Introduction:
The use of antimicrobials remains the most common means of controlling infections caused by Mycoplasma gallisepticum (MG) and M. synoviae (MS). Antimicrobial resistance has been a reported concern in many countries and a comparative overview has been recently described by Valks and Burch (ref.1). An important factor in the successful control of these infections is the correct selection and use of the antimicrobial to achieve an effective concentration in the blood of a bird so that the organism can be destroyed. Age of bird, environmental temperature, concentration of a product, and palatability are some of the variable factors that can have an effect on the water intake and dosage rate achieved. A product’s pharmacokinetic characteristics of absorption, distribution, metabolism and excretion then determines the concentrations reached in the blood.
It was the purpose of this paper to compare the blood levels achieved in chickens by various antimicrobials with the reported MICs for MG and MS.
Materials and Methods:
A comparative database of MIC ranges for tiamulin and various other antimicrobials against MG (241 isolates) and MS (105 isolates) had been set up (Valks and Burch, ref. 1). The literature was also searched for information on pharmacokinetic data of various antimycoplasmal products used in chickens. Some data were derived from gavage studies in which, the maximum concentration (C max) and concentration at 12hours (C 12) were determined. In other studies a steady state or average level was recorded after prolonged administration in the drinking water.
Results:
The comparative MIC ranges against MG and MS are recorded below.
Table 1. Comparable MIC range (µg/ml) against MG and MS
Antimicrobial
M. gallisepticum (241)
M. synoviae (105)
Tiamulin
0.0039-0.78
0.006-1.0
Tylosin
0.006-400
0.006-75
Tetracycline
0.03-0.25
0.015-5.0
Oxytetracycline
0.05-200
0.025-100
Chlortetracycline
0.05-1.56
0.05-12.5
Doxycycline
0.006-0.2
0.0125-0.78
Spectinomycin
0.39-10
0.39-6.25
Enrofloxacin
0.01-2.0
0.025-1.56
Danofloxacin
0.01-0.78
0.1-0.5
Flumequine
2.5-10
5.0-50
The comparative pharmacokinetic data for various antimicrobials are summarized below.
Table 2. Comparative pharmacokinetic data for various antimicrobials in chickens
Reference
Antimicrobial
Dose Rate (mg/kg)
Conc. Water (ppm)
C max (µg/ml)
C 12hrs (µg/ml)
Steady state (µg/ml
2
3
Tiamulin
25
50
125
250
1.7
3.56
0.65
1.4
0.17
0.59
0.38
0.78
4
3
Tylosin
50
500
4.2
0.2
0.25
0.12
5
Tetracycline
533
0.76
0.45
6
Oxytetracycline
25
50
100
0.4
0.7
2.0
0.1
0.14
1.4
6
7
8
9
Chlortetracycline
CTC/Citric acid
Chlortetracycline
25
50
100
25
25
20
16
32
64
200
400
800
0.2
0.7
2.0
0.35
1.48
0.22
0.04
0.14
0.2
0.15
0.15
0.2
0.35
0.55
10
8
11
Doxycycline
20
15
11-15
100
54.58
8.48
2.2
7.0
1.9-2.2
12
Spectinomycin
33
0.08
<0.05
13
14
Enrofloxacin
10
10
60-65
1.88
0.25
0.84
13
15
16
Danofloxacin
5
5
5
50
0.47
1.85
0.08
0.2
17
18
Flumequine
9.2
12
18
5.0
9.2
2.0
1.8
0.9
2.4
The comparison of the highest C max of the various antimicrobials with the MIC ranges against MG and MS are summarized below.
Table 3. Comparison of C max and steady state levels (µg/ml) with MIC ranges (µg/ml) of various antibiotics against MG and MS
Antibiotic
MG
MS
C max
Steady state
Tiamulin
0.0039-0.78
0.006-1.0
3.56
0.78
Tylosin
0.006-400
0.006-75
4.2
0.12
Tetracycline
0.03-0.25
0.015-5.0
0.76
0.45
Oxytetracycline
0.05-200
0.025-100
2.0
-
Chlortetracycline
0.05-1.56
0.05-12.5
2.0
0.55
Doxycycline
0.006-0.2
0.0125-0.78
54.58
2.1
Spectinomycin
0.39-10
0.39-6.25
0.08
<0.05
Enrofloxacin
0.01-2.0
0.025-1.56
1.88
0.84
Danofloxacin
0.01-0.78
0.1-0.5
1.85
0.2
Flumequine
2.5-10
5.0-50
9.2
2.4
Conclusions:
The C max varied between trials, therefore the highest reported C max for each antimicrobial was taken to make a fair comparison for each product.
Tiamulin, doxycycline and danofloxacin had MIC ranges for both MG and MS well below the C max. Tylosin, the tetracyclines and flumequine all had MIC concentrations above the C max showing some strains would be resistant to treatment. The MIC ranges for spectinomycin were completely above the C max making its efficacy very suspect. Enrofloxacin had some MICs just above the C max suggesting that there is borderline resistance and some strains may not be completely controlled.
From these results, tiamulin, doxycycline and danofloxacin would be considered very active against almost all the isolates of both MG and MS and should prove very effective. Spectinomycin is likely to be ineffective and the remaining antibiotics would have an intermediate efficacy depending on the sensitivity of the individual mycoplasma isolate.
References:
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16. Pfizer – Advocin technical booklet
17. Moutafchieva, R, Nouws, J.F.M., Keukens, H.J., Kans, C.A., Beek, W.M.J., Streutjens, E., and Hoogenboom, L.A.P. (1997) The effect of co-medication with sodium salicylate on plasma disposition, metabolism and tissue distribution of flumequine in broilers. Proceedings of the European Association of Veterinary Pharmacology and Toxicology, Edinburgh, UK. pp 78-79
18. Rhone Merieux – Imequyl technical booklet
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