Type-specific polysaccharide antigens of group B streptococci. II. The chemical basis for serological specificity of the type II HCl antigen.

The type-specific antigen of Group B Type II streptococci has been prepared free of other known cell components. This antigen is a capsular polysaccharide containing D-galactose, D-glucose, N-acetyl-D-glucosamine, and a labile component which has not been chemically characterized. Extraction of Type II streptococci with cold TCA yielded this antigen which contained two serological determinants. A partial antigen with only one of the determinants was obtained by extraction with dilute HCl at 100 degrees C. By means of the quantitative precipitin inhibition technique, a (beta-D-galactopyranoside has been established as the determinant of the HCl-extracted polysaccharide. The second determinant, present solely in the TCA antigen, has not been identified.

An immunological relationship between the group. A streptococcus and mammalian muscle.

By means of the immunofluorescent staining technique, antisera to a wide variety of serological types of Group A and A variant streptococci were found to contain an antibody which reacted with mammalian striated muscle, both skeletal and cardiac, as well as with smooth muscle in the endocardium and in the media of arterioles. Similar heart-reactive antibodies were not present in antisera to most other groups of hemolytic streptococci and to other Gram-positive cocci. Chemical and serological studies clearly pointed to the cell (protoplast) membrane of the Group A streptococcus as the locus of the antigenic determinant of this heart-reactive antibody. In addition, preliminary studies suggested that the reaction between this streptococcal antibody and cardiac tissue represented an immunological relationship between the sarcolemma, the membrane of a mammalian muscle cell and the cell membrane of a bacterium, the hemolytic streptococcus.

Osteomyelitis caused by viridans streptococci.

A 34-year-old man without known underlying disease was seen with osteomyelitis of the proximal shaft of the left femur. At operation, only viridans streptococci were isolated. The patient responded to a combination of intravenous penicillin G potassium and gentamicin sulfate therapy. To our knowledge, this is the first reported case of osteomyelitis of a long bone produced by hematogenous seeding by viridans streptococci.

Ceftizoxime elimination kinetics in continuous ambulatory peritoneal dialysis.

We investigated the kinetics of ceftizoxime, a beta-lactamase stable cephalosporin, in eight subjects undergoing continuous ambulatory peritoneal dialysis (CAPD). A single 500-mg or 1-gm dose was injected IV, or a 500-mg dose was given intraperitoneally in the CAPD fluid during a 6-hr dwell time. The ceftizoxime (500 mg) serum kinetic parameters were as follows: peak concentrations, 21 to 46 mg/l; volume of distribution, 0.27 l/kg; elimination rate constant, 0.0784 hr-1; plasma clearance, 1.66 l/kg hr-1; and t1/2, 10.2 hr. The t1/2 after 1 gm was 12 hr. Dialysate ceftizoxime concentrations rose rapidly between 0.25 and 2 hr and slowly over the next 4 hr, but only 4.04 +/- 1.8 and 7.4 +/- 2.9 mg ceftizoxime/hr was eliminated by the peritoneal route over a 6-hr dwell time after 500 mg or 1 gm IV. This represents only 4% to 5% of the dose. After intraperitoneal instillation, the antibiotic appeared in the serum within 15 min in all four subjects, and the peak serum concentrations ranged from 12 to 19.8 mg/l (mean +/- SD = 16.4 +/- 3.3) between 5 and 6 hr. Approximately 78% of ceftizoxime was absorbed from the peritoneal dialysis fluid during a single 6-hr dwell time. Rate constant for absorption, ka, was 0.3959 hr-1 and absorption t1/2 was 1.75 hr (as calculated by the residual equation). These data suggest that ceftizoxime has bidirectional exchange characteristics through the peritoneal membrane. Instillation of ceftizoxime in CAPD fluid alone may permit rapid absorption to reach therapeutic serum concentrations.

Detection of protein A-like substances on haemolytic streptococci prior to use in mixed reverse passive antiglobulin haemagglutination (MRPAH).

Before mixed reverse passive antiglobulin haemagglutination tests (MRPAH) can be used to measure the class of bacterial antibodies, the bacteria have to be shown to be free of Protein A or Protein A-like substances on their surfaces. Two basic procedures have been examined: haemagglutination of red cells coated with immunoglobulin by the bacteria, and the MRPAH reaction itself to reveal absorption of purified gamma Fc by the bacterial suspension. The use of a purified gamma Fc component has proved successful in providing a sensitive test for the detection of Protein A-like substances on the surface of bacterial. In addition to both the Cowan and Wood strains of Staph, aureus, strains of haemolytic streptococci of groups A, C and G had Protein A-like substances on their surfaces. In contrast, strains of group B and group D, as well as Strep. milleri, had no detectable Protein A-like activity.

Pathogenesis and treatment of endocarditis.

The rabbit model has been invaluable for in vivo studies in the pathogenesis and treatment of bacterial endocarditis. Both of the features of the mature bacterial vegetations in this rabbit model, i.e., absence of phagocytosis and decreased metabolic activity, provide evidence to support the concept that a rapidly bactericidal antimicrobial agent provides the optimal approach to the successful treatment of endocarditis. Imipenem, a carbapenem with a very broad spectrum of in vitro activity, has been shown to be rapidly bactericidal in animals and highly effective in the treatment of experimental bacterial endocarditis. In addition, twenty-six patients with endocarditis, caused largely by Staphylococcus aureus, have been successfully treated with imipenem/cilastatin.

Treatment of skin and soft tissue infections with imipenem/cilastatin.

Ninety-eight adult patients with skin and soft tissue infections caused by a variety of bacterial pathogens were treated with imipenem/cilastatin (71), cefazolin (21), or moxalactam (six) at three medical centers. Favorable clinical responses were observed in 87 of the 90 evaluable cases (97 percent). Most etiologic pathogens were eradicated during treatment including five of seven which demonstrated in vitro resistance to the therapeutic agent. Strains that persisted during treatment were not associated with therapeutic failure except in one cefazolin-treated patient who was infected with Bacteroides fragilis. All three drugs were well tolerated and no specific patterns of adverse reactions were observed.

Infectious antecedent of immunoblastic lymphoma. Progressive immunosuppression in a patient with lymphogranuloma venereum.

Angioimmunoblastic lymphadenopathy is a nonmalignant disease of unknown etiology often progressing to immunoblastic lymphoma. Immunologic deficiency is evident in these patients as well as in those with various infections found in association with the acquired immune deficiency syndrome (AIDS). This report describes a previously healthy young woman in whom angioimmunoblastic lymphadenopathy developed in association with lymphogranuloma venereum, with progressive loss of immunologic competence. This deterioration paralleled the evolution of angioimmunoblastic lymphadenopathy into a rapidly fatal immunoblastic lymphoma.

Treatment of serious infections with moxalactam.

In 93 hospitalized patients, 111 bacterial infections were treated with moxalactam. Eighty-three infections responded well to therapy, nine infections failed to respond to therapy or relapsed, and nine infections showed superinfection with resistant bacteria. The great majority of bacteria isolated had mean inhibitory concentrations below levels readily achieved in plasma, cerebrospinal fluid, bile, abscess fluid, and peritoneal fluid. Among the commonly identified bacteria, only Pseudomonas aeruginosa, enterococci, and Staphylococcus epidermidis had variable sensitivity to moxalactam.

Rupture of a pulmonary artery mycotic aneurysm associated with candidal endocarditis.

Candidal endocarditis can develop if candidemia occurs during Swan-Ganz catheterization. Candida endocarditis may persist for many months and is fatal unless the infected valve is resected. Herein is reported the first case of rupture of a mycotic pulmonary artery aneurysm caused by chronic candidal endocarditis. The endocarditis followed Swan-Ganz catheterization and aneurysm progressed despite appropriate medical and surgical therapy.

T lymphocyte abnormalities in disseminated histoplasmosis.

Disseminated histoplasmosis is associated with depression of T cell-mediated immunity and in some cases anergy. In this report, two patients with disseminated disease are described. Both had a depression of T cell-mediated immunity as well as other abnormalities of immune response. In one, a patient with relapse, a marked depression in the ratio of T helper to T suppressor cells was noted. Neither patient had any predisposing condition known to be associated with disseminated disease.

Oxolinic acid for the treatment of chronic gastrointestinal Shigella carriers.

Two patients were long-term gastrointestinal carriers of Shigella flexneri for 23 mo and 6 mo, respectively. Neither patient responded to oral antibiotics, despite in vitro sensitivity of the bacteria to the antibiotics administered. Oral oxolinic acid produced immediate cessation of the carrier state in both patients, with resolution of minor but persistent physical complaints.

Inhibition of platelet aggregation by moxalactam and free N-methylthiotetrazole.

The effects of moxalactam and free N-methylthiotetrazole (N-MTT) in vitro on platelet aggregation induced by adenosine diphosphate (ADP), arachidonic acid, collagen, epinephrine, or ristocetin were determined. Moxalactam at concentrations of 1.9 mM and 5.7 mM inhibited platelet aggregation induced by ADP, arachidonic acid, epinephrine, and ristocetin. Although the aggregatory activity of collagen was not inhibited with 1.9 mM moxalactam, an increase in the concentration of moxalactam to 5.7 mM significantly inhibited collagen-induced platelet aggregation. Inhibition of platelet aggregation by free N-MTT was also concentration dependent. The lowest concentration of N-MTT used in this study, 5.7 mM, inhibited platelet aggregation induced by both arachidonic acid and ristocetin. At a concentration of 28 mM, N-MTT inhibited aggregation induced by ADP, collagen, epinephrine, and ristocetin, but not by arachidonic acid. At 57 mM N-MTT, almost complete inhibition of platelet aggregation occurred for all five agonists tested.

Infection with Cryptococcus neoformans var. gattii leading to a pulmonary cryptococcoma and meningitis.

A patient who lived in Ohio, U.S.A., developed a large pulmonary cryptococcoma and meningitis as the result of infection with Cryptococcus neoformans var. gattii, an organism of subtropical and tropical distribution. He had no obvious predisposing illness or condition associated with increased susceptibility to cryptococcosis. Although he was found to have cutaneous anergy, his lymphocytes showed significant transformation responses in vitro when cultured both with mitogens and with killed cryptococci. The meningitis responded to intrathecal amphotericin B. The cryptococcoma, however, did not resolve in response to vigorous antifungal therapy during a period of more than 4 months. Eventually, the cryptococcoma was surgically removed. This case is unusual both for the finding of C. neoformans var. gattii outside its apparent endemic area as well as for the clinical features of the disease.

A Behçet-like disease presenting as ulcerative stomatitis and scarring pustular lesions of the face.

Behçet's disease is a complex multisystem disease of unknown origin. It presents clinically as oral, pharyngeal, and genital ulcerations, uveitis, and inflammatory papulopustules. Diagnosis is made clinically since laboratory and histologic observations are not specific. We present a patient who, despite the absence of eye and genital lesions, seems best viewed as having Behçet's disease.

Detection of antibiotic-induced platelet dysfunction in whole blood using flow cytometry.

Using flow cytometry and activation-dependent monoclonal antibodies, we have developed a technique based on forward angle-light scatter (FALS) and immunofluorescence that simultaneously detects human platelet activation, secretion, and aggregation in whole blood. To detect the effects of cefotetan and latamoxef, both of which contain an N-MTT side chain, and of free N-MTT and cefoxitin, which does not contain the N-MTT side chain, on platelet activation and secretion, platelets were stained by the indirect method using a murine-produced platelet specific activation-dependent monoclonal antibody, S12, and a goat anti-mouse IgG fluorescein-conjugated antibody. S12 binds to a 140kd alpha granule membrane protein (GMP-140) that is expressed during secretion. Single parameter, 256 channel, log integrated green fluorescence histograms were generated, and negative and positive fluorescent populations were defined. Latamoxef and cefotetan reduced the number of platelets expressing S12 by more than 43%. In contrast, cefoxitin reduced the number of platelets expressing S12 by only 13.5%. The inhibition of GMP-140 expression per platelet was calculated by converting the log data to linear fluorescence intensity. Latamoxef and cefotetan inhibited expression of GMP-140 by 88% and 87% respectively. Free N-MTT inhibited its expression by 68%. In contrast cefoxitin reduced GMP-140 expression per platelet by only 45%.

Autoimmune mechanisms in the pathogenesis of rheumatic fever.

The etiologic agent of acute rheumatic fever is the group A streptococcus; however, its role in the pathogenesis of this disease is not well understood. Epidemiologic and immunologic evidence suggests that there is a population at risk and that the nature of the host response to streptococcal antigens and the physicochemical nature of the streptococcal antigens all play a significant role in determining the natural history of the disease process. Furthermore, the genetic control of the interaction of the host with the streptococci is clearly involved in a set of events--as yet obscure--that result in acute rheumatic fever. Neither antibody-mediated nor cell-mediated hypersensitivity reactions have been demonstrated in vivo or in vitro that wholly reproduce the characteristics of this disease. Additional studies of the regulation of the immune response and of human immunogenetics are essential for gaining further insight into the pathogenesis of acute rheumatic fever.

Treatment of significant bacterial infections in adults with cefoxitin.

Cefoxitin is a new antimicrobial agent derived from cephamycin C. Fifty-four hospitalized patients with 63 clinically significant infections were treated with cefoxitin. Fifty-four infections (86%) were cured by therapy with cefoxitin alone or together with local therapy (i.e., heat, elevation, or surgical drainage). Six infections (10%) were not eradicated by the therapy used. Three patients could not be evaluated. Addition of oral probenecid therapy produced increases in levels of cefoxitin in serum and increased the inhibitory and bactericidal levels of cefoxitin in serum to more favorable ratios. Adverse side effects were seen in 19 patients and included positive direct Coombs' tests, increased eosinophil counts, skin rashes, vasculitis, phlebitis, elevation of liver enzymes, and drug-induced fever.

Tetanus.

While the incidence of clinical tetanus had decreased greatly, efforts to eradicate the disease will depend mainly upon continued stress on prophylaxis. Recent cases demonstrate the need for both continued vigil in prophylaxis and sensitivity to the early signs of the clinical disease. The fundamentals of treatment are: neutralize formed toxin, eradicate Clostridium tetani, debride tissues adequately, control spasm and start immunization. Complications are legion. Mortality is highest in the very young and in the elderly.