Vivaldis Cranbact 30 Capsules for Dogs & Cats | VitaCran® Cranberry Extract, Proanthocyanidins & Quinic Acid | UTI Adjunctive Therapy & Recurrent UTI Prophylaxis

FOR ANIMAL USE ONLY — Administer as directed by a veterinarian. Vivaldis Cranbact is a veterinary nutraceutical urinary tract supplement — not a veterinary antibiotic or medicine. Cranbact is not a substitute for veterinary diagnosis and treatment of urinary tract infections (UTIs). Active UTIs in dogs and cats require accurate diagnosis (urine culture and sensitivity [C&S] to identify the causative organism and antibiotic susceptibility pattern) and appropriate antibiotic therapy as prescribed by a veterinarian. Cranbact is indicated as adjunctive support alongside antibiotic therapy in active UTIs and as prophylaxis in animals with a confirmed history of recurrent UTIs — do not use as sole treatment for a confirmed active UTI without concurrent antibiotic therapy. Animals with lower urinary tract signs (haematuria, stranguria, pollakiuria, periuria) require veterinary assessment to differentiate UTI from other causes (urolithiasis, feline idiopathic cystitis [FIC — the most common cause of lower urinary tract signs in cats under 10 years, which is non-infectious and not caused by bacteria in over 95% of cases], neoplasia, or anatomical abnormalities). Keep out of reach of children.

Vivaldis Cranbact 30 Capsules for Dogs & Cats | VitaCran® Cranberry Extract, Proanthocyanidins & Quinic Acid | UTI Adjunctive Therapy & Recurrent UTI Prophylaxis

Vivaldis Cranbact is a veterinary nutraceutical urinary tract supplement manufactured by Vivaldis Animal Health (India), formulated with VitaCran® — a standardised cranberry extract (Vaccinium macrocarpon, the American cranberry) — providing a minimum 3% proanthocyanidins (PACs/OPCs) and minimum 6% quinic acid per capsule, with an ORAC (oxygen radical absorbance capacity) value of 400 mmol TE/g. Cranbact’s mechanism of action is primarily anti-adherence — the PACs prevent uropathogenic bacteria from attaching to the uroepithelial lining of the urinary tract, allowing natural elimination with urine flow — rather than bactericidal or bacteriostatic activity. This makes Cranbact effective as adjunctive therapy in active UTIs and as prophylaxis against recurrent UTIs without contributing to antibiotic resistance selection pressure. 30 capsules per pack.

Canine & Feline UTI Pathophysiology: Why Bacterial Adherence is the Critical First Step

• Uropathogenic E. coli (UPEC) — the dominant UTI pathogen in dogs and the anti-adherence target of cranberry PACs: Escherichia coli is the most common causative organism of canine UTIs (approximately 40–50% of all canine UTIs; other pathogens include Staphylococcus pseudintermedius, Proteus mirabilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus spp.); in feline UTIs (which are less common than in dogs — only approximately 1–3% of cats with lower urinary tract signs have a true bacterial UTI; the majority have feline idiopathic cystitis [FIC]), E. coli is also the most common pathogen; UPEC (uropathogenic E. coli) strains carry specific virulence factors that distinguish them from commensal E. coli and that are the molecular targets of cranberry PACs: (a) Type 1 fimbriae (mannose-sensitive fimbriae) — the FimH adhesin: Type 1 fimbriae are heteropolymeric surface appendages (fimbrial rod assembled from FimA major subunit monomers via the chaperone-usher pathway [FimC chaperone + FimD usher pore in the outer membrane]; the tip fibrillum terminates in FimF, FimG, and the adhesin FimH); FimH is a two-domain lectin: the pilin domain anchors FimH to the fimbrial tip; the lectin domain (a 156-residue beta-sandwich fold with a mannose-binding site) binds terminal α-D-mannose residues on uroplakin Ia (UPIa — the major apical surface glycoprotein of the terminally differentiated umbrella cells [superficial transitional epithelial cells] of the bladder urothelium; UPIa carries high-mannose N-linked glycans — the primary FimH ligand); FimH binding to UPIa mannose → UPEC internalisation into umbrella cells (FimH’s lectin domain undergoes a ‘catch bond’ allosteric switch under shear stress [the urinary flow tensile force] from a weak-affinity ‘off-state’ [compact/closed lectin domain conformation] to a high-affinity ‘on-state’ [open/extended conformation exposing the mannose-binding cleft] − the catch-bond mechanism means that urine flow, which should flush bacteria out, paradoxically increases FimH’s binding affinity − this is the key virulence mechanism enabling UPEC to resist mechanical clearance); after FimH-UPIa binding: UPEC is internalised into fusiform vesicles (derived from asymmetric unit membranes [AUMs] − the specialised lipid-rich vesicles of umbrella cells) → UPEC escapes into the umbrella cell cytoplasm → replicates to form intracellular bacterial communities (IBCs: dense, biofilm-like pod structures embedded in the umbrella cell cytoplasm; IBCs can contain >10,000 bacteria protected from antibiotics and host immune surveillance) → IBC bacteria exfoliate → re-enter the urine → reinfect adjacent umbrella cells or are shed in urine (the IBC cycle explains recurrent UTIs: UPEC in IBCs are shielded from both antibiotics and the host immune response, providing a persistent intracellular reservoir for relapse after antibiotic cessation); (b) P-fimbriae (Pap fimbriae — pyelonephritis-associated pili) — the Galα1-4Galβ receptor adhesin for upper UTI: P-fimbriae are structurally similar to Type 1 fimbriae but carry the PapG adhesin at the tip; PapG binds Galα1-4Galβ (globobiose) disaccharide residues on glycolipids (specifically globoside Gb4Cer and globotriaosylceramide Gb3Cer) expressed on uroepithelial cells of the upper urinary tract (collecting duct, renal pelvis, and proximal tubule brush border); P-fimbriated UPEC strains are strongly associated with pyelonephritis (ascending UTI to the renal pelvis and parenchyma) in dogs; PapG class II adhesin (the most common pyelonephritis-associated PapG variant) binds Gb4Cer with Kd approximately 10 nM; (c) other UPEC virulence factors: alpha-hemolysin (HlyA — a pore-forming RTX toxin; HlyA forms Ca2+-permeable pores in uroepithelial cell and erythrocyte membranes → cell lysis → haematuria); cytotoxic necrotising factor 1 (CNF1 — a deamidase targeting Rho GTPases [RhoA, Rac1, Cdc42] → constitutive Rho activation → actin cytoskeleton rearrangement facilitating UPEC internalisation); siderophores (aerobactin, enterobactin) for iron acquisition in the iron-limited urinary tract environment
• Recurrent UTI — the IBC reservoir and fimbrial re-adherence cycle that Cranbact targets: recurrent UTIs (defined as ≥3 UTI episodes per year or ≥2 episodes in 6 months) are common in dogs, particularly in females (the shorter, wider female canine urethra provides less mechanical resistance to ascending uroepithelial colonisation; the urethral mucosal folding and urethral-associated lymphoid tissue [UALT] provide some defence but are insufficient to prevent ascending colonisation in susceptible individuals); the molecular basis of recurrence: (a) IBC reservoir relapse — UPEC persisting in umbrella cell IBCs re-exfoliate after antibiotic treatment discontinuation (antibiotics eliminate the planktonic and luminal UPEC population but cannot penetrate the IBC biofilm matrix at therapeutic concentrations − the glycocalyx of the IBC [composed of type 1 fimbriae, curli fibres [CsgA/CsgB-assembled amyloid fibres], and cellulose] forms a diffusion barrier reducing intrabacterial antibiotic concentrations below MIC); (b) re-colonisation from the gastrointestinal or perivulvar reservoir — the dog’s faecal/perivulvar E. coli flora re-seeds the urethra between episodes; cranberry PACs’ anti-adherence activity is relevant to BOTH mechanisms: by preventing new FimH/PapG-mediated uroepithelial adhesion, PACs reduce: (i) new umbrella cell internalisation and IBC formation; (ii) recolonisation from the perivulvar reservoir

Active Ingredients & Mechanisms of Action

• VitaCran® cranberry extract (Vaccinium macrocarpon, 6% PAC standardisation) — the clinically validated cranberry ingredient and its anti-adherence PAC mechanism: VitaCran® is a proprietary standardised cranberry fruit extract (the registered cranberry ingredient in Cranbact) providing minimum 6% proanthocyanidins (type-A PACs) and 6% quinic acid per specified quantity; cranberry PACs — the type-A proanthocyanidins (the structural feature unique to Vaccinium spp.): proanthocyanidins (condensed tannins) are oligomeric and polymeric polyphenols formed by condensation of flavan-3-ol monomers ((+)-catechin and (-)-epicatechin); the critical structural distinction between cranberry PACs and grape seed/pine bark PACs (type-B PACs) is the linkage between flavan-3-ol units: type-B PACs have a single C4→C8 or C4→C6 interflavan bond; cranberry type-A PACs have an ADDITIONAL C2→O→C7 ether bond between the monomers (creating a doubly-linked A-type interflavan bond − specifically between the C-2 of the ‘upper’ unit and the O-7 of the ‘lower’ unit); this additional ether linkage creates a more rigid, constrained ring structure (the A-type PAC adopts a planar, butterfly-like conformation vs the more flexible extended chain of type-B PACs); anti-adherence mechanism of type-A PACs against FimH: the type-A PAC planar polyphenolic structure mimics the conformation of mannose-containing oligosaccharides → type-A PACs compete with the UPIa high-mannose N-glycan for binding to the FimH lectin domain’s mannose-binding site (the Phe1, Tyr48, Tyr137, Tyr140, Asp140, and Asn135 residues of FimH’s mannose-binding site that contact α-D-mannose are the same residues that contact type-A PAC’s hydroxyl groups) → FimH’s lectin domain is occupied by PAC → UPEC cannot form the initial fimbrial adhesion bond with uroepithelial UPIa → UPEC is eliminated by urine flow; type-A PACs also interfere with P-fimbriae PapG adhesin binding to Galα1-4Galβ glycolipid receptors (the polyphenolic hydroxyl groups of PACs interact with the galactose-binding site of PapG, though with lower affinity than for FimH); critically: type-B PACs (from grape seed, green tea catechins, or most commercial OPC supplements) do NOT have anti-adherence activity against FimH — the A-type double ether linkage is required for the correct spatial orientation of hydroxyl groups to occupy the FimH mannose-binding site; this explains why only cranberry-specific type-A PACs (not generic OPC supplements) have clinically validated urinary anti-adherence activity
• Proanthocyanidins/OPCs (minimum 3% in Cranbact) — the anti-adherence, antioxidant, and anti-biofilm polyphenol fraction: (a) anti-adherence: type-A PAC FimH and PapG adhesin blocking as described above; (b) anti-biofilm: PACs at sub-MIC concentrations inhibit UPEC biofilm formation on uroepithelial surfaces and on catheter/cystoscope surfaces: PACs bind to the extracellular matrix components of UPEC biofilms (type 1 fimbriae, curli fibres [amyloid], and cellulose) → PAC–curli interaction: PAC polyphenolic groups interact with the β-sheet rich CsgA amyloid structure of curli fibres via hydrogen bonding and hydrophobic stacking → inhibits CsgA fibre polymerisation → reduces biofilm structural integrity; (c) antioxidant activity: PACs are potent free radical scavengers (the catechol and pyrogallol B-ring hydroxyl groups of the flavan-3-ol units donate H• to reactive oxygen species → stable phenoxyl radicals; PACs also chelate iron and copper ions [transition metal ion chelation prevents Fenton chemistry: Fe2+ + H2O2 → •OH + Fe3+ + OH− − the Fenton reaction generates the most reactive ROS in biological systems]); ORAC value of VitaCran® at 400 mmol TE/g (trolox equivalents per gram) indicates potent antioxidant capacity relevant to the oxidative stress of UTI-associated bladder inflammation (activated neutrophils and macrophages in the inflamed bladder produce •O2− via NADPH oxidase [NOX2] − a host defence mechanism against UPEC that also damages uroepithelial cells; PAC antioxidant activity helps protect the uroepithelium from collateral ROS damage during the immune response to UTI)
• Quinic acid (minimum 6%) — urinary acidification via the hippuric acid pathway: quinic acid (1L-1(OH)-3,4/5-cyclohexanetetracarboxylic acid; MW 192.17 g/mol; a cyclitol polyhydroxy acid abundant in cranberry, coffee, and quinine bark) undergoes hepatic metabolism via: (a) quinic acid → shikimate pathway − a minor route to protocatechuic acid and catechol → further conjugation; (b) the primary urinary relevance pathway: quinic acid → gut microbial metabolism by colonic bacteria (specifically Lachnospiraceae and Ruminococcaceae [key colonic SCFA producers] that express quinic acid dehydrogenase and protocatechuate decarboxylase) → benzoic acid → hepatic mitochondrial activation to benzoyl-CoA (by medium-chain acyl-CoA synthetase [MACS/SLC27A5]) → glycine N-acyltransferase (GLYAT, a mitochondrial matrix enzyme) conjugates benzoyl-CoA with glycine → hippuric acid (N-benzoylglycine; MW 179.17 g/mol); hippuric acid is excreted in urine → urinary acidification (hippuric acid pKa approximately 3.6 − at physiological urinary pH, hippuric acid contributes to urinary acidification; acidic urine [pH <6.5] inhibits UPEC growth [UPEC’s optimal growth pH is 6.8–7.4; acidic pH inhibits UPEC outer membrane assembly and LPS lipid A biosynthesis] and reduces the ionisation of other urinary antibacterial compounds [methenamine hippurate generates formaldehyde [CH2O] only in acidic urine pH <6.0 via acid-catalysed hydrolysis − the same acidification principle applies to the natural quinic acid → hippuric acid pathway in Cranbact]); quinic acid also acts as a direct antioxidant (the polyhydroxyl cyclohexane structure’s adjacent hydroxyl groups chelate Fe3+ and Cu2+ and donate electrons to •OH radicals) and as a substrate for the antioxidant enzyme systems of the renal tubular epithelium

Indications

• Adjunctive therapy in confirmed urinary tract infections (UTIs) in dogs and cats — alongside appropriate antibiotic therapy guided by urine culture and sensitivity
• Prophylaxis against recurrent UTIs in dogs and cats with a history of ≥2 UTI episodes within 6 months or ≥3 episodes per year
• Post-antibiotic urinary tract support — maintenance of urinary tract health following completion of antibiotic therapy
• Supportive bladder health in dogs and cats at increased anatomical risk of recurrent UTI (female dogs with perivulvar fold dermatitis, dogs post-urinary catheterisation)

Directions for Use

• Administer as directed by a veterinarian or as per the Vivaldis label instructions
• Cats & small to medium dogs: 1 capsule twice daily
• Large dogs: 2 capsules twice daily
• Capsules may be administered directly or opened and mixed into food
• 30 capsules per pack; for prophylaxis, ongoing use is typically recommended with periodic veterinary review

Safety Information

• For animal use only — keep out of reach of children
• Not a substitute for veterinary diagnosis and antibiotic treatment of active UTIs
• Animals with signs of lower urinary tract disease (blood in urine, straining, frequent urination, urinating outside the litter box) require veterinary assessment to confirm the diagnosis before treatment
• Store in a cool, dry place away from direct sunlight