Christian C. Patrick

Bacillus cereus Bacteremia and Meningitis in Immunocompromised Children

Two cases of Bacillus cereus meningitis in immunocompromised children at our hospital within a 2-month period prompted us to review B. cereus--related invasive disease. We identified 12 patients with B. cereus isolated in blood cultures from September 1988 through August 2000 at our institution. Three of these patients also had B. cereus isolated from CSF specimens; 1 additional patient had possible CNS involvement (33%, group A), whereas 8 patients had no evidence of CNS involvement (67%, group B). Patients in group A were more likely to have neutropenia at the onset of sepsis and were more likely to have an unfavorable outcome. They were also more likely to have received intrathecal chemotherapy in the week before the onset of their illness. Two patients from group A died. One survived with severe sequelae. The fourth patient had mild sequelae at follow-up. No sequelae or deaths occurred among patients in group B. In patients with unfavorable outcomes, the interval from the time of recognition of illness to irreversible damage or death was short, which demonstrates a need for increased awareness, early diagnosis, and more-effective therapy, particularly that which addresses B. cereus toxins.

Oral cefixime is similar to continued intravenous antibiotics in the empirical treatment of febrile neutropenic children with cancer.

Empiric oral antibiotic therapy for febrile neutropenic cancer patients has been suggested as a means to decrease hospitalization, but the safety of this approach has not been adequately studied in children. We compared continued iv antibiotic therapy with switching treatment to orally administered cefixime in a group of selected febrile neutropenic children for whom blood cultures were sterile after 48 h of incubation. Two hundred episodes of febrile neutropenia were studied (156 patients), and 100 episodes were randomized to receive each treatment. Failure to respond to therapy was defined by documented or suspected bacterial infection, recurrent fever, or discontinuation of assigned therapy for any reason before neutropenia resolved. Rates of treatment failure were similar in the oral cefixime group (28%) and in the iv antibiotic group (27%; P=1.0). Results support the safety of oral cefixime therapy for low-risk febrile neutropenic children, a therapeutic approach that would facilitate earlier outpatient management and decrease the costs of treatment.

Respiratory Virus Infections in Pediatric Hematopoietic Stem Cell Transplantation

Respiratory virus infections (RVI) have become an increasingly appreciated problem in the hematopoietic stem cell transplant (HSCT) population. A retrospective analysis of 274 patients undergoing 281 HSCT at St. Jude Childrens Research Hospital from January 1994 through December 1997 was performed. Medical and clinical laboratory records were reviewed beginning at the onset of conditioning through the year following each HSCT, and the analysis was done for the first RVI only. Thirty-two (11%) of 281 HSCT cases developed a RVI during the first year post-HSCT. The most frequent cause of RVI was human parainfluenza virus type 3. Univariate analysis was performed to determine the association between risk factors and the cumulative incidence of RVI. Respiratory viruses are frequent causes of infections in the first year post-HSCT in the pediatric population. Only allogeneic transplant and the degree of acute or chronic graft versus host disease were found to be statistically significant risk factors for RVI.

Use of fluoroquinolones as prophylactic agents in patients with neutropenia.

BACKGROUND The use of fluorinated quinolone antibiotics to selectively decontaminate the gastrointestinal tract is a reasonable alternative to prevent infection in neutropenic patients. The fluoroquinolones represent ideal antibiotics with which to achieve the principles of selective decontamination by allowing colonization of anaerobes to inhibit the adherence, colonization and proliferation of potentially pathogenic aerobic flora. OBJECTIVE This report describes the prophylactic use of fluoroquinolones in neutropenic patients. RESULTS The majority of studies of fluoroquinolone prophylaxis in neutropenic patients have shown a reduction in documented Gram-negative bacterial infections. However, Gram-positive infections, particularly those with viridans streptococci, present a major impediment to the use of single agent prophylaxis with a quinolone. CONCLUSION Prophylaxis with fluoroquinolones in neutropenic patients was found to be advantageous, but it must be balanced against the risk of Gram-positive infections and the potential for antibiotic resistance.

Current concepts in the pathogenesis and management of brain abscesses in children.

Brain abscesses represent the most frequent intracranial suppurative process occurring in children. Improved bacteriologic techniques for isolating anaerobic microorganisms have shown that anaerobes play a major role in brain abscesses in conjunction with aerobic organisms such as alpha-streptococci. Computerized tomography has improved the diagnosis of brain abscesses and has changed the management in certain circumstances. Although surgical drainage still remains the definitive treatment modality, conservative medical management with serial CT scans has been successful. Still, the mortality and morbidity of brain abscesses remain substantial.

Management of anorectal/perineal infections caused by Pseudomonas aeruginosa in children with malignant diseases

The role of operation for anorectal infections associated with perineal gangrene and cellulitis in children with myelo-suppression from cancer chemotherapy is unclear. We evaluated anorectal/perineal infections caused by Pseudomonas aeruginosa in 16 children with malignant diseases seen over 27 years. In 12 of 16 patients, leukemia was the underlying malignancy (ALL 10, AML 2), and in 13 of 16, severe neutropenia (absolute neutrophil count less than 500/mm3) was present at diagnosis. Cultures of the lesions showed multiple organisms in 14 of 16 patients with Escherichia coli, Klebsiella species, and Enterococcus being the most frequent coexisting organisms. All positive blood cultures grew P aeruginosa exclusively. Of three patients with necrotizing infections, two had complete resolution with medical treatment alone; the other patient who developed this problem while on terminal care died. In none of the 16 patients was a major operation (debridement or diversion) performed. Five patients died, three of whom were considered terminally ill when the anorectal infections occurred. Four of the five deaths occurred before 1974. Since then, only 1 of 7 patients died. Excluding the three terminally ill patients, the success rate of medical therapy alone is 85% (11/13). The antibiotic regimen should include an aminoglycoside in synergistic combination with anti-Pseudomonas penicillin. These results suggest that operative management may have no role in the management of anorectal infections caused by P aeruginosa in children with cancer.

Stability and Sterility of a Recombinant Factor VIII Concentrate Prepared for Continuous Infusion Administration

Minipumps may facilitate cost‐effective and convenient continuous infusion (CI) therapy for severe hemophilia A. This study evaluated the in vitro sterility, ability to support bacterial growth, and specific activity stability of a recombinant factor VIII (FVIII; Bioclate™, Centeon) delivered by simulated CI at a variety of temperatures and after the addition of heparin or antibiotic. Closed system CIs of Bioclate™ (89.5 IU/ml) with and without heparin were sampled and cultured over a 6 day period. Bioclate™ (53.7 IU/ml) with and without heparin or vancomycin was inoculated with 102‐105 CFU/ml of S. aureus, S. epidermidis, Escherichia coli, E. cloacae, or Y. enterocolitica and assessed by quantitative culture after 1 and 3 days. The stability of Bioclate™ (50, 100, and 250 IU/ml) at three temperatures (21°C, 37°C, and 39°C) with and without heparin or vancomycin was tested over a period of 28 days. FVIII activity was measured in triplicate by a chromogenic assay (Coamatic® Factor VIII, Chromogenix) and purity evaluated by Western blot. No bacterial growth was detected during CI of FVIII for up to 6 days. Following bacterial inoculation, there was rapid growth (>3 log increase) of all tested bacterial species except S. aureus which only displayed a 1 log expansion at 3 days. The addition of heparin containing 9.45 μg/U benzyl alcohol had no effect on bacterial growth. The addition of vancomycin caused a modest suppression of S. aureus growth but not of E. coli. Diluent alone did not support bacterial growth. Neither concentration, increased temperature, nor the addition of heparin or vancomycin had a significant effect on FVIII activity stability. Samples retained >75% baseline activity for between 3 and 7 days, except the infusion of Bioclate™ 50 IU/ml plus heparin maintained at 21°C which remained stable for 28 days. Western blot analysis supported the activity assay findings. Standard and concentrated preparations of Bioclate™ are suitable for CI when delivered by the MiniMed® 404‐SP minipump. Because of the observed nutritive capability of this FVIII concentrate for sustaining bacterial growth, any contamination could result in systemic infection. Am. J. Hematol. 62:13–18, 1999.

The role of esophagoscopy in diagnosis and management of esophagitis in children with cancer

Esophagitis is a common complication in patients treated for cancer; however, difficulty in determining its etiology on the basis of noninvasive clinical information limits the implementation of specific therapies. We reviewed our experience with esophagoscopy and biopsy as an aid in the diagnosis and management of esophagitis in children with cancer. Of eleven episodes of esophagitis evaluated by esophagoscopy with biopsy, four (36%) had an infectious etiology (two with Candida, one with Herpes simplex virus, and one with viridans streptococci). The absolute neutrophil count, presence of oropharyngeal colonization, and appearance of the esophagus at esophagoscopy were not predictive of the etiology of esophagitis. Esophagoscopy with biopsy affected the management of 4 (36%) patients. We believe this procedure to be a valuable aid in managing esophagitis in children with cancer by providing objective data not otherwise available to the clinician.

Viridans streptococcal isolates from patients with septic shock induce tumor necrosis factor-α production by murine macrophages

Viridans streptococci are an important cause of bacteremia and septic shock in neutropenic patients, especially patients receiving chemotherapeutic agents that induce severe mucositis. The mechanisms by which viridans streptococci cause septic shock are unclear. We hypothesized that septic shock due to viridans streptococci is attributable to host cytokine production. Three clinical isolates of viridans streptococci were evaluated for their ability to induce production of tumor necrosis factor-alpha (TNF-alpha) by RAW 264.7 murine macrophages. These three strains of viridans streptococci induced TNF-alpha in a dose-dependent fashion, and the kinetics of TNF-alpha induction were similar to those observed with a clinical isolate of Escherichia coli.

Adherence kinetics of Haemophilus influenzae type b to eucaryotic cells.

ABSTRACT: Haemophilus influenzae type b (Hib) adhere in vitro to buccal epithelial cells (BEC) via pili (fimbriae). In vivo studies have conflicting lines of evidence concerning the role of pili in adherence. This study characterizes the kinetics of Hib binding to BEC and compares pilus versus nonpilus adherence. Adherence was assessed using radioactive, immunofluorescence, and electron microscopic techniques. Paired Hib strains were obtained from three children with Hib meningitis; piliated Hib were isolated from the nasopharynx and nonpiliated isolates from the cerebrospinal fluid. Piliated strains adhered avidly to BEC after a 1-h incubation, whereas nonpiliated strains adhered poorly p = 0.002). Kinetic analysis revealed increased adherence to BEC by piliated and nonpiliated strains with time, with maximum adherence occurring between 24-36 h. Immunofluorescence and electron microscopic assays visually confirmed the radioactive adherence findings. These results characterize the kinetics of Hib adherence to BEC. BEC incubated with nonpiliated Hib for 30 h were found to be coated with piliated strains, suggesting the induction of pilus production or the selection of a piliated subpopulation.