Clinical characteristics and treatment outcomes of pulmonary invasive fungal infection among adult patients with hematological malignancy in a medical centre in Taiwan, 2008–2013

Background/purposeThis study was aimed to investigate clinical characteristics and treatment outcomes of pulmonary invasive fungal infection (IFI) among patients with hematological malignancy.MethodsAll patients with hematological malignancy who were treated at a medical centre from 2008 to 2013 were evaluated. Pulmonary IFI was classified according to the European Organization for Research and Treatment of Cancer 2008 consensus.ResultsDuring the study period, 236 (11.3%) of 2083 patients with hematological malignancy were diagnosed as pulmonary IFI, including 41 (17.4%) proven, 75 (31.8%) probable, and 120 (50.8%) possible cases. Among the 116 patients of proven and probable cases of pulmonary IFI, aspergillosis alone (n = 90, 77.6%) was predominant, followed by cryptococcosis alone (n = 9, 7.8%), and mucormycosis (n = 4, 3.4%). The overall incidence of patients with pulmonary IFI was 5.9 per 100 patient-years. The highest incidence (per 100 patient-year) was found in patients with acute myeloid leukaemia (13.7) followed by acute lymphoblastic leukaemia (11.3), and myelodysplastic syndrome/severe aplastic anaemia (6.7). Fourteen (5.9%) of the 236 patients with pulmonary IFI died within 12 weeks after diagnosis of pulmonary IFI. Univariate analysis revealed that elderly age (>65 years) (P = 0.034), lack of response to anti-fungal treatment (P < 0.001), and admission to the intensive care unit (ICU) (P < 0.001) were predictors of poor prognosis. However, only admission to the ICU was an independent predictor of poor prognosis for 12-week mortality (P = 0.022) based on multivariate analysis.ConclusionPatients with acute leukaemia and myelodysplastic syndrome/severe aplastic anaemia were at high risk of pulmonary IFI.     

In vitro activities of moxifloxacin and tigecycline against bacterial isolates associated with intraabdominal infections at a medical center in Taiwan, 2001–2006

A total of 569 nonduplicate isolates recovered from patients with community-onset or hospital-onset intraabdominal infections (IAIs) from 2001 to 2006 were studied. These included 28 Staphylococcus aureus and 541 Gram-negative isolates (33.6% Escherichia coli, 29.0% Klebsiella pneumoniae, 8.1% Acinetobacter baumannii, and 6.3% Pseudomonas aeruginosa). Minimum inhibitory concentrations (MICs) of the isolates to moxifloxacin, imipenem, and ciprofloxacin were determined using the agar dilution method and to tigecycline using the broth microdilution method. Extended-spectrum β-lactamase (ESBL) producers were found in 15.5% (29 out of 182) of E. coli, 15.3% (24 out of 157) of K. pneumoniae, and 15.4% (2 out of 13) of K. oxytoca isolates. More than 85% of Enterobacteriaceae were susceptible to moxifloxacin, but this percentage was lower among E. coli (78%). The percentage of E. coli (K. pneumoniae) isolates that were not susceptible to moxifloxacin was 6% (0%) in 2001, 39% (17%) in 2003, and 21% (14%) in 2006. Tigecycline exhibited good in vitro activities against all S. aureus and >95% of all Enterobacteriaceae tested. Among the 24 isolates of ESBL-producing K. pneumoniae, 4 had tigecycline MICs ≥2 μg/ml. Eighty percent of A. baumannii isolates exhibited tigecycline MICs of ≤2 μg/ml. This study found that moxifloxacin and tigecycline exhibited good in vitro activity against bacterial isolates causing IAIs.     

Bacteremia caused by Acinetobacter junii at a medical center in Taiwan, 2000–2010

We investigated the clinical characteristics and outcomes of 43 patients with Acinetobacter junii bacteremia at a 2,500-bed tertiary care center in northern Taiwan. These organisms were confirmed to the species level by an array assay and 16S rRNA gene sequence analysis. The antimicrobial susceptibilities of the 43 A. junii isolates to 13 agents were determined using the agar dilution method. Susceptibility testing for tigecycline was determined using the broth microdilution method. Most of the patients were hospital-acquired (n?=?36, 83.7?%) or healthcare facility-related infections (n?=?6, 13.9?%), and 55.8?% had impaired immunity. Central venous access devices were present in 35 (81.4?%) patients; among the total of 43 patients with A. junii bacteremia, 8 patients were diagnosed as catheter-related bloodstream infection and 19 patients were diagnosed as catheter-associated bloodstream infection. Shock requiring inotropic agents occurred in 2 patients (4.6?%). Most patients developed bacteremia in general wards (n?=?36, 83.7?%). The overall in-hospital mortality rate was low (7?%), despite the low rate of removal of central venous devices, low rate of holding usage of original central venous devices, and high rate of inappropriate antimicrobial regimens. Carbapenems, fluoroquinolones, and amikacin had potent activity (>95?% susceptible rate) against A. junii isolates. Interestingly, 35?% of the A. junii isolates were resistant to colistin. Tigecycline exhibited low minimum inhibitory concentration (MIC) values (range, 0.06-2 μg/ml, MIC(90), 1 μg/ml) against the A. junii isolates.     

Culture-positive invasive aspergillosis in a medical center in Taiwan, 2000–2009

We reviewed 776 patients who were culture positive for Aspergillus species at the hospital from 2000 to 2009. The isolates were collected for species identification by oligonucleotide hybridization and sequence analysis. A total of 96 cases of proven or probable IA were identified according to published criteria. The incidence of IA has increased significantly during the study period. Aspergillus fumigatus and A. flavus (41.7% each) were equally prevalent causative species. IA due to unusual species including A. nidulans (n=2), A. versicolor (n=2), and A. tubingensis (n=1) were also found. Among patients with IA, 55.2% had hematological disorder, 19.8% had underlying lung disorder, and 10.4% had autoimmune disease. The isolates species (P<0.001) and underlying disease (P<0.001) significantly affect the association of a positive culture with invasive disease. The overall mortality at three months was 62.5%, which remained stable throughout the study period. Multivariate analysis identified prior steroid use (P=0.007) as a significant risk factor for death, while surgery (P=0.030) and voriconazole (P=0.012) had protective effects. In conclusion, autoimmune disorders and underlying pulmonary diseases should also be considered as important predisposing factors of IA. Further emphasis on surgery and voriconazole in the management of IA might be beneficial.     

Community-onset Clostridium difficile infection at a tertiary medical center in southern Taiwan, 2007–2015

Background

Clostridium difficile infection (CDI) is well-known as the major cause of infectious diarrhea in hospitalized patients. Community-onset CDI (CO-CDI) is an emerging threat. However, clinical information of CO-CDI in Taiwan remains scarce.

Risk factors for mortality among patients with Stenotrophomonas maltophilia bacteremia in Tokyo, Japan, 1996–2009

Stenotrophomonas maltophilia is an important nosocomial pathogen, especially among immunocompromised patients. The objective of this study was to clarify the clinical characteristics, prognosis, and prognostic factors of patients with S. maltophilia bacteremia in Japan. The microbiology records of all patients with S. maltophilia bacteremia between January 1996 and April 2009 at Toranomon Hospital, Tokyo, Japan, were retrospectively reviewed. A total of 53 cases of bacteremia were identified. Thirty patients had an underlying hematological disorder, and 23 were receiving hematopoietic transplantation. The overall mortality rate was 51%. On univariate analysis, neutropenia (p < 0.01), the presence of a central venous catheter, and mixed infection with enterococci (p < 0.05) were significantly related to the mortality. Among these variables, neutropenia (p < 0.01) and mixed infection with enterococci (p < 0.05) were independent factors associated with mortality. In contrast, all eight patients in whom S. maltophilia was the etiologic agent of catheter-related infection survived following catheter removal. S. maltophilia is an important pathogen among immunocompromised patients, especially in the neutropenic phase or mixed infection with enterococci. If a central venous catheter was present at the onset of S. maltophilia bacteremia, the prompt removal of the catheter was important.     

Clinical characteristics and outcomes of patients with vancomycin-susceptible Enterococcus faecalis and Enterococcus faecium bacteraemia—a five-year retrospective review

The purpose of this study was to assess the epidemiology and outcomes of enterococcal bacteraemia. A retrospective review of demographic, microbiological and clinical data in patients 16 years of age and over with Enterococcus faecalis or E. faecium bacteraemia at Auckland City Hospital, New Zealand, from June 2002 to May 2007 was carried out. A total of 212 patients fulfilled the inclusion criteria, with 205 being included in the analysis. E. faecalis accounted for 86% (176/205) and E. faecium 14% (29/205) of the patients. Amoxycillin resistance occurred in 69% (20/29) of E. faecium isolates. High-level gentamicin resistance was present in 38% (65/171) of E. faecalis isolates and 25% (7/28) of E. faecium isolates (P = NS). No vancomycin-resistant enterococci were isolated. Healthcare association was present in 73% (149/205) of patients. Co-morbidities were present in 86% (176/205) of patients. The 7-day mortality was 13% (27/205) and the 30-day mortality 25% (52/205). On multivariate analysis, the 7-day mortality was statistically significantly associated with cirrhosis and shorter intravenous amoxycillin therapy. The 30-day mortality was statistically significantly associated with cirrhosis, malignancy, E. faecium bacteraemia and not receiving active antimicrobial therapy. No statistically significant association between high-level gentamicin resistance and mortality was demonstrated on multivariate analysis. Enterococcal bacteraemia occurs in a co-morbid, healthcare-exposed population. Associated mortality is high, and is associated with severe underlying disease, E. faecium bacteraemia and treatment factors.     

Systemic lupus erythematosus and thyroid disease – Experience in a single medical center in Taiwan

BackgroundTo investigate the association of systemic lupus erythematosus (SLE) with thyroid diseases in a medical center in central Taiwan.MethodsThis is a retrospective cohort of 2796 SLE patients in a tertiary referral medical center from 2000 to 2013. We screened SLE by catastrophic illness registration from national insurance bureau; and thyroid diseases by ICD 9 codes, then confirmed by thyroid function test, auto-antibody, medical and/or surgical intervention. We compared the rate of hyperthyroidism, hypothyroidism and autoimmune thyroid disease (AITD) in SLE patients and the 11,184 match controls. We calculated the rate of these thyroid diseases and positive antibodies to thyroglobulin (ATGAb), thyroid peroxidase (TPOAb) in SLE patients grouped by the presence of overlap syndrome and anti-dsDNA antibody. We also compared the association of thyroid diseases to severe SLE conditions, including renal, central nervous system (CNS) involvement, and thrombocytopenia.ResultsCompared to the matched controls, the cumulative incidence of thyroid disease, including hyperthyroidism, hypothyroidism and AITD, were all higher in SLE patients (p < 0.0001). The average age of SLE patients with thyroid diseases patients were older than those without thyroid diseases (p = 0.002). Those had euthyroid AITD were younger than other patients with thyroid diseases (p = 0.02). Up to 30.3% SLE patients had overlap syndrome and had higher relative risk of thyroid diseases than those without overlap syndrome, in terms of hypothyroidism and AITD, but not hyperthyroidism. SLE patients with thyroid diseases also carry higher risk for severe complications such as renal involvement (p = 0.024) central nervous system involvement (p < 0.0001).ConclusionSLE patients had significantly higher rate of hyperthyroidism, hypothyroidism, and AITD than the matched control. Among lupus patients, the risks of thyroid diseases are even higher in the presence of overlap syndrome. SLE patients with thyroid diseases had higher risk of renal and CNS involvement.     

Genitourinary infections caused by nontuberculous mycobacteria at a university hospital in Taiwan, 1996–2008

Genitourinary infections caused by nontuberculous mycobacteria (NTM) are rarely reported. The medical records of all patients with genitourinary NTM infections treated at National Taiwan University Hospital from 1996–2008 were retrospectively reviewed. Fifteen patients were identified, of whom 10 (67%) were male. More than two-thirds of patients had underlying conditions, the most common of which was chronic renal disease. Only one patient had AIDS. Acid-fast smears of urine were negative in all patients. Eleven isolates were available for further confirmation by sequencing of the 16S rRNA gene. Mycobacterium avium complex was the most common (n = 5, 33%), followed by both Mycobacterium abscessus (n = 2; 13%) and Mycobacterium fortuitum (n = 2; 13%). Of the 12 patients receiving anti-NTM treatment, only four received adequate prescribed regimens and none died of NTM infections. Two patients died of refractory urosepsis before the urinary NTM infections were diagnosed. The clinical characteristics of the 15 patients were also compared with 43 previously reported patients with genitourinary tuberculosis. Patients with genitourinary NTM infections were more likely to report constitutional symptoms, seek medical help within 1 month after the onset of symptoms and develop leukocytosis. Patients with genitourinary tuberculosis were more likely to have ureteral strictures and abnormal chest radiographs associated with active or inactive tuberculosis. Although rare, genitourinary NTM infections pose a significant threat to life and should be considered in the differential diagnosis of genitourinary infections, especially when patients are unresponsive to conventional antibiotic treatment.     

AmpR is a dual regulator in Stenotrophomonas maltophilia with a positive role in β-lactam resistance and a negative role in virulence,biofilm and DSF production

Stenotrophomonas maltophilia intrinsic resistance to β-lactams is mediated by two chromosomal β-lactamases, L1 and L2, whose induction depends on AmpR. Its quorum sensing (QS) signal, the diffusible signal factor (DSF), has a positive role in biofilm production, virulence and induction of β-lactamases. We hypothesized that AmpR has a role in virulence, biofilm production and QS system. Studies were done on S. maltophilia K279a, K279a ampR^FS (ampR deficient mutant) and K279aM11 (constitutively active AmpR mutant). K279a ampR^FS showed the highest biofilm biomass, thickness and 3D organization. Conversely, K279aM11 was the least efficient biofilm former strain. qRT-PCR showed that spgM, related to biofilm formation and virulence, was upregulated in K279a ampR^FS and downregulated in K279aM11. A constitutively active AmpR led to a reduction of DSF production, while K279a ampR^FS was the highest producer. Consequently, qRT-PCR showed that AmpR negatively regulated rpfF expression. K279a ampR^FS presented the highest oxidative stress resistance, overexpressed sodA gene and showed the highest virulence in the Galleria mellonella killing assay. This is the first evidence of the function of AmpR as a dual regulator in S. maltophilia with a positive role in β-lactam resistance and a negative role in DSF production, biofilm formation, oxidative stress resistance and virulence.     

Clinical and microbiological characteristics of Nocardiosis including those caused by emerging Nocardia species in Taiwan, 1998–2008

The genus of Nocardia is rapidly expanding and the species distribution varies with different geographical locations. We retrospectively reviewed the laboratory records of the bacteriology laboratory at National Taiwan University Hospital from January 1998 to June 2008 to identify patients with nocardiosis. During the study period, 164 isolates of Nocardia spp. were identified from 134 patients but only 113 patients had Nocardia infection. Nocardia brasiliensis (n = 54) was the most common pathogen, followed by N. asteroides (n = 36), N. farcinica (n = 7), N. flavorosea (n = 4), N. otitidiscaviarum (n = 3), N. nova (n = 3), N. beijingensis (n = 2) and one each of N. puris, N. jinanensis and N. takedensis. The major types of infection were cutaneous infection (56.6%), pulmonary infection (33.6%) and disseminated infection (7.1%). Eighty-eight patients received sulfonamide-containing antibiotic and eight of 100 patients with available data on outcomes died during the episode of nocardiosis. In conclusion, the clinical and microbiological manifestations of Nocardiosis vary with the different Nocardia species. Accurate identification of the species is crucial to make the diagnosis.     

Epidemiological and clinical characteristics of SARS-CoV-2 infections at a testing site in Berlin,Germany, March and April 2020—a cross-sectional study

ObjectiveIn Berlin, the first public severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing site started 1 day after the first case in the city occurred. We describe epidemiological and clinical characteristics and aim at identifying risk factors for SARS-CoV-2 detection during the first 6 weeks of operation.MethodsTesting followed national recommendations, but was also based on the physician's discretion. We related patient characteristics to SARS-CoV-2 test positivity for exploratory analyses using a cross-sectional, observational study design.ResultsBetween 3 March and 13 April 2020, 5179 individuals attended the site (median age 34 years; interquartile range 26–47 years). The median time since disease onset was 4 days (interquartile range 2–7 days). Among 4333 persons tested, 333 (7.7%) were positive. Test positivity increased up to 10.3% (96/929) during the first 3 weeks and then declined, paralleling Germany's lock-down and the course of the epidemic in Berlin. Strict adherence to testing guidelines resulted in 10.4% (262/2530) test positivity, compared with 3.9% (71/1803) among individuals tested for other indications. A nightclub was a transmission hotspot; 27.7% (26/94) of one night's visitors were found positive. Smell and/or taste dysfunction indicated coronavirus disease 2019 (COVID-19) with 85.6% specificity (95% CI 82.1%–88.1%). Four per cent (14/333) of those infected were asymptomatic. Risk factors for detection of SARS-CoV-2 infection were recent contact with a positive case (second week after contact, OR 3.42; 95% CI 2.48–4.71), travel to regions of high pandemic activity (e.g. Austria, OR 4.16; 95% CI 2.48–6.99), recent onset of symptoms (second week, OR 3.61; 95% CI 1.87–6.98) and an impaired sense of smell/taste (4.08; 95% CI 2.36–7.03).ConclusionsIn this young population, early-onset presentation of COVID-19 resembled flu-like symptoms, except for smell and/or taste dysfunction. Risk factors for SARS-CoV-2 detection were return from regions with high incidence and contact with confirmed SARS-CoV-2 cases, particularly when tests were administered within the first 2 weeks after contact and/or onset of symptoms.     

Clinical manifestations and outcome of nocardiosis and antimicrobial susceptibility of Nocardia species in southern Taiwan, 2011–2021

Background/PurposeNocardiosis is an uncommon infectious disease. This study aimed to assess the clinical outcome of patients with nocardiosis and examine the antimicrobial susceptibility profiles of Nocardia spp. isolated.MethodsWe retrospectively reviewed the medical records of all inpatients diagnosed with nocardiosis between 2011 and 2021. The identification of Nocardia spp. at the species level was performed with the use of MALDI-TOF and 16S rRNA assays. The antimicrobial susceptibility of Nocardia spp. was performed using the microbroth dilution method. Factors associated with 90-day all-cause mortality were identified in multivariate logistic regression analysis.ResultsOf 60 patients with nocardiosis in the 11-year study period, the lungs (55.0%) were the most common site of involvement, followed by the skin and soft tissue (45.0%). Twenty-two patients (36.7%) died within 90 days following the diagnosis. All of the Nocardia isolates were susceptible to trimethoprim-sulfamethoxazole, linezolid, and amikacin, whereas more than 70% of the isolates were not susceptible to ciprofloxacin, imipenem-cilastatin, moxifloxacin, cefepime, and clarithromycin. Nocardiosis involving the lungs (relative risk [RR], 9.99; 95% confidence interval [CI], 1.52–65.50; p = 0.02), nocardiosis involving the skin and soft tissue (RR, 0.15; 95% CI, 0.02–0.92; p = 0.04), and treatment with trimethoprim-sulfamethoxazole (RR, 0.14; 95% CI, 0.03–0.67; p = 0.01) were independently associated with 90-day all-cause mortality.ConclusionsNocardia spp. identified between 2011 and 2021 remained fully susceptible to trimethoprim-sulfamethoxazole, linezolid, and amikacin. Nocardiosis of the lungs, skin and soft tissue infection, and treatment with trimethoprim-sulfamethoxazole were independently associated with 90-day all-cause mortality.     

Prevalence and characteristics of hepatitis B and C virus infections in treatment-na?ve HIV-infected patients

In HIV-infected treatment-na?ve patients, we analyzed risk factors for either chronic hepatitis B (HBV) infection, occult HBV infection (OHBV) or a positive hepatitis C (HCV) serostatus. A total of 918 patients of the RESINA-cohort in Germany were included in this study. Before initiating antiretroviral therapy, clinical parameters were collected and blood samples were analyzed for antibodies against HIV, HBV and HCV, HBs antigen and viral nucleic acids for HIV and HBV. Present or past HBV infection (i.e. HBsAg and/or anti-HBc) was found in 43.4% of patients. HBsAg was detected in 4.5% (41/918) and HBV DNA in 6.1% (34/554), resulting in OHBV infection in 2.9% (16/554) of patients. OHBV infection could not be ruled out by the presence of anti-HBs (50.1%) or the absence of all HBV seromarkers (25%). A HCV-positive serostatus was associated with the IVDU transmission route, non-African ethnicity, elevated liver parameters (ASL or GGT) and low HIV viral load. Replicative HBV infection and HCV-positive serostatus both correlated with HIV resistance mutations (P?=?0.001 and P?=?0.028). HBV and HCV infection are frequent co-infections in HIV treatment-naive patients. These co-infections influence viral evolution, clinical parameters and serological markers. Consequently, HIV patients should routinely be tested for HBV and HCV infection before initiating HIV treatment. OHBV infection constituted almost half of all HBV infections with detectable HBV DNA. Due to a lack of risk factors indicating OHBV infection, HBV diagnosis should not only include serological markers but also the detection of HBV DNA.