mutations in ampD and dacB predicted to lead to ampC over-expression, and mutations in OprD predicted to decrease outer membrane permeability. Following completion of a 42 day course and aortic valve replacement, the patient was deemed clinically cured without recurrence of infection at follow up 2 years later. To our knowledge, this is the first reported case to measure ceftolozane concentrations during the treatment of endocarditis which supports dose optimization approaches of severe endovascular disease due to multidrug resistant pathogens.


Assuntos
Endocardite , Infecções por Pseudomonas , Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Endocardite/tratamento farmacológico , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Ácido Penicilânico , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/genética , Tazobactam/uso terapêutico
2.
Curr Opin Infect Dis ; 34(6): 718-727, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34751185

RESUMO

PURPOSE OF REVIEW: The COVID-19 pandemic has caused multiple challenges to ICUs, including an increased rate of secondary infections, mostly caused by Gram-negative micro-organisms. Worrying trends of resistance acquisition complicate this picture. We provide a review of the latest evidence to guide management of patients with septic shock because of Gram-negative bacteria. RECENT FINDINGS: New laboratory techniques to detect pathogens and specific resistance patterns from the initial culture are available. Those may assist decreasing the time to adequate antimicrobial therapy and avoid unnecessary broad-spectrum antibiotic overuse. New antimicrobials, including ß-lactam/ß-lactamase inhibitor combinations, such as ceftolozane-tazobactam, imipenem-relebactam or meropenem-vaborbactam and cephalosporins, such as cefiderocol targeted to specific pathogens and resistance patterns are available for use in the clinical setting. Optimization of antibiotic dosing and delivery should follow pharmacokinetic and pharmacodynamic principles and wherever available therapeutic drug monitoring. Management of sepsis has brought capillary refill time back to the spotlight along with more reasoned fluid resuscitation and a moderate approach to timing of dialysis initiation. SUMMARY: Novel rapid diagnostic tests and antimicrobials specifically targeted to Gram-negative pathogens are available and should be used within the principles of antimicrobial stewardship including de-escalation and short duration of antimicrobial therapy.


Assuntos
COVID-19 , Infecções por Bactérias Gram-Negativas , Choque Séptico , Antibacterianos/uso terapêutico , Cefalosporinas , Testes Diagnósticos de Rotina , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana , Pandemias , SARS-CoV-2 , Choque Séptico/tratamento farmacológico
3.
BMC Infect Dis ; 21(1): 1037, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615472

RESUMO

BACKGROUND: Timely and accurate identification of uropathogens and determination of their antimicrobial susceptibility is paramount to the management of urinary tract infections (UTIs). The main objective of this study was to develop an assay using LAMP (Loop mediated isothermal amplification) technology for simple, rapid and sensitive detection of the most common bacteria responsible for UTIs, as well as for the detection of the most prevalent genes (encoding cefotaximases from CTX-M group 1) responsible for resistance to 3rd generation of cephalosporins. METHOD: We designed primers targeting Proteus mirabilis, while those targeting Escherichia coli, Klebsiella pneumoniae and Enterococcus faecalis and the CTX-M group 1 resistance gene were benchmarked from previous studies. The amplification reaction was carried out in a warm water bath for 60 min at 63 ± 0.5 °C. The amplicons were revealed by staining with Sybr Green I. Specificity and sensitivity were determined using reference DNA extracts spiked in sterile urine samples. The analytical performance of the assays was evaluated directly on pellets of urine samples from patients suspected of UTI and compared with culture. RESULTS: We found a high specificity (100%) for LAMP assays targeting the selected bacteria (P. mirabilis, E. coli, K. pneumoniae, E. faecalis) and the CTX-M group 1 when using DNA extracts spiked in urine samples. The sensitivities of the assays were around 1.5 103 Colony Forming Units (CFU) /mL corresponding to the cut-off value used to define bacteriuria or UTIs in patients with symptoms. Out of 161 urine samples tested, using culture as gold standard, we found a sensitivity of the LAMP techniques ranging from 96 to 100% and specificity from 95 to 100%. CONCLUSION: We showed that the LAMP assays were simple and fast. The tests showed high sensitivity and specificity using a simple procedure for DNA extraction. In addition, the assays could be performed without the need of an expensive device such as a thermal cycler. These LAMP assays could be useful as an alternative or a complementary tool to culture reducing the time to diagnosis and guiding for more effective treatment of UTIs but also as a powerful diagnostic tool in resource-limited countries where culture is not available in primary health care structures.


Assuntos
Cefalosporinas , Escherichia coli , Escherichia coli/genética , Humanos , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico
4.
Water Res ; 206: 117732, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34637972

RESUMO

Microplastics (MPs) have been recognized as a global concern due to their potential health effect, as MPs could adsorb and carry various pollutants in aquatic environment. In the present study, a new environmental behavior related to polyvinyl chloride microplastics (PVC-MPs) and the underlying mechanism were described. Our results showed that the photo-aged PVC-MPs could affect the transformation of cephalosporin antibiotics. For instance, the presence of altered PVC-MPs significantly accelerated the hydrolysis of cefazolin (CFZ), but exhibited negligible effect on the degradation of cephalexin (CFX). As indicated by in situ Fourier transform infrared spectra and theoretical calculations, hydrogen bonds could be formed between ß-lactam carbonyl of CFZ and the oxygen-containing moieties on the aged PVC-MP surfaces. The hydrogen-bonding was able to significantly increase the positive atomic Mulliken charge on the ß-lactam carbonyl carbon, thus narrowing the energy gap of CFZ hydrolysis and subsequently enhancing the disruption of ß-lactam ring. While for CFX, instead of the ß-lactam carbonyl, the amide amino group was involved in the hydrogen-bonding due to the structural difference. Therefore, in addition to increasing the adsorption capacity, the aged PVC-MPs could act as the catalyst to mediate the transformation of antibiotics. Our study would help improve the understanding for interactions between contaminants and MPs in natural environments.


Assuntos
Microplásticos , Poluentes Químicos da Água , Adsorção , Cefalosporinas , Plásticos , Cloreto de Polivinila , Poluentes Químicos da Água/análise
5.
J Avian Med Surg ; 35(3): 290-294, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34677027

RESUMO

The objective of this study was to evaluate the pharmacokinetic properties of ceftiofur crystalline free acid (CCFA) administered intramuscularly at dosages of 10 and 20 mg/kg in bald eagles (BAEAs) (Haliaeetus leucocephalus). Ceftiofur crystalline free acid is a long-acting, injectable, third-generation cephalosporin antibiotic drug. A prospective, randomized, complete crossover design was used for this pharmacokinetic investigation. CCFA (10 or 20 mg/kg) was administered intramuscularly, and blood samples were obtained from 6 adult, nonreleasable, healthy BAEAs at predetermined sampling times. After a 4-week washout period, the protocol was repeated with each bird receiving the dose not given during the initial sample collection according to the randomized crossover design. Plasma ceftiofur free acid equivalents were quantified and data were analyzed by a noncompartmental pharmacokinetic approach. The mean observed peak plasma concentrations were 9.23 µg/mL and 15.08 µg/mL for 10 and 20 mg/kg CCFA IM administration, respectively. The mean observed time to maximum plasma concentration was 18 and 17.6 hours, and the mean terminal elimination half-life was 32.38 and 38.08 hours for intramuscular administration of 10 and 20 mg/kg CCFA, respectively, in the BAEAs. Reported minimum inhibitory concentrations of raptor bacterial isolates from a prior study was used to determine the target minimum inhibitory concentration of 1 µg/mL selected for this investigation. From the previously published information, a target plasma concentration of 4 µg/mL was determined for the CCFA in the BAEAs. From the results of this study, CCFA may be dosed every 60 and 110 hours at 10 mg/kg IM, and every 80 and 160 hours at 20 mg/kg IM in BAEAs.


Assuntos
Cefalosporinas , Águias , Animais , Antibacterianos , Meia-Vida , Injeções Intramusculares/veterinária , Estudos Prospectivos
6.
Molecules ; 26(19)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34641579

RESUMO

Spiro compounds provide attractive targets in drug discovery due to their inherent three-dimensional structures, which enhance protein interactions, aid solubility and facilitate molecular modelling. However, synthetic methodology for the spiro-functionalisation of important classes of penicillin and cephalosporin ß-lactam antibiotics is comparatively limited. We report a novel method for the generation of spiro-cephalosporin compounds through a Michael-type addition to the dihydrothiazine ring. Coupling of a range of catechols is achieved under mildly basic conditions (K2CO3, DMF), giving the stereoselective formation of spiro-cephalosporins (d.r. 14:1 to 8:1) in moderate to good yields (28-65%).


Assuntos
Cefalosporinas/síntese química , Compostos de Espiro/síntese química , Catecóis/química , Estrutura Molecular , Penicilinas/química
7.
Rev Esp Quimioter ; 34 Suppl 1: 29-31, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34598420

RESUMO

Community-acquired pneumonia (CAP) is one of the leading causes of admission to emergency departments. Ceftaroline is a fifth-generation cephalosporin with a potent In vitro activity against Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus, the three most important pathogens causing CAP. Three randomized and double-blind clinical trials compared the efficacy of ceftaroline versus ceftriaxone in patients with CAP and the results of each trial and a meta-analysis, concluded the superiority of ceftaroline in terms of clinical success. In particular, the major difference was observed among patients with CAP caused by S. aureus. Accordingly, ceftaroline has been included as a first-line option in the recent clinical guidelines for the management of CAP.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia Bacteriana , Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Staphylococcus aureus
8.
Rev Esp Quimioter ; 34 Suppl 1: 32-34, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34598421

RESUMO

Ceftobiprole is a broad-spectrum, fifth-generation cephalosporin currently approved for community-acquired and non-ventilator-associated hospital-acquired pneumonia. High bactericidal and anti-biofilm activity has been exhibited in in vitro and animal models. This, together with its synergism with other antibiotics against gram-positive bacteria, makes it an ideal candidate for treatment of complex infections, such as those associated with devices or infective endocarditis. More clinical data are needed to achieve drug positioning.


Assuntos
Cefalosporinas , Endocardite Bacteriana , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Endocardite Bacteriana/tratamento farmacológico , Bactérias Gram-Positivas
9.
Rev Esp Quimioter ; 34 Suppl 1: 35-37, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34598422

RESUMO

Ceftolozane-tazobactam is currently the most active antipseudomonal agent, including multidrug-resistant extensively drug-resistant strains. Tazobactam provides additional activity against many extended-spectrum beta-lactamases Enterobacterales. Ceftolozane-tazobactam is formally approved for complicated urinary tract infection, complicated intra-abdominal infection, and hospital-acquired and ventilator-associated bacterial pneumonia. The clinical and microbiological success is over 70-80% in many series. However, resistant mutants to ceftolozane-tazobactam have been already described. Combination therapies with colistin or meropenem could be among the strategies to avoid the resistance emergence.


Assuntos
Infecções Intra-Abdominais , Infecções por Pseudomonas , Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Colistina , Humanos , Infecções Intra-Abdominais/tratamento farmacológico , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa , Tazobactam/uso terapêutico
10.
Rev Esp Quimioter ; 34 Suppl 1: 41-43, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34598424

RESUMO

Cefiderocol is a novel catechol-substituted siderophore cephalosporin that binds to the extracellular free iron, and uses the bacterial active iron transport channels to penetrate in the periplasmic space of Gram-negative bacteria (GNB). Cefiderocol overcomes many resistance mechanisms of these bacteria. Cefiderocol is approved for the treatment of complicated urinary tract infections, hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia in the case of adults with limited treatment options, based on the clinical data from the APEKS-cUTI, APEKS-NP and CREDIBLE-CR trials. In the CREDIBLE-CR trial, a higher all-cause mortality was observed in the group of patients who received cefiderocol, especially those with severe infections due to Acinetobacter spp. Further phase III clinical studies are necessary in order to evaluate cefiderocol´s efficacy in the treatment of serious infections.


Assuntos
Antibacterianos , Infecções por Bactérias Gram-Negativas , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos
11.
Rev Esp Quimioter ; 34(5): 511-524, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34693705

RESUMO

Severe infection and its evolution to sepsis are becoming more prevalent every day and are among the leading causes of critical illness and mortality. Proper management is crucial to improve prognosis. This document addresses three essential points that have a significant impact on this objective: a) early recognition of patients with sepsis criteria, b) identification of those patients who suffer from an infection and have a high risk of progressing to sepsis, and c) adequate selection and optimization of the initial antimicrobial treatment.


Assuntos
Antibacterianos , Infecção Hospitalar , Antibacterianos/uso terapêutico , Ceftazidima , Cefalosporinas , Infecção Hospitalar/tratamento farmacológico , Humanos , Tazobactam
12.
J Pharm Biomed Anal ; 206: 114358, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34534866

RESUMO

The chromatographic and lipophilicity characters of seven cephalosporins of different four classes (cephradine, cefaclor, cefprozil, cefixime, cefotaxime, ceftazidime and cefepime) were examined by salting out thin-layer chromatography (SOTLC). SOTLC using ammonium sulfate salt was employed to predict the lipophilicity of the proposed drugs via their retention behavior. The calculated RM0 values showed liner relationship with the molar concentration of ammonium sulfate in mobile phase in the range of 0.5-2.5 mol/L. Additionally, quantitative structure retention relationship (QSRR) was generated to figure out the relationship between the calculated chromatographic parameters (RM0 and C0) and log P of the studied cephalosporins. Good correlations were found between the chromatographically obtained retention parameters (RM0 and C0) and some molecular descriptors of the examined drugs. Furthermore, an efficient QSAR model was carried out using the calculated chromatographic parameters (RM0 and C0) and log P of the studied cephalosporins to predict minimum inhibitory concentration (MIC) and blood brain barrier (BBB) penetration of the examined drugs. The study was extended to separate and quantify the selected antibiotics in their pure forms and pharmaceutical formulations. Normal phase thin layer chromatographic (NP-TLC) method using a usable developing system of acetone: methanol: water: ammonium hydroxide: glacial acetic acid (90: 10: 18: 3: 2, by volume) was successfully applied to resolve the studied cephalosporins. Linearity was achieved in the range of 0.2-3 µg/mL for most of the studied antibiotics. The developed SOTLC method can be considered as a good start alternative to reversed phase thin layer chromatography (RP-TLC) for prediction of the lipophilic properties of examined cephalosporins. Moreover, the proposed NP-TLC densitometric method can be easily applied for quality control analysis of the chosen drugs and other structurally related components.


Assuntos
Cefalosporinas , Cromatografia de Fase Reversa , Cefepima , Cromatografia em Camada Delgada , Testes de Sensibilidade Microbiana
13.
Microb Pathog ; 160: 105201, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34547409

RESUMO

The emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains of animal origin that are resistant to several antibiotics is of great concern. Cefquinome is a fourth-generation cephalosporin developed specifically for veterinary use. The mechanism of MRSA resistance to cefquinome is still not established. Therefore, we designed this study to evaluate the effect of cefquinome on the transcriptome of MRSA1679a, a strain that was isolated from a chicken. The transcriptome analysis indicated that multiple efflux pumps (QacA, NorB, Bcr, and ABCb) were upregulated in MRSA1679a as a resistance mechanism to expel cefquinome. Additionally, penicillin-binding protein 1A was overexpressed, which conferred resistance to cefquinome, a ß-lactam antibiotic. Adhesion and the biofilm-forming capacity of the MRSA strain was also enhanced in addition to overexpression of many stress-related genes. Genes related to carbohydrate metabolism, secretion systems, and transport activity were also significantly upregulated in MRSA1679a. In conclusion, global transcription was triggered to overcome the stress induced by cefquinome, and the MRSA1679a showed a great genetic potential to survive in this challenging environment. This study provides a profound understanding of MRSA1679a as a potentially important pathogen and identifies key resistance characteristics of MRSA against cefquinome. Studies should be aimed to demonstrate multidrug resistance mechanisms of virulent strains by exposing to different antibiotic combinations.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Cefalosporinas/farmacologia , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , RNA-Seq
14.
J Pharm Biomed Anal ; 206: 114378, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34592571

RESUMO

Ceftiofur (CEF) residues in animal-derived foods are of great concern to farmers, regulatory agencies and consumers. In this study, an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) method was established to quickly monitor CEF residues in edible animal tissues using an easy sample preparation procedure. A monoclonal antibody, 4D5, against CEF has been produced at first, which had IC50 values for CEF, ceftriaxone, cefquinome, cefotaxime and desfuroylceftiofur of 0.78 µg/L, 0.73 µg/L, 13.6 µg/L, 8.99 µg/L and 8.89 µg/L, respectively. The limit of detection (LOD) and limit of quantitation (LOQ) in artificially contaminated animal-derived foods were 0.12-0.19 µg/L and 0.20-0.30 µg/L. The recovery rates were in the range of 89.7-109.0%. The CVs were less than 6.7%. A good correlation (R= 0.9994) between the ic-ELISA and UPLC-MS/MS showed the reliability of the developed ic-ELISA. The ic-ELISA produces a sensitive, accurate and low-cost tool for the screening of residues of CEF in animal-derived foods.


Assuntos
Anticorpos Monoclonais , Cefalosporinas/análise , Resíduos de Drogas/análise , Ensaio de Imunoadsorção Enzimática , Carne/análise , Animais , Cromatografia Líquida , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
15.
Can Vet J ; 62(9): 975-981, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34475583

RESUMO

This study investigated the pharmacokinetics of ceftiofur after intravenous regional limb perfusion (IVRLP). Six horses were involved in 3 IVRLP sessions. For each session, operators with varying clinical experience placed the tourniquet. A wide-rubber tourniquet was applied in the antebrachium as 2 g of ceftiofur in a total volume of 100 mL was injected into the cephalic vein. Plasma and metacarpophalangeal synovial fluid samples were obtained to evaluate perfusate leakage and synovial fluid concentrations of ceftiofur over 24 h. Overall, mean plasma concentrations were not significantly different before and after tourniquet removal. Mean synovial fluid ceftiofur concentrations were significantly higher 5 min and 8 h after tourniquet removal versus 24 h, after which values above the minimum inhibitory concentration (MIC) (1 µg/mL) were not detected. Concentrations above the MIC were detected in 72% and 50% of the horses at 5 min and 8 h, respectively. Overall, higher synovial fluid concentrations were obtained for the operator with the most recent clinical experience performing IVRLP.


Assuntos
Amicacina , Membro Anterior , Animais , Antibacterianos , Cefalosporinas , Cavalos , Articulação Metacarpofalângica , Perfusão/veterinária , Líquido Sinovial
16.
Nursing ; 51(10): 18-29, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34580258
17.
BMJ Open ; 11(9): e049481, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580096

RESUMO

INTRODUCTION: Alternatives to carbapenems are needed in the treatment of third-generation cephalosporin-resistant Enterobacterales (3GCR-E). Temocillin is a suitable candidate, but comparative randomised studies are lacking. The objective is to investigate if temocillin is non-inferior to carbapenems in the targeted treatment of bacteraemia due to 3GCR-E. METHODS AND ANALYSIS: Multicentre, open-label, randomised, controlled, pragmatic phase 3 trial. Patients with bacteraemia due to 3GCR-E will be randomised to receive intravenously temocillin (2 g three times a day) or carbapenem (meropenem 1 g three times a day or ertapenem 1 g once daily). The primary endpoint will be clinical success 7-10 days after end of treatment with no recurrence or death at day 28. Adverse events will be collected; serum levels of temocillin will be investigated in a subset of patients. For a 10% non-inferiority margin, 334 patients will be included (167 in each study arm). For the primary analysis, the absolute difference with one-sided 95% CI in the proportion of patients reaching the primary endpoint will be compared in the modified intention-to-treat population. ETHICS AND DISSEMINATION: The study started after approval of the Spanish Regulatory Agency and the reference institutional review board. Data will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04478721.


Assuntos
Bacteriemia , Meropeném , Penicilinas , Bacteriemia/tratamento farmacológico , Cefalosporinas/farmacologia , Ensaios Clínicos Fase III como Assunto , Enterobacteriaceae/efeitos dos fármacos , Humanos , Meropeném/uso terapêutico , Estudos Multicêntricos como Assunto , Penicilinas/uso terapêutico , Ensaios Clínicos Pragmáticos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
BMC Vet Res ; 17(1): 313, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34563197

RESUMO

BACKGROUND: Antimicrobial resistance and presence of zoonotic enteropathogens in shelter dogs pose a public health risk to shelter workers and potential adopters alike. In this study we investigated the prevalence of zoonotic bacterial pathogens and cephalosporin resistant (CefR) enteric bacteria in the feces of apparently healthy shelter dogs in the Cumberland Gap Region (CGR) in the US states of Kentucky, Tennessee and Virginia. RESULTS: Fecal samples of 59 dogs from 10 shelters in the CGR of Central and South-Central Appalachia were screened for the presence of Campylobacter jejuni, Clostridium perfringens, Salmonella and CefR enteric bacteria. C. jejuni, C. perfringens were detected by PCR based assays. Culture and PCR were used for Salmonella detection. Of 59 dogs, fecal samples from 14 (23.7%) and 8 (13.6%) dogs tested positive for cpa and hipO genes of C. perfringens and C. jejuni, respectively. Salmonella was not detected in any of the tested samples by PCR or culture. CefR enteric bacteria were isolated on MacConkey agar supplemented with ceftiofur followed by identification using MALDI-TOF. Fecal samples from 16 dogs (27.1%) yielded a total of 18 CefR enteric bacteria. Majority of CefR isolates (14/18, 77.8%) were E. coli followed by, one isolate each of Enterococcus hirae, Acinetobacter baumannii, Acinetobacter pittii, and Pseudomonas aeruginosa. CefR enteric bacteria were tested for resistance against 19- or 24-antibiotic panels using broth microdilution method. Seventeen (94.4%) CefR bacteria were resistant to more than one antimicrobial agent, and 14 (77.8%) displayed multidrug resistance (MDR). CONCLUSIONS: This study shows that shelter dogs within the CGR not only carry zoonotic bacterial pathogens, but also shed multidrug resistant enteric bacteria in their feces that may pose public health risks.


Assuntos
Infecções Bacterianas/veterinária , Zoonoses Bacterianas/microbiologia , Farmacorresistência Bacteriana , Microbioma Gastrointestinal/fisiologia , Animais , Antibacterianos/farmacologia , Região dos Apalaches/epidemiologia , Infecções Bacterianas/microbiologia , Cefalosporinas/farmacologia , Fezes/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Reação em Cadeia da Polimerase
20.
Crit Care ; 25(1): 290, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380538

RESUMO

BACKGROUND: Ceftolozane/tazobactam is approved for treatment of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) at double the dose approved for other infection sites. Among nosocomial pneumonia subtypes, ventilated HABP (vHABP) is associated with the lowest survival. In the ASPECT-NP randomized, controlled trial, participants with vHABP treated with ceftolozane/tazobactam had lower 28-day all-cause mortality (ACM) than those receiving meropenem. We conducted a series of post hoc analyses to explore the clinical significance of this finding. METHODS: ASPECT-NP was a multinational, phase 3, noninferiority trial comparing ceftolozane/tazobactam with meropenem for treating vHABP and VABP; study design, efficacy, and safety results have been reported previously. The primary endpoint was 28-day ACM. The key secondary endpoint was clinical response at test-of-cure. Participants with vHABP were a prospectively defined subgroup, but subgroup analyses were not powered for noninferiority testing. We compared baseline and treatment factors, efficacy, and safety between ceftolozane/tazobactam and meropenem in participants with vHABP. We also conducted a retrospective multivariable logistic regression analysis in this subgroup to determine the impact of treatment arm on mortality when adjusted for significant prognostic factors. RESULTS: Overall, 99 participants in the ceftolozane/tazobactam and 108 in the meropenem arm had vHABP. 28-day ACM was 24.2% and 37.0%, respectively, in the intention-to-treat population (95% confidence interval [CI] for difference: 0.2, 24.8) and 18.2% and 36.6%, respectively, in the microbiologic intention-to-treat population (95% CI 2.5, 32.5). Clinical cure rates in the intention-to-treat population were 50.5% and 44.4%, respectively (95% CI - 7.4, 19.3). Baseline clinical, baseline microbiologic, and treatment factors were comparable between treatment arms. Multivariable regression identified concomitant vasopressor use and baseline bacteremia as significantly impacting ACM in ASPECT-NP; adjusting for these two factors, the odds of dying by day 28 were 2.3-fold greater when participants received meropenem instead of ceftolozane/tazobactam. CONCLUSIONS: There were no underlying differences between treatment arms expected to have biased the observed survival advantage with ceftolozane/tazobactam in the vHABP subgroup. After adjusting for clinically relevant factors found to impact ACM significantly in this trial, the mortality risk in participants with vHABP was over twice as high when treated with meropenem compared with ceftolozane/tazobactam. TRIAL REGISTRATION: clinicaltrials.gov, NCT02070757. Registered 25 February, 2014, clinicaltrials.gov/ct2/show/NCT02070757.


Assuntos
Cefalosporinas/normas , Pneumonia Associada a Assistência à Saúde/tratamento farmacológico , Meropeném/normas , Tazobactam/normas , Idoso , Antibacterianos/farmacologia , Antibacterianos/normas , Antibacterianos/uso terapêutico , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Método Duplo-Cego , Estudos de Equivalência como Asunto , Feminino , Humanos , Modelos Logísticos , Masculino , Meropeném/farmacologia , Meropeném/uso terapêutico , Pessoa de Meia-Idade , Pneumonia Bacteriana/tratamento farmacológico , Estudos Retrospectivos , Tazobactam/farmacologia , Tazobactam/uso terapêutico
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