nystatin-a1 and Neutropenia

Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are often given prophylactically, or empirically to patients with persistent fever.. To compare the effect of fluconazole and amphotericin B on morbidity and mortality in patients with cancer complicated by neutropenia.. We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles.. Randomised clinical trials comparing fluconazole with amphotericin B.. The two review authors independently assessed trial eligibility and risk of bias, and abstracted data.. Seventeen trials (3798 patients, 381 deaths) were included. In two large three-armed trials, results for amphotericin B were combined with results for nystatin in a 'polyene' group. Because nystatin is an ineffective drug in these circumstances, this approach creates a bias in favour of fluconazole. Furthermore, most patients were randomised to oral amphotericin B, which is poorly absorbed and poorly documented. There was overlap among the 'polyene' trials but we were unable to obtain any information from the trial authors or from Pfizer, the manufacturer of fluconazole, to clarify these issues. There were no significant differences in effect between fluconazole and amphotericin B, but the confidence intervals were wide. More patients dropped out of the study when they received amphotericin B, but as none of the trials were blinded decisions on premature interruption of therapy could have been biased. Furthermore, amphotericin B was not given under optimal circumstances, with premedication to reduce infusion-related toxicity, slow infusion, and with fluid, potassium and magnesium supplements to prevent nephrotoxicity. The major harms were hepatic impairment and gastrointestinal adverse effects with fluconazole and infusion-related toxicity, renal impairment and gastrointestinal adverse effects with amphotericin B. For the 2011 and 2014 updates no additional trials were identified for inclusion.. Amphotericin B has been disfavoured in several of the trials through their design or analysis, or both. Since intravenous amphotericin B is the only antifungal agent for which an effect on mortality has been shown, and since it is considerably cheaper than fluconazole, it should be the preferred agent.

Topics: Administration, Oral; Amphotericin B; Antifungal Agents; Confidence Intervals; Fluconazole; Humans; Injections, Intravenous; Mycoses; Neoplasms; Neutropenia; Nystatin; Odds Ratio; Randomized Controlled Trials as Topic

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Candidiasis; Candidiasis, Chronic Mucocutaneous; Clinical Trials as Topic; Cryptococcosis; Double-Blind Method; Fluconazole; Humans; Itraconazole; Ketoconazole; Mucormycosis; Mycoses; Neutropenia; Nystatin; Primary Prevention; Recurrence; Retrospective Studies

Infection is the major cause of morbidity and mortality in children receiving anticancer therapy. Children who have severe neutropenia (neutrophil count less than 100/mm3) for longer than 2 weeks should receive oral antibiotic prophylaxis. At present, trimethoprim sulfamethoxazole in combination with either nystatin or amphotericin B is the best regimen for reducing the incidence of serious infections. Trimethoprim sulfamethoxazole is very effective in the prevention of Pneumocystis carinii pneumonitis. Clinicans will have to balance the advantages and disadvantages of prophylaxis in patients who are at risk for P. carinii pneumonitis.

Topics: Adolescent; Adult; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Candidiasis; Child; Compliance; Drug Combinations; Humans; Leukemia; Neoplasms; Neutropenia; Nystatin; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

We assessed the activity and safety of liposomal nystatin, a broad-spectrum antifungal agent, for invasive aspergillosis in patients refractory to or intolerant of amphotericin B. Thirty-three patients were enrolled, received at least one dose of the study drug, and were evaluable for safety. Twenty-six patients had confirmed probable or definite aspergillosis and were fully eligible. Most patients had a hematological malignancy (53.8%) or hematopoietic stem cell transplantation (23.0%), were neutropenic (61.5%), and were refractory to previous amphotericin B (92.3%). The median duration of previous amphotericin B treatment was 16.5 days (range, 5 to 64 days). Aspergillosis was definite in 3 cases and probable in 23 cases. Liposomal nystatin was initiated at a dose of 4 mg/kg of body weight/day. Twenty-five patients were evaluable for response: a complete response was achieved for one patient, and a partial response was achieved for six. Thus, the overall response rate is 7 of 25 (28%; 95% confidence interval, 12 to 49%). Seventeen (68.0%) of the 25 evaluable patients died during therapy or within 1 month after the end of therapy. The primary cause of death was invasive aspergillosis for nine patients and underlying malignancy for eight patients. The most frequent side effects included chills, shivering, and fever, leading to discontinuation of therapy for two patients. Grade 1 decline in renal function was seen for 10 (30.3%) patients, and hypokalemia was seen for 13 (39.4%). We conclude that liposomal nystatin can be effective for salvage therapy of invasive aspergillosis. Infusion-related adverse events have been observed frequently.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Cause of Death; Child; Drug Resistance, Fungal; Female; Follow-Up Studies; Humans; Liposomes; Male; Middle Aged; Neutropenia; Nystatin; Salvage Therapy; Survival; Treatment Outcome

The efficacy and safety of itraconazole oral solution and a combination of amphotericin B capsules plus nystatin oral suspension were compared in the prophylaxis of fungal infections in neutropenic patients. In an open, randomized, multicentre trial, 144 patients received itraconazole oral solution 100 mg bd, and 133 patients received amphotericin B 500 mg tds plus nystatin 2 MU qds. Overall, 65% of itraconazole-treated patients were considered to have had successful prophylaxis, compared with 53% in the polyene group. Proven deep fungal infections occurred in 5% of patients in each group. Fewer patients receiving itraconazole than amphotericin plus nystatin had superficial infections (3 versus 8%; P = 0.066). This trend in favour of itraconazole was seen in patients with profound neutropenia (neutrophil count <0.1 x 10(9) cells/L at least once) or prolonged neutropenia (neutrophil count <1.0 x 10(9) cells/L for >14 days). The median time to prophylactic failure was longer in the itraconazole group (37 days) than in the polyene group (34 days). The number of patients with fungal colonization (nose, sputum, stool) changed more favourably from baseline to endpoint in the itraconazole group than in the polyene group. Both treatments were safe and well tolerated; however, patients receiving amphotericin plus nystatin had a higher incidence of nausea and rash. In conclusion, itraconazole oral solution at doses of 100 mg bd and oral amphotericin B plus nystatin have similar prophylactic efficacy against fungal infections in neutropenic patients. On the basis of reduced incidence of superficial fungal infections, fungal colonization and specific adverse events, itraconazole may be the preferred treatment.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Female; Humans; Itraconazole; Male; Middle Aged; Mycoses; Neoplasms; Neutropenia; Nystatin

In this multicentre, randomised, double-blind study, the safety and efficacy of oral fluconazole (200 micrograms/day) and nystatin suspension (6,000,000 IU/day) for the prevention of fungal infections were compared in patients with leukaemia undergoing remission induction chemotherapy. Antifungal prophylaxis was initiated at the time chemotherapy was started and continued throughout the hospital stay or the period of neutropenia to a maximum of 42 days. Prophylaxis was successful (no evidence of fungal infection or fever of unknown origin unresponsive to antibiotics) in 38 of 56 (68%) fluconazole-treated and 25 of 53 (47%) nystatin-treated patients (P = 0.03). 2 patients (4%) in the fluconazole group and 6 (11%) patients in the nystatin group developed systemic fungal infections (P = 0.15). The overall frequency of adverse events was similar among fluconazole-treated (29%) and nystatin-treated (32%); most events in both treatment groups involved the gastrointestinal tract. These results indicated fluconazole was more effective than nystatin in preventing Candida infections in patients with leukaemia; fluconazole was well tolerated.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Candidiasis; Double-Blind Method; Female; Fluconazole; Humans; Leukemia; Male; Middle Aged; Neutropenia; Nystatin; Opportunistic Infections; Treatment Outcome

The goal of this prospective randomized single-center study was the comparison of safety and efficacy of high-dose oral/intravenous fluconazole (400 mg daily) (group A) with oral nystatin plus miconazole inhalations (group B) in the prevention of fungal infections on a hemato-oncological isolation Ward. Of 157 patients admitted to the isolation ward during the study period only 90 (57%) were eligible for randomization; 22 (14%) had a fungal infection at admission. Of the 90 randomized patients, 89 were evaluable, 43 in group A and 46 in group B. The age, sex, diagnosis, planned therapy and risk factors for fungal infections at admission as well as the duration of neutropenia were in the same proportions in both groups. Oral thrush and mucocutaneous candidiasis were prevented in all patients of both groups, and 29 patients (32%: 17 in group A, 12 in group B) were discharged after successful prophylaxis (NS). Empiric amphotericin B was given according to predetermined criteria to 45 patients (51%: 23 group A, 22 group B; NS). Fluconazole significantly delayed the time before the start of intravenous amphotericin B. It was begun after a median of 10 days (0-45 days, range) of neutropenia below 0.5 x 10(9) granulocytes/l in group A and 7.5 days (0-26, range) in group B (P < 0.05). The duration of successful prophylaxis was significantly longer in group A (26 days median) than in group B (21 days, median) (P < 0.05). Systematic fungal infection was documented in 3 patients (1 group A, 2 group B; NS).

Topics: Adolescent; Adult; Aged; Female; Fluconazole; Humans; Immunocompromised Host; Male; Miconazole; Middle Aged; Mycoses; Neutropenia; Nystatin; Prospective Studies

An open, randomized study was performed at 18 European centres to compare the efficacy, safety and tolerance of oral fluconazole with oral polyenes for the prophylaxis of fungal colonization and infection in adults at high risk of developing neutropenia. Five hundred and thirty-six hospitalized patients with malignant disease, about to receive chemotherapy, radiotherapy, or bone marrow transplantation, and who were already neutropenic or were expected to develop neutropenia were included in the study. Before therapy or transplantation, patients commenced either oral fluconazole therapy (50 mg/day as a single dose) or oral polyenes therapy (amphotericin B 2 g/day and/or nystatin 4 x 10(6) units/day in four or more divided doses), for a mean of 29.3 days and 31.3 days, respectively. After baseline clinical and mycological testing, patients were re-evaluated at least weekly during prophylaxis, at the end of prophylaxis and two to six weeks later to identify proven or suspected fungal infection and to determine rates of colonization with fungi. Fungal infection was diagnosed in 41 of 511 evaluable patients, 10 (3.9%) of 256 in the fluconazole group and 31 (12.2%) of 255 in the polyene group (P = 0.001). This total included four patients (1.6%) in the fluconazole group who developed oropharyngeal candidiasis compared with 22 (8.6%) in the polyene group (P < 0.001). Systemic infections comprised 6 (2.3%) in the fluconazole group and 9 (3.5%) in the polyene group (P = not significant), and included three Candida krusei infections in each group. Parenteral amphotericin B therapy was given empirically for persistent fevers in an additional 62 (24.2%) patients receiving fluconazole and 59 (23.1%) receiving polyenes (P = not significant). Colonization with fungi was generally similar in each treatment group, although an increased proportion of patients receiving fluconazole developed colonization of the faeces (P < 0.01). Adverse reactions, possibly related to treatment, were recorded in 15 (5.6%) of 269 patients in the fluconazole group and 14 (5.2%) of 267 in the polyene group; these necessitated discontinuation of therapy in seven patients in each group. Once-a-day fluconazole was therefore more effective than oral polyenes for the prevention of oropharyngeal fungal infection and as effective for the prevention of infections at other sites in patients with neutropenia.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Child; Female; Fluconazole; Humans; Male; Middle Aged; Mycoses; Neutropenia; Nystatin

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 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

72 patients severely immunocompromised by their underlying disease (marrow aplasia, acute leukaemia, or solid tumour) or by the treatment they were receiving, or both, were randomised to receive antifungal prophylaxis with either oral ketoconazole or conventional doses of oral amphotericin B and nystatin. All patients also had gut decontamination with non-absorbable antibiotics, skin antisepsis, sterile food, and oral cotrimoxazole. Protection against fungal infection was significantly superior with ketaconazole. When patients who had received allogeneic bone-marrow transplant were studied separately, there was no significant difference between the two treatments, probably because there was a fall-off in ketoconazole absorption from the end of the third week after the transplant. However, ketoconazole greatly reduced the likelihood of fungal infection in non-transplant patients.

Topics: Amphotericin B; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Imidazoles; Immunosuppressive Agents; Ketoconazole; Leukemia; Mycoses; Neutropenia; Nystatin; Piperazines; Random Allocation

Thirty-eight uninfected patients undergoing bone marrow transplantation were assigned at random to receive prophylactic granulocyte transfusions and oral nonabsorbable antibiotics (group 1) or oral nonabsorbable antibiotics alone (group 2) when their neutrophil count fell below 0.5 x 10(9)/liter. The two groups were comparable in terms of age, sex, underlying disease, immunosuppressive therapy and days of neutropenia. There were three cases of septicemia (all due to gram-positive organisms) in group 2 and none in group 1 (p = 0.23). There was no difference in the incidence of other documented infections, and survival between the two groups was comparable. Recipients of prophylactic granulocyte transfusions had a significantly higher incidence of cytomegalovirus (CMV) infections (13 of 18 versus six of 17, p = 0.043). These data suggest that prophylactic granulocyte transfusions may prevent septicemia, have no effect on other infections or survival in patients undergoing bone marrow transplantation, and are associated with a higher incidence of CMV infection. Oral nonabsorbable antibiotics alone are equally effective in preventing serious infections in bone marrow transplant recipients.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Blood Transfusion; Bone Marrow Transplantation; Child; Colistin; Cytomegalovirus Infections; Evaluation Studies as Topic; Female; Granulocytes; Humans; Infection Control; Male; Middle Aged; Neutropenia; Nystatin; Random Allocation; Transplantation, Homologous; Vancomycin

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

30 patients with acute leukaemia being treated with cytotoxic drugs were investigated in a randomised trial to determine whether oral administration of co-trimoxazole in addition to non-absorbable antibiotics would reduce the rate of infection. Three significant differences were observed between the co-trmoxazole and the control groups: (i) 15 of the 16 (94%) control patients but only 8 of the 14 (57%) patients on co-trimoxazole developed infections and required additional antibiotics intravenously; (ii) although the duration of severe neutropenia (neutrophils less than 0.1 times 10(9)/1) was similar in the two groups, control patients required intravenous antibiotics on average after 2 days of neutropenia, whereas patients receiving co-trimoxazole required these only after 12 days; and (iii) the only 2 patients who died of infection were in the control group. Prophylaxis with co-trimoxazole is important in preventing or delaying the development of infection in neutropenic patients receiving therapy for acute leukaemia.

Topics: Administration, Oral; Adolescent; Adult; Aged; Clinical Trials as Topic; Colistin; Cross Infection; Drug Combinations; Drug Therapy, Combination; Framycetin; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Middle Aged; Neutropenia; Nystatin; Prospective Studies; Research Design; Sulfamethoxazole; Trimethoprim

Topics: Acute Disease; Anti-Bacterial Agents; Bacitracin; Blood Cell Count; Blood Platelets; Disinfection; Drug Combinations; Fever; Germ-Free Life; Glucose; Hexetidine; Humans; Leukemia; Neomycin; Neutropenia; Nystatin; Patient Isolators; Pneumonia; Remission, Spontaneous; Respiratory Tract Infections; Sterilization; Thrombelastography; Time Factors; Xylose

Trimethoprim-sulfamethoxazole (TMP-SMX) is a combination chemotherapeutic agent, a commonly used antibiotic. Adverse drug reactions occur in 6-8% of patients. Although, the most common adverse reactions include mild gastrointestinal distress and cutaneous events, also a wide range of hematological abnormalities have been ascribed to TMP-SMX. We report a 40-year-old male patient who developed an early onset neutropenia, thrombocytopenia, generalised rash and oral candidiasis after 5 days long TMP-SMX therapy. Although generalised rash may seen more and improves with discontinuation of the therapy; severe neutropenia, thrombocytopenia and oral candidiasis are seen very rare and rarely leads to fatality as it was in our case. Despite thrombocyte transfusions, whole blood transfusions, red cell concentrates and filgrastim therapy we lost our patient. We want to underline that although the TMP-SMX combination is usually well tolerated it can also lead to fatal complications.

Topics: Adult; Anti-Infective Agents; Anti-Inflammatory Agents; Candidiasis, Oral; Cefepime; Cephalosporins; Chlorhexidine; Drug Eruptions; Escherichia coli; Escherichia coli Infections; Exanthema; Fatal Outcome; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Male; Meropenem; Neutropenia; Nystatin; Platelet Transfusion; Prednisolone; Recombinant Proteins; Thienamycins; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination

In order to develop a prospective chemotherapeutic agent against opportunistic infections, it is important to know that host factors such as degree of immunological debility as well as recovery of immune functions to normality may contribute significantly to a successful elimination of the pathogens. We demonstrated previously that concomitant delivery of antimicrobial agents and immunomodulators to the pathogen harbouring-host contributes to the complete elimination of the deep-seated fungal infections (aspergillosis and candidiasis) in animals with normal immune status. Considering that neutropenic hosts are the main targets of such infections, it can be argued about the potential of the immunomodulator-based therapy in subjects with non-functional immune system. To resolve the hypothesis, we studied the role of immunomodulator tuftsin against experimental murine candidiasis in temporarily neutropenic Balb/c mice. The neutropenic mice were challenged with an isolate of Candida albicans that was showing less susceptibility to both free and liposomised-amphotericin B. The co-administration of tuftsin increased the efficiency of liposomised-polyene antibiotics (nystatin and amphotericin B) against experimental murine candidiasis in immunocompromised Balb/c mice. Pretreatment with liposomised tuftsin prior to C. albicans infection clearly enhanced protection against candidiasis, suggesting a prophylactic role of tuftsin in normal and temporarily neutropenic animals.

Topics: Adjuvants, Immunologic; Animals; Antifungal Agents; Candida albicans; Candidiasis; Drug Synergism; Drug Therapy, Combination; Female; Liposomes; Mice; Mice, Inbred BALB C; Neutropenia; Nystatin; Treatment Outcome; Tuftsin

The activity of liposomal nystatin against invasive pulmonary aspergillosis was investigated in persistently neutropenic rabbits. Treatment groups included liposomal nystatin at dosages of 1, 2 and 4 mg/kg/day intravenously, or amphotericin B deoxycholate 1 mg/kg/day administered intravenously after normal saline loading. As compared with untreated controls, liposomal nystatin administered at 2 and 4 mg/kg/day prolonged survival and reduced fungus-mediated tissue injury and excess lung weight at post-mortem in a similar manner to amphotericin B. Although amphotericin B was superior in clearing infected lung tissue, treatment with all regimens of liposomal nystatin led to a significant reduction in pulmonary fungal tissue burden. During treatment, ultrafast CT-scan demonstrated ongoing resolution of pulmonary lesions at 2 and 4 mg/kg/day, but not at 1 mg/kg/day. With the exception of mild increases in blood urea nitrogen (BUN) and serum creatinine values during treatment at 2 and 4 mg/kg/day, which were similar to those found in amphotericin B-treated rabbits, liposomal nystatin was well tolerated. Preliminary pharmacokinetic studies in non-infected animals established linear drug disposition of liposomal nystatin in plasma over the investigated dosage range and peak plasma levels above the MIC for the test strain after multiple daily dosing for 7 days. Liposomal nystatin increased survival and provided reduced tissue injury, effective microbiological clearance and tolerable side effects in experimental pulmonary aspergillosis in persistently neutropenic rabbits, thus providing a rational basis for further investigations in clinical trials.

Topics: Amphotericin B; Animals; Antifungal Agents; Area Under Curve; Aspergillosis; Blood Urea Nitrogen; Creatinine; Drug Carriers; Female; Half-Life; Liposomes; Lung; Lung Diseases, Fungal; Neutropenia; Nystatin; Organ Size; Rabbits; Radiography; Survival Rate

Using an isolate of Aspergillus fumigatus that is less susceptible in vivo to amphotericin B than most other isolates, we compared different doses of liposomal nystatin (L-nystatin), liposomal amphotericin B (L-amphotericin), and amphotericin B lipid complex (ABLC) with amphotericin B deoxycholate. Four experiments with intravenously infected neutropenic mice were conducted. A dose of L-nystatin at 10 mg/kg of body weight was toxic (the mice had fits or respiratory arrest). The optimal dosage of L-nystatin was 5 mg/kg daily on days 1, 2, 4, and 7 (90% survival). This was superior to L-amphotericin (5 mg/kg [P = 0.24] and 1 mg/kg [P < 0.0001]), ABLC (5 mg/kg [P = 0.014] and 1 mg/kg [P < 0.0001]), and amphotericin B deoxycholate (5 mg/kg [P = 0.008]). In terms of liver and kidney cultures, L-nystatin (5 mg/kg) was superior to all other regimens (P = 0.0032 and <0.0001, respectively). Higher doses of L-amphotericin (25 and 50 mg/kg) in one earlier experiment were more effective (100% survival) than 1 mg of L-amphotericin per kg and amphotericin deoxycholate (5 mg/kg) in terms of mortality and both liver and kidney culture results and to L-amphotericin (5 mg/kg) in terms of liver and kidney culture results only. ABLC (25 mg/kg) given daily for 7 days was superior to ABLC (50 mg/kg [P = 0.03]) but not to ABLC at 5 mg/kg or amphotericin B deoxycholate in terms of mortality, although it was in terms of liver and kidney culture results. No dose-response for amphotericin B (5 and 1 mg/kg) was demonstrable. In conclusion, in this stringent model, high doses of L-amphotericin and ABLC could overcome reduced susceptibility to amphotericin B deoxycholate, but all were inferior to 5- to 10-fold lower doses of L-nystatin.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Colony Count, Microbial; Cyclophosphamide; Deoxycholic Acid; Drug Carriers; Drug Combinations; Drug Resistance, Microbial; Immunosuppressive Agents; Liposomes; Mice; Neutropenia; Nystatin

Meta-analyses may become biased if the reported data in the individual trials are biased and if overlap among trials cannot be identified. We describe the unanticipated problems we encountered in collecting data for a meta-analysis comparing a new antifungal agent, fluconazole, with amphotericin B in patients with cancer complicated by neutropenia. In 3 large trials that comprised 43% of the patients identified for the meta-analysis, results for amphotericin B were combined with results for nystatin in a "polyene" group. Because nystatin is recognized as an ineffective drug in these circumstances, this approach creates a bias in favor of fluconazole. Furthermore, 79% of the patients were randomized to receive oral amphotericin B, which is poorly absorbed and not an established treatment, in contrast to intravenous amphotericin B, which was administered in 4 of 5 placebo-controlled trials, or 86% of patients. It was unclear whether there was overlap among the "polyene" trials, and it is possible that results from single-center trials were included in multicenter trial reports. We were unable to obtain information to clarify these issues from the trial authors or the manufacturer of fluconazole. Two of 11 responding authors replied that the data were with the drug manufacturer and two indicated that they did not have access to their data because of change of affiliation. In the meta-analyses, fluconazole and amphotericin B (mostly given orally) had similar effects (13 trials), whereas nystatin was no better than placebo (3 trials). Since individual trials are rarely conclusive, investigators, institutions, and pharmaceutical companies should provide essential details about their work to ensure that meta-analyses can accurately reflect the studies conducted and that patients will realize maximum benefits from treatments. We recommend that investigators keep copies of their trial data to help facilitate accurate and unbiased meta-analyses.

Topics: Amphotericin B; Antifungal Agents; Fluconazole; Humans; Meta-Analysis as Topic; Mycoses; Neoplasms; Neutropenia; Nystatin; Opportunistic Infections; Publication Bias; Randomized Controlled Trials as Topic; Research Design

The purpose of this study was to examine the activity of liposomal nystatin against a disseminated Aspergillus fumigatus infection in neutropenic mice. Mice were made neutropenic with 5-fluorouracil and were administered the antifungal drug intravenously for 5 consecutive days beginning 24 h following infection. Liposomal nystatin, at doses as low as 2 mg/kg of body weight/day, protected neutropenic mice against Aspergillus-induced death in a statistically significant manner at the 50-day time point compared to either the no-treatment, the saline, or the empty-liposome group. This protection was approximately the same as that for free nystatin, a positive control. Histopathological results showed that liposomal nystatin cleared the lungs, spleen, pancreas, kidney, and liver of Aspergillus and that there was no organ damage at the day 5 time point, which was after only three doses of liposomal nystatin. Based on these results in mice, it is probable that liposomal nystatin will be effective against Aspergillus infection in humans.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Drug Carriers; Liposomes; Male; Mice; Mice, Inbred Strains; Microbial Sensitivity Tests; Neutropenia; Nystatin; Organ Culture Techniques

The first 25 BMTs at the Royal Liverpool Children's Hospital (Alder Hey) were performed between April 1987 and July 1991. The aim of this report is to evaluate selective decontamination of the digestive tract (SDD) during the first post-BMT month in this series of 14 allografts and 11 autografts. SDD is a method used to abolish carriage of potentially pathogenic microorganisms including yeasts, Staphylococcus aureus and Gram-negative bacilli (GNB). Chlorhexidine mouth wash was used to decontaminate the oropharynx, and neomycin, colistin (polymyxin E) and nystatin (NEOCON) were given to eradicate gut carriage. Oropharyngeal decontamination was successful in 48% of patients, gut carriage was abolished in 60%, and eradication of the carrier state at both sites was achieved in 33%. A septic response was seen in 76% of children and 36% developed septicaemia (indigenous Gram-positive cocci only). A low carriage index for the target microorganisms during the study manoeuvre of SDD was associated with negative blood cultures (p < 0.01). Acute GVHD occurred in 28% of allografts, but was seen in none of the successfully decontaminated children (p < 0.05). It is concluded that septicaemia from yeasts and GNB, but not the septic response, were successfully prevented by SDD.

Topics: Adolescent; Bone Marrow Transplantation; Carrier State; Child; Child, Preschool; Chlorhexidine; Colistin; Digestive System; Disease Susceptibility; Drug Therapy, Combination; England; Female; Graft vs Host Disease; Humans; Incidence; Infant; Male; Neomycin; Neutropenia; Nystatin; Premedication; Retrospective Studies; Sepsis; Survival Analysis

In a non-randomized study the efficacy of itraconazole in preventing fungal infections in neutropenic patients was investigated. Forty-seven patients with acute leukemia or advanced lymphoblastic lymphoma were enrolled. Ninety-two episodes of severe neutropenia after chemotherapy were observed. Mean duration of neutropenia was 24 days. Norfloxacin was administered as prophylaxis against gram-negative infections and itraconazole 200 mg b.i.d. as antifungal prophylaxis. Surveillance cultures of throat, urine, feces and vagina or prepuce were performed regularly. Four patients died, two patients due to heart failure, two patients due to staphylococcal pneumonia. Only in one case Candida albicans was cultured from bronchoalveolar lavage fluid. No systemic mycosis or Aspergillus fumigatus pneumonia was documented. In a similar group of patients treated in the preceding 18 months nystatin was used as antifungal prophylaxis. In this group of patients six cases of Aspergillus fumigatus pneumonia, two cases of Candida albicans fungemia and one case of Candida glabrata pneumonia occurred of which six patients died. Itraconazole seems to be effective in preventing fungal infections in neutropenic patients and is well tolerated.

Topics: Adolescent; Adult; Aged; Antifungal Agents; Female; Humans; Itraconazole; Ketoconazole; Male; Middle Aged; Mycoses; Neutropenia; Nystatin; Prospective Studies

Thirty-four patients with haematological malignancies were studied to investigate the effect of empirical broad-spectrum antibiotic therapy (ceftazidime and gentamicin) on the gastro-intestinal flora. Twenty-five patients with acute myeloid leukaemia or post-autologous bone-marrow transplantation were given framycetin, nystatin and colistin (Fracon), and two patients with non-Hodgkin's Lymphoma were on co-trimoxazole, as long-term gut prophylaxis. Semi-quantitative microbiology was carried out on oropharyngeal swabs and quantitative microbiology on faecal specimens. The oropharyngeal flora consisted mainly of streptococci, coagulase-negative staphylococci and coryneforms, and was little affected by ceftazidime/gentamicin. A strain of Enterobacter cloacae resistant to ceftazidime and gentamicin colonized one patient, who later developed septicaemia. The faecal flora of patients on Fracon was dominated by enterococci; the few enterobacteria present were eliminated by ceftazidime/gentamicin. The anaerobic flora was absent in 15% of patients; in the remainder, it consisted mainly of Bacteroides spp., and was little affected by ceftazidime/gentamicin. The faecal flora of patients not on Fracon always contained anaerobes, and some strains of enterobacteria persisted throughout antibiotic treatment. None of the patients was colonized by Clostridium difficile or Pseudomonas aeruginosa. Broad-spectrum therapy with ceftazidime and gentamicin appeared to have little effect on the gastro-intestinal flora, except to encourage the overgrowth of enterococci and reduce the numbers of enterobacteria.

Topics: Ceftazidime; Colistin; Enterobacter; Feces; Gentamicins; Humans; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Neutropenia; Nystatin; Oropharynx; Risk Factors; Staphylococcus; Streptococcus; Trimethoprim, Sulfamethoxazole Drug Combination

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

A regimen of oral non-absorbable prophylactic antibiotics (kanamycin-vancomycin-nystatin) was given to nine severely neutropaenic leukaemic patients on cytotoxic therapy (11 courses), in conjunction with isolation procedures. An appreciable decrease in faecal organisms, especially anaerobes, was apparent after 48 h of commencing the course, and most bacteria had disappeared from the stool after five days. There were three episodes of septicaemia, all with enteric organisms, whilst on these antibiotics; one proved fatal. The emergence of resistance to aminoglycosides in faecal flora, notably Klebsiella, in 6/11 courses constituted a major problem in the use of such prophylaxis.

Topics: Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Microbial; Feces; Female; Humans; Kanamycin; Leukemia; Male; Middle Aged; Neutropenia; Nystatin; Sepsis; 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: Adult; Anemia, Aplastic; Colistin; Drug Therapy, Combination; Framycetin; Humans; Male; Neutropenia; Nystatin; Rectal Fistula; Rectum; Sterilization