Epidemiology and hospital readmission associated with complications of Staphylococcus aureus bacteremia in pediatrics over a 25-year period.

We sought to comprehensively assess the prevalence and outcomes of complications associated with Staphylococcus aureus bacteremia (SAB) in children. Secondarily, prevalence of methicillin resistance and outcomes of complications from methicillin-resistant S. aureus (MRSA) vs. methicillin-susceptible S. aureus SAB were assessed. This is a single-center cross-sectional study of 376 patients ⩽18 years old with SAB in 1990-2014. Overall, 197 (52%) patients experienced complications, the most common being osteomyelitis (33%), skin and soft tissue infection (31%), and pneumonia (25%). Patients with complications were older (median 3 vs. 0·7 years, P = 0·05) and more had community-associated SAB (66% vs. 34%, P = 0·001). Fewer patients with complications had a SAB-related emergency department or hospital readmission (10% vs. 19%, P = 0·014). Prevalence of methicillin resistance increased from 1990-1999 to 2000-2009, but decreased in 2010-2014. Complicated MRSA bacteremia resulted in more intensive care unit admissions (66% vs. 47%, P = 0·03) and led to increased likelihood of having ⩾2 foci (58% vs. 26%, P < 0·001). From multivariate analysis, community-associated SAB increased risk and concurrent infections decreased risk of complications (odds ratio (OR) 1·82 (1·1-3·02), P = 0·021) and (OR 0·58 (0·34-0·97), P = 0·038), respectively. In conclusion, children with SAB should be carefully evaluated for complications. Methicillin resistance remains associated with poor outcomes but have decreased in overall prevalence.

Elevated intestinal fatty acid binding protein and gastrointestinal complications following cardiopulmonary bypass: a preliminary analysis.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with poorly understood alterations in gastrointestinal (GI) perfusion. Intestinal fatty acid binding protein (IFABP), a cytosolic protein uniquely located in mature small-intestinal enterocytes, has been shown to be a sensitive biochemical marker of early intestinal ischemia when assayed in urine. We hypothesized that if significant small-intestinal ischemia occurs with CPB, then urine IFABP levels should be concomitantly elevated. METHODS: Twenty-nine patients (15 low risk and 14 high risk) undergoing cardiac surgery with CPB were studied prospectively. Serial urine IFABP levels were measured and results were correlated with clinical outcomes. RESULTS: None of the low-risk patients had IFABP elevations or experienced GI complications. Five of the high-risk patients had IFABP elevations, and three of the five developed GI complications. Within the high-risk cohort, the only significant difference between patients with or without IFABP elevations was the GI complication rate (P = 0.03). Overall, patients with IFABP elevations had a significantly higher mean ASA class and significant increases in mean CPB and aortic cross-clamp times, mean time to oral intake, median ICU and postoperative lengths of stay, and GI complications. CONCLUSIONS: In low-risk bypass patients, small-bowel mucosal perfusion appeared to be maintained, while in the high-risk population, 21% of the patients sustained clinically significant mucosal compromise. In this pilot study, urine IFABP was 100% sensitive and 92% specific with respect to GI complications. Since elevated urine IFABP concentrations appeared to correlate with clinical GI complications, urine IFABP may be a useful marker to identify the patient at risk for postbypass GI complications.

Amphotericin B lipid complex for neonatal invasive candidiasis.

This study describes the safety and efficacy of amphotericin B lipid complex (ABLC) in 11 neonates with systemic Candida infections. Nine of the 11 improved clinically, and eight of nine evaluable patients had a mycological cure with ABLC. Creatinine levels improved or did not significantly change in eight of the 11 patients.

Total warm ischemia and reperfusion impairs flow in all rat gut layers but increases leukocyte-vessel wall interactions in the submucosa only.

OBJECTIVE: To study the effect of warm ischemia and reperfusion (I/R) on local perfusion and leukocyte-vessel wall interactions in vivo in all small bowel layers, and to quantify small bowel tissue injury histologically and by measuring intestinal fatty acid binding protein (I-FABP) release from the enterocytes. SUMMARY BACKGROUND DATA: Gut injury as a result of I/R plays a pivotal role in a variety of clinical conditions, such as small bowel transplantation, heart or aortic surgery, and (septic) shock. The precise mechanism behind I/R injury and the role of microvascular changes remain unclear. The influence of warm I/R of the gut on microvascular parameters in the different gut layers has not been studied before. METHODS: Anesthetized Lewis rats were either subjected to 30 minutes of ischemia and 1 hour of reperfusion or sham-treated as controls. After ligating the inferior mesenteric artery, total warm ischemia was induced by clamping the superior mesenteric artery. Intravital video microscopic measurements were obtained at intervals. Tissue injury of the small bowel and other organs was histologically evaluated afterward. In addition, plasma levels of I-FABP were determined to measure enterocyte damage. RESULTS: After ischemia, mean red blood cell velocity decreased significantly in all layers of the small bowel, but no diameter changes were observed. Leukocyte-vessel wall interactions increased in the submucosa but not in the muscle layers. Plasma levels of I-FABP significantly increased from 30 minutes of reperfusion onward. The intestinal mucosa was severely injured; no histologic damage was detected in other tissues. CONCLUSIONS: This is the first in vivo study showing that total warm ischemia of the rat gut impairs perfusion in the whole small bowel, whereas leukocyte-vessel wall interactions increase in the submucosal layer only. Therefore, the early inflammatory response to I/R seems to be limited to the submucosa. Both microvascular effects may have contributed to the severe morphologic and functional mucosal injury observed after I/R.

Plasma intestinal fatty acid binding protein in neonates with necrotizing enterocolitis: a pilot study.

BACKGROUND/PURPOSE: Intestinal fatty acid-binding protein (IFABP) is found within cells at the tip of the intestinal villi, an area commonly injured when necrotizing enterocolitis (NEC) occurs. This study was undertaken to determine if measuring IFABP concentrations in the bloodstream early in the course of NEC would differentiate patients by severity before clinical findings made it clear who had stage 3 NEC and who had milder stages. METHODS: Three plasma samples from newborn infants evaluated for NEC were obtained at symptom onset and after 8 and 24 hours. IFABP concentration was measured by radioimmunoassay. Infants were classified by the final and most severe stage of NEC, and IFABP levels were compared between groups at each sampling. RESULTS: IFABP was detectable in blood samples from all 7 infants with stage 3 NEC compared with 3 of 24 with stages 1 or 2 NEC. Elevated plasma IFABP concentrations were detectable before clinical staging could be made in 5 of the 7 subjects with stage 3 NEC. CONCLUSION: IFABP may be a specific marker for early identification of severe NEC.

Intestinal mucosal injury in critically ill surgical patients: preliminary observations.

This was a prospective study designed to evaluate the extent to which intestinal mucosal compromise occurs in adult critical care patients with and without systemic inflammatory response syndrome (SIRS) and to correlate the degree of intestinal injury with outcome. Ten patients from a university hospital surgical intensive care unit were identified who manifested SIRS at the time of admission to the intensive care unit. Five other critical care patients without SIRS were also evaluated. The Acute Physiology and Chronic Health Evaluation II score was determined. Intestinal mucosal viability was assessed by serial measurement of serum and urine iFABP intestinal fatty acid binding protein (iFABP), a sensitive and specific marker for mucosal injury. Outcome in terms of the development of multiorgan dysfunction syndrome, adult respiratory distress syndrome, and survival was determined. iFABP was detectable in the serum or urine in 8 out of 10 patients with SIRS. Among the 4 patients with detectable serum iFABP, 2 died and 1 developed severe adult respiratory distress syndrome. Nine of 11 patients without detectable serum iFABP recovered without major morbidity. iFABP was detectable in most patients with SIRS, suggesting that subclinical intestinal mucosal compromise is a frequent component of this syndrome. When iFABP was detectable, particularly in the serum, the prognosis was poor, even in the absence of SIRS, indicating that iFABP may be a relevant and independent predictor of outcome in critical care patients.

Organ failure, infection, and the systemic inflammatory response syndrome are associated with elevated levels of urinary intestinal fatty acid binding protein: study of 100 consecutive patients in a surgical intensive care unit.

BACKGROUND: Intestinal mucosal ischemia and subsequent barrier dysfunction have been related to the development of organ dysfunction and death in the critically ill. We hypothesized that urine concentrations of intestinal fatty acid binding protein (IFABP), a sensitive marker of intestinal ischemia, might predict the development of the systemic inflammatory response syndrome (SIRS) and organ dysfunction. METHODS: One hundred consecutive critically ill patients were prospectively studied for the development of infectious complications, organ dysfunction, and SIRS. Urine was collected daily for measurement of IFABP. RESULTS: A total of 58 males and 42 females (mean age, 56 years; range,16-85 years) were studied. Of these 100 patients, 40 patients developed complications and 5 patients developed SIRS. IFABP was significantly elevated in all patients with SIRS, and IFABP levels peaked an average of 1.4 days (range, 0-7 days) before the diagnosis of SIRS. CONCLUSION: Elevated concentrations of urine IFABP correlated with the clinical development of SIRS. Studies to assess the utility of IFABP as a predictor of organ dysfunction and SIRS in the critically ill are warranted.

Comparison of quantitative polymerase chain reaction, acid fast bacilli smear, and culture results in patients receiving therapy for pulmonary tuberculosis.

Quantitative-competitive polymerase chain reaction (QPCR) was performed on serial sputum samples from 22 consecutive cases of acid fast bacilli (AFB) smear-positive pulmonary tuberculosis. Of 94 specimens, 55, 72, and 83% were positive by culture, AFB smear, and QPCR, respectively. Of 52 culture-positive specimens, 6% were negative by PCR, and 13% were negative by AFB smear. Of 42 culture-negative specimens, AFB smear and QPCR were positive in 55 and 61%, respectively. AFB smear and QPCR results were strongly correlated (r = 0.75, p < 0.001), but each correlated less strongly with culture (r = 0.54, p < 0.005 for smear and r = 0.52, p < 0.005 for QPCR). When patients were classified by microbiologic response, responders tended to have less DNA in their sputum and shorter time to a negative PCR result compared to nonresponders. These data do not suggest a great advantage of QPCR over AFB smear for predicting culture results in patients with pulmonary tuberculosis.

Human intestinal fatty acid binding protein: report of an assay with studies in normal volunteers and intestinal ischemia.

BACKGROUND: Human intestinal fatty acid binding protein (hIFABP) is a cytoplasmic protein of mature small intestinal epithelium. Work with the rat demonstrated that serum levels of IFABP correlated with early phases of intestinal mucosal injury. The aim of this study was to develop an assay for hIFABP and assess its usefulness as a marker for intestinal mucosal injury in human beings. METHODS: Recombinant hIFABP (r-hIFABP) was used to produce rabbit anti-hIFABP. Specificity and avidity of binding were tested with immunoprecipitation and Scatchard analysis. r-hIFABP was labeled with 125I, and a competitive assay was developed. Urine and serum from normal volunteers and from patients with necrotizing enterocolitis (NEC), acute thromboembolic related intestinal ischemia, and systemic inflammatory response syndrome were tested for hIFABP. RESULTS: Molecular weight was 10(-12) kd, limit of detection was 1.87 ng/ml, and no cross-reactivity occurred when tested against rat IFABP or human heart FABP. Mean levels of hIFABP (ng/ml) were controls (serum less than 1.87, urine less than 1.87), NEC (serum 14.7 ng/ml), intestinal ischemia (serum 50 ng/ml, urine 52.3 ng/ml), systemic inflammatory response syndrome (serum 5.3 ng/ml, urine 13.2 ng/ml). CONCLUSIONS: This assay is quantitative for hIFABP in serum and urine. Results from both normal persons and those with various causes of intestinal ischemia parallel our previous findings in the rat. Preliminary findings suggest that hIFABP may serve as a diagnostic marker for early intestinal mucosal compromise and, in addition, that it should prove useful as a tool in developing rationale therapeutic regimens to treat these complex clinical problems.

Children hospitalized for varicella: a prevaccine review.

OBJECTIVES: To describe varicella complications in healthy and previously ill children hospitalized for varicella and to explore trends in group A beta-hemolytic streptococcus complications of varicella. METHODS: A retrospective record review of children hospitalized for varicella between January 1, 1990, and March 31, 1994, was conducted in nine large acute care hospitals in Los Angeles County, California. RESULTS: We identified 574 children hospitalized for varicella in study hospitals during the 4.25-year study period (estimated risk of hospitalization, approximately 1 in 550 cases of varicella); 53% of the children were healthy before the onset of varicella and 47% were previously ill with underlying cancers or other chronic illnesses. Children were hospitalized for treatment of complications (n = 427, 74%) or for prophylactic antiviral therapy or observation (n = 147, 26%). Systems involved in complications included skin/soft tissue (45%), neurologic (18%), respiratory (14%), gastrointestinal (10%), and hematologic, renal, or hepatic (8% or less). The mean age of children with skin/soft tissue infections was 2.7 years (range < 1 to 16 years) compared with 4.7 years (< 1 to 18 years) for other complications. Children with skin/soft tissue and neurologic complications were more often previously healthy (p < 0.05), whereas those with respiratory complications were more often previously ill (p < 0.001). Hospitalizations for skin/soft tissue infections increased during the study period. The proportion of complications as a result of group A beta-hemolytic streptococcus infection increased from 4.7% before 1993 to 12.2% for the remainder of the study period (p = 0.02). CONCLUSIONS: Prior health status was predictive of the type of complications experienced by children with varicella requiring hospitalization. Our data suggest a recent increase in skin/soft tissue complications of varicella requiring hospitalization and an increase in the proportion of complications related to group A beta-hemolytic streptococcus. Wide-scale vaccine use should reverse this trend and reduce the overall impact of varicella on both healthy and previously ill children.

Acetabular labral tears: evaluation with MR arthrography.

PURPOSE: To determine the usefulness of magnetic resonance (MR) arthrography in the diagnosis of acetabular labral tears. MATERIALS AND METHODS: MR arthrography of the hip was performed in 10 patients who underwent subsequent surgical evaluation. Eight arthrograms were obtained with intraarticular administration of gadolinium solution and two with intraarticular administration of normal saline. T1-weighted spin-echo (intraarticular gadolinium) or T2-weighted gradient-echo (intraarticular normal saline) images were obtained in the axial, sagittal, and coronal planes with use of a surface coil. Criteria for labral tears included labral blunting, absence, displacement, intrasubstance contrast material, and contrast material at the acetabular-labral junction. Labra with enlargement, intrasubstance intermediate signal intensity, or irregular margins were interpreted as degenerative. RESULTS: Labral tears were diagnosed in eight hips. Tears included six labra with contrast material that tracked at the acetabular-labral junction, one of which had associated intrasubstance extension. One tear was confined to the labral substance. The other tear exhibited absent labral tissue and an irregular remnant. One degenerative labrum and one normal labrum were identified. All MR arthrographic findings were confirmed at surgery. Extension of one anterosuperior tear into the posterosuperior labrum was not prospectively appreciated. CONCLUSION: In this preliminary study, MR arthrography appears to be a promising imaging modality for accurate diagnosis of acetabular labral tears.

Human syngeneic intestinal transplantation: evaluation of enterocyte viability with serum levels of intestinal fatty acid binding protein.

In a case of human syngeneic intestinal transplantation, the post-operative course was complicated by the Systemic Inflammatory Response System (SIRS). This syndrome was characterized by negative cultures and elevated levels of the pro-inflammatory cytokines, IL-1 beta, IL-6 and TNF. In keeping with current concepts of translocation across the enterocyte barrier as the etiology of SIRS, levels of intestinal fatty acid binding protein (I-FABP), an enterocyte-specific protein, also increased. These observations suggest that (i) a clinical syndrome consistent with translocation may occur in the absence of rejection in intestinal transplantation, and (ii) I-FABP may serve as a clinically relevant marker for enterocyte injury.

Safety and immunogenicity of a serogroups A/C Neisseria meningitidis oligosaccharide-protein conjugate vaccine in young children. A randomized controlled trial.

OBJECTIVE: To assess the safety and immunogenicity of a bivalent serogroups A/C meningococcal oligosaccharide-protein conjugate vaccine compared with the licensed meningococcal polysaccharide vaccine. DESIGN: Randomized controlled trial. STUDY POPULATION: Ninety healthy 18- to 24-month-old children who were seen at a southern California Kaiser Permanente clinic. INTERVENTIONS: Vaccination with either the meningococcal conjugate vaccine (at 1 of 2 dosages) or the polysaccharide vaccine, with 2 doses given 2 months apart. MAIN OUTCOME MEASUREMENTS: Immune response to each vaccine dose as determined by measurement of serogroup-specific total antibodies by enzyme-linked immunosorbent assay (ELISA) and by assessment of serum bactericidal activity. RESULTS: Both vaccines appeared to be safe, and nearly all children responded with greater than 4-fold increases in antibody levels. The 2 dosages of the conjugate vaccine induced similar antibody responses; therefore, the data for the 2 conjugate vaccine groups were combined. Following 2 doses, ELISA antibody levels against group C meningococcus were significantly higher in conjugate vaccine recipients than in polysaccharide vaccine recipients (16.66 microg/mL vs. 8.31 microgm/mL; P<.001), but antibody levels against group A were not significantly different 22.75 microg/mL vs 21.24 microg/mL; P=.70). The serum bactericidal assays showed striking differences between the conjugate and polysaccharide vaccine groups. Geometric mean serum bactericidal titers were significantly higher in conjugate vaccine recipients (755.6 vs 37.6 for group A, P<.001; 3197.9 vs 11.4 for group C, P<.001). CONCLUSIONS: The immune response induced by this meningococcal oligosaccharide-protein conjugate vaccine was qualitatively different from that induced by the polysaccharide vaccine, and the antibodies it elicited provided greater functional activity.

Disseminated intravascular coagulation associated with rotavirus gastroenteritis: report of two cases.

During one winter season, two children with rotavirus gastroenteritis who developed fulminant disseminated intravascular coagulation were seen at our hospital. Disseminated intravascular coagulation probably resulted from hypovolemic shock and acidosis, although extraintestinal spread of the virus cannot be excluded.

Prevalence of bone marrow signal abnormalities observed in the temporomandibular joint using magnetic resonance imaging.

PURPOSE: The purpose of this investigation was to determine the prevalence of bone marrow signal abnormalities in patients referred for temporomandibular joint (TMJ) magnetic resonance imaging (MRI). This investigation was done because of prior studies suggesting that condylar marrow signal abnormalities indicate avascular necrosis. SUBJECTS AND METHODS: Retrospective review was done of 449 consecutive TMJ MR examinations in 415 patients from 1991 to 1994. Examinations were obtained with a surface coil at 1.5 T with routine T1, T2, and T2* images. Condylar marrow signal abnormalities were reviewed and classified into either a bone marrow edema pattern (hypointense T1, hyperintense T2) or a sclerosis pattern (hypointense T1 and hypointense T2). Patients with typical findings of osteoarthritis were excluded from the sclerosis category. RESULTS: Condylar marrow signal abnormalities were present in 37 patients (9%). Twenty-six patients (6%) had the edema pattern, 14 patients (3%) had the sclerosis pattern, and 3 patients had both. Two patients with the edema pattern had a history of surgery; five patients with the sclerosis pattern had a history of surgery. The only follow-up MRIs obtained in the 37 patients were on one patient with edema at 8 months and on one patient with sclerosis at 10 months. MRI demonstrated a stable appearance of these patterns. CONCLUSION: It was concluded that condylar marrow signal abnormalities are not rare in patients referred for TMJ MRI. The clinical significance of the changes is uncertain.

The effect of laparotomy and external fixator stabilization on pelvic volume in an unstable pelvic injury.

OBJECTIVE: Determine if laparotomy further destabilizes an unstable pelvic injury and increases pelvic volume, and if reduction and stabilization restores pelvic volume and prevents volume changes secondary to laparotomy. DESIGN: Cadaveric pelvic fracture model. MATERIALS AND METHODS: Unilateral open-book pelvic ring injuries were created in five fresh cadaveric specimens by directly disrupting the pubic symphysis, left sacroliac joint, and sacrospinous and sacrotuberous ligaments. Pelvic volume was determined using computerized axial tomography for the intact pelvis, disrupted pelvis with both a laparotomy incision opened and closed, and disrupted pelvis stabilized and reduced using an external fixator with the laparotomy incision opened. MEASUREMENTS AND MAIN RESULTS: The average volume increase in the entire pelvis (from the top of the iliac crests to the bottom of the ischial tuberosities) between a nonstabilized injury with the abdomen closed and then subsequently opened was 15 +/- 5% (423 cc). The average increase in entire pelvic volume between a stabilized and reduced pelvis and nonstabilized pelvis, both with the abdomen open, was 26 +/- 5% (692 cc). The public diastasis increased from 3.9 to 9.3 cm in a nonstabilized pelvis with the abdomen closed and then subsequently opened. Application of a single-pin anterior-frame external fixator reduced the pubic diastasis anatomically and reduced the average entire and true (from the pelvic brim to the ischeal tuberosities) pelvic volumes to within 3 +/- 4 and 8 +/- 6% of the initial volume, respectively. CONCLUSIONS: We believe that the abdominal wall provides stability to an unstable pelvic ring injury via a tension band effect on the iliac wings. Our results demonstrate that a laparotomy further destabilized an open-book pelvic injury and subsequently increased pelvic volume and pubic diastasis. This could potentially increase blood loss from the pelvic injury and delay the tamponade effect of reduction and stabilization. A single-pin external fixator prevents the destabilizing effect of the laparotomy and effectively reduces pelvic volume. These data support reduction and temporary stabilization of unstable pelvic injuries before or concomitantly with laparotomy.

Effect of neonatal immunization with diphtheria and tetanus toxoids on antibody responses to Haemophilus influenzae type b conjugate vaccines.

We randomly assigned 150 newborn infants to receive diphtheria and tetanus toxoids (DT) or Hib oligosaccharide conjugate (HbOC) at birth to determine whether exposure to the Haemophilus influenzae type b (Hib) conjugate vaccines' carrier proteins would enhance immune responses to subsequent administrations of HbOC or PRP-tetanus toxoid conjugate (PRP-T) at 2, 4, and 6 months of age. Their antibody responses were compared with those of 100 children immunized with HbOC or PRP-T beginning at 2 months of age. No serious adverse reactions were associated with neonatal vaccination. Administration of HbOC at birth did not lead to earlier or higher antibody levels. Newborn immunization with DT did not prime children for enhanced antibody responses. Moreover, Hib antibody levels were lower in DT-primed children than in children immunized beginning at 2 months of age. Diphtheria antibody levels, but not tetanus antibody levels, were also lower in children immunized with DT at birth. We conclude that neonatal immunization with Hib conjugate vaccines is not a means to provide earlier protection against invasive Hib disease. Newborn DT administration does not enhance subsequent antibody responses to Hib conjugate vaccines, and may lead to suppression of Hib and diphtheria antibody responses.