Evaluación de la sensibilidad de cepas de Pseudomonas aeruginosa multi-resistentes frente a ceftolozano/tazobactam

Prado-Montoro, C Del; Ruiz-Aragón, Jesús; Rubio, Carmen Martínez; García-Martín, Sofía; Freyre‐Carrillo, Carolina; Rodríguez-Iglesias, Manuel

doi:10.4067/s0716-10182019000500551

Cited by 3 publications

(3 citation statements)

References 11 publications

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“…The isolates in these studies had low resistance to carbapenems; however, with temporal evolution, this frequency has increased, as described by Jácome et al (2016) and Lima et al (2020), reaching 53% and 40%, respectively, among hospital isolates from Recife-PE. The MDR isolates exhibited a lower frequency of resistance to aminoglycosides; this has also been verified in the studies of Siqueira et al (2018) and Montoro et al (2019). The great diversity presented in the susceptibility profile to the antimicrobial classes suggests the existence of an association of several resistance mechanisms, which was beyond the scope of this study.…”

Section: Discussionsupporting

confidence: 67%

Phenotypic and genetic analysis of virulence factors in multidrug- sensitive and multidrug-resistant clinical isolates of Pseudomonas aeruginosa

Silva

Lima

Rabelo

et al. 2021

RSD

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This study aimed to correlate the pattern of antimicrobial susceptibility, phenotypic production of virulence factors, the occurrence of virulence factors genes and the clonal profile of clinical isolates of Pseudomonas aeruginosa of a tertiary hospital in Recife-PE. The 30 clinical isolates (15 multidrug-sensitive (MDS) and 15 multidrug-resistant (MDR)) were analyzed using phenotypic methods to detect virulence factors (alkaline protease, hemolysin, phospholipase C, lipase, and pigments). The detection of the aprA, lasA, lasB, plcH, and toxA genes was performed through specific PCRs, and the clonal profile was assessed using ERIC-PCR. The results revealed cephalosporins being the class eliciting the highest percentage of resistance; the MDR isolates were all resistant. Among the MDS isolates, all were sensitive to carbapenems and quinolones. The MDR isolates produced less virulence factors such as pyocyanin and lipase, and exhibited lower expression of toxA and lasA genes, whereas the MDS isolates produced less hemolysin and phospholipase C. There was no difference between the groups for alkaline protease production and aprA gene expression. All the isolates produced pyocyanin and expressed lasB and plcH genes. A great genetic diversity was found, and it was possible to observe 28 genetic profiles. Clones were present among the MDR isolates. The occurrence of virulence factors in almost all the isolates studied suggests their high level of pathogenicity, demonstrating that this pathogen is capable of accumulating numerous virulence factors, and in some cases, is associated with multidrug resistance, which makes it difficult to treat these infections.

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Section: Discussionsupporting

confidence: 67%

Phenotypic and genetic analysis of virulence factors in multidrug- sensitive and multidrug-resistant clinical isolates of Pseudomonas aeruginosa

Silva

Lima

Rabelo

et al. 2021

RSD

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“…Se trata de la combinación de una cefalosporina de quinta generación con un clásico inhibidor de batalactamasas, el ceftolozano va a actuar como un bactericida provocando muerte bacteriana, su utilización está indicada en casos complicados de infecciones de vía urinaria, infección intraabdominal, pielonefritis, infecciones de piel, tejidos blandos y hueso, ya que es activo principalmente contra E. Coli, K. pneumoniae, Proteus mirabilis, Enterobacter, Citrobacter, Enterobacteriaceae, algunos estreptococos y escasos anaerobios, pero sobretodo tiene actividad contra Pseudomona Aeruginosa multirresistente y bacterias productoras de betalactamasas de espectro extendido. (16)(17)(18)(19) La vida media de este antibiótico es alrededor de 2,7 horas, por lo que su administración es cada 8 horas, a dosis de 1/0,5 g, sin embargo, al ser de eliminación renal, las dosis deben ser ajustadas de acuerdo al clearance de creatinina en el caso de pacientes con enfermedad renal. El uso de estos medicamentos es muy seguro, en los diversos estudios realizados entre los efectos adversos más comunes reportados tenemos náuseas, cefalea, diarrea y estreñimiento, pero no impiden que el paciente continúe con el tratamiento.…”

Section: Ceftolozano/ Tazobactamunclassified

Los nuevos antimicrobianos

Sanango

Izquierdo

2023

Salud ConCienc.

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En los últimos años, la introducción de fármacos nuevos, con un espectro de acción mucho más amplio que los ya conocidos, se ha constituido como una necesidad primordial, ya que el incremento de la aparición de microorganismos multirresistentes ha ido aumentando debido a la resistencia bacteriana, que es causada principalmente por el mal uso de los antibióticos. Si bien es cierto algunos antibióticos ya son conocidos y se encuentran principalmente dentro de las familias de las cefalosporinas, carbapenémicos, entre otros, pero su combinación con otros antibióticos de espectro amplio, los hacen una buena alternativa para tratar casos de infecciones polimicrobianas multirresistentes, constituyéndose como primera línea de tratamiento para los pacientes que presenten infecciones complicadas y graves que no puedan ser resueltas con el uso de otros antibióticos. Actualmente la aparición de medicamentos que se pueden inhalar como el ciprofloxacino, levofloxacino, tobramicina y amikacina en polvo, han sido de gran ayuda para el tratamiento de infecciones respiratorias bajas, como en el caso de las neumonías.

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“…Notwithstanding, the interaction of AMP and CRO is only understood partially, because most of the data have been derived from in vitro testing (checkerboard and time-kill curves) [8,12] and animal models of endocarditis [9,10,13,14] that have several limitations for PK/ PD analysis and the optimal translation to humans: (i) deficient bacterial growth, (ii) low statistical power due to intrinsic high variation and, (iii) the lack of a complete dose-response curve due to the small number of doses tested [15,16]. These limitations preclude the accurate estimation of pharmacodynamic parameters and the determination of the PK/PD index driving the efficacy of the combination, essential for proper extrapolation to the clinic [17,18].…”

Section: Introductionmentioning

confidence: 99%

A new pharmacodynamic approach to study antibiotic combinations against enterococci in vivo: Application to ampicillin plus ceftriaxone

et al. 2020

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The combination of ampicillin (AMP) and ceftriaxone (CRO) is considered synergistic against Enterococcus faecalis based on in vitro tests and the rabbit endocarditis model, however, in vitro assays are limited by the use of fixed antibiotic concentrations and the rabbit model by poor bacterial growth, high variability, and the use of point dose-effect estimations, that may lead to inaccurate assessment of antibiotic combinations and hinder optimal translation. Here, we tested AMP+CRO against two strains of E. faecalis and one of E. faecium in an optimized mouse thigh infection model that yields high bacterial growth and allows to define the complete dose-response relationship. By fitting Hill’s sigmoid model and estimating the parameters maximal effect (Emax) and effective dose 50 (ED50), the following interactions were defined: synergism (Emax increase ≥2 log10 CFU/g), antagonism (Emax reduction ≥1 log10 CFU/g) and potentiation (ED50 reduction ≥50% without changes in Emax). AMP monotherapy was effective against the three strains, yielding valid dose-response curves in terms of dose and the index fT>MIC. CRO monotherapy showed no effect. The combination AMP+CRO against E. faecalis led to potentiation (59–81% ED50 reduction) and not synergism (no changes in Emax). Against E. faecium, the combination was indifferent. The optimized mouse infection model allowed to obtain the complete dose-response curve of AMP+CRO and to define its interaction based on pharmacodynamic parameter changes. Integrating these results with the pharmacokinetics will allow to derive the PK/PD index bound to the activity of the combination, essential for proper translation to the clinic.

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Evaluación de la sensibilidad de cepas de Pseudomonas aeruginosa multi-resistentes frente a ceftolozano/tazobactam

Abstract: Los autores declaran no haber recibido financiación para la realización de este estudio. Los autores declaran no tener conflicto de interés alguno.

Cited by 3 publications

References 11 publications

Phenotypic and genetic analysis of virulence factors in multidrug- sensitive and multidrug-resistant clinical isolates of Pseudomonas aeruginosa

Phenotypic and genetic analysis of virulence factors in multidrug- sensitive and multidrug-resistant clinical isolates of Pseudomonas aeruginosa

Los nuevos antimicrobianos

A new pharmacodynamic approach to study antibiotic combinations against enterococci in vivo: Application to ampicillin plus ceftriaxone

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