Nosocomial

fungal

infections

Dr. ROUMI GHOSH

PG, 3rd Yr, MAMC,

New Delhi

What’s meant by Nosocomial infections orHealthcare-associated Infections ?

• Comes from 2 Greek words. “Nocos”= disease + “komeion” =take care of

• A localized or systemic condition 1) that results from adverse reaction in presence of an infectious agent(s) or its toxin(s) and 2) that was not present or incubating at the time of admission to the hospital or other health care facility.

• Infection are considered nosocomial if they first appear 48 hrs or more after hospital admission without proven prior incubation or within 30 days after discharge.

• This also includes occupational infections among staff of the facility and patient companions.

• Two special situations in which an infection is considered nosocomial:

(a) infection that is acquired in the hospital but does not become evident until after hospital discharge

(b) infection in a neonate that results from passage through the birth canal

• But infection transplacentally (e.g., toxoplasmosis, rubella, cytomegalovirus, or syphilis), becomes evident after birth not considered nosocomial.

• There are two conditions that are not infections:

1)Colonization, presence of microorganisms (on skin, mucous membranes, in open wounds, or in excretions or secretions) not causing adverse clinical signs or symptoms.

2)Inflammation, a condition that results from tissue response to injury or stimulation by noninfectious agents, such as chemicals.

Factors associated with rising trend of nosocomial infections:

• Crowded hospital conditions

• Increasing number of people with compromised immune systems

•New microorganisms

•Increasing bacterial resistance

Why do nosocomial infection occur?

Presence of microbes in hospital environment

Immunocompromisedpatients

Transmission between staff and patients and

among patients

Nosocomial infection

Five major routes of transmission

1. Contact: Direct (person-person)

Indirect (through an object)

2. Droplet

3. Airborne

4. Common vehicle

5. Vector borne

The same organism may be transmitted by more than one route

• Variety of fungi of medical importance were recovered from cockroaches (Blattella germanica) from hospital and residential area.

Cockroaches (Blattella germanica) as carriers of microorganisms of medical importance in hospitals. R. FOTEDAR', U. BANERJEE SHRINIWAS' AND A. VERMA2. Epidemiol. Infect. (1991)t 107, 181-187 181. All India Institute of Medical Sciences, New Dehli 110029, India

Types of infections

CAUTI35%

Surgical wound infection

19%

Central Line-associated

Bloodstream Infection (CLABSI)

15%

12%

others5%

Antibiotic associated diarrheaCatheter-associated Urinary Tract Infections (CAUTI)

Pneumonia14%

In general 5–10% of patients develop nosocomial infections.Magnifies several folds depending on high risk patient population

Fungal infections account for 9% of all nosocomialinfections.

Wider use of aggressive modalities of treatments

hematopoietic stem cell transplantation (HSCT)solid organ transplantation (SOT)new chemotherapeutic & broad spectrum

antimicrobial agents immunomodulatory agents

Increases immunocompromised patient population at risk for invasive fungal infection

Incidence of infections in health care facilities by moulds risen dramatically in recent years more in developing

countries.

Frequently identified risk factors for fungemia inhospitalized patients

• Antimicrobial agents: Number and Duration

• Adrenal corticosteroid

• Chemotherapy

• Hematological/solid organ malignancy

• Previous colonization

• Indwelling catheter

• Central venous catheter

• Pressure transducer/Swan-Ganz

• Total parenteral nutrition

• Neutropenia (polymorphonuclear cells,500/mm3)

• Extensive surgery or burns

• Assisted ventilation

• Hospitalization or intensive care unit stay

• Hemodialysis

• Malnutrition

• Hospitalization during construction activity

The majority of nosocomial fungal infections are caused by Candida spp. and Aspergillus spp.

EMERGING NOSOCOMIAL FUNGAL PATHOGENS

Yeasts Moulds

Hyalohyphomycosis

AspergillusMucormycotinaFusariumAcremoniumScedosproriumPseudallescheriaPaecilomyces

Phaeohyphomycosis

ExserohilumCladophialophoraCurvulariaAlternariaBipolarisChaetomium

CandidaTrichosporonRhodotorulaSaccharomycesMalasseziaPichiaGeotrichumCryptococcus

YEAST & YEAST LIKE FUNGI

Candida

Spectrum of diseases caused:

Catheter associated UTI (CAUTI)

Catheter related blood stream infection (CRBSI)

Antibiotic associated diarrhea

And other disseminated diseases: arthritis, osteomyelitis, endocarditis, endophthalmitis, meningitis.

• C. albicans is the mc cause of invasive fungal infections in hospital settings (50% - 70%)

• Emergence of non-albicans species due to selection pressure (overall 46%)

• Global Antifungal Surveillance Program-C. albicans most common (63–70%) C. glabrata (44%), C. tropicalis (6%), and C. parapsilosis (5%).

• Fluconazole resistance was noted in • C. krusei (78%)• C. glabrata (16%)• C. guilliermondii (11%)

Candida spp. causing nosocomial infectionsCandida species Affected patient population

C. tropicalis bone marrow transplantation hematologic malignancies

C. glabreta patients with solid tumors

C. parapsilosis Parenteral nutrition Post-op endophthalmitis by contaminated iol-irrigating Sol

C. krusei Hematologic malignancies, GranulocytopeniaHaving antifungal prophylaxis

OthersC. kefyrC. lusitaniaeC. guilliermondiiC. dubliniensisC. rugosaC. pelliculosaC. LipolyticaC. viswanathiiC. nivariensis

hematologic malignancies Catheter-related BSI

can be acquired from hospital gardens or potted plants

Reservoirs and Modes of Transmission

• Endogenous:

• major reservoir: g.i. tract

skin

• through a breakdown in mucosal or epithelial tissue colonized flora is the source of infection

• Strategies for prevention: decrease mucosal colonization

decreased use of broad-spectrum antimicrobials

• Exogenous:

• contaminated infusates,

• hands of health care workers

• indwelling catheter

• MC species isolated from hands of nurses was

C. parapsilosis

Reasons for Candida’s virulence

1. Versatility in adaptation to various different habitats, and formation of biofilms.

– C. albicans forms fungal biofilms most often,

– non-albicans Candida species also, specially

C. parapsilosis or C. tropicalis.

2. Secretion aspertyl proteinase (Sap): facilitate hyphal entry

3. Phenotypic switching: from budding yeast cells to hyphaeor pseudohyphae reduce phagocytosis

Fluconazole Voriconazole AMP-B Caspofungin

C glabrata Susceptible (dosedependent)to resistant

Susceptible (dose dependent)to resistant

Susceptible to intermediateSusceptibility

Susceptible*

C tropicalis Susceptible Susceptible Susceptible Susceptible*

C parapsilosis Susceptible Susceptible Susceptible Susceptible to resistant*

C krusei Resistant Susceptible (dose dependent)to resistant

Susceptible to intermediateSusceptibility

Susceptible

Candida kefyr Susceptible Susceptible Susceptible Susceptible*

C lusitaniae Susceptible Susceptible Resistant Susceptible*

C dubliniensis Susceptible (71%) to resistant

Susceptible(91%) Susceptible Susceptible

Candida rugosa Very low activity Low activity Susceptible Susceptible

C guilliermondii Low activity Susceptible Susceptible Susceptible

• C parapsilosis, C lipolytica, C lusitaniae, C glabrata and C tropicalis can cause breakthrough mycoses despite prophylactic or therapeutic use of echinocandins.

• Reports of reduced susceptibility or resistance in

– immunosuppression,

– recurrent candidaemia, and

– prolonged exposure to echinocandins.

• Resistance to amphotericin B appears to be the hallmark of C. lusitaniae

Drug-resistant fungi new hospital menaceFeb 4, 2013

• NEW DELHI: After the superbug, it might soon be the 'superfungi'. The organisms, known to be opportunistic pathogens causing infection in critically-ill patients, are fast turning drug-resistant.

• A study by microbiologists at Ganga Ram Hospital revealed several new species of fungi, become difficult to treat even with most potent antifungal medicine, such as amphotericin B.

• One particular species C. haemulonii, has also proved untreatable.

Catheter-associated UTI• 10-15% nosocomial UTI are due to Candida spp.

• Always in a diagnostic dilemma whether contamination, colonization or true infection

• No reliable methods of differentiating colonization or true UTI with Candida.

• Candida infection is more common during extreme of ages.

• Hematogenous spread is the most common route of renal candidiasis.

• Ascending infection follows catheterisation, introduce peri-urethral commensal and allow migration into bladder along surface.

• Risk of developing candemia following candiduria varies (2-50%).

• Risk factors:

urinary tract instrumentation.

(27% of all indwelling catheter associated UTI)

Use of antibiotics> suppress endogenous flora> colonization by candida

Previous surgical procudure

Diabetes mellitus> glycosuria> increase fungal growth

Predominant species isolated from our hospital:

C. tropicalis (46%), C. albicans (30%),C. kefyr, C. krusei, C. sphaerica.

In a recent study in GB Pant Hospital shows prevalence of 71.4% non-albicans Candida spp. causing UTI in ICU patients.

Mixed isolates found in 10% of patients.

Diagnosis:

Positive candida urine culture

colonizationConfirm by 2nd urine

sample

Check for pyuria

Absent

If colony count < 103

cfu/ml

Rule out Candida infection

Present

Candida infection

Localise anatomic site of infection

Asymptomatic candiduria Candida cystitis

Renal candidiasis

> 10⁵ CFU/ml+

Urine sample from asymptomatic pts without indwelling catheter

Urine sample from pts long-term indwelling or intermittent catheters

•Diagnosis of a UTI due to Candida species very difficult.

•Pyuria or quantitative urine cultures for UTI of little use.

Catheterisation

low-grade Inflammation

Presence of WBCs

As few as 10⁴ cfu/mL may mean infection 2x10⁴-10⁵ cfu/mL may mean only colonization

Many tried to co-relate with•presence of pseudohyphae•antibody-coated yeasts in the urine•casts containing yeasts

Diagnosis:

• Collection of second sample

• Second sample collection after changing catheter or by suprapubic aspiration

Helps to rule out contamination from perinealcolonization or asymptomatic adherence on catheter or foreign bodies

Bundled Interventions to Prevent Urinary Tract Infections• Place bladder catheters only

when absolutely needed, not solely for the provider's convenience.

• Use aseptic technique for catheter insertion and urinary tract instrumentation.

• Minimize manipulation or opening of drainage systems.

• Ask daily: Is the bladder catheter needed?

• Remove catheter if not needed.

Management:• Removal of catheter is strongly recommended as

soon as possible.

• Amphotericin B bladder irrigation highly effective for Candida cystitis

• Oral fluconazole, 200 to 400 mg/day for 14 days.

• In case of C. glabrata or C. krusei: Flucytocine shows excellent activity with high urinary concentration

• Echinocandins poor glomerular filtration, not very useful.

• High dose i.v. Ampho B or fluconazole recommended for pyelonephritis, but duration is not determined.

• Nephrostomy tube can be used to administer high dose of drugs locally.

Blood stream infection:• In developed countries Candida species are 4th

most common cause of BSI.

• A study from Maulana Azad Medical College, found an incidence rate of 6.9% for Candida species in BSI.

• Study from UCMS gave a prevalence rate of 18% for Candida species among blood culture isolates

• AIIMS, New Delhi, found a prevalence rate of 6% for Candida species in a 5-year study (2001-2005).

• C. albicans, most common species from BSI worldwide

• Among the non-albicans species, C. glabrata has emerged as an important opportunistic pathogen worldwide.

• It for 75% of cases of fungemia among patients receiving fluconazole as antifungal prophylaxis.

• In India, C. tropicalis is now the most common cause of nosocomial candidemia. (67-90%). Mainly among hematologic malignancies.

• C. parapsilosis found to be increasingly implicated in BSI after placement of intravascular devices and TPN infusion.

• Highest mortality was found among patients with C. krusei infection (52.9%)

• C. parapsilosis infection had the lowest mortality rate of 23.7%

Diagnosis:• Most reliable diagnostic method of CRBSI:

1. Semiquantitative (roll plate) >15 cfu

2. Quantitative or

(vortex or sonication methods)

catheter culture techniques > 10²cfu

+

• For rapid diagnosis: use of acridine orange stains

• Paired cultures of blood drawn through the iv catheter and percuteneous

1. CFU from CVS 5–10-fold greater

2. Positive culture form CVS at least 2 h earlier

signs of local or systemic infection

Bundled Interventions" to Prevent Common Health Care–Associated Infections

• Prevention of Central Venous Catheter Infections:

1) Educate personnel about catheter insertion and care.

2) Use chlorhexidine to prepare the insertion site.

3) Use maximal barrier precautions during catheter insertion.

4) Consolidate insertion supplies (e.g., in an insertion kit or cart).

5) Use a checklist to enhance adherence to the bundle.

6) Empower nurses to halt insertion if asepsis is breached.

7) Cleanse patients daily with chlorhexidine. 8) Ask daily: Is the catheter needed? Remove

catheter if not needed or used.

• New 2011 CDC guidelines has announced new guidelines to reduce the risk of catheter-associated infections.

• The guidelines now designate treatment with chlorhexidine gluconate-impregnated sponge

Prevention and Therapy• Removal of Central i.v. catheters in patients with

candidemia

• I. V. AmB or fluconazole, continued for 14 days after blood cultures have yielded no yeast

• Patients with candidemia and metastatic foci (eg, eye, bone, heart, liver, spleen) require a longer duration of therapy.

• Prophylactic fluconazole among selected leukemia or bone marrow transplant patients effective for all except C. krusei

• Posaconazole or echinocandins are preferred for the initial treatment if C. glabrata or C. krusei is identified or suspected

Antibiotic-associated diarrhea:

• Patients receiving longterm antimicrobial agents commonly develop a secretory non-bloody diarrhea

C. difficile toxin-negative

evidence of intestinal overgrowth of Candida spp.

• A study from our department reported yeast from 26.7% of nosocomial diarrhea cases.

• Respond to oral nystatin therapy

• Stoppage of persistent use of intravenous antimicrobial agents

Trichosporon species: T. asahii, T. mucoides, T. asteroides

• Most common non-candidal yeast infection in hematologic cancer patients with mortality >80%

Trichosporon species: T. asahii, T. mucoides, T. asteroides• Causes superficial infection of hair shafts, white piedra.

• Trichosporonosis (bloodstream infections, severe skin infections, endocarditis, peritonitis), becoming more common in hospitalized patients.

• Catheter related fungaemia, occur as a breakthrough invasive infection on antifungal therapy with high mortality.

• Endophthalmitis after cataract extraction, endocarditisfollowing prosthetic cardiac valves insertion also reported.

• Because of shared Ag with the capsule of Cryptococcus neoformans, a positive cryptococcal latex test can occur in patients with trichosporonosis.

• Abundant pseudohyphae,

• arthroconidia• Numerous spherical to oval budding

blastoconidia from both corner of arthroconidia

• “Rabbit ears” appearence

Fluconazole Voriconazole AMP-B Caspofungin Flucytosine

Trichosporonasahii

Low activity Susceptible Resistant Resistant Resistant

Trichosporonbeigelii(cutaneum)

Low activity Low activity Resistant Resistant Resistant

Anifungal sensitivity

•Clinical and in-vitro studies, suggest that azoles, especially voriconazole and posaconazole, have greatest effectiveness against Trichosporon. spp

Rhodotorula species: R. mucilaginosa

• In immunocompetent patients:

• Endophthalmitis

• Peritonitis (continuous ambulatory peritoneal dialysis)

• Overall mortality from rhodotorula fungaemia is 15%.

•Previously regarded as non-pathogenic.•Emerged as opportunistic pathogens•Most cases of rhodotorula infection are fungaemia associated with catheters, endocarditis, and Meningitis.

Fluconazole Voriconazole AMP-B flucytosine Caspofungin

Rhodotorulaspecies

Very low activity

Variable susceptibility/very low activity

Susceptible Susceptible Resistant

• Rhodotorula species, often resistant to fluconazole and voriconazole.

• Amphotericin is the antifungal agent of choice for treatment of rhodotorula infections.

Anifungal sensitivity

Malassezia species: M. furfur and M. pachydermatis• Causative agent of Pityriasis versicolor and seborrhoeic dermatitis

• Frequently observed as nosocomial pathogens in recent times.

• Causes invasive infections especially in NICU patients.

• Central line used for infusion of the lipid emulsion tend to grow M. furfur from LBW neonate and adult patients

Globose, oblong-ellipsoidal to cylindrical yeast cells with broad base budding from the same site at one pole (unipolar)

• Unable to synthesize long-chain fatty acids and requires exogenous lipid for growth

• Detection enhanced by growing the specimen on Sabouraud agar covered with a thin layer of sterile olive oil (lipophilic)

• Alternatively to use specialized media like Dixon's agar which contains glycerol mono-oleate

• Removal of the catheter and cessation of lipid infusion main stay of treatment

• Systemic antifungal treatment with ampho B, ketoconazole, itraconazole, voriconazole reserved for persistent infection

Pichia anomala (Hansenula anomala)

• P. anomala first reported as pathogen in nosocomialoutbreak among 379 neonates in Chandigarh (Chakrabarti et

al 2001)-

fungemia, interstitial lung disease, endocarditis, enteritis

• Fungaemia associated with a CVC is most common, mainly among neonates and ICUs.

• Later outbreak reported in paediatric ICU in Brazil in 2005

Saprophytes in environment, also found In milk, cheese, yoghurt

production of one to four hat-shaped ascospores

Fluconazole Voriconazole AMP-B Caspofungin

P anomala Fluconazole: low activity;itraconazole: very low activity

Susceptible Susceptible Susceptible

•In vitro, amphotericin, fluconazole, voriconazole, and caspofungin have activity against P anomala, although high drug concentrations required for inhibition; •itraconazole is poorly active against this yeast.

Saccharomyces cerevisiae:

• Use of live yeast capsules (Saccharomyces boulardii), taken for prevention of Clostridium difficile associated diarrhoea, leads to Fungaemia.

• Patients at risk:-in ICU,with CVC

- had broad spectrum antibiotics

• Very few data are available for drug efficacy,

• amphotericin and voriconazoleseem to be active in vitro.

Probiotic!!

Cryptococcus neoformans• Nosocomial transmission quite rare.

• Pulmonary cryptococcosis case Direct inhalation 2ndry infection in close contact

• Needlestick injury localized cuteneouscryptococcal granuloma in lab worker

• Proper sterilization hospital equipment mandatory.

Also...

Principal Criteria and Tests for Identifying Yeasts1. Culture characteristics - Colony color, shape, texture

2. Asexual structures:

a) Shape and size of cells

b) Bipolar, fission, multipolar or unipolar "budding"

c) Absence or presence of arthroconidia, ballistoconidia, blastoconidia, clamp connections, endoconidia, germ tubes, hyphae, pseudohyphae, or sporangia and sporgangiospores.

3. Sexual structures - Arrangement, cell wall ornamentation, number, shape and size of ascospores or basidiospores

4. Physiological studies

a) Sugar Assimilation

b) Sugar Fermentation

c) Cycloheximide resistance

d) Tetrazolium reduction test

e) Diazonium Blue B test

f) Nitrogen utilization

g) Urea hydrolysis

h) Temperature studies

i) CHROME Agar

YEAST MORPHOLOGY Brown to black

colony Direct Mount Yeast only Phaeococcomyces

Yeast and hyphae

AureobasidiumExophialaWangiella

Pink to red colony

Satellite colonies Present Forcibly discharged

conidia

Sporobolomyces

Absent Urease+Capsule+Inositol-

Rhodotorula

White, creamy colony

Germ Tube Test Positive C albicansC dubliensis

Negative Other Candida

Moist mycelialcolony

Direct Mount Arthroconidia Blastoconidia Trichosporon

Geotrichum

If Germ Tube test Negative

Corn Meal Agar or Rice Starch AgarIncubate at 25 C X 2-3 days

Only yeasts present Hypae, PseudohypaeOr both present

C. GlabrataC. FamataCryptococcusRhodotorulaAscomycetous yeasts

Chlamydospore present(thick wall, refractile, round)

Single, terminal Chlamydospore

Terminal, cluster of Chlamydospore

C. albicans C. dubliensis

Arthroconidia present

Blastoconidia present

TrichosporonRabbit ears” appearence

Geotrichum“Hockey stick” appearence

No ChlamydosporeNo Arthroconidia

Other CandidaSaccharomycec

PichiaMalassezia

Hypae, PseudohypaeOr both present

Ascospore +On Malt extract agarOr Na-acetate agarAt 25 CAscospore are acid fast

Spaghetti & meat ball app

Candida species Identification

C. a

lbic

ans

C. d

ub

linie

nsi

s

C. g

lab

rata

C. k

ruse

i

C. k

efyr

C. p

arap

silo

sis

C. t

rop

ical

is

C. g

uill

ierm

on

dii

C. f

amat

a

C. l

ipo

lyti

ca

Chlamydospore + + - - - - - - - -

Germ tube + + - - - - - - - -

Pellicle On broth + +

Urease + +

Fermen

tation

GluMalSucLacGalTre

FF--FF

F

--FF

F----F

F-----

F-FFF-

F-----

FFF-FF

F-F-FF

W-

W--

W

------

Assim

ilation

GluMalSucLacTre

+++++

++---

+---+

+----

+-++-

+++-+

+++-+

+++-+

+++++

+----

MOULDS

ASPERGILLUS SPECIES

• Sources of Aspergillus spores in the hospital air:

– Inadequate filtration of outside air or malfunctionning of ventilation

– Dust and places infrequently cleaned

– Vacuum cleaning

– Plants, flowers, etc.

– Periods of hospital constructions, renovations, demolition 56

No uniform definition of nosocomial aspergillosis till now, due to unknown incubation period of invasive aspergillosis

Working definition: invasive disease occurs after 1 week ofHospitalization or within 2 weeks of hospital discharge

Common Aspergillus spp.causes nosocomial infection

Aspergillus fumigatus

Aspergillus flavus

Aspergillus terreusAspergillus nidulans

Predisposing host factors• autologous bone

marrow transplants

• graft versus host disease

• solid organ transplants

• Acute leukemia, myelodyaplasticsyndrome, aplasticanaemia

• Advanced AIDS (reduced CD4 cell count < 100)

• Chronic granulomatousdisease

• Pre-existing structural lung diseases (emphysema, COPD, cavitory tuberculosis)

Immunosuppressive therapy

Defective NADPH oxidase

Co-existing diabetes, malnutrition, Steroid therapy

Severe long term granulocytopenia.

Chemotherapy & underlying hematologic disease

1,000/mm3

Clinical Diseases

• Predominately (77%)respiratory and includes necrotizing bronchopneumonia

• Postcardiac surgery endocarditis

• Surgical site Infection (5%): Burn wound, aortic graft sites, peritoneal catheter sites (use of dressings contaminated with spores)

• Cutaneous infections associated with the use of arm boards for patients with iv catheters

Pathophysiology of aspergillosis

2.5–3.0 um

Diagnosis• Chest radiograph: single or multiple rounded

densities

• Histopathology: tissue invasion by fungal hyphae in skin or lung biopsy specimens confirm diagnosis.

• Culture from bronchoalveolar lavage, sputum, or endotracheal aspirates: may represent colonization, but in conjunction with a clinical diagnosis, positive cultures probably indicate pulmonary aspergillosis

• Blood cultures are very insensitive for detecting Aspergillus spp.

• Role of routine surveillance cultures of immunocompromised patients has not been well established.

• Rapid Antigen detection:

Galactomannan, Cell-wall polysaccharide specific to Aspergillus species, correlate with clinical diagnosis and response to antifungal therapy.

Immune complexes dissociation(Heat, Acid, Alkali) and use of monoclonal antibodies increases sensitivity

A sandwich ELISA, most sensitive methods currently available to detect galactomannan(0.5 to 1.0 ng per ml of serum).

Management:

• Until recently Ampho B considered gold standard drug for invasive pulmonary aspergillosis.

• Now Voriconazole is used as 1st line therapy

(ASM & I D S A g u i d e l i n e s)

• Empirical antifungal therapy:

with AMB, itra, vori, or caspofungin

recommended for high-risk patients with prolonged neutropenia who remain persistently febrile despite broad-spectrum antibiotic therapy.

not for patients, have short durations of neutropenia (<10 days)

PREVENTION AND CONTROL • CDC has published revised recommendations for preventing nosocomial

pulmonary aspergillosis• Interrupt Transmission of Aspergillus sp. Spores: 1) maintenance of

a) HEPA filtration (99.97% efficient in filtering particles >0.3um),

b) directed room airflow,

c) positive air pressure in patients' rooms relative to the air pressure in the corridor,

d) properly sealed rooms, and

e) high rates of room-air changes (100-400/hr)

2) Minimize exposures of high-risk patients to potential sources of Aspergillus sp. (e.g., hospital construction and renovation, cleaning activities, carpets, food, potted plants, and flower arrangements)

3) Collect environmental samples from potential sources.

MucormycotinaRecent rising incidence due to continued rise of diabetics, increased use

of immunosuppressive agents and Voriconazole a broadspectrumantifungal as prophylaxis

EpidemiologyDeveloped countries

• the disease is still a rare finding

• mostly seen in patients with

• haematological malignancies undergoing chemotherapy,

• in bone marrow transplant recipients,

• in patients receiving voriconazole therapy or prophylaxis.

Developing countries

• Increasing number of mucormycosis cases

• occurring commonly in patients with uncontrolled diabetes

• Cases are also seen in patients with haematological malignancies or in transplant recipients

In India, more than 30 million poorly compliant

diabetics, at risk of developing opportunistic

mucormycosis

• Modes of infection: 1) Aerosolization of the spores > tissue invasion via the

respiratory tract (in most patients).

2) acquisition is through disrupted skin(trauma and burn)

3) Ingestion of contaminated foodstuffs

• Risk factors : 1) poorly controlled diabetes mellitus,

2) Hematologic malignancies (especially with neutropenia),

3) solid-organ or hematopoietic stem cell transplant (HSCT),

4) Deferoxamine therapy for iron or aluminum overload

5) burn wounds

6) corticosteroid therapy.

• The most dramatic presentations are in patients with diabetic ketoacidosis, tend to have rhinocerebral(rather than pulmonary) mucormycosis.

Epidemiology

• Poor infection control practices associated with injury mode of entry of mucormycetes in hospital.

• Interestingly from India many cases of cutaneousmucormycosis were reported at the site of intramuscular injection

• Very disturbing and indicates poor medical care practices in developing countries.

• It may be gradual and slowly progressive or may be aggressive and fulminant leading to necrotizing lesions and haematogenous dissemination.

• Outbreak of gastrointestinal zygomycosis due to contaminated food and drugs or even tongue depressor.

• Patients with a dual mycotic infection, i.e. Aspergilllus and a mucormycete, are not uncommon.

• Rhizopus oryzae is commonest

• Apophysomyces and Saksenaea can initiate invasive disease in apparently normal hosts who have sustained penetrating trauma during accidents.

• After the tsunami disaster in 2004, victims were found to be infected with Apophysomyces in Sri Lanka and Thailand

• The biopsy specimen should be taken from the centre of the lesion especially from black eschararea and include subcutaneous fat, as frequently invade blood vessels of the dermis and subcutis.

Irregular, broad, ribbon-like, (6-50 microns in width) Hyphae, usually devoid of septae, to invade blood vessels

Rapidly grownon agar in gray-white, brown cottonyor wooly coloniesSporangiophores may be septateColumella and rhizoids, shape of the apophysisimportant in genus identification

Apophysomyces elegans:

• is an emerging zygomycete in India

distinctive funnel- or bell-shaped apophyses, hemispherical-shaped columellae, a conspicuous pigmented sub-apical thickening which constricts the lumen of sporangiophore below the apophysis, and distinctive foot cells.

Saksenaea vasiformis

flask-shaped Sporangia with a distinctspherical venter and long-neck, darklypigmented rhizoids. Sporangiosporesdischarged through the neck followingthe dissolution of an apical mucilaginousplug.

•Sporulate rarely on routine media•Difficult to differentiate from Apophysomyces

• A special nutrient deficient growth medium (Czapek Dox agar, cornmeal-glucose-sucrose-yeast extract agar), high temperature and prolonged incubation may be used to induce sporulation.

•By using the agar block method described by Ellis and Ajello(1982).a small block of agar is cut from a well established culture grown on PDA and is placed in the centre of petri dish containing 1% distilled water agar. After 21 days at 26°C look for sporangium formation at the periphery of the petri dish.

Management• Rapid diagnosis: Diagnosis at the early stage is desirable as the mortality 83-

94% in disseminated disease.

• Remove or reduce risk factors: • rectifying diabetic ketoacidosis,• withdrawing desferrioxamine therapy • reducing the level of immunosuppression.

• Antifungal therapy and surgical debridement: • Till date Amphotericin B is the only drug effective. • Posaconazole as a substitute gaining popularity in recent years• fluconazole, voriconazole, flucytosine and the echinocandins have no

efficacy.• The best management for cutaneous zygomycosis is extensive surgical

debridement combined with antifungal.

• Adjunctive therapies: hyperbaric oxygen (HBO) treatment

Bundled Interventions" to Prevent Common Health Care–Associated Infections

• Prevention of Surgical-Site Infections:

• Choose a surgeon wisely. • Administer prophylactic antibiotics

within 1 h before surgery; discontinue within 24 h.

• Limit any hair removal to the time of surgery; use clippers or do not remove hair at all.

• Prepare surgical site with chlorhexidine-alcohol.

• Maintain normal perioperative glucose levels (cardiac surgery patients).

• Maintain perioperative normothermia(colorectal surgery patients).

Fusarium species:• Disseminated infections

among severely immunocompromisedpatients

• Postoperative endophthalmitis and peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD)

• Local invasive infection of wound, burn, ulcer.

• Diagnosis is usually made by culture of biopsy specimens or other normally sterile sites.

Hyaline, 2- to several-celled, fusiform- to sickle-shaped macroconidia, with an elongated apical cell and pedicellate basal cell

Clinical manifestations similar with disseminated aspergillosisexcept

• Associated with concomitant cellulitis or subcutaneous lesions

• More readily isolated from cultures of blood than are Aspergillus spp.

• Resistance to Amphotericin B leads to treatment and prevention failure

Clinical manifestations similar with disseminated aspergillosis, except

• Associated with concomitant cellulitis or subcutaneous lesions

• More readily isolated from cultures of blood than are Aspergillus spp.

• Resistance to Amphotericin B leads to treatment and prevention failure

Microscopically similar fungal species

Cylindrocapron: Chlamydospore +ve Acremonium: microconidia in early stage of culture

Management:

• Recovery from underlying neutropenia is main stay of treatment.

• Voriconazole and Posaconazole effective.• Combination of caspofungin with amphotericin B

showed synergistic to additive effect.

Acremonium species: A. kiliense, A. strictum•Endophthalmitis following cataract surgery as colonize soft contact lenses

long awl-shaped phialides producing cylindrical, one-celled conidia, mostly aggregated in slimy heads at the apex of each phialide

•Rarely disseminated infections in immunosuppressed patients

Fluconazole was shown to be completely inactive against Acremonium in vitro

•Recurrent cutaneous infection in renal transplant cases

Drug of choice is Ampho B

Paecilomyces lilacinus• Associated with intrinsic contamination of a

neutralizing solution for synthetic intraocular lenses, resulting postoperative endophthalmitis

Scedosporium prolificans:• Outbreaks reported in patients with leukemia undergoing

chemotherapy (anti-TNFα )

• Scedosporium is generally resistant to all available antifungal agents.

• Infection associated with nearly 100% mortality

• A Case of Scedosporium Prolificans Osteomyelitis in a Child reported from our department, Misdiagnosed as Tubercular Osteomyelitis

single-celled, clavate to ovoid conidia, borne singly or in small groups on elongate conidiophores or laterally on hyphae

Pseudallescheria boydii

• An ascomycete (anamorphs are Scedosporiumapiospermum and Graphium)

• corneal ulcers, endophthalmitis, otitis externa, sinusitis, pneumonia, and many invasive infections in immunocompromised hosts

• commonly resistant to amphotericin B but susceptible to miconazole and newer azoles

Phaeoid/ Dematiaceous/ Melanized fungi

• dark pigmentation due to presence of dihydroxynaphthalene melanin in their cell walls

• Ubiquitous saprobes, often considered contaminants

• Curvularia spp, isolated from saline-filled breast implants, resulting from contamination of saline stored beneath a water-damaged ceiling.

• Cladophialophora bantiana causes cerebral pheohyphomycosis

• Exserohilum dermatitidis, recently causes fatal meningitis outbreak after use of contaminated injection

•closely resemles Bipolaris

•strongly protruding truncate hilum

(i.e. exserted hilum)

Pneumocystis jiroveci• Recent reports of possible person-to-person

airborne transmission of infection suggested by PCR testing.

• Close contacts of HIV+ patients with Pneumocystis pneumonia, including HCWs

• Outbreaks particularly among renal transplant recipients

• But specific isolation of hospitalized patients with Pneumocystis pneumonia still not recommend.

• For Prevention: trimethoprim-sulfamethoxazoleprophylaxis is recommended for HSCT and SOT recipients especially the first 100 days after transplantation.

Isavuconazole

• a new and promising antifungal triazole for the treatment of invasive fungal infections

• currently in Phase III clinical trial

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