Anda di halaman 1dari 114

Microbial causing

respiratory tract. infection


dr Titik Nuryastuti MSi., PhD.
Microbiology Dept.
Faculty of Medicine, UGM
INFEKSI SALURAN NAFAS
Infeksi Saluran nafas meliputi:
Faringitis

Influenza

Otitis

Sinusitis

Laringitis

Bronkhitis

Pneumonia

Tuberkulosis paru
BAKTERI PENYEBAB INFEKSI
SALURAN NAFAS
S. aureus
S. pyogenes
S. pneumoniae
C. diphteriae
N. gonorrhoeae
N. meningitidis
H. influenzae
K. pneumoniae
M. tuberculosis
Mycoplasma pneumoniae
Chlamydia psittaci
B. pertusis
P. aeruginosa
STAPHYLOCOCCUS
Morfologi sel

Bentuk bulat
Tersusun: bergerombol / tersebar / dua-dua / tetrat
Tidak membentuk spora

Morfologi koloni

Koloni bulat, halus, cembung, mengkilat


Ada yang menghemolisa eritrosit, terutama
S. aureus.
Lanjutan...
Staphylococcus aureus forms a fairly large yellow colony on rich
medium, S. epidermidis has a relatively small white colony.
S. aureus is often hemolytic on blood agar; S. epidermidis is non
hemolytic.
Staphylococci are facultative anaerobes that grow by aerobic
respiration or by fermentation that yields principally lactic acid.
The bacteria are catalase-positive and oxidase-negative.
S. aureus can grow at a temperature range of 15 to 45 degrees
and at NaCl concentrations as high as 15 percent.
Nearly all strains of S. aureus produce the enzyme coagulase:
nearly all strains of S. epidermidis lack this enzyme.
S. aureus should always be considered a potential pathogen; most
strains of S. epidermidis are nonpathogenic and may even play a
protective role in their host as normal flora. Staphylococcus
epidermidis may be a pathogen in the hospital environment
Morfologi
Staphylococci are perfectly spherical cells
about 1 micrometer in diameter.
They grow in clusters because
staphylococci divide in two planes. The
configuration of the cocci helps to
distinguish staphylococci from
streptococci, which are slightly oblong
cells that usually grow in chains (because
they divide in one plane only)
catalase test
The catalase test is important in distinguishing
streptococci (catalase-negative) from
staphylococci, which are vigorous catalase-
producers.
The test is performed by adding 3% hydrogen
peroxide to a colony on an agar plate or slant.
Catalase-positive cultures produce O2 and bubble
at once. The test should not be done on blood
agar because blood itself contains catalase
IDENTIFIKASI BAKTERI KOKUS GRAM POSITIP

Bahan pemeriksaan

Agar darah BHI/ +darah

Identifikasai morfologi koloni

Cat Gram

Staphylococcus Streptococcus
Staphylococcus

I. Cat Gram
II. Katalase
III. Koagulase

(+) (-)
S. aureus Non SA

Novobiosin
S
(S. epidermidis) R
(S.saprophyticus)
Laboratory Diagnosis: Specimen
Collection and Handling
Samples must be taken from the actual site of
infection
Prevent delay in transport of collected material
from infected sites
Transport in appropriate collection device that
would prevent drying and minimize growth of
contaminating organisms
Identification of Staphylococcus in
Samples
Frequently isolated from pus, tissue
exudates, sputum, urine, and blood
Cultivation, catalase, biochemical testing,
coagulase
Laboratory Diagnosis:
Direct Smear Examination
Microscopic Examination
Gram-positive cocci
pairs and clusters Insert Figure 10-1
Numerous
polymorphonuclear cells
(PMNs)
Laboratory Diagnosis:
Cultural Characteristics
Colony morphology
Smooth, butyrous,
white to yellow,
creamy
Grow well @ 18-24
hours
S. aureus may produce
hemolysis on blood
agar

S. aureus
Laboratory Diagnosis: Cultural
Characteristics
Coagulase-negative
staphylococci
Smooth, creamy, white
Small-to medium-
sized, usually non-
hemolytic

S. saprophyticus
Smooth, creamy, may
produce a yellow
pigment
Identification Tests: Catalase
Principle: tests for enzyme catalase
2 H2O2 2 H2O + O2

Drop H2O2 onto smear

Bubbling = POS (Most bacteria, O2 generated)

No bubbling = NEG (Streptococci and other lactic


acid bacteria, no O2 generated)
Gram stain of Staphylococcus aureus in
pustular exudate
Gram stain of Staphylococcus aureus
Electron micrograph Staphylococcus aureus
TOKSIN DAN ENZIM

1. Eksotoksin menyebabkan nekrosa pada kulit


2. Leukosidin pad S. aureus mampu membunuh leukosit
3. Koagulase dapat menggumpalkan plasma-sitrat/ oksalat
gumpalan fibrin pada permukaan sel bakteri. S. aureus (+)

4. Katalase merubah H2 O2 H2O + O2


5. Hialuronidase memecah asam hialuronat (komponen jaringan ikat) dan
merupakan faktor penyebaran

6. Stafilokinase menyebabkan fibrinolisis, tetapi tidak sekuat streptokinase


7. Enzim lain seperti : proteinase, lipase, beta-laktamase
8. Toksin eksfoliatif menyebabkan desquamasi kulit
9. Sebagian besar S aureus menghasilkan Toxic shock syndrome toxin-1 (TSST-1)
yang mirip dengan enterotoksin F dan eksotoksin Pirogenik C

10. Enterotoksin ada 6 (A-F)


* dihasilkan oleh hampir 50% S. aureus,
* toksin tahan panas,
* tidak rusak oleh enzim di usus.
* disintesa bila S. aureus tumbuh dalam karbohidrat/ protein
INFEKSI STAPHYLOCOCCUS

Dapat terjadi karena kontak langsung dengan luka atau


infeksi setelah terjadi trauma

Berupa pimple/ abses/ infeksi pada folikel rambut.

Terjadi keracunan makanan karena enterotoksin


(Inkubasi 1-8 jam dengan gejala :mual, muntah, diare)

Toxic shock syndrome (TSS)


demam tinggi mendadak, muntah, diare, mialgia
S. aureus yang menyebabkan TSS dapat diisolasi dari:
vagina, tampon, luka, tenggorok / lainnya (tidak dari darah)

Infeksi saluran nafas

Bakteremia
Bila terjadi bakteremia
Endokarditis
Osteomilitis hematogen akut
Meningitis
Infeksi pulmo
TERAPI
Antibiotika gol. Penisilin dan yang lain.
Penisilin yang -laktamase : Sefalosporin, Vankomisin,
Metisilin (metilisin : S. aureus 10-20%; S. epidermisis 75%)
Staphylococcus sudah banyak yang resisten terhadap
Tetrasiklin, Penisilin, Eritromisin

Resistensi dapat disebarkan oleh plasmid atau dengan cara


transduksi

Resistensi terhadap penisilin karena :


Mutasi
-laktamase (dihasilkan oleh 90% S. aureus)
Virulence factors of S. aureus
Enzymes:
Coagulase coagulates plasma and blood;
produced by 97% of human isolates;
diagnostic
Hyaluronidase digests connective tissue
Staphylokinase digests blood clots
DNase digests DNA
Lipases digest oils; enhances
colonization on skin
Penicillinase inactivates penicillin
Virulence factors of S. aureus
Toxins:
Hemolysins (, , , ) lyse red blood cells
Leukocidin lyses neutrophils and macrophages
Enterotoxin induce gastrointestinal distress
Exfoliative toxin separates the epidermis
from the dermis
Toxic shock syndrome toxin (TSST) - induces
fever, vomiting, shock, systemic organ damage
Epidemiology and Pathogenesis
Present in most environments frequented by
humans
Readily isolated from fomites
Carriage rate for healthy adults is 20-60%.
Carriage is mostly in anterior nares, skin,
nasopharynx, intestine.
Predisposition to infection include: poor hygiene
and nutrition, tissue injury, preexisting primary
infection, diabetes, immunodeficiency.
Increase in community acquired methicillin
resistance - MRSA
Staphylococcal Disease
Range from localized to systemic
Localized cutaneous infections invade skin
through wounds, follicles, or glands
folliculitis superficial inflammation of hair follicle;
usually resolved with no complications but can progress
furuncle boil; inflammation of hair follicle or sebaceous
gland progresses into abscess or pustule
carbuncle larger and deeper lesion created by
aggregation and interconnection of a cluster of furuncles
impetigo bubble-like swellings that can break and peel
away; most common in newborns
Staphylococcus aureus: Clinical
Infections
Skin and wound
Impetigo
Furuncles/Boils
(Infection of hair
follicles usually in
areas that sweat)
Carbuncles (clusters of
boils)
Surgical wound
infections
Food poisoning: Bullous impetigo
source is infected
food handler
Staphylococcal Disease
Systemic infections
osteomyelitis infection is established in
the metaphysis; abscess forms
bacteremia - primary origin is bacteria
from another infected site or medical
devices; endocarditis possible
Staphylococcal Disease
Toxigenic disease
food intoxication ingestion of heat
stable enterotoxins; gastrointestinal
distress
staphylococcal scalded skin syndrome
toxin induces bright red flush, blisters, then
desquamation of the epidermis
toxic shock syndrome toxemia leading
to shock and organ failure
Staphylococcus aureus: Clinical Infections
Scalded skin syndrome= Ritters disease
Extensive exfoliative dermatitis
Young children and newborns
Staphylococcus aureus: Clinical
Infections
Toxic shock syndrome

Other infections
Respiratory (less often)
pneumonia
Bacteremia
Osteomyelitis/arthritis
Endocarditis
Pseudomembranous enterocolitis
Other Staphylococci
Coagulase-negative staphylococcus; frequently
involved in nosocomial and opportunistic infections
S. epidermidis lives on skin and mucous
membranes; endocarditis, bacteremia, UTI
S. hominis lives around apocrine sweat glands
S. capitis live on scalp, face, external ear
All 3 may cause wound infections by penetrating
through broken skin.
S. saprophyticus infrequently lives on skin,
intestine, vagina; UTI
Clinical Concerns and Treatment
95% have penicillinase and are
resistant to penicillin and ampicillin.
MRSA methicillin-resistant S. aureus
carry multiple resistance
Abscesses have to be surgically
perforated.
Systemic infections require intensive
lengthy therapy.
Prevention of Staphylococcal Infections
Universal precautions by healthcare
providers to prevent nosocomial infections
Hygiene and cleansing
Coagulase-Negative Staphylococci
Habitat: skin and mucous membranes
Common human isolates
S. epidermidis
S. saprophyticus
S. haemolyticus
Coagulase-Negative Staphylococci:
Staphylococcus epidermidis
Virulence factor: slime Helps to prevent
phagocytosis
Mode of transmission: implantation of medical
devices such as catheters, shunts, and prosthetic
devices
Infections are acquired nosocomially
Serious infections among immunosuppressed
patients may occur
Coagulase-Negative Staphylococci:
Staphylococcus saprophyticus
Habitat: skin and mucosal membranes
of the genitourinary tract
Common cause of urinary tract
infections in young, sexually active
females
When present in urine cultures, may
be found in low numbers, but
significant
STREPTOCOCCUS
Morfologi dan Identifikasi
Streptococcus terdiri dari 20 spesies, berdasarkan :
* Karakteristik koloni
* Tipe hemolisa pada agar darah
* Reaksi biokimia
* Reaksi spesifik antigen pada dinding sel

Sifat-sifat
Bakteri berbentuk bulat
bersifat Gram positip
tersusun berderet seperti rantai
sebagian bersifat fakultatif anaerob
Streptococcus
Hemolisa


Bile soluble Basitrasin
Bile esculin
(0,04 U)
(-) (+)
Lisis (-) S
(S. viridans) (grup D)
(S. pneumoniae)
(Strep. Grup A)
R
optochin
NaCl 6, 5%
S
(S. pneumoniae) (+) (-)
R
Enterococci) Non
(Strep. Non pnm)
Gram stain of Streptococcus pyogenes in a clinical specimen
Colonies of Streptococcus pyogenes on blood agar exhibiting beta (clear)
hemolysis
Sheep blood agar with colonies of beta-hemolytic group A
streptococcus
Hemolysis on blood agar
The type of hemolytic reaction displayed on blood
agar has long been used to classify the
streptococci.
Beta -hemolysis is associated with complete lysis of
red cells surrounding the colony,
whereas alpha-hemolysis is a partial or "green"
hemolysis associated with reduction of red cell
hemoglobin.
Nonhemolytic colonies have been termed gamma-
hemolytic.

Hemolysis is affected by the species and age of red cells,


as well as by other properties of the base medium.
Continued...
Group A streptococci are nearly always
beta-hemolytic; related Group B can manifest
alpha, beta or gamma hemolysis.
Most strains of S. pneumoniae are alpha-
hemolytic but can cause -hemolysis during
anaerobic incubation.
Most of the oral streptococci and enterococci are
non hemolytic. The property of hemolysis is not
very reliable for the absolute identification of
streptococci, but it is widely used in rapid screens
for identification of S. pyogenes and S.
pneumoniae.
Recent classsifacion based on...
colony morphology and hemolytic
reactions on blood agar
serologic specificity of the cell wall group-
specific substance and other cell wall or
capsular antigens
biochemical reactions and resistance to
physical and chemical factors
ecologic features
Kapsul Streptococci :
polisakarida.
asam hialuronat(Sebagian besar Streptococcus grup A,B,C)

Dinding sel Streptococcus mengandung :


* Protein M, T dan R
* Karbohidrat (spesifik untuk grup)
* Peptidoglikan
* Streptococcus grup A mempunyai pili
yang menembus kapsul
tersusun dari protein M
diselubungi oleh asam teikoat
penting untuk porlekatan pada sel epitel
ANTIGEN UTAMA STREPTOCOCCUS

1. KARBOHIDRAT
Sebagai dasar penggolongan grup (dari gula amino)
Grup A : ramnosa asetil glukosamin
B : ramnosa glukosamin polisakarida
C : ramnosa-N asetilgalaktosamin
D : gliserol asam teikoat mengandung d-alanin
dan glukosa
F : glukopiranosil-N-asetilgalaktosamin
2. SUBSTANSI T
tidak berhubungan dengan virulensi
tidak tahan asam dan panas.
Antigen permukaan yang lain protein R
3. PROTEIN M
* Faktor virulensi utama pada S. pyogenes grup A.
* lebih dari 80 tipe protein M.
* ada 2 kelas utama protein M (I dan II)
Antibodi terhadap M I bereaksi silang dengan
jaringan otot jantung merupakan determinan
virulensi pada demam rematik
4. NUKLEOPROTEIN
Diperoleh dengan mengekstraksi Streptococcus
dengan basa lemah.
Ekstrak tsb juga mengandung substansi P
Patogenesis dan Penyakit
A. Penyakit yang disebabkan oleh invasi S. pyogenes
infeksi cepat menyebar melalui saluran limfa darah
1. Erysipelas (bila infeksi melalui kulit): pembengkakan kecoklatan
dan cepat menyebar
2. Puerperal fever (masuk uterus setelah melahirkan
endometritis septicemia
3. Sepsis karena infeksi streptococcus pada luka / post operasi

B. Infeksi lokal oleh S. pyogenes :


1. Infeksi tenggorokan
Bakteri melekat pada sel epitel faring (asam teikoat X
fibronektin) infeksi telinga tengah
meningitis (anak)
Pada dewasa infeksi akut, 20% infeksi asimptomatis
Bila bakteri menghasilkan toksin eritrogenik dan pirogenik A-C
dapat terjadi scarlet fever rush (inflamasi,
kerusakan jaringan, abses peritonsil,
pembengkakan bagian belakang
mulut pernafasan terganggu)
2. Infeksi lokal pada kulit impetigo
Streptococcus grup A antigen M tipe 49, 57, 59, 61 dan
kemungkinan dapat menyebabkan
glomerulonefritis
C. Infeksi endokarditis
1. Endokarditis akut
2. Endokarditis sub akut
* terjadi pada 30% post cabut gigi (oleh S. viridans)
* 5-10% oleh enterococci
D. Sindrome toxic shock
shock, bakterimia, kegagalan pernafasan dan organ
kematian 30%
E. Infeksi lain : Enterococci ISK

Post infeksi Streptococcus Grup A


1. Glomerulonefritis akut
* Terjadi 3 minggu setelah infeksi streptococcus pada kulit.
* Oleh type M 12, 4, 2, K 49
* Terjadi krn reaksi antigen-AB dan membran glomerulo

2. Demam rematik
* Terjadi kerusakan pada klep dan otot jantung
* Antigen membran strain grup A otot jantung manusia
Electron micrographs of Streptococcus pyogenes

Taken from the lab.


Of Pathology and
Immunology at
Rockefeller
University
General Characteristics of Streptococci
Gram-positive spherical/ovoid cocci arranged in
long chains; commonly in pairs
Non-spore-forming, nonmotile
Can form capsules and slime layers
Facultative anaerobes
Do not form catalase, but have a peroxidase
system
Most parasitic forms are fastidious and require
enriched media.
Small, nonpigmented colonies
Sensitive to drying, heat and disinfectants
25 species
Streptococci
Lancefield classification system based
on cell wall Ag 17 groups (A,B,C,.)
Another classification system is based
on hemolysis reactions.
-hemolysis A,B,C,G and some D
strains
hemolysis S. pneumoniae and
others collectively called viridans
Human Streptococcal Pathogens
S. pyogenes
S. agalactiae
Viridans streptococci
S. pneumoniae
Enterococcus faecalis
-hemolytic S. pyogenes
Most serious streptococcal pathogen
Strict parasite
Inhabits throat, nasopharynx,
occasionally skin
Virulence Factors of -hemolytic
S. pyogenes

Produces surface antigens:


C-carbohydrates protect against
lysozyme
Fimbriae - adherence
M-protein contributes to resistance to
phagocytosis
Hyaluronic acid capsule provokes no
immune response
Virulence Factors of -hemolytic
S. pyogenes
Extracellular toxins:
streptolysins hemolysins; streptolysin O
(SLO) and streptolysin S (SLS) both cause
cell and tissue injury
pyogenic toxin (erythrogenic) induces
fever and typical red rash
superantigens strong monocyte and
lymphocyte stimulants; cause the release of
tissue necrotic factor
Virulence Factors of -hemolytic
S. pyogenes
Extracellular enzymes
streptokinase digests fibrin clots
hyaluronidase breaks down connective
tissue
DNase hydrolyzes DNA
Epidemiology and Pathogenesis
Humans only reservoir
Inapparent carriers
Transmission contact, droplets, food, fomites
Portal of entry generally skin or pharynx
Children predominant group affected for
cutaneous and throat infections
Systemic infections and progressive sequelae
possible if untreated
Scope of Clinical Disease
Skin infections
Impetigo (pyoderma) superficial lesions that
break and form highly contagious crust; often
occurs in epidemics in school children; also
associated with insect bites, poor hygiene, and
crowded living conditions
Erysipelas pathogen enters through a break in
the skin and eventually spreads to the dermis and
subcutaneous tissues; can remain superficial or
become systemic
Throat infections
Streptococcal pharyngitis strep throat
Scope of Clinical Disease
Systemic infections
Scarlet fever strain of S. pyogenes
carrying a prophage that codes for
pyrogenic toxin; can lead to sequelae
Septicemia
Pneumonia
Streptococcal toxic shock syndrome
Long-Term Complications of Group
A Infections
Rheumatic fever follows overt or
subclinical pharyngitis in children; carditis
with extensive valve damage possible,
arthritis, chorea, fever
Acute glomerulonephritis nephritis,
increased blood pressure, occasionally
heart failure; can become chronic leading to
kidney failure
Treatment and Prevention
Groups A and B are treated with
penicillin.
Sensitivity testing needed for
enterococci
Vaccines against pneumococus is still
investigated
Streptococcus pneumoniae

The pneumococci (S pneumoniae) are


gram-positive diplococci, often lancet-
shaped or arranged in chains, possessing
a capsule of polysaccharide that permits
typing with specific antisera.
Pneumococci are normal inhabitants of the
upper respiratory tract of 540% of
humans and can cause pneumonia,
sinusitis, otitis, bronchitis, bacteremia,
meningitis, and other infectious processes.
Morphology & Identification
Typical Organisms
The typical gram-positive, lancet-shaped diplococci are
often seen in specimens of young cultures. In sputum or
pus, single cocci or chains are also seen. With age, the
organisms rapidly become gram-negative and tend to lyse
spontaneously.
Autolysis of pneumococci is greatly enhanced by surface-
active agents. Lysis of pneumococci occurs in a few minutes
when ox bile (10%) or sodium deoxycholate (2%) is added
to a broth culture or suspension of organisms at neutral pH.
Viridans streptococci do not lyse and are thus easily
differentiated from pneumococci.
On solid media, the growth of pneumococci is inhibited
around a disk of Optochin; viridans streptococci are not
inhibited by Optochin.
Characteristic
Culture
Pneumococci form small round colonies, at first dome-shaped and later
developing a central plateau with an elevated rim. Pneumococci are hemolytic
on blood agar. Growth is enhanced by 510% CO2.
Variation
Pneumococcal isolates that produce large amounts of capsules produce large
mucoid colonies. Capsule production is not essential for growth on agar medium,
and capsular production is, therefore, lost after a small number of subcultures.
The pneumococci will, however, again produce capsules and have enhanced
virulence if injected into mice.
Antigenic Structure
Component Structures
The pneumococcal cell wall has peptidoglycan and teichoic acid, like other
streptococci. The capsular polysaccharide is covalently bound to the
peptidoglycan and to the cell wall polysaccharide. The capsular
polysaccharide is immunologically distinct for each of the more than 90
types.
Quellung Reaction
When pneumococci of a certain type are mixed with specific
antipolysaccharide serum of the same typeor with polyvalent antiserum
on a microscope slide, the capsule swells markedly, and the organisms
agglutinate by cross-linking of the antibodies. This reaction is useful for
rapid identification and for typing of the organisms, either in sputum or in
cultures. The polyvalent antiserum, which contains antibody to all of the
types ("omniserum"), is a good reagent for rapid microscopic determination
of whether or not pneumococci are present in fresh sputum.
Pathogenesis
Types of Pneumococci
In adults, types 18 are responsible for about 75% of cases of pneumococcal pneumonia
and for more than half of all fatalities in pneumococcal bacteremia; in children, types 6, 14,
19, and 23 are frequent causes.

Production of Disease
Pneumococci produce disease through their ability to multiply in the tissues. They produce
no toxins of significance. The virulence of the organism is a function of its capsule, which
prevents or delays ingestion by phagocytes. A serum that contains antibodies against the
type-specific polysaccharide protects against infection. If such a serum is absorbed with the
type-specific polysaccharide, it loses its protective power.

Loss of Natural Resistance


Since 4070% of humans are at some time carriers of virulent pneumococci, the normal
respiratory mucosa must possess great natural resistance to the pneumococcus.

Predisposing factor :
(1) Viral and other respiratory tract infections that damage surface cells; abnormal accumulations of
mucus (eg, allergy), which protect pneumococci from phagocytosis; bronchial obstruction (eg,
atelectasis); and respiratory tract injury due to irritants disturbing its mucociliary function.
(2) Alcohol or drug intoxication, which depresses phagocytic activity, depresses the cough reflex, and
facilitates aspiration of foreign material.
(3) Abnormal circulatory dynamics (eg, pulmonary congestion, heart failure).
(4) Other mechanisms, eg, malnutrition, general debility, sickle cell anemia, hyposplenism, nephrosis,
or complement deficiency.
Pathology
Pneumococcal infection causes a fibrinous edema
fluid into the alveoli, followed by red cells and
leukocytes, which results in consolidation of
portions of the lung. Many pneumococci are
found throughout this exudate, and they may
reach the bloodstream via the lymphatic drainage
of the lungs.
mononuclear cells actively phagocytose the
debris, and this liquid phase is gradually
reabsorbed. The pneumococci are taken up by
phagocytes and digested intracellularly.
Diagnostic Laboratory Tests
Blood is drawn for culture; CSF and sputum are collected for
demonstration of pneumococci by smear and culture. Serum
antibody tests are impractical. Sputum may be examined in
several ways.
Stained Smears
A Gram-stained film of rusty-red sputum shows typical organisms,
many polymorphonuclear neutrophils, and many red cells.
Capsule Swelling Tests
Fresh emulsified sputum mixed with antiserum causes capsule swelling
(the quellung reaction) for identification of pneumococci.
Culture
The culture is created by sputum cultured on blood agar and incubated
in CO2 or a candle jar. A blood culture is also taken.
Immunity
Immunity to infection with pneumococci is type-specific and depends
both on antibodies to capsular polysaccharide and on intact phagocytic
function. Vaccines can induce production of antibodies to capsular
polysaccharides
Treatment, prevention, control
Since pneumococci are sensitive to many antimicrobial
drugs, early treatment usually results in rapid recovery,
Penicillin G is the drug of choice, others : vancomycin.
Epidemiology,
Pneumococcal pneumonia accounts for about 60% of all
bacterial pneumonias, the healthy carrier is more important in
disseminating pneumococci than the sick patient.
It is possible to immunize individuals with type-specific
polysaccharides. Such vaccines can probably provide 90%
protection against bacteremic pneumonia. A polysaccharide
vaccine containing 23 types is licensed in the United States.
This vaccine is appropriate for elderly, debilitated, or
immunosuppressed individuals.
Mycobacterium tuberculosis

Acid fast aerobic


24-30 h doubling time
Member of tuberculosis complex
The mycobacteria are rod-shaped (in tissue), and
coccoid/filamenteous in artificial media, do not
form spores.
Although they do not stain readily, once stained
they resist decolorization by acid or alcohol and
are therefore called "acid-fast" bacilli.
Mycobacterium tuberculosis causes tuberculosis
and is a very important pathogen of humans
Mycobacterium
tuberculosis
Infections
Mycobacterium
tuberculosis
Infections (cont.)
Positive PPD + Chest X-Ray +

MDR-TB a serious
global health threat

BCG (bacille Calmette-Guerin)


= attenuated M. bovis
Typical Progression of
Pulmonary Tuberculosis
Pneumonia
Granuloma formation with fibrosis
Caseous necrosis
Tissue becomes dry & amorphous (resembling cheese)
Mixture of protein & fat (assimilated very slowly)

Calcification
Ca++ salts deposited

Cavity formation
Center liquefies & empties into bronchi
PPD Tuberculosis Skin Test Criteria

PPD = Purified Protein Derivative from M. tuberculosis


Chest X-Ray of Patient with Active
Pulmonary Tuberculosis
M. tuberculosis

KULTUR
Media Middlebrook padat / cair
Lowenstein-Jensen (media telur, + hijau malasit)
Tumbuh lambat (doubling time >24 jam)
Gol saprofit tumbuh cepat, pada 22-33oC ,
kurang tahan asam, pigmen lebih banyak
Dinding sel hidrofobik tumbuh menggerombol
Tahan kekeringan
DIAGNOSIS
1. Evidence of infection
a. Chest x-ray - hilar lymphadenopathy
calcification of primary focus/LN
b. Delayed hypersensitivity response to purified protein derivative
(PPD) MANTOUX /HEAF TEST
2. Evidence of active disease
a. Sputum for AFB using Ziehl-Neelsen technique
positive
3. Evidence of active disease
a. Indirect evidence of infection (Mantoux)
b. Direct evidence of infection PCR / culture
c. Histo-pathological evidence
Diagnosis of Tuberculosis
Acid fast staining
Eight Week Growth of Mycobacterium
tuberculosis on Lowenstein-Jensen Agar
KOMPONEN DINDING SEL

LIPID
asam mikolat
Kompleks asam mikolat + dipeptida muramil (dari
peptidoglikan) terbentuknya granuloma
wax
fosfolipid menginduksi nekrosis kaseasi
cord factor (trehalose-6,6-dimikolat) fungsi:
menghambat migrasi leukosit
granuloma kronis
sebagai ajuvan
PROTEIN: protein / protein-wax reaksi tuberkulin
POLISAKARIDA: dapat bereaksi dengan antibodi penderita
Lipid-Rich Cell Wall of Mycobacterium
Mycolic acids

mycolic acids (long-chain fatty acids C78C90),


waxes,
phosphatides

(Purified Protein Derivative)


Pathogenic Mycobacterium spp.

BCG

AIDS
patients
Pathogenesis
Inhaled aerosols
Engulfed by alveolar macrophages
Bacilli replicate
Macrophages die
Infected macrophages migrate local lymph nodes
Develop Ghons focus Primary complex
Cell mediated immune response

stops cycle of destruction and spread


Viable but non replicating bacilli present in macrophages
CLINICAL PRESENTATION
Pulmonary tuberculosis

Primary complex
Asymptomatic
HEALS

Acute pulmonary disease REACTIVATION


Systemic spread Post-primary
Aymptomatic /symptomatic tuberculosis

LATER DISEASE MILIARY TUBERCULOSIS


Renal / CNS etc Pulmonary
meningitis
DIAGNOSIS
Pulmonary tuberculosis

1 1 Primary complex
Asymptomatic
HEALS
2
3
Acute pulmonary disease REACTIVATION
Systemic spread Post-primary
Aymptomatic /symptomatic tuberculosis

LATER DISEASE MILIARY TUBERCULOSIS


3 Renal / CNS etc Pulmonary 3
meningitis
PATOLOGI

TIPE LESI
1. Eksudatif (tes tuberkulin dapat positip)
Terjadi inflamasi akut pada jaringan paru (pneumonia)
eksudat diabsorbsi nekrosa
berkembang tipe produktif
2. Produktif
Bila berkembang granuloma kronis, terdiri:
Sel giant multi nukleus berisi bakteri dibagian tengah
dikelilingi lapisan epitel
Lapisan terluar: fibroblas, limfosit, monosit
bagian ini berkembang ditengah terjadi nekrosis
kaseasi (lesi ini disebut TUBERKEL)
Tuberkel pecah ke bronkus terjadi kaviti (penyembuhan
oleh fibroblas /
kalsifikasi)
PENYEBARAN BAKTERI DI DALAM INANG

Bakteri menyebar melalui:


saluran limfa
darah distribusi miliari
bronkhi
gastrointestinal

PERTUMBUHAN INTRASELULER
Bakteri dalam sel monosit, retikuloendotelial, sel giant
menyebabkan:
kesulitan pengobatan
infeksi persisten
Granulomas: organized aggregates of immune cells that surround
foci of infected tissues; limits further dissemination of M.
tuberculosis
Diagram
of a
Granuloma
NOTE: ultimately a
fibrin layer develops
around granuloma
(fibrosis), further
walling off the
lesion.
Typical progression
in pulmonary TB
involves caseation,
calcification and
cavity formation.
Infection of M. tuberculosis: three
stages
Risk Factors for Tuberculosis
Congregate settings (prisons)
Overall health/immune system status
Poverty and unemployment
Homelessness
Alcoholism and drug abuse
HIV coinfection
Steroid (immunosuppressive use)
Genetic predisposition?
Strain virulence?
OBAT ANTI TUBERKULOSIS

Pilihan I : Rifampisin, etambutol, pirasinamid, INH

Pilihan II : Streptomisin, kanamisin, sikloserin,


ofloksasin, siprofloksasin

Mekanisme aksi
INH (isoniasid) menghambat biosintesa asam mikolat
Rifampisin menghambat awal sintesa RNA
Etambutol menghambat penempatan asam mikolat
Gol. Aminoglikosida menghambat sintesa protein
Gol. Quinolon menghambat replikasi DNA
Tuberculosis Control
Priority of TB control is to identify and treat
infected patients (active or latent)
Successful cure of infectious patients will reduce
transmission
Patients with active infection become
noninfectious within two weeks of starting
treatment; latent????
Successful treatment of active infection takes 6
months (DOTS); latent???
Need to diagnose and treat latent infection
BORDOTELLA PERTUSIS

Sifat-sifat :
Obligat aerob, batang pendek, Gram negatif
Memfermentasi glukosa dan laktosa asam, tanpa gas
Tidak memerlukan faktor X dan V

Tumbuh pada media bordet-gengou, inkubasi 36-72 jam


Koloni : kecil, mukoid, menghemolisa darah

Bahan pemeriksaan: usapan nasofaring, cough droplets


PATOGENESIS
Faktor firulensi diregulasi oleh bvg (Bordetella virulence gene):

Filamentous hemagglutinin adesi pada sel epitel


Toksin pertussis lymphositosis, adesi pada pili, aktivitas
ADP ribosylating (struktur dan mekanisme aksi mirip dengan
toksin kolera)
Toksin adenylyl cyclase
Toksin dermonecrotic
Tracheal cytotoxin menghambat sintyesa DNA pada sel
bersilia dan tidak diregulasi oleh bvg
LPS mungkin juga berperan pada kerusakan sel pada tract
resp atas
patogenesis

* B. pertusis hanya bertahan sebentar diluar tubuh


* Tidak ada vektor
* Transmisi melalui pernafasan pada tahap awal atau dari
carrier
* Melekat dan multiplikasi pada epitel trachea & bronchi
* Bakteri tidak masuk darah
* Toksin dan substansi lain menyebabkan:
batuk
lymfositosis
nekrosa sel epitel
infiltrasi PMN
inflamasi peribronchial dan interstitial pneumonia
menyebabkan penyumbatan bronchi
adanya mukus kekurangan oksigen
Infeksi 2 fase
Inkubasi lebih kurang 2 minggu
Kebanyakan menyerang anak dibawah 5 tahun

Fase catarrhal (1-2 minggu) batuk ringan dan bersin


penyebaran (pasien sangat infeksius)

Fase paroxysmal (2-6 minggu) batuk berat dan khas


(batuk rejan)

Pemeriksaan lab.:
1. Direct Fluorescent Antibody (FA) test

2. Kultur
3. Serologi dapat dilihat setelah minggui ke 3
Imunitas :
Terbentuk antibodi yang mencegah
perlekatan bakteri pada sel epitel saluran
nafas

Obat : (efektif pada fase catarrhal) :


eritromisin, ampisilin

Pencegahan : vaksin DPT


HAEMOPHILUS

Diskripsi : batang kecil, Gram negatip, aerobik, non-motil.


beberapa merupakan flora normal membran mukosa
perlu media kaya, ada yang memerlukan faktor :
X (hemin)
V (nikotinamin) dapat diganti NAD
(nikotinamide adenin nucleotide)
X dan V
Pemeriksaan Mikrobiologi
Pengecatan Pemeriksaan biokimia
Kultur Pemeriksaan
KULTUR :
Bahan pemeriksaan : darah, cairan cerebrospinal, usapan
Media : agar coklat + Iso Vitalex
Inkubasi : 36- 48 jam, 33-370 C, CO2 5-10%
Koloni : kecil, diameter 1 mm
Bentuk Sel : kultur 6-8 jam bentuk kokobasil (pendek)
lebih dari 8 jam sel lebih panjang
Kebutuhan faktor X dan V dapat diidentifikasi dengan :
1. Fenomena satelit : H. influenzae tumbuh dengan
koloni kecil-kecil disekitar koloni Staphylococcus
2. Dengan paper disc yang mengandung faktor X
atau V.
3. Tes porvirin untuk mendeteksi adanya faktor X
Pemeriksaan adanya Kapsul :
H. influenzae mempunyai kapsul polisakarida (6 tipe)
Pemeriksaan seperti reaksi Quellung pada
pneumococci (dengan antiserum) tampak
pembengkakan kapsul

Patogenesis :
H. influenzae tidak berkapsul flora normal saluran.
H. influenzae tipe b infeksi supurativ saluran nafas
(sinusitis, Laringotrakheitis, otitis)
pada anak kecil meningitis
Pada beberapa orang > 3-5 tahun darahnya bersifat
bakterisidal terhadap H. influenzae
H. influenzae sering menyebabkan meningitis
terutama pada anak-anak. Di AS 10.000/ tahun
93% oleh H. influenzae sertipe b, biotipe 1.

H. influenzae dapat juga menyebabkan :


Sinusitis Pericarditis epiglositis
otitis osteomyelitis
laringotyracheitis
uteritis (kadang-kadang juga H. parainfluenzae)

Penyebab infeksi sekunder setelah infeksi virus


influenzae
Tidak dapat menginfeksi binatang percobaan.
Obat :
Penisilin Kloramfenikol Sulfonamid
Tetrasiklin Sefalosporin

Spesies lain :
H. haemolyticus infeksi saluran nafas atas
H. parainfluenzae endokarditis
H. aegypticus konjungtivitis
H. vaginalis (Corynebacterium vaginalis) vaginitis
H. ducreyi menyebabkan chancroid (pembengkakan
kelenjar limfa pada genital)