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Biomedical subjects

G P Bodey

Publications and source records attributed to G P Bodey.

At least 109 records · Page 6Linked to original sources
PubMed1992

Evaluation of strategies for central venous catheter replacement.

OBJECTIVES: To assess the consequences of leaving a bacterially colonized central venous catheter in place and to compare the effects of three catheter replacement strategies for catheter repair control in an animal model. DESIGN: Prospective study. SETTING: Laboratory and animal facility of a large university. SUBJECTS: Eighteen healthy, female, adult sheep. INTERVENTIONS: Radiopaque-siliconized elastomer central venous catheters were inserted into the jugular veins and colonized with either Escherichia coli or Staphylococcus epidermidis. After 7 days of infection, the catheters were either: a) exchanged using a guidewire; b) removed and replaced with a new catheter in a new jugular vein site after a 48-hr interval; or c) exchanged using a guidewire and antibiotics (tobramycin, cephaloridine) injected into the catheter. Animals were euthanized 7 days after insertion of the new catheter. Quantitative microbiology was performed on blood samples collected daily from the catheters and a peripheral vein, as well as from catheters and tissue recovered from the sheep at the time of autopsy. MEASUREMENTS AND MAIN RESULT: When catheters were changed using a guidewire, they became colonized by bacteria within 48 hrs, and the sheep had embolic pneumonia and vegetative endocarditis at autopsy. Similar consequences were observed when antibiotics were administered into the catheter lumen. If colonized catheters were removed and a new catheter was inserted after a 48-hr interval, recolonization, pneumonia, and endocarditis were not observed. CONCLUSIONS: Replacement of a biofilm-colonized central venous catheter over a guidewire is associated with rapid colonization of the replacement catheter and production of detached, slime-enclosed, antibiotic-resistant aggregates that colonize other catheters or initiate endocarditis or pneumonia by dissemination in the bloodstream.

Animals↗
PubMed1992

In vitro activity of Ro 23-9424, a dual-action antibacterial agent, against bacterial isolates from cancer patients compared with those of other agents.

The in vitro activity of Ro 23-9424 against bacterial isolates from patients with cancer was compared with those of fleroxacin, ciprofloxacin, cefoperazone, and ceftazidime. Ro 23-9424 inhibited the majority of the members of the family Enterobacteriaceae and all Aeromonas isolates at a concentration of less than or equal to 1.0 micrograms/ml. It was also active against Acinetobacter spp. and Haemophilus influenzae, including beta-lactamase-producing strains. The MIC for 90% of isolates (MIC90) of Pseudomonas aeruginosa was 16.0 micrograms/ml. All group A and B streptococci were inhibited by less than or equal to 0.25 micrograms/ml, and 90% of group G streptococci and Streptococcus pneumoniae were inhibited by 1.0 micrograms/ml. All methicillin-susceptible strains of Staphylococcus aureus and 60% of methicillin-resistant strains were susceptible to 2.0 micrograms of Ro 23-9424 per ml, whereas the MIC90 for Staphylococcus epidermidis and Staphylococcus hominis isolates was 4.0 micrograms/ml. Staphylococcus haemolyticus and Enterococcus spp. were less susceptible; MIC90s for them were 16.0 and 32.0 micrograms/ml. Ro 23-9424 has a broad antibacterial spectrum and potential utility for therapy of infections in cancer patients.

Anti-Infective Agents↗
PubMed1992

Pseudomonas aeruginosa infection in cancer patients.

Pseudomonas aeruginosa is an important cause of infection in immunosuppressed patients, particularly those with cancer. However, it is being recognized with greater frequency in patients who appear to be immunocompetent. Changes in modern lifestyles have led to the appearance of some new manifestations of pseudomonas infection including corneal ulceration and keratitis associated with contact lenses, and hot-tub- or whirlpool-associated folliculitis. These represent additional hazards to patients with cancer. Many studies, both in animals and humans, have contributed to our knowledge of the pathogenesis, immunology, treatment, and prevention of pseudomonas infections. Although the aminoglycosides represented a significant step forward in the treatment of these infections, of greater importance was the discovery of the antipseudomonal penicillins. These antibiotics are more effective than the aminoglycosides in neutropenic patients, who are especially susceptible to pseudomonal infections. The older antipseudomonal penicillins (carbenicillin, tircarcillin) have largely been replaced by newer ones (mezlocillin, azlocillin, pipercillin) which are more potent in vitro against P. aeruginosa. Although the accepted therapeutic practice has been to utilize a penicillin in combination with an aminoglycoside, the introduction of newer beta lactam agents and fluoroquinolones with antipseudomonal properties offers the possibility of other approaches to combination therapy. These include the combination of a penicillin or a cephalosporin or the combination of a quinolone with an aminoglycoside or a betalactam antibiotic. However, the development of newer antimicrobial agents is not likely to be a lasting solution to the problem of pseudomonas infections. Since pseudomonas infection often progresses rapidly, optimal results will always depend upon the prompt initiation of appropriate therapy in febrile patients, particularly those who are at high risk. The use of granulocyte transfusions has proved to be of limited benefit. Early data with the use of monoclonal antibodies is promising, and the results of large-scale trials are eagerly awaited. It is hoped that continuing investigation of pseudomonas vaccines will lead to the discovery of effective prophylaxis for highly susceptible patients. It is also hoped that with the availability of GM-CSF it will become possible to reduce the period of risk for serious infections. Finally, a reduction in the frequency of microbiologically proven P. aeruginosa infections in cancer patients should not lead to the assumption that these organisms do not constitute a problem in such patients anymore. The use of prophylactic antibiotics and prompt empiric antibiotic coverage for therapy has resulted in this decline. Cultures are therefore unlikely to be positive with the same frequency as they were before antimicrobial prophylaxis and empiric antibiotic therapy became standard practice.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗
PubMed1992

Viral pneumonia in the immunocompromised adult with neoplastic disease: the role of common community respiratory viruses.

Until recently, the viruses most often identified in lower respiratory tract infections among immunocompromised adults with neoplastic disease have been the herpesviruses (cytomegalovirus, herpes simplex virus, varicella-zoster virus, human herpesvirus-6) and adenovirus. These viral pneumonias occur with greater frequency and/or severity among these adults than among immunocompetent adults. During the last decade, mounting evidence has suggested that the RNA viruses that commonly cause lower respiratory tract disease in the general population, namely influenza virus, respiratory syncytial virus, and parainfluenza virus, are also an important cause of serious community-acquired and nosocomial lower respiratory tract disease among immunocompromised adults. Because these infections are associated with considerable morbidity and mortality and are potentially preventable and treatable, it is important that they be recognized and treated promptly. Various therapies have been tried with some reported success, including amantadine (specifically for influenza A), ribavirin, and intravenous immunoglobulin. The optimal therapy or combination of therapies for these infections among immunocompromised adults remains to be defined in controlled trials.

Adult↗
PubMed1992

Lack of activity of amphotericin B in systemic murine fusarial infection.

Systemic fusarial infections have emerged as a significant cause of mortality in cancer patients. Yet, little is known about the management of these infections. The in vivo antifungal activity of amphotericin B in CF1 mice with disseminated fusarial infections was studied. Two pathogenic strains of Fusarium solani were used. Intraperitoneal administration of amphotericin B in daily doses of 0.5, 1, and 2 mg/kg for less than or equal to 10 days did not prolong survival of treated animals. Clearance of F. solani from kidneys was similar in mice treated with 1 mg/kg per day of amphotericin B and in untreated animals. These results are in agreement with the known in vitro and in vivo resistance of Fusarium species to amphotericin B.

Amphotericin B↗
PubMed1992

A comparison of imipenem to ceftazidime with or without amikacin as empiric therapy in febrile neutropenic patients.

BACKGROUND: Neutropenic patients with cancer are traditionally treated with empiric antibiotic combinations when they become febrile. The availability of broad-spectrum antibiotics such as ceftazidime and imipenem has made it possible to initiate therapy with a single agent (monotherapy). The objectives of this trial were to compare ceftazidime and imipenem as single agents for the therapy of febrile episodes in neutropenic patients and to ascertain whether the addition of an aminoglycoside (amikacin) to either of these agents would provide an advantage. METHODS: A prospective clinical trial was conducted in which eligible neutropenic patients with cancer were randomized to one of four treatment arms: ceftazidime alone; imipenem alone; ceftazidime plus amikacin; and imipenem plus amikacin. Efficacy analysis was done for 750 assessable episodes. A multivariate logistic-regression analysis was also performed to examine the unique contribution of various prognostic factors. RESULTS: The overall response rates were 76% with imipenem plus amikacin, 72% with imipenem, 71% with ceftazidime plus amikacin, and 59% with ceftazidime alone. Single-organism gram-positive infections occurred in 101 of 750 episodes. Without a change in antibiotics, the response rates were 50% with imipenem, 40% with imipenem plus amikacin, 39% with ceftazidime plus amikacin, and 38% with ceftazidime. Most responded to vancomycin or other antibiotics, and the mortality associated with gram-positive infections was only 5%. Regardless of the antibiotic regimen, the majority of uncomplicated gram-negative infections responded to therapy and the majority of complicated gram-negative infections failed to respond. Multivariate logistic-regression analysis showed that recovery of the neutrophil count was the most favorable prognostic factor in a patient's response to infection, whereas the presence of gram-positive infection, acute leukemia, pulmonary or enteric infection, and therapy with ceftazidime were unfavorable factors. CONCLUSIONS: Single-agent therapy with imipenem is as effective as more conventional combination antibiotic therapy for the empirical treatment of febrile episodes in neutropenic patients with cancer.

Adolescent↗
PubMed1991

Spectrum of Aeromonas and Plesiomonas infections in patients with cancer and AIDS.

The spectrum of infection with Aeromonas and Plesiomonas included gastroenteritis, bacteremia, biliary tract infection, perirectal infection, and disseminated disease. Most patients (86%) with bacteremia were neutropenic (less than 500 PMN/mm3). Colonization of stools and sputum also occurred. Therapy with aminoglycosides, beta-lactams, trimethoprim/sulfamethoxazole, and the newer quinolones was effective in patients with AIDS and cancer.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Clostridial bacteremia in cancer patients. A 12-year experience.

Over 12 years, 136 episodes of bacteremia caused by clostridial species were documented. Eighty-three were monomicrobial, and 53 were polymicrobial. Gastrointestinal, genitourinary carcinomas, and acute leukemia were the most common underlying malignancies. Septic shock occurred in 29% of monomicrobial bacteremias and 45% of polymicrobial bacteremias and was associated with a high mortality rate. Acute hemolysis, gas gangrene, and diffuse spreading cellulitis occurred infrequently but were associated with a 100% fatality rate. Many infections caused by Clostridium perfringens and C. septicum were associated with abdominal disease. The most commonly isolated organism was C. perfringens, followed by C. septicum and C. sporogenes. Overall survival was 58%, but it was 66% for monomicrobial episodes and 45% for polymicrobial infections. All of the patients with bacteremia due to an aerobic gram-negative bacillus in addition to the clostridial species died of their infection. The most effective antibiotics were clindamycin, penicillin, metronidazole, and moxalactam. Surgical drainage of abscesses was an important component of therapy.

Adolescent↗
PubMed1991

Review of Citrobacter bacteremia in cancer patients over a sixteen-year period.

A review was conducted of 65 episodes of Citrobacter bacteremia in cancer patients during a 16-year period. Cases of polymicrobial bacteremia were excluded from this analysis. The infection occurred most commonly in patients with acute leukemia. Most patients acquired the infection in the hospital, and 57% had received antibiotic therapy during the preceding ten days. Fever occurred in 98% of cases and shock in 17%. Thirty-eight percent of patients had concomitant pneumonia. Patients with shock, pneumonia or hemorrhage had a substantially poorer prognosis. The response rate was 72% for patients who received appropriate antibiotics. Patients who continued to have positive blood culture results while receiving appropriate antibiotic therapy had a poor prognosis. Beta-lactam antibiotics were more effective than aminoglycosides.

Adolescent↗
PubMed1991

Single agent therapy for infections in cancer patients: a prospective randomized trial comparing three extended-spectrum cephalosporins.

Three hundred and twenty patients were enrolled in a prospective randomized trial comparing cefoperazone, ceftizoxime and ceftriaxone for initial therapy of infectious episodes in cancer patients. Patients with neutropenia were excluded. In 286 evaluable episodes, the response rates associated with the three agents were 77% for cefoperazone, 70% for ceftizoxime and 72% for ceftriaxone, with no statistically significant differences between the three treatment groups. The overall response rate for all episodes of pneumonia (64%) was significantly lower than the response rate for all other infections (81%; p = 0.002), and the mortality associated with pneumonia (9%) was higher than that associated with all other episodes (2%; p = 0.01). Patients with infections due to gram-negative organisms responded well to all three agents, whereas patients with gram-positive infections responded more favorably to cefoperazone. Two different schedules of ceftriaxone were used. The clinical response did not differ significantly between patients receiving ceftriaxone once daily and those receiving it twice daily. The incidence of superinfection and relapse was extremely low and all three agents were well tolerated. It is concluded that extended spectrum cephalosporins are effective as single agents for the treatment of infections in cancer patients with adequate neutrophil counts.

Adolescent↗
PubMed1991

In vitro activity of cefpodoxime against bacterial isolates obtained from patients with cancer.

The in vitro activity of cefpodoxime, an oral cephalosporin ester, against 792 bacterial isolates representing 36 species was evaluated in comparison to that of ciprofloxacin and trimethoprim/sulfamethoxazole (TMP/SMX). Cefpodoxime inhibited the majority of Streptococcus spp., Haemophilus influenzae and Proteus mirabilis at a concentration of less than or equal to 0.12 microgram/ml. It was also active against Citrobacter diversus, Escherichia coli, Klebsiella spp., Proteus vulgaris, Serratia marcescens and methicillin-susceptible Staphylococcus aureus isolates. Overall, cefpodoxime appeared to be less active than ciprofloxacin and TMP/SMX against many pathogens common in cancer patients.

Bacteria↗
PubMed1991

Comparison of the in vitro antifungal activity of free and liposome-encapsulated amphotericin B.

One hundred and four pathogenic yeast isolates (32 Candida albicans, 20 Candida tropicalis, 20 Candida parapsilosis and 32 Cryptococcus neoformans) and 21 mould isolates (13 Aspergillus spp. and eight Fusarium spp.), most of which were isolated from patients with cancer, were tested for susceptibility to free amphotericin B and a small unilamellar liposomal formulation of amphotericin B using a microbroth dilution method. Minimal fungicidal concentrations were also determined for Candida spp. and Cryptococcus neoformans. The minimal inhibitory concentrations of liposomal amphotericin B were comparable with those of the free drug; furthermore, the fungicidal activity of these two drugs did not differ significantly.

Amphotericin B↗
PubMed1991

Fluconazole therapy for chronic disseminated candidiasis in patients with leukemia and prior amphotericin B therapy.

OBJECTIVE: To study the efficacy of fluconazole against chronic disseminated candidiasis (hepatosplenic candidiasis) in patients with leukemia in whom amphotericin B treatment had failed. DESIGN: Retrospective analysis of patients with chronic disseminated candidiasis treated with fluconazole on a compassionate investigational new drug protocol. SETTING: Multi-institutional. PATIENTS AND METHODS: Twenty consecutive patients received 100 to 400 mg of fluconazole per day for a median of 30 weeks. All had either failed to respond to treatment with more than 2 g of amphotericin B or had serious amphotericin B-related toxicities. RESULTS: Fourteen of 16 evaluable patients (88%) responded. Responses were observed in seven of nine patients in whom adequate doses of amphotericin B had failed and in all seven patients who had amphotericin B-related toxicities. In 12 patients, cytotoxic chemotherapy was continued without flare of the infection. Fluconazole was well tolerated with rare side effects. Aspergillus superinfection developed in three patients and contributed to the death of two of them. CONCLUSION: Fluconazole is a safe and effective agent with significant activity against chronic disseminated candidiasis.

Adult↗
PubMed1991

Effect of subinhibitory concentrations of clindamycin and trospectomycin on the adherence of Staphylococcus epidermidis in an in vitro model of vascular catheter colonization.

Septicemia, often due to Staphylococcus epidermidis, is a life-threatening complication associated with indwelling vascular catheters. An important factor in the development of such infections is glycocalix, or slime. An in vitro model that mimics intravenous delivery systems in humans was developed. It consisted of a modified Robbins device containing slices of silicone catheters in the removable ports, through which S. epidermidis diluted in 5% dextrose-normal saline with 10% heat-inactivated normal human serum was run, with and without clindamycin and trospectomycin. S. epidermidis was recovered from all catheters in the absence of antibiotics; no growth was detected with antibiotics. Scanning electron microscopy demonstrated significant reduction in glycocalix and no visible organisms with all concentrations except 0.5 micrograms/ml trospectomycin and 1 microgram/ml clindamycin; for those, a moderate amount of glycocalix and a few bacteria were seen. Thus, subinhibitory levels of trospectomycin and clindamycin may have a role in the prevention of microbial adherence to vascular catheters.

Anti-Bacterial Agents↗
PubMed1991

Experimental fusarial hyalohyphomycosis in a murine model.

The pathogenicity of two clinical strains of Fusarium solani was studied in normal and transiently neutropenic outbred CF1 and CD1 male mice. Three inocula (5 x 10(5), 1 x 10(6), and 5 x 10(6) spores/animal) were tested. Groups of 10 mice each were injected with a single intravenous dose of one inoculum. Mortality correlated with the dose of inoculum, as survival was significantly shorter in mice injected with 5 x 10(6) cfu/mouse than in mice that received 1 x 10(6) or 5 x 10(5) cfu/mouse (P less than .001). Necrotizing abscesses with acute branching septate hyphae, neutrophil and macrophage infiltration, and hemorrhage were observed. The median survival of neutropenic mice was shorter than that of normal mice (P less than .001). Neutropenic mice did not show evidence of an inflammatory cellular reaction and exhibited significantly higher numbers of fungi per gram of infected tissue (P less than .001). Intact host defenses in normal mice were able to confine the infection to the kidneys after initial dissemination. In contrast, disseminated infection persisted in most organs in immunosuppressed animals.

Animals↗
PubMed1991

Fluconazole susceptibility testing of Candida albicans: microtiter method that is independent of inoculum size, temperature, and time of reading.

In vitro antifungal susceptibility testing generally remains unstandardized and unreliable for directing therapy. When azoles are tested, this problem is further compounded by the lack of definite reading end points. We determined the in vitro susceptibility of 50 Candida albicans isolates (including 10 reference strains) to fluconazole by using a microbroth dilution method in which microtiter plates were agitated immediately before reading. Six fungal inoculum sizes (ranging from 2 x 10(2) to 4 x 10(5) CFU/ml), three different times of reading (24, 48, and 72 h), and two temperatures (30 and 35 degrees C) were tested. We also compared visual and spectrophotometric determinations of MIC end points. This agitation method resulted in clear-cut visual end points that were reproducible for different observers within the same laboratory, that were independent of inoculum size, temperature of incubation, and time of reading, and that correlated well with the degree of fungal inhibition as determined by spectrophotometry. Median MICs also correlated with usually achievable levels of fluconazole in serum and tissue of humans and experimental animals.

Candida albicans↗