nystatin-a1 and Agranulocytosis

In conclusion, the use of nystatin for fungal prophylaxis in hematology/oncology/bone marrow transplantation patients appears to convey little or no benefit over no therapy. Nystatin treatment significantly reduced the frequency of multiple-site colonization and of persistently positive oropharyngeal cultures, but was not able to prevent the occurrence of disseminated fungal infections. Other antifungal agents (e.g., ketoconazole, fluconazole, itraconazole, oral or intravenous amphotericin B) may be of benefit. Studies comparing nystatin with other agents are available in the literature but are beyond the scope of this review.

Topics: Agranulocytosis; Antifungal Agents; Bone Marrow Transplantation; Candidiasis; Child; Humans; Immunocompromised Host; Leukemia; Nystatin

Several prospectively randomized trials have shown that the administration of prophylactic oral nonabsorbable antibiotics may be beneficial in decreasing the incidence of infection in granulocytopenic patients, whereas others have not. Intolerable nausea and vomiting have prevented the prolonged use of these agents in some studies. Discontinuation of therapy while patients are still granulocytopenic has carried the risk of life-threatening infections, often with aminoglycoside-resistant gram-negative organisms. The benefit of selective decontamination with trimethoprim/sulfamethoxazole used prophylactically remains controversial. The use of trimethoprim/sulfamethoxazole may also be associated with the development of resistant, potentially pathogenic, organisms or prolonged neutropenia. These regimens do not appear to be indicated when patients are anticipated to be neutropenic for less than three weeks. Even in patients with prolonged neutropenia, the risks of such treatment must be weighed against potential benefits.

Topics: Acute Disease; Agranulocytosis; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Colistin; Drug Combinations; Environment, Controlled; Gentamicins; Humans; Leukemia; Neoplasms; Nystatin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Three gastrointestinal tract decontamination regimens were tested in patients with granulopenia: vancomycin 250 mg, tobramycin 75 mg, and colistin 1 million international units (regimen A); vancomycin 125 mg, tobramycin 75 mg, and colistin 1 million IU (regimen B); and colistin 1 million IU (regimen C); nystatin was added to all three regimens. Effectiveness was evaluated by stool organism counts and blood cultures to detect bacterial translocation (passage of bacteria from the intestinal tract to the bloodstream). Regimen C proved insufficiently effective. Regimen A was found to be poorly tolerated by the digestive mucosa. Regimen B was the best treatment since the low dosage of vancomycin proved effective. Nystatin satisfactorily eliminated yeasts.

Topics: Agranulocytosis; Colistin; Drug Therapy, Combination; Gastrointestinal Diseases; Humans; Nystatin; Sepsis; Tobramycin; Vancomycin

Pipemidic acid (PPA) and colistin sodium methanesulfonate (CLM) may selectively suppress aerobic gram-negative bacilli. Twenty-nine patients with acute leukemia were randomized after each course of consolidation chemotherapy to receive a single agent of nystatin (NYS) (34 courses) versus a combination of NYS, PPA and CLM (36 courses). The duration of fever over 39 degrees C was longer with the three drug combination (4.6 +/- 5.1 days) than with NYS alone (1.8 +/- 1.8 days) (P less than 0.01). Four cases of pneumonia occurred and four patients including one having pneumonia died of infection with the three drug combination, while no pneumonia or death occurred with NYS alone (P = 0.06 and P = 0.06, respectively). The combination of NYS, PPA and CLM may be less effective than NYS alone for the prevention of infection in acute leukemia patients with chemotherapy-associated granulocytopenia.

Topics: Acute Disease; Adolescent; Adult; Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Colistin; Drug Therapy, Combination; Gram-Negative Bacteria; Humans; Leukemia; Middle Aged; Nicotinic Acids; Nystatin; Pipemidic Acid; Pneumonia; Random Allocation

Topics: Adolescent; Adult; Agranulocytosis; Candidiasis, Oral; Clotrimazole; Female; Humans; Imidazoles; Male; Middle Aged; Neutropenia; Nystatin

A randomized trial was conducted comparing ketoconazole and nystatin in the prevention of oral candidiasis and appearance of invasive fungal infections in 51 neutropenic leukemic patients undergoing induction chemotherapy. Ketoconazole was administered in a 200 mg dose twice daily. Nystatin oral suspension was given in doses of 500,000 units four times daily. Surveillance cultures of the throat and urine were obtained prior to treatment and conducted weekly. Patients were enrolled in the study if the absolute granulocyte count was less than 1500/microliter, if physical examination revealed no evidence of oral candidiasis, no evidence of urinary tract infection, and there was no pulmonary infiltrate on chest x-ray. Patients were continued on study until the absolute granulocyte count reached 1500/microliter, evidence of oral candidiasis appeared, or presumed or proven invasive fungal infections appeared. Of the 46 evaluable patients, 22 received ketoconazole, 3 (14%) developed oral candidiasis, and 5 developed suspected systemic fungal infections (23%). Of 24 patients who received nystatin, 4 (17%) developed oral candidiasis and 8 (33%) developed systemic fungal infections, 4 proven and 4 suspected. Significantly more patients on the nystatin arm progressed to invasive fungal infections. Ketoconazole was not superior to nystatin in reducing the frequency of oral candidiasis but possibly reduced the frequency of invasive fungal infections.

Topics: Acute Disease; Adolescent; Adult; Aged; Agranulocytosis; Candidiasis, Oral; Female; Humans; Immune Tolerance; Ketoconazole; Leukemia; Male; Middle Aged; Neutropenia; Nystatin; Random Allocation

Topics: Administration, Oral; Adolescent; Adult; Aged; Agranulocytosis; Antineoplastic Agents; Clinical Trials as Topic; Colistin; Gentamicins; Humans; Leukemia; Middle Aged; Neutropenia; Nystatin; Sepsis; Vancomycin

In a randomized trial we compared ketoconazole (400 mg once daily, 27 patients) and nystatin (3 X 10(6) units four times daily, 29 patients) for prevention of fungal infection in neutropenic patients undergoing marrow transplantation in a protective environment. Fewer weekly surveillance cultures contained Candida species in ketoconazole recipients than in nystatin recipients (70 [26%] of 274 vs. 151 [47%] of 322; P less than .001). When all fungi were considered, the difference in colonization was less but was still significant (117 [43%] of 274 vs. 173 [54%] of 322; P = .01), primarily due to increased colonization of the rectum with Torulopsis glabrata among ketoconazole recipients (P less than .001). No difference in the incidence of local mucosal infection was seen. Two disseminated fungal infections occurred, both in nystatin recipients. Compliance with ketoconazole was significantly better than was compliance with nystatin (96% vs. 68%; P less than .001), but similar effects on colonization were found in an analysis adjusting for compliance. Ketoconazole was better tolerated and more effective than nystatin in reducing colonization due to Candida species but was also associated with significantly increased rates of colonization with T. glabrata.

Topics: Agranulocytosis; Candida albicans; Candidiasis; Clinical Trials as Topic; Environment, Controlled; Humans; Ketoconazole; Mycoses; Neutropenia; Nystatin; Patient Compliance; Random Allocation

A prospective randomized study was undertaken in neutropenic patients to evaluate the efficacy of prophylactic ketoconazole v nystatin in reducing yeast infections. Eighteen patients received 500,000 units of nystatin suspension four times daily, and 18 patients received 200 mg of ketoconazole daily. The nystatin group experienced nine local yeast infections (four thrush, three esophagitis, and two vaginitis); three patients receiving ketoconazole had thrush. No cases of disseminated candidiasis occurred in either group. Ketoconazole was better tolerated than nystatin and neither drug caused toxic effects. In addition to being nontoxic and better tolerated, ketoconazole appeared to be slightly more effective than nystatin in reducing locally severe yeast infections.

Topics: Adult; Agranulocytosis; Female; Humans; Ketoconazole; Male; Middle Aged; Mycoses; Neutropenia; Nystatin; Prospective Studies; Random Allocation

The clinical and microbiologic efficacy of trimethoprim alone and trimethoprim/sulfamethoxazole for infection prevention was evaluated in 75 patients during 92 episodes of granulocytopenia. Ultimately, 60 patients were evaluable during 77 episodes of granulocytopenia, 36 episodes in the trimethoprim group and 41 episodes in the trimethoprim/sulfamethoxazole group. The incidence of infection was higher in the trimethoprim group (50 percent) than in the trimethoprim/sulfamethoxazole group (39 percent), but this did not reach statistical significance. Trimethoprim did not appear to be as protective as trimethoprim/sulfamethoxazole when the granulocyte count was less than 100/mm3. In patients receiving trimethoprim/sulfamethoxazole, aerobic gram-negative bacilli cleared from fecal surveillance cultures more often and new aerobic gram-negative bacilli were acquired less often than in those receiving trimethoprim alone (p less than 0.05). More myelosuppression was observed among patients receiving trimethoprim/sulfamethoxazole (p less than 0.001). These observations suggest that trimethoprim alone may not be optimal for preventing colonization and infection in granulocytopenic patients and that combination with other agents may be necessary to increase the spectrum of activity. Trimethoprim/sulfamethoxazole itself may predispose toward an increased risk of infection by prolonging myelosuppression.

Topics: Adult; Agranulocytosis; Bacteria; Bacterial Infections; Clinical Trials as Topic; Drug Combinations; Feces; Female; Humans; Male; Mycoses; Nystatin; Premedication; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Several prospectively randomized trials have shown that the administration of prophylactic oral nonabsorbable antibiotics may be beneficial in decreasing the incidence of infection in granulocytopenic patients, whereas others have not. Intolerable nausea and vomiting have prevented the prolonged use of these agents in some studies. Discontinuation of therapy while patients are still granulocytopenic has carried the risk of life-threatening infections, often with aminoglycoside-resistant gram-negative organisms. The benefit of selective decontamination with trimethoprim/sulfamethoxazole used prophylactically remains controversial. The use of trimethoprim/sulfamethoxazole may also be associated with the development of resistant, potentially pathogenic, organisms or prolonged neutropenia. These regimens do not appear to be indicated when patients are anticipated to be neutropenic for less than three weeks. Even in patients with prolonged neutropenia, the risks of such treatment must be weighed against potential benefits.

Topics: Acute Disease; Agranulocytosis; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Colistin; Drug Combinations; Environment, Controlled; Gentamicins; Humans; Leukemia; Neoplasms; Nystatin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

The prevention of fungal infections in granulocytopenic patients seems necessary to improve the final outcome of neoplastic patients. In particular, aspergillosis and candidiasis represent common life-threatening infections among the patients with acute hematological malignancies. Despite extensive investigations during this last decade, the optimal approaches to prevent these complications are still controversial. This situation probably reflects and stresses the numerous factors which predispose to these opportunistic fungal infections. Therefore, the effective prophylaxis of candidiasis and aspergillosis should result from the use of basic and specific approaches. General and simple measures including well trained personnel (physicians, nurses but also individuals in charge of the housekeeping, etc.), careful patient teaching of personal hygiene and control of the food intake (limited to cooked food diet), will reduce the acquisition of potential fungal pathogens. Moreover, the isolation in a laminar air flow room seems to be the optimal specific technique to prevent the colonization as well as the development of pulmonary aspergillosis. The meticulous evaluation of the respiratory sinus status as well as surveillance cultures obtained from the nose have been shown to be helpful to predict patients at high risks. Until now, there is no systemic chemoprophylaxis available to decrease the incidence of invasive aspergillosis. However, the topical application of antifungal agent using nasal spray or aerosols should be further investigated. Exogenous candidiasis such as catheter or TPN products related yeast infections can be avoided by aseptic manipulations. Endogenous candidiasis, resulting from the dissemination of the yeasts from the gastro-intestinal tract (which represents the major reservoir), are still much more difficult to prevent.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Agranulocytosis; Amphotericin B; Aspergillosis; Candidiasis; Clinical Trials as Topic; Humans; Ketoconazole; Neoplasms; Neutropenia; Nystatin; Patient Isolation

It is well known that patients with granulocytopenia due either to bone marrow failure, acute leukemia or its treatment, or as a result of other intensive chemotherapy are at enhanced risk of serious infection. Several approaches have been designed to minimize the risk of infection in these patients by means of suppression of gastrointestinal flora. A retrospective review of infection in febrile neutropenic patients revealed a significant decrease in bacteremia in patients who had received some oral antimicrobial regimen compared with those who did not. In one large series, infection due to the four most common infecting organisms in neutropenic patients (Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Klebsiella species) occurred in 28% of 380 patients receiving some oral antibiotic regimen compared with 44% of 426 receiving no oral prophylaxis. Aminoglycosides alone or in combination with vancomycin or polymyxin and bacitracin and other agents have been utilized in gut decontaminating regimens. More recently, selective decontamination with a variety of oral agents including nalidixic acid, cotrimoxazole, colistin, etc. have been shown to be effective in some trials. Although cotrimoxazole initially was thought to be beneficial in reducing infection and bacteremia in neutropenic patients, the recently completed EORTC trial did not show a significant difference in incidence of infection or bacteremia in acute leukemia patients attendant upon the use of oral trimethoprim-sulfamethoxazole. There was a significant reduction in infections and bacteremia in patients with malignancies other than acute non-lymphocytic leukemia. Thus, there is a need for infection prevention in neutropenic patients but the optimal method for achieving this goal remains to be determined.

Topics: Administration, Oral; Agranulocytosis; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Drug Combinations; Humans; Neutropenia; Nystatin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Sixty-two profoundly granulocytopenic patients with acute leukemia undergoing induction chemotherapy were prospectively randomized to receive either trimethoprim-sulfamethoxazole plus nystatin or nalidixic acid plus nystatin for prevention of infection. Patients given trimethoprim-sulfamethoxazole plus nystatin during initial remission induction experienced an increased duration (22.6 vs. 13.6 days) of profound granulocytopenia (less than 100 granulocytes/mm3; P = 0.007). Acquisition of gram-negative bacilli was more frequent among patients treated with nalidixic acid plus nystatin while filamentous fungi were acquired more frequently by patients receiving trimethoprim-sulfamethoxazole plus nystatin (P = 0.05). The median duration of on-study time prior to documentation of first infection was longer for patients receiving trimethoprim-sulfamethoxazole plus nystatin (17 days) than for those receiving nalidixic acid plus nystatin (eight days) (P = 0.0002). Three infection-related deaths occurred among patients receiving nalidixic acid; seven occurred among patients receiving trimethoprim-sulfamethoxazole, five of which were secondary to pneumonia due to Aspergillus flavus. Both of these methods of selective antimicrobial modulation have apparent advantages, but each has disadvantages serious enough to limit their routine use.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Bacterial Infections; Child; Drug Combinations; Female; Humans; Leukemia; Male; Middle Aged; Mycoses; Nalidixic Acid; Nystatin; Patient Compliance; Prospective Studies; Random Allocation; Sulfamethizole; Sulfathiazoles; Trimethoprim

A randomized study of intestinal decontamination was undertaken in 68 children with leukemia and solid tumours. Framycetin, colymycin, nystatin, and metronidazole were given in 35 neutropenic episodes in 33 children, while co-trimoxazole and lactobacilli preparation were administered in 35 episodes in 35 children. The diseases, severity of neutropenia, and incidence of infection at entry into study were comparable in the two groups. There was no significant difference in the incidence of infections developing during the phase of neutropenia. The median and range of time required to recover from neutropenia were also not different. Co-trimoxazole and lactobacilli were significantly better tolerated, there being no nausea and vomiting, no refusal to take medication, no dose reduction or change to an alternative regimen. We conclude that co-trimoxazole and lactobacilli preparation improve quality of life during a neutropenic episode and have the additional advantage of being relatively inexpensive.

Topics: Agranulocytosis; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Biological Products; Child; Child, Preschool; Colistin; Drug Combinations; Framycetin; Humans; Lactobacillus; Neoplasms; Neutropenia; Nystatin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

The clinicopathologic characteristics of invasive oral aspergillosis in 16 immunocompromised patients who developed this infection during antileukemic chemotherapy are described. The primary site of the infection was the marginal gingiva, there was severe spontaneous pain, and the patients developed spiking fever and granulocytopenia. Necrotic ulceration of the gingiva rapidly extended to the contiguous mucosa, muscle, and bone. Microscopically, the necrotic tissue contained thrombotic vascular infarcts and there were hyphae that showed frequent transverse septa and dichotomous branching. The invasive organisms were not responsive to amphotericin B in the absence of remission of the leukemia and restoration of the depressed host defenses. In 15 patients who showed improvement of hematologic status, oral aspergillosis was controlled by the combination of antifungal chemotherapy and debridement of necrotic tissues.

Topics: Adult; Aged; Agranulocytosis; Amphotericin B; Aspergillosis; Female; Humans; Immunocompromised Host; Leukemia; Male; Middle Aged; Mouth Diseases; Necrosis; Nystatin

Selective antimicrobial decontamination with norfloxacin was compared with vancomycin/polymyxin for prophylaxis of bacterial infections in granulocytopenic patients. In the group of patients receiving norfloxacin, there were a lower number of acquired gram-negative bacillary organisms per patient (0.88 versus 1.86, p = 0.002), fewer patients with documented infection (16 of 36 versus 20 of 30, p = 0.12), and fewer cases of gram-negative septicemia (0 of 36 versus five of 30, p = 0.02). Norfloxacin was better tolerated (30 of 36 versus 16 of 30 patients highly compliant, p = 0.02), and associated with fewer gastrointestinal side effects (eight of 36 versus 14 of 36 patients, p = 0.07). These results suggest that norfloxacin is a more tolerable and efficacious oral antimicrobial agent than vancomycin/polymyxin for the prevention of serious gram-negative bacillary infections in granulocytopenic patients.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Bacterial Infections; Drug Evaluation; Drug Tolerance; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Middle Aged; Mycoses; Norfloxacin; Nystatin; Polymyxins; Vancomycin

Topics: Adult; Agranulocytosis; Anti-Infective Agents; Bacterial Infections; Digestive System; Humans; Mycoses; Nalidixic Acid; Neutropenia; Nystatin

Topics: Agranulocytosis; Amphotericin B; Animals; Granulocytes; Humans; Mice; Mice, Inbred Strains; Nalidixic Acid; Nystatin; Polymyxin B; Polymyxins

Infection in the granulocytopenic patient is often life-threatening, and the frequency and severity of infection are increased regardless of the cause of leukocyte suppression. Trimethoprim-sulfamethoxazole plus nystatin is known to be effective in preventing colonization and infection by the primary pathogens responsible for the morbidity and mortality associated with granulocytopenia. When treating granulocytopenic patients, clinicians should use proper barrier techniques to minimize nosocomial colonization. When foci of oral infection are present or bacteremia is predictable, appropriate antibiotics should be prescribed.

Topics: Agranulocytosis; Anti-Bacterial Agents; Bacterial Infections; Dental Care for Disabled; Humans; Mouth Diseases; Mycoses; Nystatin; Premedication; Sepsis; Sulfamethoxazole; Trimethoprim; Virus Diseases

Nystatin, one million units every four hours, was prospectively studied as a prophylactic antifungal agent in 164 neutropenic patients who were not initially colonized by fungi: 104 received nystatin and 60 served as controls. Fungal colonization occurred in 68/104 (65%) nystatin recipients and in 43/60 (71%) controls. However, nystatin significantly reduced multiple body site colonization and persistent oropharyngeal colonization. Despite these alterations in colonization profile, 16/104 (15%) nystatin recipients developed disseminated fungal infections, as compared to 5/60 (8%) control patients (0.5 greater than p greater than 0.1, N.S). Differences in the clinical course of colonized and non-colonized patients were observed. Eighteen of 111 (16%) colonized patients had afebrile clinical courses as compared to 16/53 (30%) non-colonized patients (p less than 0.05). Twenty-nine of 93 (31%) febrile episodes in colonized patients failed to respond to empiric antibiotic therapy as compared to 3/37 (8%) episodes in non-colonized patients (p less than 0.01). Disseminated fungal infections were diagnosed in 19/111 (17%) of colonized patients, as compared to 1/53 (2%) non-colonized patients (p less than 0.02). We conclude that colonized patients are more likely to develop febrile clinical courses, to fail to respond to empiric antibiotic therapy, and to develop disseminated fungal infection. Nystatin altered colonization patterns but did not prevent disseminated fungal infection.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Anti-Bacterial Agents; Drug Combinations; Female; Fever; Humans; Male; Middle Aged; Mycoses; Nystatin; Oropharynx; Prospective Studies; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Yeasts

During a 20-month period all acute nonlymphocytic patients (87 patient trials) receiving cytotoxic chemotherapy were placed on an oral nonabsorbable antibiotic regimen consisting of gentamicin, vancomycin, and nystatin in addition to an intensive program of infection prevention aimed at reducing exogenously acquired and body-surface potential pathogens. Although side effects of anorexia, diarrhea, and nausea were common, gentamicin-vancomycin-nystatin was ingested 80% of the study time. Microbial growth in gingival and rectal cultures was substantially reduced. The incidence of bacteremias and other serious infections was low. Pseudomonas aeruginosa, other gram-negative bacilli, and Candida species caused few infections along the alimentary canal, whereas infections of the skin (especially Staphylococcus aureus) were not reduced compared with those occurring in former years. A total of the 104 acquired gram-negative bacilli were gentamicin resistant; 5 subsequently caused infection. Thus, despite certain definite drawbacks, the use of oral nonabsorbable antibiotics to suppress alimentary tract microbial flora in combination with other infection prevention techniques in granulocytopenic cancer patients has proven feasible and tolerable and has been associated with a low order of life-threatening infections.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Agranulocytosis; Anti-Bacterial Agents; Drug Resistance, Microbial; Drug Therapy, Combination; Gentamicins; Humans; Infection Control; Infections; Leukemia; Middle Aged; Nystatin; Vancomycin

Topics: Acute Disease; Administration, Oral; Agranulocytosis; Evaluation Studies as Topic; Humans; Infection Control; Kanamycin; Leukemia; Neutropenia; Nystatin; Patient Isolators; Polymyxins; Radiation Injuries; Ristocetin

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Agranulocytosis; Anti-Bacterial Agents; Bacterial Infections; Feces; Female; Gentamicins; Humans; Leukemia; Male; Middle Aged; Mycoses; Neutrophils; Nystatin; Remission, Spontaneous; Vancomycin

Topics: Agranulocytosis; Amphotericin B; Antineoplastic Agents; Aspergillosis; Candidiasis; Cryptococcosis; Cytosine; Diabetes Complications; Glucocorticoids; Humans; Immunosuppression Therapy; Mucormycosis; Mycoses; Nystatin

Topics: Acute Disease; Agranulocytosis; Anti-Bacterial Agents; Antineoplastic Agents; Bacitracin; Bacteriological Techniques; Diet Therapy; Dietetics; Digestive System; Drug Synergism; Feces; Gastroenteritis; Gentamicins; Humans; Infection Control; Infections; Leukemia; Leukocyte Count; Neomycin; Nystatin; Polymyxins; Sterilization

Topics: Adult; Aged; Agranulocytosis; Anti-Bacterial Agents; Candidiasis; Esophageal Diseases; Female; Glucocorticoids; Humans; Male; Middle Aged; Nystatin; Radiography