RESEARCH ARTICLE For reprint orders, please contact: [email protected]
Resource-saving advice from an infectious diseases specialist team in a large university hospital: an exportable model? Massimo Fantoni1, Rita Murri*,1, Giancarlo Scoppettuolo1, Massimiliano Fabbiani1, Giulio Ventura1, Raffaella Losito1, Filippo Berloco1, Teresa Spanu1, Maurizio Sanguinetti1 & Roberto Cauda1
ABSTRACT Aim: To assess epidemiological features of patients for which a consultation by the infectious diseases consultation team was required, and the rate of clinical advice that led to resource-saving advice (R-SA): discontinuation of inappropriate therapy or prophylaxis, de-escalation and switch from parenteral to oral therapy. Materials & methods: An infectious diseases consultation team was implemented in a 1100-bed university hospital in Italy. Results: The most frequent infections for which an infectious diseases consultancy was required were pneumonia, bloodstream infections (17% by Candida) and urinary tract infections. In 828 patients (41.4%), interventions with the possibility of R-SA were suggested. Conclusion: Resource-saving advices were possible in 41% of cases. Recent surgery, having a central venous catheter, bloodstream, abdominal, surgical site or bone and joint infections were correlated to a higher probability of receiving R-SA. Earlier diagnosis and optimized treatment of infectious diseases (IDs) have been largely associated to an improved survival and favorable outcomes [1–3] . Several studies showed that antibiotic stewardship programs led to overall cost savings, decreased use of inappropriate antibiotics, reduced length of hospital stay and reduced antibiotic resistance while optimizing clinical outcomes [4–6] . However, the majority of these studies were done on very ill patients admitted to intensive care units. The magnitude of interventions leading to saving resources and the clinical situations for which ID consultation can be done in hospitalized patients not admitted in intensive care units are not completely clear. This study was conducted to describe the epidemiological features of patients for which a consultation by the ID specialist team was required. As an indirect description of the antibiotic stewardship activity, we measured the rate of clinical advice that led to resource-saving interventions, and, particularly, the advice that contributed to limit antibiotic overuse.
KEYWORDS
• antibiotic stewardship • bloodstream infections • infectious diseases
Materials & methods An inpatient infectious diseases consultation team (IDCT) was implemented in November 2012 in a 1100-bed university hospital in Rome, Italy (Policlinico A. Gemelli, Catholic University of Rome, Italy), with the goal of obtaining early diagnosis of infection and optimizing antibiotic treatment. The team is formed by four ID specialists entirely dedicated to this activity. Consultations were performed only by specialists. Using the computerized information system of the hospital, any physician of medical and surgical units can request an ID consultation that is performed by the IDCT within 24 h. A meeting of the team is scheduled daily to discuss controversial or complex Institute of Infectious Diseases, Risk Management Unit, Institute of Microbiology, Catholic University of Rome, Rome, Italy *Author for correspondence: Tel.: +39 0630154945; Fax: +39 063054519; [email protected] 1
10.2217/FMB.14.99 © 2015 Future Medicine Ltd
Future Microbiol. (2015) 10(1), 15–20
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ISSN 1746-0913
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Research Article Fantoni, Murri, Scoppettuolo et al. Table 1. Epidemiological and clinical characteristics of patients (n = 2000 patients). Variables
Patients (n)
Patients (%)
Gender
Male Female
1097 902
54.8 45.2
680 676 130 445 269 313/1867
34.0 33.8 6.5 22.2 13.4 16.8
231 69 612 204 198 330 433 72
11.5 3.4 30.6 10.2 9.9 16.5 21.6 3.6
Risk factor for nosocomial infections Recent surgery in the previous 90 days Hospitalized or admitted in LTCF in the previous 90 days Admission in ICU in the previous 30 days Antibiotic therapy in the previous 30 days Bed-ridden Central venous catheter† Comorbidities Diabetes Liver failure/cirrosis Cardiovascular diseases Renal failure Chronic respiratory diseases Dementia/neurological impairment Neoplasms Obesity
Percentage was calculated excluding patients for which data were missing. The total number for which data on central venous catheter were available was 1867. ICU: Intensive care unit; LTCF: Long-term care facilities. †
clinical cases. The microbiological results are regularly discussed with microbiologists, the management issues with clinical pharmacists and the risk management team. In a survey on prevalence of healthcare-associated infections done in November 2013 at Gemelli Hospital, an ID consultation by the IDCT was required in 85% of the cases (data not published). At the time of survey, when excluding the 60 patients with a healthcare-associated infection, 235 out of 845 admitted patients (27.8%) were taking at least one antibiotic. The following data for every consultation were prospectively collected by the team using a standardized database: patient features including age, comorbidities, risk factors for infection, site of infection, healthcare-associated infection microbiological results, antibiotic therapy course and major advices supplied by the IDCT team to the requesting physician. Healthcare-associated infections were classified according to the CDC definition [7] . A multidrug-resistant (MDR) pathogen was defined when it was resistant to more than three classes of antibiotics. We assessed the rate of cases in which the following advices were given: discontinuation of inappropriate therapy or prophylaxis,
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Future Microbiol. (2015) 10(1)
de-escalation from a broad spectrum antibiotic to a narrower one (i.e., from echinocandin to fluconazole in bloodstream infections due to fluconazole-susceptible Candida) and switch from parenteral to oral therapy. This is advice that can lead to a resource saving and to lower pharmacologic pressure on resistant bacteria or fungi strains. Consultations for which no antibiotic therapy was prescribed were also registered. An evaluation of the accuracy of our advice was not done. ●●Statistical analysis
Data analysis was performed using the SPSS software, version 17 (SPSS). Chi-square and Student’s t-test were used for statistical analysis. Odds ratio and 95% CI were used to estimate the association between saving resource advices and their possible determinants. Multiple logistic regression analysis was used to adjust odds ratio on possible confounding variables. A two-sided p < 0.05 was considered statistically significant. Results Demographic characteristics, comorbidities and possible risk factors for healthcare-associated infections of the first 2000 patients included in the cohort (from November 2012 to September 2013) are shown in Table 1.
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R-SA from an IDCT in a large university hospital The most frequent infections seen in the first 2000 patients for which an ID consultancy was required were pneumonia, bloodstream infections and urinary tract infections (Table 2) . We observed 486 cases of sepsis. Of these, 379 were bloodstream infections. In 107 cases, a bloodstream infection was suspected but blood cultures were negative and the cases were excluded from the analysis. The most frequently isolated pathogens were shown in Table 3. Seventeen percent of BSIs were caused by Candida, of these 58.7% were non-albicans. We observed 54 Clostridium difficile infections. For 4.4% of patients, fever of unknown origin with no further definitive diagnosis was the reason of the consultation request. In 445 patients (22.25%), at least one resource-saving advice (R-SA) was done either at first consultation or during the follow-up. Of these, in 225 patients (27.2%) inappropriate antibiotic therapy or prophylaxis was discontinued, in 153 patients (18.5%) antibiotic therapy was de-escalated and in 195 patients (23.5%) a parenteral-to-oral therapy switch was done. In 383 patients (19.1% of the study population), it was suggested not to prescribe antibiotic therapy. Overall, in 828 patients (41.4%), interventions with the possibility of saving resources were suggested. In Table 4, conditions in which an R-SA was more frequently performed are shown. In a recent surgery, having a central venous catheter, bloodstream, abdominal, surgical site or osteomyelitis and joint infections were correlated to a higher probability of receiving an R-SA. According to published data, a switch to oral therapy leads to saving between US$50 and US$300 [8–10] or between 1 and 3 days of hospital stay (corresponding to a cost of €800–3000) while a de-escalation leads to save around
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€250 [11] . Therefore, we estimated a crude saving of €22,250–445,000 due to the R-SA in our population during the study period. Crude mortality of the admitted patients in 2012 (2.3%) did not vary after the implementation of the ID consultation team (in 2013 [2.2%]). Discussion In a large tertiary hospital, ID consultations are requested with a high frequency even in nonintensive care units. The IDCT performed R-SA in over 22% of patients. In an additional 19% of patients for which a consultation was requested, it was suggested not to prescribe any antibiotic therapy. R-SAs were more frequently applied in patients with bloodstream, abdominal, bone and joint or surgical site infections. Several papers are published on the positive impact of the ID consultant on clinical and economical outcomes [6,12–17] . The factor that has been found to explain the better clinical outcomes related to an ID consultation is the appropriateness of antibiotic therapy. In fact, antibiotic use, especially when suboptimally prescribed, can be the cause and not only the cure of healthcare-associated infections [18] . Thus, saving useless antibiotic therapy is a mainstream in the context of antibiotic stewardship. Most of the studies on the favorable impact of ID consultation were done in intensive care units where, in more than half of the consultations, a change or withdrawal of antibiotic therapy was suggested [17,19] . Few investigations have analyzed the impact of ID consultation for hospitalized patients out of intensive care units. The magnitude of interventions leading to saving resources and the clinical situations for which ID consultation can be done in hospitalized patients
Table 2. Most frequent infections for requiring an infectious disease team consultation. Infections
Patients (n)
Patients (%)
Infections due to MDRs, n (%)
BSI CVC-related BSI Pneumonia UTI Abdominal infections Bone and joint infections SSI Clostridium difficile infection
264 115 491 289 154 73
13.2 5.75 24.5 14.5 7.7 3.6
66 (25) 67 (58.3) – 94 (32.5) 41 (26.6) 18 (24.7)
78 54
3.9< 2.7
32 (41.0) –
BSI: Bloodstream infection; CVC: Central venous catheter; MDR: Multidrug-resistant pathogen; SSI: Surgical site infection; UTI: Urinary tract infection.
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Research Article Fantoni, Murri, Scoppettuolo et al. Table 3. Most frequently isolated pathogens causing bloodstream infections. Etiologic agents
Patients (n)
Patients (%)
Coagulase-negative staphylococci Escherichia coli Fungi Staphylococcus aureus Klebsiella spp. Enterococcus faecalis Streptococci Pseudomonas spp. Enterobacter spp. Enterococcus faecium Polymicrobic Total
104 72 63 48 42 29 23 18 11 9 66 379
27.4 19.0 16.6 12.6 11.1 7.6 6.1 4.7 2.9 2.4 17.4
are not completely defined. We demonstrated that in a large proportion of patients hospitalized in nonintensive care units, an optimization of antibiotic therapy was feasible and led to a considerable cost of saving while mortality rate did not change. It is important to note that the implementation of the strategy that we considered in the analysis of the present study, the socalled R-SAs, can be applied in many hospital settings without investing extra budget. The introduction of faster diagnostic technologies, such as the next-generation sequencing methods and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) or ‘next-generation sequencing’ [20,21] as well as biomarkers such as procalcitonin or β-glucan [22,23] , have largely improved
the sensitivity, accuracy and speed of infectious diseases diagnosis. A definitive diagnosis is crucial for a successful antibiotic prescription. According to our study, bloodstream, abdominal, bone and joint and surgical site infections can be a fruitful area for stewardship interventions in hospitalized patients. Resource-saving interventions are also useful to reduce the patient exposure to broad-spectrum antibiotic and the risk of selecting antibiotic-resistant isolates. [24– 26] . In order to reduce the risk of development of antibiotic resistance and C. difficile infections, a bundle for prescribing antibiotics in acute care was proposed in 2007 and largely accepted [27] . Among others, the main bundle for the followup of patients is to consider de-escalation, parenteral-to-oral conversion or discontinuation
Table 4. Factors correlated to resource-saving advice. Factors
Recent surgery Central venous catheter Bloodstream infection Abdominal infection Bone and joint infection Surgical site infection
Discontinuation of inappropriate antibiotic therapy or prophylaxis
De-escalation
Switch to oral therapy
Any resource-saving advice
Unadj. risk, OR (95% CI)
Adj. risk, OR (95% CI)
Unadj. risk, OR (95% CI)
Adj. risk, OR (95% CI)
Unadj. risk, OR (95% CI)
Adj. risk, OR (95% CI)
Unadj. risk, OR (95% CI)
Adj. risk, OR (95% CI)
1.93 (1.46–2.56) 1.49 (1.06–2.09)
1.82 (1.35–2.45) 1.36 (0.94–1.96)
2.48 (1.78–3.46) 2.81 (1.96–4.01)
2.20 (1.54–3.14) 1.61 (1.09–2.38)
1.68 (1.25–2.27) 0.70 (0.45–1.08)
1.42 (1.03–1.97) 0.69 (0.44–1.10)
2.12 (1.73–2.61) 1.51 (1.17–1.95)
1.85 (1.49–2.31) 1.21 (0.92–1.59)
1.11 (0.81–1.53) 1.61 (1.02–2.53) 0.33 (0.10–1.06) 1.63 (0.88–3.00)
1.00 (0.71–1.41) 1.29 (0.81–2.06) 0.33 (0.10–1.08) 1.18 (0.62–2-24)
4.27 (3.05–5.98) 1.80 (1.08–2.99) 1.29 (0.58–2.87) 1.20 (0.54–2.65)
3.94 (2.73–5.70) 1.77 (1.02–3.05) 1.74 (0.76–3.99) 1.27 (0.55–2.93)
0.87 (0.61–1.25) 1.42 (0.87–2.33) 5.02 (3.01–8.39) 2.95 (1.71–5.11)
1.08 (0.74–1.58) 1.48 (0.88–2.48) 5.35 (3.16–9.03) 2.82 (1.57–5.07)
1.63 (1.30–2.04) 1.48 (1.04–2.11) 2-09 (1.30–3.37) 2.60 (1.65–4.11)
1.65 (1.29–2.10) 1.34 (0.93–1.94) 2.32 (1.42–3.78) 2.21 (1.37–3.57)
Adj.: Adjusted; OR: Odds ratio; Unadj.: Unadjusted.
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R-SA from an IDCT in a large university hospital of antibiotic therapy based on clinical signs and symptoms and laboratory test results on a daily basis. The same bundle is one of the main recommendations of the IDSA guidelines for developing an institutional program to enhance antimicrobial stewardship [28] . According to the results of the present study, R-SAs were more frequently done in people with bloodstream infection or recent surgery. Diagnosis of bloodstream infection implies the acknowledgment of the causing agent and the relative antibiogram. The availability of an IDCT can be particularly useful in identifying and applying a de-escalation. Patients with recent surgery or abdominal infection were, more frequently than other clinical conditions, discontinued from inappropriate therapy. This could be due to an overtreatment with antibiotic therapy close to surgical intervention. Results from the present study did not show a correlation between R-SA and urinary tract infections. In our opinion, this is possibly due to the fact that antibiotic therapy is initially prescribed on the basis of urine cultures and antibiogram. Due to the real-world design of the study, a control group (patients for which an ID consultation was not available in the same setting) was absent. However, we believe that the feasibility of R-SA is high. Moreover, since this is a monocentric study, generalizability of the results could be confirmed in different contexts.
achieve cost savings. We think that guidelines and internal protocols alone are not sufficient to realize these objectives for hospitals. Qualified ID specialists working in a team are in the best position to perform resource saving interventions while keeping good clinical outcomes.
Conclusion In conclusion, our results demonstrate that in a high number of patients hospitalized in nonintensive care units, an ID consultation is useful to limit the overuse of antibiotic therapy. This is a critical issue to reduce drug-related adverse events, the selection of antibiotic-resistant isolates and to
Ethical conduct of research
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Future perspective The present study demonstrated that an antibiotic stewardship is feasible even in a large hospital. We think that, in the future, the role of the ID will be greatly represented in multidisciplinary consultation teams with the aim to optimize the indications and management of antibiotics in infectious diseases of hospitalized patients. Acknowledgements We are grateful to Leonida Passeri for his technical assistance in data management.
Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. The present manuscript was revised by San Francisco Edit. This writing assistance was supported with internal funds.
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.
EXECUTIVE SUMMARY ●●
Saving useless antibiotic therapy is a mainstream in the context of antibiotic stewardship.
●●
Infectious disease (ID) consultations are requested with a high frequency even in nonintensive care units
●●
Resource-saving advice was performed by the ID team in over 22% of patients.
●●
Resource-saving advice was more frequently applied in patients with bloodstream, abdominal, bone and joint or surgical site infections.
●●
Even in a large hospital, in nonintensive care units, an optimization of antibiotic therapy was feasible and led to a considerable cost saving while mortality rate did not change.
●●
Qualified ID specialists working in a team are in the best position to perform resource saving interventions while keeping good clinical outcomes.
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Research Article Fantoni, Murri, Scoppettuolo et al. step-down therapy: converting patients from intravenous ceftriaxone to oral cefpodoxime proxetil. Ann. Pharmacother. 2(9), 561–565 (1995).
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Schramm GE, Johnson JA, Doherty JA et al. Methicillin-resistant Staphylococcus aureus sterile-site infection: the importance of appropriate initial antimicrobial treatment. Crit. Care Med. 3(4), 2069–2074 (2006). Tumbarello M, Sali M, Trecarichi EM et al. Bloodstream infections caused by extendedspectrum-beta-lactamase-producing Escherichia coli: risk factors for inadequate initial antimicrobial therapy. Antimicrob. Agents Chemother. 5(2), 3244–3452 (2008). A real-world demonstration of the crucial role of of the timing of antibiotic therapy. Rayner CR, Forrest A, Meagher AK, Birmingham MC, Schentag JJ. Clinical pharmacodynamics of linezolid in seriously ill patients treated in a compassionate use programme. Clin. Pharmacokinet. 4(2), 1411–1423 (2003). Pulcini C, Botelho-Nevers E, Dyar OJ, Harbarth S. The impact of infectious diseases specialists on antibiotic prescribing in hospitals. Clin. Microbiol. Infect. doi:10.1111/1469-0691 (2014) (Epub ahead of print).
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Pharmacoeconomic considerations associated with the use of intravenous-to-oral moxifloxacin for community-acquired pneumonia. Clin. Infect. Dis. 41(Suppl. 2), S136–S143 (2005). 11 Shine N, Kosaka T, Fujita N. De-escalation of
antimicrobial therapy for bacteremia due to difficult-to-treat Gram negative bacilli. Infection 4(1), 203–210 (2013). •
Goff DA, Bauer EE, Stevenson KB et al. Is the “low-hanging fruit” worth picking for antimicrobial stewardship programs? Clin. Infect. Dis. 5(5), 587–559 (2012).
•• The authors suggested to select the most obtainable targets (intravenous-to-oral conversions, batching of intravenous antimicrobials, therapeutic substitutions and formulary restriction) rather than confronting more complicated management issues. 6
•
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Schmitt S, McQuillen D, Nahass R et al. Infectious diseases specialty intervention is associated with decreased mortality and lower healthcare costs. Clin. Infect. Dis. 58, 22–28 (2014). A recently published study on a large population demonstrating better clinical outcomes and reduced costs for patients for which an ID intervention was performed. Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections, 1988. Am. J. Infect. Control 1(6), 128–140 (1988). www.cdc.gov/nhsn/pdfs Hendrickson JR, North DS. Pharmacoeconomic benefit of antibiotic
An interesting article on saving resources associated with de-escalation.
12 Vehreschild JJ, Morgen G, Cornely OA et al.
Evaluation of an infectious disease consultation programme in a German tertiary care hospital. Infection 4(1), 1121–1128 (2013). 13 Boyles TH, Whitelaw A, Bamford C et al.
Antibiotic stewardship ward rounds and a dedicated prescription chart reduce antibiotic consumption and pharmacy costs without affecting inpatient mortality or re-admission rates. PLoS ONE 8, e79747 (2013).
•• A very recently published review on the impact of infectious diseases specialists on quality and quantity of antibiotic use in acute care hospitals. 5
Lau BD, Pinto BL, Thiemann DR, Lehmann CU. Budget impact analysis of conversion from intravenous to oral medication when clinically eligible for oral intake. Clin. Ther. 3(3), 1792–1796 (2011).
•
An intervention study (antibiotic prescription chart use and weekly antibiotic stewardship ward rounds) demonstrating a significant decrease in antibiotic consumption.
14 Honda H, Krauss MJ, Jones JC, Olsen MA,
Warren DK. The value of infectious diseases consultation in Staphylococcus aureus bacteremia. Am. J. Med. 12(3), 631–637 (2010). 15 Robinson JO, Pozzi‐Langhi S, Phillips M
et al. Formal infectious diseases consultation is associated with decreased mortality in Staphyloccus aureus bacteraemia. Eur. J. Clin. Microbiol. Infect. Dis. 3(1), 2421–2428 (2012). 16 Jenkins T, Price C, Sabel A, Mehler P,
Burman W. Impact of routine infectious diseases services consultation on the evaluation, management, and outcomes of Staphylococcus aureus bacteremia. Clin. Infect. Dis. 4(6), 1000–1008 (2008). 17 Kaki R, Elligsen M, Walker S et al. Impact of
antimicrobial stewardship in critical care: a systematic review. J. Antimicrob. Chemother. 6(6), 1223–1230 (2011).
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•• A systematic review on antibiotic stewardship suggesting that this approach improves the antimicrobial prescription appropriateness without compromising clinical outcomes. 18 Gould IM. Controversies in infection:
infection control or antibiotic stewardship to control healthcare-acquired infection? J. Hosp. Infect. 7(3), 386–391 (2009). 19 Pulcini C, Pradier C, Samat-Long C et al.
Factors associated with adherence to infectious diseases advice in two intensive care units. J. Antimicrob. Chemother. 5(7), 546–550 (2006). 20 Mardis ER. A decade’s perspective on DNA
sequencing technology. Nature 47, 198–203 (2011). 21 Didelot X, Bowden R, Wilson DJ et al.
Transforming clinical microbiology with bacterial genome sequencing. Nat. Rev. Genet. 1(3), 601–612 (2012). 22 Wacker C, Prkno A, Brunkhorst FM,
Schlattmann P. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect. Dis. 1(3), 426–435 (2013). 23 O’Brien DJ, Gould IM. Maximizing the
impact of antimicrobial stewardship: the role of diagnostics, national and international efforts. Curr. Opin. Infect. Dis. 2(6), 352–358 (2013). 24 Gaynes R. The impact of antimicrobial use
on the emergence of antimicrobial-resistant bacteria in hospitals. Infect. Dis. Clin. North Am. 1(1), 757–765 (1997). 25 Dancer SJ. The effect of antibiotics on
methicillin-resistant Staphylococcus aureus. J. Antimicrob. Chemother. 6(1), 246–253 (2008). 26 Tacconelli E. Does antibiotic exposure
increase the risk of methicillin-resistant Staphylococcus aureus (MRSA) isolation? A systematic review and meta-analysis. J. Antimicrob. Chemother. 6(1), 26–38 (2008). 27 Cooke FJ, Holmes AH. The missing care
bundle: antibiotic prescribing in hospitals. Int. J. Antimicrob. Agents 3, 25–29 (2007). 28 Dellit TH, Owens RC, McGowan JE Jr et al.
Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin. Infect. Dis. 44, 159–77 (2007). •• The most important document on antibiotic stewardship, a comprehensive paper on the definition and details of optimization of antibiotic therapy.
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Resource-saving advice from an infectious diseases specialist team in a large university hospital: an exportable model? Massimo Fantoni1, Rita Murri*,1, Giancarlo Scoppettuolo1, Massimiliano Fabbiani1, Giulio Ventura1, Raffaella Losito1, Filippo Berloco1, Teresa Spanu1, Maurizio Sanguinetti1 & Roberto Cauda1
ABSTRACT Aim: To assess epidemiological features of patients for which a consultation by the infectious diseases consultation team was required, and the rate of clinical advice that led to resource-saving advice (R-SA): discontinuation of inappropriate therapy or prophylaxis, de-escalation and switch from parenteral to oral therapy. Materials & methods: An infectious diseases consultation team was implemented in a 1100-bed university hospital in Italy. Results: The most frequent infections for which an infectious diseases consultancy was required were pneumonia, bloodstream infections (17% by Candida) and urinary tract infections. In 828 patients (41.4%), interventions with the possibility of R-SA were suggested. Conclusion: Resource-saving advices were possible in 41% of cases. Recent surgery, having a central venous catheter, bloodstream, abdominal, surgical site or bone and joint infections were correlated to a higher probability of receiving R-SA. Earlier diagnosis and optimized treatment of infectious diseases (IDs) have been largely associated to an improved survival and favorable outcomes [1–3] . Several studies showed that antibiotic stewardship programs led to overall cost savings, decreased use of inappropriate antibiotics, reduced length of hospital stay and reduced antibiotic resistance while optimizing clinical outcomes [4–6] . However, the majority of these studies were done on very ill patients admitted to intensive care units. The magnitude of interventions leading to saving resources and the clinical situations for which ID consultation can be done in hospitalized patients not admitted in intensive care units are not completely clear. This study was conducted to describe the epidemiological features of patients for which a consultation by the ID specialist team was required. As an indirect description of the antibiotic stewardship activity, we measured the rate of clinical advice that led to resource-saving interventions, and, particularly, the advice that contributed to limit antibiotic overuse.
KEYWORDS
• antibiotic stewardship • bloodstream infections • infectious diseases
Materials & methods An inpatient infectious diseases consultation team (IDCT) was implemented in November 2012 in a 1100-bed university hospital in Rome, Italy (Policlinico A. Gemelli, Catholic University of Rome, Italy), with the goal of obtaining early diagnosis of infection and optimizing antibiotic treatment. The team is formed by four ID specialists entirely dedicated to this activity. Consultations were performed only by specialists. Using the computerized information system of the hospital, any physician of medical and surgical units can request an ID consultation that is performed by the IDCT within 24 h. A meeting of the team is scheduled daily to discuss controversial or complex Institute of Infectious Diseases, Risk Management Unit, Institute of Microbiology, Catholic University of Rome, Rome, Italy *Author for correspondence: Tel.: +39 0630154945; Fax: +39 063054519; [email protected] 1
10.2217/FMB.14.99 © 2015 Future Medicine Ltd
Future Microbiol. (2015) 10(1), 15–20
part of
ISSN 1746-0913
15
Research Article Fantoni, Murri, Scoppettuolo et al. Table 1. Epidemiological and clinical characteristics of patients (n = 2000 patients). Variables
Patients (n)
Patients (%)
Gender
Male Female
1097 902
54.8 45.2
680 676 130 445 269 313/1867
34.0 33.8 6.5 22.2 13.4 16.8
231 69 612 204 198 330 433 72
11.5 3.4 30.6 10.2 9.9 16.5 21.6 3.6
Risk factor for nosocomial infections Recent surgery in the previous 90 days Hospitalized or admitted in LTCF in the previous 90 days Admission in ICU in the previous 30 days Antibiotic therapy in the previous 30 days Bed-ridden Central venous catheter† Comorbidities Diabetes Liver failure/cirrosis Cardiovascular diseases Renal failure Chronic respiratory diseases Dementia/neurological impairment Neoplasms Obesity
Percentage was calculated excluding patients for which data were missing. The total number for which data on central venous catheter were available was 1867. ICU: Intensive care unit; LTCF: Long-term care facilities. †
clinical cases. The microbiological results are regularly discussed with microbiologists, the management issues with clinical pharmacists and the risk management team. In a survey on prevalence of healthcare-associated infections done in November 2013 at Gemelli Hospital, an ID consultation by the IDCT was required in 85% of the cases (data not published). At the time of survey, when excluding the 60 patients with a healthcare-associated infection, 235 out of 845 admitted patients (27.8%) were taking at least one antibiotic. The following data for every consultation were prospectively collected by the team using a standardized database: patient features including age, comorbidities, risk factors for infection, site of infection, healthcare-associated infection microbiological results, antibiotic therapy course and major advices supplied by the IDCT team to the requesting physician. Healthcare-associated infections were classified according to the CDC definition [7] . A multidrug-resistant (MDR) pathogen was defined when it was resistant to more than three classes of antibiotics. We assessed the rate of cases in which the following advices were given: discontinuation of inappropriate therapy or prophylaxis,
16
Future Microbiol. (2015) 10(1)
de-escalation from a broad spectrum antibiotic to a narrower one (i.e., from echinocandin to fluconazole in bloodstream infections due to fluconazole-susceptible Candida) and switch from parenteral to oral therapy. This is advice that can lead to a resource saving and to lower pharmacologic pressure on resistant bacteria or fungi strains. Consultations for which no antibiotic therapy was prescribed were also registered. An evaluation of the accuracy of our advice was not done. ●●Statistical analysis
Data analysis was performed using the SPSS software, version 17 (SPSS). Chi-square and Student’s t-test were used for statistical analysis. Odds ratio and 95% CI were used to estimate the association between saving resource advices and their possible determinants. Multiple logistic regression analysis was used to adjust odds ratio on possible confounding variables. A two-sided p < 0.05 was considered statistically significant. Results Demographic characteristics, comorbidities and possible risk factors for healthcare-associated infections of the first 2000 patients included in the cohort (from November 2012 to September 2013) are shown in Table 1.
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R-SA from an IDCT in a large university hospital The most frequent infections seen in the first 2000 patients for which an ID consultancy was required were pneumonia, bloodstream infections and urinary tract infections (Table 2) . We observed 486 cases of sepsis. Of these, 379 were bloodstream infections. In 107 cases, a bloodstream infection was suspected but blood cultures were negative and the cases were excluded from the analysis. The most frequently isolated pathogens were shown in Table 3. Seventeen percent of BSIs were caused by Candida, of these 58.7% were non-albicans. We observed 54 Clostridium difficile infections. For 4.4% of patients, fever of unknown origin with no further definitive diagnosis was the reason of the consultation request. In 445 patients (22.25%), at least one resource-saving advice (R-SA) was done either at first consultation or during the follow-up. Of these, in 225 patients (27.2%) inappropriate antibiotic therapy or prophylaxis was discontinued, in 153 patients (18.5%) antibiotic therapy was de-escalated and in 195 patients (23.5%) a parenteral-to-oral therapy switch was done. In 383 patients (19.1% of the study population), it was suggested not to prescribe antibiotic therapy. Overall, in 828 patients (41.4%), interventions with the possibility of saving resources were suggested. In Table 4, conditions in which an R-SA was more frequently performed are shown. In a recent surgery, having a central venous catheter, bloodstream, abdominal, surgical site or osteomyelitis and joint infections were correlated to a higher probability of receiving an R-SA. According to published data, a switch to oral therapy leads to saving between US$50 and US$300 [8–10] or between 1 and 3 days of hospital stay (corresponding to a cost of €800–3000) while a de-escalation leads to save around
Research Article
€250 [11] . Therefore, we estimated a crude saving of €22,250–445,000 due to the R-SA in our population during the study period. Crude mortality of the admitted patients in 2012 (2.3%) did not vary after the implementation of the ID consultation team (in 2013 [2.2%]). Discussion In a large tertiary hospital, ID consultations are requested with a high frequency even in nonintensive care units. The IDCT performed R-SA in over 22% of patients. In an additional 19% of patients for which a consultation was requested, it was suggested not to prescribe any antibiotic therapy. R-SAs were more frequently applied in patients with bloodstream, abdominal, bone and joint or surgical site infections. Several papers are published on the positive impact of the ID consultant on clinical and economical outcomes [6,12–17] . The factor that has been found to explain the better clinical outcomes related to an ID consultation is the appropriateness of antibiotic therapy. In fact, antibiotic use, especially when suboptimally prescribed, can be the cause and not only the cure of healthcare-associated infections [18] . Thus, saving useless antibiotic therapy is a mainstream in the context of antibiotic stewardship. Most of the studies on the favorable impact of ID consultation were done in intensive care units where, in more than half of the consultations, a change or withdrawal of antibiotic therapy was suggested [17,19] . Few investigations have analyzed the impact of ID consultation for hospitalized patients out of intensive care units. The magnitude of interventions leading to saving resources and the clinical situations for which ID consultation can be done in hospitalized patients
Table 2. Most frequent infections for requiring an infectious disease team consultation. Infections
Patients (n)
Patients (%)
Infections due to MDRs, n (%)
BSI CVC-related BSI Pneumonia UTI Abdominal infections Bone and joint infections SSI Clostridium difficile infection
264 115 491 289 154 73
13.2 5.75 24.5 14.5 7.7 3.6
66 (25) 67 (58.3) – 94 (32.5) 41 (26.6) 18 (24.7)
78 54
3.9< 2.7
32 (41.0) –
BSI: Bloodstream infection; CVC: Central venous catheter; MDR: Multidrug-resistant pathogen; SSI: Surgical site infection; UTI: Urinary tract infection.
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Research Article Fantoni, Murri, Scoppettuolo et al. Table 3. Most frequently isolated pathogens causing bloodstream infections. Etiologic agents
Patients (n)
Patients (%)
Coagulase-negative staphylococci Escherichia coli Fungi Staphylococcus aureus Klebsiella spp. Enterococcus faecalis Streptococci Pseudomonas spp. Enterobacter spp. Enterococcus faecium Polymicrobic Total
104 72 63 48 42 29 23 18 11 9 66 379
27.4 19.0 16.6 12.6 11.1 7.6 6.1 4.7 2.9 2.4 17.4
are not completely defined. We demonstrated that in a large proportion of patients hospitalized in nonintensive care units, an optimization of antibiotic therapy was feasible and led to a considerable cost of saving while mortality rate did not change. It is important to note that the implementation of the strategy that we considered in the analysis of the present study, the socalled R-SAs, can be applied in many hospital settings without investing extra budget. The introduction of faster diagnostic technologies, such as the next-generation sequencing methods and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) or ‘next-generation sequencing’ [20,21] as well as biomarkers such as procalcitonin or β-glucan [22,23] , have largely improved
the sensitivity, accuracy and speed of infectious diseases diagnosis. A definitive diagnosis is crucial for a successful antibiotic prescription. According to our study, bloodstream, abdominal, bone and joint and surgical site infections can be a fruitful area for stewardship interventions in hospitalized patients. Resource-saving interventions are also useful to reduce the patient exposure to broad-spectrum antibiotic and the risk of selecting antibiotic-resistant isolates. [24– 26] . In order to reduce the risk of development of antibiotic resistance and C. difficile infections, a bundle for prescribing antibiotics in acute care was proposed in 2007 and largely accepted [27] . Among others, the main bundle for the followup of patients is to consider de-escalation, parenteral-to-oral conversion or discontinuation
Table 4. Factors correlated to resource-saving advice. Factors
Recent surgery Central venous catheter Bloodstream infection Abdominal infection Bone and joint infection Surgical site infection
Discontinuation of inappropriate antibiotic therapy or prophylaxis
De-escalation
Switch to oral therapy
Any resource-saving advice
Unadj. risk, OR (95% CI)
Adj. risk, OR (95% CI)
Unadj. risk, OR (95% CI)
Adj. risk, OR (95% CI)
Unadj. risk, OR (95% CI)
Adj. risk, OR (95% CI)
Unadj. risk, OR (95% CI)
Adj. risk, OR (95% CI)
1.93 (1.46–2.56) 1.49 (1.06–2.09)
1.82 (1.35–2.45) 1.36 (0.94–1.96)
2.48 (1.78–3.46) 2.81 (1.96–4.01)
2.20 (1.54–3.14) 1.61 (1.09–2.38)
1.68 (1.25–2.27) 0.70 (0.45–1.08)
1.42 (1.03–1.97) 0.69 (0.44–1.10)
2.12 (1.73–2.61) 1.51 (1.17–1.95)
1.85 (1.49–2.31) 1.21 (0.92–1.59)
1.11 (0.81–1.53) 1.61 (1.02–2.53) 0.33 (0.10–1.06) 1.63 (0.88–3.00)
1.00 (0.71–1.41) 1.29 (0.81–2.06) 0.33 (0.10–1.08) 1.18 (0.62–2-24)
4.27 (3.05–5.98) 1.80 (1.08–2.99) 1.29 (0.58–2.87) 1.20 (0.54–2.65)
3.94 (2.73–5.70) 1.77 (1.02–3.05) 1.74 (0.76–3.99) 1.27 (0.55–2.93)
0.87 (0.61–1.25) 1.42 (0.87–2.33) 5.02 (3.01–8.39) 2.95 (1.71–5.11)
1.08 (0.74–1.58) 1.48 (0.88–2.48) 5.35 (3.16–9.03) 2.82 (1.57–5.07)
1.63 (1.30–2.04) 1.48 (1.04–2.11) 2-09 (1.30–3.37) 2.60 (1.65–4.11)
1.65 (1.29–2.10) 1.34 (0.93–1.94) 2.32 (1.42–3.78) 2.21 (1.37–3.57)
Adj.: Adjusted; OR: Odds ratio; Unadj.: Unadjusted.
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Future Microbiol. (2015) 10(1)
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R-SA from an IDCT in a large university hospital of antibiotic therapy based on clinical signs and symptoms and laboratory test results on a daily basis. The same bundle is one of the main recommendations of the IDSA guidelines for developing an institutional program to enhance antimicrobial stewardship [28] . According to the results of the present study, R-SAs were more frequently done in people with bloodstream infection or recent surgery. Diagnosis of bloodstream infection implies the acknowledgment of the causing agent and the relative antibiogram. The availability of an IDCT can be particularly useful in identifying and applying a de-escalation. Patients with recent surgery or abdominal infection were, more frequently than other clinical conditions, discontinued from inappropriate therapy. This could be due to an overtreatment with antibiotic therapy close to surgical intervention. Results from the present study did not show a correlation between R-SA and urinary tract infections. In our opinion, this is possibly due to the fact that antibiotic therapy is initially prescribed on the basis of urine cultures and antibiogram. Due to the real-world design of the study, a control group (patients for which an ID consultation was not available in the same setting) was absent. However, we believe that the feasibility of R-SA is high. Moreover, since this is a monocentric study, generalizability of the results could be confirmed in different contexts.
achieve cost savings. We think that guidelines and internal protocols alone are not sufficient to realize these objectives for hospitals. Qualified ID specialists working in a team are in the best position to perform resource saving interventions while keeping good clinical outcomes.
Conclusion In conclusion, our results demonstrate that in a high number of patients hospitalized in nonintensive care units, an ID consultation is useful to limit the overuse of antibiotic therapy. This is a critical issue to reduce drug-related adverse events, the selection of antibiotic-resistant isolates and to
Ethical conduct of research
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Future perspective The present study demonstrated that an antibiotic stewardship is feasible even in a large hospital. We think that, in the future, the role of the ID will be greatly represented in multidisciplinary consultation teams with the aim to optimize the indications and management of antibiotics in infectious diseases of hospitalized patients. Acknowledgements We are grateful to Leonida Passeri for his technical assistance in data management.
Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. The present manuscript was revised by San Francisco Edit. This writing assistance was supported with internal funds.
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.
EXECUTIVE SUMMARY ●●
Saving useless antibiotic therapy is a mainstream in the context of antibiotic stewardship.
●●
Infectious disease (ID) consultations are requested with a high frequency even in nonintensive care units
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Resource-saving advice was performed by the ID team in over 22% of patients.
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Resource-saving advice was more frequently applied in patients with bloodstream, abdominal, bone and joint or surgical site infections.
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Even in a large hospital, in nonintensive care units, an optimization of antibiotic therapy was feasible and led to a considerable cost saving while mortality rate did not change.
●●
Qualified ID specialists working in a team are in the best position to perform resource saving interventions while keeping good clinical outcomes.
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Research Article Fantoni, Murri, Scoppettuolo et al. step-down therapy: converting patients from intravenous ceftriaxone to oral cefpodoxime proxetil. Ann. Pharmacother. 2(9), 561–565 (1995).
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