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1.
PLoS Biol ; 22(1): e3002457, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38175839

RESUMO

Heteroresistance (HR) is an enigmatic phenotype where, in a main population of susceptible cells, small subpopulations of resistant cells exist. This is a cause for concern, as this small subpopulation is difficult to detect by standard antibiotic susceptibility tests, and upon antibiotic exposure the resistant subpopulation may increase in frequency and potentially lead to treatment complications or failure. Here, we determined the prevalence and mechanisms of HR for 40 clinical Staphylococcus aureus isolates, against 6 clinically important antibiotics: daptomycin, gentamicin, linezolid, oxacillin, teicoplanin, and vancomycin. High frequencies of HR were observed for gentamicin (69.2%), oxacillin (27%), daptomycin (25.6%), and teicoplanin (15.4%) while none of the isolates showed HR toward linezolid or vancomycin. Point mutations in various chromosomal core genes, including those involved in membrane and peptidoglycan/teichoic acid biosynthesis and transport, tRNA charging, menaquinone and chorismite biosynthesis and cyclic-di-AMP biosynthesis, were the mechanisms responsible for generating the resistant subpopulations. This finding is in contrast to gram-negative bacteria, where increased copy number of bona fide resistance genes via tandem gene amplification is the most prevalent mechanism. This difference can be explained by the observation that S. aureus has a low content of resistance genes and absence of the repeat sequences that allow tandem gene amplification of these genes as compared to gram-negative species.


Assuntos
Daptomicina , Infecções Estafilocócicas , Humanos , Staphylococcus aureus/genética , Vancomicina , Linezolida/uso terapêutico , Teicoplanina/uso terapêutico , Prevalência , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/tratamento farmacológico , Oxacilina/uso terapêutico , Mutação , Gentamicinas
2.
Antimicrob Agents Chemother ; 67(10): e0071623, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37655923

RESUMO

Acquisition of PBP2a (encoded by the mec gene) is the key resistance mechanism to ß-lactams in Staphylococcus aureus. The mec gene can be easily detected by PCR assays; however, these tools will miss mec-independent oxacillin resistance. This phenotype is mediated by mutations in cell wall metabolism genes that can be acquired during persistent infections under prolonged antibiotic exposure. The complex case presented by Hess et al. (Antimicrob Agents Chemother 67:e00437-23, 2023, https://doi.org/10.1128/aac.00437-23) highlights the diagnostic and therapeutic challenges in the management of mec-independent oxacillin resistance.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Oxacilina/farmacologia , Oxacilina/uso terapêutico , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Staphylococcus aureus Resistente à Meticilina/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Testes de Sensibilidade Microbiana , Proteínas de Ligação às Penicilinas/genética , Proteínas de Ligação às Penicilinas/metabolismo
3.
Antimicrob Agents Chemother ; : e0043723, 2023 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-37341623

RESUMO

Genotypic testing for mecA/mecC is heavily relied upon for rapid optimization of antimicrobial therapy in infections due to Staphylococcus aureus. Little is known regarding optimal reporting and/or therapy for patients demonstrating lack of genotypic evidence of mecA or mecC but phenotypic oxacillin resistance. We report a case of a 77-year-old patient with S. aureus bloodstream infection and infective endocarditis with discordance between mecA/mecC genotypic results and phenotypic susceptibility testing.


Assuntos
Endocardite Bacteriana , Endocardite , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Idoso , Oxacilina/farmacologia , Oxacilina/uso terapêutico , Staphylococcus aureus/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Endocardite Bacteriana/tratamento farmacológico , Reação em Cadeia da Polimerase , Staphylococcus aureus Resistente à Meticilina/genética , Proteínas de Ligação às Penicilinas/genética
4.
Drug Discov Ther ; 17(2): 144-147, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37032074

RESUMO

Staphylococcus aureus is a common clinical pathogen. Does every S. aureus infection require anti-MRSA drugs? Reported here are three cases of a community-acquired infection with S. aureus. The first case involveds a 45-year-old male who was admitted due to right ankle pain for 1 month; he was diagnosed with chronic suppurative osteomyelitis and an acute soft tissue infection of the ankle. S.aureus was cultured from the pus and was resistant to penicillin and sensitive to oxacillin and vancomycin. After receiving oxacillin, he was cured and discharged 45 days after admission. The second case involved a 44-year-old male who was admitted due to lumbar pain with right lower limb numbness for more than 1 month and fever for 1 day. S. aureus was cultured from blood specimens and was resistant to penicillin and sensitive to oxacillin and vancomycin. After receiving oxacillin, he as cured. The third case involved a 7-day-old newborn who was admitted due to skin jaundice for 6 days. S. aureus was cultured from skin secretions specimens and was resistant to penicillin and sensitive to oxacillin, erythromycin, and vancomycin. The newborn was treated with oxacillin for 4 days, and she was cured and discharged. Not all cases a suspected S. aureus infection require anti-MRSA drugs; instead, previous S. aureus susceptibility results in the area and hospital, as well as the patient's clinical profile, need to be taken into account.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Masculino , Feminino , Recém-Nascido , Humanos , Pessoa de Meia-Idade , Adulto , Staphylococcus aureus , Vancomicina/farmacologia , Vancomicina/uso terapêutico , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/diagnóstico , Oxacilina/farmacologia , Oxacilina/uso terapêutico
5.
J Clin Microbiol ; 61(4): e0003923, 2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-36988505

RESUMO

Antistaphylococcal penicillins (ASP) and cefazolin are first-line treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Borderline oxacillin resistance (i.e., oxacillin MICs 1-8 µg/mL) is observed in strains hyperproducing beta-lactamases. This mechanism is also behind the proposed inoculum effect. Minimal data exists on the comparative efficacy of cefazolin or ASP in qualitatively susceptible strains that demonstrate MICs of oxacillin of 1 to 2 µg/mL compared to strains with MIC of oxacillin < 1 µg/mL. We performed a retrospective cohort study of acute treatment outcomes in adult patients with community-acquired MSSA bacteremia treated with cefazolin or ASP, stratified by oxacillin MIC. The primary outcome was a composite of all-cause mortality during the index inpatient admission, failure to clear blood cultures within 72 h after initiating definitive therapy, and change in therapy due to perceived lack of efficacy. A total of 402 patients were included in this study, including 226 isolates with an oxacillin MIC ≥ 1 µg/mL and 176 isolates with an MIC < 1 µg/mL. There were no differences in the rate of the primary outcome occurrence between patients with an oxacillin MIC ≥ 1 µg/mL and an MIC < 1 µg/mL (16.4% versus 15.9%, P = 0.90). There was no difference in the primary outcome between high versus low oxacillin MIC groups among those who received ASP (22.9% versus 24.1%, P = 0.86) or cefazolin (10.3% versus 11.9%, P = 0.86). In our cohort of patients with MSSA bacteremia, oxacillin MIC (i.e., ≥ 1 versus < 1 µg/mL) was not associated with acute treatment outcomes, regardless of the beta-lactam selected as definitive therapy.


Assuntos
Antibacterianos , Bacteriemia , Cefazolina , Staphylococcus aureus Resistente à Meticilina , Oxacilina , Infecções Estafilocócicas , Oxacilina/efeitos adversos , Oxacilina/farmacologia , Oxacilina/uso terapêutico , Cefazolina/efeitos adversos , Cefazolina/farmacologia , Cefazolina/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Bacteriemia/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Estudos Retrospectivos
6.
Br J Ophthalmol ; 107(3): 331-336, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-34607790

RESUMO

BACKGROUND/AIMS: To understand whether the epidemiology, aetiologies, common pathogens and the antibiotic efficacy against the identified bacteria of periorbital cellulitis in adults have changed recently (2010-2019) compared with the past decade (2000-2009). METHODS: Adult patients (n=224) diagnosed with preseptal cellulitis and orbital cellulitis admitted to Kaohsiung Veterans General Hospital during 2000-2019 were retrospectively reviewed. Demographic and clinical characteristics, isolated pathogens and antibiotic susceptibility tests against the commonly cultured bacteria were analysed. RESULTS: Preseptal cellulitis showed a tendency of female predominance. Patients in their 60s showed an incidence peak; more cases were observed during winter. The most common predisposing factor was dacryocystitis (15.5%-30.5%), followed by hordeolum (15.5%-24.8%). Aetiology of sinusitis (p=0.001) decreased and that of conjunctivitis (p=0.007) increased significantly with time. Culture results of nasopharyngeal swabs and local abscess showed higher positivity rate than conjunctival swab. The most common isolates were methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, coagulase-negative staphylococci and Pseudomonas aeruginosa. Antibiotics including fluoroquinolones and vancomycin were effective; in contrast, ampicillin/sulbactam and oxacillin showed decreasing efficacy against gram-positive bacteria. For antibiotic treatment against P. aeruginosa, fluoroquinolones, ceftazidime, piperacillin and imipenem were ideal choices. CONCLUSION: In isolated pathogens, the increasing trend of methicillin-resistant S. aureus detection was compatible with reducing oxacillin efficacy against periorbital infection. In our study, the report of antibiotic efficacy against the most common identified bacteria offered empirical choices for hospitalised patients with periorbital infection before obtaining culture results.


Assuntos
Doenças Palpebrais , Staphylococcus aureus Resistente à Meticilina , Celulite Orbitária , Humanos , Adulto , Feminino , Masculino , Antibacterianos/uso terapêutico , Celulite Orbitária/diagnóstico , Celulite Orbitária/tratamento farmacológico , Celulite Orbitária/epidemiologia , Estudos Retrospectivos , Doenças Palpebrais/tratamento farmacológico , Bactérias , Oxacilina/uso terapêutico , Fluoroquinolonas , Causalidade , Testes de Sensibilidade Microbiana
7.
Pharmacotherapy ; 43(1): 96-99, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36401791

RESUMO

Neonatal sepsis remains a high cause of morbidity and mortality in preterm neonates. Methicillin-susceptible Staphylococcus aureus (MSSA) can cause persistent bloodstream infections and invasive disease in neonates. We report the first published case of persistent MSSA bacteremia in a preterm neonate successfully treated with oxacillin and ertapenem combination therapy.


Assuntos
Bacteriemia , Staphylococcus aureus Resistente à Meticilina , Osteomielite , Infecções Estafilocócicas , Recém-Nascido , Humanos , Oxacilina/uso terapêutico , Staphylococcus aureus , Ertapenem , Antibacterianos/uso terapêutico , Meticilina/farmacologia , Meticilina/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Osteomielite/tratamento farmacológico , Bacteriemia/tratamento farmacológico
8.
Chemotherapy ; 68(1): 55-60, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36001946

RESUMO

INTRODUCTION: Recent evidence has shown that oral antibiotic therapy is not inferior to IV antibiotic therapy in the treatment of complicated Staphylococcus aureus infections. Therefore, oral antibiotic therapy is now frequently prescribed in clinical practice due to cost benefit, ease of administration, decreased complication rate, and lack of need for IV access. In vitro susceptibility testing for ß-lactam oral antibiotics is not routinely performed as the guidelines provided by the Clinical and Laboratory Standards Institute (CLSI) recommend using oxacillin and cefoxitin as surrogate markers. Hence, oral antibiotic susceptibilities for cephalexin and dicloxacillin are not reported and implied based on oxacillin and cefoxitin. The objective of the current study was to determine whether susceptibilities among S. aureus isolates are predictable when comparing commonly used IV and oral beta-lactams. METHODS: Cefazolin, cephalexin, dicloxacillin, and oxacillin broth microdilution minimum inhibitory concentrations (MICs) were determined for 100 clinical isolates of methicillin-sensitive S. aureus by broth microdilution following CLSI guidelines. RESULTS: Among these isolates, median MICs for cephalexin were eight-fold higher than cefazolin MICs and median MICs for dicloxacillin were four-fold less than oxacillin MICs. Ten percent of more strains studied had a major or very major error in its susceptibility reporting when cephalexin was compared to its surrogate marker oxacillin. DISCUSSIONS/CONCLUSIONS: The variations in MICs observed compounded with the dosing and pharmacokinetic differences of oral versus IV ß-lactam suggests that establishing breakpoints for oral ß-lactam antibiotics is necessary to ensure adequate therapy is selected for the treatment of complex S. aureus infections.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Cefoxitina/farmacologia , Cefoxitina/uso terapêutico , beta-Lactamas/farmacologia , beta-Lactamas/uso terapêutico , Cefazolina/farmacologia , Cefazolina/uso terapêutico , Staphylococcus aureus , Dicloxacilina/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Oxacilina/farmacologia , Oxacilina/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Testes de Sensibilidade Microbiana , Cefalexina/farmacologia , Cefalexina/uso terapêutico , Monobactamas/uso terapêutico
9.
Arq. ciências saúde UNIPAR ; 26(3): 1218-1228, set-dez. 2022.
Artigo em Inglês | LILACS | ID: biblio-1414493

RESUMO

Bacteria that are resistant to several antibiotics are a serious One Health problem, as new alternatives for treatment do not appear at the same speed. Thus, the aim of this work was to carry out a survey of studies involving the activity of the essential oil of O. vulgare and its isolated compound carvacrol on antibiotic-resistant bacteria. To this end, a qualitative review of the literature was carried out in the PubMed database from 2015 to 2020. Both for the essential oil and for the isolated compound, the inhibitory action extends to strains often associated with difficult-to-treat infections such as oxacillin and vancomycin-resistant Staphylococcus aureus, ß-lactamase-producing strains, carbapenemases, among others. The point that distinguishes the studies is the type of methodology used in the tests, with studies with carvacrol more directed towards mechanisms of molecular action and application in cells and animals, while those with oils are more preliminary. Although these substances have potential to control resistant bacteria, more research is needed to enable their use.


Bactérias resistentes a vários antibióticos são um grave problema para a Saúde Única, pois novas alternativas de tratamento não aparecem na mesma velocidade. Assim, o objetivo deste trabalho foi realizar um levantamento de estudos envolvendo a atividade do óleo essencial de O. vulgare e seu composto isolado, carvacrol, sobre bactérias resistentes a antibióticos. Para tanto, foi realizada uma revisão qualitativa da literatura na base de dados PubMed no período de 2015 a 2020. Tanto para o óleo essencial quanto para o composto isolado, a ação inibitória se estende a cepas frequentemente associadas a infecções de difícil tratamento como Staphylococcus aureus resistente à oxacilina e vancomicina, cepas produtoras de ß-lactamase, carbapenemases, entre outras. O ponto que diferencia os estudos é o tipo de metodologia utilizada nos testes, sendo os estudos com carvacrol mais direcionados para mecanismos de ação molecular e aplicação em células e animais, enquanto os com óleos são mais preliminares. Embora essas substâncias tenham potencial para controlar bactérias resistentes, mais pesquisas são necessárias para viabilizar seu uso.


Las bacterias resistentes a diversos antibióticos son un grave problema para la Sanidad Única, ya que las nuevas alternativas de tratamiento no aparecen a la misma velocidad. Así pues, el objetivo de este trabajo fue realizar una encuesta sobre los estudios relativos a la actividad del aceite esencial de O. vulgare y su compuesto aislado, el carvacrol, sobre las bacterias resistentes a los antibióticos. Para ello, se realizó una revisión bibliográfica cualitativa en la base de datos PubMed en el periodo comprendido entre 2015 y 2020. Tanto para el aceite esencial como para el compuesto aislado, la acción inhibidora se extiende a cepas frecuentemente asociadas a infecciones de difícil tratamiento como el Staphylococcus aureus resistente a la oxacilina y a la vancomicina, cepas productoras de ß-lactamasas, carbapenemasas, entre otras. El punto que diferencia los estudios es el tipo de metodología utilizada en las pruebas, siendo los estudios con carvacrol más dirigidos a mecanismos de acción molecular y aplicación en células y animales, mientras que los de aceites son más preliminares. Aunque estas sustancias tienen potencial para controlar las bacterias resistentes, es necesario seguir investigando para que su uso sea viable.


Assuntos
Óleos Voláteis/uso terapêutico , Origanum/efeitos dos fármacos , Oxacilina/uso terapêutico , Plantas Medicinais/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/uso terapêutico , Staphylococcus aureus Resistente à Vancomicina/patogenicidade , Antibacterianos/uso terapêutico
10.
Microbiol Spectr ; 10(4): e0103922, 2022 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-35730963

RESUMO

Cephalexin and cefadroxil are oral first-generation cephalosporins used to treat methicillin-susceptible Staphylococcus aureus (MSSA) infections. Despite its shorter half-life, cephalexin is more frequently prescribed, although cefadroxil is an appealing alternative, given its slower clearance and possibility for less frequent dosing. We report comparative MIC distributions for cefadroxil and cephalexin, as well as for oxacillin, cephalothin, ceftaroline, and cefazolin, for 48 unique clinical MSSA isolates from pediatric patients with musculoskeletal infections. Both cefadroxil and cephalexin had MIC50 values of 2 µg/mL and MIC90 values of 4 µg/mL. MIC50s for oxacillin, cephalothin, and ceftaroline were ≤0.25 µg/mL, and cefazolin's MIC50 was 0.5 µg/mL. While cefadroxil and cephalexin MICs are higher than those for other active agents, the distributions of MICs for cefadroxil and cephalexin are statistically equivalent, suggesting similar in vitro MSSA activities. Cefadroxil should be further considered an alternative agent to cephalexin, although additional work is needed to identify the optimal dose and frequency of these antibiotics for the treatment of serious MSSA infections. IMPORTANCE Cephalexin and cefadroxil are oral antibiotics that are used to treat serious infections due to the bacteria MSSA. While cephalexin is used more commonly, cefadroxil is excreted from the body more slowly; this generally allows patients to take cefadroxil less frequently than cephalexin. In this study, we compared the abilities of cefadroxil, cephalexin, and several other representative intravenous antibiotics to inhibit the growth of MSSA in the laboratory. Bacterial samples were obtained from children with bone, joint, and/or muscle infections caused by MSSA. We found that cefadroxil and cephalexin inhibited the growth of MSSA at similar concentrations, suggesting similar antibacterial potencies. The selected intravenous antistaphylococcal antibiotics generally inhibited bacterial growth with lower antibiotic concentrations. Based on these results, cefadroxil should be further considered an alternative oral antibiotic to cephalexin, although future research is needed to identify the optimal dose and frequency of these antibiotics for serious infections.


Assuntos
Cefalexina , Infecções Estafilocócicas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Cefadroxila/uso terapêutico , Cefazolina/farmacologia , Cefazolina/uso terapêutico , Cefalexina/farmacologia , Cefalexina/uso terapêutico , Cefalotina/uso terapêutico , Criança , Humanos , Meticilina/uso terapêutico , Testes de Sensibilidade Microbiana , Oxacilina/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus
11.
J Card Surg ; 37(7): 2127-2130, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35393639

RESUMO

There is an increasing use of left ventricular assist devices (LVADs) as bridge to transplantation or permanent destination therapy in the heart failure patient population. Infection remains a common complication in LVADs, with Gram-positive skin flora as predominant pathogens implicated, including Staphylococcus aureus. While there is emerging evidence for synergistic antibiotic combinations with methicillin resistant S. aureus, there remains a significant gap in the literature for persistent methicillin susceptible S. aureus bacteremia. In this article, we describe the first successful treatment of persistent LVAD-related bacteremia with salvage oxacillin plus ertapenem. The salvage therapy described here must be balanced by the risks for toxicity, impact on resistance, microbiota disruption, drug shortages, and patient costs. This combination warrants further evaluation in the clinical setting to better establish its role in our expanding patient population.


Assuntos
Bacteriemia , Coração Auxiliar , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/etiologia , Ertapenem/uso terapêutico , Coração Auxiliar/efeitos adversos , Humanos , Meticilina/uso terapêutico , Oxacilina/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus
12.
Microbiol Spectr ; 10(2): e0054121, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35234502

RESUMO

Staphylococcus aureus poses a significant threat to human health due to its virulence and multidrug resistance. In addition, recalcitrant biofilm formation of S. aureus often results in chronic infection and the treatment tolerance toward the traditional antibiotics. Thus, the development of novel antimicrobial agents capable to inhibit or eradicate S. aureus biofilm formation does matter. Here, we demonstrated that clemastine showed slight bacteriostatic activity and enhanced the antibacterial activity of oxacillin against S. aureus. Moreover, the dramatic inhibition of biofilm formation was found in clinical S. aureus strains by clemastine. Clemastine inhibited the release of eDNA during the biofilm formation and decreased the S. aureus hemolytic activity. Moreover, the S. aureus SA113 treated with clemastine displayed the decreased transcriptional level of the biofilm formation relevant genes (fnbB, icaA, and icaB), virulence genes (hlg, hld, lukde, lukpvl, beta-PSM, delta-PSM, and cap5A), and the regulatory genes agrA. The proteomics analysis of SA113 treated with clemastine demonstrated the significant changes in levels of biofilm-related proteins (stress response regulators ClpB and GroS, ATP-binding proteins, and urease metabolism), virulence-related proteins (SspA, superantigen, and VWbp), and methicillin resistance-related proteins (glutamine metabolism). The genetic mutations on gdpP (cyclic di-AMP phosphodiesterase) were found in the clemastine-induced tolerant derivative isolate by whole-genome sequencing. Furthermore, the interaction between clemastine and GdpP protein was demonstrated by the molecular docking, gdpP overexpression experiment, and thermal stability assay. Conclusively, clemastine might exert its inhibitory effects against the biofilm formation and hemolysis in S. aureus through targeting GdpP protein. IMPORTANCE The biofilm formation, which protects bacteria from stresses, including antibiotics and host immune responses, can be commonly found in clinical S. aureus isolates worldwide. Treatment failure of traditional antibiotics in biofilm-associated S. aureus infections remains a serious challenge. The novel anti-biofilm drug is urgently needed to address the looming crisis. In this study, clemastine, which is a histamine receptor H1 (HRH1) antagonist, was found to have a novel role of the significant inhibition against the biofilm formation and hemolytic activity of S. aureus and enhanced antibacterial activity against S. aureus when used in combination with oxacillin by targeting the GdpP protein. The discovery of this study identified novel use and mechanism of action of clemastine as a potential anti-biofilm drug for clinical application for S. aureus infectious.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biofilmes , Clemastina/farmacologia , Clemastina/uso terapêutico , Hemólise , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Oxacilina/farmacologia , Oxacilina/uso terapêutico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus
13.
Pak J Biol Sci ; 24(6): 680-687, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34486344

RESUMO

<b>Background and Objective:</b> Detection of methicillin-resistant<i> S. aureus</i> have become a challenge in the presence of oxacillin-susceptible and <i>mecA</i>-positive <i>S. aureus </i>(OS-MRSA), concerning the misidentification events and therapeutic implications. This study aims to identify the OS-MRSA in clinical isolates of Post-viral acute rhinosinusitis, which, hopefully, can interfere with the therapeutic strategy. <b>Materials and Methods:</b> There were 60 patients diagnosed with Post-viral acute rhinosinusitis, recruited from an Ear, Nose and Throat (ENT) outpatient clinic. <i>Staphylococcus aureus</i> isolates were identified from the culture and were then tested for antibiotics susceptibility using a Kirby-Bauer disc diffusion test. The <i>mecA</i>, <i>mecC</i> and <i>blaZ</i> genes were determined using the Polymerase Chain Reaction (PCR) method. <b>Results:</b> <i>Staphylococcus aureus </i>was identified in 20 of the 60 samples from the patients (33.3%; 95% CI: 21.0-45.6). Of the 20 isolates, 19 isolates (95%) had a positive <i>mecA</i> gene, 19 (95%) had a positive <i>mecC</i> gene and 20 (100.0%) had a positive <i>blaZ </i>gene. The majority of the <i>mecA</i>-positive <i>S. aureus</i> showed an oxacillin-susceptible (85%) and 3 isolates (15.0%) were oxacillin-resistant toward the <i>S. aureus</i>. <b>Conclusion:</b> There was a high proportion of Oxacillin/cefoxitin-Susceptible <i>mecA</i>-positive <i>S. aureus</i> in the study population that indicate phenotypic susceptibility to antibiotics does not always indicate the absence of genes that carry resistant traits, thus allowing misidentification if the only phenotypic examination is carried out.


Assuntos
Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Staphylococcus aureus Resistente à Meticilina/genética , Oxacilina/uso terapêutico , Proteínas de Ligação às Penicilinas/genética , Rinite/microbiologia , Sinusite/microbiologia , Infecções Estafilocócicas/microbiologia , Viroses/complicações , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Farmacorresistência Bacteriana , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Rinite/diagnóstico , Rinite/tratamento farmacológico , Sinusite/diagnóstico , Sinusite/tratamento farmacológico , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico
15.
Int J Infect Dis ; 107: 69-71, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33878463

RESUMO

The activities of dalbavancin and comparator agents were evaluated against Staphylococcus aureus isolated from the lower respiratory tract of cystic fibrosis (CF) and non-CF patients with pneumonia. Bacterial isolates (n = 357) were collected from CF patients in 36 medical centers worldwide (2018-2019) and susceptibility tested using reference broth microdilution. Susceptibility results from these isolates were compared with those for 725 S. aureus isolates consecutively collected from non-CF patients with pneumonia from the same medical centers over the same period. Only isolates determined to be the probable cause of pneumonia were included in the study. Susceptibility profiles were very similar among isolates from CF and non-CF patients. Dalbavancin exhibited potent activity (MIC50/90, 0.03/0.03 mg/L) and complete coverage (100.0% susceptibility) against isolates from CF and non-CF patients. Ceftaroline (MIC50/90, 0.25/1 mg/L) was active against 97.8% and 98.1% of isolates from CF and non-CF patients, respectively. Oxacillin resistance (MRSA) rates were 27.7% among CF and 28.7% among non-CF patients. Among MRSA isolates from CF/non-CF patients (n = 99/208), susceptibility to ceftaroline, clindamycin, levofloxacin, and tetracycline were 91.9%/93.3%, 58.6%/64.4%, 40.4%/29.3%, and 83.8%/89.4%, respectively. Dalbavancin demonstrated high potency against S. aureus from CF and non-CF patients and may represent a valuable treatment option for CF patients with MRSA pulmonary infection.


Assuntos
Antibacterianos/uso terapêutico , Fibrose Cística/microbiologia , Pneumonia Estafilocócica/tratamento farmacológico , Staphylococcus aureus/isolamento & purificação , Teicoplanina/análogos & derivados , Cefalosporinas/uso terapêutico , Clindamicina/uso terapêutico , Farmacorresistência Bacteriana , Humanos , Levofloxacino/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Oxacilina/uso terapêutico , Pneumonia Estafilocócica/microbiologia , Teicoplanina/uso terapêutico , Tetraciclina/uso terapêutico , Ceftarolina
16.
Pediatr Infect Dis J ; 40(1): 83-84, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33186188

RESUMO

This report describes a 15-year-old with an 11.1 × 8.2 × 8.4 cm multiloculated liver abscess caused by methicillin-sensitive Staphylococcus aureus who failed extensive catheter drainage and intravenous antibiotics. Daily intra-abscess oxacillin was instilled for 7 days with rapid clinical improvement and sterilization of the abscess. One month later, an ultrasound of the abdomen revealed a normal liver.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Abscesso Hepático Piogênico/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Adolescente , Feminino , Humanos , Instilação de Medicamentos , Fígado/diagnóstico por imagem , Fígado/patologia , Abscesso Hepático Piogênico/diagnóstico por imagem , Abscesso Hepático Piogênico/patologia , Staphylococcus aureus Resistente à Meticilina , Oxacilina/administração & dosagem , Oxacilina/uso terapêutico , Infecções Estafilocócicas/diagnóstico por imagem , Infecções Estafilocócicas/patologia
17.
PLoS One ; 15(6): e0235391, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32603368

RESUMO

BACKGROUND: Neonatal septicemia is a life threatening medical emergency that requires timely detection of pathogens with urgent rational antibiotics therapy. METHODS: A cross-sectional study was conducted between March 2017 to September 2018 among 317 septicemia suspected neonates at neonatal intensive care unit, Ayder Comprehensive Specialized Hospital, Mekelle, Tigray, North Ethiopia. A 3 mL of blood was collected from each participant. Identification of bacterial species was done using the standard microbiological techniques. Antibiotic sensitivity test was done using disk diffusion method. Data were entered and analyzed using computer software SPSS version 22. Bivariate and multivariate regression analysis was applied to determine the association between variables. RESULTS: Of the 317 (190 male and 127 female) neonates, 116 (36.6%) were found to be with culture proven septicemia. Klebsiella species were the predominant etiologic agents. Length of hospital stay (AOR (adjusted odds ratio) = 3.65 (2.17-6.13), p < 0.001) and low birth weight (AOR = 1.64 (1.13-2.78), p = 0.04) were the factors associated with neonatalsepticemia. Most isolates showeda frightening drug resistance rate to the commonly used antimicrobial drugs. K. pneumoniae, E. coli, Enterobacter and Citrobacter species were 57% to100% resistant to ceftazidime, ceftriaxone, gentamycin, amoxacillin-clavulunic acid and ampicillin. All, 9 (100%) isolates of S. aureus were resistant to oxacilline, ampicillin,erythromycin and gentamycin. Furthermore, 55.6% S. aureus isolates were Methicillin Resistant Staphylococcus aureus. CONCLUSION: Neonaltal septicemia is found to be significantly high in the present study. As most of the isolates are potentially related to hospital acquired infections, prevention and control policy should have to be more strengthening in the neonatal intensive care unit.


Assuntos
Antibacterianos/uso terapêutico , Bactérias , Sepse Neonatal , Ampicilina/uso terapêutico , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Citrobacter/efeitos dos fármacos , Citrobacter/isolamento & purificação , Estudos Transversais , Farmacorresistência Bacteriana , Enterobacter/efeitos dos fármacos , Enterobacter/isolamento & purificação , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Etiópia , Feminino , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Klebsiella/efeitos dos fármacos , Klebsiella/isolamento & purificação , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Sepse Neonatal/tratamento farmacológico , Sepse Neonatal/microbiologia , Oxacilina/uso terapêutico , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação
18.
Rev Col Bras Cir ; 47: e20202374, 2020.
Artigo em Português, Inglês | MEDLINE | ID: mdl-32236292

RESUMO

OBJECTIVE: Necrotizing pneumonia (PNZ) is a severe and rare complication of a community-acquired pneumonia, affecting mainly children. We aimed to analyze medical records of children undergoing surgical treatment for PNZ and compare our results with those found in the medical literature. METHODS: Retrospective analysis of children's medical charts who underwent an operation for PNZ, between July 2006 and July 2016, in two hospitals in southern Santa Catarina, Brazil. RESULTS: A total of 26 children with a median age of 2.70 years and mostly females (61.5%) were included in the current study. The main symptoms were fever (88.5%) and cough (65.4%). There was an average use of 4.31 antibiotics per patient. The primary etiological agent was Staphylococcus aureus (23.1%), but cultures were negative in 69% of the patients. Decortication and debridement of necrotic areas were performed in 23 patients (88.5%). The mean postoperative pleural drainage was 8.12 days. The presence of bronchopleural fistula occurred in 50.0% in the preoperative period and 46.2% in the postoperative. The total length of hospital stay was, on average, 27.52 days and the postoperative length of stay was 12.60 days (mean). Postoperative complications occurred in 13 children and there was no mortality. CONCLUSION: The surgical approach is indicated to patients with no response to clinical treatment. Late surgical intervention is associated with progressive parenchyma infection and higher rates of complications. Surgery can lead to better clinical outcomes and earlier recovery.


OBJETIVO: A pneumonia necrosante (PNS) é uma grave e rara complicação da pneumonia adquirida na comunidade, acometendo principalmente crianças, sendo assim, objetivamos analisar prontuários de crianças submetidas ao tratamento cirúrgico de PNS e comparação dos resultados obtidos com os presentes na literatura médica. MÉTODOS: Análise retrospectiva dos prontuários de crianças submetidas ao tratamento cirúrgico por PNS entre julho de 2006 a julho de 2016 em dois hospitais do sul de Santa Catarina, Brasil. RESULTADOS: Do total de 26 crianças, com mediana de idade 2,70 anos, maioria mulheres (61,5%). Os principais sintomas foram febre (88,5%) e tosse (65,4%). Houve média de 4,31 antibióticos utilizados por paciente. O principal agente etiológico foi o Staphylococcus aureus (23,1%) mas as culturas foram negativas em 69% dos pacientes. Em 23 pacientes realizou-se decorticação e desbridamento das áreas necróticas (88,5%). A média de drenagem pleural pós-operatória foi 8,12 dias. Fístula broncopleural ocorreu em 50,0% no pré-operatório e 46,2% após a cirurgia. O tempo total de internação hospitalar foi, em média, de 27,52 dias e tempo pós-operatório com média de 12,60 dias. Complicações pós-operatórias ocorreram em 13 crianças e não houve mortalidade. CONCLUSÕES: Propõe-se abordagem cirúrgica nos pacientes sem resposta ao tratamento clínico, pois o atraso na intervenção cirúrgica associa-se a infecção progressiva no parênquima pulmonar e taxas maiores de complicações. A cirurgia pode conduzir a melhor evolução clínica e recuperação mais precoce.


Assuntos
Pneumonia Necrosante/cirurgia , Antibacterianos/uso terapêutico , Ceftriaxona/uso terapêutico , Pré-Escolar , Infecções Comunitárias Adquiridas/cirurgia , Estudos Transversais , Drenagem/métodos , Feminino , Humanos , Lactente , Tempo de Internação , Masculino , Prontuários Médicos , Oxacilina/uso terapêutico , Complicações Pós-Operatórias , Estudos Retrospectivos , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento , Vancomicina/uso terapêutico
19.
Pediatr Emerg Care ; 36(11): e649-e650, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29757891

RESUMO

A 9-month-old healthy female presented during winter to the emergency department with a chief complaint of fever and prominent respiratory symptoms. She was discharged on oseltamivir with a presumptive diagnosis of influenza. She returned to the emergency department 2 days later with continued fever and more upper respiratory symptoms. She was admitted for intravenous hydration to the observation unit with a diagnosis of viral illness (with viral testing that returned positive for adenovirus) and dehydration. When her high fevers continued, bloodwork that was concerning for leukocytosis, elevated inflammatory markers, and elevated alkaline phosphatase was obtained. During her workup for fever, a full body magnetic resonance imaging was performed, which revealed the diagnosis of a C3 to L5 spinal epidural abscess. This case demonstrates the difficulty of making this important diagnosis in a preverbal child presenting with a concurrent virus during winter viral season.


Assuntos
Abscesso Epidural/diagnóstico por imagem , Imageamento por Ressonância Magnética , Infecções Estafilocócicas/diagnóstico por imagem , Antibacterianos/uso terapêutico , Diagnóstico Diferencial , Serviço Hospitalar de Emergência , Abscesso Epidural/tratamento farmacológico , Abscesso Epidural/microbiologia , Feminino , Humanos , Lactente , Oxacilina/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Imagem Corporal Total
20.
Rev. Col. Bras. Cir ; 47: e20202374, 2020. tab
Artigo em Português | LILACS | ID: biblio-1091926

RESUMO

RESUMO Objetivo: A pneumonia necrosante (PNS) é uma grave e rara complicação da pneumonia adquirida na comunidade, acometendo principalmente crianças, sendo assim, objetivamos analisar prontuários de crianças submetidas ao tratamento cirúrgico de PNS e comparação dos resultados obtidos com os presentes na literatura médica. Métodos: Análise retrospectiva dos prontuários de crianças submetidas ao tratamento cirúrgico por PNS entre julho de 2006 a julho de 2016 em dois hospitais do sul de Santa Catarina, Brasil. Resultados: Do total de 26 crianças, com mediana de idade 2,70 anos, maioria mulheres (61,5%). Os principais sintomas foram febre (88,5%) e tosse (65,4%). Houve média de 4,31 antibióticos utilizados por paciente. O principal agente etiológico foi o Staphylococcus aureus (23,1%) mas as culturas foram negativas em 69% dos pacientes. Em 23 pacientes realizou-se decorticação e desbridamento das áreas necróticas (88,5%). A média de drenagem pleural pós-operatória foi 8,12 dias. Fístula broncopleural ocorreu em 50,0% no pré-operatório e 46,2% após a cirurgia. O tempo total de internação hospitalar foi, em média, de 27,52 dias e tempo pós-operatório com média de 12,60 dias. Complicações pós-operatórias ocorreram em 13 crianças e não houve mortalidade. Conclusões: Propõe-se abordagem cirúrgica nos pacientes sem resposta ao tratamento clínico, pois o atraso na intervenção cirúrgica associa-se a infecção progressiva no parênquima pulmonar e taxas maiores de complicações. A cirurgia pode conduzir a melhor evolução clínica e recuperação mais precoce.


ABSTRACT Objective: Necrotizing pneumonia (PNZ) is a severe and rare complication of a community-acquired pneumonia, affecting mainly children. We aimed to analyze medical records of children undergoing surgical treatment for PNZ and compare our results with those found in the medical literature. Methods: Retrospective analysis of children's medical charts who underwent an operation for PNZ, between July 2006 and July 2016, in two hospitals in southern Santa Catarina, Brazil. Results: A total of 26 children with a median age of 2.70 years and mostly females (61.5%) were included in the current study. The main symptoms were fever (88.5%) and cough (65.4%). There was an average use of 4.31 antibiotics per patient. The primary etiological agent was Staphylococcus aureus (23.1%), but cultures were negative in 69% of the patients. Decortication and debridement of necrotic areas were performed in 23 patients (88.5%). The mean postoperative pleural drainage was 8.12 days. The presence of bronchopleural fistula occurred in 50.0% in the preoperative period and 46.2% in the postoperative. The total length of hospital stay was, on average, 27.52 days and the postoperative length of stay was 12.60 days (mean). Postoperative complications occurred in 13 children and there was no mortality. Conclusion: The surgical approach is indicated to patients with no response to clinical treatment. Late surgical intervention is associated with progressive parenchyma infection and higher rates of complications. Surgery can lead to better clinical outcomes and earlier recovery.


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Complicações Pós-Operatórias , Oxacilina/uso terapêutico , Fatores de Tempo , Ceftriaxona/uso terapêutico , Vancomicina/uso terapêutico , Drenagem/métodos , Prontuários Médicos , Estudos Transversais , Estudos Retrospectivos , Resultado do Tratamento , Infecções Comunitárias Adquiridas/cirurgia , Estatísticas não Paramétricas , Pneumonia Necrosante/cirurgia , Tempo de Internação , Antibacterianos/uso terapêutico
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