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Multidrug Resistance in Pseudomonas aeruginosa: Resistance Mechanisms, Epidemiology, and Impact of Resistance on Virulence, Clinical Outcomes, and Treatment

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A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 13941

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Dr. Silvia Gómez-Zorrilla

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1. Infectious Diseases Department, Hospital del Mar, Passeig Maritim 25-29, 08003 Barcelona, Spain
2. Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Dr. Aiguader 88, 08003 Barcelona, Spain
Interests: antimicrobial stewardship; antibiotics; Pseudomonas aeruginosa; multidrug-resistant bacteria; host-pathogen interaction; rational use of antibiotics
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Dr. Cristina Suarez

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Consultant in Infectious Diseases and Clinical Microbiology, Barts Health NHS Trust, London, UK
Interests: Pseudomonas aeruginosa; antimicrobial resistance; use of antimicrobials; infection

Special Issue Information

Dear Colleagues,

Pseudomonas aeruginosa is one of the most common nosocomial pathogens, and continuously evolving resistance to multiple antimicrobial agents has become a significant health problem. In recent years, there has been a worryingly increase in multidrug-resistant (MDR) and extensively drug-resistant (XDR) P. aeruginosa strains that have disseminated globally. Molecular epidemiology studies have identified MDR/XDR clones with a worldwide prevalence called high-risk clones. The enveloping of MDR has a direct impact on the difficulty in treating these infections and consequently carries a heavy economic burden. MDR has been reported as an important determinant of clinical outcomes. However, the biological implications of antibiotic resistance on the pathogenicity and virulence of P. aeruginosa is complex. In fact, a possible biological cost-associated antibiotic resistance has been suggested in P. aeruginosa.

The main objective of this Special Issue is to improve our understanding of the impact of multidrug resistance in P. aeruginosa infections. For this purpose, this Special Issue considers all aspects of antibiotic resistance in P. aeruginosa. Submissions regarding resistance mechanisms, epidemiology of high-risk clones, the application of molecular diagnostic and genome sequencing, virulence determinants of P. aeruginosa, and the biological implications of resistance in virulence of P. aeruginosa are encouraged. In addition, manuscripts concerning the clinical and economic burden of multidrug resistance in P. aeruginosa infections and MDR P. aeruginosa therapeutics approaches are especially welcome.

Dr. Silvia Gómez-Zorrilla
Dr. Cristina Suarez
Guest Editors

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Keywords

Pseudomonas aeruginosa
multidrug resistant
extensively drug-resistant
virulence
biological cost
high-risk clones
molecular epidemiology
new drugs

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Published Papers (5 papers)

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Research

10 pages, 464 KiB

Open AccessArticle

Pseudomonas aeruginosa Bloodstream Infection, Resistance, and Mortality: Do Solid Organ Transplant Recipients Do Better or Worse?

by Sabina Herrera, Laura Morata, Abiu Sempere, Miguel Verdejo, Ana Del Rio, Jose Antonio Martínez, Guillermo Cuervo, Marta Hernández-Meneses, Mariana Chumbita, Cristina Pitart, Pedro Puerta, Patricia Monzó, Carles Lopera, Francesco Aiello, Scarleth Mendoza, Carolina Garcia-Vidal, Alex Soriano and Marta Bodro

Antibiotics 2023, 12(2), 380; https://doi.org/10.3390/antibiotics12020380 - 13 Feb 2023

Cited by 2 | Viewed by 2340

Abstract

Background: The prevalence of antimicrobial resistance of Pseudomonas aeruginosa (P. aeruginosa) in solid organ transplant (SOT) recipients is higher than that of the general population. However, the literature supporting this statement is scarce. Identifying patients at risk of carbapenem resistance (CR) is of great importance, as CR strains more often receive inappropriate empiric antibiotic therapy, which is independently associated with mortality in bloodstream infections (BSIs). Methods: We prospectively recorded data from all consecutive BSIs from January 1991 to July 2019 using a routine purpose-designed surveillance database. The following variables were included: age, sex, type of transplant, use of vascular and urinary catheters, presence of neutropenia, period of diagnosis, treatment with steroids, origin of BSI, source of bacteremia, septic shock, ICU admission, mechanical ventilation, previous antibiotic treatment, treatment of bacteremia, and 30-day all-cause mortality. Results: We identified 2057 episodes of P. aeruginosa BSI. Of these, 265 (13%) episodes corresponded to SOT recipients (130 kidney transplants, 105 liver, 9 hearts, and 21 kidney–pancreas). Hematologic malignancy [OR 2.71 (95% CI 1.33–5.51), p = 0.006] and prior carbapenem therapy [OR 2.37 (95% CI 1.46–3.86), p < 0.001] were associated with a higher risk of having a CR P. aeruginosa BSI. Age [OR 1.03 (95% CI 1.02–1.04) p < 0.001], urinary catheter [OR 2.05 (95% CI 0.37–3.06), p < 0.001], shock at onset [OR 6.57 (95% CI 4.54–9.51) p < 0.001], high-risk source [OR 4.96 (95% CI 3.32–7.43) p < 0.001], and bacteremia caused by CR strains [OR 1.53 (95% CI 1.01–2.29) p = 0.036] were associated with increased mortality. Correct empirical therapy was protective [OR 0.52 (95% CI 0.35–0.75) p = 0.001]. Mortality at 30 days was higher in non-SOT patients (21% vs. 13%, p = 0.002). SOT was not associated with a higher risk of having a CR P. aeruginosa BSI or higher mortality. Conclusions: In our cohort of 2057 patients with P. aeruginosa BSIs, hematologic malignancies and previous carbapenem therapy were independently associated with a risk of presenting CR P. aeruginosa BSI. Age, urinary catheter, high-risk source, bacteremia caused by carbapenem-resistant strains, and severity of the infection were independently associated with mortality, whereas correct empirical therapy was a protective factor. An increasing trend in the resistance of P. aeruginosa was found, with >30% of the isolates being resistant to carbapenems in the last period. SOT was not associated with a higher risk of carbapenem-resistant BSIs or higher mortality. Full article

(This article belongs to the Special Issue Multidrug Resistance in Pseudomonas aeruginosa: Resistance Mechanisms, Epidemiology, and Impact of Resistance on Virulence, Clinical Outcomes, and Treatment)

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21 pages, 363 KiB

Open AccessArticle

Comparative Analysis of Complicated Urinary Tract Infections Caused by Extensively Drug-Resistant Pseudomonas aeruginosa and Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae

by Elena Sendra, Inmaculada López Montesinos, Alicia Rodriguez-Alarcón, Juan Du, Ana Siverio-Parés, Mar Arenas-Miras, Esperanza Cañas-Ruano, Nuria Prim, Xavier Durán-Jordà, Fabiola Blasco-Hernando, Enric García-Alzorriz, Francesc Cots, Olivia Ferrández and Silvia Gómez-Zorrilla

Antibiotics 2022, 11(11), 1511; https://doi.org/10.3390/antibiotics11111511 - 29 Oct 2022

Cited by 3 | Viewed by 2267

Abstract

The objective was to compare clinical characteristics, outcomes, and economic differences in complicated urinary tract infections (cUTI) caused by extensively drug-resistant Pseudomonas aeruginosa (XDR P. aeruginosa) and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-K. pneumoniae). A retrospective study was conducted at a tertiary care hospital. Patients with XDR P. aeruginosa and ESBL-K. pneumoniae cUTIs were compared. The primary outcome was clinical failure at day 7 and at the end of treatment (EOT). Secondary outcomes: 30- and 90-day mortality, microbiological eradication, and economic cost. Two-hundred and one episodes were included, of which 24.8% were bloodstream infections. Patients with XDR P. aeruginosa cUTI more frequently received inappropriate empirical therapy (p < 0.001). Nephrotoxicity due to antibiotics was only observed in the XDR P. aeruginosa group (26.7%). ESBL-K. pneumoniae cUTI was associated with worse eradication rates, higher recurrence, and higher infection-related readmission. In multivariate analysis, XDR P. aeruginosa was independently associated with clinical failure on day 7 of treatment (OR 4.34, 95% CI 1.71–11.04) but not at EOT, or with mortality. Regarding hospital resource consumption, no significant differences were observed between groups. XDR P. aeruginosa cUTI was associated with worse early clinical cures and more antibiotic side effects than ESBL-K. pneumoniae infections. However, no differences in mortality or in hospitalization costs were observed. Full article

10 pages, 292 KiB

Open AccessArticle

Risk Factors and Outcomes for Multidrug Resistant Pseudomonas aeruginosa Infection in Immunocompromised Patients

by Pilar Hernández-Jiménez, Francisco López-Medrano, Mario Fernández-Ruiz, J. Tiago Silva, Laura Corbella, Rafael San-Juan, Manuel Lizasoain, Jazmín Díaz-Regañón, Esther Viedma and José María Aguado

Antibiotics 2022, 11(11), 1459; https://doi.org/10.3390/antibiotics11111459 - 23 Oct 2022

Cited by 9 | Viewed by 2445

Abstract

Background: Pseudomonas aeruginosa (PSA) infection often occurs in immunocompromised patients, which also face an increased risk of multidrug-resistant (MDR) bacteria. A deeper knowledge of the risk factors for MDR-PSA infection in this patient population may help to choose appropriate empirical antibiotic therapy. Methods: a single-center case-control (1:2) retrospective study that included 48 patients with underlying immunosuppression developing MDR-PSA infection (cases) and 96 patients also immunocompromised that were infected with non-MDR-PSA (controls) was conducted. Both groups were matched by site of infection, clinical features and type of immunosuppression. Risk factors for MDR-PSA were assessed by logistic regression. Clinical outcomes were also compared between both groups. Results: immunosuppression was due to solid cancer in 63 (43.8%) patients, solid organ transplantation in 39 (27.1%), hematological disease in 35 (24.3%) and other causes in 7 (4.9%). Independent risk factors for MDR-PSA infection were diabetes mellitus (odds ratio [OR]: 4.74; 95% confidence interval [CI]: 1.63–13.79; p = 0.004), antibiotic therapy in the previous 3 months (OR: 5.32; 95% CI: 1.93–14.73; p = 0.001), previous MDR-PSA colonization (OR: 42.1; 95% CI: 4.49–394.8; p = 0.001) and septic shock (OR: 3.73; 95% CI: 1.36–10.21; p = 0.010). MDR-PSA cases were less likely to receive adequate empirical therapy (14 [29.2%] vs. 69 [71.9%]; p < 0.001). 30-day clinical improvement was less common in MDR-PSA cases (25 [52.1%] vs. 76 [79.2%]; p = 0.001). Conclusions: diabetes mellitus, previous MDR-PSA colonization, prior receipt of antibiotics and septic shock acted as risk factors for developing MDR-PSA infections in immunocompromised patients, who have a poorer outcome than those infected with non-MDR-PSA strains. Full article

11 pages, 1236 KiB

Open AccessArticle

Genomic Analysis of Ceftazidime/Avibactam-Resistant GES-Producing Sequence Type 235 Pseudomonas aeruginosa Isolates

by Raúl Recio, Jennifer Villa, Sara González-Bodí, Patricia Brañas, María Ángeles Orellana, Mikel Mancheño-Losa, Jaime Lora-Tamayo, Fernando Chaves and Esther Viedma

Antibiotics 2022, 11(7), 871; https://doi.org/10.3390/antibiotics11070871 - 28 Jun 2022

Cited by 8 | Viewed by 2310

Abstract

The emergence of ceftazidime/avibactam (CZA) resistance among Guiana extended-spectrum β-lactamase (GES)-producing Pseudomonas aeruginosa isolates has rarely been described. Herein, we analyze the phenotypic and genomic characterization of CZA resistance in different GES-producing P. aeruginosa isolates that emerged in our institution. A subset of nine CZA-resistant P. aeruginosa isolates was analyzed and compared with thirteen CZA-susceptible isolates by whole-genome sequencing (WGS). All CZA-resistant isolates belonged to the ST235 clone and O11 serotype. A variety of GES enzymes were detected: GES-20 (55.6%, 5/9), GES-5 (22.2%, 2/9), GES-1 (11.1%, 1/9), and GES-7 (11.1%, 1/9). WGS revealed the presence of two mutations within the bla_GES-20 gene comprising two single-nucleotide substitutions, which caused aspartic acid/serine and leucine/premature stop codon amino acid changes at positions 165 (D165S) and 237 (L237X), respectively. No major differences in the mutational resistome (AmpC, OprD porin, and MexAB-OprM efflux pump-encoding genes) were found among CZA-resistant and CZA-susceptible isolates. None of the mutations that have been previously demonstrated to cause CZA resistance were observed. Different mutations within the bla_GES-20 gene were documented in CZA-resistant GES-producing P. aeruginosa isolates belonging to the ST235 clone in our institution. Although further analysis should be performed, according to our results, other resistance mechanisms might be involved in CZA resistance. Full article

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11 pages, 305 KiB

Open AccessArticle

Pseudomonas aeruginosa Community-Onset Bloodstream Infections: Characterization, Diagnostic Predictors, and Predictive Score Development—Results from the PRO-BAC Cohort

by Pedro María Martínez Pérez-Crespo, Álvaro Rojas, Joaquín Felipe Lanz-García, Pilar Retamar-Gentil, José María Reguera-Iglesias, Olalla Lima-Rodríguez, Alfonso del Arco Jiménez, Jonathan Fernández Suárez, Alfredo Jover-Saenz, Josune Goikoetxea Aguirre, Eva León Jiménez, María Luisa Cantón-Bulnes, Pilar Ortega Lafont, Carlos Armiñanzas Castillo, Juan Sevilla Blanco, Jordi Cuquet Pedragosa, Lucía Boix-Palop, Berta Becerril Carral, Alberto Bahamonde-Carrasco, Teresa Marrodan Ciordia, Clara Natera Kindelán, Isabel María Reche Molina, Carmen Herrero Rodríguez, Inés Pérez Camacho, David Vinuesa García, Fátima Galán-Sánchez, Alejandro Smithson Amat, Esperanza Merino de Lucas, Antonio Sánchez-Porto, Marcos Guzmán García, Inmaculada López-Hernández, Jesús Rodríguez-Baño, Luis Eduardo López-Cortés and on behalf of the PROBAC REIPI/GEIH-SEIMC/SAEI Group Show full author list Hide full author list

Antibiotics 2022, 11(6), 707; https://doi.org/10.3390/antibiotics11060707 - 24 May 2022

Cited by 2 | Viewed by 2487

Abstract

Community-onset bloodstream infections (CO-BSI) caused by gram-negative bacilli are common and associated with significant mortality; those caused by Pseudomonas aeruginosa are associated with worse prognosis and higher rates of inadequateempirical antibiotic treatment. The aims of this study were to describe the characteristics of patients with CO-BSI caused by P. aeruginosa, to identify predictors, and to develop a predictive score for P. aeruginosa CO-BSI. Materials/methods: PROBAC is a prospective cohort including patients >14 years with BSI from 26 Spanish hospitals between October 2016 and May 2017. Patients with monomicrobial P. aeruginosa CO-BSI and monomicrobial Enterobacterales CO-BSI were included. Variables of interest were collected. Independent predictors of Pseudomonas aeruginosa CO-BSI were identified by logistic regression and a prediction score was developed. Results: A total of 78patients with P. aeruginosa CO-BSI and 2572 with Enterobacterales CO-BSI were included. Patients with P. aeruginosa had a median age of 70 years (IQR 60–79), 68.8% were male, median Charlson score was 5 (IQR 3–7), and 30-daymortality was 18.5%. Multivariate analysis identified the following predictors of CO-BSI-PA [adjusted OR (95% CI)]: male gender [1.89 (1.14–3.12)], haematological malignancy [2.45 (1.20–4.99)], obstructive uropathy [2.86 (1.13–3.02)], source of infection other than urinary tract, biliary tract or intra-abdominal [6.69 (4.10–10.92)] and healthcare-associated BSI [1.85 (1.13–3.02)]. Anindex predictive of CO-BSI-PA was developed; scores ≥ 3.5 showed a negative predictive value of 89% and an area under the receiver operator curve (ROC) of 0.66. Conclusions: We did not find a good predictive score of P. aeruginosa CO-BSI due to its relatively low incidence in the overall population. Our model includes variables that are easy to collect in real clinical practice and could be useful to detect patients with very low risk of P. aeruginosa CO-BSI. Full article

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Multidrug Resistance in Pseudomonas aeruginosa: Resistance Mechanisms, Epidemiology, and Impact of Resistance on Virulence, Clinical Outcomes, and Treatment

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