Infective Endocarditis at a Referral Children's Hospital During 19-Year Period: Trends and Outcomes.

BACKGROUND: We noted a recent increase in cases of infective endocarditis (IE) at our institution. The purpose of the study is to examine the incidence, risk factors, microbiology and outcome of IE in our pediatric population. METHODS: Retrospective review of IE cases during 2002-2020 at Children's Hospital of Michigan, Detroit. RESULTS: 68 patients with IE were identified. There was a 2-fold increase in incidence during the 2012-2020 (late period) compared to the 2002-2011 (early period). The most common predisposing conditions were congenital heart disease (CHD) in 39 (57.4%) and central venous catheter (CVC) in 19 (27.9%). CHD was more frequent in the late period (29/43, 67.4%) compared to early period (10/25, 40.0%) (p = 0.042). In CHD patients, palliative or corrective cardiac surgery was performed prior to IE diagnosis in 4/25 (16%) in early period and 23/43 (53.5%) in the late period (p = 0.004). S. aureus was the most common causative organism (35.3%) followed by streptococci (22.1%). Valve replacement or valvuloplasty was performed in 22.1% of patients. Complications occurred in 20 (29.4%). Mortality occurred in 7 (10.3%): 3 had CHD, 3 had CVC and underlying conditions and 1 had fulminant MRSA infection. CONCLUSION(S): The higher incidence of IE during the late period is likely due to an increase in patients with CHD who had undergone prior cardiac surgery. S. aureus was the predominant pathogen in all patients including those with CHD, followed by streptococci. IE in children continues to be associated with high rates of morbidity and mortality.

A tale of two intensive care units (ICUs): Baseline Staphylococcus aureus colonization and mupirocin susceptibility in neonatal and pediatric patients requiring intensive care.

OBJECTIVE: To assess the incidence rate of S. aureus colonization at baseline along with the mupirocin susceptibility (or resistance) rate in patients in a neonatal intensive care unit (NICU) and a pediatric intensive care unit (PICU) in conjunction with the implementation of universal decolonization as the standard of care. DESIGN: Prospective cohort study. SETTING: Children's Hospital of Michigan (CHM) inpatient intensive care units (ICUs). PARTICIPANTS: Newly admitted pediatric patients to the CHM NICU or PICU aged between 1 day and ≤21 years. INTERVENTIONS: Baseline and follow-up S. aureus screening cultures were obtained before patients underwent universal decolonization with mupirocin 2% antibiotic ointment (intranasal and umbilical) and chlorhexidine baths as standard of care to reduce CLABSI rates. RESULTS: Baseline S. aureus colonization rates of new admissions to the CHM NICU and PICU were high at 32% and 29%, respectively. Baseline mupirocin susceptibility to any S. aureus growth was 98.4%. All baseline culture isolates whether positive for MRSA or MSSA, with one exception, had minimum inhibitory concentrations (MICs) of ≤0.19 µg/mL. All follow-up study cultures after universal decolonization at 7 days or beyond with any S. aureus growth had mupirocin MICs of ≤0.125 µg/mL. CONCLUSIONS: Baseline S. aureus colonization rates of new admissions to the CHM ICUs were high as was baseline mupirocin susceptibility. Follow-up cultures, albeit limited in number, did not detect increasing mupirocin MICs over 1 year, despite broad mupirocin exposure due to the implementation of universal decolonization.

Central line-associated blood stream infection (CLABSI) due to Candida sojae in an infant with short bowel syndrome: The first human case report.

Central line associated blood stream infections (CLABSIs) in infants and children with intestinal failure due to short bowel syndrome may be caused by different organisms due to intestinal translocation and skin contamination. We report what we believe the first case of candidemia in an infant with short bowel syndrome caused by the environmental yeast Candida sojae that was initially misidentified as Candida tropicalis. We discuss its possible sources including a central venous catheter (CVC) and gut translocation and the differences between the two Candida species.

Micafungin injection for the treatment of invasive candidiasis in pediatric patients under 4 months of age.

INTRODUCTION: Neonates and young infants with invasive candidiasis are particularly at increased risk of dissemination including hematogenous Candida meningoencephalitis. The echinocandins including micafungin have emerged as a preferred agent in most cases of candidemia and invasive candidiasis but data in pediatric patients under 4 months of age are limited. AREAS COVERED: In this report, we review the micafungin use in infants younger than 4 months of age. Animal studies as well as clinical data that support its use in neonatal candidiasis are reviewed. In addition, the status of FDA approval and the rationale of micafungin dosing recommendations in infants <4 months are discussed. EXPERT OPINION: A dose of 4 mg/kg was approved for treatment of candidemia, Candida peritonitis and abscesses excluding meningoencephalitis or ocular involvement in patients younger than 4 months of age. However, because of the risk of central nervous system dissemination as well as the difficulty in establishing this diagnosis, this dose is inadequate to treat ill infants with candidemia. More studies are needed to establish the safety and efficacy of micafungin daily dose of at least 10 mg/kg in infants younger than 4 months of age when hematogenous Candida meningoencephalitis or ocular involvement cannot be excluded.

Fever in the Returned Pediatric Traveler.

Global mobility has been steadily increasing in recent years. The assessment of the febrile child returning from international travel is a diagnostic challenge. The COVID-19 pandemic has profoundly affected international travel and made evaluation and management of the sick returned traveler more challenging. Children visiting friends and relatives abroad remain at higher risk of infection compared to tourists. This review presents a guidance on the initial assessment of a traveling febrile child including interpretation of medical history, physical examination, and laboratory findings. Important clues to etiology include exposure to different infectious agents, incubation periods of pathogens, and prophylaxis regimens and vaccines received. Early identification of potentially life-threatening and highly contagious infections is essential. In this article, we discuss the epidemiology, evaluation, and management of specific travel related infections such as malaria, typhoid fever, dengue fever, viral hemorrhagic fever, rickettsiosis, leptospirosis, schistosomiasis, gastrointestinal, and respiratory infections.

SARS-CoV-2-associated multisystem inflammatory syndrome in children: clinical manifestations and the role of infliximab treatment.

This study was conducted to assess the clinical spectrum, management, and outcome of SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C). We reviewed medical records of children with MIS-C diagnosis seen at the Children's Hospital of Michigan in Detroit between April and June 2020. Thirty-three children were identified including 22 who required critical care (group 1) and 11 with less intense inflammation (group 2). Children in group 1 were older (median 7.0 years) than those in group 2 (median 2.0 years). Abdominal pain was present in 68% of patients in group 1. Hypotension or shock was present in 17/22 patients in group 1. Thirteen (39.4%) had Kawasaki disease (KD)-like manifestations. Five developed coronary artery dilatation; All resolved on follow-up. Intravenous immunoglobulin (IVIG) was given to all patients in group 1 and 7/11 in group 2. Second-line therapy was needed in 13/22 (group 1) for persisting inflammation or myocardial dysfunction; 12 received infliximab. All patients recovered.Conclusion: MIS-C clinical manifestations may overlap with KD; however, MIS-C is likely a distinct inflammatory process characterized by reversible myocardial dysfunction and rarely coronary artery dilatation. Supportive care, IVIG, and second-line therapy with infliximab were associated with a favorable outcome. What is Known: • Multisystem inflammatory syndrome in children (MIS-C) manifestations include fever, gastrointestinal symptoms, shock, and occasional features of Kawasaki disease (KD). • Treatment includes immunomodulatory agents, most commonly IVIG and corticosteroids. What is New: • Spectrum of MIS-C varies from mild to severe inflammation and coronary artery dilatation occurred in 5/22 (23%) critically ill patients. • IVIG and infliximab therapy were associated with a favorable outcome including resolution of coronary dilatation; only 2/33 received corticosteroids.

Are Stethoscopes, Coats, and Pagers Potential Sources of Healthcare Associated Infections?

We conducted a study to determine the rate of bacterial colonization of stethoscopes, coats, and pagers of residents at a pediatric residency training program as compared to that of badges, sleeves, and pagers of non-patient care staff (control group). Among 213 cultures obtained from 71 residents, 27 potential pathogens were isolated from 22 residents (27/213, 12.7%) as compared to 10 potential pathogens out of 162 samples obtained from 54 control participants (10/162, 6.2%) (P = .0375). The most common pathogen isolated from residents and control participants was methicillin sensitive Staphylococcus aureus (MSSA). The source of positive cultures among the residents was the stethoscope (8/22, 36.3%), pager (8/22, 36.3%), and coat sleeve (11/22, 50%). The rates of colonization with potential pathogens were higher among residents than control participants and about 12% of residents' stethoscopes, coats and pagers were colonized with bacterial pathogens. These are potential sources of nosocomial transmission of pathogenic organisms.

Cytomegalovirus viremia and resistance patterns in immunocompromised children: An 11-year experience.

We noted a recent increase in number of immunocompromised children with CMV viremia at our institution. The purpose of this study was to determine the frequency of CMV viremia in this population and evaluate factors associated with drug-resistant mutations. A retrospective review of immunocompromised hosts, 0-21 years of age, who had CMV viremia during 2007-2017. CMV viremia was detected using PCR assays. Genetic mutation assays were performed using PCR sequencing of the phosophotransferase UL 97 gene and the polymerase UL54 gene of CMV using Quest Diagnostics (San Juan Capistrano, CA, USA) or ARUP Labs (Salt Lake City, UT, USA). Thirty-one patients were identified, including 10 (32%) during the last 2 years. Of the 31 patients, 18 had hematopoietic stem cell transplantation (HSCT), 5 had primary immunodeficiency, 4 had malignancies, 3 had heart transplantation and 1 had new Human Immunodeficiency virus (HIV) infection. Antiviral resistance testing was performed on isolates from seven patients: five with persistent viremia (>1 mo), and two prior to starting antiviral therapy. Resistance was identified in three patients' isolates: two with common variable immunodeficiency (CVID) and one with recurrent Hodgkin's lymphoma who had undergone autologous HSCT. The two patients with CVID had chronic diarrhea and malabsorption and had received prolonged oral valganciclovir courses prior to emergence of resistance. The patient with Hodgkin's lymphoma had received a prolonged IV ganciclovir course. All three tested positive for UL97 mutation and two had both UL97 and UL54 gene mutations. Majority of our patients (21/31) with CMV viremia were transplant recipients and ganciclovir resistance developed in 10%. Two had intestinal malabsorption. Treatment with oral valganciclovir should be avoided in patients with poor gut absorption as that may increase the risk of resistance.

Risk factors for community acquired urinary tract infections caused by extended spectrum ß-lactamase (ESBL) producing Escherichia coli in children: a case control study.

Background: We noted a recent increase in cases of urinary tract infection due to community-acquired ESBL-producing Escherichia coli in children treated at our institution. Risk factors of urinary tract infection due to ESBL-producing E. coli in children in the USA remain unclear. Methods: A single center retrospective case control study of UTI due to CA-ESBL-producing E. coli during a 5-year period (2012-2016). Control cases with non-ESBL-producing E. coli urinary tract infection were matched by age, gender and year of infection. Results: A total of 111 patients with ESBL-producing E coli urinary tract infection and 103 controls were included. The proportion of ESBL-producing E coli urinary tract infection ranged from 7% to 15% of all UTI cases. The distribution of ESBL cases per year: 27 in 2012; 18 in 2013; 22 in 2014; 15 in 2015 and 29 in 2016. Median age was 4 years with female predominance (84%). The ESBL group was predominantly African American (32%) followed by individuals of Middle Eastern ethnic background (31%). Risk factors by univariate analysis were vesicoureteral reflux: (20.9 ESBL group vs 6% controls; p = .002), prior antibiotic usage in the last 3 months (including ß-lactams), prior UTI (last 3 months), recent hospitalization (last 3 months) and Middle Eastern ethnic background. However, multivariate analysis showed that only prior antibiotic usage (p = .001) and Middle Eastern ethnic background (p < .001) were independent risk factors. ESBL-producing strains were more frequently resistant to trimethoprim-sulfamethoxazole (72% vs 25%) and ciprofloxacin (73% vs 5%) than strains not producing ESBL. Conclusion: Risk factors for community-acquired ESBL-producing E coli urinary tract in our pediatric patient population were antibiotic usage within the previous 3 months and Middle Eastern ethnic background. This may be related to increased risk of intestinal colonization with resistant bacterial strains.

Infectious and Noninfectious Acute Pericarditis in Children: An 11-Year Experience.

OBJECTIVE: The study was undertaken to determine the etiology, review management, and outcome in children diagnosed with acute pericarditis during 11 years at tertiary pediatric institution. METHODS: Retrospective chart review of children diagnosed between 2004 and 2014. Patients with postsurgical pericardial effusions were excluded. RESULTS: Thirty-two children were identified (median age 10yr/11mo). Pericardiocentesis was performed in 24/32 (75%) patients. The most common cause of pericarditis was infection in 11/32 (34%), followed by inflammatory disorders in 9 (28%). Purulent pericarditis occurred in 5 children including 4 due to Staphylococcus aureus: 2 were methicillin resistant (MRSA). All patients with purulent pericarditis had concomitant infection including soft tissue, bone, or lung infection; all had pericardial drain placement and 2 required pericardiotomy and mediastinal exploration. Other infections were due to Histoplasma capsulatum (2), Mycoplasma pneumoniae (2), Influenza A (1), and Enterovirus (1). Pericarditis/pericardial effusion was the initial presentation in 4 children with systemic lupus erythematosus including one who presented with tamponade and in 2 children who were diagnosed with systemic onset juvenile inflammatory arthritis. Tumors were diagnosed in 2 patients. Five children had recurrent pericarditis. Systemic antibiotics were used in 21/32 (66%) and prednisone was used in 11/32 (34%) patients. CONCLUSION: Infections remain an important cause of pericarditis in children. Purulent pericarditis is most commonly caused by Staphylococcus aureus and is associated with significant morbidity, need of surgical intervention, and prolonged antibiotic therapy. Echocardiography-guided thoracocentesis remains the preferred diagnostic and therapeutic approach. However, pericardiotomy and drainage are needed when appropriate clinical response is not achieved with percutaneous drainage.

Enhanced Identification of Group B Streptococcus and Escherichia Coli in Young Infants with Meningitis Using the Biofire Filmarray Meningitis/Encephalitis Panel.

FilmArray Meningitis/Encephalitis (ME) polymerase chain reaction (PCR) panel was tested on 62 cerebrospinal fluid (CSF) samples from young infants (0-3 months) with suspected meningitis and compared with CSF cultures. Twelve CSF samples from 9 infants were positive by ME PCR panel (10 Group B Streptococcus (GBS) and 2 Escherichia coli) of which only 5 were positive by culture. The 7 CSF samples that were positive only by ME PCR panel were obtained from infants who had received prior antibiotic treatment. The ME PCR panel can be a useful tool in the rapid diagnosis of bacterial meningitis in pretreated young infants.

Rotavirus infections in Detroit, USA, a region of low vaccine prevalence.

After a sharp drop of rotavirus (RV) infections at Children's Hospital of Michigan, Detroit, USA in 2010 season, we noted an increase in the number of cases during the 2011 season including some RV vaccine (RVV) recipients. This study was conducted to determine the circulating genotypes during 2011 season and whether the increase in RV diarrhea was caused by replacement genotypes. G and P genotypes were determined by RT PCR and nucleotide sequencing of selected strains was performed. The vaccination rate among study patients was 24 %. RV strains from 68 stool samples were genotyped including 18 from vaccinated children and 50 from unvaccinated children. The predominant G genotype was G1 (58.8 %) followed by G9 (17.7 %) and G4 (15.5 %). P[8] was the predominant P genotype (68 %) followed by P[6] (17.6 %) and P[4] (3 %). All G9 strains were associated with P[6]. The most prevalent G-P combination was G1P[8] (56 %), followed by G9P[6] (17.6 %). Similar proportions of RV genotypes were found among vaccinated and unvaccinated children. Our local data suggest that 5 years after the introduction of RVV there has been no genotype replacement. Although a small increase in G9P[6] frequency was noted, G1P[8] remained the predominant strain of RV in our inner city community in the Midwestern USA.

Nontyphoidal Salmonella infection in children: relation to bacteremia, age, and infecting serotype.

BACKGROUND: Salmonella gastroenteritis, usually self- limited, can result in bacteremia and focal disease. This study was undertaken to determine the role of age and infecting Salmonella serotype on the risk of bacteremia in children. METHODS: This was a review of medical records of children with positive nontyphoidal Salmonella cultures seen in an urban setting at the Children's Hospital of Michigan in Detroit between July 1993 and December 2007. RESULTS: Isolates recovered from 633 patients, representing 50 serotypes, included 594 positive stool cultures and 72 (11.4% of all patients) positive blood cultures. Salmonella serotype Typhimurium was the most common serotype, accounting for 29.4% (186/633) of isolates, of which only 3 (1.6%) were recovered from blood. The most common serotype recovered from blood was serotype Heidelberg (40/120 of patients with Heidelberg serotype) accounting for 55.5% (40/72) of positive blood cultures. The patients' age range was 2 weeks to 20 years, with a median of 7 months (interquartile range, IQR = 4-23 months). Bacteremic patients (n = 72) had a median age of 6.5 months (IQR = 4-11 months) and were comparable in age to non-bacteremic patients (n = 266), who had a median age of 5.5 months (IQR = 3-11 months) (p = 0.24). The odds ratio (OR) for bacteremia in patients infected with serotype Typhimurium was 0.21 and in patients with serotype Heidelberg was 4.0. Patients with serotype Heidelberg infection in the age groups < 3 months, 3-6 months, 6-12 months, and > 12 months had an OR for bacteremia of 9.2, 2.5, 3.2, and 6.0, respectively. CONCLUSION: In our patient population, children with Salmonella serotype Heidelberg infection are at higher risk of bacteremia than children infected with other Salmonella serotypes. The risk is highest during the first 3 months of life.

Pentavalent rotavirus vaccine in infants with surgical gastrointestinal disease.

OBJECTIVES: Pentavalent rotavirus vaccine (RV5) has been shown to be well-tolerated and efficacious in preventing rotavirus gastroenteritis in healthy infants. Safety and immunogenicity of RV5 in infants with surgical gastrointestinal disease have not been studied. The aim of the present study was to evaluate the safety and immunogenicity of RV5 in infants with a history of congenital or acquired intestinal disease requiring resection compared with healthy infants. METHODS: Infants with intestinal resection were matched by gestational age and chronological age to healthy infants (controls). Dose 1 of RV5 was given at 10 to 12 weeks of chronological age. Doses 2 and 3 were given at intervals of 4 to 10 weeks, with all 3 doses given by 32 weeks. All infants were monitored for adverse events (AEs) by telephone calls, clinic visits, and parental written reports during the first 42 days after each dose and monthly thereafter by telephone for 12 months. Serum anti-rotavirus immunoglobulin A (IgA) titers were measured prevaccination and 2 weeks after dose 3. RESULTS: A total of 5 infants with surgical gastrointestinal disease and 3 control subjects were enrolled. All participants (100%) mounted a 3-fold increase in serum anti-rotavirus IgA geometric mean titer postvaccination. RV5 administration to surgical infants was well tolerated with a majority of AEs being attributed to the underlying medical condition. CONCLUSIONS: Postvaccination serum anti-rotavirus IgA levels indicate that RV5 is immunogenic in infants with a history of bowel resection, despite varying lengths of residual bowel. RV5 was well tolerated with few vaccine-related AEs.

Abiotrophia endocarditis in children with no underlying heart disease: a rare but a virulent organism.

Infective endocarditis is extremely rare in children with structurally normal hearts. The most common etiological agents are staphylococcal and streptococcal species. Nutritionally variant streptococci also classified as Abiotrophia species are a group of fastidious organisms that account for only 5% to 6% of all cases of culture-negative infective endocarditis. Only seven cases of Abiotrophia infective endocarditis have been previously reported in children with no underlying structural heart disease. We report two cases of Abiotrophia infective endocarditis in children without any predisposing factors. Both patients presented with nonspecific symptoms leading to delay in diagnosis. While bacteriological clearance was achieved in both cases, both had a complicated course including development of brain mycotic aneurysms, splenic infarction, renal failure, and irreversible damage to the mitral valve. Both patients required surgical removal of the native mitral valve and replacement. We also present review of seven cases with similar diagnosis published previously in literature and highlight important differences. Our cases highlight special challenges in management of Abiotrophia endocarditis in pediatric patients. As the organism may not be isolated in routine culture media, may present with atypical clinical symptoms and may have a complicated course even without antibiotic failure, a high index of suspicion should be maintained in children with subacute symptoms even with no underlying structural cardiac disease.