Treatment of meningitis caused by methicillin-resistant Staphylococcus aureus with linezolid.

Methicillin-resistant Staphylococcus aureus (MRSA) is increasing in prevalence both in nosocomial and in community settings. Treatment of such infections, particularly in the central nervous system (CNS), is problematic, as available options are limited. Linezolid is a new antibiotic with activity against Gram-positive cocci, including MRSA, and has good penetration into the cerebrospinal fluid. To our knowledge, there are only three case reports of successful treatment of CNS infections caused by MRSA with linezolid; we report herein a fourth such case. Clinical trials to address the role of linezolid in CNS infections are urgently needed.

Soluble L-selectin, a marker of immune activation, in neonatal infection.

L-Selectin is an adhesion molecule shed from the surface of lymphocytes and granulocytes upon activation. Soluble L-selectin in the plasma can thus reflect immune activation and is elevated in several pathological states. Our objective was to evaluate plasma levels of L-selectin as an immune activation marker in neonates and to determine whether it can serve as a marker of infection, either neonatal or congenital, or if it is affected by the mode of delivery and obstetrical or perinatal complications. A solid-phase ELISA was used on 89 sera from neonates less than 2 days of age, according to the manufacturer's instructions. Levels of soluble L-selectin in the neonate were lower than those of older infants and children and comparable to the levels seen in adults. There was no difference between levels of soluble L-selectin of premature (median, 1172 ng/ml) and full-term babies (median, 1151 ng/ml) or between babies born via vaginal (median, 1233 ng/ml) or cesarean delivery (median, 1146 ng/ml). Conditions such as preeclampsia or administration of steroids to the mother did not affect the levels of L-selectin in the neonate. In contrast, the presence of maternal clinical chorioamnionitis resulted in an increase in levels of L-selectin in the neonate (median, 1377 vs 1072 ng/ml, p = 0.02), as did neonatal sepsis (median, 1331 vs 1149 ng/ml, p = 0.026). Soluble L-selectin, and thus immune activation level, is highest in neonates with neonatal infection and needs to be further evaluated as a surrogate marker for diagnosing sepsis in the neonate.

Effects of different HIV strains on thymic epithelial cultures.

The thymus is the major site for T cell development; interactions of developing thymocytes with thymic epithelial cells are critical for normal thymopoiesis. We set out to determine whether thymic epithelial cells can be infected by HIV strains that cause different patterns of disease progression in infected infants. Thymic epithelial cell monolayers were prepared from normal thymus of infants, removed at the time of cardiac surgery. We infected the thymic epithelial cell monolayers with different strains of HIV, including laboratory strains and clinical strains from 3 of our pediatric HIV-infected patients with different patterns of disease progression. We found that different strains of HIV have different ability to infect thymic epithelial cells; the ability to infect thymic epithelial cells may not be directly related to CCR5/CXCR4 usage. Different HIV strains thus appear to employ different mechanisms by which they affect thymic components.

Use of human CD3 monoclonal antibody for accurate CD4+ and CD8+ lymphocyte determinations in macaques: phenotypic characterization of the CD3- CD8+ cell subset.

Macaque monkeys are frequently used in models for studies of infectious diseases, immunity, transplantation and vaccine development. Such use is largely due to the conservation of functionally important cell surface molecules and the phylogenetic proximity of their immune systems to that of humans. Some monoclonal antibodies (mAb) raised against human leukocyte antigens can be utilized in the monkey. Until recently, many primate centers have utilized the CD2 monoclonal antibody to enumerate T lymphocytes. We have evaluated the anti-human CD3 mAb in macaques and sooty mangabeys. Using this monoclonal antibody, pigtailed macaques were found to have a much higher proportion of CD2+ CD3- CD8+ cells as compared with rhesus macaques and sooty mangabeys. Such cells comprised approximately one-half of all CD8+ cells in the pigtailed macaque, but only one-quarter of CD8+ cells in the rhesus, and one-fifth in the sooty mangabey. Use of the CD2 monoclonal antibody as the T-cell marker resulted in underestimating CD4/CD8 ratios compared with using the CD3 mAb in pigtailed macaques. Phenotypic characterization of this subset of CD3- CD8+ cells indicated that they are CD16+, CD45RA+, CD11b+, CD69+ and CD28-. This would indicate that these cells represent an activated natural killer cell subset.

Tale of a toothpick: Eikenella corrodens osteomyelitis.

Tale of a Toothpick is a case of Eikenella corrodens osteomyelitis in a young woman, that resulted from puncture of her foot with a toothpick. The epidemiology, microbiology, common clinical presentations and therapy of E. corrodens are reviewed. A brief summary of the extent of toothpick injuries and their infectious complications are also presented.

Correlation of virus load and soluble L-selectin, a marker of immune activation, in pediatric HIV-1 infection.

OBJECTIVE: HIV infections in children are characterized by high viral load and, in some perinatally infected newborns, delayed appearance of viral markers. Both phenomena may be related to different levels of immune activation affecting viral replication. This study was designed to investigate the relationship between immune activation and viral replication in pediatric HIV infection, and the role of pre-existent immune activation in facilitating HIV transmission to the fetus/newborn. DESIGN: Plasma levels of soluble L-selectin (s-LS), an immune activation marker, were determined in 100 infants with perinatally transmitted HIV infection, compared with 106 age-matched HIV-exposed uninfected controls. Included in the analysis were samples from 31 HIV-infected (10 PCR+ and 21 PCR-) and 35 uninfected newborns aged < 2 days. METHODS: To determine s-LS levels, a solid phase ELISA was performed on plasma samples of patients and controls. RESULTS: s-LS levels in uninfected children were higher than those in normal adults. HIV-infected patients had more rapidly increasing values in the first 6 months of life compared with uninfected infants. Plasma s-LS levels correlated with HIV viral loads (r, 0.50). Among newborns in the first 2 days of life, s-LS levels were lowest in those with negative PCR tests, compared with PCR-positive or uninfected infants. CONCLUSIONS: These results suggest that higher immune activation in children contributes to higher viral loads, and that the level of pre-existent immune activation may have a role in determining which infants have detectable virus in peripheral blood at birth.

Thymic dysfunction and time of infection predict mortality in human immunodeficiency virus-infected infants. CDC Perinatal AIDS Collaborative Transmission Study Group.

The effect of human immunodeficiency virus (HIV)-induced thymic dysfunction (TD) on mortality was studied in 265 infected infants in the CDC Perinatal AIDS Collaborative Transmission Study. TD was defined as both CD4 and CD8 T cell counts below the 5th percentile of joint distribution for uninfected infants within 6 months of life. The 40 HIV-infected infants with TD (15%) had a significantly greater mortality than did the 225 children without TD (44% vs. 9% within 2 years). Infants with TD infected in utero had higher mortality than did those infected intrapartum (70% vs. 37% within 2 years), while no significant difference was noted between infants without TD with either mode of transmission. The TD profile was independent of plasma virus load. Virus-induced TD by particular HIV strains and the time of transmission are likely to explain the variation in pathogenesis and patterns of disease progression and suggest the need for early aggressive therapies for HIV-infected infants with TD.

Enlargement of the thymus in a child with chronic granulomatous disease receiving interferon gamma therapy.

Both an enlarged thymus (with normal results on histologic examination) and an increase in the percentage of peripheral CD4+CD45RA+ (naive) T lymphocytes developed in a child with chronic granulomatous disease receiving long-term interferon gamma therapy. The thymic regrowth may be secondary to interferon gamma therapy or to overstimulation of his compromised immune system by recurrent infections. To our knowledge, an association between enlargement of the thymus and either chronic granulomatous disease or interferon gamma has not been previously reported.

Decreases in CD5+ B lymphocytes in children with the DiGeorge anomaly.

The authors evaluated the lymphocyte subsets in eight children with the DiGeorge anomaly, compared with 48 age-matched control infants. Of particular interest was the finding that the percentage and number of CD5+ B lymphocytes were decreased in seven of the eight cases. This observation may provide insight into thymic function and the interaction of the B and T cell systems in some forms of congenital and acquired immunodeficiencies.

The great balancing acts. The pregnant woman, placenta, fetus, and infectious agents.

This article conceptualizes the various balancing acts between the pregnant woman, the placenta, the fetus, and the infectious agents. Despite the very large number of infectious insults during pregnancy, the outcome of most interactions usually is a normal newborn. We have identified only one general immune defect of the fetus and neonate: The inability to respond to polysaccharide antigens; yet, a similar defect also is found with certain polysaccharides in older children and adults. The capacity of the neonate to control severe life-threatening diseases with most infectious agents and the ability of the fetus, when infected in utero, to mount sophisticated, immune responses make it conceptually advantageous to consider the older fetus and the newborn infant as "immunodelayed" rather than as immunodeficient or immature.

Early progression of disease in HIV-infected infants with thymus dysfunction.

BACKGROUND: Infants with congenital thymic deficiency (the DiGeorge syndrome) have immunodeficiency and a characteristic pattern of low CD4+ and CD8+ T-lymphocyte counts and low CD5+ B-lymphocyte counts. Because the thymus is essential for the generation of CD4+ cells, we sought evidence of thymus dysfunction in infants infected perinatally with the human immunodeficiency virus (HIV). METHODS: We studied the immunophenotypes of 59 infants with maternally transmitted HIV, 5 infants with the DiGeorge syndrome, and 168 infants exposed to HIV but not infected. The criteria for a presumed thymic defect were reductions in both the CD4+ and CD8+ T-cell subgroups during the first six months of life that were confirmed in a subgroup of infants by low counts of CD4+CD45RA+ and CD4+CD45RO+ T cells and CD5+ B cells. RESULTS: Of the 59 HIV-infected infants, 17 had immunophenotypes similar to those of infants with the DiGeorge syndrome. The risks of the acquired immunodeficiency syndrome (AIDS) by the ages of 12 and 24 months were 75 percent and 92 percent in these 17 infants, as compared with 14 and 34 percent in the other 42 infants (P<0.001). Nine of the HIV-infected infants with the DiGeorge-like immunophenotype (53 percent) died within six months of the progression to AIDS, as compared with only three of the other infants (7 percent, P=0.006). CONCLUSIONS: In some infants infected perinatally with HIV, a pattern of lymphocyte depletion develops that resembles the pattern in congenital thymic deficiency. Since HIV disease progresses rapidly in such infants, they may be candidates for early antiviral therapy and attempts at immune reconstitution.

Increased natural antibody activity in sera of patients with malignant non-Hodgkin's lymphomas containing paraproteins.

In view of the frequent association between malignant lymphoproliferative diseases and autoimmunity, we studied by ELISA the presence, isotype, and specificity of natural antibodies in sera from 60 patients with malignant non-Hodgkin's lymphomas and 70 healthy controls. The antigens selected were actin, tubulin, myosin, troponin, tropomyosin, keratin, thyroglobulin, single stranded DNA, and the hapten trinitrophenyl. The results of this study were compared with the presence of oligoclonal immunoglobulins in the same sera, as previously detected by Isoelectric Focusing and Immunoblotting. Our results showed that 1) there is a high proportion of autoreactive NHL sera: 28 (46.6%) exhibited high IgG natural antibody activity (Nab) against one or more panel antigens, mostly against keratin, myosin, and tropomyosin, 26 (43.3%) had high IgA Nab activity, mainly against myosin, keratin, and ssDNA, whereas 17 (28.3%) displayed a high IgM Nab activity. The great majority (> 80%) of positive sera was polyspecific, i.e., reacted with at least two panel antigens. 2) A strong correlation exists between the high serum Nab activity and the presence of paraproteins: of the 28 sera exhibiting high IgG Nab activity, 16 (57%) contained oligoclonal IgG, and of the 17 sera exhibiting high IgM Nab activity, 13 (76.4%) contained oligoclonal IgM. The Nabs detected had frequently the same heavy and light chain as the paraproteins. No relationship between the presence of paraproteins with Nab activity and the stage of disease or grade of malignancy was found. We conclude that the high incidence of clonal immunoglobulins of different isotypes with various autoantibody specificities suggests an oligoclonal lymphocyte activation involving Nab producing cells. The significance of such autoreactive clones in NHL patients remains to be elucidated.