Adjunctive Diagnostic Studies Completed Following Detection of Candidemia in Children: Secondary Analysis of Observed Practice From a Multicenter Cohort Study Conducted by the Pediatric Fungal Network.

BACKGROUND: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown. METHODS: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days to 17 years with invasive candidiasis (predominantly candidemia) from 2014 to 2017. Ophthalmologic examination (OE), abdominal imaging (AbdImg), echocardiogram, neuroimaging, and lumbar puncture (LP) were performed per clinician discretion. Adjunctive diagnostic studies performance and positive results were determined per episode, within 30 days from candidemia onset. Associations of aDS performance with episode characteristics were evaluated via mixed-effects logistic regression. RESULTS: In 662 pediatric candidemia episodes, 490 (74%) underwent AbdImg, 450 (68%) OE, 426 (64%) echocardiogram, 160 (24%) neuroimaging, and 76 (11%) LP; performance of each aDS per episode varied across sites up to 16-fold. Longer durations of candidemia were associated with undergoing OE, AbdImg, and echocardiogram. Immunocompromised status (58% of episodes) was associated with undergoing AbdImg (adjusted odds ratio [aOR] 2.38; 95% confidence intervals [95% CI] 1.51-3.74). Intensive care at candidemia onset (30% of episodes) was associated with undergoing echocardiogram (aOR 2.42; 95% CI 1.51-3.88). Among evaluated episodes, positive OE was reported in 15 (3%), AbdImg in 30 (6%), echocardiogram in 14 (3%), neuroimaging in 9 (6%), and LP in 3 (4%). CONCLUSIONS: Our findings show heterogeneity in practice, with some clinicians performing aDS selectively, potentially influenced by clinical factors. The low frequency of positive results suggests that targeted application of aDS is warranted.

AN 8-YEAR-OLD CALIFORNIA GIRL WITH ASYMPTOMATIC HEPATIC CYSTS.

Echinococcus infections are rare in the United States but may present a growing public health threat. We present the case of an 8-year-old female patient from Southern California who was diagnosed with hepatic echinococcosis after the incidental discovery of large hepatic cysts.

Multicenter Prospective Study of Biomarkers for Diagnosis of Invasive Candidiasis in Children and Adolescents.

BACKGROUND: Diagnosis of invasive candidiasis (IC) relies on insensitive cultures; the relative utility of fungal biomarkers in children is unclear. METHODS: This multinational observational cohort study enrolled patients aged >120 days and <18 years with concern for IC from 1 January 2015 to 26 September 2019 at 25 centers. Blood collected at onset of symptoms was tested using T2Candida, Fungitell (1→3)-ß-D-glucan, Platelia Candida Antigen (Ag) Plus, and Platelia Candida Antibody (Ab) Plus assays. Operating characteristics were determined for each biomarker, and assays meeting a defined threshold considered in combination. Sterile site cultures were the reference standard. RESULTS: Five hundred participants were enrolled at 22 centers in 3 countries, and IC was diagnosed in 13 (2.6%). Thirteen additional blood specimens were collected and successfully spiked with Candida species, to achieve a 5.0% event rate. Valid T2Candida, Fungitell, Platelia Candida Ag Plus, and Platelia Candida Ab Plus assay results were available for 438, 467, 473, and 473 specimens, respectively. Operating characteristics for T2Candida were most optimal for detecting IC due to any Candida species, with results as follows: sensitivity, 80.0% (95% confidence interval, 59.3%-93.2%), specificity 97.1% (95.0%-98.5%), positive predictive value, 62.5% (43.7%-78.9%), and negative predictive value, 98.8% (97.2%-99.6%). Only T2Candida and Platelia Candida Ag Plus assays met the threshold for combination testing. Positive result for either yielded the following results: sensitivity, 86.4% (95% confidence interval, 65.1%- 97.1%); specificity, 94.7% (92.0%-96.7%); positive predictive value, 47.5% (31.5%-63.9%); and negative predictive value, 99.2% (97.7%-99.8%). CONCLUSIONS: T2Candida alone or in combination with Platelia Candida Ag Plus may be beneficial for rapid detection of Candida species in children with concern for IC. CLINICAL TRIALS REGISTRATION: NCT02220790.

Pediatric Osteoarticular Infections Caused by Mycobacteria Tuberculosis Complex: A 26-Year Review of Cases in San Diego, CA.

BACKGROUND: Osteoarticular infections (OAIs) account for 10%-20% of extrapulmonary Mycobacteria tuberculosis (MTB) complex infections in children and 1%-2% of all pediatric tuberculosis infections. Treatment regimens and durations typically mirror recommendations for other types of extrapulmonary MTB, but there are significant variations in practice, with some experts suggesting a treatment course of 12 months or longer. METHODS: We conducted a retrospective review of children diagnosed with MTB complex OAI and cared for between December 31, 1992, and December 31, 2018, at a tertiary care pediatric hospital near the United States-Mexico border. RESULTS: We identified 21 children with MTB complex OAI during the study period. Concurrent pulmonary disease (9.5%), meningitis (9.5%), and intra-abdominal involvement (14.3%) were all observed. MTB complex was identified by culture from operative samples in 15/21 children (71.4%); 8/15 (53.3%) cultures were positive for Mycobacterium bovis. Open bone biopsy was the most common procedure for procurement of a tissue sample and had the highest culture yield. The median duration of antimicrobial therapy was 52 weeks (interquartile range, 46-58). Successful completion of therapy was documented in 15 children (71.4%). Nine children (42.9%) experienced long-term sequelae related to their infection. CONCLUSION: Among the 21 children with MTB complex OAI assessed, 8 of 15 (53.3%) children with a positive tissue culture had M. bovis, representing a higher percentage than in previous reports and potentially reflecting its presence in unpasteurized dairy products in the California-Baja region. Bone biopsy produced the highest culture yield in this study. Given the rarity of this disease, multicenter collaborative studies are needed to improve our understanding of the presentation and management of pediatric MTB complex OAI.

Comparison of RT-PCR Cycle Threshold Values from Respiratory Specimens in Symptomatic and Asymptomatic Children with SARS-CoV-2 Infection.

BACKGROUND: Understanding viral kinetics of SARS-CoV-2 is important to assess risk of transmission, manage treatment, and determine the need for isolation and protective equipment. The impact of viral load in asymptomatic infected children is important to understand transmission potential. We sought to determine whether children deemed to be asymptomatic had a difference in the PCR cycle threshold (Ct) value of respiratory samples from symptomatic children with SARS-CoV-2 infection. METHODS: This was a retrospective cross-sectional study to compare PCR Ct values of children who tested positive for SARS-CoV-2 by respiratory samples collected over a 4-month period at a large tertiary care children's hospital. RESULTS: We analyzed 728 children who tested positive for SARS-CoV-2 by RT-PCR from a respiratory sample over a 4-month period and for whom data was available in the electronic medical record. Overall, 71.2% of infected children were symptomatic. The mean Ct value for symptomatic patients (Ct mean 19.9, SD 6.3) was significantly lower than asymptomatic patients (Ct mean 23.5, SD 6.5) (P value < 0.001, CI 95th 2.6 - 4.6). The mean PCR Ct value was lowest in children less than 5 years of age. CONCLUSIONS: In this retrospective review of children who tested positive by RT-PCR for SARS CoV-2, the mean Ct was significantly lower in symptomatic children and was lowest in children under 5 years of age, indicating that symptomatic children and younger children infected with SARS-CoV-2 may have a higher viral load in the nasopharynx compared to asymptomatic children. Further studies are needed to assess the transmission potential from asymptomatic children.

Comparative Effectiveness of Echinocandins vs Triazoles or Amphotericin B Formulations as Initial Directed Therapy for Invasive Candidiasis in Children and Adolescents.

BACKGROUND: Invasive candidiasis is the most common invasive fungal disease in children and adolescents, but there are limited pediatric-specific antifungal effectiveness data. We compared the effectiveness of echinocandins to triazoles or amphotericin B formulations (triazole/amphotericin B) as initial directed therapy for invasive candidiasis. METHODS: This multinational observational cohort study enrolled patients aged >120 days and <18 years with proven invasive candidiasis from January 1, 2014, to November 28, 2017, at 43 International Pediatric Fungal Network sites. Primary exposure was initial directed therapy administered at the time qualifying culture became positive for yeast. Exposure groups were categorized by receipt of an echinocandin vs receipt of triazole/amphotericin B. Primary outcome was global response at 14 days following invasive candidiasis onset, adjudicated by a centralized data review committee. Stratified Mantel-Haenszel analyses estimated risk difference between exposure groups. RESULTS: Seven-hundred and fifty invasive candidiasis episodes were identified. After exclusions, 541 participants (235 in the echinocandin group and 306 in the triazole/amphotericin B group) remained. Crude failure rates at 14 days for echinocandin and triazole/amphotericin B groups were 9.8% (95% confidence intervals [CI]: 6.0% to 13.6%) and 13.1% (95% CI: 9.3% to 16.8%), respectively. The adjusted 14-day risk difference between echinocandin and triazole/amphotericin B groups was -7.1% points (95% CI: -13.1% to -2.4%), favoring echinocandins. The risk difference was -0.4% (95% CI: -7.5% to 6.7%) at 30 days. CONCLUSIONS: In children with invasive candidiasis, initial directed therapy with an echinocandin was associated with reduced failure rate at 14 days but not 30 days. These results may support echinocandins as initial directed therapy for invasive candidiasis in children and adolescents. CLINICAL TRIALS REGISTRATION: NCT01869829.

Comparison of Reverse-Transcription Polymerase Chain Reaction Cycle Threshold Values From Respiratory Specimens in Symptomatic and Asymptomatic Children With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: Understanding viral kinetics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important to assess risk of transmission, manage treatment, and determine the need for isolation and protective equipment. The impact of viral load in asymptomatic infected children is important to understand transmission potential. We sought to determine whether children deemed to be asymptomatic had a difference in the polymerase chain reaction (PCR) cycle threshold (Ct) value of respiratory samples from symptomatic children with SARS-CoV-2 infection. METHODS: This was a retrospective cross-sectional study to compare PCR Ct values of children who tested positive for SARS-CoV-2 by respiratory samples collected over a 4-month period at a large tertiary care children's hospital. RESULTS: We analyzed 728 children who tested positive for SARS-CoV-2 by reverse-transcription PCR (RT-PCR) from a respiratory sample over a 4-month period and for whom data were available in the electronic medical record. Overall, 71.2% of infected children were symptomatic. The mean Ct value for symptomatic patients (Ct mean, 19.9 [standard deviation, 6.3]) was significantly lower than for asymptomatic patients (Ct mean, 23.5 [standard deviation, 6.9]) (P < .001; 95% confidence interval, 2.6-4.6). The mean PCR Ct value was lowest in children <5 years of age. CONCLUSIONS: In this retrospective review of children who tested positive by RT-PCR for SARS-CoV-2, the mean Ct was significantly lower in symptomatic children and was lowest in children <5 years of age, indicating that symptomatic children and younger children infected with SARS-CoV-2 may have a higher viral load in the nasopharynx compared to asymptomatic children. Further studies are needed to assess the transmission potential from asymptomatic children.

Clinical application of cell-free next-generation sequencing for infectious diseases at a tertiary children's hospital.

BACKGROUND: Children affected by infectious diseases may not always have a detectable infectious etiology. Diagnostic uncertainty can lead to prolonged hospitalizations, inappropriately broad or extended courses of antibiotics, invasive diagnostic procedures, and difficulty predicting the clinical course and outcome. Cell-free plasma next-generation sequencing (cfNGS) can identify viral, bacterial, and fungal infections by detecting pathogen DNA in peripheral blood. This testing modality offers the ability to test for many organisms at once in a shotgun metagenomic approach with a rapid turnaround time. We sought to compare the results of cfNGS to conventional diagnostic test results and describe the impact of cfNGS on clinical care in a diverse pediatric population at a large academic children's hospital. METHODS: We performed a retrospective chart review of hospitalized subjects at a tertiary pediatric hospital to determine the diagnostic yield of cfNGS and its impact on clinical care. RESULTS: We describe the clinical application of results from 142 cfNGS tests in the management of 110 subjects over an 8-month study period. In comparison to conventional testing as a reference standard, cfNGS was found to have a positive percent agreement of 89.6% and negative percent agreement of 52.3%. Furthermore, 32.4% of cfNGS results were directly applied to make a clinical change in management. CONCLUSIONS: We demonstrate the clinically utility of cfNGS in the management of acutely ill children. Future studies, both retrospective and prospective, are needed to clarify the optimal indications for testing.

Use of Plasma Metagenomic Next-generation Sequencing for Pathogen Identification in Pediatric Endocarditis.

Pediatric infective endocarditis incurs significant morbidity and generally occurs among children with underlying heart disease. Identification of a pathogen is critical in determining appropriate therapy. However, standard diagnostic testing has limited sensitivity. We describe a case series of children with infective endocarditis in whom plasma next-generation sequencing (Karius, Redwood, CA) identified an organism in 8 of 10 cases.

Use of whole-genome sequencing to detect an outbreak of Malassezia pachydermatis infection and colonization in a neonatal intensive care unit-California, 2015-2016.

Whole-genome sequencing confirmed the presence of a Malassezia pachydermatis outbreak among neonates in a neonatal intensive care unit. This technology supports the importance of adhering to infection prevention measures.

Management and outcomes of pediatric septic thrombophlebitis: a case series.

Septic thrombophlebitis is a potentially life-threatening condition. Pediatric hematologists are often consulted to provide recommendations regarding anticoagulation management. We conducted a ten-year retrospective, single-center study of hospitalized pediatric patients who were treated for septic thrombophlebitis. Our primary outcome was resolution of thrombophlebitis. Twenty-eight patients were included in the study. Eighty-nine percent of patients received both antibiotic and anticoagulation therapy. The median durations of intravenous and total antibiotic therapy were 47.5 days (range 14-120) and 65 days (range 14-281), respectively, and median duration of anticoagulation therapy was 92 days (range 41-268). Resolution of thrombosis defined by magnetic resonance imaging, computed tomography, or ultrasound imaging was documented in 16 of 28 (57%) patients. Despite the high rate of persistent thrombosis, there was a low risk of relapse of infection in cases where antibiotic and/or anticoagulation was discontinued prior to complete resolution of the thrombus. Further research is needed to determine if duration of antibiotic and/or anticoagulation treatment can be shortened.

Community-acquired pneumonia in children: cell-free plasma sequencing for diagnosis and management.

Community-acquired pneumonia (CAP) is a common cause of pediatric hospital admission. Empiric antibiotic therapy for hospitalized children with serious CAP now targets the most likely pathogen(s), including those that may demonstrate significant antibiotic resistance. Cell-free plasma next-generation sequencing (CFPNGS) was first made available for Pediatric Infectious Diseases physicians in June 1, 2017, to supplement standard-of-care diagnostic techniques. A retrospective chart review was performed for children hospitalized with CAP between June 1, 2017, and January 22, 2018, to evaluate the impact of CFPNGS. We identified 15 hospitalized children with CAP without other underlying medical conditions for whom CFPNGS was performed. CFPNGS identified a pathogen in 13 of 15 (86%) children compared with 47% for those using standard culture and PCR-based methods alone. Changes in antibiotic management were made in 7 of 15 (47%) of children as a result of CFPNGS.

Visitor restriction policies and practices in children's hospitals in North America: results of an Emerging Infections Network Survey.

OBJECTIVE: To delineate the timing of, indications for, and assessment of visitor restriction policies and practices (VRPP) in pediatric facilities. DESIGN: An electronic survey to characterize VRPP in pediatric healthcare facilities. METHODS: The Infectious Diseases Society of America Emerging Infections Network surveyed 334 pediatric infectious disease consultants via an electronic link. Descriptive analyses were performed. RESULTS: A total of 170 eligible respondents completed a survey between 12 July and August 15, 2016, for a 51% response rate. Of the 104 respondents (61%) familiar with their VRPP, 92 (88%) had VRPP in all inpatient units. The respondents reported age-based VRPP (74%) symptom-based VRPP (97%), and outbreak-specific VRPP (75%). Symptom-based VRPP were reported to be seasonal by 24% of respondents and to be implemented year-round according to 70% of respondents. According to the respondents, communication of VRPP to families occurred at admission (87%) and through signage in care areas (64%), while communication of VRPP to staff occurred by email (77%), by meetings (55%), and by signage in staff-only areas (49%). Respondents reported that enforcement of VRPP was the responsibility of nursing (80%), registration clerks (58%), unit clerks (53%), the infection prevention team (31%), or clinicians 16 (16%). They also reported that the effectiveness of VRPP was assessed through active surveillance of hospital acquired respiratory infections (62%), through active surveillance of healthcare worker exposures (28%) and through patient/family satisfaction assessments (29%). CONCLUSION: Visitor restriction policies and practices vary in scope, implementation, enforcement, and physician awareness in pediatric facilities. A prospective multisite evaluation of outcomes would facilitate the adoption of uniform guidance.

Multimodal Treatment of Rhinocerebral Mucormycosis in a Pediatric Patient With Relapsed Pre-B Acute Lymphoblastic Leukemia.

A 17-year-old girl developed invasive rhinocerebral mucormycosis during intensive re-induction chemotherapy for relapsed pre-B acute lymphoblastic leukemia. Due to the high case fatality rate for invasive mucormycosis in profoundly immunosuppressed patients, an aggressive treatment regimen was pursued. In addition to the standard of care treatments with intravenous amphotericin and aggressive surgical debridements, she received intraventricular amphotericin to the brain via an Ommaya reservoir, hyperbaric oxygen treatments, filgrastim, intravenous immunoglobulin and antifungal in vitro synergy testing to allow for more targeted antifungal therapy with the addition of micafungin. After a 3-month treatment course, it was determined that her mucormycosis was under appropriate control, allowing her to continue treatment for her leukemia with hematopoietic stem cell transplant with a plan for continued intravenous antifungal therapy through engraftment.

Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats.

INTRODUCTION: Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. METHODS: Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 µL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). RESULTS: Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P < 0.001 for both) but there were no significant changes in cranial cross-sectional area (Spearman, P = 0.35), cortical gray matter stiffness (Spearman, P = 0.24) and caudate-putamen (Spearman, P = 0.11) stiffness. No significant changes in the size of brain structures were observed in the controls. CONCLUSIONS: This study showed that although brain tissue in the adult hydrocephalic rats was severely compressed, their brain tissue stiffness did not change significantly. These results are in contrast with our previous findings in juvenile hydrocephalic rats which had significantly less brain compression (as the brain circumference was able to stretch with the cranium due to the open skull sutures) and had a significant increase in caudate putamen stiffness. These results suggest that change in brain mechanical properties in hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus.

Longitudinal measurements of postnatal rat brain mechanical properties in-vivo.

Information on pediatric brain tissue mechanical properties and, more pertinently, how they change during postnatal development remains scarce despite its importance to investigate mechanisms of neural injury. The aim of this study is to determine whether brain mechanical properties change in-vivo during early postnatal development in a rat model. Rat brain viscoelastic properties were measured longitudinally in ten healthy Sprague Dawley rats at five different time points from postnatal week one to week six using magnetic resonance elastography at 800Hz. Myelination and cell density were assessed histologically at the same time points to understand how the underlying tissue microstructure may be associated with changes in mechanical properties at different brain regions. Longitudinal changes in each variable were assessed using a generalized linear model with pairwise comparisons of means between weeks. The brain shear modulus in the cortical gray matter at postnatal week one was 6.3±0.4kPa, and increased significantly from week one to week two (pairwise comparison, p<0.01), remained stable from week two to week four and decreased significantly by week six (pairwise comparison, p<0.001). In the deep gray matter, brain tissue stiffness at postnatal week one was 6.1±2.0kPa, and increased significantly from one to week four (pairwise comparison, p<0.05) before decreasing significantly by week six (pairwise comparison, p<0.001). Stiffness changes were not directly correlated to histological observations. These data suggest that brain tissue shear modulus initially increases during a period equivalent to early childhood, and then decreases during a period equivalent to adolescence.

Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus.

Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P < 0.001, for both), an alteration of the corpus callosum and periventricular white matter microstructure (CC+PVWM) and rearrangement of the cortical gray matter microstructure (P < 0.001, for both), while compression without gross microstructural alteration was evident in the caudate-putamen and ventral internal capsule (P < 0.001, for both). During hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P < 0.001), while a decrease in space was observed for the ventral internal capsule (P < 0.001). For the cortical gray matter, an increase in extracellular tissue water was significantly associated with a decrease in tissue stiffness (P = 0.001). To conclude, this study characterizes the temporal changes in tissue microstructure, water content and stiffness in different brain regions and their association with ventricular enlargement. In summary, whilst diffusion changes were larger and statistically significant for majority of the brain regions studied, the changes in mechanical properties were modest. Moreover, the effect of ventricular enlargement is not limited to the CC+PVWM and ventral internal capsule, the extent of microstructural changes vary between brain regions, and there is regional and temporal variation in brain tissue stiffness during hydrocephalus development.

Notes from the field: fatal rat-bite fever in a child - San Diego County, California, 2013.

In August 2013, the County of San Diego Health and Human Services Agency was notified of a fatal case of rat-bite fever (RBF) in a previously healthy male, aged 10 years, who owned pet rats. Two days before his death, the patient experienced rigors, fevers, vomiting, headaches, and leg pains. His physician noted a fever of 102.6°F (39.2ºC), documented a normal examination, diagnosed viral gastroenteritis, and prescribed anti-nausea medication. During the next 24 hours, the patient experienced vomiting and persistent fever. He was confused and weak before collapsing at home. Paramedics reported the patient was unresponsive and had dilated pupils; resuscitation was initiated in the field and was continued for >1 hour after arrival at the emergency department but was unsuccessful. A complete blood count performed during resuscitation revealed anemia (hemoglobin 10.0 g/dL [normal = 13.5-18.0 g/dL], thrombocytopenia (platelets 40,000/µL [normal = 140,000-440,000/µL]), leukocytosis (white blood cells 17,900 cells/µL [normal = 4,000-10,500/µL]) with 16% band neutrophils; the patient also had evidence of disseminated intravascular coagulation. No rash or skin breakdown was noted. Lung, liver, and epiglottis tissue collected postmortem was positive for Streptobacillus moniliformis DNA by polymerase chain reaction.