Biomedical subjects
Publications and source records attributed to G R Hodges.
A 35-year-old man with osteomyelitis of the calvarium, from which Acremonium kiliense was consistently isolated, was successfully treated with amphotericin-B and ketoconazole in addition to craniectomy. Subsequent acrylic cranioplasty produced a good cosmetic result.
To determine whether daily intraventricular injection of gentamicin sulfate is ototoxic, adult male rabbits were given 0.2 ml of saline (group 1; n = 8) or 0.25 mg/kg of gentamicin sulfate in 0.2 ml of saline (group 2; n = 7) by intraventricular infusion once a day for 21 d. All rabbits were also given intramuscular gentamicin sulfate, 2 mg/kg, twice daily. Before and after antibiotic treatment, brainstem auditory evoked responses (BAERs) were recorded. During the experimental period, neurologic examinations were performed on all rabbits. After treatment, the animals were euthanized; brain tissue and cochleas were then removed for histopathologic examination. The ratios of neurologic abnormalities observed in group 1 and 2 animals, respectively, were 0/8 and 5/7; of abnormal BAERs, 0/8 and 5/7; of abnormal brain morphology, 2/5 and 6/6; and of abnormal cochlear morphology, 0/6 and 7/7. The electrophysiologic evidence of auditory deficit and the structural evidence of ototoxic insult are significantly associated (p less than or equal to 0.006) with intraventricularly administered gentamicin sulfate. These data suggest that intraventricular gentamicin should be used with caution.
The correlation between clinical significance and serotype, biotype, and beta-lactamase production of 101 respiratory isolates of Hemophilus influenza from nonbacteremic patients was determined. Six of 33 (18.2%) isolates from patients with definite or probable infection were serotypable; only two of 67 (3%) isolates from colonized patients were serotypable. Eight-seven and one-half per cent of the serotypable strains were biotypes I or IV; 78.8% of nonserotypable strains were biotypes II, III, or V. Biotype distribution among isolates from patients with definite or probable infection were similar to isolates from colonized patients. beta-lactamase production was not helpful in evaluating clinical significance. Nonserotypable H. influenzae is an important cause of nonbacteremic pneumonia in elderly men.
The effects of exchange transfusion with Fluosol DA (FDA) or stroma-free hemoglobin on the outcome of pneumococcal infection in rats were determined. Rats were sham transfused or exchange transfused with 25 ml of FDA or stroma-free hemoglobin. They were then challenged intraperitoneally with Streptococcus pneumoniae type 3 and treated with penicillin for 120 h. Only 2 of 15 (13.3%) FDA-transfused rats were alive at 312 h compared with 11 of 15 (73.3%) concurrently studied sham-transfused control rats (P = 0.0016). Of 10 stroma-free hemoglobin-transfused rats and 10 concurrently studied sham-transfused control rats (P = 0.98), 8 from each group (80%) were alive at 312 h. Penicillin therapy only suppressed pneumococcal infection in FDA-transfused rats, and relapse occurred after therapy was stopped. This effect could not be attributed to interference with the bactericidal activity of penicillin against pneumococci, to an alteration in the pneumococcal burden before penicillin therapy or to an alteration of the leukocyte and polymorphonuclear leukocyte response by FDA. In contrast, pneumococcal infection in stroma-free hemoglobin-transfused rats was cured with penicillin therapy. These data showed that FDA altered the ability of rats to respond to pneumococcal infection.
Commonly used antibacterial agents may be associated with various neurotoxic reactions. Central nervous system toxicities include seizure disorders, encephalopathy, bulging fontanelles, and neuropsychiatric symptoms. These abnormalities have been associated with the use of the penicillins, cephalosporins, sulfonamides, tetracyclines, chloramphenicol, colistin, aminoglycosides, metronidazole, isoniazid, rifampin, ethionamide, cycloserine, and dapsone. Cranial nerve toxicities, such as myopia, optic neuritis, deafness, vertigo, and tinnitus, have been associated with the use of erythromycin, sulfonamides, tetracyclines, chloramphenicol, colistin, aminoglycosides, vancomycin, isoniazid, and ethambutol. Peripheral nerve symptoms consisting of paresthesias, motor weakness, or sensory impairment have been associated with the use of the penicillins, sulfonamides, chloramphenicol, colistin, metronidazole, isoniazid, ethionamide, and dapsone. Neuromuscular blockade has been associated with the use of the tetracyclines, polymyxins, lincomycin, clindamycin, and aminoglycosides. Management generally consists of supportive therapy and immediate discontinuation of therapy with the offending drug.
The oxygen-carrying resuscitation fluids, Fluosol DA 20% and stroma-free hemoglobin, are currently being evaluated for efficacy and effects in vivo. Because these fluids may be administered to trauma victims, the pharmacokinetics of morphine was studied in rats after transfusion with one of these fluids. During development of high-performance liquid chromatography assay for morphine in plasma, an in vitro interaction between plasma, Fluosol DA, or stroma-free hemoglobin and morphine was observed at pH greater than 10.5. This interaction was dependent on pH and was specific to morphine, compared with codeine. The interaction between stroma-free hemoglobin and morphine appeared to be covalent in nature. The t1/2 of morphine was significantly prolonged from 1.02 +/- 0.50 hours (mean +/- SD) to 2.46 +/- 2.68 hours (p = 0.03) after transfusion with stroma-free hemoglobin, and to 2.05 +/- 0.95 hours (p = 0.006) after transfusion with Fluosol DA. The volume of distribution was increased from 1.35 +/- 0.81 L X kg-1 to 2.99 +/- 1.45 L X kg-1 (p = 0.004) after transfusion with stroma-free hemoglobin; no such difference was observed after transfusion with fluosol DA (p = 0.86). The area under the time-concentration curve was increased from 2.37 +/- 1.78 mg X hr X L-1 to 6.02 +/- 6.61 mg X hr X L-1 (p = 0.02), and total body clearance was decreased from 1.02 +/- 0.53 L X hr-1 X kg-1 to 0.55 +/- 0.36 L X hr-1 X kg-1 (p = 0.01) after transfusion with Fluosol DA. No significant differences were observed in these parameters after transfusion with stroma-free hemoglobin (p = 0.48 and p = 0.81, respectively). These data show that stroma-free hemoglobin prolongs the t1/2 of morphine by altering the volume of distribution. In contrast, Fluosol DA prolongs the t1/2 of morphine by altering the total body clearance. These data may have important therapeutic implications.
The effects of exchange transfusion with an oxygen-carrying resuscitation fluid, Fluosol DA 20% or stroma-free hemoglobin, on the pharmacokinetics of antipyrine, diazepam, penicillin, and sulfamethazine were studied in rats. After transfusion with Fluosol DA 20% or stroma-free hemoglobin the pharmacokinetics of antipyrine, diazepam, and penicillin were unchanged when compared to control animals. After transfusion with Fluosol DA 20%, the t 1/2 of sulfamethazine was increased from 3.15 +/- 0.56 to 7.65 +/- 2.41 hr (p less than 0.05) and the Vd was increased from 60.7 +/- 17.5 to 152 +/- 16 ml (p less than 0.05). In contrast, after transfusion with stroma-free hemoglobin, the AUC of sulfamethazine was decreased from 129 +/- 28 to 80.5 +/- 27.7 micrograms X h X ml-1 (p less than 0.05) and there was an increase in Cl from 12.2 +/- 3.4 to 20.2 +/- 6.0 ml X h-1 (p less than 0.05) and Vd from 60.1 +/- 11.8 to 132 +/- 49 ml (p less than 0.05). The reason for these alterations is not clear. Fluosol DA 20% and stroma-free hemoglobin may alter the acetylation of sulfamethazine.
During a recent hepatitis B vaccination program among high-risk health care workers, the major sources of information about the vaccine were an in-service informational program, discussion with co-workers, and professional journals. Little or no information was obtained from the lay media or the product brochure. Two thirds of the personnel to whom the vaccine was offered accepted the vaccine. The major reason for accepting the vaccine was a perceived high-risk of contracting hepatitis B. In contrast, one third of the high-risk individuals offered the vaccine declined the opportunity. The major reason for not accepting the vaccine was concern with potential side effects. This information would have been helpful during the planning phase of the program.
Our series of 62 patients points out several features in the current management of tuberculosis. First, if there is a high index of suspicion for tuberculosis, protection of other health care personnel can be achieved to a large degree. Second, it is imperative that results of positive cultures for M. tuberculosis be channeled through a centralized registry so that patients with positive cultures are not overlooked because of the delay in obtaining culture results and the lack of continuity of care in certain clinical settings. This will help ensure the appropriate treatment for patients and, through public health authorities, the initiation of contact screening.
A 31-year-old white man with suspected aspiration pneumonia complicated by multiple pulmonary abscesses had profound neutropenia during a course of high-dose benzylpenicillin therapy for suspected bacterial endocarditis. Antigranulocyte antibodies were identified in the patient's serum. Leukopenia is an uncommon but potentially serious complication of therapy with this drug. We recommend weekly monitoring of blood counts during prolonged therapy with any beta-lactam antibiotic.
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The impacts of meningeal infection with Pseudomonas aeruginosa and route of drug administration on the penetration of azlocillin and mezlocillin into the cerebrospinal fluid of rabbits were evaluated. The penetration of both agents was increased to a similar degree in rabbits with meningitis compared with normal rabbits. The increase in penetration was greater after intravenous administration than after intramuscular administration.
We reviewed the charts of 163 patients with 183 episodes of Gram-negative bacillary bacteremia to determine a clinical profile that would select patients at high risk for experiencing gentamicin-sulfate-resistant Gram-negative bacillary bacteremia at our hospital. Gentamicin-resistant Gram-negative bacilli were only associated with institution-acquired bacteremia. Among institution-acquired episodes, urinary tract infection, diagnostic or therapeutic procedures of the lower respiratory tract or urinary tract, presence of pneumonic infiltrate on chest roentgenogram, prior therapy with gentamicin, and prior therapy with other antibiotics were significant risk factors. Because only two of the 29 gentamicin-resistant bacteria that were tested against amikacin base were resistant to amikacin, we advocate initial treatment with amikacin for patients with evidence of an institution-acquired Gram-negative bacteremic episode. Gentamicin is still our initial choice for a community-acquired episode.
To determine whether daily intraventricular injection of gentamicin sulfate would cause neurologic or morphologic abnormalities of the central nervous system, adult male rabbits were given gentamicin sulfate, 2 mg/kg, intramuscularly twice a day plus saline, 0.2 ml (group 1), or gentamicin, 0.05 mg/kg (group 2), 0.25 mg/kg (group 3), or 0.5 mg/kg (group 4), given as the sulfate intraventricularly once a day. The majority of the animals in group 4 developed neurologic abnormalities which progressed to death in animals that were not euthanized; neuropathologic studies revealed chemical ventriculitis and meningitis that were associated with high levels of gentamicin in the cerebrospinal fluid and tissue of the central nervous system. Similar neurologic and morphologic changes were seen in most animals of group 3 but not in rabbits of groups 1 and 2. The ototoxicity and nephrotoxicity of gentamicin are well known; these data indicate that it may be toxic to the central nervous system as well.
A 67-year-old man presented with a rash that was refractory to systemic corticosteroid therapy. Physical examination revealed sloughing skin on his hands, soles, and lower extremities. Stroking involved and uninvolved skin produced Nikolsky's sign. Skin biopsies revealed the plane of cleavage to be in the basal epidermal layer. Cultures of the patient's skin, blood, nose, and throat grew Staphylococcus aureus. These isolates produced an epidermal toxin that caused Nikolsky's sign in neonatal mice. The toxin caused cleavage in the basal epidermal layer of neonatal mice, was heat labile, and was not neutralized by exfoliatin antitoxin.
An elderly man, without heat in his home for two days, presented with cold, painful, swollen feet. Second-degree frostbite was present. After having moist packs applied to his feet for five days, the patient became febrile and hypotensive, and wet gangrene necessitated left below-knee and right above-knee amputations. Aeromonas hydrophila was isolated from the patient's blood and cultures of the pedal wounds. An etiologic role of the moist pack therapy is postulated.
Investigation of epidemic outbreaks of Legionnaires disease by Center for Disease Control personnel has resulted in the isolation of Legionella pneumophila from water in the air-conditioning cooling towers or evaporative condensers at the site of the outbreak. It is suspected that improperly maintained open, recirculating water systems may play a role in the growth and dissemination of this pathogen. The objective of this study was to determine the antimicrobial activity of three chemically different, commercially available, cooling tower microbicides against L. pneumophila. Using two in vitro test systems, a combination of N-alkyl dimethyl benzyl ammonium chloride and bis (tri-n-butyltin) oxide was found to kill L. pneumophila at a concentration 25 times less than the minimum recommended use concentration, whereas N-alkyl 1,3-propanediamine and methylene bis (thiocyanate) were active at concentrations equal to or greater than the concentrations recommended for use by the manufacturer.
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