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Shortly after its introduction into clinical practice, Staphylococcus aureus isolates gained resistance to penicillin via the acquisition of ß-lactamases. A number of centers have recently described an increase in the proportion of invasive methicillin-susceptible S. aureus (MSSA), which are also susceptible to penicillin (PSSA). Little data are available regarding the prevalence or impact of PSSA in skin and soft tissue infections (SSTI). Community-acquired MSSA SSTI isolates were obtained through a surveillance study at Texas Children's Hospital from January 2017 to December 2021. A total of 200 random isolates underwent PCR for blaZ ß-lactamase; blaZ-negative isolates then underwent penicillin susceptibility testing using macrobroth dilution. Isolates which were blaZ negative and had a penicillin MIC ≤0.125 µg/mL were regarded as PSSA with the remainder regarded as penicillin-resistant MSSA (PR-MSSA). All PSSA underwent multilocus sequence typing. Medical records were reviewed. The median age of subjects was 4.2 years (IQR: 1.6-10.5). PSSA accounted for 9% of isolates during the study period. PSSA and PR-MSSA cases were similar with respect to age, demographics, and rates of prior antibiotic exposure. PSSA isolates less often had vancomycin MIC ≥1.5 µg/mL. Furthermore, 39% of PSSA were variants of sequence type 1. In multivariable analyses, penicillin susceptibility was independently associated with both hospital admission and surgical intervention. PSSA account for a small but significant proportion of MSSA SSTI in children. Clinically distinguishing patients with PSSA and PR-MSSA SSTI is challenging. However, PSSA SSTI were independently associated with higher rates of hospital admission as well as the need for surgical intervention suggesting a significant clinical impact.IMPORTANCEThe vast majority of Staphylococcus aureus in the US are penicillin resistant with most clinical labs no longer reporting penicillin susceptibility for this organism. A number of centers, however, have reported increasing penicillin susceptibility among invasive S. aureus infections. Skin and soft tissue infections (SSTI) are far more common than invasive infections, yet the frequency and impact of penicillin-susceptible S. aureus (PSSA) in this population are uncertain. Through active surveillance at a children's hospital, we found that 9% of methicillin-susceptible S. aureus SSTI isolates were PSSA. PSSA were independently associated with hospital admission for the management of SSTI as well as the need for debridement in the operating room. Given that most SSTI are managed in the outpatient setting, these findings suggest a clinical impact of this phenotype and the need for a reassessment of the value in susceptibility testing and potentially even treatment with penicillin.
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The need for echocardiography in pediatric Staphylococcus aureus bacteremia (SAB) remains uncertain. We reviewed 331 pediatric SAB cases. Nine subjects, all with comorbidities, met echocardiogram criteria for infective endocarditis (IE). IE was associated with congenital heart disease and prolonged bacteremia, suggesting that echocardiography is unnecessary in most children with SAB.
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Objectives: To determine the diagnostic accuracy of a rapid host-protein test for differentiating bacterial from viral infections in patients who presented to the emergency department (ED) or urgent care center (UCC). Methods: This was a prospective multicenter, blinded study. MeMed BV (MMBV), a test based on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-inducible protein-10 (IP-10), and C-reactive protein (CRP), was measured using a rapid measurement platform. Patients were enrolled from 9 EDs and 3 UCCs in the United States and Israel. Patients >3 months of age presenting with fever and clinical suspicion of acute infection were considered eligible. MMBV results were not provided to the treating clinician. MMBV results (bacterial/viral/equivocal) were compared against a reference standard method for classification of infection etiology determined by expert panel adjudication. Experts were blinded to MMBV results. They were provided with comprehensive patient data, including laboratory, microbiological, radiological and follow-up. Results: Of 563 adults and children enrolled, 476 comprised the study population (314 adults, 162 children). The predominant clinical syndrome was respiratory tract infection (60.5% upper, 11.3% lower). MMBV demonstrated sensitivity of 90.0% (95% confidence interval [CI]: 80.3-99.7), specificity of 92.8% (90.0%-95.5%), and negative predictive value of 98.8% (96.8%-99.6%) for bacterial infections. Only 7.2% of cases yielded equivocal MMBV scores. Area under the curve for MMBV was 0.95 (0.90-0.99). Conclusions: MMBV had a high sensitivity and specificity relative to reference standard for differentiating bacterial from viral infections. Future implementation of MMBV for patients with suspected acute infections could potentially aid with appropriate antibiotic decision-making.
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BACKGROUND: The Streptococcus anginosus group (SAG) pathogens have the potential to cause head and neck space infections, including intracranial abscesses. Several centers noted an increase in intracranial abscesses in children during the SARS-CoV-2 pandemic, prompting a Centers for Disease Control and Prevention health alert in May 2022. We examined the epidemiology of pediatric intracranial abscesses at a tertiary care center with a focus on SAG pre- and post-pandemic. METHODS: Cases of intracranial abscesses of any microbiologic etiology admitted from January 2011 to December 2022 were identified using International Classification of Diseases 10 codes. Subjects were cross-referenced with culture results from the microbiology laboratory at Texas Children's Hospital. Cases included were those associated with either otitis media, mastoiditis or sinusitis and medical records were reviewed. RESULTS: A total of 157 cases were identified and 59.9% (n = 94) were caused by SAG. The incidence of all sinogenic/otogenic intracranial infections ( P = 0.002), and SAG-specific infections ( P = 0.004), increased from 2011 to 2022. SAG infection was more often associated with multiple surgeries, and these subjects were more likely to require craniotomy or craniectomy. Among sinogenic abscesses, S. intermedius was the most common pathogen, while among otogenic cases, S. pyogenes predominated. From March 2020 to Dec 2022, 9/49 cases tested positive for SARS-CoV-2 (18.4%); characteristics of infection were not significantly different among cases with and without SARS-CoV-2. CONCLUSIONS: Over the last decade, intracranial complications of sinusitis/otitis have been increasing, specifically those caused by SAG; this trend, however, predated the SARS-CoV-2 pandemic. SAG was associated with a greater need for surgical intervention, specifically neurosurgery. Further work is necessary to determine the cause for these rising infections.
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Absceso Encefálico , COVID-19 , Mastoiditis , Otitis Media , Sinusitis , Infecciones Estreptocócicas , Streptococcus anginosus , Humanos , Mastoiditis/epidemiología , Mastoiditis/microbiología , Niño , Femenino , Masculino , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/microbiología , Preescolar , Incidencia , Sinusitis/microbiología , Sinusitis/epidemiología , Streptococcus anginosus/aislamiento & purificación , Lactante , Otitis Media/epidemiología , Otitis Media/microbiología , Absceso Encefálico/microbiología , Absceso Encefálico/epidemiología , COVID-19/epidemiología , COVID-19/complicaciones , Adolescente , Texas/epidemiología , SARS-CoV-2 , Estudios RetrospectivosRESUMEN
Incidental appendectomies (IAs) are often performed in laparotomies to prevent future complications caused by the buildup of scar tissue. Although neoplastic findings are rare, all appendectomy specimens should be sent for histopathological analysis. We present the case of a 38-year-old man found to have an appendiceal neuroendocrine tumor (NET) after receiving an IA secondary to a traumatic rectal perforation requiring exploratory laparotomy. Well-differentiated NETs isolated to the appendix have an excellent prognosis. Appendectomies are considered curative for NETs smaller than 2 cm that have not metastasized beyond the appendix. Appendiceal NETs are capable of secreting vasoactive substances and, therefore, causing carcinoid syndrome. However, the progression to carcinoid syndrome generally coincides with metastasis to the liver, indicating a poor prognosis. While histopathological analysis of appendectomy specimens rarely yields atypical findings, this analysis is crucial to ensure that the proper treatment is selected based on tumor progression in an appendectomy specimen staining positive for somatotropin and chromogranin.
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BACKGROUND: Pelvic involvement has been reported in 3%-14% of acute hematogenous osteomyelitis (AHO) cases in children. One guideline suggests need for a longer antibiotic course in pelvic AHO, however, recent data are lacking. We describe the clinical course of children with pelvic AHO and compare it to nonpelvic AHO. METHODS: A retrospective review of patients with a diagnosis of AHO admitted to Texas Children's Hospital from January 2012 to December 2020 was conducted. Patients 6 months-<19 years old and with ≤14 days of symptoms at admission were eligible. Patients with sickle cell disease or immunocompromised were excluded. Wilcoxon rank-sum test assessed for differences between continuous variables and Fisher exact for categorical variables using STATA 17. RESULTS: We compared 104 cases of pelvic AHO to 314 cases of nonpelvic AHO. Patients had similar microbiology, length of stay and length of antibiotic therapy. Patients with pelvic AHO had pyomyositis identified by magnetic resonance imaging more often (28.8 vs. 9.4%, P < 0.001) and bone abscess less often (22.1 vs. 46.5%, P < 0.001). Rates of chronic complications were comparable between patients with pelvic AHO and nonpelvic AHO (8.4% vs. 15.1%, P = 0.1). Nineteen patients (18.3%) with pelvic AHO received ≤30 antibiotic days without complications, but they had less need for intensive care or bone abscesses than patients treated longer. CONCLUSIONS: Pelvic AHO in children may be more frequent than previously reported but is not associated with more complications. Four weeks of therapy may be sufficient in selected patients. Prospective studies to compare outcomes with different lengths of therapy are needed.
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Osteomielitis , Niño , Humanos , Lactante , Estudios Prospectivos , Estudios Retrospectivos , Osteomielitis/diagnóstico , Osteomielitis/tratamiento farmacológico , Osteomielitis/microbiología , Enfermedad Aguda , Antibacterianos/uso terapéutico , Absceso/diagnóstico , Pelvis/diagnóstico por imagenRESUMEN
Background: Invasive infections caused by Streptococcus pyogenes (invasive group A streptococcus [iGAS]) and Streptococcus pneumoniae (invasive pneumococcal disease [IPD]) decreased substantially at the beginning of the COVID-19 pandemic. Our study sought to evaluate the extent of this decrease and the trends of these infections since reversion of societal adjustments incident to the pandemic. We also wanted to compare the frequency of these infections with invasive community-onset Staphylococcus aureus (I-CO-SA) infections and common respiratory viral infections in this period. Methods: Cases of iGAS, IPD, and I-CO-SA infections were identified prospectively and retrospectively at 2 large US children's hospitals by positive cultures from July 2018 through December 2022. Admission data were used to estimate frequency. For comparison, rates of respiratory syncytial virus (RSV), influenza, and SARS-CoV-2 were estimated by the number of positive viral test results at each institution. Results: I-CO-SA infections showed little variation in the study period. Rates of iGAS infection and IPD decreased by 46% and 44%, respectively, from 2019 to 2020, coinciding with a substantial decrease in RSV and influenza. In 2022, RSV and influenza infection rates increased to prepandemic winter season rates, coinciding with a return to prepandemic rates of IPD (225% increase from 2021 to 2022) and a surge above prepandemic rates of iGAS infections (543% increase from 2021 to 2022). Conclusions: The COVID-19 pandemic had an unexpected influence on IPD and iGAS infections that was temporally related to changes in rates of viral infections.
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The cytokine IL-10 suppresses T-cell-mediated immunity, which is required to control infection with Plasmodium yoelii. Consequently, IL-10 can delay the time needed to resolve this infection, leading to a higher parasite burden. While the pathways that lead to IL-10 production by CD4+ T cells are well defined, much less is known about the mediators that suppress the expression of this potent anti-inflammatory cytokine. Here, we show that the transcription factor basic helix-loop-helix family member e40 (Bhlhe40) contributes to controlling parasite burden in response to P. yoelii infection in mice. Loss of Bhlhe40 expression in mice results in higher Il10 expression, higher peak parasitemia, and a delay in parasite clearance. The observed phenotype was not due to defects in T-cell activation and proliferation or the humoral response. Nor was it due to changes in regulatory T-cell numbers. However, blocking IL-10 signaling reversed the outcome in Bhlhe40-/ - mice, suggesting that excess IL-10 production limits their ability to control the infection properly. In addition to suppressing Il10 expression in CD4+ T cells, Bhlhe40 can promote Ifng expression. Indeed, IFN-γ production by CD4+ T cells isolated from the liver was significantly affected by the loss of Bhlhe40. Lastly, Bhlhe40 deletion in T cells resulted in a phenotype similar to that observed in the Bhlhe40-/ - mice, indicating that Bhlhe40 expression in T cells contributes to the ability of mice to control infection with P. yoelii.
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Interleucina-10 , Plasmodium yoelii , Ratones , Animales , Citocinas , Interferón gamma , Linfocitos T Reguladores/metabolismo , Ratones Endogámicos C57BL , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genéticaRESUMEN
BACKGROUND: Acute hematogenous osteomyelitis (AHO) can be associated with severe complications which can be difficult to predict in the clinical setting. The previously published predictive acute complication score ("A-SCORE") and chronic complication score ("C-SCORE") show promise, however, further external validation is needed. METHODS: We performed a retrospective study of 418 children with AHO and analyzed the performance of A-SCORE (variables included bone abscess, fever after 48 h of starting antibiotics, suppurative arthritis, disseminated disease, and delayed source control) to predict risk for acute complicated course (treatment failure, prolonged admission, and/or need for ≥2 bone debridements) and C-SCORE (includes disseminated disease, bone debridement, and CRP ≥10 mg/dL at 2-4 days after starting antibiotics) to predict chronic complications (growth restriction, pathologic fracture, chronic osteomyelitis, avascular necrosis, joint deformity, and/or frozen joint). RESULTS: An acute complicated course occurred in 106/418 (25.4%); 51/380 (13.5%) with complete follow-up data had a chronic complication. The A-SCORE performed with similar specificity (78%) and negative predictive value (NPV) (92%), and higher sensitivity (81%) and increased area under the receiver operating curve (AUC) (0.87) in our population. The C-SCORE performed with similar sensitivity (64%) and NPV (94%) but had lower specificity (86%) and AUC (0.71) than originally reported. Other variables associated with development of complications such as tibia involvement and bacteremia ≥2 days were identified but did not result in significantly improved predictive scores. CONCLUSIONS: Predictive A-SCORE and C-SCORE for AHO complications in children may help guide acute management and long-term follow-up decisions. Prospective studies are needed to determine their applicability.
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Bacteriemia , Osteomielitis , Niño , Humanos , Estudios Retrospectivos , Bacteriemia/complicaciones , Bacteriemia/tratamiento farmacológico , Osteomielitis/complicaciones , Osteomielitis/tratamiento farmacológico , Enfermedad Aguda , Antibacterianos/uso terapéuticoRESUMEN
Many health care centers have reported an association between Staphylococcus aureus isolates bearing efflux pump genes and an elevated MIC/minimal bactericidal concentration (MBC) to chlorhexidine gluconate (CHG) and other antiseptics. The significance of these organisms is uncertain, given that their MIC/MBC is typically far lower than the CHG concentration in most commercial preparations. We sought to evaluate the relationship between carriage of the efflux pump genes qacA/B and smr in S. aureus and the efficacy of CHG-based antisepsis in a venous catheter disinfection model. S. aureus isolates with and without smr and/or qacA/B were utilized. The CHG MICs were determined. Venous catheter hubs were inoculated and exposed to CHG, isopropanol, and CHG-isopropanol combinations. The microbiocidal effect was calculated as the percent reduction in CFU following exposure to the antiseptic relative to the control. The qacA/B- and smr-positive isolates had modest elevations in the CHG MIC90 compared to the qacA/B- and smr-negative isolates (0.125 mcg/ml vs. 0.06 mcg/ml, respectively). However, the CHG microbiocidal effect was significantly lower for qacA/B- and/or smr-positive strains than for susceptible isolates, even when the isolates were exposed to CHG concentrations up to 400 µg/mL (0.04%); this finding was most notable for isolates bearing both qacA/B and smr (89.3% versus 99.9% for the qacA/B- and smr-negative isolates; P = 0.04). Reductions in the median microbiocidal effect were also observed when these qacA/B- and smr-positive isolates were exposed to a solution of 400 µg/mL (0.04%) CHG and 70% isopropanol (89.5% versus 100% for the qacA/B- and smr-negative isolates; P = 0.002). qacA/B- and smr-positive S. aureus isolates have a survival advantage in the presence of CHG concentrations exceeding the MIC. These data suggest that traditional MIC/MBC testing may underestimate the ability of these organisms to resist the effects of CHG. IMPORTANCE Antiseptic agents, including chlorhexidine gluconate (CHG), are commonly utilized in the health care environment to reduce rates of health care-associated infections. A number of efflux pump genes, including smr and qacA/B, have been reported in Staphylococcus aureus isolates that are associated with higher MICs and minimum bactericidal concentrations (MBCs) to CHG. Several health care centers have reported an increase in the prevalence of these S. aureus strains following an escalation of CHG use in the hospital environment. The clinical significance of these organisms, however, is uncertain, given that the CHG MIC/MBC is far below the concentration in commercial preparations. We present the results of a novel surface disinfection assay utilizing venous catheter hubs. We found that qacA/B-positive and smr-positive S. aureus isolates resist killing by CHG at concentrations far exceeding the MIC/MBC in our model. These findings highlight that traditional MIC/MBC testing is insufficient to evaluate susceptibility to antimicrobials acting on medical devices.
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Advanced urothelial carcinoma continues to have a dismal prognosis despite several new therapies in the last 5 years. FGFR2 and FGFR3 mutations and fusions, PD-L1 expression, tumor mutational burden, and microsatellite instability are established predictive biomarkers in advanced urothelial carcinoma. Novel biomarkers can optimize the sequencing of available treatments and improve outcomes. We describe herein the clinical and pathologic features of patients with an emerging subtype of bladder cancer characterized by deletion of the gene MTAP encoding the enzyme S-Methyl-5'-thioadenosine phosphatase, a potential biomarker of response to pemetrexed. We performed a retrospective analysis of 61 patients with advanced urothelial carcinoma for whom demographics, pathologic specimens, next generation sequencing, and clinical outcomes were available. We compared the frequency of histology variants, upper tract location, pathogenic gene variants, tumor response, progression free survival (PFS) and overall survival (OS) between patients with tumors harboring MTAP deletion (MTAP-del) and wild type tumors (MTAP-WT). A propensity score matching of 5 covariates (age, gender, presence of variant histology, prior surgery, and prior non-muscle invasive bladder cancer) was calculated to compensate for disparity when comparing survival in these subgroups. Non-supervised clustering analysis of differentially expressed genes between MTAP-del and MTAP-WT urothelial carcinomas was performed. MTAP-del occurred in 19 patients (31%). Tumors with MTAP-del were characterized by higher prevalence of squamous differentiation (47.4 vs 11.9%), bone metastases (52.6 vs 23.5%) and lower frequency of upper urinary tract location (5.2% vs 26.1%). Pathway gene set enrichment analysis showed that among the genes upregulated in the MTAP-del cohort, at least 5 were linked to keratinization (FOXN1, KRT33A/B, KRT84, RPTN) possibly contributing to the higher prevalence of squamous differentiation. Alterations in the PIK3 and MAPK pathways were more frequent when MTAP was deleted. There was a trend to inferior response to chemotherapy among MTAP-del tumors, but no difference in the response to immune checkpoint inhibitors or enfortumab. Median progression free survival after first line therapy (PFS1) was 5.5 months for patients with MTAP-WT and 4.5 months for patients with MTAP-del (HR = 1.30; 95% CI, 0.64-2.63; P = 0.471). There was no difference in the time from metastatic diagnosis to death (P = 0.6346). Median OS from diagnosis of localized or de novo metastatic disease was 16 months (range 1.5-60, IQR 8-26) for patients with MTAP-del and 24.5 months (range 3-156, IQR 16-48) for patients with MTAP-WT (P = 0.0218), suggesting that time to progression to metastatic disease is shorter in MTAP-del patients. Covariates did not impact significantly overall survival on propensity score matching. In conclusion, MTAP -del occurs in approximately 30% of patients with advanced urothelial carcinoma and defines a subgroup of patients with aggressive features, such as squamous differentiation, frequent bone metastases, poor response to chemotherapy, and shorter time to progression to metastatic disease.
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BACKGROUND: Acute hematogenous osteomyelitis (AHO) is a serious infection in children. Pediatric Infectious Diseases Society guidelines recommend empiric methicillin-resistant Staphylococcus aureus (MRSA) therapy in regions where MRSA accounts for more than 10-20% of all staphylococcal osteomyelitis. We sought to examine factors present at the time of admission which may predict etiology and guide empiric treatment for pediatric AHO in a region with endemic MRSA. METHODS: We reviewed admissions with International Classification of Diseases 9/10 codes for AHO from 2011 to 2020 in otherwise healthy children. Medical records were reviewed for clinical and laboratory parameters present on the day of admission. Logistic regression was used to determine clinical variables independently associated with (1) MRSA infection and (2) non- Staphylococcus aureus infection. RESULTS: A total of 545 cases were included. An organism was identified in 77.1% of cases and S. aureus was the most common (66.2%); 18.9% of all AHO cases were MRSA. Organisms besides S. aureus were identified in 10.8% of cases. CRP >7 mg/dL, subperiosteal abscess, history of any prior skin or soft tissue infection (SSTI) and need for intensive care unit admission were independently associated with MRSA infection. Vancomycin was used as an empiric treatment in 57.6% of cases. If the above criteria were relied upon to predict MRSA AHO, empiric vancomycin use could have been reduced by 25%. CONCLUSIONS: Critical illness, CRP >7 mg/dL at the time of presentation, subperiosteal abscess and history of SSTI are suggestive of MRSA AHO, and could be considered when planning empiric therapy. Further work is needed to validate these findings before wider implementation.
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Antiinfecciosos , Staphylococcus aureus Resistente a Meticilina , Osteomielitis , Infecciones de los Tejidos Blandos , Infecciones Estafilocócicas , Niño , Humanos , Vancomicina/uso terapéutico , Staphylococcus aureus , Antibacterianos/uso terapéutico , Absceso/tratamiento farmacológico , Antiinfecciosos/uso terapéutico , Osteomielitis/tratamiento farmacológico , Osteomielitis/epidemiología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Enfermedad Aguda , Estudios RetrospectivosRESUMEN
BACKGROUND: Patients with bladder cancer (BC) who are cisplatin ineligible or have unresectable disease have limited treatment options. Previously, we showed targeting programmed death-ligand 1 (PD-L1) with durvalumab (durva) and radiation therapy (RT) combination was safe in BC. We now report results from a phase II study evaluating the toxicity and efficacy of durva and RT in localized BC. METHODS: This is a single-arm, multi-institutional phase II study; N=26. Enrolled patients had pure or mixed urothelial BC (T2-4 N0-2 M0) with unresectable tumors and were unfit for surgery or cisplatin ineligible. Patients received durva concurrently with RT ×7 weeks, followed by adjuvant durva × 1 year. PRIMARY ENDPOINTS: (A) progression-free survival (PFS) at 1 year and (B) disease control rate (DCR) post adjuvant durva. Key secondary endpoints: (A) complete response (CR) post durvaRT (8 weeks), (B) overall survival (OS), (C) PFS and (D) toxicity. Correlative studies included evaluation of baseline tumor and blood (baseline, post durvaRT) for biomarkers. RESULTS: Median follow-up was 27 months. Evaluable patients: 24/26 post durvaRT, 22/26 for DCR post adjuvant durva, all patients for PFS and OS. Post adjuvant durva, DCR was seen in 72.7%, CR of 54.5%. 1-year PFS was 71.5%, median PFS was 21.8 months. 1-year OS was 83.8%, median OS was 30.8 months. CR at 8 weeks post durvaRT was 62.5%. Node positive (N+) patients had similar median PFS and OS. DurvaRT was well tolerated. Grade ≥3 treatment-related adverse events: anemia, high lipase/amylase, immune-nephritis, transaminitis, dyspnea (grade 4-COPD/immune), fatigue, rash, diarrhea and scleritis. No difference in outcome was observed with PD-L1 status of baseline tumor. Patients with CR/PR or SD had an increase in naïve CD4 T cells, a decrease in PD-1+CD4 T cells at baseline and an increase in cytokine-producing CD8 T cells, including interferon gamma (IFNγ) producing cells, in the peripheral blood. CONCLUSION: Durva with RT followed by adjuvant durva was safe with promising efficacy in localized BC patients with comorbidities, including N+ patients. Larger randomized studies, like S1806 and EA8185, are needed to evaluate the efficacy of combining immunotherapy and RT in BC. TRIAL REGISTRATION NUMBER: NCT02891161.
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Anticuerpos Monoclonales , Antígeno B7-H1 , Neoplasias de la Vejiga Urinaria , Humanos , Anticuerpos Monoclonales/uso terapéutico , Cisplatino , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
In the late 1940s to 1950s, Staphylococcus aureus isolates first-gained resistance to penicillin. Recently, some centers have described an increase in the proportion of methicillin susceptible S. aureus (MSSA) which are also susceptible to penicillin (PSSA). There are little data on the frequency of PSSA infections in children. We investigated the prevalence of penicillin susceptibility among pediatric MSSA acute hematogenous osteoarticular infection (OAI) isolates. MSSA OAI isolates were obtained through surveillance studies at Texas Children's and St. Louis Children's Hospitals from January 2011 to December 2019. All isolates underwent PCR for blaZ ß-lactamase, PVL genes and agr group. All blaZ negative isolates then underwent penicillin MIC determination. blaZ negative isolates with penicillin MIC ≤ 0.125 µg/mL were considered PSSA. Multilocus sequence typing (MLST) was conducted on a subset of isolates. A total of 329 unique isolates were included in the study. The median patient age was 9.2 years (IQR:5.1 to 12.2). Overall, 6.7% of isolates were penicillin susceptible. No PSSA were detected prior to 2015 but increased yearly thereafter. By the final study year, 20.4% of isolates were PSSA (P = 0.001). PSSA were similar to penicillin-resistant MSSA (PR-MSSA) isolates in terms agr group and PVL carriage as well as clinical presentation and outcomes. PSSA were of distinct sequence types compared to PR-MSSA. PSSA appears to be increasing among OAI in U.S. children. Overall, PSSA isolates are associated with a similar clinical presentation as penicillin-resistant isolates. The potential for use of penicillin treatment in PSSA OAI warrants further study.
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Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Niño , Preescolar , Staphylococcus aureus/genética , Meticilina/farmacología , Meticilina/uso terapéutico , Penicilinas/farmacología , Penicilinas/uso terapéutico , Tipificación de Secuencias Multilocus , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/epidemiología , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Staphylococcus aureus Resistente a Meticilina/genéticaRESUMEN
BACKGROUND: Parenteral penicillin G (PENG) and oral amoxicillin (AMOX) are recommended as treatment for pediatric community-acquired pneumonia (CAP). With recent epidemiologic penicillin susceptibility data for Streptococcus pneumoniae, the most common etiology of CAP, the objective of this study was to evaluate optimal dosing regimens of PENG and AMOX based on population pharmacokinetics linked to current susceptibility data. METHODS: Using NONMEM v7.3, Monte Carlo simulations (N = 10,000) were conducted for AMOX 15 mg/kg/dose PO every 8 h (standard-dose), AMOX 45 mg/kg/dose PO every 12 h (high-dose), and PENG 62,500 units/kg/day IV every 6 h using six virtual subjects with ages spanning 3 months to 15 years old. The probability of target attainment (PTA) was determined for both serum and epithelial lining fluid (ELF) to achieve free drug concentrations above the minimum inhibitory concentration (%fT>MIC) across the population of pneumococci for 30%-50% of the dosing interval. RESULTS: In 2018, all 21 (100%) pneumococcal isolates were susceptible to both PENG and AMOX based on Clinical and Laboratory Standards Institute (CLSI; MIC at 2 mg/L) breakpoints, and 15 of 21 (71%) were susceptible based on EUCAST (MIC at 0.5 mg/L) breakpoints. As compared to CLSI, EUCAST breakpoints consistently achieved higher PTA for all antibiotic regimens. At 50% fT>MIC in the serum at the susceptible MICs, standard-dose AMOX achieved >4% PTA (CLSI) and >86% PTA (EUCAST); high-dose AMOX achieved >73% PTA (CLSI) and >99% PTA (EUCAST); and PENG achieved 0% PTA (using CLSI) and 100% PTA (using EUCAST). Standard-dose AMOX, high-dose AMOX, and PENG achieved >71%, >93%, and 100% PTA, respectively, in the serum at 30%-50% fT>MIC when each patient was stochastically linked to an MIC based on the frequency distribution of national susceptibility data. The PTA was consistently lower in ELF as compared with serum for all regimens. CONCLUSION: Based on the recent rates of resistance, antibiotic doses evaluated provide appropriate exposure for pediatric CAP based on the serum and ELF data associated with predicted clinical and microbiologic success for pneumococcus. High-dose AMOX may still be required to treat pediatric CAP, especially if using CLSI breakpoints. Ongoing surveillance for resistance is essential.
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Bacteriemia , Enfermedades Transmisibles , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Niño , Staphylococcus aureus , Bacteriemia/diagnóstico , Bacteriemia/tratamiento farmacológico , Derivación y Consulta , Calidad de la Atención de Salud , Infecciones Estafilocócicas/tratamiento farmacológico , Antibacterianos/uso terapéutico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Ceftaroline represents an attractive therapy option for methicillin-resistant Staphylococcus aureus (MRSA). Little data is available, however, regarding the frequency of reduced susceptibility (RS) to ceftaroline among pediatric MRSA infections. We screened invasive MRSA isolates at a tertiary children's hospital for ceftaroline RS. Ceftaroline RS occurred in 2.9% of isolates and only among health care associated infections. Ceftaroline RS isolates were more often clindamycin-resistant. Sequencing data indicated the predominance of the CC5 lineage among ceftaroline RS isolates.
Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Niño , Staphylococcus aureus Resistente a Meticilina/genética , Clindamicina , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Cefalosporinas/farmacología , Cefalosporinas/uso terapéutico , Genómica , Infecciones Estafilocócicas/tratamiento farmacológico , CeftarolinaRESUMEN
As research on race and racism in the USA has suggested that it now takes a more subtle and neoliberal form, one of the areas in which race and racism are most explicit is in dating and sex. When finding dating and sexual partners, people tend to be explicit about their rejection of potential mates along racial lines while claiming that these preferences have no connection with racism. Callander et al.'s (2015) study was the first to provide the evidence that these expressions of sexual racism, or race-based rejections of partners in sexual contexts, were in fact related to cultural racism perpetuated in society at large. Despite all of this, the study has never been replicated. We aimed to partially replicate the study in the USA, using a sample of 616 gay, bisexual, and heterosexual men. Using the Quick Discrimination Index and online sexual racism surveys referenced in the original paper, we find a correlation of - 0.129, between the two measures. This suggests that respondents who demonstrate more openness and less racist beliefs in general are also less likely to be accepting of forms of online sexual racism, a finding that is consistent with prior research. Still, the correlation between these measures is not nearly as strong as that observed in Australia in the original paper (- 0.56), raising questions that require further exploration.