Effective Antimicrobial Prophylaxis in Surgery: The Relevance and Role of Pharmacokinetics-Pharmacodynamics
Abstract
:1. Introduction
2. Dose–Response Relationship in Cefazolin Prophylaxis
Study | Study Design | Surgery (Number of Patients, Years of Enrollment) | Key Findings Regarding Cefazolin Dose and SSI |
---|---|---|---|
Cies et al., 2012 [25] | Subgroup analysis of weight-based cefazolin dosing and MSSA SSI in pediatrics (mean 12.8 years, range 3–19 years), using data from a retrospective single-center, case–control study (n = 105 and 212 controls) of BMI as a risk factor for SSI within 30 days or 1 year if instrumentation placed. 1 | Pediatric clean orthopedic surgery (n = 200, 2002–2005) |
|
Abdel Jalil et al., 2017 [26] | Prospective observational, single-center study of the frequency of SSI within 30 days and risk factors for infection including noncompliance with a new institutional guideline to use 2 g instead of 1 g of cefazolin preoperatively within 1 h for patients <120 kg. | Caesarean surgery (n = 861, 2015–2016) |
|
Rondon et al., 2018 [27] | Retrospective single-center study of cefazolin underdosing and the risk of PJI within 1 year, where underdosing was defined as cefazolin <1 g for any patient, <2 g for those between 60 kg and 120 kg, or <3 g for those ≥120 kg. 3 | Total joint arthroplasty (n = 17,393, 2005–2017) |
|
Morris et al., 2020 [28] | Retrospective study of the relationship between body weight, cefazolin dose, and SSI within 90 days, using data from a national (New Zealand), prospective surveillance and quality improvement programme, and where the recommended dose was cefazolin 1 g for patients ≥80 kg or <3 g for those ≥120 kg. 4 | Knee or hip arthroplasty (n = 38,288, 2013–2017) |
|
Karamian et al., 2022 [29] | Retrospective single-center cohort study of risk factors for SSI within 90 days, where adequate cefazolin dosing was defined as cefazolin 1 g for patients <60 kg, 2 g for those from 60 to 120 kg, and 3 g for those >120 kg. 5 | Cervical or lumbar spinal fusion (n = 2643, 2000–2020) |
|
3. Antibiotic Concentration–Response (SSI) Relationship in SAP
Study | Study Design | Antibiotic 1 | Surgery | Measured Antibiotic Concs (Analytical Assay) | Number of SSI Cases and Comparators or Controls 2 | Key Findings Regarding Antibiotic Concentration and SSI |
---|---|---|---|---|---|---|
Zelenitsky et al., 2002 [31] | PKPD subgroup analysis in a prospective double-blinded trial of a single-dose vs. multiple-dose regimen of gentamicin and metronidazole prophylaxis (n = 146) [32]. 3 | Gentamicin | Colorectal surgery | Total serum concs at least 30 min after the preoperative dose and postsurgery in recovery (fluorescence immunoassay) | 33 superficial SSIs and 10 deep SSI within 30 days vs. 91 without infection |
|
Zelenitsky et al., 2018 [33] | PKPD subgroup analysis in a prospective non-interventional PK study of cefazolin prophylaxis (n = 55) [34]. 6 | Cefazolin | CABG, cardiac valve repair or replacement 7 | Total and unbound plasma concs 30 min after the preoperative dose, prior to redosing, and within 15 min of wound closure (HPLC-tandem mass spectrometry) | 8 superficial SSIs within 30 days vs. 32 without infection |
|
Albacker et al., 2022 [35] | Prospective PK study of cefuroxime prophylaxis. 9 | Cefuroxime | CABG 7 | Total serum concs immediately before incision, before and 1 h after starting CPB, and before skin closure (analytical assay not described) | 14 SSIs (superficial within 30 days and deep/organ space within 90 days) vs. 64 without infection |
|
Takayama et al., 2022 [36] | Prospective PK study of cefmetazole prophylaxis. 11 | Cefmetazole | Colectomy (laparoscopic), proctectomy | Total serum concs at the time of incision, intestinal resection, redosing, and skin closure, and whole adipose tissue concs at the time of incision and skin closure (HPLC) | 7 superficial SSIs, 2 deep SSIs, and 4 organ space SSIs within 30 days vs. 92 without infection |
|
Sheikh et al., 2022 [40] | Prospective PK study of ceftriaxone prophylaxis in pediatrics (mean 6.1 years, range 2–12 years). 12 | Ceftriaxone | Pediatric clean or clean-contaminated surgery (multiple) | Total serum and whole adipose tissue concs simultaneously at the time of incision, mid surgery, and wound closure (HPLC) | 3 SSIs vs. 47 without infection (surveillance period not described) |
|
Sheikh et al., 2023 [41] | Prospective PK study of ceftriaxone prophylaxis. 14 | Ceftriaxone | Spinal surgery | Total serum and whole adipose tissue concs simultaneously at the time of incision, mid surgery, and wound closure (HPLC) | 4 SSIs vs. 46 without SSI (surveillance period not described) |
|
Byers et al., 2022 [42] | PK subgroup analysis in a retrospective study of extended courses of antimicrobial prophylaxis postsurgery (n = 184). 15 | Cefazolin | Megaprosthetic reconstruction | Whole tissue concs in cortical bone and adjacent skeletal muscle from punch biopsies collected during surgery (HPLC-tandem mass spectrometry) | 5 PJIs within 1 year vs. 5 procedure-matched controls without infection |
|
4. Relevance and Role of PKPD in SAP
4.1. Antimicrobial PKPD and Monte Carlo Simulations
4.2. PKPD Considerations for Improving Cefazolin Prophylaxis
4.2.1. Pharmacokinetics of Cefazolin Prophylaxis
4.2.2. Cefazolin Prophylaxis Dose and Obesity
4.2.3. Preincision Timing of Cefazolin Prophylaxis
4.2.4. Redosing Cefazolin Prophylaxis during Surgery
4.2.5. Conclusions
5. Materials and Methods
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
adjDW | Adjusted dosing weight |
ASA | American Society of Anesthesiologists score |
AUC | Area under the curve |
AUC/MIC | AUC over 24 h divided by the minimum inhibitory concentration |
BMI | Body mass index |
CABG | Coronary artery bypass grafting |
CART | Classification and regression tree (analysis) |
CCI | Charlson comorbidity index |
CI | Confidence interval |
Cmax | Maximum concentration |
Cmax/MIC | Maximum concentration divided by the minimum inhibitory concentration |
CPB | Cardiopulmonary bypass |
CTA | Cumulative target attainment |
ƒ | Free or unbound (i.e., not bound to protein) |
FTA | Fractional target attainment |
HPLC | High-performance liquid chromatography |
MIC | Minimum inhibitory concentration |
MSSA | Methicillin-susceptible Staphylococcus aureus |
OR | Odds ratio |
PD | Pharmacodynamic |
PJI | Prosthetic joint infection |
PK | Pharmacokinetic |
PKPD | Pharmacokinetic-pharmacodynamic |
ROC | Receiver operating characteristic (curve) |
SAP | Surgical antimicrobial prophylaxis |
%T>MIC | Percentage of the dosing interval that concentrations exceed the minimum inhibitory concentration |
Tmax | Time to maximum concentration |
t½ | Half-life |
Vd | Volume of distribution |
References
- Badia, J.M.; Casey, A.L.; Petrosillo, N.; Hudson, P.M.; Mitchell, S.A.; Crosby, C. Impact of Surgical Site Infection on Healthcare Costs and Patient Outcomes: A Systematic Review in Six European Countries. J. Hosp. Infect. 2017, 96, 1–15. [Google Scholar] [CrossRef] [PubMed]
- Eckmann, C.; Kramer, A.; Assadian, O.; Flessa, S.; Huebner, C.; Michnacs, K.; Muehlendyck, C.; Podolski, K.M.; Wilke, M.; Heinlein, W.; et al. Clinical and Economic Burden of Surgical Site Infections in Inpatient Care in Germany: A Retrospective, Cross-Sectional Analysis from 79 Hospitals. PLoS ONE 2022, 17, e0275970. [Google Scholar] [CrossRef] [PubMed]
- Gillespie, B.M.; Harbeck, E.; Rattray, M.; Liang, R.; Walker, R.; Latimer, S.; Thalib, L.; Andersson, A.E.; Griffin, B.; Ware, R.; et al. Worldwide Incidence of Surgical Site Infections in General Surgical Patients: A Systematic Review and Meta-Analysis of 488,594 Patients. Int. J. Surg. 2021, 95, 106136. [Google Scholar] [CrossRef] [PubMed]
- Umscheid, C.A.; Mitchell, M.D.; Doshi, J.A.; Agarwal, R.; Williams, K.; Brennan, P.J. Estimating the Proportion of Healthcare-Associated Infections That Are Reasonably Preventable and the Related Mortality and Costs. Infect. Control Hosp. Epidemiol. 2011, 32, 101–114. [Google Scholar] [CrossRef] [PubMed]
- Schreiber, P.W.; Sax, H.; Wolfensberger, A.; Clack, L.; Kuster, S.P. The Preventable Proportion of Healthcare-Associated Infections 2005–2016: Systematic Review and Meta-Analysis. Infect. Control Hosp. Epidemiol. 2018, 39, 1277–1295. [Google Scholar] [CrossRef]
- Bowater, R.J.; Stirling, S.A.; Lilford, R.J. Is Antibiotic Prophylaxis in Surgery a Generally Effective Intervention?: Testing a Generic Hypothesis Over a Set of Meta-Analyses. Ann. Surg. 2009, 249, 551–556. [Google Scholar] [CrossRef]
- Menz, B.D.; Charani, E.; Gordon, D.L.; Leather, A.J.; Moonesinghe, S.R.; Phillips, C.J. Surgical Antibiotic Prophylaxis in an Era of Antibiotic Resistance: Common Resistant Bacteria and Wider Considerations for Practice. IDR 2021, 14, 5235–5252. [Google Scholar] [CrossRef]
- Bratzler, D.W.; Dellinger, E.P.; Olsen, K.M.; Perl, T.M.; Auwaerter, P.G.; Bolon, M.K.; Fish, D.N.; Napolitano, L.M.; Sawyer, R.G.; Slain, D.; et al. Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery. Am. J. Health-Syst. Pharm. 2013, 70, 195–283. [Google Scholar] [CrossRef]
- Rodríguez-Gascón, A.; Solinís, M.Á.; Isla, A. The Role of PK/PD Analysis in the Development and Evaluation of Antimicrobials. Pharmaceutics 2021, 13, 833. [Google Scholar] [CrossRef]
- Rao, G.G.; Landersdorfer, C.B. Antibiotic Pharmacokinetic/Pharmacodynamic Modelling: MIC, Pharmacodynamic Indices and Beyond. Int. J. Antimicrob. Agents 2021, 58, 106368. [Google Scholar] [CrossRef]
- Velkov, T.; Bergen, P.J.; Lora-Tamayo, J.; Landersdorfer, C.B.; Li, J. PK/PD Models in Antibacterial Development. Curr. Opin. Microbiol. 2013, 16, 573–579. [Google Scholar] [CrossRef]
- Rizk, M.L.; Bhavnani, S.M.; Drusano, G.; Dane, A.; Eakin, A.E.; Guina, T.; Jang, S.H.; Tomayko, J.F.; Wang, J.; Zhuang, L.; et al. Considerations for Dose Selection and Clinical Pharmacokinetics/Pharmacodynamics for the Development of Antibacterial Agents. Antimicrob. Agents Chemother. 2019, 63, e02309-18. [Google Scholar] [CrossRef]
- Li, J.; Lovern, M.; Riccobene, T.; Carrothers, T.J.; Newell, P.; Das, S.; Talley, A.K.; Tawadrous, M. Considerations in the Selection of Renal Dosage Adjustments for Patients with Serious Infections and Lessons Learned from the Development of Ceftazidime-Avibactam. Antimicrob. Agents Chemother. 2020, 64, e02105-19. [Google Scholar] [CrossRef] [PubMed]
- Sumi, C.D.; Heffernan, A.J.; Lipman, J.; Roberts, J.A.; Sime, F.B. What Antibiotic Exposures Are Required to Suppress the Emergence of Resistance for Gram-Negative Bacteria? A Systematic Review. Clin. Pharmacokinet. 2019, 58, 1407–1443. [Google Scholar] [CrossRef] [PubMed]
- Crass, R.L.; Cojutti, P.G.; Pai, M.P.; Pea, F. Reappraisal of Linezolid Dosing in Renal Impairment To Improve Safety. Antimicrob. Agents Chemother. 2019, 63, e00605-19. [Google Scholar] [CrossRef] [PubMed]
- Zelenitsky, S.A.; Ariano, R.E. An Updated Vancomycin Dosing Protocol for Initiating Therapy in Patients Undergoing Intermittent High-Flux Hemodialysis. Am. J. Health-Syst. Pharm. 2022, 79, 1006–1010. [Google Scholar] [CrossRef] [PubMed]
- Parker, S.L.; Abdul-Aziz, M.H.; Roberts, J.A. The Role of Antibiotic Pharmacokinetic Studies Performed Post-Licensing. Int. J. Antimicrob. Agents 2020, 56, 106165. [Google Scholar] [CrossRef]
- Mouton, J.W.; Brown, D.F.J.; Apfalter, P.; Cantón, R.; Giske, C.G.; Ivanova, M.; MacGowan, A.P.; Rodloff, A.; Soussy, C.-J.; Steinbakk, M.; et al. The Role of Pharmacokinetics/Pharmacodynamics in Setting Clinical MIC Breakpoints: The EUCAST Approach. Clin. Microbiol. Infect. 2012, 18, E37–E45. [Google Scholar] [CrossRef] [PubMed]
- Ambrose, P.G.; Bhavnani, S.M.; Andes, D.R.; Bradley, J.S.; Flamm, R.K.; Pogue, J.M.; Jones, R.N. Old In Vitro Antimicrobial Breakpoints Are Misleading Stewardship Efforts, Delaying Adoption of Innovative Therapies, and Harming Patients. Open Forum Infect. Dis. 2020, 7, ofaa084. [Google Scholar] [CrossRef]
- Berríos-Torres, S.I.; Umscheid, C.A.; Bratzler, D.W.; Leas, B.; Stone, E.C.; Kelz, R.R.; Reinke, C.E.; Morgan, S.; Solomkin, J.S.; Mazuski, J.E.; et al. Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection, 2017. JAMA Surg. 2017, 152, 784–791. [Google Scholar] [CrossRef] [PubMed]
- World Health Organization. Global Guidelines for the Prevention of Surgical Site Infection, 2nd ed.; World Health Organization: Geneva, Switzerland, 2018; ISBN 978-92-4-155047-5. [Google Scholar]
- Calderwood, M.S.; Anderson, D.J.; Bratzler, D.W.; Dellinger, E.P.; Garcia-Houchins, S.; Maragakis, L.L.; Nyquist, A.-C.; Perkins, K.M.; Preas, M.A.; Saiman, L.; et al. Strategies to Prevent Surgical Site Infections in Acute-Care Hospitals: 2022 Update. Infect. Control Hosp. Epidemiol. 2023, 44, 695–720. [Google Scholar] [CrossRef] [PubMed]
- Winfield, R.D.; Reese, S.; Bochicchio, K.; Mazuski, J.E.; Bochicchio, G.V. Obesity and the Risk for Surgical Site Infection in Abdominal Surgery. Am. Surg. 2016, 82, 331–336. [Google Scholar] [CrossRef] [PubMed]
- Thelwall, S.; Harrington, P.; Sheridan, E.; Lamagni, T. Impact of Obesity on the Risk of Wound Infection Following Surgery: Results from a Nationwide Prospective Multicentre Cohort Study in England. Clin. Microbiol. Infect. 2015, 21, 1008.e1–1008.e8. [Google Scholar] [CrossRef]
- Cies, J.J.; Chan, S.; Hossain, J.; Brenn, B.R.; Pentima, M.C.D. Influence of Body Mass Index and Antibiotic Dose on the Risk of Surgical Site Infections in Pediatric Clean Orthopedic Surgery. Dep. Anesthesiol. Fac. Pap. 2012, 13, 371–376. [Google Scholar] [CrossRef] [PubMed]
- Abdel Jalil, M.H.; Abu Hammour, K.; Alsous, M.; Awad, W.; Hadadden, R.; Bakri, F.; Fram, K. Surgical Site Infections Following Caesarean Operations at a Jordanian Teaching Hospital: Frequency and Implicated Factors. Sci. Rep. 2017, 7, 12210. [Google Scholar] [CrossRef]
- Rondon, A.J.; Kheir, M.M.; Tan, T.L.; Shohat, N.; Greenky, M.R.; Parvizi, J. Cefazolin Prophylaxis for Total Joint Arthroplasty: Obese Patients Are Frequently Underdosed and at Increased Risk of Periprosthetic Joint Infection. J. Arthroplast. 2018, 33, 3551–3554. [Google Scholar] [CrossRef]
- Morris, A.J.; Roberts, S.A.; Grae, N.; Frampton, C.M. Surgical Site Infection Rate Is Higher Following Hip and Knee Arthroplasty When Cefazolin Is Underdosed. Am. J. Health-Syst. Pharm. 2020, 77, 434–440. [Google Scholar] [CrossRef]
- Karamian, B.A.; Toci, G.R.; Lambrechts, M.J.; Siegel, N.; Sherman, M.; Canseco, J.A.; Hilibrand, A.S.; Kepler, C.K.; Vaccaro, A.R.; Schroeder, G.D. Cefazolin Prophylaxis in Spine Surgery: Patients Are Frequently Underdosed and at Increased Risk for Infection. Spine J. 2022, 22, 1442–1450. [Google Scholar] [CrossRef]
- Goldmann, D.A.; Hopkins, C.C.; Karchmer, A.W.; Abel, R.M.; McEnany, M.T.; Akins, C.; Buckley, M.J.; Moellering, R.C. Cephalothin Prophylaxis in Cardiac Valve Surgery. A Prospective, Double-Blind Comparison of Two-Day and Six-Day Regimens. J. Thorac. Cardiovasc. Surg. 1977, 73, 470–479. [Google Scholar] [CrossRef]
- Zelenitsky, S.A.; Ariano, R.E.; Harding, G.K.M.; Silverman, R.E. Antibiotic Pharmacodynamics in Surgical Prophylaxis: An Association between Intraoperative Antibiotic Concentrations and Efficacy. Antimicrob. Agents Chemother. 2002, 46, 3026–3030. [Google Scholar] [CrossRef]
- Zelenitsky, S.A.; Silverman, R.E.; Duckworth, H.; Harding, G.K.M. A Prospective, Randomized, Double-Blind Studyof Single High Dose versus Multiple Standard Dose Gentamicin Both in Combination Withmetronidazole for Colorectal Surgicalprophylaxis. J. Hosp. Infect. 2000, 46, 135–140. [Google Scholar] [CrossRef]
- Zelenitsky, S.A.; Calic, D.; Arora, R.C.; Grocott, H.P.; Lakowski, T.M.; Lillico, R.; Ariano, R.E. Antimicrobial Prophylaxis for Patients Undergoing Cardiac Surgery: Intraoperative Cefazolin Concentrations and Sternal Wound Infections. Antimicrob. Agents Chemother. 2018, 62, e01360-18. [Google Scholar] [CrossRef] [PubMed]
- Calic, D.; Ariano, R.E.; Arora, R.C.; Grocott, H.P.; Lakowski, T.M.; Lillico, R.; Zelenitsky, S.A. Evaluation of Cefazolin Antimicrobial Prophylaxis during Cardiac Surgery with Cardiopulmonary Bypass. J. Antimicrob. Chemother. 2018, 73, 768–771. [Google Scholar] [CrossRef] [PubMed]
- Albacker, T.B.; Alqattan, H.; Alqahtani, S.A.; Alamro, S.; Alsuwaidan, N.; Alaloola, A.; Eldemerdash, A.; Bakir, B. Serum Level of Prophylactic Antibiotics in Cardiac Surgery and Its Implication on Surgical Site Infection (SSI). Am. J. Cardiovasc. Dis. 2022, 12, 233–239. [Google Scholar] [PubMed]
- Takayama, Y.; Komatsu, T.; Nakamura, T.; Tomoda, Y.; Toda, M.; Miura, H.; Sato, T.; Atsuda, K.; Okamoto, H.; Hanaki, H. Association of Serum and Fat Tissue Antibiotic Concentrations with Surgical Site Infections in Lower Gastrointestinal Surgery. Surgery 2022, 171, 1000–1005. [Google Scholar] [CrossRef] [PubMed]
- Mouton, J.W.; Theuretzbacher, U.; Craig, W.A.; Tulkens, P.M.; Derendorf, H.; Cars, O. Tissue Concentrations: Do We Ever Learn? J. Antimicrob. Chemother. 2007, 61, 235–237. [Google Scholar] [CrossRef] [PubMed]
- Jager, N.G.L.; Van Hest, R.M.; Lipman, J.; Roberts, J.A.; Cotta, M.O. Antibiotic Exposure at the Site of Infection: Principles and Assessment of Tissue Penetration. Expert Rev. Clin. Pharmacol. 2019, 12, 623–634. [Google Scholar] [CrossRef]
- Dadhwal, U.S. A Few Comments on “Association of Serum and Fat Tissue Antibiotic Concentrations with Surgical Site Infections in Lower Gastrointestinal Surgery” by Yoko Takayama et al. Surgery 2023, 173, 558–559. [Google Scholar] [CrossRef] [PubMed]
- Sheikh, S.; Majoka, R.; Tripathi, C.D.; Verma, V.; Bagga, D.; Karim, B.A.; Meshram, G.G. Variability in the Serum and Tissue Concentrations of Pre-Incisional Ceftriaxone for Surgery in Paediatric Population and Outcome of Surgical-Site Infections; An Open Labelled, Prospective, Non-Randomized, Analytical Study. Curr. Res. Pharmacol. Drug Discov. 2022, 3, 100082. [Google Scholar] [CrossRef]
- Sheikh, S.; Swapnil, K.; Tripathi, C.D.; Meshram, G.G.; Karim, B.A. Intra-Operative Drug Level Monitoring of Pre-Operative Antibiotic for Surgical Prophylaxis in the Patients of Elective Spinal Surgery. J. Basic Clin. Physiol. Pharmacol. 2023, 34, 797–804. [Google Scholar] [CrossRef]
- Byers, I.S.; Turner, N.A.; Levine, N.L.; Lazarides, A.L.; Evans, D.R.; Spasojevic, I.; Fan, P.; Jung, S.-H.; Gao, J.; Visgauss, J.D.; et al. Antibiotic Prophylaxis for Megaprosthetic Reconstructions: Drug and Dosing May Matter More than Duration. Antimicrob. Agents Chemother. 2022, 66, e00140-22. [Google Scholar] [CrossRef]
- Bulitta, J.B.; Hope, W.W.; Eakin, A.E.; Guina, T.; Tam, V.H.; Louie, A.; Drusano, G.L.; Hoover, J.L. Generating Robust and Informative Nonclinical In Vitro and In Vivo Bacterial Infection Model Efficacy Data To Support Translation to Humans. Antimicrob. Agents Chemother. 2019, 63, e02307-18. [Google Scholar] [CrossRef] [PubMed]
- Tängdén, T.; Lundberg, C.V.; Friberg, L.E.; Huttner, A. How Preclinical Infection Models Help Define Antibiotic Doses in the Clinic. Int. J. Antimicrob. Agents 2020, 56, 106008. [Google Scholar] [CrossRef] [PubMed]
- Kowalska-Krochmal, B.; Dudek-Wicher, R. The Minimum Inhibitory Concentration of Antibiotics: Methods, Interpretation, Clinical Relevance. Pathogens 2021, 10, 165. [Google Scholar] [CrossRef]
- Abdul-Aziz, M.H.; Alffenaar, J.-W.C.; Bassetti, M.; Bracht, H.; Dimopoulos, G.; Marriott, D.; Neely, M.N.; Paiva, J.-A.; Pea, F.; Sjovall, F.; et al. Antimicrobial Therapeutic Drug Monitoring in Critically Ill Adult Patients: A Position Paper#. Intensive Care Med. 2020, 46, 1127–1153. [Google Scholar] [CrossRef]
- Abdul–Aziz, M.H.; Brady, K.; Cotta, M.O.; Roberts, J.A. Therapeutic Drug Monitoring of Antibiotics: Defining the Therapeutic Range. Ther. Drug Monit. 2022, 44, 19–31. [Google Scholar] [CrossRef] [PubMed]
- Chua, H.C.; Tam, V.H. Optimizing Clinical Outcomes Through Rational Dosing Strategies: Roles of Pharmacokinetic/Pharmacodynamic Modeling Tools. Open Forum Infect. Dis. 2022, 9, ofac626. [Google Scholar] [CrossRef]
- De Velde, F.; Mouton, J.W.; De Winter, B.C.M.; Van Gelder, T.; Koch, B.C.P. Clinical Applications of Population Pharmacokinetic Models of Antibiotics: Challenges and Perspectives. Pharmacol. Res. 2018, 134, 280–288. [Google Scholar] [CrossRef]
- Sartelli, M.; Boermeester, M.A.; Cainzos, M.; Coccolini, F.; De Jonge, S.W.; Rasa, K.; Dellinger, E.P.; McNamara, D.A.; Fry, D.E.; Cui, Y.; et al. Six Long-Standing Questions about Antibiotic Prophylaxis in Surgery. Antibiotics 2023, 12, 908. [Google Scholar] [CrossRef]
- Grayson, M.L.; Cosgrove, S.; Crowe, S.; Hope, W.; McCarthy, J.; Mills, J.; Mouton, J.W.; Paterson, D. (Eds.) Kucers’ the Use of Antibiotics: A Clinical Review of Antibacterial, Antifungal, Antiparasitic, and Antiviral Drugs, 7th ed.; CRC Press: Boca Raton, FL, USA, 2017; ISBN 978-1-4987-4796-7. [Google Scholar]
- Thabit, A.K.; Fatani, D.F.; Bamakhrama, M.S.; Barnawi, O.A.; Basudan, L.O.; Alhejaili, S.F. Antibiotic Penetration into Bone and Joints: An Updated Review. Int. J. Infect. Dis. 2019, 81, 128–136. [Google Scholar] [CrossRef]
- Mannarino, M.; Montreuil, J.; Tanzer, M.; Hart, A. Local Tissue Concentrations of Cefazolin during Total Joint Arthroplasty: A Systematic Review. Can. J. Surg. 2023, 66, E415–E421. [Google Scholar] [CrossRef]
- Douglas, A.; Udy, A.A.; Wallis, S.C.; Jarrett, P.; Stuart, J.; Lassig-Smith, M.; Deans, R.; Roberts, M.S.; Taraporewalla, K.; Jenkins, J.; et al. Plasma and Tissue Pharmacokinetics of Cefazolin in Patients Undergoing Elective and Semielective Abdominal Aortic Aneurysm Open Repair Surgery. Antimicrob. Agents Chemother. 2011, 55, 5238–5242. [Google Scholar] [CrossRef]
- So, W.; Kuti, J.L.; Nicolau, D.P. Population Pharmacokinetics of Cefazolin in Serum and Tissue for Patients with Complicated Skin and Soft Tissue Infections (cSSTI). Infect. Dis. Ther. 2014, 3, 269–279. [Google Scholar] [CrossRef] [PubMed]
- Palma, E.C.; Meinhardt, N.G.; Stein, A.T.; Heineck, I.; Fischer, M.I.; de Araújo, B.; Dalla Costa, T. Efficacious Cefazolin Prophylactic Dose for Morbidly Obese Women Undergoing Bariatric Surgery Based on Evidence from Subcutaneous Microdialysis and Populational Pharmacokinetic Modeling. Pharm. Res. 2018, 35, 116. [Google Scholar] [CrossRef] [PubMed]
- Cinotti, R.; Dumont, R.; Ronchi, L.; Roquilly, A.; Atthar, V.; Grégoire, M.; Planche, L.; Letessier, E.; Dailly, E.; Asehnoune, K. Cefazolin Tissue Concentrations with a Prophylactic Dose Administered before Sleeve Gastrectomy in Obese Patients: A Single Centre Study in 116 Patients. Br. J. Anaesth. 2018, 120, 1202–1208. [Google Scholar] [CrossRef] [PubMed]
- Ryan, R.L.; Jackson, D.; Hopkins, G.; Eley, V.; Christensen, R.; Van Zundert, A.A.J.; Wallis, S.C.; Lipman, J.; Parker, S.L.; Roberts, J.A. Plasma and Interstitial Fluid Pharmacokinetics of Prophylactic Cefazolin in Elective Bariatric Surgery Patients. Antimicrob. Agents Chemother. 2022, 66, e00419-22. [Google Scholar] [CrossRef] [PubMed]
- Coates, M.; Shield, A.; Peterson, G.M.; Hussain, Z. Prophylactic Cefazolin Dosing in Obesity—A Systematic Review. Obes. Surg. 2022, 32, 3138–3149. [Google Scholar] [CrossRef] [PubMed]
- Ahmadzia, H.K.; Patel, E.M.; Joshi, D.; Liao, C.; Witter, F.; Heine, R.P.; Coleman, J.S. Obstetric Surgical Site Infections: 2 Grams Compared With 3 Grams of Cefazolin in Morbidly Obese Women. Obstet. Gynecol. 2015, 126, 708–715. [Google Scholar] [CrossRef] [PubMed]
- Peppard, W.J.; Eberle, D.G.; Kugler, N.W.; Mabrey, D.M.; Weigelt, J.A. Association between Pre-Operative Cefazolin Dose and Surgical Site Infection in Obese Patients. Surg. Infect. 2017, 18, 485–490. [Google Scholar] [CrossRef]
- Hussain, Z.; Curtain, C.; Mirkazemi, C.; Gadd, K.; Peterson, G.M.; Zaidi, S.T.R. Prophylactic Cefazolin Dosing and Surgical Site Infections: Does the Dose Matter in Obese Patients? Obes. Surg. 2019, 29, 159–165. [Google Scholar] [CrossRef]
- Naik, B.I.; Roger, C.; Ikeda, K.; Todorovic, M.S.; Wallis, S.C.; Lipman, J.; Roberts, J.A. Comparative Total and Unbound Pharmacokinetics of Cefazolin Administered by Bolus versus Continuous Infusion in Patients Undergoing Major Surgery: A Randomized Controlled Trial. Br. J. Anaesth. 2017, 118, 876–882. [Google Scholar] [CrossRef] [PubMed]
- Bauer, L.A.; Edwards, W.A.D.; Dellinger, E.P.; Simonowitz, D.A. Influence of Weight on Aminoglycoside Pharmacokinetics in Normal Weight and Morbidly Obese Patients. Eur. J. Clin. Pharmacol. 1983, 24, 643–647. [Google Scholar] [CrossRef] [PubMed]
- Brill, M.J.E.; Houwink, A.P.I.; Schmidt, S.; Van Dongen, E.P.A.; Hazebroek, E.J.; Van Ramshorst, B.; Deneer, V.H.; Mouton, J.W.; Knibbe, C.A.J. Reduced Subcutaneous Tissue Distribution of Cefazolin in Morbidly Obese versus Non-Obese Patients Determined Using Clinical Microdialysis. J. Antimicrob. Chemother. 2014, 69, 715–723. [Google Scholar] [CrossRef] [PubMed]
- Hites, M.; Deprez, G.; Wolff, F.; Ickx, B.; Verleije, A.; Closset, J.; Loi, P.; Prévost, J.; Taccone, F.S.; Racapé, J.; et al. Evaluation of Total Body Weight and Body Mass Index Cut-Offs for Increased Cefazolin Dose for Surgical Prophylaxis. Int. J. Antimicrob. Agents 2016, 48, 633–640. [Google Scholar] [CrossRef]
- Classen, D.C.; Evans, R.S.; Pestotnik, S.L.; Horn, S.D.; Menlove, R.L.; Burke, J.P. The Timing of Prophylactic Administration of Antibiotics and the Risk of Surgical-Wound Infection. N. Engl. J. Med. 1992, 326, 281–286. [Google Scholar] [CrossRef]
- Steinberg, J.P.; Braun, B.I.; Hellinger, W.C.; Kusek, L.; Bozikis, M.R.; Bush, A.J.; Dellinger, E.P.; Burke, J.P.; Simmons, B.; Kritchevsky, S.B. Timing of Antimicrobial Prophylaxis and the Risk of Surgical Site Infections: Results From the Trial to Reduce Antimicrobial Prophylaxis Errors. Ann. Surg. 2009, 250, 10–16. [Google Scholar] [CrossRef]
- De Jonge, S.W.; Gans, S.L.; Atema, J.J.; Solomkin, J.S.; Dellinger, P.E.; Boermeester, M.A. Timing of Preoperative Antibiotic Prophylaxis in 54,552 Patients and the Risk of Surgical Site Infection: A Systematic Review and Meta-Analysis. Medicine 2017, 96, e6903. [Google Scholar] [CrossRef]
- Koch, C.G.; Nowicki, E.R.; Rajeswaran, J.; Gordon, S.M.; Sabik, J.F.; Blackstone, E.H. When the Timing Is Right: Antibiotic Timing and Infection after Cardiac Surgery. J. Thorac. Cardiovasc. Surg. 2012, 4, 931–937.e4. [Google Scholar] [CrossRef]
- Koch, C.G.; Li, L.; Hixson, E.; Tang, A.; Gordon, S.; Longworth, D.; Phillips, S.; Blackstone, E.; Henderson, M.J. Is It Time to Refine? An Exploration and Simulation of Optimal Antibiotic Timing in General Surgery. J. Am. Coll. Surg. 2013, 217, 628. [Google Scholar] [CrossRef]
- Sommerstein, R.; Atkinson, A.; Kuster, S.P.; Thurneysen, M.; Genoni, M.; Troillet, N.; Marschall, J.; Widmer, A.F.; Swissnoso; Balmelli, C.; et al. Antimicrobial Prophylaxis and the Prevention of Surgical Site Infection in Cardiac Surgery: An Analysis of 21,007 Patients in Switzerland†. Eur. J. Cardio-Thorac. Surg. 2019, 56, 800–806. [Google Scholar] [CrossRef]
- Weber, W.P.; Mujagic, E.; Zwahlen, M.; Bundi, M.; Hoffmann, H.; Soysal, S.D.; Kraljević, M.; Delko, T.; Von Strauss, M.; Iselin, L.; et al. Timing of Surgical Antimicrobial Prophylaxis: A Phase 3 Randomised Controlled Trial. Lancet Infect. Dis. 2017, 17, 605–614. [Google Scholar] [CrossRef]
- De Jonge, S.W.; Boldingh, Q.J.J.; Koch, A.H.; Daniels, L.; De Vries, E.N.; Spijkerman, I.J.B.; Ankum, W.M.; Kerkhoffs, G.M.M.J.; Dijkgraaf, M.G.; Hollmann, M.W.; et al. Timing of Preoperative Antibiotic Prophylaxis and Surgical Site Infection: TAPAS, An Observational Cohort Study. Ann. Surg. 2021, 274, e308–e314. [Google Scholar] [CrossRef]
- Paasch, C.; Schildberg, C.; Lünse, S.; Heisler, S.; Meyer, J.; Kirbach, J.; Kobelt, E.; Hunger, R.; Haller, I.-E.; Helmke, C.; et al. Optimal Timing for Antimicrobial Prophylaxis to Reduce Surgical Site Infections: A Retrospective Analysis of 531 Patients. Sci. Rep. 2023, 13, 9405. [Google Scholar] [CrossRef] [PubMed]
- Weber, W.P.; Marti, W.R.; Zwahlen, M.; Misteli, H.; Rosenthal, R.; Reck, S.; Fueglistaler, P.; Bolli, M.; Trampuz, A.; Oertli, D.; et al. The Timing of Surgical Antimicrobial Prophylaxis. Ann. Surg. 2008, 247, 918. [Google Scholar] [CrossRef] [PubMed]
- Himebauch, A.S.; Nicolson, S.C.; Sisko, M.; Moorthy, G.; Fuller, S.; Gaynor, J.W.; Zuppa, A.F.; Fox, E.; Kilbaugh, T.J. Skeletal Muscle and Plasma Concentrations of Cefazolin during Cardiac Surgery in Infants. J. Thorac. Cardiovasc. Surg. 2014, 148, 2634–2641. [Google Scholar] [CrossRef] [PubMed]
- Himebauch, A.S.; Sankar, W.N.; Flynn, J.M.; Sisko, M.T.; Moorthy, G.S.; Gerber, J.S.; Zuppa, A.F.; Fox, E.; Dormans, J.P.; Kilbaugh, T.J. Skeletal Muscle and Plasma Concentrations of Cefazolin during Complex Paediatric Spinal Surgery. Br. J. Anaesth. 2016, 117, 87–94. [Google Scholar] [CrossRef] [PubMed]
- Caruso, T.J.; Wang, E.Y.; Colletti, A.A.; Sharek, P.J. Intraoperative Antibiotic Redosing Compliance and the Extended Postoperative Recovery Period: Often Overlooked Areas That May Reduce Surgical Site Infections. Pediatr. Anesth. 2019, 29, 290–291. [Google Scholar] [CrossRef] [PubMed]
- Wolfhagen, N.; Boldingh, Q.J.J.; De Lange, M.; Boermeester, M.A.; De Jonge, S.W. Intraoperative Redosing of Surgical Antibiotic Prophylaxis in Addition to Preoperative Prophylaxis Versus Single-Dose Prophylaxis for the Prevention of Surgical Site Infection: A Meta-Analysis and GRADE Recommendation. Ann. Surg. 2022, 275, 1050–1057. [Google Scholar] [CrossRef] [PubMed]
- Lanoiselée, J.; Chaux, R.; Hodin, S.; Bourayou, S.; Gibert, A.; Philippot, R.; Molliex, S.; Zufferey, P.J.; Delavenne, X.; Ollier, E. Population Pharmacokinetic Model of Cefazolin in Total Hip Arthroplasty. Sci. Rep. 2021, 11, 19763. [Google Scholar] [CrossRef] [PubMed]
- Eley, V.A.; Christensen, R.; Ryan, R.; Jackson, D.; Parker, S.L.; Smith, M.; Van Zundert, A.A.; Wallis, S.C.; Lipman, J.; Roberts, J.A. Prophylactic Cefazolin Dosing in Women With Body Mass Index >35 Kg·m−2 Undergoing Cesarean Delivery: A Pharmacokinetic Study of Plasma and Interstitial Fluid. Anesth. Analg. 2020, 131, 199–207. [Google Scholar] [CrossRef]
- Shoulders, B.R.; Crow, J.R.; Davis, S.L.; Whitman, G.J.; Gavin, M.; Lester, L.; Barodka, V.; Dzintars, K. Impact of Intraoperative Continuous-Infusion Versus Intermittent Dosing of Cefazolin Therapy on the Incidence of Surgical Site Infections After Coronary Artery Bypass Grafting. Pharmacotherapy 2016, 36, 166–173. [Google Scholar] [CrossRef] [PubMed]
- Lanckohr, C.; Horn, D.; Voeller, S.; Hempel, G.; Fobker, M.; Welp, H.; Koeck, R.; Ellger, B. Pharmacokinetic Characteristics and Microbiologic Appropriateness of Cefazolin for Perioperative Antibiotic Prophylaxis in Elective Cardiac Surgery. J. Thorac. Cardiovasc. Surg. 2016, 152, 603–610. [Google Scholar] [CrossRef] [PubMed]
- Andreas, M.; Zeitlinger, M.; Shabanian, S.; Wisser, W.; Thell, R.; Edlinger-Stanger, M.; Maier-Salamon, A.; Jaeger, W.; Kocher, A.; Laufer, G.; et al. Early Antibiotic Prophylaxis Prior to Bypass Surgery Improves Tissue Penetration. Thorac. Cardiovasc. Surg. 2020, 68, 669–673. [Google Scholar] [CrossRef] [PubMed]
- Trent Magruder, J.; Grimm, J.C.; Dungan, S.P.; Shah, A.S.; Crow, J.R.; Shoulders, B.R.; Lester, L.; Barodka, V. Continuous Intraoperative Cefazolin Infusion May Reduce Surgical Site Infections During Cardiac Surgical Procedures: A Propensity-Matched Analysis. J. Cardiothorac. Vasc. Anesth. 2015, 29, 1582–1587. [Google Scholar] [CrossRef]
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Zelenitsky, S.A. Effective Antimicrobial Prophylaxis in Surgery: The Relevance and Role of Pharmacokinetics-Pharmacodynamics. Antibiotics 2023, 12, 1738. https://doi.org/10.3390/antibiotics12121738
Zelenitsky SA. Effective Antimicrobial Prophylaxis in Surgery: The Relevance and Role of Pharmacokinetics-Pharmacodynamics. Antibiotics. 2023; 12(12):1738. https://doi.org/10.3390/antibiotics12121738
Chicago/Turabian StyleZelenitsky, Sheryl A. 2023. "Effective Antimicrobial Prophylaxis in Surgery: The Relevance and Role of Pharmacokinetics-Pharmacodynamics" Antibiotics 12, no. 12: 1738. https://doi.org/10.3390/antibiotics12121738