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1.
Medicine (Baltimore) ; 99(10): e19466, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150105

RESUMO

Multidrug-resistant bacterial (MDRB) infections have been difficult to treat clinically. Tigecycline (TIG) has several advantages, especially in the treatment of severe infections. Many clinicians have considered increasing the TIG dose to improve the efficacy of this molecule. The safety and efficacy of high-dose TIG in elderly patients with MDRB infections were investigated in this study.We conducted a retrospective analysis of the elderly patients with MDRB infections who were treated at the First Affiliated Hospital. A total of 106 patients received a conventional dose (CD-TIG group: 50 mg every 12 hours) of TIG and 51 received a high dose (HD-TIG group: 100 mg every 12 hours). The data from all patients were collected for examining the clinical features and performing the microbiological analysis. The safety profile and efficacy of the HD regimen were investigated.The clinical efficacy and microbiological eradication in the patients with MDRB infection were higher in the HD-TIG group than the CD-TIG group. The independent predictors of clinical cure were the use of TIG at HD (odd ratio [OR], 5.129; 95% confidence interval [CI] [1.890, 13.921]; P = .001) and microbiological eradication (OR, 3.049; 95% CI, [1.251, 7.430]; P = .014). In the ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) subgroups, the sole independent predictor of clinical cure was the HD of TIG, and no significant adverse events were observed. The occurrence of multidrug-resistant Acinetobacter baumannii infection and an MIC value of 1 to 2 g/mL for TIG were independently associated with clinical failure in the VAP subgroup.HDs of TIG was found to associate with better clinical efficacy and microbiological eradication than its CDs in the elderly patients with MDRB infections. In the VAP and BSIs subgroups, administration of HDs of TIG was associated with better outcomes.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Tigeciclina/uso terapêutico , APACHE , Acinetobacter baumannii/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Tigeciclina/administração & dosagem , Tigeciclina/farmacologia , Resultado do Tratamento
3.
Ann Lab Med ; 40(1): 15-20, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31432634

RESUMO

BACKGROUND: Carbapenem-resistant K. pneumoniae 2297, isolated from a patient treated with tigecycline for pneumonia, developed tigecycline resistance, in contrast to carbapenem-resistant isolate 1215, which was collected four months prior to the 2297 isolate. Mechanisms underlying tigecycline resistance were elucidated for the clinical isolates. METHODS: The tigecycline minimum inhibitory concentration (MIC) was determined using the broth microdilution method, with or without phenylalanine-arginine ß-naphthylamide (PABN), and whole-genome sequencing was carried out by single-molecule real-time sequencing. The expression levels of the genes acrA, oqxA, ramA, rarA, and rpoB were determined by reverse-transcription quantitative PCR. RESULTS: Both isolates presented identical antibiograms, except for tigecycline, which showed an MIC of 0.5 mg/L in 1215 and 2 mg/L in 2297. The addition of PABN to tigecycline-resistant 2297 caused a four-fold decrease in the tigecycline MIC to 0.5 mg/L, although acrA expression (encoding the AcrAB efflux pump) was upregulated by 2.5 fold and ramA expression (encoding the pump activator RamA) was upregulated by 1.4 fold. We identified a 6,096-bp fragment insertion flanking direct TATAT repeats that disrupted the romA gene located upstream of ramA in the chromosome of K. pneumoniae 2297; the insertion led the ramA gene promoter replacement resulting in stronger activation of the gene. CONCLUSIONS: The K. pneumoniae isolate developed tigecycline resistance during tigecycline treatment. It was related to the overexpression of the AcrAB resistance-nodulation-cell division efflux system due to promoter replacement.


Assuntos
Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana/genética , Klebsiella pneumoniae/genética , Proteínas de Membrana Transportadoras/metabolismo , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Genoma Bacteriano , Humanos , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Proteínas de Membrana Transportadoras/genética , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Regiões Promotoras Genéticas , Tigeciclina/farmacologia , Tigeciclina/uso terapêutico , Sequenciamento Completo do Genoma , beta-Lactamases/genética , beta-Lactamases/metabolismo
4.
Medicine (Baltimore) ; 98(38): e17091, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567945

RESUMO

BACKGROUND: High-dose (HD) tigecycline regimen is increasingly used in infectious diseases, however its efficacy and safety versus low-dose (LD) is still unclear. METHODS: A systematic review and meta-analysis was performed; PubMed, Embase, Cochrane Library, ScienceDirect, Web of Science, clinicalTrials.gov, Wanfang, VIP, and China National Knowledge Infrastructure (CNKI), were searched using terms "tigecycline" AND "dose" up to October 31, 2018. Eligible studies were randomized trials or cohort studies comparing mortality, clinical response, microbiological eradication and safety of different tigecycline dose regimens for any bacterial infection. The primary outcome was mortality, and the secondary outcomes were clinical response rate, microbiological eradiation rate and adverse events (AEs). Meta-analysis was done with random-effects model, with risk ratios (RR) and 95% confidence intervals (CI) calculated for all outcomes. RESULTS: Of 951 publications retrieved, 17 studies (n = 1041) were pooled in our meta-analysis. The primary outcome was available in 11 studies, and the RR for mortality was 0.67 (95% CI 0.53-0.84, P < .001). Clinical response (RR 1.46, 95% CI 1.30-1.65, P < .001) and microbiological eradication rate (RR 1.61, 95% CI 1.35-1.93, P < .001) were both higher in HD than in LD tigecycline regimen. However, non-Chinese study subgroup presented no statistical significance between HD and LD regimen, RR for mortality, clinical response and microbiological eradication were 0.79 (95% CI 0.56-1.14, P = .21), 1.35 (95% CI 0.96-1.92, P = .26), 1.00 (95% CI 0.22-4.43, P = 1.00), respectively. AEs did not differ between HD and LD tigecycline (RR 1.00, 95% CI 0.80-1.26, P = .97). CONCLUSION: HD tigecycline regimen reduced mortality meanwhile improved clinical efficacy and should be considered in serious infections caused by multidrug-resistant and extensively drug-resistant (MDR/XDR) bacteria.


Assuntos
Antibacterianos/uso terapêutico , Pneumonia Bacteriana/tratamento farmacológico , Tigeciclina/uso terapêutico , Antibacterianos/administração & dosagem , Relação Dose-Resposta a Droga , Humanos , Tigeciclina/administração & dosagem , Resultado do Tratamento
5.
Medicine (Baltimore) ; 98(40): e17436, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577763

RESUMO

BACKGROUND: Complicated intra-abdominal infections (cIAIs) are common in clinical practice, caused by a mixture of aerobic and anaerobic bacteria, increase the risk of mortality. Carbapenems and tigecycline (TGC) are recommended for antimicrobial therapies for cIAIs. OBJECTIVE: To compare the effectiveness and safety of different carbapenems vs TGC for the treatment of cIAIs. METHODS: PubMed, Embase, Medline (via Ovid SP) and Cochrane library databases were systematically searched. We included randomized controlled trials (RCTs) comparing different carbapenems vs TGC for the treatment of cIAIs. The pooled odds ratio (OR) with 95% credible interval (CrI) was calculated by Markov chain Monte Carlo methods. We estimated summary ORs using pairwise and network meta-analysis with random effects. RESULTS: Fifteen studies involving 6745 participants were included in the analysis. Five different carbapenems and TGC were ultimately evaluated in this study. Although, the efficacy of carbapenems and TGC by ORs with corresponding 95% CrIs had not yet reached statistical differences, the cumulative rank probability indicated that clinical treatment success from best to worst was doripenem (DOPM), meropenem (MEPM), imipenem/cilastatin (IC), biapenem (BAPM), TGC and imipenem/cilastatin/relebactam (ICRB); microbiological treatment success from best to worst was DOPM, MEPM, IC, BAPM, ICRB and TGC. As for the risk of adverse events (AEs), TGC showed higher risk of AEs compared with IC (OR = 1.53, 95% CrI = 1.02-2.41), the remain antibiotic agents from lower to higher was MEPM, IC, BAPM, DOPM, ICRB and TGC. The risk of mortality from lower to higher was BAPM, DOPM, MEPM, IC, TGC and ICRB. CONCLUSION: No differences in clinical and microbiological outcomes were observed between different carbapenems and TGC. Balancing the evidence for drug efficacy and side effects, DOPM appears to be the best available treatment for cIAIs. Therefore, it is reasonable to consider that DOPM is one of the best carbapenem monotherapy for cIAIs. MEPM and IC was also associated with higher rates of clinical and microbiological treatment success following DOPM. Empiric antimicrobial treatment of patients with cIAIs should be selected in light of the local bacterial epidemiology and patterns of resistance.


Assuntos
Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Infecções Intra-Abdominais/tratamento farmacológico , Tigeciclina/uso terapêutico , Teorema de Bayes , Humanos , Meta-Análise em Rede
6.
Eklem Hastalik Cerrahisi ; 30(3): 201-11, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31650915

RESUMO

OBJECTIVES: This study aims to evaluate the effects of mesenchymal stem cell (MSC) implantation on vascular graft infections caused by methicillin-resistant Staphylococcus epidermidis (MRSE) and compare with antibiotic treatment. MATERIALS AND METHODS: Healthy adult 56 Wistar rats (age, over 5 months; weighing, 300-350 g) were divided into eight groups. Group 1 was defined as the control group and group 2 was defined as the infected control group. Groups 3 and 4 were defined as Dacron grafted and MRSE infected groups, treated with tigecycline and MSCs, respectively. Groups 5 and 6 were performed polytetrafluoroethylene (PTFE) graft and infected with MRSE. These groups were also administered tigecycline and MSC treatment, respectively. Groups 7 and 8 were infected with MRSE without graft administration and were also performed tigecycline and MSC treatment, respectively. Grafts and soft tissue specimens were collected at 13 days postoperatively. Colony counts of peri-graft tissue were performed. All samples were evaluated by enzyme-linked immunosorbent assay (ELISA) for the markers that determine stem cell activity. RESULTS: The overall success of the treatments was assessed by the number of rats with MRSE recurrence, regardless of graft used. The difference between the untreated group 2, tigecycline groups (3, 5 and 7) and MSCs groups (4, 6 and 8) were statistically significant. Success of MSC and tigecycline treatments was similar in Dacron, PTFE, and non-grafted groups. There was a resistance of MRSE infection in Dacron groups to MSC and tigecycline treatments. This was considered to be indicative of the susceptibility of the Dacron grafts to infection. However, there was no significant difference between group 2 and Dacron groups in terms of bacterial colonization. ELISA results were significant in three cytokines. CONCLUSION: Mesenchymal stem cells can be considered as an alternative treatment option on its own or part of a combination therapy for control of vascular graft infections.


Assuntos
Prótese Vascular/microbiologia , Transplante de Células-Tronco Mesenquimais , Resistência a Meticilina , Infecções Relacionadas à Prótese/terapia , Infecções Estafilocócicas/terapia , Animais , Antibacterianos/farmacologia , Prótese Vascular/efeitos adversos , Células-Tronco Mesenquimais/citologia , Polietilenotereftalatos , Politetrafluoretileno , Infecções Relacionadas à Prótese/microbiologia , Ratos , Ratos Wistar , Staphylococcus epidermidis , Tigeciclina/farmacologia
7.
Emerg Microbes Infect ; 8(1): 1524-1527, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31631781

RESUMO

The recent emergence of plasmid-mediated tigecycline resistance genes, tet(X3) and tet(X4), in animals and humans in China would pose a foreseeable threat to public health. To illustrate this paradigm shift in tigecycline resistance, here, covering the period 2008-2018, we retrospectively analysed a national strain collection of Escherichia coli (n = 2254), obtained from chickens and pigs, in six representative provinces of China. The gene tet(X4) was identified in five pig isolates collected in 2016 and 2018 from the provinces of Sichuan (3/15, 2018), Henan (1/25, 2018) and Guangdong (1/28, 2016), but not in the isolates prior to 2016. None of the isolates was detected harbouring tet(X3). All tet(X4)-positive E. coli exhibited high levels of tigecycline resistance (MICs, 16-64 mg/L), and two were confirmed as colistin resistant, harbouring chromosome-borne mcr-1 gene. The gene tet(X4) was detected on a plasmid in all five isolates, whereas a co-location of tet(X4) on the chromosome of one isolate was observed. Diverse host strains and novel plasmids related to the tet(X4) gene were observed. Our timely findings of the recent emergence of tet(X4) gene in food animal support the rapid surveillance and eradication of this gene before it is established.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Infecções por Escherichia coli/veterinária , Proteínas de Escherichia coli/genética , Escherichia coli/isolamento & purificação , Doenças das Aves Domésticas/microbiologia , Doenças dos Suínos/microbiologia , Tigeciclina/farmacologia , Animais , Galinhas , China , Colistina/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/metabolismo , Plasmídeos/genética , Plasmídeos/metabolismo , Estudos Retrospectivos , Suínos
8.
PLoS Biol ; 17(10): e3000515, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31652256

RESUMO

Evolved resistance to one antibiotic may be associated with "collateral" sensitivity to other drugs. Here, we provide an extensive quantitative characterization of collateral effects in Enterococcus faecalis, a gram-positive opportunistic pathogen. By combining parallel experimental evolution with high-throughput dose-response measurements, we measure phenotypic profiles of collateral sensitivity and resistance for a total of 900 mutant-drug combinations. We find that collateral effects are pervasive but difficult to predict because independent populations selected by the same drug can exhibit qualitatively different profiles of collateral sensitivity as well as markedly different fitness costs. Using whole-genome sequencing of evolved populations, we identified mutations in a number of known resistance determinants, including mutations in several genes previously linked with collateral sensitivity in other species. Although phenotypic drug sensitivity profiles show significant diversity, they cluster into statistically similar groups characterized by selecting drugs with similar mechanisms. To exploit the statistical structure in these resistance profiles, we develop a simple mathematical model based on a stochastic control process and use it to design optimal drug policies that assign a unique drug to every possible resistance profile. Stochastic simulations reveal that these optimal drug policies outperform intuitive cycling protocols by maintaining long-term sensitivity at the expense of short-term periods of high resistance. The approach reveals a new conceptual strategy for mitigating resistance by balancing short-term inhibition of pathogen growth with infrequent use of drugs intended to steer pathogen populations to a more vulnerable future state. Experiments in laboratory populations confirm that model-inspired sequences of four drugs reduce growth and slow adaptation relative to naive protocols involving the drugs alone, in pairwise cycles, or in a four-drug uniform cycle.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Enterococcus faecalis/efeitos dos fármacos , Genoma Bacteriano , Modelos Estatísticos , Ampicilina/farmacologia , Evolução Molecular Direcionada , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Sinergismo Farmacológico , Enterococcus faecalis/genética , Enterococcus faecalis/crescimento & desenvolvimento , Enterococcus faecalis/metabolismo , Fosfomicina/farmacologia , Aptidão Genética , Testes de Sensibilidade Microbiana , Mutação , Rifampina/farmacologia , Seleção Genética , Processos Estocásticos , Tigeciclina/farmacologia , Sequenciamento Completo do Genoma
9.
Medicine (Baltimore) ; 98(39): e17339, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574872

RESUMO

INTRODUCTION: During the past decade, the rate of carbapenem resistance among Enterobacteriaceae, mostly in Escherichia coli and Klebsiella pneumoniae, has significantly increased worldwide. It is a great challenge for the choice of drug treatment especially in children.Tigecycline is the first drug in the glycylcycline class of antibiotics. For children, the China Food and Drug Administration and US Food and Drug Administration postulated that tigecycline is not recommended. It must be used only as salvage therapy for life-threatening infections in critically ill children who have no alternative treatment options. PATIENT CONCERNS: A male pediatric case of 4.5 months was blood stream infection after liver transplantation. The blood cultures obtained grew Gram-negative rods, which reportedly grew a strain of extended-spectrum ß-lactamase and carbapenemases-producing Escherichia coli within 10 hours. All bacterial isolates were found to be resistant to all antimicrobial agents except aminoglycosides and tigecycline. DIAGNOSES: Complicated intra-abdominal infection, central line-associated blood stream infection. INTERVENTIONS: The blood stream infection with carbapenem-resistant Escherichia coli after liver transplantation was cured by tigecycline. OUTCOMES: The patient's condition continued to improve, then transferred to general ward. CONCLUSION: The following report, to our knowledge, is the youngest liver transplantation patient who used tigecycline treatment around the world. It provides reference and experience for the use of tigecycline in infants with severe infections.


Assuntos
Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Escherichia coli/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Tigeciclina/uso terapêutico , Infecções por Enterobacteriaceae/microbiologia , Infecções por Escherichia coli/microbiologia , Humanos , Lactente , Transplante de Fígado/efeitos adversos , Masculino , Complicações Pós-Operatórias/microbiologia
10.
Int J Mol Sci ; 20(16)2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31430857

RESUMO

Osteoporosis is a common disorder of bone remodeling, caused by the imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Recently, we reported that matrix metalloproteinase-9 (MMP-9)-dependent histone H3 proteolysis is a key event for proficient osteoclast formation. Although it has been reported that several MMP-9 inhibitors, such as tetracycline and its derivatives, show an inhibitory effect on osteoclastogenesis, the molecular mechanisms for this are not fully understood. Here we show that tetracycline analogs, especially tigecycline and minocycline, inhibit osteoclast formation by blocking MMP-9-mediated histone H3 tail cleavage. Our molecular docking approach found that tigecycline and minocycline are the most potent inhibitors of MMP-9. We also observed that both inhibitors significantly inhibited H3 tail cleavage by MMP-9 in vitro. These compounds inhibited receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclast formation by blocking the NFATc1 signaling pathway. Furthermore, MMP-9-mediated H3 tail cleavage during osteoclast differentiation was selectively blocked by these compounds. Treatment with both tigecycline and minocycline rescued the osteoporotic phenotype induced by prednisolone in a zebrafish osteoporosis model. Our findings demonstrate that the tetracycline analogs suppress osteoclastogenesis via MMP-9-mediated H3 tail cleavage, and suggest that MMP-9 inhibition could offer a new strategy for the treatment of glucocorticoid-induced osteoporosis.


Assuntos
Histonas/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/farmacologia , Minociclina/farmacologia , Osteogênese/efeitos dos fármacos , Tigeciclina/farmacologia , Animais , Células Cultivadas , Feminino , Humanos , Masculino , Modelos Moleculares , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Peixe-Zebra
11.
Int J Infect Dis ; 86: 208-211, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31402295

RESUMO

BACKGROUND: The aim of this study was to determine the effect of colistin resistance and other predictors on fatality among patients with Klebsiella pneumoniae bloodstream infections (Kp-BSI) and to describe the effect of amikacin and tigecycline on the outcome in an OXA-48 dominant country. METHOD: This was a retrospective study performed among patients >16 years of age in a tertiary hospital with 465 beds. All cases had ≥1 positive blood culture for K. pneumoniae 48 h after admission. RESULTS: Among 210 patients with Kp-BSI, the 30-day mortality rate after isolation of the microorganism was 58%. The rate of carbapenem resistance was higher (64% vs. 38%, p < 0.001) and the colistin minimum inhibitory concentration (MIC) was elevated (7 vs. 4, p < 0.029) among the patients who died. Among the colistin-resistant K. pneumoniae, the rates of OXA-48, ST101, and NDM-1 were 78%, 67%, and 35%, respectively. Amikacin was added to the treatment of 13 patients with carbapenem and colistin-resistant Kp-BSI and 77% survived (p < 0.001). Tigecycline was added to the treatment of 24 patients with carbapenem and colistin-resistant Kp-BSI, and the 30-day mortality rate was 71% (p = 0.576). In the multivariate analysis, carbapenem resistance (odds ratio (OR) 5.2, 95% confidence interval (CI) 2.47-10.9, p < 0.001) and increasing APACHE II score (OR 1.19, 95% CI 1.12-1.26, p < 0.001) were significantly associated with 30-day mortality. The addition of amikacin to the treatment regimen (OR 0.05, 95% CI 0.01-0.23, p < 0.001) was significantly beneficial. CONCLUSIONS: Carbapenem resistance, increasing MIC of colistin, and the lungs as the source of the infection were significantly associated with 30-day mortality. The empirical use of combined active aminoglycosides was found to be beneficial in the treatment of colistin-resistant K. pneumoniae infections.


Assuntos
Antibacterianos/farmacologia , Bacteriemia/tratamento farmacológico , Colistina/farmacologia , Farmacorresistência Bacteriana , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amicacina/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Carbapenêmicos/farmacologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária , Tigeciclina/farmacologia , Adulto Jovem , beta-Lactamases/análise
12.
Indian J Med Microbiol ; 37(1): 72-90, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31424014

RESUMO

Antimicrobial resistance is on the rise across the globe. Increasing incidence of infections due to carbapenem resistance organisms is becoming difficult to treat, due to the limited availability of therapeutic agents. Very few agents such as colistin, fosfomycin, tigecycline and minocycline are widely used, despite its toxicity. However, with the availability of novel antimicrobials, beta-lactam/beta-lactamase inhibitor-based and non-beta-lactam-based agents could be of great relief. This review covers three important aspects which include (i) current management of carbapenem-resistant infections, (ii) determination of specific types of carbapenemases produced by multidrug-resistant and extensively drug-resistant Gram-negative pathogens and (iii) the currently available novel beta-lactam/beta-lactamase inhibitors and non-beta-lactam-based agents' laboratory findings, clinical outcome and implications.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Farmacorresistência Bacteriana Múltipla/genética , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/genética , Carbapenêmicos/farmacologia , Colistina/farmacologia , Fosfomicina/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Minociclina/farmacologia , Tigeciclina/farmacologia
13.
Indian J Med Microbiol ; 37(1): 91-94, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31424015

RESUMO

Tigecycline is a reserve antibiotic increasingly used for the treatment of multidrug-resistant bacteria, especially Klebsiella pneumoniae and Acinetobacter baumannii. At present, there are concerns regarding the testing and interpretation of tigecycline susceptibility to bugs such as K. pneumoniae and A. baumannii, which limit clinicians in appropriate usage. Use of appropriate method for testing such as broth microdilution is essential. In addition, tigecycline susceptibility testing is a challenge due to inconsistent results from various antimicrobial susceptibility testing automated platforms. There is a great need to define a suitable methodology along with interpretive criteria, especially for K. pneumoniae and A. baumannii. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Food and Drug Administration (FDA) breakpoints show wide variation and are defined for different set of organisms. Non-species-related pharmacokinetic/pharmacodynamic (PK/PD) breakpoints defined by the EUCAST can be used for organisms such as K. pneumoniae and A. baumannii.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Tigeciclina/farmacologia , Acinetobacter baumannii/genética , Farmacorresistência Bacteriana Múltipla/genética , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana
14.
BMC Pharmacol Toxicol ; 20(1): 50, 2019 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-31426870

RESUMO

BACKGROUND: Tigecycline, the first glycylcycline-class drug, is a broad-spectrum antibiotic with activity against multi-drug resistant (MDR) organisms. We describe a case of sustained and severe hypoglycemia in a patient treated with tigecycline for pneumonia due to MDR Klebsiella pneumoniae. CASE PRESENTATION: A 74-year-old man was admitted for treatment of pneumonia. At admission he had prediabetes. In the hospital he developed renal failure. On day 3, the patient experienced severe shortness of breath. He was intubated and transferred to the intensive care unit (ICU) for ventilator support. In the ICU the antibiotic regimen was cefoperazone and sulbactam (1 g every 12 h). Continuous Renal Replacement Therapy was started on that day. Test for anti-neutrophil cytoplasmic antibodies (ANCA) was positive, and so the nephrologist and rheumatologist agreed on a diagnosis of ANCA-associated vasculitis, with renal and pulmonary involvement and acute renal failure. Plasmapheresis, and high-dose methylprednisolone treatment were started on day 6, and there was obvious improvement in the patient's condition. The steroid regimen was gradually tapered to oral prednisone (35 mg every day) on day 19. Afterwards, the patient's pneumonia worsened. Sputum culture showed Klebsiella pneumoniae sensitive to only tigecycline. Tigecycline treatment (100 mg every 12 h) was administered on day 20. Hypoglycemia started about 37 h after the first dose of tigecycline. Infusion of 50% glucose through the femoral vein was required for over 20 h to maintain normal blood glucose concentrations. Tigecycline was stopped, but the hypoglycemia resolved only after a further 34 h. The insulin and C-peptide levels were found to be markedly elevated during the hypoglycemia. The Naranjo scale score of 7 indicated that the likelihood of tigecycline causing severe hypoglycemia was "probable." CONCLUSION: This is the first report of sustained severe hypoglycemia due to tigecycline. Oversecretion of insulin appears to have been the cause of the hypoglycemia in our patient. The mechanism needs to be investigated.


Assuntos
Antibacterianos/efeitos adversos , Hipoglicemia/induzido quimicamente , Tigeciclina/efeitos adversos , Idoso , Humanos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae , Masculino , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia
15.
Emerg Microbes Infect ; 8(1): 1219-1222, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31429665

RESUMO

Plasmid-mediated antimicrobial resistance has emerged as one of the principal global issues, posing significant threats to public health. Herein, we reported a mobile tigecycline resistance mechanism Tet(X4) on both plasmid and chromosome in Escherichia coli strains from migratory birds in China. Besides tigecycline, these tet(X4)-positive strains also exhibited elevated MICs to the FDA newly approved tetracycline antibiotics, eravacycline (4 µg/ml) and omadacycline (8 µg/ml). Worrisomely, the tet(X4)-carrying plasmids and chromosome also shared high homology with the plasmids from human. Taken together, Tet(X4) represents another emerging antimicrobial threat and collective efforts from different sectors are needed to control its further spread.


Assuntos
Antibacterianos/farmacologia , Aves/microbiologia , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Sequências Repetitivas Dispersas , Tigeciclina/farmacologia , Animais , China , Cromossomos Bacterianos , Escherichia coli/genética , Genes Bacterianos , Testes de Sensibilidade Microbiana , Plasmídeos , Homologia de Sequência , Tetraciclinas/farmacologia
16.
Zhonghua Nei Ke Za Zhi ; 58(8): 566-571, 2019 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-31365977

RESUMO

Objective: To evaluate the efficacy and safety of different antimicrobial regimens in patients with bloodstream infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Methods: The clinical date of patients with CRKP bloodstream infections were retrospectively analyzed at the First Affiliated Hospital of Zhejiang University Medical College between January 2017 and January 2018. All subjects were separated into three groups based on antibiotics regimens over 72 hours, including meropenem 2.0 g every 8 hours, tigecycline 200 mg as initial dose and 100 mg every 12 hours, and polymyxin B 1.25 mg/kg every 12 hours as salvage treatment of tigecycline. Results: A total of 86 patients were finally recruited, including 14, 52 and 20 patients in groups of meropenem, tigecycline and polymyxin B salvage, respectively. All of the strains were resistant to meropenem and susceptible to tigecycline and polymyxin B initially, while 2 of them became resistant to tigecycline during treatment. The 28-day mortality was significantly higher in meropenem group (13/14) than that in tigecycline group and polymyxin B salvage group (61.5%, 32/52) and (12/20), respectively (P<0.01), while as no significant difference was seen in the last two groups (χ(2)=0.014, P>0.05). The incidences of hepatic impairment [3.8%(2/52) vs. 1/20] and renal dysfunction (0 vs. 1/20) between tigecycline group and polymyxin B salvage group were both comparable (P>0.05). Conclusion: The meropenem-based therapy is not recommended for CRKP-related bloodstream infections. Tigecycline-based therapy is still disappointing despite salvage use of polymyxin B after 72 hours. Hepatic and nephretic toxicities caused by additional polymyxin B are acceptable.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Meropeném/uso terapêutico , Polimixinas/uso terapêutico , Tigeciclina/uso terapêutico , Antibacterianos/administração & dosagem , Bacteriemia/mortalidade , China/epidemiologia , Farmacorresistência Bacteriana Múltipla , Humanos , Infecções por Klebsiella/diagnóstico , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Resultado do Tratamento , Resistência beta-Lactâmica
18.
Medicine (Baltimore) ; 98(26): e16246, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261588

RESUMO

RATIONALE: Fusarium is the second most common cause of fungi infections in the immunocompromised patients with the mortality rate over 80%. Early identification and appropriate selection of antifungal drugs is the key to successful treatment. PATIENT CONCERNS: A 31-year-old female was diagnosed with acute lymphocytic leukemia (pro-B ALL). She developed a high fever and presented with typical painful purple nodules with central necrosis formed on the upper and lower limbs during the induction chemotherapy. DIAGNOSIS: Combining clinical manifestations with results of blood culture testing and sequencing methods, it was consistent with the diagnosis of disseminated fusariosis. INTERVENTIONS: The patient was treated with the combination of tigecycline and antifungal agents (Liposomal Amphotericin B and Voriconazole), OUTCOMES:: The skin lesions generally healed with some scar left after treating with antifungal agents for 6 weeks. The final date of follow-up was 1.5 years later, and the patient was alive with no diseases. LESSONS: This case highlights the importance of the typical cutaneous lesions for early diagnosis and proper treatment to decrease the mortality rate of this severe infection. This patient was successfully treated with the combination of tigecycline and antifungal agents, which may be the first clinical confirmation of tigecycline that improved the effectiveness of antifungal agents against fusariosis, but it requires more studies to verify. We reviewed 62 cases from literature and analyzed using logistic regression and recognized the high-risk factor for fusariosis mortality in patients with acute leukemia was non-remission of underlying disease.


Assuntos
Anfotericina B/uso terapêutico , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Fusariose/tratamento farmacológico , Tigeciclina/uso terapêutico , Voriconazol/uso terapêutico , Adulto , Feminino , Fusariose/etiologia , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Indução de Remissão
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