Clinical manifestations of common HPV types

1
BCG and antibiotics - a solution to side effects?
C. Durek
Dept. of Urology University of Schleswig Holstein
Campus Lübeck (Head Prof. Dr. med. D. Jocham)
2
BCG and antibiotics a solution to side effects?

• Open questions
• Routine administration of antibiotics during
  instillation course?
• Which antibiotics should be used to treat side
  effects of BCG ?
• Does prophylactic antibiotic treatment reduce BCG
  efficacy?

3
Material and Methods Routine administration of
antibiotics during instillation course?

• 32 antibacterial drugs
• Determination of minimal inhibitory
  concentration (MIC) against BCG-Connaught
• Radiometric BACTEC 460TB method 14CO2
  release from media proportioal to BCG growth
• MIC compared to blood and urinary concentration,
  determination of local or systemic
  susceptibility
• Cycloserin-susceptibility with 3 strains of BCG
  by modified proportion method

4
Antibacterials and viability of BCG

5
Antibacterials and viability of BCG
6
BCG susceptibility to Cycloserin
7
Which antibiotics should be used to treat side
effects? Material and methods

• Mouse model C57/bl6
• primary systemic BCG-infection i.p. injection
• Determination of the LD-50 of BCG i.p.
• Treatment with
• Flouroquinolones (100mg/kg KG/d) Prednisolone
  (100mg/kg KG/d)
• TMS (20mg/kg KG/d) Prednisolone (100mg/kg
  KG/d)
• NaCl Prednisolone (100mg/kg KG/d)

8
ResultsOral therapy of primary systemic
BCG-infection
1,0
0,8
Treatment Fluoroquinolores
Prednisolone Fluoroquinolores
Prednisolone Control
0,6
Cum. survival
0,4
0,2
0
0
2
4
6
14
16
18
20
8
10
12
Days after infection
9
ResultsOral therapy of primary systemic
BCG-infection
1,1
1,0
0,9
0,8
Treatment NaCl Ciprofloxacin Prednisolone
Ciprofloxacin
Cum. survival
0,7
0,6
0,5
0,4
0,3
0
2
4
6
14
16
18
20
8
10
12
Days after infection
10
ResultsOral therapy of primary systemic
BCG-infection
1,1
1,0
0,9
Treatment NaCl Trimetoprim Prednisolone
n.s. Trimetoprim n.s.
0,8
Cum. survival
0,7
0,6
0,5
0,4
0,3
0
2
4
6
14
16
18
20
8
10
12
Days after infection
11
Do prophylactic antibiotics reduce efficacy of
BCG Material and methods

• Mouse model C57/bl6
• Tumor model MB49 orthotopic bladder tumor model
• Intravesical BCG instillation and concomittant
  oral treatment
• Flouroquinolones (100mg/kg KG/d) Prednisolone
  (100mg/kg KG/d)
• TMS (20mg/kg KG/d) Prednisolone (100mg/kg KG/d)
  
• NaCl Prednisolone (100mg/kg KG/d)

12
The orthotopic murine bladder cancer model MB 49
i.p. pentobarbital - anesthesia
Catheterization
Electrocoagulation of the bladder wall
Intravesical instillation of MB49 cell solution
Resulting tumor implantation rate 90
13
Intravesical BCG-instillation and concomittant
oral therapy
0,7
0,6
0,5
0,4
Bladder weight (g)
0,3
0,2
0,1
0
- 0,1
0
Saline Control
BCG
Fluroquinolores / BCG
TMS / BCG
14
Intravesical BCG-instillation and concomittant
oral therapy bladder weight
0,7
0,6
0,5
0,4
Bladder weight
0,3
0,2
0,1
0
- 0,1
0
Control
BCG
Levofloxacin
Primetoprim
Prednisolone
15
Survival Intravesical BCG-instillation and
concomittant oral therapy
Cum. survival
10
20
30
40
50
60
70
0
Days after tumor implantation
Additional oral administration of antimicrobials
did not significantly affect BCG efficacy
16
Conclusion

• Avoid antibacterial adminstration during routine
  BCG- treatment.
• Local side effects (epididymitis, prostatitis,
  cystitis) should be treated early and initially
  with fluoroquinolones without risk of a reduced
  BCG-efficacy.
• Severe systemic infections require triple drug
  therapy.
• Cycloserine cannot be recommended any more.
• Hyperergic reactions in BCG-sepsis situations
  require steroid administration.