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Biomedical subjects

V T Andriole

Publications and source records attributed to V T Andriole.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

Efficacy of SCH 39304 in treatment of experimental invasive aspergillosis.

The efficacy of SCH 39304 (SCH) against Aspergillus fumigatus was assessed with an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis. Therapy with SCH at 10 or 15 mg/kg of body weight per day was begun 24 h after lethal challenge and compared with therapy with amphotericin B at 1.5 mg/kg/day. Compared with untreated controls, SCH reduced mortality and also reduced the tissue burden of A. fumigatus 100- to 1,000-fold in liver, kidney, and lung tissues. SCH at 15 mg/kg/day and amphotericin B eliminated A. fumigatus in liver, kidney, and lung tissues. In addition, both dosages of SCH significantly eliminated the organism from brain tissues, compared with controls. Both SCH and amphotericin B decreased or eliminated circulating aspergillus antigen. These results show that new azoles can be as effective as amphotericin B in eradicating the organism from tissues and offer promise in improving the treatment of invasive aspergillosis.

Amphotericin B

Clostridial infection of a locally recurrent renal cell carcinoma with sepsis.

An association between clostridial sepsis and malignancy is well established in the literature. Although anaerobes are a relatively infrequent cause of renal abscess, there have been recent reports of anaerobic abscesses occurring in renal tumor masses. The present report describes a case of sepsis due to Clostridium perfringens infection of a locally recurrent renal cell carcinoma. The infection may have originated either from tumor invasion of the adjacent bowel or by hematogenous seeding of the mass at the time of colonoscopy. Patients with bulky, necrotic tumors who have invasive diagnostic procedures relating to either the gastrointestinal or urogenital tracts, as well as those having malignancies involving these systems, are at increased risk of infection with bowel anaerobes. Clostridial abscesses with accompanying sepsis occur in this setting, and empiric antibiotic regimens should include coverage for these organisms. Early, aggressive surgical intervention is essential.

Carcinoma, Renal Cell

The epidemiology of pseudallescheriasis complicating transplantation: nosocomial and community-acquired infection.

The epidemiology of two cases of pseudallescheriasis in organ transplant patients are described and the disease in that population is reviewed. Disseminated hospital-acquired infection occurred in a liver transplant recipient and was fatal despite therapy with miconazole. A heart transplant recipient developed localized disease following soil contamination of soft tissue trauma which was cured with surgical resection and miconazole therapy. Itraconazole showed in vitro activity against Pseudallescheria boydii and should be evaluated in pseudallescheriasis. P. boydii infections are important complications of transplantation and should be considered in the differential diagnosis of community-acquired as well as nosocomial fungal infections in this population.

Adult

An update on the efficacy of ciprofloxacin in animal models of infection.

Although animal models of infection are associated with certain limitations in interpretation, properly performed studies provide important information for evaluating the efficacy of new antimicrobial agents in the treatment of human disease. The antibacterial efficacy of the newer quinolones, particularly ciprofloxacin, has undergone extensive evaluation in several animal models. Efficacy has been demonstrated in animal models of pneumonia, endocarditis, meningitis, skin and soft-tissue infections, septic arthritis, burn wound sepsis, empyema, intra-abdominal abscess, osteomyelitis, prostatitis, sinusitis, urinary tract infection, chronic gastroenteritis, granuloma pouch infection, and Pseudomonas septicemia. More recent studies have evaluated the efficacy of ciprofloxacin in animal models of tuberculosis and syphilis, as well as in infections caused by the intracellular pathogens Salmonella typhimurium, Legionella pneumophila, and Listeria monocytogenes.

Abscess

Current concepts in cryptococcosis.

Cryptococcus neoformans has become an increasingly important pathogen. Cryptococcosis is an important cause of morbidity and mortality in immunocompromised hosts and is the second most common fungal infection complicating AIDS. In recent years, research has focused on the host defenses against Cryptococcus and has led to an improved understanding of the capsular virulence of the organism, the mechanisms of T-cell defenses, and the role of phagocytic cells in the fungistasis and killing of cryptocci. Amphotericin B with or without flucytosine has clearly improved treatment of cryptococcosis, but therapy is associated with significant toxicity. Current investigation is focused on the triazoles, which may offer improved therapy for cryptococcosis. In this report, we review recent developments in the understanding of the host defenses against Cryptococcocus and discuss current recommendations for the management of cryptococcosis.

Acquired Immunodeficiency Syndrome

Treatment of experimental invasive aspergillosis with novel amphotericin B/cholesterol-sulfate complexes.

An immunosuppressed rabbit model of invasive aspergillosis was used to evaluate a novel micellar preparation of cholesterol sulfate complexed to amphotericin B. The acute LD50 of amphotericin B-deoxycholate was 5.1 mg/kg versus 20 mg/kg for the amphotericin/cholesterol-sulfate complexes. Amphotericin B-deoxycholate given iv at a dose of 1.5 mg/kg was more effective in sterilizing liver and kidney than the amphotericin/cholesterol-sulfate complexes given iv at 1.5-4.5 mg/kg, but infection persisted in the lungs of all rabbits treated with those doses. Infection persisted even when the rabbits were given a lethal dose of amphotericin B-deoxycholate (4.5 mg/kg), but a dose of 15 mg/kg of the amphotericin/cholesterol-sulfate complexes sterilized tissues and was associated with no acute lethality. Equivalent doses of the amphotericin/cholesterol-sulfate complexes were less effective than amphotericin B-deoxycholate, but a fourfold decrease in acute lethality improved the therapeutic index of amphotericin B. The amphotericin/cholesterol-sulfate complexes appear to be an improved means of amphotericin B delivery and may improve therapy for invasive aspergillosis.

Amphotericin B

The role of liposomal amphotericin B in the treatment of systemic fungal infections.

Amphotericin B remains the treatment of choice for systemic fungal infections, but amphotericin B is toxic and is often not effective in treating disseminated infections. Liposome intercalation of amphotericin B reduces the toxicity associated with amphotericin B and targets reticuloendothelial tissues most heavily involved in fungal infections. The targeted delivery and reduced toxicity of liposomal amphotericin B improves the therapeutic index of amphotericin B. Although liposomes have been shown to effectively treat a variety of experimental and human fungal infections, the optimal composition of liposomal amphotericin has not been established. Vesicle type, lipid content, size, and conditions of storage markedly affect toxicity, therapeutic efficacy, and tissue distribution. In vitro studies have been poor predictors of in vivo efficacy and toxicity. Animal models can be used to evaluate in vivo the optimal liposome preparation. Liposomal amphotericin B appears to be an improved means of amphotericin B delivery and may improve the treatment of patients with systemic fungal infections.

Amphotericin B

Cefoperazone versus ceftazidime monotherapy of nosocomial pneumonia.

Cefoperazone and ceftazidime monotherapy were compared in a randomized, prospective evaluation of patients with nosocomial pneumonia. These antibiotics were equally effective, with an overall successful treatment rate of 45 of 62 (73 percent) for cefoperazone-treated patients and 50 of 63 (79 percent) for ceftazidime-treated patients (p = 0.41). There was no difference in the incidence of side effects (including hypoprothrombinemia), superinfections, or colonization of the oropharynx with yeast, enterococcus, Staphylococcus aureus, or resistant gram-negative bacilli. When antibiotic administration, and laboratory costs are considered, cefoperazone is less expensive than ceftazidime. Both cefoperazone and ceftazidime are effective therapy for nosocomial pneumonia.

Bacteria