Diflucan scientific update |
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J Med Microbiol. 2010 Jul 15. [Epub ahead of print]
Ahmad A, Khan A, Khan LA, Manzoor N.
Jamia Millia Islamia.
[Use of fluconazole against clinical candida isolates] In vitro synergy of eugenol and methyl eugenol with fluconazole against clinical Candida isolates.
The species Candida is a group of opportunistic pathogenic commensals in immune-compromised patients. Treatment of Candida infections is becoming increasingly difficult due to antifungal drug resistance especially with fluconazole (FLC) which is a commonly used azole. The present study highlights in vitro antifungal activity of eugenol (EUG) and methyl eugenol (MEUG) alone and in combination against 64 FLC-sensitive and 34 FLC-resistant clinical Candida isolates. All the strains were susceptible to both the naturally occurring phenyl propanoids. The nature of interaction was studied from fractional inhibitory concentration indices (FICI) for both EUG-FLC and MEUG-FLC combinations calculated from checkerboard microdilution assay. FICI values depicted high synergism of FLC with both compounds and even greater with MEUG. FLC-resistant Candida isolates showed high sensitivity to both compounds. No antagonistic activity was seen in the strains tested in the present study. From these results we can suggest that EUG and MEUG have great potential as antifungals and that FLC can be supplemented with EUG and MEUG to treat FLC-resistant Candida infections.
Scand J Infect Dis. 2010 Jul 7. [Epub ahead of print]
Dutronc H, Dauchy FA, Cazanave C, Rougie C, Lafarie-Castet S, Couprie B, Fabre T, Dupon M.
Service de Maladies Infectieuses et Tropicales, Hôpital Pellegrin.
[Review of candida prosthetic infections] Candida prosthetic infections: Case series and literature review.
Abstract Candida prosthetic joint infections are considered to be rare. We retrospectively studied patients treated for Candida prosthetic infections between 1 January 1995 and 31 December 2007 in our infectious diseases department, a tertiary referral centre. We identified 7 patients, 4 with knee and 3 with hip prosthetic infections. The most frequent fungal agent was Candida albicans (4 cases), followed by Candida parapsilosis (2 cases) and Candida guillermondii (1 case). All the patients received antifungal treatment for a prolonged period. Five patients had their prosthesis removed and 3 had reimplantation, 1 patient was treated with debridement and prosthetic retention, and the last patient refused surgery. The mean follow-up time was 2.5 y. At the last evaluation, 3 patients were considered as cured, 3 patients presented a secondary bacterial infection leading to amputation for 2 of them, and 1 patient died from heart failure. During Candida prosthetic joint infections, the epidemiological characteristics and the location of the prosthesis are very similar to bacterial prosthetic infections. The benchmark antifungal therapies remain amphotericin B and/or fluconazole.
Antimicrob Agents Chemother. 2010 Jul 12. [Epub ahead of print]
Warrilow AG, Martel CM, Parker JE, Melo N, Lamb DC, Nes WD, Kelly DE, Kelly SL.
Institute of Life Science and School of Medicine, Swansea University, Swansea, Wales SA2 8PP, United Kingdom; and Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX79409-1061, USA.
[Analysis of properties of candida albicans sterol] Azole Binding Properties of Candida albicans Sterol 14-{alpha} Demethylase (CaCYP51).
Purified Candida albicans sterol 14-alpha demethylase (CaCYP51) bound the CYP51 substrates lanosterol and eburicol producing type I binding spectra with Ks values of 11 and 25 muM, respectively and a Km value of 6 muM for lanosterol. Azole binding to CaCYP51 was 'tight' with both the type II spectral intensity (DeltaAmax) and the azole concentration required to obtain half DeltaAmax being proportional to the CaCYP51 concentration. Tight binding of fluconazole and itraconazole were confirmed by IC50 determinations using CYP51 reconstitution assays. CaCYP51 had similar affinities for clotrimazole, econazole, itraconazole, ketoconazole, miconazole and voriconazole with Kd values of 10 to 26 muM under oxidative conditions compared with 47 muM for fluconazole. The affinity of CaCYP51 for fluconazole and itraconazole appeared to be 4- and 2-fold lower from CO displacement studies than by direct ligand binding under oxidative conditions. Econazole and miconazole were most readily displaced by carbon monoxide followed by clotrimazole, ketoconazole and fluconazole and then voriconazole (7.8 pmol min(-1)), but itraconzole could not be displaced by carbon monoxide. This work reports in depth the characterization of the azole binding properties of wild-type C. albicans CYP51 including voriconazole and will contribute to effective screening of new therapeutic azole antifungal agents. Preliminary comparative studies with I471T CaCYP51 protein suggested that fluconazole resistance conferred by this mutation was through a combination of increased turnover, increased affinity for substrate and a reduced affinity for fluconazole in the presence of substrate, allowing the enzyme to remain functionally active, albeit at reduced velocity, at higher fluconazole concentrations.
FEMS Immunol Med Microbiol. 2009 Jun 17. [Epub ahead of print]
Salvenmoser S, Seidler MJ, Dalpke A, Müller FM.
Pediatric Pulmonology, Department of Pediatrics III, Cystic Fibrosis Centre and Infectious Diseases, University Heidelberg, Heidelberg, Germany.
[Study of impact on toll like receptor 9 in context with caspofungin, aspergillus and candida albicans] Effects of caspofungin, Candida albicans and Aspergillus fumigatus on toll-like receptor 9 of GM-CSF-stimulated PMNs.
Abstract The possible involvement of Toll-like receptors (TLRs) 1, 2, 4 and 9 in the interaction of antifungal drugs with polymorphonuclear neutrophils (PMNs) in response to Aspergillus fumigatus and Candida albicans as stimuli was investigated. Caspofungin revealed the broadest capacity to enable C. albicans and A. fumigatus to stimulate TLR upregulation, TLR 2 by A. fumigatus and TLRs 4, 9 by C. albicans. Conventional amphotericin B (cAMB) stimulated only A. fumigatus to induce TLRs 2 and 4 upregulation; voriconazole stimulated A. fumigatus and fluconazole C. albicans to induce TLR 9 upregulation. For cAMB, only TLR 9 was upregulated by A. fumigatus, whereas in the case of voriconazole, TLRs 2, 4, 9 were upregulated. Caspofungin revealed the broadest capacity: C. albicans was stimulated to upregulate TLRs at least at one of the concentrations, and A. fumigatus was stimulated to upregulate TLRs 2, 4. TLR 9 was upregulated two to three fold by all antifungal drugs on protein, except for fluconazole at the RNA level. Candida albicans preincubated with caspofungin has additional effects on CD11b expression and IL8 chemotaxis in CpG-DNA-stimulated PMNs. These results indicate a relevant upregulation with a functional relevance of TLR 9 in the presence of C. albicans strains preincubated with caspofungin at three concentrations.
Can J Infect Dis Med Microbiol. 2009 Summer;20(2):45-50.
Labbé AC, Pépin J, Patiño C, Castonguay S, Restieri C, Laverdiere M.
Department of Microbiology-Infectious Diseases, Hôpital Maisonneuve-Rosemont;
[Analysis of candia bloodstream infections] A single-centre 10-year experience with Candida bloodstream infections.
OBJECTIVE: To describe the clinical and microbiological features associated with Candida bloodstream infections observed at Hôpital Maisonneuve-Rosemont (Montreal, Quebec) between August 1996 and July 2006. METHODS: Episodes were retrieved from the microbiology laboratory. Different patient episodes and different isolate episodes in the same patient were selected. Antifungal susceptibility was determined by the Clinical and Laboratory Standards Institute's (USA) M27A2 method. RESULTS: A total of 190 different episodes of candidemia in 185 patients were identified. Eleven (6%) episodes occurred in outpatients. Candida albicans was identified in the majority of episodes (57%). Its frequency remained stable over the years. The proportion of Candida krusei candidemia episodes increased between 2003 and 2006, but this was not statistically significant. A central venous indwelling catheter or a peripherally inserted central catheter line was present in the majority of patients (167 [88%]). Of the indwelling catheters removed at the time of diagnosis, 39% were positive for Candida species on culture. Overall, voriconazole was the most active agent (the minimum inhibitory concentration required to inhibit the growth of 90% of organisms was 0.5 mg/L). Resistance to fluconazole was observed in 26 (14%) isolates (C albicans, 4%; versus non-albicans Candida species, 27%; P<0.001). Being on the hematology-oncology unit at the time of diagnosis (adjusted OR 7.8; 95% CI 2.3 to 27.1; P=0.001) and having received fluconazole or itraconazole within the past three months (adjusted OR 8.3; 95% CI 2.8 to 24.4; P<0.001) were significantly associated with resistance to fluconazole in multivariate analysis. CONCLUSIONS: At Hôpital Maisonneuve-Rosemont, the frequency and species distribution of blood isolates of Candida remained stable over the past decade. In vitro resistance of C albicans to fluconazole and itraconazole remained minimal; resistance of non-albicans Candida species to fluconazole did not increase significantly. The new antifungal agents all had high in vitro activity against the bloodstream Candida isolates.
West Afr J Med. 2009 Sep-Oct;28(5):343-6.
Salami AK, Ogunmodele JA, Fowotade A, Nwabuisi C, Wahab KW, Desalu OO, Fadeyi A.
Department of Medicine, College of Health Sciences, University of Ilorin, Ilorin.
[A report depicting cryptococcal meningitis in AIDS patients] Cryptococcal meningitis in a newly diagnosed AIDS patient: a case report.
BACKGROUND: Cryptococcus neoformans is a very important cause of fungal meningitis in immunosuppressed patients OBJECTIVE: To describe a case of cryptococcal meningoencephalitis in an HIV/AIDS patient from the University of Ilorin Teaching Hospital. METHODS: An 18 -year -old male student presented with cough, weight loss, and fever. He was clinically assessed and had full laboratory investigations including cerebrospinal fluid CSF and then started on chemotherapy. Both the clinical and neurological evaluation of the patient was described along with the laboratory analyses of his CSF. Outcome of how he was managed was also reported. RESULTS: Cryptococcus neoformans presented as an AIDS defining fungal infection for the first time in this 18 year old undergraduate who was infected probably from transfusion of unscreened blood He had advanced HIV infection (CD4+ count of 29 cells/ul) and severe cryptococcal meningoencephalitis. He was unsuccessfully managed with fluconazole, a second choice drug for this condition, amphotericin B being not available. CONCLUSION: Nigerians should have access to effective blood transfusion services at all public and private hospitals across the country. The National Essential Drug list should be expanded to include drugs such as amphotericin B which hitherto were considered exotic.
Drugs Today (Barc). 2008 Nov;44 Suppl 4:25-30.
Solorzano Santos F, Reyna Figueroa J, Torres Munoz MJ, Diaz Luna JL.
Hospital de Pediatria CMN Siglo XXI, IMMS, Mexico, DF.
Therapeutic options of neonatal candidiasis [Neonatal candidiasis: therapeutic options] [Article in Spanish]
Diverse factors (such as preterm babies with low body weight staying for long-term periods at intensive care units, subjected to invasive procedures, receiving one or more antibiotic schemes, parenteral nutrition, etc.) are considered to pose a risk for the development of infections by opportunistic agents. Of the latter, Candida albicans is considered the main cause of neonatal candidiasis. The most frequently involved Candida species are C. albicans, C. parapsilosis and C. tropicalis. The advent of new antimycotic agents has increased the therapeutic possibilities for the treatment of candidiasis. Antimycotic agents used for the treatment of neonatal candidiasis include: amphotericin B deoxycolate, lipid-associated compounds of amphotericin B, fluconazole and itraconazol, and caspofungin.
Drugs Today (Barc). 2008 Nov;44 Suppl 4:7-21.
Gonzalez G, Becerra A, Rodriguez Melo F, Campos T.
Hospital Universitario de Nuevo Leon, Monterrey, Nuevo Leon, Mexico.
Information of antifungal in pediatric patients [Clinical mycology and antifungals in the pediatric population] [Article in Spanish]
Infections caused by Candida spp. and Aspergillus spp. account for 90% of all fungal infections and are the most significant causes of human morbidity and mortality. Candida albicans causes between 50 and 60% of all nosocomial fungal infections. The wet mount test and culture are the screening methods used in leading clinical laboratories for the detection of Candida spp. However, yeasts should be strictly classified mainly based on their physiological and biochemical characteristics, through a series of morphological and biochemical laboratory tests. As a result of the increase in systemic fungal infections and the spread of antifungal medications, it was necessary to establish standardized in vitro sensitivity tests as a guideline for the therapeutic decision-making process. Among antifungal agents available today we find antimycotics such as amphotericin B, 5-fluorocytosine (5-FC), fluconazole, voriconazole, posaconazole, and ravuconazole. Additionally, there is the recently developed group of echinocandines, which includes caspofungin, micafungin and anidulafungine.
Enferm Infecc Microbiol Clin. 2008 Dec;26 Suppl 14:44-50.
Vázquez López L, Ruiz Camps I.
Servicio de Hematología, Hospital Universitario de Salamanca, Salamanca, España. lvazlo@usal.es
Effect of anidulafungin in haematological patients [Potential of anidulafungin in hematological patients] [Article in Spanish]
Until relatively recently, the treatment available for invasive fungal infections in hematological patients consisted of amphotericin B and azoles. Each of these groups had limitations and secondary effects. The echinocandins are a new class of antifungal agent that has shown promising results in the treatment of numerous invasive fungal infections. Anidulafungin is a new echinocandin that, in addition to showing potent in vitro activity against Aspergillus spp. and Candida spp. (including fluconazole- and amphotericin B-resistant microorganisms), also provides some advantages over other candins. In humans, these drugs are degraded through biotransformation rather than a metabolic process. No drug interactions have been found. In hematological patients, anidulafungin would play a "potential" role as empirical therapy in febrile neutropenia, as is the case of caspofungin. Given the epidemiology of Candida infection in these patients, anidulafungin could be used as initial therapy in candidemia before starting treatment with oral flucozanole, if indicated by the fungigram. This drug would also be indicated in the treatment of invasive Aspergillus spp. infections in patients with hepatic or renal insufficiency or in those taking concomitant medications. The available in vitro studies also suggest an important role for this drug in combinations of antifungal agents. Given the excellent safety profile and absence of interactions of anidulafungin, this drug will undoubtedly be of great utility in the management of difficult-to-treat mycotic infections in hematological patients.
Folia Med Cracov. 2007;48(1-4):71-84.
Zwolińska-Wcisło M, Sliwowski Z, Drozdowicz D, Kwiecień S, Mazurkiewicz-Janik M, Trojanowska D, Rudnicka-Sosin L, Mach T, Budak A, Brzozowski T, Konturek SJ, Pawlik WW.
Klinika Gastroenterologii, Hepatologii i Chorób Zakaźnych, Colegium Medicum Uniwersytetu Jagiellońskiego, Kraków.
Study in laboratory of ulcerative colitis [Candidiasis in the experimental model of ulcerative colitis] [Article in Polish]
In the present study on animal model of ulcerative colitis the influence of fungal colonization on the severity of inflammatory lesions in the colon and the course of their healing was evaluated. The results of our studies revealed, that significant fungal colonization (over 10(4) CFU/ml) delayed ulcer healing in the colon. It corresponded with the decrease of colonic blood flow (CBF) in the region of lesions and increase of interleukin (IL)-1beta, tumor necrosis factor(TNF)-alpha level in the serum. Introduction of antifungal therapy (fluconazole) or probiotic in rats inoculated with Candida accelerated the process of ulcer healing in the colon, expressed through the reduction of macro- and microscopic lesions in the colon and decrease of MPO, IL-beta TNF-alpha serum level.
Can J Infect Dis Med Microbiol. 2007 Mar;18(2):149-50.
Lagrotteria D, Rotstein C, Lee CH.
Department of Medicine, McMaster University.
[Series showing treatment of micafungin and candiduria] Treatment of candiduria with micafungin: A case series.
There has been a gradual increase in the incidence of non-Candida albicans-related nosocomial infections. Candida glabrata urinary tract infections have increased in frequency, and treating these infections can be difficult because the organism may be resistant to fluconazole. A newer antifungal agent, micafungin, which belongs in the class of echinocandins, provides an alternative and effective therapy against C glabrata. The present report describes three cases of C glabrata-associated urinary tract infections successfully treated with micafungin. To the authors' knowledge, this is the first report of successful treatment of C glabrata and azole-resistant C albicans-associated urinary tract infection with an echinocandin.
Curr Clin Pharmacol. 2007 Jan;2(1):37-58.
Bellmann R.
Clinical Pharmacokinetics Unit, Inflammation Research Laboratory and Intensive Care Unit, Division of General Internal Medicine, Department of Internal Medicine, Innsbruck Medical School, Innsbruck, Austria.
[Administration of antimycotics] Clinical pharmacokinetics of systemically administered antimycotics.
Systemic fungal infections are a major threaten for immunocompromised patients. Beside the antimycotic spectrum, the pharmacokinetic properties of an antifungal drug are crucial for its clinical efficacy. Since patients with systemic mycoses frequently present with a significant co-morbidity, pharmacokinetics under special conditions such as renal insufficiency, renal replacement therapy or impaired liver function have to be considered. Amphotericin B is eliminated unchanged by the liver and the kidney. Its plasma protein binding accounts for 95 to 99 percent. Conventional amphotericin B deoxycholate has a remarkable infusion related and renal toxicity. Therefore, lipid formulations have been developed. By now, three lipid formulations are therapeutically used: liposomal amphotericin B, amphotericin B colloidal dispersion and amphotericin B lipid complex. Striking differences in their plasma pharmacokinetics have been found. These differences can be attributed to the diverse disposition of the lipid moieties, while liberated amphotericin B displays a pharmacokinetic behavior which is independent from the lipid-formulation applied. The highest amphotericin B tissue concentrations have been found in the liver and in the spleen, followed by lung, kidney and heart. Concentrations in brain tissue are very low. Flucytosine has no relevant protein binding and is eliminated by glomerular filtration. Fluconazole, itraconazole, voriconazole, posaconazole and ravuconazole are triazoles, used for treatment of systemic fungal infections. Significant drug interactions have to be considered during therapy with triazoles, particularly in patients dependent on immunosuppression. These interactions are caused by the metabolism of triazoles in the liver where the cytochrome P450 (CYP) system is involved at a different extend as well as by their mechanisms of action. Triazoles display a favorable tissue distribution with high penetration into the central nervous system. Echinocandins such as caspofungin and micafungin are rapidly taken up by peripheral tissues, particularly by the liver. In the first 24 hours this uptake appears to be the main route of elimination from plasma. Enzymatic degradation takes place, but is independent of CYP. Thus, drug interactions are a minor problem during echinocandin treatment. The highest tissue levels of caspofungin and micafungin have been measured in the liver. Moderate concentrations are achieved in lung, spleen and kidney. Penetration into the brain is relatively poor.
J Huazhong Univ Sci Technolog Med Sci. 2007;27(2):209-12.
Chen S, Li S, Liu Z, Wu Y, Tu Y, Li J.
Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
Comparison of the effects of three different anti-fungus drugs on Candida albicans of murine vaginal mucosa.
The present study is for the comparison of the therapeutic effects of three different anti-fungal drugs in the treatment of experimental vaginitis caused by Candida albicans in mice. The result showed that Itraconazole or fluconazole, but not terbinafine, is very effective for the treatment of fungal vaginitis caused by C. albicans in mice.
To compare the therapeutic effects of three different anti-fungal drugs (i.e., terbinafine, fluconazole and intraconazole) in the treatment of experimental
vaginitis caused by Candida albicans (C. albicans) in mice, the fungal vaginitis model was established in female ICR mice by intravaginal inoculation of
suspension of C. albicans after the animal had been pretreated with estradiol. Mice were divided at random into different groups and then respectively
treated with terbinafine, fluconazole and intraconazole given by gastrogavage. The burden of the fungus in the vaginal lavage fluids in the mice of the
different groups was measured dynamically at different time points after the beginning of the drug treatment. The fungal burdens in the vaginal lavage fluids
taken at different time points from the mice treated with terbinafine were significantly higher than those taken at corresponding time points from mice
treated with fluconazole or itraconazole (P<0.01). The fungal burdens in the vaginal lavage fluids taken from mice 1 week after the beginning of the
treatment with terbinafine remained at a relatively high level. A dramatic drop in the fungal burden was noted in the vaginal lavage fluids taken on the 2nd
day of the treatment from mice treated with itraconazole or fluconazole group and the fungal burden on the 3rd day of the treatment in these mice were at a
very low level, suggesting that fluconazole or itraconazole were highly effective for the treatment. However, the difference in the therapeutic effect
between the two drugs was not significant (P>0.05). Itraconazole or fluconazole, but not terbinafine, is very effective for the treatment of fungal vaginitis
caused by C. albicans in mice.
Med Mycol. 2007 May;45(3):221-4.
Gonzalez GM, Robledo E, Saldivar D, Gonzalez G, Bosques F, Garza E.
Departamento de Microbiologia, Facultad de Medicina, Universidad Autonoma de Nuevo Leon. Mexico.
Therapeutic efficacy of posaconazole against isolates of Candida albicans with different susceptibilities to fluconazole in a vaginal model.
A battery of 34 vaginal isolates of Candida albicans was tested against posaconazole (POS) and fluconazole (FLU) to determine their in vitro susceptibilities and to obtain FLU-susceptible and FLU-resistant strains for the murine in vivo studies. The study reached the conclusion that POS displayed a more effective in vivo activity than FLU in the treatment of murine C. albicans vaginitis produced by isolates with different susceptibilities to FLU.
A battery of 34 vaginal isolates of Candida albicans was tested against posaconazole (POS) and fluconazole (FLU) to determine their in vitro susceptibilities
and to obtain FLU-susceptible and FLU-resistant strains for the murine in vivo studies. FLU-resistant strains were chosen on the basis of their 48-h MICs.
The 48-h geometric mean MICs for all isolates tested were 0.016 and 0.656 microg/ml for POS and FLU, respectively. The treatment regimens for the vaginal
murine infection model were POS or FLU at 10 or 20 mg/kg of body weight/day and 20 mg/kg twice a day. All regimens with POS were effective in reducing fungal
burden of both the fluconazole-susceptible and resistant isolates of C. albicans. All FLU regimens were effective against infection induced by the
fluconazole-susceptible strain. While FLU at 10 mg/kg was ineffective against fungal burden of the resistant strain, treatment with FLU at 20 mg/kg once or
twice a day was effective against this strain. Both POS and FLU at 20 mg/kg twice a day were able to clear C. albicans from vaginas of mice infected with the
fluconazole-susceptible strain. POS displayed a more effective in vivo activity than FLU in the treatment of murine C. albicans vaginitis produced by
isolates with different susceptibilities to FLU.
Nippon Ishinkin Gakkai Zasshi. 2007;48(2):97-100.
Yaguchi T, Takizawa K, Taguchi H, Tanaka R, Kubota T, Kubota Y, Kubota M, Fukushima K.
Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University.
Antifungal Activity of the Novel Adduct, GX-95, of Silver with Nanometer-scale Particles to Peptidic Hydrolysates from Collagen.][Article in Japanese]
Scientists developed novel adduct, GX-95, of silver with nanometer-scale particles to peptidic hydrolysates from collagen and was found to possess strong and broad antifungal activities against all fungi examined with different minimal inhibitory concentrations (MICs).
Silver has long been known to have an antimicrobial activity against bacteria and other microorganisms, and has been used as eating utensils, as dental
fillings and so on. We developed a novel adduct, GX-95, of silver with nanometer-scale particles to peptidic hydrolysates from collagen. Antifungal activity
of the adduct against pathogenic yeasts and filamentous fungi was examined in terms of minimal inhibitory concentrations (MICs). GX-95 was found to possess
strong and broad antifungal activities against all fungi examined in the following MICs: 0.25 to 0.31 micro g/ml for Candida albicans including resistant
strains to fluconazole, itraconazole and flucytosine, 0.05 to 0.2 micro g/ml for Cryptococcus neoformans strains, 0.025 to 0.4 micro g/ml for Aspergillus
fumigatus strains, 0.4 micro g/ml for Trichophyton rubrum, and 0.05 micro g/ml for Cladophialophora carrionii.
Intensive Care Med. 2007 May 15;
Filioti J, Spiroglou K, Roilides E.
3rd Department of Pediatrics, Aristotle University, Hippokration Hospital, Konstantinoupoleos 49, 54642, Thessaloniki, Greece.
Invasive candidiasis in pediatric intensive care patients: epidemiology, risk factors, management, and outcome.
The incidence of candidemia in pediatric patients follows the same pattern of increase as in adults, but the rate of increase is greater. In this study using conventional and novel antifungal agents, novel antifungal agents such as second-generation triazoles and echinocandins exhibit potential as alternative agents in critically ill children with ICI.
BACKGROUND: The incidence of candidemia in pediatric patients follows the same pattern of increase as in adults, but the rate of increase is greater.
Pediatric patients in critical condition, particularly young infants, are especially vulnerable to invasive Candida infections (ICI), partly because of their
age and severe underlying disease and partly because of the invasive procedures used. DISCUSSION: Central venous catheters and arterial lines, parenteral
nutrition, mechanical ventilation and extended use of antimicrobials enhance the risk of ICI. C. albicans continues to be the most prevalent isolate.
However, an increasing role of non-C. albicans (NAC) spp., some of which are intrinsically or potentially resistant to antifungal agents, has been observed.
NAC spp., particularly C. parapsilosis and C. tropicalis, account for almost half of ICI. The increased use of antifungals in immunocompromised patients,
mainly prophylactically, is considered the strongest contributory factor to the changes in species distribution, which have subsequently affected the
mortality and choice of empirical treatment. CONCLUSIONS: Prompt removal of lines and initiation of antifungal treatment are the milestones of management.
Conventional amphotericin B remains a commonly used antifungal agent, but its lipid formulations and fluconazole are also used frequently. Novel antifungal
agents such as second-generation triazoles and echinocandins exhibit potential as alternative agents in critically ill children with ICI. Although response
rates are still far from satisfactory, improved understanding of risk factors, preventive strategies and new treatment options promise a better future
outcome.
J Antimicrob Chemother. 2006 Sep 29;
Marine M, Serena C, Pastor FJ, Guarro J.
Unitat de Microbiologia, Facultat de Medicina i Ciencies de la Salut, Universitat Rovira i Virgili, Carrer Sant Llorenc 21, 43201, Reus, Spain.
Combined antifungal therapy in a murine infection by Candida glabrata.
The scientists want to develop proper treatments for patients who do not respond to current antifungal treatments with different types of combinations and suggested that amphotericin B in combination with micafungin is promising for the treatment of disseminated C. glabrata infections.
OBJECTIVES: To develop proper treatments for patients who do not respond to current antifungal treatments, we tested new combinations of antifungal drugs for treating disseminated infections by Candida glabrata in a murine model. METHODS: Mice were rendered neutropenic by intraperitoneal cyclophosphamide and intravenous 5-fluorouracil administration. The animals were infected intravenously with 2 x 10(8) cfu of C. glabrata. The efficacies of micafungin combined with amphotericin B, fluconazole or flucytosine, and of amphotericin B combined with fluconazole were evaluated by survival and tissue burden reduction. Results and CONCLUSIONS: Micafungin plus amphotericin B was the most effective combination at reducing tissue burden. Micafungin at 10 mg/kg combined with amphotericin B at 0.75, 1.5 or 3 mg/kg prolonged survival with respect to the monotherapies, but only the second combination showed a synergistic effect in reducing fungal load in spleen and kidney. Amphotericin B at 1.5 mg/kg combined with micafungin at 5, 10 or 20 mg/kg reduced tissue burden with respect to the monotherapies, but the effects of the three combinations were very similar. These results suggest that amphotericin B in combination with micafungin is promising for the treatment of disseminated C. glabrata infections.
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