Airway Pseudomonas aeruginosa density in mechanically ventilated patients: clinical impact and relation to therapeutic efficacy of antibiotics

Abstract

Background The bacterial density of Pseudomonas aeruginosa is closely related to its pathogenicity. We evaluated the effect of airway P. aeruginosa density on the clinical course of mechanically ventilated patients and the therapeutic efficacy of antibiotics. Methods We retrospectively analyzed data of mechanically ventilated ICU patients with P. aeruginosa isolated from endotracheal aspirates. Patients were divided into three groups according to the peak P. aeruginosa density during ICU stay: low (≤ 104 cfu/mL), moderate (105‒106 cfu/mL), and high (≥ 107 cfu/mL) peak density groups. The relationship between peak P. aeruginosa density and weaning from mechanical ventilation, risk factors for isolation of high peak density of P. aeruginosa, and antibiotic efficacy were investigated using multivariate and propensity score-matched analyses. Results Four-hundred-and-sixty-one patients were enrolled. Patients with high peak density of P. aeruginosa had higher inflammation and developed more severe respiratory infections. High peak density of P. aeruginosa was independently associated with few ventilator-free days on day 28 (P < 0.01) and increased ICU mortality (P = 0.047). Risk factors for high peak density of P. aeruginosa were prolonged mechanical ventilation (odd ratio [OR] 3.07 95% confidence interval [CI] 1.35‒6.97), non-antipseudomonal cephalosporins (OR 2.17, 95% CI 1.35‒3.49), hyperglycemia (OR 2.01, 95% CI 1.26‒3.22) during ICU stay, and respiratory diseases (OR 1.9, 95% CI 1.12‒3.23). Isolation of commensal colonizer was associated with lower risks of high peak density of P. aeruginosa (OR 0.43, 95% CI 0.26‒0.73). Propensity score-matched analysis revealed that antibiotic therapy for patients with ventilator-associated tracheobronchitis improved weaning from mechanical ventilation only in the high peak P. aeruginosa group. Conclusions Patients with high peak density of P. aeruginosa had worse ventilator outcome and ICU mortality. In patients with ventilator-associated tracheobronchitis, antibiotic therapy was associated with favorable ventilator weaning only in the high peak P. aeruginosa density group, and bacterial density could be a good therapeutic indicator for ventilator-associated tracheobronchitis due to P. aeruginosa.

Limitations of Antibiotic MIC-Based PK-PD Metrics: Looking Back to Move Forward

“…The MIC is a very crude in vitro measure of the "potency" of an antibiotic that is determined in a matrix bearing little resemblance to the physiological milieu at an infection site in a patient. A low inoculum is used in the measurement of MIC; for example, in the broth microdilution assay, a small volume of an inoculum of 5 × 10 5 CFU/mL is used which may be quite different from the bacterial density prevailing in an infected patient (Migiyama et al, 2021). In addition, the small total number of bacterial cells placed into each microplate well lowers the probability of less-susceptible subpopulations being present at the start of the incubation.…”

Outcomes of Mechanically Ventilated Patients With Nosocomial Tracheobronchitis

“…Furthermore, a study by Migiyama et al looked at the risk factors leading to high Pseudomonas aeruginosa density in mechanically ventilated patients [16]. Hyperglycemia was found as a risk factor for high Pseudomonas aeruginosa density along with prolonged mechanical ventilation greater than 28 days and respiratory disorders that were diagnosed when admitted to the ICU.…”

Facemask analyses for the non-invasive detection of chronic and acute P. aeruginosa lung infections using nanoparticle-based immunoassays

“…Furthermore, the diagnosis is often based on a yes/no result (above/below a certain threshold value) because a quantitative sputum culture takes even longer, and because of this, antibiotics are not personalized according to bacterial load. 15,16 In this scenario, inadequate antibiotic coverage risks selecting the hypermuta-ble mucoid strains, whereas abusing last-generation antibiotic exacerbates antimicrobial resistant issues in the long term.…”

“…This, along with the high specificity afforded by the use of antibodies as recognition elements, overcomes the qualitative detection of Pseudomonas with electronic noses [19][20][21] and paves the way to personalize antibiotics according to bacterial load. 15,16 The proposed technology makes it easy to screen patients for Pseudomonas infections, even when they cannot produce sputum spontaneously. In turn, this will allow clinicians to fine-tune antibiotics depending on the presence of this superbug, thus changing the current prescription paradigm from empirical to evidence-based.…”