May 19, 2026

Epidemiology, Treatment, and Outcomes of Multi-drug resistant Pseudomonas aeruginosa Pneumonias and Bloodstream Infections in Solid Organ Transplant Recipients: A Systematic Review

DOI
https://dx.doi.org/10.17504/protocols.io.n2bvjk5xbgk5/v1
  • Nicholas Geremia1,2,
  • Alberto Enrico Maraolo3,
  • Mario Fernandez-Ruiz4,
  • Ligia Camera Pierotti5,
  • Gisela Serra Rodrigues Costa6,
  • Isabel Machuca7,
  • Juan José Castón7,
  • Elisa Ruiz-Arabi8,
  • Estefanía Mira-Padilla9,
  • Giusy Tiseo10,
  • Matteo Rinaldi11,
  • Cecilia Bonazzetti11,
  • Maddalena Giannella11,
  • Alessandra Mularoni12,
  • Marco Falcone10,
  • Julian Torre-Cisneros7,
  • Elena Pérez-Nadales7
  • 1Unit of Infectious Diseases, Ospedale “dell’Angelo”, Venice, Italy;
  • 2Ospedale SS. Giovanni e Paolo, Venice, Italy;
  • 3Unit of Infectious Diseases, University of Naples Federico II, Naples, Italy;
  • 4Unit of Infectious Diseases, "12 de Octubre" University Hospital, Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain;
  • 5University of São Paulo School of Medicine Hospital das Clínicas, São Paulo, Brazil;
  • 6Department of Infectious Diseases, University of São Paulo School of Medicine Hospital das Clínicas, São Paulo, Brazil;
  • 7IMIBIC/UCO/HURS, Spain;
  • 8Infectious Diseases Service and Transplantation Center, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland;
  • 9Department of Pulmonology, Hospital Universitario Reina Sofia, Córdoba, Spain;
  • 10Infectious Diseases Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Pisa, Italy;
  • 11Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy;
  • 12Unit of Infectious Diseases and Infection Control, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT-IRCCS), Palermo, Italy.
  • Nicholas geremia
Nicholas Geremia
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DOI: https://dx.doi.org/10.17504/protocols.io.n2bvjk5xbgk5/v1
Protocol Citation: Nicholas Geremia, Alberto Enrico Maraolo, Mario Fernandez-Ruiz, Ligia Camera Pierotti, Gisela Serra Rodrigues Costa, Isabel Machuca, Juan José Castón, Elisa Ruiz-Arabi, Estefanía Mira-Padilla, Giusy Tiseo, Matteo Rinaldi, Cecilia Bonazzetti, Maddalena Giannella, Alessandra Mularoni, Marco Falcone, Julian Torre-Cisneros, Elena Pérez-Nadales 2026. Epidemiology, Treatment, and Outcomes of Multi-drug resistant Pseudomonas aeruginosa Pneumonias and Bloodstream Infections in Solid Organ Transplant Recipients: A Systematic Review. protocols.io https://dx.doi.org/10.17504/protocols.io.n2bvjk5xbgk5/v1
License: This is an open access  protocol  distributed under the terms of the  Creative Commons Attribution License,  which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Protocol status: Working
We use this protocol and it's working
Created: May 19, 2026
Last Modified: May 19, 2026
Protocol  Integer ID: 317463
Keywords: Pseudomonas aeruginosa, Pseudomonas infections, Pseudomonas pneumonia, Pseudomonas bloodstream infections, solid organ transplantation, solid organ transplant recipients, SOT, solid organ transplant, antimicrobial resistance, multidrug-resistant bacteria, difficult-to-treat resistance, carbapenem resistance, transplant-related infections, systematic review pseudomonas aeruginosa infection, bloodstream infections in solid organ transplant recipient, pneumonia, data on pneumonia, mortality among solid organ transplant, aerosolized antibiotic therapy, antibiotic therapy, other solid organ transplant recipient, antimicrobial resistance, solid organ transplant recipient, increasing antimicrobial resistance, novel antibiotic, solid organ transplant, use of novel antibiotic, bloodstream infection, comparisons between mdr, transplant type, intensive care unit admission
Abstract
Pseudomonas aeruginosa infections are a major cause of morbidity and mortality among solid organ transplant (SOT) recipients, particularly in the context of increasing antimicrobial resistance. Pneumonias and bloodstream infections (BSIs) caused by multidrug-resistant (MDR) or difficult-to-treat resistant (DTR) strains represent significant therapeutic and prognostic challenges in this vulnerable population.

The review will include randomized controlled trials and observational studies published up to April 30, 2026, identified through systematic searches of PubMed, Embase, and Scopus. Studies reporting data on pneumonias and BSIs caused by P. aeruginosa in the kidney, liver, lung, heart, or other solid organ transplant recipients will be considered eligible.

The primary outcome will be 30-day all-cause mortality, while secondary outcomes will include clinical cure, recurrence rates, graft failure, and intensive care unit admission.
Special attention will be given to comparisons between MDR and non-MDR isolates, as well as to the evaluation of different treatment strategies, including monotherapy versus combination therapy, the use of novel antibiotics, and adjunctive aerosolized antibiotic therapy. Data will be synthesized through narrative analysis and, where appropriate, random-effects meta-analysis. Subgroup analyses are planned according to resistance profile, transplant type, clinical severity, and geographical region.

This review aims to provide an updated synthesis of the available evidence on the clinical burden of resistant P. aeruginosa infections in SOT recipients and to identify treatment approaches and prognostic factors associated with improved clinical outcomes.
Review questions
  • Description of the incidence, epidemiology and impact of multidrug-resistant  (MDR) P. aeruginosa pneumonias and bloodstream infections (BSIs) in solid organ transplant (SOT) recipients.
  • Description of treatment strategies used for MDR P. aeruginosa pneumonias and BSI in SOT recipients and their impact on patient outcomes (all-cause 30-day mortality).
  • Description of clinical outcomes (all-cause 30-day mortality as the main one, but also other ones will be considered, such as graft failure, ICU admissions) of P. aeruginosa pneumonias and BSI in SOT recipients, with a focus on differences according to the resistance profile of the isolates.
Definitions
MDR: P. aeruginosa MDR is defined as non-susceptibility to at least one agent in three or more antimicrobial categories.
DTR: P. aeruginosa nonsusceptibility to all standard first-line agents (piperacillin-tazobactam, ceftazidime, cefepime, aztreonam, meropenem, imipenem-cilastatin, ciprofloxacin, and levofloxacin)
Carbapenem-resistant: P. aeruginosa resistant to all carbapenems (imipenem and meropenem)
Search
We will search PubMed, Embase, and Scopus using appropriate word combinations. Studies published from inception up to 30 April 2026 will be included. In addition, a hand search of the reference lists of all relevant articles will be performed. Neither geographical nor language restrictions will be applied.
URL to search strategy
("Pseudomonas aeruginosa"[Text Word] OR "Pseudomonas"[Text Word]) AND ("solid organ transplant"[Text Word] OR "transplantation"[Text Word] OR "transplant recipients"[Text Word] OR "SOT"[Text Word] OR "kidney transplant"[Text Word] OR "liver transplant"[Text Word] OR "lung transplant"[Text Word] OR "heart transplant"[Text Word] OR "pancreas transplant"[Text Word] OR "intestinal transplant"[Text Word])
Condition or domain being studied
Pneumonias and BSIs caused by Pseudomonas aeruginosa in SOT recipients, with a focus on their epidemiology, resistance patterns, treatment strategies, and their association with all-cause 30-day mortality.
Participants/population
Human patients with clinically significant pneumonias and BSIs caused by P. aeruginosa, with a specific focus on studies that include SOT recipients. Studies must include either exclusively SOT recipients or report stratified data that allow extraction of outcomes specific to this population.
Intervention(s), exposure(s)
The primary exposures of interest are:
  • The presence of P. aeruginosa pneumonias and BSIs in SOT recipients.
  • The antimicrobial treatment strategies used to manage these infections.
We will also consider the resistance profile of the isolates (e.g., multidrug-resistant, carbapenem-resistant, or difficult-to-treat resistance phenotypes) as exposures of interest in relation to clinical outcomes.
Comparator(s)/control
Comparators will vary depending on the outcome assessed. These may include:
  • Patients infected with MDR or susceptible strains of P. aeruginosa.
  • Recipients of alternative treatment strategies (e.g., beta-lactams vs. novel agents, monotherapy vs. combination therapy, treatment with aerosolized antibiotic vs no addition of aerosolized antibiotic).
Comparators will also be stratified by infection type, transplant type, and clinical severity.
Types of study to be included
In order to assess the epidemiology, risk factors, and outcomes of Pseudomonas aeruginosa infections in SOT recipients, we will include randomized controlled trials (RCTs) and observational studies (prospective or retrospective cohorts) enrolling at least 100 SOT recipients. Case series, case reports, editorials, and reviews will be excluded.
We will include studies, regardless of design, provided they report data on consecutive episodes of P. aeruginosa pneumonias and BSIs in the SOT recipient population. In mixed-population studies, data must be stratified to allow the extraction of outcomes specific to the SOT group. In case of comparative studies, the different groups will be pooled. If multiple studies report data from overlapping cohorts or centers, we will retain the publication with the largest sample size or most complete data to avoid duplication. There will be no exclusion criteria based on publication year. Only studies published in English will be considered.
Outcomes
Main Outcome
The primary outcome will be all-cause 30-day mortality in SOT recipients with P. aeruginosa pneumonias and BSIs. Additionally, we will assess whether mortality varies by antimicrobial resistance profile, particularly between MDR and non-MDR phenotypes.
Additional outcomes
Additional outcomes will include:
  1. Describe the incidence and epidemiological trends of MDR P. aeruginosa pneumonias and BSIs in SOT recipients, including rates of carbapenem resistance.
  2. Description and comparison of treatment strategies (e.g., empirical vs. targeted therapy, use of novel antibiotics vs old antibiotics, treatment with aerosolized antibiotic vs no addition of aerosolized antibiotic) used in this population.
  3. Description of the clinical cure rate, stratified by MDR vs non-MDR P. aeruginosa phenotype and SOT defined as resolution of infection-related signs and symptoms at the end of therapy.
  4. Description of the recurrence rates of infection, stratified by MDR vs non-MDR phenotype and SOT defined as microbiologically or clinically documented recurrence within the predefined follow-up period.
Data extraction
Ten reviewers in an independent fashion will screen titles and/or abstracts according to inclusion and exclusion criteria (N.G., E.P.N., M.F.R., G.S.R.C., I.M., J.J.C., E.R.A., E.M.P., G.T, M.R., C.B.). Full papers will be obtained, read and included if relevant, following the same scheme. Any discrepancy will be solved by consensus among the entire study group.
Data from the retrieved papers will be extracted and entered into three separate Excel spreadsheets:
  • Susceptibility data
  • Resistance profiles
  • Clinical outcomes and treatment efficacy.
The following variables will be extracted:
  • First author
  • Year of publication
  • Country of study
  • Study design and study period
  • Clinical setting (e.g., ICU, general ward)
  • Bacterial subgroups (based on resistance phenotype, e.g., MDR vs. non-MDR)
  • Resistance mechanisms of Pseudomonas aeruginosa
  • Antimicrobial treatment(s) used: Monotherapy vs Combination therapy, New antibiotics vs Old antibiotics, Aerosol antibiotic therapy vs Non-aerosol antibiotic therapy
  • Clinical outcomes: all-cause 30-day mortality
  • Secondary outcomes: clinical success and recurrence of infections

Data extraction will be performed by ten researchers independently (N.G., E.P.N., M.F.R., G.S.R.C., I.M., J.J.C., E.R.A., E.M.P., G.T., M.R., C.B.) and discrepancies will be resolved by discussion or consultation with a fifth reviewer, if necessary.
Risk of bias (quality) assessment
Two reviewers (N.G., M.R.) will independently assess study quality of selected papers according to an adapted version of the the Joanna Briggs Institute tool  , and the Cochrane ROB-2 tool for randomized trials. In the event of disagreements, differences will be resolved through a consensus-based approach. The results will be presented in graphics according to each study.
Strategy for data synthesis
A narrative synthesis will be conducted to summarize the findings of the included studies, focusing on:
  • The incidence and trends of P. aeruginosa pneumonias and BSIs, including MDR and carbapenem-resistant strains.
  • Antimicrobial resistance patterns, including mechanisms of resistance when available.
  • Treatment strategies used and their impact on clinical outcomes.
  • Clinical outcomes: all-cause 30-day mortality as main one.
If appropriate and if data are sufficiently homogeneous, a meta-analysis will be performed. For incidence and resistance profiles, pooled proportions with 95% confidence intervals (CIs) and prediction intervals will be calculated.
For clinical outcomes (e.g., mortality, treatment success/failure), quantitative data will be pooled using random-effects meta-analysis (to estimate the between-study variance we will use the Restricted Maximum Likelihood [REML] estimator), and effect estimates will be expressed as odds ratios (ORs) or adjusted odds ratios (aORs) with 95% Cis if a comparison is feasible between different groups; otherwise, a pooled mortality from single-arm studies (e.g. pooled proportion) would be computed. A p-value of <0.05 will be considered statistically significant.
In studies comparing different treatment strategies, we will, where feasible, pool outcome data to assess their impact. If a meta-analysis is not feasible due to data heterogeneity or a lack of comparable metrics, a narrative synthesis will be employed instead.
All statistical analyses will be performed using R, employing appropriate meta-analytic packages such as meta and metafor.
Analysis of subgroups or subsets
Where data permit, we will conduct subgroup analyses to explore heterogeneity and assess the influence of key variables. Planned subgroup analyses include:
  • Resistance profile of Pseudomonas aeruginosa isolates (e.g., MDR vs. non-MDR).* If sufficient data are available in the literature, a subgroup analysis comparing DTR vs. non-DTR or Carbapenem-resistant vs. non-Carbapenem-resistant isolates will also be performed.
  • Treatment strategies (e.g., monotherapy vs. combination therapy, new antibiotics vs old antibiotics, aerosol antibiotic vs no aerosol antibiotic therapy).
  • Geographical region or country, to assess potential differences in resistance patterns and clinical outcomes.
  • Type of SOT, such as kidney, liver, lung, heart, or combined transplants, to determine whether infection patterns and outcomes vary by transplant type.
  • Clinical severity (i.e, septic shock vs no septic shock)
  • Study design (randomized controlled trials vs. observational studies), particularly when evaluating treatment efficacy.
Suppose appropriate and sufficient data are available. In that case, we will also perform meta-regression analyses to evaluate the impact of continuous or categorical covariates (e.g., year of publication, study size, proportion of immunosuppressed patients) on outcomes such as resistance prevalence or mortality.
These analyses aim to identify potential sources of heterogeneity and better understand contextual factors influencing the burden and management of P. aeruginosa infections in solid organ transplant recipients.
Type and method of review
Systematic review and meta-analysis
Health area of the review: Infections and Infestations.
Language
English
Country
Italy, Spain, Brazil, Switzerland
Keywords
Pseudomonas aeruginosa; Pseudomonas infections; Pseudomonas pneumonia, Pseudomonas bloodstream infections, solid organ transplantation; solid organ transplant recipients; SOT; solid organ transplant; antimicrobial resistance; multidrug-resistant bacteria; difficult-to-treat resistance; carbapenem resistance; transplant-related infections.
Funding sources/sponsors
None
Conflicts of interest
None
Acknowledgements
Funding sources/sponsors: None
Conflicts of interest: None
Collaborators: None

**Data Extraction and Analysis:**
- Ten reviewers will independently screen titles and/or abstracts according to inclusion and exclusion criteria.
- Data will be extracted and entered into three separate Excel spreadsheets: Susceptibility data, Resistance profiles, Clinical outcomes and treatment efficacy.
- Variables to be extracted include: First author, Year of publication, Country of study, Study design and study period, Clinical setting, Bacterial subgroups, Resistance mechanisms, Antimicrobial treatment(s) used, Clinical outcomes.
- Data extraction will be performed by ten researchers independently and discrepancies resolved by discussion or consultation with a fifth reviewer if necessary.

**Risk of Bias (Quality) Assessment:**
- Two reviewers will independently assess study quality using the Joanna Briggs Institute tool and the Cochrane ROB-2 tool for randomized trials.
- Results will be presented in graphics according to each study.

**Strategy for Data Synthesis:**
- A narrative synthesis will be conducted focusing on incidence and trends, antimicrobial resistance patterns, treatment strategies, and clinical outcomes.
- If appropriate, a meta-analysis will be performed using random-effects meta-analysis with the Restricted Maximum Likelihood (REML) estimator.
- Effect estimates will be expressed as odds ratios (ORs) or adjusted odds ratios (aORs) with 95% CIs.

**Analysis of Subgroups or Subsets:**
- Resistance profile of Pseudomonas aeruginosa isolates (e.g., MDR vs. non-MDR).
- Treatment strategies (e.g., monotherapy vs. combination therapy).
- Geographical region or country.
- Type of SOT (e.g., kidney, liver, lung, heart, or combined transplants).
- Clinical severity (e.g., septic shock vs no septic shock).
- Study design (randomized controlled trials vs. observational studies).

**Type and Method of Review:**
- Systematic review and meta-analysis.
- Health area of the review: Infections and Infestations.

**Language: English

**Country: Italy, Spain, Brazil, Switzerland

**Dissemination Plans: Yes

**Current Review Status: Ongoing