Pseudomonas aeruginosa (P. aeruginosa) is a common pathogen isolated from patients with nosocomial infections. Due to its intrinsic and acquired antimicrobial resistance, limited classes of antibiotics can be used for the treatment of infection with P. aeruginosa. Of these, the carbapenems are very important; however, the occurrence of carbapenem-resistant strains is gradually increasing over time. Deficiency of the outer membrane protein OprD confers P. aeruginosa a basal level of resistance to carbapenems, especially to imipenem. Functional studies have revealed that loops 2 and 3 in the OprD protein contain the entrance and/or binding sites for imipenem. Therefore, any mutation in loop 2 and/or loop 3 that causes conformational changes could result in carbapenem resistance. OprD is also a common channel for some amino acids and peptides, and competition with carbapenems through the channel may also occur. Furthermore, OprD is a highly regulated protein at transcriptional and post-transcriptional levels by some metals, small bioactive molecules, amino acids, and efflux pump regulators. Because of its hypermutability and highly regulated properties, OprD is thought to be the most prevalent mechanism for carbapenem resistance in P. aeruginosa. Developing new strategies to combat infection with carbapenem-resistant P. aeruginosa lacking OprD is an ongoing challenge.

Background The lack of knowledge regarding the pathogenesis and host immune response during SARS-CoV-2 infection has limited the development of effective treatments. Thus, we longitudinally investigated the dynamic changes in peripheral blood lymphocyte subsets and parallel changes in cytokine levels in COVID-19 patients with different disease severities to further address disease pathogenesis. Methods A total of 67 patients (10 moderate, 38 severe and 19 critical cases) with COVID-19 admitted to a tertiary care hospital in Wuhan from February 8th to April 6th, 2020 were retrospectively studied. Dynamic data of lymphocyte subsets and inflammatory cytokines were collected. Results On admission, compared with moderate cases, severe and critical cases showed significantly decreased levels of total lymphocytes, T lymphocytes, CD4+ T cells, CD8+ T cells, B cells and NK cells. IL-6 and IL-10 were significantly higher in the critical group. During the following hospitalization period, most of the lymphocyte subsets in the critical group began to recover to levels comparable to those in the severe group from the fourth week after illness onset, except for NK cells, which recovered after the sixth week. A sustained decrease in the lymphocyte subsets and an increase in IL-6 and IL-10 were observed in the nonsurvivors until death. There was a strong negative correlation between IL-6 and IL-10 and total lymphocytes, T lymphocytes, CD4+ T cells, CD8+ T cells and NK cells. Conclusions A sustained decrease in lymphocyte subsets, especially CD4+ T cells and NK cells, interacting with proinflammatory cytokine storms was associated with severe disease and poor prognosis in COVID-19.

Circulating procalcitonin (PCT) is a biomarker that can be used in diagnosing bacterial infections. We performed a quantitative meta-analysis of available randomized controlled trials to determine whether antibiotic therapy based on PCT measurements alters clinical outcomes and antibiotic use in patients with lower respiratory tract infections. We identified studies through MEDLINE (1996 to 2010), the ISI Web of Knowledge (1996 to 2010), and Ovid. Studies that met our criteria were prospective, randomized controlled trials involving patients with respiratory tract infections. Outcomes of mortality, intensive care unit (ICU) admission, length of hospital stay, number of antibiotic prescriptions, and duration of antibiotic treatment were evaluated. Eight studies randomizing 3,431 patients met our criteria for inclusion. Pooled analysis showed a significant reduction in number of antibiotic prescriptions and duration of antibiotic use in patients with PCT-guided antibiotic treatment compared to standard therapy. In addition, the use of PCT-guided antibiotic therapy did not impact mortality, ICU admission, or length of hospital stay in these studies. A high degree of heterogeneity was identified in 3 of 5 outcomes that were evaluated, and sensitivity analysis indicated that heterogeneity was decreased among studies using the same PCT-based treatment algorithm. In conclusion, PCT-guided antibiotic therapy in patients with respiratory tract infections appears to reduce antibiotic use without affecting overall mortality or length of stay in the hospital.

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