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.

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.

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.

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.

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.

Aerosolized vaccine as an unexpected source of false-positive Bordetella pertussis PCR results.

When 13 of 13 nasal wash specimens from a single pediatrician's office tested positive for low quantities of Bordetella pertussis DNA, we suspected prelaboratory contamination. Investigation revealed that Pentacel and Adacel vaccines contain high copy numbers of B. pertussis DNA, which can be aerosolized, causing false-positive B. pertussis PCR results.

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.

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.

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.

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.

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.

Infliximab treatment of intravenous immunoglobulin-resistant Kawasaki disease.

OBJECTIVE: To investigate the safety, tolerability, and pharmacokinetics of the anti-tumor necrosis factor-alpha monoclonal antibody infliximab in subjects with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD). STUDY DESIGN: We conducted a multicenter, randomized, prospective trial of second IVIG infusion (2 g/kg) versus infliximab (5 mg/kg) in 24 children with acute KD and fever after initial treatment with IVIG. Primary outcome measures were the safety, tolerability, and pharmacokinetics of infliximab. Secondary outcome measures were duration of fever and changes in markers of inflammation. RESULTS: Study drug infusions were associated with cessation of fever within 24 hours in 11 of 12 subjects treated with infliximab and in 8 of 12 subjects retreated with IVIG. No infusion reactions or serious adverse events were attributed to either study drug. No significant differences were observed between treatment groups in the change from baseline for laboratory variables, fever, or echocardiographic assessment of coronary arteries. CONCLUSIONS: Both infliximab and a second IVIG infusion were safe and well tolerated in the subjects with KD who were resistant to standard IVIG treatment. The optimal management of patients resistant to IVIG remains to be determined.

Multidrug-resistant viridans streptococcus (MDRVS) osteomyelitis of the mandible successfully treated with moxifloxacin.

Multidrug-resistant viridans group streptococcus (MDRVS) strains have emerged as important pathogens. Treatment of MDRVS infections is problematic. The use of fluoroquinolones for treatment of MDRVS osteomyelitis has not been established. We present the first case of MDRVS osteomyelitis of the mandible successfully treated with sequential intravenous then oral moxifloxacin, and review the literature on the subject.

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.

Lumboperitonial shunt infection due to Chryseobacterium indologenes.

Chryseobacterium indologenes central nervous system infection has not been reported. We present a case of lumboperitoneal shunt infection caused by C. indologenes successfully treated with trimethoprim-sulfamethoxazole and rifampin in a pediatric patient. Forty-three additional cases of C. indologenes non-central nervous system infections reported in the English medical literature were reviewed. Risk factors for C. indologenes infections include underlying medical illnesses, underlying immunocompromising conditions and presence of indwelling intravascular devices.

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.

Antibiotic susceptibilities of Yersinia enterocolitica recovered from children over a 12-year period.

Antibiotic susceptibility testing by the microdilution technique was performed on 184 Yersinia enterocolitica isolates recovered from children with gastroenteritis in the Detroit area during a 12-year period. The majority of isolates were resistant to ampicillin, ticarcillin and cefazolin. The most active agents were cefotaxime, ceftriaxone, cefepime, gentamicin, tobramycin, sulphamethoxazole/trimethoprim, imipenem and ciprofloxacin. Cefotaxime and ceftriaxone were effective in the treatment of bacteraemia in 12 patients.

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.

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.

Effect of using 2 throat swabs vs 1 throat swab on detection of group A streptococcus by a rapid antigen detection test.

OBJECTIVE: To assess the effect of using 2 throat swabs vs 1 on rapid detection of group A streptococcus by the STREP A OIA MAX (hereafter, OIA MAX) test. METHODS: Children aged 5 to 18 years with acute pharyngitis were randomized to 1 of 2 study groups. In group 1, one throat swab was obtained, streaked first on sheep blood agar, and then used for OIA MAX testing. In group 2, two throat swabs were obtained simultaneously. One swab was streaked first on sheep blood agar and then joined with the other swab for OIA MAX testing. In both groups, the pledgets in the collection-transport tube were incubated in Todd-Hewitt broth. A positive group A streptococcus culture either by sheep blood agar or Todd-Hewitt broth was confirmed by a latex agglutination test. RESULTS: Three hundred sixty-three patients were enrolled, 177 in group 1 and 186 in group 2. Cultures were positive for group A streptococcus in 154 (42.4%) of 363 patients. The sensitivity and specificity of OIA MAX testing were 94.7% and 100.0%, respectively, in group 1, and 92.4% and 96.3%, respectively, in group 2. There was no statistical difference between the sensitivity, the specificity, and the predictive values of the OIA MAX test performed with 1 swab compared with those performed with 2 swabs (P>.10). There was no association between OIA MAX test sensitivity and the severity of pharyngitis as measured by the modified Centor criterion (history of fever, absence of cough, presence of pharyngeal or tonsillar exudates, and presence of cervical lymphadenopathy) scores. CONCLUSIONS: The OIA MAX test yielded comparable sensitivity and specificity in both study groups. The use of 2 throat swabs instead of 1 swab did not increase the sensitivity of the OIA MAX test. The performance of the OIA MAX test did not depend on the severity of pharyngitis.