Predictors and Outcomes of Healthcare-Associated Infections Caused by Carbapenem-Nonsusceptible Enterobacterales: A Parallel Matched Case-Control Study.

Objectives: The increasing incidence of carbapenem-nonsusceptible Enterobacterales as major pathogens in healthcare associated infections (HAIs) is of paramount concern. To implement effective prevention strategies against carbapenem-nonsusceptible Enterobacterales (CnSE) HAIs, it is crucial to identify modifiable factors associated with these infections. We identified risk factors for CnSE-HAIs, and compared clinical outcomes of CnSE-HAI and carbapenem-sensitive Enterobacterales (CSE)-HAI patients. Methods: We conducted a multi-centre parallel matched case-control study in two 1700-bedded Singapore acute-care hospitals from 2014-2016. Patients with CnSE-HAIs and CSE-HAIs were compared to a common control group without HAIs (1:1:3 ratio), matched by time-at-risk and patient ward. Carbapenem nonsusceptible was defined as non-susceptibility to either meropenem or imipenem. Presence of healthcare associated infections were defined by the criteria provided by the European Centre for Disease Prevention and Control. Outcomes of CnSE-HAI and CSE-HAI patients were compared using multivariable logistic and cox regression; the models were adjusted for infection and treatment characteristics. Results: Eighty CnSE-HAI and 80 CSE-HAI patients were matched to 240 patients without HAIs. All CRE-HAIs patients had prior antibiotic exposure, with 44 (55.0%) with prior carbapenem exposure. The most common CnSE-HAIs were intra-abdominal infections (28.8%) and pneumonia (23.8%). The most common CnSE species was Klebsiella spp. (63.8%). In the risk factor analysis, presence of drainage devices [adjusted odds ratio (aOR), 2.19; 95% CI, 1.29 - 3.70] and prior carbapenem exposure (aOR,17.09; 95% CI, 3.06 - 95.43) independently predicted CnSE-HAIs. In the crude outcomes analysis, CnSE-HAI patients had higher all-cause in-hospital mortality and longer time to discharge compared to CSE-HAI patients. After adjusting for differences in receipt of antibiotics with reported susceptibility to the Enterobacterales, there was no significant difference in all-cause in-hospital mortality between the two groups (aOR, 1.76; 95% CI, 0.86-3.58). Time to discharge remained significantly longer in patients with CnSE-HAI (adjusted hazard ratio, 0.71; 95% CI, 0.51 - 0.98) after adjusting for disease severity, receipt of antibiotics with reported susceptibility and receipt of appropriate source control. Conclusion: Appropriate management of deep-seated Enterobacterales infections and reducing exposure to carbapenems may reduce risk of CnSE-HAIs in Singapore. Efforts to improve antimicrobial therapy in CnSE-HAI patients may improve patient outcomes.

Experience with a triplex arbovirus nucleic acid test (NAT) at a Canadian Public Health Laboratory.

BACKGROUND: Dengue, chikungunya and zika infections occur in tropical and subtropical regions of the world. We describe the utilization of an in-house nucleic acid test (NAT) targeting all three viruses for febrile returning travelers in Alberta, Canada. METHODS: NAT was performed until 40 days from symptom onset or exposure due to the prolonged duration of zika virus RNA detection. From Sept 1, 2017 to August 31, 2019, 2552 specimens from 1932 patients were tested. RESULTS: Approximately 2% of patients tested were NAT positive for dengue virus (n = 42), chikungunya virus (n = 4), and zika virus (n = 1). The majority presented with fever, myalgia and rash. Regions with the most frequent travel included SouthEast Asia (68.5%), South America (25%) and the Caribbean (6.5%). Ct values were stronger (~ 1.5 logs) for patients within 1-3 days following onset of clinical symptoms than those presenting later. Nineteen patients had urine and plasma submitted; 5 were positive for both specimens and 2 were positive only for dengue virus in the urine. Also, Ct values were lower for plasma when compared to the corresponding urine. RNA was detected until 10 days and 5 days post-exposure in plasma and urine respectively for dengue virus. CONCLUSIONS: Owing to dengue viremia detected beyond the conventional 7 days and low levels of circulating zika virus globally, a cutoff of 14 days from symptom onset to NAT is sufficient to diagnose acute cases. Inclusion of a zoonotic history form that collects appropriate clinical history results in improved test utilization.

Lewis blood group phenotype vis-a-vis biochemical and physiological parameters of coronary artery disease: A study in North Indian population.

BACKGROUND: Many studies have proposed the lack of Lewis antigen as a marker for coronary artery disease (CAD); on the contrary, some of the studies found no association in this regard. This study aims to assess the association of the expression of Lewis antigen as an independent risk factor for CAD separately in males and females. MATERIALS AND METHODS: In this cross-sectional observational study, patients with angiographically proven CAD were taken as test group, and angiographically, negative patients were included as a control group. The individuals were examined for established CAD risk factor and Lewis antigen expression on red cell. Red cell Lewis phenotyping was done using microcolumn gel agglutination technology. Statistical tests were applied to see the association between lack of Lewis antigen expression and CAD. RESULTS: Of these 232 patients included in the study, 161 patients had more than 50% luminal stenosis in a major epicardial artery on coronary angiography (Test Group), and 71 were normal on angiography (Control Group). When males and females were considered together, there was an increased frequency of Lewis-negative phenotype among the angiography-positive group (26.7%) as compared to angiography normal control group (16.9 %), though was not statistically significant (P = 0.19). When males and females were segregated in multivariate analysis, Le (a-b-) females had a higher incidence of CAD (P = 0.03) with the odds ratio of 4.97, though an association was not found significant in males (P = 0.71). CONCLUSION: The association between Lewis phenotypes and CAD was not significant in males and in among the overall study population, but this association was statistically significant in females. Further studies based on a larger sample size may substantiate as well as delineate the possible hypotheses.

Evaluation of in vitro susceptibility of Gram-positive pathogens from a tertiary care hospital in Singapore to a novel oxazolidinone, tedizolid, by a gradient diffusion method and broth microdilution.

We compared the in vitro antimicrobial activities of tedizolid and linezolid on the Sensititre broth microdilution system for Gram-positive cocci isolates (n=146) from skin and skin structure infections and bloodstream infections, bronchoalveolar lavage and sputum. These pathogens included 40 methicillin-resistant Staphylococcus aureus, 38 coagulase-negative staphylococci, 20 Enterococcus faecalis and 48 beta-haemolytic Streptococcus spp. Susceptibility was simultaneously determined for 48 vanA vancomycin-resistant enterococci isolates 2013-2016 from rectal swabs (23 E. faecalis and 25 E. faecium, of which 4 were linezolid-non-susceptible). MIC90s for tedizolid were fourfold to eightfold lower than linezolid on the Sensititre and ranged from 0.12 to 0.5 µg/mL for the different pathogen groups. All isolates were susceptible to tedizolid except two vanA E. faecium strains (MICs of 1 and 2 µg/mL, respectively). Categorical and essential agreement for tedizolid were 99.48% and 92%, respectively, between Liofilchem gradient diffusion and Sensititre methods. Overall, the drug exhibited excellent activity against the surveyed Gram-positive pathogens.

Syphilis Masquerading As Mass Lesions: The Utility of Modern-Day Imaging and Molecular Sequencing in Clinical Diagnosis.

Syphilis has been known to present in a myriad of symptoms throughout the ages, and until this day, the diagnosis remains elusive to the modern physician. We present 2 unusual cases of syphilis that posed diagnostic challenges even in the current era of new and advancing diagnostic tests.

Antifungal susceptibility of invasive Candida bloodstream isolates from the Asia-Pacific region.

Bloodstream infections caused by Candida species are of increasing importance and associated with significant mortality. We performed a multi-centre prospective observational study to identify the species and antifungal susceptibilities of invasive bloodstream isolates of Candida species in the Asia-Pacific region. The study was carried out over a two year period, involving 13 centers from Brunei, Philippines, Singapore, South Korea, Taiwan, Thailand, and Vietnam. Identification of Candida species was performed at each study center, and reconfirmed at a central laboratory. Susceptibility testing was performed using a commercial broth dilution panel (Sensititre YeastOne YST-010, Thermofisher, United Kingdom) with susceptibility categorisation (S = susceptible, S-DD = susceptible dose-dependent) applied using breakpoints from the Clinical Laboratory Standards Institute. Eight hundred and sixty-one Candida isolates were included in the study. The most common species were C. albicans (35.9%), C. tropicalis (30.7%), C. parapsilosis (15.7%), and C. glabrata (13.6%). Non-albicans species exceeded C. albicans species in centers from all countries except Taiwan. Fluconazole susceptibility was almost universal for C. albicans (S = 99.7%) but lower for C. tropicalis (S = 75.8%, S-DD = 6.1%), C. glabrata (S-DD = 94.9%), and C. parapsilosis (S = 94.8%). Echinocandins demonstrated high rates of in vitro susceptibility (S>99%) against C. albicans, C. tropicalis, and C. parapsilosis This study demonstrates that non-albicans species are the most common isolates from bloodstream infections in most countries in the Asia-Pacific region, with C. tropicalis as the predominant species. Because of the prevalence of reduced susceptibility to fluconazole in non-albicans species, the study indicates that echinocandins should be the antifungal of choice in clinically unstable or high-risk patients with documented candidemia.

Use of the data system for field management of a clinical study conducted in Kolkata, India.

BACKGROUND: Designing an appropriate data system is important to the success of a clinical study. However, little information is available on this topic. We share our experiences on designing, developing, and implementation of a data system for management of data and field activities of a complex clinical study. METHODS: The data system was implemented aiming at determining the biological basis for the underperformance of oral vaccines, such as polio and rotavirus vaccines in children at a site in Kolkata, India. The system included several functionalities to control data and field activities. It was restricted to authorized users based on their access privileges. A relational database platform was chosen, and Microsoft Visual FoxPro 7.0 (Microsoft Corporation, Seattle, WA, USA) was used to develop the system. The system was installed at the clinic and data office to facilitate both the field and data management activities. RESULTS: Data were doubly entered by two different data operators to identify keypunching errors in the data. Outliers, duplication, inconsistencies, missing entries, and linkage were also checked. Every modification and users log-in/log-out information was auto-recorded in an audit trail. The system offered tools for preparation of visit schedule of the participants. A visit considered as protocol deviation was documented by the system. The system alerted field staff to every upcoming visit date to organize the field activities and to inform participants which day to come. The system also produced a growth chart for evaluating nutritional status and referring the child to a specialized clinic if found to be severely malnourished. CONCLUSION: The data system offered unique features for controlling for both data and field activities, which led to minimize drop-out rates as well as protocol deviations. Such system is warranted for a successful clinical study.

Alcohol handrubbing and chlorhexidine handwashing are equally effective in removing methicillin-resistant Staphylococcus aureus from health care workers' hands: A randomized controlled trial.

We conducted a randomized controlled trial in a tertiary-care hospital in a real-time setting to evaluate the effectiveness of 3 hand hygiene protocols in reducing hand carriage of methicillin-resistant and methicillin-sensitive Staphylococcus aureus among health care workers. Our study shows that use of alcohol handrub, either covering all hand surfaces in no particular order or using the 7-step technique, and chlorhexidine handwashing were equally effective in removing hand carriage of these pathogens.

Nonsurgical management of mitral valve endocarditis due to Cardiobacterium valvarum in a patient with a ventricular septal defect.

Cardiobacterium valvarum is a relatively novel agent of infective endocarditis. We describe the first case of infective endocarditis due to this pathogen in the Asian Pacific. This case is unique in its involvement of the mitral valve as well as its clinical resolution exclusively resulting from treatment with antibiotics without resorting to valve replacement/explantation.

Use of meropenem Adatabs dissolved in MacConkey agar for screening NDM-1 positive Enterobacteriaceae in faecal surveillance cultures.

AIMS: Carbapenem resistance due to metallo-ß-lactamases (MBLs) in Enterobacteriaceae has gained much prominence in recent months. The emergence and subsequent spread of New Delhi metallo-ß-lactamase-1 (NDM-1) constitutes a potential threat in terms of the management of affected patients and institutional infection control efforts. We evaluated an in-house prepared meropenem impregnated MacConkey agar versus CHROMagar KPC. METHODS: The lowest limit of detection (LLD) was compared for nine clinical isolates of NDM-1 producing Enterobacteriaceae on the above mentioned agar media. RESULTS: LLD was comparable for all the nine clinical isolates on both media. The cost of the antibiotic impregnated MacConkey agar was considerably lower (US$0.39) as compared to the commercial media, while its performance remained unaltered for a period of at least 8 weeks of storage. CONCLUSION: The in-house medium proved to be a suitable and cheap alternative to the CHROMagar KPC.

Alcohol handrubbing and chlorhexidine handwashing protocols for routine hospital practice: a randomized clinical trial of protocol efficacy and time effectiveness.

BACKGROUND: The World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) recommend the use of alcohol handrubs to prevent health care-associated infections. However, the efficacy and time effectiveness of different alcohol handrubbing protocols have yet to be evaluated. METHODS: We conducted a randomized controlled trial in the general wards of a 1,300-bed, acute, tertiary care hospital to compare the effectiveness of 3 hand hygiene protocols during routine inpatient care: (1) handrubbing with alcohol covering all hand surfaces, (2) handrubbing with alcohol using the standard 7-step technique, and (3) handwashing with chlorhexidine using the standard 7-step technique. Hand samples were obtained from 60 medical and 60 nursing staff, before and after hand hygiene. Quantitative and qualitative bacterial evaluations were carried out by microbiologists blinded to the protocol. RESULTS: All 3 protocols were effective in reducing hand bacterial load (P < .01). During routine patient care, alcohol handrubbing covering all hand surfaces required less time (median, 26.0 seconds) than alcohol handrubbing using the 7-step technique (median 38.5 seconds; P = .04) and chlorhexidine handwashing (median, 75.5 seconds; P < .001). CONCLUSION: Alcohol handrubbing protocols are as efficacious as chlorhexidine handwashing. Alcohol handrubbing covering all hand surfaces is the most time-effective protocol for routine patient care activities in busy general wards.