An optimal therapy for the treatment of pneumonia caused by drug-resistant Acinetobacter baumannii remains unclear. This study aims to compare various antimicrobial strategies and to determine the most effective therapy for pneumonia using a network meta-analysis. Systematic search and quality assessment were performed to select eligible studies reporting one of the following outcomes: all-cause mortality, clinical cure, and microbiological eradication. The primary outcome was all-cause mortality. A network meta-analysis was conducted with a Bayesian approach. Antimicrobial treatments were ranked based on surface under the cumulative ranking curve (SUCRA) value along with estimated median outcome rate and corresponding 95% credible intervals (CrIs). Two treatments were considered significantly different if a posterior probability of superiority (P) was greater than 97.5%. Twenty-three studies evaluating 15 antimicrobial treatments were included. Intravenous colistin monotherapy (IV COL) was selected as a common comparator, serving as a bridge for developing the network. Five treatments ranked higher than IV COL (SUCRA, 57.1%; median all-cause mortality 0.45, 95% CrI 0.41–0.48) for reducing all-cause mortality: sulbactam monotherapy (SUL, 100.0%; 0.18, 0.04–0.42), high-dose SUL (HD SUL, 85.7%; 0.31, 0.07–0.71), fosfomycin plus IV COL (FOS + IV COL, 78.6%; 0.34, 0.19–0.54), inhaled COL plus IV COL (IH COL + IV COL, 71.4%; 0.39, 0.32–0.46), and high-dose tigecycline (HD TIG, 71.4%; 0.39, 0.16–0.67). Those five treatments also ranked higher than IV COL (SUCRA, 45.5%) for improving clinical cure (72.7%, 72.7%, 63.6%, 81.8%, and 90.9%, respectively). Among the five treatments, SUL (P = 98.1%) and IH COL + IV COL (P = 99.9%) were significantly superior to IV COL for patient survival and clinical cure, respectively. In terms of microbiological eradication, FOS + IV COL (P = 99.8%) and SUL (P = 98.9%) were significantly superior to IV COL. This Bayesian network meta-analysis demonstrated the comparative effectiveness of fifteen antimicrobial treatments for drug-resistant A. baumannii pneumonia in critically ill patients. For survival benefit, SUL appears to be the best treatment followed by HD SUL, FOS + IV COL, IH COL + IV COL, HD TIG, and IV COL therapy, in numerical order.

Objectives: The objective of this study was to investigate the association between genetic polymorphisms of N-acetyltransferase 2 ( NAT2) , cytochrome P450 2E1 ( CYP2E1) , glutathione S-transferase ( GST) and solute carrier organic anion transporter family member 1B1 ( SLCO1B1) and the risk of anti-tuberculosis drug-induced liver injury (ATDILI). Design: Systematic review and meta-analysis. Data sources: PubMed, Embase, Web of Science and Cochrane Reviews databases were searched through April 2019. Eligibility criteria: We included case-control or cohort studies investigating an association between NAT2, CYP2E1, GST or SLCO1B1 polymorphisms and the ATDILI risk in patients with tuberculosis. Data extraction and synthesis: Three authors screened articles, extracted data and assessed study quality. The strength of association was evaluated for each gene using the pooled OR with a 95% CI based on the fixed-effects or random-effects model. Sensitivity analysis was performed to confirm the reliability and robustness of the results. Results: Fifty-four studies were included in this analysis (n=26 for CYP2E1 , n=35 for NAT2 , n=19 for GST , n=4 for SLCO1B1 ). The risk of ATDILI was significantly increased with the following genotypes: CYP2E1 Rsa I /Pst I c1/c1 (OR=1.39, 95% CI 1.06 to 1.83), NAT2 slow acetylator (OR=3.30, 95% CI 2.65 to 4.11) and GSTM1 null (OR=1.30, 95% CI 1.12 to 1.52). No significant association with ATDILI was found for the genetic polymorphisms of CYP2E1 Dra I, GSTT1 , GSTM1/GSTT1 , SLCO1B1 388A>G and SLCO1B1 521T>C (p>0.05). Conclusions: ATDILI is more likely to occur in patients with NAT2 slow acetylator genotype, CYP2E1 RsaI/PstI c1/c1 genotype and GSTM1 null genotype. Close monitoring may be warranted for patients with these genotypes.

The conservative single-layered wound dressing system is decomposed when mixed in polyvinyl alcohol (PVA) solution, which means it cannot be used with a temperature-sensitive drug. The goal of this investigation was to make an amniotic membrane extract (AME)-loaded double-layered wound dressing with an improved healing result compared to the conservative single-layered wound dressing systems. The double-layered wound dressing was developed with PVA/sodium alginate using a freeze–melting technique; one layer was PVA layer and the other was the drug-loaded sodium alginate layer. Its gel properties were assessed compared to single-layered wound dressings. Moreover, in vivo wound-healing effects and histopathology were calculated compared to commercial products. The double-layered wound dressing gave a similar gel fraction and Young’s module as single-layered wound bandages developed with only PVA, and a similar inflammation ability and WVTR as single-layered wound dressings developed with PVA and sodium alginate. Our data indicate that these double-layered wound bandages were just as swellable, but more elastic and stronger than single-layered wound dressings comprised of the same polymers and quantities, possibly giving an acceptable level of moisture and accumulation of exudates in the wound zone. Compared to the commercial product, the double-layered wound dressing comprising 6.7% PVA, 0.5% sodium alginate and 0.01% AME significantly enhanced the wound-healing effect in the wound-healing test. Histological investigations showed that superior full-thickness wound-healing effects compared to the commercial product. Therefore, the double-layered wound dressing would be an outstanding wound-dressing system with improved wound healing and good gel property.