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2.
Lett Appl Microbiol ; 70(3): 189-195, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31808159

RESUMO

The aim of this study was to investigate the in vitro interactions of ambroxol hydrochloride (ABH) or amlodipine (AML) with commonly used antibacterial agents, including meropenem, imipenem-cilastatin sodium, biapenem, cefoperazone-sulbactam, polymyxin B, and tigecycline, against six carbapenem-resistant Acinetobacter baumannii (CRAB) clinical isolates. Drug interactions were interpreted using two models, that is, the fractional inhibitory concentration index (FICI) model and the percentage of growth difference (ΔE) model. The results show that a majority of the combination groups exhibited partial synergy and additive interactions, such as the combinations of carbapenems and cefoperazone-sulbactam (SCF) with ABH or AML. While the combination of PB/AML exhibited synergistic interactions against all tested isolates, and PB/ABH exhibited synergistic interactions against two isolates. The FICI and ΔE model correlated very well for the combinations of PBABH and PB/AML against AB2. The combinations of TGC with ABH or AML mainly exhibited additive and indifferent interactions. There were no antagonistic interactions observed in any of the combinations. In conclusion, this study revealed that the non-antibacterial agents ABH or AML can work synergistically or partial synergistically with antibacterial agents against CRAB. This finding is crucial for overcoming the carbapenem resistance of A. baumannii. SIGNIFICANCE AND IMPACT OF THE STUDY: Drug combination is an effective approach for the treatment of resistant bacterial infection. The significance of using drug combination is that it can reduce drug dosage requirements, reduce the toxic effects of agents and prevent or delay the emergence of drug resistance. This study measured the in vitro interactions between non-antimicrobial agents and antibacterial agents against carbapenem-resistant Acinetobacter baumannii and the results of this study provide new insight to find strategies to overcome the carbapenem resistance in A. baumannii.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Ambroxol/farmacologia , Anlodipino/farmacologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/genética , Acinetobacter baumannii/crescimento & desenvolvimento , Carbapenêmicos/farmacologia , Cefoperazona/farmacologia , Combinação Imipenem e Cilastatina/farmacologia , Combinação de Medicamentos , Sinergismo Farmacológico , Humanos , Meropeném/farmacologia , Testes de Sensibilidade Microbiana , Sulbactam/farmacologia , Tienamicinas/farmacologia
3.
Biomed Environ Sci ; 32(4): 235-241, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31217059

RESUMO

OBJECTIVE: To assess the activities of biapenem against multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis. METHODS: Biapenem/clavulanate (BP/CL) was evaluated for in vitro activity against Mycobacterium tuberculosis (Mtb) multidrug-resistant (MDR) isolates, extensively drug-resistant (XDR) isolates, and the H37RV strain. BP/CL activity against the H37Rv strain was assessed in liquid cultures, in macrophages, and in mice.. RESULTS: BP/CL exhibited activity against MDR and XDR Mtb isolates in liquid cultures. BP/CL treatment significantly reduced the number of colony forming units (CFU) of Mtb within macrophages compared with control untreated infected macrophages. Notably, BP/CL synergized in pairwise combinations with protionamide, aminosalicylate, and capreomycin to achieve a fractional inhibitory concentration for each pairing of 0.375 in vitro. In a mouse tuberculosis infection model, the efficacy of a cocktail of levofloxacin + pyrazinamide + protionamide + aminosalicylate against Mtb increased when the cocktail was combined with BP/CL, achieving efficacy similar to that of the positive control treatment (isoniazid + rifampin + pyrazinamide) after 2 months of treatment. CONCLUSION: BP/CL may provide a new option to clinically treat MDR tuberculosis.


Assuntos
Anti-Infecciosos/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Tienamicinas/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Animais , Anti-Infecciosos/farmacologia , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Macrófagos , Camundongos , Tienamicinas/farmacologia
5.
J Infect Public Health ; 12(5): 744-747, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080100

RESUMO

We report a case of Listeria meningitis related to mantle cell lymphoma. A clinical pharmacist adjusted repeatedly the patient's anti-infective therapeutic regimen by analyzing the pharmacologic and pharmacokinetic characteristics of antibacterial drugs (such as cefotaxime, meropenem, etc.) due to the patient's repeated fever during hospitalization. To the best of our knowledge, this is the first case of Listeria meningitis related to mantle cell lymphoma treated successfully with meropenem reported in China. This case aims to optimize the anti-infection treatment regimen of Listeria meningitis and to provide a reference for clinicians and clinical pharmacists to use drugs rationally.


Assuntos
Antibacterianos/uso terapêutico , Listeria monocytogenes/efeitos dos fármacos , Linfoma de Célula do Manto/microbiologia , Meningite por Listeria/diagnóstico , Meningite por Listeria/tratamento farmacológico , Meropeném/uso terapêutico , China , Quimioterapia Combinada , Febre/tratamento farmacológico , Febre/microbiologia , Humanos , Linfoma de Célula do Manto/complicações , Masculino , Pessoa de Meia-Idade , Tienamicinas/uso terapêutico , Resultado do Tratamento
6.
Artigo em Inglês | MEDLINE | ID: mdl-30420483

RESUMO

Efflux pumps contribute to antibiotic resistance in Gram-negative pathogens. Correspondingly, efflux pump inhibitors (EPIs) may reverse this resistance. D13-9001 specifically inhibits MexAB-OprM in Pseudomonas aeruginosa Mutants with decreased susceptibility to MexAB-OprM inhibition by D13-9001 were identified, and these fell into two categories: those with alterations in the target MexB (F628L and ΔV177) and those with an alteration in a putative sensor kinase of unknown function, PA1438 (L172P). The alterations in MexB were consistent with reported structural studies of the D13-9001 interaction with MexB. The PA1438L172P alteration mediated a >150-fold upregulation of MexMN pump gene expression and a >50-fold upregulation of PA1438 and the neighboring response regulator gene, PA1437. We propose that these be renamed mmnR and mmnS for MexMN regulator and MexMN sensor, respectively. MexMN was shown to partner with the outer membrane channel protein OprM and to pump several ß-lactams, monobactams, and tazobactam. Upregulated MexMN functionally replaced MexAB-OprM to efflux these compounds but was insusceptible to inhibition by D13-9001. MmnSL172P also mediated a decrease in susceptibility to imipenem and biapenem that was independent of MexMN-OprM. Expression of oprD, encoding the uptake channel for these compounds, was downregulated, suggesting that this channel is also part of the MmnSR regulon. Transcriptome sequencing (RNA-seq) of cells encoding MmnSL172P revealed, among other things, an interrelationship between the regulation of mexMN and genes involved in heavy metal resistance.


Assuntos
Piperidinas/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Compostos de Amônio Quaternário/farmacologia , beta-Lactamas/farmacologia , Imipenem/farmacologia , Testes de Sensibilidade Microbiana , Monobactamas/farmacologia , Pseudomonas aeruginosa/genética , Tazobactam/farmacologia , Tienamicinas/farmacologia , Transcriptoma/genética
7.
J Infect Chemother ; 25(1): 75-77, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30100401

RESUMO

We determined the optimal antimicrobial in the sodium mercaptoacetic acid double disk synergy test (SMA-DDST) for the detection of IMP-1-producing Pseudomonas aeruginosa isolates in Japan and evaluated the performance of the test. Fifty-four P. aeruginosa clinical isolates were tested, including 39 IMP-1 producers and 15 non-metallo-ß-lactamase (MBL)-producing carbapenem- and ceftazidime (CAZ)-resistant isolates. The SMA-DDST was performed with CAZ, cefepime (CFPM), imipenem (IPM), meropenem (MEPM), doripenem (DRPM), or biapenem (BIPM)-containing disks. The sensitivity of the SMA-DDST with CAZ, CFPM, IPM, MEPM, DRPM, and BIPM was 39/39 (100%), 36/39 (92%), 18/39 (46%), 8/39 (21%), 19/39 (49%), and 36/39 (92%), respectively. The specificity was 15/15 (100%) for all SMA-DDSTs. This suggests that the isolates may have a resistance mechanism other than MBL production for IPM, MEPM, or DRPM. Since the CAZ resistance mechanism in P. aeruginosa is the same as that of CFPM, but differs from that of carbapenems, we conclude that combining CAZ with BIPM SMA-DDSTs can prevent any failure in the detection of IMP-1-producing P. aeruginosa.


Assuntos
Antibacterianos/farmacologia , Ceftazidima/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Tienamicinas/farmacologia , Tioglicolatos/farmacologia , beta-Lactamases/metabolismo , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Japão , Sensibilidade e Especificidade
8.
Nursing ; 48(10): 32-43, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30192268

RESUMO

This article discusses eight drugs recently approved by the FDA, including their indications and contraindications, precautions, dosage, and nursing considerations. The article also includes summary charts on 14 recently approved antineoplastic drugs and four drugs approved for rare disorders.


Assuntos
Aprovação de Drogas , Acetatos/uso terapêutico , Ácidos Borônicos/uso terapêutico , Combinação de Medicamentos , Fluoroquinolonas/uso terapêutico , Humanos , Meropeném , Metronidazol/análogos & derivados , Metronidazol/uso terapêutico , Nitroimidazóis/uso terapêutico , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Peptídeos/uso terapêutico , Prostaglandinas F Sintéticas/uso terapêutico , Quinazolinas/uso terapêutico , Tienamicinas/uso terapêutico , Estados Unidos , United States Food and Drug Administration
9.
JAMA ; 320(10): 984-994, 2018 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-30208454

RESUMO

Importance: Extended-spectrum ß-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective "carbapenem-sparing" option to treat extended-spectrum ß-lactamase producers. Objectives: To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae. Design, Setting, and Participants: Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study. Interventions: Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician. Main Outcomes and Measures: The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used. Results: Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6% [1-sided 97.5% CI, -∞ to 14.5%]; P = .90 for noninferiority). Effects were consistent in an analysis of the per-protocol population. Nonfatal serious adverse events occurred in 5 of 188 patients (2.7%) in the piperacillin-tazobactam group and 3 of 191 (1.6%) in the meropenem group. Conclusions and relevance: Among patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality. These findings do not support use of piperacillin-tazobactam in this setting. Trial Registration: anzctr.org.au Identifiers: ACTRN12613000532707 and ACTRN12615000403538 and ClinicalTrials.gov Identifier: NCT02176122.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/mortalidade , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae , Ácido Penicilânico/análogos & derivados , Tienamicinas/uso terapêutico , Adulto , Idoso , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Bacteriemia/tratamento farmacológico , Causas de Morte , Ceftriaxona/farmacologia , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/mortalidade , Feminino , Humanos , Infecções por Klebsiella/mortalidade , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Meropeném , Pessoa de Meia-Idade , Ácido Penicilânico/efeitos adversos , Ácido Penicilânico/uso terapêutico , Piperacilina/efeitos adversos , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Tienamicinas/efeitos adversos
10.
Proc Natl Acad Sci U S A ; 115(39): 9797-9802, 2018 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-30201715

RESUMO

Metabolically quiescent bacteria represent a large proportion of those in natural and host environments, and they are often refractory to antibiotic treatment. Such drug tolerance is also observed in the laboratory during stationary phase, when bacteria face stress and starvation-induced growth arrest. Tolerance requires (p)ppGpp signaling, which mediates the stress and starvation stringent response (SR), but the downstream effectors that confer tolerance are unclear. We previously demonstrated that the SR is linked to increased antioxidant defenses in Pseudomonas aeruginosa We now demonstrate that superoxide dismutase (SOD) activity is a key factor in SR-mediated multidrug tolerance in stationary-phase P. aeruginosa Inactivation of the SR leads to loss of SOD activity and decreased multidrug tolerance during stationary phase. Genetic or chemical complementation of SOD activity of the ΔrelA spoT mutant (ΔSR) is sufficient to restore antibiotic tolerance to WT levels. Remarkably, we observe high membrane permeability and increased drug internalization upon ablation of SOD activity. Combined, our results highlight an unprecedented mode of SR-mediated multidrug tolerance in stationary-phase P. aeruginosa and suggest that inhibition of SOD activity may potentiate current antibiotics.


Assuntos
Farmacorresistência Bacteriana Múltipla , Pseudomonas aeruginosa/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Antibacterianos/farmacologia , Relação Dose-Resposta a Droga , Gentamicinas/farmacologia , Ligases/metabolismo , Meropeném , Testes de Sensibilidade Microbiana , Ofloxacino/farmacologia , Pseudomonas aeruginosa/enzimologia , Transdução de Sinais , Superóxido Dismutase/fisiologia , Tienamicinas/farmacologia
11.
Expert Opin Drug Metab Toxicol ; 14(10): 1007-1021, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30106599

RESUMO

INTRODUCTION: Meropenem/vaborbactam (M/V) represents the first carbapenem and ß-lactamase inhibitor combination approved for treatment of complicated urinary tract infections (cUTIs), including pyelonephritis. Vaborbactam is a novel boronic acid, ß-lactamase inhibitor with a high affinity for serine ß-lactamases, including Klebsiella pneumoniae carbapenemase (KPC). This combination, Vabomere™, was approved in August 2017 by the United States Food and Drug Administration for the treatment of cUTIs in patients 18 years or older, including pyelonephritis, caused by the following susceptible microorganisms: Escherichia coli, K. pneumoniae, and Enterobacter cloacae species complex. Areas covered: Relevant literature regarding microbiology, pharmacokinetics, pharmacodynamics, and clinical trials evaluating efficacy, safety, and tolerability will be discussed. Expert opinion: Current treatment options for KPC-producing infections such as aminoglycosides, polymyxins, fosfomycin, and tigecycline are associated with concerns regarding efficacy, toxicities, optimal dosing, and/or development of resistance. Additionally, resistance to the new combination product of ceftazidime/avibactam has also emerged. Current clinical evidence supporting the use of M/V for KPC-producing infections is limited to an open-label, randomized, phase III study in a small number of patients with serious infections due to carbapenem-resistant Enterobacteriaceae. Although M/V is not approved for KPC-producing infections, we believe that M/V will become a preferred agent for KPC-producing Enterobacteriaceae infections.


Assuntos
Antibacterianos/administração & dosagem , Ácidos Borônicos/administração & dosagem , Tienamicinas/administração & dosagem , Infecções Urinárias/tratamento farmacológico , Animais , Antibacterianos/farmacocinética , Ácidos Borônicos/farmacocinética , Combinação de Medicamentos , Farmacorresistência Bacteriana , Humanos , Meropeném , Ensaios Clínicos Controlados Aleatórios como Assunto , Tienamicinas/farmacocinética
12.
Expert Opin Pharmacother ; 19(13): 1495-1502, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30160990

RESUMO

INTRODUCTION: Meropenem-vaborbactam is a new beta-lactam/beta-lactamase inhibitor combination that combines a carbapenem antibiotic with a first-in-class, boronic acid pharmacophore, serine beta-lactamase inhibitor which has potent inhibitory activity against class A carbapenemases, especially Klebsiella pneumoniae carbapenemases (KPC), in addition to other class A and class C beta-lactamases. The US Food and Drug Administration has recently approved meropenem-vaborbactam for the treatment of adult patients with complicated urinary tract infections including acute pyelonephritis. Areas covered: A PubMed search was performed to gather the most current and relevant articles regarding meropenem-vaborbactam. In this review the authors discuss the chemistry, mechanism of action, pharmacokinetics, pharmacodynamics, antimicrobial spectrum, and efficacy and safety of meropenem-vaborbactam for the treatment of complicated urinary tract infections including acute pyelonephritis Expert opinion: Although meropenem-vaborbactam is approved for treatment for complicated urinary tract infections including acute pyelonephritis, it is unlikely, at this point, to be utilized widely beyond cases that are caused by KPC-producing Enterobacteriaceae. It may also be a potential treatment option for complicated urinary tract infections caused by KPC-producing Enterobacteriaceae that are resistant to ceftazidime-avibactam. Long-term safety data with this novel beta-lactamase inhibitor is still needed although early data suggests that it will be safe and well tolerated.


Assuntos
Ácidos Borônicos/administração & dosagem , Tienamicinas/administração & dosagem , Infecções Urinárias/tratamento farmacológico , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Compostos Azabicíclicos/administração & dosagem , Ceftazidima/administração & dosagem , Combinação de Medicamentos , Enterobacteriaceae/efeitos dos fármacos , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Meropeném , Pielonefrite/tratamento farmacológico
13.
Int J Pharm ; 548(1): 443-453, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30008433

RESUMO

Antibiotic combination therapy is promising for the treatment of lower respiratory tract infections caused by multi-drug resistant Gram-negative pathogens. Inhaled antibiotic therapy offers the advantage of direct delivery of the drugs to the site of infection, as compared to the parenteral administrations. In this study, we developed composite particle formulations of colistin and meropenem. The formulations were characterized for particle size, morphology, specific surface area, surface chemical composition, in-vitro aerosolization performance and in-vitro antibacterial activity. The combinations demonstrated enhanced antibacterial activity against clinical isolates of Acinetobacter baumannii N16870 and Pseudomonas aeruginosa 19147, when compared with antibiotic monotherapy. Spray-dried meropenem alone showed a poor aerosolization performance as indicated by a low fine particle fraction (FPF) of 32.5 ±â€¯3.3%. Co-spraying with colistin improved the aerosolization of meropenem with up to a two-fold increase in the FPF. Such improvements in aerosolization can be attributed to the enrichment of colistin on the surface of composite particles as indicated by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS), and the increases in particle porosity. Intermolecular interactions between colistin and meropenem were observed for the combination formulations as measured by FT-IR. In conclusion, our results show that co-spray drying with colistin improves the antibacterial activity and aerosol performance of meropenem and produces a formulation with synergistic bacterial killing.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/administração & dosagem , Colistina/administração & dosagem , Pseudomonas aeruginosa/efeitos dos fármacos , Tienamicinas/administração & dosagem , Acinetobacter baumannii/crescimento & desenvolvimento , Administração por Inalação , Aerossóis , Antibacterianos/química , Colistina/química , Sinergismo Farmacológico , Meropeném , Tamanho da Partícula , Porosidade , Pseudomonas aeruginosa/crescimento & desenvolvimento , Propriedades de Superfície , Tienamicinas/química
14.
Environ Pollut ; 241: 1048-1055, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30029312

RESUMO

The environment is one of the main reservoirs of antibiotic resistance genes (ARGs) but multidrug resistant (MDR) environmental isolates are barely characterised. As suggested by the name, Pedobacter species have been predominantly isolated from soils, but are also recovered from water (including drinking water), chilled food, fish, compost, sludge, glaciers and other extreme environments. The susceptibility phenotype of Pedobacter lusitanus NL19 (isolated from a deactivated uranium mine), its closely related species and the genus type strain were investigated. All strains are MDR bacteria, resistant to ß-lactams, colistin, aminoglycosides and ciprofloxacin. Therefore, Pedobacter spp. are likely intrinsically resistant to ß-lactams (including ertapenem) and to other three classes of antibiotics. 6%-8% of their total protein-encoding genes encode a diverse collection of putative ARGs, including ß-lactamases. These enzymes are highly abundant in all the other Pedobacter strains with sequenced genomes, especially class C, class B3 and class A. LUS-1 and PLN-1 were further characterised in E. coli. LUS-1 is a class A ß-lactamase and it conferred an increase in the MIC of cefotaxime, albeit very low. PLN-1 is a class B3 ß-lactamase with carbapenemase activity, conferring resistance to ertapenem and a 66x and 16x increase in the MIC of imipenem and meropenem, respectively. PLN-1 also hydrolyses ampicillin, 1st and 3rd generation cephalosporins, and at a lower extent cephamycins and 4th generation cephalosporins. Therefore, Pedobacter spp. encode a large and diverse arsenal of resistance mechanisms that make them environmental superbugs.


Assuntos
Resistência Microbiana a Medicamentos/genética , Pedobacter/fisiologia , Antibacterianos/farmacologia , Proteínas de Bactérias , Ciprofloxacino , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Ertapenem , Escherichia coli/efeitos dos fármacos , Humanos , Meropeném , Testes de Sensibilidade Microbiana , Tienamicinas , beta-Lactamases/genética , beta-Lactamas
15.
BMJ Case Rep ; 20182018 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-30021738

RESUMO

Microbial keratitis is a common corneal condition, with many known risk factors. We present a case of an 88-year-old female patient with a multidrug-resistant Achromobacter xylosoxidans corneal ulcer in a previously failed second penetrating keratoplasty, successfully managed with topical meropenem drops administered hourly around the clock, for five days preceding and then hourly day only, for five days following a repeat third penetrating keratoplasty. Topical meropenem 50 mg/mL was prepared by mixing a 500 mg vial of meropenem with 10 mL of sterile water with pharmacy advice that administration should be within an hour. To the best of our knowledge, this is the first report of the use of topical meropenem in the management of A.xylosoxidans keratitis. This case highlights the importance of the mean inhibitory concentrations for antibiotics when considering sensitivities. Topical meropenem may be a useful treatment option for multidrug-resistant bacterial corneal ulcers that are resistant to conventional therapy.


Assuntos
Achromobacter denitrificans , Antibacterianos/administração & dosagem , Úlcera da Córnea/tratamento farmacológico , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Tienamicinas/administração & dosagem , Achromobacter denitrificans/efeitos dos fármacos , Administração Oftálmica , Idoso de 80 Anos ou mais , Úlcera da Córnea/microbiologia , Úlcera da Córnea/cirurgia , Resistência a Múltiplos Medicamentos , Farmacorresistência Bacteriana Múltipla , Infecções Oculares Bacterianas/microbiologia , Feminino , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Ceratoplastia Penetrante , Meropeném , Cuidados Pré-Operatórios/métodos
16.
Medicine (Baltimore) ; 97(25): e11017, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29923989

RESUMO

RATIONALE: Klebsiella pneumonia (K. pneumonia), primarily a hospital-acquired pathogen, can cause a variety of deep-seated infections with significant morbidities. However, in the current scenario of global rise in antibiotic abuse, unexpected infection could be caused by K. pneumoniae. PATIENT CONCERNS: A 56-year-old male who presented with intermittent headache and low fever was admitted, he had transsphenoidal surgery for pituitary adenoma 3 years ago. Routine laboratory tests revealed an elevated WBC count of 10.12 × 10/L and C-reactive protein (CRP) 12.9 mg/L. computed tomography (CT) revealed the sellar region with suspicious hemorrhage. DIAGNOSES: The patient was initially diagnosed with acute residual tumor hemorrhage. But the consequent diagnose of Klebsiella pneumoniae purulent meningitis was made based on the cerebrospinal fluid lab test and cerebrospinal fluid (CSF) and blood culture, and CT scan. INTERVENTIONS: Lumbar puncture examination was made and the antibiotics were adjusted to meropenem and vancomycin according to the antibiotic sensitivity test. But because of the patient's unstable vital signs, his family refuse further lateral ventricular drainage. OUTCOMES: The infection was out of control and the patient died of spontaneous breath and heartbeat arrest. LESSONS: Through this case, we could learn that any clue of suspicious intracranial infection should be carefully considered in the current scenario of global rise in antibiotic abuse. The manifestation of intermittent headache and mild fever could be potential signs of fatal infection, and prompt appropriate measures should be taken timely.


Assuntos
Infecções Comunitárias Adquiridas/diagnóstico , Infecções por Klebsiella/diagnóstico , Klebsiella pneumoniae , Meningites Bacterianas/diagnóstico , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Evolução Fatal , Febre/etiologia , Cefaleia/etiologia , Humanos , Infecções por Klebsiella/tratamento farmacológico , Masculino , Meningites Bacterianas/tratamento farmacológico , Meropeném , Pessoa de Meia-Idade , Choque Séptico/diagnóstico , Choque Séptico/tratamento farmacológico , Tienamicinas/uso terapêutico , Vancomicina/uso terapêutico
17.
Medicine (Baltimore) ; 97(25): e11200, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29924043

RESUMO

RATIONALE: Acute calculous cholecystitis is a prevalent disease whose diagnosis and management still face significant debate. Although the overall incidence of gallstone disease is 18.8% in European women aged 30 to 69 years, there is little data and experience in managing acute calculous cholecystitis in populations over 80 years old. The incidence of acute cholecystitis among the elderly is probably increasing. For the reason, we here highlight the advantages and disadvantage of various treatment and management opens based on a 96-year-old patient. PATIENT CONCERNS: We present a rare case in which a 96-year-old woman suffered from abdominal pain, nausea, and lack of appetite for over a month. DIAGNOSES: She was diagnosed with acute calculous cholecystitis and pancreatitis. INTERVENTIONS: She was successfully treated without surgery, regaining her physical health after 5 months. OUTCOMES: The question of how to manage acute calculous cholecystitis is extremely difficult in many aspects. The patient of very advanced age presented in this paper, not very well diagnosed and with a life-threating condition, survived because of careful treatment and reasonable decision-making. LESSONS: The take-away from this case is that, in a high-risk senile patient, strict conservative therapy of cholecystitis may be successful, as it can avoid the complications of surgery and leave the patient with a good quality of life.


Assuntos
Colecistite Aguda/complicações , Colecistite Aguda/tratamento farmacológico , Tratamento Conservador/métodos , Pancreatite/complicações , Pancreatite/tratamento farmacológico , Administração Intravenosa , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Colecistite Aguda/diagnóstico , Tomada de Decisão Clínica/métodos , Confiabilidade dos Dados , Feminino , Humanos , Meropeném , Tienamicinas/administração & dosagem , Tienamicinas/uso terapêutico , Resultado do Tratamento
19.
Medicine (Baltimore) ; 97(24): e11156, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29901648

RESUMO

RATIONALE: Purulent meningitis refers infection of the subarachnoid space by various purulent bacteria and the corresponding inflammation of the leptomeninges. However, purulent meningitis due to Rhodococcus equi is extremely rare. PATIENT CONCERNS: A 40-year-old man presented with fever and intermittent headache for 6 days. Two hours prior to admission, he developed epileptic seizures. DIAGNOSES: Brain computed tomography and magnetic resonance imaging showed intracerebral malacic lesions. Bacterial culture of cerebrospinal fluid revealed the presence of R. equi. A diagnosis of purulent meningitis caused by R. equi was made. INTERVENTIONS: The patient was treated with intravenous meropenem (1000 mg every 8 hours) for 19 days; then he was discharged and instructed to continue the intravenous meropenem for two weeks. After a follow-up period of 2 months, the patient had recovered completely. OUTCOMES: After a follow-up period of 2 months, the patient had recovered completely. LESSONS: Central nervous system infection caused by R. equi is rare. Early bacterial culture of CSF is important for timely diagnosis. With sufficient antibiotic therapy, the prognosis can be favorable.


Assuntos
Infecções por Actinomycetales/diagnóstico , Meningites Bacterianas/diagnóstico , Rhodococcus equi/isolamento & purificação , Infecções por Actinomycetales/tratamento farmacológico , Adulto , Antibacterianos/uso terapêutico , Líquido Cefalorraquidiano/microbiologia , Humanos , Masculino , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/microbiologia , Meropeném , Tienamicinas/uso terapêutico
20.
Eur J Med Chem ; 155: 285-302, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29894943

RESUMO

The worldwide prevalence of NDM-1-producing bacteria has drastically undermined the clinical efficacy of the last line antibiotic of carbapenems, prompting a need to devise effective strategy to preserve their clinical value. Our previous studies have shown that ebselen can restore the efficacy of meropenem against a laboratory strain that produces NDM-1. Here we report the construction of a focused compound library of 1,2-benzisoselenazol-3(2H)-one derivatives which comprise a total of forty-six candidate compounds. The structure-activity relationship of these compounds and their potential to serve as an adjuvant to enhance the antimicrobial efficacy of meropenem against a collection of clinical NDM-1-producing carbapenem-resistant Enterobacteriaceae isolates was examined. Drug combination assays indicated that these derivatives exhibited synergistic antimicrobial activity when used along with meropenem, effectively restoring the activity of carbapenems against the resistant strains tested in a Galleria mellonella larvae in vivo infection model. The mode of inhibition of one compound, namely 11_a38, which was depicted when tested on the purified NDM-1 enzyme, indicated that it could covalently bind to the enzyme and displaced one zinc ion from the active site. Overall, this study provides a novel 1,2-benzisoselenazol-3(2H)-one scaffold that exhibits strong synergistic antimicrobial activity with carbapenems, and low cytotoxicity. The prospect of application of such compounds as carbapenem adjuvants warrants further evaluation.


Assuntos
Antibacterianos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Compostos Organosselênicos/farmacologia , Tienamicinas/farmacologia , beta-Lactamases/metabolismo , Antibacterianos/síntese química , Antibacterianos/química , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Enterobacteriáceas Resistentes a Carbapenêmicos/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células HeLa , Humanos , Meropeném , Estrutura Molecular , Compostos Organosselênicos/química , Relação Estrutura-Atividade , Tienamicinas/química
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