Predictors for temporary stomas non-closure among non-metastatic rectal cancer patients undergoing curative resection: a retrospective analysis.

BACKGROUND: The primary treatment for non-metastatic rectal cancer is curative resection. However, sphincter-preserving surgery may lead to complications. This study aims to develop a predictive model for stoma non-closure in rectal cancer patients who underwent curative-intent low anterior resection. METHODS: Consecutive patients diagnosed with non-metastatic rectal cancer between January 2005 and December 2017, who underwent low anterior resection, were retrospectively included in the Chang Gung Memorial Foundation Institutional Review Board. A comprehensive evaluation and analysis of potential risk factors linked to stoma non-closure were performed. RESULTS: Out of 956 patients with temporary stomas, 10.3% (n = 103) experienced non-closure primarily due to cancer recurrence and anastomosis-related issues. Through multivariate analysis, several preoperative risk factors significantly associated with stoma non-closure were identified, including advanced age, anastomotic leakage, positive nodal status, high preoperative CEA levels, lower rectal cancer presence, margin involvement, and an eGFR below 30 mL/min/1.73m2. A risk assessment model achieved an AUC of 0.724, with a cutoff of 2.5, 84.5% sensitivity, and 51.4% specificity. Importantly, the non-closure rate could rise to 16.6% when more than two risk factors were present, starkly contrasting the 3.7% non-closure rate observed in cases with a risk score of 2 or below (p < 0.001). CONCLUSION: Prognostic risk factors associated with the non-closure of a temporary stoma include advanced age, symptomatic anastomotic leakage, nodal status, high CEA levels, margin involvement, and an eGFR below 30 mL/min/1.73m2. Hence, it is crucial for surgeons to evaluate these factors and provide patients with a comprehensive prognosis before undergoing surgical intervention.

Upfront primary tumor resection versus upfront systemic therapy for metastatic colorectal cancer: a systematic review and meta-analysis.

PURPOSE: The standard initial treatment for metastatic colorectal cancer (mCRC) remains debated. This study investigated whether upfront primary tumor resection (PTR) or upfront systemic therapy (ST) provides better survival outcomes for patients with mCRC. METHODS: The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for studies published at any time from January 1, 2004, to December 31, 2022. Randomized controlled trials (RCTs) and prospective or retrospective cohort studies (RCSs) utilizing propensity score matching (PSM) or inverse probability treatment weighting (IPTW) were included. We evaluated overall survival (OS) and short-term (60-day) mortality in these studies. RESULTS: After reviewing 3,626 articles, we identified 10 studies including a total of 48,696 patients. OS differed significantly between the upfront PTR and upfront ST arms (hazard ratio [HR] 0.62; 95% CI: 0.57-0.68; p < 0.001). However, a subgroup analysis identified no significant difference in OS in RCTs (HR 0.97; 95% CI: 0.7-1.34; p = 0.83), whereas significant difference in OS occurred between the treatment arms in RCSs with PSM or IPTW (HR 0.59; 95% CI: 0.54-0.64; p < 0.001). Short-term mortality was analyzed in three RCTs, and 60-day mortality differed significantly between the treatment arms (risk ratio [RR] 3.52; 95% CI: 1.23-10.10; p = 0.02). CONCLUSIONS: In RCTs, upfront PTR for mCRC did not improve OS and enhanced the risk of 60-day mortality. However, upfront PTR seemed to increase OS in RCSs with PSM or IPTW. Therefore, whether upfront PTR should be used for mCRC remains unclear. Further large RCTs are required.

Comparison of clinical outcomes of stoma reversal during versus after chemotherapy for rectal cancer patients.

PURPOSE: The optimal timing of stoma closure during or after adjuvant chemotherapy for rectal cancer patients undergoing sphincter-preserving surgery remains unknown. This study aimed to investigate the influence of clinical and oncological outcomes depending on the timing of stoma closure. METHODS: Between January 2006 and December 2015, we enrolled 244 consecutive rectal cancer patients who underwent curative-intent sphincter-preserving surgery with diverting transverse colostomy and adjuvant chemotherapy. Patients with stoma closure during (During group) adjuvant chemotherapy were compared to those who had stoma closure after adjuvant chemotherapy (After group). RESULTS: Parastomal hernia occurred more frequently in the after group than in the during group. (10% vs. 2.9%, p = 0.028). Overall, no significant difference was observed in overall survival (OS) or disease-free survival (DFS) between the two groups (p = 0.911 for OS, p = 0.505 for DFS). However, an inferior OS occurred if reopen surgery was performed within 30 days of stoma closure in the during group, as compared with the after group (p = 0.004). In addition, a marginally poor DFS was observed in the group of patients who received further operations due to 30-day stoma closure complications compared to the other patients (p = 0.07). CONCLUSIONS: For rectal cancer patients who underwent sphincter-preserving surgery, attention should be given to avoid 30-day major complications after stoma reversal because patients who require reoperation during adjuvant chemotherapy may have poor long-term survival.

Improvement of ulcerative colitis control by searching and restricting of inflammatory trigger factors in daily clinical practice.

BACKGROUND/AIMS: Exacerbating factors of ulcerative colitis (UC) are multiple and complex with individual influence. We aimed to evaluate the efficacy of disease control by searching and restricting inflammation trigger factors of UC relapse individually in daily clinical practice. METHODS: Both patients with UC history or new diagnosis were asked to avoid dairy products at first doctor visit. Individual-reported potential trigger factors were restricted when UC flared up (Mayo endoscopy score ≥1) from remission status. The remission rate, duration to remission and medication were analyzed between the groups of factor restriction complete, incomplete and unknown. RESULTS: The total remission rate was 91.7% of 108 patients with complete restriction of dairy product. The duration to remission of UC history group was significantly longer than that of new diagnosis group (88.5 days vs. 43.4 days, P=0.006) in patients with initial endoscopic score 2-3, but no difference in patients with score 1. After first remission, the inflammation trigger factors in 161 relapse episodes of 72 patients were multiple and personal. Milk/dairy products, herb medicine/Chinese tonic food and dietary supplement were the common factors, followed by psychological issues, non-dietary factors (smoking cessation, cosmetic products) and discontinuation of medication by patients themselves. Factor unknown accounted for 14.1% of patients. The benefits of factor complete restriction included shorter duration to remission (P<0.001), less steroid and biological agent use (P=0.022) when compared to incomplete restriction or factor unknown group. CONCLUSIONS: Restriction of dairy diet first then searching and restricting trigger factors personally if UC relapse can improve the disease control and downgrade the medication usage of UC patients in daily clinical practice.

Preoperative risk stratification of permanent stoma in patients with non-metastatic mid and low rectal cancer undergoing curative resection and a temporary stoma.

BACKGROUND: Although a temporary stoma can mitigate the severity of anastomotic leakage, some rectal cancer patients retain a permanent stoma after sphincter-preserving surgery. Therefore, this study aimed to identify independent preoperative risk factors for permanent stoma and establish a prediction model for mid-and low-rectal cancer patients who underwent sphincter-preserving surgery and temporary stoma. METHODS: We retrospectively reviewed consecutive patients with non-metastatic rectal cancer between 2000 and 2015. The risk factors for permanent stomas were collected and analyzed. RESULTS: A total of 1020 rectal cancer patients with temporary stoma were included. The overall rate of permanent stoma was 17.5% (n = 179). Cancer progression and anastomotic complications are major causes of permanent stomas. Multivariate analysis showed that preoperative risk factors such as advanced age, male sex, preoperative CEA ≥ 10 ng/ml, T4 stage, N stage, low rectal tumor, and ASA ≥ III were independent preoperative risk factors after adjustment. The ROC curve of the risk factors and permanent stoma showed an AUC of 0.689, a cut-off value of 2.5, a sensitivity of 0.689, and a specificity of 0.622. The permanent stoma rates were significantly higher between risk scores ≤ 2 and > 2 (29.9% vs. 11.3%, p < 0.001). CONCLUSION: Preoperative CEA ≥ 10 ng/ml, T4 stage, N stage, low rectal tumor, advanced age, ASA ≥ III, and male sex were independent preoperative prognostic factors for a permanent stoma. The risk was higher with a score greater than two. Therefore, the risk of subsequent permanent stoma should be evaluated and informed to the patient prior to the primary surgery.

Association of Preoperative Physical Activity with Short- and Long-Term Outcomes in Patients Undergoing Palliative Resection for Metastatic Colorectal Cancer: An Inverse Probability of Treatment Weighting Analysis.

A lack of physical activity is a generally accepted risk factor for colorectal cancer. However, research on the effect of preoperative physical activity on postoperative and long-term outcomes is limited, especially in patients with stage IV colorectal cancer who underwent palliative surgery. Patients who underwent bowel resection for stage IV primary colorectal cancer between January 1995 and December 2016 were retrospectively enrolled. A total of 2185 patients were divided into two groups according to preoperative leisure-time weekly physical activity as assessed by metabolic equivalent of task (MET) values: MET < 12 (n = 1845) and MET ≥ 12 (n = 340). Inverse probability of treatment weighting (IPTW) was used to reduce imbalance and selection biases between the two groups. After the IPTW process, the MET < 12 group showed a higher postoperative morbidity rate (18.7% vs. 10.6%; p < 0.001) and mortality rate (2.4% vs. 0.6%; p < 0.001) than the MET ≥ 12 group. No significant difference was found in overall survival. Weekly preoperative leisure-time physical activity with MET ≥ 12 was associated with reduced short-term postoperative morbidity and mortality in patients undergoing palliative resection for metastatic colorectal cancer. However, no difference was detected in long-term survival.

The emergence of Clostridioides difficile PCR ribotype 127 at a hospital in northeastern Taiwan.

BACKGROUND: Several studies have highlighted the incidence of Clostridioides difficile infections (CDIs) in Taiwan and certain ribotypes have been related to severe clinical diseases. A study was conducted to investigate the polymerase chain reaction (PCR) ribotypes and genetic relatedness of clinical C. difficile strains collected from January 2009 to December 2015 at a hospital in northeastern Taiwan. MATERIAL AND METHODS: A modified two-step typing algorithm for C. difficile was used by combining a modified 8-plex and 3'-truncated tcdA screening PCR. In addition, MLVA typing was adopted for investigation of bacterial clonality and transmission. RESULTS: Among a total of 86 strains, 24 (28%) were nontoxigenic and 62 (72%) had both tcdA and tcdB (A + B+). No tcdA-negative and tcdB-positive (A-B+) strains were identified. Binary toxin (CDT)-producing (cdtA+/cdtB+) strains were started to be identified in 2013. The 21 (34%) A+B+ clinical strains with binary toxin and tcdC deletion were identified as RT127 strains, which contained both RT078-lineage markers and fluoroquinolone (FQ)-resistant mutations (Thr82Ile in gyrA). Multiple loci variable-number tandem repeat analysis (MLVA) for phylogenetic relatedness of RT127 strains indicated that 20 of 21 strains belonged to a clonal complex that was identical to a clinical strain collected from southern Taiwan in 2011, suggestive of a clonal expansion in Taiwan. CONCLUSION: A two-step typing method could rapidly confirm species identification and define the toxin gene profile of C. difficile isolates. The clonal expansion of RT127 strains in Taiwan indicates monitoring and surveillance of toxigenic C. difficile isolates from human, animal, and environment are critical to develop One Health prevention strategies.

Smoking cessation for less than 10 years remains a risk factor of anastomotic leakage in mid-to-low rectal cancer patients undergoing sphincter-preserving surgery.

PURPOSE: Although cigarette smoking is a well-known risk factor for anastomotic leakage during rectal surgery, the proper duration of smoking cessation that can decrease anastomotic leakage in patients undergoing sphincter-preserving surgery is unclear. This study aimed to investigate the optimal duration of smoking cessation that can reduce this complication. METHODS: Between January 1, 2000, and December 31, 2012, we enrolled 1246 consecutive patients who underwent curative-intent sphincter-preserving surgery without preventive stoma at the Division of Colorectal Surgery of a tertiary referral center in Taiwan. Questionnaires were used to record their pre-surgical smoking status. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off duration of smoking cessation. Multivariate analysis was used to verify the effect of cigarette cessation on anastomotic leakage. RESULTS: The ROC curve showed a cut-off value of 10.5 years of cessation duration. Therefore, the former-smoker group was further divided using a cessation duration of 10 years. The overall anastomotic leakage rate was 5.29%. However, the anastomotic leakage rate in current smokers (9.3%) and in those who quit for < 10 years (12.9%) was significantly higher than that in non-smokers (3.3%) and those who quit for ≥ 10 years (4.5%). On multivariate analysis, current smokers (p = 0.022), former smokers with < 10 years of smoking cessation (OR 2.725; p = 0.029), male sex (p = 0.015), and low rectal cancer (p < 0.001) were all independently related to the development of anastomotic leakage. CONCLUSION: Smoking cessation for < 10 years remains a risk factor for anastomotic leakage in patients with mid-to-low rectal cancer undergoing sphincter-preserving surgery.

Early Detection and Dynamic Changes of Circulating Tumor Cells in Transgenic NeuN Transgenic (NTTg) Mice with Spontaneous Breast Tumor Development.

BACKGROUND: This study used NeuN transgenic (NTTg) mice with spontaneous breast tumor development to evaluate the dynamic changes of circulating tumor cells (CTCs) prior to and during tumor development. METHODS: In this longitudinal, clinically uninterrupted study, we collected 75 µL of peripheral blood at the age of 8, 12, 16, and 20 weeks in the first group of five mice, and at the age of 32 weeks, the time of tumor palpability, and one week after tumor palpability in the second group of four mice. Diluted blood samples were run through a modified mouse-CMx chip to isolate the CTCs. RESULTS: The CTC counts of the first group of mice were low (1 ± 1.6) initially. The average CTC counts were 16 ± 9.5, 29.0 ± 18.2, and 70.0 ± 30.3 cells per 75 µL blood at the age of 32 weeks, the time of tumor palpability, and one week after tumor palpability, respectively. There was a significant positive correlation between an increase in CTC levels and tumor vascular density (p-value < 0.01). This correlation was stronger than that between CTC levels and tumor size (p-value = 0.076). The captured CTCs were implanted into a non-tumor-bearing NTTg mouse for xenografting, confirming their viability and tumorigenesis. CONCLUSION: Serial CTCs during an early stage of tumor progression were quantified and found to be positively correlated with the later tumor vascular density and size. Furthermore, the successful generation of CTC-derived xenografts indicates the tumorigenicity of this early onset CTC population.

An uncommon form of localized colonic eosinophilic vasculitis with extensive thrombosis of the spleen and liver: A case report and literature review.

INTRODUCTION: Localized vasculitis of the gastrointestinal tract is an uncommon disease that mainly presents as polyarteritis nodosa and is mainly located on small bowel and gall bladder. Localized eosinophilic vasculitis of the colon, which needs surgical intervention, has never been reported before. CASE PRESENTATION: A 40-year-old man was diagnosed with localized eosinophilic vasculitis of the colon with an initial presentation of necrotizing colitis of ascending colon. After right hemicolectomy, extensive thrombosis of the liver and spleen occurred with the presentation of abdominal pain. The histopathological analysis revealed ischemic colitis with eosinophilic vasculitis in medium-sized vessels throughout the colon. The thrombosis was improved after prednisolone and azathioprine were given. The results of all autoimmune tests, including those for anti-neutrophil cytoplasmic antibodies, were all negative except the elevation of serum immunoglobulin E (680 kU/L [normal, <25 kU/L]). CONCLUSION: Although the patient failed to meet the criteria of the Churg-Strauss syndrome, this case may represent an atypical localized variant of eosinophilic vasculitis of the gastrointestinal tract. Immunosuppressant therapy should be considered after surgery.

Colistin for pneumonia involving multidrug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex.

OBJECTIVES: To investigate clinical and microbiological response, and 30-day mortality of pneumonia involving multidrug-resistant (MDR) Acinetobacter calcoaceticus-Acinetobacter baumannii (Acb) complex treated with colistin, and identify associated factors of these outcomes. METHODS: A retrospective study of 183 adult patients with colistin treatment for at least 7 days between January 2014 and October 2017. RESULTS: The mean age was 76.8 years, and mean Acute Physiology and Chronic Health Evaluation II score was 17.7. Eighteen (9.8%) and 128 (69.9%) patients had intravenous (IV) colistin alone and inhaled (IH) colistin alone, respectively. Thirty-seven patients had both IV and IH colistin, including 5 (2.7%) with concurrent, and 32 (17.5%) with non-concurrent use of IV and IH colistin. The 30-day mortality rate was 19.1% and 131 (71.6%) patients had clinical response. In the 175 patients with available data, 126 (72%) had microbiological eradication. The multivariate analyses revealed that IH colistin alone was an independent predictor for 30-day survival, clinical response, and microbiological eradication, and IV colistin alone was an independent predictor for clinical failure. Patients with IV colistin alone had a significantly higher nephrotoxicity rate than IH colistin alone (37.5% vs 6.1%, P = 0.001). Sub-group analysis of 52 patients with IV colistin for ≧ 4 days revealed that 14 (26.9%) patients had inappropriate dose, and inappropriate dose was an independent predictor for 30-day mortality. CONCLUSIONS: IH colistin provided good outcomes with few side effects, and appropriate dosing of IV colistin was important to avoid excess mortality.

Preoperative Carcinoembryonic Antigen as a Poor Prognostic Factor in Stage I-III Colorectal Cancer After Curative-Intent Resection: A Propensity Score Matching Analysis.

BACKGROUND: Preoperative carcinoembryonic antigen (CEA) has yet to be used as a prognostic or adjuvant chemotherapy factor for colorectal cancer (CRC). METHODS: This retrospective cohort study included all stage I-III CRC patients with different preoperative serum CEA levels (≤ 5, 5-10, and > 10 ng/ml) at a single center between 1995 and 2010. Propensity score matching was performed in a 1:1 ratio between the two elevated CEA groups (5-10 ng/ml and > 10 ng/ml) and in a 1:2 ratio between the elevated and non-elevated groups (≤ 5 ng/ml), with a caliper of 0.05. RESULTS: After exclusion and matching, 3857 patients had preoperative CEA levels ≤ 5 ng/ml, 1121 patients had CEA levels between 5 and 10 ng/ml, and 1121 patients had CEA levels > 10 ng/ml. Elevated preoperative CEA showed an increased risk of overall survival (5-10 ng/ml: hazard ratio [HR] 1.376; > 10 ng/ml: HR 1.523; both p < 0.001), cancer-specific survival (5-10 ng/ml: HR 1.404; > 10 ng/ml: HR 1.712; both p < 0.001), and recurrence free interval (5-10 ng/ml: HR 1.190; > 10 ng/ml: HR 1.468; both p < 0.05). Patients with negative lymph node staging (LNs) and CEA > 10 ng/ml, as well as those with positive LNs and CEA ≤ 5 ng/ml, showed similar overall survival (5-year survival: 72% vs. 69%; p = 0.542) and recurrence free intervals (19.9 vs. 21.72 months; p = 0.662). CONCLUSIONS: A preoperative CEA level can be an independent prognostic factor for stage I-III CRC after curative resection. Patients with negative LNs and preoperative CEA level > 10 ng/ml should be considered for intensive follow-up or adjuvant chemotherapy.

Detection of common diarrhea-causing pathogens in Northern Taiwan by multiplex polymerase chain reaction.

Conventional methods for identifying gastroenteritis pathogens are time consuming, more likely to result in a false-negative, rely on personnel with diagnostic expertise, and are dependent on the specimen status. Alternatively, molecular diagnostic methods permit the rapid, simultaneous detection of multiple pathogens with high sensitivity and specificity. The present study compared conventional methods with the Luminex xTAG Gastrointestinal Pathogen Panel (xTAG GPP) for the diagnosis of infectious gastroenteritis in northern Taiwan. From July 2015 to April 2016, 217 clinical fecal samples were collected from patients with suspected infectious gastroenteritis. All specimens were tested using conventional diagnostic techniques following physicians' orders as well as with the xTAG GPP. The multiplex polymerase chain reaction (PCR) approach detected significantly more positive samples with bacterial, viral, and/or parasitic infections as compared to conventional analysis (55.8% vs 40.1%, respectively; P < .001). Moreover, multiplex PCR could detect Escherichia coli O157, enterotoxigenic E coli, Shiga-like toxin-producing E coli, Cryptosporidium, and Giardia, which were undetectable by conventional methods. Furthermore, 48 pathogens in 23 patients (10.6%) with coinfections were identified only using the multiplex PCR approach. Of which, 82.6% were from pediatric patients. Because the detection rates using multiplex PCR are higher than conventional methods, and some pediatric pathogens could only be detected by multiplex PCR, this approach may be useful in rapidly diagnosing diarrheal disease in children and facilitating treatment initiation. Further studies are necessary to determine if multiplex PCR improves patient outcomes and reduces costs.

High Interleukin-10 Expression in Type 2 T Helper Cells in Septic Patients.

Interleukin (IL)-10 response is associated with mortality in patients with sepsis. IL-10 is primarily produced by monocytes and type 2 T helper (Th2) cells. The aim of this study was to investigate differences in IL-10 production between monocytes and Th2 cells in patients with sepsis. Forty patients with sepsis and 35 healthy controls were enrolled. Cytokine expressions in peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry. The IL-10 expression in the Th2 cells of the septic patients was higher than in the healthy controls, but the expression of IL-10 in the monocytes of the septic patients was lower than in the healthy controls. After regression analysis, IL-10 expression in Th2 cells was positively associated with sepsis, but IL-10 expression in monocytes was not associated with sepsis or shock. In conclusion, the production of IL-10 in Th2 cells was higher in the patients with sepsis.

Pathogenic bacterial nasopharyngeal colonization and its impact on respiratory diseases in the first year of life: the PATCH Birth Cohort Study.

BACKGROUND: For acute respiratory diseases caused by bacteria, colonization in the respiratory tracts is often the first sign, although nasopharynx is the major source of secretions containing pathogens. To understand the pathogenesis of respiratory tract diseases, it is important to analyze the establishment of nasopharyngeal bacterial colonization. METHODS: Infants with nasopharyngeal swabs were examined at the age of 1, 2, 4, 6 and 12 months for the detection of pathogens, including Streptococcus pneumoniae, Hemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Staphylococcus aureus. The methods used for detection were bacterial culture and multiplex polymerase chain reaction. RESULTS: From January 2012 to August 2013, a total of 320 neonates were enrolled, and 120 of them completed the first 12-month study. Staphylococcus aureus was the most common pathogen at all 5 time points while the rates declined; in contrast, the other 4 increased during the first year of life. Of our series, the multiplex polymerase chain reaction detection rates were higher than those of bacterial culture. More than 50% of Staphylococcus aureus was methicillin-resistant, and the trend decreased in the same period. In the analysis of factors associated with the development of infant wheeze, infants with maternal atopy [odds ratio (OR): 3.26; 95% confidence interval (CI): 1.20-8.88; P = 0.02] and pneumococcal colonization (OR: 15.64; 95% CI: 3.25-75.35; P = 0.001) had higher rates of wheeze. CONCLUSIONS: Bacterial interactions may result in differing pathogen prevalence in the first year of life. In addition, nasopharyngeal pneumococcal colonization may have an effect on the risk of infant wheeze. The result could help clinicians to clarify the relation between bacterial colonization and respiratory illnesses in infancy.

Molecular epidemiology and antimicrobial resistance of methicillin-resistant Staphylococcus aureus bloodstream isolates in Taiwan, 2010.

The information of molecular characteristics and antimicrobial susceptibility pattern of methicillin-resistant Staphylococcus aureus (MRSA) is essential for control and treatment of diseases caused by this medically important pathogen. A total of 577 clinical MRSA bloodstream isolates from six major hospitals in Taiwan were determined for molecular types, carriage of Panton-Valentine leukocidin (PVL) and sasX genes and susceptibilities to 9 non-beta-lactam antimicrobial agents. A total of 17 genotypes were identified in 577 strains by pulsotyping. Five major pulsotypes, which included type A (26.2%, belonging to sequence type (ST) 239, carrying type III staphylococcal chromosomal cassette mec (SCCmec), type F (18.9%, ST5-SCCmecII), type C (18.5%, ST59-SCCmecIV), type B (12.0%, ST239-SCCmecIII) and type D (10.9%, ST59-SCCmecVT/IV), prevailed in each of the six sampled hospitals. PVL and sasX genes were respectively carried by ST59-type D strains and ST239 strains with high frequencies (93.7% and 99.1%, respectively) but rarely detected in strains of other genotypes. Isolates of different genotypes and from different hospitals exhibited distinct antibiograms. Multi-resistance to ≥3 non-beta-lactams was more common in ST239 isolates (100%) than in ST5 isolates (97.2%, P = 0.0347) and ST59 isolates (8.2%, P<0.0001). Multivariate analysis further indicated that the genotype, but not the hospital, was an independent factor associated with muti-resistance of the MRSA strains. In conclusion, five common MRSA clones with distinct antibiograms prevailed in the major hospitals in Taiwan in 2010. The antimicrobial susceptibility pattern of invasive MRSA was mainly determined by the clonal distribution.

Risk factors of mortality and comparative in-vitro efficacy of anidulafungin, caspofungin, and micafungin for candidemia.

BACKGROUND: Although echinocandins have high in vitro antifungal efficacy according to prior reports, comparative studies on the clinical cure rates of anidulafungin, caspofungin, and micafungin in systemic candida infections have not yet been reported. METHODS: Interpretation of clinical and microbiological responses to anidulafungin, caspofungin, and micafungin in 109 cases of candidemia was done according to the published criteria. The clinical cure rates between patients treated with echinocandins and patients treated with fluconazole were also compared. The minimal inhibitory concentrations (MICs) of anidulafungin, caspofungin, micafungin, and fluconazole for these 109 blood isolates of candida were determined with the Clinical and Laboratory Standards Institute M27-A reference microdilution method. Logistic regression with forward selection was used to determine the important factors of prognosis with variables such as age, underlying diseases, acute physiology and chronic health evaluation (APACHE) III score, persistent candidemia, and antimicrobial therapy. RESULTS: Among the 109 cases of candidemia, 70 were treated with echinocandins, azoles, or amphotericin B for ≥7 days. The clinical cure rate of cases treated with antifungal agents adequately (≥7 days) and inadequately (<7 days) were 44/70 (62.9%) and 4/39 (10.2%), respectively, with significant difference (p < 0.0001). Clinical cure rates of anidulafungin, caspofungin, micafungin, and fluconazole were 18/30 (60.0%), 8/9 (88.9%), 5/7 (71.4%), and 9/18 (50%), respectively. The difference in APACHE III score between treatment success and failure cases was significant. The MIC50/MIC90 of anidulafungin, caspofungin, and micafungin for all Candida spp. were 0.03/1 µg/mL, 0.06/0.5 µg/mL, and 0.008/1 µg/mL, respectively. CONCLUSION: Adequate antifungal therapy and APACHE III score are both independent factors affecting the clinical outcome. The clinical cure rate of the echinocandins group was higher than that of the fluconazole group without significant difference. Although caspofungin had the best clinical cure rate in this study, there was no significant difference between the clinical cure rates among these three echinocandins. All Candida spp. were susceptible in vitro to these three echinocandins.

Identification of vancomycin-resistant enterococci clones and inter-hospital spread during an outbreak in Taiwan.

BACKGROUND: In 2003, nosocomial infections caused by vancomycin-resistant enterococci (VRE) occurred rarely in Taiwan. Between 2003 and 2010, however, the average prevalence of vancomycin resistance among enterococci spp. increased from 2% to 16% in community hospitals and from 3% to 21% in medical centers of Taiwan. We used molecular methods to investigate the epidemiology of VRE in a tertiary teaching hospital in Taiwan. METHODS: Between February 2009 and February 2011, rectal samples and infection site specimens were collected from all inpatients in the nephrology ward after patient consent was obtained. VRE strain types were determined by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). RESULTS: A total of 59 vanA gene-containing VRE isolates (1 per patient) were obtained; 24 originated from rectal sample surveillance of patients who exhibited no symptoms (22 Enterococcus faecium and 2 Enterococcus faecalis), and 35 had developed infections over 3 days after admission (32 E. faecium, 2 E. faecalis, and 1 Enterococcus durans). The 59 VRE isolates demonstrated vancomycin minimum inhibitory concentrations (MICs) of ≥256 µg/m. The MIC range for linezolid, tigecycline, and daptomycin was 0.25-1.5 µg/mL, 0.032-0.25 and 1-4 µg/mL, respectively. For 56 isolates, the MIC for teicoplanin was >8 µg/mL. The predominant types in the nephrology ward were MLST types 414, 78, and18 as well as PFGE types A, C, and D. CONCLUSION: VREs are endemic in nephrology wards. MLST 414 is the most predominant strain. The increase VRE prevalence is due to cross-transmission of VRE clones ST 414,78,18 by undetected VRE carriers. Because similar VRE STs had been reported in a different hospital of Taiwan, this finding may indicate inter-hospital VRE spread in Taiwan. Active surveillance and effective infection control policies are important controlling the spread of VRE in high risk hospital zones. All endemic VRE strains are resistant to teicoplanin but are sensitive to daptomycin, linezolid, and tigecycline.

Interplay between mutational and horizontally acquired resistance mechanisms and its association with carbapenem resistance amongst extensively drug-resistant Pseudomonas aeruginosa (XDR-PA).

Between 2003 and 2009, the prevalence of extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) increased significantly in northern Taiwan from 1.0% to 2.1%. Molecular methods were used to investigate the genetic relatedness and carbapenem resistance mechanisms of a collection of 203 non-repetitive XDR-PA isolates available for study. Using pulsed-field gel electrophoresis (PFGE), 52 genotypes were observed; one predominant genotype (pulsotype 1) was found in 57.6% of the isolates. Polymerase chain reaction (PCR), sequencing and quantitative reverse-transcriptase PCR analyses demonstrated that one horizontally acquired mechanism [metallo-ß-lactamase (MBL) genes] and two mutational mechanisms (efflux and porins) accounted for the carbapenem resistance. The most predominant horizontally acquired mechanism was carriage of bla(VIM-3), which was found in 61.1% of isolates. Decreased expression of oprD was the most prevalent mutational mechanism and was found in 70.0% of the XDR-PA isolates, whereas overexpression of mexA was found in 27.6% of the isolates. The highlight of this study was the discovery of statistically significant relationships between certain horizontally acquired and mutational resistance mechanisms and their contribution to carbapenem susceptibility. MBL-producers expressed significantly lower MexAB and higher OprD than non-MBL-producers. Amongst isolates without an acquired ß-lactamase gene, oprD expression was significantly reduced, whilst expression of efflux pumps was increased. Reduced OprD expression alone or the production of VIM-type MBLs showed similar contributions to a low to intermediate MIC(50) (minimum inhibitory concentration for 50% of the organisms) for carbapenems. Isolates with reduced OprD expression that simultaneously harboured bla(VIM) exhibited high levels of resistance to carbapenems, which implied that these two mechanisms had a synergistic effect on the MICs.

Analysis of life-threatening complications of deep neck abscess and the impact of empiric antibiotics.

BACKGROUND: To review our experience in the treatment of deep neck abscesses, including analysis of the contributing factors related to the life-threatening complications and the effects of empiric antibiotics on the outcomes. METHODS: A retrospective study and statistical analysis of patients with deep neck abscesses treated at Chang Gung Memorial Hospital between April 2000 and April 2006. RESULTS: A total of 105 patients were enrolled in this study, including 66 males and 39 females with age ranging from 18 to 93 years. The result of logistic regression showed that old age, patients with underlying systemic diseases (p<0.05) and ineffective empiric antibiotics (p<0.01) had statistically significant correlation with life-threatening complications. When the age was older than 65 years, the empiric antibiotics were not effective, the way of drainage of the abscess was transcervical incision, the initial deep neck abscess involved more than 1 space, or the patient had underlying systemic diseases or complications, the duration of hospital stay tended to be longer (p <0.01). CONCLUSIONS: Even when adequately draining the abscess, the treatment of deep neck abscess in old-age patients more than 65 years, or the patients with ineffective empiric antibiotics or underlying systemic diseases should be more aggressive because life-threatening complications happen more frequently.