Ahmad Alhajhusain

Update on the treatment of Pseudomonas aeruginosa pneumonia

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.

Clinical outcomes of type III Pseudomonas aeruginosa bacteremia.

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 3 secretion system has been implicated with more acute and invasive infection in respiratory diseases. However, the relationship between the type 3 secretion system and clinical outcomes in P. aeruginosa bacteremia has not been investigated. Objectives:To determine the association between the type 3 secretion system virulence factor in P. aeruginosa bloodstream 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 3 exotoxins (ExoU, ExoT, and ExoS). Strain relatedness was analyzed using randomly amplified polymorphic DNA polymerase chain reaction genotyping. Antimicrobial susceptibilities were determined by means of the Kirby-Bauer disk-diffusion test. Measurements and Main Results:At least one of the type 3 secretion system proteins was detected in 37 out of the 85 isolates (44%). Septic shock was identified in 43% of bacteremic patients with type 3 secretion system+ isolates compared to 23% of patients with type 3 secretion system– isolates (p = .12). A high frequency of resistance in the type 3 secretion system+ isolates was observed to ciprofloxacin (59%), cefepime (35%), and gentamicin (38%). There was a significant difference in the 30-day cumulative probability of death after bacteremia between secretors and nonsecretors (p = .02). None of the type 3 secretion system+ patients who survived the first 30 days had a P. aeruginosa isolate which exhibited ExoU phenotype. Conclusions:The expression of type 3 secretion system exotoxins in bacteremic isolates of P. aeruginosa confers poor clinical outcomes independent of antibiotic susceptibility profile. (Crit Care Med 2012; 40:–1163)

Validity of Severity Scores in Hospitalized Patients With Nursing Home-Acquired Pneumonia

BACKGROUND Several severity scores have been advanced to predict a patients outcome from community-acquired pneumonia (CAP). The purpose of this study is to compare the accuracy of confusion, urea, respiratory rate, BP (CURB); CURB plus age ≥ 65 years (CURB-65); CURB-65 minus urea (CRB-65); and systolic BP, oxygenation, age, and respiratory rate (SOAR) scoring systems in predicting 30-day mortality and ICU admission in patients with nursing home-acquired pneumonia (NHAP). METHODS A retrospective analysis of a prospectively collected database of 457 nursing home residents hospitalized with pneumonia at two university-affiliated tertiary care facilities. Clinical and laboratory features were used to compute severity scores using the British Thoracic Society severity rules and the SOAR criteria. The sensitivity, specificity, and positive and negative predictive values were compared for need for ICU admission and 30-day mortality. RESULTS The overall 30-day mortality and ICU admission rates were 23% and 25%, respectively. CURB, CURB-65, and CRB-65 performed similarly in predicting mortality with areas under the receiver operating characteristic curves (AUCs) of 0.605 (95% CI, 0.559-0.650), 0.593 (95% CI, 0.546-0.638), and 0.592 (95% CI, 0.546-0.638), respectively, whereas SOAR showed superior accuracy with an AUC of 0.765 (95% CI, 0.724-0.803) (P < .001). The need for ICU care was also better identified with the SOAR model compared with the other scoring rules. CONCLUSIONS All three British Thoracic Society rules had lower performance accuracy in predicting 30-day mortality of hospitalized NHAP than SOAR. SOAR is also a superior alternative for better identification of severe NHAP. An improved rule for severity assessment of hospitalized NHAP is needed.

Matrix metalloproteases in bronchoalveolar lavage fluid of patients with type III Pseudomonas aeruginosa pneumonia

OBJECTIVES In patients with ventilator-associated pneumonia (VAP), Pseudomonas aeruginosa type III (TTSS) secreting isolates have been linked 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 alpha-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 alpha-2 macroglobulin at end of therapy (r=0.4, p=0.02). Patients who survived had a lower MMP-9/TIMP-1 ratio 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 P. aeruginosa VAP.

Hyperuricemia: An Early Marker for Severity of Illness in Sepsis

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.

Timing of Tracheotomy in Mechanically Ventilated Critically Ill Morbidly Obese Patients

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.