This document discusses antifungal therapies for fungal infections in organ transplant recipients. It provides classifications of fungal infections and notes that invasive fungal infections are a significant problem for transplant patients due to immunosuppression. It reviews common fungal pathogens like Candida and Aspergillus species. It also discusses various antifungal drug classes including azoles, echinocandins like caspofungin, micafungin and anidulafungin, and provides details on their mechanisms of action, dosing, efficacy and safety profiles in transplant patients.
Viral hepatitis is the leading cause of liver cancer and the most common reason for liver transplantation
In the United States, an estimated 1.2 million Americans are living with chronic Hepatitis B and 3.2 are living with chronic Hepatitis C
Many do not know they are infected
Each year an estimated 21,000 persons become infected with Hepatitis A; 35,000 with Hepatitis B, and 17,000 with Hepatitis C
Hepatitis A – fecal/oral, contaminated food, vaccine available
Hepatitis B – blood, semen, vertical (mother-child), vaccine available
Hepatitis C – blood (IV drug use, transfusion, organ donation, unsterile injecting equipment, sexual intercourse)
Hepatitis D – survives only in cells co-infected with hepatitis B
Hepatitis E* – contaminated food or water, fecal/oral
*causes short-term disease and is not a chronic carrier state
A detailed discussion and description on fungal diseases and management. The focus is kept on those facts which frequently come across an intensivist but it is also important for the Internist.
Viral hepatitis is the leading cause of liver cancer and the most common reason for liver transplantation
In the United States, an estimated 1.2 million Americans are living with chronic Hepatitis B and 3.2 are living with chronic Hepatitis C
Many do not know they are infected
Each year an estimated 21,000 persons become infected with Hepatitis A; 35,000 with Hepatitis B, and 17,000 with Hepatitis C
Hepatitis A – fecal/oral, contaminated food, vaccine available
Hepatitis B – blood, semen, vertical (mother-child), vaccine available
Hepatitis C – blood (IV drug use, transfusion, organ donation, unsterile injecting equipment, sexual intercourse)
Hepatitis D – survives only in cells co-infected with hepatitis B
Hepatitis E* – contaminated food or water, fecal/oral
*causes short-term disease and is not a chronic carrier state
A detailed discussion and description on fungal diseases and management. The focus is kept on those facts which frequently come across an intensivist but it is also important for the Internist.
Fungal infections can occur due to the increasing use of broad-spectrum antibiotics and patients with immunodeficiency. Some pathogens, such as Cryptococcus, Candida,and Fusarium, rarely cause serious diseases in the normal host, while other endemic fungi, such as Histoplasmosis, Coccidiodes,and Paracoccidiodes can cause disease in a normal host, but has a tendency to be aggressive on immunocompromise.
Candida species are normal flora that may be an apportunistic pathogen. Candidiasis occurs in some diseases such as gastrointestinal mucosal esophagitis, a fungal disease associated with the use of catheters and in - patients who have mucosal damage or obtain broad – spectrum antibiotics. Other candidiasis consist of skin candidiasis, funguria candidiasis, disseminated candidiasis and endocarditis candidiasis. Candidemia is the fourth most common cause of nosocomial bloodstream infections in the United States and in many of the developed country. Invasive candidiasis has a significant impact on patient outcomes, and it has been estimated that the mortality of invasive candidiasis is as high as 47%. The mortality rates are 15%-25% for adults and 10%-15% for neonates and children. Diagnostic approach to fungal infection is a priority. The knowledge of the changes in epidemiology and risk factors for fungal infections, has become the main reference to measure optimal treatment of fungal infections.
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.
Candida is the most common cause of fungal infection worldwide and 4th most common cause of blood stream infections in hospital setting.
Associated with 47 % mortality rate.
17 different species identified till yet.
Most common among them are C. albicans, C. glabrata, C. parapsilosis and C. tropicalis.
Candida usually develops on mucous membranes ( mouth , genitals etc).
Candida in blood stream it is known as candidemia.
When it passes from blood stream to other body parts(eyes, kidney, liver and brain etc) it is called invasive candidiasis.
detailed explanation and treatment plans for all types of fungal infections.
precaution and lifestyle modifications are explained.
well-detailed explanation of superficial and invasive types of fungal infections.
superficial infections like vulvovaginal candidiasis, oropharyngeal and esophageal candidiasis, and mycotic infections of the skin, hair, and nail.
invasive fungal infections like fungal infections in HIV patients, histoplasmosis, blastomycosis, coccidioidomycosis, cryptococcosis, candiduria, and aspergillosis.
explained with well-detailed treatment plan with patient counseling points
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.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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
2. CLASSIFICATION OF FUNGAL INFECTIONS
FUNGAL
INFECTIONS
SUPERFICIAL
INFECTIONS
On the surface of
the skin
CUTANEOUS
INFECTIONS
Dermatophytes
Ringworm infections
All Tinea sps
Candida sps
SUB CUTANEOUS
INFECTIONS
DEEP MYCOSAL
INFECTIONS
OR
SYSTEMIC
MYCOSAL
INFECTIONS
3. Invasive fungal infections
Invasive fungal infections are a significant
and often lethal problem in transplant
patients.
They are at risk for these infections as a
result of their general health status,
technical complications of surgery, and
immunosuppression.
4. FUNGAL INFECTIONS IN
TRANSPLANTATION
The incidence of invasive fungal infections in solid organ transplant
recipients varies according to the type of transplant.
Most of these infections are due to Candida spp., Aspergillus spp. or
Cryptococcus spp.
Currently, overall mortality due to invasive fungal infections in solid
organ transplant recipients ranges between 25%-80% and half of
these deaths are directly related to the fungal infection.
5.
6. CANDIDIASIS/ ASPERGILLOSIS
Candidiasis is the most common
invasive fungal infection in SOT
recipients and accounts for 50–60%
infections.
Candida species, particularly Candida
albicans, are frequent colonizers of
the human gastrointestinal,
respiratory and reproductive tracts,
and the skin.
7. CANDIDIASIS/ ASPERGILLOSIS
The majority of invasive candidiasis is
from an endogenous source – usually
the skin or gut.
Aspergillosis is the next most common
infection, accounting for 20–25% of
fungal infections.
In lung transplant recipients,
aspergillosis is the most common
infection
8. INVASIVE CANDIDA INFECTIONS
REPORTED IN VARIOUS TRANSPLANT
TYPESPrevalence,%
Liver Kidney Pancreas Lung Heart
42
17
38
8
12
*Numbers reflect data collected by TRANSNET from 2001 to 2004. Andes D, et al. ICAAC 2004. Abstract M-1014.
0
10
20
30
40
50
60
9. DISTRIBUTION OF FUNGAL PATHOGENS
CAUSING INVASIVE FUNGAL INFECTIONS IN
TRANSPLANT RECIPIENTS
Ther Adv Infect Dis (2013) 1(3) 85105
10. INCIDENCE OF INVASIVE FUNGAL
INFECTIONS
The Transplant-Associated Infection Surveillance Network conducted a 5-year
prospective study among 1,063 organ transplant recipients.
1028 were diagnosed with IFI.
The most common IFIs were:
Invasive candidiasis (53%),
Invasive aspergillosis (IA) (19%),
Cryptococcosis (8%),
Non-Aspergillus molds (8%),
Endemic fungi (5%), and
Zygomycosis (2%)
IA is a life-threatening complication in patients who undergo solid organ
transplantation, having an incidence between 0.5% and 2.2% with a mortality rate of
> 70% and a high case-fatality rate of up to 88%
11. INDIAN PROSPECTIVE
Recipients of solid organ transplants have 6–10% incidence of
opportunistic fungal infections with a very high mortality of
70–100% in the Indian subcontinent.
12. PATHOPHYSIOLOGY
Infection may be due to
reactivation of a previously
quiescent process such as
colonization or subclinical
infection, or from de
novo infection following
inhalation of fungi after
transplantation.
Donor-derived infections are
an increasingly recognized
mode of transmission .
Transplanted organs may act
as reservoirs for potentially
pathogenic fungi.
13. DIAGNOSIS OF FUNGAL INFECTIONS IN
RENAL TRANSPLANT RECIPIENTS
Fungal infections in renal transplant recipients are diagnosed on the
basis of:
Clinical and radiologic signs and symptoms that include:
Tissue invasion
Positive culture results from a deep tissue specimen such as
Blood
Cerebrospinal fluid
Peritoneal fluid, or a biopsy specimen
14. GOALS OF THERAPY IN TRANSPLANT
RECIPIENT
Prevention of fungal infections.
Individual risk assessment
Initiated early in patients with a suspected fungal infection.
Optimize the pharmacokinetics of antifungal drugs.
Assess for potential side effects.
16. ECHINOCANDINS
Newer antifungal agents that inhibit the fungal cell wall
synthesis
During fermentation process, some metabolites were found
to inhibit Candida sp., and they were named Echinocandins
The echinocandins have potent activity against Aspergillus
and most Candida species, including those species resistant
to azoles. However, they have minimal activity against other
fungi.
17. Caspofungin, micafungin, and anidulafungin are semisynthetic
echinocandin derivatives with clinical use due to their solubility,
antifungal spectrum, and pharmacokinetic properties.
All these preparations so far have low oral bioavailability, so
must be given intravenously only.
ECHINOCANDINS
18. MECHANISM OF
ACTION
Inhibits the synthesis of β 1,3 – D- glucan via noncompetitive inhibition of
the enzyme 1,3-β glucan synthase and are thus called "penicillin of
antifungals“ resulting in the inhibition of cell wall, leading to lysis and
death.
19. FUNGICIDAL AND
FUNGISTATIC ACTION
Echinocandins exhibit fungicidal activity against Candida species,
including triazole-resistant isolates, and fungistatic activity against
Aspergillus species.
20. PHARMACOKINETICS
Due to the large molecular weight of echinocandins, they have poor
oral bioavailability and are administered by intravenous infusion.
In addition, their large structures limit penetration into cerebrospinal
fluid, urine, and eyes.
In plasma, echinocandins have a high affinity to serum proteins.
Echinocandins do not have primary interactions with CYP450 or P-
glycoprotein pumps.
21. Caspofungin has triphasic nonlinear pharmacokinetics.
Micafungin and anidulafungin have linear elimination.
22. • Broad range (especially against all Candida), thus can be given
empirically in febrile neutropenia and stem cell transplant.
• Can be used in case of azole-resistant Candida or use as a second-
agent for refractory aspergillosis
• Long half-life
Not an inhibitor, inducer, or substrate of the cytochrome P450 system,
or P-glycoprotein, thus minimal drug interactions
No dose adjustment is necessary based on age, gender, race
ADVANTAGES OF
ECHINOCANDINS
26. INDICATIONS
Anidulafungin is indicated in adults for the treatment of:
Candidemia and other forms of Candida infections (intra-abdominal
abscess and peritonitis)
Esophageal candidiasis
27. DOSAGE IN CANDIDA
INFECTIONS
200 mg loading dose on Day 1,
followed by 100 mg daily dose
thereafter for at least 14 days
after the last positive culture
28. DOSAGE IN OES0PHAGEAL
CANDIDIASIS
100 mg loading dose on Day 1,
followed by 50 mg daily dose
thereafter for a minimum of 14
days and for at least 7 days
following resolution of
symptoms
The rate of infusion should not exceed 1.1 mg/minute [equivalent to 1.4 mL/minute or 84
mL/hour when reconstituted and diluted per instructions]
29. RECONSTITUTION
Anidulafungin for Injection must
be reconstituted with sterile Water
for Injection and subsequently
diluted only with 5% Dextrose
Injection, USP or 0.9% Sodium
Chloride Injection, USP (normal
saline).
30. HOW TO ADMINISTER
Dose No. of vials
required
Total
reconstituted
volume
required
Infusion
volume
Total
infusion
volume
Rate of
infusion
Minimum
duration
of
infusion
100
mg
1 30 ml 100 ml 130 ml 1.4 ml/min
or 84 ml/hr
90 min.
200
mg
2 60 ml 200 ml 260 ml 1.4 ml/min
or 84 ml/hr
180 min.
32. SUMMARY
Wider spectrum of action and lower toxicity than caspofungin.
Good in vitro antifungal activity against Candida and Aspergillus spp.
One of the most interesting features of anidulafungin in solid organ
transplant recipients is that this drug is not metabolized by or eliminated
through the kidney so that dosage adjustments are not required in these
patients, who frequently show renal function alterations.
33. SUMMARY
Moreover, anidulafungin is not metabolized in the liver and is consequently
free of interactions with other drugs metabolized in this organ.
Equally, dosage adjustments are not required in patients with severe liver
disease or in those administered immunosuppressive agents such as
prednisone, cyclosporine A, tacrolimus, mofetil mycophenolate or sirolimus.
Hence anidulafungin will be highly useful in the clinical management of
solid organ transplant recipients.
37. INDICATIONS
Micafungin is indicated for adults and paediatric patients of 4 months or
older for:
Treatment of Patients with Candidemia, Acute Disseminated
Candidiasis, Candida Peritonitis and Abscesses
Treatment of Patients with Esophageal Candidiasis
Prophylaxis of Candida Infections in Patients Undergoing
Hematopoietic Stem Cell Transplantation (HSCT)
38. ADVERSE EFFECTS
Most common adverse reactions include diarrhoea, nausea,
vomiting, pyrexia, thrombocytopenia, and headache.
Histamine-mediated symptoms including rash, pruritus, facial
swelling, and vasodilatation
The drug has no significant effect on renal function.
39. DOSAGE
Indication Dose
Adult Paediatrics 30 kg
or less
Paediatrics greater
than 30 kg
Candidemia, Acute
Disseminated Candidiasis,
Candida Peritonitis and
Abscesses
100 mg daily*
2 mg/kg/day
(maximum 100 mg daily)
Esophageal Candidiasis 150 mg daily 3 mg/kg/day 2.5 mg/kg/day
(maximum 150 mg
daily)
40. DOSAGE
Indication Dose
Adult Paediatrics 30 kg
or less
Paediatrics greater
than 30 kg
Prophylaxis of Candida
Infections in HSCT
Recipients
50 mg daily** 1 mg/kg/day
(maximum 50 mg daily)
*100 mg micafungin is equivalent to 101.73 mg micafungin sodium.
**50 mg micafungin is equivalent to 50.86 mg micafungin sodium
41. SPECIAL POPULATION
Micafungin is administered intravenously as a 1-h infusion
once daily.
Dose adjustments are not required for elderly persons or for
patients with renal dysfunction.
Likewise, mild to moderate hepatic impairment does not
warrant changes in dose.
42. SPECIAL POPULATION
Pregnancy - No human data. Adverse effects in animals. Use if
potential benefits of treatment outweigh potential fetal risk
Nursing Mothers - Caution should be exercised if administered to
a nursing woman
Safety and effectiveness in paediatric patients less than 4 months
of age have not been established
43. CONTRAINDICATION
Micacord is contraindicated
in persons with known
hypersensitivity to micafungin
sodium, any component of
micafungin, or other
echinocandins.
44.
45. Safe and effective agent for the treatment of
newly diagnosed and refractory cases of
candidemia.
46. GUIDELINES
RECOMMENDATIONS
Infectious Diseases
Society of America
(IDSA)
Candidemia in Non-neutropenic Patients
Micafungin: 100 mg daily is recommended as initial therapy for most adult
patients
Candidemia in Neutropenic Patients
Micafungin: 100 mg daily is recommended for most patients
Empirical Treatment for Suspected Invasive Candidiasis in
Non-neutropenic Patients
Micafungin (100 mg daily) is recommended as initial therapy
Stem cell transplant recipients with neutropenia,
Micafungin (50 mg daily) is recommended during the period of risk of
neutropenia
European Society of
Clinical Microbiology
and Infectious Disease
(ESCMID)
Micafungin
recommended in the treatment of candidaemia
recommended in neutropenic patients
recommended in the treatment of mucosal oropharyngeal or oesophageal
candidiasis
European Conference
on Infections in
Leukemia (ECIL)
Recommends micafungin as an alternative for empirical antifungal treatment in
febrile neutropenic patients
47. SUMMARY
US FDA approved since 2005
Fungicidal as well as fungistatic property
Effective in solid organ transplant recipients
Convenient dosing, no loading dose needed
Excellent safety profile
Recommended by IDSA, ESCMID and ECIL in the management of invasive
fungal infections.
Remarkably few drug interactions
48. SUMMARY
Equally effective as fluconazole for the treatment of esophageal candidiasis
Effective for the treatment of newly diagnosed or refractory candidemia
Better tolerated compared to Amphotericin B
Effective and safe antifungal drug in treating Invasive Aspergillosis
Equally Safe and Effective as Caspofungin
