Treatment-emergent cefiderocol resistance in carbapenem-resistant Acinetobacter baumannii is associated with insertion sequence ISAba36 in the siderophore receptor pirA.

We report the emergence of cefiderocol resistance in a blaOXA-72 carbapenem-resistant Acinetobacter baumannii isolate from a sacral decubitus ulcer. Cefiderocol was initially used; however, a newly approved sulbactam-durlobactam therapy with source control and flap coverage was successful in treating the infection. Laboratory investigation revealed cefiderocol resistance mediated by ISAba36 insertion into the siderophore receptor pirA.

Benchmark Examination of Blood Amino Acids Patterns in Phenylketonuria Neonates and Young Children on Phenylalanine-Restricted Dietary Treatment.

Background: Phenylalanine-restricted diets have been the basis of therapy for phenylketonuria; however, little is known how this treatment effects homeostasis of other amino acids. This study aimed to assess blood amino acid alterations in phenylketonuric neonates before and after treatment to identify any residual amino acid alterations with phenylalanine restriction in these treated children. Methods: Concentrations of 11 amino acids were measured using liquid chromatography-tandem mass spectrometry performed on dried blood spots. Results: Elevated blood phenylalanine, arginine, citrulline, valine, methionine concentrations and decreased tyrosine, proline concentrations were observed in phenylketonuria neonates relative to controls, of which phenylalanine, arginine, methionine, tyrosine, and proline levels could be either partially or completely restored with dietary intervention, whereas citrulline and valine were not restored and remained higher. Conclusions: Blood amino acid homeostasis is disrupted in phenylketonuria. Although dietary intervention adjusts amino acid homeostasis in the direction of a healthy equilibrium, complete restoration is not achieved.

Incidence of chorioretinitis and endophthalmitis in hospitalized patients with fungemia.

AIM/PURPOSE: Bloodstream candida infections can seed the eye via hematogenous spread and result in chorioretinitis or endophthalmitis. If undetected and untreated, this can result in permanent vision loss. Past studies evaluating incidence of ocular candidiasis among hospitalized patients with positive fungal blood cultures have demonstrated variable rates of occurrence, but recent studies have generally shown a lower incidence than was reported several decades ago. Given low rates of occurrence, the utility of screening patients with dilated fundus exams has been called into question. The primary aim of this investigation is to identify the rate of chorioretinitis and endophthalmitis based on dilated fundoscopy for patients with fungemia at a tertiary care hospital. METHODS: This study was a retrospective chart review of adult patients admitted to the medical centre of the University of Arkansas for Medical Sciences (UAMS) between May 1, 2014 and December 31, 2017, who had positive fungal blood cultures during their hospitalization. RESULTS: There were 324 positive fungal cultures in 290 patients. Of this initial group, there were 161 eye exams. Ocular examination identified 7 of 161 patients (4.3%) with chorioretinitis or endophthalmitis. DISCUSSION: These outcomes along with previous studies support the current guidelines that screening with dilated fundus examination for these patients is appropriate and necessary.

Real-World Impact of the Accelerate PhenoTest BC Kit on Patients With Bloodstream Infections in the Improving Outcomes and Antimicrobial Stewardship Study: A Quasiexperimental Multicenter Study.

BACKGROUND: Bloodstream infections (BSIs) are a leading cause of morbidity and mortality. The Improving Outcomes and Antimicrobial Stewardship study seeks to evaluate the impact of the Accelerate PhenoTest BC Kit (AXDX) on antimicrobial use and clinical outcomes in BSIs. METHODS: This multicenter, quasiexperimental study compared clinical and antimicrobial stewardship metrics, prior to and after implementation of AXDX, to evaluate the impact this technology has on patients with BSIs. Laboratory and clinical data from hospitalized patients with BSIs (excluding contaminants) were compared between 2 arms, 1 that underwent testing on AXDX (post-AXDX) and 1 that underwent alternative organism identification and susceptibility testing (pre-AXDX). The primary outcomes were time to optimal therapy (TTOT) and 30-day mortality. RESULTS: A total of 854 patients with BSIs (435 pre-AXDX, 419 post-AXDX) were included. Median TTOT was 17.2 hours shorter in the post-AXDX arm (23.7 hours) compared with the pre-AXDX arm (40.9 hours; P<.0001). Compared with pre-AXDX, median time to first antimicrobial modification (24.2 vs 13.9 hours; P<.0001) and first antimicrobial deescalation (36.0 vs 27.2 hours; P=.0004) were shorter in the post-AXDX arm. Mortality (8.7% pre-AXDX vs 6.0% post-AXDX), length of stay (7.0 pre-AXDX vs 6.5 days post-AXDX), and adverse drug events were not significantly different between arms. Length of stay was shorter in the post-AXDX arm (5.4 vs 6.4 days; P=.03) among patients with gram-negative bacteremia. CONCLUSIONS: For BSIs, use of AXDX was associated with significant decreases in TTOT, first antimicrobial modification, and time to antimicrobial deescalation.

Improving outcomes and antibiotic stewardship (IOAS) for patients with Gram-positive bloodstream infections through use of rapid testing: a quasi-experimental multicentre study of the Accelerate PhenoTest™ BC Kit.

BACKGROUND: Data from the Improving Outcomes and Antibiotic Stewardship for Patients with Bloodstream Infections: Accelerate PhenoTest™ BC Kit (AXDX) Registry Study were analysed to determine the impact of rapid organism identification and antimicrobial susceptibility testing (AST) for Gram-positive bacteraemia. PATIENTS AND METHODS: This multicentre, quasi-experimental study evaluated clinical and antimicrobial stewardship metrics following the implementation of AXDX. Data from hospitalized patients with bacteraemia were compared between groups, one that underwent testing on AXDX (post-AXDX) and one that underwent traditional identification and AST (pre-AXDX). An analysis of patients with Gram-positive bacteraemia was performed. The primary outcome was time to optimal therapy (TTOT). Secondary outcomes included time to first antibiotic modification (overall and Gram-positive), duration of unnecessary MRSA coverage, incidence of adverse events, length of stay and mortality. RESULTS: A total of 219 (109 pre-AXDX, 110 post-AXDX) patients with Gram-positive bacteraemia were included. Median TTOT was 36.3 h (IQR, 16.9-56.7) in the pre-AXDX group and 20.4 h (IQR, 7.5-36.7) in the post-AXDX group (P = 0.01). Compared with pre-AXDX, median time to first antibiotic modification (29.1 versus 15.9 h; P = 0.002), time to first Gram-positive antibiotic modification (33.2 versus 17.2 h; P = 0.003) and median duration of unnecessary MRSA coverage (58.4 versus 29.7 h; P = 0.04) were reduced post-AXDX. A trend towards decreased acute kidney injury (24% versus 13%; P = 0.06) was observed in the post-AXDX group. Groups did not differ in other secondary outcomes. CONCLUSIONS: Implementation of AXDX testing for patients with Gram-positive bacteraemia shortened the TTOT and reduced unnecessary antibiotic exposure due to faster antibiotic modifications.

Clinical Impact of Accelerate Pheno Rapid Blood Culture Detection System in Bacteremic Patients.

BACKGROUND: Accelerate Pheno blood culture detection system (AXDX) provides rapid identification and antimicrobial susceptibility testing results. Limited data exist regarding its clinical impact. Other rapid platforms coupled with antimicrobial stewardship program (ASP) real-time notification (RTN) have shown improved length of stay (LOS) in bacteremia. METHODS: A single-center, quasi-experimental study of bacteremic inpatients before and after AXDX implementation was conducted comparing clinical outcomes from 1 historical and 2 intervention cohorts (AXDX and AXDX + RTN). RESULTS: Of 830 bacteremic episodes, 188 of 245 (77%) historical and 308 (155 AXDX, 153 AXDX + RTN) of 585 (65%) intervention episodes were included. Median LOS was shorter with AXDX (6.3 days) and AXDX + RTN (6.7 days) compared to historical (8.1 days) (P = .001). In the AXDX and AXDX + RTN cohorts, achievement of optimal therapy (AOT) was more frequent (93.6% and 95.4%, respectively) and median time to optimal therapy (TTOT) was faster (1.3 days and 1.4 days, respectively) compared to historical (84.6%, P ≤ .001 and 2.4 days, P ≤ .001, respectively). Median antimicrobial days of therapy (DOT) was shorter in both intervention arms compared to historical (6 days each vs 7 days; P = .011). Median LOS benefit during intervention was most pronounced in coagulase-negative Staphylococcus bacteremia (P = .003). CONCLUSIONS: LOS, AOT, TTOT, and total DOT significantly improved after AXDX implementation. Addition of RTN did not show further improvement over AXDX and an already active ASP. These results suggest that AXDX can be integrated into healthcare systems with an active ASP even without the resources to include RTN.

Possible Transfusion-Transmitted Babesia divergens-like/MO-1 Infection in an Arkansas Patient.

A patient with asplenia and multiple red blood cell transfusions acquired babesiosis infection with Babesia divergens-like/MO-1 organisms and not Babesia microti, the common United States species. He had no known tick exposure. This is believed to be the first transfusion-transmitted case and the fifth documented case of B. divergens-like/MO-1 infection.

Flow Cytometric Panel-Reactive Antibody Results and the Ability to Find Transfusion-Compatible Platelets after Antibody-Desensitization for Allogeneic Bone Marrow Transplant.

BACKGROUND: Panel reactive antibody (PRA) reduction protocols are used to decrease anti-HLA antibodies with concomitant PRA monitoring as a measure of successful treatment prior to organ and haploidentical blood and marrow transplant (BMT). We hypothesized that the more sensitive flow cytometry (FC) based assays for PRA [FlowPRA® and Luminex® based Single Antigen Bead (SAB)] would also correlate with the ability to find compatible platelets for allosensitized recipients. METHODS: A female patient with myelodysplastic syndrome and a high HLA class I PRA [>90% PRA and cPRA by complement-dependent cytotoxicity (CDC) assay and Flow PRA] required allogeneic BMT. Baseline HLA Class I and class II antigen typing was performed and a matched sibling donor was identified. Although baseline anti-HLA class I and class II antibodies measured by FC and CDC revealed no donor specific antibodies (DSA), the decision was made to attempt antibody desensitization to facilitate platelet transfusion during BMT. FC and CDC assays were performed to determine anti-HLA class I antibodies and cPRA/%PRA prior to starting desensitization and at the end of desensitization. Over the course of desensitization and BMT, a total of 194 apheresis platelet units underwent cross-match (XM) using Capture-P®. We compared temporally-related PRA results with platelet XM results. RESULTS: High PRA by FC or CDC assays correlates with a high % of XM-positive (incompatible) platelet units. When the CDC PRA fell to 2% after desensitization, platelet XM incompatibility fell from 100% to 63% positive (incompatible). When the FC PRA fell to 5% the positive platelet XM fell to 5%. CONCLUSIONS: Antibody desensitization facilitated platelet transfusion. PRA determination by FC appeared better correlated than determination by CDC with the ability to find XM-compatible platelets.

Rhizopus Keratitis Associated with Poor Contact Lens Hygiene.

We report a case of Rhizopus keratitis in a young woman with poor contact lens hygiene. The mold was highly sensitive to treatment with amphotericin 0.15% drops, after a relatively prompt diagnosis. Obtaining cultures of both corneal infiltrates and presumably infected contact lenses may help to avoid a delay in proper treatment.

Lysinibacillus spp. Endophthalmitis: a First Reported Case.

Post-traumatic endophthalmitis (PTE) is an uncommon sequela of open globe injuries. In cases involving an intraocular foreign body (IOFB), the risk of PTE increases by up to four-fold. Typically, presentation occurs in the acute timeframe. Only three reported cases of delayed-onset PTE currently exist in the literature (two cases caused by Proprionibacterium acnes and one by Phaeoacremonium parasiticum, a fungal pathogen). We describe a case of delayed-onset post-traumatic endophthalmitis (PTE) caused by Lysinibacillus spp., an organism not previously reported in the ophthalmic literature.

Obstetric anesthesia for harlequin ichthyosis: a unique challenge.

Harlequin ichthyosis (HI) is a rare disorder of defective lipid transport resulting in severe epidermal hyperkeratosis producing large plate-like scales. Although mortality is high, improved treatments have allowed some with HI to survive into their third and fourth decades. However, until this case, there have been no known reports of pregnancy followed by birth of a healthy neonate to a mother with HI. We report one of the only approximately 25 known current HI survivors worldwide unique in having carried a pregnancy to full term and outline challenges for the anesthesiologist during labor and delivery.

Rituximab and intermediate-purity plasma-derived factor VIII concentrate (Koate®) as adjuncts to therapeutic plasma exchange for thrombotic thrombocytopenic purpura in patients with an ADAMTS13 inhibitor.

Thrombotic thrombocytopenic purpura (TTP) results from a congenital or acquired deficiency of the von Willebrand factor (vWF)-cleaving protease ADAMTS13. The disease can be fatal and hence treatment should be initiated promptly. Therapeutic plasma exchange (TPE) remains the standard treatment along with adjunct therapies including steroids and immunosuppressive drugs. Addition of rituximab to TPE has been shown to be beneficial in refractory/relapsing TTP; however, TPE results in removal of rituximab from the circulation requiring more frequent dosing of rituximab to achieve a favorable outcome. The intermediate-purity plasma-derived Factor VIII concentrate (FVIII) Koate® contains the highest amount of ADAMTS13 activity yet reported and has been used successfully in treating congenital TTP. Here we report our experience with addition of this FVIII concentrate to rituximab, corticosteroids and TPE in three TTP patients with an ADAMTS13 inhibitor to permit withholding TPE for 48 h after rituximab infusion.

First reported case of Ehrlichia ewingii involving human bone marrow.

A 65-year-old female with a history of multiple tick bites presented with fever and pancytopenia. Intracytoplasmic rickettsial morulae were detected on peripheral smear and bone marrow biopsy specimens, and PCR amplified Ehrlichia ewingii DNA from both specimens. To our knowledge, this is the first report of E. ewingii infection of human bone marrow.

Analysis of CD34+ cell collection using two mobilization regimens for newly diagnosed multiple myeloma patients reveals the separate impact of mobilization and collection variables.

Mobilization regimens for CD34+ cells have generally been judged successful based on the number of cells collected without evaluating mobilization separately from collection. Using retrospective data for patients who collected CD34+ cells on Total Therapy protocols 3a/3b (VTD-PACE) and Total Therapy 4/5 using a novel regimen that added low dose melphalan to VTD-PACE (MVTD-PACE), we analyzed mobilization and collection variables separately. A significant difference favoring MVDT-PACE was found in mean CD34+ cells/µL on day 2 of collection and in mean ratio of CD34+ cells/µL on day 2 to day 1. However, because apheresis variables and growth factor dose during collection were manipulated to optimize individual collections, the two regimens were not significantly different when the mean total CD34+ cells ×10(6) /kg collected was compared. Thus, when evaluating a chemotherapy regimen or new growth factor for mobilization, it is important to realize that total CD34+ cells collected is dependent on both mobilization and collection variables.

Bilateral optic neuritis due to malaria.

Malaria is a mosquito-borne infectious disease caused by protists of the genus Plasmodium. Malaria is widespread in tropical regions around the equator, including much of sub-Saharan Africa, Asia, and the Americas, and uncommonly seen in the developed world. Although a variety of ocular manifestations have been linked to malaria, optic neuritis is rare. We report a patient who developed bilateral optic neuritis after he was treated successfully for acute falciparum malaria.

Validation of a formula for predicting daily CD34(+) cell collection by leukapheresis.

BACKGROUND AIMS: The ability to predict how many CD34(+) cells a donor will collect on a given day is vital for efficient leukapheresis. METHODS: We validated a formula to predict daily CD34(+) cell collections by leukapheresis, calculated as follows: (peripheral blood CD34(+) cells/L) × (adjusted collection efficiency of 30%)/body weight (kg), multiplied by the number of liters processed. This validation was performed from 234 donors undergoing 30 L large volume leukapheresis (LVL) and 162 donors undergoing smaller collections (non-LVL). The LVL group consisted of 811 collection events (625 multiple myeloma, 186 non-myeloma). The non-LVL group consisted of 224 collection events (196 multiple myeloma, 28 non-myeloma). All predicted and observed CD34(+) cell collection numbers were plotted (predicted versus observed) and assessed using linear regression analyses. Linear correlation coefficients (r-values), slopes and intercepts of the regression lines were evaluated. RESULTS: Predicted versus observed data points across all quantities of CD34(+) cells/kg collected by both LVL and non-LVL had strong r-values of 0.947 and 0.913, respectively, demonstrating near perfect positive linear correlations. Data for LVL collections subgrouped by number of cells collected (poor, intermediate and good), mobilization regimen, collection day and diagnosis were analyzed the same way and showed consistent findings. CONCLUSIONS: We have validated a formula with a strong ability to predict collection of CD34(+) cells/kg that would allow for individualization of collection for any donor once the peripheral blood CD34(+) cell count and optimal goal of collection were known; to date this has not been published by other groups.