Pseudomonas aeruginosa (inhalation)

ID	Exposure Route	# of Doses	Agent Strain	Dose Units	Host type	Μodel	LD50/ID50	Optimized parameters	Response type	Reference
281	injected in eyelids	6.00	ATCC 19660	CFU	Swiss webster mice (5day old)	exponential	8.13E+03	k = 8.52E-05	death	Hazlett, L. D., Rosen, D. D., & Berk, R. S. (1978). Age-Related Susceptibility to Pseudomonas aeruginosa Ocular Infections in Mice. Infection and Immunity, 20, 1.
281,282 (pooled)	injected in eyelids	12.00	ATCC 19660	CFU	Swiss webster mice (5day old)	exponential	6.61E+03	k = 1.05E-04	death	Hazlett, L. D., Rosen, D. D., & Berk, R. S. (1978). Age-Related Susceptibility to Pseudomonas aeruginosa Ocular Infections in Mice. Infection and Immunity, 20, 1.
282	injected in eyelids	6.00	ATCC 19660	CFU	Swiss webster mice (5day old)	exponential	4.98E+03	k = 1.39E-04	death(after day 21)	Hazlett, L. D., Rosen, D. D., & Berk, R. S. (1978). Age-Related Susceptibility to Pseudomonas aeruginosa Ocular Infections in Mice. Infection and Immunity, 20, 1.
283	injected in eyelids	6.00	ATCC 19660	CFU	Swiss webster mice(10day old)	beta-Poisson	1.93E+04	a = 6.73E-01 N₅₀ = 1.93E+04	death(after day 1)	Hazlett, L. D., Rosen, D. D., & Berk, R. S. (1978). Age-Related Susceptibility to Pseudomonas aeruginosa Ocular Infections in Mice. Infection and Immunity, 20, 1.
283,284	injected in eyelids	12.00	ATCC 19660	CFU	Swiss webster mice(10day old)	beta-Poisson	1.48E+04	a = 6.01E-01 N₅₀ = 1.48E+04	death	Hazlett, L. D., Rosen, D. D., & Berk, R. S. (1978). Age-Related Susceptibility to Pseudomonas aeruginosa Ocular Infections in Mice. Infection and Immunity, 20, 1.
284	injected in eyelids	6.00	ATCC 19660	CFU	Swiss webster mice(10day old)	beta-Poisson	1.13E+04	a = 5.49E-01 N₅₀ = 1.13E+04	death(after day 2-21)	Hazlett, L. D., Rosen, D. D., & Berk, R. S. (1978). Age-Related Susceptibility to Pseudomonas aeruginosa Ocular Infections in Mice. Infection and Immunity, 20, 1.
286	contact lens	5.00	ATCC 19660	CFU	Swiss webster mice	exponential	7.88E+06	k = 8.8E-08	infection (Keratitis)	Hazlett, L. D., Rosen, D. D., & Berk, R. S. (1978). Age-Related Susceptibility to Pseudomonas aeruginosa Ocular Infections in Mice. Infection and Immunity, 20, 1.
297	contact lens	5.00		CFU	white rabbit	beta-Poisson	6.57E+03	a = 3.55E-01 N₅₀ = 6.57E+03	corneal ulceration	Lawin-Brüssel, C. A., Refojo, M. F., Leong, F. L., Hanninen, L. ., & Kenyon, K. R. (1993). Effect of Pseudomonas aeruginosa concentration in experimental contact lens-related microbial keratitis. Cornea, 12, 1.
297 & 298	contact lens	10.00		CFU	white rabbit	beta-Poisson	1.85E+04	a = 1.9E-01 N₅₀ = 1.85E+04	corneal ulceration	Lawin-Brüssel, C. A., Refojo, M. F., Leong, F. L., Hanninen, L. ., & Kenyon, K. R. (1993). Effect of Pseudomonas aeruginosa concentration in experimental contact lens-related microbial keratitis. Cornea, 12, 1.
298	contact lens	5.00		CFU	white rabbit	beta-Poisson	1.52E+05	a = 1.09E-01 N₅₀ = 1.52E+05	Severe stromal ulceration	Lawin-Brüssel, C. A., Refojo, M. F., Leong, F. L., Hanninen, L. ., & Kenyon, K. R. (1993). Effect of Pseudomonas aeruginosa concentration in experimental contact lens-related microbial keratitis. Cornea, 12, 1.
Ojielo2003	intratracheal	7.00	PA01	CFU	C57BL/6 mice	exponential		k = 3.22E-7	death	Ojielo, C. I., Cooke, K. ., Mancuso, P. ., Standiford, T. J., Olkiewicz, K. M., Clouthier, S. ., … Moore, B. B. (2003). Defective Phagocytosis and Clearance of <i>Pseudomonas aeruginosa</i> in the Lung Following Bone Marrow Transplantation. The Journal of Immunology, 171(8), 4416-4424. Retrieved from https://journals.aai.org/jimmunol/article/171/8/4416/35775/Defective-Phagocytosis-and-Clearance-of (Original work published)

Exposure Route:

injected in eyelids

# of Doses:

6.00

Agent Strain:

ATCC 19660

Dose Units:

CFU

Host type:

Swiss webster mice (5day old)

Μodel:

exponential

LD50/ID50:

8.13E+03

Optimized parameters: k = 8.52E-05

Response type:

death

Reference:

mice (5day old) / *Pseudomonas aeruginosa*
Dose	Dead	Survived	Total
2.5	0	13	13
25	0	14	14
250	0	12	12
2500	4	13	17
25000	13	2	15
250000	17	0	17

**Goodness of fit and model selection**
Model	Deviance	Δ	Degrees of freedom	χ²_0.95,1 p-value	χ²_0.95,m-k p-value
Exponential	0.802	0.0885	5	3.84 0.766	11.1 0.977
Beta Poisson	0.713	0.0885	4	3.84 0.766	9.49 0.95
Exponential is preferred to beta-Poisson; cannot reject good fit for exponential.

**Optimized k parameter for the exponential model, from 10000 bootstrap iterations**
Parameter	MLE estimate	Percentiles
Parameter	MLE estimate	0.5%	2.5%	5%	95%	97.5%	99.5%
k	8.52E-05	4.21E-05	4.99E-05	5.50E-05	1.53E-04	1.57E-04	2.05E-04
ID50/LD50/ETC*	8.13E+03	3.38E+03	4.40E+03	4.54E+03	1.26E+04	1.39E+04	1.65E+04
*Not a parameter of the exponential model; however, it facilitates comparison with other models.

Parameter histogram for exponential model (uncertainty of the parameter)

Exponential model plot, with confidence bounds around optimized model

Highest quality

Exposure Route:

injected in eyelids

# of Doses:

12.00

Agent Strain:

ATCC 19660

Dose Units:

CFU

Host type:

Swiss webster mice (5day old)

Μodel:

exponential

LD50/ID50:

6.61E+03

Optimized parameters: k = 1.05E-04

Response type:

death

Reference:

mice (5day old, day 1-21 pooled) / *Pseudomonas aeruginosa*
Dose	Dead	Survived	Total
2.5	0	13	13
2.5	0	13	13
25	0	14	14
25	0	14	14
250	0	12	12
250	0	12	12
2500	4	13	17
2500	4	13	17
25000	13	2	15
25000	15	0	15
250000	17	0	17
250000	17	0	17

**Goodness of fit and model selection**
Model	Deviance	Δ	Degrees of freedom	χ²_0.95,1 p-value	χ²_0.95,m-k p-value
Exponential	4.36	-0.000549		3.84 1	19.7 0.958
Beta Poisson	4.36	-0.000549	10	3.84 1	18.3 0.93
Exponential is preferred to beta-Poisson; cannot reject good fit for exponential.

**Optimized k parameter for the exponential model, from 500 bootstrap iterations**
Parameter	MLE estimate	Percentiles
Parameter	MLE estimate	0.5%	2.5%	5%	95%	97.5%	99.5%
k	1.05E-04	6.84E-05	7.49E-05	7.84E-05	1.48E-04	1.57E-04	1.73E-04
ID50/LD50/ETC*	6.61E+03	4.01E+03	4.40E+03	4.68E+03	8.84E+03	9.26E+03	1.01E+04
*Not a parameter of the exponential model; however, it facilitates comparison with other models.

Parameter histogram for exponential model (uncertainty of the parameter)

Exponential model plot, with confidence bounds around optimized model

Exposure Route:

injected in eyelids

# of Doses:

6.00

Agent Strain:

ATCC 19660

Dose Units:

CFU

Host type:

Swiss webster mice (5day old)

Μodel:

exponential

LD50/ID50:

4.98E+03

Optimized parameters: k = 1.39E-04

Response type:

death(after day 21)

Reference:

mice (5day old) / *Pseudomonas aeruginosa*
Dose	Dead	Survived	Total
2.5	0	13	13
25	0	14	14
250	0	12	12
2500	4	13	17
25000	15	0	15
250000	17	0	17

**Goodness of fit and model selection**
Model	Deviance	Δ	Degrees of freedom	χ²_0.95,1 p-value	χ²_0.95,m-k p-value
Exponential	2.17	-0.000196	5	3.84 1	11.1 0.825
Beta Poisson	2.17	-0.000196	4	3.84 1	9.49 0.704
Exponential is preferred to beta-Poisson; cannot reject good fit for exponential.

**Optimized k parameter for the exponential model, from 10000 bootstrap iterations**
Parameter	MLE estimate	Percentiles
Parameter	MLE estimate	0.5%	2.5%	5%	95%	97.5%	99.5%
k	1.39E-04	8.87E-05	9.90E-05	9.90E-05	2.05E-04	2.36E-04	2.73E-04
ID50/LD50/ETC*	4.98E+03	2.54E+03	2.94E+03	3.38E+03	7.00E+03	7.00E+03	7.82E+03
*Not a parameter of the exponential model; however, it facilitates comparison with other models.

Parameter histogram for exponential model (uncertainty of the parameter)

Exponential model plot, with confidence bounds around optimized model

Exposure Route:

injected in eyelids

# of Doses:

6.00

Agent Strain:

ATCC 19660

Dose Units:

CFU

Host type:

Swiss webster mice(10day old)

Μodel:

beta-Poisson

LD50/ID50:

1.93E+04

Optimized parameters: a = 6.73E-01 N₅₀ = 1.93E+04

Response type:

death(after day 1)

Reference:

mice (10day old, day1) / *Pseudomonas aeruginosa*
Dose	Dead	Survived	Total
2.5	0	10	10
25	0	16	16
250	0	15	15
2500	0	13	13
25000	12	4	16
250000	14	3	17

**Goodness of fit and model selection**
Model	Deviance	Δ	Degrees of freedom	χ²_0.95,1 p-value	χ²_0.95,m-k p-value
Exponential	21.1	13.8	5	3.84 0.000207	11.1 0.000783
Beta Poisson	7.32	13.8	4	3.84 0.000207	9.49 0.12
Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.

**Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations**
Parameter	MLE estimate	Percentiles
Parameter	MLE estimate	0.5%	2.5%	5%	95%	97.5%	99.5%
α	6.73E-01	3.02E-01	3.62E-01	3.80E-01	1.55E+00	6.30E+03	1.06E+04
N₅₀	1.93E+04	9.62E+03	1.12E+04	1.18E+04	3.42E+04	4.01E+04	5.18E+04

Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.

beta Poisson model plot, with confidence bounds around optimized model

Exposure Route:

injected in eyelids

# of Doses:

12.00

Agent Strain:

ATCC 19660

Dose Units:

CFU

Host type:

Swiss webster mice(10day old)

Μodel:

beta-Poisson

LD50/ID50:

1.48E+04

Optimized parameters: a = 6.01E-01 N₅₀ = 1.48E+04

Response type:

death

Reference:

mice (10day old, day1-21) / *Pseudomonas aeruginosa*
Dose	Dead	Survived	Total
2.5	0	10	10
2.5	0	10	10
25	0	16	16
25	0	16	16
250	0	15	15
250	0	15	15
2500	0	13	13
2500	2	11	13
25000	12	4	16
25000	13	3	16
250000	14	3	17
250000	14	3	17

**Goodness of fit and model selection**
Model	Deviance	Δ	Degrees of freedom	χ²_0.95,1 p-value	χ²_0.95,m-k p-value
Exponential	48.6	36.3	11	3.84 1.65e-09	19.7 1.09e-06
Beta Poisson	12.3	36.3	10	3.84 1.65e-09	18.3 0.265
Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.

**Optimized parameters for the beta-Poisson model, from 500 bootstrap iterations**
Parameter	MLE estimate	Percentiles
Parameter	MLE estimate	0.5%	2.5%	5%	95%	97.5%	99.5%
α	6.01E-01	3.11E-01	3.69E-01	3.97E-01	1.04E+00	1.20E+00	2.01E+00
N₅₀	1.48E+04	8.01E+03	9.07E+03	1.00E+04	2.29E+04	2.55E+04	2.83E+04

Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.

beta Poisson model plot, with confidence bounds around optimized model

Exposure Route:

injected in eyelids

# of Doses:

6.00

Agent Strain:

ATCC 19660

Dose Units:

CFU

Host type:

Swiss webster mice(10day old)

Μodel:

beta-Poisson

LD50/ID50:

1.13E+04

Optimized parameters: a = 5.49E-01 N₅₀ = 1.13E+04

Response type:

death(after day 2-21)

Reference:

mice (10day old, day2-21) / *Pseudomonas aeruginosa*
Dose	Dead	Survived	Total
2.5	0	10	10
25	0	16	16
250	0	15	15
2500	2	11	13
25000	13	3	16
250000	14	3	17

**Goodness of fit and model selection**
Model	Deviance	Δ	Degrees of freedom	χ²_0.95,1 p-value	χ²_0.95,m-k p-value
Exponential	27.3	23.1	5	3.84 1.54e-06	11.1 5.01e-05
Beta Poisson	4.19	23.1	4	3.84 1.54e-06	9.49 0.381
Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.

**Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations**
Parameter	MLE estimate	Percentiles
Parameter	MLE estimate	0.5%	2.5%	5%	95%	97.5%	99.5%
α	5.49E-01	2.38E-01	2.87E-01	3.17E-01	1.37E+00	1.13E+01	1.15E+04
N₅₀	1.13E+04	4.53E+03	5.70E+03	6.34E+03	2.17E+04	2.46E+04	3.39E+04

Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.

beta Poisson model plot, with confidence bounds around optimized model

Exposure Route:

contact lens

# of Doses:

5.00

Agent Strain:

ATCC 19660

Dose Units:

CFU

Host type:

Swiss webster mice

Μodel:

exponential

LD50/ID50:

7.88E+06

Optimized parameters: k = 8.8E-08

Response type:

infection (Keratitis)

Reference:

Swiss webster mice / *Pseudomonas aeruginosa*
Dose	Infection (keratitis)	Not Infection (keratitis)	Total
1E+04	0	8	8
1E+05	1	9	10
1E+06	1	7	8
1E+07	5	5	10
1E+08	10	0	10

**Goodness of fit and model selection**
Model	Deviance	Δ	Degrees of freedom	χ²_0.95,1 p-value	χ²_0.95,m-k p-value
Exponential	3.6	0.134	4	3.84 0.715	9.49 0.464
Beta Poisson	3.46	0.134	3	3.84 0.715	7.81 0.326
Exponential is preferred to beta-Poisson; cannot reject good fit for exponential.

**Optimized k parameter for the exponential model, from 10000 bootstrap iterations**
Parameter	MLE estimate	Percentiles
Parameter	MLE estimate	0.5%	2.5%	5%	95%	97.5%	99.5%
k	8.8E-08	3.31E-08	3.89E-08	4.53E-08	1.58E-07	1.94E-07	2.47E-07
ID50/LD50/ETC*	7.88E+06	2.81E+06	3.57E+06	4.38E+06	1.53E+07	1.78E+07	2.09E+07
*Not a parameter of the exponential model; however, it facilitates comparison with other models.

Parameter histogram for exponential model (uncertainty of the parameter)

Exponential model plot, with confidence bounds around optimized model

Exposure Route:

contact lens

# of Doses:

5.00

Agent Strain:

Dose Units:

CFU

Host type:

white rabbit

Μodel:

beta-Poisson

LD50/ID50:

6.57E+03

Optimized parameters: a = 3.55E-01 N₅₀ = 6.57E+03

Response type:

corneal ulceration

Reference:

Effect of Pseudomonas aeruginosa concentration in experimental contact lens-related microbial keratitis

White rabbit / *Pseudomonas aeruginosa*
Dose	Corneal Ulceration	Not Corneal Ulceration	Total
63.2	0	5	5
2220	2	3	5
13200	3	2	5
78000	3	2	5
462000	5	0	5

**Goodness of fit and model selection**
Model	Deviance	Δ	Degrees of freedom	χ²_0.95,1 p-value	χ²_0.95,m-k p-value
Exponential	9.41	7.02	4	3.84 0.00807	9.49 0.0516
Beta Poisson	2.39	7.02	3	3.84 0.00807	7.81 0.495
Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.

**Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations**
Parameter	MLE estimate	Percentiles
Parameter	MLE estimate	0.5%	2.5%	5%	95%	97.5%	99.5%
α	3.55E-01	1.53E-01	1.76E-01	1.91E-01	4.52E+00	1.73E+07	1.35E+11
N₅₀	6.57E+03	7.71E+02	1.44E+03	1.70E+03	2.55E+04	4.30E+04	8.32E+04

Parameter histogram for exponential model (uncertainty of the parameter)

Exponential model plot, with confidence bounds around optimized model

Highest quality

Exposure Route:

contact lens

# of Doses:

10.00

Agent Strain:

Dose Units:

CFU

Host type:

white rabbit

Μodel:

beta-Poisson

LD50/ID50:

1.85E+04

Optimized parameters: a = 1.9E-01 N₅₀ = 1.85E+04

Response type:

corneal ulceration

Reference:

Effect of Pseudomonas aeruginosa concentration in experimental contact lens-related microbial keratitis

Pooled data of White rabbit / *Pseudomonas aeruginosa*
Dose	Corneal Ulceration	Not Corneal Ulceration	Total
63.2	0	5	5
63.2	0	5	5
2220	2	3	5
2220	2	3	5
13200	3	2	5
13200	1	4	5
78000	3	2	5
78000	1	4	5
462000	5	0	5
462000	4	1	5

**Goodness of fit and model selection**
Model	Deviance	Δ	Degrees of freedom	χ²_0.95,1 p-value	χ²_0.95,m-k p-value
Exponential	30.9	20.8	9	3.84 5.11e-06	16.9 0.000312
Beta Poisson	10.1	20.8	8	3.84 5.11e-06	15.5 0.26
Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.

**Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations**
Parameter	MLE estimate	Percentiles
Parameter	MLE estimate	0.5%	2.5%	5%	95%	97.5%	99.5%
α	1.9E-01	9.63E-02	1.15E-01	1.24E-01	3.86E-01	5.51E-01	2.50E+00
N₅₀	1.85E+04	3.18E+03	4.73E+03	6.01E+03	7.05E+04	8.98E+04	1.97E+05

Parameter histogram for exponential model (uncertainty of the parameter)

Exponential model plot, with confidence bounds around optimized model

Exposure Route:

contact lens

# of Doses:

5.00

Agent Strain:

Dose Units:

CFU

Host type:

white rabbit

Μodel:

beta-Poisson

LD50/ID50:

1.52E+05

Optimized parameters: a = 1.09E-01 N₅₀ = 1.52E+05

Response type:

Severe stromal ulceration

Reference:

Effect of Pseudomonas aeruginosa concentration in experimental contact lens-related microbial keratitis

White rabbit / *Pseudomonas aeruginosa*
Dose	Severe Stromal Ulceration	Not Corneal Ulceration	Total
63.2	0	5	5
2220	2	3	5
13200	1	4	5
78000	1	4	5
462000	4	1	5

**Goodness of fit and model selection**
Model	Deviance	Δ	Degrees of freedom	χ²_0.95,1 p-value	χ²_0.95,m-k p-value
Exponential	13.2	8.73	4	3.84 0.00313	9.49 0.0105
Beta Poisson	4.43	8.73	3	3.84 0.00313	7.81 0.219
Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.

**Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations**
Parameter	MLE estimate	Percentiles
Parameter	MLE estimate	0.5%	2.5%	5%	95%	97.5%	99.5%
α	1.09E-01	4.05E-02	5.23E-02	5.72E-02	9.05E+06	4.82E+07	2.53E+12
N₅₀	1.52E+05	4.66E+03	1.13E+04	1.55E+04	1.55E+07	6.25E+07	1.96E+09

Parameter histogram for exponential model (uncertainty of the parameter)

Exponential model plot, with confidence bounds around optimized model

Exposure Route:

intratracheal

# of Doses:

7.00

Agent Strain:

PA01

Dose Units:

CFU

Host type:

C57BL/6 mice

Μodel:

exponential

LD50/ID50:

Optimized parameters: k = 3.22E-7

Response type:

death

Reference:

Defective Phagocytosis and Clearance of <i>Pseudomonas aeruginosa</i> in the Lung Following Bone Marrow Transplantation

**Table 1: Goodness of fit**
Model	Deviance	Δ	Degrees of freedom	χ²_0.95,1 p-value	χ²_0.95,m-k p-value
Exponential	16.88	0.001	6	3.84 0.98	12.6 0.009
Beta Poisson	16.88	0.001	5	3.84 0.98	11.1 0.004
Neither model provides a good fit to the data

**Table 2: Multi-hit dose response statistics**
Model	Deviance	Δ	DF	χ²_0.95,df	χ²_0.95,1	Good fit?	Parameters	LD50
Multi-hit	1.09	15.69	5	11.1	3.84	Yes	k = 4.12 × 10⁻⁶ k_min=11	2,588,047

Figure 1. The multi-hit dose response model with 95% and 99% confidence bands

Figure 2. Histogram of the k parameter estimates after bootstrapping

Pseudomonas aeruginosa (inhalation) Dose response experiments

References