State-of-the-Art Review: Use of Antimicrobials at the End of Life.

Navigating antibiotics at the end of life is a challenge for infectious disease (ID) physicians who remain deeply committed to providing patient-centered care and engaging in shared decision making. ID physicians, who often see patients in both inpatient and outpatient settings and maintain continuity of care for patients with refractory or recurrent infections, are ideally situated to provide guidance that aligns with patients' goals and values. Complex communication skills, including navigating difficult emotions around end-of-life care, can be used to better direct shared decision making and assist with antibiotic stewardship.

Elucidating the Clinical Interpretation and Impact of a Positive Plasma Cell-Free DNA Metagenomics Test Result-A Single Center Retrospective Study.

BACKGROUND: The Karius Test (KT), a cell-free DNA metagenomic next-generation sequencing assay, has potential to improve diagnostic evaluation of infectious diseases. Published data describing clinical impact of positive KT results are limited. We attempt to elucidate the clinical interpretation and impact of positive KT results based on types and patterns of detected pathogens and patient characteristics. METHODS: All positive KT results from a single institution in 2022 were screened. Patients with results that met predefined categories were included for review by a panel of 3 infectious diseases physicians and one clinical microbiologist. Predefined categories included reports with fungal, parasitic, notable bacterial, notable viral pathogens, or polybacterial results (≥3 bacteria). Polybacterial results were further classified into patterns of microbiome detected. Clinical impact and its correlation with result or patient characteristics were explored. RESULTS: Ninety-two patients met the inclusion criteria, most were immunocompromised (73%). Positive KT results that met predefined categories had the following clinical impact: positive in 30.4%, negative in 2.2%, and none in 65.2%. Polybacterial results, especially interpreted as oral flora had lowest clinical impact (7.1% and 0.0%, respectively), while detection of parasites or notable bacterial pathogens had the highest clinical impact (100% and 77.8%, respectively). There was no correlation between patient characteristics and clinical impact. CONCLUSIONS: Among a cohort of largely immunocompromised patients, we were able to demonstrate clinical impact of specific KT result types and patterns but did not find correlation between patient characteristics and clinical impact. Our results should be confirmed in future larger cohorts.

Catheter-related Aspergillus Fungemia: Case Report and Literature Review.

BACKGROUND: Aspergillus fungemia is encountered infrequently in clinical practice, even in the setting of invasive and disseminated disease. Prolonged Aspergillus fungemia secondary to a central venous catheter is notably rarer. METHODS: We describe the case of a 13-year-old boy with Aspergillus fungemia in the setting of a central venous catheter who was found to have pulmonary aspergillosis upon evaluation. We reviewed the literature for published cases of catheter-related Aspergillus fungemia and summarized the findings. We also sought to differentiate true fungemia from pseudofungemia and explored the clinical significance of aspergillemia. RESULTS: We found 6 published cases of catheter-related Aspergillus fungemia in addition to the 1 discussed in this report. Based on the review of case findings, we propose an algorithm for an approach to a patient with a positive blood culture for Aspergillus spp. CONCLUSIONS: True aspergillemia is infrequent even in the setting of disseminated aspergillosis among immunocompromised patients and the presence of aspergillemia does not necessarily portend more severe clinical disease course. The management of aspergillemia should involve a determination of the possibility of contamination, and if deemed genuine, a thorough workup to define the extent of the disease process. Treatment durations should be based on tissue sites of involvement and could be shorter in the absence of tissue-invasive disease.

Correlation of Polymorphonuclear Cell Burden and Microbial Growth to the Inflammatory Cytokines in Tracheal Aspirates from Ventilated Preterm Infants.

OBJECTIVE: The significance of the presence of microorganisms and polymorphonuclear cells in the tracheal aspirates (TAs) of ventilated preterm infants is not well known. Our aim was to correlate information about the presence of polymorphonuclear cells with microbial growth and the cytokine milieu in the TAs of infants who have been intubated for >7 days. STUDY DESIGN: TAs were collected from infants who had been intubated for 7 days or longer. Respiratory cultures were performed, and infants were stratified based on the presence and abundance of polymorphonuclear cells and microbial growth. Cytokines were measured in the TAs of each of the respective groups. RESULTS: In the 19 infants whose TAs were collected, the presence of at least moderate WBC with presence of microbial growth was positively associated with the presence of interleukin (IL)-10, IL-1ß, IL-8, and tumor necrosis factor (TNF)-α. The presence of at least moderate WBC, with or without microbial growth, was correlated positively with the presence of IL-8 and TNF-α. CONCLUSION: There are higher levels of proinflammatory cytokines (especially, IL-10, IL-1ß, and TNF-α) in TAs with higher cell counts and presence of microbial growth. The findings suggest that the presence of microbial growth correlated with inflammatory burden and warrant a larger study to see if treatment of microbial growth can ameliorate the inflammatory burden. KEY POINTS: · Concomitant evaluation of inflammatory cells, microbial growth, and cytokines in tracheal aspirates.. · Moderate TA WBC with presence of microbial growth associated with IL-10, IL-1ß, IL-8, and TNF-α.. · Moderate TA WBC, with/without microbial growth, correlated with the presence of IL-8 and TNF-α.. · Higher levels of IL-10, IL-1ß, and TNF-α correlated with higher TA cell counts and microbial growth..

Evaluation of the applicability of the current CDC pediatric ventilator-associated events (PedVAE) surveillance definition in the neonatal intensive care unit population.

BACKGROUND: There is limited data on pediatric ventilator-associated events (PedVAE) in the neonatal intensive care unit (NICU) setting, since the CDC mandated state reporting of these events in January 2019. This study sought to describe PedVAE rates and characteristics in the NICU population. METHODS: Single-center case-control study of infants requiring mechanical ventilation in a 39-bed level IV NICU between January 1, 2018 and December 31, 2020. Baseline infant demographic, respiratory support and antibiotic use data was obtained and comparisons were performed between patients with potential PedVAEs and those without events. RESULT: Two hundred and nine infants were mechanically ventilated. Two of the 126 patients ventilated for ≥4 days met CDC criteria for PedVAEs with a total of 3 events, and 32 (25%) received antibiotics with escalation of respiratory support, primarily for tracheitis. CONCLUSION: NICU-specific data on PedVAE is limited. Only 2 infants in the study period met the current CDC criteria for PedVAE with a rate of 0.9 events per 1000 ventilator days. The current CDC PedVAE definition might be inadequate to identify actionable VAEs to inform prevention efforts in the NICU population, and alternate indices could better characterize these events.

Acute Respiratory Failure With Hemoptysis in a Teenager Due to Cystic Echinococcosis.

A previously healthy 14-year-old male presented with abrupt onset respiratory failure with hemoptysis and anaphylaxis. Imaging demonstrated a large, cystic lesion with bronchopleural fistula that was consistent with cystic echinococcosis. He underwent thoracotomy for cyst removal and bronchopleural fistula repair, then completed 3 months of albendazole therapy. He developed recurrence of a bronchopleural fistula 4 months after surgery which improved over time with conservative management. This case highlights pathognomonic imaging and pathology findings for cystic echinococcosis.

Frequency of Multifocal Disease and Pyogenic Arthritis of the Hip in Infants with Osteoarticular Infection in Three Neonatal Intensive Care Units.

OBJECTIVE: To describe the clinical features of osteoarticular infection in infants cared for in neonatal intensive care units (NICUs) and to assess the presence of multifocal infection. STUDY DESIGN: Retrospective medical record review with structured data abstraction of infants with osteomyelitis or pyogenic arthritis or both in NICUs at 3 children's hospitals over a 29-year period. RESULTS: Of the 45 cases identified, 87% occurred in prematurely born infants, with a median gestational age of 27.4 weeks (IQR, 26, 31 weeks). Median postnatal age at diagnosis of infection was 33 days (IQR, 20, 50 days). Osteomyelitis was present without joint involvement in 53% and with joint involvement in 44% of cases. Methicillin-susceptible Staphylococcus aureus (71%) was the predominant pathogen, despite prevalent methicillin-resistant S aureus in community-associated infections. More than 1 bone was infected in 34% of cases. The femur (in 50% of patients) was the most frequently involved bone and the hip (in 20% of patients) was the most frequently involved joint. Bacteremia persisted for 4 or more days in 54% of patients with a positive blood culture despite active antimicrobial therapy. CONCLUSIONS: Among infants with osteoarticular infection in NICUs, multifocal disease is common and frequently is unsuspected. Search for additional sites of infection including the hip is warranted following the diagnosis of osteoarticular infection at a single site. Involvement of contiguous joints should be suspected in cases of osteomyelitis; conversely the presence of pyogenic arthritis usually indicates extant osteomyelitis in a contiguous bone.

Pharmacokinetics of the Meropenem Component of Meropenem-Vaborbactam in the Treatment of KPC-Producing Klebsiella pneumoniae Bloodstream Infection in a Pediatric Patient.

Meropenem-vaborbactam is a new ß-lactam/ß-lactamase inhibitor combination designed to target Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae. Meropenem-vaborbactam was United States Food and Drug Administration-approved for complicated urinary tract infections in patients 18 years of age or older. An understanding of the pharmacokinetics of meropenem when given in combination with vaborbactam is important to understanding the dosing of meropenem-vaborbactam. In addition, the safety and efficacy of meropenem-vaborbactam in a pediatric patient have yet to be described in the literature. The authors conducted a retrospective single-patient chart review for a 4-year-old male patient with short bowel syndrome, colostomy and gastrojejunal tube, bronchopulmonary dysplasia, and a central line for chronic total parenteral nutrition and hydration management, complicated with multiple central line-associated bloodstream infections (BSIs). The patient was brought to our medical center with fever concerning for a BSI. On day 2, the patient was started on meropenem-vaborbactam at a dosage of 40 mg/kg every 6 hours infused over 3 hours for KPC-producing K. pneumoniae BSI. Meropenem serum concentrations obtained on day 5 of meropenem-vaborbactam therapy, immediately following the completion of the infusion and 1 hour after the infusion, were 51.3 and 13.6 µg/ml, respectively. Serum concentrations correlated to a volume of distribution of 0.59 L/kg and a clearance of 13.1 ml/min/kg. Repeat blood cultures remained negative, and meropenem-vaborbactam was continued for a total of 14 days. A meropenem-vaborbactam regimen of 40 mg/kg every 6 hours given over 3 hours was successful in providing a target attainment of 100% for meropenem serum concentrations above the minimum inhibitory concentration for at least 40% of the dosing interval and was associated with successful bacteremia clearance in a pediatric patient.

Transition of Care: Pediatric Ambulatory Center to Emergency Department.

BACKGROUND: Little is known about the characteristics, clinical course, and the disposition of sick children transferred from pediatricians' offices to the emergency department (ED). OBJECTIVES: The purpose of the study was to determine the clinical profile, ED course, and disposition of children transferred from a hospital-based pediatric clinic to the ED. METHODS: We conducted a retrospective cohort study involving all sick children transferred from a hospital-based clinic to the hospital's ED from January 2012 to December 2013. Data collected included demographics, acuity of illness, ED course, diagnoses, and disposition of all children. RESULTS: A total of 179 patients were transferred to and received care in the ED: boys, 56%; median age, 18 months; mean age, 58 months; 68% were younger than 60 months; African American, 83%; Hispanic, 12%. Sixty-eight percent of the patients were triaged as Emergency Severity Index 3 (urgent) and 13% were Emergency Severity Index 2 (high risk), with the rest categorized as nonurgent. Forty-three percent (78) were discharged home, and 57% were admitted. Age younger than 60 months, need for intravenous antibiotics, inhaled medications, plain x-rays, respiratory viral panel polymerase chain reaction (PCR), supplemental oxygen, and blood work in the ED were associated with being admitted (P < 0.05). The top 3 primary diagnoses were respiratory distress (40%), skin and soft tissue infections (15%), and other infections (10%). CONCLUSIONS: Children transferred from a hospital-based pediatric clinic to the ED at an urban academic medical center had a high level of acuity, and almost 60% were admitted for inpatient care. Improvement in the provision of pretransfer care can potentially decrease transfers to the ED.

Association of postpartum maternal tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine administration and timeliness of infant immunization.

A retrospective cohort study was conducted on infants of mothers delivering at an inner-city hospital in October 2009 where postpartum maternal tetanus toxoid, reduced diptheria toxoid and acellular pertussis (Tdap) vaccination had been initiated in May 2008. We compared mothers and infants in a Tdap intervention group discharged July 2008 (n=250) with a pre-Tdap control group discharged July 2007 (n=238). Postpartum maternal Tdap impacted positively timeliness of early infant immunization.