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Cost-effectiveness of 30- compared to 20-milliliter blood cultures: a retrospective study 1 2

Anita Cheruvankya, Thomas J. Kirna,b, Melvin P. Weinsteina,b, # 3 Department of Medicinea and Department of Pathology and Laboratory Medicineb, 4 Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA 5

6 7 8 9 10 Running Head: Cost effectiveness of 30-ml blood cultures 11 12 13 14 #Address correspondence to Melvin P. Weinstein, [email protected]. 15 16 17 18 19 20 21 22

JCM Accepted Manuscript Posted Online 21 October 2015J. Clin. Microbiol. doi:10.1128/JCM.02024-15Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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Abstract 23 Background 24 The importance of blood culture volume for detection of bloodstream infections (BSIs) is 25 documented. Recently, improved diagnostic sensitivity was demonstrated for 30 vs. 20 26 ml blood cultures (BCs) in adults (4). Hospitals receive higher reimbursement for patients 27 with documented septicemia. We determined the cost-effectiveness of 30 ml versus 20 ml 28 BCs using results from our institution and previously published data. 29 30 Materials and Methods 31 Positive BC results from 292 bacteremic episodes were reviewed. Costs of reagents, 32 equipment, phlebotomist and technologist time were determined. The Medical Records 33 Department provided Medicare reimbursement (MR) data for patients with selected ICD-34 9 codes. These data provided an estimate of the annualized increase in MR versus costs 35 associated with conversion to 30 ml BCs. 36 37 Results 38 MR for 464 annual primary BSIs was $24,808/episode. An expected 7.2% increase in 39 BSIs detected using 30 ml BCs would detect 34 additional cases annually and increase 40 MR by $843,472. Comparative MR data where septicemia complicated another diagnosis 41 were available for 4 ICD-9 codes: laparoscopic cholecystectomy, biliary tract disorders, 42 pneumonia, and cellulitis. Mean incremental MR was $9667 per episode, which projected 43 a $483,350 revenue increase annually. The annual cost associated with conversion to 30 44

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ml BCs was estimated to be $157,798. Thus, the potential net increase in hospital 45 revenue would be $1,169,031 for 30 ml vs. 20 ml BCs. 46 47 Conclusion 48 Our results suggest that conversion to 30 ml BCs may not only improve patient care by 49 detecting more BSIs but also substantially increase hospital revenue. 50 51 52 53 54 55 56 57 58 59 60 61 Introduction 62

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According to the CDC, sepsis affects more than 800,000 Americans annually and is the 63 ninth leading cause of disease-related deaths ( 2 ) . The Agency for Healthcare Research 64 and Quality lists sepsis as the most expensive condition treated in U.S. hospitals, costing 65 more than $20 billion in 2011( 2 ) . Blood culture (BC) remains the standard means of 66 detecting sepsis secondary to bloodstream infections (BSIs) (3). Prior studies have 67 shown that several variables influence the detection of bacteremia, including skin 68 preparation prior to venipuncture, the method and site of collection, the types of media 69 utilized, the number of cultures collected and, most importantly, the volume of blood 70 cultured (4). 71 All studies have indicated that as the volume of blood cultured increases, the likelihood 72 of detecting bacteremia also increases (5-9; 12, 15, 17-19). Patel et al. recently 73 demonstrated that two 30 ml BC sets with 3 bottles per set (2 aerobic and 1 anaerobic) 74 had improved pathogen detection for both non-conditional (not requiring detection in 75 more than one set to be considered positive) and conditional (requiring detection in at 76 least two positive blood cultures for classification as a pathogen and otherwise 77 categorized as a contaminant) pathogens with an improved yield of 7.9% and 11.0%, 78 respectively (4).. 79 However, , inoculation of only two 20-ml sets of BCs is standard practice in our 80 institution and we suspect at many other similar institutions (4). This practice is most 81 likely secondary to the notion that increasing the number of blood culture bottles per 82 episode of bacteremia will result in a significant increase in cost and inconvenience for 83 both the health care facility and the patient (21). 84

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85 The failure to obtain 30-ml of blood for each adult blood culture can result in lower 86 microbial recovery. Given the superior sensitivity of 30-ml BC sets compared to 20-ml 87 BC sets reported by Patel et al, we hypothesized that the institution of 30-ml BCs would 88 result in increased third party reimbursement for our hospital. Accordingly, we assessed 89 the costs and potential financial benefits associated with conversion from 20-ml to 30-ml 90 blood cultures in our institution. To our knowledge, this type of cost-benefit analysis has 91 not previously been reported. 92 93 94 95 96 97 98 99 100 101 102 MATERIALS AND METHODS 103

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Study Design. This study reviewed blood culture results from a retrospective cohort of 104 adult patients (≥18 years) from 1st January, 2012 to 1st March 2012 at Robert Wood 105 Johnson University Hospital (RWJUH) in New Brunswick, NJ. A blood culture (BC) 106 was defined as a set of two or three culture bottles which, when optimally filled with 107 blood, would have a total volume of 20-ml (2-bottle set) or 30-ml (3-bottle set).. 108 For each adult blood culture at RWJUH, twenty milliliters of blood was obtained 109 aseptically and equally distributed to one Bactec Plus Aerobic/F resin (hereafter referred 110 to as aerobic) bottle and one Bactec Lytic/10 Anaerobic/F (hereafter referred to as 111 anaerobic) bottle (Becton Dickinson, Sparks, MD) and incubated for 5 days in a 112 BACTEC FX instrument. This study was approved by the Rutgers Robert Wood Johnson 113 Medical School Institutional Review Board. 114 Microorganisms isolated from cultures were identified by standard techniques. Single 115 culture isolates of coagulase-negative staphylococci, diphtheroids and nonpneumococcal 116 alpha-hemolytic streptococci were classified as contaminants (4). However, in instances 117 where the same organism was isolated from 2 or more blood culture sets within a 48 hour 118 period, they were classified as true positives if they were the same species and had the 119 same biotype and antibiogram (13, 22). Pathogens not requiring two or more positive sets 120 to be classified as such (e.g., Staphylococcus aureus, Escherichia coli, Pseudomonas 121 aeruginosa) were also categorized as true positives (13, 22). 122 Most health care facilities including ours receive much of their reimbursement via 123 Medicare billing. In addition to Medicare, many other third party payers also reimburse 124 using a DRG based payment plan. Additionally, the ICD-9 codes – 125

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bacteremia/septicemia/severe sepsis - all fall under the same classification of Major 126 Complications and Comorbid Conditions (MCC) for determination of their DRG weights. 127 128 Calculations. Medicare reimbursement data based on RWJUH institutional rates were 129 obtained from the Medical Records and Accounts Receivable departments during the 130 study period for all patients with a primary DRG diagnosis of 131 bacteremia/septicemia/severe sepsis and for several common ICD-9 codes: laparoscopic 132 cholecystectomy with and without MCC; kidney urinary tract infections with and without 133 MCC; disorders of the biliary tract with and without MCC; simple pneumonia with and 134 without MCC; other respiratory system diagnoses with and without MCC; cellulitis with 135 and without MCC; major joint replacement or reattachment of the lower extremities with 136 and without MCC; syncope and collapse with and without MCC and fever of unknown 137 origin . However, we include herein only four of these diagnoses (laparoscopic 138 cholecystectomy, disorders of the biliary tract, simple pneumonia and cellulitis) in our 139 calculations since they were the only ones that had septicemia as a secondary MCC 140 during the study period. 141 142 The cost of additional BC bottles, equipment, phlebotomist and technologist time and 143 effort were obtained from the Microbiology Laboratory. 144 145 These data then were used to provide an estimate of the annualized increase in MR and 146 costs associated with conversion to 30 ml BCs. For annualized calculations, data acquired 147 during the study period were multiplied by 4. 148

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149 Additionally, we assumed an improved sensitivity of detecting bloodstream infections 150 based on the recent report by Patel et al. (3) who determined that an additional 67 non-151 conditional and 10 conditional pathogen bacteremic episodes were detected with 30 ml 152 BCs compared to 20 ml BCs out of a total of 1063 total episodes (917 caused by non-153 conditional and 146 caused by conditional pathogens). We thus calculated the percent 154 increase in sensitivity for 30 ml BCs to be 7.2% (77/(917+146) x 100%). 155 156 157 158 159 160 161 162 163 164 RESULTS 165 Results of 8068 blood cultures submitted to the RWJUH microbiology laboratory during 166

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the study period were analyzed; 584 were true positives, 228 were categorized as 167 contaminants, and 23 were of uncertain clinical significance. 168 Based on the assumption that each BSI episode would have 2 positive blood cultures, we 169 estimated that there would have been 292 bacteremic episodes during the 3-month period, 170 or 1168 episodes annually. 171 According to the data obtained from the Medical Records and Accounts Receivable 172 departments, there were 116 episodes of primary septicemia during the 3-month study 173 period for which Medicare reimbursed an average of $24,808 per episode. On an 174 annualized basis and given an expected 7.2% increase associated with the use of 30-ml 175 blood cultures, 34 additional septicemias ([116x4]x.072) would be detected and would 176 have been associated with an increase in Medicare reimbursement of $843,472. 177 178 We were also able to evaluate MR data where septicemia was a complication of another 179 diagnosis for four common ICD-9 codes: laparoscopic cholecystectomy, disorders of the 180 biliary tract, simple pneumonia, and cellulitis. The mean reimbursements for the four 181 ICD-9 codes without and with bacteremias are shown in Table 1. The average MR for 182 these episodes was $9667. A 7.2% increase in each of these secondary BSIs based on 30-183 ml blood cultures would result in detection of 50 additional cases ([1168-464] x .072) and 184 an increased MR of $483,350 (50 x $9667) annually. Additionally, this reimbursement 185 likely would be larger in a study that was designed to capture differences in 186 reimbursement over a longer period of time and which was inclusive of other ICD-9 187 diagnostic codes. 188

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189 We determined the capital and operational costs associated with conversion to 30-ml 190 blood cultures. The RWJUH Microbiology Laboratory processes an average of 2514 191 adult blood cultures each month. Each BC bottle costs $2.58, so an increase from 2 to 3 192 bottle BC sets would result in an additional expense of $77,833 annually (1 additional BC 193 bottle for each blood culture). The annualized cost of additional phlebotomist time and 194 effort was estimated to be $13,827, and the annualized cost of additional Microbiology 195 technologist time and effort was estimated to be $47,138 (Table 2.). The cost of an 196 additional BACTEC FX incubator stack is estimated to be $95,000; amortizing this 197 expense over 5 years resulted in a calculated cost of $19,000/year. Taken together, the 198 total annualized cost of labor, supplies and equipment during a 5 year period associated 199 with conversion to 30-ml blood cultures was estimated to be $157,798. 200 201 Therefore, based upon all of our in-house and calculated data, we estimated that 202 conversion to 30-ml blood cultures would result in a net increase in our institution’s 203 revenue by $1,169,031 ($843,479 + $483,350 - $157,789). The actual increase would 204 likely be higher since only 4 ICD-9 codes with MCC were captured during the 3 month 205 study period. 206 207 208 Discussion. 209 Bloodstream infections can be life threatening and result in serious complications 210

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including multisystem organ failure resulting in significant morbidity and mortality (21). 211 Accordingly, it is critical to detect the etiologic pathogen and institute directed 212 antimicrobial therapy .(21). Patel et al. recently showed that 30-ml compared with 20-ml 213 blood cultures lead to a 7.2% improvement in BSI detection (4). . In that study the cost 214 effectiveness of 30-ml blood cultures was not assessed. 215 The results of this study have shown that at our hospital a 7.2 % increase in detection of 216 primary BSIs would result in the annual detection of 34 additional BSI episodes and an 217 increased MR of $843,479. Revenue increases associated with enhanced detection of 218 secondary BSIs are more difficult to calculate given the small number of ICD-9 codes for 219 which we had comparative data. Only 9 out 709 episodes were from secondary blood 220 stream infections. That said, for just four ICD-9 codes, the calculated annual increase in 221 hospital revenue was $483,350. Accounting for the costs associated with conversion 222 from 20-ml to 30-ml blood cultures, the net increase in MR to the hospital would be 223 $1,169,031. 224 It is important to consider that drawing higher volumes of blood increases the risk of 225 nosocomial anemia, therefore the potential benefits with higher volume blood cultures 226 must be balanced against this risk, especially in patients with comorbid conditions 227 associated with anemia. Additionally, difficult venous access, poor collection technique 228 and the lack of appreciation for the importance of obtaining adequately filled blood 229 culture bottles on the part of those collecting specimens often leads to inadequate blood 230 volume collection. These issues may be exacerbated by a requirement to obtain greater 231 volumes of blood. 232

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233 There were several limitations in this study. We have not taken into account the 234 additional cost of processing false positives i.e. contaminants with the addition of a 3rd 235 bottle in each culture set. Patel et al. have reported that the number of contaminants 236 associated with 43,158 blood cultures increased from 61 to 75 for 30-ml blood cultures 237 (1, 10, 11, 20). 238 239 240 Additionally the number of observations for secondary BSIs was relatively small as 241 mentioned, and the reimbursement rate in each of these categories was highly variable, 242 i.e. the mean additional reimbursement maybe less accurate as a result. 243 244 Future studies comparing and assessing the Medicare reimbursement for 20-ml vs. 30-ml 245 blood culture volumes over a longer period of time, in different health care settings 246 (community hospital vs tertiary care center), including special populations such as 247 neutropenic patients and MCC for additional diagnoses would shed further light on our 248 observations. 249 250 Although conversion to 30-ml blood cultures will result in increased institutional costs, 251 our data suggest that these costs will be more than offset by the increased reimbursement 252 that will occur as a consequence of documenting additional bloodstream infections. We 253 conclude that the institution of 30-ml blood culture is a cost effective approach to 254 improving patient care. 255

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256 Acknowledgments. 257 No financial support was received for the research and publication of this study. 258 A.C., T.J.K. and M.P.W. have no conflicts of interest. 259 We acknowledge the outstanding contributions of the medical records team and the 260 Microbiology Laboratory staff, in particular Kim Joho and Suzanne Mount, at Robert 261 Wood Johnson University Hospital. 262 263 264 265 266 267 268 269 270 271 272 273 274 275 References. 276

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1. Bates, D. W., L. Goldman, and T. H. Lee. 1991. Contaminant blood cultures 277 and resource utilization: the true consequences of false-positive results. JAMA 278 265:365-369. 279

2. Hall MJ, Williams SN, DeFrances CJ, Golosinskiy A. 2011. NCHS data brief, 280 no 62, Inpatient care for septicemia or sepsis: A challenge for patients and 281 hospitals. National Center for Health Statistics, Hyattsville, MD. 282

3. Riedel S, Carroll KC. 2010. Blood cultures: key elements for best practices and 283 future directions. J. Infect. Chemother. 16:301–316. 284

4. Patel R, Vetter EA, Harmsen WS, Schleck CD, Fadel HJ, Cockerill FR. 2011. 285 Optimized pathogen detection with 30- compared to 20-milliliter blood culture 286 draws. J Clin Microbiol. 49: 4047-51. 287

5. Cockerill FR, Wilson JW, Vetter EA, Goodman KM, Torgerson CA, 288 Harmsen WS, Schleck CD, IIstrup DM, Washington JA, Wilson WR. 2004. 289 Optimal testing parameters for blood cultures. Clin. Infect. Dis. 38:1724–1730. 290

6. Hall MM, Ilstrup DM, Washington JA. 1976. Effect of volume of blood 291 cultured on detection of bacteremia. J. Clin. Microbiol. 3:643–645. 292

7. Ilstrup DM, Washington JA. 1983. The importance of volume of blood cultured 293 in the detection of bacteremia and fungemia. Diagn. Microbiol. Infect. Dis. 294 1:107–110. 295

8. Lee A, Mirrett S, Reller LB, Weinstein MP. 2007. Detection of bloodstream 296 infections in adults: how many blood cultures are needed? J. Clin. Microbiol. 297 45:3546–3548. 298

9. Li J, Plorde JJ, Carlson LG. 1994. Effects of volume and periodicity on blood 299

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cultures. J. Clin. Microbiol. 32:2829–2831. 300 10. MacGregor, R. R., and H. N. Beaty. 1972. Evaluation of positive blood 301

cultures. Guidelines for early differentiation of contaminated from valid positive 302 cultures. Arch. Intern. Med. 130:84-87. 303

11. Martin, M. A., M. A. Pfaller, and R. P. Wenzel. 1989. Coagulase-negative 304 staphylococcal bacteremia: mortality and hospital stay. Ann. Intern. Med. 110:9-305 16. 306

12. Plorde JJ, Tenover FC, Carlson LG. 1985. Specimen volume versus yield in 307 the BACTEC blood culture system. J. Clin. Microbiol. 22:292–295. 308

13. Richter, S. S., S. E. Beekmann, J. L. Croco, D. J. Diekema, F. P. Koontz, M. 309 A. Pfaller, and G. V. Doern. 2002. Minimizing the workup of blood culture 310 contaminants: implementation and evaluation of a laboratory-based 311 algorithm. J. Clin. Microbiol. 40:2437-2444. 312

14. Rupp, M. E., and G. L. Archer. 1994. Coagulase-negative staphylococci: 313 pathogens associated with medical progress. Clin. Infect. Dis. 19:231-243. 314

15. Sandven P, Hoiby EA. 1981. The importance of blood volume cultured on 315 detection of bacteraemia. Acta Pathol. Microbiol. Scand. B 89:149–152. 316

16. Souvenir, D., D. E. Anderson, Jr., S. Palpant, H. Mroch, S. Askin, J. 317 Anderson, J. Claridge, J. Eiland, C. Malone, M. W. Garrison, P. Watson, 318 and D. M. Campbell. 1998. Blood cultures positive for coagulase-negative 319 staphylococci: antisepsis, pseudobacteremia, and therapy of patients. J. Clin. 320 Microbiol. 36:1923-1926. 321

17. Tenney JH, Reller LB, Mirrett S, Wang WL, Weinstein MP. 1982. Controlled 322

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evaluation of the volume of blood cultured in detection of bacteremia and 323 fungemia. J. Clin. Microbiol. 15:558–561. 324

18. Weinstein MP, Mirrett S, Wilson ML, Reimer LG, Reller LB. 1994. 325 Controlled evaluation of 5 versus 10 milliliters of blood cultured in aerobic 326 BacT/Alert blood culture bottles. J. Clin. Microbiol. 32:2103–2106. 327

19. Weinstein, M. P., L. B. Reller, J. R. Murphy, and K. A. Lichtenstein. 1983. 328 The clinical significance of positive blood cultures: a comprehensive analysis of 329 500 episodes of bacteremia and fungemia in adults. I. Laboratory and 330 epidemiologic observations. Rev. Infect. Dis. 5:35-53. 331

20. Weinstein, M. P., M. L. Towns, S. M. Quartey, S. Mirrett, L. G. Reimer, G. 332 Parmagiani, and L. B. Reller. 1997. The clinical significance of positive blood 333 cultures in the 1990s: a prospective comprehensive evaluation of the 334 microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. 335 Clin. Infect. Dis. 24:584-602. 336

21. Wegner DL. 2004. Practical approaches to improving the hospital's bottom line. 337 Clinical Microbiology Newsletter. 26: 105-108. 338

22. Weinstein MP. 2003. Minireview: Blood Culture Contamination: Persisting 339 Problems and Partial Progress. 41: 2275-2278. 340

341 342 343 TABLE 1 RWJUH mean Medicare reimbursement for four common disease conditions 344 with and without bacteremia as a major clinical complication 345

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346 Diagnosis N Mean

reimbursement without bacteremia

Mean reimbursement with bacteremia

Mean difference per episode

Additional reimbursement

Cholecystectomy 2 $7441 $27,390 $19,949 $39,898 Biliary tract disorders

3 $4406 $57,346 $52,939 $158,817

Pneumonia 2 $3351 $13,923 $10,571 $21,142 Cellulitis 2 $3181 $6630 $3449 $6898 347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 TABLE 2 Labor costs associated with conversion from a 20-ml to 30-ml blood culture 363 system 364

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365 Hourly salary Time for inoculating/processing

1 extra blood culture bottle Cost annualized

Phlebotomist $27.50 1 minute $13,827 Micro tech $37.50 2.5 minutes $47,138 366 367

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Erratum for Cheruvanky et al., Cost-Effectiveness of 30- Compared to20-Milliliter Blood Cultures: a Retrospective Study

Anita Cheruvanky,a Thomas J. Kirn,a,b Melvin P. Weinsteina,b

Department of Medicinea and Department of Pathology and Laboratory Medicine,b Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA

Volume 54, no. 1, p. 64 – 67, 2016. Page 64, abstract, lines 2– 4: The parenthetical reference at the end of the sentence beginning“Recently, . . .” should read “(R. Patel, E. A. Vetter, W. S. Harmsen, C. D. Schleck, H. J. Fadel, and F. R. Cockerill III, J Clin Microbiol49:4047– 4051, 2011, http://dx.doi.org/10.1128/JCM.01314-11).”

Citation Cheruvanky A, Kirn TJ, Weinstein MP. 2016. Erratum for Cheruvanky et al.,Cost-effectiveness of 30- compared to 20-milliliter blood cultures: a retrospectivestudy. J Clin Microbiol 54:821. doi:10.1128/JCM.00004-16.

Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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