Patrick J. Gavin

Systemic Arterial Expression of Matrix Metalloproteinases 2 and 9 in Acute Kawasaki Disease

Objective—Coronary artery aneurysms are the major complication of Kawasaki disease (KD). Matrix metalloproteinases (MMPs) regulate remodeling and degradation of the extracellular matrix. We hypothesized that MMP-9 expression is increased in acute KD aneurysms when compared with KD nonaneurysmal arteries and arteries from control children. Methods and Results—MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 were immunolocalized in coronary arteries from children with fatal acute KD and controls. In KD coronary aneurysms, MMP-2 expression was prominent in the thickened neointima and in endothelial cells of new capillaries in areas of angiogenesis. MMP-9 was absent in control coronary arteries but was expressed in coronary artery aneurysms, nonaneurysmal coronary and noncoronary arteries, and cardiac nerves in acute KD, without an increase in TIMP-1 expression. Conclusions—MMP-2 likely participates in remodeling of the arterial wall in acute KD, particularly in the processes of neointimal proliferation and angiogenesis. MMP-9 may play a role in the development of coronary aneurysms, but its expression is not confined to aneurysmal arteries. Systemic arterial expression of MMP-9 in acute KD, even in the absence of inflammatory changes in the vessel, suggests induction by a circulating factor, or possibly by an infectious agent with tropism for arterial tissue.

Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: A large patient cohort study

Background: Activated phosphoinositide 3‐kinase &dgr; syndrome (APDS) is a recently described combined immunodeficiency resulting from gain‐of‐function mutations in PIK3CD, the gene encoding the catalytic subunit of phosphoinositide 3‐kinase &dgr; (PI3K&dgr;). Objective: We sought to review the clinical, immunologic, histopathologic, and radiologic features of APDS in a large genetically defined international cohort. Methods: We applied a clinical questionnaire and performed review of medical notes, radiology, histopathology, and laboratory investigations of 53 patients with APDS. Results: Recurrent sinopulmonary infections (98%) and nonneoplastic lymphoproliferation (75%) were common, often from childhood. Other significant complications included herpesvirus infections (49%), autoinflammatory disease (34%), and lymphoma (13%). Unexpectedly, neurodevelopmental delay occurred in 19% of the cohort, suggesting a role for PI3K&dgr; in the central nervous system; consistent with this, PI3K&dgr; is broadly expressed in the developing murine central nervous system. Thoracic imaging revealed high rates of mosaic attenuation (90%) and bronchiectasis (60%). Increased IgM levels (78%), IgG deficiency (43%), and CD4 lymphopenia (84%) were significant immunologic features. No immunologic marker reliably predicted clinical severity, which ranged from asymptomatic to death in early childhood. The majority of patients received immunoglobulin replacement and antibiotic prophylaxis, and 5 patients underwent hematopoietic stem cell transplantation. Five patients died from complications of APDS. Conclusion: APDS is a combined immunodeficiency with multiple clinical manifestations, many with incomplete penetrance and others with variable expressivity. The severity of complications in some patients supports consideration of hematopoietic stem cell transplantation for severe childhood disease. Clinical trials of selective PI3K&dgr; inhibitors offer new prospects for APDS treatment.

A Laboratory-Based, Hospital-Wide, Electronic Marker for Nosocomial Infection The Future of Infection Control Surveillance?

Faced with expectations to improve patient safety and contain costs, the US health care system is under increasing pressure to comprehensively and objectively account for nosocomial infections. Widely accepted nosocomial infection surveillance methods, however, are limited in scope, not sensitive, and applied inconsistently. In 907 inpatient admissions to Evanston Northwestern Healthcare hospitals (Evanston, IL), nosocomial infection identification by the Nosocomial Infection Marker (MedMined, Birmingham, AL), an electronic, laboratory-based marker, was compared with hospital-wide nosocomial infection detection by medical records review and established nosocomial infection detection methods. The sensitivity and specificity of marker analysis were 0.86 (95% confidence interval [CI 95], 0.76-0.96) and 0.984 (CI 95, 0.976, 0.992). Marker analysis also identified 11 intensive care unit-associated nosocomial infections (sensitivity, 1.0; specificity, 0.986). Nosocomial Infection Marker analysis had a comparable sensitivity (P > .3) to and lower specificity (P < .001) than medical records review. It is important to note that marker analysis statistically outperformed widely accepted surveillance methods, including hospital-wide detection by Study on the Efficacy of Nosocomial Infection Control chart review and intensive care unit detection by National Nosocomial Infections Surveillance techniques.

Clinical Correlation of the CLSI Susceptibility Breakpoint for Piperacillin- Tazobactam against Extended-Spectrum-β-Lactamase-Producing Escherichia coli and Klebsiella Species

ABSTRACT We assessed infections caused by extended-spectrum-β-lactamase-producing Escherichia coli or Klebsiella spp. treated with piperacillin-tazobactam to determine if the susceptibility breakpoint predicts outcome. Treatment was successful in 10 of 11 nonurinary infections from susceptible strains and in 2 of 6 infections with MICs of >16/4 μg/ml. All six urinary infections responded to treatment regardless of susceptibility.

Neonatal Sepsis Caused by Streptococcus bovis Variant (Biotype II/2): Report of a Case and Review

ABSTRACT Streptococcus bovis is an uncommon cause of infection in neonates. However, S. bovis is capable of causing fulminant neonatal sepsis or meningitis that is indistinguishable clinically from that caused by group B streptococcus. S. bovis and S. bovis variant (sometimes referred to as S. bovis biotypes I and II, respectively) are phenotypically similar but may be differentiated by expanded testing. In adults, specific associations between disease states and different biotypes of S. bovis are apparent. No data exist on possible differences or clinical relevance of neonatal infection caused by different biotypes or newer species of S. bovis. We report a 3-day-old neonate with bacteremia and meningitis caused by S. bovis variant (S. bovis biotype II/2) and review the literature.

Microbiologic Surveillance Using Nasal Cultures Alone Is Sufficient for Detection of Methicillin-Resistant Staphylococcus aureus Isolates in Neonates

ABSTRACT During an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in the neonatal intensive care units at two hospitals, we assessed several sites for detection of MRSA colonization. Nasal cultures found 32 of 33 MRSA-colonized patients (97%). Rectal cultures detected 29% of 24 MRSA-colonized patients identified by paired rectal and nasal samples and axillary samples found 22% of 9 MRSA-colonized patients identified by axillary samples paired with nasal swabs. There were no positive umbilical samples.

Evaluation of Performance and Potential Clinical Impact of ProSpecT Shiga Toxin Escherichia coli Microplate Assay for Detection of Shiga Toxin-Producing E. coli in Stool Samples

ABSTRACT Shiga toxin-producing Escherichia coli bacteria (STEC) are emerging pathogens capable of producing sporadic and epidemic diarrhea, hemorrhagic colitis, and potentially life-threatening hemolytic-uremic syndrome. Although the presence of E. coli O157 can be readily detected in stool by sorbitol-MacConkey agar culture (SMAC), STEC non-O157 serotypes cannot. In contrast to culture, testing for the presence of Shiga toxins 1 and 2 in stool detects both O157 and non-O157 STEC serotypes capable of causing disease. Over two consecutive summers, we evaluated the performance of the ProSpecT Shiga toxin E. coli Microplate assay (Alexon-Trend, Ramsey, Minn.), an enzyme immunoassay for the detection of Shiga toxins 1 and 2, on all stools submitted for culture of enteric pathogens, and the potential clinical impact of Shiga toxin detection. Twenty-nine stool specimens were STEC positive by ProSpecT assay. Twenty-seven of 29 STEC-positive isolates were confirmed by SMAC and serotyping or by a second enzyme immunoassay and PCR (positive predictive value, 93%). Thirteen of 27 confirmed Shiga toxin-producing strains were serotype O157. The remaining 14 strains represented 8 other serotypes. The ProSpecT assay was 100% sensitive and specific for detection of E. coli O157 in stool (7 of 7) compared to SMAC. In addition, the ProSpecT assay detected twice as many STEC as SMAC. Fifty-two percent of confirmed STEC-positive stools were nonbloody. Thus, in our population, screening strategies that test only visibly bloody stools for STEC would miss a majority of cases. Eleven (41%) STEC-positive patients were hospitalized, and eight (30%) developed severe disease (two developed hemolytic-uremic syndrome, and six developed hemorrhagic colitis). Prior to detection of STEC infection, seven (26%) and eight patients (30%) underwent unnecessary diagnostic procedures or received potentially deleterious empirical treatment, respectively. We propose that establishing a specific diagnosis of STEC may have prevented these potentially harmful interventions. We conclude that the ProSpecT assay is sensitive and specific for the detection of Shiga toxins 1 and 2 in stool and has potentially significant clinical impact for the individual patient and public health. Shiga toxin assays should be considered for routine use in settings where prevalence of STEC disease warrants testing.

Eye findings of diffuse unilateral subacute neuroretinitis and multiple choroidal infiltrates associated with neural larva migrans due to Baylisascaris procyonis

PURPOSE To report childhood infection with Baylisascaris procyonis (raccoon round worm) manifesting as diffuse unilateral subacute neuroretinitis (DUSN) and choroidal infiltrates in association with neurologic disease (neural larva migrans). METHOD Observational case series, one with eye manifestations of DUSN, the other with choroidal infiltrates, both with severe neurologic degeneration. RESULTS Indirect immunofluorescence assays on serum and cerebrospinal fluid were positive for B. procyonis in one and serially positive and increasing in the other. Both children had a history of pica and raccoon exposure. CONCLUSIONS Baylisascaris procyonis infection is associated with two cases of severe neurologic degeneration with ocular lesions: DUSN and choroidal infiltrates. Although B. procyonis is known to cause DUSN, these cases indicate that concomitant ocular migration may accompany neural larva migrans. These are the third and forth cases in the US literature of neural larva migrans due to B. procyonis with eye findings.

Neural larva migrans caused by the raccoon roundworm Baylisascaris procyonis.

Baylisascaris procyonis, the common raccoon roundworm, is a rare cause of devastating or fatal neural larva migrans in infants and young children. We describe the clinical features of two children from suburban Chicago who developed severe, nonfatal B. procyonis neural larva migrans. Despite treatment with albendazole and high dose corticosteroids, both patients are neurologically devastated. In many regions of North America, large populations of raccoons with high rates of endemic B. procyonis infection live in proximity to humans, which suggests that the risk of human infection is probably substantial. In the absence of effective treatment, prevention of infection remains the most important public health strategy.

Evaluation of the Vitek 2 System for Rapid Identification of Clinical Isolates of Gram-Negative Bacilli and Members of the Family Streptococcaceae

Abstract. Accuracy of the Vitek 2 automated system (bioMérieux Vitek, USA) for rapid identification of bacteria was evaluated using a collection of 858 epidemiologically unrelated gram-negative and 99 gram-positive clinical isolates. Isolates were tested after subculturing to ensure purity. Conventional agar-based biochemical tests (Steers replicator) were used as a reference method of identification. Gram-negative bacteria were identified to the species level with 95.3% accuracy by the system (Enterobacteriaceae, 95.9%; and non-Enterobacteriaceae, 92.5%), and gram-positive isolates with 72% accuracy. Although Vitek 2 identified routine clinical isolates of gram-negative bacilli and Enterococcus faecalis and Enterococcus faecium reliably, rapidly, and reproducibly, improvement is required in the identification of less common species of enterococci and viridans group streptococci.