common) S hominis S lugdunensis S capitis Oral Streptococcal Most common cause in CHD species (Viridans Often sensitive to penicillin and third-generation cephalosporin, but resistance to group) both agents has been observed Streptococcus oralis/mitis Streptococcus sanguinis/mutans group Enterococci More common in adults E faecalis Difficult to treat due to relative tolerance to β-lactam antimicrobials and increasing E faecium resistance in E faecium Nutritionally Difficult to isolate and culture Concerns over relative resistance to β-lactams variant organism High relapse rate, need to treat as for enterococcal IE Abiotrophia spp Granulicatella spp Other Infrequent but very aggressive cause if IE with severe tissue destruction requiring streptococcal surgical intervention species Streptococcus pneumoniae Streptococcus pyogenes Streptococcus milleri group HACEK Affects both prosthetic valves and native valves Generally better prognosis than Haemophilus spp some causes of IE Aggregatibacter spp Some strains are β-lactamase positive Cardiobacterium spp Hard to grow in laboratory, often require prolonged culture Good pick-up on Eikenella corodens resected material by molecular methods Kingella spp Gram negative More likely in immune-compromised and neonates Enterobacteriaceae Antimicrobial resistance an issue (Coliforms) Specialist advice on combination therapy and length Pseudomonas spp Fungal Candida spp Cause of both NVE and PVE; very difficult to treat, requiring surgical resection in most cases, apart from mural IE in neonates Filamentous fungi Very difficult to manage, almost always requires surgical debridement and aggressive antifungal therapy Other causes Often part of noncultivable or culture-negative endocarditis Serologic testing Bartonella sp available for some Coxiella burnetii Good rate of pick-up on molecular testing of resected material Tropheryma whipplei Combine with epidemiologic exposure for optimal diagnosis Mycoplasma spp Brucella spp Emerging M chimaera recently identified as a cause of IE due to contaminated heater cooler units pathogens and bypass circuits used in cardiac surgery Mycobacterium chimaera CHD, Congenital heart disease; IE, infective endocarditis; NVE, native valve endocarditis; PVE, prosthetic valve endocarditis Table 56.5 Summary of Pediatric-Specific Cohort Studies Evaluating Changes in Incidence, Risk Factors and Causative Agents of IE Study Day et al93 Time Period, Study Type Number of IE Episodes 2000 and N = 1588 (causative 2003, US organisms in 662 cases) retrospective cohort Gupta et 2000–2010, al94 US CHD Retrospective cohort Sakai 2001–2012, Bizmark interrupted et al95 time series retrospective cohort N = 3840 estimated N = 3748 (weighted according to whether IE appears in any primary, secondary, or tertiary discharge code) % of Patients With Findings/Comments Preexisting Cardiac Disease/None 42%/58% IE episodes with coded organisms, n = 622 ■ Staphylococcus aureus, 362 (57%) ■ Viridans Streptococcus, 124 (20%) ■ Coagulase-negative Staphylococcus, 91 (14%) ■ Mortality highest in tetralogy of Fallot with PA and TOF ■ In non-CHD cases, highest mortality in infants, especially premature ones and with S aureus infections 53.5%/46.5% ■ 30.2% no organism (culture negative) ■ S aureus, 36.6% (of those, 46.9% had no underlying cardiac defect, 28.1% with no defect) ■ Other Staphylococcus spp., 6.5% equally distributed between those with and without preexisting cardiac defect ■ Viridans Streptococcus, 26% (32.7% in children with underlying cardiac defects, 17.9% in those without) ■ Trend over study period for increase in streptococcal IE ■ Highest mortality in S aureus IE 50.2%/49.8% ■ Staphylococcus IE, 33.6% ■ Streptococcus, 27.4% (VGS 20.4) ■ Culture negative, 30.4% ■ Main finding was that incidence has not changed but decrease in staphylococcal and increase in streptococcal IE in the 10to 17-year-old age group post–2007 guideline CHD, Congenital heart disease; IE, infective endocarditis; PA, pulmonary atresia; TOF, tetralogy of Fallot; VGS, viridans group streptococci Laboratory Diagnostic Procedures BC remains the gold standard investigation for patients with suspected IE; however, optimal sampling techniques, volumes (based on age of child), and culture conditions are essential for an accurate diagnosis In children the following volumes and frequency are recommended: Volumes: Infants and young children: 1 to 3 mL per bottle Older children: 5 to 7 mL per bottle (up to 30 mL blood/day) Frequency: Three sets of separate venipunctures over 24 hours, ideally with one set 12 hours apart, but with at least the first and last set 1 hour apart If the patient is unstable and presentation is acute, take two BCs at separate sites immediately and a third at least 1 hour later and commence empiric therapy as soon as feasible New Laboratory Diagnostic Techniques Techniques such as broad-range bacterial (16S rDNA) and fungal (18s rDNA) polymerase chain reactions (PCRs), pathogen-specific real-time PCRs, and proteomics (matrix-assisted laser desorption/ionization time-of-flight analysis [MALDI-TOF]) have become widely available and should be used in conjunction with standard culture techniques Gene-specific primers and amplification are more sensitive and do not always require a sequence step and so are more rapid Molecular methodologies can detect bacterial DNA directly in blood, and, although they have advanced in recent years, ■ They are still somewhat insensitive,96 the likely reason due to the low circulating load of bacteria in IE ■ Broad-range PCR techniques, bacterial (16S rDNA) and fungal (18S rDNA), are designed to amplify both conserved and variable regions of ribosomal DNA but in general are rather insensitive and in addition require a sequencing step to identify the pathogen ■ Contamination with environmental DNA can be problematic, particularly for fungal 18S DNA Optimal sampling, ...Table 56.5 Summary of Pediatric- Specific Cohort Studies Evaluating Changes in Incidence, Risk Factors and Causative Agents of IE