Exploring the real costs of healthcare-associated infections: an international review

João Mouraa, Pilar Baylina b and Paulo Moreira c,d

aAssociação de Politécnicos do Norte, Instituto Politécnico do Porto, Portugal; bEscola Superior de Saúde do Porto, Instituto Politécnico doPorto, Portugal; cInstituto para as Políticas Públicas e Sociais, ISCTE – Instituto Universitário de Lisboa, Lisboa, Portugal; dUniversidadeAtlântica, Lisboa, Portugal

ABSTRACTPurpose: Healthcare-associated infections acquired a high degree of dissemination, being considered a serious public health problem and assumed as one of the most common adverse events associated with healthcare. They have a significant impact on health systems by increasing hospital expenses, and compromising the healthcare quality and effectiveness. Surgical site infections (SSI) are considered one of the most serious complications that can occur after an orthopaedic surgery. The aim of this study is to contribute to the development of a framework to analyse the costs of infections related to hip and knee arthroplasties. Methods: A literature review was conducted on databases, and articles published between January 2005 and April 2016 were searched.Findings: A total of 14 articles met the inclusion criteria. Costs were grouped in hospitalization and treatment dimensions. For hospitalization, the indicators were the length of stay (LOS) and/or monetary costs; For treatment, the indicators were number of surgeries and LOS, or monetary costs. We observed that LOS is the most commonly used to estimate SSI direct costs. Patients who developed hip or knee arthroplasty infections remained in hospital 2.5–3 times longer and incurred hospital costs almost three times higher, when compared with an uninfected patient.

KEYWORDSHip and knee arthroplasties;healthcare-associatedinfections (HAI); surgical siteinfections (SSI); length ofstay; costs

Introduction

Nosocomial infections, currently named by healthcare-associated infections (HAI), are according to the Euro-pean Centre of Disease Prevention and Control(ECDC) and the National Nosocomial Infection Sur-veillance (NNIS), those arising from adverse reactionsto the presence of an infectious agent or its toxins,but they were not expressed neither undergoing anincubation period, at the time of patient’s admissionto the hospital [1,2].

Currently, these have acquired a high degree of dis-semination, being considered a serious public healthproblem. HAIs are assumed as one of the most com-mon adverse events associated with healthcare and isestimated that about one in ten hospitalized patientswill acquire an infection after admission. Its high trans-cendence is due to its high morbidity and mortality,having become one of the major causes of death in hos-pitalized patients [3–5]. Also, these have a very signifi-cant impact on health systems by increasing hospitalexpenses and may compromise the healthcare qualityand effectiveness. These extra costs are justified bythe increase of the length of stay (LOS) in about 4–8days for each infected patient, and the additional diag-nostics and therapeutic interventions. As a result,patients who developed HAI remained in hospital 2.5

times longer than uninfected patients and incurredhospital costs almost three times higher [3,6,7].

Although it is a very current topic, since the begin-ning of the 1990s several international projects havebeen developed in order to improve knowledge aboutHAI and at the same time, developed surveillance strat-egies to promote and guide efforts towards the preven-tion and control of this kind of infection [8,9]. In thismatter is noteworthy the work done by WHO, CDC,OECD, and the Council of Europe in the developmentof these projects [9], emerged in 1994 in Europe thefirst international programme of HAI active surveil-lance, the Hospitals in Europe Link for Infection Con-trol through Surveillance (HELICS), that has beenexpanding and suffering continuous improvementsince then [10]. Since the creation of HELICS, otherprogrammes have been developed, such as ‘FirstPatient Safety Challenge: Clean Care is Safer Care’[11] and ‘Second Patient Safety Challenge: Safe Surgerysaves lives’ [12] by the WHO, ‘Prohibit’ [13], and‘BURDEN’ [14] by the European Union and theHAI-net [15] by ECDC.

However, the impact of these programmes has notbeen as expected. A group of researchers, through areview article, identified a number of barriers to thesuccess of these programmes, clustered in three

dimensions: structure, processes, and results [16]. Withregard to structures, they referred to the lack of qualityof hospital infrastructure; lack of human resources,especially nurses dedicated full-time to HAI preventionand control programmes; hospital environmental con-tamination and the organization’s own culture. Withregard to processes, they indicated failures in clinicalprocesses and management processes, such as poorinfection control practices, wards management, health-care teams’ management, hospital and cleaning ser-vices management and the inappropriate use ofresources. With regard to results, all identified barriersare related with the lack of effective surveillance sys-tems and the unreliability of epidemiological data [16].

There are four major groups of HAI: ventilator-associated pneumonia (VAP), catheter-associatedurinary tract infections, surgical site infections (SSI),and bloodstream infections (CLABSI). In this systema-tic literature review, our attention turned to the SSI,focusing on the orthopaedics area, selecting onlythose associated with hip or knee arthroplasties.

This work is organized in four major chapters: thefirst is a brief introduction to hip and knee arthroplastyinfections; in the second is presented the methodologyused, including database search, data collection, andanalysis; the third chapter is dedicated to results pres-entation; and in the final chapter are presented thestudy’s conclusions.

Hip and knee arthroplasty infections

As the average life expectancy is increasing in industri-alized countries, the number of patients who needorthopaedic implant surgery also increases, accentuat-ing the risk of developing a greater number of infec-tions [17].

SSI are considered one of the most serious compli-cations that can occur after arthroplasty [18] andbetween 1.5 and 2.5% of all knee and hip arthroplastiestend to become infected [19]. In agreement with pre-vious reports, these values can range between 2 and6% [20].

The LOS is one of the factors that suffers the biggestchanges when the patient gets an infection, and it is theindicator most commonly used to estimate the directcosts of SSI [21].

Despite the increase of the hospitalization costs, SSIalso represent a major clinical problem leading to pain-ful and persistent symptoms in infected patients, needfor new surgical interventions, extra antibiotic treat-ments, and casual removal or replacement of the pros-thesis and, in more severe cases to save the patient, alocal amputation is performed [22–24].

The presence of microorganisms on the prosthesissurface is one of the preconditions for the infectionoccurrence. The most often bacteria related with ortho-paedic implant infections are Staphylococcus aureus and

Staphylococcus epidermidis, particularly the first agentthat is responsible for most of these infections, whichare especially difficult to treat when caused byMethicil-lin-resistant Staphylococcus aureus (MRSA) [20,25].

There is evidence that, for example, if the screeningand the decolonization of Staphylococcus aureus in hipor knee replacement surgeries was carried out, aboutseven times the costs of the prevention programmeimplementation could be avoided [26]. According toSlover et al. [27] the cost of SSI associated with theseprocedures is so great that the cost of a screening pro-gramme would be recovered by only a small decrease ininfection rate. Reducing the infections will decreasehospitalization time and increase the availability ofbeds for more days. With this, patients would enterand leave the hospital at a faster rate, reducing the aver-age cost per patient treated [26].

It is also crucial to develop methods for the earlydetection of arthroplasty’s infection, based on symp-toms such as fever, pain, and tumefaction. If early detec-tion was achieved, the infection could be treated bydebridement and implant retention. In this way, costswould be significantly reduced, shortening the recoveryperiod, and avoiding the costly two-stage revisions [18].Hereupon, every effort is justified in order to preventinfection such as strict epidemiological surveillanceand prevention programmes to avoid factors that maycontribute to the onset of infection and, above all, bestclinical practices of all staff involved in surgery [28].

In view of the increased costs related with theseinfections, the aim of this study is to perform a sys-tematic review about the infection costs of hip andknee arthroplasties in several countries around theworld, in order to better understand their economicimpact.

Methodology

The systematic literature review was done according tothe PRISMA guidelines [29].

Database search

Research was carried out in April 2016 using B-ON,PubMed, and Science Direct databases in order tofind articles related with hip or knee arthroplasty infec-tion costs, published between January 2005 and April2016. To carry out this research, a combination ofterms (Table 1) and an inclusion criterion (publicationperiod) were applied. In each database, searches wereperformed separately for hip and knee arthroplasties.After carrying out both searches within each one ofthese databases, the articles that are repeated wereexcluded.

As a result of this research method, 37 articles wereidentified from PubMed, 38 from B-ON, and 29 fromScience Direct.

To the articles obtained from this initial researchmethod, more inclusion and exclusion criteria wereapplied (Table 2). In order to keep only one copy ofeach article, we exclude the repetition of the samearticle in different databases. A final number of 31articles were obtained: PubMed [17], B-ON [4], andScience Direct [10].

After verification and further evaluation of the 31articles, only 16 fulfilled every criteria of inclusion:PubMed [10], B-ON [1], and Science Direct [5], asshown in Figure 1.

Data collection and analysis

After the analysis of each article, the following datawere extracted in an excel file: article name, publicationyear, country, setting (hospitals, teaching hospitals, ter-tiary care centre), study methodology, keywords, sum-mary, and topics (key points).

Results

Through the literature review performed, we identifieda number of key issues responsible for the increasedhospitalization costs, as well as the costs of some treat-ments and prevention methods for hip or knee arthro-plasty infections, which can reduce costs and patientsuffering.

Costs for hospitalization and infectiontreatment

In Table 3 are presented the results of different studiesin several countries, divided into two major dimen-sions: hospitalization and treatment. With regard tohospitalization, the charges will be presented in LOSand/or monetary costs. With regard to treatment, thecharges will be presented in number of surgeries andLOS, or monetary costs.

Infection prevention and control

In Table 4 are presented the results of a study con-ducted in Australia. The researchers evaluated thecost-effectiveness of implemented strategies claimingto reduce the risk of deep SSI in hip arthroplasties.

Discussion

Through the literature review performed, we identifiedthemain costs caused byHAI in hip and knee arthroplas-ties and the costs of some treatments and preventionmethods for these situations. In agreement with the cur-rent state of the art, this review identified LOS as the indi-cator most commonly used to estimate the direct costs ofSSIs, and according to some authors, this happensbecause, in addition to the direct relationship betweenthe LOS and the risk of HAI, the extension of hospitaliz-ation days is an easily understood measure either byphysicians or by hospital managers, which translates inthe consumption of health resources to treat a compli-cation [21,35,43]. According to Plowman [6], patientswho developed HAI remained in hospital 2.5 timeslonger and incurred hospital costs almost three timeshigher, when compared with an uninfected patient whounderwent the same surgical procedure. According tothe articles reviewed, and with regard to LOS andHAI’s treatment costs, the results were very similar tothose found in the literature related with HAI issues.

Table 1. MeSH and terms related.Cross infectionHAIHospital infectionSSIHip arthroplastyKnee arthroplastyHip replacementKnee replacementCost

Table 2. Inclusion and exclusion criteria.Inclusion criteria

. Publication year: January 2005 toApril 2016;

. Language: English, Portuguese,and Spanish;

. Contain abstract;

. Only apply to hospitals withOrthopaedic services/department;

. Be published and available in ajournal in public domain;

. Discuss about costs for hip orknee arthroplasty;

. Discuss about costs for infectionstreatment applied to hip or kneearthroplasty;

. Discuss about cost-effectivenessof strategies claiming to reducethe risk of hip or knee arthroplastyinfections.

Exclusion criteria

. Articles not related with hip orknee arthroplasty infections;

. Articles with description ofmethods, models, and theorieswithout empirical data;

. Other healthcare entities thatare not hospitals.

Figure 1. Search strategy.

Table 3. Costs for hospitalization and infection treatment.Costs

Dim Authors Study description Arthroplasty without HAI Arthroplasty with HAI

Hospitalization Jodra et al.[21]

Study conducted in Madrid, between January2000 and June 2004. Additional cost forinfection treatment based on excess LOSattributable to hip arthroplasty infections wasestimated.

Hip:Average LOS: 17 daysThe mean cost per day for apatient admitted to theorthopaedic unit: 437.44 €.

Hip:Average LOS: 53 daysAdditional cost per patient whodevelops SSI : 14,216.80 €

Irribaren et al.[28]

Comparative case–control study carried out inChile, between January 2000 and December2004 about excessive direct costs attributed tohip arthroplasty infections.

Hip:Average LOS: 13 daysAverage cost: $2354

Hip:Average LOS: 54 daysAverage cost: $6174,8 (additionalcost : $3820,1)

Coello et al.[30]

Study conducted in England, based onsurveillance data of SSI from 140 Englishhospitals, included in NINSS (NationalNosocomial Infection Surveillance Service),between October 1997 and June 2001.

Hip:Average LOS: 11.1 daysKnee:Average LOS: 10.3 days

Hip:Average LOS: 22.6 daysAdditional cost: $3342Knee:Average LOS: 21.2 daysAdditional cost : $3168

Alp et al. [31] Study conducted in Turkey, between April 2011and April 2013, to evaluate the incidence andeconomic burden of prosthetic joint infections.

Hip and Knee:Average LOS: 7 daysAverage cost: $5937

Hip and Knee:Average LOS: 49 daysAverage cost: $16999

Poultsideset al. [32]

Study conducted in USA to analyse thehospitalization data from the National InpatientSample (NIS) for hip and knee arthroplastiesbetween 1998 and 2007.

Hip:Average LOS: 4.2 daysAverage cost: $14,286Knee:Average LOS: 4 daysAverage cost: $1,334

Hip:Average LOS: 13.4 daysAverage cost: $31432Knee:Average LOS: 9.7 daysAverage cost: $24 458

Kurtz et al.[33]

Study conducted in USA, based on NIS to identifythe primary and revision arthroplastyperformed between January 2001 andDecember 2009 and to predict the economicimpact of periprosthetic joint infection on theUS health system.

– Hip:Average of cost and LOS:2001: $31 300; 11.5 days2009: $30 300; 9.5 daysKnee:Average of cost and LOS:2001: $25 300; 9.3 days2009: $24 200; 7.2 days

Kapadia et al.[34]

Study with a group control conducted in USA,between January 2007 and December 2011.The impact of periprosthetic joint infections onthe LOS, readmissions and associated costsmeasured.

Knee:Average LOS: 3 daysDays in hospital (mean): 3.4daysReadmissions (mean): 0.14Average cost: $28 249.57

Knee:Average LOS: 5.3 daysDays in hospital (mean): 23.7 daysReadmissions (mean): 3.43Average cost: $116 382. 65

Dal-Paz et al.[35]

Study conducted between 2006 and 2007 inBrazil to estimate the direct costs of the 34patients’ treatment who acquired kneearthroplasty infections, by analyzing medicalrecords.

– Knee:Average LOS: 29,7 daysAdditional Average |Cost: $2,701.29

Garrido-Gómez et al.[18]

Retrospective study conducted between January2005 and January 2010 in Spain, with 79patients who were diagnosed and treated forknee arthroplasty infection.

– Knee:Average Cost: 40 542 €.

Klouche et al.[36]

Retrospective study conducted in Francebetween January and December 2006, todetermine the cost of revision of infected hiparthroplasty and to compare these costs tothose of primary and revision of non-infectedhip arthroplasty.

Hip:Average cost of primaryarthroplasty: 9028€Average cost of asepticrevision : 12 409 €

Hip:Average Cost of septic revision: 32546€

Peel et al. [37] Study conducted at St. Vincent’s HospitalMelbourne, between January 2011 and June2012, to evaluate the direct hospital costs in thefirst 30-day follow-up of patients undergoingtotal hip and knee arthroplasties (data wereextrapolated for Australian population).

– Hip and Knee:SSI raise the arthroplasty’s costaround 76% in the hip, and around54% in the knee.The estimated average cost in thefirst 30 days following surgery toAustralian population: $97.2 millionAU

González-Vélez et al.[38]

A matched case–control study conducted atRamon y Cajal University Hospital in Spainbetween 1 January 2005 and 31 December2011. The researchers estimated the excessdirect costs of hip arthroplasty

Hip:Average LOS: 21 daysAverage Cost : 10 828 €

Hip:Average LOS: 58 daysAverage Cost :25 288 €

Gow et al. [39] Retrospective case–control study conducted atAuckland City Hospital (New Zealand) todetermine the excess costs attributable to hipand knee arthroplasty infections.

– Hip and Knee:Excess Average LOS: 42 daysExcess Average Cost: $40,121

(Continued )

It can also be concluded that comparing the LOS andtreatment costs between hip arthroplasty infection andknee arthroplasty infection, the first were, in general,higher. Also, and being more specific, patients whodeveloped deep incisional and organ/space SSI, in caseof hip or knee arthroplasties, remained in hospital twotimes longer than those with superficial SSI [21,30].

In addition to the LOS average cost, some articlesreviewed were even more specific, discriminating theantimicrobial costs, readmission’s number, laboratorytests and even the influence of age, gender, and racein HAI’s treatment costs. According to Iribarren et al.[28], in cases of arthroplasty infection, only the antimi-crobial’s additional costs was about $2421 per patienttreated. According to Dal-Paz et al. [35], the additionalcosts in antibiotic therapy and laboratory tests to treatinfections of a knee replacement, were approximately$600 per patient.

Besides the extension of the LOS, the readmission’snumber also undergo a considerable change. Kapadiaet al. [34], in his study about knee arthroplasty infec-tions, concluded that the readmission’s rate increasedabout four times in infected patients.

Besides the costs previously referenced, anotherUSA-based study went further and concluded thatthere are other factors related to the patient and withits geographical location, even within the same country,whichwill affect theHAI’s treatment costs [33]: Patientsfrom different geographic locations generate differentcosts, e.g. patients living in the South or the Midwesthad a lower cost ($4000–$5000) than those in theWest or the Northeast. The patient’s race also has aninfluence on costs, e.g. Asian and African-Americanpatients generated, on average, an additional expense

of $4700 and $1700, respectively, when comparedwith caucasian patients. Another important issues areage and gender, e.g. at a given age level, female patientsincurred a higher HAI’s treatment cost than malepatients, with particular emphasis in the ranges betweenthe ages 45 and 54 years and the ages 75 and 79 years.

Treatment

Regarding HAI’s treatment method, as mentioned pre-viously, the state of art reveals that if early detectionwas achieved, the infection could be treated by debride-ment and implant retention [18]. According to Merol-lini et al. [40] study, four HAIs treatment methods wereapplied. They concluded that the treatment with debri-dement, antibiotics, and implant retention, had anaverage cost around $19,688 AU and a two-stage revi-sion had an average cost of $ 44,744 AU, which is morethan double than the first one. The importance of pri-mary prevention should not be ignored, because theoccurrence of SSI might be reduced by introducingmore cost-effective infection prevention measures.

According to Moojen et al. [41], we should aimtreatment strategies that are both efficient and cost-effective. They concluded that the strategy of a singledebridement appears to be at least as successful forretention of the primary implant and control of infec-tion as a strategy with multiple surgical debridements,without compromising the clinical effectiveness. How-ever, considering equal clinical results, the first one willreduce the costs of multiple surgeries (2 less surgeries),hospitalizations (2 times lower), and revision implants.The single debridement will also reduce the morbidityand psychological discomfort of the patient.

Table 3. Continued.Costs

Dim Authors Study description Arthroplasty without HAI Arthroplasty with HAI

Treatment Merollini et al.[40]

Study conducted in Australia, with patientsundergoing primary hip arthroplasty andtreatment for infection between January 2006and December 2009. Different treatments costswere identified from 114 patients with deephip arthroplasty infection.

– Hip:Debridement, antibiotics and implantretention:Average cost per patient: $19 688AU1-stage revision:Average cost per patient: $26 722AU2-stage revision:Average cost per patient: $44 744AUexcision of arthroplasty:Average cost per patient: $23 805AU

Moojen et al.[41]

Retrospective study of a prospective databaseconducted in two large teaching hospitals inHolland, between 2001 and 2008. Data from 68patients treated to a deep postoperativeinfection of a total hip arthroplasty wereobtained. One of the hospitals used a singlesurgical debridement to treat the infection, theother used a system with multiple surgicaldebridement.

– Hip:Single surgical debridement:Average number of surgeries: 1Average length of antibiotictreatment: 13 weeks;Average LOS: 29 days.Multiple surgical debridement:Average number of surgeries: 3Average length of antibiotictreatment: 23 weeks;Average LOS: 59 days

Prevention

Regarding infection prevention and control methods,several studies show resources or costs that may besaved through effective prevention programmes. How-ever, authors do not provide information about the costof infection prevention efforts or number and quality-of-life years gained through those investments [26].

If costs are reduced by the implemented changes,there is no need to show the health benefits in termsof years of life gained or quality-adjusted life yearsgained. However, in cases where the cost savings donot compensate the increase of total costs, the healthoutcomes need to be demonstrated [26].

According to Merollini, Crawford et al. [42], scarceresources should be used efficiently and for this, it isimportant to establish a cost-effective approach to pre-venting SSI in the total hip arthroplasty. The preven-tion of these infections can not only be centred incosts reduction but also in patient’s suffering reduction.The additional use of antibiotic-impregnated (AP+ABC), compared with only antibiotic prophylaxis(AP), would prevent 46 deep SSI and save $3,909 foreach QALY gained, leading to cost savings. Using anti-biotic cement in addition to antibiotic prophylaxis (AP+ ABC) would generate an extra 32 QALYs while sav-ing over AUD $123,000. Not using AP would increasecosts by approximately $1.5 million with a 163 QALYslost. Using laminar air operating rooms (AP+ LOR)would increase costs by approximately $4.6 million,and 127 QALYs are lost. If all hospitals adopted theantibiotic-impregnated cement strategy (AP+ ABC),besides improving health outcomes among hospital-ized patients and save lives, they could save manyresources that could be used in other areas in need.

Conclusion

Quantifying the exact economic impact of HAI is anongoing international challenge and the use of thedirect hospitalization costs has been suggested as thebest method to estimate the direct HAI’s costs. Theserepresent the real costs to the hospital for the items

and services used by each patient and have a directimpact on hospital budget.

This study has some limitations, mainly related withthe difficulties to obtain articles related with HAI costanalysis from databases, and limited access to costinformation (e.g. no cost discrimination).

In the majority of the articles reviewed in this study,the cost analyses of HAI, more specifically about hipand knee arthroplasties infections, focus primarily ondirect hospitalization costs. The LOS was the mostcommonly used indicator to estimate the direct costsof these SSIs in the reviewed articles. By using this indi-cator, evidence suggests that patients who developedHAI remained in hospital 2.5–3 times longer andincurred hospital costs almost three times higher,when compared with an uninfected patient who under-went the same surgical procedures. However, this indi-cator is restricted to the direct medical costs, and doesnot include information with regard to the real cost topatients and society in lost earnings (indirect costs).

The measurement of indirect cost is indeed a funda-mental healthcare management challenge as there ishigh degree of difficult to account for exact cost and,generally, these are assumed to be much higher thandirect costs. Thus, evidence gathered in this articleallows us to argue that the cost analysis of HAI per-formed in international studies has been continuouslyunderestimating real economic impacts of HAI in hipand knee arthroplasties. This key idea can no longerbe ignored by healthcare managers and decisionmakers and further research must be done to explorebetter these issues.

Table 4. Cost of strategies to prevent infection.Authors Study description Strategies Costs QALY* Savings per QALY*

Merolliniet al. [42]

At this study, the researchers simulated long-term health and cost outcomes of ahypothetical cohort of 30,000 patientsundergoing total hip arthroplasty.Baseline use of AP was compared with no AP,antibiotic-impregnated cement (AP + ABC),and laminar air operating rooms (AP + LOR).

AP vs. noAP

No AP wouldincrease costs byabout $1.5 millionAU

No AP would lose163 QALYs.

–

AP vs. (AP+ ABC)

(AP + ABC) wouldsave about $126000 AU

(AP + ABC) wouldgenerate anextra 32 QALYs

The use of (AP + ABC) wouldprevent 46 deep infectionsand would save $3,909 AUper QALY gained

AP vs. (AP+ LOR)

(AP + LOR) wouldincrease costs byabout $4.6 millionAU

(AP + LOR) wouldlose 127 QALYs.

–

*QALY – quality-adjusted life years.

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