Staphylococcal Bacteremia Research Articles

Bacteraemia and fungemia in patients with cardiac implantable electronic devices: A retrospective cohort study

ObjectivesThe risk of cardiac implantable electronic device (CIED) infection in the setting of any bloodstream infection (BSI) is unclear. Previous studies have mainly focused on Staphylococcus aureus. The aim of this study is to evaluate the risk of CIED infection and the outcome during BSIs caused by any pathogen. MethodsAll positive blood culture results of patients with a CIED implantation or modification procedure between January 2013 and September 2021 in Tampere Heart Hospital occurring after the recorded procedure date until September 30th 2022 were identified. The primary outcome was the occurrence of a CIED infection within 90 days from the onset of BSI, defined according to the 2019 International CIED Infection Criteria. Secondary outcomes were all-cause death and recurrence of BSI. ResultsThe study included 630 BSIs with 16 CIED infections (incidence 2.5 %) during the follow-up period. The bacteraemias were most commonly caused by Escherichia coli (161 cases, 26 %) and Staphylococcus aureus (132 cases, 21 %). The risk of CIED infection was highest with staphylococcal bacteraemia (8.2 %) and lowest with gram-negative bacteria (0.4 %). CIED removal did not influence the overall mortality (P = 0.14) or the recurrence of bacteraemia: recurrence occurred in 14 % of the cases (2/14) if the CIED was removed and in 4 % (25/616) if it was not. ConclusionsThe risk of CIED infection associated with BSI was generally low, but dependent on the causing pathogen. The occurrence of BSI in a patient with CIED does not automatically warrant removal of the CIED.

Investigation and control of an outbreak of methicillin-susceptible Staphylococcus aureus skin and soft tissue infections in a level IV NICU

Background: Neonatal intensive care units (NICU) outbreaks caused by methicillin-susceptible Staphylococcus aureus (MSSA) are less commonly reported than outbreaks caused by methicillin-resistant S. aureus. We report an unusual outbreak of MSSA skin and soft tissue infections (SSTIs) in a level IV NICU investigated by whole genome sequencing (WGS) and molecular typing. Methods: An investigation was initiated in a 56-single-bed NICU after four patients developed MSSA SSTIs in Week 1. Case-patients had positive MSSA cultures identified by clinical cultures or surveillance sampling (bilateral nares, axillae, umbilicus, and groin), and antibiotic susceptibility testing was performed. WGS and assessment of isolate relatedness through mutation event analysis and multi-locus sequence typing (MLST) was performed by the NYS DOH. Demographic and isolate characteristics were compared using Wilcoxon rank sum test, Fisher’s exact test and Pearson’s Chi-squared test, as appropriate. Results: From Week 2 to Week 32, 9 rounds of surveillance for MSSA colonization were conducted. In all, 30 case-patients had MSSA colonization and 16 infants developed infections including impetigo (n=7), pustules (n=5), staphylococcal scalded skin syndrome (SSSS, n=2), abscess (n=1), and bacteremia (n=1). All SSTI cases presented on infants’ faces, all of whom were on non-invasive respiratory support. MLST identified 4 distinct types including MLST 121 (n=12), MLST 398 (n=10), MLST 30 (n=6), and MLST 15 (n=6). Eight isolates were unrelated to other isolates. MLST 398 and MLST 30 included isolates not closely related (>9 mutation events). The 12 MLST 121 isolates were closely related (≤9 mutational events between all isolates), harbored the mupA gene, and were mupirocin-resistant (MIC>1024 ug/ml). Clinical infection and mupirocin resistance were associated with MLST 121 (Table 1). Multiple infection control measures were implemented, including increased availability of alcohol-based hand sanitizers, introducing bare-below-the-elbows practice for staff, contact precautions for case-patients, decolonization with mupirocin and chlorhexidine baths, environmental cleaning/disinfection, and removing excess equipment and supplies. No new cases of mupirocin-resistant or MLST 121 SSTIs occurred after Week 25. Conclusion: We report a MSSA outbreak associated with multiple MLST types and a predominant mupirocin-resistant strain. This report highlights the ability of molecular typing to characterize strains causing infections versus colonization and the potential loss of mupirocin as a control measure when outbreaks are caused by mupirocin-resistant strains. WGS analysis allows for increased discrimination of mutation events allowing for improved resolution of case relatedness compared to other typing methods. Successful control of this outbreak was achieved with a multitude of infection prevention and control.

Clinical Impact of Vancomycin MIC on Outcomes in Patients With Coagulase-negative Staphylococcal Bacteremia

Coagulase-negative staphylococci (CoNS) are Gram-positive organisms that are a known component of normal skin flora and the most common cause of nosocomial bacteremia. For CoNS species, the vancomycin MIC breakpoint for susceptibility set by the Clinical and Laboratory Standards Institute is ≤4 µg/mL. There has been published reports of vancomycin heteroresistance in CoNS with vancomycin MICs of 2 to 4 µg/mL. The aim of this retrospective cohort analysis was to assess the clinical impact of vancomycin MICs <2 µg/mL versus ≥2 µg/mL in adult patients with CoNS bloodstream infections. Adult patients admitted to University Medical Center New Orleans with a blood culture positive for CoNS were assessed. The primary outcome was difference in 30-day mortality. Secondary outcomes were in-hospital, all-cause mortality; duration of bacteremia; hospital length of stay; and percentage of oxacillin-resistant CoNS. There was no difference in mortality in the vancomycin MIC <2 µg/mL group versus the vancomycin MIC ≥2 µg/mL group at 30 days (15.4% vs 17.4%; P = 1). In-hospital, all-cause mortality was also not different between groups (11.5% vs 13%; P = 1). Hospital length of stay between groups was 28.2 days versus 21 days (P = 0.692). Median duration of bacteremia was 1 day in both groups (P = 0.975), and median scheduled duration of antibiotic therapy was 14.9 days and 19.5 days (P = 0.385). The source and mode of acquisition of CoNS were similar between groups. Of all CoNS isolates, 58.7% (44 of 75) were oxacillin resistant. Staphylococcus epidermidis was the most common CoNS species at 66.7% (50 of 75). Of all isolates, 30.7% (23 of 75) had a vancomycin MIC ≥2 µg/mL, and 87% (20 of 23) of these were S. epidermidis. There was a higher percentage of S. epidermidis in the vancomycin MIC ≥2 µg/mL group than in the MIC <2 µg/mL group (87% vs 57.7%; P = 0.012). CoNS with a vancomycin MIC ≥2 µg/mL were also more likely to be oxacillin resistant (78.3% vs 50%; P = 0.005). There was no difference in clinical outcomes in adult patients with a CoNS bloodstream infection with a vancomycin MIC <2 µg/mL versus ≥2 µg/mL. At present, vancomycin remains appropriate empiric therapy for CoNS bloodstream infection. Further research is needed to determine if there is a true clinical impact of a vancomycin MIC ≥2 µg/mL in CoNS infections.

Daptomycin Use for Persistent Coagulase-Negative Staphylococcal Bacteremia in a Neonatal Intensive Care Unit.

During the last two decades, the incidence of late-onset sepsis (LOS) has increased due to improved survival of premature neonates. Persistent bacteremia (PB) in LOS is defined as more than two positive blood cultures obtained on different calendar days during the same infectious episode. Although rare, PB should be treated aggressively to prevent adverse outcomes. Daptomycin, a lipopeptide antibiotic, has been used in neonates with persistent coagulase-negative staphylococci (CoNS) bacteremia with promising results, but studies reporting on the efficacy and safety of the agent are scarce. The purpose of this study was to evaluate the efficacy and safety of daptomycin use for persistent CoNS bacteremia in a neonatal cohort. This is a retrospective, observational, single-center study of neonates treated with daptomycin during 2011-2022 in the Tertiary Neonatal Intensive Care Unit (NICU) of the University General Hospital of Patras, Greece. For the years 2011-2022, there were 3.413 admissions to the NICU. During the last 3 years (2020-2022)-the active epidemiological surveillance period-123 infants (out of 851 admissions, 14.4%) developed CoNS bacteremia (LOS). During the study period, twelve infants with PB were treated with daptomycin. They had a median gestational age of 32 weeks (IQR 31-34) and mean (SD) birth weight of 1.840 (867) grams. CoNS bacteremia isolates were s. epidermidis (50%), s. haemolyticus (20%), s. hominis (20%) and s. warneri (10%). The decision to start daptomycin (6 mg/kg/dose twice daily) was taken on median day 10 (ΙQR 7-15) of infection. None of the infants had focal complications or meningitis. Daptomycin therapy caused no renal, hepatic, muscular or gastrointestinal adverse events. One neonate developed seizures, and one death occurred due to multiple complications of prematurity. Most infants (11/12) were successfully treated and eventually had negative blood culture. Daptomycin monotherapy showed an adequate cure rate in premature neonates with persistent CoNS bacteremia in a tertiary NICU. In our study, daptomycin was effective and well tolerated; the safety profile, however, needs to be confirmed in larger studies and randomized controlled trials.

MEndoB, a chimeric lysin featuring a novel domain architecture and superior activity for the treatment of staphylococcal infections.

Bacterial infections are a growing global healthcare concern, as an estimated annual 4.95 million deaths are associated with antimicrobial resistance (AMR). Methicillin-resistant Staphylococcus aureus is one of the deadliest pathogens and a high-priority pathogen according to the World Health Organization. Peptidoglycan hydrolases (PGHs) of phage origin have been postulated as a new class of antimicrobials for the treatment of bacterial infections, with a novel mechanism of action and no known resistances. The modular architecture of PGHs permits the creation of chimeric PGH libraries. In this study, the chimeric enzyme MEndoB was selected from a library of staphylococcal PGHs based on its rapid and sustained activity against staphylococci in human serum. The benefit of the presented screening approach was illustrated by the superiority of MEndoB in a head-to-head comparison with other PGHs intended for use against staphylococcal bacteremia. MEndoB displayed synergy with antibiotics and rapid killing in human whole blood with complete inhibition of re-growth over 24 h at low doses. Successful treatment of S. aureus-infected zebrafish larvae with MEndoB provided evidence for its in vivo effectiveness. This was further confirmed in a lethal systemic mouse infection model in which MEndoB significantly reduced S. aureus loads and tumor necrosis factor alpha levels in blood in a dose-dependent manner, which led to increased survival of the animals. Thus, the thorough lead candidate selection of MEndoB resulted in an outstanding second-generation PGH with in vitro, ex vivo, and in vivo results supporting further development.IMPORTANCEOne of the most pressing challenges of our era is the rising occurrence of bacteria that are resistant to antibiotics. Staphylococci are prominent pathogens in humans, which have developed multiple strategies to evade the effects of antibiotics. Infections caused by these bacteria have resulted in a high burden on the health care system and a significant loss of lives. In this study, we have successfully engineered lytic enzymes that exhibit an extraordinary ability to eradicate staphylococci. Our findings substantiate the importance of meticulous lead candidate selection to identify therapeutically promising peptidoglycan hydrolases with unprecedented activity. Hence, they offer a promising new avenue for treating staphylococcal infections.

(Invited) Pathogen Agnostic Biodetection at the Point of Need

Emerging pathogens are a constant threat to global health and human life, as exemplified by the recent COVID-19 pandemic. The availability of rapid testing - including in home tests - was instrumental in facilitating return to our 'normal' way of life. Diagnostics - especially those that can quickly and effectively inform on the condition at the point of need, enhance situational awareness and guide decision making and mitigation strategies can greatly impact our ability to counter emerging threats, epidemics and pandemics. Yet, current diagnostics are largely targeted- meaning they are tailored to identify a limited repertoire of anticipated threats. For true preparedness, it is important that the strategies we develop are pathogen agnostic and can be readily used against any organism quickly. Our team has sought inspiration from the human innate immune system in order to develop truly agnostic diagnostics. Innate immunity is medicated by pattern recognition receptors that have evolved to recognize evolutionarily conserved signatures on pathogens - allowing for their early identification. These germline receptors bind with conserved pathogen associated molecular patterns – PAMPs – produced by all pathogens, and result in the development of an associated cytokine and chemokine response. Innate immunity is thus a universal biosensor. Drawing inspiration from this natural system, our team has developed diagnostic assays for all pathogens. This involved understanding of common mechanisms of host-pathogen interactions, which then lead to the design of curated novel assay modalities - membrane insertion and lipoprotein capture - for the detection of pathogen. Beyond assay development and characterization of the response, we have evaluated the feasibility of these methods to detect signatures in blinded clinical samples for a variety of diseases (tuberculosis, invasive Salmonella, Shiga toxin carrying E. coli, Staphylococcal bacteremia, and others) with excellent sensitivity as compared to benchmark assays. These outcomes and strategies for pathogen agnostic detection will be presented.Transitioning this platform for field use, our team engineered a portable waveguide-based optical biosensor platform with integrated microfluidics for sample processes. The platform named Portable EnGineered Analytical Sensor with aUtomated Sampling (PEGASUS, R&D100 2021). This platform uses single mode planar optical waveguides as the sensing element, and builds on a bench top instrument that has been developed at the Los Alamos National Laboratory. PEGASUS miniaturizes this benchtop sensor, with integrated sample processing, moving us toward the goal of developing a truly fieldable biosensor. PEGASUS uses a different, smaller waveguide mounting apparatus, miniaturized robust components, sensing hardware and software.PEGASUS integrates Catch-all, the first ever sample processing system capable of lipid separation with ultra-sensitive optical detection of complex bioanalytes at the point of need. a microfluidic device capable of centrifugal separation of serum from blood at the point of need with a system that is compatible with biomarkers that are both hydrophilic and hydrophobic. The cross-flow filtration device separates serum from blood as efficiently as traditional methods and retains amphiphilic biomarkers in serum for detection.Whereas the scope of targets is extremely broad, the platform still relies on the use of reagents, which complicates field use in some instances. Therefore, we are beginning to explore multi-wavelength spectroscopy as a tool for the measurement of complex clinical signatures - within seconds, without reagents. Preliminary data from this development will also be presented.

2401. The Role of Quantitative Microbial Cell-free DNA (mcfDNA) Sequencing (Seq) from Plasma in the Diagnosis (Dx) of Staphylococcal Cardiac Implantable Electronic Device Infective Endocarditis (CIED IE)

Abstract Background Optimal treatment (rx) of staphylococcal CIED IE requires removing the entire CIED. Difficulty of dx plus cost and potential morbidity of rx make treatment challenging. Complicated staphylococcal bacteremia is associated with prolonged detection of plasma mcfDNA during antibiotic rx. To assess for IE, we studied plasma mcfDNA kinetics in CIED patients (pts) with staphylococcal bacteremia undergoing CIED removal. Methods With written consent, CIED pts (no persistent confounding infection) with bacteremia in the prior ≤ 7 days (d) and planned CIED removal had serial plasma specimens collected [Figure]. Quantitative mcfDNA-Seq was done using the Karius Test® at Karius CLIA certified Laboratory (Redwood City,CA) on batched pt specimens. Clinical data were obtained from the electronic medical record. CIEDs were removed through sterile pockets or surgically except in pt 012. Definite CIED IE was defined by multiple d of bacteremia plus a definite lead / tricuspid vegetation per echocardiogram, direct inspection or lead tip culture; multiple d bacteremia or a definite vegetation defined possible CIED IE. Results Nine pts with definite CIED IE had bacteremia 3-13 d (median 6 d) with Staphylococcus aureus (7 pts) or S. epidermidis (2 pts: 012 who due to retained lead fragment relapsed after rx 021) [Table 1]. At consent, after 2-11 d rx (median 6 d) mcfDNA was detected in 8 of 9 pts; in all 9, on CIED extraction mcfDNA increased significantly from consent and pre-extraction levels [Table3]. Five pts with possible S.aureus CIED IE had 1-3 d (median1 d) bacteremia [Table 2]. None had plasma mcfDNA after 5 d rx and 4 of 5 had no mcfDNA detectable on device extraction [Table3]. McfDNA patterns in definite CIED IE (8 of 9 pos on consent / pre-extraction and had an increase on extraction) differed from those in possible CIED IE (4 of 5 neg at 5 d of rx and none detected on extraction) [p=0.023 Fisher Exact]. Conclusion Quantitative mcfDNA patterns can help distinguish definite from possible CIED IE and absence of mcfDNA in plasma of possible CIED IE on device extraction suggests that the CIED may not be infected. After 5 days of rx, plasma mcfDNA-Seq in CIED pts with staphylococcal bacteremia coupled with clinical features may identify patients that can be effectively treated without device removal - a testable hypothesis. Disclosures Adolf W. Karchmer, MD, DeBiopharma: Advisor/Consultant|DeBiopharma: Honoraria|Karius: Grant to Institution for this study Jason D. Matos, MD, Merck: Wife is an employee Nicholas R. Degner, MD, MPH, MS, Karius: Employer

Mosunetuzumab and Polatuzumab Vedotin Demonstrates Preliminary Efficacy in Elderly Unfit/Frail Patients with Previously Untreated Diffuse Large B-Cell Lymphoma

Background: Treatment options for elderly unfit/frail (U/F) patients (pts) with diffuse large B-cell lymphoma (DLBCL) are often limited due to comorbidities or functional decline. Less toxic, efficacious alternatives to full-dose chemoimmunotherapy (CIT) are needed. Mosunetuzumab (Mosun) is a first-in-class CD20xCD3 T-cell engaging bispecific antibody that redirects T cells to eliminate B cells. Mosun monotherapy has demonstrated efficacy, durable complete responses (CR), and manageable safety in U/F pts with untreated DLBCL (NCT03677154; Olszewski et al. ASH 2022). Subgroup analysis from an ongoing Phase Ib/II study (NCT03671018) of Mosun plus polatuzumab vedotin (Pola; M-Pola) in pts with relapsed/refractory DLBCL demonstrated efficacy and a manageable safety profile in pts ≥65 years (yrs) (Olszewski et al. ASH 2022). We report preliminary efficacy and safety data from the M-Pola cohort of study NCT03677154 in elderly U/F pts with newly diagnosed DLBCL. Methods: Eligible pts were ≥80 yrs, or 65-79 yrs and ineligible for full-dose CIT/unfit per simplified Geriatric Assessment (sGA; Merli et al. J Clin Oncol 2021) ( Table). Pre-phase prednisone was allowed. Pts were enrolled in two safety cohorts with escalating doses of Mosun subcutaneous (SC; Cohort 1 and 2), followed by an expansion (Exp) phase. Pts received Cycle (C) 1 step-up dosing with Mosun SC on Day (D) 1/8/15 (Cohort 1: 5/15/45mg; Cohort 2 and Exp: 5/45/45mg) then 45mg on D1 of C2-8 plus 1.8mg/kg intravenous Pola on D1 of C1-6. Pts with CR stopped Mosun after 8 cycles; pts with partial response (PR) or stable disease could continue Mosun for up to 17 cycles in the absence of progressive disease (PD). Primary endpoints included safety and objective response rate (ORR) by independent review committee (IRC; assessed by positron emission tomography-computed tomography [Lugano 2014 criteria]) at end of treatment (EOT). CR rate, progression-free survival, and overall survival were secondary endpoints (IRC- and investigator [INV]-assessed). Best overall response (BOR) and EOT responses are reported in pts who received first treatment with a sufficient time interval to be eligible for the relevant response evaluation. Cytokine release syndrome (CRS) was assessed by ASTCT criteria (Lee et al. Biol Blood Marrow Transplant 2019). Results: Pts were enrolled from Feb 2021 to Jan 2023. As of the clinical cutoff date (CCOD; Feb 17, 2023), 108 pts received M-Pola (Cohort 1: n=7; Cohort 2: n=13; Exp: n=88). Median age was 81 yrs (range: 66-94); 52% of pts were female; 81% had an ECOG PS of 0-1; and 66% had Ann Arbor stage III-IV disease. Per sGA, 59% were unfit and 40% frail ( Table). Median (range) number of cycles was 7.5 (1-14) for Mosun and 6 (1-6) for Pola. Most frequent treatment-emergent adverse events (AEs) (≥20%) were neutropenia (32%), CRS (30%), and injection site reaction (20%). Grade (Gr) 3-4 AEs occurred in 43% of pts (most frequent: neutropenia [28%]). Serious AEs occurred in 41% of pts; most frequent (≥5%) were CRS (14%) and infections (21%), including COVID-19 pneumonia (10%) and COVID-19 infection (7%). Most CRS events occurred in C1; 30/32 pts had Gr 1-2 events; two pts had Gr 3 events. All CRS events resolved within a median of 2 days (range: 1-6); management included tocilizumab (7/32) and corticosteroids (3/32). AEs leading to discontinuation of Mosun or Pola occurred in 15% and 12% of pts, respectively. Fatal AEs occurred in 15 pts (14%): eight COVID-19/COVID-19 pneumonia events; two unexplained deaths; and one event each of Staphylococcal bacteremia, sepsis, pneumonia, pulmonary embolism, and suicide. Range of onset date for fatal AEs was D8-251. At the CCOD, median follow-up was 7.5 months (range: 0-21). In 90 evaluable pts from Cohort 2 and Exp, BOR and best CR rate per INV were 80% (72/90) and 61% (55/90), respectively. EOT response assessments per INV in 56 evaluable pts showed ORR in 55% (31/56); CR in 45% (25/56); PD in 9% (5/56); PR in 11% (6/56); and 36% (20/56) without EOT assessment (withdrawal of consent: 4/20; AEs: 13/20; early discontinuation per INV: 2/20; PD in C1: 1/20) ( Figure). Conclusions: Chemotherapy-freeM-Pola demonstrated preliminary efficacy in elderly U/F pts with previously untreated DLBCL. Overall, the safety profile of M-Pola was consistent with that of the individual drugs. However, COVID-19 remains a high risk in elderly U/F pts treated for DLBCL. Biomarker analyses and long-term follow-up data will be presented.

Real-Life Vancomycin Therapeutic Drug Monitoring in Coagulase-Negative Staphylococcal Bacteremia in Neonatal and Pediatric Intensive Care Unit: Are We Underestimating Augmented Renal Clearance?

Bloodstream infections (BSI) from coagulase-negative-staphylococci (CoNS) are among the most frequent healthcare-related infections. Their treatment involves the use of vancomycin, a molecule whose optimal pharmacokinetic/pharmacodynamic (PK/PD) target for efficacy and safety is an area-under-curve/minimum inhibitory concentration (AUC/MIC) ratio ≥ 400 with AUC < 600. BSIs from CoNS in pediatric and neonatal intensive care unit that occurred at the Gaslini Institute over five years were evaluated to investigate the efficacy of vancomycin therapy in terms of achieving the desired PK/PD target and determining whether any variables interfere with the achievement of this target. AUC/MIC ≥ 400 with AUC < 600 at 48 and 72 h after therapy initiation was achieved in only 21% of the neonatal population and 25% of the pediatric population. In the pediatric population, an inverse correlation emerged between estimated glomerular filtration rate (eGFR) and achieved AUC levels. Median eGFR at 72 h was significantly higher (expression of hyperfiltration) in events with AUC < 400, compared with those with AUC ≥ 400 (p < 0.001). A cut-off value of eGFR in the first 72 h has been identified (145 mL/min/1.73 m2), beyond which it is extremely unlikely to achieve an AUC ≥ 400, and therefore a higher dose or a different antibiotic should be chosen.

Abstract #1413762: Acute Mesenteric Ischemia: A Rare Presentation of Severe Hypothyroidism

Hypothyroidism has been associated with several gastrointestinal symptoms (GI) including constipation, ileus, atrophic gastritis, atony and dilation in various parts of the GI tract including myxedema megacolon. A more rarely reported association is ischemic colitis. We present a case of suspected mesenteric ischemia secondary to severe hypothyroidism. 65-year-old female with a history of oropharyngeal cancer treated with radiation therapy and Superior Mesenteric Artery syndrome with stent, presented with abdominal pain, nausea and vomiting for ten days. Imaging showed severe constipation with fluid-filled thick-walled small bowel loops. She was hemodynamically stable but with an elevated lactate (4 mmol/L) that improved with intravenous fluids. Overnight, she became disoriented, dyspneic and her abdominal pain worsened. She was upgraded to the ICU with suspected bowel ischemic. Her lactate was elevated but repeat CT was unchanged. Later, thyroid function tests were obtained showing an elevated TSH of 35.5 uIU/ml, low free T3 0.8 pg/ml and undetectable free T4. She was given a dose of intravenous levothyroxine that resulted in marked improvement in her abdominal pain and mental status by the next day. She was switched to oral levothyroxine. Over the course of her hospitalization, she developed staphylococcal bacteremia and later became obtunded requiring intubation. Over the subsequent days, she developed edema, hypothermia, bradycardia, and hypotension. Imaging showed bilateral pleural effusions, a new pericardial effusion, and ascites. She was diagnosed to be in myxedema coma and restarted on IV levothyroxine with high-dose steroids. After several days with minimal improvement in her condition, her family opted for palliative extubation. Hypothyroidism can result in decreased intestinal motility due to loss of gap junctions resulting in constipation and intestinal edema and can develop years after completion of radiation therapy as seen with our patient. We suspect that our patient’s symptoms were because of mechanical compression of the vascular supply of the small intestine due to severe dilation of the bowel wall as reported previously in cases of hypothyroidism-associated ischemic colitis. Given that the major focus was on the diagnosis of acute obstructive mesenteric ischemia, there was a delay in the diagnosis of severe hypothyroidism that later progressed to myxedema coma triggered by bacteremia. This case highlights the importance of checking thyroid function in patients with evidence of bowel dilation and ileus, since a delayed diagnosis of hypothyroidism can be fatal if left untreated.

Usefulness of leadless pacemaker implantation to continue chemotherapy for Burkitt's lymphoma without device infection despite repeated systemic infections.

Usefulness of leadless pacemaker implantation to continue chemotherapy for Burkitt's lymphoma without device infection despite repeated systemic infections.

Clinical Characteristics and Outcomes of Persistent Staphylococcal Bacteremia in a Tertiary Care Hospital

Clinical outcomes of persistent staphylococcal bacteremia vary depending on the causative organism. This secondary data analysis study compared the clinical characteristics of persistent Staphylococcus aureus (S. aureus)- and coagulase-negative staphylococci (CoNS)-caused bacteremia, focusing on the methicillin-resistant status. This study used data collected from patients who underwent blood cultures between January 2012 and December 2021 at Tohoku University Hospital, Japan. Patients with persistent staphylococcal bacteremia were divided into groups based on the pathogen and methicillin-resistant status, and their characteristics were analyzed. The primary outcomes were early (30-day), late (30-90 days), and 90-day mortality rates. The early, late, and 90-day mortality rates were similar between the persistent CoNS and S. aureus bacteremia groups. Patients with persistent methicillin-resistant S. aureus (MRSA) bacteremia tended to have higher early, late, and 90-day mortality rates than those with persistent methicillin-susceptible S. aureus bacteremia (not statistically significant). No differences were observed between the methicillin-resistant and-susceptible CoNS groups. In patients with persistent CoNS bacteremia, mortality tended to increase, especially in debilitated or immunocompromised patients with distant metastases, underscoring the importance of infection source control. Mortality tended to be high in patients with persistent MRSA bacteremia, especially when persistent bacteremia clearance was not confirmed, illustrating the need for careful therapeutic management.

Overview Methicillin-Resistant Staphylococcus Aureus Combination Treatment Options in Vivo and in Vitro

The spread of multidrug-resistant Staphylococcus aureus continues to threaten global health. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the common causes of bacterial infections in hospitals and communities. Despite vancomycin being an effective treatment for MRSA, from 2006 to 2020, vancomycin-resistant MRSA increased 3.5-fold, from 5% to 7%. Bacterial genome mutations, as well as bacteria’s ability to transfer genetic material with other bacteria, allowing them to obtain resistance genes from different strains, are all factors contributing to the development of vancomycin resistance in MRSA. As a result, combination therapy may be a potential treatment for MRSA infection. We searched in PubMed and Google Scholar, and our search yielded 92 articles, out of which 74 full-text articles were reviewed and 56 were selected for this study. This literature review examines combination therapies for MRSA infections, such as -Lactams with vancomycin, linezolid and imipenem, daptomycin and ceftaroline. The review yielded several studies looking at the synergy between -lactams and vancomycin. Although linezolid and rifampicin demonstrate synergy against MRSA in vivo and in vitro in various invasion diseases, more clinical research is required to prove their efficacy. Furthermore, daptomycin plus ceftaroline shows synergy for refractory staphylococcal bacteremia in vivo and in vitro. Combining ceftaroline and daptomycin has two benefits: they work synergistically together and make the innate host defense peptide cathelicidin leucine-leucine-37 (LL-37) more sensitizing. Ceftaroline plus daptomycin was recently used in MRSA biofilm infections, demonstrating a potentially promising treatment as the first combination used without side effects in humans. Keywords: Bacteremia, Vancomycin, Daptomycin, Ceftaroline, Staphylococcus aureus, MRSA.

Erythema Nodosum Associated with Staphylococcus Species Infection in a Child

Abstract Erythema nodosum (EN) is a poly-etiological disease with an acute flow that is characterized by symmetric emergence of painful nodules often in pretibial areas. A twenty-month-old male child was admitted to hospital for evaluation of the eruptive skin changes in the lower extremities and forearms. The disease began 10 days before getting febricity and loose stools. The laboratory analysis showed an elevated erythrocyte sedimentation rate and leukocytosis. Blood cultures demonstrated the presence of coagulase-negative Staphylococcus, while Proteus vulgaris was isolated in urine cultures. After initiation of the empiric antibiotic therapy and then, the targeted antibiotic therapy according to the antibiogram, there was a significant improvement in a general condition and regression of cutaneous lesions. Erythema nodosum in the present case, is the result of staphylococcal bacteremia although Proteus vulgaris cannot be excluded as a cause.

Efficacy of Teicoplanin Lock Therapy in the Treatment of Port-related Coagulase-negative Staphylococci Bacteremia in Pediatric Oncology Patients.

The number of studies evaluating teicoplanin lock therapy in coagulase-negative staphylococcus-associated catheter infection in pediatric malignancies is limited. The aim of this study was to evaluate the efficacy of teicoplanin lock therapy in pediatric cancer cases. Twenty-two patients with coagulase-negative staphylococcus-associated totally implantable venous access device infection, who had undergone teicoplanin closure treatment, were included in the study. Demographic data, number of lock treatment days, and treatment success data were obtained from the medical files of the patients. Fourteen of the patients (63.6%) had acute lymphocytic leukemia, 3 (13.6%) had acute myelocytic leukemia, and 5 (22.7%) had solid cancer. The median neutrophil count was 240×10 3 /μL (interquartile range: 0 to 1195×10 3 /μL). Between patients with and without catheter removal, no statistically significant difference was found in terms of baseline C-reactive protein, absolute neutrophil count, and the day of starting systemic teicoplanin treatment ( P >0.05). The overall port survival rate of teicoplanin lock therapy was 72.7%. Within an average of 4 days, negative cultures of 16 (72.7%) patients whose catheters had not been removed were obtained. In conclusion, we suggest that teicoplanin lock therapy is an effective and safe treatment for catheter-related infections, caused by methicillin-resistant coagulase-negative staphylococcus.

Persistent Coagulase-Negative Staphylococcal Bacteremia in Neonates: Clinical, Microbiological Characteristics and Changes within a Decade.

Atypical outbreaks of persistent coagulase-negative staphylococci (CoNS) bacteremias, defined as three or more consecutive positive blood cultures with the same CoNS species, at least 48 h apart, have been reported in neonatal intensive-care units (NICUs). Our aim was to describe the profile of these cases in our NICU over a two-year period with the objective of assessing possible changes within a decade. Demographics, clinical and microbiological data were recorded for all CoNS bacteremias in our tertiary NICU during 2016–2017 and compared with the results of the same study in 2006–2007. Fifty-six cases of CoNS sepsis were recorded. Fourteen (25%) of them were persistent. There were no significant differences in demographic and clinical characteristics between cases with persistent vs. non-persistent bacteremia. Staphylococcus epidermidis was the most common species. In logistic regression analysis, biofilm production (β = 2.464, p = 0.04) was the most significant determinant for the development of persistent CoNS bacteremia. Our isolates were less likely to produce biofilm and carry ica operon as compared to those of 2006–2007. The cases of persistent CoNS sepsis have decreased within a decade, which could be attributed to the implementation of intensive infection control practices. Biofilm production remains the most important risk factor.

Host environment induces daptomycin tolerance in Staphylococcus aureus

Daptomycin is a last-resort antibiotic for the treatment of invasive diseases caused by methicillin-resistant Staphylococcus aureus. However, despite potent activity in vitro,daptomycin fails to resolve up to 30% of cases of staphylococcal bacteraemia, suggesting that the host environment reduces bacterial susceptibility to the antibiotic. Using human serum as a model of bacteraemia, we demonstrated that the host environment induced daptomycin tolerance via activation of the GraRS two-component system. Testing of various antimicrobial peptides present in serum revealed that the human cathelicidin LL-37 was able to bind GraS, induce GraRS signalling and confer daptomycin tolerance. Activation of GraRS by serum led to daptomycin tolerance via changes in the staphylococcal cell envelope. For example, GraRS-dependent increases in positive surface charge and peptidoglycan content occurred in serum, leading to reduced daptomycin binding. Additionally, incubation in serum led to a Cls2-dependent increase in the cardiolipin content of the membrane which contributed to daptomycin tolerance. Finally, inhibition of both peptidoglycan and cardiolipin synthesis together completely abolished acquisition of daptomycin tolerance in serum, demonstrating that these processes fully explain the tolerance phenotype. In summary, host LL-37 activates staphylococcal GraRS signalling, causing changes in the cell surface which confer daptomycin tolerance. This demonstrates how host defences can compromise antibiotic efficacy, and also provides a rationale for combination therapies to prevent the development of daptomycin tolerance and reduce rates of treatment failure.

W132 Rapid screening detection of staphylococcal bacteremia virulence factors using novel CPA amplification with SPR biosensor methodology

W132 Rapid screening detection of staphylococcal bacteremia virulence factors using novel CPA amplification with SPR biosensor methodology

Human Plasma Significantly Reduces Bacteriophage Infectivity Against Staphylococcus aureus Clinical Isolates.

Bacteriophage therapy has been regaining interest as a potential therapeutic in treating a wide range of infections. However, there is a paucity of knowledge regarding numerous aspects of bacteriophage therapy, thereby hindering the development of proper treatment protocols and effective clinical trials. In this report, the activities of three bacteriophages are evaluated against clinical bacterial isolates in the presence and absence of human plasma (HP). The bacteriophages used in this experiment were residual therapeutic doses from the United States Food and Drug Administration (FDA) approved compassionate use cases to treat recalcitrant prosthetic joint infections (PJIs). Herein we demonstrate that in the presence of HP, the infectivity of these Staphylococcal bacteriophages was significantly reduced compared to the infectivity in the absence of HP. Inhibition of infectivity ranged from 48% to 81% for two methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates independently infected with the same bacteriophage and 98% for a third MRSA clinical isolate infected with a different bacteriophage. In contrast, bacteriophage infectivity of an Enterococcus faecalis clinical isolate was not affected by the presence of HP. We hypothesize that the inhibition is correlated with plasma proteins binding to Staphylococcal surface proteins masking the receptors associated with bacteriophage attachment, thereby reducing infectivity. This has clinical ramifications for bacteriophage therapy use in treating Staphylococcal bacteremia and periprosthetic joint infections.

Direct tube coagulase testing on blood cultures in suspected staphylococcal bacteraemia

Background: Staphylococci are common isolates from blood cultures, appearing as Gram positive cocci (GPC) in clusters. The most clinically important species, Staphylococcus aureus, is identified by a positive tube coagulase or latex agglutination from plate culture, whereas less virulent species are mostly negative. This initial distinction may influence clinical management, but can take up to 48 hours. We proposed tube coagulase testing directly on blood culture broth at the time of flagging, which may reduce the time to reporting coagulase activity by 12 or more hours.