Revisión de un nuevo triazol, Isavuconazol para tratamiento de aspergilosis y mucormicosis. Se abren njuevas opciones para estas infecciones muy severas en especial en pacientes oncologicos
This comprehensive lecture explain the basic antiviral, antifungal, and steroid medications used commonly to treat oral conditions. It is directed to the level of mind of undergraduate dentist
Etiologia de la celulitis y Predicción clínica de la enfermedad Estreptocócic...Alex Castañeda-Sabogal
Etiologia de la celulitis. Estudio prospectivo y predicción clínica de la infeccion por Estreptococcus basado en la frecuencia encontrada de las especies de estreptococo
This comprehensive lecture explain the basic antiviral, antifungal, and steroid medications used commonly to treat oral conditions. It is directed to the level of mind of undergraduate dentist
Etiologia de la celulitis y Predicción clínica de la enfermedad Estreptocócic...Alex Castañeda-Sabogal
Etiologia de la celulitis. Estudio prospectivo y predicción clínica de la infeccion por Estreptococcus basado en la frecuencia encontrada de las especies de estreptococo
Presentation by Phil Smart to the Geotourism Workshop of SEGRA 2015 about the Gondwana Fossil Walk and other geotourism developments at Ulladulla, New South Wales
INFORMATION:
Author : Subhananda Bera From Mystic Wellbeing
Date : 14 - July - 2010
Pages : 15
Format : PDF
Table Of Contents
Forewords ................................ 04
To Quit or Not To Quit ................... 05
Welcome ...................................06
Why Blame Smoking Only? .................. 07
Fight for Right ...........................08
Smoking Alone Doesn’t Kill ............... 09
Special Ones? – Say “My Heart Aches…”......10
Cover Point ...............................11
Imagine … There’s No Cigarette ............12
So, You Understand? .......................14
Author’s Box ..............................15
Written By Subhananda Bera
Mysticboard.com
http://MysticBoard.com
http://tinyurl.com/mysticboard
If You Are Thinking Of Anything Mystic - Think MysticBoard.com
The 10 Trends Shaping the Future of South African Brands in 2012The Added Value Group
Why track trends? Because, great brands are constantly evolving. They anticipate change. And the strongest indicator of change is culture. Our role is to help clients take a more future focussed approach to their brand strategy and positioning by tracking the evolution of culture. We use cultural insight to understand how the world is changing and pull out the patterns of change that are going to be important for a brand in the future.
DRIE Central Luncheon, June 2011
Presenter: Michael Dudley, Research Associate, Institute of Urban Studies, University of Winnipeg
How many recent natural disasters that have befallen
metropolitan areas in the past several years (forest fires, floods and earthquakes) aren't so much "natural" but are instead the result of (or
exacerbated by) poor planning decisions in the past, such as building on flood plains and other vulnerable locations, but that our "psychology of
previous investment" prevents us from altering our building patterns? As well, our rigid, centralized "big pipes" approach to city building,
infrastructure and commodities makes our cities vulnerable to shocks and
system breakdowns, such as those associated with energy prices and availability. The presentation will argue for the incorporation of resilience principles in urban planning, which in many ways will mean a return to historical practices and forms.
Multidrug Resistance Pattern of Staphylococcus Aureus Isolates in Maiduguri ...Scientific Review SR
Multi drug-resistant (MDR) isolates of Staphylococcus aureus are on rise and are becoming a
challenge for timely and appropriate treatment. The present study was carried out with an objective to isolate
Staphylococcus aureus from clinical samples and determine their sensitivity. Out of 110 samples collected, 44
were shown to contained S. aureus. The isolates were subjected to antibiotic sensitivity tests using 10 different
and commonly used antibiotics by modified Kirby- Bauer disc diffusion technique. Out of the total isolates (42)
tested, only 7.1% were susceptible to all the antibiotics. Multiple resistance was eminent in over 92% with
highest occurrence in 4.8% where the entire antibiotics were resisted. Multiple antibiotic resistance indixes
(MAR index) indicated that 0.6 index occurred most (23.8%) followed by 0.5 (19.0%). On the other hand, 0.1
and 0.8 indexes were the lowest with 0.0% and 1.0% occurrence respectively. Ciprofloxacin was resisted by
most of the organisms (64.3%) while amoxicillin (64.3%) and streptomycin (61.9%) were most efficacious. With
over 90% isolate having MAR index ≥ 0.2, the multiple drug resistance by the S. aureus is quite alarming and
might suggest inappropriate antibiotic usage by the sampled population. Therefore, the need to strategize the
nature of antibiotic treatment against S. aureus and massive campaign on indiscriminate antibiotic use is urgent.
Multidrug Resistance Pattern of Staphylococcus Aureus Isolates in Maiduguri M...Scientific Review
Multi drug-resistant (MDR) isolates of Staphylococcus aureus are on rise and are becoming a challenge for timely and appropriate treatment. The present study was carried out with an objective to isolate Staphylococcus aureus from clinical samples and determine their sensitivity. Out of 110 samples collected, 44 were shown to contained S. aureus. The isolates were subjected to antibiotic sensitivity tests using 10 different and commonly used antibiotics by modified Kirby- Bauer disc diffusion technique. Out of the total isolates (42) tested, only 7.1% were susceptible to all the antibiotics. Multiple resistance was eminent in over 92% with highest occurrence in 4.8% where the entire antibiotics were resisted. Multiple antibiotic resistance indixes (MAR index) indicated that 0.6 index occurred most (23.8%) followed by 0.5 (19.0%). On the other hand, 0.1 and 0.8 indexes were the lowest with 0.0% and 1.0% occurrence respectively. Ciprofloxacin was resisted by most of the organisms (64.3%) while amoxicillin (64.3%) and streptomycin (61.9%) were most efficacious. With over 90% isolate having MAR index ≥ 0.2, the multiple drug resistance by the S. aureus is quite alarming and might suggest inappropriate antibiotic usage by the sampled population. Therefore, the need to strategize the nature of antibiotic treatment against S. aureus and massive campaign on indiscriminate antibiotic use is urgent.
Disinfectants play an important role in health careassociated
infection control by either minimizing or preventing
microorganism dissemination. This article to study the
morphological changes which may be related to the lose of
antibiotic resistance after disinfectant exposure using SEM.
Showed all isolates resistant to ampicillin, amoxicillin, cloxacillin,
cephalexin, tetracycline, doxycycline, rifampin, chloramphenicol,
trimethoprim cefotaxime and erythromycin, while one of burn
isolates was susceptible for gentamicin, chloramphenicol and
trimethoprim, and 15 of burn, 6 of wound, 5 of ear, and all urine
isolates were susceptible to gentamicin using Kirby-Bauer
method.
The MICs of four common in use disinfectants (Hexatane,
Dettol, Savlon and Povidone – Iodine) were determined for all
isolates. The results showed that the MICs of Hexatane ranged
from (64–512) µg/ml, Dettol (2048–16384) µg/ml,
Savlon (4096:40960)–(32768:327680) µg/ml and for Povidone –
Iodine MICs were (8192–32768) µg/ml. It has been found that
burn and urine isolates were more resistant to disinfectants than
wound and ear isolates. According to the effect of subMICs of
disinfectants at different exposure patterns on antibiotic
resistance, the results showed lose of resistance to tetracycline,
doxycycline, rifampin, chloramphenicol, cefotaxime and
trimethoprim in %72, %72, %68, %22, %28 and %36 of isolates,
respectively. The results of SEM micrograph showed normal
morphology and small sized bacteria with nub formation on some
of them when exposed to dettol, and shape changes in cells with
bulging in exposed to Povidone-iodine, while elongation and
deformation were recorded in some cells in exposed to
Savlon(chlorohexidine/ cetrimide) and Hexatane (chlorohexidine/
gluconate), respectively.
Comparision of in vitro antibacterial activity of cefoperazone and levofloxac...pharmaindexing
Cefoperazone (a third generation cephalosporin) has effective in vitro activity against majority of pathogens. Levofloxacin (a flouroquinolone) is one which prescribed more due to its increased antibacterial activity against Gram-positive, Gram-negative, and atypical bacteria. Microbial resistance to antibiotics is now prevalent and poses a serious clinical threat. An attempt has been made to evaluate sensitivity of Cefoperazone and Levofloxacin against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi. A total of 120 isolates were collected from different pathological laboratories and medical centers in Karachi, Pakistan. The above stated clinical isolates were extracted from urine/stool, skin, blood and sputum samples. Results show least resistance of Levofloxacin as compare to Cefoperazone against Escherichia coli (32.5% and 42.5%) and Pseudomonas aeruginosa (36% and 48%) while Staphylococcus aureus is still susceptible towards Cefoperazone and least sensitive to Levofloxacin by showing 26.6% and 50% resistance respectively. Study concluded that the prevalent pathogens are still susceptible towards Levofloxacin and Cefoperazone but the gradual increase in resistance is alarming to the general practice of prescribing antibiotic which require routine evaluation and surveillance to ensure the effectiveness of the antibacterial agents.
Synergism Between Calcineurin Inhibitor (FK506) & Azole Antifungals – an appr...Tanya Hasija
Synergism Between Calcineurin Inhibitor (FK506) & Azole Antifungals – an approach to Combination Therapy to overcome Azole Resistance in C. albicans, C. krusei, & C. glabrata – Emerging Nosocomial Threats to the Immunocompromised.
Un estudio sobre las caracteristicas del tratamiento sde la TB XDR en sudafrica y el pronostico de vida de los pacientes segun las estrategias terapeuticas
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
2. Yeasts
Isavuconazole appears to be active against all Candida species
(Table 1). In general, isavuconazole activity against most
Candida species is comparable to that of voriconazole and
posaconazole [2–4]. The minimum inhibitory concentration
(MIC) values for 90% (MIC90) of almost 3000 unique Candida
isolates collected from 2011 and 2012 by the global SENTRY
Antimicrobial Surveillance Program were ≤1 µg/mL for all
Candida species, with the exception of C. glabrata [3, 4]. For
most Candida species, the MIC90 values were ≤0.12 µg/mL;
the MIC90 for C. krusei and C. guilliermondii was 1 µg/mL,
and for C. glabrata, 2 µg/mL. Isavuconazole MIC values for
those isolates of C. glabrata that were resistant to fluconazole
and/or voriconazole ranged from 1 µg/mL to ≥8 µg/mL [4]. It
appears that for C. glabrata especially, isavuconazole is similar
to other azoles in regard to the development of resistance.
Isavuconazole shows in vitro activity against Cryptococcus
neoformans and Cryptococcus gattii; most isolates are suscepti-
ble to <0.25 µg/mL [5, 7]. Low MIC values against less common
yeasts, including Trichosporon species, Geotrichum capitatum,
Saccharomyces cerevisiae, Rhodotorula species, and Pichia
species have been reported [3, 6, 8] (Table 1).
Molds
Isavuconazole appears to have potent in vitro activity against
the most common Aspergillus species, A. fumigatus and
A. flavus [2, 3, 9–12] (Table 2). The MIC90 for these Aspergillus
species was 1 µg/mL. Higher MIC values have been observed
with A. niger (MIC90 2 µg/mL) [3, 10–12]. In one study, isavu-
conazole retained activity against preselected A. fumigatus iso-
lates that were resistant to other azoles [9], but cross-resistance
was shown in another study of azole-resistant isolates [12].These
resistant isolates were shown to have mutations of the CYP51
gene, leading to azole cross-resistance, an emerging problem
mostly in Europe, but also described in India [12, 15, 16].
The spectrum of activity of isavuconazole includes some
other hyaline molds, such as Paecilomyces lilacinus and Scedo-
sporium apiospermum, but the drug has limited in vitro activity
against Fusarium species [2, 11]. Scedosporium prolificans ap-
pears to be resistant to isavuconazole, as it is to most antifungal
agents [11]. Dematiaceous molds, including Bioplaris spicifera,
Alternaria species, Curvularia lunata, and Exophiala species,
have MICs that vary from 0.25 µg/mL to 16 µg/mL to isavuco-
nazole [13, 17, 18] (Table 3). MIC90 values for most pigmented
molds range from 1 µg/mL to 4 µg/mL. Additionally, isavuco-
nazole has activity against many dermatophytes [19].
Genera in the family Mucoraceae (order Mucorales) are
resistant to most azoles, with the exception of posaconazole.
In vitro studies with isavuconazole show that this drug is
active against many genera of Mucoraceae [10, 11, 13, 14]
(Table 2). However, the MICs vary widely within a given genera.
For example, some isolates in the genus Rhizopus have MIC
Table 1. In Vitro Susceptibilities of Isavuconazole Against Candida Species, Cryptococcus Species, and Less Common Yeasts
Organism No. MIC50, µg/mL MIC90, µg/mL MIC Range, µg/mL Reference
Candida spp
C. albicans 1249 0.015 0.03 ≤0.008–1 [3, 4]
C. glabrata 557 0.5 2 0.015–8 [3, 4]
C. parapsilosis 498 0.06 0.12 ≤0.008–1 [3, 4]
C. tropicalis 252 0.06 0.12 ≤0.008–4 [3, 4]
C. krusei 77 0.5 1 0.06–2 [3, 4]
C. lusitaniae 52 0.03 0.06 ≤0.008–0.12 [3, 4]
C. dubliniensis 35 0.015 0.03 ≤0.008–0.06 [3, 4]
C. kefyr 29 0.015 0.03 ≤0.008–0.03 [3, 4]
C. guilliermondii 22 0.5 1 0.12–4 [3, 4]
Cryptococcus spp
C. neoformans 1308 0.03 0.06 <0.008–0.5 [5]
C. gattii 406 0.03 0.12 <0.008–0.5 [5]
Uncommon yeasts
Trichosporon asahii 40 0.12 0.12 0.03–0.25 [6]
Trichosporon mucoides 10 0.06 0.25 0.03–0.25 [6]
Trichosporon inkin 4 . . . . . . 0.03–0.12 [6]
Geotrichum capitatum 7 . . . . . . 0.03–0.5 [6]
Saccharomyces cerevisiae 20 0.06 0.25 0.03–1 [6]
Rhodotorula spp 14 0.03 0.03 0.03–0.12 [6]
Pichia spp 11 0.03 0.03 0.03–0.25 [6]
Abbreviation: MIC, minimum inhibitory concentration.
REVIEWS OF ANTI-INFECTIVE AGENTS • CID 2015:61 (15 November) • 1559
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3. values as low as 0.12 µg/mL, but others have MIC values as high
as 32 µg/mL.
Dimorphic Fungi
The MICs of isavuconazole for Histoplasma capsulatum and
Coccidioides species range from 0.12 µg/mL to 2 µg/mL [13]
(Table 3). Only 6 isolates of Blastomyces dermatitidis have
been studied, and MIC values ranged from 0.5 µg/mL to 4 µg/
mL. MICs against a small number of isolates of Sporothrix spe-
cies were reported to be high for isavuconazole and similar to
those noted with voriconazole [2].
PHARMACOLOGY
Isavuconazonium sulfate, the prodrug of isavuconazole, is avail-
able in both intravenous and oral formulations. The dosage
strength of 372 mg isavuconazonium sulfate corresponds to
200 mg of isavuconazole, the active component, in both formu-
lations. The capsules each contain 186 mg isavuconazonium
sulfate (100 mg isavuconazole). The recommended dosing reg-
imen for both oral and intravenous formulations is a loading
dose of 600 mg, given as 200 mg every 8 hours, for 2 days fol-
lowed by 200 mg daily thereafter [20].
Unlike voriconazole and posaconazole, the prodrug, isavuco-
nazonium sulfate, is highly water soluble, and therefore the in-
travenous formulation does not require solubilization by a
cyclodextrin vehicle. This is an advantage as this eliminates
the concerns of nephrotoxicity from the cyclodextrin vehicle,
which is used in the intravenous formulations of voriconazole
and posaconazole [21].
After intravenous infusion, the prodrug is broken down
quickly to the active component, isavuconazole, and an inactive
cleavage product. In healthy adults, plasma concentrations of
the prodrug and the inactive cleavage product are detectable
only during the intravenous infusion and are not detectable
30 minutes later. Following oral administration, plasma concen-
trations of the active compound reach maximum concentra-
tions (Cmax) by 2–3 hours; the prodrug and cleavage product
are not measurable in plasma after oral administration.
In healthy adult volunteers, isavuconazole exhibits linear and
dose-proportional pharmacokinetics. The oral bioavailability of
isavuconazole is 98% [22, 23]. Absorption of isavuconazole is
not affected by food intake. In addition to excellent bioavailabil-
ity, isavuconazole serum concentrations show low intersubject
variability. In healthy volunteers, the Cmax at steady state was
2.5 ± 1.0 µg/mL [23]. In a small number of patients with acute
myeloid leukemia and neutropenia, similar pharmacokinetic
profiles for intravenous isavuconazole were found [24].
Isavuconazole has a large volume of distribution, is >99%
protein bound, and has a long terminal half-life of 100–130
hours [22, 23]. Consistent with this long terminal elimination
half-life, tissue levels persist long after plasma levels become un-
detectable [25]. The route of elimination in humans has not
been established, but animal studies have shown that excretion
occurs primarily via feces. Urine elimination of isavuconazole is
negligible, and thus this agent is unlikely to be useful for the
treatment of urinary tract infections.
Table 2. In Vitro Susceptibilities of Isavuconazole Against Hyaline Molds and Mucorales
Organism No. MIC50, µg/mL MIC90, µg/mL MIC Range, µg/mL Reference
Aspergillus spp
A. fumigatus 855 0.5 1 0.06–≥8 [12]
A. flavus 444 0.5 1 0.12–4 [12]
A. nidulans 106 0.125 1 0.06–1 [12]
A. niger 207 1 2 0.06–≥8 [12]
A. versicolor 75 0.25 0.5 0.03–≥8 [12]
A. terreus 384 0.25 0.5 0.06–2 [12]
Fusarium spp 50 16 >16 1–>16 [11, 13]
Paecilomyces lilacinus 22 1 2 0.2–2 [13]
Scedosporium apiospermum 44 2 4 0.5–8 [11, 13]
Scedosporium prolificans 6 . . . . . . >16 [11]
Mucorales
Absidia spp 80 1 8 0.03–16 [14]
Cunninghamella spp 18 2 16 0.12–16 [14]
Mucor spp 79 4 16 <0.015–>128 [14, 15]
Rhizomucor spp 29 2 16 0.015–64 [14]
Rhizopus spp 199 1 4 0.12–32 [14, 15]
Abbreviation: MIC, minimum inhibitory concentration.
1560 • CID 2015:61 (15 November) • Miceli and Kauffman
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4. Metabolism of isavuconazole takes place in the liver via the
CYP enzyme family, specifically CYP3A4 and CYP3A5 isoen-
zymes. The metabolites do not have antifungal activity. Data
suggest that patients with liver disease have higher exposure
to isavuconazole. The clearance of isavuconazole in patients
with mild to moderate hepatic impairment (Child-Pugh class
A and B) is impaired [26], but no dosage adjustment is recom-
mended for these patients. There are no data for patients who
have Child-Pugh class C liver disease.
Area under the curve (AUC) values and Cmax are not sig-
nificantly affected in patients with renal impairment; no dose
adjustment is necessary in this patient group [20]. Isavucona-
zole is likely not dialyzable by either hemodialysis or continuous
hemofiltration; however, no pharmacokinetic studies have been
reported in patients undergoing renal replacement therapy.
Similar to observations with voriconazole, the metabolism of
isavuconazole may be affected by race. Compared with healthy
white subjects, Chinese subjects were found to have a lower clear-
ance of isavuconazole (2.6 L/h vs 1.6 L/h, respectively) and a 50%
higher AUC [21]. However, at this point, no dosage adjustment
has been recommended based on race. Age and sex minimally
affect the pharmacokinetics of isavuconazole. No pharmacoki-
netic studies of isavuconazole have been reported in children.
Isavuconazole is considered a pregnancy class C drug and
should not be given to pregnant women. Because the drug
was found in breast milk of lactating rats, it should not be
used in women who are breastfeeding.
DRUG–DRUG INTERACTIONS
Isavuconazole is a substrate for CYP3A4, so inhibitors of this
enzyme lead to increased levels of isavuconazole and should
be used with caution (Table 4).
Potent inducers of CYP3A4, such as rifampin, carbamaz-
epine, and long-acting barbiturates, significantly decrease
isavuconazole serum levels and should not be used with this
antifungal [21].
Isavuconazole is a moderate inhibitor of CYP3A4 and inhib-
its to a variable extent the metabolism of sirolimus, tacrolimus,
and cyclosporine, which can lead to higher levels of these drugs.
Serum levels need to be monitored if these drugs are given with
isavuconazole. The effects on other CYP3A4 substrates, such as
midazolam and atorvastatin, appear to be mild and dosage
Table 3. In Vitro Activity of Isavuconazole Against Dematiaceous Molds and Dimorphic Fungi
Organism No. MIC50, µg/mL MIC90, µg/mL MIC Range, µg/mL Reference
Dematiaceous molds
Exophiala spp 106 2 4 0.25–16 [18]
Alternaria alternata 30 1 1 0.5–2 [13]
Alternaria infectoria 50 4 4 2–4 [17]
Bipolaris spicifera 30 2 4 0.5–4 [13]
Curvularia lunata 24 2 4 1–4 [13]
Dimorphic fungi
Blastomyces dermatitidis 6 . . . . . . 0.5–4 [13]
Histoplasma capsulatum 28 0.5 2 0.12–2 [13]
Coccidioides posadasii 30 0.25 0.5 0.12–1 [13]
Abbreviation: MIC, minimum inhibitory concentration.
Table 4. Drug–Drug Interactions With Isavuconazole
Type of Interaction, Drug Recommendation
Increases isavuconazole level
Lopinavir/ritonavir Use with caution
Decreases isavuconazole level
Rifampin Contraindicated
Carbamazepine
Long-acting barbiturates
St John’s wort
Levels increased by isavuconazole
Sirolimus Use with caution. Monitor
serum levels of these drugs
and adjust dose when given
with isavuconazole
Tacrolimus
Cyclosporine
Mycophenolate mofetil
Digoxin
Colchicine Use with caution. May require
dose adjustmentDagibatran
Atorvastatin No dose adjustment
recommended when given
with isavuconazole; monitor
patient
Midazolam
Levels decreased by isavuconazole
Bupropion Use with caution. Dose increase
of bupropion may be
necessary.
Lopinavir/ritonavir Use with caution
Source: Adapted from [21].
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5. adjustment is not recommended [27]. However, patients should
be monitored for adverse effects if these drugs are used concom-
itantly with isavuconazole.
Isavuconazole has a minimal effect on CYP2C9 and
CYP2C19, and thus can be used with warfarin and omeprazole
without dosage adjustment of these drugs [28]. Isavuconazole is
a weak inhibitor of P-glycoprotein, and if given with digoxin
may lead to higher serum digoxin levels [21]. Overall, when
compared with voriconazole and posaconazole, isavuconazole
seems to have fewer drug–drug interactions.
SIDE EFFECTS
Isavuconazole appears to be relatively safe and well tolerated.
The most common side effects reported are gastrointestinal, in-
cluding nausea, vomiting, and diarrhea, but these rarely have
led to discontinuation of the drug [23, 29–31] (Table 5).
Other common side effects reported to be associated with isa-
vuconazole in <15% of volunteers and patients include head-
ache, rash, and peripheral edema [23, 29–31]. Commonly
noted side effects with voriconazole, such as visual disturbances,
hallucinations, and photosensitivity, have not been described
with isavuconazole.
Elevations in hepatic enzyme levels can occur with isavuco-
nazole therapy, as with other azoles. The usual pattern is
elevation of alanine aminotransferase and aspartate amino-
transferase, but elevations in alkaline phosphatase levels also
have been noted. There are reports of a few patients who
had severe hepatotoxicity, but whether this was caused solely
by isavuconazole or was related to other underlying illness is
not clear [20]. Liver enzymes should be monitored in patients
taking isavuconazole, as is recommended for all other azole
drugs.
Differing from other triazoles that cause QTc segment
prolongation, isavuconazole has been noted to cause dose-
dependent QTc shortening by as much as 13 msec with 200 mg
daily and 24.6 msec with 600 mg daily in healthy volunteers
[20]. Among 257 patients treated with isavuconazole in a clini-
cal trial of invasive mold infections, 17 (7.5%) had QTc short-
ening >60 msec from baseline [21]. At this point, the clinical
significance of QTc shortening is unclear, except for patients
who have the rare disease familial short QT syndrome, who
should not receive isavuconazole.
Infusion reactions that include acute respiratory distress,
chills, dyspnea, and hypotension have been noted in a few pa-
tients [21].Whether these reactions are related to particulates in
the intravenous formulation, which are composed of isavucona-
zole that has been cleaved from the prodrug while being infused,
is not clear [21]. It is recommended that an in-line filter (0.2–
1.2 µm) be used for the infusion of isavuconazole [20].
CLINICAL USES
Aspergillosis
Isavuconazole has been approved for the treatment of invasive
aspergillosis based on the results of a randomized, double-blind,
noninferiority clinical trial that compared isavuconazole with
voriconazole for primary treatment of invasive aspergillosis
and other invasive mold infections [21, 32–34]. A total of 516
adult patients with proven, probable, or possible invasive fungal
disease, as defined by European Organization for Research and
Treatment of Cancer/Mycoses Study Group (EORTC/MSG)
criteria [35], were randomized 1:1 to receive isavuconazole or
voriconazole. The primary endpoint of the study was all-cause
mortality at day 42 for this entire population.
The analysis of efficacy for treating invasive aspergillosis fo-
cused on the subset of 272 patients who had proven (65 patients)
or probable (207 patients) invasive fungal infection [21]. Prob-
able infection was based on a positive galactomannan assay in
half of the patients in both treatment arms. Efficacy was defined
as success at the end of treatment by EORTC/MSG criteria [36]
and was adjudicated by a blinded data review committee.
It should be noted that the actual number of patients who had
proven or probable aspergillosis was 231; the other 41 patients
included in the analysis of efficacy at the end of treatment had
other invasive mold infections. Of the 231 patients who had in-
vasive aspergillosis, 123 received isavuconazole and 108 re-
ceived voriconazole, and 16% had proven infection and 84%
had probable infection.
Hematological malignancies were the most common under-
lying condition (84%); 65% were neutropenic and 20% had re-
ceived an allogeneic hematopoietic cell transplant. The median
Table 5. Adverse Effects Associated With Isavuconazole
Most frequent side effects or other abnormalities
Gastrointestinal
Nausea
Vomiting
Diarrhea
Headache
Rash
Elevation of liver enzymes
QTc shortening
Less common side effects or other abnormalities
Peripheral edema
Hypokalemia
Infusion reactions
Acute respiratory distress
Chills
Dyspnea
Hypotension
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6. duration of intravenous therapy was 5 days in both arms, and
the total duration of antifungal treatment was 45 and 46.5
days for isavuconazole and voriconazole, respectively.
Day 42 all-cause mortality for all patients who received study
drug did not differ significantly (18.6% for the isavuconazole
arm and 20.2% for the voriconazole arm). Similarly, the overall
success (complete and partial response) at the end of treatment
was not different (35% and 36.4% for the isavuconazole and
voriconazole arms, respectively). For the 231 patients who
had proven or probable invasive aspergillosis, both the 42-day
mortality (18.7% and 22.2%) and success at the end of treat-
ment (35% vs 38.9%) were not different between the isavucona-
zole and voriconazole arms, respectively.
Mucormycosis
The data on which the approval for the treatment of invasive
mucormycosis is based are not as strong as those for aspergillo-
sis. In large measure this is because of the rarity of mucormy-
cosis and resultant inability to enroll enough cases into a
randomized controlled treatment trial. The study that was
used for licensing was an open-label, noncomparative trial
that evaluated isavuconazole for treatment of invasive aspergil-
losis in patients with renal impairment and for treatment of in-
vasive fungal infections caused by rare molds, including
members of the order Mucorales [21, 30]. This study allowed
both primary treatment of invasive mold infections and salvage
treatment of patients who were intolerant of or failing prior an-
tifungal therapy. Of 149 patients enrolled in this study, 37 had
proven (86%) or probable (14%) invasive mucormycosis by
EORCT/MSG criteria [35]. Twenty-one of the 37 had not re-
ceived prior antifungal therapy, 11 had refractory disease, and
5 were intolerant of prior therapy. A hematologic malignancy
was present in 59%; 35% had received a hematopoietic cell
transplant, and 27% were neutropenic. Diabetes was a risk fac-
tor in only 4 patients. Pulmonary involvement was present in 22
patients (59%), and half of those patients also had another site of
infection, mainly sinus, ocular, and central nervous system. The
median duration of treatment was 84 days (range, 2–882 days).
The endpoints of this study were all-cause mortality at day 42
and overall response at day 42 as assessed by an independent
data review committee. The mortality at day 42 was 38%;
mortality was higher among patients who had refractory disease
or were intolerant of prior therapy (43.7%) compared with
those who were treated for primary mucormycosis (33.3%).
The overall response rate at day 42, as judged by the data review
committee, was 31.4%.
A matched case-control analysis was performed comparing
the 21 patients who had primary treatment with isavuconazole
with the cases of 33 patients who were treated with ampho-
tericin B and whose data had been entered into the global
Fungiscope Registry, an ongoing observational database.
Matching was done by severity of infection, hematologic malig-
nancy, and whether surgical debridement was performed. In
this analysis, isavuconazole-treated and amphotericin B–treated
patients had similar mortality (33.3% vs 41.3%, respectively).
These mortality rates are consistent with historical data showing
mortality rates of 35%–45% in patients who were treated with
amphotericin B [37, 38] and in those who were entered into
several posaconazole salvage studies [39, 40].
Other Fungal Infections
The data on the role of isavuconazole for the treatment of pa-
tients with invasive mold infection caused by Fusarium and Sce-
dosporium species are limited to 9 and 3 patients, respectively
[41]. Only 3 patients with fusariosis and 1 with scedosporiosis
had a complete or partial response at the end of therapy [41].
Twenty-nine patients with endemic mycoses—paracoccidioi-
domycosis (10), coccidioidomycosis (9), histoplasmosis (7), and
blastomycosis (3)—were entered into the rare molds treatment
trial [31]. Disseminated infection was present in 70% and 57%
of patients with paracoccidioidomycoses and histoplasmosis,
respectively. Successful response at the end of therapy was
64%, but 3 patients died from progression of disease (2 with
paracoccidioidomycosis and 1 with blastomycosis). These data
suggest that isavuconazole could be an alternative for the treat-
ment of dimorphic fungi infections, but the number of patients
treated is too small to recommend the use of this agent at this
time.
A phase 2, randomized, double-blind, multicenter trial that
evaluated 3 dosing regimens of isavuconazole compared with
fluconazole in 160 immunocompromised patients with esoph-
ageal candidiasis noted an overall 96% clinical and microbiolog-
ical success rate [29]. However, given the efficacy of fluconazole,
it seems unlikely that isavuconazole will assume a major role in
the treatment of mucosal candidiasis.
SUMMARY
Isavuconazole has been approved by the FDA for the treatment
of invasive aspergillosis and mucormycosis. Advantages of this
triazole are the availability of a water-soluble intravenous for-
mulation, excellent bioavailability of the oral formulation, pre-
dictable pharmacokinetics, and, to date, few adverse effects.
However, clinical experience is limited for the treatment of in-
vasive fungal infections when compared with voriconazole and
posaconazole. Voriconazole remains the drug of choice for the
treatment of invasive aspergillosis, but isavuconazole could be
considered an attractive alternative for patients who cannot
tolerate voriconazole. Lipid formulations of amphotericin B
remain the treatment of choice for mucormycosis. Posaconazole
is typically used for step-down therapy and for those patients
who cannot tolerate amphotericin B. Isavuconazole is an
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7. acceptable alternative to posaconazole in those patients. The
role of isavuconazole in treating endemic mycoses and other
fungal infections should be clarified by further studies.
Note
Potential conflict of interest. Both authors: No reported conflicts.
Both authors have submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest. Conflicts that the editors consider relevant to the con-
tent of the manuscript have been disclosed.
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