Cost Savings MALDI
Cost Savings MALDI
Cost Savings MALDI
Matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry (MS) is an emerging technology for rapid
identification of bacterial and fungal isolates. In comparison to conventional methods, this technology is much less labor intensive and
can provide accurate and reliable results in minutes from a single isolated colony. We compared the cost of performing the bioMérieux
Vitek MALDI-TOF MS with conventional microbiological methods to determine the amount saved by the laboratory by converting to
the new technology. Identification costs for 21,930 isolates collected between April 1, 2013, and March 31, 2014, were directly compared
for MALDI-TOF MS and conventional methodologies. These isolates were composed of commonly isolated organisms, including com-
monly encountered aerobic and facultative bacteria and yeast but excluding anaerobes and filamentous fungi. Mycobacterium tuber-
culosis complex and rapidly growing mycobacteria were also evaluated for a 5-month period during the study. Reagent costs and
a total cost analysis that included technologist time in addition to reagent expenses and maintenance service agreement costs
were analyzed as part of this study. The use of MALDI-TOF MS equated to a net savings of $69,108.61, or 87.8%, in reagent costs
annually compared to traditional methods. When total costs are calculated to include technologist time and maintenance costs,
traditional identification would have cost $142,532.69, versus $68,886.51 with the MALDI-TOF MS method, resulting in a labo-
ratory savings of $73,646.18, or 51.7%, annually by adopting the new technology. The initial cost of the instrument at our usage
level would be offset in about 3 years. MALDI-TOF MS not only represents an innovative technology for the rapid and accurate
identification of bacterial and fungal isolates, it also provides a significant cost savings for the laboratory.
amined the cost savings encountered when reagents and total cost
were calculated.
$69,108.61, or 87.8%, in reagent costs compared to the use of tra- isolate. The direct cost from MALDI-TOF MS was only $1,403.20,
ditional methods (Table 1). When analyzed by organism type, the or $35.08 per isolate, which equates to a 74.0% savings. These
largest savings were realized among Gram-negative GNFs, with a savings were reflected by the reduced cost of reagents required for
92.9% reduction in reagent costs with MALDI-TOF MS. Tradi- MALDI-TOF MS versus molecular sequencing methods, since
tional costs for identifying these organisms mainly involved Vitek technologist times were similar between the two methods (23 and
2 and 16S molecular sequencing. This large percentage of savings 25 min, respectively). Each isolate that required 16S sequencing
was expected, since the use of MALDI-TOF MS for identification cost the UNCH CMIL $61.39 in reagents, while use of hsp65 dou-
of bacteria and yeasts from culture utilizes a minimal amount of bled that cost. Even with the additional reagents required for per-
reagents. forming MALDI-TOF MS, reagent costs accounted for only
Direct cost analysis. If total costs were calculated to include $11.33 per isolate, or 89.7% less than molecular sequencing.
technologist time, traditional identification would have cost Therefore, even during a short period of 5 months, the laboratory
$142,532.69, compared to $39,186.51 for identification with was able to save nearly $4,000, or $100 per identification, by elim-
MALDI-TOF MS (Table 2). Therefore, the implementation of MS inating the need for molecular sequencing.
for identification of bacteria and yeasts netted a savings of Cost per sample. We also calculated the average cost per sam-
$103,346.18, or 72.5%. Again, Gram-negative GNFs yielded the ple identified for the various scenarios described. This simply rep-
largest savings with MALDI-TOF MS, where 80.9% total cost sav- resents the mean of the total costs, including reagent, technologist,
ings was observed. and maintenance costs, for all isolates identified during the study
The above calculations represent an estimation of the annual period. Reagent costs for the traditional methods utilized aver-
savings without the maintenance agreement contracts, which aged $3.59 per isolate and those for MALDI-TOF MS were only
would apply to the first year after purchase of the instrument, $0.43 (Fig. 3). Total costs with traditional methods, including re-
since maintenance is included during the initial year of operation. agent, technologist time, and maintenance agreement contracts,
To properly calculate the cost savings of each subsequent year, were determined to be $6.50 per isolate reported, compared to
beginning with year 2, the annual budget of the maintenance con- $3.14 for with MALDI-TOF MS.
tract needs to be added in. With the additional service contracts
added, the laboratory savings fell to $73,646.18, or 51.7% (Table DISCUSSION
3). Interestingly, there was a loss of 4.4% in savings for the iden- The transition from conventional microbiological methods to
tification of Staphylococcus spp. when maintenance agreement MALDI-TOF MS technology resulted in significant cost savings.
contracts were added to the calculation. There were no other re- The laboratory savings estimate was $73,646.18 (51.7%) in total
markable differences among the other categories. costs during the 12-month study (Table 3). This included reagent,
Acid-fast bacilli. Through traditional methods utilizing mo- technologist, and maintenance agreement costs. Workflow, which
lecular sequencing, it would have cost the CMIL $5,392.08 to affects the amount of time a technologist spends on identifying an
properly identify the 40 RGM and MTC specimens, or $134.80 per isolate, is an important aspect that has direct implications for total
TABLE 3 Total cost comparison between traditional and MALDI-TOF MS methods, including maintenance agreement costs
Total cost ($) Cost savings
No. of
Organism samples Traditional MALDI-TOF $ %
Enterobacteriaceae 7,503 51,717.18 23,516.72 28,200.46 54.5
Enterococcus spp. 1,454 13,072.16 4,557.29 8,514.87 65.1
GNFa 3,489 32,458.39 10,936.89 21,521.50 66.3
Staphylococcus spp. 5,790 17,383.04 18,147.65 ⫺764.61 ⫺4.4
Streptococcus spp. 2,332 17,704.82 7,309.21 10,395.61 58.7
Yeast 1,362 10,197.09 4,418.75 5,778.34 56.7
FIG 3 Mean reagent and total costs (with and without maintenance costs) per identification of isolates by traditional and MALDI-TOF MS methods.
costs. This includes but is not limited to the number of touches the methods. Although the technologist time and reagent costs were
technologist performs during the process of isolate determina- similar for both methods, addition of the maintenance contract
tion. The UNCH CMIL underwent a Lean assessment that was increased the cost of MALDI-TOF MS identification above that
conducted by bioMérieux as part of the purchase of the MALDI- for conventional identification of Staphylococcus species. How-
TOF MS, which helped the laboratory refine protocols to maxi- ever, traditional methods of identification of Staphylococcus sap-
mize time and efforts when identifying specimens with the rophyticus and Staphylococcus lugdunensis required more technol-
MALDI-TOF MS. ogist time and biochemical tests, which delayed identification of
Laboratories can maximize resources and minimize costs by these organisms for up to 48 h. Additionally, the Vitek MS pro-
batching runs and waiting for all of the sample spots within an vided our laboratory with the ability to identify coagulase-nega-
acquisition group on the target slide to be filled prior to loading tive Staphylococcus isolates to the species level, which was not done
the slides onto the MS; the remaining AGs would be accessible for previously. This is beneficial for blood and sterile body fluid iso-
additional runs at a later time. This helps boost slide usage effi- lates to help differentiate between true infection and contamina-
ciency and provides more savings. This philosophy should be tion of blood and sterile body fluid cultures when multiple colo-
possible for most runs throughout the day without impacting nial morphologies were detected (12–14). For us, these benefits far
turnaround time significantly. An optimal scenario assumes max- outweigh the added costs of MALDI-TOF MS. Additionally, some
imum utilization of reagents and technologist time; i.e., all sample rapid biochemical tests, such as spot indole for Escherichia coli and
spots on the disposable slide are utilized, and 100% of the spots PYR for Streptococcus pyogenes, may be less expensive than MS.
result in a reportable identification (Fig. 2). If this scenario were The inclusion and exclusion of certain organisms in this new
true, then the total cost savings would be $80,894.12, or 56.8%, methodology is something that each laboratory should consider
annually instead of $73,646.18. Realistically, we believe the actual and incorporate into implementation protocols, because MALDI-
cost savings are between this optimal scenario and our study cal- TOF MS reagent costs, workflow, and maintenance contracts vary
culations, since it is not feasible to expect that every spot will be significantly.
utilized on each slide and result in a reportable identification. Verification studies. Verification studies for implementation
Not surprisingly, implementation of MALDI-TOF MS re- of MALDI-TOF MS began in June 2012, and the laboratory went
duced reagent costs by 88% compared to the costs of conventional live with the first set of organisms in October 2012. For this vali-
methods. This is because the only consumables utilized in our dation, we included 731 organisms across 3,411 sample spots.
laboratory for MALDI-TOF MS were the disposable target slides, Through June 2013, the verifications cost an estimated $4,357.78,
matrix, formic acid (mainly for yeasts), pipette tips, and tooth- and more organisms continue to be verified as we encounter them
picks for spotting organisms. in the laboratory.
Interestingly, there was only one category where it was less Acid-fast bacilli. Because of the expense of identifying rapidly
expensive to perform traditional identification than identification growing mycobacteria and Mycobacterium tuberculosis by molec-
with MALDI-TOF MS. Identification of Staphylococcus spp. by ular means, this group of AFB is likely to be more efficiently iden-
MS cost $764.61 more than by the traditional latex agglutination tified by MALDI-TOF MS. Our laboratory cultures AFB through
traditional mycobacterial methods utilizing liquid (Bactec MGIT that were generated. This was not possible for us due to resource
960 mycobacterial detection system) and solid (Lowenstein-Jen- constraints. We were, however, able to audit all of the spots gen-
sen medium; Becton, Dickinson and Company, Franklin Lakes, erated over a 7-day period and found that 79.6% of the spots
NJ) media. Once positive growth is verified via a Kinyoun stain, generated a reportable identification. Similarly, a 2-month audit
the organism is subcultured to 7H11 medium. After sufficient of our slide usage efficiency revealed that 89.8% of sample spots
growth, the organisms are prepared for identification by MALDI- were utilized. These surveys showed that our estimate of 75% total
TOF MS. The rate of growth determines whether the organism is slide efficiency was relatively close to what actually occurs in our
an RGM, and colony morphology helps determine whether MTC laboratory. However, without prospective monitoring of slide
is in the differential. consumption and efficiency throughout the study period, it is im-
In February 2014, RGM and MTC were added to the menu of possible to accurately calculate this value.
approved organisms for identification on MALDI-TOF MS. These It should be noted that this was a cost-savings study that
identifications utilize the research-use-only (RUO) Saramis data- estimated the amount saved by the laboratory after routine
base v4.12 and incur a higher total cost due to a time-consuming implementation of MALDI-TOF MS for identification of the
extraction technique required to process and inactivate the AFB more common organisms encountered in the clinical microbi-
prior to organism identification by MALDI-TOF MS. These costs ology laboratory. It is not a true cost-effectiveness study that
still represent a significant 74% reduction in direct costs after examines costs compared to a defined clinical or natural out-
moving to MALDI-TOF MS from traditional molecular sequenc- come to improve health (15). A cost-effectiveness study would
ing methods while reducing the turnaround time. require evaluation of the turnaround time to results and how it
Capital costs. The main stumbling block with implementing impacts patient care, which is beyond the scope of this paper.
MALDI-TOF MS in the clinical microbiology setting is the capital Further and more in-depth studies, such as that by Tan et al.
cost of acquiring the instrument. With an approximate $270,000 (9), are needed to determine the cost-effectiveness of this new
price tag for the instrument and associated in vitro diagnostics and technology.
RUO software databases, the initial financial hurdle may be too MALDI-TOF MS not only represents an innovative technology
high for some laboratories to overcome. Moreover, laboratories for the rapid and accurate identification of bacterial and fungal
must be mindful of the maintenance that is associated with the isolates, it also provides significant cost savings for the laboratory.
MALDI-TOF MS. The UNCH CMIL pays an additional $29,700 Despite the high capital cost of the instrument, the ease of perfor-
annually for instrument and database/software maintenance. Our mance, the rapid turnaround time to results, and the modest cost
laboratory requires MALDI-TOF MS fine-tuning every 3 to 4 of testing for each sample make this new methodology a paradigm
weeks and has undergone a full laser and three linear detector shift in the field of clinical microbiology.
replacements in the ⬍3 years that the instrument has been in use.
The fine-tuning process, which takes several hours, does not in- ACKNOWLEDGMENTS
terrupt workflow or increase cost in our laboratory, as we batch We thank the laboratory staff at the UNCH CMIL for their contributions,
specimens and test them once the instrument is ready for opera- continued diligence, and dedication to their craft, which helped tremen-
tion again. We estimate that the MALDI-TOF MS was nonfunc- dously with our cost savings.
tional for extended periods (i.e., ⬎18 h) for a total of 4 days during REFERENCES
the study period. During these times, we reverted to traditional 1. Shah HN, Gharbia S. 15 June 2010. Mass spectrometry for microbial
methods of identification. Maintenance is an integral part of proteomics. John Wiley & Sons, Inc., Chichester, United Kingdom. http:
the cost calculation for MALDI-TOF MS and needs to be //dx.doi.org/10.1002/9780470665497.
strongly considered by every laboratory planning on imple- 2. Karas M, Hillenkamp F. 1988. Laser desorption ionization of proteins
with molecular masses exceeding 10,000 daltons. Anal Chem 60:2299 –
menting this technology. It should be noted that maintenance 2301.
costs begin in year 2, since the first year is covered by the man- 3. Buchan BW, Ledeboer NA. 2013. Advances in identification of clinical
ufacturer warranty. yeast isolates by use of matrix-assisted laser desorption ionization-time of
Therefore, understanding the cost savings after implementa- flight mass spectrometry. J Clin Microbiol 51:1359 –1366. http://dx.doi
.org/10.1128/JCM.03105-12.
tion of MALDI-TOF MS is important because of its large initial
4. De Carolis E, Vella A, Vaccaro L, Torelli R, Spanu T, Fiori B, Posteraro
fiscal investment. With an annual savings estimate of $73,646.18, B, Sanguinetti M. 2014. Application of MALDI-TOF mass spectrometry
coupled with the initial year’s savings of $103,346.18, we antici- in clinical diagnostic microbiology. J Infect Dev Ctries 8:1081–1088. http:
pate that the capital cost of the instrument would be offset in just //dx.doi.org/10.3855/jidc.3623.
⬎3 years. The net savings will only increase as we continue to 5. Chao QT, Lee TF, Teng SH, Peng LY, Chen PH, Teng LJ, Hsueh PR.
2014. Comparison of the accuracy of two conventional phenotypic meth-
validate more organisms by MALDI-TOF MS that will ultimately ods and two MALDI-TOF MS systems with that of DNA sequencing anal-
require less molecular sequencing and labor-intensive technolo- ysis for correctly identifying clinically encountered yeasts. PLoS One
gist time for identification. 9:e109376. http://dx.doi.org/10.1371/journal.pone.0109376.
Limitations. There are several limitations to the study. We 6. Cherkaoui A, Hibbs J, Emonet S, Tangomo M, Girard M, Francois P,
Schrenzel J. 2010. Comparison of two matrix-assisted laser desorption
were limited by database inquiries and our financial test cost anal-
ionization-time of flight mass spectrometry methods with conventional
yses. The laboratory information system has limited querying ca- phenotypic identification for routine identification of bacteria to the spe-
pabilities. While we were able to identify the number of isolates cies level. J Clin Microbiol 48:1169 –1175. http://dx.doi.org/10.1128/JCM
reported during the study period, we were unable to identify ex- .01881-09.
actly how many sample spots were utilized for identification of the 7. Eigner U, Holfelder M, Oberdorfer K, Betz-Wild U, Bertsch D, Fahr
AM. 2009. Performance of a matrix-assisted laser desorption ioniza-
organisms that were reported. The only way to track this is to tion-time-of-flight mass spectrometry system for the identification of
prospectively audit the number of spots that were utilized and bacterial isolates in the clinical routine laboratory. Clin Lab 55:289 –
cross-reference that number with the number of isolate reports 296.
8. Seng P, Drancourt M, Gouriet F, La Scola B, Fournier PE, Rolain JM, taneous infections caused by rapidly growing mycobacteria. Eur J Clin Micro-
Raoult D. 2009. Ongoing revolution in bacteriology: routine identifica- biol Infect Dis 32:161–188. http://dx.doi.org/10.1007/s10096-012-1766-8.
tion of bacteria by matrix-assisted laser desorption ionization time-of- 12. Abdul Rahman Z, Hamzah SH, Hassan SA, Osman S, Md Noor SS.
flight mass spectrometry. Clin Infect Dis 49:543–551. http://dx.doi.org/10 2013. The significance of coagulase-negative staphylococci bacteremia in a
.1086/600885. low resource setting. J Infect Dev Ctries 7:448 – 452. http://dx.doi.org/10
9. Tan KE, Ellis BC, Lee R, Stamper PD, Zhang SX, Carroll KC. 2012. .3855/jidc.2535.
Prospective evaluation of a matrix-assisted laser desorption ionization– 13. Al Wohoush I, Rivera J, Cairo J, Hachem R, Raad I. 2011. Comparing
time of flight mass spectrometry system in a hospital clinical microbiology clinical and microbiological methods for the diagnosis of true bacteraemia
laboratory for identification of bacteria and yeasts: a bench-by-bench among patients with multiple blood cultures positive for coagulase-
study for assessing the impact on time to identification and cost- negative staphylococci. Clin Microbiol Infect 17:569 –571. http://dx.doi
effectiveness. J Clin Microbiol 50:3301–3308. http://dx.doi.org/10.1128 .org/10.1111/j.1469-0691.2010.03372.x.
/JCM.01405-12. 14. Usha MG, Shwetha DC, Vishwanath G. 2013. Speciation of coagulase
10. Janda JM, Abbott SL. 2007. 16S rRNA gene sequencing for bacterial negative Staphylococcal isolates from clinically significant specimens and
identification in the diagnostic laboratory: pluses, perils, and pitfalls. J their antibiogram. Indian J Pathol Microbiol 56:258 –260. http://dx.doi
Clin Microbiol 45:2761–2764. http://dx.doi.org/10.1128/JCM.01228-07. .org/10.4103/0377-4929.120383.
11. Kothavade RJ, Dhurat RS, Mishra SN, Kothavade UR. 2013. Clinical and 15. Gold MR. 1996. Cost-effectiveness in health and medicine. Oxford Uni-
laboratory aspects of the diagnosis and management of cutaneous and subcu- versity Press, New York, NY.