ABSTRACT
AIM: To describe and evaluate the clinical characteristics, treatment management and clinical outcomes of ceftazidime-avibactam (CZA) in the treatment of patients with multidrug-resistant gram-negative bacterial (MDR-GNB) infections. METHODS: A retrospective cohort study was performed on patients hospitalized in the Affiliated Hospital of Xuzhou Medical University from September 2019 to December 2021. Adult patients who received CZA for ≥ 72 hours consecutively were eligible for inclusion. The primary outcome was clinical failure, defined as a composite of 30-day all-cause mortality, microbiological failure and / or failure to resolve or improve signs and symptoms of infection during treatment with CZA. RESULTS: A total of 198 patients with MDR-GNB infections were described and evaluated, including 132 in the carbapenem-resistant Enterobatceriaceae (CRE) cohort and 66 in the Pseudomonas spp. cohort. The main infection sites were lung infection (92.42%), abdominal infection (10.61%), and intracranial infection (10.61%), among which 63 patients (31.82%) were positive for blood culture. Clinical failure, 30-day all-cause mortality and microbiological failure occurred in 61 (30.81%), 33(16.67%) and 11(5.56%) patients, respectively. Body mass index (BMI), acute physiology and chronic health evaluation scoring system (APACHE Ⅱ) and polymicrobial infections were positively associated with clinical outcome failureadjusted OR 1.109, 95%CI 1.017, 1.209; adjusted OR 1.071, 95%CI 1.015, 1.129; adjusted OR 2.844, 95%CI 1.391, 5.814, however, initiation of CZA within 48 hours of admission was protective (adjusted OR 0.424, 95%CI 0.205, 0.879). A total of 15 patients had adverse reactions possibly related to CZA, including 2 cases of rash, 6 cases of nausea and vomiting, and 7 cases of antibiotic-related diarrhea. CONCLUSION: CZA can be used to treat infections caused by a range of MDR-GNB, including Pseudomonas spp. and CRE.
ABSTRACT
The present study aimed to explore the neuroprotective effect and possible mechanisms of rhGLP-1 (7–36) against transient ischemia/reperfusion injuries induced by middle cerebral artery occlusion (MCAO) in type 2 diabetic rats. First, diabetic rats were established by a combination of a high-fat diet and low-dose streptozotocin (STZ) (30 mg/kg, intraperitoneally). Second, they were subjected to MCAO for 2 h, then treated with rhGLP-1 (7–36) (10, 20, 40 µg/kg i.p.) at the same time of reperfusion. In the following 3 days, they were injected with rhGLP-1 (7–36) at the same dose and route for three times each day. After 72 h, hypoglycemic effects were assessed by blood glucose changes, and neuroprotective effects were evaluated by neurological deficits, infarct volume and histomorphology. Mechanisms were investigated by detecting the distribution and expression of the nuclear factor erythroid-derived factor 2 related factor 2 (Nrf2) in ischemic brain tissue, the levels of phospho-PI3 kinase (PI3K)/PI3K ratio and heme-oxygenase-1 (HO-l), as well as the activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA). Our results showed that rhGLP-1 (7–36) significantly reduced blood glucose and infarction volume, alleviated neurological deficits, enhanced the density of surviving neurons and vascular proliferation. The nuclear positive cells ratio and expression of Nrf2, the levels of P-PI3K/PI3K ratio and HO-l increased, the activities of SOD increased and the contents of MDA decreased. The current results indicated the protective effect of rhGLP-1 (7–36) in diabetic rats following MCAO/R that may be concerned with reducing blood glucose, up-regulating expression of Nrf2/HO-1 and increasing the activities of SOD.