Hogeveen, H.

Steeneveld, W.

Werven, T., van

English

van Werven, T.

NARCIS 

Economic optimization of antibiotic treatment for clinical mastitis

Name not available

Wageningen Yield 

 1 
Economic optimization of antibiotic treatment for clinical mastitis  
W Steeneveld1, T van Werven1 and H Hogeveen1,2 
1Department of Farm Animal Health, Utrecht University, Utrecht, the Netherlands 
2Business Economics Group, Wageningen University, Wageningen, the Netherlands 
Abstract 5 
Most clinical mastitis (CM) cases are treated in the same way, following a farm-
specific treatment protocol. Cure rates, however, are strongly influenced by several 
cow factors. Therefore each CM case should be treated in the most appropriate way, 
based on those specific cow factors. The objective of this research was to develop a 
simulation model to determine the optimal treatment for each CM case in terms of 10 
total costs. Total costs of 4 different antibiotic treatment regimes (standard 
intramammary, extended intramammary, combination intramammary + parenterally, 
and combination extended intramammary + parenterally) were compared by 
simulating 5,000 CM cases. All input for the model was based on literature 
information and authors’ knowledge. Bacteriological cure for each individual cow 15 
depended on the choice of treatment, the causal pathogen and the cow factors parity, 
SCC and CM history. Total costs for each individual case were dependent on 
treatment costs, milk production losses and costs for culling. Mean total costs for the 
4 treatments were €170, €189, €190 and €209, respectively. For 65% of CM cases the 
3-day intramammary antibiotic treatment had the lowest costs and was defined as 20 
optimal. For 23% of the cases an extended intramammary treatment was optimal, 
while for 10% and 1% of the cases the combination intramammary + parenterally and 
the combination extended intramammary + parenterally were optimal, respectively. 
For 1% of the CM cases, immediate culling was optimal. For cows producing more 
than 35 kg, for cows which had previous CM cases and for cows in the first months of 25 
 2 
lactation, the more intensive antibiotic treatments became more advantageous. The 
results show the potential of a cow-specific treatment of CM. 
Introduction 
Most clinical mastitis (CM) cases are treated in the same way, following a farm-
specific treatment protocol. It is, however, known that the cure rate of CM is highly 30 
cow dependent (Bradley and Green, 2009). By taking into account cow factors, it is 
possible to optimize the choice and duration of treatment. For instance, it is likely that 
a heifer with a low SCC and no CM history will cure by using a standard antibiotic 
treatment, while an older cow with a high SCC and a history of CM might need an 
extended antibiotic treatment to cure.  35 
Optimizing the choice of treatment for each CM case, which also includes the option 
to cull a cow with CM immediately (Bar et al., 2008b), can result in more prudent use 
of antibiotics. The optimal treatment of CM is often measured in terms of clinical or 
bacteriological cure. Dairy farming is, however, an economic enterprise, and it could 
be argued that the real measure of cure should be the cost-benefit of treatment 40 
(Barkema et al., 2006).  
In the current study, a stochastic Monte Carlo model was developed to simulate CM 
cases treated with one of four different antibiotic treatment regimes or immediately 
culled. Subsequently, this model was used to determine for which cows which option 
for CM is optimal in terms of total costs.  45 
Material and Methods 
Model development 
The model described in this paper was built using Microsoft Excel with @Risk add-in 
software (Palisade, 2002). All discrete events and variability at the cow level were 
triggered stochastically, using random numbers drawn from distributions. Input for 50 
 3 
these distributions was based on knowledge of the model domain, information from 
literature and expertise of the authors.  
Model outcomes were generated in 3 steps. First, every iteration (5,000 in total) 
during the simulation process gave a specific cow with CM caused by streptococci, 
Staphylococcus aureus or Escherichia coli. In the second step the follow up of this 55 
CM case for each of the five treatments (4 different antibiotic treatment regimes and 
immediate culling) were simulated. The third step involved calculation of the 
associated costs for each of the five treatments for this case. Finally, for each 
simulated CM case, the optimal treatment was defined as the option with the lowest 
total costs.   60 
Simulation of CM cases 
By using a discrete probability distribution, for each CM case the causal pathogen was 
simulated (streptococci (40%), S. aureus (30%) or E. coli (30%)). Subsequently, for 
each cow with CM, the parity, the day in milk, the most recent SCC, the 305-day milk 
production, the calving interval and whether it was a repeated CM case or not (Döpfer 65 
et al., 1999; Swinkels et al., 2005a; Swinkels et al., 2005b) were determined. Daily 
milk production at day of CM and the remaining milk production during the rest of 
lactation were estimated by Wood’s lactation curve (Wood, 1967).  
Simulation of effect of treatment of a CM case 
Four different treatment regimes were defined, differing in route of application, 70 
duration, costs, treatment time, days of milk withdrawal and bacteriological cure rate 
(Table 1).  
 
 
 75 
 4 
Table 1. Characteristics of the four defined antibiotic treatment regimes.  
 Antibiotic treatment regime 
 INT1 INT2 INT_PAR1 INT_PAR2 
Application 
(number) 
Intramammary 
(3) 
Intramammary 
(5) 
Intramammary (3) 
+ parenterally (3) 
Intramammary (5) 
+ parenterally (3) 
Total costs         
antibiotics (€) 15 25 45 55 
# days milk 
withdrawal 5 7 5 7 
Total treatment 
time (minutes) 42 62 45 65 
Bacteriological 
cure (%)1 
    Streptococci 
    S. aureus 
    E. coli 
 
 
75 
40 
80 
 
 
80 
50 
85 
 
 
80 
60 
85 
 
 
85 
70 
90 
1 Bacteriological cure rates assumed for heifers, with somatic cell count <200,000 
cells/mL and no clinical mastitis before. 
 
For each CM case, treated with the four defined antibiotic regimes, it was determined 80 
whether it was cured bacteriologically or not. If the cow was not cured 
bacteriologically, the cow had an 80% probability to be clinically cured. All non-
clinically cured CM cases were treated again with the same antibiotic treatment.  If 
after retreatment no clinical cure had occurred, the cow had a 5% chance of dying and 
a 95% probability that the infected quarter would be dried-off. Cows with dried-off 85 
quarters had a probability of being culled during the remainder of the lactation of 
33%. All completely cured CM cases had a probability varying between 5 and 25%, 
depending on the number of CM cases, of being culled during the remainder of the 
lactation. All non-bacteriologically cured CM cases had a probability of having a 
clinical flare-up later in lactation of 10%, 12% and 5% for streptococci, S. aureus and 90 
E. coli, respectively (Döpfer et al., 1999; Swinkels et al., 2005a; Swinkels et al., 
2005b). Additionally, cows not cured bacteriologically had a probability of being 
culled during the remainder of lactation. This probability was 16% for cows with 1 
previous CM case and 20% for cows with 2 previous CM cases. If an antibiotic 
 5 
treatment of the second clinical flare-up did not result in bacteriological cure, the cow 95 
was culled immediately (Table 2 + Figure 1).  
Bacteriological cure rates from literature were used (Bradley and Green, 2009; 
McDougall et al., 1998; McDougall et al., 2003; McDougall et al., 2007; Sol et al., 
2000) as basis for the success rate of the four defined antibiotic regimes. Based on 
those cure rates, the maximum bacteriological cure for CM cases caused by 100 
streptococci, S. aureus and E. coli was determined based on expertise of the authors 
for all four antibiotic regimes. The maximum cure was assumed for heifers with a 
SCC below 200,000 cells/mL and no CM case before (Table 1). Thereafter, that 
maximum bacteriological cure rate was adapted, based on the literature (Barkema et 
al., 2006; Bradley and Green, 2009) and expertise of the authors, for the parity of the 105 
cow, the most recent SCC and whether it was a repeated case or not. In comparison 
with the maximum, for CM cases in older cows the cure rate was reduced by 10%, for 
CM cases after a SCC between 200,000 and 500,000 cells/mL the cure rate was 
reduced by 10%, for CM cases after a SCC above 500,000 cells/mL the cure rate was 
reduced by 15% and for repeated CM cases the cure rate was divided by two.  110 
Costs of CM 
The costs for CM included costs for antibiotics (Table 1), costs for discarded milk 
(€0.17 per kg), labour (hourly rate of €18), costs for milk production losses (€0.12 per 
kg) and costs for culling. 
The costs for each culled cow were expressed using the retention pay-off (RPO) value 115 
of a cow. The RPO is defined as the maximum amount of money that should be spent 
to keep a cow in case of health problems. The RPO was calculated with a stochastic 
model developed by Houben et al. (1994). 
 6 
The effect of CM on the degree of milk losses varies, depending on the causal 
pathogen (Schukken et al., 2009), the parity, time after CM case (Bar et al., 2007) and 120 
whether the cow was cured bacteriologically or not. For bacteriologically cured 
streptococci in heifers milk production losses varied between 6% (month 1) and 1% 
(month ≥8). For bacteriologically cured S. aureus and E. coli in heifers, 2% and 4% 
more production losses were assumed for each month after treatment of CM, 
respectively. For older cows, 5% more production losses were added. For non-125 
bacteriologically cured CM cases 5% more production losses were added. Cows with 
dried-off quarters had in total 15% milk production losses in the remaining of 
lactation. By using the percentages, the total milk production losses for the remaining 
lactation were calculated based on Wood’s lactation curve.  
 130 
Table 2. Values and source of value of parameters used in the simulation model for 
antibiotic treatment of a clinical mastitis (CM) case.  
Parameter Value Source 
Probability of clinical cure for non- 
      bacteriological cured CM cases 
80% Expertise 
 
Probability of clinical flare-up for non-   
bacteriological cured CM cases 
      Streptococci 
      S. aureus 
      E. coli 
 
 
10% 
12% 
5% 
 
 
Swinkels et al., 2005b 
Swinkels et al., 2005a 
Döpfer et al., 1999 
Probability of being culled for non-
bacteriological cured CM cases 
      1 previous CM case 
      2 previous CM cases 
 
 
16% 
20% 
 
 
Bar et al., 2008a + Expertise 
Probability of being culled for  
      completely cured CM cases 
5-25%1 Bar et al., 2008a + Expertise 
Probability of dying for non-clinical 
      cured retreated CM cases 
5% Bar et al., 2008a + Expertise  
Probability of drying-off quarter for  
      non-clinical cured retreated CM cases 
95% Expertise 
 
1Dependent on the number of previous CM cases.  
 7 
 
Figure. 1. Schematic representation of the simulation model for antibiotic treatment 135 
of a clinical mastitis (CM) case. (bact. = bacteriological, clin.= clinical). Culling 
represents a probability to be culled.  
 
Treatment of CM 
Bact. + clin.  
cure 
Bact. + clin.  
cure 
Bact. + clin.  
cure 
Dry-off quarter  
Direct culling 
 Retreatment  
Treatment of 
clin. flare-up 
No bact. cure, 
no clin. cure 
No bact. cure, 
no clin. cure 
No bact. cure, 
no clin. cure 
No bact. cure, 
no clin. cure 
Bact. + clin.  
cure 
No bact. cure, 
clin. cure 
No bact. cure, 
clin. cure 
No bact. cure, 
clin. cure 
No bact. cure, 
clin. cure 
Treatment of 
clin. flare-up 
No bact. cure, 
no clin. cure 
Bact. + clin.  
cure 
No bact. cure, 
clin. cure 
No  
clin. flare-up  
No  
clin. flare-up  
 Dying 
Dry-off quarter  
No culling  
No culling  
Culling    
Culling    
Culling    
Culling    
Culling    
Culling    
Culling    
Culling    Direct culling 
Culling    
 Retreatment  
Dying 
 8 
Results 
The mean total costs of the four treatment regimes varied between €170 and €209, the 140 
mean costs for immediate culling was €599. The costs for milk production losses and 
culling decreased with the more intensive treatments (Table 3). The mean 
bacteriological cure rates of the four treatments were 51%, 59%, 64% and 73%, 
respectively.  
 145 
Table 3. Mean total costs (€) for the four antibiotic treatment regimes and for 
immediately culling. Also costs for the different cost factors (5% and 95% percentiles 
given between brackets).  
 Treatment regimes  
 INT1 INT2 INT_PAR1 INT_PAR2 Culling 
Antibiotics 17 
(15; 30) 
28 
(25; 50) 
50 
(45; 90) 
60 
(55; 110) 
- 
Milk withdrawal 27 
(9; 55) 
37 
(12; 73) 
27 
(9; 52) 
37 
(12; 61) 
- 
Labour 15 
(13; 25) 
21 
(19; 37) 
15 
(14; 27) 
21 
(20; 39) 
- 
Milk production 
losses 
71 
(19; 147) 
68 
(19; 143) 
66 
(19; 136) 
63 
(18; 126) 
- 
Culling 40 
(0; 383) 
35 
(0; 381) 
32 
(0; 365) 
28 
(0; 350) 
- 
Total costs 170 
(61; 535) 
189 
(80; 543) 
190 
(90; 532) 
209 
(110; 530) 
599 
(176; 1020) 
 
The input variables on costs of culling, probability of culling and amount of milk 150 
production losses had an effect on the total mean costs of the four defined antibiotic 
treatment regimes for CM (Table 4).  
 
 
 155 
 
 
 
 9 
Table 4. The effect of different input variables on the mean total costs (€) for the four 
antibiotic treatment regimes. 160 
 Antibiotic treatment regime 
 INT1 INT2 INT_PAR1 INT_PAR2 
Default 170 189 190 209 
Costs culling  
    + €100 
    - €100 
 
182 
158 
 
197 
184 
 
199 
182 
 
220 
203 
Probability culling  
    + 5% 
    - 5% 
 
188 
153 
 
207 
171 
 
211 
172 
 
231 
193 
Milk production losses  
    + 5% 
    - 5% 
 
197 
142 
 
221 
165 
 
221 
160 
 
238 
180 
 
In total, for 65% of all 5,000 simulated CM cases the 3-day intramammary antibiotic 
treatment had the lowest costs and was defined optimal. For 23% of the cases an 
extended intramammary treatment was optimal, while for 10% and 1% of the cases 
the combination intramammary + parenterally and the combination extended 165 
intramammary + parenterally were optimal, respectively. For 1% of the cases 
immediate culling was optimal (Table 5). By looking to specific cow characteristics, 
the more intensive antibiotic treatments became more advantageous, for instance, for 
cows producing more than 35 kg, for cows with a repeated CM case and for cows in 
the first three months of lactation (Table 5).   170 
Discussion 
The costs of CM and, therefore, the choice of optimal treatment regime are highly 
influenced by the costs for milk production losses and costs of culling (Table 3). In 
the current study, probabilities of culling were included in the model. Culling, 
however, is a complex phenomenon, and the probability of cows being culled is farm 175 
dependent. To include culling in a more realistic way, farm-specific culling rules can 
be included or culling decisions can be optimized (Bar et al., 2008b).  
 
 
 10 
Table 5. Effect of cow factors on the optimal treatment option for clinical mastitis. 180 
 Optimal option (%) 
 INT1 INT2 INT_PAR1 INT_PAR2 Culling 
Default 65 23 10 1 1 
Causal pathogen 
    Streptococci 
    S. aureus 
    E. coli 
 
72 
52 
75 
 
20 
26 
20 
 
6 
16 
5 
 
1 
4 
0 
 
1 
2 
0 
Daily milk production (kg) 
    <20 
    20-25 
    25-30 
    30-35 
    35-40 
    >40 
 
74 
77 
75 
70 
63 
56 
 
19 
13 
17 
17 
26 
27 
 
4 
7 
6 
8 
10 
14 
 
1 
0 
0 
1 
1 
3 
 
2 
3 
2 
4 
0 
0 
Clinical mastitis history 
     No 
     Yes 
 
66 
58 
 
22 
26 
 
9 
12 
 
2 
3 
 
1 
1 
Month in lactation 
     1 
     2 
     3 
     4 
     5 
     6 
     7 
     ≥8 
 
55 
57 
58 
74 
79 
77 
79 
74 
 
26 
28 
28 
19 
14 
13 
12 
21 
 
14 
12 
12 
5 
5 
7 
7 
3 
 
3 
2 
2 
1 
0 
1 
1 
1 
 
2 
1 
0 
1 
2 
2 
1 
1 
 
For the current study, information on cure rates for four different antibiotic treatments 
was needed for cows with different parity, SCC history and CM history. Results of 
several clinical trials on effectiveness of antibiotic treatments were reported (e.g., Sol 
et al., 2000; McDougall et al., 2007; Bradley and Green, 2009), but such detailed 185 
information on cure rates was not available. Therefore, in the current study expertise 
of the authors was used to estimate the cure rates. The cure rates had a large influence 
on the optimal treatment. Because such detailed information on cure rates is not 
available, for further study it will be good to use more expert knowledge on cure 
rates.  190 
In conclusion, the results of the current study show the potential for cow-specific 
treatment of CM. On average, for 35% of the CM cases the standard 3-day 
 11 
intramammary antibiotic treatment did not have the lowest costs. By taking into 
account specific cow information, it was possible to determine for which cows with 
CM the more intensive antibiotic treatment regimes were advantageous.  195 
Acknowledgements 
This research was supported by the Dutch Technology Foundation STW, applied 
science division of NWO, and the Technology Program of the Dutch Ministry of 
Economic Affairs.  
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1967 


Economic optimization of antibiotic treatment for clinical mastitis

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