Dorzagliatin for Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Phase II/III Trials.

PURPOSE: Dorzagliatin is a glucokinase agonist with effects on type 2 diabetes mellitus (T2DM). This study included a meta-analysis on the efficacy and safety of dorzagliatin in the treatment of T2DM. METHODS: The Cochrane Central Registry of Controlled Trials, PubMed, and Embase were searched from inception to July 25, 2022. A total of 3 studies including 1333 patients were identified in this meta-analysis. FINDINGS: Overall, the meta-analysis showed that dorzagliatin remarkably reduced glycated hemoglobin levels versus placebo by 0.66%. The results of the meta-analysis showed a significant reduction in fasting plasma glucose of 6.77 mg/dL between dorzagliatin and placebo. In addition, dorzagliatin reduced 2-hour postprandial glucose (2h-PPG) by 43.87 mg/dL compared with placebo. Furthermore, the meta-analysis of available data revealed a significant reduction in the Homeostasis Model Assessment of Insulin Resistance of 0.07 between dorzagliatin and placebo. The risk of adverse events was slightly higher with dorzagliatin than with placebo. IMPLICATIONS: Dorzagliatin significantly reduced glycated hemoglobin levels, fasting plasma glucose levels, 2h-PPG, and homeostasis model assessment 2 of insulin resistance in patients with T2DM. It was well tolerated and had good liver and kidney safety profiles.

Weight loss efficiency and safety of tirzepatide: A Systematic review.

OBJECTIVE: Tirzeptide is a novel glucagon-like peptide-1 receptor (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) drug, which shows good efficiency for weight loss. Therefore, we aim to investigate the efficacy and safety of tirzepatide for weight loss in type 2 diabetes mellitus (T2DM) and obesity patients in this meta-analysis study. METHODS: Cochrane Library, PubMed, Embase, Clinical Trials, and Web of Science were searched from inception to October 5, 2022. All randomized controlled trials (RCTs) were included. The odds ratio (OR) was calculated using fixed-effects or random-effects models by Review Manager 5.3 software. RESULTS: In total, ten studies (12 reports) involving 9,873 patients were identified. A significant loss body weight in the tirzepatide group versus the placebo by -9.81 kg (95% CI (-12.09, -7.52), GLP-1 RAs by -1.05 kg (95% CI (-1.48, -0.63), and insulin by -1.93 kg (95% CI (-2.81, -1.05), respectively. In sub-analysis, the body weight of patients was significantly reduced in three tirzepatide doses (5 mg, 10 mg, and 15 mg) when compared with those of the placebo/GLP-1 RA/insulin. In terms of safety, the incidence of any adverse events and adverse events leading to study drug discontinuation was higher in the tirzepatide group, but the incidence of serious adverse events and hypoglycaemia was lower. Additionally, the gastrointestinal adverse events (including diarrhea, nausea, vomiting and decreased appetite) of tirzepatide were higher than those of placebo/basal insulin, but similar to GLP-1 RAs. CONCLUSION: In conclusion, tirzeptide can significantly reduce the weight of T2DM and patient with obesity, and it is a potential therapeutic regimen for weight-loss, but we need to be vigilant about its gastrointestinal reaction.

Omadacycline for treatment of acute bacterial infections: a meta-analysis of phase II/III trials.

OBJECTIVE: This study aims to assess the clinical efficacy and safety of omadacycline for the treatment of acute bacterial infections. METHODS: A search of PubMed, Embase, Cochrane Library, and Clinical Trials was conducted up to July 1, 2022. We included only randomized controlled trials (RCTs), in which omadacycline and other antibiotics were evaluated for treating acute bacterial infections in adults. The primary outcomes were clinical response and microbiological response, whereas the secondary outcome was the risk of adverse events (AEs). RESULTS: A total of seven RCTs involving 2841 patients with acute bacterial infection were included. Overall, our study illustrated that the clinical cure ratio of omadacycline was similar to the comparators in the treatment of acute bacterial infections (OR = 1.18, 95%CI = 0.96, 1.46, I2 = 29%). Omadacycline had a microbiological eradication rate similar to comparators in the treatment of acute bacterial infections (OR = 1.02, 95%CI = 0.81, 1.29, I2 = 42%). No statistical differences were observed between omadacycline and the comparators in terms of infection caused by Staphylococcus aureus (OR = 1.14, 95%CI = 0.80, 1.63, I2 = 0%), methicillin-resistant S. aureus (MRSA, OR = 1.28, 95%CI = 0.73, 2.24, I2 = 0%), methicillin-susceptible S. aureus (MSSA, OR = 1.12, 95%CI = 0.69, 1.81, I2 = 0%), and Enterococcus faecalis (OR = 2.47, 95%CI = 0.36, 16.97, I2 = 7%). A significant difference was found between omadacycline and the comparators for the risk of any AEs and treatment related AEs. The risk of discontinuation of the study drug due to an AEs was lower for omadacycline than for the comparators. CONCLUSION: Omadacycline is as good as comparators in terms of efficacy and tolerance in the treatment of acute bacterial infections in adult patients. Thus, omadacycline is an appropriate option for antibiotic therapy in adult patients with acute bacterial infections.

Effect of traditional Chinese medicine monomers interfering with quorum-sensing on virulence factors of extensively drug-resistant Acinetobacter baumannii.

The antimicrobial resistance of Acinetobacter baumannii (A. baumannii) clinical isolates has emerged as a great threat to public health. Quorum sensing (QS) is one of the resistance mechanisms for drug-resistant A. baumannii. Interfering with QS is a promising strategy to combat infections caused by drug-resistant bacteria. This study explored the QS inhibition ability of thirty-four traditional Chinese medicine monomers (TCMMs) and assessed the effect of QS inhibitors (QSIs) on the virulence factors of twelve extensively drug-resistant A. baumannii (XDRAB) strains. Nine traditional Chinese medicine monomers, such as caffeic acid, cinnamic acid, and myricetin, were found to be able to inhibit the bacterial QS. Then, at 1/8 of the minimal inhibitory concentration, we found that these QSIs inhibited extensively drug-resistant A. baumannii adhesion and biofilm formation and downregulated the expression levels of virulence-associated genes (abaI, abaR, csuE, pgaA, and bap). In conclusion, nine traditional Chinese medicine monomers have QS inhibitory activity and may downregulate QS genes to interfere with the QS system, which could inhibit the expression of extensively drug-resistant A. baumannii virulence factors. These results suggest that traditional Chinese medicine monomers could develop as novel anti-virulence compounds to control extensively drug-resistant A. baumannii infections.

Efficacy and safety of dulaglutide compared with the first-line hypoglycemic drugs in Asian patients with type 2 diabetes: a systematic review and meta-analysis.

To assess the efficacy and safety of dulaglutide in the treatment of Asian type 2 diabetes mellitus (T2DM), along with first-line hypoglycemic drugs. Systematic review and meta-analysis. Cochrane Library, Pubmed, Embase, and www.clinicaltrials.gov databases were searched from inception to September 27, 2022. The studies evaluating adults (≥ 18 years) undergoing dulaglutide (0.75 mg and 1.5 mg) and first-line hypoglycemic drugs were considered. There were only English languages. We used Stata 12.0 software to detect the risk of bias. 4 randomized controlled trials (RCTs), and 1 observational study. Both dulaglutide 0.75 mg dose group and 1.5 mg dose group could significantly reduce HbA1c [Dulaglutide 0.75 mg: WMD = - 0.20, 95% CI (- 0.28, - 0.11), P < 0.0001; Dulaglutide 1.5 mg: WMD = - 0.49, 95% CI (- 0.67, - 0.30), P < 0.0001] in Asian T2DM patients. In reducing fasting blood glucose (FBG) level, there was no significant difference observed in 2 dose groups. The body weight of patients in both dulaglutide dose groups was significantly reduced. In safety, the incidence of adverse events in the dulaglutide 0.75 mg dose group was slightly higher than that in the first-line drug group, but there was no statistically significant difference in the incidence of adverse events between the 1.5 mg dose group and the first-line drug group. Furthermore, the incidences of hypoglycemic events in both groups were higher than that in the first-line drug group. Two doses of dulaglutide showed better efficacy for Asian T2DM patients, but patients should be vigilant about the occurrence of hypoglycemia and gastrointestinal discomfort. However, more number and better quality of RCTs are suggested to confirm long-term safety and efficacy.

In Vitro Activity of Peptide Antibiotics in Combination With Other Antimicrobials on Extensively Drug-Resistant Acinetobacter baumannii in the Planktonic and Biofilm Cell.

Acinetobacter baumannii is one of the most dangerous opportunistic pathogens in the global health care setup. Its drug resistance and biofilm-forming capability are often associated with chronic infections that are difficult to treat. Therefore, the clinical treatments for highly drug-resistant A. baumannii are limited. Antimicrobial peptides are broad-spectrum antibacterial agents combined with antibiotics that minimize selective bacterial resistance and enhance antibacterial efficacy. The current study evaluated the synergistic antibacterial activities of clinically important peptide antibiotics combined with other antimicrobials against nine extensively drug-resistant A. baumannii strains in planktonic and biofilm cells in vitro. Polymyxin B and E combined with imipenem showed 100% synergy in the planktonic cell with the checkerboard. Moreover, polymyxin E with rifampicin and bacitracin with imipenem or meropenem showed 100% additive effects. In the biofilm cell, polymyxin B and E combined with azithromycin showed 100% synergy, when vancomycin with azithromycin, rifampicin, and bacitracin with azithromycin or rifampicin, and teicoplanin with tigecycline or rifampicin, all showed 100% additive effects. Therefore, peptide antibiotics combined with other antimicrobials have synergistic or additive effects on extensively drug-resistant A. baumannii in planktonic and biofilm cells. In addition, the combination of polymyxins with carbapenems or azithromycin could be an ideal therapy against extensively drug-resistant A. baumannii infections.

Network pharmacology study on the mechanism of the Chinese medicine Radix Isatidis (Banlangen) for COVID-19.

ABSTRACT: Radix Isatidis (Banlangen) is a well-known traditional Chinese medicine for the treatment of different diseases and prevention of many body disorders. Besides, it also plays a pivotal role in novel coronavirus pneumonia, coronavirus disease 2019 (COVID-19). However, few researchers know its active ingredients and mechanism of action for COVID-19. To find whether Banlangen has a pharmacological effect on COVID-19. In this research, we systematically analyze Banlangen and COVID-19 through network pharmacology technology. A total of 33 active ingredients in Banlangen, 92 targets of the active ingredients, and 259 appropriate targets of COVID-19 were obtained, with 11 common targets. The analysis of the biological process of gene ontology and the enrichment of Kyoto Encyclopedia of Genes and Genomes signaling pathway suggests that Banlangen participated in the biological processes of protein phosphatase binding, tetrapyrrole binding, the apoptotic process involving cysteine-type endopeptidase activity, etc. The COVID-19 may be treated by regulating advanced glycation end products/a receptor for advanced glycation end products signaling pathway, interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, sphingolipid signaling pathway, and p53 signaling pathway. Banlangen has a potential pharmacological effect on COVID-19, which has the value of further exploration in the following experiment and clinical application.

Combination inhibition activity of chlorhexidine and antibiotics on multidrug-resistant Acinetobacter baumannii in vitro.

BACKGROUND: Chlorhexidine is a widely used disinfectant in clinical settings and a broad-spectrum antimicrobial agent effective against aerobic and anaerobic bacteria. However, disinfectant resistant or non-susceptible bacteria, including antibiotic-resistant Acinetobacter baumannii, have been found. This study aimed to develop a new technique to prevent and control A. baumannii infection in the hospital setting. METHODS: Chlorhexidine combined with minocycline, doxycycline, meropenem, imipenem, levofloxacin and ciprofloxacin were tested against the 30 multidrug-resistant and extremely drug-resistant A. baumannii clinical isolates. The checkerboard test was used to calculate the fractional inhibitory concentration index according to the minimum inhibitory concentration value for chlorhexidine combined with antibiotics. RESULTS: The combination of chlorhexidine with minocycline, doxycycline, meropenem, or ciprofloxacin showed synergistic responses in all clinical isolates, and more than 50% of isolates showed FICI ≤0.5. However, chlorhexidine together with imipenem or levofloxacin showed indifferent responses in 10% and 3.33% clinical isolates, respectively. In all tests, combinations of chlorhexidine with each of the above six antibiotics showed synergistic and additive effects, and inhibited the clinical isolates. CONCLUSIONS: We concluded that, chlorhexidine combined with antibiotics could be used to control the risk of infection with A. baumannii.

In vitro activity of biofilm inhibitors in combination with antibacterial drugs against extensively drug-resistant Acinetobacter baumannii.

Acinetobacter baumannii is a common pathogen of nosocomial infection, and its ability to form biofilms further contributes to its virulence and multidrug resistance, posing a great threat to global public health. In this study, we investigated the inhibitory effects of five biofilm inhibitors (BFIs) (zinc lactate, stannous fluoride, furanone, azithromycin, and rifampicin) on biofilm formation of nine extensively drug-resistant A. baumannii (XDRAB), and assessed the synergistic antibacterial effects of these BFIs when combined with one of four conventional anti-A. baumannii antibiotics (imipenem, meropenem, tigecycline, and polymyxin B). Each of the five BFIs tested was found to be able to significantly inhibit biofilm formation of all the clinical isolates tested under sub-minimal inhibitory concentrations. Then, we observed synergistic effects (in 22%, 56% and 11% of the isolates) and additive effects (56%, 44% and 44%) when zinc lactate, stannous fluoride and furanone were combined with tigecycline, respectively. When zinc lactate and stannous fluoride were each used with a carbapenem (imipenem or meropenem), in 33% and 56-67% of the isolates, they showed synergistic and additive effects, respectively. Additivity in > 50% of the isolates was detected when rifampicin was combined with imipenem, meropenem, tigecycline, or polymyxin B; and a 100% additivity was noted with azithromycin-polymyxin B combination. However, antagonism and indifference were noted for polymyxin B in its combination with zinc lactate and stannous fluoride, respectively. In conclusion, five BFIs in combination with four antibacterial drugs showed different degrees of in vitro synergistic and additive antibacterial effects against XDRAB.

Pharmacokinetics and metabolism of ulixertinib in rat by liquid chromatography combined with electrospray ionization tandem mass spectrometry.

The purpose of this study was to develop and validate a simple and sensitive liquid chromatography tandem mass spectrometry method for the determination of ulixertinib in rat plasma. The plasma samples were precipitated with acetonitrile and then separated on a C18 column with water containing 0.1% formic acid and acetonitrile as mobile phase at a flow rate of 0.3 mL/min. Analytes were monitored on a TSQ Vantage triple quadrupole tandem mass spectrometer operated in positive electrospray ionization mode. Selected reaction monitoring transitions were m/z 433.1→262.1 for ulixertinib and m/z 450.1→260.1 for internal standard. The assay achieved good linearity over the concentration range of 0.1-1000 ng/mL with correlation coefficient > 0.9991. The validated assay has been successfully applied to pharmacokinetic study of ulixertinib in rat after oral and intravenous administration. The results revealed that ulixertinib showed high exposure in rat plasma, low clearance, moderate oral bioavailability (45.13%), and dose-independent pharmacokinetic profiles over the oral dose range of 1-15 mg/kg. In addition, six metabolites from rat plasma and hepatocytes were detected and structurally identified by ultra-high performance liquid chromatography combined with high-resolution mass spectrometry. The metabolic pathways of ulixertinib referred to hydroxylation and dealkylation and glucuronidation.

Molecular Characterization of Reduced Susceptibility to Biocides in Clinical Isolates of Acinetobacter baumannii.

Active efflux is regarded as a common mechanism for antibiotic and biocide resistance. However, the role of many drug efflux pumps in biocide resistance in Acinetobacter baumannii remains unknown. Using biocide-resistant A. baumannii clinical isolates, we investigated the incidence of 11 known/putative antimicrobial resistance efflux pump genes (adeB, adeG, adeJ, adeT1, adeT2, amvA, abeD, abeM, qacE, qacEΔ1, and aceI) and triclosan target gene fabI through PCR and DNA sequencing. Reverse transcriptase quantitative PCR was conducted to assess the correlation between the efflux pump gene expression and the reduced susceptibility to triclosan or chlorhexidine. The A. baumannii isolates displayed high levels of reduced susceptibility to triclosan, chlorhexidine, benzalkonium, hydrogen peroxide, and ethanol. Most tested isolates were resistant to multiple antibiotics. Efflux resistance genes were widely distributed and generally expressed in A. baumannii. Although no clear relation was established between efflux pump gene expression and antibiotic resistance or reduced biocide susceptibility, triclosan non-susceptible isolates displayed relatively increased expression of adeB and adeJ whereas chlorhexidine non-susceptible isolates had increased abeM and fabI gene expression. Increased expression of adeJ and abeM was also demonstrated in multiple antibiotic resistant isolates. Exposure of isolates to subinhibitory concentrations of triclosan or chlorhexidine induced gene expression of adeB, adeG, adeJ and fabI, and adeB, respectively. A point mutation in FabI, Gly95Ser, was observed in only one triclosan-resistant isolate. Multiple sequence types with the major clone complex, CC92, were identified in high level triclosan-resistant isolates. Overall, this study showed the high prevalence of antibiotic and biocide resistance as well as the complexity of intertwined resistance mechanisms in clinical isolates of A. baumannii, which highlights the importance of antimicrobial stewardship and resistance surveillance in clinics.

Coexistence of blaOXA-23 with armA in quinolone-resistant Acinetobacter baumannii from a Chinese university hospital.

A total of 101 Acinetobacter baumannii isolates were collected to determine the mechanisms of quinolone resistance and investigate the occurrence of carbapenem and high-level aminoglycoside resistance genes among quinolone-resistant strains. Among 77 quinolone-resistant A. baumannii harbored mutations of gyrA and parC, 41 isolates, which belonged to European clone II, had resistance to aminoglycosides and carbapenems due to the expression of armA and acquisition of blaOXA-23. Most of sequence type belonged to clonal complex 92. These results suggested hospital dissemination of multidrug-resistant A. baumannii carrying blaOXA-23, armA, and mutations of quinolone resistance-determining regions in western China.

Prevalence of carbapenemases among high-level aminoglycoside-resistant Acinetobacter baumannii isolates in a university hospital in China.

The prevalence of aminoglycoside resistant enzymes has previously been reported and extended-spectrum ß-lactamase among Acinetobacter baumannii. To track the risk of multidrug-resistant A. baumannii, the present study aimed to determine the prevalence of carbapenemases in high-level aminoglycoside resistant A. baumannii over two years. A total of 118 strains of A. baumannii were consecutively collected in the First Affiliated Hospital of Chengdu Medical College, Chengdu, China. These isolates were investigated on the genetic basis of their resistance to aminoglycosides. The results showed that 75 (63.56%) isolates were high-level resistant to aminoglycosides, including gentamicin and amikacin (minimum inhibitory concentration, ≥256 µg/ml). Aminoglycoside-resistant genes ant(2″)-Ia, aac(6')-Ib, aph(3')-Ia, aac(3)-Ia, aac(3)-IIa, armA, rmtA, rmtB, rmtC, rmtD, rmtE, rmtF, rmtG, rmtH and npmA, and carbapenem-resistant genes blaOXA-23, blaOXA-24, blaOXA-51, blaOXA-58, blaSIM, blaIMP, blaNDM-1 and blaKPC, were analyzed using polymerase chain reaction. The positive rate of ant(2″)-Ia, aac(6')-Ib, aph(3')-Ia, aac(3)-Ia and aac(3)-IIa was 66.95, 69.49, 42.37, 39.83 and 14.41%, respectively. armA was present in 72.0% (54/75) of A. baumannii isolates with high-level resistance to aminoglycosides. The remaining nine 16S ribosomal RNA methlyase genes (rmtA, rmtB, rmtC, rmtD, rmtE, rmtF, rmtG, rmtH and npmA) and aminoglycoside-modifying enzyme gene aac(6')-Ib-cr were not detected. Among the 54 armA-positive isolates, the prevalence of the carbapenem resistant blaOXA-23 and blaOXA-51 genes was 79.63 and 100%, respectively. armA, ant(2″)-Ia and aac(6')-Ib were positive in 43 isolates. The results of multilocus sequence typing revealed 31 sequence types (STs) in all clinical strains. Among these STs, the high-level aminoglycoside-resistant A. baumannii ST92, which mostly harbored blaOXA-23, was the predominant clone (29/75). In conclusion, A. baumannii harboring carbapenemases and aminoglycoside-resistant enzymes are extremely prevalent in western China, emphasizing the need to adopt surveillance programs to solve the therapeutic challenges that this presents.

Characterization of carbapenem-resistant Acinetobacter baumannii isolates in a Chinese teaching hospital.

Carbapenem-resistant Acinetobacter baumannii (CRAB) presents a serious therapeutic and infection control challenge. In this study, we investigated the epidemiological and molecular differences of CRAB and the threatening factors for contributing to increased CRAB infections at a hospital in western China. A total of 110 clinical isolates of A. baumannii, collected in a recent 2-year period, were tested for carbapenem antibiotic susceptibility, followed by a molecular analysis of carbapenemase genes. Genetic relatedness of the isolates was characterized by multilocus sequence typing. Sixty-seven of the 110 isolates (60.9%) were resistant to carbapenems, 80.60% (54/67) of which carried the bla OXA-23 gene. Most of these CRAB isolates (77.62%) were classified as clone complex 92 (CC92), and sequence type (ST) 92 was the most prevalent STs, followed by ST195, ST136, ST843, and ST75. One CRAB isolate of ST195 harbored plasmid pAB52 from a Chinese patient without travel history. This plasmid contains toxin-antitoxin elements related to adaptation for growth, which might have emerged as a common vehicle indirectly mediating the spread of OXA-23 in CRAB. Thus, CC92 A. baumannii carrying OXA-23 is a major drug-resistant strain spreading in China. Our findings indicate that rational application of antibiotics is indispensable for minimizing widespread of drug resistance.

Prevalence of 16S rRNA methylase, modifying enzyme, and extended-spectrum beta-lactamase genes among Acinetobacter baumannii isolates.

Multidrug-resistant Acinetobacter baumannii has become a worldwide problem, and methylation of 16S rRNA has recently emerged as a new mechanism of resistance to aminoglycosides, which is mediated by a newly recognized group of 16S rRNA methylases. 16S rRNA methylase confers a high-level resistance to all 4,6-substituted deoxystreptamine aminoglycosides that are currently used in clinical practice. Some of the A. baumannii isolates have been found to coproduce extended-spectrum beta-lactamases (ESBLs), contributing to their multidrug resistance. The aim of this study was to detect the determinants of the 16S rRNA methylase genes armA, rmtA, rmtB, rmtC, rmtD, rmtE, and npmA, the modifying enzyme genes aac(6')-Ib, ant(3″)-Ia, aph(3')-I, and the extended-spectrum beta-lactamase genes bla(TEM), bla(SHV), and bla(CTX-M-3) among A. baumannii isolates in northeastern Sichuan, China. Minimum inhibitory concentrations (MICs) of 21 different antimicrobial agents against the A. baumannii isolates were determined. The clinical isolates showed a high level of resistance (MIC≧256 µg/ml) to aminoglycosides, which ranged from 50·1 to 83·8%. The resistances to meropenem and imipenem, two of the beta-lactam antibiotics and the most active antibiotics against A. baumannii, were 9·1 and 8·2%, respectively. Among 60 amikacin-resistant isolates, only the 16S rRNA methylase gene armA was found to be prevalent (66·7%), but the other 16S rRNA methylase genes rmtA, rmtB, rmtC, rmtD, rmtE, and npmA were not detected. The prevalences of the modifying enzyme genes aac (6')-Ib, ant (3″)-Ia, and aph (3')-I were 51·7, 81·7, and 58·3%, respectively, which are different from a previous study in which the occurrences of these genes were 3, 64, and 72%, respectively. Among the 40 isolates that were armA-positive, the prevalences of bla(TEM), bla(SHV), and bla(CTX-M-3) genes were detected for the first time in China, and their occurrences were 45, 65, and 52·5%, respectively. In all, A. baumannii with all the 16S rRNA methylase, modifying enzyme, and ESBL genes is extremely prevalent in northeastern Sichuan, China, posing a serious clinical concern with a major therapeutic threat in the future.

Distribution of the multidrug efflux pump genes, adeABC, adeDE and adeIJK, and class 1 integron genes in multiple-antimicrobial-resistant clinical isolates of Acinetobacter baumannii-Acinetobacter calcoaceticus complex.

Of 112 non-repetitive clinical isolates of Acinetobacter baumannii-Acinetobacter calcoaceticus complex, 80% were resistant to a variety of structurally unrelated antimicrobials although all isolates were susceptible to minocycline and polymyxin. Resistance to carbapenems occurred in 8% of the isolates. The presence of adeSR-adeABC, adeDE and adeIJK drug efflux system genes and class 1 integron genes (integrase gene int1) was assessed by polymerase chain reaction (PCR) in relation to the susceptibility of the isolates to 20 antimicrobials. The majority of isolates (75%) with high levels of multidrug resistance were positive for adeSR-adeABC and adeIJK as well as int1 and thus belong to A. baumannii (i.e. genomospecies 2). Positive adeE was only observed in adeSR-adeABC/adeIJK/int1-negative isolates (8%; likely belonging to Acinetobacter genomospecies 3) that were relatively susceptible to several agents, and adeE expression was undetectable. The results reveal a possible association between adeABC/adeIJK and int1 in multidrug-resistant isolates of A. baumannii. In addition, differential distribution of the resistance-nodulation-cell division (RND) genes can likely be used as indicators for differentiating Acinetobacter species.

Molecular characterization of extended-spectrum beta-lactamases produced by clinical isolates of Enterobacter cloacae from a Teaching Hospital in China.

Of 59 clinical isolates of Enterobacter cloacae from a teaching hospital in Sichuan, China, 18 isolates were shown to be resistant to oxyimino cephalosporins and aztreonam. Enterobacterial repetitive consensus PCR revealed that these isolates comprised 7 distinct genotypes. The presence of plasmids in the 18 clinical isolates was revealed by conjugational transfer of plasmids from E. cloacae to Escherichia coli with the further isolation of the plasmids in the transconjugants. Subsequent nucleotide sequencing and beta-lactamase isoelectric focusing indicated that the plasmids encoded blaSHV, blaCTX-M and/or blaTEM genes, including genes for CTX-M-22 (13 strains), TEM-1 (12 strains), TEM-29 (1 strain), TEM-141 (1 strain), TEM-157 (1 strain), SHV-5 (1 strain), SHV-12 (1 strain), and SHV-70 (1 strain). The widespread presence of extended-spectrum beta-lactamases in E. cloacae isolated from the southwest of China was likely due to the dissemination of resistance plasmids with the predominant genotype of blaCTX-M-22.

Characterization of CTX-M-22 and TEM-141 Encoded by a single plasmid from a clinical isolate of Enterobacter cloacae in China.

We analyzed the resistance to expanded-spectrum cephalosporins of an Enterobacter cloacae clinical isolate, EC002, by transconjugation, isoelectric-focusing analysis, and cloning experiments. It produced two beta-lactamases with isoelectric point values of 5.4 and 8.7, corresponding to TEM-141, a novel variant of TEM-1, and CTX-M-22, encoded by a transferable plasmid.

Bacterial endotoxin lipopolysaccharide induces up-regulation of glyceraldehyde-3-phosphate dehydrogenase in rat liver and lungs.

Bacterial endotoxin or lipopolysaccharide (LPS) can trigger inflammatory responses and cause damage in organs such as liver and lungs when it is introduced into mammals, but the exact molecular events that mediate these responses have remained obscure. In this study, by using 2D gel electrophoresis and cDNA microarray analysis, we found that both protein and mRNA levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were significantly increased in rat liver and lungs after treatment with LPS. The results were further confirmed by Western blot and Northern blot. Given the known role of GAPDH in inducing apoptosis, our results suggest that LPS-induced GAPDH up-regulation may be an important mechanism responsible for the damage induced by Gram negative bacteria in mammalian tissue and GAPDH may be involved in the signaling pathway of LPS induced apoptosis. Our results also demonstrate that GAPDH is not a suitable internal control in gene expression studies, especially when bacterial infection is involved.