Comparison of Cefepime-Cefpirome and Carbapenem Therapy for Acinetobacter Bloodstream Infection in a Multicenter Study.

Carbapenems are currently the preferred agents for the treatment of serious Acinetobacter infections. However, whether cefepime-cefpirome can be used to treat an Acinetobacter bloodstream infection (BSI) if it is active against the causative pathogen(s) is not clear. This study aimed to compare the efficacy of cefepime-cefpirome and carbapenem monotherapy in patients with Acinetobacter BSI. The population included 360 patients with monomicrobial Acinetobacter BSI receiving appropriate antimicrobial therapy admitted to four medical centers in Taiwan in 2012 to 2017. The predictors of 30-day mortality were determined by Cox regression analysis. The overall 30-day mortality rate in the appropriate antibiotic treatment group was 25.0% (90/360 patients). The crude 30-day mortality rates for cefepime-cefpirome and carbapenem therapy were 11.5% (7/61 patients) and 26.3% (21/80 patients), respectively. The patients receiving cefepime-cefpirome or carbapenem therapy were infected by Acinetobacter nosocomialis (51.8%), Acinetobacter baumannii (18.4%), and Acinetobacter pittii (12.1%). After adjusting for age, Sequential Organ Failure Assessment (SOFA) score, invasive procedures, and underlying diseases, cefepime-cefpirome therapy was not independently associated with a higher or lower 30-day mortality rate compared to that with the carbapenem therapy. SOFA score (hazard ratio [HR], 1.324; 95% confidence interval [CI], 1.137 to 1.543; P < 0.001) and neutropenia (HR, 7.060; 95% CI, 1.607 to 31.019; P = 0.010) were independent risk factors for 30-day mortality of patients receiving cefepime-cefpirome or carbapenem monotherapy. The incidence densities of 30-day mortality for cefepime-cefpirome versus carbapenem therapy were 0.40% versus 1.04%, respectively. The therapeutic response of cefepime-cefpirome therapy was comparable to that with carbapenems among patients with Acinetobacter BSI receiving appropriate antimicrobial therapy.

Tumor lysis syndrome as a risk factor for very early mortality in HIV-associated non-Hodgkin's lymphoma: A 10-year single-center experience.

BACKGROUND: Despite the effectiveness of combination antiretroviral therapy, persons living with human immunodeficiency virus (PLWHIV) remain at a high risk of developing non-Hodgkin lymphoma (NHL). We aimed to analyze the demographics and outcomes of the HIV-associated NHLs. METHODS: Between 2005 and 2014, PLWHIV with NHLs were retrospectively enrolled at a tertiary referral center. Characteristics and survival were reviewed and analyzed. RESULTS: Twenty-two HIV-associated NHLs were identified, with a median follow-up of 14 months (range, 0.1-139.7), including eight diffuse large B-cell lymphomas (DLBCLs), eight primary central nervous system lymphomas (PCNSLs), and six Burkitt's lymphomas (BLs). Nine patients (40.9%) were diagnosed with NHLs and HIV infection concurrently. The prognosis of DLBCL patients tended to be better prognosis than that of BL and PCNSL patients (median overall survival: not reached vs. 3.5 months, p = 0.056). Very early mortality (death within 14 days after NHL diagnosis) was noted in five patients (22.7%), and tumor lysis syndrome (TLS) is a predictive factor for very early mortality among PLWHIV (hazard ratio:11.3, 95% confidence interval: 1.1-114.4, p = 0.04). CONCLUSION: Management of the early treatment phase of HIV-associated NHLs remains a major challenge. Careful intervention to patients with TLS might be the key to improve treatment outcomes.

Shall I trust the report? Variable performance of Sanger sequencing revealed by deep sequencing on HIV drug resistance mutation detection.

BACKGROUND: The clinical utilisation of deep sequencing in HIV treatment has been hindered due to its unknown correlation with standard Sanger genotyping and the undetermined value of minority drug resistance mutation (DRM) detection. OBJECTIVES: To compare deep sequencing performance to standard Sanger genotyping with clinical samples, in an effort to delineate the correlation between the results from the two methods and to find the optimal deep sequencing threshold for clinical utilisation. METHODS: We conducted a retrospective study using stored plasma collected from August 2014 to March 2018 for HIV genotyping with the commercial Sanger genotyping kit. Samples with available Sanger genotyping reports were further deep sequenced. Drug resistance was interpreted according to the Stanford HIV drug resistance database algorithm. RESULTS: At 15-25% minority detection thresholds, 9-15% cases had underestimated DRMs by Sanger sequencing. The concordance between the Sanger and deep sequencing reports was 68-82% in protease-reverse transcriptase region and 88-97% in integrase region at 5-25% thresholds. The undetected drug resistant minority variants by Sanger sequencing contributed to the lower negative predictive value of Sanger genotyping in cases harbouring DRMs. CONCLUSIONS: Use of deep sequencing improved detection of antiretroviral resistance mutations especially in cases with virological failure or previous treatment interruption. Deep sequencing with 10-15% detection thresholds may be considered a suitable substitute for Sanger sequencing on antiretroviral DRM detection.

Influenza vaccination and secondary prevention of cardiovascular disease among Taiwanese elders-A propensity score-matched follow-up study.

The present study aimed to evaluate the association between influenza vaccination and the secondary prevention of cardiovascular disease (CVD) among elderly persons. This retrospective cohort study used the Geriatric Dataset of Taiwan's National Health Insurance Research Database (2000-2013). Patients aged ≥ 65 years who had been hospitalized for the first episodes of myocardial infarction were eligible. The vaccinated cohort comprised patients who received one dose of influenza vaccine within 180 days after discharge. The unvaccinated cohort included those who did not receive influenza vaccination and was propensity score-matched (1:1) for known CVD risk factors. All-cause death, acute myocardial infarction or cardiovascular death, and hospitalization for heart failure were assessed 1 year after the 181st day after hospital discharge. Compared with the matched cohort (n = 4,350), the vaccinated cohort (n = 4,350) had significantly lower incidences of all-cause death (hazard ratios [HR] 0.82, 95% CI [confidence interval] 0.73-0.92), myocardial infarction or cardiovascular death (HR 0.84, 95% CI 0.74-0.96), and hospitalization for heart failure (HR 0.83, 95% CI 0.74-0.92). The association between influenza vaccination and reduction of CVDs was similar across different subgroups. Cumulative incidence curves of the CVDs of interest for the two cohorts separated within the initial 3 months of follow-up (P < 0.05). Influenza vaccination was associated with a reduced risk of CVD in the elderly population with previous myocardial infarction.

Use of lipid-lowering agents is not associated with improved outcomes for tuberculosis patients on standard-course therapy: A population-based cohort study.

OBJECTIVES: Animal and ex vitro studies suggested lipid-lowering agents (LLAs) may be used as an adjunct to standard anti- tuberculosis (TB) treatment. No human study has been conducted to date. Using the Taiwan National Health Insurance Research Database (NHIRD), the current population-based cohort study sought to examine the association between use of LLAs and outcomes of patients with pulmonary TB receiving anti-TB treatment. METHODS: Using a NHIRD from 2003 to 2010, this population-based cohort study retrospectively examined the association between LLAs (statins or fibrates) and the outcomes of patients with pulmonary TB receiving anti-TB treatment. RESULTS: A total of 1452 adult patients newly diagnosed with pulmonary TB during the study period were identified and compared with 5808 matched patients. In the LAA cohort, 1258 received statin, and 295 received fibrate. Compared with patients who did not take LLA, patients who took oral LLAs had similar incidence of treatment completion at 9, 12, and 24 months. CONCLUSIONS: Neither statins nor fibrates provide clinical benefit superior to that achieved with standard anti-tuberculosis treatment. Future clinical trials should investigate the effects of statins and fibrates on short-course standard anti-TB therapy.

Impact of reduced tigecycline susceptibility on clinical outcomes of Acinetobacter bacteremia.

The higher 14-day mortality rate for patients with Acinetobacter bacteremia receiving tigecycline appropriately compared to other appropriate antibiotics (36.4% versus 14.2%, P = 0.028) was due to the poor effect of tigecycline for isolates with a minimum inhibitory concentration of 2 µg/mL (63.6% of 11 versus 14.2% of 127, P = 0.001).

Implementation and outcomes of an antimicrobial stewardship program: Effectiveness of education.

BACKGROUND: Unnecessary use of antibiotics is a common occurrence in hospitals. Implementation of antibiotic stewardship programs (ASPs) has been shown to reduce both unnecessary antibiotic use and drug-resistant bacteria. Education is a fundamental component of an ASP. However, the effectiveness of proper uses of antibiotics education has not been clearly analyzed. METHODS: In a 520-bed university hospital located in northeastern Taiwan, a significantly increasing prescription of carbapenems, specifically imipenem and meropenem, was observed. An educational program highlighting the judicious use of carbapenems was started, beginning in October 2013. A multidisciplinary ASP was implemented starting in January 2014. The consumption of antibiotics, measured by defined daily dose per 1000 occupied bed-days, was compared among the pre-educational, posteducational, and post-ASP periods. RESULTS: Compared with the pre-educational period, there was a significant reduction in antibiotics consumption of 13% total inpatient antibiotics (p = 0.008), 29.8% carbapenems (p = 0.001), 34.9% imipenem and meropenem (p < 0.001), and 27% glycopeptides (p = 0.015), in the posteducational and post-ASP periods. The major reduction emerged during the posteducational period and was sustained after the ASP. The percentage of inpatients prescribed with antibiotics was significantly decreased (16.2%; p < 0.001). The rate of carbapenem-resistant Acinetobacter baumannii decreased from 70.8% to 29.6% within 7 months. CONCLUSION: A focused educational program is effective in controlling the prescription of specific antibiotic classes in the early phase of a multidisciplinary ASP.

Verapamil Use Is Associated With Reduction of Newly Diagnosed Diabetes Mellitus.

Objective: The mechanism of the beneficial effect of calcium-channel blockers (CCBs), especially verapamil, on the development of type 2 diabetes mellitus (T2DM) has been described. This study compared the incidence of T2DM in adults prescribed oral verapamil and propensity score-matched adults prescribed other oral CCBs. Methods: This retrospective population-based cohort study used Taiwan's National Health Insurance Research Database from 2000 to 2011. T2DM was defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification. Results: During follow-up periods of 41,958 and 42,118 person-years, 269 of 4930 patients in the verapamil cohort and 340 of 4930 patients in the matched cohort, respectively, developed T2DM. The incidence rates were 6.41 and 8.07 per 1000 population per year among verapamil and other CCB users, respectively. The adjusted hazard ratio (HR) for T2DM associated with use of verapamil (vs. other CCBs) was 0.80 [95% confidence interval (CI), 0.68 to 0.94; P = 0.006]. After exclusion of patients followed for <180 days or <365 days (to avoid bias derived from delayed diagnosis), adjusted HRs remained significant [0.79 (95% CI, 0.67 to 0.93; P = 0.005) and 0.77 (95% CI, 0.65 to 0.91; P = 0.002), respectively]. Only the interaction term for age was significant (P = 0.009). Verapamil had a more prominent effect on patients aged older than 65 years (P < 0.001). Conclusions: In patients with no known history of diabetes mellitus, oral verapamil use was associated with a decreased incidence of T2DM compared with other CCBs.

Risk factors and clinical outcome of sulbactam nonsusceptibility in monomicrobial Acinetobacter nosocomialis bacteremia.

BACKGROUND: Sulbactam is an effective antimicrobial agent against multidrug-resistant Acinetobacter spp. This retrospective study evaluated the risk factors of sulbactam nonsusceptibility (SNS) in monomicrobial Acinetobacter nosocomialis bacteremia and its related outcome. METHODS: This 9-year retrospective study included 267 patients who were admitted to a large teaching hospital in Taiwan with monomicrobial A. nosocomialis bacteremia. A. nosocomialis was identified to the species level using molecular methods. Antimicrobial susceptibilities were determined by the agar dilution method. To identify the risk factors of acquiring resistant strains, significant clinical variables derived from univariate analysis were entered into multivariate analysis. Polymerase chain reaction was used to identify blaTEM. Clonality was determined by pulsed-field gel electrophoresis. RESULTS: A total of 41 of the 267 patients (15.4%) had SNS A. nosocomialis bacteremia. Compared to those with susceptible strains, these patients had higher 14-day mortality (17.1% vs. 7.5%, p = 0.049), were more likely to have higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, were more frequently admitted to the intensive care unit, and had previously received broad-spectrum antibiotics and underwent invasive procedures. In multivariate analysis, the independent risk factors were high APACHE II score and prior use of arterial line [odds ratio (OR), 1.048; 95% confidence interval (CI), 1.007-1.091; p = 0.022 and OR, 2.936; 95% CI, 1.339-6.441; p = 0.007, respectively]. No outbreak was identified and SNS isolates did not harbor blaTEM. CONCLUSION: For monomicrobial A. nosocomialis bacteremia, the mortality of patients with SNS strains was higher. The SNS strains are more commonly recovered from patients with higher APACHE score and receiving more invasive procedures, especially arterial line.

Clinical features of patients with carbapenem nonsusceptible Klebsiella pneumoniae and Escherichia coli in intensive care units: a nationwide multicenter study in Taiwan.

BACKGROUND: Patients in intensive care units (ICUs) are especially prone to colonization and infection by carbapenem-resistant Enterobacteriaceae. We conducted a multicenter investigation to study the clinical and microbiological characteristics of patients with carbapenem nonsusceptible Klebsiella pneumoniae and Escherichia coli in ICUs of Taiwanese hospitals. METHODS: Patients with carbapenem nonsusceptible K. pneumoniae and E. coli in ICUs from nine medical centers and eight regional hospitals in Taiwan were enrolled in 2012. Carbapenem nonsusceptibility was defined as a minimum inhibitory concentration of at least 2 mg/L for imipenem or meropenem. Clinical characteristics and risk factors for 30-day mortality were analyzed. Isolates were screened for antibiotic susceptibility and ß-lactamase genes. RESULTS: A total of 66 cases infected (n = 46) or colonized (n = 20) with carbapenem nonsusceptible K. pneumoniae (n = 60) and E. coli (n = 6) were identified during the study period. Nineteen isolates had genes that encoded carbapenemases (28.8%), including Klebsiella pneumoniae carbapenemase-2 (KPC-2) (n = 14), imipenemase-8 (IMP-8) (n = 1), Verona integron-encoded metallo-ß-lactamase (VIM) (n = 3), and New Delhi metallo-ß-lactamase-1 (NDM-1) (n = 1). The in-hospital mortality associated with non-susceptible K. pneumoniae and E. coli was 50%. The 30-day mortality of the 46 patients with infection was 50%. Septic shock was the only independent risk factor for 30-day mortality in patients with infection. The 30-day mortality rate was similar between patients with combination therapy and monotherapy. CONCLUSION: Patients who acquired carbapenem nonsusceptible K. pneumoniae and E. coli in ICUs have a high mortality rate. Further clinical study is needed to deal with this emerging challenge.

Clinical characteristics and economic consequence of Klebsiella pneumoniae liver abscess in Taiwan.

BACKGROUND: Klebsiella pneumoniae liver abscess (KPLA) has emerged as an endemic disease in Taiwan, and its prevalence has been increasing in east Asian countries in the past three decades. The utilization of healthcare resources associated with KPLA is assumed to be substantial, and may be of future concern. This study investigated the clinical characteristics and economic burden of KPLA in Taiwan in 2011 and 2012. METHODS: Adult patients with KPLA were identified retrospectively in a tertiary medical center in Taiwan from January 2011 to December 2012. The clinical characteristics, total and daily hospitalization expenditure, and the risk factors for the costs of KPLA were analyzed. RESULTS: Among patients with KPLA, the median cost was $5290.80 in US dollars, and the mean cost was $6337.50 ± $4363.40. Length of hospital stay was the only independent risk factor for the high total hospitalization expenditure. The duration of antibiotic use was nearly the same as the length of hospital stay. The prolonged stay in the general ward (≥21 days) also contributed to the high total cost of hospitalization. The independent risk factors for the high average daily cost of hospitalization were a higher Charlson Comorbidity Index and the requirement of intensive care on admission. CONCLUSION: The current study is the first to demonstrate the high economic burden resulting from KPLA in a medical center in Taiwan. Standardizing the treatment protocol for KPLA inpatients and introducing an outpatient parenteral antimicrobial therapy center to reduce the length of stay may reduce costs, whereas development of a vaccine may be necessary to tackle endemic KPLA in the future.