This document discusses diagnosis and treatment of metritis in dairy cows. It provides details on several studies that examined the impacts of metritis including lower dry matter intake before and after calving, associations with specific bacteria and virulence factors, and negative effects on milk production and reproduction. The document also summarizes research on treatments for metritis, finding that systemic antibiotics like ceftiofur and ampicillin effectively resolve clinical signs in the majority of cases but do not consistently improve pregnancy rates. Non-antibiotic intrauterine treatments with povidone-iodine or a uterotonic fluid showed promise based on one recent study.

1. Diagnosis and treatment of
metritis
Stephen LeBlanc
University of Guelph

2. Cows with post-partum metritis had
lower DMI during the post- and pre-
partum periods
0
4
8
12
16
20
-13 -10 -7 -4 -1 2 5 8 11 14 17 20
Healthy
Mildly Metritic
Severely Metritic
DMI(kg)
Day from Calving
Clinical signs of
infection
Huzzey et al. 2007

3. Hour
AverageDMIateachhour(kg)During the week before calving cows that develop
post-partum severe metritis (n=12) consume less
feed during the period immediately following fresh
feed delivery (F.D.)
F.D. F.D.
Huzzey et al. 2007
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
0:00 4:00 8:00 12:00 16:00 20:00
Healthy
Mildly Metritic
Severely Metritic
Courtesy of Dr. M. von
Keyserlingk

4. Transition Health and CR at 1st AI
5719 cows in 7 US herds
Santos et al RepDomRum 2010
Prevalence
56
27
17
15
16
20
21
12
10
7
3
2

5. Risk factors for uterine disease
 Species of bacteria
 Virulence factors
 Strain
 Level of
contamination
 Dry matter intake
 Energy and lipid
metabolic health
 Stressors & hormonal
changes
 Hypocalcemia
Bacteria
Immune response
Regulation of inflammation

6. Uterine E coli
Are the E coli associated with metritis and endometritis
specific uterine pathogens or do they have specific virulence
factors?
1. Silva et al 2009 – 72 isolates from 12 healthy cows and 18
with metritis – no associations of phylogenetic group or
specific virulence factors
– Strain associations with herd
2. Sheldon et al 2010 – 114 isolates from 64 cows from 1 herd
sampled at weeks 1 – 4
– Association of 1 group with metritis
– Strains found in cows with metritis were more adherent and
invasive to epithelium and LPS induced greater inflammatory
response in culture
3. Bicalho et al 2010
– 611 E coli isolates from 374 cows in week 1 in 4 herds, screened
for 32 virulence genes; subset of 117 cows screened for PVD in
week 4
– 6 virulence genes associated with reproductive tract disease
– Adherence factor (fimH) was the single strongest predictor of
metritis (OR = 6)

7. Vaccination against reproductive
tract disease
• Total of 371 heifers from 1 herd vaccinated at ~ 50
and 20 d before calving with vaccine containing
whole killed E. coli, F. necrophorum and T.
Pyogenes ±FimH, leukotoxin, and pyolysin
• SC vaccination with bacteria ± proteins
– decreased metritis incidence
• 12 to ~4% (Dx only at 6 DIM)
• 28 to 16% (daily Dx by farm staff)
– Decreased time to pregnancy
• 120 to 94 median DIM
– No effect on clinical endometritis (lavage visual at 35
DIM; 9%) or on prevalence of E. coli or F. necro at 2 or
6 DIM, or T. pyo ay 35 DIM
Machado et al 2014

8. Neutrophil myeloperoxidase (iodination)
activity – a measure of killing activity
Cows with
subclinical
endometritis at
28 DIM n = 43
Cows with metritis
< 14 DIM n = 18
Cows with normal
uterine health n = 22

9. Neutrophil myeloperoxidase (iodination)
activity – a measure of killing activity
Cows in the highest
quartile of DMI in the 3
weeks before calving
Cows in the lowest
quartile of DMI in the 3
weeks before calving

10. Associations of subclinical
hypocalcemia with immune function
and metritis
• Martinez et al JDS 2012
• 110 cows in 1 herd in Florida
• Pair-matched “high risk” (twins, stillbirth,
dystocia, RP) with low risk cows
• Subclinical hypo-Calcemia = ≤ 2.15
mmol/L at least once 1 – 3 DIM

11. Martinez et al JDS
2012

12. Martinez et al JDS
2012

13. Postpartum fever
• 10-45% overall prevalence of fever (Kinsel, 2001; LeBlanc,
2002; Sheldon, 2004)
• Not a good correlation between fever and
bacterial infection 1 to 10 DIM (Sheldon et al 2004)
– 56% of pyrexic cows had infection
– Prevotella was associated with fever
• Is fever alone a problem that requires antibiotics?
• Are there cows that would benefit from
antibiotics that do not have a fever?
• Is there a useful threshold to distinguish these
cows?
– > 39.7 or 40 at any time? > 39.5 for 2 days?
– Fetid discharge with or without fever?
– Milk production? Attitude? Other clinical signs?

14. Physiology vs. pathology
• Almost all cows have bacterial contamination of
the uterus after calving
• The same immune system mediators appear to
be involved in healthy and affected cows
– TLR4; IL1, 6, 8 , 10; (TNFα)
• Difference lies in the magnitude, regulation,
duration and effectiveness of the response
Involution
Pathological
inflammation

15. Metritis diagnosis - repeatability
• 6 samples of postpartum vaginal discharge
(3 healthy, 2 metritis (1 repeated))
• 10 repetitions of each sample, randomized
• 15 vets and final year vet students
Kappa Colour
32 point chart
Smell
1 – 5 scale
Viscosity
1 – 5 scale
Kappa statistic
Inter-rater 0.15 0.27 0.44
Intra-rater 0.35 0.39 0.60
A central diagnostic criterion has
only fair reliability
Sannmann &
Heuwieser JDS
2015

16. Metritis diagnosis - Temperature
• Considered separately, rectal temperature
associated with
– Parity (0.2 C greater in lact=1)
– Ketosis (higher in ketotic in lact=1)
– Environmental THI (higher in June and July)
• Must be interpreted in context
Burfeind et al Therio 2014

17. RP and Metritis Impacts on
Reproduction & Culling
RP Metritis
No Yes P-value No Yes P-value
Pregnancy risk (%)
First service 34.7 29.4 0.02 35.3 27.2 < 0.01
120 DIM 46.5 33.2 < 0.01 46.0 36.3 < 0.01
300 DIM 83.5 76.0 < 0.01 80.4 82.6 0.02
Culling risk (%)
30 DIM 3.2 6.3 0.34 3.6 4.5 0.70
63 DIM 6.4 9.0 0.71 6.8 7.2 0.92
300 DIM 16.9 18.5 0.69 17.0 18.0 0.83
No full-lactation effects when parity, production, DA,
endometritis, pregnancy accounted for
Dubuc et al, 2010

18. Metritis and Production
Wittrock et al JDS 2011

19. Impact of Metritis on Milk Production
Multiparous
(metritis)
Primiparous
(metritis)
26
28
30
32
34
36
38
40
1 2 3 4
Milkproduction(kg/d).
DHI test-days
No metritis Metritis
250 kg less milk per
lactation for multiparous
cows with metritis
34
36
38
40
42
44
46
48
50
1 2 3 4
Milkproduction(kg/d)
Dubuc et al, 2010

20. Impact of metritis
• 1600 cow dry lot dairy in Argentina, TMR-fed
• 303 cows examined at 5, 6, 7 DIM: T and gloved
hand
– “Clinical metritis” = fetid discharge (n=29; 10%)
– “Puerperal metritis” = fetid discharge + T > 39.2 C
(n=90; 30%)
• Both randomly assigned to ceftiofur 2.2. mg/kg IM
x 3 d or untreated
• Cure = clear discharge at 21 DIM
• No effect of ceftiofur on clinical cure (69%; n=100)
or milk yield to 90 DIM; tended to increase CR at
1st TAI

21. Giuliodori et al JDS 2013
Impact of different forms of metritis

22. Prevalence of Uterine Disease
Classification of risk
for uterine disease
Low risk
High Risk
(Dystocia, twins, RP)
Metritis 12% 28%
EXAM 35 DIM n=1116 n=956
Endometritis only 13% 13%
PVD only 5% 15%
Both 4% 10%
Total 22% 38%
Dubuc et al, 2010

23. Concepts of inflammatory response
1 42 3 5
UterineInflammation
weeks
Healthy
Endometritis –
excessive
inflammation
Endometritis –
inadequate response

24. What impact does
this have on this cow?
Can we improve her
outcomes?

25. Metritis treatment
• Case definition = T > 39.5 + fetid discharge
• 1) n = 406 cows (8 large herds) randomized
to control, 1.1 or 2.2. mg/kg ceftiofur for 5 d
Chenault et al , 2004
• 2) n = 982 cows (15 herds) randomized to 2
doses CCFA (3 d apart) or saline control
McLaughlin et al JDS 2012
• Clinical cure (no fever; no fetid discharge) at
day 14:
–Ceftiofur:77% Saline: 62%
–CCFA: 74% Saline: 55%

26. Wait and see?
• 1 herd in Germany; daily metritis detection; Rx = 1
dose of CCFA (Sannmann et al Therio 2013)
• 12 treated at Dx 1-4 DIM
• 19 not treated at Dx 1-4 DIM
– 12 never treated as no metritis at 5 – 10 DIM
– 7 with delayed treatment at 5-10 DIM
• 48 treated at Dx 5-10 DIM
• No difference in fever at 4 d after Dx or clinical
outcomes to 28 DIM
• Ability to apply this likely depends on
– Presence of complicating factors
– Sensitivity of detection of worsening clinical condition
– Heat stress
• Larger scale study needed

27. Metritis treatment
• n = 528 cases of fetid discharge (n=312) or
metritis (fetid + T ≥ 39.5 C; n=216) from 1
large dairy in Florida; 268 matched healthy
cows in comparison group
• Blocked by metritis type, randomly assigned
to 11 mg/kg ampicillin or 2.2 mg/kg ceftiofur
q 24 h x 5 d
• PreSynch 50 and 64 DIM, bred on estrus after
2nd PGF or 5-d Ovsynch with TAI at 84 DIM
Lima et al JDS 2014

28. Metritis treatment
• Among cows with fetid discharge only,
53% developed ≥ 1 day of fever while on
antibiotics
Lima et al JDS 2014

29. Metritis
treatment
Clinical cure
Lima et al JDS 2014
• Ampicillin >
ceftiofur days 5 and
7
• Cure at day 12 not
different ~67%
• No interactions of
treatment with
metritis type, parity,
dystocia

30. Metritis
treatment
PVD and
endometritis
Lima et al JDS 2014
• Lower prevalence of
PVD at 32 d with
ampicillin than
ceftiofur
• No difference in
endometritis at day
39

31. Metritis treatment – Reproductive
performance
Outcome Ampicillin Ceftiofur Healthy
comparison
P
Cyclic 64 DIM 75% 76% 75% 0.96
Pregnant 1st AI
30 d 29% 29% 32% 0.87
60 d 28% 28% 31% 0.91
Loss 6% 6% 11% 0.52
Lima et al JDS 2014
These outcomes not different between
fetid discharge and metritis

32. Metritis IU – Non-antibiotic
• n = 220 cases of metritis (fetid discharge T >
39.5 C, systemic illness) from 1 large organic
dairy in Texas, randomly assigned to 200 ml
povidone iodine in 2 L water or 3.75 ml
Optimum UterFlush in 117 ml water, each q
48 h x 3 d (Days 1,3,5)
• All received hypertonic saline + dextrose IV
and 5 Aspirin/d (duration = ?)
• Tail chalk , estrus detection only
Pinedo et al JDS 2015

33. Metritis IU – Non-antibiotic
Outcome UterFlush Iodine Statistics (OR from
models)
Healthy
comparison group
Day 6 T > 39.5 C 31% 20%
Fetid discharge 28% 11% OR = 0.2 {.09 - .45}
Cure 70% 49% P = 0.003
Culled 4% 11% OR = 4.7 {1.4 - 16}
Day 14 T > 39.5 C 12% 8% P = 0.38
Fetid discharge 1% 9% OR = .08 {.01 - .63}
Cure 76% 66% P = 0.18
Culled 13% 22% OR = 2.8 {1.3 – 6.1}
Day 30 Culled 16% 27% OR=3.1 {1.2 – 8.0} 2%
AI by 150 DIM 62% 57% P=0.27 93%
Pregnant 1st AI 38% 23% P =0.05 39%
Pregnant 150 DIM 45% 30% OR=1.8{1.04-3.2} 75%
Pregnant 300 DIM 59% 44% OR=1.9 {1.1-3.4} 90%
Pinedo et al JDS 2015

34. Metritis Treatment Summary
• Diagnostic criteria inconsistent and not
well validated (Sannmann et al 2012)
• Systematic review (Haimerl & Heuwieser
2014)
– 23 studies; narrow set of research questions
but overall high quality of evidence

35. Mastitis Treatment Summary
• Cows with  2 of : T > 39.5; fetid discharge;
dullness/off-feed can rationally be treated
with systemic antibiotics
• Ceftiofur, ampicillin, or penicillin likely to
be similarly efficacious (Smith et al 1998; Drillich
et al 2001; Chenault et al 2004; Lima et al 2014; review by
Reppert VCNA 2015)

36. Metritis Treatment Summary
• Expected outcomes:
– Absence of fever in 80 – 100% of cows 2-6
days after treatment
– Absence of fetid discharge 33 – 77%
– No difference pregnancy rate between
ceftiofur and ampicillin (Lima et al 2014)
• More field research is needed to refine
treatment selection criteria, and assess
antimicrobial resistance, animal welfare,
and economics