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1.  Effectiveness of tigecycline-based versus colistin- based therapy for treatment of pneumonia caused by multidrug-resistant Acinetobacter baumannii in a critical setting: a matched cohort analysis 
BMC Infectious Diseases  2014;14:102.
Background
Colistin and tigecycline have both been shown good in vitro activity among multi-drug resistant Acinetobacter baumannii (MDRAB). A comparative study of colistin versus tigecycline for MDRAB pneumonia is lacking.
Methods
The study enrolled adults with MDRAB pneumonia admitted to intensive care units at a referral medical center during 2009–2010. Since there were no standardized minimum inhibitory concentration (MIC) interpretation criteria of tigecycline against A. baumannii, MIC of tigecycline was not routinely tested at our hospital. During the study periods, MIC of colistin was not routinely tested also. We consider both colistin and tigecycline as definite treatments of MDRAB pneumonia. Patients who received tigecycline were selected as potential controls for those who had received colistin. We performed a propensity score analysis, by considering the criteria of age, gender, underlying diseases, and disease severity, in order to match and equalize potential prognostic factors and severity in the two groups.
Results
A total of 294 adults with MDRAB pneumonia were enrolled, including 119 who received colistin and 175 who received tigecycline. We matched 84 adults who received colistin with an equal number of controls who received tigecycline. The two well matched cohorts share similar characteristics: the propensity scores are colistin: 0.37 vs. tigecycline: 0.37, (P = .97); baseline creatinine (1.70 vs. 1.81, P = .50), and the APACHE II score (21.6 vs. 22.0, P = .99). The tigecycline group has an excess mortality of 16.7% (60.7% vs. 44%, 95% confidence interval 0.9% – 32.4%, P = .04). The excess mortality of tigecycline is significant only among those with MIC >2 μg/mL (10/12 vs. 37/84, P = .01), but not for those with MIC ≦ 2 μg/mL (4/10 vs. 37/84, P = .81).
Conclusions
Our data disfavors the use of tigecycline-based treatment in treating MDRAB pneumonia when tigecycline and colistin susceptibilities are unknown, since choosing tigecycline-based treatment might result in higher mortality. The excess mortality of tigecycline-based group may be related to higher MIC of tigecycline (> 2 μg/mL). Choosing tigecycline empirically for treating MDRAB pneumonia in the critical setting should be cautious.
doi:10.1186/1471-2334-14-102
PMCID: PMC3936940  PMID: 24564226
Acinetobacter baumannii; Pneumonia; Colistin; Tigecycline; Mortality; Nephrotoxicity
2.  Safety and efficacy of high-dose daptomycin as salvage therapy for severe gram-positive bacterial sepsis in hospitalized adult patients 
Background
Increasing the dosage of daptomycin may be advantageous in severe infection by enhancing bactericidal activity and pharmacodynamics. However, clinical data on using daptomycin at doses above 6 mg/kg in Asian population are limited.
Methods
A retrospective observational cohort study of all hospitalized adult patients treated with daptomycin (> 6 mg/kg) for at least 72 hours was performed in Taiwan.
Results
A total of 67 patients (40 males) with a median age of 57 years received a median dose of 7.61 mg/kg (range, 6.03-11.53 mg/kg) of daptomycin for a median duration of 14 days (range, 3–53 days). Forty-one patients (61.2%) were in intensive care units (ICU). Sites of infections included complicated skin and soft tissue infections (n = 16), catheter-related bacteremia (n = 16), endocarditis (n = 11), primary bacteremia (n = 10), osteomyelitis and septic arthritis (n = 9), and miscellaneous (n = 5). The median Pitt bacteremia score among the 54 (80.6%) patients with bacteremia was 4. The most common pathogen was methicillin-resistant Staphylococcus aureus (n = 38). Fifty-nine patients (88.1%) were treated with daptomycin after glycopepetide use. Overall, 52 (77.6%) patients achieved clinical success. The all-cause mortality rate at 28 day was 35.8%. In multivariate analysis, the significant predictors of in-hospital mortality in 54 bacteremic patients were malignancies (P = 0.01) and ICU stay (P = 0.02). Adverse effects of daptomycin were generally well-tolerated, leading to discontinuation in 3 patients. Daptomycin-related creatine phosphokinase (CPK) elevations were observed in 4 patients, and all received doses > 8 mg/kg.
Conclusions
Treatment with high dose daptomycin as salvage therapy was generally effective and safe in Taiwan. CPK level elevations were more frequent in patients with dose > 8 mg/kg.
doi:10.1186/1471-2334-13-66
PMCID: PMC3571896  PMID: 23379510
Daptomycin; High dose; Creatine phosphokinase; Treatment outcomes
3.  Emergence of extensively drug-resistant Acinetobacter baumannii complex over 10 years: Nationwide data from the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program 
BMC Infectious Diseases  2012;12:200.
Background
Acinetobacter baumannii complex (ABC) has emerged as an important pathogen causing a variety of infections. Longitudinal multicenter surveillance data on ABC from different sources in Taiwan have not been published. Using data from the Taiwan Surveillance of Antimicrobial Resistance (TSAR) conducted biennially, we investigated the secular change in resistance of 1640 ABC from 2002 to 2010 (TSAR period III to VII) to different antimicrobial agents and identified factors associated with imipenem-resistant and extensively drug-resistant ABC (IRABC and XDRABC).
Methods
Isolates were collected by TSAR from the same 26 hospitals located in all 4 regions of Taiwan. Minimum inhibitory concentrations (MIC) were determined by reference broth microdilution method. Isolates nonsusceptible to all tested aminoglycosides, fluoroquinolones, β-lactam, β-lactam/β-lactam inhibitors, and carbapenems were defined as extensively drug-resistant (XDR). Multivariate logistic regression analysis was performed to assess the relationship between predictor variables among patients with resistant ABC and patients with non-resistant ABC.
Results
The prevalence of IRABC increased from 3.4% in 2002 to 58.7% in 2010 (P < 0.001; odds ratio [OR], 2.138; 95% confidence interval [CI], 1.947 to 2.347) and that of XDRABC increased from 1.3% in 2002 to 41.0% in 2010 (P < 0.001; OR, 1.970; 95% CI, 1.773-2.189). The rates of non-susceptibility to other antimicrobial agents remained high (>55%) over the years with some fluctuations before and after TSAR V (2006) on some agents. Multivariate analysis revealed that recovery from elderly patients, origins other than blood, from ICU settings, or geographic regions are independent factors associated with IRABC and XDRABC. Although the prevalence of XDRABC increased in all four regions of Taiwan over the years, central Taiwan had higher prevalence of XDRABC starting in 2008. Susceptibility to polymyxin remained high (99.8%).
Conclusions
This longitudinal multicenter surveillance program revealed significant increase and nationwide emergence of IRABC and XDRABC in Taiwan over the years. This study also identified factors associated with IRABC and XDRABC to help guide empirical therapy and at-risk groups requiring more intense interventional infection control measures with focused surveillance efforts.
doi:10.1186/1471-2334-12-200
PMCID: PMC3462144  PMID: 22929085
Extensively drug-resistant; Acinetobacter baumannii complex; Antimicrobial resistance
4.  Clinical characteristics and outcomes of Mycobacterium tuberculosis disease in adult patients with hematological malignancies 
BMC Infectious Diseases  2011;11:324.
Background
Diseases caused by Mycobacterium tuberculosis (TB) among adult patients with hematological malignancies have rarely been investigated.
Methods
Adult patients with hematological malignancies at National Taiwan University Hospital between 1996 and 2009 were retrospectively reviewed. Patients with positive serology for HIV were excluded. TB disease is diagnosed by positive culture(s) in the presence of compatible symptoms and signs. The demographics, laboratory and, microbiological features, were analyzed in the context of clinical outcomes.
Results
Fifty-three of 2984 patients (1.78%) were diagnosed with TB disease. The estimated incidence was 120 per 100,000 adult patients with hematological malignancies. Patients with acute myeloid leukemia had a significantly higher incidence of TB disease than other subtypes of hematological malignancies (2.87% vs. 1.21%, p = 0.002, odds ratio, 2.40; 95% confidence interval, 1.39-4.41). Thirty-eight patients (72%) with non-disseminated pulmonary TB disease presented typically with mediastinal lymphadenopathy (53%), pleural effusion (47%) and fibrocalcific lesions (43%) on chest imaging. The 15 (28%) patients with extra-pulmonary disease had lower rates of defervescence within 72 h of empirical antimicrobial therapy (13% vs 45%, p = 0.03) and a higher 30-day in-hospital mortality (20% vs. 0%, p = 0.004) compared to those with disease confined to the lungs.
Conclusions
TB disease is not uncommon among patients with hematological malignancies in Taiwan. Patients who received a diagnosis of extra-pulmonary TB suffered higher mortality than those with pulmonary TB alone. Clinicians should consider TB in the differential diagnoses of prolonged fever in patients with hematological malignancies, particularly in regions of high endemicity.
doi:10.1186/1471-2334-11-324
PMCID: PMC3241214  PMID: 22111760
Mycobacterium tuberculosis (TB); Hematological malignancy; Febrile neutropenia
5.  Invasive fungal sinusitis in patients with hematological malignancy: 15 years experience in a single university hospital in Taiwan 
BMC Infectious Diseases  2011;11:250.
Background
Risk factors and outcomes in hematological patients who acquire invasive fungal sinusitis (IFS) are infrequently reported in the modern medical era.
Method
A retrospective study of hospitalized patients with hematological disease was conducted at National Taiwan University Hospital between January 1995 and December 2009.
Results
Clinical characteristics and outcomes with their associated radiographic and microbiological findings were analyzed. Forty-six patients with IFS and 64 patients with chronic non-invasive sinusitis were enrolled as comparsion. IFS developed more commonly in patients with acute myeloid leukemia (AML) and with prolonged neutropenia (absolute neutrophil count less than 500/mm3 for more than 10 days) (p < 0.001). Aspergillus flavus was the most common pathogen isolated (44%). Serum Aspergillus galactomannan antigen was elevated in seven of eleven patients (64%) with IFS caused by aspergillosis but negative for all three patients with mucormycosis. Bony erosion and extra-sinus infiltration was found in 15 of 46 (33%) patients on imaging. Overall, 19 of 46 patients (41.3%) died within 6 weeks. Patients with disease subtype of AML (p = 0.044; Odds Ratio [OR], 5.84; 95% confidence interval [95% CI], 1.02-30.56) and refractory leukemia status (p = 0.05; OR, 4.27; 95% CI, 1.003-18.15) had worse prognosis. Multivariate analysis identified surgical debridement as an independent good prognostic factor (p = 0.047) in patients with IFS.
Conclusions
Patients of AML with prolonged neutropenia (> 10 days) had significantly higher risk of IFS. Early introduction of anti-fungal agent and aggressive surgical debridement potentially decrease morbidity and mortality in high risk patients with IFS.
doi:10.1186/1471-2334-11-250
PMCID: PMC3196720  PMID: 21939544
Invasive fungal sinusitis (IFS) ; hematological disease;  Aspergillus galactomanan
6.  Nosocomial methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in Taiwan: Mortality analyses and the impact of vancomycin, MIC = 2 mg/L, by the broth microdilution method 
BMC Infectious Diseases  2010;10:159.
Background
Previous studies regarding the prognosis of patients infected with MRSA isolates characterized by a high minimum inhibitory concentration (MIC) for vancomycin have generally used a commercial Etest. Little research has been conducted on determining the vancomycin susceptibility of MRSA using a reference microdilution. Additionally, there is discordance between the MIC result from an Etest and the value determined using the reference microdilution method.
Methods
Using a reference microdilution method, we determined the MIC of vancomycin for isolates from 123 consecutive patients with nosocomial MRSA bacteremia. The clinical features and outcome for these patients were recorded and the MRSA isolates were genotyped.
Results
Among the 123 non-duplicated isolates, 21.1% had a MIC = 2 mg/L, 76.4% had a MIC = 1 mg/L and 2.4% had MIC = 0.5 mg/L. Patients with MRSA bacteremia in the ICU or those who had been hospitalized for a long time were more likely to be infected with strains of high vancomycin MIC MRSA (MIC = 2 mg/L; p < 0.05). Cox regression analysis demonstrated that the high MIC group had a significantly higher 30-day mortality than the low MIC group (HR: 2.39; 95% CI: 1.20-4.79; p = 0.014). Multivariate analyses indicated that the presence of high MIC isolates, pneumonia, post-cardiothoracic surgery and a high Charlson comorbidity index were all independent predictors of a 30-day mortality. Genotyping of these high vancomycin MIC isolates demonstrated that SCCmec III, spa type037, was the predominant strain (> 80%). The rates of resistance to trimethoprim/sulfamethoxazole, gentamicin, levofloxacin, rifampin and tetracycline were also higher in the high MIC group than in the isolates belonging to low MIC group (p < 0.05).
Conclusions
In a high vancomycin MIC group in Taiwan, SCCmec III, spa type t037, was the predominant strain of MRSA identified. Patients with MRSA bacteremia in the ICU or who had prolonged hospitalization were more likely to be infected with S. aureus strains with high vancomycin MICs. The mortality rate was higher among patients infected with these strains compared to patients infected with low MIC strains.
doi:10.1186/1471-2334-10-159
PMCID: PMC2890009  PMID: 20529302
7.  Impact of first-line protease inhibitors on predicted resistance to tipranavir in HIV-1-infected patients with virological failure 
Background
Tipranavir (TPV) is a recently approved nonpeptidic protease inhibitor (PI) of HIV-1 and has been indicated for those infected with PIs-resistant HIV-1. However, in clinical practice, whether the HIV-1 from the patients with virological failure to the regimens containing first-line PIs remains susceptible to TPV/r may be questionable.
Methods
To assess the resistance levels to TPV of HIV-1 from patients with treatment failure to first-line PIs, patients who experienced virological failure were tested for genotypic resistance of HIV-1 since August 2006 in National Taiwan University Hospital. Patients were enrolled for this analysis if their failed regimens contained > 12 weeks of atazanavir or lopinavir/ritonavir (defined as ATV group and LPV/r group, respectively), but were excluded if they experienced both or other PIs. The levels of genotypic resistance to TPV/r were determined by TPV mutation score.
Results
Till May 2008, 21 subjects in ATV group and 20 subjects in LPV/r group were enrolled. The TPV mutation scores in subjects in LPV/r group were significantly higher than these in ATV group (median, 3 vs 1, P = 0.007). 95.2% subjects in ATV group and only 45% subjects in LPV/r group had an estimated maximal virological response to TPV/r (P < 0.001). The resistance levels to TPV/r correlated with the duration of exposure to first-line PIs, whether in ATV or LPV/r group.
Conclusion
Cross-resistance from first-line PIs may impede the effectiveness of TPV/r-containing salvage therapy. TPV/r should be used cautiously for patients with virological failure to LPV/r especially long duration of exposure.
doi:10.1186/1471-2334-9-154
PMCID: PMC2749855  PMID: 19751502
8.  Association between amebic liver abscess and Human Immunodeficiency Virus infection in Taiwanese subjects 
Purpose
Invasive amebiasis is an emerging parasitic disorder in Taiwan, especially in patients diagnosed with human immunodeficiency virus (HIV) infection. Thirty-three Taiwanese subjects with amebic liver abscess (ALA) were examined and a possible correlation between ALA and HIV infection was investigated.
Results
Among ALA patients, the proportion of HIV-positive individuals increased during the study period. ALA was the first major clinical presentation in 54% of HIV patients with ALA. Overall, 58% (14/24) of HIV-infected patients had a CD4+ count > 200 cells/μL and 82.1% (23/28) had no concurrent opportunistic infection or other evidence of HIV infection. There was no marked difference in clinical characteristics between HIV-positive and HIV-negative ALA patients except the level of leukocytosis.
Conclusion
While the clinical characteristics described herein cannot be used to determine whether ALA patients have HIV infection, routine HIV testing is recommended in patients with ALA, even in the absence of HIV symptoms.
doi:10.1186/1471-2334-8-48
PMCID: PMC2374788  PMID: 18416821
9.  Clinical features and outcome of sporadic serogroup W135 disease Taiwan 
Background
Few published reports have evaluated the clinical features and outcome of serogroup W135 meningococcal disease. In Taiwan, W135 is the second most prevalent meningococcal disease serogroup.
Method
A nationwide study was conducted to retrospectively analyze epidemiologic data from 115 patients with laboratory confirmed meningococcal disease that occurred from 2001 through 2003.
Results
Serogroup W135 accounted for 26% of all cases and most (76.7%) were older than 20 years. There were no cases of serogroup W135 meningococcal disease associated with Hajj pilgrims, and all cases were sporadic. In 88 patients with complete case records, we compared the presenting symptoms, signs, laboratory data, and outcomes between W135 and non-W135 patients. There were no differences in presenting symptoms except for the higher prevalence of pneumonia found in W135 patients (23.8% vs. 1.5%; OR: 20.6; 95%CI: 2.3–189.0; p = 0.003). The distribution of inflammatory cells in CSF in patients with meningitis was also different between W135 and non-W135 patients. W135 patients had a trend toward more intubations and shock but it did not achieve statistical significance. In multivariate analysis of factors associated with death, three independent factors were found: bacteremia without meningitis, altered mental status, and petechiae or purpura on admission.
Conclusion
Sporadic serogroup W135 meningococcal disease is an important component of the meningococcal disease burden in Taiwan, but it is not directly associated with Hajj pilgrims. Compared with patients infected by other serogroups of meningococci, patients with serogroup W135 were older and more likely to have extrameningeal involvement such as pneumonia.
doi:10.1186/1471-2334-6-7
PMCID: PMC1373656  PMID: 16420709

Results 1-9 (9)