Intravenous Miconazole Research Articles

Rare case of fungal keratitis caused by Plectosporium tabacinum

A rare case of fungal keratitis caused by Plectosporium tabacinum is reported. A 78-year-old female gardener presented with conjunctivitis and an oval infiltrate with irregular margins in the nasal half of the cornea in the right eye. Light microscopy of corneal scrapings revealed a filamentous fungus, and a diagnosis of fungal keratitis was made. The patient was admitted into our hospital on February 19, 2008. Treatment with topical miconazole, topical fluconazole, pimaricin ointment, intravenous miconazole, and corneal debridement was commenced. One week later, the infiltrate improved, but the central part of the infiltrate was still deep. Topical fluconazole was switched to topical voriconazole, and intravenous miconazole was switched to intravenous voriconazole. One month after admission, the causative organism was identified by morphology and molecular biological analysis as Plectosporium tabacinum. The corneal infiltrate resolved 3 months after admission. A stromal scar persisted for 3 months after the patient was discharged. This is the first detailed report of fungal keratitis caused by P. tabacinum. Voriconazole was effective in treating this refractory keratitis.

Exophiala dermatitidis infection in non-cystic fibrosis bronchiectasis

A 54-year-old female presented with an exacerbation of right middle lobe bronchiectasis. A bronchoscopic bronchial washing and repeated trials of sputum culture consistently recovered no other infectious agent except Exophiala dermatitidis. Her illness was improved by administrations of intravenous miconazole and nebulized amphotericin B when sputum cultures yielded no fungi, demonstrating a pathogenic role of the fungi. The present case illustrates E. dermatitidis as a pathogenic agent in non-cystic fibrosis bronchiectasis.

The future of antifungal therapy.

In the late 1970s the options for systemic antifungal therapy doubled with the addition of intravenous miconazole and oral ketoconazole to the two previously available agents, amphotericin B and flucytosine. The 1980s ushered in the next generation of triazole antifungals, fluconazole and itraconazole. These are the present-day mainstays of treatment for some of the most serious systemic fungal infections. However, the increase in the numbers and types of fungal pathogens, and especially the emergence of azole-resistant fungi, have prompted a continuing search for new therapeutic options. This search has yielded more-potent triazole antifungals, new vehicles for both polyenes and triazoles, and entirely new classes of agents such as the echinocandin derivatives; in addition, it has prompted the evaluation of new combinations of present-day antifungals and exploration of the use of immunomodulators for treatment of fungal infections. Rapid developments in molecular mycology are permitting a concentrated search for more targets for antifungals. We are entering a new era of antifungal therapy in which we will continue to be challenged by systemic fungal diseases but will have greatly expanded options for treatment.

Use of Antifungal Therapy in Hospitalized Patients I. Results Prior to the Marketing of Fluconazole

To evaluate the use of antifungal agents in hospitalized patients prior to marketing of fluconazole and to assess characteristics associated with their use. A cohort of hospitalized patients receiving topical or systemic antifungal therapy was monitored concurrently. Sixty-nine hospitals ranging in size from 100 to more than 500 beds, 70.1 percent affiliated with medical schools. Participating clinical pharmacists each identified 15 consecutive patients receiving systemic antifungal therapy and 5 consecutive patients receiving topical antifungal therapy at their institutions. Data collection began October 1989 and ended March 1990. All data collected were observational in nature, and no patient intervention was required. Characteristics of patients receiving antifungal therapy were compared using t-tests and chi-square tests. Utilization and patterns of use of antifungal therapy were reported. The most common risk factors necessitating antifungal therapy, in descending order, were: administration of broad-spectrum antibiotics and/or presence of invasive catheters, carcinoma, AIDS, leukemia or lymphoma, diabetes mellitus, solid organ or bone marrow transplantation, and chronic obstructive pulmonary disease. Five hundred seventeen patients received systemic therapy and 464 (89.7 percent) received a single systemic agent. Of these, 242 (52.2 percent) received amphotericin B, 215 (46.3 percent) received ketoconazole, 6 (1.3 percent) received flucytosine, and 1 (0.2 percent) received intravenous miconazole. Fifty-three patients received two systemic agents either concurrently or consecutively. Ketoconazole was most often used for presumed or documented oral, urogenital, or esophageal infections and amphotericin B was the preferred agent for disseminated infections and fungemia (p < 0.001). Almost half of the patients receiving amphotericin B or ketoconazole (48.3 percent) received these drugs as empiric therapy. Documented infections were more likely to be treated with amphotericin B (54.8 percent) than with ketoconazole (27.4 percent) (p < 0.001). The predominant fungal isolates were Candida albicans, Candida spp., and unspecified yeasts. Amphotericin B toxicity led to discontinuation of drug therapy in only 5.1 percent of cases. Two hundred sixty-nine patients (34.2 percent) received topical antifungal therapy only. Nystatin oral suspension was prescribed to 65.3 percent of the patients, clotrimazole troches to 23.0 percent, amphotericin B irrigation to 10.9 percent, and nystatin tablets to 0.8 percent. The utilization patterns of antifungal agents in this survey follow established therapeutic guidelines. Prior to the introduction of fluconazole, amphotericin B was the agent of choice for documented systemic fungal infections. Ketoconazole was more often used for prophylaxis of fungal infections and treatment of oral and esophageal infections.

Invasive fungal disease in pediatric acute leukemia patients with fever and neutropenia during induction chemotherapy: a multivariate analysis of risk factors.

We evaluated the courses of 115 consecutive cases of pediatric acute leukemia treated with induction chemotherapy. Seventy-two patients developed fever associated with neutropenia; 15 developed systemic fungal infections. We reviewed multiple demographic and treatment characteristics of these patients in an attempt to identify potential risk factors for the development of invasive fungal disease (IFD). Risk factors identified in a univariate analysis included duration of neutropenia after first fever (P less than .0001), diagnosis of acute nonlymphocytic leukemia (ANLL) (P = .003), onset of fever and neutropenia within 5 days of starting induction chemotherapy (P = .009), and multiple (greater than one) surveillance culture sites positive for fungal organisms (P = .02). In a multiple logistic regression analysis, duration of neutropenia (P less than .001) remained a significant risk factor. The study group of patients had a significantly higher risk of fungal infections than a matched group of leukemia patients developing fever with neutropenia due to postremission consolidation chemotherapy (P = .003). In the first 48 patients, 14 (29%) developed IFD. In the subsequent patients (n = 24), intravenous miconazole (5 mg/kg every 8 hours) was begun at the time of the first fever. One of the 24 patients (4%) given miconazole developed IFD. The use of miconazole was a negative risk factor for the development of IFD in univariate (P = .01) and multivariate (P = .05) analysis. We conclude that pediatric leukemia patients who develop fever associated with neutropenia during induction chemotherapy are at high risk for developing IFD. The role of intravenous miconazole at the time of the first fever in this group deserves further study.

Prevention of fungal sepsis in patients with prolonged neutropenia: A randomized, double-blind, placebo-controlled trial of intravenous miconazole

Patients treated with cytotoxic therapy expected to produce neutropenia lasting two or more weeks were randomly assigned in a double-blind study to receive intravenous miconazole or placebo concomitant with empiric antibiotics to test whether miconazole can prevent fungal sepsis. The study drug was initiated at the time of first fever along with antibiotics and was continued until neutropenia resolved, fungal sepsis occurred, or persistent or recurrent unexplained fever after six or more days prompted substitution of the study drug by amphotericin B. Two hundred eight treatment courses in 180 patients were evaluated. Fungal sepsis occurred in only one patient receiving miconazole compared with eight patients receiving placebo (p = 0.03). Fatal fungal sepsis occurred in four patients receiving placebo and in none of the patients receiving miconazole (p = 0.08). There was no evidence for the development of resistance to polyenes or imidazoles in fungal isolates recovered from patients in this randomized trial or an increase in Aspergillus infections in patients who received miconazole in this randomized trial or in 121 subsequently treated patients who received unblinded use of miconazole. Thus, intravenous miconazole was more effective than placebo in preventing fungal sepsis in patients with chemotherapy-induced prolonged neutropenia.

Successful Treatment of Paecilomyces Lilacinus Endophthalmitis Following Cataract Extraction With Intraocular Lens Implantation

We report a case of mycotic endophthalmitis caused by Paecilomyces lilacinus after cataract surgery. Treatment consisted of early vitrectomy, multiple intravitreal injections of amphotericin B and miconazole, intravenous miconazole and, later, oral ketoconazole. The intraocular lens, which initially appeared uninvolved, was removed six weeks after initiation of therapy and found to contain causative organisms. Final visual acuity was 20/20. We recommend aggressive therapy consisting of early vitrectomy, intravitreal injections repeated as necessary, removal of the intraocular lens, avoidance of intraocular steroid, and administration of systemic antifungal agents.

A fatal case of pulmonary penicilliosis.

A 19-year-old male developed acute lymphocytic leukemia complicated with pulmonary penicilliosis. Marked leukopenia with a high fever continued for more than two weeks. A strain of Candida glabrata was isolated from blood culture. Treatment was initiated by combination therapy with antifungal drugs and anticancer drugs. To treat the suspected infection with this fungus, oral flucytosine and intravenous miconazole were administered, but the clinical symptoms were not alleviated. Thus oral fluconazole was added to the regimen. X-ray examinations revealed that the infiltration in the middle and lower fields of the right lung gradually became localized, and the findings suggested the formation of a fungus ball. The patient died of right pneumothorax on the 66th hospital day.At autopsy, mass lesions were detected in the thoracic cavity about 4×4×5cm in size in the right middle lobe and about 1×1×3cm in size in the left upper lobe. These mass lesions were filled with necrotic lung tissues, and they thus differed in nature from the so-called fungus ball. Those lesions and the cavity wall contained numerous fungal elements consisting of dichotomous septated hyphae. Two morphologically different fungi were isolated from the mass lesion in the right lung : one isolate was identified as Penicillium citrinum and the other was a Penicillium species without reaching the final identification. The morphology of these two isolates was examined in detail with an electron microscope.This seems to be the first reported case of pulmonary penicilliosis due to P. citrinum and an unidentified Penicillium sp.

Do the Imidazoles have a Role in the Management of Genitourinary Fungal Infections?

The imidazoles have demonstrated antifungal activity against a number of fungi that are pathogenic for man. Effective clinical use has been demonstrated in patients with cutaneous and systemic candidiasis, aspergillosis, blastomycosis, coccidioidomycosis, cryptococcus and histoplasmosis.We report our experience with the oral imidazole agent ketoconazole in the management of 8 patients with significant urinary candidiasis as judged by elevated urinary candidal counts (greater than 15,000/ml.). Only 4 of the 8 patients had resolution of candiduria with ketoconazole therapy.Intravenous miconazole, another imidazole, has been available for treatment of systemic and genitourinary fungal infections. Limited success (50 per cent) with intravenous miconazole has been noted in the treatment of systemic candidiasis with urinary involvement. Miconazole also has been used as a systemic and local irrigant in the treatment of bladder and renal candidiasis.Based on these observations and our own studies, we believe that the imidazoles have a limited role in the management of patients with significant fungal involvement of the urinary tract.

Intravenous miconazole therapy for experimental keratomycosis in rabbits.

Intravenous miconazole (90 mg daily for 3 weeks) reduced the intensity of experimental fungal keratitis due to Candida albicans in a group of 10 rabbits. Clinical scores of affected eyes were statistically significantly lower in the treated group than in a control group of 10 untreated rabbits. All cultures of corneal scrapings were negative on 18th day after inoculation in the treated group, but four cultures were still positive on the 21st day in the control animals. Histopathological examination of eyes from treated and untreated rabbits showed great differences in the severity of inflammatory changes in the two groups.

The Effects of Intravenous Miconazole on Fungal Keratitis

Two patients, a 44-year-old man and a 53-year-old man, with fungal keratitis were successfully treated with intravenously infused miconazole, a synthetic imidazole derivative. In these cases healing and regression of the corneal ulcer began four or five days after initiation of miconazole treatment. The clinical evidence of corneal infection disappeared completely after four weeks and visual acuities improved markedly (from 20/500 to 20/20 in Case 1 and from 20/400 to 20/40 in Case 2). Aside from a transient increase of serum triglycerides and beta-lipoproteins, the drug appeared to be well tolerated.

Petriellidium (Allescheria) Boydii Orbital and Brain Abscess Treated with Intravenous Miconazole

A previously healthy 4-year-old boy suffered a penetrating injury to his left orbit and left frontal lobe, which resulted in an infection by Petriellidium boydii. The patient was successfully treated with intravenous miconazole and multiple debridements.

Miconazole in the treatment of coccidioidomycosis.

Intravenous miconazole can produce responses in patients with various manifestations of coccidioidal disease, even if they have failed to respond to amphotericin B. In 4 large series of 33, 33, 46 and 31 courses of miconazole for skin and soft tissue, chronic pulmonary, meningeal and skeletal coccidioidomycosis, response rates of 40, 72, 31 and 32%, respectively, were achieved; 60, 75, 78 and 56%, respectively, of those responding subsequently relapsed at the site(s) of earlier involvement. This suggests that the therapeutic effect of the relatively brief courses used (mean, 1 to 3 months) is fungistatic in vivo. Common side effects of intravenous miconazole include phlebitis, pruritus, anaemia, thrombocytosis, hyponatraemia, nausea, hyperlipidaemia, vomiting, central nervous system effects, and rashes. The place of miconazole relative to amphotericin B and ketoconazole has not been determined, and requires further comparative studies. Information on the results of different regimens, particularly longer courses, would also be of interest.

Neonatal meningitis due to Candida albicans, associated with osteomyelitis; failure to respond to miconazole

Summary The failure of intravenous and intrathecal miconazole to sterilise the cerebrospinal fluid of an infant with Candida albicans meningitis and associated osteomyelitis is reported. The patient subsequently responded to a short course of amphotericin B. The clinical features of disseminated candidiasis are described.

Pulmonary candidiasis complicating a severe burn treated with miconazole

A 3 3 4 -year-old boy received a 50 per cent body surface area burn in a house fire. On the eighteenth day post burn he was moribund and a diagnosis of pulmonary candidiasis was made following tracheal cultures and X-ray changes after a period of progressive deterioration during which he had received multiple antibiotics and assisted ventilation. Treatment of this pulmonary candidiasis was with intravenous miconazole. The child's clinical condition rapidly improved over the following 24–48 hours and the X-ray changes resolved. He was subsequently discharged fully healed.

Miconazole in cryptococcosis and systemic candidiasis: a word of caution.

Excerpt An article in a recent issue of this journal reported the use of intravenous miconazole in cryptococcosis (1). Use of this new antifungal drug in the treatment of systemic candidiasis as we...

Fungal retinitis: a case of Torulopsis glabrata infection treated with miconazole.

Presumptive embolic chorioretinal Torulopsis glabrata infection is described in a patient who had received prolonged intravenous antibiotic therapy. The ocular findings are compared and contrasted with embolic lesions due to Candida albicans. The patient was treated for 6 weeks with intravenous miconazole. During this time there was shrinkage of the ocular lesions, some improvement in vision and abolition of fungaemia. Improvement in tests of immune function during treatment suggests that an early immunological deficit was secondary to the infection. Intravenous miconazole is a relatively nontoxic alternative to amphotericin and deserves further evaluation in the treatment of ocular mycosis.

Miconazole therapy for systemic candidiasis in a conjoined (Siamese) twin and a premature newborn

A 2.5 kg thoracopagus (Siamese) twin and a 0.73 kg premature newborn developed systemic candidiasis and were treated with intravenous miconazole. The conjoined twin was in a state of severe metabolic acidosis, respiratory distress, jaundice, anuria, abdominal distension, and shock. The 0.73 kg premature infant was also in a state of severe metabolic acidosis, respiratory distress, and oliguria. Miconazole was used in this desperate situation for the treatment of life-threatening candidiasis. Both infants responded well to treatment and recovered. All parameters of their diseases improved during therapy despite pre-existing multiple organ dysfunction. Miconazole can be a safe alternative to amphotericin B for the treatment of systemic candidiasis in neonatal infants, including those with impaired renal function.

Drug therapy reviews: Clinical pharmacology and therapeutic use of antimycotic drugs

Indications, pharmacology, mechanism of action, adverse reactions, administration and dosage ot SIX antimycotic drugs (amphotericin B, flucytosine, nystatin, clotrimazole, miconazole nitrate and griseofulvin) are reviewed. The availability and cost of commercial preparations are listed. Amphotericin B is the single most effective drug against the following systemic fungal infections: blastomycosis, histoplasmosis, cryptococcosis, candidiasis, sporotrichosis, aspergillosis, mucormycosis and coccidioidomycosis. Some Candida sp are sensitive to flucytosine, but the drug IS useful only occasionally in the treatment of systemic candidal infections. Flucytosine may be effective in the treatment of Aspergillus pneumonia and meningitis, hut this drug alone is not the best treatment. Nystatin has been used topically to treat superficial candidal infections of the oral mucosa (thrush) and esophagus, and candidal stomatitis, pharyngitis and vaginitis; aerosols have been used to treat systemic aspergillosis and candidiasis. Clotrimazole. IS useful topically for Candida, Tricophyton or Microsporum skin infections, and vaginally tor vaginal candidiasis. Intravenous miconazole is used most commonly against Coccidioides immitis infections involving pulmonary, osseous and meningeal sites; topically, miconazole has the same Uses as clotrimazole. Griseofulvin is most effective for tinea and ringworm infections caused by Tricophyton sp and Microsporum sp. No other antiinfective drug causes toxic reactions as often as amphotericin B; however, the drug does have unique uses that often outweigh its risks. Flucytosine may depress the bone marrow and cause leukopenia, neutropenia and thrombocytopenia. Nystatin causes few adverse reactions; systemic absorption is minimal. There are few side effects with topical use of Clotimazole. Phlebitits often occurs after i.v administration of miconazole nitrate. Griseofulvin produces few adverse effects

Combined Intravenous Miconazole and Intrathecal Amphotericin B for Treatment of Disseminated Coccidioidomycosis

A patient received a previously unreported combination of intravenous miconazole and intrathecal amphotericin B for the treatment of disseminated coccidioidomycosis with central nervous system involvement. After first having been treated with amphotericin B, followed by a course of miconazole therapy, the patient responded with remarkable clinical and serologic improvement to the combination of intrathecal amphotericin B and intravenous miconazole. The combination should be considered in the treatment of disseminated coccidioidomycosis with central nervous system involvement.