Koh Okamoto

Cryptococcus gattii Genotype VGIIa Infection in Man, Japan, 2007

We report a patient in Japan infected with Cryptococcus gattii genotype VGIIa who had no recent history of travel to disease-endemic areas. This strain was identical to the Vancouver Island outbreak strain R265. Our results suggest that this virulent strain has spread to regions outside North America.

High plasma linezolid concentration and impaired renal function affect development of linezolid-induced thrombocytopenia

OBJECTIVES Thrombocytopenia is sometimes observed during linezolid therapy. Here, we aimed to investigate the factors affecting linezolid-induced thrombocytopenia. METHODS A prospective observational study was performed between October 2009 and February 2011; 30 patients were included. Plasma linezolid trough concentrations were measured on days 3, 7 and 14 after initial drug administration. Platelet counts and haemoglobin levels were also monitored. RESULTS Thrombocytopenia occurred in 17 patients (56.7%). Median linezolid trough concentrations on day 3 were significantly higher in patients with renal impairment (creatinine clearance <60 mL/min) than in patients without renal impairment (14.7 versus 4.8 mg/L; P < 0.0001). Median linezolid trough concentrations on day 3 in patients who developed thrombocytopenia were also significantly higher than those in patients who did not (13.4 versus 4.3 mg/L, P < 0.0001). Development of thrombocytopenia occurred significantly more frequently in patients with linezolid trough concentration >7.5 mg/L (OR, 90.0; P < 0.0001) and renal impairment (OR, 39.0; P = 0.0002). The Kaplan-Meier plot showed that the median time from the initiation of therapy to development of thrombocytopenia was 11 days. CONCLUSIONS Patients with renal impairment are more likely to have a high plasma linezolid concentration. In addition, a high plasma linezolid concentration and renal impairment significantly affected the development of linezolid-induced thrombocytopenia. Further studies are required to evaluate whether therapeutic drug monitoring-guided dosage adjustment of linezolid decreases the adverse effects while maintaining treatment efficacy in patients with renal dysfunction.

Infective Endocarditis by Bartonellaquintana Masquerading as Antineutrophil Cytoplasmic Antibody-Associated Small Vessel Vasculitis

The Bartonella species have been recently recognized as important causative agents of culture-negative bacterial endocarditis. Antineutrophil cytoplasmic antibodies (ANCAs) have been associated with the spectrum of idiopathic small vessel vasculitis. However, a variety of infections can result in a false-positive ANCA test, and especially subacute bacterial endocarditis (SBE) with the presence of ANCAs occasionally mimics the clinical manifestations of an ANCA-associated vasculitis such as skin purpura and glomerulonephritis. In contrast, noninfectious endocardial involvement is known to be part of the spectrum of the manifestations of the ANCA-associated vasculitis. Therefore, it is crucial to distinguish an ANCA-positive SBE from an ANCA-associated vasculitis with endocardial compromise, because the misdiagnosis of an SBE as an ANCA-associated vasculitis can lead to an inappropriate immunosuppressive therapy with catastrophic consequences. The differential diagnosis is sometimes difficult, especially in the case of culture-negative infective endocarditis with a positive ANCA test. We describe here a case of a culture-negative SBE caused by Bartonellaquintana, accompanied with a positive cytoplasmic ANCA test and clinical findings masquerading as ANCA-associated vasculitis. Both a serological test for Bartonella and polymerase chain reaction restriction fragment length polymorphism analysis were helpful for a correct diagnosis and appropriate treatment.

Unadjuvanted pandemic H1N1 influenza vaccine in HIV-1-infected adults

We evaluated the immune response to a 2009 influenza A (H1N1) unadjuvanted vaccine in HIV-infected patients and assessed the boosting effect of a second dose. HIV-infected adults were enrolled and scheduled to receive the H1N1 unadjuvanted vaccine containing 15μg of A/California/7/2009 haemagglutinin. Anti-H1N1 antibody titers were measured at enrollment and 4-8 weeks after each vaccination by using haemagglutination inhibition (HI) and virus neutralization (NT) assays. One hundred and four patients were analyzed. Seroconversion, as measured by using HI and NT assays, was observed in 52 (50.0%) patients and 49 (47.1%) patients, respectively, after the first dose. Seroconversion rate evaluated by using NT, but not HI, antibody titers was associated with HIV RNA levels of <400copies/ml (odds ratio, 3.21; 95% CI, 1.15-8.96). Other parameters, including CD4 cell count, were not associated with seroconversion. In a cohort that received two vaccine doses at a 4-8-week interval (n=54), the seroconversion rate and geometric mean titer for HI antibodies were 44.4% (95% CI, 30.8-58.1%) and 30.5 (95% CI, 19.9-46.9) after the first dose, respectively, and 48.1% (95% CI, 34.4-61.9%) and 39.0 (95% CI, 26.1-58.2) after the second dose, respectively. Among HIV-infected patients, the seroconversion rate was around 50% after the first dose of unadjuvanted vaccine. A second dose of vaccine had a limited boosting effect on immunity in this patient cohort.

Modifiable Risk Factors for the Spread of Klebsiella pneumoniae Carbapenemase-Producing Enterobacteriaceae Among Long-Term Acute-Care Hospital Patients

OBJECTIVE To identify modifiable risk factors for acquisition of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae (KPC) colonization among long-term acute-care hospital (LTACH) patients. DESIGN Multicenter, matched case-control study. SETTING Four LTACHs in Chicago, Illinois. PARTICIPANTS Each case patient included in this study had a KPC-negative rectal surveillance culture on admission followed by a KPC-positive surveillance culture later in the hospital stay. Each matched control patient had a KPC-negative rectal surveillance culture on admission and no KPC isolated during the hospital stay. RESULTS From June 2012 to June 2013, 2,575 patients were admitted to 4 LTACHs; 217 of 2,144 KPC-negative patients (10.1%) acquired KPC. In total, 100 of these patients were selected at random and matched to 100 controls by LTACH facility, admission date, and censored length of stay. Acquisitions occurred a median of 16.5 days after admission. On multivariate analysis, we found that exposure to higher colonization pressure (OR, 1.02; 95% CI, 1.01-1.04; P=.002), exposure to a carbapenem (OR, 2.25; 95% CI, 1.06-4.77; P=.04), and higher Charlson comorbidity index (OR, 1.14; 95% CI, 1.01-1.29; P=.04) were independent risk factors for KPC acquisition; the odds of KPC acquisition increased by 2% for each 1% increase in colonization pressure. CONCLUSIONS Higher colonization pressure, exposure to carbapenems, and a higher Charlson comorbidity index independently increased the odds of KPC acquisition among LTACH patients. Reducing colonization pressure (through separation of KPC-positive patients from KPC-negative patients using strict cohorts or private rooms) and reducing carbapenem exposure may prevent KPC cross transmission in this high-risk patient population. Infect Control Hosp Epidemiol 2017;38:670-677.

Differential Effects of Chlorhexidine Skin Cleansing Methods on Residual Chlorhexidine Skin Concentrations and Bacterial Recovery

BACKGROUND Bathing intensive care unit (ICU) patients with 2% chlorhexidine gluconate (CHG)-impregnated cloths decreases the risk of healthcare-associated bacteremia and multidrug-resistant organism transmission. Hospitals employ different methods of CHG bathing, and few studies have evaluated whether those methods yield comparable results. OBJECTIVE To determine whether 3 different CHG skin cleansing methods yield similar residual CHG concentrations and bacterial densities on skin. DESIGN Prospective, randomized 2-center study with blinded assessment. PARTICIPANTS AND SETTING Healthcare personnel in surgical ICUs at 2 tertiary-care teaching hospitals in Chicago, Illinois, and Boston, Massachusetts, from July 2015 to January 2016. INTERVENTION Cleansing skin of one forearm with no-rinse 2% CHG-impregnated polyester cloth (method A) versus 4% CHG liquid cleansing with rinsing on the contralateral arm, applied with either non-antiseptic-impregnated cellulose/polyester cloth (method B) or cotton washcloth dampened with sterile water (method C). RESULTS In total, 63 participants (126 forearms) received method A on 1 forearm (n=63). On the contralateral forearm, 33 participants received method B and 30 participants received method C. Immediately and 6 hours after cleansing, method A yielded the highest residual CHG concentrations (2500 µg/mL and 1250 µg/mL, respectively) and lowest bacterial densities compared to methods B or C (P<.001). CONCLUSION In healthy volunteers, cleansing with 2% CHG-impregnated cloths yielded higher residual CHG concentrations and lower bacterial densities than cleansing with 4% CHG liquid applied with either of 2 different cloth types and followed by rinsing. The relevance of these differences to clinical outcomes remains to be determined. Infect Control Hosp Epidemiol 2018;39:405-411.

Longitudinal comparison of the microbiota during Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) acquisition in Long-Term Acute Care Hospital (LTACH) patients

Abstract Background Colonization with KPC-Kp precedes infection and represents a potential target for intervention. To identify microbial signatures associated with KPC-Kp acquisition, we conducted a prospective, longitudinal study of the fecal microbiota in LTACH patients at risk of acquiring KPC-Kp. Methods We collected admission and weekly rectal swab samples from patients admitted to one LTACH from May 2015 to May 2016. Patients were screened for KPC-Kp by PCR at each sampling time. KPC acquisition was confirmed by culture of KPC-Kp. To assess changes in the microbiota related to acquisition, we sequenced the 16S rRNA gene (V4 region) from collected rectal swabs. Diversity, intra-individual changes, and the relative abundance of the operational taxonomic unit (OTU) that contains KPC-Kp were compared in patients who were KPC-Kp negative upon admission and who had at least one additional swab sample collected. Results 318 patients (1247 samples) were eligible for analysis; 3.7 samples (mean) were collected per patient. Sixty-two patients (19.5%) acquired KPC-Kp (cases) and 256 patients remained negative for all carbapenem-resistant Enterobacteriaceae throughout their stay (controls). Median length of stay before KPC-Kp detection was 14.5 days. At time of KPC-Kp acquisition, levels of an Enterobacteriaceae OTU increased significantly compared with pre-acquisition samples and to samples from control patients (Wilcoxon test, P < 0.0001). Similarly, we observed a decrease in total diversity of the fecal microbiota at time of acquisition in cases (P < 0.01). Compared with controls, cases exhibited decreased intra-individual fecal microbiota similarity immediately prior to acquisition of KPC-Kp (P < 0.01). Comparison of microbial features at time of admission using random forest revealed a higher abundance of Enterococcus and Escherichia OTUs in controls vs cases. Conclusion We observed intra-individual changes in the fecal microbiota of case patients prior to acquisition of KPC-Kp. Compared with patients who did not acquire KPC-Kp, cases exhibited significant changes in microbiota diversity and increased abundance of potential KPC-Kp at acquisition. Our results suggest that shifts in the microbiota may precede colonization by KPC-Kp. Disclosures N. M. Moore, Cepheid: Research Contractor, Funded and provided reagents for associated research projects; R. A. Weinstein, OpGen: Receipt of donated laboratory services for project, Research support; CLorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; M. Y. Lin, Sage, Inc.: receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; OpGen, Inc.: receipt of in-kind laboratory services, Conducting studies in healthcare facilities that are receiving contributed product; M. K. Hayden, OpGen, Inc.: Receipt of donated laboratory services for project, Research support; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product.

Role of Race/Ethnicity in Pulmonary Nontuberculous Mycobacterial Disease

To the Editor: We read with interest the study of gender and age in nontuberculous mycobacterial (NTM) lung disease case-patients in Taiwan (1). NTM lung disease is relatively uncommon; however, the exact prevalence of NTM lung disease and causative organisms are largely unknown in many regions of the United States because the disease is not reportable. A recent study using Medicare claims data in the United States showed that the annual prevalence of NTM lung disease increased from 20 cases/100,000 persons in 1997 to 47 cases/100,000 persons in 2007 (2). The study also showed that Hawaii had the highest period prevalence of cases (396 cases/100,000 persons), which was at least partially attributed to the large Asian/Pacific Islander population (2). During June–December 2011, we conducted a cross-sectional study to evaluate the epidemiologic and clinical significance of NTM isolated from patients in Honolulu, Hawaii; the patients had suspected pulmonary tuberculosis (TB) and were in airborne isolation at a university-affiliated, tertiary-care hospital. NTM cases were defined according to the 2007 criteria of the American Thoracic Society/Infectious Diseases Society of America (3). The process required to establish a diagnosis of NTM lung disease is sometimes lengthy; thus, patients who did not initially meet the disease criteria but who had cultures positive for NTM were reviewed again 1 year after the original data were collected to see if follow-up microbiological and radiographic studies would confirm the presence of NTM lung disease. Descriptive statistics were used to describe categorical and continuous variables. During June–December 2011, a total of 113 patients with suspected pulmonary TB were placed into isolation at the tertiary-care hospital. Of these patients, 85 (75.2%) were men and 28 (24.8%) were women; the median age was 59.8 ± 17 years. Eighteen (15.9%) patients were white, 92 (81.4%) were Asian/Pacific Islander, and 1 (0.9%) was African American; for 2 (1.8%) patients, race/ethnicity was classified as not specified/other. Of the 113 isolated patients, 21 (18.6%) were positive for mycobacteria. Of these 21 patients, 14 (66.7%) were men and 7 (33.3%) were women; the median age was 64.3 ± 17.3 years. Three (14.3%) of these patients were white, and 18 (85.7%) were Asian/Pacific Islander. Mycobacterium tuberculosis and NTM were identified in samples from 3 (14.3%) and 18 (85.7%) of the 21 patients, respectively. Of the 18 patients with NTM-positive samples, 4 (22.2%) had definite NTM lung disease (all of these patients were Asian/Pacific Islander); 2 (11.1%) had probable NTM lung disease; and 12 (66.7%) had possible NTM lung disease. M. chelonae (identified by DNA sequencing) was the causative agent for most of the definite cases (n = 3, 75%), and the largest proportion of possible cases was caused by M. avian complex bacteria (n = 5, 41.7%). Our finding that 22.2% (4/18) of the patients in Honolulu with NTM-positive clinical samples during June–December 2011 received a definite diagnosis of NTM lung disease is slightly higher than but consistent with reports from other regions, which show that 9.8%–17.0% of such patients receive a definite NTM disease diagnosis (4,5). For unclear reasons, the number of NTM disease cases appears to be highest in Asian/Pacific Islander populations. Determining the reason(s) for this discrepancy should be the subject of future research efforts.