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Background: Chlorhexidine is one of the most essential ingredients in infection control applications. Except qacA, the effects of other various efflux-medicated biocide genes (including qacB, qacC, qacEΔ1, qacH or norA) on biguanides resistance are still controversial. In addition, most of the studies have discussed the effect of qacA/B on clinical S. aureus isolates but not that qacA or qacB individually. Methods: In total, 254 methicillin-resistant Staphylococcus aureus (MRSA), selected 30 methicillin-susceptible S. aureus (MSSA) clinical isolates from different patients during 2014–2015 and 15 S. aureus quality control strains (including Mu3 and Mu50) were included in the study. Various biocide genes, including qacA/B, qacC, qacH, qacEΔ1, and different types of norA, were determined through conventional PCR. S. aureus isolates with qacA/B (+) were analyzed using high-resolution melting curve (HRM) to differentiate qacA from qacB. The chlorhexidine MIC was determined using the agar dilution method. Univariate and multivariate statistics were analyzed to see which biocide resistant genes had effects on chlorhexidine MIC. Results: Results of all HRM analyses (n = 22) were consistent with those of Sanger sequencing for differentiation of qacA from qacB. None of the isolates harbored qacH and only one MRSA harbored qacEΔ1. The harboring rate of qacA, qacB, and qacC among MRSA/MSSA isolates was 7.1% (n = 18)/0%, 38.2% (n = 97)/0%, and 7.5% (n = 19)/3.3% (n = 1), respectively. The most type of norA was norAI (n = 158), followed by norAIII (n = 87) and norAII (n = 9) among MRSA isolates. Based on the results of multivariate logistic regression analyses, only qacA and qacB would increase chlorhexidine MIC from ≤ 1 ug/ml to ≥ 2 ug/ml in MRSA isolates (P < 0.001) but not qacC or norA types (P=0.976 and 0.633 or 0.933, respectively). In addition, only qacA but not qacB was contributed to elevate chlorhexidine from ≤ 1 ug/ml to 4 ug/ml in MRSA isolates (P < 0.001 and 0.017, respectively). Conclusion: HRM analysis can be a great method to differentiate qacA from qacB. The biocide gene with the most effect on chlorhexidine MIC in S. aureus isolates was qacA, followed by qacB, but qacC and different types of norA did not have any effect on chlorhexidine susceptibility. Further investigation on the influence of qacB, qacC and types of norA on chlorhexidine susceptibility is necessary.

The increasing emergence of multidrug-resistant (MDR) bacteria has been recognized as a public health threat worldwide. Hospitalized patients and outpatients are commonly infected by non-fermenting Gram-negative bacilli (NFGNB), particularly the Acinetobacter calcoaceticus-Acinetobacter baumannii complex (ACB) and Pseudomonas aeruginosa. Antimicrobial agents are critical for treating the nosocomial infections caused by NFGNB. The aim of this study was to assess antimicrobial resistance and the use of antimicrobial agents. The bacterial isolates of 638,152 specimens from both inpatients and outpatients, retrieved from 2001 to 2008 at a medical center in central Taiwan, were examined for their susceptibility to various antimicrobial agents, including cefepime, imipenem, ciprofloxacin, gentamicin, amikacin, meropenem, and levofloxacin. Administrated prescriptions of the monitored antibiotics were analyzed using the Taiwan National Health Insurance Research Database (NHIRD). Our results show that the defined daily doses (DDDs) for cefepime, imipenem, and ciprofloxacin increased with time, and a trend toward reduced antimicrobial sensitivities of both ACB and P. aeruginosa was noticeable. In conclusion, the antimicrobial sensitivities of ACB and P. aeruginosa were reduced with the increased use of antibiotics. Continuous surveillance of antibiotic prescriptions and the prevalence of emerging resistance in nosocomial infections is warranted.

Backgrounds: Candida guilliermondii is rarely isolated from clinical specimen. C. guilliermondii fungemia is seldom reported in the literature. The aims of this study were to report the clinical features, antifungal susceptibility, and outcomes of patients with C. guilliermondii fungemia. Methods: From 2003 to 2015, we retrospectively analyzed the clinical and laboratory data of patients with C. guilliermondii fungemia in a tertiary hospital in mid-Taiwan. We performed a multivariable logistic regression analysis to identify the risk factors of mortality. The Sensititre YeastOne microtiter panel assessed the susceptibility of antifungal agents. Results: In this study, we identified 36 patients with C. guilliermondii fungemia. The median age of patients was 50.5 years (range, 17 days to 96 year) and 20 cases (56%) were male. The incidence of C. guilliermondii fungemia was 0.05 per 1000 admissions. Malignancy was the most common co-morbidity, and 25 (69%) patients had central venous catheter in place. Thirty-day overall mortality was 16.7%. In multivariate logistical regression analysis, catheter retention was an independent risk factor of mortality. According to epidemiological cutoff values, most clinical isolates (21/22, 95.5%) belonged to the wild-type MIC distributions for amphotericin B and flucytosine; however, the isolates were less susceptible to fluconazole (68%) and echinocandins (77–91%). Conclusion: Despite the lower mortality rate associated with C. guilliermondii fungemia, the removal of a central venous catheter remained an independent factor influencing the outcome of patients. The clinical significance of less susceptibility of C. guilliermondii to triazoles and echinocandins remains to be elucidated. Keywords: Candida guilliermondii, Fungemia, Clinical features, Mortality rate, In vitro susceptibility

Objective: To investigate the clinical features and microbiology of patients with diarrheal diseases in Taiwan. Methods: From March 2014 to October 2014, patients with diarrheal diseases referred from the community clinics were enrolled into our prospective study. Demographics and clinical features of the participants were acquired. Stool samples were examined by the Luminex Gastrointestinal Pathogen Panel assay. Data were analyzed by SAS version 9.4. Results: A total of 545 patients were enrolled into this study. Male and adults accounted for 52.3% and 82.6% of patients, respectively. The median age was 36 years. Enteropathogen(s) was identified in 43.3% of patients and 8.5% of them had more than one agent in their stool samples. Viruses, especially norovirus GI/GII, were the predominant agents of gastroenteritis. Moreover, Campylobacter species was the most common bacterial agent. Bloody stool was frequently reported in patients with bacterial diarrhea (P = 0.002); contrarily, watery stool was significantly associated with viral diarrhea (P

Staphylococcus aureus is a versatile pathogen which can cause various mild to life-threatening infectious diseases. The evolution of S. aureus resistance is notorious, from penicillin and oxacillin to vancomycin. Vancomycin, introduced in 1956, was once considered a most reliable antibiotic for methicillin-resistant S. aureus (MRSA); unfortunately, the first strain of S. aureus with decreased susceptibility to vancomycin emerged in 1996. Vancomycin has been approved in Taiwan since 1983, and the prevalence rates of heteroresistant vancomycin-intermediate S. aureus (hVISA) and vancomycin-intermediate S. aureus (VISA) in 2003 were 0.7% and 0.2%, respectively. However, a ten-fold increase of hVISA and VISA to 10% and 2.7%, respectively, in 2012–2013 could indicate a challenging clinical situation in Taiwan. The most commonly reported staphylococcal cassette chromosome mec (SCCmec) types of hVISA and VISA are usually SCCmec type III or II, typical nosocomial MRSA strains. Preventing the spread of resistant pathogens through infection control interventions and judicious antibiotic stewardship is a serious medical issue.

Background/Purpose The aim of this study was to investigate clinical presentation, serotype distribution and genetic correlation of group B streptococcus (GBS) diseases. Since serotype VI prevalence far exceeded that reported in prior studies, genetic relationship of isolates was further analyzed. Methods GBS isolates obtaining from patients with invasive diseases and pregnant women with colonization between June 2007 and December 2010 were analyzed. All isolates were tested for serotypes by multiplex PCR assay and pulsed-field gel electrophoresis (PFGE). Serotype VI isolates were further analyzed by multilocus sequence typing (MLST). Results A total of 134 GBS isolates were recovered from blood of 126 patients with invasive disease (94.0%) and anogenital swabs of 8 pregnant women (6.0%). Most common serotype was Ib (21.6%), followed by V (20.1%), VI (18.7%), III (15.7%), II (11.9 %), Ia (11.2%), and IX (0.7%). Serotype VI was also the leading type in infants with early onset disease (EOD; 3/8, 37.5%) and colonizing pregnant women (3/8, 37.5%). PFGE distinguished 33 pulsotypes, reflecting genetic diversity among GBS isolates. Among 25 serotype VI isolates tested, 14 were ST-1, seven were ST-679, three were ST-678, one was ST-681, and distributed into four PFGE pulsotypes. ST-678, ST-679, and ST-681 were novel sequence types; ST-678 and ST-679 are single-locus variants of ST-1 that belongs to clonal complex (CC) 1. Conclusion CC1 dissemination of serotype VI GBS thus emerges as an important invasive pathogen in infants and nonpregnant adults in central Taiwan. Serotype prevalence of GBS must be continuously monitored geographically to guide prevention strategy of GBS vaccines.

Background Staphylococcus aureus is a versatile bacterium, which can lead to various infectious diseases. Various molecular typing methods are applied to the evolution and epidemiology surveys of S. aureus , mostly for methicillin-resistant S. aureus (MRSA). However, methicillin-susceptible S. aureus (MSSA) is still an important pathogen, but their molecular typing is evaluated infrequently. Methods Pulsed-field gel electrophoresis (PFGE), spa typing, and detection of five virulent genes for 95 MRSA and 56 MSSA isolates (July–December 2008 and July 2008–December 2009, respectively) during an overlapping period were performed. Results More diversity was found in MSSA isolates (23 pulsotypes and 25 spa types, excluding 4 new-type and 1 nontypable isolates for spa typing) than in MRSA isolates (19 pulsotypes and 16 spa types, excluding 1 new-type and 1 nontypable isolates for spa typing). By spa typing, t002 ( n = 30), t037 ( n = 23), t437 ( n = 21), t234 ( n = 3), t1081 ( n = 3), and t1094 ( n = 3) were the six major MRSA clones. For MSSA isolates, t189 ( n = 13), t437 ( n = 4), t084 ( n = 3), t213 ( n = 3), t701 ( n = 3), and t7200 ( n = 3) were the six major types. Combining PFGE and spa typing, there were five combinations (pulsotype + spa type) that contained both MRSA and MSSA isolates (pulsotype 9-t437, pulsotype 15-t037, pulsotype 19-t002, pulsotype 21-t002, and pulsotype 28-t1081). For all 151 S. aureus or 95 MRSA isolates, the PFGE typing had more discrimination power, but spa typing had larger discrimination index for 56 MSSA isolates. Conclusion In conclusion, there were different predominant MRSA and MSSA clones clinically. Continuing longitudinal tracking of molecular typing is necessary for elucidating the evolution of this important clinical pathogen.

Background Janus kinase 2 (JAK2) plays an important role in normal hematopoietic growth factor signaling. The detection of the JAK2 V617F mutation (c.1849GNT, GTC TTC) is crucial for the diagnosis of myeloproliferative neoplasm (MPN) and has become the essential criteria for diagnosis of MPN by the WHO. High-resolution melt (HRM) curve analysis is a nongel-based, closed-tube method, in which PCR amplification and subsequent analysis are sequentially performed in the well, making it more convenient than other scanning methodologies. Methods We evaluated JAK2 V617F mutation by HRM. Twenty-nine patients diagnosed with MPN were examined. We studied the analytical sensitivity of the HRM analysis using real-time polymerase chain reaction (PCR) for identifying the JAK2 V617F mutation. Additionally, the sensitivity of HRM analysis and allele-specific PCR (AS-PCR) assay was compared. Results The JAK2 V617F mutation was successfully discriminated at an abundance of 6% or above in HRM analysis. Both HRM analysis and AS-PCR showed 100% accuracy with detection limits of 6% and 2.5%, respectively. Conclusion HRM analysis is a fast, simple, reliable, and nonexpensive method for the detection of the JAK2 V617F mutation. However, more validation of the detection limits of HRM analysis should be performed before declaration of the analytic sensitivity of the method.

Objective: Breast cancer is one of the most common malignancies and a leading cause of cancer-related death in women worldwide. Both hormone-related factors and genetic aberrations could cause breast cancer. We investigated copy number alternations (CNAs) on four breast cancer-susceptible loci, namely 2q35-rs13387042, 3p24-rs4973768, 17q23-rs6504950, and fibroblast growth factor receptor 2 (FGFR2)-rs2981578, in Taiwanese women. Patients and Methods: Breast cancer tissues and blood samples from 66 patients and their clinical data were collected from a human biobank. The copy numbers of the germline samples (from blood) and cancer tissues from each patient on the susceptible loci – 2q35, 3p24, 17q23, and FGFR2 – were obtained using TaqMan probes in the Applied Biosystems Inc., (ABI) StepOnePlus Real-Time Polymerase Chain Reaction instrument and CopyCaller® Software v1.0 (ABI, CA, USA). Results: The mean copy numbers output by CopyCaller® Software v1.0 of the cancer tissues on these susceptible loci (2q35, 3p24, 17q23, and FGFR2) from the 66 patients were higher than those of the blood samples (2.0 vs. 1.9); however, significantly higher copy numbers for cancer tissues compared with germline samples were discovered only on 2q35-rs13387042 (P = 0.035). In addition, patients with advanced breast cancers had relatively many CNAs between their cancer tissues and germline samples on 17q23-rs6504950 (P = 0.008). Multivariate analysis revealed that the risk factor for patients with advanced breast cancers was CNAs between cancer tissues and germline samples on 17q23-rs6504950 (odds ratio = 13.337, 95% confidence interval: 1.525–122.468). Conclusions: CNAs on 17q23-rs6504950 between cancer tissues and germline samples could affect cancer progression in Taiwanese women with breast cancer. Further investigations regarding the role of CNAs on 17q23-rs6504950 in cancer progression are necessary to elucidate the pathogenesis of breast cancer.

Background/Purpose Streptococcus dysgalactiae subsp. equisimilis (SDSE) is increasingly recognized as a human pathogen responsible for invasive infection and streptococcal toxic shock syndrome (STSS). The pathogen possesses virulence genes that resemble those found in Streptococcus pyogenes (GAS). We analyzed the association between these specific toxic genes, clinical presentations, and outcome in patients with SDSE infections. Methods Patients (older than 18 years) with community-acquired invasive bacteremia caused by SDSE bacteremia who were undergoing treatment at China Medical University Hospital from June 2007 to December 2010 were included in this study. Multiplex polymerase chain reaction was performed to identify virulence genes of the SDSE isolates. Demographic data, clinical presentations, and outcome in patients with SDSE infections were reviewed and analyzed. Results Forty patients with 41 episodes of SDSE bacteremia were reviewed. The median age of the patients with SDSE infection was 69.7 years; 55% were female and 78% had underlying diseases. Malignancy (13, 33%) and diabetes mellitus (13, 33%) were the most common comorbidities. The 30-day mortality rate was 12%. Compared with the survivors, the non-survivors had a higher rate of diabetes mellitus (80% vs. 26%), liver cirrhosis (60% vs.11%), shock (60% vs.17%), STSS (60% vs. 8%), and a high Pittsburgh bacteremia score >4 (40% vs. 6%). Most isolates had scpA , ska , saga , and slo genes, whereas speC , speG , speH , speI , speK , smez , and ssa genes were not detected. speA gene was identified only in one patient with STSS (1/6, 17%). All isolates were susceptible to penicillin, cefotaxime, levofloxacin, moxifloxacin, vancomycin, and linezolid. Conclusion In invasive SDSE infections, most isolates carry putative virulence genes, such as scpA , ska , saga , and slo . Clinical SDSE isolates in Taiwan remain susceptible to penicillin cefotaxime, and levofloxacin.

Background: In Taiwan, studies about hematogenous pyogenic vertebral osteomyelitis (HPVO) are limited. We conducted a retrospective study to evaluate the clinical presentations, treatment, and outcomes of patients with the diagnosis of HPVO. Method: This 12.5-year retrospective study included patients with a diagnosis of HPVO. Medical records of all HPVO patients were thoroughly reviewed and their clinical data were analyzed by the SPSS software. Result: 414 HPVO cases were included and the mean age was 61.6 ± 13.4 years. The mean duration of symptoms was 29 ± 35.3 days and pain over the affected site was reported by most patients (86.0%). Gram-positive bacteria, especially Staphylococcus aureus (162/399 = 40.6%), were the main HPVO pathogens. Escherichia coli (42/399 = 10.5%) was the most common gram-negative isolate. Surgery was performed in 68.8% of cases and the mean duration of total antibiotic treatment was 104.7 ± 77.7 days. All-cause mortality and recurrence rates were 6.3% and 18.8%, respectively. In multivariate analysis, polymicrobial infection (OR: 4.154, 95% CI: 1.039–16.604, p = 0.044), multiple vertebral body involvement (OR: 2.202, 95% CI: 1.088–4.457, p = 0.028), abscess formation treated with antibiotics alone (OR: 2.912, 95% CI: 1.064–7.966, p = 0.037), and the duration of antimicrobial treatment less than 4 weeks (OR: 3.737, 95% CI: 1.195–11.683, p = 0.023) were associated with HPVO recurrence. Conclusion: In Taiwan, HPVO mainly affected the elderly and S. aureus remained the most common HPVO pathogen. In patients with risk factors associated with HPVO recurrence, a longer duration (≥6 weeks) of antimicrobial therapy is suggested. Keywords: Osteomyelitis, Spondylitis, Pyogenic, Hematogenous, Spine

Objectives Staphylococcus lugdunensis, a species of CoNS, has become an important hospital pathogen because of increasing resistance to β-lactam antibiotics such as methicillin and oxacillin. Methicillin resistance is mainly due to the acquisition of the staphylococcal cassette chromosome (SCC) mec (SCCmec). Little is known about the structure of SCCmec in methicillin- or oxacillin-resistant CoNS. Methods WGS was performed to determine the structure of SCCmec elements of two clinical S. lugdunensis isolates: CMUH-22 and CMUH-25. Results These elements were found to be flanked by DRs and IRs with unique mosaic structures and a common integration site in the 3' end of the rlmH gene. The sequences of the regions located between rlmH and the ISSau4-like transposase genes of both elements were similar to those of SCCmec Vt of Staphylococcus aureus PM1. The SCCmec (type V, 5C2&4) of CMUH-25 harboured a novel ccrC complex and a C2-like mec complex in opposite orientations, similar to the type V SCCmec of S. aureus WIS. The sequences of the ccrA4B4 genes and J1 and J2 regions of CMUH-25 were similar to those of the SCC element of Staphylococcus haemolyticus NCTC 11042. In contrast, portions of the sequence of the J1 region of type Vt (5C2) SCCmec in strain CMUH-22 were highly similar to portions of those of Staphylococcus epidermidis RP62A and the composite SCCmec type V of S. aureus WAMRSA40. Conclusions These observations suggest that the SCCmec elements of CMUH-25 and CMUH-22 evolved separately and assembled through different recombination events.

BackgroundBlood culture volume is the most important variable in detecting bacteremia and fungemia. However, the majority of hospitals in Taiwan do not meet the criteria for an ideal blood culture volume (8–10 mL per bottle, two bottles per set) during collection.MethodsThe object of this study is to initiate an educational program for healthcare workers to increase blood volume collection and to evaluate the relationship between blood volumes and bacteremia recovery rate for detecting bacteremia and fungemia effectively by using the BD BACTEC 9240 blood culture system.ResultsAfter education, the blood sample volume ≥5 mL group increased from 2.93% to 71.24%. For a total of 4,844 bottles, the relative improvement in recovery rate for detection has increased by 17.81% between the 10 mL) groups are 13.31%, 15.02%, 17.68%, and 14.96%, respectively.ConclusionWith good blood collection practice, our study found that blood volume obtained was in direct proportion to recovery rate for the detection of bacteremia and fungemia.

Background/Purpose Tuberculosis (TB) is endemic in Taiwan and usually affects the lung, spinal TB accounting for 1–3% of all TB infections. The manifestations of spinal TB are different from those of pulmonary TB. The purpose of this study was to define the epidemiological molecular types of mycobacterial strains causing spinal TB. Methods We retrospectively reviewed the medical charts of adult patients diagnosed with spinal TB from January 1998 to December 2007. Patients with positive culture results and/or pathological findings characteristic of TB were enrolled in this study. Spoligotyping was performed to type the Mycobacterium tuberculosis isolates. Results A total of 38 patients with spinal TB were identified. Their mean age was 68 years, and their median duration of symptoms was 60 days (range 3–720 days). The lumbar and thoracic spine accounted for 76% of the sites involved. Thirteen specimens (from seven male and six female patients) were available for typing. Spoligotyping of these 13 specimens revealed three Beijing (23%) and 10 non-Beijing types (77%). The non-Beijing types included two EAI2 Manilla (15%), two H3 (15%), two unclassified (15%), and one each of BOVIS1, U, T2, and orphan type. No significant predominant strain was found in this study, and no drug-resistant Beijing strains were identified. Conclusion TB spondylitis was found to occur in older patients. Spoligotyping results showed that most of the TB spondylitis cases were caused by non-Beijing type Mycobacterium tuberculosis .

Numerous genomic and clinical cancer data have been generated and available through The Cancer Genome Atlas (TCGA). However, these datasets are difficult to access and interpret. Most of the existing tools provide resources for exploring, visualizing, and analyzing multidimensional genomics data for all cancer samples. Here we present an integrative pan-cancer analysis of DNA copy number, messenger RNA and microRNA (miRNA) expression, DNA methylation, protein expression and clinical characteristics for studying gene regulation and expression based survival analysis in paired tumor and normal samples. Clinical researchers have a simple way to evaluate the TCGA data for their genes or candidate biomarkers of interest.

Background: Next-generation sequencing (NGS) testing has two analytical processes, wet bench and bioinformatics process. Exome sequencing covers about 20000 human protein-coding gene sequences. Since these sequences are only 2% of human genome, but can predict 85% of human gene related diseases, whole exome sequencing is the most cost-effective test to diagnose unknown genetic diseases. Methods: Analysis methods developed by the Department of Laboratory Medicine of China Medical University Hospital (CMUH) with compliance of the molecular pathology checklists of the College of American Pathologists (CAP). Results: We developed the exome sequencing analysis workflow. First, single nucleotide polymorphism, SNP known with a minor allele frequency (MAF) >1%, was excluded. Second, variants other than SNP detected by NGS are submitted to the ClinVar database, which divided the relationships between variants and clinical significances into five categories: benign, likely benign, uncertain, likely pathogenic, and pathogenic. Third, all pathogenic variants, also confirmed by Sanger sequencing, might be current clinical relevance or incidental findings. Fourth, uncertain clinical significance variants with a MAF 30% were underwent further analysis by three pathogenicity predictions software: SIFT, PolyPhen, and CADD_PHRED. The final report from of exome sequencing contain sections of summary, clinical relevance (pathogenic), incidental finding (pathogenic), benign / likely benign, GWAS-related diseases, uncertain significance (including the results of three pathogenic software analysis), and the performance of the NGS platform. Conclusions: we demonstrated a reasonable working flow and a clinical practicable reporting format of exome sequencing by NGS.

Staphylococcus aureus isolates with discordant susceptibility results between oxacillin and cefoxitin obtained using automated microbiology systems are infrequently observed. From April 2013 to December 2014, 1956 methicillin-resistant S. aureus (MRSA) and 1761 methicillin-susceptible S. aureus isolates were obtained from different patients. Forty isolates (1.1% and 2% in case of S. aureus and MRSA, respectively) with discordant susceptibility results (oxacillin susceptible and cefoxitin resistant) and carrying mecA gene were obtained. Except 2 SCCmec type IV isolates, 38 MRSA isolates were all SCCmec type V (VT or non-VT), which were further divided into VT (n=22) and non-VT (n=16). The most common spa type in VT and non-VT isolates were t437 (n=19) and t1081 (n=13), respectively. Only 55% of patients received effective antimicrobial agents; 2 mortalities were not attributable to MRSA infection. Using standard agar dilution, 17 MRSA isolates (0.46% and 0.87% in case of S. aureus and MRSA, respectively) had oxacillin MIC in the susceptible ranges (oxacillin-susceptible MRSA [OS-MRSA]); all carried SCCmec type V (VT, n=8; non-VT, n=9). The most common spa-MLST types of OS-MRSA in VT and non-VT were t437-ST59 (n=4) and t1081-ST45 (n=7), respectively. Concomitant testing by both cefoxitin- and oxacillin-based methods is a practical strategy for OS-MRSA detection in the clinical laboratories. Continuous monitoring of OS-MRSA isolates is necessary to elucidate their impact in clinical infectious diseases.

Background Breast cancer is a heterogeneous disorder for which the underlying genetic basis remains unclear. We developed a method for identifying adenomatous polyposis coli (APC) mutations and we evaluated the possible association between APC genetic variants and breast cancer susceptibility. Methods Genomic DNA was extracted from tumor and matched peripheral blood samples collected from 89 breast cancer patients and from peripheral blood samples collected from 50 controls. All samples were tested for mutations in exons 1–14 and the mutation cluster region of exon 15 by HRM analysis. All mutations were confirmed by direct DNA sequencing. Results We identified a new single nucleotide polymorphism (SNP), c.465A>G (K155K), in exon 4 and seven known SNPs: c.573T>C (Y191Y) in exon 5, c.1005A>G (L335L) in exon 9, c.1458T>C (Y486Y) and c.1488A>T (T496T) in exon 11, c.1635G>A (A545A) in exon 13, and c.4479G>A (T1493T) and c.5465T>A (V1822D) in exon 15. The following alterations were found in 2, 1, 2, and 1 patients, respectively: c.465A>G, c.573T>C, c.1005A>G, and c.1488A>T. There was no observed association between breast cancer risk and any of these APC SNPs. Conclusions APC mutations occur at a low frequency in Taiwanese breast cancer cases. HRM analysis is a powerful method for the detection of APC mutations in breast. Electronic supplementary material The online version of this article (doi:10.1186/s12935-016-0297-2) contains supplementary material, which is available to authorized users.

Chlorhexidine has been widely used for infection control. Although the use of chlorhexidine-impregnated catheters has reduced catheter-related infections, chlorhexidine-resistant Staphylococcus aureus has emerged. The correlation between the existence of the chlorhexidine-resistant genes qacA and qacB ( qacA/B ) in methicillin-resistant Staphylococcus aureus (MRSA) isolates and the effectiveness of chlorhexidine-impregnated catheters in the prevention of MRSA infections is unknown. Sixty methicillin-sensitive Staphylococcus aureus (MSSA) and 96 MRSA isolates from the blood cultures of different patients were collected, and a case-control study was conducted to determine whether more clinical S. aureus isolates from chlorhexidine-impregnated catheter-related bloodstream infections (CRBSI) have the biocide-resistant genes ( qacA/B or smr ) than those from other infections. The chlorhexidine MIC 50 s of MSSA and MRSA isolates were 1 μg/ml and 2 μg/ml, respectively. Results of PCR analyses showed that 3.3% ( n = 2) of MSSA and 43.8% ( n = 42) of MRSA isolates harbored qacA/B and 5% ( n = 3) of MSSA and 25% ( n = 24) of MRSA isolates contained smr . With multivariate logistic regression analyses, the significant risk factors for definite CRBSI with chlorhexidine-impregnated catheters were determined to be S. aureus isolates with qacA/B and a chlorhexidine MIC of ≥2 μg/ml (odds ratios [OR], 9.264 and 8.137, respectively, in all 156 S. aureus isolates and 6.097 and 4.373, respectively, in the 96 MRSA isolates). Further prospective studies are needed to investigate the transmission of these biocide-resistant genes.

Background/PurposeProsthetic joint infection (PJI) has become an important issue in the management of patients who receive prostheses. We compared the clinical outcomes of PJIs caused by Gram-negative bacteria (GN PJIs) and Gram-positive bacteria (GP PJIs).MethodsPatients with culture-proven PJIs admitted to China Medical University Hospital between March 2001 and March 2009 were included in this retrospective study.ResultsFifty-nine patients were diagnosed with PJI during the study period. Nineteen patients had GN PJIs (mean age: 68 years) and 40 had GP PJIs (mean age: 61 years). The most common comorbid condition was diabetes mellitus (23.7%) and the most common presentation was joint pain (79.7%). Staphylococcus aureus was the most common pathogen, whereas Klebsiella pneumoniae was the most common Gram-negative pathogen. The GN PJI group included more cases of hematogenous infection (36.8% vs. 20%; p

Background and PurposeSome studies have reported that the risk factors for neurosyphilis in patients with human immunodeficiency virus (HIV) and syphilis co-infection, include CD4 cell counts ≤350cells/μL and rapid plasma reagin (RPR) titer ≥1:32. However, neurosyphils can develop even in patients with CD4 cell counts >350cells/μL or RPR titer 20cells/μL in the cerebrospinal fluid (CSF) sample or elevated Venereal Disease Research Laboratory (VDRL) titers of the CSF samples. Treatment failure was defined as less than 4-fold decrease in the serum RPR titer at or beyond 12 months post-treatment in case of early syphilis, and, at or beyond 24 months in case of late syphilis.ResultsOne hundred and twenty-one HIV-infected patients (average age, 32 years) with syphilis were included in this study. Of 63 patients who had follow-up of serologic responses, 30 (47.6%) failed to respond to treatment. CD4 cell counts ≤200cells/μL was the indicator for treatment failure (P=.029). Lumbar puncture was performed in 65 patients, and 14 patients were diagnosed with neurosyphilis. At the time of lumbar puncture, 31 and 19 of the 65 patients showed CD4 cell counts of >350cells/μL and RPR of 350cells/μL, and particularly when the HIV VL ≥10000copies/mL.

Background and Purpose Cryptococcus species are the most common causative agents of fungal meningitis. Different populations may show different clinical manifestations and outcomes. In this retrospective study, we investigated these differences in patients with and without HIV infection. Methods From 1995 to 2009, we collected data from HIV-infected or HIV-uninfected patients aged 18 years or over who had cryptococcal meningitis (CM) in a medical center in Taiwan. We reviewed and analyzed their demographic data, clinical manifestations, therapeutic strategies and outcomes. Results Among the 72 patients with CM, 19 HIV-infected patients were predominantly younger males, and all of them had AIDS status when CM was diagnosed. In contrast, the 53 HIV-uninfected patients were mostly older males with underlying diseases. The time from initial symptoms to diagnosis was shorter in HIV-infected patients (median 10 vs. 18 days, p = 0.048). The HIV-infected patients presented with less pleocytosis ( p = 0.003) and lower protein levels in the cerebrospinal fluid (CSF), but a higher proportion had positive results for cryptococci in the CSF (90% vs. 60%, p = 0.02) and blood (53% vs. 21%, p = 0.009) cultures. Surgical drains and repeated lumbar punctures for the management of increased intracranial pressure were performed in 47% of the HIV-infected patients and 38% of the HIV-uninfected patients. A lower mortality rate was observed in the HIV-infected patients ( p = 0.038). On multivariate analysis, initial CD4 count ≤20/mm 3 was an indicator of death or relapse in HIV-infected patients. In the HIV-uninfected group, the initial high cryptococcal antigen titer in the CSF (≥1:512) and hydrocephalus were related to unsatisfactory outcomes. Conclusion In addition to well-known differences, we found a lower mortality in HIV-infected patients than in HIV-uninfected patients. Cryptococci and inflammation in the central nervous system may play important roles in the pathogenesis of CM. Low intensity of inflammation and effective surgical CSF drains for increased intracranial pressure and cryptococci removal may contribute to lower mortality in HIV-infected patients.

Rapid identification of community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA), hospital-associated (HA) MRSA, and vancomycin-intermediate S. aureus (VISA) is essential for proper therapy and timely intervention of outbreaks. In this study, peptide biomarkers for rapid identification of methicillin-resistant and vancomycin-intermediate S. aureus strains were discovered by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The results showed that the 1774.1 and 1792.1 m/z peaks corresponding to the phenol-soluble modulin α1 and phenol-soluble modulin α2 peptides, respectively, were present in the majority (95%, 121 of 127) of SCCmec types IV and V isolates, but only in 8% (15 of 185) of SCCmec types I-III isolates. Since SCCmec types I-III isolates are recognized as HA-MRSA and most CA-MRSA isolates belong to SCCmec types IV and V, these two peptides may serve as markers for discrimination between HA-MRSA and CA-MRSA isolates. The 1835.0 and 1863.0 m/z peaks were present in 50% (4 of 8) of heterogeneous VISA and 88% (14 of 16) of VISA isolates. The peptides of these two peaks were identified as proteolytic products of the acyl carrier protein. The results of this study provide the possibility to develop methods for identification of CA-MRSA, HA-MRSA, and vancomycin-resistant S. aureus isolates based on the presence of these peptides.

Summary We investigated the trends in antimicrobial resistance among species of Gram-negative bacilli isolated from patients with hepatobiliary tract infections in Taiwan during the period 2006–2010 as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART). During the study period, 1032 isolates of Gram-negative bacilli that had been collected from patients with hepatobiliary infections were tested for susceptibility to 12 antimicrobial agents in accordance with the Clinical and Laboratory Standards Institute guidelines. Enterobacteriaceae accounted for the majority ( n = 874, 84.7%) of isolates and Escherichia coli was the most common pathogen ( n = 323, 31.3%). There were significantly more E. coli ( P = 0.001) and Proteus mirabilis ( P = 0.031) isolates collected from patients who had been hospitalized for less than 48 h and significantly more Serratia marcescens ( P = 0.035) and Pseudomonas aeruginosa ( P = 0.008) isolates collected from patients who had been hospitalized for 48 h or longer. The prevalence of extended–spectrum β–lactamase (ESBL)-producing pathogens was low. The decline in susceptibility rates with time was remarkable for ceftazidime ( P = 0.036), ciprofloxacin ( P = 0.029), and levofloxacin ( P = 0.018). The most effective antibiotics, i.e., those that were active against more than 90% of Enterobacteriaceae, were amikacin, cefepime, imipenem, ertapenem, and piperacillin–tazobactam. Susceptibility of P. aeruginosa to anti-pseudomonal agents was greater than 80%. In this study, we found an overall increase in resistance to antimicrobial agents among Gram-negative bacilli isolated from patients with hepatobiliary tract infections in Taiwan. Surveillance of antimicrobial susceptibility and updates of treatment guidelines are recommended to help achieve optimal therapy for patients with hepatobiliary infections.

In 2009, the Study for Monitoring Antimicrobial Resistance Trends (SMART) was expanded to include surveillance of Gram-negative pathogens causing urinary tract infections (UTIs) in the Asia-Pacific region. A total of 1762 isolates were collected from 38 centers in 11 countries from patients with UTIs in 2009 and 2010. In vitro susceptibilities were determined by the broth microdilution method and susceptibility profiles were determined using minimum inhibitory concentration (MIC) interpretive criteria, as recommended by the Clinical and Laboratory Standards Institute (CLSI) in 2010 (M100-S20), in 2011 (M100-S21), and in 2012 (M100-S22). Enterobacteriaceae comprised 86.0% of the isolates, of which Escherichia coli (56.5%) and Klebsiella pneumoniae (13.8%) were the two most common species. Amikacin was the most effective antibiotic (91.7%), followed by ertapenem (86.9%), imipenem (86.6%), and piperacillin-tazobactam (84.9%). Rates of susceptibility were 50.3% for cefoxitin and ranged from 50.3% to 74.2% for the third- and fourth-generation cephalosporins. For ciprofloxacin and levofloxacin, the susceptibility rates were 51.4% and 54.4%, respectively. Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae comprised 28.2% of all isolates. We also found a high rate of resistance to carbapenems among Acinetobacter baumannii and Pseudomonas aeruginosa causing UTI. Interestingly, according to 2012 CLSI breakpoints, approximately 33.4% of ESBL producers were still susceptible to ceftazidime. However, this in vitro efficacy of ceftazidime needs to be validated in vivo by clinical data. The lowered CLSI interpretive breakpoints for piperacillin-tazobactam, carbapenems, and some cephalosporins in 2011-2012 for Enterobacteriaceae resulted in an approximate 5% drop in susceptibility rates for each drug, with the exception of imipenem for which the susceptibility rate dropped from 99.4% according to 2010 criteria to 91.2% according to 2011 criteria. With the updated CLSI criteria, the antimicrobial resistance threat from UTI pathogens in the Asia Pacific area was revealed to be more prominent.

Background/Purpose Tuberculosis (TB) is an endemic disease in Taiwan and it usually affects the lung. Spinal TB accounts for 1-3% of all TB infections. The purpose of this study was to investigate the clinical manifestations, management, outcomes and drug susceptibility of Mycobacterium tuberculosis in non-HIV-infected patients with spinal TB. Methods From January 1998 to December 2007, we retrospectively reviewed the medical charts of adult patients with a diagnosis of spinal TB. Only those with positive culture results and/or characteristic pathologic findings were enrolled. Demographic data, clinical manifestations and susceptibility to anti-TB drugs were reviewed and analyzed. Results During the study period, 38 patients (23 men, 15 women) with spinal TB were identified and the mean age was 68 years. The median duration of symptoms was 60 days (range, 3-720 days). Amongst the 38 patients, back pain (100%) was the most common clinical symptom, followed by weakness (53%) and numbness (26%). The lumbar spine (15 patients, 39%) was the most commonly involved site, followed by the thoracic spine (14 patients, 37%). Concomitant pulmonary TB was found in 12 patients (32%). Three patients (8%) had concurrent bacterial or fungal infections. Almost all of the patients (35 patients, 92%) were successfully treated with surgery and anti-TB medications. The erythrocyte sedimentation rate was followed up in 16 patients before and after therapy and a significant decline was observed after treatment ( p = 0.004). No mortality was related to spinal TB. Conclusion Insidious clinical course and ambiguous manifestations of spinal TB often delay and hinder the accuracy of diagnosis of spinal TB. In addition to pyogenic osteomyelitis, spinal TB should be included in the differential diagnosis especially in elderly patients with chronic back pain accompanied by elevated erythrocyte sedimentation rate, and those living in the TB endemic area.

Objective.To investigate a nosocomial outbreak of infection with multidrug-resistant (MDR)Acinetobacter baumanniiin the intensive care units at China Medical University Hospital in Taiwan.Design.Prospective outbreak investigation.Setting.Three intensive care units in a 2,000-bed university hospital in Taichung, Taiwan.Methods.Thirty-eight stable patients in 3 intensive care units, all of whom had undergone an invasive procedure, were enrolled in our study. Ninety-fourA. baumanniistrains were isolated from the patients or the environment in the 3 intensive care units, during the period from January 1 through December 31, 2006. We characterizedA. baumanniiisolates by use of repetitive extragenic palindromic–polymerase chain reaction (REP-PCR) and random amplified polymorphic DNA (RAPD) fingerprinting. The clinical characteristics of the source patients and the environment were noted.Results.All of the clinical isolates were determined to belong to the same epidemic strain of MDRA. baumanniiby the use of antimicrobial susceptibility tests, REP-PCR, and RAPD fingerprinting. All patients involved in the infection outbreak had undergone an invasive procedure. The outbreak strain was also isolated from the environment and the equipment in the intensive care units. Moreover, an environmental survey of one of the intensive care units found that both the patients and the environment harbored the same outbreak strain.Conclusion.The outbreak strain ofA. baumanniimight have been transmitted among medical staff and administration equipment. Routine and aggressive environmental and equipment disinfection is essential for preventing recurrent outbreaks of nosocomial infection with MDRA. baumannii.

Background There have been many different mutations reported for the large adenomatous polyposis coli (APC) tumor suppressor gene. APC mutations result in inactivation of APC tumor suppressor action, allowing the progression of tumorigenesis. The present study utilized a highly efficient method to identify APC mutations and investigated the association between the APC genetic variants Y486Y, A545A, T1493T, and D1822V and susceptibility to oral squamous cell carcinoma (OSCC). Methods High-resolution melting (HRM) analysis was used to characterize APC mutations. Genomic DNA was extracted from 83 patient specimens of OSCC and 50 blood samples from healthy control subjects. The 14 exons and mutation cluster region of exon 15 were screened by HRM analysis. All mutations were confirmed by direct DNA sequencing. Results Three mutations and 4 single nucleotide polymorphisms (SNPs) were found in this study. The mutations were c.573T>C (Y191Y) in exon 5, c.1005A>G (L335L) in exon 9, and c.1488A>T (T496T) in exon 11. Two SNPs, c.4479G>A (T1493T) and c.5465A>T (D1822V), were located in exon 15, whereas c.1458T>C (Y486Y) and c.1635G>A (A545A) were located in exon 11 and 13, respectively. There was no observed association between OSCC risk and genotype for any of the 4 APC SNPs. Conclusions The mutation of APC is rare in Taiwanese patients with OSCC. HRM analysis is a reliable, accurate, and fast screening method for APC mutations.

To investigate the driver gene mutations associated with colorectal cancer (CRC) in the Taiwanese population.In this study, 103 patients with CRC were evaluated. The samples consisted of 66 men and 37 women with a median age of 59 years and an age range of 26-86 years. We used high-resolution melting analysis (HRM) and direct DNA sequencing to characterize the mutations in 13 driver genes of CRC-related pathways. The HRM assays were conducted using the LightCycler® 480 Instrument provided with the software LightCycler® 480 Gene Scanning Software Version 1.5. We also compared the clinicopathological data of CRC patients with the driver gene mutation status.Of the 103 patients evaluated, 73.79% had mutations in one of the 13 driver genes. We discovered 18 novel mutations in APC, MLH1, MSH2, PMS2, SMAD4 and TP53 that have not been previously reported. Additionally, we found 16 de novo mutations in APC, BMPR1A, MLH1, MSH2, MSH6, MUTYH and PMS2 in cancerous tissues previously reported in the dbSNP database; however, these mutations could not be detected in peripheral blood cells. The APC mutation correlates with lymph node metastasis (34.69% vs 12.96%, P = 0.009) and cancer stage (34.78% vs 14.04%, P = 0.013). No association was observed between other driver gene mutations and clinicopathological features. Furthermore, having two or more driver gene mutations correlates with the degree of lymph node metastasis (42.86% vs 24.07%, P = 0.043).Our findings confirm the importance of 13 CRC-related pathway driver genes in the development of CRC in Taiwanese patients.

Background Saffold cardiovirus (SAFV) belongs to the Cardiovirus genus of Picornaviridae family, and may be a relevant new human pathogen; Thus far, eleven genotypes have been identified. The SAFV type 3 (SAFV-3) is thought to be the major genotype and is detected relatively frequently in children with acute gastroenteritis and respiratory illness. The epidemiology and pathogenicity of SAFV-3 remain unclear. Objectives To investigate the genomic and epidemiologic profiles of SAFV-3 infection in Taiwan. Study design Virus was detected in respiratory samples from children suffering for URI. SAFV-3 isolates were detected by isolation on cell culture and IF assay. The molecular typing was performed by RT-PCR and was sequenced to compare with reference strains available in the NCBI GeneBank. Serum samples were collected from 2005 to 2013 in Taiwan for seroprevalence investigation. Results A total of 226 specimens collected from children with URIs, 22 (9.73%) were positive for SAFV-3. The majority of SAFV-3 infections were found in children less than 6 years of age (14 of 22, 63.6%). Genetic analysis of VP1 coding region of Taiwanese isolates shown an 83.2–97.7% difference from other available SAFV-3 sequences in NCBI GenBank. Phylogenetic analysis revealed there is three genetic groups of SAFV-3 co-circulated in Taiwan during the study period. In addition, seroprevalence investigation results indicated that SAFV-3 infection occurs early in life and 43.7–77.8% of children aged between 6 months to 9 years old, had neutralizing antibodies against SAFV-3. Conclusion SAFV-3 may have circulated in Taiwan for some time and it appears to be one of the etiological agents responsible for URIs in children.

Background/Purpose Methicillin-resistant Staphylococcus aureus (MRSA) typing is an important epidemiologic tool for monitoring trends and preventing outbreaks. However, the efficiency of various MRSA typing methods for each SCC mec MRSA isolate is rarely evaluated. Materials and methods A total of 157 MRSA isolates from four different regions in Taiwan were typed with five different molecular methods, including SCC mec typing, multilocus sequence typing (MLST), spa typing, mec -associated direct repeat unit ( dru ) copy number determination, and staphylococcal interspersed repeat unit (SIRU) profiling. Results There were four SCC mec types, eight MLST types, 15 spa types, 11 dru types, and 31 SIRU profiles. The most common type determined by each molecular typing method was SCC mec III (115 isolates, 73.2%), ST239 (99 isolates, 63.1%), t037 (107 isolates, 68.2%), 14 dru copies (76 isolates, 48.4%), and SIRU profile 3013722 (102 isolates, 65%), respectively. When using the combination of MLST, spa typing, and dru copy number, ST5-t002-4 ( n = 8), ST239-t037-14 ( n = 68), ST59-t437-9 ( n = 9), and ST59-t437-11 ( n = 6) were found to be the most common types of SCC mec types II ( n = 9), III ( n = 115), IV ( n = 21), and V T ( n = 11) isolates, respectively. SCC mec type III isolates were further classified into 11 dru types. Of the 21 SCC mec type IV isolates, 14 SIRU profiles were found. Seven SIRU patterns were observed in the 11 SCC mec type V T isolates. Conclusion Different typing methods showed a similar Hunter–Gaston discrimination index among the 157 MRSA isolates. However, dru and SIRU typing methods had a better discriminatory power for SCC mec type III and SCC mec types IV and V T isolates, respectively, suggesting that dru and SIRU can be used to further type these isolates.

A nosocomial outbreak of multi-drug-resistant Acinetobacter calcoaceticus-A. baumannii (MDR-ACB) complex infection occurred in a newly constructed building at a 2,500-bed tertiary medical center in Taiwan.An investigation was carried out by molecular approaches to trace the bacteria. Antimicrobial susceptibilities, risk factors, and the occurrence of nosocomial MDR-ACB infections were investigated. From January to December 2009, 53 patients were infected with MDR-ACB, and 23 environmental surveys were performed in two surgical intensive care units (ICUs) within the new building. Forty-two clinical isolates were obtained from patients and 22 samples from nine environmental surveys.Forty clinical isolates (95.2%) and 18 environmental samples (81.8%) were positive for MDR-ACB of type A, the predominant outbreak strain. This strain was identical to that isolated in an outbreak in the old hospital in 2006, as proved by repetitive extragenic palindromic-based polymerase chain reaction and pulsed-field gel electrophoresis. Although the outbreak isolates contained blaOXA-23-like and blaOXA-51-like genes, analysis of the antimicrobial susceptibilities demonstrated increases in resistance to cefepime and imipenem-cilastatin in MDR-ACB isolated in the later outbreak.Not only patients or healthcare workers, but also medical equipment, might have carried the predominant outbreak strain from the old district to the new building. Therefore, even in a new environment, infection control programs must be enforced continually, and healthcare providers must be educated repeatedly to prevent recurrent outbreaks of MDR-ACB infection in the hospital setting.

Supplemental Digital Content is available in the text, Neutralizing anti-interferon-γ autoantibody (nAIGA)-associated immunodeficiency is an emerging medical issue worldwide. In the present study, we describe and discuss the clinical features and outcomes of patients with nAIGAs and disseminated infections by nontuberculous mycobacteria (dNTM). We thoroughly reviewed the medical records of all patients. Microorganisms and nAIGAs were identified using previously described methods with modifications. All data were calculated and analyzed using SPSS software. Among 46 adult patients with dNTM infections, we identified 45 cases (97.8%) with nAIGAs. The average patient age was 58.6 years, and there was no sex predominance. Cervical lymphadenitis (81.8%) was the most common clinical manifestation. Endocrine disorder was the leading comorbidity (7 cases). Malignancies were found in 4 patients, and all of the malignancies originated from the T-cell/macrophage lineage. More than half of the identifiable isolates were slow-growing NTMs. Twenty-eight (62.2%) and 18 (40.0%) patients had a history of zoster and salmonellosis, respectively. A high proportion of patients with recurrent episodes of NTM infection or a history of zoster and dNTM infection had initial nAIGA titers ≥10–5 dilution (P

The FLT3 gene with internal tandem duplication (ITD) is a poor prognostic factor in patients with acute myeloid leukemia (AML), and the efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) for AML patients with FLT3-ITD is controversial. We examined 122 AML patients; 34 patients had FLT3-ITD and 39 patients received allogeneic HSCT. The median overall survival (OS) of patients with wtFLT3/nonHSCT, wtFLT3/HSCT, FLT3-ITD/nonHSCT and FLT3-ITD/HSCT was 40.7 months, 53.4 months, 9.8 months and not reached, respectively (p=0.006). Compared to the wtFLT3/nonHSCT patients, the hazard ratio (95% CI) of OS for wtFLT3/HSCT, FLT3-ITD/nonHSCT and FLT3-ITD/HSCT was 1.39 (0.61-3.18), 3.57 (1.58-8.10) and 0.40 (0.11-1.59), respectively, after adjustment of age, sex, WBC, LDH, karyotype, NPM, and FAB classification. This result indicated that patients with FLT3-ITD/nonHSCT had a significantly worse outcome, but allogeneic HSCT improved the prognosis for patients with FLT3-ITD.

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.