ObjectiveTo systematically review the efficacy and safety of extended or continuous intravenous infusion (EI/CI) versus short-term intravenous infusion (STI) of imipenem/meropenem in adult patients with severe lung infection. MethodsWe electronically searched databases including PubMed, EMbase, The Cochrane Library (Issue 6, 2015) and CBM from inception to June, 2015, to collect random controlled trials (RCTs) about EI/CI versus STI of imipenem/meropenem for severe infection. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.2 software. ResultsA total of 6 RCTs involving 442 patients were included. The results of meta-analysis showed that, compared with the STI group, the EI/CI could significantly improve the microbiological success rate (RR=1.16, 95%CI 1.02 to 1.32, P=0.02) without increasing adverse drug reaction (RR=0.99, 95%CI 0.65 to 1.52, P=0.97). There were no significant differences in clinical effective rate (RR=1.12, 95%CI 0.97 to 1.28, P=0.13), survival rate (RR=1.03, 95%CI 0.92 to 1.16, P=0.62) and hospital stays (MD=-0.43, 95%CI-1.29 to 0.42, P=0.32) between the two groups. Conclusions There is no significant difference in clinical effect between EI/CI and STI for severe lung infection. While, the infections caused by gram-negative bacteria with high MIC could benefit more from EI/CI. Due to the limited quantity and quality of the included studies, the above conclusion still need to be further verified by more high quality studies.
ObjectiveTo explore the relationship between imipenem-resistant Pseudomonas aeruginosa (IRPA) and outer membrane porin protein OprD2 gene mutation.MethodsIRPA strains (n=30) and imipenem-sensitive Pseudomonas aeruginosa strains (n=30) isolated from the clinical specimens in the First Affiliated Hospital of Chengdu Medical College from December 2018 to December 2019 were collected. Bacteria identification and drug sensitivity experiments were performed by VITEK-2 Compact combined with Kirby-Bauer method. Quantitative real-time polymerase chain reaction was used to detect the expression levels of OprD2 gene in the imipenem-resistant group and the imipenem-sensitive group, and then the strains with decreased expression were sequenced.ResultsThe expression level of OprD2 gene in the imipenem-resistant group was significantly lower than that in the imipenem-sensitive group (P=0.048). Compared with the X63152 sequence, all the 11 Pseudomonas aeruginosa strains with significantly decreased OprD2 expression carried genetic variation, which occurred in coding regions. The variation sites presented diversity. The missense mutation of c.308C→G, c.344A→C, c.379G→C, c.471G→C, c.508T→C, c.553G→C, c.556-558CCG→GGC and c.565-566TG→AC caused amino acid change in the loop L2 and L3 of OprD2 porin, which affected the binding to imipenem. In addition, the mutations at 127, 169-171, 175, 177, 604, 628-630, 688, 719, 785, 826, 828, 842-843, 886, 901, 928-930, 934, 936, 944-945, 1039, 1041 and 1274 all resulted in the changes of amino acid. We also detected a deletion (c.1114-1115delAT) and other nonsense mutations. Large fragment deletion of OprD2 gene occurred in Strain 12. ConclusionsThe mutation and deletion of OprD2 gene can reduce the expression lever of OprD2 gene, leading to the resistance to imipenem of Pseudomonas aeruginosa. The variation of OprD2 gene of IRPA from clinical strains is diverse.