Showing papers in "The Journal of Infectious Diseases in 1989"

Epidemiology of Otitis Media During the First Seven Years of Life in Children in Greater Boston: A Prospective, Cohort Study

Abstract: To determine the epidemiology of acute otitis media (AOM) and duration of middle ear effusion (MEE), we followed consecutively enrolled children from shortly after birth until 7 y of age. Because some children dropped out of the study, data were analyzed for 877 children observed for at least 1 y; 698 were observed for at least 3 y, and 498 were observed until 7 y of age. By 1 y of age, 62% of the children had greater than or equal to 1 episode of AOM and 17% had greater than or equal to 3 episodes; by 3 y of age, 83% had greater than or equal to 1 episode of AOM and 46% had greater than or equal to 3 episodes. The peak incidence occurred during the second 6-mo period of life. Significantly increased risk (by multivariate analysis) for AOM was associated with male gender, sibling history of recurrent AOM, early occurrence of AOM, and not being breast fed. MEE persisted after onset of AOM for weeks to months; prolonged duration of MEE was associated with male gender, sibling history of ear infection, and not being breast fed.

An Enzyme-Linked Immunoelectrotransfer Blot Assay and Glycoprotein Antigens for Diagnosing Human Cysticercosis (Taenia solium)

Abstract: An enzyme-linked immunoelectrotransfer blot (EITB) assay was developed for immunodiagnosing human cysticercosis. The assay uses lentil-lectin, affinity-purified glycoprotein antigens. A battery of 532 serum and 46 cerebrospinal fluid (CSF) samples (148 cases of parasitologically confirmed cysticercosis, 54 healthy controls, and 18 types of heterologous infections [376 cases]) were used to ascertain the assay's efficacy. All but three of the samples from cases of confirmed cysticercosis were positive; none of the samples from healthy controls or heterologous infections reacted to any of the diagnostic bands. Thus, the assay is 98% sensitive and 100% specific. We identified seven major glycoprotein bands that are commonly recognized by virtually all serum and/or CSF samples from patients with confirmed cysticercosis. There was no significant difference in test performance when CSF was compared with serum. The EITB assay is highly reproducible and simple to perform, and the reagents (including the antigens blotted onto strips) are very stable.

Plasma Endotoxin as a Predictor of Multiple Organ Failure and Death in Systemic Meningococcal Disease

Abstract: We studied prospectively the quantitative relation of circulating endotoxin (lipooligosaccharides [LOSs]) and the development of multiple organ failure and death in 45 consecutively admitted patients with bacteriologically verified systemic meningococcal disease (SMD). A plasma LOS level of greater than 700 ng/L correlated with development of severe septic shock (P less than .0001), adult respiratory distress syndrome (P = .0035), a pathologically elevated serum creatinine level (P less than .0001), or death as a consequence of multiple organ failure (P = .0002). Initial plasma LOS levels of less than 25, 25-700, 700-10,000, and greater than 10,000 ng/L were associated with 0%, 14%, 27%, and 86% fatality, respectively. The LOS half-life after initiation of antibiotic therapy was 1-3 h. Increasing plasma LOS levels were never seen. These observations suggest that LOS quantitation using the limulus amebocyte lysate assay with a chromogenic substrate gives important progsnotic information and may provide new insight concerning pathophysiological aspects of SMD.

Melioidosis: A Major Cause of Community-Acquired Septicemia in Northeastern Thailand

Abstract: In a prospective study of all patients with Pseudomonas pseudomallei infections admitted to a large provincial hospital in northeastern Thailand, 63 cases of septicemic melioidosis and 206 patients with other community-acquired septicemias were documented during a 1-y period. Apart from P. pseudomallei, the spectrum of bacteria isolated from blood cultures and the overall mortality (32%) were similar to those previously reported elsewhere. Death from septicemia was associated with failure to develop a leukocytosis or pyrexia over 38 degrees C, azotemia, hypoglycemia, and jaundice. Septicemic melioidosis presented mainly in the rainy season, occurred predominantly in rice farmers or their families, and was significantly associated with preexisting diabetes mellitus or renal failure (P = .03). Blood-borne pneumonia and visceral abscesses were common and the mortality was high (68%; P less than .001). The response to appropriate treatment was slow (median fever clearance time 5.5 d) and the median duration of hospital stay was 4 w. Septicemic melioidosis is a major cause of morbidity and mortality in northeast Thailand.

Toxin genotypes and plasmid profiles as determinants of systemic sequelae in Escherichia coli O157:H7 infections.

Abstract: In 1987, 93 Escherichia coli O157:H7 isolates were collected during routine surveillance for this pathogen in the state of Washington. Toxin genotypes and plasmid profiles were correlated with the clinical sequelae of illness in 88 of the 93 patients from whom these strains were isolated. Thirteen plasmid patterns were observed among the 88 tested isolates; four patterns accounted for 82% of the isolates. Genetic probing for Shiga-like toxins (SLT) I and II demonstrated the presence of both genes in 67 (76%), SLT I alone in three (3%), and SLT II alone in 18 (20%). The hemolytic uremic syndrome or thrombotic thrombocytopenic purpura developed in seven (39%) of 18 patients infected with isolates having only the SLT II gene, while these complications occurred in only four (6%) of 70 patients infected with isolates having the other two genotypes (relative risk, 6.8; 95% confidence interval, 1.9, 26.4). This study shows that E. coli O157:H7 isolates systematically collected from a single geographic region over a defined time period exhibit considerable diversity in plasmid content and toxin genotype and that the toxin genotype of the infecting strain may influence the risk of developing microangiopathic sequelae.

Comparative Antibiotic Dose-Effect Relations at Several Dosing Intervals in Murine Pneumonitis and Thigh-Infection Models

Abstract: Animal studies that compare antibiotics have used only a limited number of doses administered at intervals chosen without regard for their pharmacodynamic effects of pharmacokinetic profiles. We compared the relative efficacy and potency of three beta-lactams and two aminoglycosides in lung and thigh-infection models in neutropenic mice by defining the maximum attainable antimicrobial effect at 24 h (Emax) and the total dose required to reach 50% of maximum effect (P50) at several dosing intervals. For beta-lactams, Emaxs were similar, whereas P50s increased 10- to 50-fold with longer intervals in both models. Aminoglycosides were significantly more bactericidal in the lung than in the thigh, and dosing interval had little impact on P50s in either model. Recognizing the variable impact of dosing interval on efficacy for different classes of antibiotics is mandatory for the proper design and interpretation of comparative trials.

Enteroaggregative Escherichia coli associated with persistent diarrhea in a cohort of rural children in India

Abstract: A cohort of 452 rural children was followed longitudinally for 13 mo to ascertain the role of HEp-2 cell adherent Escherichia coli and other pathogens in causing acute (less than or equal to 14 d) and persistent (greater than 14 d) diarrhea. Aeromonas, Campylobacter jejuni, E. coli manifesting localized adherence to HEp-2 cells and enterotoxigenic E. coli were significantly associated with acute diarrhea. E. coli strains that exhibit aggregative adherence, so-called enteroaggregative E. coli, a newly-described category of diarrheagenic E. coli distinct from enterotoxigenic, enteroinvasive, enterohemorrhagic, and enteropathogenic E. coli, were found significantly more often in patients with persistent diarrhea (29.5%) than with acute diarrhea (12.8%) (P = .0052) or controls (9.9%) (P = .0006).

Recent Primary Toxoplasma Infection Indicated by a Low Avidity of Specific IgG

Abstract: An unusual assay was developed for the serologic diagnosis of recent primary infection by Toxoplasma gondii This test measures the antigen-binding avidity of toxoplasma-specific IgG antibodies Serum samples from 5 patients with recent primary toxoplasma infection were compared with those from 21 subjects with preexisting toxoplasma immunity Patients with primary infection exhibited a low avidity of toxoplasma-specific IgG, which persisted for several months after the onset of symptoms of toxoplasmosis In contrast, all subjects with past immunity had a high avidity of toxoplasma-IgG This IgG avidity assay should assist in the diagnosis of acquired toxoplasmosis and may be used to identify pregnancies that are at risk for congenital toxoplasmosis

Compartmentalization of Intraalveolar and Systemic Lipopolysaccharide-Induced Tumor Necrosis Factor and the Pulmonary Inflammatory Response

Abstract: Tumor necrosis factor-alpha (TNF), a monokine produced by lipopolysaccharide (LPS)-stimulated macrophages, is an activator of phagocytic functions and may modulate host responses during infection. To determine the effects of LPS on TNF activity and the pulmonary inflammatory response in vivo, we challenged rats systemically or intratracheally with LPS. Intravenous LPS significantly increased serum TNF content from nondetectable levels in control specimens to peak levels at 90 min, which declined to baseline by 3 h. In response to intratracheal LPS, levels of TNF both in bronchoalveolar lavage fluid and associated with alveolar macrophages increased significantly from near nondetectable levels in control animals. Increases in TNF levels were confined to the LPS-challenged compartment. Intravenous LPS resulted in a decrease in the number of peripheral blood neutrophils and in sequestration of these cells within the pulmonary vasculature. In contrast, intratracheal LPS elicited a marked intraalveolar inflammatory response.

Isolation of Human Immunodeficiency Virus from Genital Ulcers in Nairobi Prostitutes

Abstract: Recent epidemiologic studies have implicated genital/anorectal ulcer disease as an important cofactor for acquisition and transmission of human immunodeficiency virus (HIV) during sexual intercourse. To better understand the mechanism for the association between genital ulcers and HIV, exudates from 62 genital ulcers of 56 HIV-seropositive prostitutes in Nairobi (Kenya) were cultured for HIV. Twenty-six ulcer cultures could not be evaluated for the presence of HIV because of bacterial or fungal contamination. HIV was isolated from 4 (11%) of the 36 remaining uncontaminated ulcer cultures (2 introital, 1 vaginal, and 1 cervical) from 4 separate women. HIV was isolated from the cervical os from only 2 of the 4 women. HIV p24 antigen was detected in exudate from 1 of the 4 culture-positive ulcers and 0 of 32 culture-negative ulcers. Genital ulcers in seropositive patients should be regarded as potential sources of HIV, which could be important in transmission of HIV during intercourse. Public health measures aimed at controlling sexually transmitted genital ulcer diseases should be an integral part of acquired immunodeficiency syndrome (AIDS) prevention programs.

Host factors selectively increase staphylococcal adherence on inserted catheters: a role for fibronectin and fibrinogen or fibrin

Abstract: Intravascular catheters are prone to staphylococcal infections. To study the role in staphylococcal adherence played by fibrinogen or fibrin and fibronectin deposited on inserted catheters, 187 peripheral or central cannulae were prospectively removed from hospitalized patients. Compared with uninserted catheters, which allowed only minimal adherence, previously inserted catheters promoted significant adherence of staphylococcal isolates from patients with intravenous device infection. Adhesion-promoting properties were studied with laboratory strains having well-defined affinities for either fibronectin or fibrinogen: adherence of Staphylococcus aureus Cowan I, which has the highest affinity for both adhesins, was more strongly promoted (10- to 50-fold) on inserted cannulae than was that of S. aureus Wood 46 (4- to 10-fold) or Staphylococcus epidermidis Rp 12 (2.2-fold), which has no affinity for fibrinogen but does for fibronectin. Although all types of cannulae contained significant amounts of fibrin, which may promote adherence of coagulase-positive staphylococci, results obtained with coagulase-negative isolates suggested that in vivo-deposited fibronectin is also a critical determinant in this process.

The Effects of Acute and Chronic Alcoholism on Tumor Necrosis Factor and the Inflammatory Response

Abstract: Ethanol intoxication has been shown to suppress selected functions of the immune system, thereby compromising host defenses against bacterial infections. Because the macrophage secretory protein, tumor necrosis factor (TNF), plays a central role in the inflammatory cascade, the effect of acute and chronic alcoholism on lipopolysaccharide (LPS)-induced TNF activity was studied. Saline or ethanol was given intraperitoneally to normal or chronic alcoholic rats followed 30 min later by either intravenous or intratracheal LPS. Intravenous LPS caused a substantial increase in serum TNF at 90 min in both normal and chronic alcoholic rats. In marked contrast, peak serum TNF levels were significantly suppressed in normal and chronic alcoholic rats given an acute injection of ethanol. When LPS was instilled intratracheally into normal rats, high levels of TNF appeared in the bronchoalveolar lavage fluid. Similar levels of TNF were found in chronic alcoholic rats after intratracheal LPS. However, acute ethanol intoxication significantly inhibited LPS-induced TNF in bronchoalveolar lavage fluid. In a similar manner, acute ethanol intoxication, but not chronic alcohol consumption, markedly inhibited both systemic and intrapulmonary polymorphonuclear leukocyte aggregation in response to either intravenous or intratracheal LPS. Alcohol-induced inhibition of TNF is a potential mechanism of the antiinflammatory effects of ethanol.

A Specific and Sensitive Assay for the Lyme Disease Spirochete Borrelia burgdorferi Using the Polymerase Chain Reaction

Abstract: A highly specific and sensitive assay for Borrelia burgdorferi, the causative agent of Lyme disease, was developed using the polymerase chain reaction (PCR). The target DNA sequence was of chromosomal origin and conserved, by hybridization analyses, among all strains of B. burgdorferi tested but was not present in the most closely related member of the genus, B. hermsii. The PCR assay developed from this sequence reacted with 17 of 18 strains of B. burgdorferi but not with any other Borrelia species tested. The assay was sensitive to fewer than five copies of the B. burgdorferi genome, even in the presence of a 10(6)-fold excess of eukaryotic DNA. This assay should greatly facilitate the accurate diagnosis of Lyme disease and provide a means with which to investigate the pathogenesis, transmission, and basic biology of B. burgdorferi.

Tuberculosis and Human Immunodeficiency Virus Infection

Abstract: Progressive human immunodeficiency virus infection eventually leads to activation and dissemination of a wide variety of microorganisms normally held in check by the cellular immune system. Mycobacterium tuberculosis is one of these pathogens, and the disease caused by it has become a common presenting infection in the patient with AIDS. Dr. Richard E. Chaisson and Dr. Gary Slutkin have studied tuberculosis in the United States and worldwide, respectively. In this AIDS Commentary they address the unique nature of this infection, its diagnosis, and its treatment in the patient with AIDS.

Latent and Replicating Forms of Epstein-Barr Virus DNA in Lymphomas and Lymphoproliferative Diseases

Abstract: Epstein-Barr virus (EBV) is associated with lymphomas and lymphoproliferative diseases that occur mainly in immunocompromised patients, but the role EBV plays in their pathogenesis is unclear. The evidence linking EBV etiologically to these disorders includes the presence of EBV DNA and nuclear antigens in the lesions and serologic evidence that some patients with these lesions are experiencing primary or reactivated EBV infections. These syndromes may represent proliferation of cells latently infected with EBV, but the possibility of viral replication has not been rigorously studied. DNA extracted from biopsies of 35 lymphoproliferative diseases was probed with regions of the EBV genome capable of distinguishing circular, episomal DNA found in latency from linear, replicating EBV DNA. All samples contained restriction fragments characteristic of fused termini, indicative of circular, latent genomes. Thirteen samples contained additional restriction fragments diagnostic of linear EBV DNA. Therefore, replicating EBV DNA is found in ^40^0 of EBV-associated lymphoproliferative disorders. Epstein-Barr virus (EBV) can manifest two different life cycles: latent and replicative. In lymphoid cells in tissue culture, EBV is predominantly latent: The cells grow continuously, the genome is maintained at a constant copy number within the cell, a limited number of regions of the genome are transcribed, and a relatively small number of EBV-associated proteins (latent membrane and nuclear antigens) are pro

Complement activation and endotoxin levels in systemic meningococcal disease.

Abstract: The activation state of the complement system in 39 consecutively admitted patients with systemic meningococcal disease was studied prospectively using two monoclonal antibodies reacting with neoepitopes exposed during complement activation. The fluid-phase C3 activation products and SC5b-9 (terminal complement complex) were strongly correlated to the levels of endotoxin (lipooligosaccharides, LOS) in plasma on admission (r = .79, P less than .0001 and r = .76, P less than .0001, respectively) and to fatality. Maximum complement activation in survivors occurred 7h (median; range 0-44 h) after initiation of antibiotic treatment. The most severely ill patients had the capacity to activate the whole complement cascade. In nonsurvivors, high-grade activation often continued until the patients died. The results suggest that LOS are important activators of complement in systemic meningococcal disease and that complement-activating products, in concert with other mediators, may contribute to the multiple organ failure and death occurring in the most severe cases.

Association of tuberculosis and M. tuberculosis-specific antibody levels with HLA.

Abstract: In the search for HLA-linked immune response genes that control susceptibility to tuberculosis, we performed HLA typing and measured antibody titers to well-defined Mycobacterium tuberculosis antigenic determinants in 101 patients with sputum smear-positive pulmonary tuberculosis and 64 healthy controls from Surabaya, Indonesia. HLA-DR2 and DQw1 were associated with sputum smear-positive pulmonary tuberculosis (attributable risk = 36% and 39%, respectively), while DQw3 was associated even more strongly with the control group (preventive fraction = 57%). Antibody titers to the TB71 and TB72 epitopes of the 38-kDa protein, present only on tubercle bacilli, were strongly associated with DR2 (Pcorr = .001 and .024, respectively). The association of both the disease and the antibody response to the 38-kDa antigen of M. tuberculosis with Class II HLA genes HLA-DR2 indicates that Ir-gene-mediated regulation of the immune response to this antigen may be of pathogenic significance for the development of sputum smear-positive tuberculosis.

Hemolytic Uremic Syndrome and Diarrhea in Argentine Children: The Role of Shiga-like Toxins

Abstract: Shiga-like toxin-producing Escherichia coli have been associated with hemorrhagic colitis and the hemolytic uremic syndrome (HUS). Because Argentina has the highest reported frequency of HUS in the world, Argentine children were prospectively studied during the HUS seasons for evidence of Shiga-like toxin-related diseases. On the basis of serology, fecal cytotoxin neutralization, stool cultures, and DNA hybridization of colony lysates, most children with HUS had evidence of infection with Shiga-like toxin-producing organisms. Children with spring-summer diarrhea also commonly (32%, confidence interval 18%-46%) had clear-cut evidence of such infection. No controls (children without gastrointestinal, renal, or hemolytic disease) had free fecal cytotoxin, positive cultures for E. coli O157:H7, or DNA probe-positive organisms; 20% of them had low serum titers of antibodies to Shiga-like toxins. E. coli O157:H7 was not common in either HUS or diarrhea patients. The high frequency of Shiga-like toxin-induced diarrhea in young children in Argentina probably explains the high incidence of HUS in this country and suggests that HUS is a relatively uncommon complication of Shiga-like toxin-related disease.

Detection of HIV-1 RNA in the Lamina Propria of Patients with AIDS and Gastrointestinal Disease

Abstract: Thirty formaldehyde-fixed, paraffin-embedded endoscopic biopsy specimens from the colon and rectum of 25 patients with acquired immunodeficiency syndrome were examined using a [35S]HIV-RNA in situ hybridization procedure. Nine of the specimens contained cells that bound significant amounts of probe. Cells were considered positive if more than 50 grains of silver (over background) per 200 micron 2 were seen over cells that did not stain with eosin. Most of the positive cells resembled macrophages, although cells with condensed nuclei resembling lymphocytes were found. No epithelial cells expressing viral RNA were detected. Formaldehyde-fixed eosinophils gave spurious signals that could be reduced with sulfhydryl modifying agents. HIV-1 may be disseminated in the lamina propria of the gut at low concentrations in some patients but may not be detectable in others. The lower gut lining may be both a portal of initial infection with HIV and a target of disseminated HIV infection.

Modulation of inflammation and cachectin activity in relation to treatment of experimental Hemophilus influenzae type b meningitis

Abstract: By use of an experimental lapin model, the effect of ceftriaxone therapy on inflammation during Hemophilus influenzae type b (Hib) meningitis was evaluated. Meningitis was induced by intracisternal inoculation of 2 x 10(4) to 2 x 10(5) colony-forming units of Hib. Administration of ceftriaxone 6 h after infection provoked rapid bacterial lysis associated with greatly increased concentrations of bacteria-free endotoxin (lipooligosaccharide) and tumor necrosis factor alpha (TNF) in the cerebrospinal fluid (CSF). CSF TNF activity peaked 2 h after initiation of antibiotic therapy (24.4 +/- 2 ng/ml), was significantly higher than that in untreated controls (1.4 +/- 1.1 ng/ml; P less than .05), and was associated with a substantially increased inflammatory response as reflected by higher CSF white blood cell count (24,500 +/- 8,151 vs. 1,920 +/- 644 in untreated controls; P less than .05), lower glucose, and higher protein and lactate concentrations. Simultaneous administration of dexamethasone with antibiotic therapy resulted in a significant reduction in CSF TNF activity that was associated with a substantial reduction in CSF white blood cell count. These data suggest that initiation of ceftriaxone therapy in experimental Hib meningitis exacerbates the meningeal inflammatory response, which can be modulated by concurrent dexamethasone administration.

Protective Effects of Towne Cytomegalovirus Vaccine Against Low-Passage Cytomegalovirus Administered as a Challenge

Abstract: To test the protective effect of Towne live attenuated human cytomegalovirus (HCMV) vaccine in normal individuals, we developed a parenteral challenge consisting of a low-passage isolate (Toledo stain) inoculated subcutaneously in graded doses. This challenge virus caused a mild mononucleosis syndrome in seronegative individuals at doses of 10 or 100 pfu. The illness was accompanied by atypical lymphocytosis, raised hepatic enzymes, excretion of HCMV and HCMV-specific immune responses. Naturally seropositive volunteers also developed clinical and laboratory evidence of infection after challenge with 1,000 pfu of Toledo but resisted 10 or 100 pfu. Volunteers who had been vaccinated 1 y earlier also were resistant to disease caused by 10 or 100 pfu of Toledo, although some were asymptomatically infected by the 100 pfu dose. Vaccine-induced immunity to HCMV was as complete as naturally induced immunity when the challenge dose of Toledo was 10 pfu.

A Prospective, Randomized Study Comparing Transparent and Dry Gauze Dressings for Central Venous Catheters

Abstract: Patients having central venous catheters for three or more days were prospectively randomized to receive a transparent (n = 58) or gauze (n = 57) dressing to compare the incidence of insertion site colonization, local catheter-related infection, and catheter-related sepsis. Quantitative cultures of the catheter insertion site (25 cm2) revealed significantly greater colonization (P less than or equal to .009) after 48 h in the transparent versus the gauze dressing group. Local catheter-related infection occurred significantly more often (P = .002) in the transparent (62%) than in the gauze group (24%). Seven episodes of catheter-related bacteremia occurred in the transparent group (16.6%) and none in the gauze group (P = .015). Stepwise logistic regression analysis revealed that cutaneous colonization at the insertion site of greater than or equal to 10(3) cfu/mL (relative risk, 13.16) and difficulty of insertion (relative risk, 5.39) were significant factors for catheter-related infection. These data suggest that transparent dressings are associated with significantly increased rates of insertion site colonization, local catheter-related infection, and systemic catheter-related sepsis in patients with long-term central venous catheters.

Vaccination against Hepatitis B: Comparison of Three Different Vaccination Schedules

Abstract: Three different hepatitis B vaccination schedules employing injections at months 0, 1, 2, and 12, at months 0, 1, and 6, or at months 0, 1, and 12 were compared in 89 healthy young adults. Concentrations of antibodies to hepatitis B surface antigen (anti-HBs) after the third injection were dependent on the interval between the second and the third dose; geometric mean titers (GMTs) in the three groups were 53 IU/l, 5,846 IU/l, and 19,912 IU/l, respectively, when the third dose was given at month 2, 6, or 12. Whereas the anti-HBs responses to the third dose at month 6 or 12 were typical booster reactions, the kinetics after a third dose given at month 2 resembled those after only two doses but on a significantly higher level. A fourth dose given at month 12 to the individuals vaccinated at months 0, 1, and 2 led to a prompt anti-HBs response similar in height to the response in those vaccinated at months 0, 1, and 12. Thus, for achieving a high anti-HBs concentration guaranteeing its long-lasting persistence, vaccination at months 0, 1, and 12 seems to be preferable to vaccination at months 0, 1, and 6. For individuals at high risk of hepatitis B infection, vaccination at months 0, 1, 2, and 12 might be considered for obtaining an optimal early seroconversion as well as long-term protection.

Investigation of an Outbreak of Listeriosis: New Hypotheses for the Etiology of Epidemic Listeria monocytogenes Infections

Abstract: From December 1986 to March 1987 an outbreak of Listeria monocytogenes infection occurred in the Philadelphia metropolitan area. A patient-control study showed patients were more likely than controls to have had an ill family member and to have used antidiarrheal medication during the month before their illness. Diet histories showed patients were significantly more likely to have eaten ice cream or salami than were controls, and to have shopped at one grocery store chain. Subtyping of L. monocytogenes isolates of patients showed no predominant strain, and cultures of food products eaten by patients were negative except for Brie cheese eaten by one patient. With no predominant strain of L. monocytogenes in the patients, a common source for this outbreak is unlikely. Thus, the identified risk factors may have been associated with carriage of L. monocytogenes and a coinfecting organism may have precipitated disseminated disease. Possible cofactors should be considered in investigations of future outbreaks of listeriosis.

Evaluation of Antibiotic Diffusion into Cardiac Vegetations by Quantitative Autoradiography

Abstract: The reason bacterial endocarditis is difficult to cure has been controversial for many years. One explanation could be that antibiotic diffusion inside the vegetations is heterogeneous. This hypothesis was investigated by means of an autoradiographic study of diffusion of labeled antibiotics into large infected cardiac vegetations of nutritionally variant Streptococcus endocarditis in rabbits. Ten days after infection, 653 microCi of [3H]penicillin, 410 microCi of [3H]tobramycin, or 174 microCi of [14C]teicoplanin were injected iv over 30 min. Thirty minutes after the end of infusion (T30), vegetation/blood radioactivity ratios were 2.48 +/- 1.27, 2.49 +/- 0.67, and 3.94 +/- 1.19 for penicillin, tobramycin, and teicoplanin, respectively. Autoradiography clearly showed that distribution of the three drugs was different: Tobramycin was homogeneously distributed; penicillin was more concentrated at the periphery but still reached the center of vegetations; teicoplanin was concentrated only at the periphery. The same distribution pattern was observed with teicoplanin at T120 (i.e., one t1/2 beta later) and also after simultaneous infusion of a therapeutic dose (15 mg/kg) of cold teicoplanin. The diffusion gradient exhibited by some antibiotics could explain the difficulty in sterilizing vegetations despite high local concentrations, and the deleterious effect of the size of the vegetations on the therapeutic response.

The effect of concurrent human immunodeficiency virus infection on chronic hepatitis B: a study of 150 homosexual men.

Abstract: To determine the influence of concurrent human immunodeficiency virus (HIV) infection on chronic hepatitis B virus (HBV) infection, 150 male homosexual chronic hepatitis B surface antigen (HBsAg) carriers were studied. Of these, 82 subjects (55Vo) tested positive for antibodies to HIV. They were more likely to express hepatitis B "e" antigen (HBeAg) (i^ .001) and HBV-DNA (/^ .0005) in serum than were HIV-seronegative individuals. However, the degree of immune suppression did not influence HBeAg-HBV-DNA expression. In HBeAg-seropositive subjects, concurrent HIV infection was associated with lower serum alanine transferase levels (P < .001). This effect increased with the degree of immune suppression as determined by CD4* lymphocyte counts. Conversely, in patients negative for HBeAg, there was a weak trend towards higher alanine transferase levels with concurrent HIV. This study suggests that chronic hepatitis B may be less severe when accompaned by HIV infection; however, greater viral replication may make it more contagious and resistant to antiviral therapy. These data support an immune-mediated pathogenesis for hepatitis B and have implications for its control. In the USA, western Europe, and Australia, both human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are transmitted mainly by sexual or parenteral routes. The epidemiologies of the two infections overlap such that <90% of persons with the acquired immunodeficiency syndrome (AIDS) have

Diversity and Sources of Rapidly Growing Mycobacteria Associated with Infections Following Cardiac Surgery

Abstract: Eighty-nine isolates of rapidly growing mycobacteria associated with cardiac bypass-related infections were characterized. Isolates from sporadic infections belonged to eight taxonomic groups and displayed numerous multilocus enzyme genotypes, plasmid profiles, and heavy metal and antibiotic resistance patterns. Compared with 449 noncardiac wound isolates, 45 sporadic cardiac isolates were more likely to be Mycobacterium fortuitum and M. smegmatis and less likely to be M. chelonae. About 80% of cardiac and noncardiac isolates were from southern coastal states. Eight outbreaks of cardiac bypass-related infections were identified. Strains from each outbreak were genotypically distinctive, and five outbreaks involved more than one strain. In two outbreaks, isolates from environmental sources and noncardiac infections were similar or identical to isolates from sternal wound infections. The heterogeneity of these isolates suggests that most isolates are unrelated and are derived from local environmental sources rather than from contaminated commercial surgical materials or devices.

Resistance of Influenza A Virus to Amantadine and Rimantadine: Results of One Decade of Surveillance

Abstract: All clinical isolates of influenza A viruses from patients in Huntington, West Virginia, during the decade 1978-1988 were tested, and 65 of 65 H1N1 and 176 of 181 H3N2 viruses were susceptible to the antiviral action of amantadine and rimantadine The five resistant viruses were obtained from three members of a family undergoing therapy or prophylaxis with rimantadine Resistant influenza emerged during treatment with rimantadine and spread to two family contacts, causing typical influenza with fever, myalgia, and cough of 5 days' or less duration Genetic characterization of the resistant viruses when compared to the susceptible virus isolated on day 1 from the index case revealed a single amino acid change in the transmembrane portion of the M2 protein In vitro studies showed that rimantadine was significantly more active than amantadine against both H1N1 and H3N2 viruses Although this resistant influenza was transmitted and caused illness in one family, the absence of naturally occurring resistant viruses suggests that the emergence of new strains of influenza A each few years may prevent the widespread emergence of resistant influenza A virus