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Biomedical subjects

R J Duma

Publications and source records attributed to R J Duma.

At least 37 records · Page 2Linked to original sources

Primaxin in the treatment of acute bacterial pneumonia in adults.

Imipenem (N-Formimidoyl thienamycin) (MK-0787) is a new beta-lactam carbapenem antibiotic. When it is combined with the renal dipeptidase inhibitor cilastatin (MK-0791) the combination is known as primaxin. In this study 28 adult patients (24 males and 4 females) with acute bacterial pneumonia were treated with primaxin. Twenty-one patients were evaluable and 20 (95%) were clinically cured of their pneumonia. Bacteriological cures were demonstrated in 84% of the cases. One patient with a susceptible Pseudomonas aeruginosa failed. Major complications or toxic reactions included antibiotic associated diarrhoea in one patient; hypotension in one patient; increased grand mal seizures in one patient and elevated liver function studies in one patient. Results of this study suggest that primaxin will be useful in the treatment of a variety of serious Gram-positive and Gram-negative pneumonias. The true incidence of possible toxic reactions with this drug is not known at this time and awaits further experience.

Adult↗

Penetration of aztreonam into cerebrospinal fluid of patients with and without inflamed meninges.

Aztreonam was administered as a single, 2-g intravenous dose to 25 patients with noninflamed meninges and to 9 patients with inflamed meninges. It was well tolerated and was detected in the cerebrospinal fluid at the initial sampling period at 1 h after the end of infusion. Aztreonam levels in the cerebrospinal fluid of patients with inflamed meninges were four times higher than those recorded for the same time period in patients with noninflamed meninges. Aztreonam concentrations in cerebrospinal fluid in the presence of normal and inflamed meninges exceeded the inhibitory and bactericidal concentrations for most gram-negative bacteria. Thus, a multiple-dose treatment regimen with 2-g intravenous doses every 6 h appears to be appropriate for clinical trials of aztreonam for the treatment of gram-negative bacillary meningitis which is caused by susceptible organisms.

Adult↗

Epidemic typhus in the United States associated with flying squirrels.

Between July 1977 and January 1980, seven cases of sporadic, nonepidemic "epidemic" typhus (Rickettsia prowazekii) were discovered in Virginia, West Virginia, and North Carolina. The reservoir seemed to be the southern flying squirrel (Glaucomys volans), an animal indigenous to the eastern United States; however, the vector or mode of acquisition was not evident. Diagnosis was established principally through complement fixation, indirect immunofluorescence, and toxin neutralization tests. Patients' ages were 11 to 81 years. Most were white women. Six had abrupt onset of illness. Headaches, fever, myalgias, and exanthems were among the presenting complaints. The disease seemed milder than classic louse-born epidemic typhus, but in some instances, it was life-threatening. All patients responded to tetracycline or chloramphenicol. This entity probably is more common than reported, is difficult to recognize, and is produced by an organism seemingly identical to that producing louse-born epidemic typhus.

Adolescent↗

The evolution of pulmonary cryptococcosis: clinical implications from a study of 41 patients with and without compromising host factors.

Over 14 years 41 patients were diagnosed as having pulmonary cryptococcosis. Cryptococcus neoformans remained localized to the lung in 12 cases and disseminated in the remaining 29. Thirty-four patients were compromised hosts. Disseminated disease developed in 28 of these 34, and four of these 28 patients with disseminated disease presented with concomitant pulmonary and meningeal infections. In all the remaining 24 central nervous system involvement developed 2 to 20 weeks after the finding of an abnormal chest roentgenogram. Seven patients were normal hosts, and in six of these cases disease remained localized to the lung. Four important conclusions were drawn from this study: pulmonary cryptococcosis is rarely considered in the differential diagnosis of an abnormal chest roentgenogram, thereby leading to missed diagnoses and therapeutic errors; the natural history of untreated pulmonary cryptococcosis in compromised hosts is extrapulmonic dissemination; compromised hosts with pulmonary cryptococcosis should receive antifungal therapy because of a high propensity for dissemination; and normal hosts in whom dissemination has been excluded generally do not need antifungal therapy.

Adolescent↗

Human infection from an unidentified erythrocyte-associated bacterium.

A 49-year-old splenectomized man had an infection from an unidentified, gram-positive, rod-shaped bacterium that adhered to the majority of his peripheral-blood erythrocytes. On transmission electron microscopy, the bacterium was seen to be extra-erythrocytic and was 0.2 micrometer wide by 1.0 to 1.7 micrometer long. It possessed a thick, granular cell wall, a trilamellar membrane external to the cell wall and prominent mesosomes. Attempts to cultivate the organism in vitro or to duplicate the patient's disease in splenectomized animals were unsuccessful. The patient's response suggested that the bacterium was susceptible to cell-wall-active antibiotics and to chloramphenicol but not to tetracycline. This bacterium may be the cause of other chronic, fever-producing, multisystem diseases of unknown origin.

Animals↗

A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptoccal meningitis.

We compared amphotericin B therapy for cryptococcal meningitis with a newer regimen containing both amphotericin B and flucytosine. In 50 patients with 51 courses of therapy adherent to the protocol, 27 courses were with amphotericin B and 24 with the combination. Even though the combination regimen was given for only six weeks and amphotericin B for 10 weeks, the combination cured or improved more patients (16 vs 11), produced fewer failures or relapses (three vs. 11), more rapid sterilization of the cerebrospinal fluid (P less than 0.001) and less nephrotoxicity (P less than 0.05) than did amphotericin B alone. The number of deaths was the same (five) with each regimen. Adverse reactions to flucytosine occurred in 11 of 34 patients but were not life threatening. We conclude that combined flucytosine-amphoericin B therapy is the regimen of choice in cryptococcal meningitis.

Adolescent↗

Tetracycline. Another example of generic bioinequivalence.

Because of the Food and Drug Administration batch certification assurances, state government systems generally purchase antibiotics from the lowest bidder. A tetracycline hydrochloride tablet purchased in this manner is shown to be inferior to the innovator capsule product.

Biological Availability↗

Comparison of cephalothin and cefamandole prophylaxis during insertion of prosthetic heart valves.

Cefamandole nafate (CM) and cephalothin sodium (CP) were administered as prophylaxis in a randomized, prospective study to 30 consecutive patients undergoing prosthetic cardiac valve insertion. A single dose of 20 mg/kg was given intramuscularly during anesthesia induction, and serial plasma antibiotic concentrations, atrial muscle and cardiac valve tissue antibiotic levels, plasma bactericidal activity against pathogenic staphylococci, and infectious complications were determined and compared for the two drugs. Both antibiotics produced high plasma levels (>20 mug/ml 30 min after injection) which fell less than 25% during the period of cardiopulmonary bypass. However, CM levels were significantly higher at most time periods (P<0.05) than CP levels. CP levels were undetectable in atrial muscle from 14 of 15 patients and in valves from 10 of 15 patients. In contrast, CM bioactivity was found in all tissues. Differences in tissue antibiotic concentration could not be accounted for by differences in plasma concentrations or by CP tissue binding and were assumed to be caused by differences in penetration. Plasma bactericidal activity against staphylococci was equal for the two drugs (median titer, 1:16). No infections were seen in either group. CM appeared to be an effective and perhaps preferable prophylactic antibiotic for use during cardiac surgery.

Adolescent↗

Therapeutic failures with miconazole.

A retrospective review of therapeutic failures of miconazole in three patients is presented. Miconazole, a new imidazole derivative, is a broad-spectrum antifungal agent purportedly effective topically, orally, and parenterally against a number of species of fungi. Three patients with the following culturally proven deep fungal infections were treated with miconazole: (i) destructive arthritis (Sporothrix schenckii), (ii) meningoencephalitis (Cryptococcus neoformans), and (iii) disseminated aspergillosis (Aspergillus fumigatus). All the organisms were susceptible in vitro to 1.56 mug or less of miconazole per ml using a broth dilution technique. In each patient, miconazole administered intravenously in dosages of 30 mg/kg per day failed to control or eradicate infection. Miconazole serum levels ranged from <0.5 to 4.35 mug/ml as determined by radial diffusion bioassay. Cerebrospinal fluid levels were virtually undetectable. In one patient (C. neoformans), miconazole was given intraventricularly in doses of 15 mg without response. Therapeutic failures were attributed to suboptimal body fluid levels of miconazole. The reason(s) for such low levels of activity was not clear, but may have been poor penetrance into tissues, in vitro inactivation, and/or unusually rapid excretion. Untoward reactions from miconazole included fever, chills, nausea, vomiting, and phlebitis.

Adult↗

Meningoencephalitis and brain abscess due to a free-living amoeba.

A 47-year-old diabetic woman developed fatal meningoencephalitis due to a free-living amoeba. The responsible organism appeared to be neither Naegleria nor Acanthamoeba-Hartmannella. Both acute and chronic (granulomatous) inflammatory reactions of the brain were present, and both cysts and trophozoite forms were readily visualized. The latest classification and methods of identification of such amoebae are reviewed and their threat to public health underscored. It should be realized that a variety of free-living amoebae exist in nature, which potentially can produce meningoencephalitis in humans, and that none of these organisms should be labeled or considered as "avirulent" or "nonpathogenic" until proved otherwise.

Amebiasis↗

Experimental Acanthamoeba infections in mice pretreated with methylprednisolone or tetracycline.

Human infections due to free-living amebas of the genus Acathamoeba have been reported sporadically, occasionally in individuals with underlying diseases. To determine if such infections may be considered opportunistic, groups of laboratory mice were pretreated with either methylprednisolone or tetracycline and inoculated intranasally with 1.075 times 10(4) Acanthamoeba castellanii isolated from a natural fresh water well. Results were compared with controls receiving either drug or amebas alone and with controls receiving saline injections with and without amebas. The mortality rate for those animals receiving methylprednisolone and amebas (50%) was found to be greater than the mortality in ameba controls (10%) (P equal 0.074). Similarly, the mortality rate for animals receiving tetracycline and amebas (60%) was higher than the mortality in the ameba controls (10%) (P equal 0.0286). Precise mechanisms for the increased mortality were unknown but were suspected to be due to the capacity of either corticosteroids or tetracycline to suppress host defenses, particularly those depending on neutrophils. The findings suggest a potentially pathogenic role for naturally occurring Acanthamoeba sp in humans with depressed host immunity.

Amebiasis↗

Endocarditis due to accidental penetrating foreign bodies.

A 15 year old boy had an eight month history of recurrent fever, malaise and poor appetite. Chest roentgenogram revealed a foreign object overlying the right ventricle. Multiple blood cultures grew Enterobacter cloacae. The patients condition improved and blood cultures became negative following gentamicin and carbenicillin therapy. E. cloacae was isolated from the foreign body (a finishing nail) at surgery. Antimicrobial therapy was continued for a total of 30 days, and the patient made an uneventful recovery.

Adolescent↗

In vitro susceptibility of pathogenic Naegleria and Acanthamoeba speicies to a variety of therapeutic agents.

Six pathogenic strains of Naegleria fowleri, two of Acanthamoeba castellanii, and three of Acanthamoeba polyphaga were tested in vitro for susceptibility to a variety of potentially useful therapeutic agents. Minimal motility inhibitory concentrations and minimal inhibitory concentrations were determined by a technique of subculturing pure clones of amoebae in plastic tissue culture chamber slides containing liquid axenic media and serially diluted drug, incubating at 30 degrees C for Acanthamoeba and at 37 degrees C for Naegleria, and observing on an inverted microscope at 6 h for inhibition of motility and at 24 and 48 h for inhibition of growth. Drug concentrations were selected on the basis of fluid levels achievable in humans. Amphotericin B, clotrimazole, and miconazole were the most effective drugs against Naegleria, whereas polymyxin B sulfate and pentamidine isethionate were somewhat effective against pathogenic Acanthamoeba. Our results suggest that amphotericin B is the most effective agent against Naegleria, but few agents are effective against Acanthamoeba.

Antiprotozoal Agents↗