Evaluation of Five Host Inflammatory Biomarkers in Early Diagnosis of Ventilator-Associated Pneumonia in Critically Ill Children: A Prospective Single Center Cohort Study.

Background: Early diagnosis of ventilator-associated pneumonia (VAP) remains a challenge due to subjective clinical criteria and the low discriminative power of diagnostic tests. We assessed whether rapid molecular diagnostics in combination with Clinically Pulmonary Index Score (CPIS) scoring, microbiological surveillance and biomarker measurements of PTX-3, SP-D, s-TREM, PTX-3, IL-1ß and IL-8 in the blood or lung could improve the accuracy of VAP diagnosis and follow-up in critically ill children. Methods: A prospective pragmatic study in a Pediatric Intensive Care Unit (PICU) was conducted on ventilated critically ill children divided into two groups: high and low suspicion of VAP according to modified Clinically Pulmonary Index Score (mCPIS). Blood and bronchial samples were collected on days 1, 3, 6 and 12 after event onset. Rapid diagnostics were used for pathogen identification and ELISA for PTX-3, SP-D, s-TREM, IL-1ß and IL-8 measurements. Results: Among 20 enrolled patients, 12 had a high suspicion (mCPIS > 6), and 8 had a low suspicion of VAP (mCPIS < 6); 65% were male; and 35% had chronic disease. IL-1ß levels at day 1 correlated significantly with the number of mechanical ventilation days (rs = 0.67, p < 0.001) and the PICU stay (r = 0.66; p < 0.002). No significant differences were found in the levels of the other biomarkers between the two groups. Mortality was recorded in two patients with high VAP suspicion. Conclusions: PTX-3, SP-D, s-TREM, IL-1ß and IL-8 biomarkers could not discriminate patients with a high or low suspicion of VAP diagnosis.

Infections of respiratory or abdominal origin in ICU patients: what are the differences?

INTRODUCTION: There are few data related to the effects of different sources of infection on outcome. We used the Sepsis Occurrence in Acutely ill Patients (SOAP) database to investigate differences in the impact of respiratory tract and abdominal sites of infection on organ failure and survival. METHODS: The SOAP study was a cohort, multicenter, observational study which included data from all adult patients admitted to one of 198 participating intensive care units (ICUs) from 24 European countries during the study period. In this substudy, patients were divided into two groups depending on whether, on admission, they had abdominal infection but no respiratory infection or respiratory infection but no abdominal infection. The two groups were compared with respect to patient and infection-related characteristics, organ failure patterns, and outcomes. RESULTS: Of the 3,147 patients in the SOAP database, 777 (25%) patients had sepsis on ICU admission; 162 (21%) had abdominal infection without concurrent respiratory infection and 380 (49%) had respiratory infection without concurrent abdominal infection. Age, sex, and severity scores were similar in the two groups. On admission, septic shock was more common in patients with abdominal infection (40.1% vs. 29.5%, P = 0.016) who were also more likely to have early coagulation failure (17.3% vs. 9.5%, P = 0.01) and acute renal failure (38.3% vs. 29.5%, P = 0.045). In contrast, patients with respiratory infection were more likely to have early neurological failure (30.5% vs. 9.9%, P < 0.001). The median length of ICU stay was the same in the two groups, but the median length of hospital stay was longer in patients with abdominal than in those with respiratory infection (27 vs. 20 days, P = 0.02). ICU (29%) and hospital (38%) mortality rates were identical in the two groups. CONCLUSIONS: There are important differences in patient profiles related to the site of infection; however, mortality rates in these two groups of patients are identical.

Use of Tigecycline in Pediatric Patients With Infections Predominantly Due to Extensively Drug-Resistant Gram-Negative Bacteria.

BACKGROUND.: Emergence of extensively drug-resistant (XDR) bacteria has forced clinicians to use off-label antimicrobial agents such as tigecycline. We present our experience on salvage use of tigecycline for the treatment of infections caused by XDR Gram-negative bacteria in critically ill children and review published cases. METHODS.: We conducted a retrospective chart review in pediatric departments of a tertiary level hospital from January 2009 to May 2014. Patients were identified using pharmacy database. For the literature review, relevant articles were identified from PubMed. RESULTS.: In our case series, 13 children (7 males) with a median age of 8 years (range, 2.5 months-14 years) received tigecycline for ≥2 days as treatment for healthcare-associated infections including 5 bacteremias, 6 lower respiratory tract infections, and 3 other infections. Isolated pathogens were XDR Gram-negative bacteria except 1. A loading dose (range, 1.8-6.5 mg/kg) was given in all except 2 cases. Maintenance dose was given at 1-3.2 mg/kg q12 h. Other antimicrobials including colistin and aminoglycosides (85% and 62%, respectively) were coadministered to all patients. No serious adverse events were detected in these very ill children. Twenty cases of children treated with tigecycline were previously published, mostly for multidrug-resistant/XDR bacteria. An episode of acute pancreatitis and neutrophil engraftment delay in 2 cases were reported during tigecycline treatment. Analyzing reported and all our cases together, mortality in bloodstream infections was 86%, whereas in nonbacteremic cases it was 24% (P = .009). CONCLUSIONS.: Tigecycline, given at the range of administered doses as salvage therapy and in combination with other antimicrobial agents, seemed to be well tolerated in a series of mainly critically ill pediatric patients and demonstrated relatively good clinical response in nonbacteremic patients.