Wei-Lun Liu

Multicenter Study in Taiwan of the In Vitro Activities of Nemonoxacin, Tigecycline, Doripenem, and Other Antimicrobial Agents against Clinical Isolates of Various Nocardia Species

ABSTRACT The aim of this study was to assess the in vitro activities of nemonoxacin (a novel nonfluorinated quinolone), doripenem, tigecycline, and 16 other antimicrobial agents against Nocardia species. The MICs of the 19 agents against 151 clinical isolates of Nocardia species were determined by the broth microdilution method. The isolates were identified to the species level using 16S rRNA gene sequencing analysis. The results showed that N. brasiliensis (n = 60; 40%) was the most common species, followed by N. cyriacigeorgica (n = 24; 16%), N. farcinica (n = 12; 8%), N. beijingensis (n = 9), N. otitidiscaviarum (n = 8), N. nova (n = 8), N. asiatica (n = 7), N. puris (n = 6), N. flavorosea (n = 5), N. abscessus (n = 3), N. carnea (2), and one each of N. alba, N. asteroides complex, N. rhamnosiphila, N. elegans, N. jinanensis, N. takedensis, and N. transvalensis. The MIC90s of the tested quinolones against the N. brasiliensis isolates were in the order nemonoxacin = gemifloxacin < moxifloxacin < levofloxacin = ciprofloxacin, and the MIC90s of the tested carbapenems were in the order doripenem = meropenem < ertapenem < imipenem. Tigecycline had a lower MIC90 (1 μg/ml) than linezolid (8 μg/ml). The MIC90s of the tested quinolones against N. cyriacigeorgica isolates were in the order nemonoxacin < gemifloxacin < moxifloxacin < levofloxacin < ciprofloxacin, and the MIC90s of the tested carbapenems were in the order imipenem < doripenem = meropenem < ertapenem. Nemonoxacin had the lowest MIC90 values among the tested quinolones against the other 17 Nocardia isolates. Among the four tested carbapenems, imipenem had the lowest MIC90s. All of the clinical isolates of N. beijingensis, N. otitidiscaviarum, N. nova, and N. puris and more than half of the N. brasiliensis and N. cyriacigeorgica isolates were resistant to at least one antimicrobial agent. The results of this in vitro study suggest that nemonoxacin, linezolid, and tigecycline are promising treatment options for nocardiosis. Further investigation of their clinical role is warranted.

Time to positivity of blood cultures of different Candida species causing fungaemia

This study investigated the time to positivity (TTP) for different species of Candida causing bloodstream infection and whether TTP can help differentiate fluconazole-resistant Candida glabrata and Candida krusei from other Candida species. We conducted this study at the National Taiwan University Hospital, a 2500-bed tertiary care medical centre in northern Taiwan. Patients with candidaemia were identified by central laboratory personnel from July 2010 to March 2011. TTP in each patient was determined using an automated blood culture instrument. Each patient was included only once at the time of detection of the first bloodstream infection. During the study period, a total of 329 sets of blood cultures positive for Candida were isolated from 176 patients. The mean TTP for all isolates causing candidaemia was 25.9±24.9 h. The TTP for C. glabrata was significantly longer than the TTP of the other species. In contrast, the TTP of C. tropicalis was significantly shorter than that of the other three species. The diagnostic sensitivity of TTP for C. glabrata isolates in patients with candidaemia was 93.9% (95% CI 0.798-0.993), the specificity was 66.4% (95% CI 0.581-0.741), the positive predictive value was 39.2% (95% CI 0.286-0.509), and the negative predictive value was 97.9% (95% CI 0.92-0.996) with a TTP cut-off value of >27.7 h. In conclusion, the different TTP values of different Candida species causing bloodstream infection may be helpful in differentiating C. glabrata from other Candida species.

Epidemiology and Prognostic Factors of Candidemia in Cancer Patients

Aim The study of candidemia in cancer patients has been limited. This retrospective study aims to investigate the epidemiologic characteristics and prognostic factors of candidemia among cancer patients. Materials and Methods From 2009 to 2012, cancer patients with candidemia were identified at a hospital in Taiwan. The medical records of all patients with bloodstream infections due to Candida species were retrospectively reviewed. Results During the four-year period, a total of 242 episodes of candidemia were identified among cancer patients. Half of these patients were classified as elderly (≥65 years old), and more than 95% of the candidemia episodes were classified as healthcare-associated infections. Among the 242 cancer patients with candidemia, head and neck cancer was the most common, followed by gastrointestinal tract and lung cancer. Additionally, most of the patients had variable underlying conditions, such as the presence of CVC (99%) or prior exposure to broad-spectrum antibiotics (93%) and were receiving an immunosuppressant (86%). Overall, C. albicans (n = 132, 54.5%) was the most common pathogen, followed by C. tropicalis (n = 52, 21.5%), C. parapsilosis (n = 38, 15.7%), and C. glabrata (n = 29, 12.0%). Seventeen patients had polycandidal candidemia, and 77 patients had concomitant bacteremia. Approximately one-third of the patients required admission to the intensive care unit (ICU) or mechanical ventilation, and the overall in-hospital mortality was 50.8%. Multivariable analysis showed that the in-hospital mortality was significantly associated with only the non-use of antifungal agents and acute respiratory failure (P<.001). Conclusions Candidemia can develop in patients with both solid cancer and hematological malignancy, especially for patients with underlying conditions. Overall, the associated morbidity and mortality due to Candidemia remain high. It was also determined that the non-use of antifungal agents and acute respiratory failure conditions were associated with in-hospital mortality.

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.

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.

The impact of inadequate terminal disinfection on an outbreak of imipenem-resistant Acinetobacter baumannii in an intensive care unit.

Background This study was conducted to investigate an outbreak caused by imipenem-resistant Acinetobacter baumannii (IRAB) in a medical intensive care unit (ICU) in a regional hospital. Methods In response to an IRAB outbreak from October 2012 to February 2013, we developed several infection control measures, including an extensive review process of environmental cleaning and disinfection, and used molecular methods to identify each clinical and environmental IRAB isolate. Results During this five-month period, 22 patients were colonized with IRAB and 18 patients had IRAB infections. The in-hospital mortality rate was significantly higher among patients with infections rather than colonizations (44.4% vs 9.1%, p = 0.028). Additionally, nine environmental specimens, including five specimens collected after terminal disinfection, were positive for IRAB. 12 environmental isolates and 28 of 36 available clinical isolates belonged to one unique pulsotype A, which was confirmed by molecular methods. We found the concentration of disinfectant, 0.08% sodium hypochlorite, was inadequate. After correcting the environmental cleansing methods, the surveillance study showed no further IRAB isolates on the control panel surfaces of the medical equipment or in patients in the ICU. Additionally, an in vitro study of IRAB immersed in different concentrations of sodium hypochlorite showed that 0.5% sodium hypochlorite eradicates IRAB after 30 seconds of inoculation, but 0.08% sodium hypochlorite only reduces the bacterial load. Conclusions This study highlights the importance of the preparation of disinfectants to adequately achieve environmental disinfection in the control of IRAB outbreaks in the ICU.

Diagnostic performance of procalcitonin for bacteremia in patients with bacterial infection at the emergency department.

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A multidisciplinary team care bundle for reducing ventilator-associated pneumonia at a hospital in southern Taiwan

We read with great interest the article in the Journal of Microbiology, Immunology and Infection by Wu et al, reporting a decreasing incidence of catheter-related bloodstream infections (CRBSIs) after the introduction of standardization of the process of center venous catheter implantation in an intensive care unit (ICU) in a medical center in center Taiwan. In addition to CRBSIs, ventilatorassociated pneumonia (VAP) is another common type of healthcare-associated infections, and is the leading cause of mortality for device-associated infections. Therefore, we feel this issue needs to be addressed, in addition to CRBSI. However, study on the impact of bundle-care interventions on the development of VAP in Taiwan is lacking. This project was carried out in a medical-surgical ICU with 63 beds at the Chi Mei Medical Center, Liouying branch, located in southern Taiwan. VAP was identified according to the Centers for Disease Control/National Healthcare Safety Network standard definitions. The numbers of patient-days, device-days, and VAP cases have been collected monthly from the infection-control practitioner. We compared the rates of VAP, from April 2010 to October 2010, for a 7-month period prior to the initiation of the VAP prevention bundles, with the VAP rates after intervention from November 2010 to December 2011 (a 14month period). The bundle-care interventions for prevention of VAP included: (1) maintenance of patients in a semi-recumbent position, 30e45 elevation of the head to the bed; (2) daily interruption of sedation and assessment for continuation; (3) daily spontaneous breathing trials; (4) performance of oral care three times a day with an antiseptic solution (0.2% chlorhexidine gluconate); (5) maintenance of endotracheal tube cuff pressure above 20 cm H2O; and (6) assessment on the reduction of prophylactic use of histamine receptor 2-blocking agent or proton pump inhibitor for stress ulcers in high risk patients. Additionally, educational programs were arranged in November 2010 for the staff in all ICUs, including attending physicians, respiratory therapists, and nurse practitioners. The implementation of the VAP prevention bundle resulted in the reduction of the VAP rate from a mean of 11.05 cases/1000 ventilator-days in the preintervention period to 2.81 cases/1000 ventilator-days in the postintervention period (p < 0.0001). The surveillance showed a significant decreasing incidence of VAP after the introduction of intervention. In the present work, we have one major finding. Similar to Wu et al’s study, which showed a decreasing incidence of CRBSI after the introduction of standardization of the process of center venous catheter implantation, we demonstrated that the introduction of bundle-care interventions with a multidisciplinary team approach can effectively prevent the development of VAP. It suggests that this effective preventive strategy should be implemented in the ICU to reduce the occurrence of VAP.

Bacteremic pneumonia caused by Nocardia veterana in an HIV-infected patient

Disseminated Nocardia veterana infection has rarely been reported. We describe the first reported case of N. veterana bacteremic pneumonia in an HIV-infected patient. The isolate was confirmed by 16S rRNA sequencing analysis. The patient initially responded well to trimethoprim-sulfamethoxazole treatment (minimum inhibitory concentration 0.25 μg/ml), but died of ventilator-associated pneumonia.

Spontaneous bacterial empyema due to non-O1, non-O139 Vibrio cholerae in a cirrhotic patient with hepatocellular carcinoma

Vibrio cholerae is known as a common etiology of epidemic diarrheal disease and rarely causes extra-intestinal infections. In this report, we described a cirrhotic patient with hepatocellular carcinoma who developed spontaneous bacterial empyema due to non-O1, non-O139 V. cholerae. The patient was successfully treated with antimicrobial agents and percutaneous drainage.