Association of dynamics of anellovirus loads with hospital-acquired pneumonia in brain-injured patients during the intensive care unit stay.

BACKGROUND: Critical illness induces immune disorders associated with an increased risk of hospital-acquired pneumonia (HAP) and acute respiratory distress syndrome (ARDS). Torque Teno Virus (TTV), from the Anelloviridae family, are proposed as a biomarker to measure the level of immunosuppression. Our objective was to describe the kinetics of TTV DNA loads and their association with critical-illness related complications. METHODS: We performed a longitudinal study in 115 brain-injured patients from a prospective cohort, collected endotracheal and blood samples at three time points (T1, T2, T3) during the two weeks post-admission in intensive care unit, and measured viral DNA loads using the TTV R-gene® kit (Biomerieux) and a pan-Anelloviridae in house qRT-PCR. RESULTS: TTV DNA was detected in the blood of 69, 71, and 64% of brain-injured patients at T1, T2 and T3 respectively. Time-associated variations of TTV and Anellovirus (AV) DNA loads were observed. Using a linear mixed-effects model, we found that HAP and ARDS were associated with lower blood AV DNA loads. CONCLUSION: Our results show that HAP or ARDS in critically ill patients are associated to changes in AV DNA loads, and should be evaluated further as a biomarker of immune disorders leading to these complications.

Hospital- and Ventilator-associated Pneumonia early after Lung Transplantation: a prospective Study on Incidence, Pathogen Origin and Outcome.

BACKGROUND: Hospital- (HAP) and ventilator-associated pneumonia (VAP) are important complications early (<30 days) after lung transplantation (LT). However, current incidence, associated factors and outcomes are not well reported. METHODS: LT recipients transplanted at our institution (07/2019-01/2020 and 10/2021-11/2022) were prospectively included. We assessed incidence and presentation of pneumonia and evaluated the impact of associated factors using regression models. In addition, we evaluated molecular relatedness of respiratory pathogens collected peri-transplant and at pneumonia occurrence using pulsed-field-gel-electrophoresis (PFGE). RESULTS: In the first 30 days post-LT, 25/270 (9.3%) recipients were diagnosed with pneumonia (68% [17/25] VAP; 32% [8/25] HAP). Median time to pneumonia was 11 days (IQR 7-13). 49% (132/270) of donor and 16% (44/270) of recipient respiratory peri-transplant cultures were positive. However, pathogens associated with pneumonia were not genetically related to either donor or recipient cultures at transplant, as determined by PFGE.Diagnosed pulmonary hypertension (HR 4.42, 95% CI 1.62-12.08) and immunosuppression use (HR 2.87, 95% CI 1.30-6.56) were pre-transplant factors associated with pneumonia.Pneumonia occurrence was associated with longer hospital stay (HR 5.44, 95% CI 2.22-13.37) and VAP with longer ICU stay (HR 4.31, 95% CI: 1.73-10.75) within the first 30 days post-transplant; 30- and 90-day mortality were similar. CONCLUSIONS: Prospectively assessed early pneumonia incidence occurred in around 10% of LT. Populations at increased risk for pneumonia occurrence include LT with pre-transplant pulmonary hypertension and pre-transplant immunosuppression. Pneumonia was associated with increased healthcare use, highlighting the need for further improvements by preferentially targeting higher-risk patients.

Preventability of Hospital Deaths in Patients with Non-Ventilator Hospital-Acquired Pneumonia.

BACKGROUND: Crude and adjusted mortality rates for patients with non-ventilator hospital-acquired pneumonia (NV-HAP) are amongst the highest of all healthcare-associated infections, leading to calls for greater prevention. Patients prone to NV-HAP, however, tend to be severely ill at baseline making it unclear whether their high mortality rates are due to NV-HAP, underlying conditions, or both. METHODS: Two infectious disease physicians conducted detailed medical record reviews on 150 randomly selected adults from 4 hospitals who died in-hospital following an NV-HAP event between April 2016 and May 2021. Reviewers abstracted risk factors, estimated the preventability of NV-HAP, identified causes of death, and adjudicated the preventability of death. RESULTS: Patients' median age was 69.3 (IQR 60.7-77.4) and 43.3% were female. Comorbidities were common: 57% had cancer, 30% chronic kidney disease, 29% chronic lung disease, and 27% heart failure. At least one hospice-eligible condition was present before NV-HAP in 54% and "Do Not Resuscitate" orders in 24%. Most (99%) had difficult-to-modify NV-HAP risk factors: 76% altered mental status, 35% dysphagia, and 27% nasogastric/orogastric tubes. NV-HAP was deemed possibly or probably preventable in 21% and hospital death likely or very likely preventable in 8.6%. CONCLUSIONS: Most patients who die following NV-HAP have multiple, severe underlying comorbidities and difficult-to-modify risk factors for NV-HAP. Only 1 in 5 NV-HAPs that culminated in death and 1 in 12 deaths following NV-HAP were judged potentially preventable. This does not diminish the importance of NV-HAP prevention programs but informs expectations about the potential magnitude of their impact on hospital deaths.

Understanding blaNDM-1 gene regulation in CRKP infections: toward novel antimicrobial strategies for hospital-acquired pneumonia.

BACKGROUND: The escalating challenge of Carbapenem-resistant Klebsiella pneumoniae (CRKP) in hospital-acquired pneumonia (HAP) is closely linked to the blaNDM-1 gene. This study explores the regulatory mechanisms of blaNDM-1 expression and aims to enhance antibacterial tactics to counteract the spread and infection of resistant bacteria. METHODS: KP and CRKP strains were isolated from HAP patients' blood samples. Transcriptomic sequencing (RNA-seq) identified significant upregulation of blaNDM-1 gene expression in CRKP strains. Bioinformatics analysis revealed blaNDM-1 gene involvement in beta-lactam resistance pathways. CRISPR-Cas9 was used to delete the blaNDM-1 gene, restoring sensitivity. In vitro and in vivo experiments demonstrated enhanced efficacy with Imipenem and Thanatin or Subatan combination therapy. RESULTS: KP and CRKP strains were isolated with significant upregulation of blaNDM-1 in CRKP strains identified by RNA-seq. The Beta-lactam resistance pathway was implicated in bioinformatics analysis. Knockout of blaNDM-1 reinstated sensitivity in CRKP strains. Further, co-treatment with Imipenem, Thanatin, or Subactam markedly improved antimicrobial effectiveness. CONCLUSION: Silencing blaNDM-1 in CRKP strains from HAP patients weakens their Carbapenem resistance and optimizes antibacterial strategies. These results provide new theoretical insights and practical methods for treating resistant bacterial infections.

Effects of clinically achievable pulmonary antibiotic concentrations on the recovery of bacteria: in vitro comparison of the BioFire FILMARRAY Pneumonia Panel versus conventional culture methods in bronchoalveolar lavage fluid.

Empiric antibiotics may affect bacterial pathogen recovery using conventional culture methods (CCMs), while PCR-based diagnostics are likely less affected. Herein, we conducted an in vitro study of bronchoalveolar lavage fluid (BAL) inoculated with bacteria and clinically relevant antibiotic concentrations to compare the recovery between the BioFire FILMARRAY Pneumonia Panel (Pn Panel) and CCMs. Remnant clinical BAL specimens were inoculated to ~105 cfu/mL using 12 clinical isolates. Isolates consisted of one wild-type (WT) and one or more resistant strains of: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus. Piperacillin-tazobactam, cefepime, meropenem, levofloxacin, or vancomycin was added to achieve pulmonary epithelial lining fluid peak and trough concentrations. Post-exposure cfu/mL was quantified by CCMs and simultaneously tested by the PN Panel for identification and semi-quantitative genetic copies/mL. CCM results were categorized as significant growth (SG) (≥1 × 104), no significant growth (NSG) (≥1 × 103, <1 × 104), or no growth (NG) (<1 × 103). The PN Panel accurately identified all isolates, resistance genes, and reported ≥106 genetic copies/mL regardless of antibiotic exposure. The CCM also identified all S. aureus strains exposed to vancomycin. For WT Gram-negative isolates exposed to antibiotics, SG, NSG, and NG were observed in 7/52 (13%), 18/52 (35%), and 27/52 (52%) of CCM experiments, respectively. For resistant Gram-negatives isolates, SG, NSG, and NG were observed in 62/88 (70%), 17/88 (19%), and 9/88 (10%), respectively. These in vitro data demonstrate that the PN Panel is able to identify Gram-negative pathogens in the presence of clinically significant antibiotic concentrations when CCM may not.

Current and novel therapies for management of Acinetobacter baumannii-associated pneumonia.

Acinetobacter baumannii is a common pathogen associated with hospital-acquired pneumonia showing increased resistance to carbapenem and colistin antibiotics nowadays. Infections with A. baumannii cause high patient fatalities due to their capability to evade current antimicrobial therapies, emphasizing the urgency of developing viable therapeutics to treat A. baumannii-associated pneumonia. In this review, we explore current and novel therapeutic options for overcoming therapeutic failure when dealing with A. baumannii-associated pneumonia. Among them, antibiotic combination therapy administering several drugs simultaneously or alternately, is one promising approach for optimizing therapeutic success. However, it has been associated with inconsistent and inconclusive therapeutic outcomes across different studies. Therefore, it is critical to undertake additional clinical trials to ascertain the clinical effectiveness of different antibiotic combinations. We also discuss the prospective roles of novel antimicrobial therapies including antimicrobial peptides, bacteriophage-based therapy, repurposed drugs, naturally-occurring compounds, nanoparticle-based therapy, anti-virulence strategies, immunotherapy, photodynamic and sonodynamic therapy, for utilizing them as additional alternative therapy while tackling A. baumannii-associated pneumonia. Importantly, these innovative therapies further require pharmacokinetic and pharmacodynamic evaluation for safety, stability, immunogenicity, toxicity, and tolerability before they can be clinically approved as an alternative rescue therapy for A. baumannii-associated pulmonary infections.

Association between nurse staffing level in intensive care settings and hospital-acquired pneumonia among surgery patients: result from the Korea National Health Insurance cohort.

This study examined the association between the number of nursing staff in intensive care units (ICUs) and hospital-acquired pneumonia (HAP) among surgical patients in South Korea. Data were obtained between 2008 and 2019 from the Korean National Health Insurance Service Cohort Database; 37,706 surgical patients who received critical care services were included in the analysis. Patients with a history of pneumonia 1 year prior to surgery or those who had undergone lung-related surgery were excluded. The ICU nursing management fee is an admission fee that varies based on the grading determined by nurse-to-bed ratio. Using this grading system, we classified four groups from the highest to the lowest level based on the proportion of beds to nurses (high, high-mid, mid-low, and low group). HAP was defined by the International Classification of Disease, 10th revision (ICD-10) code. Multilevel logistic regression was used to investigate the relationship between the level of ICU nurse staffing and pneumonia, controlling for variables at the individual and hospital levels. Lower levels of nurse staffing were associated with a greater incidence of HAP than higher levels of nurse staffing (mid-high, OR: 1.33, 95% CI: 1.12-1.57; mid-low, OR: 1.61, 95% CI: 1.27-2.04; low, OR: 2.13, 95% CI: 1.67-2.71). The intraclass correlation coefficient value was 0.177, and 17.7% of the variability in HAP was accounted for by the hospital. Higher ICU nursing management fee grades (grade 5 and above) in general and hospital settings were significantly associated with an increased risk of HAP compared to grade 1 admissions. Similarly, in tertiary hospitals, grade 2 and higher ICU nursing management fees were significantly associated with an increased risk of HAP compared to grade 1 admissions. Especially, a lower level of nurse staffing was associated with bacterial pneumonia but not pneumonia due to aspiration. In conclusion, this study found an association between the level of ICU nurse staffing and HAP among surgical patients. A lower level of nurse staffing in the ICU was associated with increased rates of HAP among surgical patients. This indicates that having fewer beds assigned to nurses in the ICU setting is a significant factor in preventing HAP, regardless of the size of the hospital.

Single-drug versus combination antimicrobial therapy in critically ill patients with hospital-acquired pneumonia and ventilator-associated pneumonia due to Gram-negative pathogens: a multicenter retrospective cohort study.

KEY MESSAGES: In this study including 391 critically ill patients with nosocomial pneumonia due to Gram-negative pathogens, combination therapy was not associated with a reduced hazard of death at Day 28 or a greater likelihood of clinical cure at Day 14. No over-risk of AKI was observed in patients receiving combination therapy. BACKGROUND: The benefits and harms of combination antimicrobial therapy remain controversial in critically ill patients with hospital-acquired pneumonia (HAP), ventilated HAP (vHAP) or ventilator-associated pneumonia (VAP) involving Gram-negative bacteria. METHODS: We included all patients in the prospective multicenter OutcomeRea database with a first HAP, vHAP or VAP due to a single Gram-negative bacterium and treated with initial adequate single-drug or combination therapy. The primary endpoint was Day-28 all-cause mortality. Secondary endpoints were clinical cure rate at Day 14 and a composite outcome of death or treatment-emergent acute kidney injury (AKI) at Day 7. The average effects of combination therapy on the study endpoints were investigated through inverse probability of treatment-weighted regression and multivariable regression models. Subgroups analyses were performed according to the resistance phenotype of the causative pathogens (multidrug-resistant or not), the pivotal (carbapenems or others) and companion (aminoglycosides/polymyxins or others) drug classes, the duration of combination therapy (< 3 or ≥ 3 days), the SOFA score value at pneumonia onset (< 7 or ≥ 7 points), and in patients with pneumonia due to non-fermenting Gram-negative bacteria, pneumonia-related bloodstream infection, or septic shock. RESULTS: Among the 391 included patients, 151 (38.6%) received single-drug therapy and 240 (61.4%) received combination therapy. VAP (overall, 67.3%), vHAP (16.4%) and HAP (16.4%) were equally distributed in the two groups. All-cause mortality rates at Day 28 (overall, 31.2%), clinical cure rate at Day 14 (43.7%) and the rate of death or AKI at Day 7 (41.2%) did not significantly differ between the groups. In inverse probability of treatment-weighted analyses, combination therapy was not independently associated with the likelihood of all-cause death at Day 28 (adjusted odd ratio [aOR], 1.14; 95% confidence interval [CI] 0.73-1.77; P = 0.56), clinical cure at Day 14 (aOR, 0.79; 95% CI 0.53-1.20; P = 0.27) or death or AKI at Day 7 (aOR, 1.07; 95% CI 0.71-1.63; P = 0.73). Multivariable regression models and subgroup analyses provided similar results. CONCLUSIONS: Initial combination therapy exerts no independent impact on Day-28 mortality, clinical cure rate at Day 14, and the hazard of death or AKI at Day 7 in critically ill patients with mono-bacterial HAP, vHAP or VAP due to Gram-negative bacteria.

Evaluating the Diagnostic Performance of Nasal Methicillin-Resistant Staphylococcus aureus Polymerase Chain Reaction in Hospital-Acquired Pneumonia Within the Intensive Care Unit. A Retrospective Study.

Background: The methicillin-resistant Staphylococcus aureus (MRSA) accounts for 20% to 40% of all hospital-acquired pneumonia (HAP) cases with mortality rates up to 55%. Prompt and accurate diagnosis is essential, especially in intensive care unit (ICU) patients. Nasal MRSA polymerase chain reaction (PCR) diagnostic utility evidence is conflicting in the literature for HAP due to a low number of HAP patients included in prior studies or due to the lack of high-yield gold standard cultures defined for comparisons. Methods: This was a retrospective cohort study conducted in a 65-bed medical ICU, and encompassing all adult patients admitted from January 2015 to March 2023 for HAP. Respiratory cultures included were those obtained by bronchoalveolar lavage or endotracheal suction within 7 days of nasal MRSA PCR testing. Results: The study included 412 patients; 56.8% were males and 65% were Whites. The mean age was 60.5 years. Most patients (82.5%) underwent MRSA-PCR before intubation, and the average time between MRSA-PCR and lower respiratory cultures was 2.15 days. The diagnostic performance of nasal MRSA PCR in diagnosing HAP in the ICU yielded a sensitivity (Sen) of 47.83%, specificity (Sp) of 92.29%, positive predictive value (PPV) of 26.83%, and negative predictive value (NPV) of 96.77%. For nonventilator HAP (nv-HAP) cases sensitivity was at 50%, specificity 92.83%, PPV 28.57%, and NPV at 97.00%. In ventilator-acquired pneumonia (VAP-HAP), the corresponding values were 42.86%, 90.91%, 23.08%, and 96.15%, respectively. Conclusion: The nasal MRSA PCR shows a high NPV and low false negative rate, suggesting it is a reliable tool for ruling out MRSA HAP in ICU patients. Care should be taken into account for disease prevalence and clinical context, as these factors may influence test performance. Further validation through prospective large-sample studies utilizing high-yield lower respiratory tract cultures is necessary to confirm our findings.

Risk factors for hospital-acquired pneumonia in hip fracture patients: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to systematically assess the incidence and risk factors for hospital-acquired pneumonia (HAP) in hip fracture patients by meta-analysis. METHODS: Systematically searched four English databases (PubMed, EMBASE, The Cochrane Library, and Web Of Science) and four Chinese databases (CNKI, CQVIP, Sinomed, and WAN FANG) from inception until 20 November 2023. All studies involving risk factors of HAP in patients with hip fractures were considered. Newcastle-Ottawa Scale was used to evaluate the quality of the included studies. The results were presented with the pooled odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: Of 35 articles (337,818 patients) included in this study, the incidence of HAP was 89 per 1000 cases. Twenty-three risk factors were eventually involved in the meta-analysis, and 21 risk factors were significant. Our study has identified four significant risk factors (advanced age, preoperative time, COPD, and hypoalbuminemia) associated with HAP, as follows: Advanced age as a continuous variable (OR 1.07, 95% CI 1.05-1.10), Advanced age > 70 years (OR 2.34, 95% CI 1.77-3.09), Advanced age > 80 years (OR 2.98, 95% CI 2.06-4.31), Chronic obstructive pulmonary disease (COPD) (OR 3.44, 95% CI 2.83-4.19), Time from injury to operation as a continuous variable (OR 1.09, 95% CI 1.07-1.12), Time from injury to operation ≥48 h (OR 3.59, 95% CI 2.88-4.48), Hypoalbuminemia < 3.0 g/dL (OR 3.03, 95% CI 1.93-4.73), and Hypoalbuminemia < 3.5 g/dL (OR 2.68, 95% CI 2.15-3.36). However, it is important to note that all the studies included in our research were retrospective in nature, which introduces certain limitations to the level of evidence and the ability to establish causal inferences. DISCUSSION: Patients who have suffered hip fractures are at an increased risk of developing postoperative hospital-acquired pneumonia, which can lead to prolonged hospital stays and adverse clinical outcomes. Consequently, the identification of these risk factors offers novel insights and methodologies for healthcare professionals in terms of both prevention and treatment. TRIAL REGISTRATION: Registration number: INPLASY2022100091.

Implementation of a structured oral hygiene program through nursing assistant education to address non-ventilator hospital-acquired pneumonia: A quasi-experimental study.

INTRODUCTION: Non-ventilator hospital-acquired pneumonia (NV HAP) is a common complication for hospitalized patients. NV HAP develops when patients aspirate oral secretions containing pathogenic bacteria. Appropriate oral hygiene can help mitigate NV HAP development. Hospital staff, including nursing assistants, play an important role in ensuring that these cares are completed. DESIGN: A quasi-experimental pre-post design was used to evaluate outcomes before and after implementation of a structured oral hygiene education program. METHODS: A structured oral hygiene program was developed and implemented in a large quaternary hospital. Change in NA knowledge, attitudes, and behaviors before and after implementation of the oral hygiene program was evaluated. Retrospective patient outcomes before and after the intervention were analyzed to detect changes in NV HAP rates. RESULTS: Following the education, nursing assistant knowledge of recommended frequency of oral care for patients who are NPO increased (67.2% vs. 82.1%, p = 0.003). NAs were more likely to report oral hygiene tools including oral suctioning (80.8% vs. 90.2%, p = 0.005) and toothbrushes (89.3% vs. 95.3%, p = 0.031). The unadjusted incidence of NV HAP was significantly lower in the post-intervention cohort (0.25%) compared to the pre-intervention cohort (0.74%), p < 0.001. In the adjusted model, non-invasive positive pressure ventilation increased the odds of NV HAP by nearly sevenfold (AOR = 6.88, 95% CI: 3.99, 11.39). CONCLUSION: Focused education for NAs is an effective strategy to increase knowledge related to oral hygiene. Implementing a structured oral hygiene program for NAs appears to be a promising practice to decrease NV HAP.

Oral condition at admission predicts functional outcomes and hospital-acquired pneumonia development among acute ischemic stroke patients.

INTRODUCTION: Oral care is crucial for the prevention of cardiovascular events and pneumonia. However, few studies have evaluated the associations between multidimensional assessments of oral status or functional outcomes and hospital-acquired pneumonia (HAP). METHODS: Consecutive patients with acute ischemic stroke (AIS) were retrospectively analyzed. We evaluated the modified oral assessment grade (mOAG) and investigated its association with a modified Rankin scale (mRS) score of 0‒2 (good stroke outcome) and HAP. The mOAG was developed to evaluate 8 categories (lip, tongue, coated tongue, saliva, mucosa, gingiva, preservation, and gargling) on a 4-point scale ranging from 0 to 3. We analyzed the effectiveness of the mOAG score for predicting stroke outcome or HAP using receiver operating characteristic (ROC) curve analysis. RESULTS: In total, 247 patients with AIS were analyzed. The area under the ROC curve of the mOAG for predicting poor outcomes was 0.821 (cutoff value: 7), and that for HAP incidence was 0.783 (cutoff value: 8). mOAG (a one-point increase) was associated with poor stroke outcome (odds ratio [OR] 1.31, 95% confidence interval [CI] 1.17‒1.48, P < 0.001) and HAP (OR 1.21, 95% CI 1.07‒1.38, P = 0.003) after adjusting for baseline clinical characteristics, including age and stroke severity. CONCLUSIONS: Lower mOAG scores at admission were independently associated with good outcomes and a decreased incidence of HAP. Comprehensive oral assessments are essential for acute stroke patients in clinical settings.

Polymyxin B Plus Aerosolized Colistin vs Polymyxin B Alone in Hospital-acquired Pneumonia ("AEROCOL" Study): A Feasibility Study.

Introduction: In hospital-acquired pneumonia (HAP) due to extensively drug resistant gram-negative pathogens, can treatment with high-dose colistin aerosolization using specific aerosol delivery protocol, improve clinical outcome in addition to systemic polymyxin-B? Materials and methods: In a randomized control trial, invasively ventilated adult ICU patients with HAP in whom clinicians decided to start systemic polypeptide antibiotics, were randomized to receive either intravenous polymyxin-B plus high-dose colistin nebulization (5-MIU 8-hourly) using specific protocol or intravenous polymyxin-B alone. Results: The study was closed early after recruiting 60% of planned patients because of slow rate of recruitment (24 patients in over 30 months). Treatment success (Primary outcome) was nonsignificantly higher in intervention group (63.66 vs 30.77%; p = 0.217). There was higher rate of microbiological cure in intervention group (60 vs 9.09%: p = 0.018). Numerically better secondary outcomes including fever-free days, ventilator- or vasopressor free days at day-7, ICU and hospital mortality also did not reach statistical significance. Two episodes of transient hypoxia were seen during aerosol delivery. However, overall incidences of adverse effects were not different between groups. Conclusion: This study could not confirm superiority of high-dose colistin aerosolization plus systemic polymyxin-B strategy over polymyxin-B alone in treating HAP due to extensive drug resistance (XDR) gram-negative pathogens. How to cite this article: Ghosh S. Polymyxin B Plus Aerosolized Colistin vs Polymyxin B Alone in Hospital-acquired Pneumonia ("AEROCOL" Study): A Feasibility Study. Indian J Crit Care Med 2024;28(8):792-795.

Less Is More? Antibiotic Treatment Duration in Pseudomonas aeruginosa Ventilator-Associated Pneumonia.

Recommended antimicrobial treatment durations for ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa have evolved over the past few decades. In this Viewpoint, we provide a narrative review of landmark trials investigating antimicrobial treatment durations for VAP caused by P. aeruginosa, and appraise iterations of expert consensus guidelines based on these data. We highlight strengths and weaknesses of existing data on this topic and provide recommendations for future avenues of study.

Individual meropenem epithelial lining fluid and plasma PK/PD target attainment.

It is unclear whether plasma is a reliable surrogate for target attainment in the epithelial lining fluid (ELF). The objective of this study was to characterize meropenem target attainment in plasma and ELF using prospective samples. The first 24-hour T>MIC was evaluated vs 1xMIC and 4xMIC targets at the patient (i.e., fixed MIC of 2 mg/L) and population [i.e., cumulative fraction of response (CFR) according to EUCAST MIC distributions] levels for both plasma and ELF. Among 65 patients receiving ≥24 hours of treatment, 40% of patients failed to achieve >50% T>4xMIC in plasma and ELF, and 30% of patients who achieved >50% T>4xMIC in plasma had <50% T>4xMIC in ELF. At 1xMIC and 4xMIC targets, 3% and 25% of patients with >95% T>MIC in plasma had <50% T>MIC in ELF, respectively. Those with a CRCL >115 mL/min were less likely to achieve >50%T>4xMIC in ELF (P < 0.025). In the population, CFR for Escherichia coli at 1xMIC and 4xMIC was >97%. For Pseudomonas aeruginosa, CFR was ≥90% in plasma and ranged 80%-85% in ELF at 1xMIC when a loading dose was applied. CFR was reduced in plasma (range: 75%-81%) and ELF (range: 44%-60%) in the absence of a loading dose at 1xMIC. At 4xMIC, CFR for P. aeruginosa was 60%-86% with a loading dose and 18%-62% without a loading dose. We found that plasma overestimated ELF target attainment inup to 30% of meropenem-treated patients, CRCL >115 mL/min decreased target attainment in ELF, and loading doses increased CFR in the population.

Metagenomics for the microbiological diagnosis of hospital-acquired pneumonia and ventilator-associated pneumonia (HAP/VAP) in intensive care unit (ICU): a proof-of-concept study.

BACKGROUND: Hospital-acquired and ventilator-associated-pneumonia (HAP/VAP) are one of the most prevalent health-care associated infections in the intensive care unit (ICU). Culture-independent methods were therefore developed to provide faster route to diagnosis and treatment. Among these, metagenomic next-generation sequencing (mNGS) has shown considerable promise. METHODS: This proof-of-concept study describes the technical feasibility and evaluates the clinical validity of the mNGS for the detection and characterization of the etiologic agents causing hospital-acquired and ventilator-associated pneumonia. We performed a prospective study of all patients with HAP/VAP hospitalized in our intensive care unit for whom a bronchoalveolar lavage (BAL) was performed between July 2017 and November 2018. We compared BAL fluid culture and mNGS results of these patients. RESULTS: A total of 32 BAL fluids were fully analyzed. Of these, 22 (69%) were positive by culture and all pathogens identified were also reported by mNGS. Among the culture-positive BAL samples, additional bacterial species were revealed by mNGS for 12 patients, raising the issue of their pathogenic role (colonization versus coinfection). Among BALF with culture-negative test, 5 were positive in mNGS test. CONCLUSIONS: This study revealed concordant results for pneumonia panel pathogens between mNGS and culture-positive tests and identified additional pathogens potentially implicated in pneumonia without etiologic diagnosis by culture. mNGS has emerged as a promising methodology for infectious disease diagnoses to support conventional methods. Prospective studies with real-time mNGS are warranted to examine the impact on antimicrobial decision-making and clinical outcome.

A 600 mg of fixed-dose linezolid in renally impaired patients versus 15 mg/kg intermittent dose-optimized vancomycin in renally non-impaired patients: A single centre retrospective analysis for adult patients with hospital-acquired pneumonia due to methicillin-resistant Staphylococcus aureus.

OBJECTIVES: Both linezolid and vancomycin are approved by USFDA and IDSA guidelines for the management of nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA) in clinical practice. Baseline creatinine clearance is the criterion for prescribing vancomycin or linezolid for hospital-acquired pneumonia in our institution. However, patients with renal function impairment are far more difficult to manage in intensive care. Thus, the objectives of the study were to compare the clinical efficacy and safety of 600 mg of fixed-dose linezolid with intermittent dose-optimised vancomycin in hospital-acquired pneumonia due to MRSA and to evaluate parameters of clinical cure. METHODS: Analysis of a review of patients' charts. Patients with creatinine clearance <80 ml/min received 600 mg linezolid/12 h (n = 139, LN cohort), and patients with creatinine clearance ≥80 ml/min received intravenous 15 mg/kg vancomycin/12 h for 1-2 weeks consecutively or 3 weeks in case of bacteremia (n = 152, VC cohort) for management of hospital-acquired pneumonia due to MRSA. RESULTS: A 59% of patients from the LN cohort and 47% of patients from the VC cohort were clinically cured. Administration of systemic steroids (p = 0.0412) and ≥ 80 ml/min creatinine clearance (p = 0.0498) were the independent parameters for the clinical cure of patients. Nephrotoxicity was higher among patients of the VC cohort than the LN cohort (p = 0.0464). Treatment failed in 41% of patients from the LN cohort and in 53% of patients from the VC cohort (p = 0.0200). CONCLUSIONS: A 600 mg of fixed-dose linezolid is an ideal alternative to intermittent dose-optimised vancomycin for better clinical outcomes for patients with hospital-acquired pneumonia due to MRSA, especially for patients with renal impairment.

Using Methicillin-Resistant Staphylococcus aureus Nasal Screens to Rule Out Methicillin-Resistant S aureus Pneumonia in Surgical Intensive Care Units.

INTRODUCTION: The methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) has a high negative predictive value (NPV). We aimed to understand if there was a difference in the NPV of the MRSA screen in surgical intensive care units (ICUs) and to determine its role in antibiotic de-escalation. METHODS: We performed a single-center, retrospective cohort study of adults with a positive respiratory culture and MRSA nasal PCR admitted to a surgical ICU from 2016 to 2019. Patients were stratified by surgical ICU: cardiothoracic/cardiovascular intensive care unit (CVICU) or transplant/acute care surgery intensive care unit (ACS-ICU). Our primary outcome was the NPV of MRSA screen. Secondary outcome was the duration of empiric MRSA-targeted therapy. RESULTS: We analyzed 61 patients: 42.6% (n = 26) ACS-ICU and 57.4% (n = 35) CVICU. There were no differences in age, comorbidities, prior MRSA infection, recent antibiotic use, immunocompromised status, or renal replacement therapy. At pneumonia diagnosis, more patients in the ACS-ICU were hospitalized ≥5 d (65.4% versus 8.6%, P < 0.0001) and more patients in the CVICU were in septic shock (88.6% versus 34.5%, P < 0.0001) and thrombocytopenic (40% versus 11.5%, P = 0.02). NPV of the PCR was similar (ACS-ICU: 0.92 [0.75-0.98], CV-ICU 0.89 [0.73-0.96]). On multivariable linear regression, the CVICU was associated with longer empiric therapy (ß 1.5, 95% CI 0.8-2.3, P < 0.0001), as was hospitalization for ≥5 d (ß 0.73, 95% CI 0.06-1.39, P = 0.03). CONCLUSIONS: The MRSA nasal PCR screen has a high NPV for ruling out MRSA pneumonia in critically ill surgical patients. However, patients in the CVICU and patients hospitalized ≥5 d had a longer time to de-escalation of MRSA-targeted therapy, potentially due to higher clinical risk profile.

Prevalence and Etiology of Community- and Hospital-Acquired Pneumonia in Saudi Arabia and Their Antimicrobial Susceptibility Patterns: A Systematic Review.

(1) Background and Objectives: Pneumonia is a major cause of morbidity and mortality worldwide, including in Saudi Arabia, and the prevalence and etiology of the disease varies depending on the setting. The development of effective strategies can help reduce the adverse impact of this disease. Therefore, this systematic review was conducted to explore the prevalence and etiology of community-acquired and hospital-acquired pneumonia in Saudi Arabia, as well as their antimicrobial susceptibility. (2) Materials and Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations were followed for this systematic review. Several databases were used to perform a thorough literature search, and papers were then assessed for eligibility by two independent reviewers. The Newcastle-Ottawa Scale (NOS) was used to extract the data from the relevant research and evaluate its quality. (3) Results: This systematic review included 28 studies that highlighted the fact that gram-negative bacteria, particularly Acinetobacter spp. and Pseudomonas aeruginosa, were the common cause of hospital-acquired pneumonia, while Staphylococcus aureus and Streptococcus spp. were responsible for community-acquired pneumonia in children. The study also found that bacterial isolates responsible for pneumonia showed high resistance rates against several antibiotics, including cephalosporins and carbapenems. (4) Conclusions: In conclusion, the study found that different bacteria are responsible for community- and hospital-acquired pneumonia in Saudi Arabia. Antibiotic resistance rates were high for several commonly used antibiotics, highlighting the need for rational antibiotic use to prevent further resistance. Moreover, there is a need to conduct more regular multicenter studies to assess etiology, resistance, and susceptibility patterns of pneumonia-causing pathogens in Saudi Arabia.

Risk Factors of Postoperative Hospital-Acquired Pneumonia in Patients Undergoing Cardiac Surgery.

Background and Objectives. Hospital-acquired pneumonia is one of the complications that may occur in the postoperative period in patients undergoing heart valve surgery, which may result in prolonged hospitalization, development of respiratory failure requiring mechanical ventilation or even death. This study investigated the preoperative risk factors of postoperative pneumonia after heart valve surgery. Materials and Methods: This was a prospective study in a group of consecutive patients with hemodynamically significant valvular heart disease undergoing valve surgery. The primary endpoint at the in-hospital follow-up was hospital-acquired pneumonia after heart valve surgery. Logistic regression analysis was used to assess which variables were predictive of the primary endpoint, and odds ratios (ORdis) were calculated with a 95% confidence interval (CI). Multivariate analysis was based on the results of single-factor logistic regression, i.e., in further steps all statistically significant variables were taken into consideration. Results: The present study included 505 patients. Postoperative pneumonia occurred in 23 patients. The mean time to diagnosis of pneumonia was approximately 3 days after heart valve surgery (±2 days). In multivariate analysis, preoperative level of high-sensitivity Troponin T (hs-TnT) (OR 2.086; 95% CI 1.211-3.593; p = 0.008) and right ventricular systolic pressure (RVSP) (OR 1.043; 95% CI 1.018-1.067; p 0.004) remained independent predictors of the postoperative pneumonia. Of the patients with postoperative pneumonia, 3 patients died due to the development of multiple organ dysfunction syndrome (MODS). Conclusions: Preoperative determination of serum hs-TnT concentration and echocardiographic measurement of the RVSP parameter may be useful in predicting postoperative pneumonia in patients undergoing heart valve surgery.