Prolonged infusion of fosfomycin 16 - 24g combined with extended carbapenem infusion could be used in non-MDR PA treatment with CRPA.

Background Acinetobacter baumannii has emerged as one of the common multidrug resistance pathogens causing hospital-acquired infections. This study was conducted to elucidate the distribution of antimicrobial resistance genes in the bacterial population in Thailand. Multidrug-resistant A. baumannii (MDR A. baumannii) isolates were characterized phenotypically, and the molecular epidemiology of clinical isolates in 11 tertiary hospitals was investigated at a country-wide level. Methods A total of 135 nonrepetitive MDR A. baumannii isolates collected from tertiary care hospitals across 5 regions of Thailand were examined for antibiotic susceptibility, resistance genes, and sequence types. Multilocus sequence typing (MLST) was performed to characterize the spread of regional lineages. Results ST2 belonging to IC2 was the most dominant sequence type in Thailand (65.19%), and to a lesser extent, there was also evidence of the spread of ST164 (10.37%), ST129 (3.70%), ST16 (2.96%), ST98 (2.96%), ST25 (2.96%), ST215 (2.22%), ST338 (1.48%), and ST745 (1.48%). The novel sequence types ST1551, ST1552, ST1553, and ST1557 were also identified in this study. Among these, the blaoxa-23 gene was by far the most widespread in MDR A. baumannii, while the blaoxa-24/40 and blaoxa-58 genes appeared to be less dominant in this region. The results demonstrated that the predominant class D carbapenemase was blaOXA-23, followed by the class B carbapenemase blaNDM-like, while the mcr-1 gene was not observed in any isolate. Most of the MDR A. baumannii isolates were resistant to ceftazidime (99.23%), gentamicin (91.85%), amikacin (82.96%), and ciprofloxacin (97.78%), while all of them were resistant to carbapenems. The results suggested that colistin could still be effective against MDR A. baumannii in this region. Conclusion This is the first molecular epidemiological analysis of MDR A. baumannii clinical isolates at the national level in Thailand to date. Studies on the clonal relatedness of MDR A. baumannii isolates could generate useful data to understand the local epidemiology and international comparisons of nosocomial outbreaks.

PurposeExtended-spectrum β-lactamases (ESBLs) have become an issue in community worldwide due to an increase in antibiotic resistance over the past decade. This study was aimed to investigate the phenotypic and genotypic characteristics of ESBL-producing Escherichia coli in Thailand.Materials and methodsIn this study, all clinical isolates collected from tertiary hospitals in Thailand were identified as E. coli by biochemical tests and MALDI-TOF mass spectrometry. ESBL-producing E. coli was preliminary screened with disk diffusion method by cephalosporin disks and confirmed by the method of combination disk diffusion. Antimicrobial susceptibility test was used to determine MIC values of all ESBL-producing E. coli. For genotypic detection, a variety of ESBL genes were determined by PCR. Moreover, multilocus sequence typing (MLST) analysis was performed on internal portions of seven housekeeping genes for the diversity and phylogenetic relatedness of E. coli clonal group.ResultsOf the 285 ESBL-producing E. coli, most were susceptible to carbapenems. These strains showed a high resistance rate to ciprofloxacin (85.26%). The most frequently detected gene was bla CTX-M1 group at about 71.23% followed by blaCTX-M9 group (38.95%). The blaTEM, bla PER, bla GES, bla VEB, and bla SHV genes were identified in 31.93%, 5.96%, 4.56%, 3.51%, and 0.70% of ESBL-producing isolates, respectively. The bla OXA-10 gene was detected in only one strain. ESBL-producing E. coli isolates with high antimicrobial resistance were further investigated. Among those, E. coli sequence type ST38 was mostly found, followed by ST405, ST410, and ST131. It is noteworthy that the blaCTX-M gene was mainly detected in all four ST-type E. coli clones (ST38, ST405, ST410, and ST131).ConclusionThis study provided a recent evidence of the genetic diversity of ESBL-producing E. coli in Thailand. In addition, the profile related to antimicrobial resistance pattern in this region was also demonstrated.

Carbapenem resistant Pseudomonas aeruginosa were isolated among multidrug-resistant (CR-MDR) organisms from tertiary hospitals in Thailand. Decreased expression of oprD mRNA (93.65%) was predominant followed by increased expression of mexAB-oprM mRNA (92.06%) and mexXY mRNA (63.49%). Interestingly, 23 of 126 (18.25%) isolates were susceptible to imipenem with down-regulated oprD expression and non-up-regulated mexCD-oprJ mRNA expression. Metallo-β-lactamases production was clearly positive in 24 isolates (18.46%) and weakly positive in 12 isolates (9.23%). Among both of these sets of isolates, imp-1, imp-14 and vim-2 were identified. Hyperproduction of AmpC β-lactamase had the lowest prevalence rate (3.97%). It was concluded that CR-MDR P. aeruginosa clinical isolates in Thailand possess multifactorial resistance mechanisms.

Critical Care 2017, 21(Suppl 1):P349 Introduction Imbalance in cellular energetics has been suggested to be an important mechanism for organ failure in sepsis and septic shock. We hypothesized that such energy imbalance would either be caused by metabolic changes leading to decreased energy production or by increased energy consumption. Thus, we set out to investigate if mitochondrial dysfunction or decreased energy consumption alters cellular metabolism in muscle tissue in experimental sepsis. Methods We submitted anesthetized piglets to sepsis (n = 12) or placebo (n = 4) and monitored them for 3 hours. Plasma lactate and markers of organ failure were measured hourly, as was muscle metabolism by microdialysis. Energy consumption was intervened locally by infusing ouabain through one microdialysis catheter to block major energy expenditure of the cells, by inhibiting the major energy consuming enzyme, N+/K + -ATPase. Similarly, energy production was blocked infusing sodium cyanide (NaCN), in a different region, to block the cytochrome oxidase in muscle tissue mitochondria. Results All animals submitted to sepsis fulfilled sepsis criteria as defined in Sepsis-3, whereas no animals in the placebo group did. Muscle glucose decreased during sepsis independently of N+/K + -ATPase or cytochrome oxidase blockade. Muscle lactate did not increase during sepsis in naïve metabolism. However, during cytochrome oxidase blockade, there was an increase in muscle lactate that was further accentuated during sepsis. Muscle pyruvate did not decrease during sepsis in naïve metabolism. During cytochrome oxidase blockade, there was a decrease in muscle pyruvate, independently of sepsis. Lactate to pyruvate ratio increased during sepsis and was further accentuated during cytochrome oxidase blockade. Muscle glycerol increased during sepsis and decreased slightly without sepsis regardless of N+/K + -ATPase or cytochrome oxidase blocking. There were no significant changes in muscle glutamate or urea during sepsis in absence/presence of N+/K + -ATPase or cytochrome oxidase blockade. ConclusionsThese results indicate increased metabolism of energy substrates in muscle tissue in experimental sepsis. Our results do not indicate presence of energy depletion or mitochondrial dysfunction in muscle and should similar physiologic situation be present in other tissues, other mechanisms of organ failure must be considered. , and long-term follow up has shown increased fracture risk [2]. It is unclear if these changes are a consequence of acute critical illness, or reduced activity afterwards. Bone health assessment during critical illness is challenging, and direct bone strength measurement is not possible. We used a rodent sepsis model to test the hypothesis that critical illness causes early reduction in bone strength and changes in bone architecture. Methods 20 Sprague-Dawley rats (350 ± 15.8g) were anesthetised and randomised to receive cecal ligation and puncture (CLP) (50% cecum length, 18G needle single pass through anterior and posterior wa...