Background Pseudomonas aeruginosa bacteremia is a serious and life-threatening infection associated with high mortality. Among the multitude of virulence determinants possessed by P. aeruginosa, the type III secretion system (TTSS) has been implicated with more acute and invasive infection in respiratory diseases. However, the relationship between TTSS and clinical outcomes in P. aeruginosa bacteremia has not been investigated. Objectives To determine the association between the TTSS virulence factor in P. aeruginosa blood stream infection and 30-day mortality. Design Retrospective analysis of 85 cases of P. aeruginosa bacteremia. Setting Tertiary care hospital. Interventions Bacterial isolates were assayed in vitro for secretion of type III exotoxins (ExoU, ExoT, and ExoS). Strain-relatedness was analyzed using randomly amplified polymorphic DNA PCR genotyping. Antimicrobial susceptibilities were determined by means of the Kirby-Bauer disk-diffusion test. Measurements and Main results At least one of the TTSS proteins was detected in 37 out of the 85 isolates (44%). Septic shock was identified in 43% of bacteremic patients with TTSS+ isolates compared to 23% of patients with TTSS− isolates (p=0.12). A high frequency of resistance in the TTSS+ isolates was observed to ciprofloxacin (59%), cefipime (35%), and gentamycin (38%). There was a significant difference in the 30-day cumulative probability of death after bacteremia between secretors and nonsecretors (p=0.02). None of the TTSS+ patients who survived the first 30 days had a P. aeruginosa isolate which exhibited ExoU phenotype. Conclusions The expression of TTSS exotoxins in bacteremic isolates of P. aeruginosa confers poor clinical outcomes independent of antibiotic susceptibility profile.

Pseudomonas aeruginosa is an important cause of nosocomial pneumonia associated with a high morbidity and mortality rate. This bacterium expresses a variety of factors that confer resistance to a broad array of antimicrobial agents. Empirical antibiotic therapy is often inadequate because cultures from initial specimens grow strains that are resistant to initial antibiotics. Surveillance data, hospital antibiogram and individualization of regimens based on prior antibiotic use may reduce the risk of inadequate therapy. The use of combination therapies for P. aeruginosa pneumonia has been a long-advocated practice, but the potential increased value of combination therapy over monotherapy remains controversial. Doripenem and biapenem are new carbapenems that have excellent activity against P. aeruginosa; however, they lack activity against strains that express resistance to the currently available carbapenems. The polymyxins remain the most consistently effective agents against multidrug-resistant P. aeruginosa. Strains that are panantibiotic-resistant are rare, but their incidence is increasing. Antibiotic combinations that yield some degree of susceptibility in vitro are the recourse, although the efficacy of these regimens has yet to be established in clinical studies. Experimental polypeptides may provide a new therapeutic approach. Among these, the anti-PcrV immunoglobulin G antibody that blocks the type III secretion system-mediated virulence of P. aeruginosa has recently entered Phase I/II clinical trials.

Background. Uric acid can acutely activate various inflammatory transcription factors. Since high levels of oxyradicals and lower antioxidant levels in septic patients are believed to result in multiorgan failure, uric acid levels could be used as a marker of oxidative stress and poor prognosis in patients with sepsis. Design. We conducted a prospective cohort study on Medical Intensive Care Unit (MICU) patients and hypothesized that elevated uric acid in patients with sepsis is predictive of greater morbidity. The primary end point was the correlation between hyperuricemia and the morbidity rate. Secondary end points were Acute Kidney Injury (AKI), mortality, Acute Respiratory Distress Syndrome (ARDS), and duration of stay. Results. We enrolled 144 patients. 54 (37.5%) had the primary end point of hyperuricemia. The overall morbidity rate was 85.2%. The probability of having hyperuricemia along with AKI was 68.5% and without AKI was 31.5%. Meanwhile the probability of having a uric acid value <7 mg/dL along with AKI was 18.9% and without AKI was 81.1% (p value < 0.0001). Conclusion. We report that elevated uric acid levels on arrival to the MICU in patients with sepsis are associated with poor prognosis. These patients are at an increased risk for AKI and ARDS.

No abstract

No abstract

Background. The optimal timing of tracheotomy and its impact on weaning from mechanical ventilation in critically ill morbidly obese patients remain controversial. Methods. We conducted a retrospective chart review of morbidly obese subjects (BMI ≥ 40 kg/m2 or BMI ≥ 35 kg/m2 and one or more comorbid conditions) who underwent a tracheotomy between July 2008 and June 2013 at a medical intensive care unit (ICU). Clinical characteristics, rates of nosocomial pneumonia (NP), weaning from mechanical ventilation (MV), and mortality rates were analyzed. Results. A total of 102 subjects (42 men and 60 women) were included; their mean age and BMI were 56.3 ± 15.1 years and 53.3 ± 13.6 kg/m2, respectively. There was no difference in the rate of NP between groups stratified by successful weaning from MV (P = 0.43). Mortality was significantly higher in those who failed to wean (P = 0.02). A cutoff value of 9 days for the time to tracheotomy provided the best balanced sensitivity (72%) and specificity (59.8%) for predicting NP onset. Rates of NP and total duration of MV were significantly higher in those who had tracheostomy ≥ 9 days (P = 0.004 and P = 0.002, resp.). Conclusions. The study suggests that tracheotomy in morbidly obese subjects performed within the first 9 days may reduce MV and decrease NP but may not affect hospital mortality.

SUMMARY Objectives In patients with ventilator associated pneumonia (VAP), Pseudomonas aeruginosa type III (TTSS) secreting isolates have been li nked to poor clinical outcomes. Differential expression of matrix metalloproteinases (MMPs) induced by type III effector proteins may herald an irreversible lung injury. Methods Serial bronchoalveolar lavage fluids collected from 41 patients with P. aeruginosa at onset of VAP, day 4, and day 8 after antibiotic therapy were assayed for MMP-8, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and α-2 macroglobulin levels. Results At the onset of VAP, isolates secreting ExoU had the highest MMP-9 levels. The response to antimicrobial therapy showed a differential drop in MMPs with significant decrease in MMP-8 and MMP-9 levels on days 4 and 8 in patients with TTSS− compared to TTSS+ phenotype. The ratio of MMP-9/TIMP-1 was significantly associated with α-2 macroglobulin at end of therapy (r=0.4, p=0.02). Patients who survived had a lower MMP-9/TIMP-1ratio than those who died (p=0.003). Conclusions VAP linked to P. aeruginosa Type III phenotype portrays a divergent antibiotic treatment response in regards to the concentrations of metalloproteinases in the alveolar space. The imbalance between MMP-9 and TIMP-1 may determine the intensity of alveolocapillary damage and ultimate outcome of Pseudomonas aeruginosa VAP.

Cigarette smoking is the leading cause of chronic obstructive pulmonary disease (COPD) worldwide. Smoking cessation is thus integral to the treatment of COPD. Nicotine addiction is a disease dependent on the complex interactions of neurotransmitter pathways, conditioned behaviors, environmental cues, genetic predisposition, and personal life circumstances, which render some more susceptible to tobacco abuse than others. The most successful smoking cessation programs are individualized, comprehensive, and utilize combinations of clinician counseling, behavioral reinforcement, community resources, advanced technology support (eg, smartphone apps, and Internet Web sites), and pharmacotherapy (both nicotine-based and nonnicotine medications). E-cigarettes were introduced to the US market in 2006 and touted as a safer alternative to tobacco cigarette smoking. Unfortunately, over the last 5 to 10 years, recreational e-cigarette use, or “vaping,” has increased in popularity, especially among adolescents. This has introduced nicotine addiction to an entire generation of nonsmokers and resulted in numerous cases of acute lung disease, now known as e-cigarette or vape product use-associated lung injury (EVALI). In light of these adverse events, e-cigarettes and vape products are not currently recommended as a smoking cessation aid.