Meng-Rui Lee

Mycobacterium abscessus Complex Infections in Humans

New treatments, rapid and inexpensive identification methods, and measures to contain nosocomial transmission and outbreaks are urgently needed.

CNS infections caused by Mycobacterium abscessus complex: clinical features and antimicrobial susceptibilities of isolates

OBJECTIVES CNS infections caused by non-tuberculous mycobacteria (NTM) are rare and only three cases of CNS infections due to Mycobacterium abscessus complex have been reported. METHODS We searched the Mycobacteriology Database of the National Taiwan University Hospital and identified patients with CNS infections due to NTM. RESULTS A total of 15 patients, namely 4 HIV-seropositive patients and 11 HIV-seronegative patients, with CNS infections caused by NTM were identified during 2000-10. All of the HIV-seropositive patients had disseminated Mycobacterium avium complex infections. Among the 11 HIV-seronegative patients, NTM CNS infections were due to M. abscessus complex in 8 patients, M. avium complex in 2 patients and Mycobacterium kansasii in 1 patient. All the six preserved M. abscessus complex isolates were confirmed to be Mycobacterium massiliense by erm(41) PCR and 23S rRNA gene sequence analysis. Among the eight patients with infections due to M. abscessus complex, three had otolaryngological diseases, four had received neurosurgery and one had disseminated disease. Five patients received surgical debridement or intracranial device removal and three patients died of M. abscessus complex CNS infection. Among the five patients who survived, all received clarithromycin-based combination therapy with a median duration of 12 months and four received surgical intervention. All six isolates available for drug susceptibility testing showed uniform susceptibility to clarithromycin and five were susceptible to amikacin. CONCLUSIONS Our study revealed that M. abscessus complex isolates, particularly M. massiliense, should be considered potential pathogens causing CNS infections. Long-duration clarithromycin-based combination therapy plus surgical intervention may provide the best chance of cure.

Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Can Accurately Differentiate between Mycobacterium masilliense (M. abscessus subspecies bolletti) and M. abscessus (Sensu Stricto)

ABSTRACT Among 36 Mycobacterium masilliense and 22 M. abscessus isolates identified by erm(41) PCR and sequencing analysis of rpoB and 23S rRNA genes, the rate of accurate differentiation between these two subspecies was 100% by cluster analysis of spectra generated by Bruker Biotyper matrix-assisted laser desorption ionization–time of flight mass spectrometry.

Bacteraemia caused by Weissella confusa at a university hospital in Taiwan, 1997-2007

Human infections caused by Weissella confusa are rarely reported. Ten patients with bacteraemia caused by W. confusa who were treated at a tertiary-care hospital in Taiwan during 1997-2007 were studied. All isolates were initially misidentified as various Lactobacillus and Leuconostoc species by two commercial automated identification methods, and were confirmed to be W. confusa by 16S rRNA sequencing analysis. MICs of these isolates for ten antimicrobial agents were determined by the agar dilution method. The characteristics of these patients included underlying malignancy (n = 4), presence of a central catheter (n = 6), surgery within the previous 3 months (n = 4) and concomitant polymicrobial bacteraemia (n = 5, 50%). Mortality was directly attributed to bacteraemia in two patients. All isolates exhibited high trimethoprim-sulphamethoxazole and ceftazidime MICs (≥ 128 mg/L) and were inhibited by linezolid, daptomycin, ceftobiprole and tigecycline at 4, 0.12, 2 and 0.12 mg/L, respectively. In conclusion, W. confusa should be included in the list of organisms causing bacteraemia in immunocompromised hosts. Novel antibiotics, including daptomycin, moxifloxacin, doripenem and tigecycline, exert good activity against W. confusa.

Clinical characteristics of infections caused by Tsukamurella spp. and antimicrobial susceptibilities of the isolates

To investigate the clinical and microbiological characteristics of infections caused by Tsukamurella spp., the computerised database of the Bacteriology Laboratory at National Taiwan University Hospital (Taipei, Taiwan) was reviewed retrospectively to identify patients with infections caused by this species during the period January 1997 to December 2008. All of the isolates had been initially misidentified as Rhodococcus spp. Identification of Tsukamurella isolates to species level was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the heat shock protein gene (hsp65) as well as 16S rRNA gene sequencing. During the study period, a total of eight patients with Tsukamurella infection and two patients with Tsukamurella colonisation were identified. Tsukamurella tyrosinosolvens (n=6) was the most prevalent species, followed by Tsukamurella spumae (n=3) and Tsukamurella pulmonis (n=1). Keratitis was the most common type of infection (n=3), followed by catheter-related bloodstream infection (n=2). One of the patients with Tsukamurella infection died due to bacteraemia; the other seven patients with Tsukamurella infection had favourable outcomes. The three species had different drug susceptibility patterns; T. pulmonis was the most resistant pathogen, with higher minimum inhibitory concentrations of clindamycin (>2 mg/L), erythromycin (2 mg/L) and tetracycline (8 mg/L) than those for the other Tsukamurella spp. In conclusion, strains of Tsukamurella spp., including T. spumae, are uncommon causative agents of ocular infections and bacteraemia in cancer patients. Molecular diagnostic methods are essential to distinguish species in the Tsukamurella genus from species in other phylogenetically related genera such as Rhodococcus.

High levels of serum macrophage migration inhibitory factor and interleukin 10 are associated with a rapidly fatal outcome in patients with severe sepsis

OBJECTIVES The aim of this study was to delineate the association between high macrophage migration inhibitory factor (MIF) and interleukin 10 (IL-10) levels in the early phase of sepsis and rapidly fatal outcome. METHODS One hundred and fifty-three adult subjects with the main diagnosis of severe sepsis (including septic shock) admitted directly from the emergency department of two tertiary medical centers and one regional teaching hospital between January 2009 and December 2011, were included prospectively. MIF and IL-10 levels were measured and outcomes were analyzed by Cox regression analysis according to the following outcomes: rapidly fatal outcome (RFO, death within 48 h), late fatal outcome (LFO, death between 48 h and 28 days), and survival at 28 days. RESULTS Among the three outcome groups, IL-10 levels were significantly higher in the RFO group (p < 0.001) and no significant differences were seen between the LFO and survivor groups. After Cox regression analysis, each incremental elevation of 1000 pg/ml in both IL-10 and MIF was independently associated with RFO in patients with severe sepsis. Each incremental elevation of 1000 pg/ml in IL-10 increased the RFO risk by a factor of 1.312 (95% confidence interval 1.094-1.575; p=0.003); this was the most significant factor leading to RFO in patients with severe sepsis. CONCLUSIONS Patients with RFO exhibited simultaneously high MIF and IL-10 levels in the early phase of severe sepsis. Incremental increases in both IL-10 and MIF levels were associated with RFO in this patient group, and of the two, IL-10 was the most significant factor linked to RFO.

Infections caused by unusual Methylobacterium species

ABSTRACT We describe six patients with hospital-acquired bacteremia caused by Methylobacterium species, including M. radiotolerans (n = 2), M. thiocyanatum (n = 2), M. aminovorans (n = 1), and M. lusitanum (n = 1), which were confirmed to species level by 16S rRNA gene sequence analysis. Among these patients, five had catheter-related bacteremia and all had favorable outcomes.

Factors Associated with Lung Function Decline in Patients with Non-Tuberculous Mycobacterial Pulmonary Disease

Background There is paucity of risk factors on lung function decline among patients with non-tuberculous mycobacteria (NTM) pulmonary disease in literature. Methods Patients with NTM pulmonary disease between January 2000 and April 2011 were retrospectively selected. Sixty-eight patients had at least two pulmonary function tests within a mean follow-up period of 47 months. Results Sixty-eight patients were included. They had a median age of 65 years and 65% had impaired lung function (Forced expiratory volume in 1 second [FEV1] <80% of predicted value). The mean FEV1 decline was 48 ml/year. By linear regression, younger age (beta: 0.472, p<0.001), initial FEV1>50% of predicted value (beta: 0.349, p = 0.002), male sex (beta: 0.295, p = 0.018), bronchiectasis pattern (beta: 0.232, p = 0.035), and radiographic score >3 (beta: 0.217, p = 0.049) were associated with greater FEV1 decline. Initial FEV1>50% of predicted value (beta: 0.263, p = 0.032) was also associated with greater FVC annual decline, whereas M. kansasii pulmonary disease was marginally associated with greater annual FVC decline (beta: 0.227, p = 0.062). Conclusions NTM pulmonary disease is associated with greater decline in lung function in patients who are young, male, with bronchiectasis, and with a high radiographic score. Special attention should be given to patients with these risk factors.

Clinical and Microbiological Characteristics of Bacteremia Caused by Eggerthella, Paraeggerthella, and Eubacterium Species at a University Hospital in Taiwan from 2001 to 2010

ABSTRACT We describe 16 patients with bacteremia caused by Eggerthella lenta (n = 7), Paraeggerthella hongkongensis (n = 3), Eubacterium limosum (n = 4), Eubacterium callanderi (n = 1), and concomitant Eubacterium limosum/Eggerthella lenta (n = 1). Nine (56%) patients had polymicrobial bacteremia. The overall 60-day mortality rate was 19%, and all deaths occurred in patients with E. lenta bacteremia.

Differences in drug resistance profiles of Mycobacterium tuberculosis isolates causing pulmonary and extrapulmonary tuberculosis in a medical centre in Taiwan, 2000–2010

Few studies have investigated the drug resistance profiles of Mycobacterium tuberculosis (MTB) isolates recovered from different sites of infection. A total of 4521 non-duplicate MTB isolates, including 3723 (82.3%) from respiratory specimens and 798 (17.7%) from non-respiratory sources, were recovered from patients treated at a medical centre in Taiwan from 2000 to 2010. Trend analysis showed a significant decrease (P<0.05) in the rates of resistance to isoniazid, rifampicin and ethambutol, a decrease in resistance to any one of four agents, namely isoniazid, rifampicin, ethambutol or streptomycin, and a decrease in resistance to both isoniazid and rifampicin (multidrug resistance) amongst pulmonary MTB isolates. A similar decrease in resistance to isoniazid and ethambutol was noted amongst non-pulmonary isolates. Rates of drug resistance were significantly higher amongst MTB isolates recovered from respiratory specimens than amongst those from non-respiratory specimens to 0.2 μg/mL isoniazid (15.3% vs. 9.4%; P<0.0001), 1 μg/mL rifampicin (5.5% vs. 3.3%; P=0.0108), 5 μg/mL ethambutol (7.3% vs. 3.8%; P=0.0004), and both isoniazid and rifampicin (4.8% vs. 2.5%; P=0.0051). Resistance rates amongst isolates causing tuberculous lymphadenitis were significantly lower than amongst those causing genitourinary tuberculosis (TB) to isoniazid (3.5% vs. 19.4%, P=0.0012) and to isoniazid, rifampicin, ethambutol or streptomycin (9.6% vs. 22.6%, P=0.0003). In conclusion, the rates of resistance to first-line anti-TB agents and to multiple agents differed amongst MTB isolates obtained from different infectious sources. Continuous monitoring of resistance of MTB isolates from various sites is necessary in order to establish an effective TB surveillance programme.