Impact of Cefazolin Shortage on Clinical Outcomes of Adult Patients with Bacteremia Caused by Methicillin-Susceptible Staphylococcus aureus in a Tertiary Care University Hospital
Abstract
:1. Introduction
2. Results
3. Discussion
4. Methods
4.1. Setting and Patients
4.2. Definition
4.3. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Melzer, M.; Welch, C. Thirty-Day Mortality in UK Patients with Community-Onset and Hospital-Acquired Meticillin-Susceptible Staphylococcus aureus Bacteraemia. J. Hosp. Infect. 2013, 84, 143–150. [Google Scholar] [CrossRef]
- Baddour, L.M.; Wilson, W.R.; Bayer, A.S.; Fowler, V.G.; Tleyjeh, I.M.; Rybak, M.J.; Barsic, B.; Lockhart, P.B.; Gewitz, M.H.; Levison, M.E.; et al. Infective endocarditis in adults: Diagnosis, Antimicrobial Therapy, and Management of Complications. Circulation 2015, 132, 1435–1486. [Google Scholar] [CrossRef]
- Gudiol, F.; Aguado, J.M.; Almirante, B.; Bouza, E.; Cercenado, E.; Domínguez, M.Á.; Gasch, O.; Lora-Tamayo, J.; Miró, J.M.; Palomar, M.; et al. Diagnosis and Treatment of Bacteremia and Endocarditis Due to Staphylococcus aureus. A Clinical Guideline from the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC). Enferm. Infecc. Microbiol. Clín. 2015, 33, 625.e1–625.e23. [Google Scholar] [CrossRef] [PubMed]
- Mermel, L.A.; Allon, M.; Bouza, E.; Craven, D.E.; Flynn, P.; O’Grady, N.P.; Raad, I.I.; Rijnders, B.J.A.; Sherertz, R.J.; Warren, D.K. Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection: 2009 Update by the Infectious Diseases Society of America. Clin. Infect. Dis. 2009, 49, 1–45. [Google Scholar] [CrossRef] [PubMed]
- The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG2020). Available online: https://www.jsicm.org/news/news210225.html (accessed on 24 September 2021). (In Japanese).
- Schweizer, M.L.; Furuno, J.P.; Harris, A.D.; Johnson, J.K.; Shardell, M.D.; McGregor, J.C.; Thom, K.A.; Cosgrove, S.E.; Sakoulas, G.; Perencevich, E.N. Comparative Effectiveness of Nafcillin or Cefazolin versus Vancomycin in Methicillin-Susceptible Staphylococcus aureus Bacteremia. BMC Infect. Dis. 2011, 11, 279. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- McDanel, J.S.; Perencevich, E.N.; Diekema, D.J.; Herwaldt, L.A.; Smith, T.C.; Chrischilles, E.A.; Dawson, J.D.; Jiang, L.; Goto, M.; Schweizer, M.L. Comparative Effectiveness of Beta-Lactams Versus Vancomycin for Treatment of Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections Among 122 Hospitals. Clin. Infect. Dis. 2015, 61, 361–367. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Griffith, M.M.; Gross, A.E.; Sutton, S.H.; Bolon, M.K.; Esterly, J.S.; Patel, J.A.; Postelnick, M.J.; Zembower, T.R.; Scheetz, M.H. The Impact of Anti-Infective Drug Shortages on Hospitals in the United States: Trends and Causes. Clin. Infect. Dis. 2012, 54, 684–691. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nichi-Iko Pharmaceutical Co., Ltd. Available online: https://www.nichiiko.co.jp/medicine/files/o-cefazoli_i-20190228cI1.pdf (accessed on 14 April 2021). (In Japanese).
- Honda, H.; Murakami, S.; Tokuda, Y.; Tagashira, Y.; Takamatsu, A. Critical National Shortage of Cefazolin in Japan: Management Strategies. Clin. Infect. Dis. 2020, 71, 1783–1789. [Google Scholar] [CrossRef] [PubMed]
- Tsutsui, A.; Yahara, K.; Shibayama, K. Trends and Patterns of National Antimicrobial Consumption in Japan from 2004 to 2016. J. Infect. Chemother. 2018, 24, 414–421. [Google Scholar] [CrossRef]
- Ministry of Health, Labour and Welfare: A List of Alternative Agents for Cefazolin. Available online: https://www.mhlw.go.jp/content/10900000/000498133.pdf (accessed on 24 December 2020). (In Japanese).
- Barber, K.E.; Bell, A.M.; Travis King, S.; Parham, J.J.; Stover, K.R. Impact of Piperacillin-Tazobactam Shortage on Meropenem Use: Implications for Antimicrobial Stewardship Programs. Braz. J. Infect. Dis. 2016, 20, 631–634. [Google Scholar] [CrossRef] [Green Version]
- Plüss-Suard, C.; Pannatier, A.; Ruffieux, C.; Kronenberg, A.; Mühlemann, K.; Zanetti, G. Changes in the Use of Broad-Spectrum Antibiotics after Cefepime Shortage: A Time Series Analysis. Anti-Microb. Agents Chemother. 2012, 56, 989–994. [Google Scholar] [CrossRef]
- WHO Model List of Essential Medicines. Available online: https://aware.essentialmeds.org/groups (accessed on 14 April 2021).
- Uda, A.; Shigemura, K.; Kitagawa, K.; Osawa, K.; Onuma, K.; Yan, Y.; Nishioka, T.; Fujisawa, M.; Yano, I.; Miyara, T. Risk Factors for the Acquisition of Enterococcus faecium Infection and Mortality in Patients with Enterococcal Bacteremia: A 5-Year Retrospective Analysis in a Tertiary Care University Hospital. Antibiotics 2021, 10, 64. [Google Scholar] [CrossRef] [PubMed]
- Uda, A.; Tokimatsu, I.; Koike, C.; Osawa, K.; Shigemura, K.; Kimura, T.; Miyara, T.; Yano, I. Antibiotic De-Escalation Therapy in Patients with Community-Acquired Nonbacteremic Pneumococcal Pneumonia. Int. J. Clin. Pharm. 2019, 41, 1611–1617. [Google Scholar] [CrossRef]
- Nakarai, H.; Yamada, K.; Tonosu, J.; Abe, H.; Watanabe, K.; Yoshida, Y.; Ohya, J.; Sato, Y.; Hara, N.; Okazaki, R.; et al. The Impact of Cefazolin Shortage on Surgical Site Infection Following Spine Surgery in Japan. Spine 2021. Epub ahead of printing. [Google Scholar] [CrossRef] [PubMed]
- Gross, A.E.; Johannes, R.S.; Gupta, V.; Tabak, Y.P.; Srinivasan, A.; Bleasdale, S.C. The Effect of a Piperacillin/Tazobactam Shortage on Antimicrobial Prescribing and Clostridium difficile Risk in 88 US Medical Centers. Clin. Infect. Dis. 2017, 65, 613–618. [Google Scholar] [CrossRef]
- Moriyama, Y.; Ishikane, M.; Mezaki, K.; Ohmagari, N. Comparison of Penicillins (Penicillin G and Ampicillin) and Cefazolin as a Definitive Therapy against Penicillin-Susceptible Staphylococcus aureus (PSSA) Bacteremia in Japan: A Retrospective Cohort Study. J. Infect. Chemother. 2020, 26, 358–362. [Google Scholar] [CrossRef]
- Henderson, A.; Harris, P.; Hartel, G.; Paterson, D.; Turnidge, J.; Davis, J.S.; Tong, S.Y.C. Benzylpenicillin versus Flucloxacillin for Penicillin-Susceptible Staphylococcus aureus Bloodstream Infections from a Large Retrospective Cohort Study. Int. J. Antimicrob. Agents 2019, 54, 491–495. [Google Scholar] [CrossRef]
- Alston, W.K.; Ahern, J.W. Increase in the Rate of Nosocomial Clostridium Difficile-Associated Diarrhoea during Shortages of Piperacillin–Tazobactam and Piperacillin. J. Antimicrob. Chemother. 2004, 53, 549–550. [Google Scholar] [CrossRef]
- Vardakas, K.Z.; Trigkidis, K.K.; Boukouvala, E.; Falagas, M.E. Clostridium Difficile Infection Following Systemic Antibiotic Administration in Randomised Controlled Trials: A Systematic Review and Meta-Analysis. Int. J. Antimicrob. Agents 2016, 48, 1–10. [Google Scholar] [CrossRef] [PubMed]
- Lee, C.E.; Zembower, T.R.; Fotis, M.A.; Postelnick, M.J.; Greenberger, P.A.; Peterson, L.R.; Noskin, G.A. The Incidence of Antimicrobial Allergies in Hospitalized Patients: Implications Regarding Prescribing Patterns and Emerging Bacterial Resistance. Arch. Intern. Med. 2000, 160, 2819. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Macy, E. Penicillin and Beta-Lactam Allergy: Epidemiology and Diagnosis. Curr. Allergy Asthma. Rep. 2014, 14, 476. [Google Scholar] [CrossRef] [PubMed]
- Beganovic, M.; Cusumano, J.A.; Lopes, V.; LaPlante, K.L.; Caffrey, A.R. Comparative Effectiveness of Exclusive Exposure to Nafcillin or Oxacillin, Cefazolin, Piperacillin/Tazobactam, and Fluoroquinolones Among a National Cohort of Veterans with Methicillin-Susceptible Staphylococcus aureus Bloodstream Infection. Open Forum Infect. Dis. 2019, 6, ofz270. [Google Scholar] [CrossRef] [PubMed]
- Bader, M.S. Staphylococcus aureus Bacteremia in Older Adults: Predictors of 7-Day Mortality and Infection with a Methicillin-Resistant Strain. Infect. Control Hosp. Epidemiol. 2006, 27, 1219–1225. [Google Scholar] [CrossRef] [PubMed]
- Sprung, C.L.; Peduzzi, P.N.; Shatney, C.H.; Schein, R.M.; Wilson, M.F.; Sheagren, J.N.; Hinshaw, L.B. Impact of Encephalopathy on Mortality in the Sepsis Syndrome. The Veterans Administration Systemic Sepsis Cooperative Study Group. Crit. Care Med. 1990, 18, 801–806. [Google Scholar] [CrossRef]
Pre-Shortage Group (n = 39) | Post-Shortage Group (n = 36) | p | |
---|---|---|---|
Male sex, n (%) | 27 (69) | 23 (64) | 0.81 |
Age, median years (IQR) | 69 (56–80) | 69 (54–75) | 0.54 |
Hospitalization ward at the onset of bacteremia, n (%) | |||
Medical ward | 22 (56) | 13 (36) | 0.13 |
Surgical ward | 14 (36) | 15 (42) | 0.78 |
Intensive care unit | 3 (8) | 8 (22) | 0.11 |
Hospital stay before the onset of bacteremia, median days (IQR) | 3 (0–20) | 3 (0–21) | 0.63 |
Immunosuppression, n (%) | |||
Immunosuppressive treatment | 1 (3) | 4 (11) | 0.19 |
Corticosteroid treatment | 11 (28) | 7 (19) | 0.54 |
Chemotherapy | 7 (18) | 2 (6) | 0.16 |
Recent surgery, n (%) | 4 (10) | 4 (11) | 1 |
Hemodialysis, n (%) | 3 (8) | 5 (14) | 0.47 |
Invasive devices, n (%) | |||
Central venous catheter | 8 (21) | 13 (36) | 0.21 |
Urinary tract infections | 6 (15) | 6 (17) | 1 |
Mechanical ventilation | 1 (3) | 1 (3) | 1 |
Vasopressor use, n (%) | 7 (18) | 6 (17) | 1 |
qSOFA score ≥2, n (%) | 12 (31) | 14 (39) | 0.62 |
Altered mental status, n (%) | 4 (10) | 7 (19) | 0.34 |
Source of bacteremia, n (%) | |||
Catheter-related bloodstream infection | 10 (26) | 12 (33) | 0.63 |
Skin and soft tissue infection | 7 (18) | 6 (17) | 1 |
Bone infection | 3 (8) | 5 (14) | 0.47 |
Infectious endocarditis | 4 (10) | 2 (6) | 0.68 |
Respiratory tract infection | 2 (5) | 2 (6) | 1 |
Febrile neutropenia | 3 (8) | 0 (0) | 0.24 |
Unknown | 4 (10) | 6 (17) | 0.51 |
Others | 5 (13) | 2 (6) | 0.43 |
Susceptibility to ampicillin, n (%) | 17 (44) | 20 (56) | 0.42 |
Empirical antibiotic therapy, n (%) | |||
Ampicillin/sulbactam | 4 (10) | 11 (31) | 0.042 |
Piperacillin/tazobactam | 8 (21) | 6 (17) | 0.9 |
Cefazolin | 12 (31) | 3 (8) | 0.021 |
Cefotiam | 0 (0) | 3 (8) | 0.11 |
Meropenem | 1 (3) | 2 (6) | 0.61 |
Vancomycin | 19 (49) | 13 (36) | 0.071 |
Daptomycin | 3 (8) | 1 (3) | 0.62 |
Linezolid | 0 (0) | 1 (3) | 0.48 |
Pre-Shortage Group (n = 39) | Post-Shortage Group (n = 36) | p | |
---|---|---|---|
Time to fever resolution, median days (IQR) | 2 (1–4) | 3 (1–4) | 0.98 |
Time to WBC count normalization, median days (IQR) | 4 (0–13) | 2 (0–7) | 0.28 |
Time to detect negative blood culture results, median days (IQR) | 5 (3–7) | 4 (3–5) | 0.07 |
Persistent bacteremia (≥7 days), n (%) | 3 (8) | 0 (0) | 0.24 |
Alternative antibiotic therapy for presumed treatment failure, n (%) | 6 (15) | 10 (28) | 0.31 |
Time to initial antibiotic therapy, median days (IQR) | 0 (0–1) | 0 (0–0) | 0.95 |
Total duration of antibiotic therapy, median days (IQR) | 22 (16–35) | 17 (15–33) | 0.46 |
Hospital length after the onset of bacteremia until discharge, median days (IQR) | 35 (22–59) | 32 (19–46) | 0.68 |
Readmission within 90 days after discharge, n (%) | 7 (18) | 7 (19) | 1 |
Treatment failure, n (%) | 7 (18) | 11 (31) | 0.31 |
Daily antimicrobial cost, median USD (IQR) | 8 (5–17) | 11 (4–20) | 0.46 |
Adverse drug reactions, n (%) | |||
Clostridioides difficile infection | 1 (3) | 1 (3) | 1 |
Diarrhea | 6 (15) | 5 (14) | 1 |
Skin rash | 1 (3) | 1 (3) | 1 |
Definitive antibiotic therapy, n (%) | |||
Benzylpenicillin | 0 (0) | 7 (19) | 0.004 |
Ampicillin | 2 (5) | 6 (17) | 0.14 |
Ampicillin/sulbactam | 0 (0) | 2 (6) | 0.23 |
Piperacillin/tazobactam | 2 (5) | 7 (19) | 0.08 |
Cefazolin | 32 (82) | 19 (53) | 0.014 |
Cefotiam | 0 (0) | 1 (3) | 0.48 |
Vancomycin | 5 (13) | 3 (8) | 0.71 |
Linezolid | 0 (0) | 1 (3) | 0.48 |
Treatment Success (n = 57) | Treatment Failure (n = 18) | p | Adjusted OR (95% CI) | p | |
---|---|---|---|---|---|
Male sex, n (%) | 36 (63) | 14 (78) | 0.39 | ||
Age, median years (IQR) | 69 (56–76) | 69 (56–80) | 0.44 | ||
Admission to intensive care unit, n (%) | 7 (12) | 4 (22) | 0.51 | ||
Vasopressor use, n (%) | 6 (11) | 7 (39) | 0.016 | 1.67 (0.30–9.28) | 0.56 |
Altered mental status, n (%) | 3 (5) | 8 (44) | <0.001 | 12.7 (2.24–71.9) | 0.004 |
qSOFA score ≥2, n (%) | 17 (30) | 9 (50) | 0.19 | ||
Ampicillin-resistant MSSA, n (%) | 30 (53) | 8 (44) | 0.74 | ||
Unknown source of bacteremia, n (%) | 8 (14) | 2 (11) | 1 | ||
Shortage of cefazolin, n (%) | 32 (56) | 11 (61) | 0.31 | ||
Empirical antibiotic therapy, n (%) | |||||
Ampicillin/sulbactam | 11 (9) | 4 (22) | 0.75 | ||
Piperacillin/tazobactam | 11 (19) | 3 (17) | 1 | ||
Cefazolin | 12 (21) | 3 (17) | 0.25 | ||
Vancomycin | 26 (46) | 6 (33) | 0.23 | ||
Definitive antibiotic therapy, n (%) | |||||
Piperacillin/tazobactam | 2 (4) | 7 (39) | <0.001 | 17 (2.61–111) | 0.003 |
Cefazolin | 41 (72) | 10 (56) | 0.31 | ||
Vancomycin | 5 (9) | 3 (17) | 0.39 |
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Uda, A.; Onuma, K.; Shigemura, K.; Kitagawa, K.; Yan, Y.; Osawa, K.; Yano, I.; Miyara, T. Impact of Cefazolin Shortage on Clinical Outcomes of Adult Patients with Bacteremia Caused by Methicillin-Susceptible Staphylococcus aureus in a Tertiary Care University Hospital. Antibiotics 2021, 10, 1247. https://doi.org/10.3390/antibiotics10101247
Uda A, Onuma K, Shigemura K, Kitagawa K, Yan Y, Osawa K, Yano I, Miyara T. Impact of Cefazolin Shortage on Clinical Outcomes of Adult Patients with Bacteremia Caused by Methicillin-Susceptible Staphylococcus aureus in a Tertiary Care University Hospital. Antibiotics. 2021; 10(10):1247. https://doi.org/10.3390/antibiotics10101247
Chicago/Turabian StyleUda, Atsushi, Kenichiro Onuma, Katsumi Shigemura, Koichi Kitagawa, Yonmin Yan, Kayo Osawa, Ikuko Yano, and Takayuki Miyara. 2021. "Impact of Cefazolin Shortage on Clinical Outcomes of Adult Patients with Bacteremia Caused by Methicillin-Susceptible Staphylococcus aureus in a Tertiary Care University Hospital" Antibiotics 10, no. 10: 1247. https://doi.org/10.3390/antibiotics10101247
APA StyleUda, A., Onuma, K., Shigemura, K., Kitagawa, K., Yan, Y., Osawa, K., Yano, I., & Miyara, T. (2021). Impact of Cefazolin Shortage on Clinical Outcomes of Adult Patients with Bacteremia Caused by Methicillin-Susceptible Staphylococcus aureus in a Tertiary Care University Hospital. Antibiotics, 10(10), 1247. https://doi.org/10.3390/antibiotics10101247