Yung-Chih Wang

Impact of vancomycin MIC creep on patients with methicillin-resistant Staphylococcus aureus bacteremia

BACKGROUND/PURPOSE To date, vancomycin is still the standard treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections, but minimum inhibitory concentration (MIC) creep is becoming a major concern. The aims of this study were to investigate trends in vancomycin use and MIC values over the last decade at our institute and to evaluate the outcomes of bacteremic patients infected with MRSA isolates with reduced vancomycin susceptibility. METHODS Vancomycin use and density were evaluated using the defined daily doses (DDD) method. Patients with MRSA bacteremia were enrolled retrospectively. Patient demographic data and clinical outcomes were analyzed. The first isolate from each patient was collected for E-testing in order to determine vancomycin MIC. MIC trends were assessed as MIC(50), MIC(90), and the geometric mean. RESULTS Vancomycin use has increased over the last decade. One hundred and forty patients were enrolled and their respective isolates were retrieved, including isolates from 45 patients in 2001, 46 patients in 2005, and 49 patients in 2009. The geometric mean (± standard deviation) of the vancomycin MIC for MRSA isolates obtained in 2009 was 1.39 ± 0.30 μg/mL, which is significantly higher than the mean vancomycin MIC obtained in 2001 (1.19 ± 0.34 μg/mL, p < 0.01) and 2005 (1.99 ± 0.25 μg/mL, p < 0.001). There were no significant differences in terms of the in-hospital mortality rate between patients with MRSA isolates with MICs ≥ 1.5 μg/mL or < 1.5 μg/mL. CONCLUSION We identified a significant upward trend in the use of vancomycin and its MIC over the last decade. This study shows that patients infected with MRSA isolates with high MICs (≥1.5 μg/mL) do not have a significantly higher mortality rate compared with isolates with low MICs (<1.5 μg/mL).

Risk factors and outcomes of cytomegalovirus viremia in cancer patients: a study from a medical center in northern Taiwan.

BACKGROUND Cytomegalovirus (CMV) is a pathogen and can cause life-threatening infection in the patients with malignancies. This study was conducted to investigate the risk factors and outcomes of CMV viremia in patients with malignancies. METHODS Data were collected with retrospective analysis from adults suffering from CMV viremia with underlying malignancies. A total of 107 patients were enrolled in a tertiary medical center in northern Taiwan from March 2008 to December 2009. RESULTS Among the 107 patients who suffered with CMV viremia with an overall mortality rate of 56.1% (60/107), 75 patients (70.1%) had solid organ malignancies and 32 (29.9%) had hematological malignancies. Mechanical ventilation (p=0.048), leukocytosis (p=0.004), and lack of appropriate early treatment (p=0.011) were independent predisposing factors associated with higher mortality rate. CONCLUSIONS CMV viremia predicts high mortality rate in cancer patients, especially in those with mechanical ventilation, leukocytosis, and lack of appropriate early treatment. Appropriate early antiviral therapy is recommended to improve outcomes.

Helicobacter pylori infection increases the risk of adult-onset asthma: a nationwide cohort study

Helicobacter pylori infection (HPI) appears to reduce risk of childhood-onset asthma, but the relationship between HPI and adult-onset asthma is inconclusive. This study explored the potential association between HPI and risk of adult-onset asthma. We conducted a national insurance retrospective cohort study using the longitudinal health insurance database (LHID 2000) in Taiwan. We enrolled the HPI group consisting of 1664 patients with HPI diagnosis between 2000 and 2007, and the non-HPI group consisting of 6,656 age- and sex-matched subjects without HPI. All study participants had been followed up from index date to the diagnostic date of asthma, withdrawal from the National Health Insurance program, or the end of 2011, which came first. We analyzed risk of adult-onset asthma with respect to sex, age, and comorbidities by using Cox models. Cigarette smoking status, which could not be obtained from the program, was adjusted indirectly by considering chronic obstructive pulmonary diseases in our statistical models because the disease is related to heavy smoking. After adjustment for sex, age, and comorbidities, HPI was significantly associated with an increased 1.38-fold risk of adult-onset asthma. Moreover, among people without comorbidities, the 1.85-fold risk of adult-onset asthma remained higher for the HPI population compared with the non-HPI population. In this study, patients with HPI exhibited a significantly higher risk of adult-onset asthma than did the subjects without HPI.

Methicillin-resistant Staphylococcus aureus bacteremia in hemodialysis and nondialysis patients

BACKGROUND/PURPOSE Increased mortality has been reported in patients treated with vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with high minimum inhibitory concentration (MIC) values within the susceptibility range. However, this finding has not been verified in hemodialysis patients, who have much higher invasive MRSA infection rates than nondialysis patients. We aimed at comparing vancomycin MICs between hemodialysis and nondialysis patients, and identifying predictors of high vancomycin MICs and infection-related mortality in hemodialysis patients with MRSA bacteremia. METHODS Patients with MRSA bacteremia from January 2008 through December 2009 were enrolled. Vancomycin MIC was determined for each first isolate using the Etest method. Clinical characteristics and vancomycin MICs were compared between hemodialysis and nondialysis patients. Factors associated with high vancomycin MIC (2 μg/mL) and infection-related mortality in hemodialysis patients were analyzed. RESULTS A total of 162 MRSA bacteremia episodes were identified. Forty-four (27.0%) isolates were obtained from hemodialysis patients and 118 (73.0%) from nondialysis patients. Diabetes (63.3% vs. 39.8%, p = 0.007) and prior vancomycin exposure in 30 days (31.8% vs. 12.7%, p = 0.005) were more prevalent in hemodialysis group than in nondialysis group. A higher prevalence of vancomycin MIC of 2 μg/mL was observed in hemodialysis group in comparison with nondialysis group (11.4% vs. 1.7%, p = 0.016). In following analyses of hemodialysis group, patients with initial presentation of septic shock had a higher risk of vancomycin MIC of 2 μg/mL than nonseptic shock patients (100.0% vs. 38.5% p = 0.014). Infection-related mortality was associated with age, Acute Physiology and Chronic Health Evaluation II (APACHE-II) score >15, presence of septic shock, receipt of mechanical ventilation, and failure to remove source of bacteremia in univariate analysis. CONCLUSION Hemodialysis patients with MRSA bacteremia are more likely to have a high vancomycin MIC (2 μg/mL) compared with nondialysis patients. Infection-related mortality is associated with the patients clinical manifestations, including age, APACHE-II score >15, presence of septic shock, receipt of mechanical ventilation, and failure to remove source of bacteremia. Treatment selection should be tailored according to the patients clinical condition.

Molecular epidemiology of carbapenem non-susceptible Acinetobacter nosocomialis in a medical center in Taiwan

The mechanism by which carbapenem non-susceptible Acinetobacter nosocomialis (CNSAN) is disseminated is rarely described in the literature. In this study, we delineated the molecular epidemiology of CNSAN isolated from patients in a medical center in Taiwan. Fifty-four non-duplicate bloodstream isolates of CNSAN were collected at the Taipei Veterans General Hospital between 2001 and 2007. Pulsed-field gel electrophoresis (PFGE) was performed to determine their clonal relationship. Carbapenem-resistance genes and associated genetic structures were detected by polymerase chain reaction (PCR) mapping. Southern hybridization was performed to determine the plasmid location of carbapenem-resistance genes. Transmissibility of these genes to Acinetobacterbaumannii was demonstrated by conjugation tests. The overall carbapenem non-susceptibility rate among A. nosocomialis isolates during the study period was 21.6% (54/250). PFGE revealed three major pulsotypes: H (n=23), I (n=10), and K (n=8). The most common carbapenem-resistance gene was blaOXA-58 (43/54, 79.6%), containing an upstream insertion sequence IS1006 and a truncated ISAba3 (IS1006-ΔISAba3-like-blaOXA-58). All isolates belonging to the pulsotypes H, I, and K carried plasmid located IS1006-ΔISAba3-like-blaOXA-58. A common plasmid carrying ISAba1-blaOXA-82 was found in six isolates, which belonged to five pulsotypes. A type 1 integron that carried blaIMP-1 was detected in different plasmids of seven isolates, which belonged to five pulsotypes. Plasmids carrying these carbapenem-resistant determinants were transmissible from A. nosocomialis to A. baumannii via conjugation. In this medical center, CNSAN mainly emerged through clonal dissemination; propagation of plasmids and integrons carrying carbapenem-resistant determinants played a minor role. This study showed that plasmids carrying carbapenem-resistant determinants are transmissible from A. nosocomialis to A. baumannii.

Prevalence and Mortality-Related Factors of Multiple Myeloma in Taiwan

In this retrospective cohort study based in Taiwan, we reported the current epidemiology of patients with multiple myeloma and analyzed the factors affecting mortality. We identified 7285 patients with newly diagnosed multiple myeloma (MM) between 1997 and 2013 in Taiwan. Privileges data from the National Health Institute Research Database was used, as it is made readily available to the public in electronic format for research purposes. From 1997 to 2013, the average incidence of MM per 100,000 people was 1.83. The mortality accounted for an average of 0.44 per 100,000 deaths. In all 7285 inpatients with MM, the proportion of male patients was greater than that of female (59.90% vs. 40.10%); the mean age was 68.71 years with the proportion of those >55 years of age was 85.11%; and the proportion of a catastrophic illness was 66.51%. The death risk of the inpatient dialysis group was 3.044 times that of patients without dialysis (P <0.001). Moreover, the risk of death to men in the hospital setting was 1.162 times that of women (P = 0.012), and in the group of patients aged >55 years, the risk of in-hospital death was 1.511 times more than that in those aged ≤55 years (P <0.001). The risk of hospital death due to catastrophic illness was 1.347 times that of a non-catastrophic illness (P <0.001). Male patients and those >55 years of age had the most common prevalence of MM in Taiwan. Hemodialysis treatment, male sex, old age, and catastrophic illness were independent predictors of hospital mortality in patients with MM.

Individual or combined effects of meropenem, imipenem, sulbactam, colistin, and tigecycline on biofilm-embedded Acinetobacter baumannii and biofilm architecture

ABSTRACT Acinetobacter baumannii biofilms are difficult to eradicate. We investigated the effects of meropenem (2 mg/liter), imipenem (2 mg/liter), sulbactam (4 mg/liter), colistin (2 mg/liter), and tigecycline (2 mg/liter), alone or in combination, on biofilm-embedded carbapenem-resistant and carbapenem-susceptible A. baumannii (CRAb and CSAb, respectively) cells, as well as on the architecture of the biofilms. A. baumannii ATCC 15151 (Ab15151) and its OXA-82-overproducing transformant, along with two clinical CSAb and two clinical CRAb isolates of differing clonalities, were used. The minimal bactericidal concentrations for biofilm-embedded cells of the six tested isolates were >50-fold those of their planktonic cells. When used individually, meropenem exhibited a higher killing effect than the other four antimicrobials on biofilm-embedded CSAb cells in the colony biofilm assay. For two clinical CRAb isolates, meropenem plus sulbactam or sulbactam plus tigecycline showed >100-fold the bactericidal effect exhibited by these agents used alone after 48 h of treatment. The effect of antimicrobials on the architecture of Ab15151 biofilm emitting green fluorescence was determined by confocal laser scanning microscopy using COMSTAT software. Significant decreases in the maximum biofilm thickness were observed after exposure to meropenem and imipenem. Meropenem plus sulbactam significantly decreased the biomass and mean thickness and increased the roughness coefficient of biofilms, but sulbactam plus tigecycline only decreased the maximum and mean biofilm thickness compared to any of these agents used alone. Meropenem was active against biofilm-embedded CSAb, whereas meropenem plus sulbactam exhibited synergism against biofilm-embedded CRAb and caused significantly more damage to the biofilm architecture than did any of the agents used alone.

Chryseobacterium indologenes peritonitis in a patient with malignant ascites

Chryseobacterium indologenes is an uncommon pathogen of human disease and is usually associated with indwelling devices or immunocompromised hosts. We report here an unusual case of C. indologenes peritonitis in an oncological patient with malignant ascites. The patient was treated successfully by trimethoprim–sulfamethoxazole without removal of the catheter.

Carbapenem Breakpoints for Acinetobacter baumannii Group: Supporting Clinical Outcome Data from Patients with Bacteremia

The carbapenem breakpoints set by different organizations for Acinetobacter are discordant, but supporting clinical data are lacking. This study aimed to provide the first clinical outcome data to support the carbapenem breakpoints for Acinetobacter baumannii (Ab) group in patients with bacteremia. This study included 117 adults who received carbapenems for treatment of Ab group bacteremia in Taipei Veterans General Hospital over an 8-year period. We analyzed 30-day mortality rates among patient groups acquiring isolates with different carbapenem minimal inhibitory concentrations (MICs). The carbapenem MIC breakpoint derived from classification and regression tree (CART) analysis to delineate the risk of 30-day mortality was between MICs of ≤ 4 mg/L and ≥ 8 mg/L. Mortality rate was higher in patients acquiring isolates with carbapenem MIC ≥ 8 mg/L than ≤ 4 mg/L, by bivariate (54.9% [28/51] vs 25.8% [17/66]; P = 0.003) and survival analysis (P = 0.001 by log-rank test). Multivariate analysis using logistic regression and Cox regression models including severity of illness indices demonstrated that treating patients with Ab group bacteremia caused by isolates with a carbapenem MIC ≥ 8 mg/L with carbapenem was an independent predictor of 30-day mortality (odds ratio, 5.125; 95% confidence interval [CI], 1.946–13.498; P = 0.001, and hazard ratio, 2.630; 95% CI, 1.431–4.834; P = 0.002, respectively). The clinical outcome data confirmed that isolates with MIC ≤ 4 mg/L were susceptible to carbapenem, and those with MIC ≥ 8 mg/L were resistant in patients with Ab group bacteremia.

Multicenter Study of Clinical Features of Breakthrough Acinetobacter Bacteremia during Carbapenem Therapy

ABSTRACT Breakthrough Acinetobacter bacteremia during carbapenem therapy is not uncommon, and it creates therapeutic dilemmas for clinicians. This study was conducted to evaluate the clinical and microbiological characteristics of breakthrough Acinetobacter bacteremia during carbapenem therapy and to assess the efficacy of various antimicrobial therapies. We analyzed 100 adults who developed breakthrough Acinetobacter bacteremia during carbapenem therapy at 4 medical centers over a 6-year period. Their 30-day mortality rate was 57.0%, and the carbapenem resistance rate of their isolates was 87.0%. Among patients with carbapenem-resistant Acinetobacter bacteremia, breakthrough bacteremia during carbapenem therapy was associated with a significantly higher 14-day mortality (51.7% versus 37.4%, respectively; P = 0.025 by bivariate analysis) and a higher 30-day mortality (P = 0.037 by log rank test of survival analysis) than in the nonbreakthrough group. For the treatment of breakthrough Acinetobacter bacteremia during carbapenem therapy, tigecycline-based therapy was associated with a significantly higher 30-day mortality (80.0%) than those with continued carbapenem therapy (52.5%) and colistin-based therapy (57.9%) by survival analysis (P = 0.047 and 0.045 by log rank test, respectively). Cox regression controlling for confounders, including severity of illness indices, demonstrated that treatment with tigecycline-based therapy for breakthrough Acinetobacter bacteremia was an independent predictor of 30-day mortality (hazard ratio, 3.659; 95% confidence interval, 1.794 to 7.465; P < 0.001). Patients with breakthrough Acinetobacter bacteremia during carbapenem therapy posed a high mortality rate. Tigecycline should be used cautiously for the treatment of breakthrough Acinetobacter bacteremia that develops during carbapenem therapy.