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1.
Medicine (Baltimore) ; 98(37): e17140, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517855

RESUMO

RATIONALE: Interface keratitis after lamellar keratoplasty is one of the causes of graft failure. We report the first case of microbiologically proven Enterococcus faecium infection following deep anterior lamellar keratoplasty (DALK) and review the available literature. PATIENT CONCERNS: A 37-years-old Caucasian man presented with pain, redness and severe vision loss in his right eye. Five weeks before, he underwent DALK using the FEMTO LDV Z8 in the same eye for the surgical correction of keratoconus. DIAGNOSES: Upon presentation, slit-lamp biomiscroscopy revealed corneal graft edema with multiple infiltrates located in the graft-host interface. INTERVENTIONS: Therapeutic penetrating keratoplasty (PKP) was carried out in addition with cultures of the donor lenticule removal. Laboratory results isolated a multi-resistant Enterococcus faecium interface infection. According to the antibiogram, the patient was treated with systemic Tigecycline and Linezolid for 7 days. OUTCOMES: During the following weeks, clinical features improved over time and no signs of active infection were visible seven months postoperatively. LESSONS: Early PKP showed to be a good therapeutic option with great anatomic and functional outcomes.


Assuntos
Transplante de Córnea , Farmacorresistência Bacteriana Múltipla , Enterococcus faecium , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecção da Ferida Cirúrgica/tratamento farmacológico , Adulto , Antibacterianos/uso terapêutico , Infecções Oculares Bacterianas/etiologia , Infecções por Bactérias Gram-Positivas/etiologia , Humanos , Masculino
2.
Medicine (Baltimore) ; 98(35): e16911, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464925

RESUMO

RATIONALE: Actinomyces odontolyticus and Parvimonas micra are very rare causative organisms of lung abscess and acute respiratory failure. PATIENT CONCERNS: A 49-year-old male patient visited the emergency room with a complaint of sudden onset of shortness of breath, and he developed acute respiratory failure rapidly. DIAGNOSIS: An abscess in the left lower lung field was diagnosed on the computed tomography scan of chest. INTERVENTIONS: Immediate treatment with intravenous antibiotics was initiated along with a pigtail catheter insertion for pus drainage. OUTCOMES: A odontolyticus was cultured on the drained pus and P micra was identified by a blood culture. The patient was successfully weaned from the mechanical ventilator and the lung abscess was completely resolved. LESSONS: To the best of our knowledge, this is the first case report of mixed infection with A odontolyticus and P micra, which caused acute respiratory failure in an immune-competent patient. Therefore, physicians should consider the possibility of these organisms as causative pathogens of a fulminant pulmonary infection even in an immune-competent patient.


Assuntos
Actinomicose/diagnóstico , Infecções por Bactérias Gram-Positivas/diagnóstico , Abscesso Pulmonar/diagnóstico por imagem , Insuficiência Respiratória/microbiologia , Actinomyces/isolamento & purificação , Actinomicose/tratamento farmacológico , Administração Intravenosa , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Coinfecção/tratamento farmacológico , Coinfecção/microbiologia , Firmicutes/isolamento & purificação , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Abscesso Pulmonar/tratamento farmacológico , Abscesso Pulmonar/microbiologia , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Insuficiência Respiratória/terapia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
3.
Internist (Berl) ; 60(10): 1111-1117, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31444523

RESUMO

Despite many novel diagnostic strategies and advances in treatment, infective endocarditis (IE) remains a severe disease. The epidemiology of IE has shifted and staphylococci have replaced streptococci as the most common cause and nosocomially acquired infections, invasive procedures, indwelling cardiac devices and acquired infections due to intravenous drug abuse are more frequent. The incidence of IE has steadily increased in recent years and the patients affected are older and have more comorbidities. The modern treatment of IE is interdisciplinary. The pharmacotherapy of IE depends on the pathogen and its sensitivity. The presence of a bioprosthetic valve and implantable cardiac devices plays a significant role in selection of antibiotics and duration of treatment. This article provides an update and overview of the current clinical practice in diagnostics and pharmacotherapy of IE in adults with a special focus on partial oral therapy and the role of aminoglycosides.


Assuntos
Antibacterianos/uso terapêutico , Endocardite/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Micoses/tratamento farmacológico , Adulto , Comorbidade , Endocardite/diagnóstico , Endocardite/epidemiologia , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/epidemiologia , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Incidência , Micoses/diagnóstico , Micoses/epidemiologia
4.
BMC Infect Dis ; 19(1): 485, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31146691

RESUMO

BACKGROUND: Bordetella trematum is an infrequent Gram-negative coccobacillus, with a reservoir, pathogenesis, a life cycle and a virulence level which has been poorly elucidated and understood. Related information is scarce due to the low frequency of isolates, so it is important to add data to the literature about this microorganism. CASE PRESENTATION: We report a case of a 74-year-old female, who was referred to the hospital, presenting with ulcer and necrosis in both legs. Therapy with piperacillin-tazobactam was started and peripheral artery revascularization was performed. During the surgery, a tissue fragment was collected, where Bordetella trematum, Stenotrophomonas maltophilia, and Enterococcus faecalis were isolated. After surgery, the intubated patient was transferred to the intensive care unit (ICU), using vasoactive drugs through a central venous catheter. Piperacillin-tazobactam was replaced by meropenem, with vancomycin prescribed for 14 days. Four days later, levofloxacin was added for 24 days, aiming at the isolation of S. maltophilia from the ulcer tissue. The necrotic ulcers evolved without further complications, and the patient's clinical condition improved, leading to temporary withdrawal of vasoactive drugs and extubation. Ultimately, however, the patient's general condition worsened, and she died 58 days after hospital admission. CONCLUSIONS: Despite being a rare finding, B. trematum is typically associated with the clinical manifestation of disorders that predispose to ulcer development, which can be infected by microorganisms. The combination of antibiotic therapy and surgical debridement plays a key role in preventing systemic infections. Monitoring the appearance of new cases of B. trematum is essential, since it can be an emerging microorganism. Isolating and defining the clinical relevance of unusual bacteria yields a more accurate perspective in the development of new diagnostic tools and allows for assessment of proper antimicrobial therapy.


Assuntos
Infecções por Bordetella/diagnóstico , Bordetella , Idoso , Antibacterianos/uso terapêutico , Bordetella/isolamento & purificação , Infecções por Bordetella/tratamento farmacológico , Infecções por Bordetella/microbiologia , Coinfecção , Pé Diabético/complicações , Pé Diabético/diagnóstico , Pé Diabético/tratamento farmacológico , Pé Diabético/microbiologia , Enterococcus faecalis/isolamento & purificação , Evolução Fatal , Feminino , Infecções por Bactérias Gram-Negativas/complicações , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Positivas/complicações , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Unidades de Terapia Intensiva , Testes de Sensibilidade Microbiana , Necrose/diagnóstico , Necrose/microbiologia , Combinação Piperacilina e Tazobactam/uso terapêutico , Stenotrophomonas maltophilia/isolamento & purificação , Úlcera/diagnóstico , Úlcera/microbiologia
5.
Nat Commun ; 10(1): 2733, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227716

RESUMO

Cell wall antibiotics are crucial for combatting the emerging wave of resistant bacteria. Yet, our understanding of antibiotic action is limited, as many strains devoid of all resistance determinants display far higher antibiotic tolerance in vivo than suggested by the antibiotic-target binding affinity in vitro. To resolve this conflict, here we develop a comprehensive theory for the bacterial cell wall biosynthetic pathway and study its perturbation by antibiotics. We find that the closed-loop architecture of the lipid II cycle of wall biosynthesis features a highly asymmetric distribution of pathway intermediates, and show that antibiotic tolerance scales inversely with the abundance of the targeted pathway intermediate. We formalize this principle of minimal target exposure as intrinsic resistance mechanism and predict how cooperative drug-target interactions can mitigate resistance. The theory accurately predicts the in vivo efficacy for various cell wall antibiotics in different Gram-positive bacteria and contributes to a systems-level understanding of antibiotic action.


Assuntos
Vias Biossintéticas/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Bactérias Gram-Positivas/metabolismo , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Parede Celular/metabolismo , Bactérias Gram-Positivas/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/microbiologia , Modelos Biológicos , Uridina Difosfato Ácido N-Acetilmurâmico/análogos & derivados , Uridina Difosfato Ácido N-Acetilmurâmico/biossíntese
6.
Int J Infect Dis ; 85: 127-131, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31096056

RESUMO

OBJECTIVES: Daptomycin has shown clinical efficacy in diabetic foot infections (DFI). However, only limited data are available on its bone penetration in this particular population. The aim of this study was to determine daptomycin bone concentrations in patients with DFI undergoing surgery after multiple daptomycin infusions and to determine bone daptomycin inhibitory quotients (IQs) for the predominant gram-positive species involved in DFI. METHODS: Fourteen adult patients hospitalized with DFI treated with daptomycin and requiring surgical bone debridement and amputation were included in this single-centre prospective study. Daptomycin concentrations in serum and bone were determined by HPLC at steady state. Bone IQs were then calculated according to different minimum inhibitory concentrations (MICs; range 0.25-4mg/l) that are representative of the main MICs for Staphylococcus aureus, coagulase-negative staphylococci (CoNS), and Enterococcus sp populations. RESULTS: Residual and peak concentrations varied from 4.5mg/l to 39.9mg/l and from 31.8mg/l to 110.9mg/l, respectively. Bone daptomycin concentrations at the moment of surgery varied from 1.2mg/l to 17mg/l. Up to a MIC of 1mg/l, which is the epidemiological cut-off value (ECOFF) and breakpoint value for S. aureus and CoNS, all bone daptomycin IQs were positive. The highest bone IQs were observed with Staphylococcus species. Calculated bone IQs for Enterococcus species were often weak at MIC values near the ECOFF. CONCLUSIONS: Daptomycin penetrates bone well in patients treated for DFI. At an initially recommended dosage of 6mg/kg, bone concentrations are likely to be effective against staphylococcal infections and infections due to low-MIC Enterococcus.


Assuntos
Antibacterianos/farmacocinética , Osso e Ossos/metabolismo , Daptomicina/farmacocinética , Pé Diabético/complicações , Doenças do Pé/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Idoso , Antibacterianos/uso terapêutico , Daptomicina/uso terapêutico , Enterococcus/efeitos dos fármacos , Feminino , Doenças do Pé/complicações , Doenças do Pé/metabolismo , Doenças do Pé/cirurgia , Infecções por Bactérias Gram-Positivas/complicações , Infecções por Bactérias Gram-Positivas/metabolismo , Infecções por Bactérias Gram-Positivas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Staphylococcus/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
7.
Clin Nephrol ; 92(1): 44-51, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31131821

RESUMO

BACKGROUND: Peritoneal dialysis-associated peritonitis (PDAP) is one of the major causes of peritoneal dialysis (PD) failure and death. Therefore, it is important to determine how to effectively treat patients with PDAP. MATERIALS AND METHODS: We analyzed the pathogen spectrum and bacterial resistance in 203 PDAP cases that were enrolled in this study from January 1, 2015 to December 31, 2017. All patients were infected with peritonitis and had been treated with antibiotics while at our center. Bacterial culture results of PD fluid and pathogen drug resistance were collected and analyzed. A total of 159 cases (78.3%) had a positive bacterial culture of PD fluid. RESULTS: A total of 47 pathogens were identified, including 19 (40.4%) Gram-positive cocci strains (the most common was Staphylococcus spp.), 15 (31.9%) Gram-negative bacilli strains (the most common was Escherichia coli, 4 fungal strains, and 9 other strains. The drug sensitivity test showed that Gram-positive cocci were sensitive to vancomycin (94.9%), but had a high resistance to cefazolin (67.7%). Gram-negative bacilli were sensitive to imipenem (96.2%), but had a high resistance to ceftriaxone (60.0%). Voriconazole and itraconazole were sensitive in fungal infections. A total of 162 cases were cured, 37 cases were unresponsive to antibiotic treatment and converted to hemodialysis after Tenckhoff catheter removal, and 4 cases resulted in death. CONCLUSION: Gram-positive cocci are still the primary pathogen of PDAP cases in our center, but demonstrate a high resistance to first-generation cephalosporin, which is the suggested treatment per International Society for Peritoneal Dialysis 2016 Peritonitis Recommendations. Therefore, an individualized treatment based on the distribution of pathogens and drug resistance in different centers is more conducive to improve the cure rate of PDAP.


Assuntos
Antibacterianos/uso terapêutico , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Cocos Gram-Positivos/efeitos dos fármacos , Diálise Peritoneal/efeitos adversos , Peritonite/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Antifúngicos/uso terapêutico , Infecções Bacterianas , Cefazolina/uso terapêutico , Ceftriaxona/uso terapêutico , Farmacorresistência Bacteriana , Feminino , Humanos , Imipenem/uso terapêutico , Itraconazol/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Peritonite/etiologia , Vancomicina/farmacologia , Voriconazol/uso terapêutico , Adulto Jovem
8.
mSphere ; 4(3)2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31092603

RESUMO

Intraocular infections are prevalent after traumatic injuries or after common ocular surgeries. Infections cause inflammation that can damage the retina and architecture of the eye, often resulting in poor visual outcomes. Severe cases may result in blindness or require enucleation of the eye. Treatments for intraocular infections include intravitreal antibiotics and corticosteroids or surgical vitrectomy in serious cases. The increase in multidrug-resistant infections calls for novel treatment options. In the present study, a biomimetic erythrocyte-derived nanosponge was tested for the ability to neutralize pore-forming toxins from the most frequent Gram-positive bacterial causes of intraocular infections (Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, and Bacillus cereus). Nanosponge pretreatment of supernatants reduced hemolytic activity in vitro. In a murine sterile endophthalmitis model, nanosponge pretreatment of injected supernatants resulted in greater retinal function and less ocular pathology compared to that in eyes injected with untreated supernatants from all pathogens except methicillin-resistant S. aureus In a murine bacterial endophthalmitis model, treatment with gatifloxacin and gatifloxacin-nanosponges reduced intraocular bacterial burdens, except in the case of methicillin-sensitive S. aureus For all pathogens, eyes in both treatment groups showed decreased ocular pathology and inflammation. Overall, reductions in retinal function loss afforded by gatifloxacin-nanosponge treatment were significant for E. faecalis, S. pneumoniae, and methicillin-resistant S. aureus but not for B. cereus and methicillin-sensitive S. aureus These results suggest that clinical improvements in intraocular infections following nanosponge treatment were dependent on the complexity and types of toxins produced. Nanosponges might serve as an adjunctive therapy for the treatment of ocular infections.IMPORTANCE Endophthalmitis is a blinding consequence of bacterial invasion of the interior of the eye. Because of increases in the numbers of ocular surgeries and intraocular injections, the incidence of endophthalmitis is steadily increasing. Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, and Bacillus cereus are leading causes of infection following ocular procedures and trauma and are increasingly more difficult to treat due to multidrug resistance. Each of these pathogens produces pore-forming toxins that contribute to the pathogenesis of endophthalmitis. Treatment of these infections with antibiotics alone is insufficient to prevent damage to the retina and vision loss. Therefore, novel therapeutics are needed that include agents that neutralize bacterial pore-forming toxins. Here, we demonstrate that biomimetic nanosponges neutralize pore-forming toxins from these ocular pathogens and aid in preserving retinal function. Nanosponges may represent a new form of adjunct antitoxin therapy for serious potentially blinding intraocular infections.


Assuntos
Toxinas Bacterianas/antagonistas & inibidores , Materiais Biomiméticos , Infecções Oculares Bacterianas/tratamento farmacológico , Nanoestruturas/uso terapêutico , Animais , Eritrócitos/química , Gatifloxacina/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Nanoestruturas/química , Nanotecnologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Polímeros/química , Coelhos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos
9.
Vet J ; 248: 42-47, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31113561

RESUMO

Enterococci have been increasing in prevalence in foal sepsis over the past three decades. There are no published studies in the peer-reviewed literature documenting common sites of infection, antimicrobial susceptibility, or outcome specifically associated with enterococcal infections in foals. Our objectives were to evaluate the sites of origin, antimicrobial susceptibility, and survival outcome to discharge in foals with enterococcal infections compared with foals with sepsis of another bacterial etiology. Seventy-five foals 0-30 days of age with cultures positive for Enterococcus and 170 control foals 0-30 days of age with cultures positive for other bacteria were included. Enterococcus was 2.67 times (95% confidence interval [CI], 1.49-4.80; P = 0.0012) more likely to be isolated from the lower urogenital tract of foals than were other bacteria. Enterococci were less likely to be isolated from blood cultures than other bacteria, with an odds ratio (OR) of 0.17 (95% CI 0.09-0.35; P < 0.0001). For Enterococcus isolates, 48% (n = 29/61) had a multiple antimicrobial resistance (MAR) index of ≥30% and 46% (n = 28/61) had a multiple drug resistance (MDR) index of ≥30%. Foals with enterococcal infections were less likely to survive to discharge (49.9% vs. 63.5%; P = 0.03). Enterococcus is commonly isolated from the lower urogenital tract of foals, is often multidrug resistant, and foals with enterococcal infections were less likely to survive. Multidrug resistance is common among enterococcal isolates, and therefore antimicrobial susceptibility testing of cultured isolates is warranted.


Assuntos
Antibacterianos/farmacologia , Enterococcus/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/veterinária , Doenças dos Cavalos/tratamento farmacológico , Animais , Animais Recém-Nascidos , Antibacterianos/uso terapêutico , Estudos de Casos e Controles , Resistência a Múltiplos Medicamentos , Enterococcus/isolamento & purificação , Feminino , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Doenças dos Cavalos/microbiologia , Cavalos , Masculino , Testes de Sensibilidade Microbiana/veterinária , Estudos Retrospectivos
10.
Int J Antimicrob Agents ; 53(6): 761-766, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30954636

RESUMO

BACKGROUND: The efficacy of vancomycin compared with ampicillin for enterococcal infections is unknown. This study aimed to compare their efficacy among patients with enterococcal bacteraemia. METHODS: Retrospective cohort study including adults aged >16 years with enterococcal bacteraemia, treated with ß-lactam antibiotics active against Enterococcus spp. or vancomycin. Treatment classification was based on the first antibiotic used for >4 days in the 7 days after blood culture collection. Subgroup analyses for patients with penicillin-susceptible enterococcal bacteraemia and patients with monomicrobial penicillin-susceptible enterococcal bacteraemia were performed. The dependent variable was 30-day all-cause mortality. The propensity score (PS) for vancomycin treatment was calculated. Univariate and multi-variate analyses adjusted for PS were performed. RESULTS: In total, 516 patients with enterococcal bacteraemia were included. Mortality was similar for patients treated with ß-lactams (123/315, 39%) and vancomycin (82/201, 40.8%). Independent factors significantly associated with mortality included healthcare-associated or hospital-acquired infection, age, female sex, Charlson Comorbidity Index, dialysis, SOFA score and low albumin. After adjustment for these factors and PS, the odds ratio (OR) for death in patients treated with vancomycin was 0.95 [95% confidence interval (CI) 0.56-1.59]. Results were similar among patients with penicillin-susceptible enterococcal bacteraemia and patients with monomicrobial penicillin-susceptible enterococcal bacteraemia (n=237, adjusted OR 0.59, 95% CI 0.25-1.43). CONCLUSION: No difference in mortality was observed following treatment with a ß-lactam or vancomycin among patients with enterococcal bacteraemia. Vancomycin is not recommended for the treatment of penicillin-susceptible enterococcal infections; however, when needed, it is not inferior to ß-lactams and the addition of a ß-lactam is not necessary.


Assuntos
Ampicilina/administração & dosagem , Antibacterianos/administração & dosagem , Bacteriemia/tratamento farmacológico , Enterococcus/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Vancomicina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/microbiologia , Enterococcus/isolamento & purificação , Feminino , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
11.
Dtsch Med Wochenschr ; 144(8): 553-560, 2019 04.
Artigo em Alemão | MEDLINE | ID: mdl-30986864

RESUMO

Enterococci with special resistance patterns (mainly vancomycin-resistant enterococci) play an important role in everyday clinical practice. Rising resistance rates to linezolid, daptomycin or tigecycline are also increasingly reported. Therapeutically, linezolid and daptomycin are the most important substances mainly in infections due to vancomycin-resistant enterococci. Several systematic meta-analyses of bloodstream infections showed discrepant results in the comparison of mortality of linezolid and daptomycin-treated bacteraemias. The containment of enterococci with special resistance patterns is currently receiving great attention. The key hygienic issue in all recommendations for dealing with multidrug-resistant enterococci can be summarized very simply: current scientific evidence is often inconsistent and studies that have clearly tested a single intervention for efficacy are lacking. The present work gives an insight into the current epidemiology and therapeutic strategies. Furthermore, the recently published German KRINKO recommendations are presented.


Assuntos
Antibacterianos/farmacologia , Enterococcus/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/microbiologia , Antibacterianos/uso terapêutico , Daptomicina/farmacologia , Daptomicina/uso terapêutico , Farmacorresistência Bacteriana , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/prevenção & controle , Humanos , Linezolida/farmacologia , Linezolida/uso terapêutico , Lipoglicopeptídeos/farmacologia , Lipoglicopeptídeos/uso terapêutico , Oxazolidinonas/farmacologia , Oxazolidinonas/uso terapêutico , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Tigeciclina/farmacologia , Tigeciclina/uso terapêutico , Resistência a Vancomicina
12.
Molecules ; 24(7)2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30987239

RESUMO

Phloretin is a natural chalcone with antibacterial and anti-inflammatory effects. This study investigated the anti-acne activity of phloretin against Propionibacterium acnes-induced skin infection and the potential target proteins of its anti-inflammatory and antibacterial effects. Phloretin potently inhibited the growth of P. acnes and P. acnes-induced Toll-like receptor (TLR) 2-mediated inflammatory signaling in human keratinocytes. Secreted embryonic alkaline phosphatase assay confirmed that the anti-inflammatory activity of phloretin is associated with the P. acnes-stimulated TLR2-mediated NF-κB signaling pathway. Phloretin significantly decreased the level of phosphorylated c-Jun N-terminal kinase (JNK), showing a binding affinity of 1.184 × 10-5 M-1. We also found that phloretin binds with micromolar affinity to P. acnes ß-ketoacyl acyl carrier protein (ACP) synthase III (KAS III), an enzyme involved in fatty acid synthesis. Conformation-sensitive native polyacrylamide gel electrophoresis showed that phloretin reduced KAS III-mediated 3-ketoacyl ACP production by over 66%. A docking study revealed that phloretin interacts with the active sites of JNK1 and KAS III, suggesting their involvement in P. acnes-induced inflammation and their potential as targets for the antibacterial activity of phloretin. These results demonstrate that phloretin may be useful in the prevention or treatment of P. acnes infection.


Assuntos
Antibacterianos/farmacologia , Infecções por Bactérias Gram-Positivas/metabolismo , Infecções por Bactérias Gram-Positivas/microbiologia , Floretina/farmacologia , Propionibacterium acnes/efeitos dos fármacos , Dermatopatias Bacterianas/metabolismo , Dermatopatias Bacterianas/microbiologia , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/antagonistas & inibidores , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/química , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/metabolismo , Antibacterianos/química , Sítios de Ligação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citocinas/biossíntese , Relação Dose-Resposta a Droga , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Floretina/química , Propionibacterium acnes/enzimologia , Propionibacterium acnes/imunologia , Ligação Proteica , Dermatopatias Bacterianas/tratamento farmacológico , Relação Estrutura-Atividade , Receptor 2 Toll-Like/metabolismo
13.
Diagn Microbiol Infect Dis ; 94(3): 277-286, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30940414

RESUMO

We evaluated the microbiological efficacy of tedizolid compared with that of linezolid against common and emerging pathogens using pooled data from 2 phase 3 trials (NCT01170221 and NCT01421511) in patients with acute bacterial skin and skin structure infections. Patients received tedizolid 200 mg once daily for 6 days (n = 664) or linezolid 600 mg twice daily for 10 days (n = 669). Favorable microbiological outcome in both treatment groups, defined as eradication or presumed eradication at the end of treatment and at the posttherapy evaluation, exceeded 85% for most pathogens, including methicillin-resistant Staphylococcus aureus. Favorable microbiological response was observed for staphylococci and streptococci at tedizolid minimal inhibitory concentration values ≤0.5 mg/L and 0.25 mg/L, respectively. The studies demonstrated positive microbiological outcomes against common pathogens with a 6-day, once-daily regimen of tedizolid phosphate in patients with acute bacterial skin and skin structure infections.


Assuntos
Antibacterianos/administração & dosagem , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Linezolida/administração & dosagem , Oxazolidinonas/administração & dosagem , Dermatopatias Bacterianas/tratamento farmacológico , Infecções dos Tecidos Moles/tratamento farmacológico , Tetrazóis/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Ensaios Clínicos Fase III como Assunto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto Jovem
14.
BMC Infect Dis ; 19(1): 301, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30943906

RESUMO

BACKGROUND: Lactococcus garvieae is an unusual cause of infective endocarditis (IE). No current diagnostic and therapeutic guidelines are available to treat IE caused by these organisms. Based on a case report, we provide a review of the literature of IE caused by L. garvieae and highlight diagnostic and treatment challenges of these infections and implications for management. CASE PRESENTATION: A 50-year-old Asian male with mitral prosthetic valve presented to the hospital with intracranial haemorrhage, which was successfully treated. Three weeks later, he complained of generalized malaise. Further work up revealed blood cultures positive for Gram-positive cocci identified as L. garvieae by MALDI-TOF. An echocardiogram confirmed the diagnosis of IE. Susceptibility testing showed resistance only to clindamycin. Vancomycin plus gentamicin were started as empirical therapy and, subsequently, the combination of ceftriaxone plus gentamicin was used after susceptibility studies were available. After two weeks of combination therapy, ceftriaxone was continued as monotherapy for six additional weeks with good outcome. CONCLUSIONS: Twenty-five cases of IE by Lactococcus garvieae have been reported in the literature. Compared to other Gram-positive cocci, L. garvieae affects more frequently patients with prosthetic valves. IE presents in a subacute manner and the case fatality rate can be as high as 16%, comparable to that of streptococcal IE (15.7%). Reliable methods for identification of L. garvieae include MALDI-TOF, 16S RNA PCR, API 32 strep kit and BD Automated Phoenix System. Recommended antimicrobials for L. garvieae IE are ampicillin, amoxicillin, ceftriaxone or vancomycin in monotherapy or in combination with gentamicin.


Assuntos
Endocardite Bacteriana/diagnóstico , Infecções por Bactérias Gram-Positivas/diagnóstico , Lactococcus/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Quimioterapia Combinada , Ecocardiografia , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/microbiologia , Gentamicinas/farmacologia , Gentamicinas/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Próteses Valvulares Cardíacas , Humanos , Lactococcus/química , Lactococcus/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Vancomicina/farmacologia , Vancomicina/uso terapêutico
15.
Adv Clin Exp Med ; 28(7): 907-912, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30986000

RESUMO

BACKGROUND: Infections in critically ill patients are the main reasons for a lack of therapeutic success and increased mortality in intensive care units (ICUs). There have been many analyses of the incidence of infections in ICUs; however, no large studies of this kind have been conducted either in Poland or in Eastern and Central Europe. OBJECTIVES: The aim of the research was to undertake a one-day study of the prevalence of infections in ICUs in Warszawa and the Mazovian region of Poland. MATERIAL AND METHODS: A prospective questionnaire survey analysis - a one-day prevalence study of infections - was carried out on June 25, 2014, in 28 ICUs in Poland. RESULTS: Among 205 ICU patients (193 adults and 12 children), 134 infections were found in 101 patients (99/193 adults (51.30%) and 2/12 children (16.70%)), and bacterial colonization in 19/205 (9.3%) patients. In 66.42% of the cases, more than 1 site of infection was diagnosed. On the day of the study, 75.40% of the diagnosed infections had positive microbiological results. The most frequent were respiratory tract infections (53.73%), wound infections (18.65%) and bloodstream infections (14.92%). Most of the infections (64.10%) were caused by Gram-negative bacteria (GN), followed by Gram-positive bacteria (GP; 31.80%) and fungi (4.10%). The most frequently reported GN microorganisms were Enterobacteriaceae (44.7%). Methicillin-resistant Staphylococcus aureus (MRSA) infections were found in 8.80% of the patients. Antibiotics were administered to 75.60% of the adult patients, in 69.20% as targeted treatment. Mechanical ventilation, central vein catheterization and urinary bladder catheterization were used in 67.80%, 85.85% and 94.63% of the patients, respectively. CONCLUSIONS: On the day of the study, more than half of the patients had infections, mostly from GN bacteria. Respiratory tract infections were the main type found. In about 2/3 of the patients, antibiotics were administered, mainly as targeted therapy.


Assuntos
Infecção Hospitalar/epidemiologia , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/epidemiologia , Bactérias Gram-Positivas/isolamento & purificação , Infecções por Bactérias Gram-Positivas/epidemiologia , Unidades de Terapia Intensiva/estatística & dados numéricos , Infecções Respiratórias/epidemiologia , Infecções Urinárias/epidemiologia , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Criança , Cuidados Críticos , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Staphylococcus aureus Resistente à Meticilina , Pessoa de Meia-Idade , Micoses , Polônia/epidemiologia , Prevalência , Estudos Prospectivos , Infecções Respiratórias/microbiologia , Inquéritos e Questionários , Infecções Urinárias/microbiologia , Adulto Jovem
17.
Int J Mol Sci ; 20(6)2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30871132

RESUMO

Since their discovery in the early 20th century, antibiotics have been used as the primary weapon against bacterial infections. Due to their prophylactic effect, they are also used as part of the cocktail of drugs given to treat complex diseases such as cancer or during surgery, in order to prevent infection. This has resulted in a decrease of mortality from infectious diseases and an increase in life expectancy in the last 100 years. However, as a consequence of administering antibiotics broadly to the population and sometimes misusing them, antibiotic-resistant bacteria have appeared. The emergence of resistant strains is a global health threat to humanity. Highly-resistant bacteria like Staphylococcus aureus (methicillin-resistant) or Enterococcus faecium (vancomycin-resistant) have led to complications in intensive care units, increasing medical costs and putting patient lives at risk. The appearance of these resistant strains together with the difficulty in finding new antimicrobials has alarmed the scientific community. Most of the strategies currently employed to develop new antibiotics point towards novel approaches for drug design based on prodrugs or rational design of new molecules. However, targeting crucial bacterial processes by these means will keep creating evolutionary pressure towards drug resistance. In this review, we discuss antibiotic resistance and new options for antibiotic discovery, focusing in particular on new alternatives aiming to disarm the bacteria or empower the host to avoid disease onset.


Assuntos
Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Animais , Enterococcus faecium/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Terapia de Alvo Molecular/métodos , Infecções Estafilocócicas/tratamento farmacológico
18.
J Med Microbiol ; 68(4): 549-554, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30806614

RESUMO

To determine micro-organisms attached to removed urethral catheters and relate this to patient-specific information. Indwelling urethral catheters were collected from patients at a UK teaching hospital. The balloon and lumen were sonicated, and micro-organisms were enumerated. Catheter specimen urine results were retrospectively reviewed. Escherichia coli and Enterococcus faecalis were the most common isolates from 61 catheters. 19.7% of patients received antibiotics and 25 % of those had a multi-drug-resistant (MDR) organism in the lumen. Only 2.04% of catheters from patients not receiving antibiotics had a MDR organism. All lumens were colonized irrespective of antibiotic use. Symptom presentation did not correlate with numbers of colonizing organisms or species. Despite heavy colonization, only 8/61 patients were symptomatic. Indwelling urinary catheters in place for ≥10 days were universally colonized and there was no correlation with symptom presentation. Symptom presentation remains the most important factor for defining catheter-associated urinary tract infection.


Assuntos
Infecções Assintomáticas/terapia , Cateteres de Demora/microbiologia , Infecções por Enterobacteriaceae/urina , Infecções por Bactérias Gram-Positivas/urina , Cateteres Urinários/microbiologia , Adulto , Idoso , Antibacterianos/uso terapêutico , Aderência Bacteriana/efeitos dos fármacos , Contagem de Colônia Microbiana , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/isolamento & purificação , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/urina , Feminino , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Cateterismo Urinário/efeitos adversos , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
19.
Int J Infect Dis ; 81: 210-214, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30794940

RESUMO

Dalbavancin, a lipoglycopeptide with prolonged half-life approved for the treatment of acute bacterial skin and soft tissue infections, can be used for the treatment of infections caused by gram-positive bacteria requiring long term treatment such as endocarditis, prosthetic joint infections (PJI) or osteomyelitis. Clinical data are limited in these settings. OBJECTIVES: To evaluate indications, safety, tolerability and long-term outcomes of dalbavancin-treated patients. Patients and methods Our multicenter, retrospective study includes patients who received dalbavancin in Austria from September 2016 to March 2018. 90-day outcomes and tolerability were determined. RESULTS: A total of 101 patients were included in 3 centers (57% male, median age 65 years). The treated infections were PJI (31%), osteomyelitis (29%), endocarditis (25%) and acute bacterial skin and soft tissue infections (12%). Concomitant use of other antimicrobial substances was common (63%). The mean total cumulative dose of dalbavancin was 3,357mg (±2,283mg). Clinical success rate was 89%. Side effects occurred in 3/101 patients. CONCLUSION: In this real-life study dalbavancin was primarily used in off-label indications for treatment of PJI, osteomyelitis and endocarditis. Success rate was high (89%), tolerability and safety were excellent in this setting. Dalbavancin may therefore be used in these off-label indications as alternative treatment approach.


Assuntos
Antibacterianos/administração & dosagem , Bactérias Gram-Positivas/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Teicoplanina/análogos & derivados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Áustria , Criança , Feminino , Bactérias Gram-Positivas/genética , Bactérias Gram-Positivas/isolamento & purificação , Bactérias Gram-Positivas/fisiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteomielite/microbiologia , Estudos Retrospectivos , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções dos Tecidos Moles/microbiologia , Teicoplanina/administração & dosagem , Teicoplanina/efeitos adversos , Adulto Jovem
20.
Fish Shellfish Immunol ; 87: 401-409, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30711494

RESUMO

In this study, therapeutic effects of aqueous methanolic extracts of beard lichen (Usnea barbata) against Lactococcus garvieae (ATCC 43921) in rainbow trout (Onchorhynchus mykiss) were investigated. Six different experimental groups [0 mg/100 µL (Control), 4 mg/100 µL, 8 mg/100 µL, 12 mg/100 µL, 6 mg/100 µL florfenicol (positive control), 6 mg/100 µL erythromycin (positive control)] were set up to determine effects of lichen extract on immune responses and survival rate. In the study, superoxide radical production was increased in fish treated with 12 mg beard lichen extract, florfenicol and erythromycin compared to that of control (P < 0.05). Lysozyme activity was generally decreased (P < 0.05) or no differences were observed in all experimental groups compared to that of control (P > 0.05). Myeloperoxidase was significantly increased in all antibiotic treated groups. No differences were observed in liver histology of experimental groups compared to control. Cytokine gene expressions were elevated in all experimental groups compared to that of control (P < 0.05), except IL-1ß expression at 10th day sampling time. Other immune related genes (IL-8, TGF- ß, IL-12 Beta, TNFα1, IL-10, COX-2, IL-6, TLR5, C3, IGM, MHC-II, iNOS, IgT, IFN1, IFN2, IFN reg) were also elevated in all experimental groups compared to that of control group. The survival rates obtained in 4 mg beard lichen treated group, 8 mg beard lichen treated group and erythromycin treated group were 73.08, 65.38 and 80.77% respectively. Our results suggest that beard lichen methanolic extract could be an effective therapeutic agent to be used against L. garvieae infection in rainbow trout at the dose of 4 mg/17.41 ±â€¯0.3 g body weight/day.


Assuntos
Doenças dos Peixes/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/veterinária , Lactococcus/efeitos dos fármacos , Oncorhynchus mykiss , Usnea/química , Animais , Relação Dose-Resposta a Droga , Doenças dos Peixes/imunologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/imunologia , Lactococcus/fisiologia
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