Rifaximin is a semi-synthetic rifamycin antibiotic produced by Amycolatopsis mediterranei. It is non-absorbable and acts locally in the gut due to its unique chemical properties. Rifaximin has broad-spectrum activity against gram-positive and gram-negative bacteria as well as protozoa through inhibition of bacterial RNA polymerase. Its localized activity and lack of systemic absorption helps preserve other antibiotics and limits development of resistance. Rifaximin also has anti-inflammatory properties through activation of the pregnane X receptor, reducing levels of pro-inflammatory cytokines. Fatroximin dry cow is a rifaximin formulation developed for intramammary administration as dry cow therapy to

1. Fatro worldwide exclusive antibiotic
Roberto Farina - Fatro

2. RIFAXIMIN
• Class: Rifamycins
• Subclass of the larger family
Ansamycins
• Antibiotics produced by the Gram+
bacterium Amycolatopsis
mediterranei
• Particularly potent against
– Multi-resistant Staph. Aureus
– Mycobacteria
• Rifaximin: semi-synthetic derivative
of rifamycin SV

3. RIFAXIMIN
Physiochemical Properties
Zwitterion
Pyrido nitrogen positively charged
Imidazo nitrogen negatively charged
Phenolic hydroxyls
Strong tendency to self-associate
Ionized at all pH values
Additional pyridoimidazole moiety makes it
NON-ABSORBABLE
ion trapping
Acts locally and does not pass into the circulation

4. RIFAXIMIN
Mechanism Of Action
• Prevents transcription
– the process by which the information in DNA is copied into
messenger RNA (mRNA) for protein production.
• Inhibits RNA and protein synthesis
Binds to the β subunit of prokaryotic
DNA-dependent RNA polymerase
TRANSCRIPTION
ANIMATION

5. RIFAXIMIN
Antimicrobial Activity
• Broad spectrum of antibacterial action:
– Gram+ and Gram-
– Both Aerobes and Anaerobes
• Susceptibility of resistant strains of Staph. aureus is
particularly interesting
• Protozoa
– Cryptosporidium, Blastocystis
• Reverse transcriptase of certain RNA viruses
(retrovirus)

6. RIFAXIMIN
Antimicrobial killing activity
• Rapidly kills fast-dividing bacteria as well as “persisters”
cells, which remain biologically inactive for long periods
evading antibiotic activity
– [Pozniak 1999]
• Bactericidal
• Actually kills
bacteria
Image

7. RIFAXIMIN
Not Absorbed Systemically
• Valuable for therapies applied locally to
body surfaces
– Skin or mucosae
• High local bioavailability
• Localized targeting of pathogens
• Absence of residues in non-treated
organs
• Reduced incidence of undesired side
effects
Scarpignato & Pelosini 2005
100% TOPICAL ANTIMICROBIAL

8. TOPICAL THERAPY & ANTIBIOTIC RESISTANCE
A NOVEL APPROACH TO JUDICIOUS PRESCRIBING PRACTICE
• Limited selective pressure for the development of
wide-spread bacterial resistance
• Preservation of critically important antimicrobials
for systemic therapy
• Antimicrobial is sequestered in target organs
• Very high local concentrations
• Circumscribed antimicrobial activity

9. ANTIMICROBIAL RESISTANCE
Resistance of a microorganism to an antimicrobial
medicine to which it was previously sensitive (WHO)
One of the main problems associated with antibiotics use
• Therapeutic failure
• Infections persist and may spread
Impact on
animal health
and productivity
• Emergence of resistant microorganisms
that can infect people (Superbugs)
• Great clinical, economic, political and
environmental implications
Possible impact
on human
health

10. PROPER ANTIMICROBIAL SELECTION
FIGHTS RESISTANCE
Ability to lead to the development
of resistant mutants
Spread of resistance
Stability of the mutants
Effect on the susceptibility of other
antimicrobial agents
Relevant factors that determine the therapeutic
value of antibacterials
ANTIMICROBIAL
RESISTANCE

11. DEVELOPMENT OF RESISTANCE TO RIFAXIMIN
• Studied in detail on several Gram- and
Gram+, aerobic and anaerobic strains
• Resistance to Rifaximin is rare
– [Hoover 1993; Ruiz 2008; Marchese 2000; Ouyang-Latimer 2011; Valentin 2011]
• More easily with sub-inhibitory concentrations
• Anaerobic atmosphere hinders the selection of
rifaximin-resistant bacteria
• High concentrations in in an oxygen-deficient milieu:
in-vivo occurrence of bacterial resistance with
rifaximin is an infrequent phenomenon

12. Staph. aureus
SUSCEPTIBILITY TO ANTIMICROBIALS
6%
31%
31%
8%
36%
77%
36%
84%
86%
89%
94%
92%
82%
93%
99%
0%
25%
50%
75%
100%
Sulfa
Penicillin
Ampicillin
Spectinomycin
Streptomycin
Tetracycline
Spiramycin
Erythromycin
Kanamycin
Tylosin
Cloxacillin
Nafcillin
Cefoperazone
Flumequine
Rifaximin
R %
I %
S %
Bertocchi, Varisco, Farina 2000
Kirby-Bauer agar diffusion test
Strains isolated from the milk of dairy cows with mastitis (IZS – Brescia, Italy)

13. SPREAD OF RESISTANCE TO RIFAXIMIN
• Resistance due to a chromosomal alteration
in the drug target, the DNA-RNA polymerase
(rpoB gene)
– [Al-Orainey 1990]
• Different from the plasmid-mediated
resistance common to other antibiotics
– [Smith 2002]
• The spread of resistance is less frequent than
that due to plasmid-mediated transfer
(transferred within the same generation, even
between different bacterial species)
– [Collignon PJ 2002]
Not disseminated by plasmids but mediated chromosomally
Sulfa
Β-lactamTetracycline
Fenicol
Aminoglicoside
multi-R
Plasmid

14. STABILITY OF RIFAXIMIN RESISTANT MUTANTS
• Resistance to rifaximin
disappear after drug
administration is
terminated.
• Poorer viability of
rifaximin-resistant mutants
relative to nonresistant
(wild-type) bacteria
• Resistance to rifaximin
doesn’t persist beyond a
few weeks after cessation
of therapy (specific time-
dependent on species of
bacteria)
De Leo 1986
Disappearance of rifaximin-resistant
bacteria after stopping the antibiotic
treatment (week 0)
RIFAXIMIN

15. ANNUAL VARIATION OF STAPH. AUREUS
SENSITIVITY TO RIFAXIMIN
From cows with mastitis
IZS Tre Venezie
Barberio 2000
Year Susceptible
1996 98.9 %
1997 93.4 %
1998 98.1 %
1999 98.7 %
Carnevali Nocetti 2001
Year Susceptible
1996 96.95 %
1997 100.0 %
1998 99.49 %
1999 98.88 %
2000 98.28 %
From cows with mastitis
APA Modena

16. EFFECT ON THE SUSCEPTIBILITY LEVELS OF
OTHER ANTIMICROBIAL AGENTS
• There is no evidence of cross-resistance to other
non-rifamycin classes of antibiotics
– Herbert DuPont 2003
• No-systemic involvement
• Preserves other antimicrobial agents, which are able to be
used to treat systemic infections, diminishing their
pressure on the microorganisms, favoring a lower
selection of resistant strains
• It does not alter the microbiota population (other than
those based in the treated compartment)

17. NON-ANTIBIOTIC EFFECTS OF RIFAXIMIN
• Rifaximin, besides acting
against microorganisms, has
also beneficial effects on
Host Cells
• In addition to its
antibacterial activity
rifaximin exerts
antiinflammatory and
immunomodulatory effects
Scarpignato 2005
BACTERIA
ANIMAL CELLS

18. RIFAXIMIN MODULATES THE
INFLAMMATORY RESPONSE
• Rifamycins are able to modulate neutrophil
functions and display anti-inflammatory actions
– [Spisani 1997]
• Intra-articular rifamycin has been successfully used
in chronic arthritis (juvenile rheumatoid arthritis and
ankylosing spondylitis)
– [Caruso 1997]
• Rifaximin reduces overall inflammatory status
modulating pro-inflammatory cytokine release
– IL-6, IL-1β, IL-8, IL-12 and interferon-γ, TNFα, chemokines
– [Brown 2010; Vitali 2009]

19. RIFAXIMIN MODULATES INFLAMMATION
THROUGH PXR ACTIVATION
• Pregnane-X-Receptor mediates
the anti-inflammatory activities
of Rifaximin
– [Cheng 2010; Mencarelli 2011]
• PXR is a nuclear receptor (ligand-
activated transcription factor)
• NR are sensing systems that
govern the interactions between
genome and internal
environment
• PXR is activated by different
xenobiotics and endobiotics
RXR
GENE
TRANSCRIPTION
XRE
RFX
PXR
Expression of proteins
involved in detoxification
of foreign toxic substances

20. PREGNANE X RECEPTOR
• Master supervisor of
detoxification of xenobiotics
• Orchestrate energy metabolism
and immune responses to
stresses caused by xenobiotic
• Inhibits nuclear factor NF-κB
signaling (nuclear factor kappa-light-chain-
enhancer of activated B cells), a first
responder to harmful cellular
stimuli (DAMPs, PAMPs)
• PXR activation results in lower
expression of proinflammatory
cytokines and chemokines
Wahli 2008; Mencarelli 2010
TLR
NF-κBPXR
XENOBIOTIC
RESPONSE
PROINFLAMMATORY
CYTOKINES
CHEMOKINES
Mutual negative crosstalk
between NF-κB and PXR
DAMPs
PAMPs
HOST CELL
ANTIINFLAMMATORYDETOXIFICATION

21. RIFAXIMIN REDUCES THE EXPRESSION OF INFLAMMATORY GENES
IN EPITHELIAL CELLS ACTIVATED BY LIPOPOLISACCARIDES
Rifaximin (100 μM) was added to colon biopsies for 3 h, before LPS stimulation (100 μg/ml)
for 16 h. At the end of incubation the mRNA was extracted for the quantification
*P<0.05 versus untreated biopsies; **P<0.05 versus LPS treated biopsies

22. Rifaximin antiinflammatory effect in a TNBS-
induced colitis model (hPXR mice)
TNBS: 2,4,6-Trinitrobenzenesulfonic acid
TNBS TNBS + RIFAX
H&E-stained
colon sections
Cheng 2010

23. INFLAMMATION ROLE IN CLINICAL MASTITIS
• The systemic and local inflammatory responses
contribute to etiology and pathophysiology of clinical
mastitis.
• The risk of developing clinical mastitis, from either
chronic infections or from new environmental
infections, is greatest during the peripartum period
– [Shpigel 1998]
• The inflammatory response is more aggressive during
the peripartum period than late lactation
– [Sordillo et al. 1995; , Lehtolainen et al. 2003]
• An enhanced inflammatory response with concomitant
suppression in other immune responses is involved in
the etiology and severity of the clinical mastitis
observed in peripartum cows
– [Ballou 2012]

24. INFLAMMATION & METABOLIC DISORDERS
• During infections the local release of pro-inflammatory
cytokines also trigger an acute phase reaction
• Systemic inflammation increases lipolysis and impairs
hepatic metabolism, predisposing cows to lipid-related
metabolic diseases [Jiang 2008]
– reduced feed intake, energy diversion toward febrile
response, increased catabolism in adipose tissue and skeletal
muscle, acute phase protein synthesis in hepatic tissue and
impaired liver function
INCREASED RISK OF DEVELOPING KETOSIS AND FATTY LIVER

25. PXR ACTIVATION BY RIFAXIMIN MAINTAINS
EPITHELIAL BARRIER INTEGRITY
• Epithelial cells are the first
line of defense against
harmful agents (bacteria
products and toxins) and act
as a “barrier” against bacteria
• Remarkably similar to
hepatocytes in their ability to
carry out detoxification
• Epithelial cells may become
unable to detoxify toxic
metabolites in inflammation
[Mencarelli 2010]
RXR
TRANSCRIPTION
OF GENES
INVOLVED IN
EPITHELIAL
DETOXIFICATION
AND PROTECTION
XRE
RFX
PXR

26. RIFAXIMIN PRETREATMENT REDUCES
BACTERIA BINDING TO EPITHELIAL CELLS
p<0.0001 (†) and <0.03 (§) Brown, E., Xue, Q., & Jiang, Z. (2010)
Many pathogenic
bacteria need to
attach to or
invade host
epithelial cells as
a first step in the
disease process
Escherichia coli (enteroaggregative E. Coli EAEC O42)
HEp-2 (laryngeal)
HCT-8 (ileocecal)
A549 (lung)
HeLa (cervical)

27. RIFAXIMIN PRETREATMENT REDUCES
BACTERIAL ADHERENCE AND
INTERNALIZATION TO EPITHELIAL CELLS
A549 lung epithelial cells Brown, E., Xue, Q., & Jiang, Z. (2010)P < 0.002
Bacillus anthracis

28. MULTIPLE ACTIONS OF RIFAXIMIN
IN FIGHTING INFECTION
PATHOGEN
KILLING
ANTIINFLAMATORY
ACTION
EPITHELIAL BARRIER
PROTECTION
EPITHELIAL
PROTECTION
EPITHELIAL
DETOX

29. RIFAXIMIN IN VETERINARY THERAPY

30. FATROXIMIN DRY COW
FATROXIMIN INTRAMAMMARY OINTMENT
INTRAMAMMARY DRY COW THERAPY

31. THE ROLE OF DRY COW TERAPY
1. Cure of existing IMIs present at drying off
– Higher cure rate than that during lactation, particularly
for Staph. aureus
– A higher dose of antibiotic can be used
– Retention time of the antibiotic in the udder is longer
– Risk of residues in milk is reduced
2. Prevention of new IMIs during the dry period
– Greatest risk of new IMIs during the early and latter
portions of the dry period
– Fewer new infections during the dry period
– Reduced incidence of clinical mastitis at freshening

32. Route of Administration of Dry Cow Therapy
• Advantages
– Well researched
– Allows delivery of high local concentrations of
antibiotic
– Allows the use of antibiotics that would not normally
partition to the udder when administered
systemically.
• Disadvantages
– Physiological/anatomical damage to the streak canal
– Inoculation of organisms at the time of infusion
THE INTRAMAMMARY ROUTE IS THE BEST CHOICE FOR DCT
INTRAMAMMARY vs. SYSTEMIC
FATROXIMIN DC IS SPECIFICALLY DEVELOPED FOR TOPICAL
INTRAMAMMARY THEPAPY

33. IDEALDRYCOWTHERAPY High and Rapid initial
antimicrobial concentrations
throughout the udder
Prolonged period of antibiotic
activity
The antibiotic should be retained
within the udder - no systemic
absorption
Rapidly milked out following
calving
to kill
existing
pathogens
to prevent
new
infections
IDEAL DRY COW
THERAPY

34. DRUG ACTION
Pharmacodynamic Phase
• The effect of the drug against
bacteria in the infection site
Pharmacokinetic Phase
• Absorption (milk:plasma)
• Distribution (local and systemic)
• Metabolism (systemic)
• Excretion (local and systemic)
Pharmaceutical Phase
• Disintegration of the formulation
• Drug dissolution and liberation of the drug in milk
The end effect of a
drug depends on its
ultimate concentration
at the site of action

35. COMMON DRY COW FORMULATIONS
vaselin oil, peanut oil
petroleum jelly
lanolin beeswax
aluminium monostearate
polysorbate
Pyorala S. J Vet Pharmacol Ther. 1987
• All of them, more or less, are irritant
• May cause inflammation (chemical mastitis)
• Increased SCC when tested in lactation
Long acting
formulations
EXIPIENTS
Slow disintegration
Slow dissolution

36. FATROXIMIN DC
COMPOSITION
Active
substance
Rifaximin
100 mg
Excipients
Glyceril monostearate 40 -55
550 mg
Macrogol Cetostearyl Ether
75 mg
Liquid paraffin light
q.s. to 5 ml
Pharmaceutical form:
Ointment with active substance in suspension
Sterile PE
5 ml
syringe
EP-0222712

37. FATROXIMIN DC : Pharmaceutical Technology
EXCIPIENTS
Glycerol
Monostearate 40 - 55
•Mixture of mono
,di, triglycerides of palmitic and
stearic acid
•It confers ideal rheological
characteristics and maintains
the suspension
Macrogol Cetostearyl
ether
•Ether of Polyethylene glycol
(PEG) with fatty alcohols
•Hydrophilic emulsifier
•It permits high dispersibility
of active substance
Light Liquid Paraffin
• Very highly refined
mineral oil
• It is a vehicle for active
substance with emollient
properties
Potentially usable for both lactating and dry cow ointments
HLB: Hydrophilic-Lipophilic Balance is similar to that of milk
RAPID
DISPERSION
RATE IN
MILK
FAST
DISINTEGRATION
FAST
DISSOLUTION
INSTANT HIGH CONCENTRATIONS
AT THE SITE OF ACTION

38. IN VITRO DISSOLUTION STUDY
Dry Udder Secretion Model And Milk
Phosphate
buffered
saline
solution
(model of
secretions
during dry
period)
Milk as a
milieu at
dry off
Volume : 900 ml
Temperature : 40°C

39. 0:00:00

40. 0:30:00

41. 4:00:00

42. 8:00:00

43. 24:00:00

45. FATROXIMIN vs. COMPETITORS
DISSOLUTION AND RELEASE TEST
30’ 1 h 2 h 4 h 8 h 24 h
Product 2 0.00% 0.00% 3.60% 4.40% 4.70% 5.30%
Product 3 0.00% 0.00% 0.60% 0.70% 0.60% 0.80%
FATROX 23.60% 52.20% 72.80% 87.30% 99.50% 100.00%
0.00%
25.00%
50.00%
75.00%
100.00%
%ofrelease
Liquid medium :
phosphate buffered saline
solution in 900 ml beakers
Method of analysis :
HPLC: High-performance
liquid chromatography

46. Minimal Inhibitory Concentrations (MIC)
MIC50 MIC90 MIC Range
Staphylococcus aureus 0.081 0.55 0.012-6.25
Streptococcus uberis 0.18 0.55 0.024-25
Streptococcus agalactiae 0.21 0.46 0.097-1.56
Streptococcus dysgalactiae 0.04 0.45 0.024-6.25
Minor pathogens * 0.023 0.65 0.0007->25
E. Coli 1.56-6.25
* Corynebacterium spp. - CNS - Streptococcus spp.
Concentrations of rifaximin are several times higher than the MIC,
which makes the in vitro differences of activity between this and
other antimicrobials meaningless from a clinical standpoint
Concentrations
at the site of
action largely
exceeds MICs
observed in vitro
Rifaximin is
NONABSORBED

47. PK/PD FATROXIMIN DC
0.01
0.1
1
10
0 7 14 21 28 35 42
Staph.aureus
S. uberis
S. agalactiae
S. disgalactiae
E. coli
MICs
Log10µg/ml
Days from DCT

48. Staphylococcus aureus can invade host cells and
persist intracellularly for various periods of time
Invasion of a MAC-T cell by S. aureus
(TEM analysis ×5,000)
Bayles 1998, American Society for Microbiology
• Staphylococcus aureus is able to invade alveolar epithelial cells
and also survive engulfment by professional phagocytes such
as neutrophils and monocytes
• It survives in acidic media, including phagolysosomes (pH 5.0 )
S. aureus within alveolar epithelial cells
in a mouse model of mastitis
(Light microscope, Gram stain)
Brouillette 2003
IMAGE IMAGE

49. RIFAXIMIN ALSO ENTERS CELLS
Despite non-absorbed
there is evidence that
Rifaximin penetrates
cells, including epithelial
cells and leukocytes
Mencarelli 2010
Activity of rifaximin is only
slightly affected by
pH, conversely from what
is observed with other
antibiotics
Scarpignato 1999
Extraordinary
activity against
Staph. aureus
Low MICs
High local
concentrations
Long action

50. HIGH THERAPEUTIC EFFICACY
Cure of existing IMIs present at drying off
73%
100%
100%
90%
100%
88%
100%
Bacteriological cure rate (554 quarters)
Sol 1997

51. HIGH PREVENTIVE EFFICACY
Prevention of new IMIs during the dry period
5
1
2
6
7
554
Staph. Aureus
Pen Resistant…
S. uberis
CNS
E.coli
Total quarters
New IMIs
Sol 1997
Only 3 % of
new IMIs
The long persistence of Fatroximin in the udder allows effective
prevention of new IMIs during the dry period
Rifaximin is not
absorbed and
metabolized very slowly
Ultra-Long Action

52. IMPROVEMENT IN MILK QUALITY
LOWER SCC
1,253
1,901
604
290 263 196
H1 - 151 cows H2 - 227 cows H3 - 118 cows
SCCx1,000
Before Dry Off Fresh Cows
• High antibiotic efficacy
• Antiinflammatory
action
• Non-irritant vehicle
Drastic reduction in
SCC at lactation
Zecconi

53. • Eliminated totally with
colostrum just after calving
• Milk free from inhibitory
substances
• No systemic distribution
• NO residues in meat
• Rifaximin was the first
antibiotic included in Annex II
of the MRL regulation
(substances non subjected to MRL)
IMPROVEMENT IN MILK QUALITY
NO RESIDUES IN MILK AND MEAT

54. TWINSERT
An innovative system of administration
Allows partial insertion of the cannula reducing
the risk of carrying bacteria into the udder

55. COMPLETE
INSERTION
PARTIAL
INSERTION
Boddie 1986

56. New IMIs after treatment with a short
cannula or with a conventional cannula
Complete insertion
Partial insertion
Partial insertion may reduce new IMIs by over 50%.
Boddie & Nickerson 1991

57. CEFAXIMIN L
INTRAMMAMMARY THERAPY DURING
LACTATION
• Antimicrobial combination
– Cefacetrile
– Rifaximin
• Specifically studied for
intramammary use during
lactation

58. CEFACETRILE - CEPHACETRILE
• First-generation
Cephalosporin
• Marked activity against
Gram+
• Streptococcus agalactiae
• Streptococcus spp.
• Staph. aureus
• CNS
• Pretty active against Gram-
• E. coli
• Klebsiella spp.
Inhibition of cell wall
synthesis of bacteria
Bactericidal activity

59. SYNERGISTIC EFFECTS OF CEFACETRILE
AND RIFAXIMIN IN COMBINATION
MIC
Cefacetrile
MIC
Rifaximin
MIC Cefaximin-L 2/1
Cefacetrile Rifaximin
Staph. aureus 0.474 0.0122 0.0138 0.0069
Str. agalactiae 0.4069 0.1322 0.08345 0.0416
Str. dysgalactiae 0.19532 0.0317 0.0586 0.0292
Str. uberis 1.1718 0.3256 0.506 0.2848
The combination potentiates the activity of the antimicrobials alone by
several times, showing high synergistic effects against udder pathogens:
• Cefacetrile: 2.5 - 34 times
• Rifaximin: 1.5 - 9 times

60. CEFACETRILE: IMM PHARMACOKINETICS
• Rapidly absorbed
• Rapidly distributes throughout the mammary
tissues, including deep parenchyma
• High concentrations are found in mammary tissues
up to 24-36 hours after treatment
Cefacetrile mammary PK/PD
for Staphylococcus aureus

61. CEFAXIMIN-L
Two formulations to meet all therapeutic needs
• Vehicle highly
soluble in milk
• Rapid dissolution
and liberation of
the drugs in milk
• Crosses any occlusions
of inflammatory nature
• Rapid and widespread
diffusion even in case
of clogged milk ducts
SPRAY
OINTMENT

62. CEFAXIMIN-L: THERAPEUTIC SYSTEM
COW-MARKERS
Soft rubber markers to be applied
to the cow for reliable compliance
with withdrawal times
SINGLE-USE ANTISEPTIC WIPES
Pre-moistened wipes for teat
preparation soaked in
chlorhexidine for a fast kill of
mastitis-causing microorganisms

63. EFFICACY OF CEFAXIMIN-L IN THE TREATMENT
OF MASTITIS DURING LACTATION
78%
76%
88%
92%
62%
Str. agalactiae Staph. aureus Strept. spp. (NA) CNS Gram-
Zecconi 1992
Bacteriological cure rates
after a single treatment with CEFAXIMIN-L ointment
BY PATHOGEN

64. EFFICACY OF CEFAXIMIN-L IN THE TREATMENT
OF MASTITIS DURING LACTATION
89%
74%
65%
ACUTE SUBACUTE CHRONIC
Bacteriological cure rates
after a single treatment with CEFAXIMIN-L ointment
BY CLINICAL COURSE

65. IN-VIVO ULTRASONOGRAPHIC STUDY OF
MAMMARY DISTRIBUTION & PERSISTENCE
Results showed widespread
distribution of Cefaximin-L
Spray within the udder
, including most deep
mammary areas, for at least 24
After intramammary
application of one can of
Cefaximin L
Spray, ultrasound was
performed immediately
after and each 8h, for 2 days

72. RIFAXIMIN IN PREVENTION AND THERAPY OF
DISORDERS OF THE FEMALE REPRODUCTIVE SYSTEM
• Rifaximin does not cross organic barriers, thus
remains longer and completely active in the uterus
• Rifaximin reach concentrations several times higher
than MICs for common uterine pathogens
• No residues in milk and meat
High and long-lasting
intrauterine antibiotic
activity with no
withdrawal times

73. FATROXIMIN IU FOAM
FATROXIMIN I.U. VAGINAL EMULZION
• Single-dose spray antimicrobial for intrauterine
use
• Rapid expansion foaming formulation

74. INFUSION WITH
TRADITIONAL PRODUCTS
FATROXIMIN
IU FOAM
It spreads all over the endometrium, in every
uterine area, including the dorsal wall, horns
extremities and endometrial folds

75. TEST ON EXCISED BOVINE UTERUS

76. ASSESSMENT OF ANTIBIOTIC ACTIVITY
• Sterile filter paper disks
soaked in uterine secretions
• Fragments of endometrial
mucosa
• From the body of the uterus
and from the medial and
apical portions of the uterine
horns
• 6-12-18-24-48-72 h after
treatment
Clear inhibition zones
in all samples
Samples from cows culled 72 h after treatment
LONG-LASTING ANTIBIOTIC ACTIVITY
THROUGHOUT THE UTERINE CAVITY

77. FATROXIMIN INTRAUTERINE PESSARIES
• Small volume & Easy application
• Under all operative conditions
• In all species for which it is
indicated
• Controlled Effervescence System
• Rapid release
• Complete and uniform distribution
throughout the endometrium and
vaginal epithelium

78. FATROXIMIN TOPIC SPRAY
Prevention
& Treatment
of skin infections
170-g spray-can

79. FATROXIMIN TOPIC SPRAY
• Broad spectrum bactericidal
antimicrobial highly active against
microorganisms responsible for
skin infections
• Not absorbed through the skin
• No residues in milk and meat
• No withdrawal periods