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Biomedical subjects

V T Andriole

Publications and source records attributed to V T Andriole.

At least 37 records · Page 2Linked to original sources
PubMed1996

Efficacy of UK-109496, a new azole antifungal agent, in an experimental model of invasive aspergillosis.

The efficacy of UK-109496, a new azole antifungal agent, was evaluated in an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis. Oral therapy with UK-109496 at a dosage of 10 or 15 mg/kg of body weight every 8 h was begun 24 h after a lethal or sublethal challenge, and results were compared with those for amphotericin B therapy and untreated controls. UK-109496 eliminated mortality and also reduced the tissue burden of Aspergillus fumigatus 10- to 100-fold in liver and kidney tissues and to a lesser degree in lung tissue, and at the higher dose, no viable organisms were recovered from brain tissue from these animals. Both dosages of UK-109496 decreased or eliminated circulating antigen. The half-life of UK-109496 in rabbits was 2.5 to 3 h, and no accumulation of drug was seen even after 15 doses in either uninfected or infected animals. Thus, UK-109496 shows activity in this rabbit model of invasive aspergillosis. Additional studies are needed to determine the potential of the drug for use in the treatment of this infection.

Animals↗
PubMed1996

Aspergillus infections: problems in diagnosis and treatment.

Invasive aspergillosis is a common infection in patients who are immunocompromised, particularly in oncology patients, patients receiving other immunosuppressive therapy, bone marrow transplant patients, and HIV-infected patients. The diagnosis of invasive aspergillosis is difficult in the absence of tissue biopsy and histologic confirmation. Therefore, the need for and progress in recent advances in the development of highly sensitive and specific serodiagnostic tests for the early diagnosis of invasive aspergillosis have been reviewed. Anti-Aspergillus antibody detection lacks the utility to lead to early diagnosis of invasive aspergillosis. However, sensitive methods that detect significant amounts of Aspergillus antigen in body fluids, primarily serum, of high risk patients are currently being evaluated and may provide a noninvasive early diagnostic test that is both sensitive and specific. Our recent results with an inhibition enzyme-linked immunosorbent assay, which detects small but significant amounts of Aspergillus antigen in serum, in 35 patients with invasive aspergillosis are discussed. Also, current antifungal agents with anti-Aspergillus activity that have the potential for use as therapy or prophylaxis are briefly reviewed.

Animals↗
PubMed1995

Aspergillus antigen detection in the diagnosis of invasive aspergillosis.

The utility of serum Aspergillus antigen in invasive aspergillosis was determined by identifying patients with >50 ng/mL Aspergillus carbohydrate antigen by ELISA. Patients were identified from a university hospital over a 65-month period. Nineteen patients with antigenemia had proven invasive aspergillosis, 16 had probable invasive aspergillosis, and 14 had an indeterminate diagnosis. There were 5 patients with false-positive results. Antigen levels were higher in disseminated infection than in invasive pulmonary aspergillosis (median levels, 500 and 121 ng/mL, respectively). Survival also correlated with antigenemia. Serial samples were obtained from 31 of 35 patients with proven or probable invasive aspergillosis. Fifteen of 19 patients with rising or persistent antigenemia died, whereas only 1 of 12 patients who cleared antigenemia died. Higher antigen levels were useful in predicting disseminated disease, and the course of antigenemia correlated with clinical outcome. Antigen detection may be a useful addition in the management of invasive aspergillosis.

Antigens, Fungal↗
PubMed1995

Bacterial urinary tract infections in diabetes.

Bacterial UTIs are a common problem in patients with diabetes mellitus. Bacteriuria is more common in diabetic women than in non-diabetics owing to a combination of host and local risk factors. Upper tract disease is also more common in this group. Diabetics are at higher risk for intrarenal abscess, with a spectrum of disease ranging from acute focal bacterial pyelonephritis to renal corticomedullary abscess to the renal carbuncle. A number of uncommon complicated UTIs, such as emphysematous pyelonephritis and emphysematous pyelitis, occur more frequently in diabetics. Because of the frequency and severity of UTI in diabetics, prompt diagnosis and early therapy is warranted.

Abscess↗
PubMed1993

Infections with Aspergillus species.

Invasive aspergillosis is a common infection in patients who are immunocompromised. The diagnosis of invasive aspergillosis is difficult in the absence of confirmation by tissue biopsy and histological studies. Therefore, recent advances that may be important for the development of highly sensitive and specific serodiagnostic tests for the early diagnosis of invasive aspergillosis are reviewed. The inability of the detection of antibody to Aspergillus to lead to early diagnosis of invasive aspergillosis also is emphasized. However, sensitive methods that reliably detect significant amounts of aspergillus antigen in body fluids of high-risk patients are currently being evaluated and may provide a noninvasive early diagnostic test that is both sensitive and specific. Also, current antifungal agents with anti-aspergillus activity that have potential as therapeutic or prophylactic agents are reviewed briefly.

Antibodies, Fungal↗
PubMed1993

Combination therapy in experimental invasive aspergillosis.

Combination antifungal therapy was assessed in an immunosuppressed rabbit model of invasive aspergillosis. Treatment with fluconazole, amphotericin B, or a combination of both significantly prolonged survival of animals lethally challenged with Aspergillus fumigatus. High-dose amphotericin B was the most effective therapy for invasive aspergillosis. Although no antagonism was seen when fluconazole was given prophylactically or therapeutically in combination with amphotericin B, combination therapy did not augment the antifungal activity of amphotericin B. Animals given a sublethal challenge of A. fumigatus had lower mortality rates when given amphotericin B, fluconazole as treatment or prophylaxis, or various combination therapies. Only animals treated with flucytosine had mortality rates comparable to those of controls. No antagonism was observed with combinations of fluconazole and amphotericin B, flucytosine and amphotericin B, or fluconazole and flucytosine. These observations provide evidence that fluconazole, flucytosine, and amphotericin B used in various combinations are not antagonistic and may provide some insight into the treatment of invasive aspergillosis in humans.

Amphotericin B↗
PubMed1993

Case report: pentamidine and polymorphic ventricular tachycardia revisited.

Pentamidine isethionate has been associated with ventricular tachyarrhythmias, including torsade de pointes. This article reports two cases of this complication and reviews all reported cases to date. Pentamidine-induced torsade de pointes may be related to serum magnesium levels and hypomagnesemia may synergistically induce torsade. Torsade de pointes occurred after an average of 10 days of treatment with pentamidine. In these patients, no other acute side effects of pentamidine were observed. Torsade de pointes can be treated when recognized early, possibly without discontinuation of pentamidine. When QTc interval prolongation is observed, early magnesium supplementation is advocated.

Adult↗
PubMed1993

The future of the quinolones.

This review attempts to predict the future of the newer fluoroquinolones by examining what we have learned about this class of compounds during the past decade, as well as what we are currently learning from research and developmental efforts. The molecular mechanism of action of these compounds provides the potential for use in clinical medicine in areas other than their role as antibacterial agents. The newer fluoroquinolones that are currently available and those that have been introduced into the pipeline are categorised by their current stage of development. Also listed are those compounds that have been withdrawn from further investigation. Office practice physicians consider the oral fluoroquinolones to be very effective therapeutic agents for many of their patients. Thus, the future of the fluoroquinolones looks promising because of their unique mechanism of action, the possibility of developing novel and improved compounds in this class, and the acceptance of these compounds as effective therapeutic agents by clinicians.

Anti-Infective Agents↗
PubMed1992

Urinary tract infections in the 90s: pathogenesis and management.

Urinary tract infections are one of the most common types of infection encountered in the practice of medicine. Recent discussions have focused on our current knowledge of natural host defenses that function during normal physiologic conditions in an attempt to prevent urinary infections. However, increased susceptibility to these infections may result from intrinsic risk factors that alter host defenses, or from extrinsic risk factors. Advances in the treatment of urinary infections have focused on short course therapy for women with uncomplicated lower tract infections, and on oral therapy in women with mild acute uncomplicated pyelonephritis. Also, in the area of prevention, reasonable candidates for antimicrobial prophylaxis have been identified. Even so, further studies are needed to define more clearly our understanding of the pathogenesis, treatment, and prevention of infections of the urinary tract.

Female↗
PubMed1992

Cefoperazone versus ceftriaxone monotherapy of nosocomial pneumonia.

Ceftriaxone and cefoperazone monotherapy was compared in a multicentered, randomized, nonblinded, prospective study of patients with nosocomial pneumonia. These antibiotics were equally effective, with an overall successful treatment rate of 48 (80%) of 60 for the cefoperazone-treated patients and 35 (70%) of 50 for the ceftriaxone-treated patients. Patients with nursing-home-acquired pneumonia had similar bacterial pathogens and an almost identical cure rate to those patients with hospital-acquired infection. There was no statistical difference in the incidence of side effects of superinfections. The development of secondary pneumonia with resistant bacteria was low, 3% with cefoperazone and 4% with ceftriaxone. When antibiotic, administrative, and laboratory costs were calculated, cefoperazone was slightly less expensive than ceftriaxone. Both cefoperazone and ceftriaxone are effective therapy for the treatment of nosocomial pneumonia.

Adult↗
PubMed1992

Evaluation of new anti-infective drugs for the treatment of urinary tract infection. Infectious Diseases Society of America and the Food and Drug Administration.

The term urinary tract infection (UTI) encompasses a broad range of clinical entities that share one characteristic: a positive urine culture. Clinical manifestations and responses to therapy are diverse even when comparable numbers of a particular bacterial species are identified on urine culture. These guidelines include discussion of acute uncomplicated cystitis, acute uncomplicated pyelonephritis, and complicated infections of the urinary tract. It is proposed that the finding of > or = 10(3) cfu/mL of urine defines significant bacteriuria in acute uncomplicated cystitis, > or = 10(4) cfu/mL in acute uncomplicated pyelonephritis and UTI in men, and > or = 10(5) cfu/mL in complicated UTI. The preferred clinical study design is prospective, randomized, and controlled with an active agent. Ideally, treatment with antimicrobial agents should eradicate the infecting organism, bring about the resolution of clinical signs and symptoms, have few adverse effects, and prevent reinfection.

Adult↗
PubMed1992

Animal models: usefulness for studies of fungal pathogenesis and drug efficacy in aspergillosis.

This review describes our experience during the past 8 years with an immunocompromised rabbit model of invasive aspergillosis. We have used the model to evaluate the efficacy of a variety of antifungal therapies, including amphotericin B-deoxycholate, a liposomal amphotericin B preparation, some of the newer azoles (i.e., fluconazole, saperconazole, and the experimental compound SCH 39304), and combination therapy with amphotericin B-deoxycholate plus fluconazole. The model provides a rigorous test of efficacy when animals receive a lethal challenge; permits studies of the kinetics of aspergillar antigenemia in response to therapy with each antifungal agent or regimen; allows comparison of the relation of antigenemia to the extent of disease in target organs; and is useful in correlating the timing of antifungal therapy with the success of treatment. These observations in our animal model may provide some insight into the treatment of invasive aspergillosis in humans.

Animals↗
PubMed1992

Saperconazole therapy in a rabbit model of invasive aspergillosis.

The efficacy of orally and intravenously administered saperconazole against Aspergillus fumigatus was assessed in an immunosuppressed temporarily leukopenic rabbit model of invasive aspergillosis and compared with that of amphotericin B. Oral saperconazole at dosages of 5, 10, and 15 mg/kg of body weight per day improved survival compared with that of controls. In addition, saperconazole at 10 and 15 mg/kg/day reduced the tissue burden and reduced levels of circulating antigen, which correlated with increasing dosages of saperconazole. Intravenous saperconazole produced levels in serum more than 10-fold that of oral therapy. Intravenous saperconazole not only improved survival and reduced antigen levels but also significantly eradicated A. fumigatus from tissues compared with those of controls and was as effective as amphotericin B in these studies. Saperconazole was effective in the treatment of experimental invasive aspergillosis and demonstrates the potential of the newer azoles in therapy for invasive aspergillosis.

Administration, Oral↗
PubMed1991

Use of quinolones in treatment of prostatitis and lower urinary tract infections.

The newer quinolones, ciprofloxacin, enoxacin, fleroxacin, lomefloxacin, norfloxacin, ofloxacin and pefloxacin are highly effective antimicrobial agents against the majority of bacteria responsible for urinary tract infections and bacterial prostatitis. The pharmacokinetic properties of these agents after oral administration result in high concentrations in human urine, as well as in prostatic fluid and prostatic tissue. Ciprofloxacin, enoxacin and lomefloxacin produce the highest concentrations in prostatic tissue, followed by norfloxacin, ofloxacin and fleroxacin. More than 400 patients with chronic bacterial prostatitis have been treated with one of the newer quinolones in varying doses for 10 to 84 days. The results indicate a cure rate of approximately 70%, although the follow-up period is quite variable in these studies. Clinical trials of short-term (single dose vs three days) therapy with the newer quinolones conducted in women with uncomplicated lower urinary tract infections were reviewed. Although bacteriologic cure rates were high with single doses of ciprofloxacin, fleroxacin, norfloxacin, ofloxacin and pefloxacin, approximately one in five women with suspected uncomplicated lower urinary tract infection experience failure of single-dose therapy. In contrast, a three-day regimen with these agents is more effective than a single-dose in the treatment of uncomplicated lower urinary tract infections in women.

4-Quinolones↗
PubMed1991

Epidemiology, natural history, and management of urinary tract infections in pregnancy.

The urinary tract undergoes profound physiologic and anatomic changes during pregnancy that facilitate the development of symptomatic UTIs in women with bacteriuria. Although the adverse effects of asymptomatic bacteriuria on maternal and fetal health continue to be debated, it is clear that asymptomatic bacteriuria is the major risk factor for developing symptomatic UTI and that symptomatic infections are associated with significant maternal and fetal risks. Because the majority of symptomatic UTIs develop in women with bacteriuria earlier in pregnancy, treatment of bacteriuria is undertaken to prevent symptomatic infections. All women should be screened at the first antenatal visit, which is reliably and inexpensively done with a dipstick culture. Short-course therapy is as effective as prolonged therapy and should be followed with a repeat culture to document clearing of the bacteriuria. Failure to eliminate bacteriuria with repeated therapy or recurrence with the same organism is indicative of renal parenchymal infection or a structural abnormality. All women with persistent bacteriuria or recurrent infection should have follow-up cultures and a complete urologic evaluation after delivery.

Bacterial Infections↗
PubMed1991

The role of fluconazole in the early treatment and prophylaxis of experimental invasive aspergillosis.

The efficacy of fluconazole against Aspergillus fumigatus was assessed in an immunosuppressed temporarily leukopenic rabbit model of invasive aspergillosis. Therapy with fluconazole at 60 or 120 mg/kg/day was begun 24 h after lethal challenge and compared to that with amphotericin B at 1.5 mg/kg/day. Fluconazole reduced mortality compared with that in untreated controls and at 120 mg/kg/day reduced the tissue burden of A. fumigatus 10- to 100-fold in liver, kidney, and lung. However, amphotericin B was more effective in sterilizing tissues. Both fluconazole and amphotericin B dramatically decreased or eliminated circulating aspergillus antigen. Prophylaxis with fluconazole, begun 48 h before sublethal challenge, sterilized liver and kidney tissues and significantly reduced the tissue burden in lung. Early treatment with fluconazole reduced mortality and reduced antigenemia but did not sterilize tissues. Fluconazole prophylaxis at these doses prevented dissemination of invasive aspergillosis. Fluconazole was shown to have activity in the early treatment and prophylaxis of experimental invasive aspergillosis.

Animals↗