Infective endocarditis caused by Streptococcus bovis resistant to the lethal effect of penicillin G.

Penicillin G alone is generally recommended for the treatment of infective endocarditis caused by Streptococcus bovis because clinical isolates of S bovis are represented as being uniformly and markedly susceptible to penicillin G. However, two strains of S bovis recovered from two patients with bacterial endocarditis were resistant to the lethal effect of penicillin G. Combination therapy, cefazolin sodium and gentamicin sulfate in patient 1 and penicillin G and gentamicin in patient 2, was necessary; synergy, as manifested by lethal activity against the infecting strains, was demonstrated in the laboratory. We stress the need to determine the minimal lethal concentration of penicillin G for clinical isolates of S bovis. Until such information is available, particularly in life-threatening infections, combination drug therapy, consisting of an aminocyclitol added to a beta-lactam antimicrobic, should be used.

Use of radiologic modalities in coccidioidal meningitis.

The diagnostic utility of pentetate indium trisodium in 111 CSF studies, technetium Tc 99m brain scans, and computerized tomographic (CT) scans was evaluated in eight patients in whom coccidioidal meningitis developed following a dust storm in the Central Valley of California. The 111In flow studies and the CT scans demonstrated hydrocephalus in five patients with clinical findings suggesting this complication. Ventriculitis has not previously been diagnosed before death in patients with coccidioidal meningitis; however, it was demonstrated in two patients by the technetium Tc 99m brain scan. Basal meningitis, which is indicative of fungal infection, is also detectable on contrast-enhanced CT scan. The finding that communicating hydrocephalus occurs early in meningitis and interferes with CSF flow into infected basilar regions has important therapeutic implications in that antifungal agents injected into the lumbar subarachnoid space may not reach these regions.

Recovery from encephalomyelitis caused by Herpesvirus simiae. Report of a case.

A 29-year-old monkey handler developed an acute encephalomyelitis with neuromuscular dysfunction that progressed to respiratory arrest on the 18th day of illness. Thereafter, with supportive care, the patient's condition improved steadily. The titer of neutralizing antibodies to H simiae rose from 1:4 (eighth day of illness) to 1:512 (47th day of illness). Apparently the fifth known survivor of H simiae (herpesvirus B) encephalomyelitis, this patient is also remarkable because of virtually complete recovery, apparently the second documented instance of a good outcome.

Cellular receptors to the anaphylatoxins C3a and C5a.

A single component in the plasma membrane of human polymorphonuclear leukocytes (hPMN) has been identified as the binding site for C5a. Labelled human C5a can be cross-linked to a 48,000-Mr membrane component on the hPMN surface by using the bifunctional reagent ethylene glycol bis(succinimidyl succinate). The membrane component is believed to be the C5a receptor or the binding subunit of a C5a receptor complex. Our ligand-uptake data indicate that the hPMN has high-affinity binding sites for C5a with a Kd of the order of 1-2 nM and an estimated 50,000-113,000 binding sites/cell. Preliminary binding studies of C3a and C5a to rat peritoneal mast cells indicate that non-specific uptake by these cells is so great that it obscures characterization of specific receptor interactions. Data recently reported [Gervasoni, Conrad, Hugli, Schwartz & Ruddy (1986) J. Immunol. 136, 285-292] suggest that non-specific binding of C3a to mast cells is caused by electrostatic interactions between the cationic ligand and anionic heparin-proteoglycan on the cell surface, with an additional complication of the bound ligand undergoing proteolytic degradation. It is therefore proposed that synthetic analogue peptides designed to minimize non-specific interactions with the cell will be useful tools for demonstrating anaphylatoxin receptors on mast cells and may prove essential for receptor isolation.

Penetration of antimicrobial agents into bronchial secretions.

The entry of ampicillin, cephalothin and gentamicin into traceobronchopulmonary secretions/exudates was assessed in 22 patients during 28, episodes of pneumonia or bronchitis. Specimens were collected from the lower respiratory tract via tracheostomies or endotracheal tubes using either the flexible fiberoptic bronchoscope (50 specimens) or an intratracheal catheter (59 specimens). Venous blood was obtained at the same time. The concentrations in the bronchial specimens were less than those in the corresponding serums, amounting to about 10 per cent with ampicillin, 25 per cent with cephalothin and equal to or greater than 40 per cent with gentamicin.

Bioactive complement fragments in immunoregulation.

Several fragments derived from complement components have been identified as potent effector substances in in vitro assays that measure cell proliferation and antibody synthesis. The anaphylatoxin C3a suppresses the immune response but fails to influence T- or B-cell proliferation. The factor C5a augments both antibody production and antigen-induced, but not mitogen-induced, T-cell proliferation. C3a-mediated suppression occurs through the activation of a suppressor T-cell cascade with macrophage collaboration. C5a-mediated enhancement, depending upon the in vitro system studied, acts at the level of the helper T cell and/or macrophage. A fragment generated from treating iC3b with kallikrein (c3d-K) has aided in defining a structural region of the C3b molecule that can influence the level of circulating leukocytes. The factor C3d-K is also capable of suppressing both specific and non-specific T-cell proliferative responses and mitogen-induced B cell growth. The mechanism of C3d-K action is defined as a direct effect on "activated" T cells, even though IL-2 synthesis of treated cells is diminished. The effect of C3d-K is long lasting, non-reversible and requires only a short exposure to the target cell.

Treatment of fungal infections with semisynthetic derivatives of amphotericin B alpha.

AME appeared to be as effective as AmB in the treatment of mycoses in humans. AME was much less nephrotoxic than AmB, and was better tolerated in terms of rapid onset and reversible adverse reactions. AME may be more ototoxic than AmB. AME, even as AmB and OAME, may cause neurotoxicity and leukoencephalopathy, particularly when high doses are given for long periods.

Current principles of antimicrobic therapy.

The bases for successful antimicrobial therapy are reviewed. The impact of antimicrobics on the resident microbiota of the body and the development of resistance are considered. The phenomenon of tolerance to antimicrobics is described and a pharmacotherapeutic response is outlined. The distribution and penetration of antimicrobics is related to therapeutic needs. Finally, the choice of antimicrobics for use in obstetric and gynecologic infections is discussed.

Effect of recombinant human interleukin 2 in experimental murine coccidioidomycosis.

The therapeutic effect of recombinant human interleukin 2 (rH IL-2) was assessed in experimental murine coccidioidomycosis by daily IV injection for 30 days of doses ranging decimally from 2.5 X 10(1) to 2.5 X 10(5) units. The treatment with rH IL-2 had neither adverse nor salutary effects.

Comparative efficacy of forphenicinol, cyclosporine, and amphotericin B in experimental murine coccidioidomycosis.

Cohorts of ten mice, uninfected and infected (intratracheal injection of coccidioidal arthroconidia), were treated for 23 days by intravenous injections of either 5% glucose solution, an immunostimulant (forphenicinol), an immunodepressant (cyclosporine), or amphotericin B. All mice were autopsied (survivors at 26 days postinoculation) and suspensions of lungs, livers, and spleens were cultured. All uninfected animals survived and gained weight, whereas, only 20% of the infected controls survived, and all lost weight. Treatment with forphenicinol had no effect on survival or weight. Cyclosporine secured 90% survival at the lowest dose and 60% at the higher doses, with no net loss of weight; however, all cultures of organs yielded heavy growth of Coccidioides immitis. With amphotericin B, all mice survived and gained weight; four mice from each of the two treatment groups yielded modest growth of C. immitis from the lungs, and one mouse of each group yielded sparse growth from liver and spleen. The paradox of no effect from an immunostimulant and therapeutic effect from an immunodepressant correlated with susceptibility testing of C. immitis in vitro.

Successful treatment of progressive disseminated histoplasmosis with amphotericin B methyl ester.

Amphotericin B methyl ester (AME) has been used to treat fungal infections, most often those caused by Coccidioides immitis. We describe the only patient with disseminated histoplasmosis who has been treated with AME. After having had alarming reactions to amphotericin B, the patient was treated and cured with AME without adverse drug effect or later relapse.

Toxicity of amphotericins on chronic administration to mongrel dogs.

Conditioned mongrel dogs were given 30 i.v. injections of either AMB (amphotericin B, 0.75 mg/kg body weight), AME (amphotericin B methyl ester, 10 mg/kg body weight), or 5% glucose solution without antimicrobic. Severe loss of body weight and nephrotoxicity occurred with AMB; hepatic dysfunction resulted with AME; astrogliosis and pallor of the myelin were found in dogs given AME and 5% glucose solution.

Acquisition of coccidioidomycosis at necropsy by inhalation of coccidioidal endospores.

Coccidioidomycosis is accepted as being noncontagious because the infectious arthroconidial form of Coccidioides immitis is not produced in humans and other mammalian hosts. However, disseminated coccidioidomycosis developed in a veterinarian who autopsied a horse with disseminated disease but without draining lesions or productive cough. We postulate transmission occurred by inhalation of tissue-phase endospores aerosolized in the course of dissection.

Ovine pulmonary transit of tetracycline and minocycline.

Following cannulation of the right external jugular vein and the efferent duct of the right caudal mediastinal lymph node (the caudal end of this node was ligated to cut off the inflow of systemic lymph, i.e., 90%-95% of the efferent lymph was of pulmonary origin), sheep were given either tetracycline or minocycline as single doses of 5 mg/kg body weight infused intravenously over 30 min. Venous blood plasma and pulmonary lymph collected contemporaneously before infusion and from 5 min to 24 hr postinfusion were assayed by a well-agar diffusion method using Bacillus cereus. Peak concentrations of both drugs were observed in both plasma and lymph at 5 min postinfusion. Tetracycline penetrated into the lymph better than minocycline (percent penetration 67.3% of cf. 38.2%). The concentration of tetracycline was significantly higher in lymph during and 5 min postinfusion (p less than 0.01), a factor that may be of importance when selecting a tetracycline for the treatment of a pulmonary infection.

Bear meat trichinosis with a concomitant serologic response to Toxoplasma gondii.

A severe case of trichinosis occurred following the ingestion of raw meat from a common black bear, Ursus americanus, that was shot in Butte County, California. Examination of steaks cut from the bear revealed heavy infection with T. spiralis. A good clinical response was obtained following treatment with prednisone (1 mg/kg body weight per day) and thiabendazole (50 mg/kg body weight per day); no toxic effects were observed. In comparison with the pre-treatment biopsy, a more intense inflammatory response was seen following the administration of thiabendazole. Nevertheless, a muscle biopsy taken several months after discharge still showed well-encapsulated, morphologically intact larvae. In addition to the expected immunological responses to T spiralis, a marked rise in titer of antibodies to Toxoplasms gondii was observed by the fluorescent antibody and Sabin-Feldman dye test methods. Since toxoplasma infection of muscle is widespread in man, it is possible that an unrelated disease of muscle could result in stimulation of anti-toxoplasma antibodies similar to the findings in polymyositis and dermatomyositis. Alternatively, the possibility that a dual infection was acquired from the bear meat cannot be excluded.

Pericarditis caused by beta-lactamase-producing Haemophilus influenzae: report of two cases in adults and review of the literature.

Two adult patients with pericarditis caused by beta-lactamase producing Haemophilus influenzae are reported and their management reviewed. Both had pharyngitis, epiglottitis, pneumonia, empyema, or septicemia and were cured with antimicrobics and pericardial drainage (one by catheter and one by surgery). Eleven previously reported cases of pericarditis caused by Haemophilus influenzae are also reviewed. In reviewing this rare cause of bacteria pericarditis, it is important to recognize the antibiotic resistance profile, the incidence of pericardial tamponade, and the use of surgical drainage. Antibiotic selection for this organism is also discussed, as well as the importance of biotyping.