rifampin and Mycoses

Rifampin has limited use in monotherapy because of the rapid development of resistance. In combination therapy with a variety of antimicrobials, it has many applications for treatment of serious infections.

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Bacterial Infections; Drug Therapy, Combination; Humans; Mycoses; Rifampin; Tuberculosis

Topics: Amphotericin B; Aspergillosis; Candidiasis; Cryptococcosis; Drug Synergism; Drug Therapy, Combination; Flucytosine; Humans; Mycoses; Prospective Studies; Rifampin

We report the first know case of disseminated fungal infection due to Fusarium proliferatum in a bone marrow transplant recipient to our knowledge. Fusarium was cultured from the blood, a paranasal sinus, and necrotic skin lesions. The isolate was sensitive to amphotericin B and on further sensitivity testing, synergy was demonstrated using rifampin in combination with amphotericin B. The patient had this infection while she was receiving alternate-day amphotericin, rifampin, and 5-flucytosine (5-FC) therapy. The infection was documented within 48 h of discontinuing daily granulocyte transfusions, which she had received for 3 weeks. The 5-FC was discontinued when sensitivities showed the organism resistant. After 6 weeks of treatment she showed complete remission of the infection, although neutrophil counts remained below 0.25 X 10(9)/L. From this case and from a review of the literature, it appears that synergic antifungal agents combined with leukocyte transfusions may be beneficial in the successful treatment of fusariosis in the compromised host.

Topics: Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Bone Marrow Transplantation; Child, Preschool; Combined Modality Therapy; Female; Fusarium; Humans; Mycoses; Neutropenia; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Rifampin; Skin; Spider Bites; Staphylococcal Infections

A review of the published literature has allowed the identification of a number of non-tubercular indications where rifampicin (trade mark Ciba-Geigy: Rimactane) has been successfully used in combination with other chemotherapeutic agents. The cases reviewed with regard to effectiveness sum 562. The most frequently combined drugs were aminoglycosides (mainly gentamicin), cotrimoxazole, colistine, vancomycin and fusidic acid, these two latter in cases due to Staphylococcus spp. The main indications where combined rifampicin treatment led to favourable results were UTI (success rate 64.9%), bone infections (86.9%), staphylococcal endocarditis (85.0%), respiratory tract infections often due to gram-negative rods (97.7%) as well as skin and soft tissue infections (83.3%), and bacterial meningitis (100%). Very favourable results were obtained in a non-life-threatening though epidemiologically important condition, i.e. salmonella carriers, where a 100% conversion rate was reached in an average period of 6 weeks. Special attention may deserve the combined treatment of fungal infections with rifampicin and amphotericin B. Tolerability was evaluated on a total of 650 cases. It appears to be good for daily doses up to 1,200 mg/day, even on long-term treatment; less so for the highest doses used (1,800 or 30 mg/kg a day). The clinical results, which are in good agreement with the results of the in vitro tests, indicate that rifampicin may have an important role in the combined treatment of severe non-mycobacterial infections. Further prospective, whenever possible, comparative studies are warranted for a thorough appraisal of its possible usefulness.

Topics: Anti-Infective Agents; Bacterial Infections; Drug Combinations; Humans; Mycoses; Rifampin

The literature on the clinical use of rifampicin in combination for the treatment of non-mycobacterial diseases is reviewed. From the published evidence, the most promising associations are, for staphylococcal infections, gentamicin, erythromycin, kanamycin and fusidic acid. In the field of Gram-negative infections, Psuedomonas-induced sepsis in particular, data are not so impressive but promising results have been obtained with the associated use of rifampicin and gentamicin or colistin. Some systemic fungal diseases may be successfully treated with rifampicin in combination with amphotericin-B. Although only few reports are available on this subject, the importance of such an application is stressed in view of the severity of these diseases and of the lack of appropriate treatments.

Topics: Amphotericin B; Cephalosporins; Chloramphenicol; Colistin; Drug Therapy, Combination; Endocarditis, Bacterial; Erythromycin; Gentamicins; Humans; Kanamycin; Lincomycin; Mycoses; Nalidixic Acid; Penicillins; Pseudomonas Infections; Respiratory Tract Infections; Rifampin; Staphylococcal Infections; Sulfamethoxazole; Tetracyclines; Trimethoprim; Urinary Tract Infections; Vancomycin

Topics: Amphotericin B; Animals; Bicarbonates; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Infusions, Parenteral; Injections, Intra-Articular; Injections, Intravenous; Injections, Spinal; Kidney; Mannitol; Meningitis; Mycoses; Rifampin

Antimicrobial central venous catheters are discussed as a device to reduce catheter-related infections. Previously we have reported a study with 223 adult surgical patients randomized to receive either a rifampicin-miconazole-loaded central venous catheter (CVC) (n=118) or a standard CVC (n=105). The antimicrobial CVC was shown to reduce catheter colonization (CC) and catheter-related local infection (CRI) significantly even at long-term catheterization. Here, we present further evaluation of the study focusing on possible benefits for high-risk patients. Subgroup analyses showed a pronounced reduction of CC and CRI in male, overweight and oncology patients. Important covariates were skin colonization for CC and oncological disease for CRI. Odds ratio (OR) for reducing CC was 0.076 (95% CI: 0.016-0.360) and CRI was reduced from 26% to 2.3% (p=0.001) in the cancer subgroup. Ex vivo long-term antimicrobial activity of modified catheters exceeded 4 weeks.. Immunocompromized patients suffering from cancer, transplantation, and dialysis patients with a long-term vascular access may mostly benefit from rifampicin-miconazole-releasing catheters.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibiotics, Antitubercular; Antifungal Agents; Bacterial Infections; Catheterization, Central Venous; Catheters, Indwelling; Coated Materials, Biocompatible; Equipment Contamination; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Miconazole; Middle Aged; Mycoses; Neoplasms; Rifampin; Risk Factors; Young Adult

Central venous catheters (CVC) are a major cause of nosocomial bloodstream infections. Catheters modified with miconazole and rifampicin that constantly and slowly release antimicrobial substances are assumed to be beneficial in reducing rates of colonization and catheter-related infections.. Prospective controlled non-blinded randomized clinical trial in two German university hospitals.. 223 adult inpatients with CVC between October 2000 and February 2002. Baseline characteristics, APACHE II score and therapeutic interventions were comparable.. Randomization to receive either a miconazole and rifampicin modified catheter (n=118) or a standard triple-lumen CVC (n=105). MEASUREMENTS, DEFINITIONS: Microbiological evaluation was done after CVC removal. A catheter was considered colonized if growth of > or =15 cfu was found by semi-quantitative roll-plate technique from a proximal or distal catheter segment. A catheter-related infection (CRI) was defined as a colonized catheter with local signs of inflammation. A catheter-related bloodstream infection (CR-BSI) was defined as a colonized catheter with isolation of the same organism from the patient's blood with accompanying clinical signs of infection.. A colonization of CVC was observed in six patients (5.1%) with a modified catheter and 38 patients (36.2%) with a standard catheter (P < 0.001). Five patients in the modified group (4.2%) and 18 in the standard group (17.1%) developed CRI (P=0.002). One assumed CR-BSI was detected in the standard group, with none in the modified group. No adverse effects related to the modified catheters and no antimicrobial resistance were observed.. CVC supersaturated with miconazole and rifampicin were associated with a significantly lower risk for catheter colonization and catheter-related infections compared to standard catheters.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Bacterial Infections; Catheterization, Central Venous; Catheters, Indwelling; Equipment Contamination; Female; Humans; Male; Miconazole; Middle Aged; Mycoses; Prospective Studies; Rifampin; Sepsis; Treatment Outcome

Topics: Amphotericin B; Aspergillosis; Candidiasis; Cryptococcosis; Drug Synergism; Drug Therapy, Combination; Flucytosine; Humans; Mycoses; Prospective Studies; Rifampin

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antibiotics, Antitubercular; Antifungal Agents; Dose-Response Relationship, Drug; Drug Interactions; Fluconazole; HIV Infections; Humans; Mycoses; Rifampin; Sertraline; Tuberculosis

A series of novel morpholinoquinoline based conjugates with pyrazoline moiety were synthesized under microwave irradiation. The newly synthesized compounds were screened for their preliminary in vitro antibacterial activity against a panel of pathogenic strains of bacteria and fungi, antituberculosis activity against Mycobacterium tuberculosis H37Rv and antimalarial activity against Plasmodium falciparum. Most of them exhibited significant antibacterial activity as compared to the first line drugs. Compounds 6a and 9d were found to possess excellent antibacterial activity potency as compared to ampicillin (286 μM), chloramphenicol (154 μM) and ciprofloxacin (150 μM). In antifungal screening, against Candida albicans, compounds 6c, 7c, 8a, 8b, 8c and 9b showed significant activity as compared to griseofulvin (1147 μM). Compounds 8b, 6b, 9d, 6a, 9b, 7b and 8a displayed brilliant activity against P. falciparum strain as compared to chloroquine (IC50 0.062 μM) as well as quinine (IC50 0.826 μM). Compounds 6d, 7b, 8b, 9c and 9d exhibited superior antitubercular activity. Among them 8b was found to be equipotent to rifampicin with 95% inhibition. The cytotoxicity of the synthesized compounds was tested using bioassay of Schizosaccharomyces pombe cells at cellular level.

Topics: Anti-Infective Agents; Antimalarials; Antitubercular Agents; Bacteria; Bacterial Infections; Fungi; Humans; Malaria, Falciparum; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Mycoses; Plasmodium falciparum; Pyrazoles; Quinolines; Structure-Activity Relationship; Tuberculosis

In this paper we report the SAR studies of a series of N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)amide and N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)sulfonamide derivatives 6(a-o) and 7(a-o), were synthesized in good yields and characterized by (1)H NMR, (13)C NMR and mass spectral analyses. The preparation of the key intermediate highlights an optimized palladium catalyzed (Pd₂(dba)₃/RuPhos) Buchwald cross-coupling of intermediate 2 and 3. The newly synthesized compounds were evaluated for their in vitro antibacterial activity against Staphylococcus aureus, (Gram-positive), Escherichia coli and Klebsiella pneumoniae (Gram-negative), antifungal activity against Candida albicans, Aspergillus flavus and Rhizopus sp. and antitubercular activity against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis, Mycobacterium fortuitum and MDR-TB strains. The synthesized compounds displayed interesting antimicrobial activity. The compounds 7d, 7f, 7h and 7n displayed significant activity against Mycobacterium tuberculosis H37Rv strain.

Topics: Amides; Anti-Infective Agents; Antitubercular Agents; Bacteria; Bacterial Infections; Fungi; Humans; Imidazoles; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Mycoses; Structure-Activity Relationship; Sulfonamides

A series of (2-aminothiazol-4-yl)methylester (5a-t) derivatives were synthesized in good yields and characterized by (1)H NMR, (13)C NMR, mass spectral and elemental analyses. The crystal structure of 5a was evidenced by X-ray diffraction study. The compounds were evaluated for their preliminary in vitro antibacterial, antifungal activity and were screened for antitubercular activity against Mycobacterium tuberculosis H37Rv strain. The synthesized compounds displayed interesting antimicrobial activity.

Topics: Anti-Infective Agents; Antitubercular Agents; Bacteria; Bacterial Infections; Crystallography, X-Ray; Fungi; Humans; Microbial Sensitivity Tests; Models, Molecular; Mycobacterium tuberculosis; Mycoses; Thiazoles; Tuberculosis

Voriconazole is a first-line agent in the treatment of many invasive fungal infections and is known to display highly variable pharmacokinetics. Previous studies of voriconazole therapeutic drug monitoring (TDM) have suggested concentration monitoring to be clinically useful but have been limited by small patient samples at a single institution. This multicenter retrospective study aimed to investigate relationships between voriconazole concentration and clinical outcomes and adverse events and to assess clinical factors and drug interactions that may affect voriconazole concentration. Medical records were reviewed for patients who received voriconazole and had at least 1 concentration measured at seven hospitals in Australia. The study included 201 patients with 783 voriconazole trough concentrations. Voriconazole concentrations of <1.7 mg/liter were associated with a significantly greater incidence of treatment failure (19/74 patients [26%]) than concentrations of ≥1.7 mg/liter (6/89 patients [7%]) (P < 0.01). Neurotoxic adverse events (visual and auditory hallucinations) occurred more frequently at voriconazole concentrations of >5 mg/liter (10/31 patients [32%]) than at concentrations of ≤5 mg/liter (2/170 patients [1.2%]) (P < 0.01). Multiple regression analysis of voriconazole concentration identified associations between increasing patient weight, oral administration of voriconazole, and coadministration of phenytoin or rifampin and significantly reduced concentrations, and associations between increasing patient age and coadministration of proton pump inhibitors and increased concentrations. Coadministration of glucocorticoids was found to significantly reduce voriconazole concentrations, inferring a previously unreported drug interaction between glucocorticoids and voriconazole.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antifungal Agents; Australia; Drug Interactions; Drug Monitoring; Female; Glucocorticoids; Humans; Male; Middle Aged; Mitosporic Fungi; Mycoses; Nucleic Acid Synthesis Inhibitors; Phenytoin; Pyrimidines; Retrospective Studies; Rifampin; Treatment Outcome; Triazoles; Voltage-Gated Sodium Channel Blockers; Voriconazole

Posaconazole has an important role in the prophylaxis and salvage treatment of invasive fungal infections (IFIs), although poor and variable bioavailability remains an important clinical concern. Therapeutic drug monitoring of posaconazole concentrations has remained contentious, with the use of relatively small patient cohorts in previous studies hindering the assessment of exposure-response relationships. This multicenter retrospective study aimed to investigate relationships between posaconazole concentration and clinical outcomes and adverse events and to assess clinical factors and drug interactions that may affect posaconazole concentrations. Medical records were reviewed for patients who received posaconazole and had ≥1 concentration measured at six hospitals in Australia. Data from 86 patients with 541 posaconazole concentrations were included in the study. Among 72 patients taking posaconazole for prophylaxis against IFIs, 12 patients (17%) developed a breakthrough fungal infection; median posaconazole concentrations were significantly lower than in those who did not develop fungal infection (median [range], 289 [50 to 471] ng/ml versus 485 [0 to 2,035] ng/ml; P < 0.01). The median posaconazole concentration was a significant predictor of breakthrough fungal infection via binary logistic regression (P < 0.05). A multiple linear regression analysis identified a number of significant drug interactions associated with reduced posaconazole exposure, including coadministration with proton pump inhibitors, metoclopramide, phenytoin or rifampin, and the H(2) antagonist ranitidine (P < 0.01). Clinical factors such as mucositis, diarrhea, and the early posttransplant period in hematopoietic stem cell transplant recipients were also associated with reduced posaconazole exposure (P < 0.01). Low posaconazole concentrations are common and are associated with breakthrough fungal infection, supporting the utility of monitoring posaconazole concentrations to ensure optimal systemic exposure.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Australia; Dose-Response Relationship, Drug; Drug Monitoring; Drug Therapy, Combination; Female; Fungi; Humans; Logistic Models; Male; Metoclopramide; Middle Aged; Mycoses; Phenytoin; Ranitidine; Retrospective Studies; Rifampin; Triazoles

Fusarium species are common hyaline soil saprophytes and plant pathogens that are opportunistic fungal pathogens of immunocompromised patients. The treatment for fusariosis remains uncertain with an unfavourable prognosis; new possibilities for treatment, such as various synergistic drug interactions, must be uncovered. In this study, we evaluated the in vitro interactions of amphotericin B with caspofungin, ketoconazole, 5-flucytosine, itraconazole, miconazole, rifampin, fluconazole, terbinafine and voriconazole against isolates of Fusarium spp. using the chequerboard method with interactions evaluated by fractional inhibitory concentration indices. The highest percentages of synergistic interactions were observed for the combinations of amphotericin B and caspofungin (68.7%), amphotericin B and rifampin (68.7%), amphotericin B plus 5-flucytosine (59.3%) and amphotericin B with voriconazole (37.5%). The pattern of susceptibility to antifungal agents among Fusarium species and their consequence on the effects of drug combinations are also discussed.

Topics: Amphotericin B; Antifungal Agents; Drug Interactions; Fusarium; Humans; Mycoses; Rifampin

In the treatment of disseminated Fusarium infections, amphotericin B either alone or in combination with flucytosine and rifampin is the drug therapy most frequently used. The efficacy of these antifungal drugs was evaluated in a murine disseminated-infection model, with five strains of Fusarium solani. All the treatments were clearly ineffective.

Topics: Amphotericin B; Animals; Antibiotics, Antitubercular; Antifungal Agents; Drug Therapy, Combination; Flucytosine; Fusarium; Male; Mice; Mycoses; Rifampin

Twelve patients receiving therapy with an azole agent (ketoconazole, itraconazole, and/or fluconazole) for systemic mycoses experienced drug interactions with rifampin, phenytoin, and/or carbamazepine resulting in substantial decreases in azole concentrations in serum. All four patients receiving azoles and concurrent phenytoin and/or carbamazepine failed to respond to treatment or suffered a relapse of their fungal infection. Four of five patients with cryptococcosis who received itraconazole and rifampin responded despite decreases in their serum itraconazole concentrations; synergy between itraconazole and rifampin was documented by in vitro analysis of inhibition and of killing of Cryptococcus neoformans isolates from all patients receiving this combination. In contrast, two patients with coccidioidomycosis failed to respond to itraconazole/rifampin. Moreover, two patients with cryptococcosis suffered a relapse or persistence of seborrheic dermatitis while receiving itraconazole/rifampin. The latter combination showed synergy in vitro in the inhibition of the mycelial phase of Coccidioides immitis and, to a lesser extent, of the pathogenic spherule phase of this fungus; synergy in the killing of C. immitis was not noted, nor was synergy seen against Malassezia furfur, the purported etiologic agent of seborrheic dermatitis. These findings illustrate several drug interactions that may affect clinical outcome and that must be considered in the management of antifungal therapy.

Topics: Adult; Aged; Antifungal Agents; Azoles; Carbamazepine; Coccidioides; Cryptococcus neoformans; Drug Interactions; Drug Therapy, Combination; Female; Fluconazole; Humans; Itraconazole; Ketoconazole; Malassezia; Male; Middle Aged; Mycoses; Phenytoin; Rifampin

The serum levels of two imidazoles, ketoconazole and Bayer n7133, when administered alone or in combination with rifampin, were measured in volunteers and the serum antifungal activity was determined against various fungal strains. Serum levels were measured by high pressure liquid chromatography and correlated with serum fungistatic activity as determined in microtiter plates. Ketoconazole showed a wide range of serum levels, suggesting individual variations. The addition of two doses of rifampin significantly decreased serum levels of both imidazoles and no synergism was observed. Serum fungicidal activity could only occasionally be demonstrated against one strain of Candida albicans and Candida stellatoidea. Serum fungistatic activity significantly correlated with the serum levels of both imidazoles. This approach should be investigated in patients to establish its potential clinical relevance for managing invasive fungal infections.

Topics: Aspergillus fumigatus; Candida; Candida albicans; Chromatography, High Pressure Liquid; Cryptococcus neoformans; Drug Evaluation; Drug Synergism; Drug Therapy, Combination; Humans; Ketoconazole; Mucorales; Mycoses; Rifampin; Triazoles

Wangiella dermatitidis is an infrequently encountered dematiacious fungus that usually causes localized infections of the skin and subcutaneous tissues. This report presents the first well-documented case of natural valve infection caused by this organism as it occurred in intravenous drug abuser. His course has been complicated by relapsing infection of two aortic prostheses and dissemination to the vertebral spine. Treatment with a combination of amphotericin B, rifampin, and ketoconazole has arrested the progression of his infection. The microbiologic features and existing clinical information regarding this fungus are reviewed and in vitro susceptibility data for the present isolate are presented.

Topics: Adult; Amphotericin B; Aortic Valve; Drug Therapy, Combination; Endocarditis; Heart Valve Diseases; Heroin Dependence; Humans; Ketoconazole; Male; Mitosporic Fungi; Mycoses; Recurrence; Reoperation; Rifampin

A thrush-like oral infection with subsequent alveolar abscess formation and a positive blood culture due to Trichosporon capitatum developed in a patient with acute myelogenous leukaemia. Later T. capitatum was identified by indirect immunofluorescence in multiple splenic abscesses. The infection was controlled by immediate aggressive treatment with amphotericin B, flucytosine and rifampicin and by splenectomy. This case of systemic T. capitatum infection resembles somewhat the invasive mycosis due to candida.

Topics: Abscess; Adult; Amphotericin B; Blood; Female; Flucytosine; Humans; Leukemia, Myeloid, Acute; Mitosporic Fungi; Mycoses; Rifampin; Splenic Diseases

Topics: Amphotericin B; Clotrimazole; Drug Therapy, Combination; Flucytosine; Humans; Kidney Diseases; Meningitis; Miconazole; Mycoses; Rifampin; Thrombophlebitis

Topics: Amphotericin B; Antifungal Agents; Cytosine; Drug Synergism; Flucytosine; Humans; Mycoses; Rifampin