University of Groningen Pharmacoeconomics of prophylactic, empirical, and diagnostic-based antibiotic treatments Purba, Abdul

Pharmacoeconomics of prophylactic, empirical, and diagnostic-based antibiotic treatments

Purba, Abdul

DOI:

10.33612/diss.128518764

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Publication date: 2020

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Purba, A. (2020). Pharmacoeconomics of prophylactic, empirical, and diagnostic-based antibiotic

treatments: Focus on surgical site infection and hospitalized community-acquired pneumonia. University of Groningen. https://doi.org/10.33612/diss.128518764

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CHAPTER 2

The burden and costs of sepsis and

reimbursement of its treatment in a

developing country: An observational

study on focal infections in Indonesia

Abdul Khairul Rizki Purba Nina Mariana

Gestina Aliska Sonny Hadi Wijaya Riyanti Retno Wulandari Usman Hadi

Hamzah

Cahyo Wibisono Nugroho Jurjen van der Schans Maarten J. Postma

ABSTRACT

Objectives: This study aimed to determine the burden of sepsis with focal infections in the resource-limited context of Indonesia and to propose national prices for sepsis reimbursement. Methods: A retrospective observational study was conducted from 2013-2016 on cost of surviving and non-surviving sepsis patients from a payer perspective using inpatient billing records in four hospitals. The national burden of sepsis was calculated, and proposed national prices for reimbursement were developed.

Results: Of the 14,076 sepsis patients, 5,876 (41.7%) survived and 8.200 (58.3%) died. The mean hospital costs incurred per surviving and deceased sepsis patient were US$1,011 (SE +23.4) and US$1,406 (SE +27.8), respectively. The national burden of sepsis in 100,000 patients was estimated to be US$130 million. Sepsis patients with multifocal infections and a single focal lower-respiratory tract infection (LRTI) were estimated as being the two with the highest economic burden (US$48 million and US$33 million, respectively, within 100,000 sepsis patients). Sepsis with cardiovascular infection was estimated to warrant the highest proposed national price for reimbursement (US$4,256).

Conclusions: Multifocal infections and LRTIs are the major focal infections with the highest burden of sepsis. This study showed varying cost estimates for sepsis, necessitating a new reimbursement system with adjustment of the national prices taking the particular foci into account.

INTRODUCTION

Sepsis is estimated to involve 31.5 million cases each year worldwide.1 _{Of these cases, 19.4 million}

are characterized by severe sepsis, accounting for 5.3 million deaths annually.1 _{These estimates are}

derived from data compiled for high-income countries. However, the highest mortalities occur in

low-income countries, followed by low-middle income countries (LMICs).2 _{There is a surprising lack}

of data on mortality and costs among sepsis patients in LMICs, such as most African and Asian

countries, including Indonesia.1,3 _{Indonesia, which is the most populated country in Southeast Asia}

and the fourth most populated country globally, has a high incidence of communicable diseases.4,5

Ascertaining the granularity of the sepsis burden in Indonesia has become essential in light of the

government’s introduction of a new national health insurance system (Jaminan Kesehatan Nasional).6

In 2018, universal health coverage (UHC), provided by a single national payer, became available for

203 million people.7 _{During the period 2019-2020, coverage will be extended to the entire Indonesian}

population (approximately 264 million people).4,7 _{Accordingly, a national reimbursement price for}

each disease will need to be accounted for within the reimbursement system.7–9

The economic burden of sepsis, which includes providing medication and fluid resuscitation

during hospitalization, has been reported to be very high.10 _{In the United States, hospitalization}

costs for sepsis patients were approximately US$20 billion in 2011.11 _{A previous systematic review,}

which mostly included studies performed in the United States, revealed that an essential analysis of the economic burden of sepsis concerned an evaluation between survivors and non-survivors, because of a major difference in the mean total hospital costs per day (US$351 vs. US$948,

respectively).12 _{The difference in burden between survivors and non-survivors is unknown in LMICs.}

International budgetary guidelines for sepsis management mostly apply to developed countries and therefore may require cost adjustments of service bundles relating to sepsis management in

resource-limited settings.13,14

A focal infection terminology was firstly introduced in 1910 by William Hunter, who elaborated the

relationship between focal infections and systemic diseases.15 _{A focal infection is a potential source}

of microorganisms that may disseminate into deep tissue and spread to the bloodstream. A further impact of the dissemination of the microorganisms and their toxin in the bloodstream is activation of

the inflammatory mediators and worsening organ dysfunction due to sepsis.16 _{According to the third}

consensus definitions for sepsis and septic shock17_{, sepsis has at least an underlying focal infection as}

an entry of the pathogen to the systemic circulation. Each focal infection causing sepsis comes with different complications, with a wide range of costs. Therefore, the reimbursement of sepsis needs cost adjustments according to the underlying focal infection. In Indonesia, sepsis and the associated focal infections are not coded together when calculating the national price of diseases, resulting

in possible under-budgeting for sepsis-related expenditure.18 _{Therefore, a reevaluation of the costs}

for sepsis has become urgent for countries like Indonesia, including dealing with underlying focal infections. This study analyzed costs for surviving and deceased sepsis patients, explicitly considering underlying focal infections. In addition, it then estimated national prices for reimbursement under UHC based on the analyzed burden and costs of sepsis.

METHODS

Study design

A retrospective observational study was conducted on patients with sepsis in four Indonesian medical centers: (1) Dr. Soetomo General Academic Hospital in Surabaya, a national healthcare referral center, with 1,514 beds, serving eastern Indonesia; (2) Universitas Airlangga Hospital in Surabaya, a teaching medical center with 180 beds in Surabaya; (3) The Prof. Dr. Sulianti Saroso National Center for Infectious Diseases Hospital, with 180 beds in Jakarta; and (4) Dr. M. Djamil Hospital in Padang, a national referral center with 800 beds, serving western Indonesia. Inpatient registries and hospital discharge data were obtained from the Department of Medical Records for the period 01 January 2013 to 31 December 2016. The dataset covered patients demographics, diagnoses, hospital-discharge mortalities, laboratory tests, and medications.

Criteria for selecting patients

All patients with sepsis and aged > 18 years were included. The diagnosis of sepsis was clarified by the physicians. Previously, in Indonesia, the physician used sepsis criteria based on International Sepsis Definition Conference 2001 supported by the Society of Critical Care Medicine, the European Society of Intensive Care Medicine, the American College of Chest Physicians, the

American Thoracic Society and the Surgical Infection Society.19 _{The pathophysiology of sepsis has}

systematically defined from systemic inflammatory response syndrome (SIRS) to shock sepsis. SIRS

was defined at least two of the following clinical signs: the body temperature < 36o_{C or >38}o_C,

tachycardia (heart rate > 90beats/min), tachypnoea (>20 breaths/min or PaCO2 <30 mmHg or with mechanical ventilation), white blood cells <4,000 cells/µL or >12,000 cells/µL or >10% of band

forms.20 _{Sepsis was defined as SIRS with focal infections.}21 _{Severe sepsis was defined as sepsis with}

organ dysfunctions or hypoperfusion (oliguria, lactic acidosis, acute mental status alteration) or sepsis-induced hypotension (systolic blood pressure lower 90mmHg). In addition, septic shock is defined as severe sepsis with a condition which requires vasopressor administration after

adequate fluid resuscitation.17 _{In 2016 and afterwards, the criteria for sepsis diagnosis followed}

the Indonesian Ministry of Health adopted Third International Consensus Definitions for Sepsis

and Shock, Sepsis-3 17_{, and diagnostic criteria for sepsis entailed in the Sequential Organ Failure}

Assessment (SOFA) score that includes at least two of the following three ‘quick’ SOFA (qSOFA) criteria: systolic blood pressure ≤ 100 mmHg, respiratory rate ≥ 22 breaths per minute, and

incorporating altered mentation (Glasgow Coma Scale score < 15).22 _{In this study, the source}

infection of sepsis was pointed as focal infection.

The study categorized single focal infections per site of the infections as cardiovascular infections (CVIs), gastrointestinal tract infections (GTIs), lower-respiratory tract infections (LRTIs), neuromuscular infections (NMIs), urinary tract infections (UTIs), and wound infections (WIs). WIs recognized at the sites of surgery were subclassified as surgical site infections (SSIs). The physicians

confirmed SSI diagnoses according to the Centers for Diseases Control and Prevention.23 _Focal

involved soft tissues such as nerves and muscles. Sepsis patients with two or more focal infections were grouped into sepsis with multifocal infections. Moreover, an unspecified focal infection was labeled as an unidentified focal infection (UFI). The International Classification of Diseases version 10 was applied to determine and record focal infections (see supplement 2.1).

Cost calculation

Cost was analyzed from a payer perspective using billing records that included the costs of beds, drugs, laboratory and radiology procedures, other medical facilities, and total costs. Bed costs encompassed hospital administration fees, daily room services, nursing and medical staff care, and technicians’ services. Drug costs were extracted from the pharmacy department’s budget that covered expenses relating to drugs, fluids, blood products for transfusion, disposable devices, mechanical ventilators, oxygen therapy, and pharmacy services. Physiotherapists’ – as rehabilitation specialists – consultancy costs were recorded and considered under patients bed service costs. Costs for administrations, patient transfer, and ambulance, and other expenses were included in the costs for other medical facilities. The hospitalization costs per admission were analyzed, considering the day spent in an intensive care unit (ICU), presence of SSIs, types of focal infections, and whether the patient survived or not. The 2016 currency exchange rate (US$1 = 13,308.33 IDR) was used, as applied by the Organization for Economic Cooperation and

Development (OECD) to convert Indonesian Rupiahs (IDR) into US Dollars (US$)24_{, with inflation}

rates of 6.40% for 2013, 6.42% for 2014, 6.38% for 2015, and 3.53% for 2016.25 _{The economic burden}

of sepsis was assessed according to the distribution of disease incidence over focal infections and

the mean cost of each focal infection using a denominator of 100,000 patients with sepsis.26

Extrapolation of the cost to the national level

The national costs for sepsis were analyzed based on the rates defined by the Indonesian Health Ministry for Indonesia Case Base Groups (INA-CBGs). The INA-CBGs’ rates were used as national projections for extrapolating the sepsis costs – obtained from patient’s billing records – into Proposed National Prices (PNPs) for sepsis reimbursements by considering the following four

aspects.18 _{The first aspect concerned the room classes in the hospital, which were divided into}

three classes. Class I, patients had more privacy within one room, accommodating up to two patients. Class II accommodating three or four people; Class III service accommodating five or

six people in a room.18,27 _{This study provided the PNP in Class III as the reference. It calculated the}

actual costs from Classes I, II, and III ) ( CP )– obtained from patient’s billing records – and divided

them by the specific factor (α) according to the INA-CBGs at 1.4, 1.2, and 1.0, respectively.18

The second aspect concerned the private or public sector ownership of the hospital. In the INA-CBG system, reimbursement provided by the government through subsidies was 1.03 (β) times

higher for private healthcare services compared with the public healthcare services.18 _{The third}

and fourth aspects concerned the type of hospital and the region where the hospital is located, to

correspond with the specific INA-CBG prices (ICP_y) that were published by the Indonesian Ministry

of Health in 2016.18 _{The classification of hospital type in Indonesia was categorized into types A,}

26

B, C and D on the basis of the medical specialist services (see Supplement 2.2).18,27,28 _{There were}

five INA-CBG regions covering 34 provinces in total (Figure 2.1).18 _{The ICP for the Hospital Type A in}

Region I was used as the denominator reference for ICP in the calculation of a PNP, since the actual costs were obtained from the hospitals with type A located in the INA-CBG Region I. Eventually, for a particular focal infection inpatient, in a class of room, in a specific type of hospital in a certain region under the private or the public sectors, a PNP for sepsis with an x focal infection was defined as in the following Formula 2.1:

11"

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8+:9'7";7*:"='*88"M,+=7"!"#

$$$$HO"2)7"8M7=+K+="K*=23,"GvH"3K"7*=)"5'*88",33;O"2)7"8M7=+K+="AF#@5EN"

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*:%"K+67",79+3:8H"K3,",7+;$&,87;7:2"3K"87M8+8"J+2)"M*,2+=&'*,"K3=*'"+:K7=2+3:8"+:"2)7"K+67"AF#@

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-79+3:"!"G+:"9,77:H"=3;M,+878"E*:27:O"k*/*,2*O"`782"k*6*O"57:2,*'"k*6*O"x39?*/*,2*O"*:%"D*82"

k*6*<"-79+3:"1"G+:"$'&7H"=3;M,+878"`782"B&;*2,*O"-+*&O"B3&2)"B&;*2,*O">*;M&:9O"E*'+O"*:%"

`782"F&8*"I7:99*,*<"-79+3:"V"G+:",7%H"=3;M,+878"#=7)"L*,&88*'*;O"F3,2)"B&;*2,*O"k*;$+O"

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$72J77:"8&,6+6+:9"*:%"%7=7*87%"87M8+8"M*2+7:28<"!OTTT"8*;M'78"J7,7"$33282,*MM7%O"*:%"+:"=*878"

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Formula 2.1 The four aspects for developing a PNP were the mean actual costs reflecting the single mean class price( CP ), the specific factor (α) of each Class room, the specific INA-CBG prices (ICPy),

and the government subsidy factor (β).

This study developed 280 PNPs (seven focal infections, four types of hospitals, two sectors, and five regions) for reimbursement of sepsis with particular focal infections in the five INA-CBG regions. To compare with the reference ICPs, the PNPs were categorized into three groups: those with a small difference with the ICP of <US$500, a medium difference of US$500 - 1,000, and a major difference >US$1,000.

Figure 2.1 The five regions covered in the Indonesia Case Base Group (INA-CBG) system. Region 1 (in green) comprises Banten, Jakarta, West Java, Central Java, Yogyakarta, and East Java. Region 2 (in blue) comprises West Sumatra, Riau, South Sumatra, Lampung, Bali, and West Nusa Tenggara. Region 3 (in red) comprises Aceh Darussalam, North Sumatra, Jambi, Bengkulu, Bangka Belitung, Riau Islands, West Kalimantan, North Sulawesi, Central Sulawesi, Southeast Sulawesi, West Sulawesi, South Sulawesi, and Gorontalo. Region 4 (in yellow) comprises South Kalimantan, East Kalimantan, North Kalimantan, and Central Kalimantan. Region 5 (in purple) comprises East Nusa Tenggara, Maluku, North Maluku, Papua, and West Papua. The map was created in mapchart.net.

Statistical analyses

Data were analyzed using IBM SPSS statistics 25, providing descriptive data on baseline characteristics in percentages. Chi-square tests were performed to determine the differences between surviving and deceased sepsis patients. 1,000 samples were bootstrapped, and in cases where the data were overly skewed, the standard error (SE) was adjusted for the mean cost. An Independent Sample T-test was applied to evaluate the statistical cost difference between the surviving and deceased patient groups. Subgroup analyses of hospitalization costs relating to ICU treatment, having SSIs, and types of focal infections were performed. Statistical significance was defined when the p-value was < 0.05.

RESULTS

Of the 14,076 patients with sepsis, 5,876 (41.7%) survived and 8,200 (58.3%) died. The patients were predominantly male (53%). The average age among all patients was 49.4 (+18.9) years. Surviving and deceased sepsis patients evidenced statistical differences for the following single focal infections: LRTIs (38% vs. 62%, respectively, p <0.001), UTIs (56% vs. 44%, respectively, p <0.001), and WIs (18% vs. 82%, respectively, p <0.001). Thirty-one percent of the sepsis patients were diagnosed with multifocal infections with a significant difference between surviving and deceased patients (40% vs. 60%, respectively, p <0.001). Of the 2,138 sepsis patients with SSIs, 74.2% died. Also, patients with sepsis who were hospitalized in an ICU demonstrated a high case fatality rate (69%). Table 2.1 presents a summary of the clinical characteristics of surviving and deceased sepsis patients.

Table 2.1. Baseline characteristics of surviving and deceased sepsis patients

Characteristics _(n=14,067)All cases % Survivors _(n=5,876) % Deceased _(n=8,200) % p-value

Sex

Male 7,467 53.0 3,115 41.7 4,352 58.3 0.943

Female 6,609 47.0 2,761 41.8 3,848 58.2

Aged >60 years 1,638 11.6 626 38.2 1,012 61.8 0.002

Single focal infections

CVI 110 0.8 39 35.5 71 64.5 0.179 GTI 1,328 9.4 565 42.5 763 57.5 0.534 LRTI 3,932 27.9 1,486 37.8 2,446 62.2 <0.001* NMI 368 2.6 153 41.6 215 58.4 0.947 UTI 1,348 9.6 755 56.0 593 44.0 <0.001* WI 1,049 7.5 191 18.2 858 81.8 <0.001* Multifocal infections 4,304 30.6 1,700 39.5 2,604 60.5 <0.001* UFI sepsis 1,637 11.6 987 60.3 650 39.7 <0.001* Having SSIs 2,138 15.2 551 25.8 1,587 74.2 <0.001* ICU 4,297 30.8 1,328 30.9 2,969 69.1 <0.001*

Note: CVI = cardiovascular infections, GTI = gastrointestinal tract infection, ICU = intensive care unit, LRTI = lower-respiratory tract infection, NMI = neuromuscular infection, SSI = surgical site infection, UFI = unidentified focal infection, UTI = urinary tract infection, and WI = wound infection.

*Statistically significant, p < 0.05

Hospitalization costs

The costs per admission for surviving and deceased sepsis patients were, respectively, US$1,011 (+23.4) and US$1,406 (+27.8) (i.e., a difference of US$396, p <0.001). The mean cost for all sepsis cases was US$1,253 (+19.4). Among non-ICU sepsis patients, the average cost was lower for surviving patients (US$960 [+24.3]) compared with that of deceased patients (US$1,189 [+23.6]) per admission (p <0.001). For ICU sepsis patients, the cost per admission was US$1,618 (+47.9), with respective mean costs of US$1,187 (+61.7) and US$1,785.5 (+56.3) for surviving and deceased patients (p <0.001). The cost incurred for patients with sepsis who had SSIs was higher compared with that incurred for patients who did not have SSIs (US$2,938 vs. US$926). Table 2.2 shows these costs divided into unit costs for beds, laboratory and radiology, pharmacy, and other medical facilities.

The national burden of sepsis

The analyses of the treatment costs per admission for sepsis patients with focal infections (see Table 2.2) indicated that the cost was highest for sepsis patients with CVIs (US$1,731), followed by those with WIs (US$1,703), multifocal infections (US$1,584), LRTIs (US$1,122), NMIs (US$986), UTIs (US$748), and GTIs (US$720). The national burden of sepsis revealed a total budget of US$130 million (+US$5,7 million) per 100,000 patients. Sepsis with multifocal infections had the highest national burden of disease within 100,000 sepsis patients (US$48 million), followed by sepsis with LRTIs (US$33 million), UFIs (US$15 million), UTIs (US$11 million), GTIs (US$10.7 million), WIs (US$8.6 million), NMIs (US$2.7 million), and CVIs (US$0.9 million). Figure 2.2 depicts the economic burden of sepsis with focal infections.

Figure 2.2 The economic burden of sepsis with particular focal infections for 100,000 patients with survived (in green) and deceased (in blue).

Note: CVI = cardiovascular infections, GTI = gastrointestinal tract infection, LRTI = lower-respiratory tract infection, NMI = neuromuscular infection, UFI = unidentified focal infection, UTI = urinary tract infection, and WI = wound infection.

Table 2.2 Hospitalization costs for sepsis patients per admission (in 2016 US$)

Hospitalization cost _mean(SE)All cases _mean(SE)Survived Deceased_mean(SE) Cost difference p-value Non-ICU stay

Bed costs 222.12(3.72) 196.31(5.17) 242.16(4.95) 45.85(7.49) <0.001 Laboratory and radiology

costs 327.29(6.24) 276.49(8.65) 366.49(8.28) 90.01(12.55) <0.001 Pharmacy costs 404.61(7.15) 369.76(10.37) 431.74(9.53) 61.98(14.40) <0.001 Other medical facilities costs 142.14(2.30) 126.49(3.24) 154.29(3.07) 27.80(4.64) <0.001 ICU stay

Bed costs 330.29(9.81) 243.08(13.05) 364.27(11.52) 121.19(21.76) <0.001 Laboratory and radiology

costs 416.60(14.29) 297.47(18.40) 462.711(16.77) 165.25(31.74) <0.001 Pharmacy costs 662.612(20.59) 491.54(26.36) 729.47(24.19) 237.93(45.64) <0.001 Other medical facilities costs 207.33(6.07) 151.53(7.56) 229.08(7.12) 77.56(13.45) <0.001 Having SSIs

No 925.92(13.13) 838.59(19.75) 988.55(17.18) 149.96(26.58) <0.001* Yes 2,937.89(88.80) 2,595.84(133.88) 3,042.17(101.32) 446.33(209.61) 0.033* Types of focal infections

CVI 1,731.09(90.18) 1,634.30(168.91) 1,750.87(98.95) 116.57(240.24) 0.628 GTI 719.76(25.12) 618.06(33.50) 792.711(32.77) 174.65(50.70) 0.001* LRTI 1,122.47(29.76) 818.83(30.51) 1,306.77(37.42) 487.94(60.88) <0.001* NMI 985.62(73.65) 855.84(101.65) 1,076.29(95.69) 220.45(149.21) 0.140 UTI 747.83(29.81) 733.51(41.95) 765.31(44.42) 31.81(59.91) 0.595 WI 1,702.58(221.88) 1,579.36(264.01) 1,765(272.84) 186.60(468.17) 0.690 Multifocal infections 1,583.51(19.36) 1,363.16(51.83) 1,723.78(56.05) 395.64(39.58) <0.001* UFI 1,268.26(65.14) 1,315.27(84.09) 1,197.25(102.94) 118.02(133.11) 0.375

Note: CVI = cardiovascular infections, GTI = gastrointestinal tract infection, ICU = intensive care unit, LRTI = lower-respiratory tract infection, NMI = neuromuscular infection, SSI = surgical site infection, SE = standard error, UFI = unidentified focal infection, UTI = urinary tract infection, and WI = wound infection.

*Statistically significant, p < 0.05

The prospective national price for sepsis patients

The lowest price within the INA-CBG system (ICP) was for UFI sepsis with the ICP at US$298 in a type D public hospital in Region 1, for which a PNP of US$803 was estimated (difference: US$505). The highest PNP was for sepsis with CVIs in type A private hospitals in Region 5 (US$4,256), compared with the ICP of US$2,270 (difference: US$1,986). A remarkable difference between the PNP and ICP was evident for healthcare services relating to sepsis with WIs in type A private hospitals in Region 5 (US$3,995 vs. US$1,421; difference: US$2,574). Reimbursement levels under the overall PNP for sepsis were higher for all types of private hospitals compared with those for public hospitals (all types) in all INA-CBG regions. Out of 280 PNPs, 87 (31.1%) had major differences from the reference ICPs (>US$1,000). PNPs with a major difference were predominantly for reimbursement of sepsis with WIs (Table 2.3). Supplement 2.3 presents the details between the PNPs and the rates specified for the ICPs for sepsis with focal infections in all five regions of Indonesia.

Ta ble 2.3 T he p ro po sed na tio na l p ric e per pa tient fo r sep

sis with foca

l infectio ns in a ll fiv e r egio ns of Indo

nesia (in 2016 US$)

Re gio nal H osp ita l S ep si s w ith G TI S ep si s w ith N M I S ep si s w ith U TI U FI sep si s S ep si s w ith L RT I S ep si s w ith C VI Se psi s w ith W I* Re gi on 1 P ub lic A 1 ,2 96 .9 1 ,77 0.9 2 ,0 84 .1 1 ,7 21 .0 3 ,0 23 .6 3 ,8 97. 8 3 ,6 59 .4 P riv at e A 1, 33 5.9 1 ,8 24 .1 2 ,14 6. 7 1 ,77 2. 6 3 ,11 4. 3 4 ,014 .7 3 ,76 9. 2 P ub lic B 1 ,0 03 .8 1 ,2 39 .3 1 ,3 46.6 1 ,2 04 .3 1 ,75 4. 6 2 ,7 27 .7 2, 65 4.4 P riv at e B 1, 03 3. 9 1, 27 6. 5 1, 32 9.9 1 ,2 40 .5 1 ,8 07. 2 2 ,6 68 .6 2 ,73 4. 0 P ub lic C 80 6. 2 9 95. 3 1 ,17 2.1 9 67. 2 1 ,59 4. 7 2, 11 8.4 2 ,2 81 .1 P riv at e C 83 0. 3 1 ,0 25 .2 1 ,2 07. 2 9 96 .2 1 ,6 42 .6 2 ,18 1.9 2 ,34 9. 6 P ub lic D 6 69. 8 8 27. 0 1 ,019 .4 80 3.6 1 ,3 95 .4 1 ,8 20 .1 1 ,77 0. 4 P riv at e D 6 89. 9 8 51 .8 1 ,050 .0 8 27. 7 1 ,43 7.2 1 ,8 74 .7 1 ,8 23 .5 Re gi on 2 P ub lic A 1, 30 8. 6 1 ,78 6.9 2 ,10 2.9 1 ,7 36 .5 3 ,050 .8 3 ,932 .9 3 ,6 92 .4 P riv at e A 1 ,34 7.9 1 ,8 40 .5 2 ,16 6. 0 1 ,788. 5 3 ,14 2. 3 4 ,050 .9 3 ,8 03 .2 P ub lic B 1 ,012 .8 1, 25 0. 5 1 ,30 2. 8 1 ,215 .2 1 ,77 0. 4 2 ,75 2. 2 2 ,67 8. 3 P riv at e B 1 ,0 43 .2 1 ,2 88. 0 1 ,34 1.9 1 ,2 51 .6 1 ,8 23 .5 2 ,83 4. 8 2 ,75 8. 6 P ub lic C 8 13 .4 1, 00 4. 3 1, 18 2. 6 9 75 .9 1 ,6 09 .1 2 ,13 7.4 2 ,3 01 .7 P riv at e C 8 37. 8 1 ,0 34 .4 1 ,21 8.1 1 ,0 05 .2 1 ,6 57. 3 2 ,2 01. 6 2 ,37 0. 7 P ub lic D 6 75 .8 83 4. 4 1 ,0 28 .6 8 10 .8 1 ,4 07 .9 1, 83 6. 5 1, 78 6. 3 P riv at e D 6 96 .1 8 59 .4 1 ,0 59 .4 83 5. 2 1 ,45 0. 2 1 ,8 91 .6 1 ,8 39 .9 Re gi on 3 P ub lic A 1 ,312 .5 1 ,79 2. 2 2 ,10 9. 2 1 ,741 .6 3 ,0 59 .8 3 ,9 44 .6 3 ,70 3. 4 P riv at e A 1, 35 1.9 1 ,8 46 .0 2, 17 2.4 1 ,79 3.9 3 ,15 1.6 4 ,0 62 .9 3 ,8 14 .5 P ub lic B 1 ,015 .8 1 ,2 54 .2 1 ,3 06 .7 1 ,21 8.8 1 ,7 75 .6 2, 76 0.4 2, 68 6. 3 P riv at e B 1, 04 6. 3 1 ,2 91 .8 1 ,34 5.9 1 ,2 55 .3 1 ,8 28 .9 2 ,8 43 .3 2 ,76 6. 9 P ub lic C 8 15 .8 1 ,0 07. 2 1 ,18 6.1 97 8. 8 1 ,613 .9 2 ,14 3. 8 2 ,3 08. 5 P riv at e C 8 40. 3 1 ,0 37. 4 1, 22 1.7 1, 00 8. 2 1 ,66 2. 3 2 ,2 08 .1 2 ,37 7.8 P ub lic D 6 77. 8 8 36 .9 1 ,0 31 .6 8 13 .3 1 ,412 .1 1 ,8 41 .9 1 ,79 1.6 P riv at e D 69 8. 2 8 62 .0 1 ,0 62 .6 8 37. 7 1 ,45 4. 5 1 ,8 97. 2 1 ,8 45 .4

Re gio nal H osp ita l S ep si s w ith G TI S ep si s w ith N M I S ep si s w ith U TI U FI sep si s S ep si s w ith L RT I S ep si s w ith C VI Se psi s w ith W I* Re gi on 4 P ub lic A 1 ,3 32 .0 1 ,8 18 .8 2, 14 0.4 1 ,76 7.4 3 ,10 5. 2 4 ,0 03 .0 3 ,75 8. 3 P riv at e A 1 ,37 1.9 1 ,8 73 .3 2 ,20 4. 6 1 ,8 20 .4 3 ,19 8. 4 4 ,12 3.1 3 ,8 71. 0 P ub lic B 1 ,0 30 .9 1 ,2 72 .8 1 ,32 6.1 1 ,2 36 .9 1 ,8 02 .0 2, 80 1.4 2 ,7 26 .1 P riv at e B 1 ,0 61 .8 1 ,311 .0 1 ,3 65 .9 1 ,2 74 .0 1 ,8 56 .0 2, 88 5.4 2 ,8 07. 9 P ub lic C 8 27. 9 1, 02 2. 2 1 ,2 03 .7 9 93 .3 1 ,6 37. 8 2 ,17 5. 6 2 ,34 2. 7 P riv at e C 6 87. 9 8 49. 3 1 ,0 46. 9 82 5. 3 1 ,43 3.1 2 ,10 3.1 1 ,8 18 .2 P ub lic D 6 87. 9 8 49. 3 1, 04 6. 9 82 5. 3 1 ,43 3.1 1 ,8 69 .2 1 ,8 18 .2 P riv at e D 70 8. 5 8 74 .8 1 ,07 8. 3 8 50 .1 1 ,47 6.1 1 ,92 5. 3 1 ,8 72 .7 Re gi on 5 P ub lic A 1 ,374 .8 1 ,8 77. 2 2 ,2 09. 2 1, 82 4. 2 3, 20 5. 0 4 ,13 1.7 3 ,87 9. 0 P riv at e A 1 ,41 6. 0 1 ,93 3. 5 2 ,2 75 .5 1 ,8 78 .9 3 ,3 01 .1 4 ,2 55 .6 3 ,9 95 .4 P ub lic B 1 ,0 64 .0 1 ,313 .7 1 ,3 68. 7 1 ,2 76.6 1 ,8 59 .9 2, 89 1.4 2 ,8 13 .7 P riv at e B 1 ,0 95 .9 1 ,3 53 .1 1 ,40 9.8 1 ,31 4.9 1 ,915 .7 2 ,97 8.1 2 ,8 98 .1 P ub lic C 85 4. 5 1 ,0 55 .0 1 ,24 2. 4 1 ,0 25 .2 1 ,6 90 .4 2 ,24 5. 5 2 ,41 8. 0 P riv at e C 8 80 .1 1 ,0 86. 7 1 ,27 9. 6 1 ,0 56. 0 1 ,741 .1 2 ,312 .8 2 ,49 0. 5 P ub lic D 7 10 .0 8 76.6 1 ,0 80 .6 8 51 .8 1 ,47 9.1 1 ,92 9. 3 1 ,8 76.6 P riv at e D 7 31 .3 9 02 .9 1 ,11 3. 0 8 77. 4 1 ,5 23 .5 1 ,9 87. 2 1 ,93 2.9 *I nc lu di ng sur gi ca l s ite inf ec tio ns N ote: T he co lo rs in di ca te th e di ffe re nc e be tw ee n th e PN P fo r s ep sis w ith fo ca l i nf ec tio ns w ith th e ra te s sp ec ifi ed fo r t he IN A-CB G s ( th e gr ee n in di ca te s a gr ou p of lo w PN Ps w ith a sm al l d iffe re nc e (< US $5 00 ), t he b lu e i nd ic at es a g ro up o f m id dl e P N Ps w ith a m ed iu m d iffe re nc e ( S$ 5 00 a nd U S$ 1 ,0 00 ), a nd t he r ed i nd ic at es a g ro up o f h ig h P N Ps w ith a m aj or d iffe re nc e ( >U S$ 1, 00 0) ). T he co m pa ris on b et w ee n P N P a nd I N A-CB G r at es i s p rov id ed i n S up pl em en t 3 . CV I = c ar di ov as cu la r i nf ec tio ns , G TI = g as tro in te st in al t ra ct i nf ec tio n, I CU = i nt en sive c ar e u ni t, I N A-CB G s = I nd on es ia C as e B as e G ro up s, L RT I = l ow er -re sp ira to ry t ra ct i nf ec tio n, N M I = ne ur om us cul ar inf ec tio n, P NP = p ro po se d na tio na l p ric e, U FI = un id en tifi ed fo ca l i nf ec tio n, U TI = ur inar y t ra ct inf ec tio n, an d W I = w oun d i nf ec tio n.

2

DISCUSSION

In this study, the economic burden for focal infections associated with sepsis was comprehensively determined in the resource-limited setting, in Indonesia. Sepsis was mostly induced by LRTIs, accounting for the high associated total cost per patient. Besides LRTIs, the findings indicated a strong correlation between high costs and having SSIs. The costs especially increased for patients with multifocal infections. In the broader scale, the economic burden of sepsis with focal infections was higher for deceased patients than for surviving patients. In the new Indonesian UHC system, the reimbursement for sepsis entails four aspects: class of patient’s room, government subsidies, type of hospital, and the INA-CBG region. Moreover, the current findings show the great difference in costs between PNP and ICP especially for sepsis-related costs with the focal infections of WIs and CVIs.

There is convincing evidence of a positive correlation between LRTIs and sepsis with regard

to mortality outcome.29 _{Over the last decade, LRTIs have been the most prevalent communicable}

disease in Indonesia.30 _{The economic burden of sepsis with LRTIs in ICUs in a developing country}

such as Turkey was estimated at US$2,722 per patient.31 _{In addition, LRTIs such as}

community-acquired pneumonia contributes high morbidity in terms of more hospitalizations for ICU

admissions, requiring mechanical ventilators, and further sepsis complications.32–34 _{In addition,}

elevated hospitalization costs for ICU patients with LRTIs were strongly associated with the use

of a mechanical ventilator, presence of severe sepsis and septic shock.31 _{Confirming these results,}

some studies have reported that in addition to being induced by LRTIs, sepsis also originates from

WIs, GTIs, and UTIs (approximately 16.5%, 16.7%, and 28.3%, respectively).29,35,36 _{Sepsis arising from}

GTIs and WIs is mostly associated with surgical wounds.29,37 _{Infections on the site of surgeries}

after elective and emergency procedures that contribute to sepsis account for 5.8% and 24.8%,

respectively.35 _{A previous study covering 6.5 million elective surgeries performed in the United}

States reported an incidence of 1.2% of post-surgical sepsis cases with a high mortality rate of

26%.38 _{The current data revealed a high case fatality rate of sepsis with SSI. SSI-related costs that}

include medicines, prolonged length of stay, and readmission could rise to US$22,130 per patient.39

In the current study, sepsis with CVIs presented the highest cost per inpatient but accounted for the lowest national economic burden for sepsis, with focal infections giving relatively low numbers. In a previous systematic review, endocarditis was reported to be a rare disease with costly

consequences.40 _{Sepsis with UTIs, or urosepsis commonly causes kidney dysfunction, leading to}

high mortality rates. In the current study, the urinary tract ranked third in incidence as an infection site associated with sepsis. The incidence of urosepsis in the United States is about 30% and is

higher among women compared with men.41,42 _{The study was in line with the current findings,}

where among UTIs the female and male ratio was at 2:1. The incidence of sepsis-associated with multifocal infections remains unknown, particularly in developing countries, but it we found that they are the costliest. Identifying multisource infections with sepsis prior to the occurrence of

organ dysfunction is thus an urgent task.43

budget to support private and public healthcare services. In 2016, Indonesia’s health expenditure

was approximately US$111.6 billion or 3.1% of its GDP.44 _{Thus, establishing sufficient healthcare}

facilities to support the care of sepsis patients is a challenge. According to the National Health Account data published by the OECD in 2016, Indonesia’s inpatient expenditure amounted to

IDR158,499.2 billion (or US$11.9 billion).24,44 _{This expenditure accounts for 40.9% of the country’s}

national total health expenditure of IDR387,648.5 billion or US$29.1 billion.44 _{For the sepsis}

inpatient expenditure, the current findings suggest that the prices in the current INA-CBGs should be upwardly adjusted as well as made specific for infection sites. As a specific item in the INA-CBGs, each individual pays health coverage according to the class of service selected. The service class categories merely relate to the provision of rooms with specific numbers of beds. Therefore, this categorization is ineffective, as all patients receive the same medical services or even when they are placed in ICUs or isolated rooms. Additionally, community healthcare centers, which play an essential role in resource-limited settings in preventing infection complications such as sepsis, could potentially serve as a budget control mechanism by averting hospital infections and then

reducing inpatient costs.41

It is believed that this is the first study to assess the burden of disease, incorporating the costs and mortality outcomes of sepsis with focal infections in a resource-limited setting. Notably, it offers a robust methodology for calculating the national price for sepsis based on a consideration of particular focal infections. However, the study had several limitations. First, it did not assess the costs associated with losses in productivity during hospitalization, and indirect costs were not recorded. Moreover, infrastructure costs – such as security systems, parking, and transportation costs – were not included. Second, post-sepsis impact on individual patients’ occupational or educational trajectories, and those of their relatives, was not assessed because the data obtained from the hospitals were not linked to the socioeconomic statuses of individual patients. Third, the national price was modeled with reference to four referral centers. Nevertheless, the resulting national model seemed reasonable. Forth, it was a retrospective study and potential bias could have existed such as misdiagnosis and under-reported focal infections. However, the study was conducted with a big sample size to provide epidemiological and health economic findings that are needed by the Indonesian government for improving the new health insurance system with a resource-limited setting. Last, it did not consider following hospital discharge, particularly for ICU patients. Evidently, the higher mortality rate among sepsis patients after being discharged was a

late-onset outcome of their ICU stays.45–47

CONCLUSIONS

It is essential to consider mortality and focal infections in an assessment of the burden of sepsis. Each underlying focal infection determines the particular course of sepsis. In a resource-limited context such as that of Indonesia, where a new UHC system has been introduced, the adequate provision of healthcare services requires a reevaluation and recalculation of the price for sepsis.

Furthermore, in context, sepsis cases with multifocal infections and LRTIs should be categorized as high-burden sepsis cases, reflecting the most obvious examples requiring adjustments to the national price for private and public healthcare services reimbursement.

ETHICAL APPROVAL

The study was approved by the ethical committee of Dr. Soetomo General Academic Hospital, Surabaya (No. 418/Panke.KKE/VII/2017), Airlangga University Hospital (No. 114/KEH/2017), and the National Center of Infectious Diseases at Prof. Dr. Sulanti Saroso Hospital, Jakarta (No. 02/ xxxviii.10/5/2018). The study met the Indonesian governmental requirements on conducting research and the ethical principles for medical research involving human subjects under the

Helsinki Declaration.48 _{All data was deidentified to guarantee patient anonymity.}

Abbreviations:

CVI: Cardiovascular infection

GTI: Gastrointestinal tract infection

IDR: Indonesian Rupiah

ICP: INA-CBG price

ICU: Intensive care unit

INA-CBG: Indonesia Case Base Group

LMIC: Low-Middle Income Country

LRTI: Lower-respiratory tract infection

NMI: Neuromuscular infection

OECD: Organization for Economic Cooperation and Development

PNP: Proposed National Price

qSOFA: quick Sequential Organ Failure Assessment

SIRS: Systemic inflammatory response syndrome

SOFA: Sequential Organ Failure Assessment

SSI: Surgical site infection

UHC: Universal health coverage

UTI: Urinary tract infection

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SUPPLEMENT 2.1

International Classification of Diseases version 10 for patient selection Sepsis

- A41.x: other sepsis - A40.x: Streptococcal sepsis - A02.1: Salmonella sepsis - A22.7: Anthrax sepsis - A24.1: Melioidosis sepsis - A54.8: Gonococcal sepsis - B37.7: Candidal sepsis

- R65.1: Systemic inflammatory response syndrome of infectious origin with organ failure severe

- R65.20: severe sepsis without septic shock - R65.21: severe sepsis with septic shock

- T81.12XA: postprocedural septic shock, initial encounter - T81.12XD: postprocedural septic shock, subsequent encounter - T81.12XS: postprocedural septic shock, sequela

- R65.10: SIRS of noninfectious origin without acute organ dysfunction - R65.11: SIRS of noninfectious origin with acute organ dysfunction Sites of infections:

1. Infections in the gastrointestinal tract - A00: cholera

- A01: typhoid

- A02: other salmonella infections - A03: shigellosis

- A04: other bacterial intestinal infections - A05: other bacterial foodborne intoxications - A06: amoebiasis

- A07: other protozoal intestinal diseases

- A08: viral and other specified intestinal infections (A08.0 rotavirus enteritis) - A09: other infections in gastrointestinal tracts

- B15-B19: viral hepatitis

- K21.0: Gastro-oesophageal reflux disease with oesophagitis 2. Infections in the lower respiratory tract

- A15-A19: tuberculosis

- J00-J99: lower and upper respiratory diseases 3. Infections in the urinary tracts

- N39: urinary tract infections

4. Nervous systems

- A39: bacteremia meningococcal

- A80-A89: infections of the central nervous system - G00-G09: bacterial meningitis

o G01: meningitis in bacterial diseases classified elsewhere

o G02-G04: meningitis in other infectious and parasitic diseases classified elsewhere o G05: encephalitis, myelitis, and encephalomyelitis in diseases classified elsewhere 5. Musculoskeletal

- M01: direct infections of joint in infectious and parasitic diseases classified elsewhere - M00-M03: infectious arthropathies

6. Oral sites

- K04.7: Abscess in alveolar, apical, dental, dentoalveolar, lateral (alveolar), periapical, periodontal, teeth-root, infection of a tooth, and dental infection

- K11.3: abscess of salivary gland - K14.0: Abscess of tongue - K04.6-K04.7: periapical abscess - K05.21: periodontal abscess - J36: peritonsillar abscess 7. Wound

- L00-L08: infections of the skin and subcutaneous tissue - T20-T32: burns

- T8: complications of surgical and medical care, not classified elsewhere o T81: wound infections

o T82: Infection and inflammatory reaction due to other cardiac and vascular devices, implants and grafts

o T85.7: Infection and inflammatory reaction due to other internal prosthetic devices, implants and grafts

o T87: post-amputation infection - O86: obstetric surgical wound infection 8. Cardiovascular dan cardiovascular systems

- I30: acute pericarditis

- I31: other diseases of the pericardium

- I32: pericarditis in diseases classified elsewhere - I33: acute and subacute endocarditis

- I38: endocarditis, valve unspecified

- I39: endocarditis and heart valve disorders in diseases classified elsewhere - I40: acute myocarditis

SUPPLEMENT 2.2

Medical specialties for minimum requirements in Hospitals Type A, B, C and D (Health Ministry of Republic of Indonesia 2019)

Hospital type

Type A Type B Type C Type D

Primary medical specialties - Internist

- Pediatric - Surgeon

- Obstetrician and gynecologist

- Internist - Pediatric - Surgeon - Obstetrician and gynecologist - Internist - Pediatric - Surgeon - Obstetrician and gynecologist - Internist - Pediatric

Secondary medical specialties - Ophthalmologist - Otolaryngologist - Neurologist - Cardiologist - Dermatologist - Psychiatrist - Pulmonologist - Orthopedic - Urologist - Neurosurgeon - Plastic surgeon

- Cardiothoracic and vascular surgeon

- Ophthalmologist - Otolaryngologist - Neurologist - Cardiologist - Dermatologist - Psychiatrist - Pulmonologist - Orthopedic N/A N/A

Tertiary medical specialties - Anesthesiologist

- Physical medicine and rehabilitation specialist - Radiologist - Clinical pathologist - Anatomy pathologist - Clinical microbiologist - Clinical nutritionist - Clinical parasitologist - Clinical pharmacologist - Anesthesiologist - Physical medicine and

rehabilitation specialist - Radiologist - Clinical pathologist - Anatomy pathologist - Clinical microbiologist Anesthesiologist N/A

Quaternary medical specialties or Sub-medical specialties - A surgeon with a digestive subspecialist

- An internist with a gastroenterohepatology subspecialist

- An internist with hypertension and nephrology subspecialist

- A pediatrician with a neonatology subspecialist - An obstetrician with a fetomaternal subspecialist - An ophthalmologist with a subspecialist - A pulmonologist with a subspecialist

- An anesthesiologist with a subspecialist in intensive therapy

N/A N/A N/A

Source: Ministry of Health of the Republic of Indonesia. The classification and license for the hospital No. 30, 2019. Available:http:// hukor.kemkes.go.id/uploads/produk_hukum/PMK_No__30_Th_2019_ttg_Klasifikasi_dan_Perizinan_Rumah_Sakit.pdf. Published 2019. Accessed January 3, 2020.

Note: N/A = not available

SU

PPL

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T 2

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sis with foca

l infectio ns with the r at es specified fo r the Indo nesia C ase Base Gr oup s in a ll fiv e r egio ns of Indo

nesia (in US$)

H osp ita l Se psi s w ith L RT I Se psi s w ith U TI Se psi s w ith G TI Se psi s w ith N M I Se psi s w ith W I Se psi s w ith C VI U FI sep si s IC P PN P D iff IC P PN P D iff IC P PN P D iff IC P PN P D iff IC P PN P D iff IC P PN P D iff IC P PN P D iff R eg io n 1 P ub lic A 1,6 90 .8 3, 02 3.6 1,3 32 .8 1,34 7.8 2, 08 4.1 73 6. 3 1,0 88 .5 1,2 96 .9 20 8. 4 1,36 4. 2 1,77 0. 9 40 6.7 1,3 01 .8 3, 659 .4 2, 35 7.7 2, 07 9. 0 3, 89 7.8 1, 81 8. 8 63 9.1 1,7 21 .0 1,0 81 .9 P riv at e A 1,7 41 .5 3,11 4. 3 1,3 72 .8 1,3 88 .3 2,1 46 .7 75 8. 4 1,12 1. 2 1,335 .9 214 .7 1,4 05 .2 1, 82 4.1 41 8. 9 1,34 0. 8 3, 76 9. 2 2, 42 8.4 2,1 41 .4 4, 014 .7 1, 87 3. 4 65 8. 3 1,7 72 .6 1,11 4. 3 P ub lic B 98 1. 2 1,7 54 .6 773 .4 87 0. 8 1,34 6. 6 47 5. 7 842 .5 1,0 03 .8 161 .3 95 4.7 1,2 39 .3 28 4. 6 94 4. 3 2, 65 4.4 1,7 10 .2 1,4 54 .9 2, 72 7.7 1,2 72 .8 44 7.2 1,2 04 .3 75 7.1 P riv at e B 1,0 10 .6 1, 80 7.2 79 6. 6 86 0.1 1,3 29 .9 46 9.9 86 7.7 1,0 33 .9 16 6. 2 983 .3 1,2 76 .5 29 3.1 97 2. 6 2, 73 4. 0 1,7 61 .5 1,4 23 .4 2, 66 8. 6 1,2 45 .3 46 0.7 1,2 40 .5 77 9. 8 P ub lic C 89 1. 8 1,5 94 .7 703 .0 75 8. 0 1,17 2.1 41 4.1 676 .6 80 6. 2 12 9. 6 76 6. 7 99 5. 3 228 .6 811 .5 2, 28 1.1 1,4 69 .7 1,12 9.9 2,1 18 .4 98 8. 5 35 9. 2 96 7.2 60 8. 0 P riv at e C 918 .5 1,6 42 .6 724 .0 78 0. 7 1,2 07. 2 42 6. 5 69 6.9 83 0. 3 13 3. 4 78 9. 7 1,0 25 .2 235 .4 83 5. 8 2,34 9. 6 1,5 13 .8 1,1 63 .8 2,1 81 .9 1,0 18 .2 37 0. 0 99 6. 2 62 6. 3 P ub lic D 78 0. 3 1,3 95 .4 615 .1 659 .2 1,0 19 .4 36 0. 2 562 .2 66 9. 8 10 7.7 63 7.0 82 7.0 18 9.9 62 9. 8 1,77 0. 4 1,1 40 .6 97 0. 8 1, 82 0.1 84 9. 3 29 8. 4 80 3.6 505 .2 P riv at e D 80 3. 7 1,4 37. 2 633 .5 67 9. 0 1,05 0. 0 37 1.0 57 9. 0 68 9.9 11 0. 9 65 6. 2 851 .8 19 5. 6 64 8.7 1, 82 3. 5 1,17 4. 8 999 .9 1, 874 .7 874 .8 30 7.4 82 7.7 52 0. 3 Re gi on 2 P ub lic A 1,7 06 .0 3, 05 0. 8 1,34 4. 8 1,3 60 .0 2,1 02 .9 74 3. 0 1,0 98 .3 1,3 08 .6 210 .3 1,3 76 .5 1,7 86 .9 41 0. 4 1,3 13 .5 3, 69 2. 4 2, 37 8. 9 2, 09 7.7 3, 932 .9 1, 83 5. 2 64 4. 8 1,7 36 .5 1,0 91 .6 P riv at e A 1,7 57. 2 3,1 42 .3 1,3 85 .1 1,40 0.8 2,1 66 .0 76 5. 2 1,13 1. 3 1,34 7.9 216 .6 1,4 17. 8 1, 84 0. 5 42 2. 7 1,3 52 .9 3, 80 3. 2 2, 45 0. 3 2,1 60 .6 4, 05 0. 9 1, 89 0. 2 66 4. 2 1,7 88 .5 1,12 4. 3 P ub lic B 99 0. 0 1,77 0. 4 78 0. 4 842 .6 1,30 2. 8 46 0. 3 85 0. 0 1,0 12 .8 16 2. 8 963 .3 1,2 50 .5 28 7.2 95 2. 8 2, 67 8. 3 1,7 25 .5 1,4 68 .0 2, 75 2. 2 1,2 84 .3 451 .3 1,2 15 .2 76 3. 9 P riv at e B 1,0 19 .7 1, 82 3. 5 80 3. 8 86 7.8 1,34 1.9 474 .1 875 .6 1,0 43 .2 16 7.7 99 2. 2 1,2 88 .0 295 .8 98 1. 3 2, 75 8. 6 1,777 .3 1,5 12 .0 2, 83 4. 8 1,3 22 .8 46 4. 8 1,2 51 .6 78 6. 8 P ub lic C 89 9. 8 1,6 09 .1 70 9. 3 76 4. 8 1,1 82 .6 41 7.8 682 .7 813 .4 13 0. 7 773 .6 1,0 04 .3 230 .6 818 .8 2, 30 1.7 1,4 82 .9 1,1 40 .1 2,1 37 .4 99 7.4 36 2. 4 975 .9 613 .5 P riv at e C 92 6. 8 1,6 57. 3 73 0. 5 78 7.7 1,2 18 .1 43 0. 3 703 .2 83 7.8 13 4. 7 79 6. 8 1,0 34 .4 23 7.5 84 3. 3 2, 37 0. 7 1,5 27. 4 1,17 4. 3 2, 20 1.6 1,0 27. 3 37 3. 3 1,0 05 .2 631 .9 P ub lic D 78 7.3 1,4 07. 9 62 0. 6 665 .2 1,0 28 .6 363 .4 56 7.2 675 .8 10 8. 6 642 .8 83 4. 4 19 1.6 635 .4 1,7 86 .3 1,15 0. 8 97 9. 5 1, 83 6. 5 85 7.0 30 1.1 810 .8 50 9.7 P riv at e D 810 .9 1,4 50 .2 63 9. 2 68 5.1 1,0 59 .4 374 .3 58 4. 2 69 6.1 111 .9 66 2.1 859 .4 19 7.4 65 4. 5 1, 83 9.9 1,1 85 .4 1,0 08 .9 1, 89 1.6 882 .7 31 0.1 83 5. 2 52 5. 0 R eg io n 3 P ub lic A 1,7 11 .1 3, 059 .8 1,34 8. 8 1,36 4. 0 2,1 09 .2 74 5. 2 1,1 01 .6 1,3 12 .5 210 .9 1,3 80 .6 1,7 92 .2 411 .6 1,3 17. 4 3,7 03. 4 2, 38 6. 0 2,1 03 .9 3,9 44 .6 1, 84 0. 7 64 6. 8 1,7 41 .6 1,0 94 .9 P riv at e A 1,7 62 .4 3,15 1.6 1,3 89 .2 1,4 04 .9 2,1 72 .4 76 7.5 1,13 4. 6 1,3 51 .9 21 7.3 1,4 22 .0 1, 84 6. 0 42 3. 9 1,3 56 .9 3, 814 .5 2, 45 7.6 2,1 67. 1 4, 062 .9 1, 89 5. 9 666 .2 1,7 93. 9 1,1 27. 7 P ub lic B 99 2. 9 1,7 75 .6 78 2. 7 84 5.1 1,3 06 .7 461 .7 85 2. 6 1,0 15 .8 16 3. 3 96 6. 2 1,2 54 .2 28 8. 0 955 .6 2, 68 6.3 1,7 30 .7 1,4 72 .3 2, 76 0.4 1,2 88 .1 45 2. 6 1,2 18 .8 76 6. 2 P riv at e B 1,0 22 .7 1, 82 8. 9 80 6. 2 87 0. 4 1,34 5. 9 47 5. 5 87 8. 2 1,0 46 .3 16 8. 2 99 5.1 1,2 91 .8 29 6.7 98 4. 3 2, 76 6. 9 1,7 82 .6 1,5 16 .5 2, 84 3. 3 1,3 26 .7 46 6. 2 1,2 55 .3 78 9. 2 P ub lic C 902 .5 1,6 13 .9 711 .4 76 7.1 1,1 86 .1 419 .1 68 4.7 815 .8 13 1.1 775 .9 1,0 07. 2 231 .3 82 1. 2 2, 30 8. 5 1,4 87. 3 1,1 43 .4 2,1 43 .8 1,000 .4 363 .5 97 8. 8 615 .3 P riv at e C 92 9. 6 1,6 62 .3 732 .7 79 0.1 1,2 21 .7 431 .6 70 5. 2 84 0. 3 13 5.1 79 9. 2 1,0 37. 4 238 .2 845 .8 2, 37 7.8 1,5 31 .9 1,1 77. 7 2, 20 8.1 1,0 30 .4 374 .4 1,0 08 .2 633 .8

H osp ita l Se psi s w ith L RT I Se psi s w ith U TI Se psi s w ith G TI Se psi s w ith N M I Se psi s w ith W I Se psi s w ith C VI U FI sep si s IC P PN P D iff IC P PN P D iff IC P PN P D iff IC P PN P D iff IC P PN P D iff IC P PN P D iff IC P PN P D iff P ub lic D 78 9. 7 1,4 12 .1 62 2. 5 66 7.2 1,0 31 .6 36 4. 5 56 8.9 67 7.8 10 8. 9 64 4.7 83 6.9 19 2. 2 63 7.3 1,7 91 .6 1,15 4. 3 982 .4 1, 841 .9 859 .5 30 2. 0 813 .3 511 .2 P riv at e D 813 .4 1,4 54 .5 641 .1 68 7.2 1,0 62 .6 37 5. 4 58 6. 0 69 8. 2 11 2. 2 66 4. 0 862 .0 19 8. 0 65 6. 5 1, 84 5. 4 1,1 88 .9 1,0 11 .9 1, 89 7.2 88 5. 3 311 .1 83 7.7 52 6. 6 R eg io n 4 P ub lic A 1,7 36 .5 3,1 05 .2 1,3 68 .8 1,3 84 .2 2,1 40 .4 75 6. 2 1,11 7.9 1,3 32 .0 21 4.1 1,4 01 .1 1, 81 8. 8 41 7.7 1,3 36 .9 3, 75 8. 3 2, 42 1. 3 2,13 5.1 4, 00 3. 0 1, 86 7.9 65 6. 4 1,7 67. 4 1,111 .1 P riv at e A 1,7 88 .5 3,19 8. 4 1,40 9.8 1,4 25 .7 2, 20 4. 6 778 .9 1,15 1.4 1,3 71 .9 220 .5 1,4 43 .1 1, 87 3. 3 43 0. 2 1,3 77. 0 3, 87 1.0 2, 49 4. 0 2,19 9. 2 4,12 3.1 1,9 24 .0 676 .0 1, 82 0. 4 1,1 44 .4 P ub lic B 1,0 07. 7 1, 80 2. 0 79 4. 3 85 7.6 1,3 26 .1 46 8.5 865 .2 1,0 30 .9 16 5. 7 980 .5 1,2 72 .8 29 2. 3 96 9. 8 2, 72 6.1 1,7 56 .3 1,4 94 .2 2, 80 1.4 1,3 07. 2 459 .3 1,2 36 .9 777 .5 P riv at e B 1,0 37. 9 1, 85 6. 0 81 8.1 883 .3 1,3 65 .9 482 .6 89 1. 2 1,0 61 .8 17 0. 7 1,0 09 .9 1,3 11 .0 30 1.1 99 8.9 2, 80 7.9 1, 80 9. 0 1,5 39 .0 2, 88 5.4 1,34 6. 4 47 3.1 1,2 74 .0 80 0.9 P ub lic C 915 .9 1,6 37. 8 72 1.9 778 .4 1,2 03 .7 42 5. 3 69 4.9 82 7.9 13 3.1 78 7.4 1,0 22 .2 23 4.7 833 .4 2,34 2. 7 1,5 09 .3 1,1 60 .4 2,17 5. 6 1,0 15 .2 36 8.9 993 .3 624 .4 P riv at e C 80 1.4 1,4 33 .1 631 .7 67 7.0 1,0 46 .9 36 9.9 57 7.3 68 7.9 11 0. 6 65 4. 2 84 9. 3 19 5. 0 64 6. 8 1, 81 8. 2 1,17 1.4 1,12 1.7 2,1 03 .1 98 1.4 30 6. 5 82 5. 3 518 .8 P ub lic D 80 1.4 1,4 33 .1 631 .7 67 7.0 1,0 46 .9 36 9.9 57 7.3 68 7.9 11 0. 6 65 4. 2 84 9. 3 19 5. 0 64 6. 8 1, 81 8. 2 1,17 1.4 99 7.0 1, 86 9. 2 87 2. 2 30 6. 5 82 5. 3 518 .8 P riv at e D 82 5. 4 1,4 76 .1 65 0. 6 69 7.4 1,0 78 .3 38 1.0 59 4. 7 70 8. 5 11 3. 9 67 3. 9 874 .8 20 0.9 666 .2 1, 87 2. 7 1,2 06 .5 1,0 26 .9 1,9 25 .3 89 8. 4 315 .7 85 0.1 53 4. 4 R eg io n 5 P ub lic A 1,7 92 .2 3, 20 5. 0 1,4 12 .7 1,4 28 .7 2, 20 9. 2 780 .5 1,15 3. 8 1,3 74 .8 22 0.9 1,4 46 .1 1, 87 7.2 43 1.1 1,3 79 .9 3, 87 9. 0 2, 49 9.1 2, 20 3. 7 4,13 1.7 1,9 28 .0 67 7.4 1, 82 4. 2 1,1 46 .8 P riv at e A 1, 84 6. 0 3, 30 1.1 1,4 55 .1 1,4 71 .5 2, 275 .5 80 3. 9 1,1 88 .4 1,41 6. 0 22 7.6 1,4 89 .5 1,9 33 .5 444 .0 1,4 21 .3 3,9 95 .4 2, 574 .1 2,2 69 .8 4, 255 .6 1,9 85 .8 69 7.8 1, 87 8. 9 1,1 81 .2 P ub lic B 1,0 40 .0 1, 85 9.9 819 .8 88 5.1 1,3 68 .7 483 .6 893 .0 1,0 64 .0 17 1.0 1,0 12 .0 1,3 13 .7 30 1.7 1,000 .9 2, 813 .7 1, 812 .8 1,5 42 .2 2, 89 1.4 1,34 9. 2 474 .1 1,2 76 .6 80 2.5 P riv at e B 1,0 71 .3 1,9 15 .7 84 4.4 911 .7 1,40 9.8 49 8.1 919 .8 1,0 95 .9 17 6.1 1,0 42 .4 1,3 53 .1 31 0. 7 1,0 30 .9 2, 89 8.1 1, 86 7.2 1,5 88 .4 2, 97 8.1 1,3 89 .7 488 .3 1,3 14 .9 82 6. 6 P ub lic C 945 .3 1,6 90 .4 74 5.1 80 3.5 1,2 42 .4 43 8. 9 71 7.2 85 4. 5 13 7.3 812 .7 1,0 55 .0 24 2. 3 86 0. 2 2, 41 8. 0 1,5 57. 8 1,1 97. 7 2, 24 5. 5 1,0 47. 8 38 0.7 1,0 25 .2 64 4. 5 P riv at e C 97 3. 7 1,7 41 .1 76 7.5 82 7.6 1,27 9. 6 45 2.1 73 8.7 88 0.1 141 .4 83 7.1 1,0 86 .7 24 9. 6 886 .0 2, 49 0. 5 1,6 04 .6 1,2 33 .6 2, 312 .8 1,0 79 .2 39 2. 2 1,0 56 .0 66 3.9 P ub lic D 82 7.1 1,4 79 .1 65 2. 0 69 8. 8 1,0 80 .6 38 1. 8 59 5. 9 710 .0 11 4.1 675 .3 876 .6 20 1. 3 66 7.6 1, 87 6. 6 1,2 09 .0 1,0 29 .0 1,9 29 .3 90 0. 3 31 6. 3 851 .8 535 .5 P riv at e D 851 .9 1,5 23 .5 67 1.5 719 .8 1,11 3. 0 393 .2 613 .8 731 .3 11 7.5 69 5. 5 902 .9 20 7.3 68 7.6 1,9 32 .9 1,2 45 .3 1,0 59 .9 1,9 87. 2 92 7.3 32 5. 8 87 7.4 551 .6 N ote: C VI = c ar di ov as cu la r i nf ec tio ns , d iff = d iffe re nc e, G TI = g as tro in te st in al t ra ct i nf ec tio n, I CP = I N A-CB G p ric e. L RT I = l ow er -re sp ira to ry t ra ct i nf ec tio n. N M I = n eu ro m us cu la r i nf ec tio n, P N P = pr op os ed n at io na l p ric e, S SI = s ur gi ca l s ite i nf ec tio n, U FI = u ni de nt ifi ed f oc al i nf ec tio n, U TI = u rin ar y t ra ct i nf ec tio n, a nd W I = w ou nd i nf ec tio n.

2

2

Part

Prophylactic antibiotics

for surgical site

infection prevention