Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections

Horcajada, Juan Pablo; Montero, Milagro; Oliver, Antonio; Sorlí, Luisa; Luque, Sònia; Gómez-Zorrilla, Sílvia; Benito, Natividad; Grau, Santiago

doi:10.1128/cmr.00031-19

Cited by 641 publications

(507 citation statements)

References 360 publications

(532 reference statements)

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“…(26,28) Apart from areas with a high prevalence of MBL in P. aeruginosa, the presence of Class A ESBL b-lactamases can result in resistance to ceftolozanetazobactam. (14) Avibactam is an e cient inhibitor of Class A b-lactamases and hence ceftazidime-avibactam combination retains its activity in this situation but not ceftolozane-tazobactam. (29,30) In a report from Spain of 24 extremely-drug resistant ST235 P. aeruginosa isolates, 13% were susceptible to ceftolozane-tazobactam and 58% to ceftazidime-avibactam and the predominant b-lactamases identi ed were VIM-2 (42%) and the Class A ESBL GES-5 (46%).…”

Section: Discussionmentioning

confidence: 99%

“…(13) Multiple resistance mechanisms are frequently present in concert resulting in simultaneous resistance to multiple agents. (14) In many settings, P. aeruginosa resistance to b-lactam antibiotics is increasing at alarming rates. In particular, the increasing prevalence of horizontallyacquired b-lactamase genes is especially concerning.…”

Section: Introductionmentioning

confidence: 99%

“…In particular, the increasing prevalence of horizontallyacquired b-lactamase genes is especially concerning. (14) In one report, the epidemiology of b-lactamases was closely related to the distribution of certain high-risk international clones. (15) In this study, we used whole-genome sequencing (WGS) to identify the predominant sequence types (STs) and b-lactamase genes in multi-drug resistant (MDR) P. aeruginosa clinical isolates from Qatar.…”

Section: Introductionmentioning

confidence: 99%

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β-lactamase-mediated Resistance in MDR-Pseudomonas Aeruginosa from Qatar

Ahmed

Khan

Sultan

et al. 2020

Preprint

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Background: Anti-pseudomonal b-lactam antibiotics are of paramount importance in the management of Pseudomonas aeruginosa infections. The distribution of b-lactam resistance genes in P. aeruginosa is often closely related to the distribution of certain high-risk international clones. In the present study whole-genome sequencing (WGS) was used to identify the predominant sequence types (STs) and b-lactamase genes in clinical isolates of multidrug-resistant (MDR)-P. aeruginosa from QatarMethods: Microbiological identification and susceptibility tests were performed by automated BD PhoenixTM system and manual Liofilchem MIC Test Strips. Seventy-five MDR-P. aeruginosa isolates were subsequently processed for WGS. Results: Among 75 MDR-P. aeruginosa isolates; the largest proportions of susceptibility were to ceftazidime-avibactam (n=36, 48%), followed by ceftolozane-tazobactam (30, 40%), ceftazidime (n=21, 28%) and aztreonam (n=16, 21.33%). Almost all isolates possessed Class C and Class D b-lactamases (n=72, 96% each), while metallo-β-lactamases were detected in 20 (26.67%) isolates. Eight (40%) metallo-β-lactamases producers were susceptible to aztreonam and did not produce any concomitant extended-spectrum b-lactamases. The most frequent sequence types identified were ST235 (n=16, 21.33%), ST357 (n=8, 10.67%), ST389 and ST1284 (6, 8% each). Nearly all ST235 (15/16; 93.75%) were resistant to all tested b-lactams.Conclusion: MDR-P. aeruginosa isolates from Qatar are highly resistant to antipseudomonal b-lactams. Global high-risk STs are predominant in Qatar and their associated multi-resistant phenotypes are a cause for considerable concern. The molecular epidemiology trends of P. aeruginosa should be surveillance at national levels to track their trends and institute the appropriate control strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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β-lactamase-mediated Resistance in MDR-Pseudomonas Aeruginosa from Qatar

Ahmed

Khan

Sultan

et al. 2020

Preprint

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“…Increasing rates of antibiotic resistance among Gram-negative pathogens such as Pseudomonas aeruginosa represent a serious risk to worldwide health (1,2). The prevalence of multi-drug-resistant (MDR) strains capable to inactivating a broad array of antibiotics has stimulated the development of alternative therapies (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Structural and functional analysis of pyocin S8 fromPseudomonas aeruginosa: requirement of a glutamate in the H-N-H motif for the DNase activity

Turano

Fomes

Domingos

et al. 2020

Preprint

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Multi-drug resistance (MDR) is a serious threat to global public health, making the development of new antimicrobials an urgent necessity. Pyocins are protein antibiotics produced by Pseudomonas aeruginosa strains to kill closely related cells during intraspecific competition. Here, we report an in depth biochemical, microbicidal and structural characterization of a new S-type pyocin, named S8. Initially, we described the domain organization and secondary structure of S8. Subsequently, we observed that a recombinant S8 composed of the killing subunit in complex with the immunity (Im) protein killed the strain PAO1. Furthermore, mutation of a highly conserved glutamic acid to alanine (Glu100Ala) completely inhibited this antimicrobial activity. Probably the integrity of the H-N-H motif is essential in the killing activity of S8, as Glu100 is a highly conserved component of this structure. Next, we observed that S8 is a metal-dependent endonuclease, as EDTA treatment abolished its ability to cleave supercoiled pUC18 plasmid. Supplementation of apo S8 with Ni 2+ strongly induced this DNase activity, whereas Mn 2+ and Mg 2+ exhibited moderate effects and Zn 2+ was inhibitory. Additionally, S8 bound Zn 2+ with a higher affinity than Ni 2+ and the Glu100Ala mutation decreased the affinity of S8 for these metals as shown by isothermal titration calorimetry (ITC). Finally, we describe the crystal structure of the Glu100Ala pyocin-S8DNase-Im complex at 1.38 Å, which gave us new insights into the endonuclease activity of S8. Our results reinforce the possible use of S8 as an alternative antibiotic for MDR Pseudomonas aeruginosa strains, while leaving commensal human microbiota intact.

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“…It is also known that the P. aeruginosa infections can be critical, with high mortality in cases of ventilator-associated pneumonia [2] or bacteremia [7,8]. effective for treating P. aeruginosa infections, has become a serious problem [9,10]. This resistance in P. aeruginosa is attributed to a variety of mechanisms, including the production of antibiotic-inactivating enzymes such as cephalosporinases, the constitutive expression of various e ux pumps, and the low permeability of the outer membrane [11].…”

Section: Introductionmentioning

confidence: 99%

Clinical Significance of Rapid and Sensitive Quantification of Pseudomonas aeruginosa by Quantitative Reverse Transcription PCR Targeting of rRNA Molecules

Niikura

Atobe

Takahashi

et al. 2020

Preprint

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Background: For Pseudomonas aeruginosa, nosocomial infection control and appropriate antimicrobial treatment have become important issues. Diagnosis is critical in managing P. aeruginosa infection, but conventional methods are not highly accurate or rapid. A novel P. aeruginosa quantification system based on 23S rRNA-targeted quantitative reverse transcription PCR (qRT-PCR) is a candidate diagnostic tool for managing P. aeruginosa infection. Here, we assessed the performance and potential impact of qRT-PCR on antibiotic therapy administered to ICU patients.Methods: We first evaluated specificity and detection sensitivity of the 23S rRNA-targeted qRT-PCR system in vitro and determined whether P. aeruginosa viable counts detected by this system reflect the inflammatory response of infected cells. Next, we utilized this system on fecal samples collected from 65 septic ICU patients and 44 healthy volunteers to identify the ICU infection status. Additionally, we monitored drug-resistant P. aeruginosa in 4 ICU patients. The trend was compared with trends in fecal microbiota composition, antibiotic use, and mechanical ventilator use.Results: The 23S rRNA-targeted qRT-PCR system quantified P. aeruginosa directly from clinical samples with high sensitivity (blood, 1 cell/mL; stool, 100 cells/g) without cross-reaction (within 6 h). Additionally, P. aeruginosa numbers detected under antibacterial treatment correlated well with the inflammatory response compared to other detection methods such as culturing and qPCR. Using this system, we confirmed that the P. aeruginosa detection ratio in ICU patients was significantly higher than that in healthy volunteers (49.2% vs. 13.6%, P<0.05). While some ICU patients had high P. aeruginosa numbers in feces (108 cells/g of feces), some patients had very low P. aeruginosa numbers (102 cells/g of feces) as observed in healthy volunteers. P. aeruginosa counts in feces of ICU patients monitored by this system correlated negatively with the proportion of total obligate anaerobes and positively with facultative anaerobes and aerobes. Additionally, trends in P. aeruginosa counts accurately reflected various treatment backgrounds of ICU patients.Conclusion: Our results suggest that this new 23S rRNA-targeted qRT-PCR system is beneficial for early diagnosis and evaluation of appropriate antibacterial treatment and may be a useful tool in combating P. aeruginosa infection.

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Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections

Cited by 641 publications

References 360 publications

β-lactamase-mediated Resistance in MDR-Pseudomonas Aeruginosa from Qatar

β-lactamase-mediated Resistance in MDR-Pseudomonas Aeruginosa from Qatar

Structural and functional analysis of pyocin S8 fromPseudomonas aeruginosa: requirement of a glutamate in the H-N-H motif for the DNase activity

Clinical Significance of Rapid and Sensitive Quantification of Pseudomonas aeruginosa by Quantitative Reverse Transcription PCR Targeting of rRNA Molecules

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