Utilization of serum procalcitonin as a biomarker in the diagnosis and treatment of children with bacterial hospital-acquired pneumonia.

Hospital-acquired pneumonia (HAP) is one of the common infections in hospitalized patients. Early and prompt diagnosis of HAP is important because it aids in the appropriate selection of antibiotics and decreases the mortality and morbidity of patients. The investigation on serum procalcitonin (PCT) levels in pediatric patients is limited. Herein we aimed to evaluate the role of PCT in the early diagnosis of children with bacterial HAP. The study enrolled 264 children (< 14 years old) who were radiographically detected by pulmonary condensation chest X-rays. The HAP patients were stratified by patterns of microbiological detection of pathogens. Baseline white blood cell (WBC) count, neutrophil proportion, PCT, and C-reactive protein (CRP) were measured on admission. The laboratory findings and microbiological findings were analyzed and compared among groups. The median PCT concentration of patients with typical bacterial pathogens (3.95 ± 3.75 ng/mL) was significantly higher than the one of the patients with other pathogen types (median lower than 1.20 ng/mL). Correlation analysis indicated a significant correlation between PCT concentrations and the main inflammation makers including WBC count, neutrophil proportion, and CRP. PCT level was significantly decreased to 0.86 ± 1.46 ng/mL in post-treatment patients (p < 0.001). This cohort study with 264 pediatric HAP patients demonstrated the reliability of PCT level as a biomarker in patients with typical bacterial pathogens. Specifically, PCT cutoffs of 2 ng/mL accurately identified HAP children with typical bacterial pathogens. This finding suggested that PCT may serve as a reliable biomarker for the early diagnosis and treatment indicator of children with HAP.

Comparison of blood cultures versus T2 Candida Panel in management of candidemia at a large community hospital.

The T2 Candida Panel (T2CP) has high sensitivity and specificity to detect candidemia. Its role in the diagnosis and management of candidemia compared to blood cultures (BC) remains unclear. The purpose of this study was to evaluate the T2CP versus BC in detecting and treating candidemia. A retrospective, observational cohort study was conducted to compare clinical outcomes in patients with candidemia identified by BC versus T2CP. Patients with a positive BC or T2CP for Candida spp. from January 2012 to August 2020 were grouped by initial method of detection (BC vs T2CP). Co-primary endpoints assessed included time to detection of candidemia and time to antifungal therapy. Key secondary endpoints included length of stay (LOS), ICU LOS, and mortality. One hundred sixty-three patients with a positive BC and 89 patients with a positive T2CP were included in the evaluation. The average time to detection of candidemia was significantly shorter in the T2CP group compared to BC group (9 vs 41 h, p < 0.001). The time to antifungal was also significantly shorter in the T2CP group compared to the BC group (4 vs 37 h, p < 0.001). However, LOS was significantly shorter in the BC positive group than the T2CP group with no difference in ICU LOS. There was no difference in in-hospital or 30-day mortality between the two groups. Of patients diagnosed with candidemia at our large community hospital, identification by T2CP led to faster detection and initiation of antifungal compared to blood cultures without improvement in LOS or mortality.

Hepatitis B virus infection and its associated factors among medical waste collectors at public health facilities in eastern Ethiopia: a facility-based cross-sectional study.

BACKGROUND: The risk of hepatitis B virus infection among medical waste handlers who undergo collection, transportation, and disposal of medical wastes in the health institutions is higher due to frequent exposure to contaminated blood and other body fluids. There is limited evidence on the seroprevalence of hepatitis B among medical waste handlers in eastern Ethiopia. The study was aimed at studying the seroprevalence of Hepatitis B Virus and associated risk factors among medical waste collectors at health facilities of eastern Ethiopia. METHODS: A facility-based cross-sectional study was conducted among randomly selected medical waste collectors from public health facilities in eastern Ethiopia from March to June 2018. A pre-tested and well-structured questionnaire was used to collect data on socio-demographic characteristics and hepatitis B infection risk factors. A2.5ml venous blood was also collected, centrifuged and the serum was analyzed for hepatitis B surface antigen using the instant hepatitis B surface antigen kit. Descriptive summary measures were done. Chi-square and Fisher exact tests were used to assess the risk of association. Multivariate logistic regression was conducted with 95% CI and all value at P-value < 0.05 was declared statistically significant. RESULTS: From a total of 260 (97.38%) medical waste collectors participated, HBV was detected in 53 (20.4%) of the participants [95%CI; 15.8, 25.6]. No significant differences were observed in the detection rates of HBV with respect to socio-demographic characteristics. In both bivariate and multivariable logistic regression analysis, being unvaccinated (AOR = 6.35; 95%CI = [2.53-15.96], P = 0.001), history of blood transfusion (receiving) (AOR; 3.54; 95%CI; [1.02-12.24], P = 0.046), history of tattooing (AOR = 2.86; 95%CI = [1.12-7.27], p = 0.03), and history of multiple sexual partner (AOR = 10.28; 95%CI = [4.16-25.38], P = 0.001) remained statistically significantly associated with HBsAg positivity. CONCLUSION: This cross-sectional study identified that HBV infection is high among medical waste collectors in eastern Ethiopia. Immunization and on job health promotion and disease prevention measures should be considered in order to control the risk of HBV infection among medical waste collectors in eastern Ethiopia.

Asymptomatic central line-associated bloodstream infections in children implanted with long term indwelling central venous catheters in a teaching hospital, Sri Lanka.

BACKGROUND: Indwelling central venous catheters (CVC) are used to provide long term hemodialysis. The commonest and the severe complication of CVC is the central line-associated bloodstream infection (CLABSI). This study was done to assess the etiology and infectious complications of CVC in children on long term hemodialysis. METHODS: Children newly undergoing hemodialysis and having indwelling CVC were included. They were followed up to a period of 2-years to assess infectious complications. Catheter bundle care approach was employed to prevent infections and other complications. Automated culture from the central catheter and peripheral vein and 2D echocardiography were done in each hemodialysis. Serial procalcitonin (PCT) was measured. Differential time of positivity (DTP) was used to detect CLABSI. During homestay in weekly telephone conversations were done to assess features of infection, and whenever having, we have asked to admit to the tertiary care unit. Logistic regression was performed, and the significant outcome variable was considered following multivariable analysis as a risk factor. RESULTS: Blood cultures were positive in 1090 (74.5%) out of 1462 children. According to DTP, 410 (28%) were having CLABSI, while 520 (35.6%) were having bacteremia without CLABSI. Out of 410 CLABSI patients, 79 (19.2%) were asymptomatic. Coagulase-negative Staphylococcus spp. (CoNS) bacteremia was significantly associated with asymptomatic CLABSI. Right-sided infective endocarditis (RS-IE) was significantly associated with asymptomatic CLABSI and asymptomatic bacteremia without CLABSI. CoNS was associated significantly in RS-IE following asymptomatic CLABSI and asymptomatic bacteremia. PCT was in asymptomatic CLABSI was 1.8 ± 0.9 ng/mL while in symptomatic CLABSI was 11.3 ± 2.5 ng/ml (P = 0.02). CoNS bloodstream infection, tunneled CVC, peripherally inserted central catheter, femoral site, the number of line days > 90, receipt of vancomycin, meropenem, or linezolid in the 5 days before CLABSI diagnosis and recurrent bacteremia were risk factors for asymptomatic CLABSI. CONCLUSIONS: Asymptomatic CLABSI could be a rare occurrence. CoNS was predominantly isolated in patients with asymptomatic CLABSI. RS- IE is a well-known complication in long term indwelling CVC. CoNS was significantly associated with RS-IE following asymptomatic CLABSI. Regular procalcitonin, microbiological, and imaging studies would be essential to detect infectious complications in both symptomatic and asymptomatic patients implanted with long term indwelling CVCs.

Construction of Genomic Library and High-Throughput Screening of Pseudomonas aeruginosa Novel Antigens for Potential Vaccines.

Hospital-acquired infections with Pseudomonas aeruginosa have become a great challenge in caring for critically ill and immunocompromised patients. The cause of high mortality is the presence of multi-drug resistant (MDR) strains, which confers a pressing need for vaccines. Although vaccines against P. aeruginosa have been in development for more than several decades, there is no vaccine for patients at present. In this study, we purified genomic DNA of P. aeruginosa from sera of patients affected, constructed genome-wide library with random recombinants, and screened candidate protein antigens by evaluating their protective effects in vivo. After 13-round of screening, 115 reactive recombinants were obtained, among which 13 antigens showed strong immunoreactivity (more than 10% reaction to PcrV, a well-characterized V-antigen of P. aeruginosa). These 13 antigens were: PpiA, PtsP, OprP, CAZ10_34235, HmuU_2, PcaK, CarAd, RecG, YjiR_5, LigD, KinB, RtcA, and PscF. In vivo studies showed that vaccination with PscF protected against lethal P. aeruginosa challenge, and decreased lung inflammation and injury. A genomic library of P. aeruginosa could be constructed in this way for the first time, which could not only screen candidate antigens but also in a high-throughput way. PscF was considered as an ideal promising vaccine candidate for combating P. aeruginosa infection and was supported for further evaluation of its safety and efficacy.

'Lost in Nasal Space': Staphylococcus aureus sepsis associated with Nasal Handkerchief Packing.

INTRODUCTION: Staphylococcus aureus frequently causes infections in outpatient and hospital settings and can present as a highly variable entity. Typical manifestations are endocarditis, osteoarticular infections or infection of implanted prostheses, intravascular devices or foreign bodies. A thorough diagnostic evaluation with early focus identification is mandatory to improve patient outcome. CASE REPORT: We report a case of a 68-year old patient with a history of double allogeneic stem cell transplant for acute myeloid leukemia who developed a S. aureus bacteremia with dissemination, severe sepsis and lethal outcome due to nasal handkerchief packing after nose bleeding. CONCLUSION: A thorough medical examination with further diagnostic work-up is most important in S. aureus blood stream infection to identify and eradicate the portal(s) of entry, to rule out endocarditis, to search for spinal abscesses, osteomyelitis or spondylodiscitis. Adherence to management guides for clinicians must be of major importance to achieve optimal quality of clinical care, and thus improve patient outcome.

Daptomycin Plasma and CSF Levels in Patients with Healthcare-Associated Meningitis.

BACKGROUND: There are currently few data concerning the cerebrospinal fluid (CSF) penetration of daptomycin in patients with healthcare-associated meningitis. This study aims (1) to better characterize the pharmacokinetics of daptomycin in humans during a 7-day intravenous (IV) therapy course, and (2) to study the penetration of daptomycin in the CSF after IV infusion at the dose of 10 mg/kg. RESULTS: In this prospective observational study, we enrolled nine patients with an implanted external ventricular drainage and a diagnosis of a healthcare-associated meningitis. Daptomycin was administered at 10 mg/kg for a maximum of 7 days. The pharmacokinetic of daptomycin was studied using a two-compartment population/pharmacokinetic (POP/PK) model and by means of a nonlinear mixed effects modeling approach. A large inter-individual variability in plasma area under the curve (Range: 574.7-1366.3 h mg/L), paralleled by high-peak plasma concentration (Cmax) (all values > 60 mg/L), was noted. The inter-individual variability of CSF-AUC although significant (range: 1.17-6.81 h mg/L) was narrower than previously reported and with a late occurrence of CSF-Cmax (range: 6.04-9.54 h). The terminal half-life between plasma and CSF was similar. tmax values in CSF did not show a high inter-individual variability, and the fluctuations of predicted CSF concentrations were minimal. The mean value for daptomycin penetration obtained from our model was 0.45%. CONCLUSIONS: Our POP/PK model was able to describe the pharmacokinetics of daptomycin in both plasma and CSF, showing that daptomycin (up to 7 days at 10 mg/kg) has minimal penetration into central nervous system. Furthermore, the observed variability of AUC, tmax and predicted concentration in CSF was lower than what previously reported in the literature. Based on the present findings, it is unlikely that daptomycin could reach CSF concentrations high enough to have clinical efficacy; this should be tested in future studies.

Procalcitonin Concentration Measured Within the First Days of Cardiac Surgery Is Predictive of Postoperative Infections in Neonates: A Case-Control Study.

Increased procalcitonin concentration (PCT) is known to be reliable for the identification of infections even in the presence of the non-specific systemic inflammatory response seen after cardiopulmonary bypass (CPB), whereas increased C-reactive protein concentration (CRP) is not. The present work explored the ability of neonate PCT measured early after cardiac surgery to identify postoperative infections. This was a retrospective case-control study, where PCT was matched between patients with and without infections according to the patient's age, the CPB length, the use of deep hypothermic circulatory arrest (DHCA), and the postoperative day (POD). The accuracy in the prediction of infections was ascertained and cutoff thresholds were identified. 144 neonates were eligible, and 89 pairs of measurements from 94 patients were analyzed. PCT was a good predictor of infections within POD4, and was a better predictor when compared with CRP at POD1 and POD2. The sum of PCT (pg mL-1) and CRP (mg L-1) > 33 on POD1 or POD2 predicted infections with a 0.68 sensitivity and a 0.82 specificity, and a sum > 49.36 on POD3 or POD4 predicted infections with a 0.82 sensitivity and a 0.93 specificity. In patients with DHCA, PCT was higher than in those without DHCA, and was not predictive of infections. The accuracy of PCT to identify infections after neonatal cardiac surgery is better than that of CRP when measured within 48 h of surgery. The sum of the two markers measured early after surgery is an excellent predictor of postoperative infections.

Approach to Positive Blood Cultures in the Hospitalized Patient: A Review.

The use of blood cultures as a diagnostic tool has increased over the years along with improvements in techniques and results. The diagnostic dilemma arises when blood cultures are positive and there is possibility of contamination. Hence obtaining blood cultures in the appropriate setting and the interpretation of blood cultures by the hospitalist is imperative to the management of the hospitalized patient.

A Case-Control Study: Clinical Characteristics of Nosocomial Bloodstream Infections Versus Non-bloodstream Infections of Acinetobacter spp.

Background: Acinetobacter spp. are among the most common causes of bacterial nosocomial infections, including pneumonia and bloodstream infections. Previous studies on the risk factors of bloodstream Acinetobacter spp. infections (BSAcIs) primarily compared uninfected patients to those with BSAcIs. However, the identified risk factors contribute to either BSIs or Acinetobacter spp. infections. To the best of our knowledge, this is the first study to analyze the risk factors of BSAcIs in comparison to non-bloodstream Acinetobacter infections (non-BSAcIs). Methods: We retrospectively reviewed 10 years of medical records of BSAcIs from a teaching hospital in Shanghai. Clinical characteristics and treatment outcomes were compared between BSAcIs and non-BSAcIs. Treatment outcomes of carbapenem- and sulbactam-based regimens were also evaluated. Results: Respiratory tract infections (43.1%, 44/102) were the most common source of BSAcIs. The in-hospital mortality rate of BSAcIs (22.5%, 23/102) was significantly higher than that of non-BSAcIs (10.8%, 24/204). Compared with non-BSAcIs, the previous use of corticoids, proton pump inhibitor (PPI) usage, and the implementation of intracranial drainage were independent risk factors for BSAcIs. The clinical efficacy rate of antimicrobial treatment of carbapenem-susceptible BSAcIs was significantly higher than that of carbapenem-non-susceptible (CNS) BSAcIs (74.0% vs 44.3%). Sulbactam-based regimens had similar clinical efficacy rates as carbapenem-based regimens for treating CNS-BSAcIs (50.0% vs 45.8%). Conclusions: The in-hospital mortality rate of BSAcIs was significantly higher than that of non-BSAcIs. Glucocorticoids, PPI usage, and intracranial drainage were independent risk factors for BSAcIs. Sulbactam-based regimens had similar clinical efficacy rates as carbapenem-based regimens for treating CNS-BSAcIs.

A "Culture" Shift: Broad Bacterial Detection, Identification, and Antimicrobial Susceptibility Testing Directly from Whole Blood.

BACKGROUND: The time required for bloodstream pathogen detection, identification (ID), and antimicrobial susceptibility testing (AST) does not satisfy the acute needs of disease management. Conventional methods take up to 3 days for ID and AST. Molecular diagnostics have reduced times for ID, but their promise to supplant culture is unmet because AST times remain slow. We developed a combined quantitative PCR (qPCR)-based ID+AST assay with sequential detection, ID, and AST of leading nosocomial bacterial pathogens. METHODS: ID+AST was performed on whole blood samples by (a) removing blood cells, (b) brief bacterial enrichment, (c) bacterial detection and ID, and (d) species-specific antimicrobial treatment. Broad-spectrum qPCR of the internal transcribed spacer between the 16S and 23S was amplified for detection. High-resolution melting identified the species with a curve classifier. AST was enabled by Ct differences between treated and untreated samples. RESULTS: A detection limit of 1 CFU/mL was achieved for Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus. All species were accurately identified by unique melting curves. Antimicrobial minimum inhibitory concentrations were identified with Ct differences of ≥1 cycle. Using an RNA target allowed reduction of AST incubation time from 60 min to 5 min. Rapid-cycle amplification reduced qPCR times by 83% to 30 min. CONCLUSIONS: Combined, sequential ID+AST protocols allow rapid and reliable detection, ID, and AST for the diagnosis of bloodstream infections, enabling conversion of empiric to targeted therapy by the second dose of antimicrobials.

Tight glycemic control in critically ill pediatric patients: a meta-analysis and systematic review of randomized controlled trials.

BACKGROUND: There still are controversies in the impact of tight glycemic control (TGC) in critically ill children. The aim of this study was to assess the benefits and risks of TGC compared with conventional glycemic control (CGC) in critically ill pediatric patients admitted to the pediatric intensive care unit (PICU) by using data retrieved from randomized controlled trials (RCTs). METHOD: EMBASE, CNKI, PubMed, and the Cochrane Database were searched for RCTs comparing TGC with CGC in critically ill children in PICU. RESULT: The meta-analysis included five RCTs representing 3933 patients and compared TGC with CGC. Our result revealed that TGC did not reduce the 30-day mortality rates (OR 0.99, 95% CI 0.74-1.32, P = 0.95) and was not associated with decreasing health care-associated infections (OR 0.80, 95% CI 0.64-1.00, P = 0.05) compared with CGC, but significantly increased the incidence of hypoglycemia (OR 6.37, 95% CI 4.41-9.21, P < 0.001). CONCLUSION: Tight glycemic control was not associated with reducing the 30-day mortality rates and acquired infections compared with CGC in critically ill children. Significant increase of the incidence of hypoglycemia was revealed in TGC group. The conclusion should be interpreted with caution for the methodological heterogeneity among trials.

Significance of blood cultures in nursing home-acquired pneumonia.

The significance of blood cultures in nursing home-acquired pneumonia (NHAP) is incompletely understood. We retrospectively analyzed the clinical and laboratory features of 515 patients with NHAP admitted to our hospital over an 11-year period. Blood cultures were obtained from 336 patients (65.2%). We compared 13 and 323 patients with positive and negative blood cultures, respectively. The former showed lower systolic blood pressure and higher blood urea nitrogen (BUN), creatinine, C-reactive protein (CRP), and A-DROP scores than the latter. With regard to A-DROP parameters, patients with positive blood cultures showed significantly higher rates of dehydration (BUN ≥ 21 mg/dL) and low blood pressure (systolic blood pressure ≤ 90 mmHg). Multivariate analysis identified CRP values and low blood pressure as independent predictors of bacteremia: CRP (odds ratio [OR] 1.11; 95% confidence interval [CI] 1.04-1.19, P = 0.003) and low blood pressure (OR 6.03; 95% CI 1.06-34.25, P = 0.04). A receiver operating characteristic curve indicated that CRP was of moderate accuracy (area under the curve = 0.75), and its diagnostic accuracy was optimal at a cut-off point of 19.2 mg/dL (sensitivity 69%, specificity 87%). Since the probability of true bacteremia is very low in NHAP, obtaining blood cultures from all patients with NHAP is unnecessary. However, our results suggest blood cultures are warranted from patients with high CRP values (≥20 mg/dL) or low blood pressure.

Implementation of an empirical antimicrobial protocol in a critical care setting: A single-center retrospective observational cohort study in bacteremic patients.

In the treatment of severe infections in critical care settings, the selection of initial empirical antimicrobials affects patient outcomes and antimicrobial overuse. The application of a comprehensive treatment guidance might facilitate appropriate antimicrobial selection. Therefore, we developed such an antimicrobial guidance for use in emergency and critical care center and verified its efficacy. We retrospectively analyzed the data of 195 patients (96 patients before guidance introduction [control group] and 99 after guidance introduction [intervention group]) who were ultimately diagnosed with bacteremia to assess the effects of the guidance (the intervention). The appropriateness of the empirical therapy was greater in the intervention than in the control group (96% vs. 90%, respectively; P = 0.10). Moreover, the rate of carbapenem use was significantly lower in the intervention than in the control group (6% vs. 20%, respectively; P < 0.01). The control and intervention groups had similar 28-day survival rates of 81% and 85%, respectively; P = 0.50). These findings imply that introducing an empirical antimicrobial guidance in emergency outpatient and emergency intensive care settings could improve antimicrobial stewardship without affecting patient mortality. The data of this study can be used as a reference for establishing the study design of a large-scale prospective trial, aimed at verifying guidance efficacy.

Comprehensive analysis of prognostic factors in hospitalized patients with pneumonia occurring outside hospital: Serum albumin is not less important than pneumonia severity assessment scale.

PURPOSE: This study aimed to elucidate factors related to 30-day mortality of pneumonia occurring outside hospital by comprehensively analyzing data considered relevant to prognosis. METHODS: Data considered relevant to prognosis were retrospectively examined from clinical charts and chest X-ray images of all patients with pneumonia occurring outside hospital admitted to our hospital from 2010 to 2016. The primary outcome was 30-day mortality. RESULTS: Data were collected from 534 patients (317 community-acquired pneumonia and 217 nursing- and healthcare associated pneumonia patients; 338 men (63.3%); mean age, 76.2 years-old). Eighty-three patients (9.9%) died from pneumonia within 30 days from the date of admission. The numbers of patients with pneumonia severity index (PSI) classes of I/II/III/IV/V and age, dehydration, respiratory failure, orientation disturbance, pressure (A-DROP) scores of 0/1/2/3/4/5 were 29/66/127/229/83, and 71/107/187/132/30/7, respectively. Mean (standard deviation) body mass index (BMI), serum albumin, blood procalcitonin, white blood cell and C-reactive protein were 20.00 (4.12) kg/m2, 3.16 (0.60) g/dL, 3.69 (13.15) ng/mL, 11559.4 (5656.9)/mm3, and 10.92 (8.75) mg/dL, respectively. Chest X-ray images from 152 patients exhibited a pneumonia shadow over a quarter of total lung field. Logistic regression analysis revealed that PSI class or A-DROP score, BMI, serum albumin, and extent of pneumonia shadow were related to 30-day mortality. Receiver operating characteristics curve analysis revealed that serum albumin was superior to PSI class or A-DROP score for predicting 30-day mortality. CONCLUSION: Serum albumin is not less important than PSI class or A-DROP score for predicting 30-day mortality in hospitalized patients with pneumonia occurring outside hospital.

Early Expansion of Circulating Granulocytic Myeloid-derived Suppressor Cells Predicts Development of Nosocomial Infections in Patients with Sepsis.

RATIONALE: Sepsis induces a sustained immune dysfunction responsible for poor outcome and nosocomial infections. Myeloid-derived suppressor cells (MDSCs) described in cancer and inflammatory processes may be involved in sepsis-induced immune suppression, but their clinical impact remains poorly defined. OBJECTIVES: To clarify phenotype, suppressive activity, origin, and clinical impact of MDSCs in patients with sepsis. METHODS: Peripheral blood transcriptomic analysis was performed on 29 patients with sepsis and 15 healthy donors. A second cohort of 94 consecutive patients with sepsis, 11 severity-matched intensive care patients, and 67 healthy donors was prospectively enrolled for flow cytometry and functional experiments. MEASUREMENTS AND MAIN RESULTS: Genes involved in MDSC suppressive functions, including S100A12, S100A9, MMP8, and ARG1, were up-regulated in the peripheral blood of patients with sepsis. CD14posHLA-DRlow/neg monocytic (M)-MDSCs were expanded in intensive care unit patients with and without sepsis and CD14negCD15pos low-density granulocytes/granulocytic (G)-MDSCs were more specifically expanded in patients with sepsis (P < 0.001). Plasma levels of MDSC mediators S100A8/A9, S100A12, and arginase 1 were significantly increased. In vitro, CD14pos- and CD15pos-cell depletion increased T-cell proliferation in patients with sepsis. G-MDSCs, made of immature and mature granulocytes expressing high levels of degranulation markers, were specifically responsible for arginase 1 activity. High initial levels of G-MDSCs, arginase 1, and S100A12 but not M-MDSCs were associated with subsequent occurrence of nosocomial infections. CONCLUSIONS: M-MDSCs and G-MDSCs strongly contribute to T-cell dysfunction in patients with sepsis. More specifically, G-MDSCs producing arginase 1 are associated with a higher incidence of nosocomial infections and seem to be major actors of sepsis-induced immune suppression.

The Host Response in Patients with Sepsis Developing Intensive Care Unit-acquired Secondary Infections.

RATIONALE: Sepsis can be complicated by secondary infections. We explored the possibility that patients with sepsis developing a secondary infection while in the intensive care unit (ICU) display sustained inflammatory, vascular, and procoagulant responses. OBJECTIVES: To compare systemic proinflammatory host responses in patients with sepsis who acquire a new infection with those who do not. METHODS: Consecutive patients with sepsis with a length of ICU stay greater than 48 hours were prospectively analyzed for the development of ICU-acquired infections. Twenty host response biomarkers reflective of key pathways implicated in sepsis pathogenesis were measured during the first 4 days after ICU admission and at the day of an ICU-acquired infection or noninfectious complication. MEASUREMENTS AND MAIN RESULTS: Of 1,237 admissions for sepsis (1,089 patients), 178 (14.4%) admissions were complicated by ICU-acquired infections (at Day 10 [6-13], median with interquartile range). Patients who developed a secondary infection showed higher disease severity scores and higher mortality up to 1 year than those who did not. Analyses of biomarkers in patients who later went on to develop secondary infections revealed a more dysregulated host response during the first 4 days after admission, as reflected by enhanced inflammation, stronger endothelial cell activation, a more disturbed vascular integrity, and evidence for enhanced coagulation activation. Host response reactions were similar at the time of ICU-acquired infectious or noninfectious complications. CONCLUSIONS: Patients with sepsis who developed an ICU-acquired infection showed a more dysregulated proinflammatory and vascular host response during the first 4 days of ICU admission than those who did not develop a secondary infection.

Host and Pathogen Biomarkers for Severe Pseudomonas aeruginosa Infections.

Pseudomonas aeruginosa is among the leading causes of severe nosocomial infections, particularly affecting critically ill and immunocompromised patients. Here we review the current knowledge on the factors underlying the outcome of P. aeruginosa nosocomial infections, including aspects related to the pathogen, the host, and treatment. Intestinal colonization and previous use of antibiotics are key risk factors for P. aeruginosa infections, whereas underlying disease, source of infection, and severity of acute presentation are key host factors modulating outcome; delayed adequate antimicrobial therapy is also independently associated with increased mortality. Among pathogen-related factors influencing the outcome of P. aeruginosa infections, antibiotic resistance, and particularly multidrug-resistant profiles, is certainly of paramount relevance, given its obvious effect on the chances of appropriate empirical therapy. However, the direct impact of antibiotic resistance in the severity and outcomes of P. aeruginosa infections is not yet well established. The interplay between antibiotic resistance, virulence, and the concerning international high-risk clones (such as ST111, ST175, and ST235) still needs to be further analyzed. On the other hand, differential presence or expression of virulence factors has been shown to significantly impact disease severity and mortality. The likely more deeply studied P. aeruginosa virulence determinant is the type III secretion system (T3SS); the production of T3SS cytotoxins, and particularly ExoU, has been well established to determine a worse outcome both in respiratory and bloodstream infections. Other relevant pathogen-related biomarkers of severe infections include the involvement of specific clones or O-antigen serotypes, the presence of certain horizontally acquired genomic islands, or the expression of other virulence traits, such as the elastase. Finally, recent data suggest that host genetic factors may also modulate the severity of P. aeruginosa infections.

Antibiotic dosing for multidrug-resistant pathogen pneumonia.

PURPOSE OF REVIEW: Nosocomial pneumonia caused by multidrug-resistant pathogens is increasing in the ICU, and these infections are negatively associated with patient outcomes. Optimization of antibiotic dosing has been suggested as a key intervention to improve clinical outcomes in patients with nosocomial pneumonia. This review describes the recent pharmacokinetic/pharmacodynamic data relevant to antibiotic dosing for nosocomial pneumonia caused by multidrug-resistant pathogens. RECENT FINDINGS: Optimal antibiotic treatment is challenging in critically ill patients with nosocomial pneumonia; most dosing guidelines do not consider the altered physiology and illness severity associated with severe lung infections. Antibiotic dosing can be guided by plasma drug concentrations, which do not reflect the concentrations at the site of infection. The application of aggressive dosing regimens, in accordance to the antibiotic's pharmacokinetic/pharmacodynamic characteristics, may be required to ensure rapid and effective drug exposure in infected lung tissues. SUMMARY: Conventional antibiotic dosing increases the likelihood of therapeutic failure in critically ill patients with nosocomial pneumonia. Alternative dosing strategies, which exploit the pharmacokinetic/pharmacodynamic properties of an antibiotic, should be strongly considered to ensure optimal antibiotic exposure and better therapeutic outcomes in these patients.

The current status of biomarkers for the diagnosis of nosocomial pneumonias.

PURPOSE OF REVIEW: Nosocomial pneumonia is a frequent and severe nosocomial infection divided in two distinct groups: hospital-acquired pneumonia and ventilator-associated pneumonia (VAP). In this context, the VAP is notoriously difficult to diagnose clinically, resulting from the lack of a 'gold standard' method of diagnosis. RECENT FINDINGS: The use of biomarkers may potentially improve the early diagnosis of infections allowing earlier and better identification and treatment. An exhausting list of biomarkers has been studied and although far from perfect, procalcitonin (PCT) and C-reactive protein (CRP) are the most studied biomarkers used in clinical practice. Data coming from literature suggests the use of PCT for VAP prognosis and as a based algorithm tool for the reduction of duration of pneumonia therapy, as well as, the use of the CRP dynamics to the early prediction of VAP and the response to the antibiotics. SUMMARY: The evidence for the use of biomarkers to diagnose nosocomial pneumonia as a stand-alone tool is low to moderate. Improved performance for both PCT and CRP can be obtained by using them in association with clinical features or scoring systems but prospective studies are still needed to validate this hypothesis.