Performance of ePlex® blood culture identification panels in clinical isolates and characterization of antimicrobial stewardship opportunities.

We assessed the performance of GenMark's ePlex® Blood Culture Identification (BCID) Panels for overall agreement of organism identification and resistance mechanism detection with standard microbiologic methods. This study included patients with a positive blood culture from May 2020 to January 2021. The primary outcomes were to assess concordance of ePlex® organism identification with standard identification methods and concordance of ePlex® genotypic resistance mechanism detection with standard phenotypic susceptibility testing. Secondary outcomes included panel specific performance and characterization of antimicrobial stewardship opportunities. The overall identification concordance rate in 1276 positive blood cultures was 98.1%. The overall concordance for the presence of resistance markers was 98.2% and concordance for the absence of resistance markers was 100%. A majority of ePlex® results (69.5%) represented opportunities for potential antimicrobial stewardship intervention. High concordance rates between the ePlex® BCID panels and standard identification and susceptibility methods enable utilization of results to guide rapid antimicrobial optimization.

Do age, gender, BMI and disease duration influence the clinical outcomes in patients of knee osteoarthritis treated with serial injections of autologous platelet rich plasma?

Purpose: To study whether age, gender, body mass index(BMI) and disease duration influence the clinical outcomes in kellgren-Lawrence(K-L) grade II,III knee osteoarthritis(KOA) patients treated with serial injections of platelet rich plasma(PRP). Patients and methods: 65 patients were given three monthly intra-articular injections of PRP in this prospective interventional study. The patients were divided into subgroups depending on the factor studied: by age(in years) into young <45(n = 7), middle age 45-60(n = 35), and elderly >60(n = 23): by BMI(in kg/m2) into; normal <25(n = 25), overweight 25-30(n = 27) and obese >30(n = 13) and disease duration; less(n = 32) or more than 1 year(n = 33) symptom duration. Visual analogue scale (VAS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were used as outcome measures and assessed before each injection and then at 6 and 9 months post injection. Groups were homogenous with respect to baseline characteristics. Results: Mean VAS and WOMAC scores showed a statistically significant improvement (P < 0.0001) across all groups and subgroups (age,gender,BMI,disease duration) at follow up. On intra-subgroup comparison, we found no significant differences(P > 0.05) among age, BMI or gender subgroups, however the scores were significantly better in patients with disease duration of less than 1 year than those with more than 1 year duration at both 6 and 9 months[P < 0.001(RC = 9.630,95% CI = 4.037-15.222,P = 0.001)]. Conclusion: PRP injections if given serially can improve the short term subjective scores of VAS and WOMAC scores in patients with K-L grade II and III KOA irrespective of age, gender, BMI or disease duration, however, clinical benefits can be maximized if given early in the disease course.

Clinical and Biochemical Correlation of Intra-articular Platelet-Rich Plasma and Corticosteroid Using Serum Matrix Metalloproteinase 3 (MMP-3) Levels in Osteoarthritis of Knee.

Introduction Osteoarthritis (OA) in humans is an inevitable consequence of ageing and can now be effectively managed with advancements in knowledge and understanding of the disease. The major concern in a patient suffering from this disease is the functional impairment caused by the pain. The goals in the management of OA knee include symptom relief with preservation of joint function. Despite there being a number of studies on the effectiveness of PRP and CS for knee OA, most of them have focused on patient-reported functional outcomes only. Hence, we conducted this study to assess the potential and effectiveness of a single intra-articular injection of PRP and CS in the functional improvement of knee OA patients using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Visual Analogue Scale (VAS) and to establish the bio-modulatory effects of intra-articular PRP and CS in knee OA patients by estimating the serum matrix metalloproteinase-3 (MMP-3) levels. Methodology Patients attending the outpatient department with complaints of knee pain were screened. Standing anteroposterior and lateral radiographs of the knees were obtained. Patients with Kellgren and Lawrence (K-L) grades II and III were enrolled in our study. A total of 96 patients were included in the study after fulfilling the inclusion and exclusion criteria. Patients were divided into two groups (PRP and CS) by randomisation. There were 48 each in the PRP and CS groups, out of which nine were lost to follow-up, two from the PRP group and seven from the CS group. A total of 87 patients fulfilling the inclusion criteria were finally enrolled in the study and followed up for nine months after a single intra-articular injection. The biochemical assessment of serum levels of MMP-3 was done at baseline and in the ninth month. Accordingly, patients in the PRP group were injected with freshly prepared PRP (3 ml) within two hours of preparation, whereas those in the CS received 80 mg of methylprednisolone acetate. VAS and WOMAC were measured at baseline, and then in the first, third, sixth, and ninth month post-injection follow-ups. MMP-3 level was estimated before the injection and at the ninth-month post-injection follow-up. Data collected for both groups were analysed and compared with each other. Conclusion PRP is unquestionably a better option than CS in OA of the knee based on boosting functional activity, lowering stiffness, and reducing pain, all three of which are denoted by the WOMAC and VAS scores as the effect of PRP lasts longer than CS injections for the aforesaid issues. We could not find any significant change in levels of MMP3 post PRP and CS injections, which signifies that these two modalities do not have any effect in either preventing cartilage degeneration or promoting cartilage regeneration. Our findings have shown that PRP injections are safe, minimally invasive, and effective treatment modalities for OA knee.

Transforaminal Injections of Platelet-Rich Plasma Compared with Steroid in Lumbar radiculopathy: A Prospective, Double-Blind Randomized Study.

Purpose: To evaluate and compare the clinical efficacy of transforaminal steroid and platelet-rich plasma (PRP) injections in patients with discogenic lumbar radiculopathy. Methods: 60 patients were randomized to be treated with single transforaminal injection of PRP (n = 29) or steroid (methylprednisolone acetate [n = 31]). Clinical assessment was done with Visual analogue scale (VAS), modified Oswestry low back pain disability index (MODI), and straight leg raise test (SLRT). Baseline assessment of outcomes was done followed by post-intervention evaluation at 1, 3, and 6 months. Both groups had similar baseline characteristics. Results: There was a significant statistical improvement of VAS and MODI in both groups at follow-up (P < 0.05). In PRP group, minimal clinically important change (> 2 cm difference of mean for VAS and > 10-point change in MODI) for both outcome scores was achieved at all follow-up intervals (1, 3, 6 months), while as in steroid group, it was seen only at 1 and 3 months for both VAS and MODI. On intergroup comparison, better results were seen in steroid group at 1 month (P < 0.001 for both VAS and MODI), and in PRP group at 6 months (P < 0.001 for both VAS and MODI) with non-significant difference at 3 months (P = 0.605 for MODI and P = 0.612 for VAS). More than 90% tested SLRT negative in PRP group and 62% in steroid group at 6 months. No serious complications were seen. Conclusion: Transforaminal injections of PRP and steroid improve short-term (up to 3 months) clinical outcome scores in discogenic lumbar radiculopathy, but clinically meaningful improvements sustaining for 6 months were provided by PRP only.

Characteristics of Decedents With COVID-19-Related Mortality in Kentucky, July 1-August 13, 2021.

OBJECTIVE: Although vaccination reduces the risk of severe COVID-19, fatal COVID-19 cases after vaccination can occur. We examined the characteristics of decedents with COVID-19-related mortality to help inform discussions about vaccination, boosters, and mitigation strategies. METHODS: We examined COVID-19-related deaths in Kentucky resulting from infections occurring from July 1 through August 13, 2021. We used records from case investigations, medical records, the Kentucky Health Information Exchange, and the Kentucky Immunization Registry to determine demographic information, vaccination status, and underlying health conditions, including calculation of the Charlson Comorbidity Index (CCI). We calculated mortality incidence rates by vaccination status by using data for unvaccinated and fully vaccinated populations in Kentucky as of July 1, 2021. RESULTS: In total, 777 COVID-19-related deaths occurred in Kentucky during the study period; 592 (76.2%) occurred among unvaccinated people. Compared with unvaccinated decedents, fully vaccinated decedents were older (median age, 77 vs 65 years; P < .001), had higher comorbidity levels (median CCI, 3 vs 1; P < .001), and were more likely to have immunocompromised health status (26.4% vs 16.0%; P = .003). Diabetes, hypertension, heart disease, and chronic lung disease were more common among vaccinated decedents than among unvaccinated decedents. Unvaccinated adults had a significantly higher risk of death than fully vaccinated adults (incidence rate ratio for age 20-49 years: 20.5 [95% CI, 6.5-64.8]; 50-64 years: 14.6 [95% CI, 9.4-22.7]; ≥65 years: 10.2 [95% CI, 8.3-12.4]). CONCLUSIONS: Immunocompromised health status, older age, and higher comorbidity were prevalent among fully vaccinated decedents, suggesting adults with these characteristics may benefit from additional protection strategies. Further understanding of the protection of additional and booster doses is needed.

Combining Community Wastewater Genomic Surveillance with State Clinical Surveillance: A Framework for SARS-CoV-2 Public Health Practice.

This study aimed to develop a framework for combining community wastewater surveillance with state clinical surveillance for the confirmation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants within the community and to provide recommendations on how to expand on such research and apply the findings in public health responses. Wastewater samples were collected weekly from 17 geographically resolved locations in Louisville/Jefferson County, Kentucky (USA), from February 10 to December 13, 2021. Genomic surveillance and quantitative reverse transcription PCR (RT-qPCR) platforms were used to screen for SARS-CoV-2 in wastewater, and state clinical surveillance was used for confirmation. The study results highlighted an increased epidemiological value of combining community wastewater genomic surveillance and RT-qPCR with conventional case-auditing methods. The spatial scale and temporal frequency of wastewater sampling provided promising sensitivity and specificity for gaining public health screening insights about SARS-CoV-2 emergence, seeding, and spread in communities. Improved national surveillance systems are needed against future pathogens and variants, and wastewater-based genomic surveillance exhibits great potential when coupled with clinical testing. This paper presents evidence that complementary wastewater and clinical testing are cost-effectively enhanced when used in combination, as they provide a strong tool for a joint public health framework. Future pathogens of interest may be examined in either a targeted fashion or using a more global approach where all pathogens are monitored. This study has also provided novel insights developed from evidence-based public health practices.

Laboratory markers predictive of fulminant Clostridioides difficile infection refractory to fluid resuscitation.

BACKGROUND: Old age, leucocytosis, hypoalbuminemia, and elevated creatinine have been identified as risk factors for fulminant Clostridioides difficile infection (CDI). High ATLAS scores have also been linked to fatal disease. The affiliated studies, however, involved patients prescribed metronidazole - a regimen no longer standard of care. The variables were thus reassessed in patients prescribed optimal therapy. METHODS: Adults hospitalized with CDI at University of Kentucky Medical Center were retrospectively reviewed. Enrolled subjects were separated according to disease classification i.e. non-severe/severe versus fulminant CDI. Fulminant patients were further subdivided into hypotensive persons responsive to fluid resuscitation, and those with sequent shock, ileus, or megacolon. Following partition, the cohorts underwent correlation analysis. FINDINGS: Forty-five subjects had non-severe/severe disease. Thirteen fulminant CDI patients responded to fluid resuscitation. Seventeen fulminant CDI patients developed shock, ileus, or megacolon. Median WBC counts, albumin values, and ATLAS scores varied among the cohorts. Although WBC counts were similar among the fulminant subsets, declining albumin values and increasing ATLAS scores mirrored disease worsening. Logistic regression revealed albumin values < 20 g/L (odds ratio [OR] 3.91) and ATLAS scores ≥ 6 (OR 5.03) to predict critical illness in hypotensive persons. CONCLUSION: Median WBC counts, albumin values, and ATLAS scores differed in patients separated by CDI severity. A notable variance in albumin values and ATLAS scores between fluid responsive fulminant disease and critical illness was moreover seen. The finding suggests hypoalbuminemia and high ATLAS scores in hypotensive CDI patients may herald shock, ileus, or megacolon.

Changing demographics and risk factors for cryptococcosis: A 12-year review at a tertiary care centre.

BACKGROUND: Cryptococcosis is classically associated with the immunocompromised patients but there is a rising appreciation for its impact on the immunocompetent hosts. We sought to analyse the trends, diagnosis, treatment of different hosts and the effect of immunodeficiency and chronic liver disease on relapse and in-house mortality. METHODS: This is a retrospective study of 12 years of patients with cryptococcosis, divided into three different groups: HIV-infected, transplant and non-HIV non-transplant (NHNT). Data were analysed with Chi-square, unpaired parametric t test, simple and multivariate logistic regression analysis. RESULTS: Of 114 identified patients, 23 (20.2%) had HIV infection, 11 (9.6%) had transplant, 80 (70.2%) were NHNT patients. Overall, mortality was 28.1% (32/114) and relapse occurred in 10.5% (12/114) of patients. The mortality trend was higher (OR = 2.346, p = .287) in the transplant group (45.5%, 5/11) than in HIV (26.1%, 6/23) and NHNT groups (26.3%, 21/80). HIV was associated with relapse; 30.4% (7/23) for HIV-positive patients and 5.5% (5/91) for HIV-negative patients (OR = 7.525, p = .002). Chronic liver disease had a large and statistically significant association with mortality on multivariate analysis (OR = 3.583, p = .013) which was more pronounced than the HIV or transplant groups. It was independently associated with mortality by chi-square analysis (OR 3.137, p = .012). CONCLUSION: Chronic liver disease represented 30.7% (35/114) of all studied patients. It was a risk factor for in-hospital mortality. HIV infection and transplant were not statistically significant for mortality. Relapse was highest in the HIV-infected patients at 30.4% (7/23). These data highlight the effect of type and degree of immunocompromise on cryptococcosis.

A Novel Approach to Improve Newborn Screening for Congenital Hypothyroidism by Integrating Covariate-Adjusted Results of Different Tests into CLIR Customized Interpretive Tools.

Newborn screening for congenital hypothyroidism remains challenging decades after broad implementation worldwide. Testing protocols are not uniform in terms of targets (TSH and/or T4) and protocols (parallel vs. sequential testing; one or two specimen collection times), and specificity (with or without collection of a second specimen) is overall poor. The purpose of this retrospective study is to investigate the potential impact of multivariate pattern recognition software (CLIR) to improve the post-analytical interpretation of screening results. Seven programs contributed reference data (N = 1,970,536) and two sets of true (TP, N = 1369 combined) and false (FP, N = 15,201) positive cases for validation and verification purposes, respectively. Data were adjusted for age at collection, birth weight, and location using polynomial regression models of the fifth degree to create three-dimensional regression surfaces. Customized Single Condition Tools and Dual Scatter Plots were created using CLIR to optimize the differential diagnosis between TP and FP cases in the validation set. Verification testing correctly identified 446/454 (98%) of the TP cases, and could have prevented 1931/5447 (35%) of the FP cases, with variable impact among locations (range 4% to 50%). CLIR tools either as made here or preferably standardized to the recommended uniform screening panel could improve performance of newborn screening for congenital hypothyroidism.

COVID-19 Outbreak Associated with a SARS-CoV-2 R.1 Lineage Variant in a Skilled Nursing Facility After Vaccination Program - Kentucky, March 2021.

Although COVID-19 mRNA vaccines demonstrated high efficacy in clinical trials (1), they were not 100% efficacious. Thus, some infections postvaccination are expected. Limited data are available on effectiveness in skilled nursing facilities (SNFs) and against emerging variants. The Kentucky Department for Public Health (KDPH) and a local health department investigated a COVID-19 outbreak in a SNF that occurred after all residents and health care personnel (HCP) had been offered vaccination. Among 83 residents and 116 HCP, 75 (90.4%) and 61 (52.6%), respectively, received 2 vaccine doses. Twenty-six residents and 20 HCP received positive test results for SARS-CoV-2, the virus that causes COVID-19, including 18 residents and four HCP who had received their second vaccine dose >14 days before the outbreak began. An R.1 lineage variant was detected with whole genome sequencing (WGS). Although the R.1 variant has multiple spike protein mutations, vaccinated residents and HCP were 87% less likely to have symptomatic COVID-19 compared with those who were unvaccinated. Vaccination of SNF populations, including HCP, is critical to reduce the risk for SARS-CoV-2 introduction, transmission, and severe outcomes in SNFs. An ongoing focus on infection prevention and control practices is also essential.

Amikacin target achievement in adult cystic fibrosis patients utilizing Monte Carlo simulation.

AIM: Pseudomonas aeruginosa (PsA) is a common pathogen in cystic fibrosis (CF). Management of an acute pulmonary exacerbation (APE) caused by PsA is dual anti-pseudomonal antibiotics, a beta-lactam plus aminoglycoside. Aminoglycoside dosing in CF differs from the general population due to altered pharmacokinetics. The primary objective of this study was to utilize pharmacokinetic data from adult CF patients that received amikacin to determine the probability of target attainment for APEs caused by PsA. METHODS: This was a single-center, non-randomized, retrospective cohort study of patients >18 years with CF that received intravenous amikacin between January 2010 and July 2016. Amikacin dose, frequency, and serum concentrations were used to calculate pharmacokinetic parameters assuming a one-compartment model. Monte Carlo simulation was conducted with MIC values from CF patients with a PsA positive sputum culture between January 2014 and September 2016 to predict concentration-time profiles for different doses of amikacin. RESULTS: This study included pharmacokinetic parameters for 14 amikacin courses administered to six unique patients. The average empiric dose of amikacin was 24.3 ± 14.6 mg/kg, achieving a peak:MIC ratio ≥8 at a rate of 37% (median 5.87; IQR 3.05-10.96). A dose of 45 mg/kg/day was needed to achieve target peak:MIC ratios 90% of the time for a PsA MIC of 8 mg/L. CONCLUSION: Our data suggests it may not be clinically feasible to utilize amikacin for PsA isolates with a MIC of 16 mg/L. Current guideline dosing recommendations of amikacin 30-35 mg/kg/day are only adequate for PsA with a MIC ≤4 mg/L.

Inhibition of biofilm formation by esomeprazole in Pseudomonas aeruginosa and Staphylococcus aureus.

Staphylococcus aureus and Pseudomonas aeruginosa are common nosocomial pathogens responsible for biofilm-associated infections. Proton pump inhibitors (PPI), such as esomeprazole, may have novel antimicrobial properties. The objective of this study was to assess whether esomeprazole prevents sessile bacterial growth and biofilm formation and whether it may have synergistic killing effects with standard antibiotics. The antibiofilm activity of esomeprazole at 0.25 mM was tested against two strains each of S. aureus and P. aeruginosa. Bacterial biofilms were prepared using a commercially available 96-peg-plate Calgary biofilm device. Sessile bacterial CFU counts and biomass were assessed during 72 hours of esomeprazole exposure. The killing activities after an additional 24 hours of vancomycin (against S. aureus) and meropenem (against P. aeruginosa) treatment with or without preexposure to esomeprazole were also assessed by CFU and biomass analyses. P. aeruginosa and S. aureus strains exposed to esomeprazole displayed decreased sessile bacterial growth and biomass (P < 0.001, each parameter). After 72 h of exposure, there was a 1-log(10) decrease in the CFU/ml of esomeprazole-exposed P. aeruginosa and S. aureus strains compared to controls (P < 0.001). After 72 h of exposure, measured absorbance was 100% greater in P. aeruginosa control strains than in esomeprazole-exposed strains (P < 0.001). Increased killing and decreased biomass were observed for esomeprazole-treated bacteria compared to untreated controls exposed to conventional antibiotics (P < 0.001, each parameter). Reduced biofilm growth after 24 h was visibly apparent by light micrographs for P. aeruginosa and S. aureus isolates exposed to esomeprazole compared to untreated controls. In conclusion, esomeprazole demonstrated an antibiofilm effect against biofilm-producing S. aureus and P. aeruginosa.

A real-world evaluation of oral vancomycin for severe Clostridium difficile infection: implications for antibiotic stewardship programs.

STUDY OBJECTIVE: To assess antibiotic treatment patterns and clinical outcomes of patients with Clostridium difficile infection (CDI) based on underlying severity of CDI disease. DESIGN: Retrospective analysis of data from a prospective cohort study. SETTING: Large tertiary care university hospital. PATIENTS: One hundred forty-four patients (mean ± SD age 63 ± 17 yrs) with CDI who received metronidazole (intravenous or oral) or oral vancomycin as their initial therapy option between 2006 and 2008. MEASUREMENTS AND MAIN RESULTS: Patients were stratified by severity of illness and treatment, and outcomes assessed were clinical response, relapse of disease, all-cause inpatient mortality, and length of hospital stay. Mild-moderate CDI disease was present in 85 patients (59%) and severe disease in 59 patients (41%). Overall, oral vancomycin was given to 16 patients (11%); use of this drug did not differ according to severity of infection. Among patients with severe disease, clinical success occurred in 32 (63%) of 51 patients given metronidazole and in all 8 patients (100%) given vancomycin (p=0.04). Inpatient mortality and hospital length of stay were lower in patients with severe CDI who were given oral vancomycin, although these results were not statistically significant. CONCLUSION: Oral vancomycin was not commonly used for severe CDI. An improved clinical response rate was observed in patients with severe CDI given oral vancomycin; this outcome supported results from clinical trials. Antibiotic stewardship teams could play a major role in providing guidance on CDI treatment based on severity.

A randomized, double-blind, placebo-controlled pilot study to assess the ability of rifaximin to prevent recurrent diarrhoea in patients with Clostridium difficile infection.

BACKGROUND: Uncontrolled case series have demonstrated decreased Clostridium difficile infection (CDI) recurrence in patients given rifaximin after standard antibiotic therapy. However, clinical trials assessing whether rifaximin decreases recurrent diarrhoea in patients with CDI have not been performed. The purpose of this study was to assess rates of recurrent diarrhoea in patients with CDI given rifaximin versus placebo immediately after standard therapy. METHODS: This was a randomized, double-blind, placebo-controlled pilot study. Patients with CDI and a Horn's index ≥1 were randomized to receive rifaximin 400 mg three times daily or placebo for 20 days given immediately after finishing standard anti-CDI antibiotics. Patients were followed for 3 months and assessed for recurrent diarrhoea that included CDI recurrence (return of diarrhoea with a positive toxin test) and patient self-reported return of non-CDI diarrhoea after a period of wellness. RESULTS: Sixty-eight patients aged 61 ± 18 years (50% male) were given rifaximin (n = 33) or placebo (n = 35). Twenty-four of 68 (35%) patients had recurrent diarrhoea either due to recurrent CDI (23.5%) or self-reported diarrhoea (11.5%). Recurrent diarrhoea occurred in 17 of 35 (49%) patients given placebo and 7 of 33 (21%) given rifaximin (P = 0.018). CDI recurrence occurred in 11 of 35 (31%) patients given placebo and 5 of 33 (15%) patients given rifaximin (P = 0.11). Self-reported diarrhoea occurred in 6 of 35 (17%) of patients given placebo and 2 of 33 (6%) given rifaximin (P = 0.15). CONCLUSIONS: Patients with CDI given a rifaximin chaser regimen experienced a decreased incidence of recurrent diarrhoea compared with placebo.

A common polymorphism in the interleukin-8 gene promoter is associated with an increased risk for recurrent Clostridium difficile infection.

BACKGROUND: Neutrophil recruitment coordinated by intestinal interleukin (IL)-8 secretion is a key component in the pathogenesis of Clostridium difficile infection (CDI). We hypothesized that a common single-nucleotide polymorphism (SNP) in the -251 region of the IL-8 gene promoter may be predictive of recurrent CDI. METHODS: This was a prospective cohort study of hospitalized adult patients with CDI who were admitted to a large, university-affiliated medical center from 2007 through 2008. Patients were monitored for 3 months after diagnosis of CDI and assessed for recurrent CDI (defined as a return of diarrhea that required treatment after initial symptom resolution). DNA was isolated from blood samples, and genetic sequencing was performed using polymerase chain reaction and pyrosequencing. The association between IL-8 genotype and recurrent CDI was assessed using univariate and multivariate statistics. RESULTS: Ninety-six patients with a mean (± standard deviation) age of 61 ± 16 years (54% of whom were female and 63% of whom were white) were identified. The overall incidence of recurrent CDI was 24%. IL-8 allele frequency was similar to previously reported findings (for A/A, 27%; for A/T, 53%; and for T/T, 20%). The incidence of recurrent CDI was 38% in patients with the A/A allele and 19% in all other patients (relative risk, 2.1; 95% confidence interval, 1.04-4.13) (P = .043). CONCLUSIONS: This study indicates that a common SNP in the IL-8 gene promoter is an independent predictor of recurrent CDI. Our results could offer risk stratification for patients at high risk for recurrent CDI.