Polyclonal Burkholderia cepacia Complex Outbreak in Peritoneal Dialysis Patients Caused by Contaminated Aqueous Chlorhexidine.

Whether Burkholderia cepacia complex should be an objectionable organism in antiseptic solutions with acceptable total bacterial counts is controversial. By using next-generation sequencing, we documented a polyclonal B. cepacia complex outbreak affecting peritoneal dialysis patients in Hong Kong that was caused by contaminated chlorhexidine solutions. Epidemiologic investigations at a manufacturing site identified a semiautomated packaging machine as the probable source of contamination in some of the brands. Use of whole-genome sequencing differentiated the isolates into 3 brand-specific clonal types. Changes in exit site care recommendations, rapid recall of affected products, and tightening of regulatory control for chlorhexidine-containing skin antiseptics could prevent future similar outbreaks. Environmental opportunistic pathogens, including B. cepacia complex, might be included in regular surveillance as indicator organisms for monitoring environmental contamination.

Donor-Derived Genotype 4 Hepatitis E Virus Infection, Hong Kong, China, 2018.

Hepatitis E virus (HEV) genotype 4 (HEV-4) is an emerging cause of acute hepatitis in China. Less is known about the clinical characteristics and natural history of HEV-4 than HEV genotype 3 infections in immunocompromised patients. We report transmission of HEV-4 from a deceased organ donor to 5 transplant recipients. The donor had been viremic but HEV IgM and IgG seronegative, and liver function test results were within reference ranges. After a mean of 52 days after transplantation, hepatitis developed in all 5 recipients; in the liver graft recipient, disease was severe and with progressive portal hypertension. Despite reduced immunosuppression, all HEV-4 infections progressed to persistent hepatitis. Four patients received ribavirin and showed evidence of response after 2 months. This study highlights the role of organ donation in HEV transmission, provides additional data on the natural history of HEV-4 infection, and points out differences between genotype 3 and 4 infections in immunocompromised patients.

Whole-genome sequencing data-based modeling for the investigation of an outbreak of community-associated methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit in Hong Kong.

We describe a nosocomial outbreak of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) ST59-SCCmec type V in a neonatal intensive care unit (NICU) in Hong Kong. In-depth epidemiological analysis was performed by whole-genome sequencing (WGS) of the CA-MRSA isolates collected from patients and environment during weekly surveillance and healthcare workers from the later phase of the outbreak. Case-control analysis was performed to analyze potential risk factors for the outbreak. The outbreak occurred from September 2017 to February 2018 involving 15 neonates and one healthcare worker. WGS analysis revealed complicated transmission dynamics between patients, healthcare worker, and environment, from an unrecognized source introduced into the NICU within 6 months before the outbreak. In addition to enforcement of directly observed hand hygiene, environmental disinfection, cohort nursing of colonized and infected patients, together with contact tracing for secondary patients, medical, nursing, and supporting staff were segregated where one team would care for CA-MRSA-confirmed/CA-MRSA-exposed patients and the other for newly admitted patients in the NICU only. Case-control analysis revealed use of cephalosporins [odds ratio 49.84 (3.10-801.46), p = 0.006] and length of hospitalization [odds ratio 1.02 (1.00-1.04), p = 0.013] as significant risk factors for nosocomial acquisition of CA-MRSA in NICU using multivariate analysis. WGS facilitates the understanding of transmission dynamics of an outbreak, providing insights for outbreak prevention.

Japanese Encephalitis Virus Transmitted Via Blood Transfusion, Hong Kong, China.

Japanese encephalitis virus (JEV) is a mosquitoborne virus endemic to China and Southeast Asia that causes severe encephalitis in <1% of infected persons. Transmission of JEV via blood transfusion has not been reported. We report transmission of JEV via blood donation products from an asymptomatic viremic donor to 2 immunocompromised recipients. One recipient on high-dose immunosuppressive drugs received JEV-positive packed red blood cells after a double lung transplant; severe encephalitis and a poor clinical outcome resulted. JEV RNA was detected in serum, cerebrospinal fluid, and bronchoalveolar lavage fluid specimens. The second recipient had leukemia and received platelets after undergoing chemotherapy. This patient was asymptomatic; JEV infection was confirmed in this person by IgM seroconversion. This study illustrates that, consistent with other pathogenic flaviviruses, JEV can be transmitted via blood products. Targeted donor screening and pathogen reduction technologies could be used to prevent transfusion-transmitted JEV infection in highly JEV-endemic areas.

Fatal Talaromyces marneffei Infection in a Patient with Autoimmune Hepatitis.

Talaromyces marneffei, previously known as Penicillium marneffei, is the most important pathogenic thermally dimorphic fungus causing systemic mycosis in Southeast Asia. Traditionally, T. marneffei infection in human was mainly associated with acquired immunodeficiency syndrome caused by HIV infection. In recent years, there has been an increasing number of T. marneffei infections reported in non-HIV-infected patients with other immunocompromised conditions, including autoantibodies against interferon-gamma, systemic lupus erythematosis, solid organ transplantation, Job's syndrome, hematological malignancies, and use of novel targeted therapies. In this article, we describe the first case of fatal T. marneffei infection in a patient with underlying autoimmune hepatitis, presented as fever without localizing features. The diagnosis of talaromycosis was confirmed with the identification of the fungi isolated from the blood culture specimen by conventional methods and using matrix-assisted laser desorption-ionization time-of-flight mass spectrometer. This case shows the importance of a high index of suspicion, particularly for such a highly fatal but potentially treatable fungal infection.

Seasonal Outbreak of Bacillus Bacteremia Associated With Contaminated Linen in Hong Kong.

BACKGROUND: A high seasonal incidence of Bacillus bacteremia was associated with the use of contaminated hospital linens. METHODS: An outbreak investigation was conducted to study the incidence and source of Bacillus bacteremia during the baseline, outbreak, and postoutbreak period from 1 January 2012 through 31 July 2016 at a university-affiliated teaching hospital in Hong Kong. Replicate organism detection and counting plates were used for microbial screening of linen samples. The Bacillus species isolated from patient and linen samples were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and were phylogenetically analyzed. RESULTS: During the study period, a total of 113 207 blood cultures were collected from 43 271 patients, of which 978 (0.86%) specimens from 744 (1.72%) patients were identified as Bacillus species. The incidence of Bacillus bacteremia per 10 000 patient admissions and per 10 000 patient-days was significantly higher during the summer outbreak as compared with baseline and 1 year postoutbreak after cessation of the linen supply from the designated laundry and change of laundry protocol (39.97 vs 18.21 vs 2.27; 13.36 vs 5.61 vs 0.73; P < .001). The mean total aerobic bacterial count per 100 cm2 was significantly higher among the 99 linen samples screened during the outbreak period compared to the 100 screened in the postoutbreak period (916.0 ± 641.6 vs 0.6 ± 1.6; P < .001). Blood culture isolates of Bacillus cereus group in 14 of 87 (16.1%) patients were phylogenetically associated with 9 linen sample isolates. CONCLUSIONS: Suboptimal conditions of hospital laundry contributed to the seasonal outbreak of Bacillus bacteremia.

Rapid Differentiation of Haemophilus influenzae and Haemophilus haemolyticus by Use of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry with ClinProTools Mass Spectrum Analysis.

Haemophilus influenzae is associated with severe invasive disease, while Haemophilus haemolyticus is considered part of the commensal flora in the human respiratory tract. Although the addition of a custom mass spectrum library into the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system could improve identification of these two species, the establishment of such a custom database is technically complicated and requires a large amount of resources, which most clinical laboratories cannot afford. In this study, we developed a mass spectrum analysis model with 7 mass peak biomarkers for the identification of H. influenzae and H. haemolyticus using the ClinProTools software. We evaluated the diagnostic performance of this model using 408 H. influenzae and H. haemolyticus isolates from clinical respiratory specimens from 363 hospitalized patients and compared the identification results with those obtained with the Bruker IVD MALDI Biotyper. The IVD MALDI Biotyper identified only 86.9% of H. influenzae (311/358) and 98.0% of H. haemolyticus (49/50) clinical isolates to the species level. In comparison, the ClinProTools mass spectrum model could identify 100% of H. influenzae (358/358) and H. haemolyticus (50/50) clinical strains to the species level and significantly improved the species identification rate (McNemar's test, P < 0.0001). In conclusion, the use of ClinProTools demonstrated an alternative way for users lacking special expertise in mass spectrometry to handle closely related bacterial species when the proprietary spectrum library failed. This approach should be useful for the differentiation of other closely related bacterial species.

Hospital Outbreak of Pulmonary and Cutaneous Zygomycosis due to Contaminated Linen Items From Substandard Laundry.

BACKGROUND: Healthcare laundry-related infection is rare, and pulmonary zygomycosis due to contaminated hospital linens has never been reported. METHODS: We reported an outbreak investigation of zygomycosis in a university-affiliated teaching hospital. Air samplers, sponge swabs and Replicate Organism Detection and Counting (RODAC) contact plates were used for environmental sampling. The fungal isolates from clinical and environmental samples were identified by morphology, MALDI-TOF MS, and ITS1-5.8S-ITS2 rRNA gene cluster sequencing. RESULTS: From 2 June 2015 to 18 July 2015, 6 immunosuppressed patients developed pulmonary (n = 4) and/or cutaneous (n = 3) infection by a spore-forming mold, Rhizopus microsporus, through direct inhalation and skin contact of contaminated linen items supplied by a designated laundry. Seventy (27.8%) of 252 freshly laundered clothing and 15 (3.4%) of 443 nonclothing laundered linen items (pillow case, bed sheet, draw sheet) were contaminated by R. microsporus, which was significantly higher than those from other hospital laundries (0%, n = 451; P < .001) supplying linen to hospitals with no cases of zygomycosis reported during the same period. The fungal isolates from patients and linens were phylogenetically related. In sum, 61% of environmental samples and 100% of air samples at the designated laundry were also positive for zygomycetes, suggesting heavy environmental contamination. RODAC contact plates revealed mean total viable bacteria counts of freshly laundered items (1028 ± 611 CFU/100 cm(2)) far exceeded the "hygienically clean" standard of 20 CFU/100 cm(2) set by the US healthcare textile certification requirement. CONCLUSIONS: Suboptimal conditions of washing, drying, and storage contributed to the massive linen contamination and the outbreak of zygomycosis.

Clinical Evaluation of the New High-Throughput Luminex NxTAG Respiratory Pathogen Panel Assay for Multiplex Respiratory Pathogen Detection.

A broad range of viral and bacterial pathogens can cause acute respiratory tract infection. For rapid detection of a broad respiratory pathogen spectrum, multiplex real-time PCR is ideal. This study evaluated the performance of the new Luminex NxTAG Respiratory Pathogen Panel (NxTAG-RPP) in comparison with the BioFire FilmArray Respiratory Panel (FA-RP) or singleplex real-time PCR as reference. A total of 284 clinical respiratory specimens and 3 influenza A/H7N9 viral culture samples were tested. All clinical specimens were processed and analyzed in parallel using NxTAG-RPP and the reference standard method. The H7N9 viral culture samples were tested using NxTAG-RPP only. Overall, the NxTAG-RPP demonstrated ≥93% sensitivity and specificity for all respiratory targets except human coronavirus OC43 (HCoV-OC43) and HCoV-HKU1. The H7N9 virus was detected by the influenza A virus matrix gene target, while other influenza A virus subtyping gene targets in the panel remained negative. Complete concordance between NxTAG-RPP and FA-RP was observed in 98.8% (318/322) of positive results (kappa = 0.92). Substantial agreement was found for most respiratory targets, but significant differences were observed in human metapneumovirus (P = 0.001) and parainfluenza virus type 3 (P = 0.031). NxTAG-RPP has a higher sample throughput than FA-RP (96 samples versus 1 sample per run) while the turnaround times for NxTAG-RPP and FA-RP were 5 h (up to 96 samples) and 1 h (for one sample), respectively. Overall, NxTAG-RPP demonstrated good diagnostic performance for most respiratory pathogens. The high sample throughput with reasonable turnaround time of this new assay makes it a suitable multiplex platform for routine screening of respiratory specimens in hospital-based laboratories.

Metabolomic Profiling of Plasma from Melioidosis Patients Using UHPLC-QTOF MS Reveals Novel Biomarkers for Diagnosis.

To identify potential biomarkers for improving diagnosis of melioidosis, we compared plasma metabolome profiles of melioidosis patients compared to patients with other bacteremia and controls without active infection, using ultra-high-performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry. Principal component analysis (PCA) showed that the metabolomic profiles of melioidosis patients are distinguishable from bacteremia patients and controls. Using multivariate and univariate analysis, 12 significant metabolites from four lipid classes, acylcarnitine (n = 6), lysophosphatidylethanolamine (LysoPE) (n = 3), sphingomyelins (SM) (n = 2) and phosphatidylcholine (PC) (n = 1), with significantly higher levels in melioidosis patients than bacteremia patients and controls, were identified. Ten of the 12 metabolites showed area-under-receiver operating characteristic curve (AUC) >0.80 when compared both between melioidosis and bacteremia patients, and between melioidosis patients and controls. SM(d18:2/16:0) possessed the largest AUC when compared, both between melioidosis and bacteremia patients (AUC 0.998, sensitivity 100% and specificity 91.7%), and between melioidosis patients and controls (AUC 1.000, sensitivity 96.7% and specificity 100%). Our results indicate that metabolome profiling might serve as a promising approach for diagnosis of melioidosis using patient plasma, with SM(d18:2/16:0) representing a potential biomarker. Since the 12 metabolites were related to various pathways for energy and lipid metabolism, further studies may reveal their possible role in the pathogenesis and host response in melioidosis.

Development of Conventional and Real-Time Quantitative PCR Assays for Diagnosis and Monitoring of Scabies.

Scabies remains the most prevalent, endemic, and neglected ectoparasitic infestation globally and can cause institutional outbreaks. The sensitivity of routine microscopy for demonstration of Sarcoptes scabiei mites or eggs in skin scrapings is only about 50%. Except for three studies using conventional or two-tube nested PCR on a small number of cases, no systematic study has been performed to improve the laboratory diagnosis of this important infection. We developed a conventional and a real-time quantitative PCR (qPCR) assay based on the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of S. scabiei. The cox1 gene is relatively well conserved, with its sequence having no high levels of similarity to the sequences of other human skin mites, pathogenic zoonotic mites, or common house dust mite species. This mitochondrial gene is also present in large quantities in arthropod cells, potentially improving the sensitivity of a PCR-based assay. In our study, both assays were specific and were more sensitive than microscopy in diagnosing scabies, with positive and negative predictive values of 100%. The S. scabiei DNA copy number in the microscopy-positive specimens was significantly higher than that in the microscopy-negative specimens (median S. scabiei DNA copy number, 3.604 versus 2.457 log10 copies per reaction; P = 0.0213). In the patient with crusted scabies, the qPCR assay performed on lesional skin swabs instead of scrapings revealed that the parasite DNA load took about 2 weeks to become negative after treatment. The utility of using lesional skin swabs as an alternative sample for diagnosis of scabies by PCR should be further evaluated.

Fatal empyema thoracis caused by Schizophyllum commune with cross-reactive cryptococcal antigenemia.

We report a fatal case of Schizophyllum commune empyema thoracis with cross-reactive cryptococcal antigenemia. In vitro testing confirmed the ability of the fungus to cause a positive cryptococcal antigen latex agglutination system (CALAS) test result. Such a result may lead to delay in diagnosis and treatment, as most strains of S. commune are resistant to fluconazole.

Decolonization of gastrointestinal carriage of vancomycin-resistant Enterococcus faecium: case series and review of literature.

BACKGROUND: Prolonged asymptomatic carriage of vancomycin-resistant enterococci (VRE) in the gastrointestinal tract and the lack of effective decolonization regimen perpetuate the endemicity of VRE in the healthcare settings. CASE PRESENTATION: We report a regimen for decolonization of gastrointestinal carriage of VRE by a combination of environmental disinfection, patient isolation, bowel preparation to wash-out the fecal bacterial population using polyethylene glycol, a five-day course of oral absorbable linezolid and non-absorbable daptomycin to suppress any remaining VRE, and subsequent oral Lactobacillus rhamnosus GG to maintain the colonization resistance in four patients, including two patients with end-stage liver cirrhosis, one patient with complication post liver transplant, and one patient with complicated infective endocarditis. All patients had clearance of VRE immediately after decolonization, and 3 of them remained VRE-free for 23 to 137 days of hospitalization, despite subsequent use of intravenous broad-spectrum antibiotics without anti-VRE activity. CONCLUSION: This strategy should be further studied in settings of low VRE endemicity with limited isolation facilities.

Prevalence and Outcomes of Infections in Critically-ill Paediatric Oncology Patients: A Retrospective Observation Study.

PURPOSE: The survival of paediatric oncology patients has improved substantially in the past decades due to advances in the field of oncology. Modern cancer treatments often come with life-threatening complications, of which infection is one of the most common causes in this patient population. This study aims to investigate the prevalence and outcomes of common infections in haemato-oncology patients during their stay in paediatric intensive care unit (PICU) and to identify any factors associated with these infections. METHODS: A retrospective observational study was conducted on all children with a haemato-oncology diagnosis or who underwent haematopoietic stem cell transplantation (HSCT) and who were admitted to the Hong Kong Children's Hospital PICU over a one-year period. Infection characteristics and patient outcomes were evaluated and compared between different sub-groups. Univariable and multi-variable analyses were employed to identify risk factors associated with the development of active infection. RESULTS: Forty-five (36.3%) of 124 critically ill haemato-oncology admissions to PICU were associated with infections, of which 31 (25%) admissions involved bacterial infections, 26 (20.9%) involved viral infections and 6 (4.8%) involved fungal infections. Bloodstream infection was the most common type of infection. More than half (61.3%) of the bacterial infections were due to an antibiotic-resistant strain. After adjusting for confounding variables, post-HSCT status and neutropenia were significantly associated with active infections. CONCLUSION: Infections in critically-ill haemato-oncological patients are associated with post haematopoietic stem cell transplant status and neutropenia. Further study is warranted to review effective strategies that may mitigate the likelihood of infection in this patient population.

Mycobacterium abscessus bacteremia after receipt of intravenous infusate of cytokine-induced killer cell therapy for body beautification and health boosting.

BACKGROUND: We report the first series of Mycobacterium abscessus bacteremia after cytokine-induced killer cell therapy for body beautification and health boosting. METHODS: The clinical manifestations, laboratory and radiological investigations, cytokine/chemokine profiles, and outcomes were described and analyzed. RESULTS: Four patients were admitted, and 3 patients had septic shock. Chest radiographs showed pulmonary infiltrates in all patients. Three patients developed peripheral gangrene, and 1 patient required lower limb and finger amputations. Patient 1 also developed disseminated infection including meningitis and urinary tract infection. Postmortem examination of patient 1 showed focal areas of pulmonary hemorrhage and diffuse alveolar damage, splenic infarct, adrenal necrosis, and hemorrhage, and acid-fast bacilli (AFB) were seen in the lung, liver, kidney, and adrenal gland. Patient 2 developed inguinal granulomatous lymphadenitis about 40 days after onset of lower limb gangrene. Wedge-shaped pulmonary infarcts were found in patient 3, and retinitis and subcutaneous lesions developed in patient 4. Patients in septic shock had dysregulated cytokine/chemokine profiles. Patient 4 with relatively milder presentation had increasing levels of interleukin 17 and cytokines in the interferon-γ/interleukin 12 pathway. All survivors required prolonged intravenous antibiotics. Blood cultures grew M. abscessus for all patients, and admission peripheral blood smear revealed AFB for 3 patients. Mycobacterium abscessus was also isolated from respiratory specimens (2 patients), urine (1 patient), and cerebrospinal fluid (1 patient). Time to initial blood culture positivity (patients 1, 2, and 3: ≤52 hours; patient 4: 83 hours) appeared to correlate with disease severity. CONCLUSIONS: Empirical coverage for rapidly growing mycobacteria should be considered in patients with sepsis following cosmetic procedures.

Use of nasopharyngeal aspirate for diagnosis of pneumocystis pneumonia.

Quantitative PCR on nasopharyngeal aspirate (NPA) can achieve high sensitivity and specificity in diagnosing Pneumocystis pneumonia (PCP) compared to microscopic examination of bronchoscopic specimens in a population with low HIV prevalence. Since NPA is a minimally invasive procedure, it is ideal as a screening test for PCP.

Transmission of methicillin-resistant Staphylococcus aureus in the long term care facilities in Hong Kong.

BACKGROUND: The relative contribution of long term care facilities (LTCFs) and hospitals in the transmission of methicillin-resistant Staphylococcus aureus (MRSA) is unknown. METHODS: Concurrent MRSA screening and spa type analysis was performed in LTCFs and their network hospitals to estimate the rate of MRSA acquisition among residents during their stay in LTCFs and hospitals, by colonization pressure and MRSA transmission calculations. RESULTS: In 40 LTCFs, 436 (21.6%) of 2020 residents were identified as 'MRSA-positive'. The incidence of MRSA transmission per 1000-colonization-days among the residents during their stay in LTCFs and hospitals were 309 and 113 respectively, while the colonization pressure in LTCFs and hospitals were 210 and 185 per 1000-patient-days respectively. MRSA spa type t1081 was the most commonly isolated linage in both LTCF residents (76/121, 62.8%) and hospitalized patients (51/87, 58.6%), while type t4677 was significantly associated with LTCF residents (24/121, 19.8%) compared with hospitalized patients (3/87, 3.4%) (p<0.001). This suggested continuous transmission of MRSA t4677 among LTCF residents. Also, an inverse linear relationship between MRSA prevalence in LTCFs and the average living area per LTCF resident was observed (Pearson correlation -0.443, p=0.004), with the odds of patients acquiring MRSA reduced by a factor of 0.90 for each 10 square feet increase in living area. CONCLUSIONS: Our data suggest that MRSA transmission was more serious in LTCFs than in hospitals. Infection control should be focused on LTCFs in order to reduce the burden of MRSA carriers in healthcare settings.

Epidemiology of Klebsiella oxytoca-associated diarrhea detected by Simmons citrate agar supplemented with inositol, tryptophan, and bile salts.

We studied the clinical and epidemiological characteristics of Klebsiella oxytoca-associated diarrhea in hospitalized patients in Hong Kong. Between 1 November 2009 and 30 April 2011, all inositol-fermenting colonies found on Simmons citrate agar supplemented with inositol, tryptophan, and bile salts (SCITB agar) used for the culturing of diarrheal stool samples were screened by a spot indole test for K. oxytoca. The overall sensitivity of SCITB agar plus the spot indole test (93.3%) for the detection of K. oxytoca in stool samples was superior to that of MacConkey agar (63.3%), while the specificities were 100% and 60.4%, respectively. The former achieved a 23-fold reduction in the workload and cost of subsequent standard biochemical identifications. Cytotoxin production and the clonality of K. oxytoca were determined by a cell culture cytotoxicity neutralization assay using HEp-2 cells and pulsed-field gel electrophoresis (PFGE), respectively. Of 5,581 stool samples from 3,537 patients, K. oxytoca was cultured from 117/5,581 (2.1%) stool samples from 104/3,537 (2.9%) patients. Seventy-six of 104 (73.1%) patients with K. oxytoca had no copathogens in their diarrheal stool samples. Twenty-four (31.6%) of 76 patients carried cytotoxin-producing strains, which were significantly associated with antibiotic therapy after hospital admission (50% versus 21.2%; P = 0.01). Health care-associated diarrhea was found in 44 (42%) of 104 patients with K. oxytoca, but there was no epidemiological linkage suggestive of a nosocomial outbreak, and PFGE showed a diverse pattern. None of the patients with cytotoxin-producing K. oxytoca developed antibiotic-associated hemorrhagic colitis, suggesting that K. oxytoca can cause a mild disease manifesting as uncomplicated antibiotic-associated diarrhea with winter seasonality.