Apoptotic effects of protocatechuic acid (PCA) at 1, 2, 4, 8 micromol/L on human breast cancer MCF7 cell, lung cancer A549 cell, HepG2 cell, cervix HeLa cell, and prostate cancer LNCaP cell were examined. Results showed that PCA concentration-dependently decreased cell viability, increased lactate dehydrogenase leakage, enhanced DNA fragmentation, reduced mitochondrial membrane potential, and lowered Na(+)-K(+)-ATPase activity for these cancer cells (P < 0.05). PCA also concentration-dependently elevated caspase-3 activity in five cancer cells (P < 0.05), but this agent at 2-8 micromol/L significantly increased caspase-8 activity (P < 0.05). PCA concentration-dependently decreased intercellular adhesion molecule level in test cancer cells (P < 0.05) but significantly inhibited cell adhesion at 2-8 micromol/L (P < 0.05). PCA also concentration-dependently lowered the levels of interleukin (IL)-6 and IL-8 in five cancer cells (P < 0.05), but this agent at 2-8 micromol/L significantly suppressed vascular endothelial growth factor production (P < 0.05). These findings suggest that PCA is a potent anticancer agent to cause apoptosis or retard invasion and metastasis in these five cancer cells.

Background Staphylococcus aureus causes a variety of severe infections such as bacteremia and sepsis. At present, 60–80% of S. aureus isolates from Taiwan are methicillin resistant (MRSA). It has been shown that certain MRSA clones circulate worldwide. The goals of this study were to identify MRSA clones in Taiwan and to correlate the molecular types of isolates with their phenotypes.MethodsA total of 157 MRSA isolates from bacteremic patients were collected from nine medical centers. They were typed based on polymorphisms in agr, SCCmec, MLST, spa, and dru. Phenotypes characterized included Panton-Valentine leucocidin (pvl), inducible macrolide-lincosamide-streptogramin B resistance (MLSBi), vancomycin (VA) and daptomycin (DAP) minimal inhibitory concentrations (MIC), and superantigenic toxin gene profiles. Difference between two consecutive samples was determined by Mann-Whitney-U test, and difference between two categorical variables was determined by Fisher's exact test.ResultsFour major MRSA clone complexes CC1, CC5, CC8, and CC59 were found, including 4 CC1, 9 CC5, 111 CC8, and 28 CC59 isolates. These clones had the following molecular types: CC1: SCCmecIV and ST573; CC5: SCCmecII and ST5; CC8: SCCmecIII, ST239, and ST241, and CC59: SCCmecIV, SCCmecVT, ST59, and ST338. The toxin gene profiles of these clones were CC1: sec-seg-(sei)-sell-selm-(seln)-selo; CC5: sec-seg-sei-sell-selm-(seln)-selp-tst1; CC8: sea-selk-selq, and CC59: seb-selk-selq. Most isolates with SCCmecVT, ST59, spat437, and dru11 types were pvl + (13 isolates), while multidrug resistance (≥4 antimicrobials) were associated with SCCmecIII, ST239, spa t037, agrI, and dru14 (119 isolates) (p<0.001). One hundred and twenty four isolates with the following molecular types had higher VA MIC: SCCmecII and SCCmecIII; ST5, ST239, and ST241; spa t002, t037, and t421; dru4, dru10, dru12, dru13, and dru14 (p<0.05). No particular molecular types were found to be associated with MLSBi phenotype.ConclusionsFour major MRSA clone complexes were found in Taiwan. Further studies are needed to delineate the evolution of MRSA isolates.

Production of extended-spectrum ␤-lactamases and plasmid-mediated AmpC enzymes was investigated among 291 Escherichia coli and 282 Klebsiella pneumoniae isolates that showed decreased susceptibilities to extended-spectrum cephalosporins from seven Taiwanese medical centers. CTX-M-type and SHV-type enzymes were the most prevalent extended-spectrum ␤-lactamases. CMY-2-like and DHA-1-like ␤-lactamases were the most prevalent AmpC-type enzymes.The increasing prevalence of extended-spectrum ␤-lactamases (ESBLs) and plasmid-mediated AmpC ␤-lactamases in members of the family Enterobacteriaceae is a matter of great concern worldwide (1, 2, 10). In Taiwan, TEM-, SHV-, and CTX-M-type ESBLs and CMY-and DHA-type AmpC ␤-lactamases have been reported in Escherichia coli and Klebsiella pneumoniae isolates from a few individual institutions (3,(17)(18)(19)(20). The present multicenter study was conducted to determine the distribution of ESBLs and AmpC ␤-lactamases among clinical isolates of E. coli and K. pneumoniae that showed decreased susceptibilities to extended-spectrum cephalosporins in Taiwan.Isolates that were suspected of ESBL production by the CLSI (formerly NCCLS) screening method (8) with disks of ceftazidime, cefotaxime, ceftriaxone, aztreonam, and/or cefpodoxime were considered to exhibit decreased susceptibilities to extended-spectrum cephalosporins and consecutively collected between March and August 2003 from seven medical centers in Taiwan. These hospitals were chosen because they represent the largest referral medical centers in each region of Taiwan. A total of 291 E. coli and 282 K. pneumoniae isolates were obtained (Table 1). Each isolate came from a unique patient.All isolates were tested for ESBL production by the CLSIrecommended disk diffusion confirmatory test (8), and 171 E. coli and 260 K. pneumoniae isolates were considered ESBL producers. All putative non-ESBL producers were tested further by the double-disk synergy test with ceftazidime, cefotaxime, aztreonam, and cefepime disks placed 20 mm from an amoxicillin-clavulanate disk (13). The method has been shown to be capable of detecting false negatives which are caused by coproduction of different classes of ␤-lactamases in the CLSI method (20). Five E. coli and five K. pneumoniae isolates gave a positive result in the double-disk synergy test. Thus, ESBL production was detected in 176 (60.5%) of the 291 E. coli isolates and 265 (94.0%) of the 282 K. pneumoniae isolates.The expression of ␤-lactamases was detected by isoelectric focusing as described previously (6,18). PCR was performed with the previously reported oligonucleotide primers to detect bla TEM (5), bla SHV (9), and bla genes related to bla CTX-M-1 (12), bla CTX-M-9 (12), bla CMY-1 (17), bla CMY-2 (16), bla DHA-1 (4), and bla . The PCR-NheI method was used to discriminate between bla SHV-ESBL and bla SHV-non-ESBL genes (9).Overall, the production of ESBLs and AmpC-like enzymes was confirmed in 60.5% (176 isolates) and 43.6% (127 isolates), respectively, of the 291 E. coli isolates, and ...

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Tigecycline (TG) has been shown to be active in vitro against Acinetobacter baumannii, although data on the clinical efficacy of TG alone or in combination for the treatment of infections due to multidrug-resistant A. baumannii (MDRAB) remain limited. The purpose of this study was to investigate the clinical outcomes of patients with healthcare-associated infections (HAIs) caused by MDRAB who were treated with imipenem/cilastatin and sulbactam, and TG alone or in combination with other antibiotics. A total of 386 patients with HAIs caused by MDRAB were retrospectively analyzed and grouped into TG and non-TG groups, depending on whether they received TG treatment. Of the 266 patients in the TG group, 108 were treated with TG alone and 158 were treated with TG in combination with ceftazidime, ceftriaxone, piperacillin/tazobactam, or a carbapenem. All 120 patients in the non-TG group were treated with imipenem/cilastatin and sulbactam. The primary outcome measure was 30-day mortality after TG treatment and the secondary outcome was clinical outcome. There were no significant differences in survival rates between the two groups. However, the rate of unfavorable outcome was significantly lower (p < 0.05) among patients in the TG group than among patients in the non-TG group. The most significant predictor of unfavorable outcome was sepsis, whereas TG treatment and microbial eradication were the most significant predictors of favorable outcomes. Our study represents the largest study of patients with MDRAB infection treated with TG and expands our understanding of the role of TG therapy alone or in combination with other agents for the treatment of HAI caused by MDRAB.

Cytotoxic effects of protocatechuic acid (PCA) upon 3 nonsmall cell lung cancer (NSCLC) cell lines, A549, H3255, and Calu-6 cell lines, were examined. PCA at 1, 2, 4, and 8 μM was used to treat these cells. Results showed that PCA dose-dependently reduced cell growth; and at 2-8 μM enhanced protein expression of Bax and cleaved caspase-3; as well as diminished Bcl-2 expression. This compound destabilized mitochondrial membrane via increasing caspase-3 activity, decreasing mitochondrial membrane potential and Na(+)-K(+)-ATPase activity in these cells. PCA treatments dose-dependently decreased protein expression of vascular endothelial growth factor and fibronectin, as well as lowered interleukin (IL)-6 and IL-8 release; and at 2-8 μM suppressed protein expression of basic fibroblast growth factor, matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, PCA treatments dose-dependently downregulated nuclear factor kappa (NF-κ)B p50 and NF-κB p65 protein expression, and at 2-8 μM suppressed protein expression of p-p38, p-JNK, and p-focal adhesion kinase (FAK). Our data revealed that PCA declined FAK, mitogen-activated protein kinase, and NF-κB activation, which subsequently decreased the production of cytokines and growth factors, and consequently inhibited proliferation of 3 test NSCLC cells. These findings suggest that PCA could provide wide-ranging anti-NSCLC potency.

PTX3 may be able to play a role in the diagnosis and clinical assessment of the severity of CAP, which could potentially guide the development of treatment strategies.

The predominant causes of E. coli liver abscess were biliary diseases. This report also highlights that E. coli liver abscess has a relatively high mortality rate, which is associated with underlying malignancy, multiple abscesses and profound hypoalbuminemia.