Association of antibiotic duration and all-cause mortality in a prospective study of patients with ventilator-associated pneumonia in a tertiary-level critical care unit in Southern India.

OBJECTIVES: To estimate all-cause mortality in ventilator-associated pneumonia (VAP) and determine whether antibiotic duration beyond 8 days is associated with reduction in all-cause mortality in patients admitted with VAP in the intensive care unit. DESIGN: A prospective cohort study of patients diagnosed with VAP based on the National Healthcare Safety Network definition and clinical criteria. SETTING: Single tertiary care hospital in Southern India. PARTICIPANTS: 100 consecutive adult patients diagnosed with VAP were followed up for 28 days postdiagnosis or until discharge. OUTCOME MEASURES: The incidence of mortality at 28 days postdiagnosis was measured. Tests for association and predictors of mortality were determined using χ2 test and multivariate Cox regression analysis. Secondary outcomes included baseline clinical parameters such as age, underlying comorbidities as well as measuring total length of stay, number of ventilator-free days and antibiotic-free days. RESULTS: The overall case fatality rate due to VAP was 46%. There was no statistically significant difference in mortality rates between those receiving shorter antibiotic duration (5-8 days) and those on longer therapy. Among those who survived until day 9, the observed risk difference was 15.1% between both groups, with an HR of 1.057 (95% CI 0.26 to 4.28). In 70.4% of isolates, non-fermenting Gram-negative bacilli were identified, of which the most common pathogen isolated was Acinetobacter baumannii (62%). CONCLUSION: In this hospital-based cohort study, there is insufficient evidence to suggest that prolonging antibiotic duration beyond 8 days in patients with VAP improves survival.

Desirability of Outcome Ranking and Response Adjusted for Antibiotic Risk (DOOR/RADAR) Post Hoc Analysis Supports Equipoise for Antibiotic Initiation Strategies in Intensive Care Unit-Acquired Pneumonia.

Background: Pneumonia is the most common intensive care unit (ICU)-acquired infection and source of potential sepsis in ICU populations but can be difficult to diagnose in real-time. Despite limited data, rapid initiation of antibiotic agents is endorsed by society guidelines. We hypothesized that a post hoc analysis of a recent randomized pilot study would show no difference between two antibiotic initiation strategies. Patients and Methods: The recent Trial of Antibiotic Restraint in Presumed Pneumonia (TARPP) was a pragmatic cluster-randomized pilot of antibiotic initiation strategies for patients with suspected ICU-acquired pneumonia. Participating ICUs were cluster-randomized to either an immediate initiation protocol or a specimen-initiated protocol where a gram stain was required for initiation of antibiotics. Patients in the study were divided into one of seven mutually exclusive outcome rankings (desirability of outcome ranking; DOOR): (1) Survival, No Pneumonia, No adverse events; (2) Survival, Pneumonia, No adverse events; (3) Survival, No Pneumonia, ventilator-free-alive days ≤14; (4) Survival, Pneumonia, ventilator-free-alive days ≤14; (5) Survival, No Pneumonia, Subsequent episode of suspected pneumonia; (6) Survival, Pneumonia, Subsequent episode of suspected pneumonia; and (7) Death. These rankings were further refined using the duration of antibiotics prescribed for pneumonia (response adjusted for antibiotic risk; RADAR). Results: There were 186 patients enrolled in the study. After applying the DOOR analysis, a randomly selected patient was equally likely to have a better outcome in specimen-initiated arm as in the immediate initiation arm (DOOR probability: 50.8%; 95% confidence interval [CI], 42.7%-58.9%). Outcome probabilities were similar after applying the RADAR analysis (52.5%; 95% CI, 44.2%-60.6%; p = 0.31). Conclusions: We found that patients for whom antibiotic agents were withheld until there was objective evidence (specimen-initiated group) had similar outcome rankings to patients for whom antibiotic agents were started immediately. This supports the findings of the TARPP pilot trial and provides further evidence for equipoise between these two treatment strategies.

Antibiotic definitive treatment in ventilator associated pneumonia caused by AmpC-producing Enterobacterales in critically ill patients: a prospective multicenter observational study.

BACKGROUND: Ventilator associated pneumonia (VAP) due to wild-type AmpC-producing Enterobacterales (wtAE) is frequent in intensive care unit (ICU) patients. Despite a low level of evidence, definitive antimicrobial therapy (AMT) with third generation cephalosporins (3GCs) or piperacillin is discouraged. METHODS: Observational prospective study including consecutive wtAE VAP patients in 20 French ICUs. The primary objective was to assess the association of the choice of definitive AMT, i.e. piperacillin ± tazobactam (PTZ), 3GCs or other molecule (4GCs, carbapenems, quinolones, cotrimoxazole; control group), with treatment success at day-7. Recurrence of infection was collected as a secondary outcome, and analyzed accounting for the competing risk of death. RESULTS: From February 2021 to June 2022, 274 patients were included. Enterobacter cloacae was the most prevalent specie (31%). Seventy-eight patients (28%) had PTZ as definitive AMT while 44 (16%) had 3GCs and 152 (56%) were classified in the control group. Day-7 success rate was similar between the 3 groups (74% vs. 73% vs. 68% respectively, p = 0.814). Recurrence probability at day-28 was 31% (95% CI 21-42), 40% (95% CI 26-55) and 21% (95% CI 15-28) for PTZ, 3GCs and control groups (p = 0.020). In multivariable analysis, choice of definitive AMT was not associated with clinical success, but definitive AMT with 3GCs was associated with recurrence at day-28 [csHR(95%CI) 10.9 (1.92-61.91)]. CONCLUSION: Choice of definitive antimicrobial therapy was not associated with treatment success at day 7. However, recurrence of pneumonia at day-28 was higher in patients treated with third generation cephalosporins with no differences in mortality or mechanical ventilation duration.

Understanding the nebulisation of antibiotics: the key role of lung microdialysis studies.

BACKGROUND: Nebulisation of antibiotics is a promising treatment for ventilator-associated pneumonia (VAP) caused by multidrug-resistant organisms. Ensuring effective antibiotic concentrations at the site of infection in the interstitial space fluid is crucial for clinical outcomes. Current assessment methods, such as epithelial lining fluid and tissue homogenates, have limitations in providing longitudinal pharmacokinetic data. MAIN BODY: Lung microdialysis, an invasive research technique predominantly used in animals, involves inserting probes into lung parenchyma to measure antibiotic concentrations in interstitial space fluid. Lung microdialysis offers unique advantages, such as continuous sampling, regional assessment of antibiotic lung concentrations and avoidance of bronchial contamination. However, it also has inherent limitations including the cost of probes and assay development, the need for probe calibration and limited applicability to certain antibiotics. As a research tool in VAP, lung microdialysis necessitates specialist techniques and resource-intensive experimental designs involving large animals undergoing prolonged mechanical ventilation. However, its potential impact on advancing our understanding of nebulised antibiotics for VAP is substantial. The technique may enable the investigation of various factors influencing antibiotic lung pharmacokinetics, including drug types, delivery devices, ventilator settings, interfaces and disease conditions. Combining in vivo pharmacokinetics with in vitro pharmacodynamic simulations can become feasible, providing insights to inform nebulised antibiotic dose optimisation regimens. Specifically, it may aid in understanding and optimising the nebulisation of polymyxins, effective against multidrug-resistant Gram-negative bacteria. Furthermore, lung microdialysis holds promise in exploring novel nebulisation therapies, including repurposed antibiotic formulations, bacteriophages and immunomodulators. The technique's potential to monitor dynamic biochemical changes in pneumonia, such as cytokines, metabolites and inflammation/infection markers, opens avenues for developing theranostic tools tailored to critically ill patients with VAP. CONCLUSION: In summary, lung microdialysis can be a potential transformative tool, offering real-time insights into nebulised antibiotic pharmacokinetics. Its potential to inform optimal dosing regimen development based on precise target site concentrations and contribute to development of theranostic tools positions it as key player in advancing treatment strategies for VAP caused by multidrug-resistant organisms. The establishment of international research networks, exemplified by LUMINA (lung microdialysis applied to nebulised antibiotics), signifies a proactive step towards addressing complexities and promoting multicentre experimental studies in the future.

Interleukin-36 receptor antagonist stimulation in vitro inhibits peripheral and lung-resident T cell response isolated from patients with ventilator-associated pneumonia.

Interleukin-36 (IL-36) cytokine family members play an immunomodulatory function to immune cells through IL-36 receptor signaling pathway. However, the regulatory role of IL-36 exerted on T cells is not completely elucidated in patients with ventilator-associated pneumonia (VAP). For this purpose, this study enrolled 51 VAP patients and 27 controls. IL-36 levels were measured by ELISA. The mRNA levels of IL-36 receptor subunits were determined by real-time PCR. CD4+ and CD8+ T cells were enriched, and stimulated with recombinant IL-36 receptor antagonist (IL-36RA). The influence of IL-36RA on transcription factors and cytokine secretions by CD4+ T cells was investigated. The modulatory function of IL-36RA on CD8+ T cells was assessed by measuring target cell death and cytokine secretions. There were no significant differences in serum IL-36 levels between VAP patients and controls. Only IL-36RA, but not IL-36α, IL-36ß, or IL-36γ, in bronchoalveolar lavage fluid was elevated in infection site of VAP patients. IL-36 receptor subunits in CD4+ and CD8+ T cells were comparable between VAP patients and controls. 10 ng/mL of IL-36RA stimulation dampened peripheral effector CD4+ T cell response isolated from both VAP patients and controls. Target cell death mediated by CD8+ T cells isolated from BAFL of VAP patients was suppressed by 100 ng/mL of IL-36RA stimulation in vitro. The down-regulations of perforin, granzyme B, interferon-γ, tumor necrosis factor-α, and Fas ligand following IL-36RA stimulation in vitro were responsible for reduced CD8+ T cell-mediated cytotoxicity. IL-36RA revealed an immunosuppressive property for T cell response in vitro, and may be involved in the protective mechanism in VAP patients.

ICU-acquired infections in immunocompromised patients.

Immunocompromised patients account for an increasing proportion of the typical intensive care unit (ICU) case-mix. Because of the increased availability of new drugs for cancer and auto-immune diseases, and improvement in the care of the most severely immunocompromised ICU patients (including those with hematologic malignancies), critically ill immunocompromised patients form a highly heterogeneous patient population. Furthermore, a large number of ICU patients with no apparent immunosuppression also harbor underlying conditions altering their immune response, or develop ICU-acquired immune deficiencies as a result of sepsis, trauma or major surgery. While infections are associated with significant morbidity and mortality in immunocompromised critically ill patients, little specific data are available on the incidence, microbiology, management and outcomes of ICU-acquired infections in this population. As a result, immunocompromised patients are usually excluded from trials and guidelines on the management of ICU-acquired infections. The most common ICU-acquired infections in immunocompromised patients are ventilator-associated lower respiratory tract infections (which include ventilator-associated pneumonia and tracheobronchitis) and bloodstream infections. Recently, several large observational studies have shed light on some of the epidemiological specificities of these infections-as well as on the dynamics of colonization and infection with multidrug-resistant bacteria-in these patients, and these will be discussed in this review. Immunocompromised patients are also at higher risk than non-immunocompromised hosts of fungal and viral infections, and the diagnostic and therapeutic management of these infections will be covered. Finally, we will suggest some important areas of future investigation.

A quasi-experimental study of a bundled diagnostic stewardship intervention for ventilator-associated pneumonia.

OBJECTIVES: Diagnostic error in the use of respiratory cultures for ventilator-associated pneumonia (VAP) fuels misdiagnosis and antibiotic overuse within intensive care units. In this prospective quasi-experimental study (NCT05176353), we aimed to evaluate the safety, feasibility, and efficacy of a novel VAP-specific bundled diagnostic stewardship intervention (VAP-DSI) to mitigate VAP over-diagnosis/overtreatment. METHODS: We developed and implemented a VAP-DSI using an interruptive clinical decision support tool and modifications to clinical laboratory workflows. Interventions included gatekeeping access to respiratory culture ordering, preferential use of non-bronchoscopic bronchoalveolar lavage for culture collection, and suppression of culture results for samples with minimal alveolar neutrophilia. Rates of adverse safety outcomes, positive respiratory cultures, and antimicrobial utilization were compared between mechanically ventilated patients (MVPs) in the 1-year post-intervention study cohort (2022-2023) and 5-year pre-intervention MVP controls (2017-2022). RESULTS: VAP-DSI implementation did not associate with increases in adverse safety outcomes but did associate with a 20% rate reduction in positive respiratory cultures per 1000 MVP days (pre-intervention rate 127 [95% CI: 122-131], post-intervention rate 102 [95% CI: 92-112], p < 0.01). Significant reductions in broad-spectrum antibiotic days of therapy per 1000 MVP days were noted after VAP-DSI implementation (pre-intervention rate 1199 [95% CI: 1177-1205], post-intervention rate 1149 [95% CI: 1116-1184], p 0.03). DISCUSSION: Implementation of a VAP-DSI was safe and associated with significant reductions in rates of positive respiratory cultures and broad-spectrum antimicrobial use. This innovative trial of a VAP-DSI represents a novel avenue for intensive care unit antimicrobial stewardship. Multicentre trials of VAP-DSIs are warranted.

Combination eravacycline therapy for ventilator-associated pneumonia due to carbapenem-resistant Acinetobacter baumannii in patients with COVID-19: A case series.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia is associated with poor clinical outcomes and increased mortality. Clinical data regarding the optimal treatment of CRAB is limited, and combination therapy is often preferred. Eravacycline has demonstrated in-vitro activity against A. baumannii and has been considered for the treatment of pulmonary infections caused by CRAB. OBJECTIVE: The objective of this case series was to describe clinical outcomes associated with eravacycline when utilized as part of a combination regimen for the treatment of CRAB pneumonia at a county hospital. METHODS: A retrospective chart review was conducted from April 1, 2020, to October 1, 2020, which included hospitalized patients ≥18 years of age, diagnosed with coronavirus disease 2019 (COVID-19), with a sputum culture positive for CRAB, and receipt of at least one dose of eravacycline. The primary outcome studied was clinical resolution of CRAB pneumonia. A key secondary outcome was microbiological resolution. RESULTS: A total of 24 patients received combination eravacycline therapy for a median of 10.5 days. Overall, 17 (71%) patients demonstrated clinical resolution of CRAB pneumonia. Repeat sputum cultures post-treatment were collected in 17 (71%) patients, of which 12 (71%) achieved microbiological resolution. No adverse events attributable to eravacycline were identified. CONCLUSION: With limited viable salvage treatment options, combination eravacycline therapy showed favorable microbiological and clinical outcomes in patients with CRAB pneumonia. In light of this, eravacycline could be considered as a potential treatment option when designing CRAB pneumonia salvage therapy regimens.

Cost-effectiveness of linezolid to ventilator-associated pneumonia in Colombia.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is a prominent cause of morbidity and mortality in intensive care unit (ICU) patients. Due to the increase in Methicillin resistant Staphylococcus aureus infection, it is important to consider other more effective and safer alternatives compared to vancomycin. This motivates evaluating whether the use of an apparently more expensive drug such as linezolid can be cost-effective in Colombia. METHODS: A decision tree was used to simulate the results in terms of the cost and proportion of cured patients. In the simulation, patients can receive antibiotic treatment with linezolid (LZD 600 mg IV/12 h) or vancomycin (VCM 15 mg/kg iv/12 h) for 7 days, patients they can experience events adverse (renal failure and thrombocytopenia). The model was analyzed probabilistically, and a value of information analysis was conducted to inform the value of conducting further research to reduce current uncertainties in the evidence base. Cost-effectiveness was evaluated at a willingness-to-pay (WTP) value of US$5180. RESULTS: The mean incremental cost of LZD versus VCM is US$-517. This suggests that LZD is less costly. The proportion of patients cured when treated with LZD compared with VCM is 53 vs. 43%, respectively. The mean incremental benefit of LZD versus VCM is 10 This position of absolute dominance (LZD has lower costs and higher proportion of clinical cure than no supplementation) is unnecessary to estimate the incremental cost-effectiveness ratio. There is uncertainty with a 0.999 probability that LZD is more cost-effective than VCM. Our base-case results were robust to variations in all assumptions and parameters. CONCLUSION: LNZ is a cost-effective strategy for patients, ≥ 18 years of age, with VAP in Colombia- Our study provides evidence that can be used by decision-makers to improve clinical practice guidelines.

Association of biofilm formation, antimicrobial resistance, clinical characteristics, and clinical outcomes among Acinetobacter baumannii isolates from patients with ventilator-associated pneumonia.

INTRODUCTION: Biofilm formation is an important virulence factor of Acinetobacter baumannii. Here, we examined the biofilm formation of archived A. baumannii causing ventilator-associated pneumonia (VAP). METHODS: Eighteen and twenty isolates of A. baumannii causing bacteremic pneumonia and non-bacteremic pneumonia were included, respectively. Antimicrobial susceptibility testing was performed by broth microdilution method, while biofilm formation was evaluated by microtiter dish biofilm formation assay. RESULTS: All 38 isolates were still susceptible to colistin and tigecycline, whereas almost all isolates were non-susceptible (intermediate to resistant) to several antimicrobial agents, especially ceftriaxone and cefotaxime. Approximately, 44% of bacteremic isolates and 50% of non-bacteremic isolates were classified as carbapenem-resistant A. baumannii (CRAB). Biofilm formation was detected in 42% of the studied isolates. Bacteremia among the patients infected with biofilm-producing isolates was significantly higher than in those infected with non-biofilm-producing isolates. The antimicrobial susceptibilities of A. baumannii with biofilm formation were lower than those without biofilm formation, but the differences did not have statistical significance. The patients infected with non-biofilm-producing isolates had good clinical and non-clinical outcomes than those infected with biofilm-producing isolates. The survival rate of patients diagnosed with VAP due to biofilm-producing A. baumannii was lower than in those patients diagnosed with VAP due to non-biofilm-producing isolates. CONCLUSION: Biofilm formation of A. baumannii causing VAP was associated with antimicrobial resistance and bacteremia as well as unfavorable clinical outcomes.

Carbapenem vs. non-carbapenem antibiotics for ventilator-associated pneumonia: A systematic review with meta-analysis.

BACKGROUND: Carbapenem is recommended as one of the first-line regimens for ventilator-associated pneumonia (VAP), but no recent systematic review has fully investigated its efficacy. This systematic review aims to evaluate the efficacy of carbapenem compared with non-carbapenem for VAP treatment. METHODS: We performed a systematic review and meta-analysis of studies comparing the efficacy and the safety between carbapenem and non-carbapenem with activity to Pseudomonas aeruginosa in the treatment for VAP. The main outcome was mortality, and the additional outcomes were the clinical cure of pneumonia, length of intensive care unit stay, recurrence, adverse effects, and the development of resistant bacteria. This study was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Of the initial 1,730 publications, 9 randomized control trials were enrolled. In the meta-analysis, no difference was observed between the carbapenem and non-carbapenem regimens in improving mortality (odds ratio, 0.83; 95 % confidence interval (CI) 0.67-1.02). While the carbapenem regimen was superior to the non-carbapenem regimen in studies reporting the resolution of pneumonia (odds ratio, 1.09; 95 % CI 1.01-1.17), the effectiveness of carbapenem treatment was not evident in studies assessing the other outcomes. CONCLUSIONS: Carbapenem might have no superiority in survival when treating VAP. Moreover, non-carbapenem antibiotics with activities to P. aeruginosa have a potential option to avoid inducing carbapenem-resistant pathogens.

The Role of Biomarkers in the Diagnosis and Management of Pneumonia.

Biomarkers are used in the diagnosis, severity determination, and prognosis for patients with community-acquired pneumonia (CAP). Selected biomarkers may indicate a bacterial infection and need for antibiotic therapy (C-reactive protein, procalcitonin, soluble triggering receptor expressed on myeloid cells). Biomarkers can differentiate CAP patients who require hospital admission and severe CAP requiring intensive care unit admission. Biomarker-guided antibiotic therapy may limit antibiotic exposure without compromising outcome and thus improve antibiotic stewardship. The authors discuss the role of biomarkers in diagnosing, determining severity, defining the prognosis, and limiting antibiotic exposure in CAP and ventilator-associated pneumonia patients.

Management of Ventilator-Associated Pneumonia: Guidelines.

Two recent major guidelines on diagnosis and treatment of ventilator-associated pneumonia (VAP) recommend consideration of local antibiotic resistance patterns and individual patient risks for resistant pathogens when formulating an initial empiric antibiotic regimen. One recommends against invasive diagnostic techniques with quantitative cultures to determine the cause of VAP; the other recommends either invasive or noninvasive techniques. Both guidelines recommend short-course therapy be used for most patients with VAP. Although neither guideline recommends use of procalcitonin as an adjunct to clinical judgment when diagnosing VAP, they differ with respect to use of serial procalcitonin to shorten the length of antibiotic treatment.

Association of mean RDW values and changes in RDW with in-hospital mortality in ventilator-associated pneumonia (VAP): Evidence from MIMIC-IV database.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is a hospital-acquired infection with high mortality, and remains a challenge for clinical treatment. Red blood cell distribution width (RDW) was associated with worse outcomes in several diseases. The purpose of this study was to investigate the relationship between mean RDW values, changes in RDW (delta RDW), and in-hospital mortality among patients with VAP. METHODS: In the present study, we enrolled 1266 VAP patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. All patients were categorized into low group, medium group, and high group according to tertiles of mean RDW values. The primary outcome was all-cause in-hospital mortality. Univariate logistic regression analysis, multivariate logistic regression analysis, and restricted cubic spline (RCS) curve were performed to determine the association between mean RDW values and in-hospital mortality in VAP. Moreover, RCS curve was plotted to explore the dose-response relationship between delta RDW and in-hospital mortality in VAP. RESULTS: Among the VAP patients included in the study, the in-hospital mortality was 20.85% with 264 non-survivors and 1002 survivors. The non-survivors exhibited significantly higher mean RDW values and delta RDW values compared to survivors. Multivariate logistic regression analysis indicated that mean RDW values were positively associated with in-hospital mortality in VAP after adjusting for relevant covariates. The RCS curve demonstrated a dose-response relationship between mean RDW and the mortality in VAP. Moreover, a linear relationship was observed between delta RDW and in-hospital mortality in VAP. CONCLUSION: Higher mean RDW values were significantly associated with an increased risk of in-hospital mortality in VAP. Additionally, a linear relationship was found between delta RDW values and in-hospital mortality. These findings suggest that RDW can be used to identify high-risk patients with poorer outcomes in VAP.

UK clinicians' attitudes towards the application of molecular diagnostics to guide antibiotic use in ICU patients with pneumonias: a quantitative study.

BACKGROUND: Molecular diagnostic tests may improve antibiotic prescribing by enabling earlier tailoring of antimicrobial therapy. However, clinicians' trust and acceptance of these tests will determine their application in practice. OBJECTIVES: To examine ICU prescribers' views on the application of molecular diagnostics in patients with suspected hospital-acquired and ventilator-associated pneumonia (HAP/VAP). METHODS: Sixty-three ICU clinicians from five UK hospitals completed a cross-sectional questionnaire between May 2020 and July 2020 assessing attitudes towards using molecular diagnostics to inform initial agent choice and to help stop broad-spectrum antibiotics early. RESULTS: Attitudes towards using molecular diagnostics to inform initial treatment choices and to stop broad-spectrum antibiotics early were nuanced. Most (83%) were positive about molecular diagnostics, agreeing that using results to inform broad-spectrum antibiotic prescribing is good practice. However, many (58%) believed sick patients are often too unstable to risk stopping broad-spectrum antibiotics based on a negative result. CONCLUSIONS: Positive attitudes towards the application of molecular diagnostics to improve antibiotic stewardship were juxtapositioned against the perceived need to initiate and maintain broad-spectrum antibiotics to protect unstable patients.

The global epidemiology of ventilator-associated pneumonia caused by multi-drug resistant Pseudomonas aeruginosa: A systematic review and meta-analysis.

OBJECTIVES: The objective of this systematic review and meta-analysis was to estimate the global prevalence of multi-drug resistant (MDR) Pseudomonas aeruginosa causing ventilator-associated pneumonia (VAP). METHODS: The systematic search was conducted in four databases. Original studies describing MDR P. aeruginosa VAP prevalence in adults from 2012- 2022 were included. A meta-analysis, using the random effects model, was conducted for overall, subgroups (country, published year, study duration, and study design), and European data, respectively. Univariate meta-regression based on pooled estimates was also conducted. Systematic review registered in International Prospective Register of Systematic Review (CRD42022384035). RESULTS: In total of 31 studies, containing a total of 7951 cases from 16 countries, were included. The overall pooled prevalence of MDR among P. aeruginosa causing VAP was 33% (95% confidence interval [CI] 27.7-38.3%). The highest prevalence was for Iran at 87.5% (95% CI 69-95.7%), and the lowest was for the USA at 19.7% (95% CI 18.6-20.7%). The European prevalence was 29.9% (95% CI 23.2-36.7%). CONCLUSIONS: This review indicates that the prevalence of MDR P. aeruginosa in patients with VAP is generally high and varies significantly between countries; however, data are insufficient for many countries. The data in this study can provide a reference for VAP management and drug customisation strategies.

Is Zero Ventilator-Associated Pneumonia Achievable? Updated Practical Approaches to Ventilator-Associated Pneumonia Prevention.

Ventilator-associated pneumonia (VAP) remains a significant clinical entity with reported incidence rates of 7% to 15%. Given the considerable adverse consequences associated with this infection, VAP prevention became a core measure required in most US hospitals. Many institutions took pride in implementing effective VAP prevention bundles that combined at least head of bed elevation, hand hygiene, chlorhexidine oral care, and subglottic drainage. Spontaneous breathing and awakening trials have also consistently been shown to shorten the duration of mechanical ventilation and secondarily reduce the occurrence of VAP.