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NOCARDIA, ACTINOMYCES
AND STREPTOMYCES
DR SIMA RUGARABAMU
NOCARDIA, ACTINOMYCES
AND STREPTOMYCES
DR SIMA RUGARABAMU
ACTINOMYCETES
Nocardia Actinomyces Streptomyces
ACTINOMYCETES
1. LARGE GROUP = CHARACTERISTICS OF
BACTERIA AND FUNGI
2. FORM BRANCHES OR FILAMENTS = HYPHAE
3. INFECTIONS RESEMBLE FUNGAL DISEASES
1. CHRONIC SUPPURATIVE DISEASE + SINUSES
4. BACTERIAL = PROCARYOTIC CELL WALL
1. LACK OF MITOCHONDRIA/MEMBRANE BOUND
NUCLEUS
5. SUSCEPTIBLE TO PENICILLIN LIKE BACTERIA
ACTINOMYCETES
• BIOCHEMISTRY
• THE ORGANISMS ARE IDENTIFIED BASED ON SUGAR FERMENTATIONS AND
HYDROLYSIS REACTIONS (CASEINE, TYROSINE, ETC.)
• CLINICAL SIGNIFICANCE
• MYCETOMA – ORGANISM ENTERS THE BODY THROUGH BREAKS IN THE SKIN AND
CAUSES A LOCALIZED INFECTION INVOLVING SKIN, CUTANEOUS, AND
SUBCUTANEOUS TISSUE.
• THE THREE MOST CHARACTERISTIC FEATURES SEEN ARE SWELLING,
DRAINING SINUSES AND GRANULES.
• THIS DISEASE CAN ALSO BE CAUSED BY FUNGI AS WELL AS NOCARDIA,
ACTINOMADURA, AND STREPTOMYCES.
ACTINOMYCETES
• ACTINOMYCES SPECIES
• NOCARDIA SPECIES
• STREPTOMYCES SPECIES
GRAM POSITIVE FILAMENTOUS BACTERIA
GENUS OXYGEN GRANULE ACIDFAST
Actinomyces ANAEROBE YES no
Nocardia aerobe sometime PARTIALLY
Streptomyces aerobe YES no
ACTINOMYCETES
ACTINOMYCES
ANAEROBIC, FILAMENTOUS, GRAM POSITIVE BACILLUS
• EXHIBIT TRUE BRANCHING
• “MYKES” – GREEK FOR “FUNGUS”
• THOUGHT BY EARLY MICROBIOLOGIST TO BE FUNGI
BECAUSE OF:
• MORPHOLOGY
• DISEASE THEY CAUSE
• A ISRAELII – ACTINOMYCOSIS
• A BOVIS – LUMPY JAW, IN CATTLES
• A VISCOSUS – DENTAL DISEASES
• A NAESLUNDII - DENTAL DISEASES
ACTINOMYCOSIS
A CHRONIC SUPPURATIVE AND GRANULOMATOUS
DISEASE OF THE CERVICO-FACIAL, THORACIC OR
ABDOMINAL AREAS
ACTINOMYCOSIS
• SWELLING →FLUCTUANT →SINUS TRACT
• 50% OF CASES - CERVICOFACIAL ACTINOMYCOSIS
• 20% OF CASES - THORACIC ACTINOMYCOSIS
• 20% OF CASES – ABDOMINAL ACTINOMYCOSIS
1. ACTINOMYCOSIS
• ACTINOMYCES ISRAELII AND OTHERS
• CERVICOFACIAL = MOST COMMON, LOWER JAW =
ABSCESS FORMATION, SINUS TRACTS THAT
REACH THE SKIN
• THORACIC = ASPIRATION INTO LUNG, EXTENSION
OF CERVICOFACIAL, HEMATOGENOUS
• ABDOMINAL = TRAUMA OF INTESTINE OR
ABDOMINAL WALL
• GENITAL = INTRAUTERINE DEVICES =
INFLAMMATION
• DIAGNOSIS - EXAMINE PUS FOR WHITE OR
YELLOW GRANULES/GRAM STAIN =
FILAMENTOUS/CULTURE = LOOK FOR
G+/IDENTIFY BY IMMUNOFLUORESCENCE
ACTINOMYCOSIS
NOT HIGHLY VIRULENT
(OPPORTUNIST)
• COMPONENT OF ORAL FLORA
• PERIODONTAL POCKETS
• DENTAL PLAQUE
• TONSILAR CRYPTS
• TAKE ADVANTAGE OF INJURY
TO PENETRATE MUCOSAL
BARRIERS
• COINCIDENT INFECTION
• TRAUMA
• SURGERY
ACTINOMYCOSIS
• A CHRONIC SUPPURATIVE AND GRANULOMATOUS肉芽
肿DISEASE OF THE CERVICO-FACIAL, THORACIC OR
ABDOMINAL AREAS
ACTINOMYCOSIS
FORM INDURATED MASSES WITH FIBROUS WALLS AND
CENTRAL LOCULATIONS WITH PUS
• PUS CONTAINS "SULFUR GRANULES"
• GRITTY, YELLOW WHITE
• AVERAGE DIAMETER - 2MM
• COMPOSED OF MINERALIZED “MYCELIAL” MASS
CHRONIC INFECTION
• FORM BURROWING SINUS TRACTS TO SKIN OR MUCUS
MEMBRANES
• DISCHARGE PURULENT MATERIAL
ACTINOMYCOSIS - SULFUR GRANULE
PULMONARY ACTINOMYCOSIS
• 15% OF CASES
• ASPIRATION OF ORGANISM
FROM THE OROPAHARYNX
• SLOWLY PROGRESSIVE
PROCESS INVOLVING LUNG
AND PLEURA
• MAY BE MISTAKEN FOR
MALIGNANCY
• CHEST PAIN, FEVER, WGT
LOSS AND HEMOPTYSIS
LAB DIAGNOSIS
• PUS FROM LESIONS, SINUS TRACKS, FISTULAS, SPUTUM OR BIOSPY MATERIALS
• MICROSCOPIC EXAMINATION – SULPHUR GRANULES
• CULTURE: THIOGLYCOLATE MEDIUM, ANAEROBICALLY, FOR 2 WEEKS
ACTINOMYCOSIS/TREATMENT
• SURGICAL DEBRIDEMENT OF DAMAGED TISSUE IS A
PREREQUISITE TO ANTIBIOTIC THERAPY
• PENICILLIN G FOR 3-4 WEEKS = TREATMENT OF
CHOICE/TRIMETHOPRIM AND SULFAMETHOXAZOLE
RESULTS IN A MORE RAPID CURE
DENTAL CARIES
PERIODONTAL DISEASE
NORCADIA
• THIN, G+, BRANCHING FILAMENTS
• PARTIAL ACID FAST – 1% H2SO4
• DOES NOT FORM GRANULES
• GROW AEROBIALLY
• FOUND ON SOIL
• MAY CAUSE
• NORCADIOSIS
• MYCETOMA
Nocardia
• Can cause pulmonary, systemic or cutaneous
disease.
• Special request for modified acid-fast stain.
• Special request for Nocardia culture.
– Grow on Sab agar and LJ agar
– White, orange “chalky” colonies
– Will grow on blood, chocolate but can take over a
week and normal sputum culture plates only held 48
hours.
• After suspect an actinomycetes will do further
tests to determine genus/species (e.g.,
lysozyme sensitivity, casein decomposition)
ACTINOMYCETES
• THE AEROBIC GENERA: NOCARDIA, ACTINOMADURA, AND
STREPTOMYCES. THERE ARE THREE CLINICALLY IMPORTANT
SPECIES OF NOCARDIA – N. ASTEROIDES, N. BRASILENSIS, AND
N. CAVIAE
• MORPHOLOGY AND CULTURAL CHARACTERISTICS
• G+ BRANCHING BACILLUS THAT MAY FRAGMENT TO BACILLARY OR
COCCOID FORMS
• AEROBIC
• SPECIMENS SHOULD BE INOCULATED ONTO 7H10 AGAR OR LOWENSTEIN-
JENSEN AGAR AND BRAIN HEART INFUSION AGAR.
• COLONIES PRODUCED ARE TYPICALLY ORANGE, DRY, CRUMBLY, AND
ADHERENT.
• THE ORGANISMS ARE WEAKLY ACID FAST OR NON ACID FAST
NOCARDIOSIS
• SUBCUTANEOUS INFECTIONS, PULMONARY INFECTIONS, AND BRAIN ABSCESSES
PATHOGENESIS AND CLINICAL FINDINGS
• NORCADIOSIS – PULMONARY INFECTION – PNEUMONIA
• HEMATOGENOUS SPREAD MAY LEAD TO BRAIN ABSCESS
• DISEASE MAINLY IN IMMUNOCOMPROMISED INDIVIDUALS
• AIDS, LEUKEMIA, LYMPHOMA, STEROIDS
ACTINOMYCETES
• NOCARDIOSIS – IS A LOCALIZED OR DISSEMINATED DISEASE OCCURRING AFTER INHALATION OF
ORGANISMS.
• PULMONARY INFECTIONS RESEMBLE TUBERCULOSIS AND CAN REMAIN CONFINED TO THE
LUNGS OR MAY DISSEMINATE, WITH A PREDILECTION FOR THE BRAIN AND MENINGES.
• THE DISEASE IS CHARACTERIZED BY MULTIPLE CONFLUENT ABSCESSES AND INTENSE
SUPPURATION.
• IT IS USUALLY A DISEASE OF COMPROMISED HOSTS.
• ANTIMICROBIC SUSCEPTIBILITY/TREATMENT
• MYCETOMA – AMINOGLYCOSIDES
• NOCARDIOSIS – SULFONAMIDES OR SXT
NOCARDIOSIS
• N. ASTEROIDES – PULMONARY
• N. BRASILIENSIS - ABSCESSES
LAB. DIAGNOSIS
• CLINICAL SPECIMENS:SPUTUM,PUS,BIOPSY TISSUE
Sulfamethoxazole-Trimethoprim
CLINICAL SPECIMENS
• SPUTUM
• PUS
• BIOPSY TISSUE
DRUG OF CHOICE
SULFAMETHOXAZOLE-TRIMETHOPRIM
ACTINOMYCETES/INFECTIONS
• NOCARDIOSIS/TREATMENT
• SURGICAL DEBRIDEMENT
• EARLY DIAGNOSIS IMPORTANT;
POOR RECOVERY AFTER SYSTEMIC
INFECTION
• TREAT WITH COTRIMAZOLE OR
SULFADIAZINE/ RESPIRATORY
INFECTIONS MAY REQUIRE
SEVERAL MONTHS
STREPTOMYCOSIS
STREPTOMYCES SPECIES
MORPHOLOGY
HIGHLY HETEROMORPHOUS IN CONTRAST TO
UNICELLULAR ORGANISMS
IN SUBMERGED CULTURES,
HYPHAE ARE PRESENT AS
MYCELIUM: DISPERSED
HYPHAL FILAMENTS
PELLET: SPHERICAL
AGGLOMERATE OF HYPHAL ELEMENTS
COMMERCIAL IMPORTANCE OF
STREPTOMYCES
BIOSYNTHESIS OF
ANTIBIOTICS (STREPTOMYCIN, ERYTHROMYCIN,
TETRACYCLINE, CHLORAMPHENICOL, ETC.)
ANTIFUNGALS (AMPHOTERICIN B)
ALKALOIDS (PHYSOSTIGMINE)
ANTI-CANCER COMPOUNDS (MIGRASTATIN)
USED AS HOST FOR HETEROLOGOUS GENE
EXPRESSION (CURR OPIN BIOTECHNOL 2 (5): 674-81)
MAY CAUSE MYCETOMA
STREPTOMYCES
MAY INVADE BONE
CLINICAL SPECIMENS
PUS
BIOPSY MATERIAL
SEROLOGICAL TEST
NONE AVAILABLE
SEROLOGICAL TEST
NONE AVAILABLE
The streptomyces species usually cause the
disease entity known as mycetoma (fungus
tumor). These infections are usually
subcutaneous, but they can penetrate deeper
and invade the bone. Some species produce a
protease which inhibits macrophages. Material
sent to the lab is pus or skin biopsy. The
streptomycetes are aerobic like Nocardia, and
can grow on both bacterial and fungal (SDA)
media.
They produce a chalky aerial mycelium with
much branching. It is important to let the lab
know the organism you suspect because most
bacterial pathogens will grow out overnight, but
the actinomycetes take longer to be visible on
the culture plates (48-72 h).
• THE VARIOUS SPECIES OF STREPTOMYCES
PRODUCE GRANULES OF DIFFERENT SIZE,
TEXTURE AND COLOR. THESE GRANULES ALONG
WITH COLONIAL GROWTH AND BIOCHEMICAL
TESTS ALLOW THE BACTERIOLOGIST OR
MYCOLOGIST TO IDENTIFY EACH SPECIES. THE
ORGANISMS ARE FOUND WORLD-WIDE. THERE
ARE NO SEROLOGICAL TESTS, AND THE
DRUGS OF CHOICE ARE THE
• COMBINATION OF
SULFAMETHOXAZOLE/TRIMETHOPRIM OR
AMPHOTERICIN B. IN THE TROPICS THIS
DISEASE MAY GO UNDIAGNOSED OR
UNTREATED FOR SO LONG THAT SURGICAL
AMPUTATION MAY BE THE ONLY EFFECTIVE
TREATMENT.
GENERAL PROPERTIES
• THEY ARE FILAMENTOUS BACTERIA
• THEIR MORPHOLOGY RESEMBLES THAT OF FILAMENTOUS
FUNGI- ALSO KNOWN AS RAY FUNGI
• HIGH G+C CONTENT THAN ANY OTHER BACTERIA
• SOURCE OF MOST OF CURRENTLY USED ANTIBIOTICS ALSO
PRODUCE METABOLITES THAT ARE ANTICANCER,
ANTHELMINTHIC AND IMMUNOSUPPRESSIVE COMPLEX LIFE
CYCLE
• GRAM POSITIVE
• SAPROPHYTIC AND MAINLY ACTING AS DECOMPOSERS IN THE
SOIL
• WIDE SPECTRUM ANTIBIOTIC ARE COMMERCIALLY PRODUCED
FROM STREPTOMYCES
• INTERMEDIATE GROUP BETWEEN BACTERIAL AND FUNGI
• REPRESENTATIVE GENERA FOR THIS PRESENTATION;
STREPTOMYCES, NORCADIA,ACTINOMYCES
ACTINOMYCETES
• IRREGULAR, NON SPORE FORMING GRAM POSITIVE RODS ,EITHER AS AEROBIC OR AS
FACULTATIVE ANAEROBIC ISOLATES
• NOCARDIA ARE CLOSELY RELATED TO THE GENERA MYCOBACTERIUM AND
CORYNEBACTERIUM BUT DIFFER DISTINCTLY FROM ACTINOMYCES IN CELL WALL CHEMICAL
CHARACTERISTICS AND PERCENTAGES OF GUANINE AND CYTOSINE
• MYCOBACTERIUM SPECIES DIFFER BY THE PRESENCE OF RODS RATHER THAN OF FRAGMENTING
MYCELIUM, BY RELATIVELY POOR GRAM-STAINING, AND BY STRONG ACID-FASTNESS
• ACTINOMYCES- ANAEROBIC, NORMAL FLORA
• NOCARDIA- AEROBIC, SAPROPHYTES-PARTIALY ACID FAST
• STREPTOMYCES- AEROBIC, SAPROPHYTES
NOCARDIA AND STREPTOMYCES
● OBLIGATE AEROBIC SAPROPHYTES, FOUND IN SOIL
● A FEW SPECIES ARE RARE OPPORTUNIST PATHOGENS, CAUSING DISEASE IN CASES IN WHICH
PREDISPOSING FACTORS SUCH AS IMMUNITY OR NORMAL BODY DEFENSE MECHANISMS ARE
GROSSLY IMPAIRED
●COLONIES VARY FROM HEAPED, WAXY, AND VARIABLY PIGMENTED TO DENSE, WHITE
MYCELIAL, AND MOLD LIKE
● ALL GENERALLY GROW IN 3-5 DAYS AT 37°C AND ARE CATALASE POSITIVE.
● NOCARDIA ARE MOST COMMONLY ENCOUNTERED, BUT STREPTOMYCES MAY BE CULTURED
FROM MYCETOMAS IN TROPICAL AREAS
NORCADIA
• THE PATHOGENIC NOCARDIA ARE OFTEN ACID-FAST (OR PARTIALLY SO),
• GRAM-POSITIVE,
• UREASE POSITIVE
• BRANCHING FILAMENTOUS RODS THAT BREAK UP INTO BACILLARY OR COCCOID
FORMS.
• THEY ARE STRICTLY AEROBIC
• FOUND IN THE SOIL.
• THE SPECIES OF IMPORTANCE IS N. ASTEROIDS.
NORCADIOSIS
• BRONCHOPULMONARY
IMMUNOCOMPROMISED PATIENTS ;POTENTIAL FOR DISSEMINATION TO THE CNS
DX; PNEUMONIA WITH CAVITATION
• CUTANEOUS OR SUB CUTANEOUS LESIONS;
• CAN OCCUR IN HEALTHY INDIVIDUAL WITH TRAUMATIC INJURY LEAD T
MYCETOMAS
• PAINLESS ,SUBCUTANEOUS SINUS
PATHOGENICITY
NOCARDIOSIS IS USUALLY A CHRONIC, PROGRESSIVE
DISEASE CHARACTERIZED BY SUPPURATING,
GRANULOMATOUS LESIONS.
THE ORGANISM PRODUCES ACUTE AND CHRONIC MASTITIS
WITH GRANULOMATOUS LESIONS AND DRAINING SINUS
TRACTS
LOCALIZED SUBCUTANEOUS LESIONS OR LYMPH NODE
INVOLVEMENT, OR BOTH, ARE SEEN.
GENERALIZED NOCARDIOSIS CHARACTERIZED BY
PNEUMONIA AND THE ACCUMULATION OF LARGE
QUANTITIES OF RED FLUID IN THE THORACIC OR
ABDOMINAL CAVITY,
THE FLUID IN THESE CAVITIES IS SEROSANGUINOUS AND
INFREQUENTLY CONTAINS SMALL (<1 MM) SULFUR LIKE
GRANULES.
CARE MUST BE TAKEN TO DISTINGUISH ANY 'NOCARDIA'
ISOLATED FROM A. VISCOUS
DIRECT EXAMINATION
• GRANULES, IF PRESENT, ARE EXAMINED AS DESCRIBED EARLIER.
• GRAM-STAINED SMEARS OF PUS OR CRUSHED GRANULES REVEAL GRAM-
POSITIVE BRANCHING FILAMENTS, WITH OR WITHOUT CLUBS
• THE MODIFIED ACID-FAST STAIN OFTEN SHOWS THE RETENTION OF SOME
CARBOLFUCHSIN, BUT THIS IS NOT A RELIABLE CHARACTERISTIC OF
NOCARDIA.
• PUS CONTAINING THE CHARACTERISTIC ELEMENTS IS INOCULATED ONTO
SEVERAL BLOOD SLANTS OR PLATES AND SABOURAUD DEXTROSE AGAR
WITHOUT INHIBITORS. INCUBATE AT ROOM TEMPERATURE AND AT 37°C
FOR UP TO A WEEK.
CULTURAL CHARACTERISTICS
• GROWTH IS EVIDENT IN 4-5 DAYS, AND COLONIES ARE IRREGULARLY FOLDED, RAISED, AND
SMOOTH OR GRANULAR.
• THE COLOR VARIES FORM WHITE THROUGH YELLOW TO DEEP ORANGE.
• GRAM-POSITIVE, PARTIALLY ACID-FAST MYCELIAL FILAMENTS, WHICH BREAK UP INTO BACILLARY
FORMS, ARE EVIDENT UNDER OIL IMMERSION.
• THE PRESENCE OF MYCELIAL ELEMENTS DISTINGUISHES NOCARDIA
• FROM SAPROPHYTIC AND ATYPICAL MYCOBACTERIA. THE MYCELIAL FORMS OF THE NOCARDIA CAN
BE READILY SEEN IN SLIDE CULTURES ON SABOURAUD DEXTROSE AGAR. THE SPECIES GROWS WELL
AT 45°C.
• IDENTIFICATION; A HIGHLY PRESUMPTIVE IDENTIFICATION OF N. ASTEROIDES INFECTION IS BASED
ON PATHOLOGY, DEMONSTRATION OF TYPICAL ORGANISMS, AND COLONIAL, CULTURAL, AND
MORPHOLOGICAL CHARACTERISTICS.
ANTIBIOTIC SUSCEPTIBILITY
• BROTH MICRODILUTION METHOD IS RECOMMENDED BY THE CLSI FOR
ANTIMICROBIAL SUSCEPTIBILITY TESTING FOR NOCARDIA SPP
• A STUDY OF IN VITRO SUSCEPTIBILITY HAS SHOWN THAT ALL N. ASTEROIDES
TESTED WERE SENSITIVE TO SULFIXAZOLE, TRIMETHOPRIM-SULFAMETHAZOLE,
DOXYCYCLINE, AND MINOCYCLINE AND MOST TO AMPICILLIN; ABOUT HALF
WERE RESISTANT TO TETRACYCLINE
ACTINOMYCES
• ARE GRAM-POSITIVE, DIPHTHEROIDAL OR BRANCHING FILAMENTOUS RODS, 0.2-1.0 ΜΠΊ IN
DIAMETER.
• SHORT RODS, WHICH MAY SHOW CLUBBED ENDS, ARE COMMON AND MAY OCCUR SINGLY,
IN DIPHTHEROIDAL PAIRS, IN SHORT CHAINS, OR IN CLUSTERS. ACTINOMYCES PYOGENES
ARE COMMONLY COCCOBACILLARY IN AN AEROBIC ATMOSPHERE.
• ACTINOMYCES ARE FACULTATIVE ANAEROBIC, WITH MOST SPECIES BEING PREFERENTIALLY
ANAEROBIC ALTHOUGH SOME SPECIES GROW WELL IN AIR; 10% C02 IMPROVES GROWTH OF
AERO TOLERANT SPECIES AND IS REQUIRED FOR AERO TOLERANT STRAINS OF
PREFERENTIALLY ANAEROBIC SPECIES
• ACTINOMYCES ARE THUS FERMENTATIVE IN METABOLISM WHEREAS NOCARDIA ARE
OXIDATIVE.
• COLONIES MY BE EITHER ROUGH AND DRY OR SOFT AND MUCOID, WITH TRANSITIONAL
FORMS BEING COMMON.
• ACTINOMYCES CAUSE CHRONIC INFECTIONS OF SOFT AND HARD TISSUES, OFTEN WITH THE
FORMATION OF SULFUR GRANULES.
ACTINOMYCOSIS
• THE PRESENCE OF SULFUR GRANULES, WHILE STRIKING, IS NOT
DIAGNOSTIC OF ACTINOMYCES INFECTIONS BUT ALSO OCCURS IN
NOCARDIA OR STREPTOMYCES INFECTIONS.
• ACTINOMYCES INFECTIONS ARE OFTEN ASSOCIATED WITH THE PRESENCE
OF FOREIGN BODIES USUALLY DISRUPTED BY TRAUMA OR SURGERY OR
DENTISTRY OR OTHER INFECTION
• INFECTION IS ENDOGENOUS
• CERVICOFACIAL;
• ‘’LUMPY JAW’’ ASSOCIATED WITH RECENT DENTAL WORK, JAW TRAUMA,
POOR ORAL HYGIENE
• ‘’ SULFUR GRANULES’’
Gram Stain and Macroscopic Colonies
of Actinomyces
NOTE: Molar tooth appearance of
colonies on agar can help remind us that
the oral cavity is a common niche for
Actinomyces.
Cervicofacial Actinomycosis
NOTE: Sinus tract originating in oral cavity has
made it’s way to the surface at the jawline.
ACTINOMYCOSIS
• PELVIC; ASSOCIATED WITH PLACEMENT OF IUDS
• CNS; NOT COMMON; PRESENTS AS SOLITARY BRAIN ABSCESS
TREATMENTS, PREVENTION AND CONTROL
1. DRAINAGE OF ABSCESS/DEBRIDEMENT
2.PROLONGED PENICILLIN TREATMENT .OTHERS ARE
CLINDAMYCIN,CARBAPENEMS.
STREPTOMYCES
• THE LARGEST GENUS OF ACTINOBACTERIA AND THE TYPE GENUS OF THE FAMILY
STREPTOMYCETACEAE.
• OVER 500 SPECIES OF STREPTOMYCES BACTERIA HAVE BEEN DESCRIBED.[
• FOUND PREDOMINANTLY IN SOIL AND DECAYING VEGETATION,
• MOST STREPTOMYCETES PRODUCE SPORES, AND ARE NOTED FOR THEIR DISTINCT "EARTHY"
ODOR THAT RESULTS FROM PRODUCTION OF A VOLATILE METABOLITE, GEOSMIN.
• STREPTOMYCETES ARE CHARACTERISED BY A COMPLEX SECONDARY METABOLISM.THEY
PRODUCE OVER TWO-THIRDS OF THE CLINICALLY USEFUL ANTIBIOTICS OF NATURAL ORIGIN
(E.G., NEOMYCIN, CYPEMYCIN, GRISEMYCIN, BOTTROMYCINS AND CHLORAMPHENICOL).
•
STREPTOMYCES
• THE ANTIBIOTIC STREPTOMYCIN TAKES ITS NAME DIRECTLY FROM
STREPTOMYCES. STREPTOMYCES'S ARE INFREQUENT PATHOGENS, THOUGH
INFECTIONS IN HUMANS, SUCH AS MYCETOMAS, CAN BE CAUSED BY S.
SOMALIENSIS AND S. SUDANENSIS, AND IN PLANTS CAN BE CAUSED BY S.
CAVISCABIES, S. ACIDISCABIES, S. TURGIDISCABIES AND S. SCABIES.
STREPTOMYCES IN MEDICINE
• STREPTOMYCES IS THE LARGEST ANTIBIOTIC-PRODUCING GENUS,
PRODUCING ANTIBACTERIAL, ANTIFUNGAL, AND ANTIPARASITIC DRUGS,
AND ALSO A WIDE RANGE OF OTHER BIOACTIVE COMPOUNDS, SUCH AS
IMMUNOSUPPRESSANTS.
• ALMOST ALL OF THE BIOACTIVE COMPOUNDS PRODUCED BY
STREPTOMYCES ARE INITIATED DURING THE TIME COINCIDING WITH THE
AERIAL HYPHAL FORMATION FROM THE SUBSTRATE MYCELIUM.
• STREPTOMYCETES PRODUCE NUMEROUS ANTIFUNGAL COMPOUNDS OF
MEDICINAL IMPORTANCE, INCLUDING NYSTATIN (FROM S. NOURSEI),
AMPHOTERICIN B (FROM S. NODOSUS),AND NATAMYCIN (FROM S.
NATALENSIS).
• CLAVULANIC ACID (FROM S. CLAVULIGERUS) IS A DRUG USED IN
COMBINATION WITH SOME ANTIBIOTICS (LIKE AMOXICILLIN) TO BLOCK
AND/OR WEAKEN SOME BACTERIAL-RESISTANCE MECHANISMS BY
IRREVERSIBLE BETA-LACTAMASE INHIBITION. NOVEL ANTIINFECTIVES
CURRENTLY BEING DEVELOPED INCLUDE GUADINOMINE (FROM
STREPTOMYCES SP. K01-0509), A COMPOUND THAT BLOCKS THE TYPE III
• MEMBERS OF THE GENUS STREPTOMYCES ARE THE SOURCE FOR NUMEROUS
ANTIBACTERIAL, ANTIPARASITIC ANTICANCER ETC. PHARMACEUTICAL AGENTS;
• CHLORAMPHENICOL (FROM S. VENEZUELAE),DAPTOMYCIN (FROM
S.ROSEOSPORUS),FOSFOMYCIN (FROM S. FRADIAE),LINCOMYCIN (FROM S.
LINCOLNENSIS),NEOMYCIN (FROM S. FRADIAE)
• S. AVERMITILIS IS RESPONSIBLE FOR THE PRODUCTION OF ONE OF THE MOST
WIDELY EMPLOYED DRUGS AGAINST NEMATODE AND ARTHROPOD INFESTATIONS,
IVERMECTIN.
• LESS COMMONLY, STREPTOMYCETES PRODUCE COMPOUNDS USED IN OTHER
MEDICAL TREATMENTS: MIGRASTATIN (FROM S. PLATENSIS) AND BLEOMYCIN
(FROM S. VERTICILLUS) ARE ANTINEOPLASTIC (ANTICANCER) DRUGS; BOROMYCIN
(FROM S. ANTIBIOTICUS) EXHIBITS ANTIVIRAL ACTIVITY AGAINST THE HIV-1
STRAIN OF HIV, AS WELL AS ANTIBACTERIAL ACTIVITY. STAUROSPORINE (FROM
S.STAUROSPOREUS) ALSO HAS A RANGE OF ACTIVITIES FROM ANTIFUNGAL TO
ANTINEOPLASTIC (VIA THE INHIBITION OF PROTEIN KINASES).
• S. HYGROSCOPICUS AND S. VIRIDOCHROMOGENES PRODUCE THE NATURAL
HERBICIDE BIALAPHOS
STREPTOMYCES IN MEDICINE …..
THANKS YOU !!!!

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Nocardia, Actinomyces and Streptomyces Latest1.pptx

  • 4. ACTINOMYCETES 1. LARGE GROUP = CHARACTERISTICS OF BACTERIA AND FUNGI 2. FORM BRANCHES OR FILAMENTS = HYPHAE 3. INFECTIONS RESEMBLE FUNGAL DISEASES 1. CHRONIC SUPPURATIVE DISEASE + SINUSES 4. BACTERIAL = PROCARYOTIC CELL WALL 1. LACK OF MITOCHONDRIA/MEMBRANE BOUND NUCLEUS 5. SUSCEPTIBLE TO PENICILLIN LIKE BACTERIA
  • 5. ACTINOMYCETES • BIOCHEMISTRY • THE ORGANISMS ARE IDENTIFIED BASED ON SUGAR FERMENTATIONS AND HYDROLYSIS REACTIONS (CASEINE, TYROSINE, ETC.) • CLINICAL SIGNIFICANCE • MYCETOMA – ORGANISM ENTERS THE BODY THROUGH BREAKS IN THE SKIN AND CAUSES A LOCALIZED INFECTION INVOLVING SKIN, CUTANEOUS, AND SUBCUTANEOUS TISSUE. • THE THREE MOST CHARACTERISTIC FEATURES SEEN ARE SWELLING, DRAINING SINUSES AND GRANULES. • THIS DISEASE CAN ALSO BE CAUSED BY FUNGI AS WELL AS NOCARDIA, ACTINOMADURA, AND STREPTOMYCES.
  • 6. ACTINOMYCETES • ACTINOMYCES SPECIES • NOCARDIA SPECIES • STREPTOMYCES SPECIES
  • 7. GRAM POSITIVE FILAMENTOUS BACTERIA GENUS OXYGEN GRANULE ACIDFAST Actinomyces ANAEROBE YES no Nocardia aerobe sometime PARTIALLY Streptomyces aerobe YES no
  • 9. ACTINOMYCES ANAEROBIC, FILAMENTOUS, GRAM POSITIVE BACILLUS • EXHIBIT TRUE BRANCHING • “MYKES” – GREEK FOR “FUNGUS” • THOUGHT BY EARLY MICROBIOLOGIST TO BE FUNGI BECAUSE OF: • MORPHOLOGY • DISEASE THEY CAUSE
  • 10. • A ISRAELII – ACTINOMYCOSIS • A BOVIS – LUMPY JAW, IN CATTLES • A VISCOSUS – DENTAL DISEASES • A NAESLUNDII - DENTAL DISEASES
  • 11. ACTINOMYCOSIS A CHRONIC SUPPURATIVE AND GRANULOMATOUS DISEASE OF THE CERVICO-FACIAL, THORACIC OR ABDOMINAL AREAS
  • 12. ACTINOMYCOSIS • SWELLING →FLUCTUANT →SINUS TRACT • 50% OF CASES - CERVICOFACIAL ACTINOMYCOSIS • 20% OF CASES - THORACIC ACTINOMYCOSIS • 20% OF CASES – ABDOMINAL ACTINOMYCOSIS
  • 13. 1. ACTINOMYCOSIS • ACTINOMYCES ISRAELII AND OTHERS • CERVICOFACIAL = MOST COMMON, LOWER JAW = ABSCESS FORMATION, SINUS TRACTS THAT REACH THE SKIN • THORACIC = ASPIRATION INTO LUNG, EXTENSION OF CERVICOFACIAL, HEMATOGENOUS • ABDOMINAL = TRAUMA OF INTESTINE OR ABDOMINAL WALL • GENITAL = INTRAUTERINE DEVICES = INFLAMMATION • DIAGNOSIS - EXAMINE PUS FOR WHITE OR YELLOW GRANULES/GRAM STAIN = FILAMENTOUS/CULTURE = LOOK FOR G+/IDENTIFY BY IMMUNOFLUORESCENCE
  • 14. ACTINOMYCOSIS NOT HIGHLY VIRULENT (OPPORTUNIST) • COMPONENT OF ORAL FLORA • PERIODONTAL POCKETS • DENTAL PLAQUE • TONSILAR CRYPTS • TAKE ADVANTAGE OF INJURY TO PENETRATE MUCOSAL BARRIERS • COINCIDENT INFECTION • TRAUMA • SURGERY
  • 15. ACTINOMYCOSIS • A CHRONIC SUPPURATIVE AND GRANULOMATOUS肉芽 肿DISEASE OF THE CERVICO-FACIAL, THORACIC OR ABDOMINAL AREAS
  • 16. ACTINOMYCOSIS FORM INDURATED MASSES WITH FIBROUS WALLS AND CENTRAL LOCULATIONS WITH PUS • PUS CONTAINS "SULFUR GRANULES" • GRITTY, YELLOW WHITE • AVERAGE DIAMETER - 2MM • COMPOSED OF MINERALIZED “MYCELIAL” MASS CHRONIC INFECTION • FORM BURROWING SINUS TRACTS TO SKIN OR MUCUS MEMBRANES • DISCHARGE PURULENT MATERIAL
  • 18. PULMONARY ACTINOMYCOSIS • 15% OF CASES • ASPIRATION OF ORGANISM FROM THE OROPAHARYNX • SLOWLY PROGRESSIVE PROCESS INVOLVING LUNG AND PLEURA • MAY BE MISTAKEN FOR MALIGNANCY • CHEST PAIN, FEVER, WGT LOSS AND HEMOPTYSIS
  • 19. LAB DIAGNOSIS • PUS FROM LESIONS, SINUS TRACKS, FISTULAS, SPUTUM OR BIOSPY MATERIALS • MICROSCOPIC EXAMINATION – SULPHUR GRANULES • CULTURE: THIOGLYCOLATE MEDIUM, ANAEROBICALLY, FOR 2 WEEKS
  • 20. ACTINOMYCOSIS/TREATMENT • SURGICAL DEBRIDEMENT OF DAMAGED TISSUE IS A PREREQUISITE TO ANTIBIOTIC THERAPY • PENICILLIN G FOR 3-4 WEEKS = TREATMENT OF CHOICE/TRIMETHOPRIM AND SULFAMETHOXAZOLE RESULTS IN A MORE RAPID CURE
  • 23. NORCADIA • THIN, G+, BRANCHING FILAMENTS • PARTIAL ACID FAST – 1% H2SO4 • DOES NOT FORM GRANULES • GROW AEROBIALLY • FOUND ON SOIL • MAY CAUSE • NORCADIOSIS • MYCETOMA
  • 24. Nocardia • Can cause pulmonary, systemic or cutaneous disease. • Special request for modified acid-fast stain. • Special request for Nocardia culture. – Grow on Sab agar and LJ agar – White, orange “chalky” colonies – Will grow on blood, chocolate but can take over a week and normal sputum culture plates only held 48 hours. • After suspect an actinomycetes will do further tests to determine genus/species (e.g., lysozyme sensitivity, casein decomposition)
  • 25. ACTINOMYCETES • THE AEROBIC GENERA: NOCARDIA, ACTINOMADURA, AND STREPTOMYCES. THERE ARE THREE CLINICALLY IMPORTANT SPECIES OF NOCARDIA – N. ASTEROIDES, N. BRASILENSIS, AND N. CAVIAE • MORPHOLOGY AND CULTURAL CHARACTERISTICS • G+ BRANCHING BACILLUS THAT MAY FRAGMENT TO BACILLARY OR COCCOID FORMS • AEROBIC • SPECIMENS SHOULD BE INOCULATED ONTO 7H10 AGAR OR LOWENSTEIN- JENSEN AGAR AND BRAIN HEART INFUSION AGAR. • COLONIES PRODUCED ARE TYPICALLY ORANGE, DRY, CRUMBLY, AND ADHERENT. • THE ORGANISMS ARE WEAKLY ACID FAST OR NON ACID FAST
  • 26. NOCARDIOSIS • SUBCUTANEOUS INFECTIONS, PULMONARY INFECTIONS, AND BRAIN ABSCESSES
  • 27. PATHOGENESIS AND CLINICAL FINDINGS • NORCADIOSIS – PULMONARY INFECTION – PNEUMONIA • HEMATOGENOUS SPREAD MAY LEAD TO BRAIN ABSCESS • DISEASE MAINLY IN IMMUNOCOMPROMISED INDIVIDUALS • AIDS, LEUKEMIA, LYMPHOMA, STEROIDS
  • 28. ACTINOMYCETES • NOCARDIOSIS – IS A LOCALIZED OR DISSEMINATED DISEASE OCCURRING AFTER INHALATION OF ORGANISMS. • PULMONARY INFECTIONS RESEMBLE TUBERCULOSIS AND CAN REMAIN CONFINED TO THE LUNGS OR MAY DISSEMINATE, WITH A PREDILECTION FOR THE BRAIN AND MENINGES. • THE DISEASE IS CHARACTERIZED BY MULTIPLE CONFLUENT ABSCESSES AND INTENSE SUPPURATION. • IT IS USUALLY A DISEASE OF COMPROMISED HOSTS. • ANTIMICROBIC SUSCEPTIBILITY/TREATMENT • MYCETOMA – AMINOGLYCOSIDES • NOCARDIOSIS – SULFONAMIDES OR SXT
  • 29. NOCARDIOSIS • N. ASTEROIDES – PULMONARY • N. BRASILIENSIS - ABSCESSES
  • 30.
  • 31.
  • 32. LAB. DIAGNOSIS • CLINICAL SPECIMENS:SPUTUM,PUS,BIOPSY TISSUE Sulfamethoxazole-Trimethoprim
  • 33. CLINICAL SPECIMENS • SPUTUM • PUS • BIOPSY TISSUE
  • 35. ACTINOMYCETES/INFECTIONS • NOCARDIOSIS/TREATMENT • SURGICAL DEBRIDEMENT • EARLY DIAGNOSIS IMPORTANT; POOR RECOVERY AFTER SYSTEMIC INFECTION • TREAT WITH COTRIMAZOLE OR SULFADIAZINE/ RESPIRATORY INFECTIONS MAY REQUIRE SEVERAL MONTHS
  • 37. MORPHOLOGY HIGHLY HETEROMORPHOUS IN CONTRAST TO UNICELLULAR ORGANISMS IN SUBMERGED CULTURES, HYPHAE ARE PRESENT AS MYCELIUM: DISPERSED HYPHAL FILAMENTS PELLET: SPHERICAL AGGLOMERATE OF HYPHAL ELEMENTS
  • 38. COMMERCIAL IMPORTANCE OF STREPTOMYCES BIOSYNTHESIS OF ANTIBIOTICS (STREPTOMYCIN, ERYTHROMYCIN, TETRACYCLINE, CHLORAMPHENICOL, ETC.) ANTIFUNGALS (AMPHOTERICIN B) ALKALOIDS (PHYSOSTIGMINE) ANTI-CANCER COMPOUNDS (MIGRASTATIN) USED AS HOST FOR HETEROLOGOUS GENE EXPRESSION (CURR OPIN BIOTECHNOL 2 (5): 674-81)
  • 44. The streptomyces species usually cause the disease entity known as mycetoma (fungus tumor). These infections are usually subcutaneous, but they can penetrate deeper and invade the bone. Some species produce a protease which inhibits macrophages. Material sent to the lab is pus or skin biopsy. The streptomycetes are aerobic like Nocardia, and can grow on both bacterial and fungal (SDA) media. They produce a chalky aerial mycelium with much branching. It is important to let the lab know the organism you suspect because most bacterial pathogens will grow out overnight, but the actinomycetes take longer to be visible on the culture plates (48-72 h).
  • 45. • THE VARIOUS SPECIES OF STREPTOMYCES PRODUCE GRANULES OF DIFFERENT SIZE, TEXTURE AND COLOR. THESE GRANULES ALONG WITH COLONIAL GROWTH AND BIOCHEMICAL TESTS ALLOW THE BACTERIOLOGIST OR MYCOLOGIST TO IDENTIFY EACH SPECIES. THE ORGANISMS ARE FOUND WORLD-WIDE. THERE ARE NO SEROLOGICAL TESTS, AND THE DRUGS OF CHOICE ARE THE • COMBINATION OF SULFAMETHOXAZOLE/TRIMETHOPRIM OR AMPHOTERICIN B. IN THE TROPICS THIS DISEASE MAY GO UNDIAGNOSED OR UNTREATED FOR SO LONG THAT SURGICAL AMPUTATION MAY BE THE ONLY EFFECTIVE TREATMENT.
  • 46. GENERAL PROPERTIES • THEY ARE FILAMENTOUS BACTERIA • THEIR MORPHOLOGY RESEMBLES THAT OF FILAMENTOUS FUNGI- ALSO KNOWN AS RAY FUNGI • HIGH G+C CONTENT THAN ANY OTHER BACTERIA • SOURCE OF MOST OF CURRENTLY USED ANTIBIOTICS ALSO PRODUCE METABOLITES THAT ARE ANTICANCER, ANTHELMINTHIC AND IMMUNOSUPPRESSIVE COMPLEX LIFE CYCLE • GRAM POSITIVE • SAPROPHYTIC AND MAINLY ACTING AS DECOMPOSERS IN THE SOIL • WIDE SPECTRUM ANTIBIOTIC ARE COMMERCIALLY PRODUCED FROM STREPTOMYCES • INTERMEDIATE GROUP BETWEEN BACTERIAL AND FUNGI • REPRESENTATIVE GENERA FOR THIS PRESENTATION; STREPTOMYCES, NORCADIA,ACTINOMYCES
  • 47. ACTINOMYCETES • IRREGULAR, NON SPORE FORMING GRAM POSITIVE RODS ,EITHER AS AEROBIC OR AS FACULTATIVE ANAEROBIC ISOLATES • NOCARDIA ARE CLOSELY RELATED TO THE GENERA MYCOBACTERIUM AND CORYNEBACTERIUM BUT DIFFER DISTINCTLY FROM ACTINOMYCES IN CELL WALL CHEMICAL CHARACTERISTICS AND PERCENTAGES OF GUANINE AND CYTOSINE • MYCOBACTERIUM SPECIES DIFFER BY THE PRESENCE OF RODS RATHER THAN OF FRAGMENTING MYCELIUM, BY RELATIVELY POOR GRAM-STAINING, AND BY STRONG ACID-FASTNESS • ACTINOMYCES- ANAEROBIC, NORMAL FLORA • NOCARDIA- AEROBIC, SAPROPHYTES-PARTIALY ACID FAST • STREPTOMYCES- AEROBIC, SAPROPHYTES
  • 48. NOCARDIA AND STREPTOMYCES ● OBLIGATE AEROBIC SAPROPHYTES, FOUND IN SOIL ● A FEW SPECIES ARE RARE OPPORTUNIST PATHOGENS, CAUSING DISEASE IN CASES IN WHICH PREDISPOSING FACTORS SUCH AS IMMUNITY OR NORMAL BODY DEFENSE MECHANISMS ARE GROSSLY IMPAIRED ●COLONIES VARY FROM HEAPED, WAXY, AND VARIABLY PIGMENTED TO DENSE, WHITE MYCELIAL, AND MOLD LIKE ● ALL GENERALLY GROW IN 3-5 DAYS AT 37°C AND ARE CATALASE POSITIVE. ● NOCARDIA ARE MOST COMMONLY ENCOUNTERED, BUT STREPTOMYCES MAY BE CULTURED FROM MYCETOMAS IN TROPICAL AREAS
  • 49. NORCADIA • THE PATHOGENIC NOCARDIA ARE OFTEN ACID-FAST (OR PARTIALLY SO), • GRAM-POSITIVE, • UREASE POSITIVE • BRANCHING FILAMENTOUS RODS THAT BREAK UP INTO BACILLARY OR COCCOID FORMS. • THEY ARE STRICTLY AEROBIC • FOUND IN THE SOIL. • THE SPECIES OF IMPORTANCE IS N. ASTEROIDS.
  • 50. NORCADIOSIS • BRONCHOPULMONARY IMMUNOCOMPROMISED PATIENTS ;POTENTIAL FOR DISSEMINATION TO THE CNS DX; PNEUMONIA WITH CAVITATION • CUTANEOUS OR SUB CUTANEOUS LESIONS; • CAN OCCUR IN HEALTHY INDIVIDUAL WITH TRAUMATIC INJURY LEAD T MYCETOMAS • PAINLESS ,SUBCUTANEOUS SINUS
  • 51. PATHOGENICITY NOCARDIOSIS IS USUALLY A CHRONIC, PROGRESSIVE DISEASE CHARACTERIZED BY SUPPURATING, GRANULOMATOUS LESIONS. THE ORGANISM PRODUCES ACUTE AND CHRONIC MASTITIS WITH GRANULOMATOUS LESIONS AND DRAINING SINUS TRACTS LOCALIZED SUBCUTANEOUS LESIONS OR LYMPH NODE INVOLVEMENT, OR BOTH, ARE SEEN. GENERALIZED NOCARDIOSIS CHARACTERIZED BY PNEUMONIA AND THE ACCUMULATION OF LARGE QUANTITIES OF RED FLUID IN THE THORACIC OR ABDOMINAL CAVITY, THE FLUID IN THESE CAVITIES IS SEROSANGUINOUS AND INFREQUENTLY CONTAINS SMALL (<1 MM) SULFUR LIKE GRANULES. CARE MUST BE TAKEN TO DISTINGUISH ANY 'NOCARDIA' ISOLATED FROM A. VISCOUS
  • 52. DIRECT EXAMINATION • GRANULES, IF PRESENT, ARE EXAMINED AS DESCRIBED EARLIER. • GRAM-STAINED SMEARS OF PUS OR CRUSHED GRANULES REVEAL GRAM- POSITIVE BRANCHING FILAMENTS, WITH OR WITHOUT CLUBS • THE MODIFIED ACID-FAST STAIN OFTEN SHOWS THE RETENTION OF SOME CARBOLFUCHSIN, BUT THIS IS NOT A RELIABLE CHARACTERISTIC OF NOCARDIA. • PUS CONTAINING THE CHARACTERISTIC ELEMENTS IS INOCULATED ONTO SEVERAL BLOOD SLANTS OR PLATES AND SABOURAUD DEXTROSE AGAR WITHOUT INHIBITORS. INCUBATE AT ROOM TEMPERATURE AND AT 37°C FOR UP TO A WEEK.
  • 53. CULTURAL CHARACTERISTICS • GROWTH IS EVIDENT IN 4-5 DAYS, AND COLONIES ARE IRREGULARLY FOLDED, RAISED, AND SMOOTH OR GRANULAR. • THE COLOR VARIES FORM WHITE THROUGH YELLOW TO DEEP ORANGE. • GRAM-POSITIVE, PARTIALLY ACID-FAST MYCELIAL FILAMENTS, WHICH BREAK UP INTO BACILLARY FORMS, ARE EVIDENT UNDER OIL IMMERSION. • THE PRESENCE OF MYCELIAL ELEMENTS DISTINGUISHES NOCARDIA • FROM SAPROPHYTIC AND ATYPICAL MYCOBACTERIA. THE MYCELIAL FORMS OF THE NOCARDIA CAN BE READILY SEEN IN SLIDE CULTURES ON SABOURAUD DEXTROSE AGAR. THE SPECIES GROWS WELL AT 45°C. • IDENTIFICATION; A HIGHLY PRESUMPTIVE IDENTIFICATION OF N. ASTEROIDES INFECTION IS BASED ON PATHOLOGY, DEMONSTRATION OF TYPICAL ORGANISMS, AND COLONIAL, CULTURAL, AND MORPHOLOGICAL CHARACTERISTICS.
  • 54. ANTIBIOTIC SUSCEPTIBILITY • BROTH MICRODILUTION METHOD IS RECOMMENDED BY THE CLSI FOR ANTIMICROBIAL SUSCEPTIBILITY TESTING FOR NOCARDIA SPP • A STUDY OF IN VITRO SUSCEPTIBILITY HAS SHOWN THAT ALL N. ASTEROIDES TESTED WERE SENSITIVE TO SULFIXAZOLE, TRIMETHOPRIM-SULFAMETHAZOLE, DOXYCYCLINE, AND MINOCYCLINE AND MOST TO AMPICILLIN; ABOUT HALF WERE RESISTANT TO TETRACYCLINE
  • 55. ACTINOMYCES • ARE GRAM-POSITIVE, DIPHTHEROIDAL OR BRANCHING FILAMENTOUS RODS, 0.2-1.0 ΜΠΊ IN DIAMETER. • SHORT RODS, WHICH MAY SHOW CLUBBED ENDS, ARE COMMON AND MAY OCCUR SINGLY, IN DIPHTHEROIDAL PAIRS, IN SHORT CHAINS, OR IN CLUSTERS. ACTINOMYCES PYOGENES ARE COMMONLY COCCOBACILLARY IN AN AEROBIC ATMOSPHERE. • ACTINOMYCES ARE FACULTATIVE ANAEROBIC, WITH MOST SPECIES BEING PREFERENTIALLY ANAEROBIC ALTHOUGH SOME SPECIES GROW WELL IN AIR; 10% C02 IMPROVES GROWTH OF AERO TOLERANT SPECIES AND IS REQUIRED FOR AERO TOLERANT STRAINS OF PREFERENTIALLY ANAEROBIC SPECIES • ACTINOMYCES ARE THUS FERMENTATIVE IN METABOLISM WHEREAS NOCARDIA ARE OXIDATIVE. • COLONIES MY BE EITHER ROUGH AND DRY OR SOFT AND MUCOID, WITH TRANSITIONAL FORMS BEING COMMON. • ACTINOMYCES CAUSE CHRONIC INFECTIONS OF SOFT AND HARD TISSUES, OFTEN WITH THE FORMATION OF SULFUR GRANULES.
  • 56. ACTINOMYCOSIS • THE PRESENCE OF SULFUR GRANULES, WHILE STRIKING, IS NOT DIAGNOSTIC OF ACTINOMYCES INFECTIONS BUT ALSO OCCURS IN NOCARDIA OR STREPTOMYCES INFECTIONS. • ACTINOMYCES INFECTIONS ARE OFTEN ASSOCIATED WITH THE PRESENCE OF FOREIGN BODIES USUALLY DISRUPTED BY TRAUMA OR SURGERY OR DENTISTRY OR OTHER INFECTION • INFECTION IS ENDOGENOUS • CERVICOFACIAL; • ‘’LUMPY JAW’’ ASSOCIATED WITH RECENT DENTAL WORK, JAW TRAUMA, POOR ORAL HYGIENE • ‘’ SULFUR GRANULES’’
  • 57. Gram Stain and Macroscopic Colonies of Actinomyces NOTE: Molar tooth appearance of colonies on agar can help remind us that the oral cavity is a common niche for Actinomyces.
  • 58. Cervicofacial Actinomycosis NOTE: Sinus tract originating in oral cavity has made it’s way to the surface at the jawline.
  • 59. ACTINOMYCOSIS • PELVIC; ASSOCIATED WITH PLACEMENT OF IUDS • CNS; NOT COMMON; PRESENTS AS SOLITARY BRAIN ABSCESS TREATMENTS, PREVENTION AND CONTROL 1. DRAINAGE OF ABSCESS/DEBRIDEMENT 2.PROLONGED PENICILLIN TREATMENT .OTHERS ARE CLINDAMYCIN,CARBAPENEMS.
  • 60. STREPTOMYCES • THE LARGEST GENUS OF ACTINOBACTERIA AND THE TYPE GENUS OF THE FAMILY STREPTOMYCETACEAE. • OVER 500 SPECIES OF STREPTOMYCES BACTERIA HAVE BEEN DESCRIBED.[ • FOUND PREDOMINANTLY IN SOIL AND DECAYING VEGETATION, • MOST STREPTOMYCETES PRODUCE SPORES, AND ARE NOTED FOR THEIR DISTINCT "EARTHY" ODOR THAT RESULTS FROM PRODUCTION OF A VOLATILE METABOLITE, GEOSMIN. • STREPTOMYCETES ARE CHARACTERISED BY A COMPLEX SECONDARY METABOLISM.THEY PRODUCE OVER TWO-THIRDS OF THE CLINICALLY USEFUL ANTIBIOTICS OF NATURAL ORIGIN (E.G., NEOMYCIN, CYPEMYCIN, GRISEMYCIN, BOTTROMYCINS AND CHLORAMPHENICOL). •
  • 61. STREPTOMYCES • THE ANTIBIOTIC STREPTOMYCIN TAKES ITS NAME DIRECTLY FROM STREPTOMYCES. STREPTOMYCES'S ARE INFREQUENT PATHOGENS, THOUGH INFECTIONS IN HUMANS, SUCH AS MYCETOMAS, CAN BE CAUSED BY S. SOMALIENSIS AND S. SUDANENSIS, AND IN PLANTS CAN BE CAUSED BY S. CAVISCABIES, S. ACIDISCABIES, S. TURGIDISCABIES AND S. SCABIES.
  • 62. STREPTOMYCES IN MEDICINE • STREPTOMYCES IS THE LARGEST ANTIBIOTIC-PRODUCING GENUS, PRODUCING ANTIBACTERIAL, ANTIFUNGAL, AND ANTIPARASITIC DRUGS, AND ALSO A WIDE RANGE OF OTHER BIOACTIVE COMPOUNDS, SUCH AS IMMUNOSUPPRESSANTS. • ALMOST ALL OF THE BIOACTIVE COMPOUNDS PRODUCED BY STREPTOMYCES ARE INITIATED DURING THE TIME COINCIDING WITH THE AERIAL HYPHAL FORMATION FROM THE SUBSTRATE MYCELIUM. • STREPTOMYCETES PRODUCE NUMEROUS ANTIFUNGAL COMPOUNDS OF MEDICINAL IMPORTANCE, INCLUDING NYSTATIN (FROM S. NOURSEI), AMPHOTERICIN B (FROM S. NODOSUS),AND NATAMYCIN (FROM S. NATALENSIS). • CLAVULANIC ACID (FROM S. CLAVULIGERUS) IS A DRUG USED IN COMBINATION WITH SOME ANTIBIOTICS (LIKE AMOXICILLIN) TO BLOCK AND/OR WEAKEN SOME BACTERIAL-RESISTANCE MECHANISMS BY IRREVERSIBLE BETA-LACTAMASE INHIBITION. NOVEL ANTIINFECTIVES CURRENTLY BEING DEVELOPED INCLUDE GUADINOMINE (FROM STREPTOMYCES SP. K01-0509), A COMPOUND THAT BLOCKS THE TYPE III
  • 63. • MEMBERS OF THE GENUS STREPTOMYCES ARE THE SOURCE FOR NUMEROUS ANTIBACTERIAL, ANTIPARASITIC ANTICANCER ETC. PHARMACEUTICAL AGENTS; • CHLORAMPHENICOL (FROM S. VENEZUELAE),DAPTOMYCIN (FROM S.ROSEOSPORUS),FOSFOMYCIN (FROM S. FRADIAE),LINCOMYCIN (FROM S. LINCOLNENSIS),NEOMYCIN (FROM S. FRADIAE) • S. AVERMITILIS IS RESPONSIBLE FOR THE PRODUCTION OF ONE OF THE MOST WIDELY EMPLOYED DRUGS AGAINST NEMATODE AND ARTHROPOD INFESTATIONS, IVERMECTIN. • LESS COMMONLY, STREPTOMYCETES PRODUCE COMPOUNDS USED IN OTHER MEDICAL TREATMENTS: MIGRASTATIN (FROM S. PLATENSIS) AND BLEOMYCIN (FROM S. VERTICILLUS) ARE ANTINEOPLASTIC (ANTICANCER) DRUGS; BOROMYCIN (FROM S. ANTIBIOTICUS) EXHIBITS ANTIVIRAL ACTIVITY AGAINST THE HIV-1 STRAIN OF HIV, AS WELL AS ANTIBACTERIAL ACTIVITY. STAUROSPORINE (FROM S.STAUROSPOREUS) ALSO HAS A RANGE OF ACTIVITIES FROM ANTIFUNGAL TO ANTINEOPLASTIC (VIA THE INHIBITION OF PROTEIN KINASES). • S. HYGROSCOPICUS AND S. VIRIDOCHROMOGENES PRODUCE THE NATURAL HERBICIDE BIALAPHOS STREPTOMYCES IN MEDICINE …..