Amikacin treatment in patients with Enterobacterales bacteraemia: impact of MIC on mortality.

BACKGROUND: Recently, breakpoints of Enterobacterales to amikacin were changed from MIC ≤ 16 mg/L to MIC ≤ 4 mg/L based mainly on laboratory data with little supporting clinical evidence. Our aim was to investigate the relation between MIC of Enterobacterales to amikacin and mortality among patients with Enterobacterales bacteraemia from a urinary tract source treated with amikacin. PATIENTS AND METHODS: This retrospective, single-centre study included patients with Enterobacterales urinary source bacteraemia treated with amikacin, with Low (MIC ≤ 4 mg/L) and High (MIC 8 or 16 mg/L) MICs. A cohort of patients treated with ertapenem was used to assess if amikacin MIC is a marker of severity independent of antimicrobial treatment. The primary outcome was 30-day mortality. Multivariate logistic regression analysis was done to assess risk factors for mortality. RESULTS: We included 85 patients, 46 (54.1%) were male, and mean age was 79.0 years (SD 11.7). Sixty-one patients (71.8%) had Low MIC and 24 (28.2%) had High MIC. Thirty-day mortality was 8.2% and 29.2% in the Low and High MIC groups, respectively (P = 0.031). Risk factors for 30-day mortality were age, infection by Enterobacterales other than Escherichia coli and high amikacin MIC. In a cohort of 88 patients treated with ertapenem, amikacin MIC was not associated with 30-day mortality. CONCLUSIONS: We demonstrated a relation between higher amikacin MIC levels (8 and 16 mg/L) and increased 30-day mortality in patients treated with amikacin for bacteraemia secondary to a urinary source. These findings support the new CLSI breakpoint change of Enterobacterales to amikacin.

The impact of Boric Acid tubes on quantitative urinary bacterial cultures in hospitalized patients.

INTRODUCTION: The accuracy of urine culture results can be affected by pre-analytical factors such as transport delays and storage conditions. The objectives of this study were to analyze urine collection practices and assess the impact of introducing boric acid tubes for urine collection on quantitative urinary bacterial cultures of hospitalized patients in medical wards. METHODS: A quasi-experimental pre-post study conducted in an acute care facility. In the pre-intervention phase (2020-2021), urine samples were transported without preservatives at room temperature. In 2022 (post-intervention), we transitioned to boric acid transport tubes, evaluating its effect on significant bacterial growth (≥ 105 CFU/ml). Bivariate and multivariate analyses identified predictors of culture positivity. RESULTS: Throughout the duration of the study, a total of 12,660 urine cultures were analyzed. Date and time documentation was complete for 38.3% of specimens. Culture positivity was higher with longer processing times: positivity was 21.3% (220/1034) when specimens were processed within 4 h, 28.4% (955/3364) when processed in 4-24 h, and 32.9% (137/417) when processed after 24 h (p < 0.0001). For 4-24-hour processing, positivity decreased from 30.4% (704/2317) pre-intervention to 24.0% (251/1047) post-intervention (p < 0.001), with no significant changes in < 4 or ≥ 24-hour specimens. Stratified analysis by processing time revealed that the intervention was associated with reduced positivity only in cultures processed within 4-24 h (OR 0.80, 95% CI 0.67-0.94; p = 0.008). CONCLUSION: The introduction of boric acid transport tubes predominantly influenced cultures transported within a 4-24-hour window. This presents an opportunity to improve urine tract infection diagnostic practices in healthcare settings.

Blood stream Infections in chronic hemodialysis patients - characteristics and outcomes.

INTRODUCTION: Bloodstream Infections (BSI) are a major cause of death and hospitalization among hemodialysis (HD) patients. The rates of BSI among HD patients vary and are influenced by local patient and pathogen characteristics. Modifications in local infection prevention protocols in light of active surveillance of BSI has been shown to improve clinical outcomes. The aim of this study was to further explore factors associated with BSI in a contemporary cohort of HD patients at a public teaching hospital dialysis center in Israel. METHODS: This was a retrospective cohort study of HD patients with a BSI in the years 2014 to 2018. The primary outcome was the occurrence of BSI. Secondary outcomes were to describe the causative pathogens of BSI, and to assess for risk factors for BSI, and mortality. RESULTS: Included were 251 patients. The mean age was 68.5 ± 13.4 years, 66.9% were male. The mean time from initiation of dialysis was 34.76 ± 40.77 months, interquartile range (IQR) 1-47.5 months and the follow up period of the cohort was 25.17 ± 15.9 months. During the observation period, 44 patients (17.5%) developed 54 BSI events, while 10 of them (3.9% of the whole cohort) developed recurrent BSI events. Gram-negative microorganisms caused 46.3% of all BSI events. 31.4% of these BSI were caused by resistant bacteria. In a multivariate logistic regression analysis, patients receiving dialysis through a central line had a significantly increased risk for BSI adjusted Odds Ratio (aOR) 3.907, p = 0.005, whereas patients' weight was mildly protective (aOR 0.971, p = 0.024). CONCLUSIONS: We noted an increased prevalence of gram-negative pathogens in the etiology of BSI in HD patients. Based on our findings, additional empirical antibiotics addressing gram negative bacteria have been added to our empirical treatment protocol. Our findings highlight the need to follow local epidemiology for implementing appropriate preventative measures and for tailoring appropriate empiric antibiotic therapy.

A Randomized Controlled Study Assessing Convalescent Immunoglobulins vs Convalescent Plasma for Hospitalized Patients With Coronavirus 2019.

BACKGROUND: It is unknown whether convalescent immunoglobulins (cIgGs) are better than convalescent plasma (CP) for patients with coronavirus 2019 (COVID-19). METHODS: In this randomized controlled trial, we assigned high risk COVID-19 patients with ≤10 days of symptoms, to receive cIgGs or CP. The primary endpoint was improvement on day 14 according to the World Health Organization scale. Secondary endpoints were survival on day 14, and improvement, survival, and percent of ventilated patients on day 28, and treatment response in unvaccinated and vaccinated patients. RESULTS: A total of 319 patients were included: 166 received cIgGs and 153 CP. Median age was 64 to 66 years. A total of 112 patients (67.5%) in the cIgG group and 103 patients (67.3%) in the CP group reached the primary endpoint. Difference between groups was 0.1 (95% confidence interval, -10.1 to 10.4; P = .026), failing to reach noninferiority. More patients receiving cIgG improved by day 28 (136 patients [81.9%] and 108 patients [70.6%], respectively; 95% confidence interval, 1.9-20.7; P < .001; for superiority P = .018). Seventeen patients in the cIgG group (10.2%) and 25 patients (16.3%) in the CP group required mechanical ventilation (P = .136). Sixteen (9.6%) and 23 (15%) patients, respectively, died (P = .172). More unvaccinated patients improved by day 28 in the cIgG group (84.1% vs 66.1%; P = .024), and survival was better in the cIgG group (89.9% vs 77.4%; P = .066). CONCLUSIONS: cIgGs failed to reach the primary noninferiority endpoint on day 14 but was superior to CP on day 28. Survival and improvement by day 28 in unvaccinated patients treated with cIgGs were better. In the face of new variants, cIgGs are a viable option for treating COVID-19. TRIAL REGISTRATION NUMBER: My Trials MOH_2021-01-14_009667.

Short- and long-term mortality in patients with urosepsis caused by Escherichia coli susceptible and resistant to 3rd generation cephalosporins.

BACKGROUND: The aim of this study was to compare short- and long-term mortality among patients with urosepsis caused by Escherichia coli susceptibile (EC-SC) and resistant (EC-RC) to 3rd generation cephalosporins. METHODS: A retrospective cohort study that included all patients with E. coli urosepsis admitted to a 700-bed hospital from January 2014 until December 2019. Mortality up to 30 days, 6 months and 1 year was assessed using logistic multivariate regression analysis and Cox regression analysis. RESULTS: A total of 313 adult were included, 195 with EC-SC and 118 patients with EC-RC. 205 were females (74%), mean age was 79 (SD 12) years. Mean Charlson score was 4.93 (SD 2.18) in the EC-SC group and 5.74 (SD 1.92) in the EC-RC group. Appropriate empiric antibiotic therapy was initiated in 245 (78.3%) patients, 100% in the EC-SC group but only 42.5% in the EC-RC group. 30-day mortality occurred in 12 (6.3%) of EC-SC group and 15 (12.7%) in the EC-RC group. Factors independently associated with 30-day mortality were Charlson score, Pitt bacteremia score, fever upon admission and infection with a EC-RC. Appropriate antibiotic therapy was not independently associated with 30-day mortality. Differences in mortality between groups remained significant one year after the infection and were significantly associated with the Charlson co-morbidity score. CONCLUSIONS: Mortality in patients with urosepsis due to E. coli is highly affected by age and comorbidities. Although mortality was higher in the EC-RC group, we could not demonstrate an association with inappropriate empirical antibiotic treatment. Mortality remained higher at 6 months and 1 year long after the infection resolved but was associated mainly with co-morbidity.

Aminoglycoside versus carbapenem or piperacillin/tazobactam treatment for bloodstream infections of urinary source caused by Gram-negative ESBL-producing Enterobacteriaceae.

OBJECTIVES: We studied the performance of aminoglycosides in treating bloodstream infections (BSIs) of urinary source caused by ESBL-producing Enterobacteriaceae (ESBL-EB). METHODS: In a retrospective study of 193 patients with a clinical diagnosis of urinary tract infection, pyelonephritis or urosepsis and blood and urine cultures positive for ESBL-EB, patients were grouped according to whether they were treated with an aminoglycoside, a carbapenem or piperacillin/tazobactam. Multivariate analysis was used to define risk factors for mortality with inverse probability of treatment weighting used to minimize confounding. The primary efficacy outcome was 30 day mortality. The primary safety outcome was acute kidney injury (AKI) at 14 days. RESULTS: Mean age was 79.3 years. Dementia, chronic kidney disease and the presence of a urinary catheter were common. Thirty-two (16.6%) patients died and risk factors for mortality included age, high Charlson score, presentation with severe sepsis/septic shock and infection with bacteria other than Escherichia coli. Aminoglycosides were non-inferior compared with other antibiotics regarding 30 day mortality [13.0% versus 21.2%, respectively; adjusted risk difference=10.29% (-0.82% to 21.41%)], but did not reach non-inferiority for bacteriuria recurrence [48.9% versus 44.7%, respectively; adjusted risk difference=-8.72% (-30.87% to 13.43%)]. AKI developed at a similar rate in both treatment groups: 12.0% versus 10.6%, respectively [OR=1.14 (0.46-2.81)]. Aminoglycosides were more efficacious in E. coli infections compared with other ESBL-EB. CONCLUSIONS: We demonstrated the efficacy and safety of aminoglycosides in treating BSI of urinary source caused by ESBL-EB. This carbapenem-sparing approach can assist in avoiding excessive carbapenem use without compromising outcomes.

Gram-negative bloodstream infections in hemodialysis patients: A retrospective study
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BACKGROUND: Bloodstream infections (BSIs) are an important cause of hospitalizations and mortality among hemodialysis (HD) patients. Epidemiology of these infections is changing, with increasing rates of Gram-negative pathogens, including resistant ones. Few studies have focused on the characteristics and outcomes of these infections. OBJECTIVE: We aimed to document the causative pathogens of BSIs in HD patients and their clinical outcomes during 2008 - 2015, and to compare risk factors, clinical features, appropriateness of therapy, and outcomes between patients with Gram-negative vs. Gram-positive BSIs. MATERIALS AND METHODS: A single-center retrospective cohort study. Charts of 120 HD patients hospitalized with first BSI were reviewed. RESULTS: A total of 120 patients were included, 61 episodes of Gram-negative (51.8%) and 59 episodes of Gram-positive bacteria (49.2%). Source of infection was significantly more likely to be urinary or abdominal among patients with Gram-negative infection. Otherwise, no statistically significant differences were documented between groups in terms of baseline characteristics, presentation of infection and outcomes. Most Gram-negative BSIs were caused by enterobacteriaceae, followed by Pseudomonas spp. Previous clinical or surveillance cultures added little to accurate prediction of the causative organism. CONCLUSION: In a cohort of HD patients with BSI, no significant differences were found between Gram-negative and Gram-positive BSIs, besides source of infection. A urinary or abdominal source strongly suggests a Gram-negative pathogen. Otherwise, patient's characteristics, clinical presentation, and previous cultures, all cannot accurately predict the causative pathogen of BSI, and broad-spectrum antibiotics should be used empirically.
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Phosphorus Sorption Characteristics in Aluminum-based Water Treatment Residuals Reacted with Dairy Wastewater: 1. Isotherms, XRD, and SEM-EDS Analysis.

We examined P sorption characteristics in Al-based water treatment residuals (Al-WTR) generated from slightly alkaline surface water and in an organic residual composite (WW-Al/O-WTR), produced by using the Al-WTR to treat organic-rich and high P concentration dairy wastewater. Solids from both residuals were examined using scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) and X-ray diffraction (XRD), and exposed to P additions of 0 to 4000 mg L in a sorption experiment. The Al-WTR removed ∼97% of the added P, whereas WW-Al/O-WTR removed only 78% of the added P in the addition range of 0 to 100 mg P L. With P additions of ≥100 mg L, the removal rate declined to <38% by Al-WTR and to 16% by WW-Al/O-WTR, possibly implying a change in sorption mechanisms. Analysis by XRD indicated that the major mineral was calcite, with some silica and poorly crystalline Al hydroxides. Analysis by SEM-EDS, which used three-element overlay maps of the residual surfaces, indicated that P was sparsely sorbed on both calcic and Al (hydr)oxide surfaces, along with a few clusters, even at low P concentrations of the treated waters. Ternary clusters of P, Al, and Ca were more abundant on the WW-Al/O-WTR. Carbon distribution suggested that organic substances covered Al surfaces. Sorption of P onto WW-Al/O-WTR may be reversible due to relatively weak Ca-P and Al-P bonds induced by the slight alkaline nature and in the presence of organic moieties, enhancing the WW-Al/O-WTR potential to act as a P source, rather than a P sink, in agricultural applications.

Phosphorus Sorption to Aluminum-based Water Treatment Residuals Reacted with Dairy Wastewater: 2. X-Ray Absorption Spectroscopy.

Phosphorus capture from wastewater can decrease water pollution and provide a P-rich fertilizer alternative for use in agricultural production. This study was conducted to elucidate P retention mechanisms in Al-based water treatment residuals (Al-WTR) to gain insight regarding P sorption and the potential for P release from Al-WTR after reaction with dairy wastewater. Synchrotron-based microfocused X-ray fluorescence (micro-XRF) spectrometry, bulk P -edge X-ray absorption near edge structure spectroscopy (XANES), and P -edge micro-XANES spectroscopy were used to determine P distribution and speciation within the Al-WTR materials. Bulk XANES analyses indicated a shift from ∼56 P atom % Ca-associated P in the initial Al-WTR to ∼32% P atom % Ca-associated P after reaction with wastewater; Al-associated P made up the remainder of the P species. According to XANES analyses, adsorption appeared to be the primary P retention mechanism in the Al-WTR materials. However, micro-XANES analyses depicted a more complicated picture of P retention mechanisms, with regions of primarily Al-associated P, regions of primarily Ca-associated P, regions of mixed Al- and Ca-associated P, and distinct apatite- or octocalcium phosphate-like P grains. Synchrotron micro-XRF mapping further suggested that exposure of the aggregate exteriors to wastewater caused P to diffuse into the porous Al-WTR aggregates. Organic P species were not explicitly identified via P -edge XANES despite high organic matter content, suggesting that organic P may have been predominantly associated with mineral surfaces. Although diffusion and sorption to Al may decrease P bioavailability, Ca-associated P may increase P bioavailability from Al-WTR that is reused as a soil amendment.

Infants Born with Esophageal Atresia with or without Tracheo-Esophageal Fistula: Short- and Long-Term Outcomes.

BACKGROUND: The estimated incidence of esophageal atresia (EA) with or without tracheo-esophageal fistula (TEF) is 1:3500 live births. During childhood these patients have various co-morbidities, but the overall quality of life among adults is similar to that of the general population. OBJECTIVES: To evaluate short- and long-term co-morbidities and quality of life among infants born with EA ± TEF at a large single medical center. METHODS: Medical records of 65 children born over a 21 year period were reviewed for short- and long-term medical data. Telephone interviews were conducted with 46 of their parents regarding medical problems and quality of life after home discharge. RESULTS: The main long-term co-morbidities during the first 2 years of life, 4-6 years of age, and during adolescence (12-16 years) included gastro-esophageal reflux disease (GERD) in 56.5%, 35.8%, and 18.7%, respectively; stridor in 84.8%, 45.2%, and 12.5%, respectively; hyper-reactive airway disease (HRAD) in 43.5%, 35.5%, and 36.5%, respectively; recurrent pneumonia in 43.5%, 32.3%, and 18.8%, respectively; and overall recurrent hospitalizations in 87%, 41.9%, and 25%, respectively. The quality of life was reportedly affected among 100%, 75%, and 33.3% respectively. CONCLUSIONS: Long-term follow-up of patients with EA ± TEF indicates a high burden of co-morbidities during the first 6 years of life, with a gradual decrease in symptoms thereafter. Nevertheless, HRAD continued to impact the daily life of about one-third of the older adolescents, and GERD one-fifth. A long-term multidisciplinary follow-up should be conducted to prevent late onset complications that may affect the quality of life.

Genome sequence of two novel virulent clinical strains of Burkholderia pseudomallei isolated from acute melioidosis cases imported to Israel from India and Thailand.

OBJECTIVE: Burkholderia pseudomallei, the etiological cause of melioidosis, is a soil saprophyte endemic in South-East Asia, where it constitutes a public health concern of high-priority. Melioidosis cases are sporadically identified in nonendemic areas, usually associated with travelers or import of goods from endemic regions. Due to extensive intercontinental traveling and the anticipated climate change-associated alterations of the soil bacterial flora, there is an increasing concern for inadvertent establishment of novel endemic areas, which may expand the global burden of melioidosis. Rapid diagnosis, isolation and characterization of B. pseudomallei isolates is therefore of utmost importance particularly in non-endemic locations. DATA DESCRIPTION: We report the genome sequences of two novel clinical isolates (MWH2021 and MST2022) of B. pseudomallei identified in distinct acute cases of melioidosis diagnosed in two individuals arriving to Israel from India and Thailand, respectively. The data includes preliminary genetic analysis of the genomes determining their phylogenetic classification in rapport to the genomes of 131 B. pseudomallei strains documented in the NCBI database. Inspection of the genomic data revealed the presence or absence of loci encoding for several documented virulence determinants involved in the molecular pathogenesis of melioidosis. Virulence analysis in murine models of acute or chronic melioidosis established that both strains belong to the highly virulent class of B. pseudomalleii.

Method for the analysis of oxygen isotopic composition of soil phosphate fractions.

The isotopic signature of oxygen in phosphate (δ(18)O(P)) of various soil fractions may shed light on P transformations, including phosphorus (P) recycling by soil microorganisms, uptake by plants and P adsorption, precipitation and release by oxides and minerals, thus increasing our understanding on P cycling and lability in soils. We developed and tested a protocol to extract and purify inorganic phosphate (Pi) from different soil fractions distinguished by binding strength and precipitate it as silver phosphate (Ag(3)PO(4)) for δ(18)O(P) analysis. Soil P is extracted sequentially using water, NaHCO(3), NaOH and HCl and Pi in each solution is purified and precipitated as Ag(3)PO(4). The unique characteristics and possible interferences of the soil solution extracts are addressed. Two agricultural soil samples receiving reclaimed wastewater or fresh water were analyzed, and results indicate that all soil fractions analyzed have been impacted to some degree by biologically enzyme mediated cycling of P in the soil.

Assessing modified aluminum-based water treatment residuals as a plant-available phosphorus source.

Inorganic phosphorus (P) fertilizers are a finite resource; alternative means of creating P fertilizers from current municipal and agricultural waste sources may reduce our reliance on phosphate rock mining, and improve waste disposal and nutrient cycling. Previous research demonstrated that organic aluminum water treatment residual composites (Al/O-WTR), created by mixing aluminum water treatment residuals (Al-WTR) with swine wastewater, have the potential to be a source of plant-available P. A greenhouse study was conducted to compare spring wheat (Triticum aestivum L.) growth with increasing application rates of swine wastewater-derived Al/O-WTR and commercial P fertilizer (both applied at 34, 67, and 135 kg P2O5 ha-1) in either sandy loam or sandy clay loam soil. Spring wheat straw and grain P uptake were comparable across all treatments in the sandy loam, while straw and grain P uptake were lower with Al/O-WTR in the sandy clay loam. The Al/O-WTR did not affect soil organic P concentrations, but did increase phosphatase activity in both soils. Increased phosphatase activity suggests that Al/O-WTR application stimulated microorganisms and enhanced the extent to which microbial communities mineralized Al/O-WTR-bound organic P. Overall, these results suggest that Al-WTR can be used to make P fertilizer, combining two "waste" products to create a useful product. Phosphorus harvesting via Al/O-WTR may be a feasible future alternative to mining phosphate rock, while avoiding unnecessary waste disposal and improving agricultural nutrient cycling.

Innovative approach for recycling phosphorous from agro-wastewaters using water treatment residuals (WTR).

Phosphorus capture from polluting streams and its re-use using industrial byproducts has the potential to also reduce environmental threats. An innovative approach was developed for P removal from soil leachate and dairy wastewater using Al-based water treatment residuals (Al-WTR) to create an organic-Al-WTR composite (Al/O-WTR), potentially capable of serving as a P fertilizer source. Al-WTR was mixed with either soil leachate, or with dairy wastewater, both of which contained elevated P concentrations (e.g., 7.6-43.5 mg SRP L-1). The Al-WTR removed ∼95% inorganic P, above 80% organic P, and over 60% dissolved organic carbon (DOC) from the waste streams. P removal was correlated with P concentration in the waste streams and was consistent with an increase in Al/O-WTR P content as determined by X-ray fluorescence (XRF) and surface analysis using scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS). Organic C was a major constituent in the original Al-WTR (31.4%) and increased by 1% in the Al/O-WTRs. Organic C accumulation on particles surfaces possibly enhanced weak P bonding. Desorption experiments indicated an initial and substantial P release (30 mg SRP kg-1 Al/O-WTR), followed by relatively constant low P solubility (ca. 10 mg kg-1). Organic C was continuously released to the solution (over 8000 mg kg-1), concomitantly with Ca and other electrolytes, possibly indicating dissolution from inner pores, accounting for the highly porous nature of the Al-WTR, evident by SEM images. The potential of P-loading on Al/O-WTR to promote P recycling should be further studied.