RIVALTA TEST
If the
Certain diseases can cause excessive
accumulations of fluid in areas of the
body such as the abdomen (ascites) or
the pleural space around the lungs
(pleural effusion) or the pericardial
space around the heart. An estimate of
the concentration of protein in such
fluids can narrow the differential
diagnosis and assist the clinician in
establishing a diagnosis. For example,
fluid accumulations due to congestive
heart failure and liver failure (cirrhosis)
are typically lower in protein content
and are called transudates whereas
fluid accumulations due to cancer and
tuberculosis are typically higher in
protein content and are called
exudates. The Rivalta Test is a simple,
inexpensive method that can be used
in resource-limited settings to
differentiate a transudate from
an exudate.[1] It is a simple,
inexpensive method that does not
require special laboratory equipment
and can be easily performed in private
practice. The test was originally
developed by the Italian researcher
Rivalta around 1900 and was used to
differentiate transudates and exudates
in human patients. It is also useful in
cats to differentiate between effusions
due to FIP and effusions caused by
other diseases.[2] Not only the high
protein content, but high
concentrations of fibrinogen and
inflammatory mediators lead to a
positive reaction.
METHOD
A test tube is filled with
distilled water and acetic acid is added.
To this mixture one drop of the
effusion to be tested is added.
drop dissipates, the test is negative,
indicating a transudate. If the drop
precipitates, the test is positive,
indicating an exudate.[3]
Using a pH 4.0 acetic acid solution, 8
types of proteins were identified in
Rivalta reaction-positive turbid
precipitates: C-reactive
protein(CRP), Alpha 1-
antitrypsin (alpha1-
AT), Orosomucoid ((Alpha-1-acid
glycoprotein or
AGP)), haptoglobin (Hp), transferrin (Tf)
, ceruloplasmin (Cp), fibrinogen (Fg),
and hemopexin (Hpx). Since those
are Acute-phase proteins, a positive
Rivalta's test may be suggestive
of inflammation.[4]
PROCEDURE
To perform this test, a transparent
reagent tube (volume 10 ml) is filled
with approximately 7–8 ml distilled
water, to which 1 drop of acetic acid
(98%) is added and mixed thoroughly.
On the surface of this solution, 1 drop
of the effusion fluid is carefully layered.
If the drop disappears and the solution
remains clear, the Rivalta's test is
defined as negative. If the drop retains
its shape, stays attached to the surface
or slowly floats down to the bottom of
the tube (drop- or jelly-fish-like), the
Rivalta's test is defined as positive.
The Rivalta's test had a high positive
predictive value (86%) and a very high
negative predictive value for FIP (96%)
in a study in which cats that presented
with effusion were investigated
(prevalence of FIP 51%).[2] Positive
Rivalta's test results can occur in cats
with bacterial peritonitis or lymphoma.
TRANSUDAT DAN
EKSUDAT
Rongga-rongga serosa dalam badan normal
mengandung sejumlah kecil cairan. Cairan itu
terdapat pada rongga pericardium,rongga
pleura, rongga perut berfungsi sebagai
pelumas agar membran-membran mesotel
dapat bergerak tanpa bergeser. Jumlah cairan
cairan dalam keadaan normal hamper tidak
dapat diukur karena sangat sedikit. Jumlahnya
mungkin bertambah pada beberapa keadaan
dan berupa transudat atau eksudat.
Transudat terjadi terjadi akibat proses bukan
radang melainkan karena gangguan
keseimbangan cairan badan(tekanan osmotic
koloid, statis kapiler atau tekanan hidrostatis,
kerusakan endotel), sedangkan eksudat
behubungan dengan proses peradangan.
Pemeriksaan cairan yang tersangka eksudat
atau transudat bertujuan untuk menenetukan
jenis untuk mendapatkan keterangan tentang
causanya.
Ciri-ciri spesifik transudat :
Cairan jernih, encer, kuning muda, berat
jenis<1018, tidak ada bekuan, kadar protein <
2,5 g/dl, kadar glukosa kira-kira sama seperti
kadar glukosa plasma darah, jumlah sel kecil,
steril
Ciri-ciri spesifik eksudat :
Cairan keruh(mungkin berkepin-keping,
purulen, cyloid), kental, warna bermacam-
macam, BJ>1018, sering ada bekuan, kadar
protein lebih dari 4 g/dl, kadar glukosa < kadar
glukosa plasma darah, mengandung banyak
sel, dan sering ada bakteri.
Cara Memperoleh Bahan :
-Bahan dari (rongga perut, pleura,
perikardium, sendi, kista, hidrocycle), di dapat
dengan pungsi.
-Sebagai tempat gunakan penampung biasa ,
untuk biakan digunakan penampung steril, dan
juga penampung dengan anti koagulan( Citrat
20% atau heparin steril)
-Pengambilan harus secara steril
Macam-macamPemeriksaan
1. Pemeriksaan Makrokopis
a. Jumlah : Jumlah semua cairan menentukan
luas kelainan
b. Warna:
- Warna transudat kekuningan
- eksudat warna bermacam-macam
terkantung penyebabnya. Eksudat
karena radang ridangan tidak jauh
berbeda dengan eksudat
c. Kejernihan:
- Transudat murni: Kelihatan jernih
-Eksudat :Keruh
d. Bau : Biasanya transudat maupun eksudat
tidak memiliki bau bermakna, Timbulnya bau
mengarah pada eksudat
e. Berat Jenis : Harus segera di periksa
sebelum terjadi bekuan, Jika sampel
mencukupi dapat dilakukan dengan
urinometer, jika hanya sedikit sebaiknya
digunkan refraktometer.
f. Bekuan : Perhatikan terjadi bekuan (
Renggang, berkeping, atau sangat halus).
Bekuan itu tersusun dari fibrin dan di dapat
pada Eksudat
2. Pemeriksaan Kimia
a. Tes Rivalta
Tujuan : Membedakan transudat dan eksudat
Prinsip : Seromucin dengan asam asetat akan
terbentuk kekeruhan
Cara Kerja:
-10 ml aquadest + 1tts asetat glacial + 1 tts Cairan Transudat biasanya mengandung
cairan rongga, lihat di sekitar tetesan. kurang dari 500 sel/ml. Eksudat lebih tinggi.

Hasil pemeriksaan (Sekitar tetesan) : 4. Bakterioskopi

Transudat: Negatif (tidak keruh/jernih) Pengecatan Gram atau Ziehl-neelsen

Eksudat : Positif(Keruh) Sumber : Petunjuk Laboratorium Klinik (R.

Gandasebrata) dan Prosedur Kerja.
b. Pemeriksaan Glukosa

Cara Kerja

1.Sampel : 10 (µl) sampel + 1000 (µl) reagen

2.Standar: 10 (µl) standar + 1000(µl) reagen -

Campur, inkubasi 20 menit (suhu 20-25 0C)

atau 10 menit (37 0 C), Ukur absorban λ =560
nm, menggunakan bkangko reagen

Kadar Glukosa = Absorban sampel/Absoran

stadar X Konsentrasi standar

c. Kadar Protein

Cara Kerja
PEWARNAAN BAKTERI
1.Sampel : 20 (µl) sampel + 1000 (µl)
monoreagen
TAHAN ASAM (BTA)
2.Standar: 20 (µl) standar + 1000(µl) Bakteri tahan asam (BTA)
monoreagen
merupakan bakteri yang memiliki ciri-ciri
Campur, inkubasi 5 menit (suhu 20- yaitu berantai karbon (C) yang panjangnya
25 0C/37 0 C), Ukur absorban λ =540 nm 8 - 95 dan memiliki dinding sel yang tebal
dengan blangko monoreagen,
yang terdiri dari lapisan lilin dan asam
Kadar Protein total = Absorban lemak mikolat, lipid yang ada bisa
sampel/Absoran standar X Konsentrasi mencapai 60% dari berat dinding sel.
standar
Bakteri yang termasuk BTA antara lain
Catatan: Jika BJ ≤1010 sampel harus Mycobacterium tuberculose,
diencerkan 5-10 kali, jika berat jenis > 1010
perlu pengenceran 20X(jangan lupa Mycobacterium bovis, Mycobacterium
pegenceran masuk perhitungan) leprae, Nocandia meningitidis, dan
Nocandia gonorrhoeae. Mycobacterium
3. Mikroskopis :
tuberculose adalah bakteri patogen yang
Hanya bisa di lakukan pada cairan jernih atau dapat menyebabkan penyakit tuberculose,
agak keruh saja (Purulent tidak bisa).
Pada cairan jernih : penegnceran seperti
dan bersifat tahan asam sehingga
hitung leukosit darah atau cairan otak digolongkan sebagai bakteri tahan asam
(BTA). Penularan Mycobacterium
Pada Cairan yang agak keruh Gunakan
pengenceran yang sesuai (NaCl 0.9%),
tuberculose terjadi melalui jalan pernafasan tebal sehingga alkohol sukar menembus
(Syahrurachman, 1994). dinding sel bakteri tersebut dan warna
Pewarnaan Ziehl Neelson atau merah akibat pemberian carbol fuchsin
pewarnaan tahan asam memilahkan tidak hilang. Tujuan pemberian methylen
kelompok Mycobacterium dan Nocandia blue adalah memberi warna background
dengan bakteri lainnya. Kelompok bakteri (Pelczar dan Chan, 1986).
ini disebut bakteri tahan asam karena dapat Mewarnai bakteri yang tahan
mempertahankan zat warna pertama (carbol terhadap asam digunakan cara pewarnaan
fuchsin) sewaktu dicuci dengan larutan Ziehl Neelson. Pewarnaan Ziehl Neelson
pemucat (alkohol asam). Larutan asam terdapat beberapa perlakuan dan zat kimia
terlihat berwarna merah, sebaliknya pada yang diberikan. Fiksasi bertujuan untuk
bakteri yang tidak tahan asam karena mematikan bakteri tetapi tidak mengubah
larutan pemucat (alkohol asam) akan struktur sel bakteri. Perlakuan pencucian
melakukan reaksi dengan carbol fuchsin dengan menggunakan aquades mengalir
dengan cepat, sehingga sel bakteri tidak bertujuan untuk menutup kembali
berwarna (Lay, 1994). lemaknya (Pelczar dan Chan, 1986).
Uji bakteri tahan asam (BTA) pada Reagensia : Larutan Zat warna
praktikum kali ini menggunakan prosedur karbol fukhsin
pewarnaan Ziehl Neelson yaitu dengan Larutan Hc1 Alkohol
memberi larutan pewarna carbol fuchsin, Oil imersi
alkohol asam, dan methylen blue. Hasil Methylen blue
yang diperoleh saat praktikum yaitu positif Alat – alat :
1 dan positif 2 yang dilaporkan secara Mikroskop
kuantitatif menurut IUAT, yaitu: Ose bulat
Negatif: apabila tidak ditemukan BTA. Objek glass
Positif: apabila terdapat 1 – 9 BTA / 100 Bunsen
lapang pandang. Hand skun
Positif 1: apabila terdapat 10 – 90 BTA / Masker
100 lapang pandang. Pingset
Positif 2: apabila terdapat 1 – 9 BTA / 1 Paper lens
lapang pandang. Tissue
Positif 3: apabila terdapat > 10 BTA / 1 Cara kerja :
lapang pandang.  Mula – mula ambil mikroskop dilemari
dengan seksama, kemudian letakkan diatas
Tujuan pemberian carbol fuchsin meja dengan hati – hati
0,3% adalah untuk mewarnai seluruh sel  Buka iris diafrogma, kemudian atur cahaya
bakteri. Tujuan pemberian alkohol asam  Ambil objek glass dan dengan bersihkan
3% adalah meluruhkan warna dari carbol dengan alcohol agar bebas dari lemak
fuchsin, tetapi pada golongan BTA tidak  Beri etiket dan lingkari objek glass dengan
terpengaruh pemberian alkohol asam 0,3% spidol permanen kira - kira 1 – 2cm
karena memiliki lapisan lipid yang sangat dibelakang objek glass
 Oles sampel sputum diatas objek glass dan
keringkan pada suhu kamar
 Fixasi diatas api selama 3x berturut – turut
 Teteskan karbol fukhsin kuat pada sediaan
sambil diuapkan selama 5 menit. Lalu
bilas menggunakan aquadest
 Kemudia tetesin Hc1 alkohol pada sediaan.
Lalu tunggu selama 30 detik kemudian
bilas dengan aquadest
 Setelah itu teteskan methyien blue pada
sediaan dan biarkan selama 2 menit lalu
bilas menggunakan auadest.
 Tunggu sampai kering dan periksa
dibawah mikroskop dengan menggunakan
imersi dan pembesaran 100 x.
Hasil pengamatan :
Pewarna BTAada 4 macam
 Pewarna ziehl Neelsen
 Pewarna kinyoun
 Gabbett
 Tan tiam hok
Yang termasuk bakteri tahan asam (BTA)
 Mycobacterium tuberculosis
 Mycobacterium leprae
 Saprolphil usus
1. Menurut Ziehl Neelsen
Bakteri genus mycobacterium dan
beberapa spesies nocardia pada dinding
selnya mengandung banyak zat lipoid
(lemak) sehingga bersifat permiable dengan
pewarnaan biasa. Bakteri tersebut bersifat
tahan asam (+) terhadapa pewarnaan tahan
asam. Pewarnaan tahan asam dapat
digunakan untuk membantu menegakkan
diagnosa tuberkulosis. Pewarnaan tahan
asam menggunakan larutan ziehl-Neelsen
A (cat karbol fuchsin), Ziehl-Neelsen B
(alkohol asam :HCL 3% dalam metanol
95%) dan ziehl –neelsen C (cat biru
metilen). Hasil pewarnaan maka bakteri
tahan asam akan berwarna merah dan
bakteri tidak tahan asam akan berwarna
biru.
Alat dan bahan:
 Gelas benda, lampu spirtus,
mikroskop
 Jarum ose
 Akuades steril, larutan Ziehl-neelsen
A,B,C
 Biakan murni : Stapylococcus
aureus, Mycobacterium tuberculosis
Cara kerja
a. Bersihkan gelas benda dengan alkohol
agar bebas lemak
b. Buat preparat smear dari biakkan yang
ada secara aseptik
c. Preparat smear tersebut
dikeringudarakan
d. Lakukan fiksasi di atas nyala api
spirtus
e. Preparat smear di tetesi 2-3 tetes zat Ziehl-
Neelsen A dan panaskan di atas nyala api
spirtus selama 5-10 menit jaga pemanasan
jangan sampai mendidih
f. Cuci dengan air dan tiriskan
g. Tetesi dengan ziehl Neelsen B samapi
olesan berwarna merah muda. Lalu cuci
dengan air mengalir dan tiriskan.
h. Tetesi dengan zat Ziehl-Neelsen
selama 2 menit
i. Cuci dengan air mengalir dan tiriskan
j. Preparat dikeringudarakan
k. Lihat dengan perbesaran kuat+minya
emersi
Hasil pengamatan
2. Menurut Kinyoun Gabbet
 Dinding bakteri yang tahan asam
mempunyai lapisan lilin dan lemak yang
sukar ditembus cat. Oleh karena pengaruh
fenol dan kadar cat yang tinggi maka
lapisan lilin dan lemak itu dapat ditembus
cat basic fuchsin. Pada waktu pencucian
lapisan lilin dan lemak yang terbuka akan
merapat kembali. Pada pencucian dengan
asam alkohol warna fuchsin tidak dilepas.
Sedangkan pada bakteri tidak tahan asam
akan luntur dan mengambil warna biru dari
methylen blue.
Cara Kerja :
• Dibuat sediaan kuman dan difiksasi.
• Diwarnai dengan Kinyoun selama 3
menit
• Sediaan dicuci dengan air.
• Diwarnai dengan Gabbet selama 1 menit.
• Dicuci dan dikeringkan
• Diperiksa di bawah mikroskop.
Sediaan yang telah diperiksa
kemudian direndam dengan xylol selama
15-30 menit, lalu disimpan dalam kotak
sediaan.
Interpretasi hasil : BTA : warna merah dan
Non BTA : warna biru
MDR TB
Multi-drug-resistant tuberculosis (MDR-
TB) is a form of tuberculosis (TB) infection
caused by bacteria that are resistant to
treatment with at least two of the most
powerful first-line anti-TB
medications (drugs), isoniazid and rifampin.
Some forms of TB are also resistant
to second-linemedications, and are called
extensively drug-resistant TB (XDR-TB).[1]
Tuberculosis is caused by infection with the
bacteria Mycobacterium tuberculosis.
Almost one in four people in the world are
infected with TB bacteria.[1] Only when the
bacteria become active do people become ill
with TB. Bacteria become active as a result
of anything that can reduce the
person's immunity, such as HIV, advancing
age, diabetes or other immunocompromising
illnesses. TB can usually be treated with a
course of four standard, or first-line, anti-TB
drugs (i.e., isoniazid, rifampin and
any fluoroquinolone).[2]
However, beginning with the first
antibiotic treatment for TB in 1943, some
strains of the TB bacteria developed
resistance to the standard drugs through
genetic changes
(see mechanisms.)[2][3][4]Currently the majority
of multidrug-resistant cases of TB are due to
one strain of TB bacteria called the Beijing
lineage.[5][6] This process accelerates if
incorrect or inadequate treatments are used,
leading to the development and spread of
multidrug-resistant TB (MDR-TB). Incorrect
or inadequate treatment may be due to use
of the wrong medications, use of only one
medication (standard treatment is at least
two drugs), not taking medication
consistently or for the full treatment period
(treatment is required for several
months).[7][8][9] Treatment of MDR-TB requires
second-line drugs
(i.e., fluoroquinolones, aminoglycosides, and
others), which in general are less effective,
more toxic and much more expensive than
first-line drugs.[7] Treatment schedules for
MDR-TB involving fluoroquinolones and
aminoglycosides can run for 2 years,
compared to the 6 months of first-line drug
treatment, and cost over US$100,000.[10] If
these second-line drugs are prescribed or
taken incorrectly, further resistance can
develop leading to XDR-TB.
Resistant strains of TB are already present
in the population, so MDR-TB can be
directly transmitted from an infected person
to an uninfected person. In this case a
previously untreated person develops a new
case of MDR-TB. This is known as primary
MDR-TB, and is responsible for up to 75%
of cases.[11]Acquired MDR-TB develops
when a person with a non-resistant strain of
TB is treated inadequately, resulting in the
development of antibiotic resistance in the
TB bacteria infecting them. These people
can in turn infect other people with MDR-
TB.[4][7]
MDR-TB caused an estimated 600,000 new
TB cases and 240,000 deaths in 2016 and
MDR-TB accounts for 4.1% of all new TB
cases and 19% of previously treated cases
worldwide.[12] Globally, most MDR-TB cases
occur in South America, Southern Africa,
India, China, and the former Soviet Union.[13]
Treatment of MDR-TB requires treatment
with second-line drugs, usually four or more
anti-TB drugs for a minimum of 6 months,
and possibly extending for 18–24 months if
rifampin resistance has been identified in the
specific strain of TB with which the patient
has been infected.[8] Under ideal program
conditions, MDR-TB cure rates can
approach 70%
MECHANISM
he TB bacteria has natural defenses against
some drugs, and can acquire drug
resistance through genetic mutations. The
bacteria does not have the ability to transfer
genes for resistance between organisms
through plasmids (see horizontal transfer).
Some mechanisms of drug resistance
include:[14]
1. Cell wall: The cell wall of M.
tuberculosis (TB) contains
complex lipid molecules which act
as a barrier to stop drugs from
entering the cell.
2. Drug modifying &
inactivating enzymes: The TB
genome codes for enzymes
(proteins) that inactivate drug
molecules. These enzymes usually
phosphorylate, acetylate, or
adenylate drug compounds.
3. Drug efflux systems: The TB cell
contains molecular systems that
actively pump drug molecules out of
the cell.
4. Mutations: Spontaneous mutations
in the TB genome can alter proteins
which are the target of drugs,
making the bacteria drug
resistant.[15]
One example is a mutation in the rpoB gene,
which encodes the beta subunit of the
bacteria's RNA polymerase. In non-resistant
TB, rifampin binds the beta subunit of RNA
polymerase and disrupt transcription
elongation. Mutation in the rpoB gene
changes the sequence of amino acids and
eventual conformation of the beta subunit. In
this case rifampin can no longer bind or
prevent transcription, and the bacteria is
resistant.
Other mutations make the bacterium
resistant to other drugs. For example, there
are many mutations that confer resistance to
isoniazid (INH), including in the
genes katG, inhA, ahpC and others. Amino
acid replacements in the NADH binding site
of InhA apparently result in INH resistance
by preventing the inhibition of mycolic acid
biosynthesis, which the bacterium uses in its
cell wall. Mutations in the katG gene make
the enzyme catalase peroxidase unable to
convert INH to its biologically active form.
Hence, INH is ineffective and the bacteria is
resistant.[16][17] The discovery of new
molecular targets is essential to overcome
drug resistant problems.[18]
In some TB bacteria, the acquisition of these
mutations can be explained other mutations
in the DNA recombination, recognition and
repair machinery.[19]Mutations in these genes
allow the bacteria to have a higher overall
mutation rate and to accumulate mutations
that cause drug resistance more quickly.[20][21]
EXTENSIVELY DRUG-RESISTANCE TB
MDR-TB can become resistant to the
major second-line TB drug
groups: fluoroquinolones (moxifloxacin, oflox
acin) and injectable aminoglycoside or
polypeptide drugs
(amikacin, capreomycin, kanamycin). When
MDR-TB is resistant to at least one drug
from each group, it is classified
as extensively drug-resistant
tuberculosis (XDR-TB).[7]
In a study of MDR-TB patients from 2005 to
2008 in various countries, 43.7% had
resistance to at least one second-line
drug.[22] About 9% of MDR-TB cases are
resistant to a drug from both classes and
classified as XDR-TB.[1][23]
In the past 10 years TB strains have
emerged in Italy, Iran, India, and South
Africa which are resistant to all available first
and second line TB drugs, classified as
totally drug-resistant tuberculosis, though
there is some controversy over this
term.[24][25][26] Increasing levels of resistance in
TB strains threaten to complicate the current
global public health approaches to TB
control. New drugs are being developed to
treat extensively resistant forms but major
improvements in detection, diagnosis, and
treatment will be needed.[25]

PREVENTION
There are several ways that drug
resistance to TB, and drug resistance in
general, can be prevented:[27][28]
1. Rapid diagnosis & treatment of TB:
One of the greatest risk factors for
drug resistant TB is problems in
treatment and diagnosis, especially
in developing countries. If TB is
identified and treated soon, drug
resistance can be avoided.
2. Completion of treatment: Previous
treatment of TB is an indicator of
MDR TB. If the patient does not
complete his/her antibiotic
treatment, or if the physician does
not prescribe the proper antibiotic
regimen, resistance can develop.
Also, drugs that are of poor quality
or less in quantity, especially in
developing countries, contribute to
MDR TB.
3. Patients with HIV/AIDS should be
identified and diagnosed as soon as
possible. They lack the immunity to
fight the TB infection and are at
great risk of developing drug
resistance.
4. Identify contacts who could have
contracted TB: i.e. family members,
people in close contact, etc.
5. Research: Much research and
funding is needed in the diagnosis,
prevention and treatment of TB and
MDR TB.
"Opponents of a universal tuberculosis
treatment, reasoning from misguided notions
of cost-effectiveness, fail to acknowledge
that MDRTB is not a disease of poor people
in distant places. The disease is infectious
and airborne. Treating only one group of
patients looks inexpensive in the short run,
but will prove disastrous for all in the long
run."— Paul Farmer [29]
DOTS-Plus[edit]
Community-based treatment programs such
as DOTS-Plus, a MDR-TB-specialized
treatment using the popular Directly
Observed Therapy – Short Course(DOTS)
initiative, have shown considerable success
in the world. In these locales, these
programs have proven to be a good option
for proper treatment of MDR-TB in poor,
rural areas. A successful example has been
in Lima, Peru, where the program has seen
cure rates of over 80%.[30]
However, TB clinicians[who?] have expressed
concern in the DOTS program administered
in the Republic of Georgia because it is
anchored in a passive case finding. This
means that the system depends on patients
coming to health care providers, without
conducting compulsory screenings. As
medical anthropologists like Erin Koch have
shown, this form of implementation does not
suit all cultural structures. They urge that the
DOTS protocol be constantly reformed in the
context of local practices, forms of
knowledge and everyday life.[31]
Erin Koch has utilized Paul Farmer's
concept of "structural" violence as a
perspective for understanding how
"institutions, environment, poverty, and
power reproduce, solidify, and naturalize the
uneven distribution of disease and access to
resources". She has also studied the
effectiveness of the DOTS protocol in the
widespread disease of tuberculosis in the
Georgian prison system.[32] Unlike the DOTS
passive case finding utilized for the general
Georgian public, the multiple-level
surveillance in the prison system has proven
more successful in reducing the spread of
tuberculosis while increasing rates of
cure.[citation needed]
Koch critically notes that because the DOTS
protocol aims to change the individual's
behavior without addressing the need to
change the institutional, political, and
economic contexts, certain limitations arise,
such as MDR tuberculosis.[citation needed]
Treatment[edit]
See also: Tuberculosis treatment
Usually, multidrug-resistant tuberculosis can
be cured with long treatments of second-line
drugs, but these are more expensive
than first-line drugs and have more adverse
effects.[33] The treatment and prognosis of
MDR-TB are much more akin to those for
cancer than to those for infection. MDR-TB
has a mortality rate of up to 80%, which
depends on a number of factors, including:
1. How many drugs the organism is
resistant to (the fewer the better)
 2. How many drugs the patient is given
(patients treated with five or more
drugs do better)
3. Whether an injectable drug is given
or not (it should be given for the first
three months at least)
4. The expertise and experience of the
physician responsible
5. How co-operative the patient is with
treatment (treatment is arduous and
long, and requires persistence and
determination on the part of the
patient)
6. Whether the patient is HIV-
positive or not (HIV co-infection is
associated with an increased
mortality).
The majority of patients suffering from multi-
drug-resistant tuberculosis do not receive
treatment, as they are found in
underdeveloped countries or in poverty.
Denial of treatment remains a
difficult human rights issue, as the high cost
of second-line medications often precludes
those who cannot afford therapy.[34]
A study of cost-effective strategies for
tuberculosis control supported three major
policies. First, the treatment of smear-
positive cases in DOTS programs must be
the foundation of any tuberculosis control
approach, and should be a basic practice for
all control programs. Second, there is a
powerful economic case for treating smear-
negative and extra-pulmonary cases in
DOTS programs along with treating smear-
negative and extra-pulmonary cases in
DOTS programs as a new WHO "STOP TB"
approach and the second global plan for
tuberculosis control. Last, but not least, the
study shows that significant scaling up of all
interventions is needed in the next 10 years
if the millennium development goal and
related goals for tuberculosis control are to
be achieved. If the case detection rate can
be improved, this will guarantee that people
who gain access to treatment facilities are
covered and that coverage is widely
distributed to people who do not now have
access.[35]
In general, treatment courses are measured
in months to years; MDR-TB may require
surgery, and death rates remain high
despite optimal treatment. However, good
outcomes for patients are still possible.[36]
The treatment of MDR-TB must be
undertaken by physicians experienced in the
treatment of MDR-TB. Mortality and
morbidity in patients treated in non-specialist
centers are significantly higher to those of
patients treated in specialist centers.
Treatment of MDR-TB must be done on the
basis of sensitivity testing: it is impossible to
treat such patients without this information.
When treating a patient with suspected
MDR-TB, pending the result of laboratory
sensitivity testing, the patient could be
started on SHREZ
(Streptomycin+ isonicotinyl
Hydrazine+ Rifampicin+Ethambutol+ pyraZi
namide) and moxifloxacinwith cycloserine.
There is evidence that previous therapy with
a drug for more than a month is associated
with diminished efficacy of that drug
regardless of in vitro tests indicating
susceptibility.[37] Hence, a detailed
knowledge of the treatment history of each
patient is essential. In addition to the
obvious risks (i.e., known exposure to a
patient with MDR-TB), risk factors for MDR-
TB include HIV infection, previous
incarceration, failed TB treatment, failure to
respond to standard TB treatment, and
relapse following standard TB treatment.
A gene probe for rpoB is available in some
countries. This serves as a useful marker for
MDR-TB, because isolated RMP resistance
is rare (except when patients have a history
of being treated with rifampicin alone). If the
results of a gene probe (rpoB) are known to
be positive, then it is reasonable to omit
RMP and to use SHEZ+MXF+cycloserine.
The reason for maintaining the patient on
INH is that INH is so potent in treating TB
that it is foolish to omit it until there is
microbiological proof that it is ineffective
(even though isoniazid resistance so
commonly occurs with rifampicin
resistance).
For treatment of RR- and MDT-TB, WHO
treatment guidelines are as follows: "a
regimen with at least five effective TB
medicines during the intensive phase is
recommended, including pyrazinamide and
four core second-line TB medicines – one
chosen from Group A, one from Group B,
and at least two from Group C3 (conditional
recommendation, very low certainty in the
evidence). If the minimum number of
effective TB medicines cannot be composed
as given above, an agent from Group D2
and other agents from Group D3 may be
added to bring the total to five. It is
recommended that the regimen be further
strengthened with high-dose isoniazid
and/or ethambutol (conditional
recommendation, very low certainty in the
evidence)." [38] Medicines recommended are
the following:
 Group A: Fluoroquinolones
(levofloxacinm moxifloxicin, gatifloxacin)
 Group B: Second-line injectable agents
(amikacin, capreomycin, kanamycin,
streptomycin)
 Group C: Other core second-line agents
(ethionamide/prothionamide,
cycloserine/terizidone, linezolid,
clofazimine)
 Group D: Add-on agents (not part of the
core MDR-TB regimen)(pyrazinamide,
ethambutol, high-dose isoniazid [D1];
bedaquiline, delamanid [D2; p-
aminosalicylic acid, imipenem–cilastatin,
meropenem, amoxicillin-clavulanate,
thioacetazone [D3])
For patients with RR-TB or MDR-TB, "not
previously treated with second-line drugs
and in whom resistance to fluoroquinolones
and second-line injectable agents was
excluded or is considered highly unlikely, a
shorter MDR-TB regimen of 9–12 months
may be used instead of the longer regimens
(conditional recommendation, very low
certainty in the evidence)." [39]
In general, resistance to one drug within a
class means resistance to all drugs within
that class, but a notable exception is
rifabutin: Rifampicin-resistance does not
always mean rifabutin-resistance, and the
laboratory should be asked to test for it. It is
possible to use only one drug within each
drug class. If it is difficult finding five drugs to
treat then the clinician can request that high-
level INH-resistance be looked for. If the
strain has only low-level INH-resistance
(resistance at 0.2 mg/l INH, but sensitive at
1.0 mg/l INH), then high dose INH can be
used as part of the regimen. When counting
drugs, PZA and interferon count as zero;
that is to say, when adding PZA to a four-
drug regimen, another drug must be chosen
to make five. It is not possible to use more
than one injectable (STM, capreomycin or
amikacin), because the toxic effect of these
drugs is additive: If possible, the
aminoglycoside should be given daily for a
minimum of three months (and perhaps
thrice weekly thereafter). Ciprofloxacin
should not be used in the treatment of
tuberculosis if other fluoroquinolones are
available. As of 2008, Cochrane reports that
trials of other fluoroquinolones are
ongoing.[40]
There is no intermittent regimen validated
for use in MDR-TB, but clinical experience is
that giving injectable drugs for five days a
week (because there is no-one available to
give the drug at weekends) does not seem
to result in inferior results. Directly observed
therapy helps to improve outcomes in MDR-
TB and should be considered an integral
part of the treatment of MDR-TB.[41]
Response to treatment must be obtained by
repeated sputum cultures (monthly if
possible). Treatment for MDR-TB must be
given for a minimum of 18 months and
cannot be stopped until the patient has been
culture-negative for a minimum of nine
months. It is not unusual for patients with
MDR-TB to be on treatment for two years or
more.[citation needed]
Patients with MDR-TB should be isolated in
negative-pressure rooms, if possible.
Patients with MDR-TB should not be
accommodated on the same ward as
immunosuppressed patients (HIV-infected
patients, or patients on immunosuppressive
drugs). Careful monitoring of compliance
with treatment is crucial to the management
of MDR-TB (and some physicians insist on
hospitalisation if only for this reason). Some
physicians will insist that these patients
remain isolated until their sputum is smear-
negative, or even culture-negative (which
may take many months, or even years).
Keeping these patients in hospital for weeks
(or months) on end may be a practical or
physical impossibility, and the final decision
depends on the clinical judgement of the
physician treating that patient. The attending
physician should make full use of
therapeutic drug monitoring (in particular, of
the aminoglycosides) both to monitor
compliance and to avoid toxic effects.
Some supplements may be useful as
adjuncts in the treatment of tuberculosis,
but, for the purposes of counting drugs for
MDR-TB, they count as zero (if four drugs
are already in the regimen, it may be
beneficial to add arginine or vitamin D or
both, but another drug will be needed to
make five). Supplements poor.[58] The simple truth is that almost all
are: arginine[42] (peanuts are a good tuberculosis deaths result from a lack of
source), vitamin D,[43] Dzherelo,[44] V5 access to existing effective therapy.
Immunitor.[45]
The drugs listed below have been used in
desperation, and it is uncertain as to
whether they are effective at all. They are
used when it is not possible to find five
drugs from the list above. imipenem,[46] co-
amoxiclav,[47][48] clofazimine,[49][50][51] prochlorpe
razine,[52] metronidazole.[53]
On 28 December 2012, the U.S. Food and
Drug Administration (FDA)
approved bedaquiline (marketed as Sirturo
by Johnson & Johnson) to treat multi-drug
resistant tuberculosis, the first new
treatment in 40 years. Sirturo is to be used
in a combination therapy for patients who
have failed standard treatment and have no
other options. Sirturo is an adenosine
triphosphate synthase (ATP synthase)
inhibitor.[54][55]
The following drugs are experimental
compounds that are not commercially
available, but may be obtained from the
manufacturer as part of a clinical trial or on a
compassionate basis. Their efficacy and
safety are
unknown: pretomanid[56] (manufactured
by Novartis, developed in partnership
with TB Alliance),[57]and delamanid.
In cases of extremely resistant disease,
surgery to remove infection portions of the
lung is, in general, the final option. The
center with the largest experience in this is
the National Jewish Medical and Research
Center in Denver, Colorado. In 17 years of
experience, they have performed 180
operations; of these, 98 were lobectomies
and 82 were pneumonectomies. There is a
3.3% operative mortality, with an additional
6.8% dying following the operation; 12%
experienced significant morbidity (in
particular, extreme breathlessness). Of 91
patients who were culture-positive before
surgery, only 4 were culture-positive after
surgery.
The resurgence of tuberculosis in the United
States, the advent of HIV-related
tuberculosis, and the development of strains
of TB resistant to the first-line therapies
developed in recent decades—serve to
reinforce the thesis that Mycobacterium
tuberculosis, the causative organism, makes
its own preferential option for the