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1.
Z Gastroenterol ; 58(2): 160-170, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-32050286

RESUMO

Typhoid fever and paratyphoid fever are systemic infectious diseases of global significance caused by Salmonella enterica subspecies enterica Serovar Typhi (short name: Salmonella Typhi) or Serovar Paratyphi (short name: Salmonella Paratyphi). The course of these fecal-orally transmitted diseases is mainly characterized by a high fever. Left untreated, the course of typhoid fever can be severe and lethal. The infection is almost always acquired outside of Europe (mainly in India) and is notifiable in Germany, Austria and Switzerland. Paratyphoid is an attenuated disease of typhoid fever caused by Salmonella Paratyphi. Available vaccines only protect against Salmonella Typhi. Antibiotic resistance reflects the situation in endemic countries and shows a worrying increase of multi-drug resistant isolates. Currently, third-generation cephalosporins such as ceftriaxone are recommended as first-line therapy; if sensitive to quinolones, fluoroquinolones such as ciprofloxacin may continue to be administered. Crucial preventive measures for travelers to endemic regions include consistent water and food hygiene as well as vaccination, whereby only protection rates of 50-70 % are achieved by currently available vaccines. In the light of increasing multi-drug resistance, a more effective conjugate vaccine against Salmonella Typhi with cross-reactivity against Salmonella Paratyphi is needed more than ever.


Assuntos
Antibacterianos/farmacologia , Febre Paratifoide/tratamento farmacológico , Febre Paratifoide/prevenção & controle , Salmonella paratyphi A/efeitos dos fármacos , Salmonella typhi/efeitos dos fármacos , Febre Tifoide/tratamento farmacológico , Febre Tifoide/prevenção & controle , Vacinas Conjugadas/administração & dosagem , Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Fluoroquinolonas/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Febre Paratifoide/diagnóstico , Febre Paratifoide/microbiologia , Quinolonas/uso terapêutico , Salmonella enterica , Salmonella paratyphi A/isolamento & purificação , Salmonella typhi/isolamento & purificação , Febre Tifoide/diagnóstico , Febre Tifoide/microbiologia
2.
Int J Antimicrob Agents ; 55(3): 105885, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923568

RESUMO

We previously reported the detection of Escherichia coli and Klebsiella pneumoniae that displayed in vitro piperacillin-tazobactam (TZP) resistance but were susceptible to third-generation cephalosporins (TZP-R/Ceph3-S). In this study, we assessed the phenotypic and genotypic profiles of 12 clinical non-clonal TZP-R/Ceph3-S E. coli and K. pneumoniae isolates derived from bloodstream infections. Whole-genome sequencing revealed that most of the TZP-R/Ceph3-S E. coli and K. pneumoniae isolates examined harbored blaTEM-1 and blaSHV-1 genes, respectively, but none harbored extended-spectrum ß-lactamase, AmpC ß-lactamase or carbapenemase genes. Increasing the tazobactam concentration from 4 mg/L to 16 mg/L restored TZP in vitro susceptibility among E. coli isolates expressing TEM-1, but had minimal impact on the susceptibility of K. pneumoniae to TZP. Real-time qPCR analysis showed that blaTEM-1 expression was amplified in TZP-R E. coli upon incubation with sub-inhibitory TZP concentrations. Using an immunocompetent murine septicemia model, the efficacy of TZP against TZP-R/Ceph3-S isolates was assessed using TZP doses that mimicked human plasma exposures following intravenous (IV) administration of TZP 4.5 g q6h over 0.5 h for 24 h. Efficacy was assessed by survival through 96 h. There was high mortality in untreated control mice for all tested isolates. Compared with controls, TZP human-simulated exposure significantly improved survival for all TZP-R/Ceph3-S E. coli and K. pneumoniae isolates examined (P < 0.05). Thus, TZP was associated with remarkable in vivo activity against TZP-R/Ceph3-S E. coli and K. pneumoniae despite the observed resistance in vitro.


Assuntos
Cefalosporinas/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Combinação Piperacilina e Tazobactam/farmacologia , Animais , Proteínas de Bactérias/genética , Cefalosporinas/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Escherichia coli/genética , Humanos , Klebsiella pneumoniae/genética , Camundongos , Combinação Piperacilina e Tazobactam/uso terapêutico , beta-Lactamases/genética
3.
Int J Antimicrob Agents ; 55(3): 105891, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923569

RESUMO

Ceftolozane/tazobactam (C/T) is a novel ß-lactam/ß-lactamase inhibitor combination targeting Enterobacteriaceae and Pseudomonas aeruginosa (PA). It is approved in adult patients for complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs) as well as for nosocomial pneumonia. It displays excellent activity against PA, even multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. The aim of this systematic review (PROSPERO protocol no. CRD42019117350) was to summarise the available evidence from observational studies regarding the efficacy and safety of off-label use of C/T when administered to treat MDR- or XDR-PA infections. The MEDLINE and Embase databases were screened from inception up to 30 June 2019. Studies were deemed eligible if they described real-life use of C/T in the case of MDR- or XDR-PA infections for non-approved indications. Exclusion criteria were cIAIs, cUTIs, pneumonia (unless occurring in a paediatric population) and infections by non-MDR/XDR-PA. Thirty articles fulfilled the inclusion criteria. In total, 130 cases of MDR- or XDR-PA infections treated with C/T in 128 patients were described. The most relevant off-label uses were skin and soft-tissue infection (49/30; 37.7%), bone and joint infection (42/130; 32.3%) and bloodstream infection (23/130; 17.7%). Five cases involved paediatric patients. The overall clinical success rate was 76.2%. The most common adverse event was hypokalaemia (4.2%, in 48 evaluable cases). C/T may be a useful therapeutic option for difficult-to-treat infections by PA even outside the framework of approved indications. Further studies are necessary to better define new indications for the drug.


Assuntos
Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/efeitos dos fármacos , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Tazobactam/uso terapêutico , Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Humanos , Infecções Intra-Abdominais/tratamento farmacológico , Estudos Observacionais como Assunto , Infecções dos Tecidos Moles/tratamento farmacológico , Tazobactam/farmacologia , Infecções Urinárias/tratamento farmacológico
4.
Int J Antimicrob Agents ; 55(3): 105883, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923574

RESUMO

The aim of this study was to investigate the susceptibility of respiratory Gram-negative bacteria to ceftolozane/tazobactam and other antibiotics in the Asia-Pacific region during 2015-2016. MICs were determined using the CLSI standard broth microdilution method and interpreted accordingly. Pseudomonas aeruginosa (1574 isolates), Klebsiella pneumoniae (1226), Acinetobacter baumannii (627) and Escherichia coli (476) accounted for 73.1% of 5342 Gram-negative respiratory pathogens. Susceptibility to ceftolozane/tazobactam of individual Enterobacteriaceae was >80%, except for Enterobacter cloacae (76.6%). Ceftolozane/tazobactam inhibited 81.9% of K. pneumoniae and 91.9% of E. coli, with respective MIC50/MIC90 values of 0.5/>32 and 0.25/2 mg/L. For carbapenem-susceptible, ESBL-producing K. pneumoniae and E. coli, susceptibility was 65.5% and 93.3%, respectively, and respective MIC50/MIC90 values were 2/>32 and 0.5/2 mg/L. BlaCTX-M-1 group was most prevalent in selected ESBL-producing K. pneumoniae (40 of 54 isolates) and E. coli (15 of 22 isolates), with ceftolozane/tazobactam susceptibility rates of 50% and 80%, respectively. BlaSHV-ESBL was the second most prevalent, and ceftolozane/tazobactam inhibited 20% of 20 K. pneumoniae isolates with blaSHV-ESBL. The only effective antibiotics for carbapenem-non-susceptible K. pneumoniae (111 isolates) and E. coli (24 isolates) were amikacin and colistin. Ceftolozane/tazobactam was effective against almost all tested P. aeruginosa and carbapenem-non-susceptible strains, with susceptibility of 92.3% and 72.8%, respectively; the respective MIC50/MIC90 values were 1/4 and 2/>32 mg/L. The high susceptibility of ceftolozane/tazobactam remained in different age groups, patient locations, recovery times and countries, except Vietnam. In conclusion, ceftolozane/tazobactam was effective against most respiratory Gram-negative pathogens in the Asia-Pacific region; however, the emergence of carbapenem resistance mandates ongoing surveillance.


Assuntos
Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções Respiratórias/tratamento farmacológico , Tazobactam/farmacologia , Antibacterianos/uso terapêutico , Ásia , Cefalosporinas/uso terapêutico , Enterobacteriaceae/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Infecções Respiratórias/microbiologia , Tazobactam/uso terapêutico
5.
Int J Antimicrob Agents ; 55(3): 105887, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31926283

RESUMO

The STEP surveillance study was designed to increase knowledge about distribution of multidrug-resistant (MDR) Enterobacterales and Pseudomonas aeruginosa in Portugal, focusing on the intensive care unit (ICU). Antimicrobial susceptibility of common agents was also evaluated and compared with that of one of the latest therapeutic introductions, ceftolozane-tazobactam (C/T). Clinical isolates of Enterobacterales (n=426) and P. aeruginosa (n=396) from patients admitted in Portuguese ICUs were included. Activity of C/T and comparators was investigated using standard broth microdilution. Isolates were recovered from urinary tract (UTI, 36.9%), intra-abdominal (IAI, 24.2%) and lower respiratory tract (LRTI, 38.9%) infections. In P. aeruginosa, overall distribution of MDR/extremely-drug resistant (XDR)/pan-drug resistant (PDR) isolates accounted for 21.2%, 23.2% and 0.8%, respectively. C/T was the most potent agent tested against P. aeruginosa and MDR/XDR/PDR phenotypes. In Escherichia coli, extended-spectrum beta-lactamases (ESBL) and carbapenemase (CP) phenotypes accounted for 16.6% and 1.7%, respectively, whereas in Klebsiella spp., ESBL and CP-phenotypes represented 28.5% and 17.9%, respectively. Overall, susceptibility of C/T against Enterobacterales was 86.9%. C/T was the least affected agent in E. coli (99.4% susceptibility), whereas its activity was moderate in Klebsiella spp. (71.5%) and Enterobacter spp. (70.4%), due in part to a high rate of ESBL and CP-phenotypes. In Enterobacterales, blaKPC was the most prevalent CP gene (63.0%), followed by blaOXA-48 (33.3%) and blaVIM (3.7%). These microbiological results reinforce C/T as a therapeutic option in ICU patients with UTI, IAI or LRTI due to P. aeruginosa or Enterobacterales isolates, but not for CP producers.


Assuntos
Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/efeitos dos fármacos , Infecções Intra-Abdominais/tratamento farmacológico , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Infecções Respiratórias/tratamento farmacológico , Tazobactam/farmacologia , Infecções Urinárias/tratamento farmacológico , Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Enterobacteriaceae/microbiologia , Humanos , Unidades de Terapia Intensiva , Portugal , Infecções por Pseudomonas/microbiologia , Tazobactam/uso terapêutico
6.
Int J Infect Dis ; 90: 71-76, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31655112

RESUMO

OBJECTIVES: Our study aimed to assess antibiotic use in adult inpatients in the context of limited laboratory services at the main tertiary hospital in Sierra Leone. DESIGN: A cross-sectional study of consecutive adult inpatients (≥18 years) between October 2017 and February 2018 at Connaught Hospital in Freetown. RESULTS: A total of 920 patients were interviewed, of which 753 (81.8%) had at least one antibiotic. Complete data was captured for 688 (91.0%) patients. The median age was 41 years and 52.8% were male. Fever was reported in 41.5% of patients, though 85.1% had no leukocyte count prior to antibiotic use and none had a bacterial culture. Indications for prescribing were surgical prophylaxis (15.7%), pneumonia (15.1%), and trauma (5.8%). Cephalosporins (25.9%), penicillins (23.2%), and imidazoles (20.8%) were commonly prescribed. CONCLUSION: We found high rates of antibiotic use, of which most was not based on laboratory evidence. Lack of oversight and microbiological support are drivers of poor prescribing in many developing countries, which lack financial resources and serve a sicker population. Greater investments are needed to establish antimicrobial stewardship programs and provide clinicians with diagnostic support to enable improvements in patient outcomes and curb the spread of antibiotic resistance.


Assuntos
Antibacterianos/uso terapêutico , Adulto , Cefalosporinas/uso terapêutico , Serviços de Laboratório Clínico , Estudos Transversais , Feminino , Hospitalização , Humanos , Imidazóis/uso terapêutico , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Penicilinas/uso terapêutico , Serra Leoa , Adulto Jovem
7.
BMC Infect Dis ; 19(1): 980, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752716

RESUMO

BACKGROUND: Intra-abdominal infections (IAIs) represent a most frequent gastrointestinal emergency and serious cause of morbimortality. A full classification, including all facets of IAIs, does not exist. Two classifications are used to subdivide IAIs: uncomplicated or complicated, considering infection extent; and community-acquired, healthcare-associated or hospital-acquired, regarding the place of acquisition. Adequacy of initial empirical antibiotic therapy prescribed is an essential need. Inadequate antibiotic therapy is associated with treatment failure and increased mortality. This study was designed to determine accuracy of different classifications of IAIs to identify infections by pathogens sensitive to current treatment guidelines helping the selection of the best antibiotic therapy. METHODS: A retrospective cohort study including all adult patients discharged from hospital with a diagnosis of IAI between 1st of January and 31st of October, 2016. All variables potentially associated with pre-defined outcomes: infection by a pathogen sensitive to non-pseudomonal cephalosporin or ciprofloxacin plus metronidazole (ATB 1, primary outcome), sensitive to piperacillin-tazobactam (ATB 2) and hospital mortality (secondary outcomes) were studied through logistic regression. Accuracy of the models was assessed by area under receiver operating characteristics (AUROC) curve and calibration was tested using the Hosmer-Lemeshow goodness-of-fit test. RESULTS: Of 1804 patients screened 154 met inclusion criteria. Sensitivity to ATB 1 was independently associated with male gender (adjusted OR = 2.612) and previous invasive procedures in the last year (adjusted OR = 0.424) (AUROC curve = 0,65). Sensitivity to ATB 2 was independently associated with liver disease (adjusted OR = 3.580) and post-operative infections (adjusted OR = 2.944) (AUROC curve = 0.604). Hospital mortality was independently associated with age ≥ 70 (adjusted OR = 4.677), solid tumour (adjusted OR = 3.127) and sensitivity to non-pseudomonal cephalosporin or ciprofloxacin plus metronidazole (adjusted OR = 0.368). The accuracy of pre-existing classifications to identify infection by a pathogen sensitive to ATB 1 was 0.59 considering place of acquisition, 0.61 infection extent and 0.57 local of infection, for ATB 2 it was 0.66, 0.50 and 0.57, respectively. CONCLUSION: None of existing classifications had a good discriminating power to identify IAIs caused by pathogens sensitive to current antibiotic treatment recommendations. A new classification, including patients' individual characteristics like those included in the current model, might have a higher potential to distinguish IAIs by resistant pathogens allowing a better choice of empiric antibiotic therapy.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Intra-Abdominais/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Infecções Bacterianas/microbiologia , Cefalosporinas/uso terapêutico , Feminino , Humanos , Infecções Intra-Abdominais/microbiologia , Masculino , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , beta-Lactamas/uso terapêutico
8.
J Dairy Sci ; 102(12): 11476-11482, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31629523

RESUMO

The objective of this study was to describe weekly quarter-level somatic cell count (QSCC) after occurrence of nonsevere clinical mastitis (CM) that was diagnosed as culture negative, or caused by Escherichia coli or Klebsiella pneumoniae. All cases occurred in cows enrolled in negatively, controlled randomized clinical trials. We hypothesized that after occurrence of CM, QSCC patterns would vary among etiologies and this effect would not be mitigated by treatment using intramammary (IMM) ceftiofur. Data from two previously published randomized clinical trials performed on 3 Wisconsin dairy farms were used. Only cases confirmed as culture negative (NG) or E. coli or Kleb. pneumoniae (GRAMNEG) were used for analysis. In NG, cows were assigned to no antimicrobial treatment (negative control, n = 44) or 5 d of once daily IMM (n = 41) infusions with an approved product containing ceftiofur hydrochloride. In GRAMNEG, cows were assigned to IMM treatment with the same ceftiofur product for 2 different durations (2 d, n = 36; or 8 d, n = 38) or no antimicrobial treatment (negative control, n = 36). For quarters enrolled in NG, no significant differences were identified for weekly QSCC between quarters in the treated or negative control groups (5.4 log10SCC for both groups). For quarters enrolled in GRAMNEG, no significant differences were identified for QSCC between quarters that received the 2-d (6.2 log10SCC) or 8-d (6.3 log10SCC) IMM treatment or were in the negative control group (6.0 log10SCC). At the pathogen level, regardless of treatment, QSCC varied among pathogens and log10SCC were 5.4 (culture negative), 5.8 (E. coli), and 6.2 (Kleb. pneumoniae). Patterns of QSCC of CM diagnosed as culture negative and E. coli were similar in magnitude and time to resolution of the inflammatory response. In conclusion, as compared to CM diagnosed as culture negative or caused by E. coli, CM caused by Kleb. pneumoniae was associated with poorer outcomes. Regardless of IMM ceftiofur treatment, the immune response of the cow resulted in rapid reduction of SCC of quarters diagnosed as culture negative and quarters with CM caused by E. coli. In contrast, the SCC remained elevated for quarters with CM caused by Kleb. pneumoniae and a greater proportion of those cases remained chronically infected.


Assuntos
Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Infecções por Escherichia coli/veterinária , Infecções por Klebsiella/veterinária , Klebsiella pneumoniae , Mastite Bovina/tratamento farmacológico , Animais , Bovinos , Contagem de Células/veterinária , Escherichia coli , Infecções por Escherichia coli/tratamento farmacológico , Feminino , Infecções por Klebsiella/tratamento farmacológico , Estudos Longitudinais , Glândulas Mamárias Animais/patologia , Mastite Bovina/epidemiologia , Mastite Bovina/microbiologia , Leite/citologia
9.
Hosp Pract (1995) ; 47(4): 186-191, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31578888

RESUMO

Objectives: This study compared hospital readmission and mortality for patients with sepsis who received ceftaroline or daptomycin as first-line MRSA therapy.Methods: This retrospective comparative-effectiveness study included adults ≥18 years old hospitalized in the United States Veterans Health Care System with sepsis between 10/1/2010-9/30/2014, who received ceftaroline or daptomycin within 14 days of hospital admission as the first antibiotic effective against methicillin resistant Staphylococcus aureus (MRSA). Patients with pneumonia, and those who received both study drugs, were excluded. Baseline characteristics were compared using Chi-square, Fischer's exact, Student's t, and Wilcoxon Rank Sum tests. Patient outcomes were compared with multivariable logistic regression models.Results: 409 patients were included (ceftaroline = 67, daptomycin = 342). Ceftaroline patients were older, less likely to be Black, more likely to have diabetes with complications, and had higher Charlson comorbidity scores. Median (interquartile range) time from admission to drug initiation was 1 (0-1) day for ceftaroline and 1 (1-3) day for daptomycin (p = 0.01). Unadjusted hospital readmission rates for ceftaroline and daptomycin, respectively, were: 30-day (25%/37%, p = 0.06), 60-day (27%/44%, p = 0.008), and 90-day (28%/46%, p = 0.01). Unadjusted mortality rates were: in-hospital (7%/12%, p = 0.4), 30-day (3%/9%, p = 0.1), 60-day (6%/12%, p = 0.2), and 90-day (7%/15%, p = 0.1). In multivariable models with all divergent baseline characteristics included as covariates, patients treated with ceftaroline were less likely to experience (OR, 95% CI): 30/60/90-day hospital readmission (0.54, 0.29-0.98; 0.42, 0.23-0.76; 0.42, 0.23-0.75) and 30/60/90-day mortality (0.23, 0.04-0.82; 0.34, 0.10-0.93; 0.34, 0.11-0.86).Conclusion: In patients with sepsis, ceftaroline was associated with fewer hospital readmissions and lower mortality as compared to daptomycin. Prospective investigations in larger, more generalized cohorts are needed to examine outcomes with specific MRSA therapies.


Assuntos
Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Daptomicina/uso terapêutico , Staphylococcus aureus Resistente à Meticilina , Sepse/tratamento farmacológico , Sepse/microbiologia , Idoso , Comorbidade , Grupos de Populações Continentais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Estudos Retrospectivos , Fatores Socioeconômicos , Tempo para o Tratamento , Estados Unidos , United States Department of Veterans Affairs
10.
Expert Opin Pharmacother ; 20(17): 2169-2184, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31500471

RESUMO

Introduction: Antimicrobial resistance in Gram-negative pathogens is a significant threat to global health. ß-Lactams (BL) are one of the safest and most-prescribed classes of antibiotics on the market today. The acquisition of ß-lactamases, especially those which hydrolyze carbapenems, is eroding the efficacy of BLs for the treatment of serious infections. During the past decade, significant advances were made in the development of novel BL-ß-lactamase inhibitor (BLI) combinations to target ß-lactamase-mediated resistant Gram-negatives.Areas covered: The latest progress in 20 different approved, developing, and preclinical BL-BLI combinations to target serine ß-lactamases produced by Gram-negatives are reviewed based on primary literature, conference abstracts (when available), and US clinical trial searches within the last 5 years. The majority of the compounds that are discussed are being evaluated as part of a BL-BLI combination.Expert opinion: The current trajectory in BLI development is promising; however, a significant challenge resides in the selection of an appropriate BL partner as well as the development of resistance linked to the BL partner. In addition, dosing regimens for these BL-BLI combinations need to be critically evaluated. A revolution in bacterial diagnostics is essential to aid clinicians in the appropriate selection of novel BL-BLI combinations for the treatment of serious infections.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Inibidores de beta-Lactamases/uso terapêutico , Ácidos Borônicos/química , Ácidos Borônicos/uso terapêutico , Cefalosporinas/química , Cefalosporinas/uso terapêutico , Ensaios Clínicos como Assunto , Combinação de Medicamentos , Compostos Heterocíclicos com 1 Anel/química , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Humanos , Meropeném/química , Meropeném/uso terapêutico , Tazobactam/química , Tazobactam/uso terapêutico
11.
BMC Vet Res ; 15(1): 272, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370843

RESUMO

BACKGROUND: Ceftiofur Sodium is widely used in China. Our aim was to determine Ceftiofur Sodium activity and optimize dosing regimens against the pathogen Haemophilus parasuis using an in vitro and ex vivo pharmacokinetics/pharmacodynamics modeling approach. By adopting these strategies, we wanted to extend the effective life of Ceftiofur Sodium in reduce drug-resistance in pigs. RESULTS: We established an H. parasuis infection model in pigs, and assessed the pharmacokinetics of Ceftiofur Sodium in both healthy and infected animals. After Ceftiofur Sodium (10 mg/kg, i.m.) administration to healthy and H. parasuis-infected pigs, plasma based desfuroylceftiofur (a metabolite of Ceftiofur Sodium) was measured by High Performance Liquid Chromatography. The pharmacokinetics of Ceftiofur Sodium (desfuroylceftiofur) was consistent with a two-compartment open model, with first-order absorption. We observed no significant differences (P > 0.05) in pharmacokinetic parameters between healthy and infected pigs. Pharmacodynamics data showed that Ceftiofur Sodium was highly inhibitory against H. parasuis, with MIC, MBC, and MPC values of 0.003125, 0.0125 and 0.032 µg/mL, respectively. Desfuroylceftiofur in plasma also had strong bactericidal activity. Almost all H. parasuis cultured in plasma medium of Ceftiofur Sodium-inoculated healthy pigs, at each time point, were killed within 24 h. A weaker antibacterial activity was measured in infected-pig plasma medium at 18, 24, 36, and 48 h, after Ceftiofur Sodium inoculation. Pharmacokinetic parameters were combined with ex vivo pharmacodynamic parameters, and the bacteriostatic effect (36.006 h), bactericidal effect (71.637 h) and clearance (90.619 h) within 24 h, were determined using the Hill equation. Dose-calculation equations revealed the optimal dose of Ceftiofur Sodium to be 0.599-1.507 mg/kg. CONCLUSIONS: There were no significant differences in Ceftiofur Sodium pharmacokinetic parameters between healthy and infected pigs, although pharmacokinetics/pharmacodynamics fitting curves showed obviously differences. The optimal dose of Ceftiofur Sodium was lower than recommended (3 mg/kg), which may provide improved treatments for Glässers disease, with lower drug-resistance possibility.


Assuntos
Cefalosporinas , Infecções por Haemophilus/veterinária , Modelos Biológicos , Animais , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cefalosporinas/farmacocinética , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Infecções por Haemophilus/tratamento farmacológico , Infecções por Haemophilus/microbiologia , Haemophilus parasuis/efeitos dos fármacos , Suínos , Doenças dos Suínos/tratamento farmacológico , Doenças dos Suínos/microbiologia
12.
Rev Esp Quimioter ; 32 Suppl 3: 17-23, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31364337

RESUMO

Ceftobiprole is a fifth-generation cephalosporin with potent antimicrobial activity against Gram positive and Gram-negative bacteria. It has been approved in major European countries for the treatment of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP), excluding ventilator-associated pneumonia (VAP). Ceftobiprole is currently in a phase 3 clinical program for registration in the U.S. In 2015, it was designated as an infectious disease product qualified for the treatment of lung and skin infections by the FDA. The efficacy of ceftobiprole in pneumonia has been demonstrated in two-phase III clinical trials conducted in patients with CAP and HAP. The recommended dose in the adult with pneumonia is 500 mg every 8 h infused in 2 h; in case of renal failure, the regimen of administration must be adjusted according to the patient's renal function. It is not necessary to adjust the dose according to gender, age, body weight or liver failure. In case of hyperfiltration, an extension to 4 h infusion of the 500mg TID is required.


Assuntos
Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Antibacterianos/administração & dosagem , Antibacterianos/metabolismo , Cefalosporinas/administração & dosagem , Cefalosporinas/metabolismo , Ensaios Clínicos como Assunto , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Estado Terminal , Infecção Hospitalar/microbiologia , Esquema de Medicação , Humanos , Pneumonia Bacteriana/microbiologia , Insuficiência Renal/metabolismo
13.
Rev Esp Quimioter ; 32 Suppl 3: 24-28, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31364338

RESUMO

Ceftobiprole is a new cephalosporin with an extended spectrum activity against the majority of microorganisms isolated in bacteremia including methicillin-susceptible (MSSA) and -resistant S. aureus (MRSA). This antibiotic has demonstrated a potent activity against MRSA in animal models of endocarditis in monotherapy but particularly in combination with daptomycin, suggesting that this combination could be a future option to improve the outcome of staphylococcal endovascular infections. In addition, the extended-spectrum ceftobiprole activity, including coagulase-negative staphylococci, Enterococcus faecalis, Enterobacteriaceae and Pseudomonas aeruginosa represents an advantage for use as empirical therapy in bacteremia potentially caused by a broad spectrum of microorganisms, such as in catheter-related bacteremia.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Cefalosporinas/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Bacteriemia/microbiologia , Daptomicina/uso terapêutico , Quimioterapia Combinada/métodos , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Infecções Estafilocócicas/microbiologia , Staphylococcus/efeitos dos fármacos , Staphylococcus/enzimologia , Staphylococcus aureus/efeitos dos fármacos
14.
Rev Esp Quimioter ; 32 Suppl 3: 29-33, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31364339

RESUMO

Ceftobiprole is a fifth-generation cephalosporin approved for the treatment of adult community-acquired pneumonia and non-ventilator associated hospital-acquired pneumonia. However, its microbiological and pharmacokinetic profile is very attractive as armamentarium for empirical monotherapy treatment in other infections too. Among these, the following scenarios could be considered complicated skin and soft tissue infections, moderate-severe diabetic foot infections without bone involvement, vascular-catheter-associated-bloodstream infections, and fever without apparent focus in the hospitalized patient without septic shock or profound immunosuppression.


Assuntos
Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecção Hospitalar/microbiologia , Pé Diabético/complicações , Pé Diabético/tratamento farmacológico , Febre de Causa Desconhecida/tratamento farmacológico , Humanos , Pacientes Internados , Pneumonia Bacteriana/microbiologia , Dermatopatias Bacterianas/tratamento farmacológico , Infecções dos Tecidos Moles/tratamento farmacológico
15.
Rev Esp Quimioter ; 32 Suppl 3: 34-36, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31364340

RESUMO

Ceftobiprole is a fifth generation cephalosporin with a series of characteristics differentiating it from other beta-lactams, including its antibacterial activity, mainly against methicillin-resistant Staphylococcus aureus, resistant Streptococcus pneumoniae and also Gram-negative microorganisms such as Pseudomonas aeruginosa. This antibiotic has been subjected to various clinical trials and the results of these have led to its approval in Spain for the treatment of nosocomial pneumonia, excluding that associated with mechanical ventilation, and community-acquired pneumonia. The results of various ceftobiprole clinical studies provide consistent information on efficacy and tolerability. Ceftobiprole as monotherapy has been shown to be non-inferior to comparator antibiotics in different settings. Information is available on its compatibility with other drugs in Y-site administration, important from the point of view of the intravenous treatment of patients who present venous access limitation. On the other hand, and in contrast to other cephalosporins, ceftobiprole presents a low risk of infection due to Clostridium difficile and, in comparison with ceftaroline, neutropenia has not been reported to present any significant issues.


Assuntos
Antibacterianos/efeitos adversos , Cefalosporinas/efeitos adversos , Administração Intravenosa , Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase III como Assunto , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecção Hospitalar/tratamento farmacológico , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Neutropenia/induzido quimicamente , Pneumonia Bacteriana/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Streptococcus pneumoniae/efeitos dos fármacos
16.
Int J Antimicrob Agents ; 54(4): 410-422, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31404620

RESUMO

Staphylococcus aureus (S. aureus), including methicillin-resistant S. aureus (MRSA), is an important aetiological cause of community-acquired pneumonia (CAP) and associated with significant morbidity and mortality. Empiric therapy for CAP frequently consists of ß-lactam monotherapy or ß-lactam/macrolide combination therapy. However, such agents are often ineffective against S. aureus and do not reflect the emergence and increasing prevalence of MRSA in the community setting. Ceftaroline fosamil is a fifth-generation parenteral cephalosporin with broad-spectrum activity against Gram-positive pathogens - such as S. aureus (including MRSA), Streptococcus pneumoniae and Streptococcus pyogenes - and typical Gram-negative pathogens, including Haemophilus influenzae and Moraxella catarrhalis. The approval of ceftaroline fosamil in the United States and Europe for the treatment of adults with moderate-to-severe CAP was based on two phase 3 trials (FOCUS 1 and 2), which demonstrated that ceftaroline fosamil was non-inferior to ceftriaxone, a standard empiric treatment for CAP, while exhibiting a comparable safety profile. Although head-to-head trials of ceftaroline fosamil versus comparators against MRSA CAP are lacking, the effectiveness of ceftaroline fosamil in subpopulations of patients not covered by phase 3 trials (e.g. those with MRSA CAP or severe renal impairment) has been demonstrated in the Clinical Assessment Program and Teflaro Utilization Registry (CAPTURE) study. As ineffective empiric therapy is associated with adverse outcomes, including mortality and increased costs, ceftaroline fosamil, with its extended spectrum of activity, is an attractive alternative to standard antibiotic CAP regimens.


Assuntos
Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Pneumonia Estafilocócica/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Ensaios Clínicos Fase III como Assunto , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Humanos , Resultado do Tratamento
17.
Ann Clin Microbiol Antimicrob ; 18(1): 20, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31269955

RESUMO

BACKGROUND: Despite their critical role in antimicrobial stewardship programs, data on antimicrobial consumption among the pediatric and neonatal population is limited internationally and lacking in Saudi Arabia. The current study was done as part of our antimicrobial stewardship activities. OBJECTIVES: To calculate overall and type-specific antimicrobial consumption. METHODS: A prospective surveillance study was conducted at King Abdulaziz Medical City, Riyadh, Saudi Arabia, between October 2012 and June 2015 in two pediatric and one neonatal intensive care units (ICUs). Consumption data were collected manually on a daily basis by infection control practitioners. Data were presented as days of therapy (DOT) per 1000 patient-days and as frequency of daily consumption. RESULTS: During the 33 months of the study, a total of 30,110 DOTs were monitored during 4921 admissions contributing 62,606 patient-days. Cephalosporins represented 38.0% of monitored antimicrobials in pediatric ICUs followed by vancomycin (21.9%), carbapenems (14.0%), aminoglycosides (8.8%), and piperacillin/tazobactam (8.8%). Their consumption rates were 265.1, 152.6, 97.6, 61.4, and 61.4 DOTs per 1000 patient-days (respectively). Aminoglycosides represented 45.4% of monitored antimicrobials in neonatal ICU followed by cephalosporins (30.4%) vancomycin (13.6%), and carbapenems (8.3%). Their consumption rates were 147.5, 98.7, 44.3, and 27 DOTs per 1000 patient-days (respectively). CONCLUSION: Cephalosporins are frequently used in pediatric ICU while aminoglycosides are frequently used in neonatal ICU. The local consumption of cephalosporins and carbapenems in both ICUs is probably higher than international levels. Such data can help in establishing and monitoring the functions of antimicrobial stewardship activities aiming to ensure judicious consumption of antimicrobials.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecção Hospitalar/tratamento farmacológico , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Adolescente , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Carbapenêmicos/uso terapêutico , Cefalosporinas/uso terapêutico , Criança , Pré-Escolar , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Monitoramento Epidemiológico , Feminino , Humanos , Lactente , Masculino , Pediatria/estatística & dados numéricos , Estudos Prospectivos , Arábia Saudita/epidemiologia , Vancomicina/uso terapêutico
18.
Zhonghua Er Ke Za Zhi ; 57(8): 592-596, 2019 Aug 02.
Artigo em Chinês | MEDLINE | ID: mdl-31352743

RESUMO

Objective: To investigate the clinical characteristics of invasive Haemophilus influenzae (HI) infection in children. Methods: The clinical manifestations, laboratory examinations and treatment outcomes of 84 children with HI infection confirmed by bacterial culture in 7 tertiary children's hospitals from 2014 to 2018 were analyzed retrospectively. Results: Among the 84 cases, 50 were males. The age was 1.54 years (ranged from 5 days to 13 years).Twenty cases (24%) had underlying diseases and 48 cases (57%) had not received antibiotics before collecting specimens. Eighty-two cases (98%) had fever and 75 cases (89%) had clear infection foci, among which 31 cases (37%) had meningitis and 27 cases (32%) had pneumonia. Blood culture was positive in 62 cases (74%), cerebrospinal fluid culture was positive in 10 cases (12%), blood culture and cerebrospinal fluid culture were both positive in 11 cases (13%). Antibiotics susceptibility test showed that 27% (22/82) of all HI strains produced ß-lactamases and 48% (37/77) strains were resistant to ampicillin. The drug resistance rates to cefuroxime, ampicillin-sulbactam, trimethoprim-sulfamethoxazole and azithromycin were 25% (20/80) , 20% (9/45) , 71% (44/62) and 19%(11/58), respectively. All strains were sensitive to meropenem, levofloxacin and ceftriaxone. After sensitive antibiotic therapy, 83% (70/84) of all patients were cured and improved, the mortality rate and loss of follow-up rate were 13% (11/84) and 4% (3/84) respectively. Conclusions: Meningitis and pneumonia are common presentation of invasive HI infections in children. Mortality in HI meningitis children is high and the third generation of cephalosporins, such as ceftriaxone can be used as the first choice for the treatment of invasive HI infection.


Assuntos
Antibacterianos/uso terapêutico , Ceftriaxona/uso terapêutico , Infecções por Haemophilus/diagnóstico , Infecções por Haemophilus/tratamento farmacológico , Haemophilus influenzae/isolamento & purificação , Adolescente , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Criança , Pré-Escolar , Farmacorresistência Bacteriana , Feminino , Infecções por Haemophilus/epidemiologia , Haemophilus influenzae/efeitos dos fármacos , Humanos , Lactente , Masculino , Meningite/epidemiologia , Testes de Sensibilidade Microbiana , Pneumonia/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , beta-Lactamases/metabolismo
19.
J Vet Diagn Invest ; 31(5): 681-687, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31342869

RESUMO

Salmonella enterica resistance to extended-spectrum cephalosporins (ESC) conferred by cefotaximases (blaCTX-M) is a growing concern in the United States. Among food-producing animals, poultry are a major reservoir of ESC-resistant Salmonella. A retrospective study was carried out to further characterize 38 ceftiofur-resistant clinical Salmonella enterica isolates obtained from poultry during 2007-2018. Of the isolates tested, 31 displayed resistance to ceftriaxone and harbored blaCMY-2, whereas 7 isolates demonstrated resistance or reduced susceptibility to cefepime in addition to ceftriaxone resistance. These 7 isolates displayed extended-spectrum ß-lactamase activity, harbored blaCTX-M-1, and were recovered only from recent poultry diagnostic submissions made in 2011-2018 as opposed to the 31 isolates that were recovered in 2007-2018. Further characterization of the blaCTX-M-1 gene determined that it was located on conjugative IncN/ST1 and IncI1/ST87 plasmids in the isolates from commercial turkeys and broilers, respectively. These plasmids have been responsible for extensive spread of blaCTX-M-1 in livestock, poultry, and humans in Europe. Potential transfer of IncN and IncI1 plasmids and/or nontyphoidal Salmonella carrying these plasmids through the food chain, or by other means to humans, may result in treatment failures. Our study demonstrates the importance of further characterization of ceftiofur-resistant S. enterica isolates detected by veterinary diagnostic laboratories to identify the sources of blaCTX-M-1 and to mitigate the spread of ESC-resistant Salmonella in the poultry production pyramid.


Assuntos
Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Doenças das Aves Domésticas/microbiologia , Salmonella enterica/enzimologia , beta-Lactamases/isolamento & purificação , Animais , Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Europa (Continente) , Humanos , Testes de Sensibilidade Microbiana/veterinária , Aves Domésticas , Doenças das Aves Domésticas/tratamento farmacológico , Fatores R , Estudos Retrospectivos , Salmonella enterica/efeitos dos fármacos , Salmonella enterica/genética , beta-Lactamases/genética
20.
BMC Res Notes ; 12(1): 452, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337435

RESUMO

OBJECTIVE: This was a 5 year retrospective study of patients' hospital records to find out how patients with cellulitis are managed and the care provided by nurses to these patients in some hospitals in Fako, Cameroon. RESULTS: Of the 236 cases of cellulitis identified from a study of hospital records, 202 were included in the study. Most of the participants (55%) were female and the mean (SD) age was 43 (1.1) years. Cellulitis accounted for 2.3% of admissions in this study. The predisposing factors identified were; the presence of trauma (60.5%), HIV infection (18.6%), alcohol consumption (8.4%) and tobacco use (4.8%). Commonly recorded complications were necrosis (32.2%), sepsis (23%), abscess formation (19.5%), and ulcer development (19.5%). Medical management was with antibiotic therapy, including mostly penicillin (26.5%), aminoglycoside (22.1%), nitroimidazole (20.2%) and cephalosporin (19.6%). Debridement (46.7%), and incision and drainage (44.4%) were the most implemented surgical interventions. Nursing care, as found in patients' hospital records were predominantly on medication administration (98.0%), vital signs assessment (90.5%) and patient assessment (53%). Cellulitis therefore was found among a substantial number of patients and management was predominantly with combination antibiotics therapy and inadequate nursing care.


Assuntos
Antibacterianos/uso terapêutico , Celulite (Flegmão)/terapia , Desbridamento/métodos , Drenagem/métodos , Papel do Profissional de Enfermagem/psicologia , Abscesso/diagnóstico , Abscesso/patologia , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/fisiopatologia , Aminoglicosídeos/uso terapêutico , Camarões , Celulite (Flegmão)/etiologia , Celulite (Flegmão)/cirurgia , Cefalosporinas/uso terapêutico , Gerenciamento Clínico , Feminino , Infecções por HIV/complicações , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Necrose/diagnóstico , Necrose/patologia , Nitroimidazóis/uso terapêutico , Enfermeiras e Enfermeiros/organização & administração , Penicilinas/uso terapêutico , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/patologia , Estudos Retrospectivos , Fatores de Risco , Sepse/diagnóstico , Sepse/patologia , Fumar/efeitos adversos , Fumar/fisiopatologia , Úlcera/diagnóstico , Úlcera/patologia , Ferimentos e Lesões/complicações , Ferimentos e Lesões/patologia
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