Cost-effectiveness of ceftolozane/tazobactam plus metronidazole compared with piperacillin/tazobactam as empiric therapy for the treatment of complicated intra-abdominal infections based on the in-vitro surveillance of bacterial isolates in the UK

Figures & data

Figure 1. Model structure.

Figure 2. Treatment pathway diagram.

Table 1. Treatment pathway for patients with a gram-negative abdominal culture.

Patients who receive appropriate therapy continue with the initial therapy (if the initial therapy is the cheapest), or switch (de-escalate) to the cheapest susceptible alternative (Figure 2).		Patients who receive inappropriate therapy are switched (escalated) to the cheapest susceptible alternative or to salvage therapy, if no susceptible alternative exists (Figure 2).
If the patient responds adequately after 3 days of observation and if there is no cheaper susceptible alternative, the patient continues treatment until the symptoms are resolved or the patient dies.	If the patient has a recurrence of infection after 3 days of observation it is assumed that this is due to inadequate initial source control. In this case, the patient is sent for imaging and re-intervention for source control. The patient continues their treatment (no change in antibiotic) until symptoms are resolved or until the patient dies.	If a patient is not responding to the new escalated treatment after 3 days of observation, they are sent for imaging and subsequent re-intervention for source control (it is assumed that the lack of response is due to insufficient initial source control). The patient continues with their treatment until symptoms are resolved or until the patient dies.	If a patient responds adequately after 3 days of observation, then they continue treatment until symptoms are resolved or until they die.

Table 2. Clinical and economic inputs.

	Mean	Lower bound	Upper bound	Source
Mortality rates
Mortality rate with appropriate empiric treatment	0.270	0.230	0.320	Edelsberg et al.^7
Mortality rate with inappropriate empiric antibiotic	0.470	0.400	0.530	Edelsberg et al.^7
Duration of therapy				Source
Duration of empiric therapy	3 days	3 days	3 days	Edelsberg et al.^7
Total LOS for IAAT (including empiric therapy)	9 days	7 days	14 days	Edelsberg et al.^7
Additional LOS associated with inappropriate therapy	4.7 days	4.7 days	4.7 days	Edelsberg et al.^7
Quality-of-life adjustment				Source
Health utility for survivors	0.85	0.70	1.00	Assumption
Discount rate for benefits (per annum)	3.5%	0.0%	6.0%	Scottish Medicines Consortium^22
Hospital costs				Source
Hospital cost per day (average)	£326.00	£260.80	£391.20	NHS reference costs^19
Ceftolozane/tazobactam plus metronidazole	£204.75			MIMS^20
Ceftriaxone	£38.36			MIMS^20
Ciprofloxacin	£69.00			MIMS^20
Colistin	£97.20			MIMS^20
Imipenem	£96.00			MIMS^20
Meropenem	£48.00			MIMS^20
Piperacillin/tazobactam	£23.73			MIMS^20
Tigecycline	£64.42			MIMS^20
Salvage^a	£145.20			MIMS^20

^a Salvage therapy consists of meropenem + colistin for cost purposes.

LOS, Length of stay.

Table 3. Results.

	Ceftolozane/tazobactam + metronidazole	Piperacillin/tazobactam	Incremental ceftolozane/tazobactam + metronidazole - Piperacillin/tazobactam
Summary of results
Total costs per patient	£2,576	£2,168	£408
Totally life years per patient (undiscounted)	28.05	27.85	0.20
Total QALYs per patient (undiscounted)	23.83	23.67	0.16
Total QALYs per patient (discounted)	14.31	14.21	0.10
Incremental Cost Effectiveness Ratio (Cost per discounted QALY saved)	—	—	£4,350
Hospitalization days saved per patient	—	—	0.36
Distribution of patients based on empiric treatment
Resistant to initial therapy (%)	29.6	37.3	—
Susceptible to initial therapy (%)	70.4	62.7	—
Costs
Hospital costs per patient	£1,887	£2,005	–£118
Drug costs per patient	£689	£163	£526
Total costs per patient	£2,576	£2,168	£408

QALY, Quality Adjusted Life Year; IAAT, Initial appropriate antibiotic therapy; IIAT, Initial inappropriate antibiotic therapy.

Figure 3. Ceftolozane/tazobactam vs piperacillin/tazobactam: influence of variables on ICER (cost per discounted QALY). ICER, Incremental cost-effectiveness ratio; QALY, Quality Adjusted Life Year; LoS, Length of Stay.

Figure 4. Cost-effectiveness plane. QALY, Quality Adjusted Life Year.

Figure 5. Cost-effectiveness acceptability curve. QALY, Quality Adjusted Life Year; WTP, Willingness to pay.

Table 4. Scenario analysis results.

	Ceftolozane/tazobactam + metronidazole	Piperacillin/tazobactam	Incremental ceftolozane/tazobactam + metronidazole - Piperacillin/tazobactam
Results for patients using nosocomial isolates
Total costs per patient	£2,573	£2,258	£315
Total QALYs per patient (discounted)	14.09	13.94	0.15
Incremental Cost Effectiveness Ratio (Cost per discounted QALY saved)	—	—	£2,036
Results for high risk patients (aged 65 years and requiring an ICU stay) using nosocomial isolates
Total costs per patient	£2,581	£2,317	£264
Total QALYs per patient (discounted)	11.56	11.41	0.15
Incremental Cost Effectiveness Ratio (Cost per discounted QALY saved)	—	—	£1,742

QALY, Quality Adjusted Life Year.

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