Role of Efflux Pumps on Antimicrobial Resistance in Pseudomonas aeruginosa.

Antimicrobial resistance is an old and silent pandemic. Resistant organisms emerge in parallel with new antibiotics, leading to a major global public health crisis over time. Antibiotic resistance may be due to different mechanisms and against different classes of drugs. These mechanisms are usually found in the same organism, giving rise to multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria. One resistance mechanism that is closely associated with the emergence of MDR and XDR bacteria is the efflux of drugs since the same pump can transport different classes of drugs. In Gram-negative bacteria, efflux pumps are present in two configurations: a transmembrane protein anchored in the inner membrane and a complex formed by three proteins. The tripartite complex has a transmembrane protein present in the inner membrane, a periplasmic protein, and a porin associated with the outer membrane. In Pseudomonas aeruginosa, one of the main pathogens associated with respiratory tract infections, four main sets of efflux pumps have been associated with antibiotic resistance: MexAB-OprM, MexXY, MexCD-OprJ, and MexEF-OprN. In this review, the function, structure, and regulation of these efflux pumps in P. aeruginosa and their actions as resistance mechanisms are discussed. Finally, a brief discussion on the potential of efflux pumps in P. aeruginosa as a target for new drugs is presented.

Sobrevida e características ecocardiográficas de gatos com e sem cardiomiopatias / Survival and echocardiographic characteristics of cats with and without cardiomyopathies

Cardiopatias felinas apresentam importante relevância na rotina veterinária, todavia os seus aspectos epidemiológicos em gatos não são conhecidos regionalmente. O objetivo do estudo foi descrever a frequência das cardiopatias na região Norte e Vale do Itajaí no estado de Santa Catarina e determinar a sobrevida de pacientes cardiopatas e não cardiopatas. O estudo contou com a análise retrospectiva de 74 laudos ecocardiográficos e prontuários médicos de gatos oriundos de estabelecimentos veterinários da região, de janeiro de 2017 a dezembro de 2019. Tutores ou veterinários responsáveis foram contatados para averiguar a sobrevida dos animais. Os animais do estudo em sua maioria eram machos (n=40/74) e sem raça definida (n=47/74). Cardiomiopatia foi o diagnóstico mais comum (n=21/74), com destaque para o fenótipo hipertrófica (n=13/21). As cardiomiopatias foram diagnosticadas mais comumente em gatos acima de oito anos de idade. Os principais sinais clínicos nos gatos sintomáticos (n=41/74) foram sopro (n=15/41) e dispneia (n=6/41). Os principais achados ecocardiográficos foram hipertrofia concêntrica da parede livre do ventrículo esquerdo (n=18/41) e dilatação do átrio esquerdo (n=12/41). A mediana de sobrevida dos 74 gatos foi de 303±209.8 dias, estando altamente relacionado com a classe do estadiamento clínico (P=0,006). Gatos com fenótipo dilatada tiveram menor média de sobrevida (180.5 dias). As doenças concomitantes mais observadas foram doença renal crônica (n=7/15), hipertensão (n=5/15) e/ou hipertireoidismo (n=3/15). Gatos com cardiomiopatias, sintomáticos e com estágios mais avançados de remodelamento cardíaco, demostraram viver menos se comparados com aqueles em estágio inicial da cardiopatia. Bem como pacientes com doenças de base associada apresentaram menor expectativa de vida.

Feline cardiopathies are relevant on veterinary practice although lack of regional epidemiogical description. The purpose of this study is to determine cardiopathy prevalence and survival of cardiac and non-cardiac patients on Santa Catarina's northern and Itajai valley regions. The retrospective study included 74 echocardiographic exams and medical records from January 2017 to December 2019. Veterinarians and owners were contacted to check survival on cardiac and non-cardiac patients. The animals were most male (n=40/74) and mongrel (n=47/74). Cardiomyopathies were the most common diagnosis (n=21/74), specially the hypertrophic phenotype (n=13/21). The cardiomyopathy diagnosis was evidenced in cats above eight years old. The most usual clinical findings on symptomatic patients (n=41/74) were cardiac murmur (n=15/41) and dyspnea (n=6/41). Left ventricular free wall concentric hypertrophy (n=18/41) and left atrium dilation (n=12/41) were the main echocardiographic findings. Median survival from 74 cats was 303±209,8 days and related to clinical staging (p=0,006). Cats with dilated cardiomyopathy phenotype presented lower mean survival (180,5 days). Concomitant diseases included chronic renal disease (n=7/15), systemic arterial hypertension (n=5/15) and/or hyperthyroidism (n=3/15). In conclusion, cats with cardiomyopathies, symptomatic and with more advanced stages of cardiac remodeling, have shown to live less than those in early stage of heart disease. As well as patients with associated concomitant diseases, they had a lower life expectancy.

Sobrevida e características ecocardiográficas de gatos com e sem cardiomiopatias / Survival and echocardiographic characteristics of cats with and without cardiomyopathies

Cardiopatias felinas apresentam importante relevância na rotina veterinária, todavia os seus aspectos epidemiológicos em gatos não são conhecidos regionalmente. O objetivo do estudo foi descrever a frequência das cardiopatias na região Norte e Vale do Itajaí no estado de Santa Catarina e determinar a sobrevida de pacientes cardiopatas e não cardiopatas. O estudo contou com a análise retrospectiva de 74 laudos ecocardiográficos e prontuários médicos de gatos oriundos de estabelecimentos veterinários da região, de janeiro de 2017 a dezembro de 2019. Tutores ou veterinários responsáveis foram contatados para averiguar a sobrevida dos animais. Os animais do estudo em sua maioria eram machos (n=40/74) e sem raça definida (n=47/74). Cardiomiopatia foi o diagnóstico mais comum (n=21/74), com destaque para o fenótipo hipertrófica (n=13/21). As cardiomiopatias foram diagnosticadas mais comumente em gatos acima de oito anos de idade. Os principais sinais clínicos nos gatos sintomáticos (n=41/74) foram sopro (n=15/41) e dispneia (n=6/41). Os principais achados ecocardiográficos foram hipertrofia concêntrica da parede livre do ventrículo esquerdo (n=18/41) e dilatação do átrio esquerdo (n=12/41). A mediana de sobrevida dos 74 gatos foi de 303±209.8 dias, estando altamente relacionado com a classe do estadiamento clínico (P=0,006). Gatos com fenótipo dilatada tiveram menor média de sobrevid

Feline cardiopathies are relevant on veterinary practice although lack of regional epidemiogical description. The purpose of this study is to determine cardiopathy prevalence and survival of cardiac and non-cardiac patients on Santa Catarina’s northern and Itajai valley regions. The retrospective study included 74 echocardiographic exams and medical records from January 2017 to December 2019. Veterinarians and owners were contacted to check survival on cardiac and non-cardiac patients. The animals were most male (n=40/74) and mongrel (n=47/74). Cardiomyopathies were the most common diagnosis (n=21/74), specially the hypertrophic phenotype (n=13/21). The cardiomyopathy diagnosis was evidenced in cats above eight years old. The most usual clinical findings on symptomatic patients (n=41/74) were cardiac murmur (n=15/41) and dyspnea (n=6/41). Left ventricular free wall concentric hypertrophy (n=18/41) and left atrium dilation (n=12/41) were the main echocardiographic findings. Median survival from 74 cats was 303±209,8 days and related to clinical staging (p=0,006). Cats with dilated cardiomyopathy phenotype presented lower mean survival (180,5 days). Concomitant diseases included chronic renal disease (n=7/15), systemic arterial hypertension (n=5/15) and/or hyperthyroidism (n=3/15). In conclusion, cats with cardiomyopathies, symptomatic and with more advanced stages of cardiac remodeling, have shown to live less than those in early stage of heart disease. As well as patients with associated concomitant diseases, they had a lower life expectancy.