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.

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.

Do Antibiotics Prevent Infectious Complications in Critically Injured Patients With Blunt Nonoperative Midfacial Trauma?

BACKGROUND: While recent literature suggests antibiotics are not needed in patients with nonoperative facial fractures involving sinuses, the existing studies do not focus on critically injured patients who are known to be at higher risk for sinusitis and ventilator-associated pneumonia, which could be exacerbated by facial fractures. PURPOSE: The purpose of this study was to determine if antibiotics reduce the rate of infectious complications in critically injured patients who have blunt midfacial trauma treated nonoperatively. STUDY DESIGN, SETTING, SAMPLE: The authors conducted a retrospective cohort study consisting of patients admitted to the trauma intensive care unit who sustained blunt midfacial injuries managed nonoperatively at an urban Level 1 trauma center from August 13th, 2012, to July 30th, 2020. Adults who were critically injured on admission and sustained a midfacial fracture involving a sinus were included in the study. Patients who underwent operative repair of any facial fracture were excluded. PREDICTOR VARIABLE: The predictor variable was the use of antibiotics. MAIN OUTCOME VARIABLE: The primary outcome variable was the development of infectious complications, such as sinusitis, soft tissue infection, or any type of pneumonia, including ventilator-associated pneumonia (VAP). ANALYSES: The data were analyzed using Wilcoxon rank sum tests, Fisher exact tests, and multivariable logistic regression as appropriate for analysis type with significance level set at <0.05. RESULTS: The study included 307 patients, with a mean age of 40.6 years. Men accounted for 85.0% of the study population. Antibiotics were administered to 229 (74.6%) of the study population. Complications developed in 13.6% of the patients, which included sinusitis (0.3%), VAP (7.5%), and other types of pneumonia (5.9%). Clostridioides difficile colitis developed in 2 patients (0.6%). Antibiotics were not associated with a decrease in infectious complications in either the unadjusted analysis (13.1% in antibiotic group, 15.4% in no antibiotic group, RR = 0.85 [95% confidence interval = 0.5 to 1.6], P = .7) or the adjusted analysis (odds ratio 0.74 [0.34 to 1.62]). CONCLUSIONS AND RELEVANCE: Even in this critically injured patient population thought to be at elevated risk for infectious complications from their midfacial fractures, the rates of infectious complications in those who received antibiotics and those who did not were no different. These results suggest that consideration of more judicious use of antibiotics is warranted in critically ill patients with nonoperative midface fractures.

GAT107-mediated α7 nicotinic acetylcholine receptor signaling attenuates inflammatory lung injury and mortality in a mouse model of ventilator-associated pneumonia by alleviating macrophage mitochondrial oxidative stress via reducing MnSOD-S-glutathionylation.

Supraphysiological concentrations of oxygen (hyperoxia) can compromise host defense and increase susceptibility to bacterial and viral infections, causing ventilator-associated pneumonia (VAP). Compromised host defense and inflammatory lung injury are mediated, in part, by high extracellular concentrations of HMGB1, which can be decreased by GTS-21, a partial agonist of α7 nicotinic acetylcholine receptor (α7nAChR). Here, we report that a novel α7nAChR agonistic positive allosteric modulator (ago-PAM), GAT107, at 3.3 mg/kg, i.p., significantly decreased animal mortality and markers of inflammatory injury in mice exposed to hyperoxia and subsequently infected with Pseudomonas aeruginosa. The incubation of macrophages with 3.3 µM of GAT107 significantly decreased hyperoxia-induced extracellular HMGB1 accumulation and HMGB1-induced macrophage phagocytic dysfunction. Hyperoxia-compromised macrophage function was correlated with impaired mitochondrial membrane integrity, increased superoxide levels, and decreased manganese superoxide dismutase (MnSOD) activity. This compromised MnSOD activity is due to a significant increase in its level of glutathionylation. The incubation of hyperoxic macrophages with 3.3 µM of GAT107 significantly decreases the levels of glutathionylated MnSOD, and restores MnSOD activity and mitochondrial membrane integrity. Thus, GAT107 restored hyperoxia-compromised phagocytic functions by decreasing HMGB1 release, most likely via a mitochondrial-directed pathway. Overall, our results suggest that GAT107 may be a potential treatment to decrease acute inflammatory lung injury by increasing host defense in patients with VAP.

Early pneumonia diagnosis decreases ventilator-associated pneumonia rates in trauma population.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a source of morbidity and mortality for trauma patients. Aspiration events are also common because of traumatic brain injury, altered mental status, or facial trauma. In patients requiring mechanical ventilation, early pneumonias (EPs) may be erroneously classified as ventilator associated. METHODS: A prospective early bronchoscopy protocol was implemented from January 2020 to January 2022. Trauma patients intubated before arrival or within 48 hours of admission underwent bronchoalveolar lavage (BAL) within 24 hours of intubation. Patients with more than 100,000 colony-forming units on BAL were considered to have EP. RESULTS: A total of 117 patients underwent early BAL. Ninety-three (79.5%) had some growth on BAL with 36 (30.8%) meeting criteria for EP. For the total study population, 29 patients (24.8%) were diagnosed with VAP later in their hospital course, 12 of which had previously been diagnosed with EP. Of EP patients (n = 36), 21 (58.3%) were treated with antibiotics based on clinical signs of infection. Of EP patients who had a later pneumonia diagnosed by BAL (n = 12), seven (58.3%) grew the same organism from their initial BAL. When these patients were excluded from VAP calculation, the rate was reduced by 27.6%. Patients with EP had a higher rate of smoking history (41.7% vs. 19.8%, p < 0.001) compared with patients without EP. There was no difference in median hospital length of stay, intensive care unit length of stay, ventilator days, or mortality between the two cohorts. CONCLUSION: Early pneumonia is common in trauma patients intubated within the first 48 hours of admission and screening with early BAL identifies patients with aspiration or pretraumatic indicators of pneumonia. Accounting for these patients with early BAL significantly reduces reported VAP rates. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Randomized control study of nebulized colistin as an adjunctive therapy in ventilator-associated pneumonia in pediatric postoperative cardiac surgical population.

Background: Ventilator-associated pneumonia (VAP) with multidrug-resistant (MDR) gram negative organisms is a common problem in intensive care unit (ICU). Aerosolized antibiotics enhance the efficacy of systemic antibiotics when added as adjuvants. Aim: The primary objective of the study was to compare the clinical and bacteriological outcome of patients with VAP who were administered intravenous (IV) antibiotics alone with those patients who were treated with adjunctive nebulized colistin (NC) along with IV antibiotics. The secondary objective was to study the occurrence of any adverse events during colistin nebulization. Settings and Design: The study was a prospective, randomized, double-blinded controlled study conducted at a tertiary-care teaching institution. Materials and Methods: Ninety-eight children from surgical ICU aged less than 12 years who were diagnosed with VAP due to gram negative bacteria following cardiac surgery were chosen and divided randomly into two groups. The experimental group (NC group) was treated with systemic antibiotics along with NC, whereas the control group (NS group) was administered systemic antibiotics with nebulized normal saline (NS). Clinical and bacteriological outcomes were noted. Statistical analysis was done using SPSS Version 20.0 software. The patient characteristics were compared using independent Student's t test and Chi-square test. Results: There was a statistically significant reduction in the duration of mechanical ventilation, postoperative ICU and hospital stay (P < 0.05) in the NC group compared with the NS group. Conclusion: Aerosolized colistin may be considered as an adjunct to systemic IV antibiotics in pediatric patients with VAP due to gram negative bacteria susceptible to colistin.

Time to Look for Another Infectious Source? White Blood Cell Trends during Ventilator-Associated Pneumonia.

Background: Ventilator-associated pneumonia (VAP) continues to plague patients in intensive care units (ICUs) throughout the world. Persistent leukocytosis despite antibiotic treatment for VAP can have many etiologies including normal inflammatory response, inadequate VAP antimicrobial therapy, and the presence of additional infectious diagnoses. Hypothesis: Surgical patients with VAP and a second infectious source have a different white blood cell count (WBC) trend than patients with VAP alone. Patients and Methods: Retrospective, single-center study of surgical ICU patients diagnosed with VAP (>104 CFU/mL on semi-quantitative culture) between January 2019 and June 2020. Chart review identified additional infections diagnosed during VAP treatment. White blood cell count values were compared between patients treated for VAP alone (VAP-alone) and those with additional infections (VAP-plus) using a Wilcoxon test. Univariable analysis compared admission type, surgeries, and steroid use between cohorts. Results: Eighty-eight VAPs were included for analysis; 61 (69%) were VAP-alone and 27 (31%) VAP-plus. Average age was 47.1 ± 16.7 years, 78% were male, and 93% were trauma admissions. Median hospital day of VAP diagnosis was six (interquartile range [IQR], 4-10). Nearly all patients (99%) were started on initial antibiotic agents to which the VAP organism was sensitive. Daily WBC was higher for VAP-plus compared with VAP-alone on days five, six, and seven of treatment. The maximum WBC was higher for VAP-plus (21.6 k/mcL vs. 16.1 k/mcL; p = 0.02). There were no differences in admission types, number of surgeries, or steroid use between groups. Conclusions: Providers should have increased suspicion for additional sources of infection when ICU patients with a VAP continue to have elevated WBC despite appropriate antibiotic therapy.

Investigation of pharmacokinetic and clinical outcomes of various meropenem regimens in patients with ventilator-associated pneumonia and augmented renal clearance.

INTRODUCTION: Augmented renal clearance (ARC) defined as creatinine clearance (Clcr) above 130 mL/min/1.73m2 may lead to suboptimal antibacterial treatment. The aim of this study was to determine a strategy for meropenem administration to achieve both pharmacodynamic-pharmacokinetic (PK-PD) target (50%fT > MIC) and better clinical outcomes in patients with VAP and ARC. MATERIALS AND METHODS: In this randomized clinical trial, patients with VAP and high risk for ARC were recruited. An 8-h urine collection was performed on the 1st, 3rd, and 5th days of study to measure Clcr. Included patients were divided into three groups: (1) 1 g meropenem, 3-h infusion, (2) 2 g meropenem, 3-h infusion, (3) 1 g meropenem, 6-h infusion. On the 2nd, 3rd, and 5th days of treatment, peak and trough blood samples were collected to undergo HPLC assay. MICs were assessed using microdilution method. Patients were also clinically monitored for 14 days. RESULTS: Forty-five patients were included. Group 3 showed significanty higher rate of patients achieving fT > MIC > 50% (100% for group 3 versus 40% for group 2 and 13% for group 1; p = 0.0001). Mean fT > MIC% was significantly higher in group 3 (78.77 ± 5.87 for group 3 versus 49.6 ± 7.38 for group 2 and 43.2 ± 7.98 for group 1; p = 0.0001). Statistical analysis showed no significant differences among groups regarding clinical improvement. CONCLUSION: According to the findings of this trial, prolonged meropenem infusion is an appropriate strategy compared to dose elevation among ARC patients.

Invasive Pulmonary Aspergillosis in Hospital and Ventilator-Associated Pneumonias.

Pneumonia is the commonest nosocomial infection complicating hospital stay, with both non-ventilated hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) occurring frequently amongst patients in intensive care. Aspergillus is an increasingly recognized pathogen amongst patients with HAP and VAP, and is associated with significantly increased mortality if left untreated.Invasive pulmonary aspergillosis (IPA) was originally identified in patients who had been profoundly immunosuppressed, however, this disease can also occur in patients with relative immunosuppression such as critically ill patients in intensive care unit (ICU). Patients in ICU commonly have several risk factors for IPA, with the inflamed pulmonary environment providing a niche for aspergillus growth.An understanding of the true prevalence of this condition amongst ICU patients, and its specific rate in patients with HAP or VAP is hampered by difficulties in diagnosis. Establishing a definitive diagnosis requires tissue biopsy, which is seldom practical in critically ill patients, so imperfect proxy measures are required. Clinical and radiological findings in ventilated patients are frequently non-specific. The best-established test is galactomannan antigen level in bronchoalveolar lavage fluid, although this must be interpreted in the clinical context as false positive results can occur. Acknowledging these limitations, the best estimates of the prevalence of IPA range from 0.3 to 5% amongst all ICU patients, 12% amongst patients with VAP and 7 to 28% amongst ventilated patients with influenza.Antifungal triazoles including voriconazole are the first-line therapy choice in most cases. Amphotericin has excellent antimold coverage, but a less advantageous side effect profile. Echinocandins are less effective against IPA, but may play a role in rescue therapy, or as an adjuvant to triazole therapy.A high index of suspicion for IPA should be maintained when investigating patients with HAP or VAP, especially when they have specific risk factors or are not responding to appropriate empiric antibacterial therapy.

Population Pharmacokinetic Modeling and Probability of Pharmacodynamic Target Attainment for Ceftazidime-Avibactam in Pediatric Patients Aged 3 Months and Older.

Increasing prevalence of infections caused by antimicrobial-resistant gram-negative bacteria represents a global health crisis, and while several novel therapies that target various aspects of antimicrobial resistance have been introduced in recent years, few are currently approved for children. Ceftazidime-avibactam is a novel ß-lactam ß-lactamase inhibitor combination approved for adults and children 3 months and older with complicated intra-abdominal infection, and complicated urinary tract infection or hospital-acquired ventilator-associated pneumonia (adults only in the United States) caused by susceptible gram-negative bacteria. Extensive population pharmacokinetic (PK) data sets for ceftazidime and avibactam obtained during the adult clinical development program were used to iteratively select, modify, and validate the approved adult dosage regimen (2,000-500 mg by 2-hour intravenous (IV) infusion every 8 hours (q8h), with adjustments for renal function). Following the completion of one phase I (NCT01893346) and two phase II ceftazidime-avibactam studies (NCT02475733 and NCT02497781) in children, adult PK data sets were updated with pediatric PK data. This paper describes the development of updated combined adult and pediatric population PK models and their application in characterizing the population PK of ceftazidime and avibactam in children, and in dose selection for further pediatric evaluation. The updated models supported the approval of ceftazidime-avibactam pediatric dosage regimens (all by 2-hour IV infusion) of 50-12.5 mg/kg (maximum 2,000-500 mg) q8h for those ≥6 months to 18 years old, and 40-10 mg/kg q8h for those ≥3 to 6 months old with creatinine clearance > 50 mL/min/1.73 m2 .

The Pharmacokinetic Profile and Bioavailability of Enteral N-Acetylcysteine in Intensive Care Unit.

Background and Objectives: N-acetylcysteine (NAC) is a mucolytic agent used to prevent ventilator-associated pneumonia in intensive care units. This study aimed to evaluate the oral bioavailability of NAC in critically ill patients with pneumonia, isolated acute brain injury and abdominal sepsis. Materials and Methods: This quantitative and descriptive study compared NAC's pharmacokinetics after intravenous and enteral administration. 600 mg of NAC was administered in both ways, and the blood levels for NAC were measured. Results: 18 patients with pneumonia, 19 patients with brain injury and 17 patients with abdominal sepsis were included in the population pharmacokinetic modelling. A three-compartmental model without lag-time provided the best fit to the data. Oral bioavailability was estimated as 11.6% (95% confidence interval 6.3-16.9%), similar to bioavailability in healthy volunteers and patients with chronic pulmonary diseases. Conclusions: The bioavailability of enteral NAC of ICU patients with different diseases is similar to the published data on healthy volunteers.

Ceftolozane/tazobactam probability of target attainment and outcomes in participants with augmented renal clearance from the randomized phase 3 ASPECT-NP trial.

BACKGROUND: The randomized, double-blind, phase 3 ASPECT-NP trial evaluated the efficacy of 3 g of ceftolozane/tazobactam (C/T) versus 1 g of meropenem infused every 8 h for 8 to 14 days for treatment of adults with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP). We assessed the probability of target attainment and compared efficacy outcomes from ASPECT-NP in participants with augmented renal clearance (ARC) versus those with normal renal function. METHODS: Baseline renal function was categorized as normal renal function (creatinine clearance 80-130 mL/min) or ARC (creatinine clearance > 130 mL/min). Population pharmacokinetic models informed Monte Carlo simulations to assess probability of target attainment in plasma and pulmonary epithelial lining fluid. Outcomes included 28-day all-cause mortality and clinical cure and per-participant microbiologic cure rates at the test-of-cure visit. RESULTS: A > 99% and > 80% probability of target attainment was demonstrated for ceftolozane and tazobactam, respectively, in simulated plasma and epithelial lining fluid. Within treatment arms, 28-day all-cause mortality rates in participants with normal renal function (C/T, n = 131; meropenem, n = 123) and ARC (C/T, n = 96; meropenem, n = 113) were comparable (data comparisons presented as rate; treatment difference [95% CI]) (C/T: normal renal function, 17.6%; ARC, 17.7%; 0.2 [- 9.6 to 10.6]; meropenem: normal renal function, 20.3%; ARC, 17.7%; - 2.6 [- 12.6 to 7.5]). Clinical cure rates at test-of-cure were also comparable across renal function groups within treatment arms (C/T: normal renal function, 57.3%; ARC, 59.4%; - 2.1 [- 14.8 to 10.8]; meropenem: normal renal function, 59.3%; ARC, 57.5%; 1.8 [- 10.6 to 14.2]). Per-participant microbiologic cure rates at test-of-cure were consistent across renal function groups within treatment arms (C/T: normal renal function, 72.2% [n/N = 70/97]; ARC, 71.4% [n/N = 55/77]; 0.7 [- 12.4 to 14.2]; meropenem: normal renal function, 75.0% [n/N = 66/88]; ARC, 70.0% [n/N = 49/70]; 5.0 [- 8.7 to 19.0]). CONCLUSIONS: C/T and meropenem resulted in 28-day all-cause mortality, clinical cure, and microbiologic cure rates that were comparable between participants with ARC or normal renal function. In conjunction with high probability of target attainment, these results confirm that C/T (3 g) every 8 h is appropriate in patients with HABP/VABP and ARC. Trial registration ClinicalTrials.gov identifier: NCT02070757, registered February 25, 2014; EudraCT: 2012-002862-11.

Emergence of blaNDM-1 and blaVIM producing Gram-negative bacilli in ventilator-associated pneumonia at AMR Surveillance Regional Reference Laboratory in India.

INTRODUCTION: Ventilator-associated pneumonia (VAP) may be a life threatening nosocomial infection encountered in intensive care units. Currently the emergence of carbapenem-resistant Gram-negative pathogens has become worrisome threat worldwide. MATERIAL AND METHODS: Endotracheal aspirates samples were collected from patients who were under mechanical ventilation for > 48 h. The bacterial isolates were identified by MALDI-TOF-MS and antibiotic susceptibility testing performed. All carbapenem resistant isolates were tested by Modified Hodge test (MHT), modified carbapenem inactivation method (mCIM), and EDTA-CIM (eCIM) and PCR were performed to detect blaIMP, blaVIM and blaNDM producing MBL genes. RESULTS: VAP occurred in 172/353(48.7%), 23.3% had early-onset VAP and 76.7% had late-onset VAP. Males (69.2%) were found to suffer more from VAP. Prior antibiotic therapy, CPI>6, prior surgery and tracheostomy were associated with VAP. The mortality in VAP (58.1%) contrasted with non-VAP (40%). 99/169 (58.6%) Gram-negative isolates were resistant to carbapenems. Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae were common pathogens found in late onset VAP, whereas K. pneumoniae, A. baumannii and Staphylococcus aureus were common in early onset VAP. The PCR results detected blaNDM in 37/172(21.5%) and blaVIM in 30/172(17.4%); 15/172(8.7%) isolates carried both genes. CONCLUSION: The blaNDM-1 and blaVIM genes are the main antibiotic-resistance genes that induce resistance patterns to carbapenems in VAP, highlighting CRE strains of potential public health concern and therapeutic challenge. Diagnostic laboratories in India must get on high caution for early MBL detection as it may limit the wide dispersal of MBL genes.

Clinical characteristics and outcomes of neonates with polymicrobial ventilator-associated pneumonia in the intensive care unit.

BACKGROUND: Ventilator associated pneumonia (VAP) caused by more than one microorganisms is not uncommon and may be potentially challenging, but the relevant data is scarce in ventilated neonates. We aimed to investigate the clinical characteristics and outcomes of polymicrobial VAP in the neonatal intensive care unit (NICU). METHODS: All neonates with definite diagnosis of VAP from a tertiary level neonatal intensive care unit (NICU) in Taiwan between October 2017 and September 2020 were prospectively observed and enrolled for analyses. All clinical features, therapeutic interventions and outcomes were compared between the polymicrobial VAP and monomicrobial VAP episodes. Multivariate regression analyses were used to find the independent risk factors for treatment failure. RESULTS: Among 236 episodes of neonatal VAP, 60 (25.4%) were caused by more than one microorganisms. Polymicrobial VAP episodes were more likely to be associated with multidrug-resistant pathogens (53.3% versus 34.7%, P = 0.014), more often occurred in later days of life and in neonates with prolonged intubation and underlying bronchopulmonary dysplasia. Otherwise most clinical characteristics of polymicrobial VAP were similar to those of monomicrobial VAP. The therapeutic responses and treatment outcomes were also comparable between these two groups, although modification of therapeutic antibiotics were significantly more common in polymicrobial VAP episodes than monomicrobial VAP episodes (63.3% versus 46.2%; P < 0.001). None of any specific pathogens was significantly associated with worse outcomes. Instead, it is the severity of illness, including presence of concurrent bacteremia, septic shock, and requirement of high-frequency oscillatory ventilator and underlying neurological sequelae that are independently associated with treatment failure. CONCLUSIONS: Polymicrobial VAP accounted for 25.4% of all neonatal VAP in the NICU, and frequently occurred in neonates with prolonged intubation and underlying bronchopulmonary dysplasia. In our cohort, most clinical features, therapeutic responses and final outcomes of neonates with monomicrobial and polymicrobial VAP did not differ significantly.

Prediction models of methicillin sensitive Staphylococcus aureus ventilator associated pneumonia relapse in trauma and brain injury patients: A retrospective analysis.

PURPOSE: To describe the incidence and risk factors of methicillin sensitive Staphylococcus aureus ventilator associated pneumonia (MSSA-VAP) relapse in trauma and non-traumatic brain injury patients. MATERIALS AND METHODS: Retrospective observational monocentric cohort study of consecutive ICU patients who developed a first episode of MSSA-VAP after trauma and non-traumatic brain injury. MSSA-VAP relapse encompass MSSA-VAP treatment failure (persistence or recurrence of MSSA) or other pathogen - VAP. RESULTS: A total of 165 patients (71% of trauma and 29% of non-traumatic brain injury) with MSSA-VAP were included. MSSA-VAP relapse occurred in 54 (33%) patients, including 28 (17%) MSSA-VAP treatment failure and 46 (28%) other pathogen-VAP. Empirical first-line antibiotic therapy was appropriate in 96% of cases. In multivariate analysis, the presence of Streptococcus species (Odds ratio [OR] 7.37) and oropharyngeal flora (OR 3.64) as initial MSSA co-pathogen, suggested aspiration at the time of admission and independently predicted MSSA-VAP treatment failure. Initial Glasgow coma scale (OR 0.89), need for emergent surgery (OR 5.71) and the presence of an acute respiratory distress syndrome at the time of the first MSSA-VAP (3.99), independently predicted the onset of other pathogen - VAP. CONCLUSION: Early and simple factors may help to identify patients with high-risk of MSSA-VAP relapse.

Procalcitonin as a biomarker for ventilator associated pneumonia in COVID-19 patients: Is it an useful stewardship tool?

Ventilator associated pneumonia(VAP) is a severe complication that can lead to high mortality when not early identified or when therapy is delayed. The aim of this study was to evaluate procalcitonin(PCT) as a biomarker for VAP development. In total, 73 hospitalized patients with COVID-19 were analyzed. PCT levels greater than 0.975ng/mL were more related to VAP. No association was found for C-reactive protein (CRP). The results show that procalcitonin may be a pertinent biomarker for VAP diagnosis and can be a helpful tool for antibiotic withdrawal.

Efficacy and safety of the point-of-care procalcitonin test for determining the antibiotic treatment duration in patients with ventilator-associated pneumonia in the intensive care unit: a randomised controlled trial.

INTRODUCTION: This study was conducted to assess the efficacy of point-of-care (POC) procalcitonin (PCT) serial measurement in determining the antibiotic treatment duration in patients with ventilator-associated pneumonia (VAP). MATERIAL AND METHODS: One hundred patients were randomly recruited and then further randomly divided into two groups of 50 patients each. The first group used the POC PCT test along with the standard sepsis parameter monitoring, while the second group had the standard monitoring only (C-reactive protein [CRP] level, total white count, temperature and tracheal aspirate culture). Serial PCT test results and CRP levels were monitored on days 1, 3, 7 and 9. The patients were followed up for 28-day mortality. RESULTS: Eighty-five patients completed the trial, of whom 43 were in the PCT group and 42 were in the control group. The PCT group had a significantly lower mean (SD) antibiotic treatment duration (10.28 [2.68] days) than the control group (11.52 [3.06]). The mean (SD) difference was -1.25 (95% confidence interval [CI], -2.48 to 0.01; t-statistic [df] = -1.997 [83]; P = 0.049). The PCT group also had a higher number of antibiotic-free days alive during the 28 days after VAP onset than the control group (mean [SD], 10.79 [7.61] vs. 8.72 [6.41]). The Sequential Organ Failure Assessment score was the sole factor for the decrease in duration after VAP onset (regression coefficient ß [95% CI], -0.70 [-1.19 to -0.20]; P = 0.006). CONCLUSIONS: The POC procalcitonin test can reduce the antibiotic treatment duration in patients with VAP.