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Objectives : Aeromonas bacteraemia is not a common infectious disease, but can cause a grave outcome in infected cases. In this study, clinical presentations and prognostic factors of cases of monomicrobial Aeromonas bacteraemia were analysed. Also, the impact of β-lactam and aminoglycoside in combination and of emerging cephalosporin-resistance during therapy was discussed. Methods : From 1989 to 1998 in a medical centre in southern Taiwan, those cases with monomicrobial Aeromonas bacteraemia were included for study. Results : A total of 104 episodes of monomicrobial Aeromonas bacteraemia, accounting for 74% of all Aeromonas bacteraemia, were encountered. The infections usually occurred in the patients with hepatic cirrhosis (54%) or malignancy (21%) and were community-acquired (74%). Cases of community-acquired bacteraemia were more likely to have cirrhosis, a high severity score at onset, and a worse prognosis than those of nosocomial bacteraemia did and nosocomial isolates were less susceptible to cefoxitin and cefotaxime. Forty-three percent of cases had a concomitant infection focus, such as primary peritonitis, invasive cellulitis or necrotizing fasciitis, biliary tract or burn wound infections. Crude fatality rate within 2 weeks after the onset was 30%. Secondary bacteraemia and a higher severity score (≥4) for illness at the first presentation were independently associated with a fatal outcome. The therapeutic superiority of β-lactam and aminoglycoside in combination cannot be demonstrated in patients with Aeromonas bacteraemia. Cefotaxime resistance emerged in 3.4% of 58 patients treated with a cephalosporin for at least 72 h. None of the community-acquired isolates, but one-quarter of the nosocomial isolates, were resistant to cefotaxime. Conclusions : Aeromonas bacteraemia usually occurred in patients with liver cirrhosis or malignancy, and heralded a poor prognosis, especially while associated with a relevant infectious source or with a higher severity score at presentation. The superiority of aminoglycoside and β-lactam in combination cannot be demonstrated while treating those patients, and the emergence of antimicrobial resistance to cephalosporin was a rare event during cephalosporin therapy. Thus, a broad-spectrum cephalosporin remains one of the antimicrobial alternatives for invasive community-acquired Aeromonas infections.

Sharps injuries are a major cause of transmission of hepatitis B and C viruses and human immunodeficiency virus in health-care workers. To determine the yearly incidence and causes of sharps injuries in health-care workers in Taiwan, we conducted a questionnaire survey in a total of 8645 health care workers, including physicians, nurses, laboratory technicians, and cleaners, from teaching hospitals of various sizes. The reported incidence of needlestick and other sharps injuries was 1·30 and 1·21 per person in the past 12 months, respectively. Of most recent episodes of needlestick/sharps injury, 52·0% were caused by ordinary syringe needles, usually in the patient units. The most frequently reported circumstances of needlestick were recapping of needles, and those of sharps injuries were opening of ampoules/vials. Of needles which stuck the health-care workers, 54·8% had been used in patients, 8·2% of whom were known to have hepatitis B or C, syphilis, or human immunodeficiency virus infection. Sharps injuries in health-care workers in Taiwan occur more frequently than generally thought and risks of contracting blood-borne infectious diseases as a result are very high.

Suppurative thyroiditis is rare, and the major pathogens are Staphylococcus and Streptococcus species. We present a case caused by Acinetobacter baumanii, which has never before been reported. We review another 191 cases from the English-language literature (1980 to April 1997) and make a comparison with a review of 224 cases (1900-1980). As the numbers of immunocompromised patients increase, cases of suppurative thyroiditis are increasing. Pneumocystis carinii has become an important pathogen. Most patients (83.1%) with bacterial infections were euthyroid, whereas those with fungal or mycobacterial infections tended to be hypothyroid (62.5%) and hyperthyroid (50%), respectively.

Although Taiwan is not an area where cholera is endemic, from October 1988 to October 1997 30 episodes of non-O1, non-O139 Vibrio cholerae infection were noted at the National Cheng Kung University Hospital in Taiwan. Infections generally occurred in hot seasons, and two episodes were concomitant with Vibrio vulnificus infection. Three major clinical presentations were found: bacteremia with concurrent spontaneous bacterial peritonitis or invasive soft-tissue infections that occurred solely in cirrhotic patients; self-limited acute febrile gastroenteritis that occurred in patients with no underlying medical disease; and necrotizing fasciitis or cellulitis that often resulted from a wound on extremities. Other manifestations included fatal pneumonitis in a drowned man and acute pyosalpinx. The differential diagnosis of invasive infections in cirrhotic patients should include infections due to non-O1 V. cholerae or V. vulnificus, and a third-generation cephalosporin and a tetracycline analogue or a fluoroquinolone alone is recommended for treatment of severe vibrio infections.

We reviewed the clinical features of 44 patients with invasive group A streptococcal (GAS) disease who were treated at two teaching hospitals in southern Taiwan from 1991 to 1994. Genes encoding streptococcal pyrogenic exotoxin types A (speA), B (speB), C (speC), and F (speF) and serotypes of M1, M6, and M12 were determined by polymerase chain reaction to target specific sequences in the 44 isolates recovered from these patients and in 28 isolates recovered from upper respiratory sites in 28 additional patients during the study period. The protease activity of these isolates was tested by using the casein plate method. Of the 44 patients with invasive diseases, 25 (57%) had no obvious underlying diseases, and 14 (32%) had preexisting neoplastic diseases or had previously used steroids. Twenty-five patients (57%) presented with cellulitis or necrotizing fasciitis, 24 (55%) had bacteremia, and eight (18%) had streptococcal toxic shock syndrome (STSS). Eight patients (18%) died of invasive GAS disease; seven had STSS, and seven had underlying diseases. All eight patients died within 48 hours after hospitalization. The presence of speA, speC, or speF was not implicated in any particular clinical syndrome in patients with invasive GAS disease. High-level protease activity and the M1 serotype of the isolates were significantly associated with the clinical signs of STSS and with mortality. M1 serotype and protease activity, as well as host immune status, might play significant roles in the pathogenesis of invasive GAS disease in Taiwan.

Background This study was conducted to investigate an outbreak caused by imipenem-resistant Acinetobacter baumannii (IRAB) in a medical intensive care unit (ICU) in a regional hospital. Methods In response to an IRAB outbreak from October 2012 to February 2013, we developed several infection control measures, including an extensive review process of environmental cleaning and disinfection, and used molecular methods to identify each clinical and environmental IRAB isolate. Results During this five-month period, 22 patients were colonized with IRAB and 18 patients had IRAB infections. The in-hospital mortality rate was significantly higher among patients with infections rather than colonizations (44.4% vs 9.1%, p = 0.028). Additionally, nine environmental specimens, including five specimens collected after terminal disinfection, were positive for IRAB. 12 environmental isolates and 28 of 36 available clinical isolates belonged to one unique pulsotype A, which was confirmed by molecular methods. We found the concentration of disinfectant, 0.08% sodium hypochlorite, was inadequate. After correcting the environmental cleansing methods, the surveillance study showed no further IRAB isolates on the control panel surfaces of the medical equipment or in patients in the ICU. Additionally, an in vitro study of IRAB immersed in different concentrations of sodium hypochlorite showed that 0.5% sodium hypochlorite eradicates IRAB after 30 seconds of inoculation, but 0.08% sodium hypochlorite only reduces the bacterial load. Conclusions This study highlights the importance of the preparation of disinfectants to adequately achieve environmental disinfection in the control of IRAB outbreaks in the ICU.

We conducted time-kill studies to evaluate the inhibitory activities of either cefotaxime or minocycline alone and the two drugs in combination against a clinical strain of Vibrio vulnificus. The MICs of cefotaxime and minocycline were 0.03 and 0.06 microg/ml, respectively. When approximately 5 x 10(5) CFU of V. vulnificus per ml was incubated with cefotaxime at 0.03 or 0.05 microg/ml, the bacterial growth was inhibited during the initial 2 and 8 h, respectively. Thereafter, V. vulnificus regrew and the level of growth reached that of the control. Within the dose range of less than five times the MIC, the duration of the inhibitory effect of cefotaxime was proportional to its concentration. When minocycline at 0.015, 0.03, 0.045, and 0.06 microg/ml was used to evaluate the inhibitory effect, a similar trend was observed. Either antibiotic at a concentration of five times the MIC or greater prevented the regrowth of V. vulnificus for at least 48 h. When cefotaxime at 0.05 microg/ml and minocycline at 0.045 microg/ml were combined in the same culture, the inhibitory effect against V. vulnificus persisted for more than 48 h, with no regrowth noted. The use of a combination of these two antibiotics resulted in the reduction of growth by 6 orders of magnitude compared to the use of either of the two antibiotics alone, and the number of surviving organisms in the presence of the antibiotics combined was approximately 3 orders of magnitude less than that in the starting inoculum. We conclude that cefotaxime and minocycline acted synergistically in inhibiting V. vulnificus in vitro.

A gene (vllY) encoding a novel hemolysin of Vibrio vulnificus CKM-1 has been cloned and sequenced. When the vllY gene was expressed in minicells, a unique peptide of approximately 40 kDa was identified. Subcellular fractionation of Escherichia coli cells carrying the vllY gene indicated that the VllY protein was distributed in both the cytoplasmic and the periplasmic fractions, with the notable ability to appear in the latter compartment. Nucleotide sequence analysis predicted a single open reading frame of 1,071 bp encoding a 357-amino acid polypeptide with an estimated pI of 5.02. The deduced amino acid sequence of VllY showed high similarity to the sequence of legiolysin, responsible for hemolysis, pigment production, and fluorescence in Legionella pneumophila. The enzyme also exhibited sequence homology to the MelA protein sequence of Shewanella colwelliana and the sequences of 4-hydroxyphenylpyruvate dioxygenase family proteins from various organisms. PCR screening and Southern blotting of V. vulnificus strains revealed that all of the 41 V. vulnificus clinical isolates contained vllY-like genes.

A gene ( empV ) encoding the extracellular metalloprotease of Vibrio vulnificus CKM-1 has been cloned and sequenced. When the empV gene was expressed in minicells, a unique peptide of approx. 46 kDa was identified. Protease activity staining experiments also indicated a similar M r for the protease. The empV gene product (EmpV) is secreted into the periplasm of Escherichia coli , but not out of it. The crude enzyme prepared from the periplasmic fraction of recombinant E. coli was inhibited by a metalloprotease inhibitor and Zn 2+ is essential for its protease activity. Nucleotide sequence analysis predicted a single open reading frame (ORF) of 1818 bp encoding a 606 amino acid (aa) polypeptide, with a potential 24 aa signal peptide followed by a long `pro' sequence consisting of 172 aa. The N-terminal 20 aa sequence for the elastolytic protease (EepV), purified from the culture supernatant of V. vulnificus ATCC 29307, completely identified the beginning of the predicted mature protein within the deduced aa sequence except for 1 aa residue difference. The estimated p I and molecular weight of the predicted mature protein were 5.86 and 44.3 kDa, respectively, which are nearly identical to those of V. vulnificus L-180 extracellular neutral metalloprotease (EnmV) and of strain ATCC 29307 EepV. The estimated molecular weight also closely matches that determined by SDS-PAGE analysis of the minicells and by protease activity staining. The deduced aa sequence of EmpV showed high homology to V. anguillarum metalloprotease (EmpA), V. cholerae HA/protease (HprC), and V. proteolyticus neutral protease (NprP), particularly with respect to active-site residues, zinc-binding residues, and cysteine residues.

The structural gene encoding the extracellular lipase of Aeromonas hydrophila MCC-2 was cloned and found to be expressed in Escherichia coli using its own promoter. When the cloned gene (lip) was expressed in E. coli minicells, an 80 kDa protein was identified. Subcellular fractionation of E. coli carrying the lip gene indicated that the Lip protein was mainly associated with the membrane fraction. Nucleotide sequence analysis revealed that the gene is 2253 bp long, coding for a 79.9 kDa protein with an estimated pl of 10.36. The deduced protein contains two putative signal peptide cleavage sites; one is a typical signal peptidase cleavage site and the other bears a strong resemblance to known lipoprotein leader sequences. Radioactivity from [3H]palmitate was incorporated into the Lip protein when expressed in E. coli. The deduced protein contains a sequence of VHFLGHSLGA which is very well conserved among lipases. It shows 67% and 65% overall identity to the amino acid sequences of lipase from A. hydrophila strains H3 and JMP636, respectively, but shows little homology to those of other lipases. The Lip protein was purified to homogeneity from both A. hydrophila and recombinant E. coli. In hydrolysis of p-nitrophenyl esters and triacylglycerols, using purified enzyme, the optimum chain lengths for the acyl moiety on the substrate were C10 to C12 for ester hydrolysis and C8 to C10 for triacylglycerol hydrolysis.

Infections due to Prototheca spp. are ubiquitous in nature, occurring in both immunocompetent and immunocompromised patients. The study cohort consisted of 14 cases of Prototheca algaemia reported over the past 5 decades and 2 recent cases from study hospitals. Prototheca wickerhamii was the most common species. The overall mortality rate was 62.5%. Prototheca algaemia, a healthcare-associated infection, was observed in immunocompromised patients and was associated with a poor prognosis.

Background The global spread and increasing incidence of carbapenem-resistant Enterobacteriaceae have resulted in treatment and public health concerns. Here, we present an investigation of the molecular mechanisms and clonality of carbapenem-non-susceptible Escherichia coli (CnSEC) based on a nationwide survey in Taiwan. Methods We collected 32 and 43 carbapenem-non-susceptible E. coli isolates in 2010 and 2012, respectively. The genes encoding cabapenemases and plasmidic AmpC-type and extended-spectrum β-lactamases (EBSLs) were analyzed by polymerase chain reaction (PCR). The major porin channels OmpF and OmpC were evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Molecular typing was performed with pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Results The resistance rates of CnSEC isolates to cefazolin, cefotaxime, cefoxitin, ceftazidime, and ertapenem were all 100%, and most (94.7%) isolates were CMY producers. The main mechanism of CnSEC in Taiwan is via plasmidic AmpC β-lactamase CMY-2 and DHA-1 in combination with the loss of OmpC/F. In 2010, one isolate was confirmed to harbor bla IMP-8; a KPC-2 producer and an NDM-1 producer were detected in 2012. No isolate had VIM- or OXA-carbapenemases. ST131 was the predominant ST type (33.3%). PFGE revealed no large cluster in CnSEC isolates in Taiwan. Conclusions The co-existence of plasmidic AmpC β-lactamase and outer membrane protein loss is the main mechanism for CnSEC in Taiwan. The emergence of KPC-2 and NDM-1 in 2012 and the predominance of ST131 warrant close monitoring and infection control.

To compare the in vitro antibacterial efficacies and resistance profiles of rifampin-based combinations against methicillin-resistant Staphylococcus aureus (MRSA) in a biofilm model, the antibacterial activities of vancomycin, teicoplanin, daptomycin, minocycline, linezolid, fusidic acid, fosfomycin, and tigecycline alone or in combination with rifampin against biofilm-embedded MRSA were measured. The rifampin-resistant mutation frequencies were evaluated. Of the rifampin-based combinations, rifampin enhances the antibacterial activities of and even synergizes with fusidic acid, tigecycline, and, to a lesser extent, linezolid, fosfomycin, and minocycline against biofilm-embedded MRSA. Such combinations with weaker rifampin resistance induction activities may provide a therapeutic advantage in MRSA biofilm-related infections.

This study investigated the in vitro susceptibilities of methicillin-resistant Staphylococcus aureus (MRSA) to nine antimicrobial agents in Taiwan. A total of 1,725 isolates were obtained from 20 hospitals throughout Taiwan from 2006 to 2010. The minimum inhibitory concentrations (MICs) of the nine agents were determined by the agar dilution method. The MICs of mupirocin and tyrothricin were determined for 223 MRSA isolates collected from 2009 to 2010. For vancomycin, 99.7 % were susceptible; however, 30.0 % (n = 517) exhibited MICs of 2 μg/ml and 0.3 % (n = 6) demonstrated intermediate susceptibility (MICs of 4 μg/ml). Nearly all isolates (≥ 99.9 %) were susceptible to teicoplanin, linezolid, and daptomycin. The MIC90 values were 2 μg/ml for ceftobiprole and 1 μg/ml for nemonoxacin. The MIC90 values of mupirocin and tyrothricin were 0.12 and 4 μg/ml, respectively. MIC creep was noted for daptomycin during this period, but not for vancomycin, teicoplanin, linezolid, or tigecycline. For isolates with vancomycin MICs of 2 μg/ml, the MIC90 values were 2 μg/ml for teicoplanin, 0.5 μg/ml for daptomycin, and 0.5 μg/ml for tigecycline. Those values were four- to eight-fold higher than those among isolates with vancomycin MICs of 0.5 μg/ml (2, 0.06, and 0.12 μg/ml, respectively). Of the nine MRSA isolates exhibiting non-susceptibility to vancomycin (n = 6), teicoplanin (n = 1), daptomycin (n = 2), or tigecycline (n = 1), all had different pulsotypes, indicating the absence of intra-hospital or inter-hospital spread. The presence of a high proportion of MRSA isolates with elevated MICs (2 μg/ml) and MIC creep of daptomycin might alert clinicians on the therapy for serious MRSA infections in Taiwan.

Xanthone derivatives have been shown to be potent inhibitors of tumour growth. Oxygenated xanthones and [3-(dialkylamino)-2-hydroxypropoxy]xanthones have been prepared and tested for in-vitro inhibition of human PLC/PRF/5, KB and 212 cells. Structure-activity analysis indicated epoxidation of the hydroxyxanthone increased cytotoxicity against tumour cells but ring-opening of the epoxide group with dialkylamine did not enhance the anti-tumour activity. Further evaluation of three of the most active compounds 2, 6-, 3, 6-, and 3, 5-di(2,3-epoxypropoxy)xanthone (compounds 10a, 11a, and 12a, respectively) in DNA, RNA and protein synthesis of tumour cells showed potent inhibitory activity. The 3,5-di(2,3-epoxypropoxy)xanthone also showed potent inhibitory activity against 212 cells, a Ha-ras oncogene-transformed NIH 3T3 cell line. The results indicated that compounds 10a and 12a are potent anti-tumour agents which not only suppressed cellular DNA, RNA and protein synthesis but also specifically inhibited the Ha-ras oncogene in 212 cells.

OBJECTIVES: The global spread and increasing incidence of carbapenem non-susceptible Klebsiella pneumoniae (CnSKP) has made its treatment difficult, increasing the mortality. To establish nationwide data on CnSKP spread and carbapenem-resistance mechanisms, we conducted a national surveillance study in Taiwanese hospitals. METHODS: We collected 100 and 247 CnSKP isolates in 2010 and 2012, respectively. The tests performed included antibiotic susceptibility tests; detection of carbapenemase, extended-spectrum β-lactamases (ESBL), and AmpC β-lactamases genes; outer membrane porin profiles; and genetic relationship with pulsed-field gel electrophoresis and multilocus sequence type. RESULTS: The resistance rate of CnSKP isolates to cefazolin, cefotaxime, cefoxitin, ceftazidime, and ciprofloxacin was over 90%. Susceptibility rate to tigecycline and colistin in 2010 was 91.0% and 83.0%, respectively; in 2012, it was 91.9% and 87.9%, respectively. In 2010, carbapenemase genes were detected in only 6.0% of isolates (4 bla IMP-8 and 2 bla VIM-1). In 2012, carbapenemase genes were detected in 22.3% of isolates (41 bla KPC-2, 7 bla VIM-1, 6 bla IMP-8, and 1 bla NDM-1). More than 95% of isolates exhibited either OmpK35 or OmpK36 porin loss or both. Impermeability due to porin mutation coupled with AmpC β-lactamases or ESBLs were major carbapenem-resistance mechanisms. Among 41 KPC-2-producing K. pneumoniae isolates, all were ST11 with 1 major pulsotype. CONCLUSIONS: In 2010 and 2012, the major mechanisms of CnSKP in Taiwan were the concomitance of AmpC with OmpK35/36 loss. KPC-2-KP dissemination with the same ST11 were observed in 2012. The emergence and rapid spread of KPC-2-KP is becoming an endemic problem in Taiwan. The identification of NDM-1 K. pneumoniae case is alarming.

Fifty-nine episodes of bacteremia due to Aeromonas species occurred within a 5-year period in one medical center in southern Taiwan. Underlying diseases in the 58 patients included hepatic cirrhosis (36%) and cancer (24%). Patients with aeromonas bacteremia more often had underlying hepatic cirrhosis than did those with bacteremia due to other gram-negative bacilli. Males (67%) outnumbered females. The cases appeared to cluster in the summer and fall months. Thirty-two percent were polymicrobial infections; often the Aeromonas pathogens were accompanied by other gram-negative bacilli. Aeromonas hydrophila was the most common species isolated (69%). In addition to fever, hypotension and jaundice were the common clinical manifestations of aeromonas sepsis. In cirrhotic patients, spontaneous bacterial peritonitis, altered mental status, and jaundice were most common, and aeromonas bacteremia in such patients was monomicrobial and community-acquired more often than in noncirrhotic patients. In vitro aeromonads were generally susceptible to aminoglycosides, cefuroxime, the third-generation cephalosporins, and quinolones. The overall crude fatality rate was 36%. Predictors of fatal outcome for cirrhotic patients included spontaneous bacterial peritonitis, hypotension on admission, diabetes mellitus, and high Pugh scores.

We report a 5 year experience of 10 cases of mycotic aneurysms of the aorta caused by salmonella infection. Of the 10 patients, nine were males and one was female in an age range from 60 to 80 years with a mean of 71 years. The major clinical manifestations were fever, abdominal or back pain, pulsatile abdominal mass and leucocytosis. The diagnosis was based on clinical symptoms and signs and positive blood or tissue cultures. The main confirmatory procedure was computed tomography (CT). Two year survival rate was 20%. Five patients died during hospitalisation, without surgery. Three patients died within 2 months of surgery. The other two patients, treated surgically and by intensive antibiotic therapy, survived. Death resulted usually from recurrent infection and graft leakage. Contrary to previous reports, salmonella mycotic aneurysms is still common in this geographical area and the prognosis is poor.

The Study for Monitoring Antimicrobial Resistance Trends (SMART) is a worldwide surveillance program designed to longitudinally monitor the in vitro activity of antimicrobial agents against pathogens that cause intra-abdominal infections (IAIs). In this study, trends in antimicrobial resistance during the period 2006 to 2010 were analyzed at five tertiary-care hospitals in Taiwan. Enterobacteriaceae accounted for the majority (80.9%) of the 2417 Gram-negative isolates, and the two most common species were Escherichia coli (38.8%) and Klebsiella pneumoniae (23.5%). The rates of susceptibility of Enterobacteriaceae isolates to cephalosporins decreased during the study period. Although carbapenems, fluoroquinolones, piperacillin-tazobactam, and amikacin were active in vitro against more than 80% of the Enterobacteriaceae isolates, the activity of carbapenems declined during the study period. Extended-spectrum β-lactamase (ESBL) production in E. coli was steady, but that in K. pneumoniae decreased during the study period. The rate of ESBL-producing species was three-fold higher among patients with nosocomial IAIs than among patients with community-acquired IAIs. The majority of isolates from liver were K. pneumoniae (69%) and very few of those isolates were ESBL producers (0.9%). Pseudomonas aeruginosa (9.3%) and Acinetobacter baumannii (3.8%) were the two most common non-Enterobacteriaceae. P. aeruginosa showed improved susceptibility, whereas A. baumannii showed a rapid development of resistance during the study period. There was marked geographic variation in resistance patterns of the isolates obtained during the study period. Northern Taiwan had the highest rate of ESBL producers and the highest rate of ceftazidime resistance among P. aeruginosa isolates. Central Taiwan had the lowest rate of ESBL producers but the highest rates of carbapenem resistance among P. aeruginosa and A. baumannii isolates. Continuous monitoring and regular updates of epidemiological data are needed to guide appropriate empiric antimicrobial therapy.

We investigated the trend in resistance to carbapenems among isolates of Enterobacteriaceae that had been collected from patients with intra-abdominal infections at five medical centers in Taiwan from 2006 to 2010 and evaluated the correlation between resistance to carbapenems and consumption of said agents as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART). During the study period, the usage of ertapenem and that of total carbapenems (ertapenem, imipenem, and meropenem) increased significantly from 6.13 to 13.38 defined daily doses per 1000 patient-days for ertapenem and from 20.43 to 34.25 defined daily doses per 1000 patient-days for total carbapenems. The most common species were Escherichia coli (n = 1095), Klebsiella spp. (n = 663), and Enterobacter spp. (n = 202). The susceptibility of all isolates to ertapenem and to imipenem varied during the study period. For ertapenem, the rates of nonsusceptibility ranged from 3.5% to 10.3% and those for imipenem ranged from 3.5% to 10.7%. Although the use of carbapenems increased during the study period, there was no marked increase in resistance to carbapenems. Continuous monitoring of resistance trends is necessary so that antimicrobial prescription policies can be adjusted and infection control intervention programs can be implemented.

The Study for Monitoring Antimicrobial Resistance Trends (SMART) is an international surveillance study designed to monitor resistance trends among aerobic and facultative Gram-negative bacilli (GNB) isolated from intra-abdominal infections. During 2003-2010, a total of 20710 GNB isolates were collected at medical centers in China, Hong Kong, Korea, New Zealand, and Taiwan. The susceptibility profiles of 2252 isolates of non-Enterobacteriaceae GNB were determined. At least 10 isolates of a given organism were required for that organism to be included in the analysis. Pseudomonas aeruginosa was the leading organism (49.2% of non-Enterobacteriaceae GNB), followed by Acinetobacter baumannii (21.5%), Aeromonas spp. (11.6%), and Stenotrophomonas maltophilia (9.1%). All the other species/genera made up less than 2%. The rates of susceptibility of the four major organisms were examined for two different time periods and according to whether the isolates had been obtained48 h after hospitalization or ≥ 48 h after hospital admission. P. aeruginosa, Aeromonas spp., and S. maltophilia showed sustained levels of susceptibility to several antimicrobial agents in the two time periods, whereas A. baumannii exhibited very high rates of resistance to most antimicrobial agents including imipenem. Nosocomial P. aeruginosa and A. baumannii were more resistant than community-acquired pathogens, although this was not the case for Aeromonas spp. and S. maltophilia. Worldwide and regional surveillance is necessary to guide empirical antimicrobial therapy for infections due to non-Enterobacteriaceae GNB.

This study examined the rates of susceptibility to third-generation cephalosporins and carbapenems among Enterobacteriaceae isolates that had been obtained from patients with intraabdominal infections in the Asia-Pacific region as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART). Susceptibility profiles obtained using 2009 Clinical and Laboratory Standards Institute (CLSI) breakpoints were compared with those obtained using the 2011 CLSI breakpoints. From 2002 to 2010, Escherichia coli and Klebsiella pneumoniae together accounted for more than 60% of the 13714 Enterobacteriaceae isolates analyzed during the study period. Extended-spectrum β-lactamase (ESBL) producers comprised 28.2% of E. coli isolates and 22.1% of K. pneumoniae isolates in the Asia-Pacific region, with China (55.6% and 33.7%, respectively) and Thailand (43.1% and 40.7%, respectively) having the highest proportions of ESBL producers. Based on the 2011 CLSI criteria, 77.2% of the Enterobacteriaceae isolates, 40.4% of ESBL-producing E. coli, and 25.2% of ESBL-producing K. pneumoniae isolates were susceptible to ceftazidime. Carbapenems showed in vitro activity against >90% of Enterobacteriaceae isolates in all participating countries, except for ertapenem in South Korea (susceptibility rate 82.2%). Marked differences (>5%) in susceptibility of ESBL-producing E. coli and K. pneumoniae isolates to carbapenems were noted between the profiles obtained using the 2009 CLSI criteria and those using the 2011 CLSI criteria. Continuous monitoring of antimicrobial resistance is necessary in the Asia-Pacific region.

The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, a nationwide, prospective surveillance during 2006 to 2010, collected a total of 7,793 clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA) ( n = 1,834), penicillin-resistant Streptococcus pneumoniae (PRSP) ( n = 423), vancomycin-resistant enterococci (VRE) ( n = 219), extended-spectrum β-lactamase (ESBL)-producing Escherichia coli ( n = 1,141), ESBL-producing Klebsiella pneumoniae ( n = 1,330), Acinetobacter baumannii ( n = 1,645), and Stenotrophomonas maltophilia ( n = 903), from different specimens from 20 different hospitals in Taiwan. MICs of tigecycline were determined following the criteria of the U.S. Food and Drug Administration (FDA) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST-2011). Among drug-resistant Gram-positive pathogens, all of the PRSP isolates were susceptible to tigecycline (MIC 90 , 0.03 μg/ml), and only one MRSA isolate (MIC 90 , 0.5 μg/ml) and three VRE isolates (MIC 90 , 0.125 μg/ml) were nonsusceptible to tigecycline. Among the Gram-negative bacteria, the tigecycline susceptibility rates were 99.65% for ESBL-producing E. coli (MIC 90 , 0.5 μg/ml) and 96.32% for ESBL-producing K. pneumoniae (MIC 90 , 2 μg/ml) when interpreted by FDA criteria but were 98.7% and 85.8%, respectively, when interpreted by EUCAST-2011 criteria. The susceptibility rate for A. baumannii (MIC 90 , 4 μg/ml) decreased from 80.9% in 2006 to 55.3% in 2009 but increased to 73.4% in 2010. A bimodal MIC distribution was found among carbapenem-susceptible A. baumannii isolates, and a unimodal MIC distribution was found among carbapenem-nonsusceptible A. baumannii isolates. In Taiwan, tigecycline continues to have excellent in vitro activity against several major clinically important drug-resistant bacteria, with the exception of A. baumannii .

Minimal inhibitory concentration (MIC) creep in meticillin-resistant Staphylococcus aureus (MRSA) isolates has been observed in recent years. The potential roles of vancomycin-based combination regimens as well as linezolid and tigecycline against five clinical MRSA isolates with vancomycin MICs of 2 μg/mL (VA2-MRSA) were evaluated and compared in vitro. Antimicrobial susceptibility was studied by the agar dilution method. Anti-MRSA activities of linezolid, tigecycline, vancomycin, minocycline, rifampicin and fosfomycin alone as well as of three vancomycin-based combinations were studied by time-kill method and using a biofilm model. When VA2-MRSA at an inoculum of 1×10(5)colony-forming units (CFU)/mL was incubated with vancomycin, tigecycline, linezolid or rifampicin alone, bactericidal activity lasted for 48 h in time-kill analysis. At a higher inoculum of 1×10(7) CFU/mL, only linezolid demonstrated a bacteriostatic effect at 24 h and the inhibitory activity lasted for 36 h. However, bacterial growth was inhibited ≥2log(10) at 24 h and was even undetectable at 48 h with vancomycin plus fosfomycin or rifampicin. In biofilm studies, vancomycin plus fosfomycin or minocycline at susceptible breakpoint concentrations demonstrated an enhanced antibacterial effect comparable with linezolid and better than tigecycline. In conclusion, vancomycin plus fosfomycin or rifampicin exhibited a synergistic and better antibacterial effect than linezolid or tigecycline alone against high-inoculum planktonic VA2-MRSA. Vancomycin plus fosfomycin or minocycline compared with linezolid exhibited a similar inhibitory effect, better than tigecycline alone, against biofilm-embedded VA2-MRSA. Evaluating the toxicity and efficacy of high-dose vancomycin monotherapy for VA2-MRSA, the fosfomycin combination exhibited a rapid killing effect in both conditions and may provide another therapeutic choice.

Background Patients infected with Vibrio vulnificus (V. vulnificus) show severe inflammatory responses characterised by the upregulation of proinflammatory cytokines. Macrophage migration inhibitory factor (MIF), an upstream proinflammatory regulator, increases the inflammation caused by sepsis. Whether MIF regulates responses to V. vulnificus infection and the actual mechanism by which V. vulnificus initiates these MIF-modulated proinflammatory cytokines remain unclear. Results MIF increased inflammation during V. vulnificus infection in vivo. In V. vulnificus-infected mice, MIF was produced earlier than tumour necrosis factor (TNF)-α and interleukin (IL)-6 and was expressed in a time-dependent manner. ISO-1 ((S, R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester), a small-molecule inhibitor of MIF, significantly decreased IL-6, IL-8, and TNF-α production in a time- and dose-dependent manner in human peripheral blood cells infected with V. vulnificus. The induction of IL-6, IL-8, and TNF-α production by V. vulnificus infection was mediated via the NF-κB- and p38 MAPK-regulated pathways but not via the Akt pathway. ISO-1-treated human peripheral blood cells showed lower V. vulnificus-induced NF-κB activation, IL-6 mRNA expression, and IκB phosphorylation, but they did not show lower p38 MAPK activation. Conclusions We conclude that MIF regulates V. vulnificus-induced IL-6 production via NF-κB activation and that p38 MAPK activation in V. vulnificus infection is not MIF dependent.

Escherichia coli remains one of the most common etiologies of secondary peritonitis. CMY-2 is the most prevalent AmpC enzyme identified in nosocomial E. coli isolates causing bacteremia in Taiwan. This report is of a patient who underwent surgery for intestinal perforations due to blunt abdominal trauma and developed unexpected CMY-2-producing E. coli septicemia in the early postoperative period. The AmpC-type CMY-2 enzyme might partially contribute to the poor response to antimicrobial therapy of amoxicillin-clavulanic acid or flomoxef. Late changes in antibiotic therapy to an appropriate regimen of cefpirome based on the culture results did not result in a positive outcome and the patient died. Whether selection of an anti-AmpC regimen is appropriate as first-line treatment for traumatic abdomen-associated septicemia should be an area of further investigation in Taiwan.

purpose: Acute bacterial nephritis (ABN) represents localized, nonliquefied renal infection, and the subsequent alteration of tissue densities can be readily detected by computed tomography (CT). In recent literature, a variety of renal parenchymal alterations observed on CT were reported. However, previous reports on the clinical course of ABN were inconsistent and lacked correlation with radiologic findings. In this investigation, we attempt to correlate the severity of clinical manifestations with CT findings in ABN and draw some conclusions regarding the natural history, pathophysiology, and clinical management of this disease. patients and methods: From July 1988 to June 1991, 30 cases of ABN were evaluated at our institute. On the basis of postcontrast-enhanced CT findings, 28 cases were grouped into (1) Group I (7 cases), wedge-shaped lesions (focal or diffuse); (2) Group II (12 cases), focal mass-like lesions; and (3) Group III (9 cases), diffuse (multifocal) mass-like lesions. The clinical features and outcomes of the three groups were compared. The positive detecting rates and clinical usefulness of ultrasonographic (US) and urographic examinations were also studied in each group. results: An excellent correlation can be demonstrated between the clinical parameters (including underlying diseases, maximum temperature and leukocyte count, duration of fever, flank pain, leukocytosis, and pyuria; the incidence of septic shock, diabetic ketoacidosis, and acute renal failure; and outcome) and the pattern of renal parenchymal abnormalities detected on CT. The clinical features in Group I patients displayed many similarities with those in uncomplicated acute pyelonephritis (APN) reported previously, and responded to antibiotic therapy promptly. Most patients in Group II were successfully treated with antibiotics but had a protracted clinical course with a slower clinical improvement than Group I. Only one case with a Group II lesion was noted to progress to renal abscess formation and extrarenal involvement. In comparison, 33% of the patients in Group III died despite antibiotic therapy. Our data also show that US examination is sensitive in detecting Group II ABN lesions (62% positive rate), and revealed marked renal enlargement in most Group III lesions (89%). It is therefore a useful initial imaging modality in providing information vital to clinical decision making. conclusion: Our experiences suggest that renal bacterial infection may show the continuum of severity from uncomplicated APN to ABN, demonstrated on postcontrast CT scan as wedge-shaped lesions to mass-like lesions, and possibly, finally to frank abscess formation. We classify ABN into three subgroups according to CT findings, and good correlation with clinical severity is demonstrated. These findings deliver valuable concepts regarding the pathophysiology and clinical management of this disease.

To compare efficacy and safety of a tigecycline regimen with an imipenem/cilastatin regimen in hospital-acquired pneumonia patients, a phase 3, multicenter, randomized, double-blind, study evaluated 945 patients. Coprimary end points were clinical response in clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure. Cure rates were 67.9% for tigecycline and 78.2% for imipenem (CE patients) and 62.7% and 67.6% (c-mITT patients), respectively. A statistical interaction occurred between ventilator-associated pneumonia (VAP) and non-VAP subgroups, with significantly lower cure rates in tigecycline VAP patients compared to imipenem; in non-VAP patients, tigecycline was noninferior to imipenem. Overall mortality did not differ between the tigecycline (14.1%) and imipenem regimens (12.2%), although more deaths occurred in VAP patients treated with tigecycline than imipenem. Overall, the tigecycline regimen was noninferior to the imipenem/cilastatin regimen for the c-mITT but not the CE population; this difference appears to have been driven by results in VAP patients.

We conducted an active, population-based laboratory surveillance study to evaluate the epidemiologic features of invasive pneumococcal disease (IPD) in Taiwan. Concurrently, nasopharyngeal colonization of Streptococcus pneumoniae was evaluated among 1128 healthy children agedor=5 years. The overall incidence was highest among children aged 2-4 years (15.6/100,000). Serotype 19A, which had never been reported in Taiwan previously, caused a substantial fraction of the invasive diseases (OR, 9.6; 95% CI, 3.1-29.4) among children aged 2-4 years. Comparing serotype distributions of the isolates from nasopharyngeal colonization among children agedor=5 years, serotypes 14 (OR, 17.3; 95% CI, 5.2-57.9) and 19A (OR, 14.9; 95% CI, 1.9-117) had the highest invasive potential. The study found that serotype 19A expanded in Taiwan, a country with a low 7-valent conjugate pneumococcal vaccine coverage. The 7-valent conjugate pneumococcal vaccines covered 73% of cases in children aged between 2 and 4 years, and 64.7% of cases in children aged2 years. Among patients agedor=65 years, the 23-valent pneumococcal polysaccharide vaccine covered 70.4% of cases. In the future, a broader pneumococcal vaccine is needed.

Background Lactoferrin (LF) is an iron-binding glycoprotein that plays an important role in combating a wide range of pathogens and contributes innate protective defenses of mammals. Methods We cloned and sequenced the full-length cDNA for LF from Taiwan macaque. The antimicrobial activity and iron-binding ability of the purified recombinant macaque LF (rmLF) were determined and compared with those of human LF (hLF). Results and conclusions The complete mLF cDNA (GenBank: EU523857) encoded a 710-aa precursor with a 19-aa signal peptide. The nucleotide sequence of mLF showed the highest identity to the rhesus monkey LF (98%), whereas the putative amino acid sequence of mLF showed the highest identity to the hLF (90%). The rmLF and natural hLF showed almost equivalent antibacterial activities against Klebsiella pneumoniae and mLF presented a slightly lower activity against Listeria monocytogenes than natural hLF. In addition, the patterns of iron release from mLF and hLF were nearly identical.

persons: Primary septicemia and wound infection, both associated with high mortality2,3) Vibrio vulnificus infection is not rare in the Southwestern coast of Taiwan in our own experience) . Here we report a "characteristi c" victim with extensive cellulitis and septic shock caused by Vibrio vulnificus infection , who was successfully resuscitated by early recognition , appropriate antibiotics and prompt surgical intervention.

Tigecycline In-vitro Surveillance in Taiwan (TIST), initiated in 2006, is a nationwide surveillance programme designed to monitor longitudinally the in-vitro activity of tigecycline against commonly encountered resistant bacteria. This study compared the in-vitro activity of tigecycline against clinical isolates of resistant Gram-negative bacteria determined by the broth microdilution and Etest methods. A total of 622 isolates were collected from patients treated at 20 teaching hospitals. Tigecycline had excellent in-vitro activity against extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (N = 275) with MIC(90) 0.5 microg/mL and a 99.6% susceptibility rate, and also against ESBL-producing Klebsiella pneumoniae (N = 324) with MIC(90) 2 microg/mL and a 98.5% susceptibility rate. For ESBL-producing Proteus mirabilis (N = 15) the MIC(90) was 4 microg/mL with a 73.3% susceptibility rate. For ESBL-producing Klebsiella oxytoca (N = 8) the MIC(50) and MIC(90) were 0.5 and 1 microg/mL, respectively, with a 100% susceptibility rate. Limited agreement (

We performed susceptibility testing using the microdilution method to determine the in-vitro activity of tigecycline against 393 Acinetobacter baumannii clinical isolates collected in 2006 from 19 hospitals in Taiwan. Significant proportions of the isolates were resistant to imipenem (44%), ciprofloxacin (75%), amikacin (69%), sulbactam (34%) and all four antibiotics (22%), and susceptibility to tigecycline among these different resistant phenotypes of A. baumannii varied from 71% to 82%. The minimum inhibitory concentration (MIC) of tigecycline ranged from 0.6 to 16 microg/mL (MIC(50) 2 microg/mL; MIC(90) 4 microg/mL). The cumulative curve of tigecycline MICs showed that when the MIC cut-offs were set at 2 microg/mL and 4 microg/mL, 80.9% and 93.1% of the isolates were susceptible, respectively. As tigecycline will be used in the future for infections caused by multidrug-resistant A. baumannii because of limited antibiotic choice, and as resistance to tigecycline in A. baumannii isolates may develop following antibiotic exposure, continuous monitoring of the susceptibility of A. baumannii isolates to tigecycline is warranted.

Klebsiella pneumoniae causes a wide spectrum of infections, including abscess and non-abscess formation. This study investigated the clinical spectrum and molecular characteristics of community-acquired Klebsiella infection with primary extrahepatic abscess.From April 2004 through March 2007, a total of 18 strains of K. pneumoniae, 11 from blood and 7 from focal purulent specimens, were recovered from a medical center in southern Taiwan. The clinical data were collected from medical records. Hypermucoviscosity phenotype was defined as positive string test. The virulence genes, including rmpA (regulator of mucoid phenotype), magA (specific to K1 capsule serotype), k2A (specific to K2 capsule serotype), and kfu (an iron uptake system) were amplified by polymerase chain reaction using specific primers.Twelve men and 6 women with ages ranging from 37 to 74 years were enrolled. Fifteen patients had underlying diabetes mellitus. The duration of hospitalization ranged from 1 to 96 days. Three patients died by the end of treatment. All of the K. pneumoniae strains carried rmpA and 16 strains showed the hypermucoviscosity phenotype. Of the 18 strains, 7 strains were positive for k2A and 4 strains carried magA. kfu was identified in 4 magA-positive strains and 2 magA-negative/k2A-negative strains.Diabetes mellitus was the most frequent underlying disease among our patients. The rmpA and/or hypermucoviscosity phenotype were the most common virulence factors in K. pneumoniae isolates causing extrahepatic abscesses, among which K2 capsule serotype (k2A+) was more prevalent than K1 capsule serotype (magA+).

Strains of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae have spread widely in Taiwan hospitals. In this study, we evaluated the in vitro antimicrobial activity of tigecycline against ESBL-producing Enterobacteriaceae, including Klebsiella pneumoniae, Serratia marcescens and Enterobacter cloacae.104 confirmed ESBL-producing bacteria were isolated from 4 hospitals in mid- and southern Taiwan between 2000 and 2006. The in vitro activity of tigecycline against these ESBL producers was tested by use of Etest strips.The minimal tigecycline concentration at which 50% of isolates were inhibited and minimal concentration at which 90% of isolates were inhibited for ESBL-producing isolates ranged from 0.38 to 0.75 microg/mL and 0.5 to 1.5 microg/mL, respectively.Tigecycline, a new semisynthetic glycylcycline, may be considered an alternative drug of choice for patients infected with ESBL-producing bacteria.

Background Type 1 fimbriae are the most commonly found fimbrial appendages on the outer membrane of Salmonella enterica serotype Typhimurium. Previous investigations indicate that static broth culture favours S. Typhimurium to produce type 1 fimbriae, while non-fimbriate bacteria are obtained by growth on solid agar media. The phenotypic expression of type 1 fimbriae in S. Typhimurium is the result of the interaction and cooperation of several genes in the fim gene cluster. Other gene products that may also participate in the regulation of type 1 fimbrial expression remain uncharacterized. Results In the present study, transposon insertion mutagenesis was performed on S. Typhimurium to generate a library to screen for those mutants that would exhibit different type 1 fimbrial phenotypes than the parental strain. Eight-two mutants were obtained from 7,239 clones screened using the yeast agglutination test. Forty-four mutants produced type 1 fimbriae on both solid agar and static broth media, while none of the other 38 mutants formed type 1 fimbriae in either culture condition. The flanking sequences of the transposons from 54 mutants were cloned and sequenced. These mutants can be classified according to the functions or putative functions of the open reading frames disrupted by the transposon. Our current results indicate that the genetic determinants such as those involved in the fimbrial biogenesis and regulation, global regulators, transporter proteins, prophage-derived proteins, and enzymes of different functions, to name a few, may play a role in the regulation of type 1 fimbrial expression in response to solid agar and static broth culture conditions. A complementation test revealed that transforming a recombinant plasmid possessing the coding sequence of a NAD(P)H-flavin reductase gene ubiB restored an ubiB mutant to exhibit the type 1 fimbrial phenotype as its parental strain. Conclusion Genetic determinants other than the fim genes may involve in the regulation of type 1 fimbrial expression in S. Typhimurium. How each gene product may influence type 1 fimbrial expression is an interesting research topic which warrants further investigation.

Background: Sepsis is a major cause of mortality in the intensive care unit. Oxidative stress plays an important role in the pathogenesis of organ failure during sepsis. Sesame oil decreases circulating oxygen free radicals in septic rats; however, its effect on hepatic oxidative status is unknown. The authors examined the effect of sesame oil on hepatic lipid peroxidation in septic rats. Methods: Hepatic injury was induced using cecal ligation and puncture (CLP). Rats were divided into 4 groups: sham, rats given a sham operation without CLP; SO, rats given sesame oil alone; CLP, rats given saline and then CLP; and CS, rats given sesame oil and then CLP. All rats were first given a 1-week daily oral supplement of sesame oil or saline (4 mL/kg/d) and then CLP or a sham operation. The authors assessed hepatic oxidative stress by determining hepatic lipid peroxidation, hydroxyl radical, superoxide anion, and nitric oxide levels 12 hours after CLP. They also assessed xanthine oxidase activity and nitric oxide synthase expression. Results: Hepatic lipid peroxidation (P < .0001), hydroxyl radical (P < .05), superoxide anion (P < .05), and nitrite (P < .05) levels were significantly lower in sesame oil–treated septic rats. Furthermore, sesame oil significantly reduced xanthine oxidase activity (P < .01) and inducible nitric oxide synthase expression (P < .005) in septic rats. Conclusions: Sesame oil might attenuate hepatic lipid peroxidation by inhibiting superoxide anion and nitric oxide, at least partially, in experimental septic rats. (JPEN J Parenter Enteral Nutr. 2008;32:154-159)

Ciprofloxacin, moxifloxacin and levofloxacin are recognized immunomodulators. Their effects in acute lung injuries have not been tested. This study compared the immunoprotective effects of these agents in mice with lung injuries induced by LPS by measuring the cytokine profiles in the injured lung and the associated mortality.The development of lung injury and mortality was compared in mice pretreated with either ciprofloxacin, levofloxacin, moxifloxacin or saline (control group) after the intratracheal administration of LPS. BALF and serum were collected at 1, 3 and 6 h to measure the concentrations of tumour necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6, IL-10 and macrophage inflammatory protein-2 (MIP-2) using enzyme-linked immunoassay.Levels of TNF-alpha, IL-1beta and MIP-2 in the BAL of the ciprofloxacin group were significantly lower compared with those of controls (all P0.0083) at 3 and 6 h after LPS challenge. There were no significant differences in the levels of these cytokines in the moxifloxacin and levofloxacin groups compared with controls. Overall, the 96-h survival for the mice pretreated with ciprofloxacin, but not for those pretreated with moxifloxacin or levofloxacin, was significantly greater than that of the control animals (P = 0.019).In the setting of LPS-induced lung injuries, ciprofloxacin appears to provide better anti-inflammatory properties and survival benefits than the other fluoroquinolones tested.

Prostate infection caused by Aeromonas sobria has not been reported in the literature. We presented a 44-year-old healthy man with a habit of alcoholic consumption who was admitted because of primary A. sobria prostatitis with septicemia. The patient was successfully treated with intravenous ofloxacin and was uneventful after a half-year follow-up. Based on our rare case, we suggest to clinical physicians that prostatitis might be considered in healthy male patients with A. sobria bacteremia and a vague primary infection focus.

Resistance of Serratia marcescens, a nosocomial pathogen of Enterobacteriaceae, to the extended-spectrum beta-lactams is usually mediated by an overproduced AmpC cephalosporinase. We aimed to characterize the molecular epidemiology and AmpC of S. marcescens isolates recovered from 1 medical center in southern Taiwan. AmpC-encoding genes for SRT families were investigated by polymerase chain reaction and DNA sequencing. From August 1999 through July 2003, 69 nonrepetitive bloodstream isolates were enrolled. Excluding 11 isolates, which also produced an extended-spectrum beta-lactamase, 58 isolates carried an AmpC-encoding gene, including a novel S4 gene with 98% identity to SRT-1 gene (n = 50), SRT-2 gene (n = 3), SST-1 gene (n = 1), and others (n = 4). Isolates with S4 exhibited a phenotype of resistance to cefotaxime (CTX) but not ceftazidime. Genotype analysis by pulsed-field gel electrophoresis revealed that 45 (90%) of the isolates carrying S4 gene belonged to 2 major epidemic clones, including types A (n = 28) and B (n = 17). In conclusion, the AmpC-like S4 beta-lactamase may confer CTX resistance of the S. marcescens population. Strains carrying the S4 gene with prolonged dissemination were closely related.

Melioidosis has been well known to be endemic in Thailand and Northern Australia, and was reported sporadically in Taiwan before 2005. We retrospectively analyzed 58 patients with melioidosis in southern Taiwan from 2000 to 2005, including 40 clustered and 18 sporadic cases, for clinical characteristics and antimicrobial susceptibility. Fifty-one (88%) cases were found during the rainy season, and there was a significant correlation between the average monthly rainfalls and the case number (r = 0.37; p = 0.001). Diabetes mellitus was the most common underlying disease (35 cases, 60%). The majority (52 cases, 90%) had never traveled abroad before illness, indicating indigenous acquisition of Burkholderia pseudomallei. In comparison, clustered cases were older, less often had underlying diabetes mellitus and had a shorter duration of clinical symptoms before admission than sporadic cases. Acute form of melioidosis predominated, and shock at admission was independently associated with a grave prognosis. Overall, 22% of 58 patients died in hospitals. Ceftazidime, imipenem, meropenem, amoxicillin/clavulanic acid, co-trimoxazole, and doxycycline, as previously recommended, were the potentially therapeutic choices. The role of piperacillin/ tazobactam for melioidosis remains undefined. Melioidosis can occur sporadically or in a cluster in diabetic patients during rainy seasons in Taiwan.

Vibrio vulnificus causes primary bacteremia and necrotizing wound infection, leading to high morbidity and mortality in humans. This study aimed to evaluate the antimicrobial effect of cefotaxime and minocycline on proinflammatory cytokine levels in a murine model of V. vulnificus infection.We investigated the dynamics of proinflammatory cytokines and their modulation by antimicrobial agents using a murine model of V. vulnificus infection. The change in cytokine levels was followed over a time course to identify the antimicrobial activity of the drugs against V. vulnificus. BALB/c female mice were challenged with an intraperitoneal infection using a clinical invasive isolate of Vv05191, and their cytokine levels were assayed over various time points.Serum levels of tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6 post-infection were found to be inoculum dose-dependent and positively correlated to the subsequent fatality rate in the infected mice. With an inoculum of 6.6 x 10(6) colony-forming units and intraperitoneal administration of cefotaxime, minocycline, or both, the serum and peritoneal fluid cytokine levels increased and then declined gradually. Comparison of the 3 antimicrobial regimens revealed that the magnitude of reduction in cytokine levels was greatest in mice treated with cefotaxime-minocycline combination. Moreover, the peritoneal fluid cytokine level in the combination group was significantly lower than that in the groups treated with minocycline or cefotaxime alone.The current results support the superiority of the combination therapy in treating invasive V. vulnificus infections.

Little is known about the possible synergism of baicalein, a bioactive flavone of Scutellariae radix (a Chinese herb), when used in conjunction with other antimicrobial agents against vancomycin-resistant Enterococcus (VRE). This in vitro study examined the possible synergism of the combination of baicalein and gentamicin against VRE.Minimal inhibitory concentrations (MICs) of baicalein as well as gentamicin were determined against 39 clinical isolates of VRE by the agar dilution method. Synergistic activities were determined using the checkerboard method based on the fractional inhibitory concentration indices and also the time-kill method. Further time-kill studies were conducted with these two agents against one randomly chosen clinical isolate, VRE-096.Minimal concentrations inhibiting 50% (MIC(50)) and 90% (MIC(90)) of isolates for baicalein and gentamicin were all256 microg/mL. Synergism between baicalein and gentamicin was demonstrated against four clinical isolates of VRE (VRE-70, VRE-940, VRE-096 and VRE-721). When approximately 5 x 10(5) colony-forming units/mL of VRE-096 was incubated with both baicalein at a concentration of 32 microg/mL (1/8 x MIC) and gentamicin at a concentration of 128 microg/mL (1/2 x MIC), there was an inhibitory effect against VRE that persisted for 48 h. At 48 h, the combination of baicalein and gentamicin at these respective concentrations resulted in a reduction of growth by approximately 2 orders of magnitude compared to that for the starting inoculum and by 3 orders of magnitude compared to that for baicalein alone, the more active single agent.This study demonstrated that baicalein and gentamicin can act synergistically in inhibiting VRE in vitro.

The impact of antimicrobial treatment on the outcome of carbapenem nonsusceptible Klebsiella pneumoniae (CnsKP) infections needs to be elucidated. This nationwide, multicenter study was conducted to evaluate the impact of appropriate antimicrobial therapy on 14-day mortality among patients with CnsKP infection in Taiwan. Patients with CnsKP infections from 11 medical centers and 4 regional hospitals in Taiwan were enrolled in 2013. Carbapenem nonsusceptibility was defined as a minimum inhibitory concentration of ≥2 mg/L for imipenem or meropenem. Predictors of 14-day mortality were determined using the Cox proportional regression model. The influence of infection severity on the impact of appropriate use of antimicrobials on 14-day mortality was determined using the Acute Physiology and Chronic Health Evaluation (APACHE) II score. Overall 14-day mortality was 31.8% (49/154). Unadjusted mortality for appropriate antimicrobial therapy was 23.1% (18/78 patients). Appropriate therapy was independently associated with reduced mortality (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.24–0.80; P = 0.007). A subgroup analysis revealed that the benefit of appropriate therapy was limited to patients with higher APACHE II scores (HR for patients with scores >15 and ≤35, 0.46; 95% CI 0.23–0.92; and for those with scores >35, 0.14; 95% CI, 0.02–0.99). In conclusion, appropriate antimicrobial therapy significantly reduces 14-day mortality for CnsKP infections. Survival benefit is more notable among more severely ill patients.

Immunocompromised patients with Vibrio vulnificus septicemia are at high risk for fatality. When a hemorrhagic bullous necrotic cutaneous lesion (HBNCL) and decreased blood pressure develop, approximately 50% of V vulnificus septicemic patients die within 48 hours. This study aimed to evaluate the risk factor(s) for fatality among patients with V vulnificus septicemia, emphasizing the role of prescribed antimicrobial agents in general and the therapeutic efficacy of the combination of a third-generation cephalosporin and tetracycline or its analogue in particular.Patients with the diagnosis of V vulnificus infection admitted to 5 large medical centers in Taiwan between 1995 and 2003 were included in this retrospective study. Patients were divided into 2 groups: those without [corrected] HBNCLs (group 1) [corrected] and those with [corrected] HBNCLs (group 2) [corrected]Patients were further divided into subgoups with [corrected] fatalities (fatal subgroup) and those without fatalities (nonfatal subgroup).A total of 93 patients participated in the study. In group 1, the fatal subgroup had higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (P = .006) and a higher proportion of shock at arrival at the medical center (P = .015) than the nonfatal subgroup. In group 2, the effect of a first- or second-generation cephalosporin plus an aminoglycoside was negative (P = .01) and that of combined third-generation cephalosporin and tetracycline or its analogue was positive (P.001); significant differences were found between the fatal and nonfatal subgroups in the APACHE II score (P.001), number who were in shock at arrival at the medical center (P = .02), delayed surgical intervention (P = .03), and peripheral leukocytosis (P = .03). Shock at arrival at the medical center (odds ratio [OR], 19.25; 95% confidence interval [CI], 1.768-209.54; P = .02) was an independent risk factor for fatality in patients without HBNCLs. Use of a third-generation cephalosporin and tetracycline or its analogue significantly reduced fatality rates in patients with HBNCLs (OR, 0.037; 95% CI, 0.007-0.192; P.001).Septic shock is a determinant of fatality in patients with V vulnificus septicemia without HBNCLs; our data suggest that the combination of a third-generation cephalosporin and tetracycline or its analogue may be a better choice in antimicrobial treatment of V vulnificus septicemic patients with HBNCLs.