Molecular epidemiological survey of bacteremia by multidrug resistant Pseudomonas aeruginosa: the relevance of intrinsic resistance mechanisms

Dantas, Raquel Cristina Cavalcanti; Silva, Rebecca Tavares e; Ferreira, Melina Lorraine; Gonçalves, Iara Rossi; Araújo, Bruna Fuga; Campos, Paola Amaral de; Royer, Sabrina; Batistão, Deivid William da Fonseca; Gontijo-Filho, Paulo Pinto; Ribas, Rosineide Marques

doi:10.1371/journal.pone.0176774

Cited by 34 publications

(23 citation statements)

References 53 publications

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“…39 Although the MexXY-OprM system is known as a substantial element in aminoglycoside resistance in only P. aeruginosa, 40 it is also over-expressed in multi-drug resistant P. aeruginosa 41 and similar reports to our study have shown its over-expression in carbapenemresistant P. aeruginosa strains. 7,42,43 MexAB-OprM over-expression was observed in 21.8% of the isolates, concurring with Xavier and co-workers. 44 In contrast, Dantas et al 7 and Chalhoub et al 32 reported a much higher frequency of MexAB-OprM over-expression in P. aeruginosa isolates.…”

Section: Discussionsupporting

confidence: 87%

“…Downregulation of oprD generally causes resistance to imipenem and meropenem. 7 Another major mechanism of Carbapenem resistance in P. aeruginosa is decreasing the antibiotic concentration through efflux systems belonging to the resistance-nodulation-division (RND) family (MexAB-OprM, MexCD-OprJ, MexEF-OprN, MexXY-OprM, MexJK and MexVW). 8 Meropenem is affected by high regulation of MexAB-OprM, MexCD-OprJ, and MexXY-OprM, whilst imipenem is not affected.…”

Section: Introductionmentioning

confidence: 99%

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Molecular Epidemiology and Mechanisms of High-Level Resistance to Meropenem and Imipenem in Pseudomonas aeruginosa

Hassuna¹,

Darwish²,

Sayed³

et al. 2020

IDR

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Purpose: Pseudomonas aeruginosa possesses a large number of resistance mechanisms to different antimicrobials with carbapenems being the most powerful in treating resistant P. aeruginosa. Hence, it is imperative to explore different mechanisms of carbapenemsresistance in P. aeruginosa to achieve successful treatment through the design of new drugs acting on this interaction to combat against antimicrobial resistance. Strains and Methods: A total of 634 P. aeruginosa clinical isolates were collected from various patient sources and their MIC levels were measured. Molecular evaluation of carbapenem resistance was assessed by investigating the presence of bla IMP1 , bla IMP2 , bla VIM1 , bla VIM2 , bla SPM and bla NDM genes and the gene expression of the following multidrug efflux pump systems: MexAB-OprM, MexCD-OprJ, MexEF-OprN and MexXY-OprM and its correlation with MIC. Isolates were typed by Random Amplified Polymorphic DNA (RAPD)-typing. Results: Carbapenem resistance was detected in 32 (5%) isolates, which were all imipenem resistant (of which 29 were meropenem resistant). High-level resistance (≥64mg/mL) to imipenem was found in 27 (84.3%) isolates, and to meropenem in 28 (96.5%) isolates. The carbapenemase bla VIM-1 was found in 31 isolates, while bla NDM was detected in 4 isolates. None of the isolates possessed either bla-VIM-2 , bla IMP-1 , bla IMP-2 or bla SPM. The majority of the isolates displayed over-expression of MexCD-OprJ (75%) followed by MexXY-OprM efflux pump (62%), while MexAB-OprM and MexEF-OprN efflux pumps were overexpressed in 21.8% and 18.7% of the isolates, respectively, with no down-regulation of oprD in any of the isolates. A strong correlation was found between CDJ efflux pump expression and meropenem, imipenem resistance (r=0.532, 0.654, p<0.001, <0.001) respectively. Four major clusters were detected by RAPD-typing: group 1(10 isolates), group 3 (9 isolates), group 2 (8 isolates) while the fourth group (4) included 4 isolates (12.5% polymorphism). Conclusion: High-level carbapenem resistance reported in this study was allied to multiple mechanisms including carbapenemase production and efflux-pump over-expression. Threatening cross-infection is possible inside the hospital and stringent infection control measures are crucial.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Molecular Epidemiology and Mechanisms of High-Level Resistance to Meropenem and Imipenem in Pseudomonas aeruginosa

Hassuna¹,

Darwish²,

Sayed³

et al. 2020

IDR

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“…This high consumption of antimicrobials results in a higher incidence of resistant bacteria [4]. The rate of carbapenem resistance differs in distinct geographic regions.…”

Section: Discussionmentioning

confidence: 99%

“…The P. aeruginosa porin OprD is a substrate-specific porin that facilitates the diffusion of basic amino acids, small peptides, and carbapenems into the cell. OprD mediated resistance occurs as a result of decreased transcriptional expression of oprD and/or function mutations that disrupt protein activity [4,5].…”

Section: Introductionmentioning

confidence: 99%

Role of efflux pump and OprD porin expression in carbapenem resistance of Pseudomonas aeruginosa clinical isolates

Müderris

Durmaz

Özdem

et al. 2018

J Infect Dev Ctries

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Introduction: In recent years, the prevalence of multidrug-resistant P. aeruginosa has remarkably increased. Thus, we wanted to investigate the carbapenem resistance mechanisms and clonal relationship among 80 carbapenem-resistant P. aeruginosa strains. Methodology: Carbapenemase production was detected using the Modified Hodge Test (MHT), EDTA combined disc method (ECD), and PCR. Expression levels of efflux and porin genes were mesured by real-time reverse transcription PCR. Clonal relationship of the isolates was investigated by pulsed-field gel electrophoresis (PFGE). Results: Carbapenemase production was detected in 7.5% of the isolates with MHT/ECD tests and in 11.3% of the isolates with PCR. Although the specificity of MHT/ECD was high, the sensitivitivity was low. oprD downregulation and mexB, mexY, and mexD overexpression were demonstrated in 55%, 16.3%, 2.5%, and 2.5% of the isolates, respectively. Multiple carbapenem resistance mechanisms were found in nearly a quarter of the isolates. PFGE typing of the 80 P. aeruginosa isolates yielded 61 different patterns. A total of 29 isolates (36.3%) were classified in 10 clusters, containing 2 to 7 strains. We could not find a strict relationship between PFGE profile and carbapenem resistance mechanisms. Conclusions: Although oprD downregulation and MexAB-OprM overexpression were the most common mechanisms, carbapenem resistance was associated with multiple mechanisms in the study. MHT/ECD tests should not be used alone for investigation of carbapenemase production in P. aeruginosa. Rapid tests with high sensitivity and specificity should be developed for the detection of carbapenemase production in P. aeruginosa.

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“…Geralmente em países de baixa e média renda, como o Brasil, diferentes fatores podem levar a emergência e disseminação de clones resistentes, especialmente nas UTIs. Entre alguns desses fatores estão a alta densidade de uso de antibióticos, que resultam frequentemente na pressão seletiva que favorece a emergência de cepas resistentes e multirresistentes, adicionada a existência de clones dominantes e falhas nas práticas básicas de prevenção e controle de infecções, que podem em parte justificar a disseminação desses micro-organismos no ambiente hospitalar (DANTAS et al, 2017). O HC-UFU apresenta todas essas características proporcionando ambiente ideal para a disseminação de clones de alto risco.…”

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Patogênese de infecções de corrente sanguínea relacionada ao cateter venoso central por Staphylococcus epidermidis em neonatos críticos

Oliveira¹

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Introduction: The hospital bloodstream infeccions (BSI) are responsible for significant frenquencies of morbidity and mortality in Neonatal Intensive Care Units (NICU), resulting in prolonged hospitalization and increased costs, especially in low birth weight infants. Objective:The present study proposed to determine the pathogenesis of catheter-related bloodstream infections (CR-BSI) caused by Staphylococcus epidermidis using the PFGE technique ("Pulsed Field Gel Electrophoresis ") as well as to evaluate the risk factors for mortality among neonates with weights ≤ 1500 grams and > 1500 grams. Methods: The study included neonates from the ICU of Hospital de Federal University of Uberlândia during the period from October 2010 to August 2012. For the study of the pathogenesis, were used samples of S. epidermidis recovered from blood, skin at the insertion site, hub, as well as the mucosa of the nostril and gut, from 48 hours to 14 days after the use of the Catheter or until obtaining a positive culture for S. epidermidis and catheter tip obtained after removal. In addition, were determined the risk factors for the development of BSI caused by S. epidermidis using case study x paired control. In addition to verifying the presence of mecA genes and ACME (Arginine Catabolic Mobile Element) by polymerase chain reaction (PCR), in S.epidermidis. Results: In total, 125 neonates developed BSI (27.0%), with 98 (78.4%) defined as hospital-type, totaling 124 episodes. Sepsis preterm affected 20% of newborns with BSI with 48% mortality, mainly in neonates weighing ≤ 1500 grams. The presence of mechanical ventilation and clinical sepsis were the factors associated with mortality among the heaviest neonates. In the case study x paired control, all variables analyzed [Hospitalization time (P <0.0001), time of mechanical ventilation (P = 0.0003), parenteral nutrition time (P <0.0001), CVC use time (P <0.0001) and use of antibiotics (P <0.0001), except CVC use were significant by univariate analysis. From the total of 53 samples tested in the PCR, 67.9% were positive for the mecA gene (oxacillin resistant) with higher frequency between the samples of mucosa 39.9%. Only 7.6% of the samples had genes for ACME (characterized as ACME type II), 17% associated with skin. Among 19 cases of primary BSI, the origin of the infection was identified in only 36.8% of the cases, where two were characterized as definitive intraluminal, one definitive extraluminal and four had the origin from the mucous membranes, defined as translocation. In the majority (63.2%) of the cases the origin of the infection could not be determined. The cross-transmission was a frequent event observed in the Unit. Conclusion: Despite the clinical and epidemiological importance of the BSI in the critical neonates and the magnitude of the study, in the majority of cases it was not possible to determine the origin of the microorganism present in the blood and although it has been observed high clonal diversity among the S. epidermidis samples, the cross-transmission was a...

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Molecular epidemiological survey of bacteremia by multidrug resistant Pseudomonas aeruginosa: the relevance of intrinsic resistance mechanisms

Cited by 34 publications

References 53 publications

<p>Molecular Epidemiology and Mechanisms of High-Level Resistance to Meropenem and Imipenem in <em>Pseudomonas aeruginosa</em></p>

<p>Molecular Epidemiology and Mechanisms of High-Level Resistance to Meropenem and Imipenem in <em>Pseudomonas aeruginosa</em></p>

Role of efflux pump and OprD porin expression in carbapenem resistance of Pseudomonas aeruginosa clinical isolates

Patogênese de infecções de corrente sanguínea relacionada ao cateter venoso central por Staphylococcus epidermidis em neonatos críticos

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