PubMed Health⌕ Search

Biomedical subjects

J D Dick

Publications and source records attributed to J D Dick.

At least 37 records · Page 2Linked to original sources

Protein binding of vancomycin in a patient with immunoglobulin A myeloma.

Atypical vancomycin pharmacokinetics were observed in an immunoglobulin A myeloma patient. Drug concentrations in serum were extremely elevated, the elimination half-life was prolonged despite normal renal function, and the vancomycin therapy was ineffective. Extensive binding of vancomycin, presumably by high concentrations of an aberrant immunoglobulin A protein, may have accounted for these observations.

Bacterial Infections↗

Management of infectious complications of acute leukemia and antileukemia therapy.

The patient with acute leukemia is predisposed to infection by bone marrow failure that leads to absence of granulocytes, by extramedullary leukemia infiltration that leads to barrier breakdown, and by cytotoxic antileukemia therapy that exaggerates both the hematopoietic and the tissue mucosal defects. Empiric approaches tailored to treat commonly occurring bacterial and fungal infections have successfully decreased the morbidity and mortality from overwhelming infection in these compromised patients. More recently, prophylaxis directed against dissemination of pathogens from specific sites has had a positive impact in preventing the clinical and microbiological manifestations of infection during profound aplasia. The approaches that have been successful in preventing and treating bacterial infections are being applied to the increasingly prevalent fungal infections that occur later during the granulocytopenic course, with encouraging results.

Acute Disease↗

Listeriosis in the setting of malignant disease. Changing issues in an unusual infection.

Thirteen cases of Listeria monocytogenes infection occurred at the Johns Hopkins Oncology Center over a 10-year period, representing 0.09% of all admissions. These cases principally occurred in patients with underlying hematologic of lymphoreticular malignancy, but in all patients other causes of immune suppression were also present. Corticosteroids were the most frequent exogenous cause of immune suppression. Bacteremia was detected more frequently than meningitis and in contrast to earlier reports, bacteriologic cure was achieved in 12 of 13 patients. Therapeutic success appeared to be related to early institution of effective antimicrobial agents. Despite eradication of infection, seven of the patients were dead within three months from progression of their underlying disease. The overall survival rate of cancer patients with listeriosis is therefore a function of the underlying malignancy and not the infection.

Adult↗

Vibrio cholerae non-serogroup O1 cystitis.

We report a case of a patient who developed cystitis caused by non-serogroup O1 Vibrio cholerae after swimming in the Chesapeake Bay. Treatment was empirical, with complete symptomatic resolution. Genitourinary tract infections by Vibrio spp. are uncommon but should be considered when cystitis occurs after saltwater exposure in appropriate geographic regions.

Adult↗

High resolution deuterium NMR studies of bacterial metabolism.

High resolution deuterium NMR spectra were obtained from suspensions of five bacterial strains: Escherichia coli, Clostridium perfringens, Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus aureus. Deuterium-labeled D-glucose at C-1, C-2, and C-6 was used to monitor dynamically anaerobic metabolism. The flux of glucose through the various bacterial metabolic pathways could be determined by following the disappearance of glucose and the appearance of the major end products in the 2H NMR spectrum. The presence of both labeled and unlabeled metabolites could be detected using 1H NMR spectroscopy since the proton resonances in the labeled species are shifted upfield due to an isotopic chemical shift effect. The 1H-1H scalar coupling observed in both the 2H and 1H NMR spectra was used to assign definitively the resonances of labeled species. An increase in the intensity of natural abundance deuterium signal of water can be used to monitor pathways in which a deuteron is lost from the labeled metabolite. The steps in which label loss can occur are outlined, and the influence these processes have on the ability of 2H NMR spectroscopy to monitor metabolism are assessed.

Bacteria↗

Use of collagen corneal shields in the treatment of bacterial keratitis.

We used an animal model of Pseudomonas keratitis to compare treatment by topical tobramycin with and without the presence of a commercially available collagen corneal shield. Pilot studies showed a significant, 30-fold increase in penetration of tobramycin into the anterior chamber in eyes with a collagen shield in place. Twenty albino rabbit eyes were inoculated with P. aeruginosa to produce stromal keratitis. After 12 hours of topical tobramycin dosing, eyes with a collagen corneal shield in place had a statistically significant (P less than .01) decrease in colony forming unit counts in comparison to treated eyes without a shield and control eyes.

Animals↗

Topical imipenem therapy of aminoglycoside-resistant Pseudomonas keratitis in rabbits.

We used a rabbit model of bacterial keratitis to assess in vivo efficacy of topical imipenem, a highly potent beta-lactam antibiotic with an unusually broad spectrum of activity, including aminoglycoside-resistant Pseudomonas aeruginosa. Albino rabbits received intrastromal injections of 5 x 10(2) organisms of an aminoglycoside-resistant strain of P. aeruginosa. At five hours postinoculation, imipenem (5 mg/ml) therapy was initiated using one drop per 30 minutes for 12 hours. Corneal tissue was then excised for colony forming unit counts. Imipenem was highly effective in reducing colony forming unit counts to zero in comparison to 4.1 x 10(5) organisms for untreated controls. A second regimen beginning 24 hours postinoculation of one drop per hour for 24 hours was also successful in significantly reducing colony forming units vs controls (P less than .05). These data suggest that topical imipenem may have clinical applicability in the treatment of P. aeruginosa keratitis.

Administration, Topical↗

Topical ciprofloxacin treatment of Pseudomonas keratitis in rabbits.

Ciprofloxacin is a new quinolone antibiotic that is highly active in vitro against Pseudomonas aeruginosa. A rabbit model of bacterial keratitis was used to assess the in vivo efficacy of topical ciprofloxacin. Albino rabbits received intrastromal injections of 5 X 10(2) aminoglycoside-resistant P aeruginosa organisms. At five hours after inoculation, ciprofloxacin (3 mg/mL) therapy was initiated (one drop every 30 minutes for 12 hours). Corneal tissue was then excised for bacterial colony counts. No organisms were recovered from ciprofloxacin-treated eyes, compared with an average of 3.1 X 10(7) organisms per milliliter recovered from untreated controls. This model suggests that topical ciprofloxacin may be clinically useful in the treatment of aminoglycoside-resistant P aeruginosa keratitis.

Administration, Topical↗

Use of collagen corneal shields versus soft contact lenses to enhance penetration of topical tobramycin.

We compared the corneal penetration in rabbits of topical tobramycin in the presence of collagen corneal shields and bandage soft contact lenses. A collagen corneal shield was placed on six albino rabbit eyes, while therapeutic soft contact lenses (61.4% poly-2-hydroxyethyl-methacrylate/38.6% water) were placed on six eyes. Four control eyes received no shield or contact lens. Topical tobramycin was applied to all 16 eyes every five minutes for six doses. Samples of aqueous humor were removed at 15 and 60 minutes following the last dose. Collagen corneal shields allowed a significant (P less than .05) increase in tobramycin penetration into the anterior chamber at 60 minutes compared with hydrophilic soft contact lenses or controls.

Administration, Topical↗

Bacterial and host factors affecting Pseudomonas aeruginosa colonization versus bacteremia in granulocytopenic patients.

In order to evaluate bacterial factors which might predispose to P. aeruginosa colonization or bacteremia in the granulocytopenic patient, 132 isolates recovered from 44 oncology patients were evaluated for antigenic serotype, iron correctable sensitivity to pooled human serum, antibiotic susceptibility, production of lecithinase, elastase, protease, gelatinase, pyocyanin and pyoverdin. Similarly, potential host factors, primarily total iron binding capacity, were evaluated in a subpopulation of acute leukemia patients composed of 13 control patients without P. aeruginosa cultured during their hospital course, 11 colonization only patients and 15 P. aeruginosa bacteremia patients. No significant differences were observed between strains recovered from bacteremia vs. colonization patients for extracellular enzyme activity, pigment production, serum sensitivity and antigenic serotype. Significant differences were observed between bacteremia and colonizing strains for antibiotic susceptibility to ticarcillin, 40% vs. 76% (P less than 0.002); piperacillin, 44% vs. 86% (P less than 0.006); and cefsulodin, 60% vs. 90% (P less than 0.02). Of the host factors evaluated in the acute leukemia patients, significant differences were observed between the TIBC nadir of control patients and both colonization patients (P less than 0.0002) and bacteremia patients (P less than 0.0004). P. aeruginosa bacteremia was associated with the temporal occurrence of TIBC nadir and the detection of the organism. These data suggest a possible role for beta-lactam antibiotic resistance and host iron binding capacity as determinants and possible predictors of P. aeruginosa sepsis in the granulocytopenic patient.

Adult↗

Systemic infection and colonization with and without prophylactic norfloxacin use over time in the granulocytopenic, acute leukemia patient.

Patients undergoing intensive antileukemic chemotherapy and profound granulocytopenia are susceptible to overwhelming infections, particularly those arising from disease- and therapy-related gastrointestinal tract damage. We have previously demonstrated that the ability to suppress bacterial colonization of this site with oral norfloxacin prophylaxis (400 mg every 12 h) affects the incidence and distribution of aerobic gram-negative bacterial infections and the overall management of infectious complications in this patient population. We have now determined the broad impact of continuous, long-term use of oral norfloxacin on aerobic gram-negative bacterial infection and colonization, overall management of presumed and documented infections during marrow aplasia and emergence of clinically significant antibiotic resistant pathogens during intensive antileukemic chemotherapy. Oral norfloxacin prophylaxis administered throughout the course of induced granulocytopenia continues to afford effective protection by suppressing the development of aerobic gram-negative infections, particularly those arising from the gastrointestinal tract, and preventing the acquisition or emergence of multiply resistant pathogens. A long-range effect of norfloxacin on pathogens colonizing the respiratory tract is also detected, with inhibition of acquired drug resistance occurring at that site as well. For these reasons, norfloxacin continues to be an excellent agent for oral prophylactic use in this patient population.

Administration, Oral↗

Empiric use of vancomycin during prolonged treatment-induced granulocytopenia. Randomized, double-blind, placebo-controlled clinical trial in patients with acute leukemia.

Because gram-positive infections cause morbidity following intensive antileukemic chemotherapy, the effects of vancomycin versus placebo were evaluated in a randomized, double-blind, placebo-controlled trial in 60 adult patients with acute leukemia and first infectious fever during prolonged (mean of 32 days) granulocytopenia. Gram-positive sepsis was associated with first fever in 17 (28 percent) of the 60 patients. None of 31 patients randomly assigned to receive vancomycin demonstrated gram-positive infection, whereas 16 of 22 patients randomly assigned to receive placebo subsequently had gram-positive infection (seven had sepsis, and nine had local infections; p less than 0.005). All patients with gram-positive infection were then given vancomycin, and all showed prompt clinical responses. The predominant gram-positive organism causing infection was beta-lactam-resistant Staphylococcus epidermis (19 of 44 isolates). Patients randomly assigned to receive vancomycin had more rapid resolution of first infectious fever and fewer total febrile days during the granulocytopenic course than did patients randomly assigned to receive placebo. Although vancomycin had no effect on the presence or absence of documented fungal infection, patients treated with vancomycin received empiric amphotericin B for recurrent or persistent fever later (mean of 14 days after initial antibiotic coverage was begun) than did patients receiving placebo (mean of 9.9 days; p less than 0.005), and thus received fewer total days of empiric amphotericin B therapy (mean of 16.3 days) than did patients given placebo (mean of 24.6 days; p less than 0.01). These data demonstrate that empiric use of vancomycin reduces the morbidity of gram-positive infections following intensive antileukemic therapy and decreases the need for empiric use of toxic amphotericin B.

Adult↗

Determination of norfloxacin and ciprofloxacin concentrations in serum and urine by high-pressure liquid chromatography.

A high-pressure liquid chromatographic method for the determination of norfloxacin or ciprofloxacin concentrations in body fluids was developed and compared with a standard bioassay. The high-pressure liquid chromatographic assay utilizes a reverse-phase C18 column, an internal standard, and fluorescence detection, with reproducibility studies yielding coefficients of variation ranging from 0.6 to 3.7% and 0.9 to 2.7% for norfloxacin and ciprofloxacin, respectively. Correlation coefficients with the bioassay were 0.966 for norfloxacin and 0.952 for ciprofloxacin.

Chromatography, High Pressure Liquid↗

Determination of ticarcillin levels in serum by high-pressure liquid chromatography.

A high-pressure liquid chromatographic method for determining the concentrations of ticarcillin in serum was developed and compared, with 93 patient sera, to a standard agar well diffusion bioassay. For analysis, serum plus temocillin, the internal standard, were extracted with chloroform-n-amyl alcohol and back extracted into phosphate buffer. A reverse-phase C18 column and an ammonium acetate-methanol mobile phase were used with detection at 242 nm. Reproducibility studies yielded coefficients of variation ranging from 2.4 to 4.7% for low, mid, and high controls. Although cefoxitin, cephalothin, and cefuroxime exhibited retention similar to that of ticarcillin, a wide range of commonly administered antibiotics and other drugs did not interfere. The high-pressure liquid chromatographic assay is an accurate, reproducible method for determining the concentration of ticarcillin in serum during multiple antibiotic therapy or when rapid results are required.

Chromatography, High Pressure Liquid↗

Prolonged elimination of piperacillin in a patient with renal and liver failure.

A 22-year-old female with acute leukemia was admitted to the oncology center for evaluation and treatment. Piperacillin was used during her admission for treatment of Pseudomonal sepsis. The patient's renal and liver function deteriorated during the hospital course, requiring large dose adjustments of piperacillin. The elimination half-life of piperacillin was estimated to be 32 hours. Patients with both liver and renal disease require only small doses of piperacillin to achieve therapeutic plasma concentration.

Adult↗