Evaluating the Inappropriate Prescribing and Utilization of Caspofungin, a Four-Year Analysis at a Teaching Hospital in Saudi Arabia
Abstract
:1. Introduction
2. Results
2.1. Patients
2.2. Indications
2.3. Caspofungin Duration and Doses
2.4. Appropriateness Evaluation in the Definitive Therapy Group
2.5. Inpatient All-Cause Mortality at 30-Days
3. Discussion
4. Materials and Methods
4.1. Study Design, Settings, and Data Collection
4.2. Study Definitions
4.3. Study Outcome
4.4. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Pappas, P.G.; Kauffman, C.A.; Andes, D.R.; Clancy, C.J.; Marr, K.A.; Ostrosky-Zeichner, L.; Reboli, A.C.; Schuster, M.G.; Vazquez, J.A.; Walsh, T.J.; et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin. Infect. Dis. 2016, 62, e1–e50. [Google Scholar] [CrossRef]
- Magill, S.S.; Edwards, J.R.; Bamberg, W.; Beldavs, Z.G.; Dumyati, G.; Kainer, M.A.; Lynfield, R.; Maloney, M.; McAllister-Hollod, L.; Nadle, J.; et al. Multistate Point-Prevalence Survey of Health Care–Associated Infections. N. Engl. J. Med. 2014, 370, 1198–1208. [Google Scholar] [CrossRef] [Green Version]
- Bailly, S.; Maubon, D.; Fournier, P.; Pelloux, H.; Schwebel, C.; Chapuis, C.; Foroni, L.; Cornet, M.; Timsit, J.F. Impact of antifungal prescription on relative distribution and susceptibility of Candida spp.—Trends over 10 years. J. Infect. 2016, 72, 103–111. [Google Scholar] [CrossRef] [PubMed]
- Fridkin, S.K.; Kaufman, D.; Edwards, J.R.; Shetty, S.; Horan, T. Changing incidence of Candida bloodstream infections among NICU patients in the United States: 1995–2004. Pediatrics 2006, 117, 1680–1687. [Google Scholar] [CrossRef] [PubMed]
- Al Thaqafi, A.H.O.; Farahat, F.M.; Al Harbi, M.I.; Al Amri, A.F.W.; Perfect, J.R. Predictors and outcomes of Candida bloodstream infection: Eight-year surveillance, western Saudi Arabia. Int. J. Infect. Dis. 2014, 21, 5–9. [Google Scholar] [CrossRef] [Green Version]
- Omrani, A.S.; Makkawy, E.A.; Baig, K.; Baredhwan, A.A.; Almuthree, S.A.; Elkhizzi, N.A.; Albarrak, A.M. Ten-year review of invasive Candida infections in a tertiary care center in Saudi Arabia. Saudi Med. J. 2014, 35, 821–826. [Google Scholar]
- U.S. Food Drug Administration. Caspofungin Acetate for Injection. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/206110Orig1s000TOC.cfm (accessed on 21 April 2021).
- Dellit, T.H.; Owens, R.C.; McGowan, J.E.; Gerding, D.N.; Weinstein, R.A.; Burke, J.P.; Huskins, W.C.; Paterson, D.L.; Fishman, N.O.; Carpenter, C.F.; 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. 2007, 44, 159–177. [Google Scholar] [CrossRef] [PubMed]
- Valerio, M.; Munoz, P.; Rodriguez, C.G.; Caliz, B.; Padilla, B.; Fernandez-Cruz, A.; Sánchez-Somolinos, M.; Gijón, P.; Peral, J.; Gayoso, J.; et al. Antifungal stewardship in a tertiary-care institution: A bedside intervention. Clin. Microbiol. Infect. 2015, 21, 492.e1–492.e9. [Google Scholar] [CrossRef] [Green Version]
- Sutepvarnon, A.; Apisarnthanarak, A.; Camins, B.; Mondy, K.; Fraser, V.J. Inappropriate use of antifungal medications in a tertiary care center in Thailand: A prospective study. Infect. Control Hosp. Epidemiol. 2008, 29, 370–373. [Google Scholar] [CrossRef]
- Barlam, T.F.; Cosgrove, S.E.; Abbo, L.M.; MacDougall, C.; Schuetz, A.N.; Septimus, E.J.; Srinivasan, A.; Dellit, T.H.; Falck-Ytter, Y.T.; Fishman, N.O.; et al. Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 2016, 62, e51–e77. [Google Scholar] [CrossRef]
- Allison, M.G.; Heil, E.L.; Hayes, B.D. Appropriate Antibiotic Therapy. Emerg. Med. Clin. North Am. 2017, 35, 25–42. [Google Scholar] [CrossRef] [PubMed]
- Ierano, C.; Thursky, K.; Marshall, C.; Koning, S.; James, R.; Johnson, S.; Imam, N.; Worth, L.J.; Peel, T. Appropriateness of Surgical Antimicrobial Prophylaxis Practices in Australia. JAMA Netw. Open 2019, 2, e1915003. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Valerio, M.; Rodriguez-Gonzalez, C.G.; Muñoz, P.; Caliz, B.; Sanjurjo, M.; Bouza, E.; COMIC Study Group. Evaluation of antifungal use in a tertiary care institution: Antifungal stewardship urgently needed. J. Antimicrob. Chemother. 2014, 69, 1993–1999. [Google Scholar] [CrossRef] [Green Version]
- Ascioglu, S.; Chan, K.A. Utilization and Comparative Effectiveness of Caspofungin and Voriconazole Early after Market Approval in the U.S. PLoS ONE 2014, 9, e83658. [Google Scholar] [CrossRef]
- Muñoz, P.; Valerio, M.; Vena, A.; Bouza, E. Antifungal stewardship in daily practice and health economic implications. Mycoses 2015, 58, 14–25. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mba, I.E.; Nweze, E.I. Mechanism of Candida pathogenesis: Revisiting the vital drivers. Eur. J. Clin. Microbiol. Infect. Dis. 2020, 39, 1797–1819. [Google Scholar] [CrossRef]
- Colombo, A.L.; Guimarães, T.; Silva, L.R.; de Almeida Monfardini, L.P.; Cunha, A.K.B.; Rady, P.; Alves, T.; Rosas, R.C. Prospective observational study of candidemia in São Paulo, Brazil: Incidence rate, epidemiology, and predictors of mortality. Infect. Control Hosp. Epidemiol. 2007, 28, 570–576. [Google Scholar] [CrossRef]
- León, C.; Ruiz-Santana, S.; Saavedra, P.; Almirante, B.; Nolla-Salas, J.; Álvarez-Lerma, F.; Garnacho-Montero, J.; León, M.Á.; EPCAN Study Group. A bedside scoring system (“Candida score”) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization. Crit. Care Med. 2006, 34, 730–737. [Google Scholar] [CrossRef] [PubMed]
- Nivoix, Y.; Launoy, A.; Lutun, P.; Moulin, J.C.; Phai Pang, K.A.; Fornecker, L.M.; Wolf, M.; Levêque, D.; Letscher-Bru, V.; Beretz, L.; et al. Adherence to recommendations for the use of antifungal agents in a tertiary care hospital. J. Antimicrob. Chemother. 2012, 67, 2506–2513. [Google Scholar] [CrossRef] [PubMed]
- Gustot, T.; Heine R ter Brauns, E.; Cotton, F.; Jacobs, F.; Brüggemann, R.J. Caspofungin dosage adjustments are not required for patients with Child-Pugh B or C cirrhosis. J. Antimicrob. Chemother. 2018, 73, 2493–2496. [Google Scholar] [CrossRef] [Green Version]
- Martial, L.C.; Brüggemann, R.J.; Schouten, J.A.; van Leeuwen, H.J.; van Zanten, A.R.; de Lange, D.W.; Muilwijk, E.W.; Verweij, P.E.; Burger, D.M.; Aarnoutse, R.E.; et al. Dose Reduction of Caspofungin in Intensive Care Unit Patients with Child Pugh B Will Result in Suboptimal Exposure. Clin. Pharm. 2016, 55, 723–733. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lortholary, O.; Desnos-Ollivier, M.; Sitbon, K.; Fontanet, A.; Bretagne, S.; Dromer, F. Recent Exposure to Caspofungin or Fluconazole Influences the Epidemiology of Candidemia: A Prospective Multicenter Study Involving 2441 Patients. Antimicrob. Agents Chemother. 2011, 55, 532–538. [Google Scholar] [CrossRef] [Green Version]
- Ananda-Rajah, M.R.; Slavin, M.A.; Thursky, K.T. The case for antifungal stewardship. Curr. Opin. Infect. Dis. 2012, 25, 107–115. [Google Scholar] [CrossRef]
- Morrell, M.; Fraser, V.J.; Kollef, M.H. Delaying the empiric treatment of candida bloodstream infection until positive blood culture results are obtained: A potential risk factor for hospital mortality. Antimicrob. Agents Chemother. 2005, 49, 3640–3645. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wenzel, R.P.; Edmond, M.B. Antibiotics for Abdominal Sepsis. N. Engl. J. Med. 2015, 372, 2062–2063. [Google Scholar] [CrossRef] [PubMed]
Study Variables | Total | Indications | ||
---|---|---|---|---|
Overall, n = 355, (100%) | Empiric Therapy (ET) n = 270, (76.1%) | Definitive Therapy (DT) n = 85, (23.9%) | ||
Age Range 18–96 | median | 54 years | 53 years | 56 years |
Age > 65 years | 97 (27.3%) | 68 (25.2%) | 29 (34.1%) | |
Age ≤ 65 years | 258 (72.7%) | 202 (74.8%) | 56 (65.9%) | |
Sex | Female | 173 (48.7%) | 131 (48.5%) | 42 (49.4%) |
Male | 182 (51.3%) | 139 (51.5%) | 43 (50.6%) | |
Child- Pugh Score | Score ≥ 7 points | 57 (16.1%) | 44 (16.3%) | 13 (15.3%) |
Score < 7 points | 298 (83.9%) | 226 (83.7%) | 72 (84.7%) | |
Site of care | Critical Care | 203 (57.2%) | 162 (60%) | 41 (48.2%) |
Ward | 152 (42.8%) | 108 (40%) | 44 (51.8%) | |
Duration of Therapy | Median days | 7 days | 6 days | 12 days |
Cumulative Doses | 3458 doses | 2279 doses | 1179 doses | |
Duration ≤ 14 days | 283 (79.7%) | 229 (84.8%) | 54 (63.5%) | |
Duration > 14 days | 72 (20.3%) | 41 (15.2%) | 31 (36.5%) | |
Dosing * | Correct Loading Dosing | 328 (92.4%) | 252 (93.3%) | 76 (89.4%) |
Correct Maintenance Dosing | 286 (80.6%) | 217 (80.4%) | 69 (81.2%) | |
Appropriate dose (ApD) ** | 261 (73.5%) | 201 (74.4%) | 60 (70.6%) | |
Outcome at 30 days | Death | 118 (33.2%) | 101 (37.4%) | 17 (20%) |
Survived | 237 (66.8%) | 169 (62.6%) | 68 (80%) |
Parameter | n (%) | |
---|---|---|
Number of risk factors | One risk factor | 120 (44.4) |
Two risk factors | 91 (33.7) | |
Three risk factors | 35 (13) | |
Four risk factors | 5 (1.9) | |
Empirical therapy with no risk factors | 19/270 (7) | |
No single risk factor among ET group | Median duration (range) | 4 (2–18) days |
Empirical therapy out of critical care units | 10/19 patients | |
Cumulative doses | 117 doses | |
Category of risk factor | Central venous line | 161 (59.9) |
Recent abdominal surgery within 90 days | 121 (44.8) | |
Solid malignancy | 49 (18.1) | |
Renal Replacement Therapy | 40 (14.8) | |
Hematologic malignancy | 24 (8.9) | |
Total parental therapy | 23 (8.5) | |
Corticosteroids equivalent to Prednisolone 20 mg daily | 7 (2.6) | |
Human Immunodeficiency virus | 2 (0.7) | |
Duration | Five days or less. | 118 (43.7) |
Extended beyond 5 days, | 152 (56.3) | |
| 10.5 days | |
| 1131 doses | |
| 92/152 (60.5%) | |
| 51/152 (33.6%) |
Parameter | n (%) | |
---|---|---|
Diagnosis | Candidemia | 39 (45.9) |
Invasive candidiasis infections (ICI) | 38 (44.7) | |
Esophageal candidiasis | 5 (5.9) | |
Proven invasive aspergillosis | 3 (3.5) | |
Species | C. Albicans | 29 (34.5) |
C. Glabrata | 22 (25.3) | |
C. Tropicalis | 10 (11.5) | |
C. Krusei | 6 (6.9) | |
C. Parapsillosis | 5 (5.7) | |
Other Candida | 10 (12.6) | |
Aspergillus species | 3 (3.4) | |
Caspofungin course | Continued, not shifted to another agent | 41/85 (50.6) |
| 17/41 | |
| 24/41 | |
Shifted to another agent | 44/85 (49.4) | |
| 37/44 | |
| 4/44 | |
| 2/44 | |
| 1/44 | |
Appropriateness Criteria | Prescriptions met appropriate duration of therapy (ApDur) | 70/85 (82.4) |
Prescriptions met appropriate agent selection (ApS) | 65/85 (76.5) | |
Prescriptions met appropriate initiation time (ApI) | 64/85 (75.3) | |
Prescriptions met Appropriate dosing (ApD) | 60/85 (70.6) | |
Prescriptions met all four criteria | 33/85 (38.8) |
Predictors | Univariate Analysis | Multivariate Analysis | |||||
---|---|---|---|---|---|---|---|
p-Value (0.05) | Odds Ratio (95% CI) | Coeff (B) | Standard Error (SE) | Wald X2 | p-Value (0.05) | Adjusted Odds Ratio (95% CI) | |
Age above 65 years | <0.001 | 3.2 (1.94–5.14) | 1.044 | 0.279 | 13.965 | <0.001 | 2.84 (1.64–4.92) |
Female sex | 0.572 | - | - | - | - | - | - |
Therapy duration shorter than 14 days | 0.167 | - | - | - | - | - | - |
Child-Pugh score ≥ 7 points | <0.001 | 7.4 (3.9–13.86) | 1.728 | 0.357 | 23.461 | <0.001 | 5.63 (2.80–11.33) |
Admission to Intensive care unit | <0.001 | 4.6 (2.75–7.71) | 1.439 | 0.286 | 25.261 | <0.001 | 4.22 (2.41–7.39) |
Incorrect loading dose | 0.199 | - | - | - | - | - | - |
Incorrect maintenance dose | <0.001 | 2.7 (1.59–4.65) | - | - | - | - | - |
inappropriate dose | <0.001 | 2.5 (1.55–4.09) | 0.606 | 0.290 | 4.372 | 0.037 | 1.83 (1.04–3.24) |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Aldrees, A.; Ghonem, L.; Almajid, F.; Barry, M.; Mayet, A.; Almohaya, A.M. Evaluating the Inappropriate Prescribing and Utilization of Caspofungin, a Four-Year Analysis at a Teaching Hospital in Saudi Arabia. Antibiotics 2021, 10, 1498. https://doi.org/10.3390/antibiotics10121498
Aldrees A, Ghonem L, Almajid F, Barry M, Mayet A, Almohaya AM. Evaluating the Inappropriate Prescribing and Utilization of Caspofungin, a Four-Year Analysis at a Teaching Hospital in Saudi Arabia. Antibiotics. 2021; 10(12):1498. https://doi.org/10.3390/antibiotics10121498
Chicago/Turabian StyleAldrees, Abdulwahab, Leen Ghonem, Fahad Almajid, Mazin Barry, Ahmed Mayet, and Abdulellah M. Almohaya. 2021. "Evaluating the Inappropriate Prescribing and Utilization of Caspofungin, a Four-Year Analysis at a Teaching Hospital in Saudi Arabia" Antibiotics 10, no. 12: 1498. https://doi.org/10.3390/antibiotics10121498
APA StyleAldrees, A., Ghonem, L., Almajid, F., Barry, M., Mayet, A., & Almohaya, A. M. (2021). Evaluating the Inappropriate Prescribing and Utilization of Caspofungin, a Four-Year Analysis at a Teaching Hospital in Saudi Arabia. Antibiotics, 10(12), 1498. https://doi.org/10.3390/antibiotics10121498