£10103 2029/98/10 Meta-Analysis of Cirical Trials Comparing Cefazalin to Cofuroxime, Ceftriaxone, and Cofamandale for Surgical Ste Infoctio, As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice Antibiotics (Basel). 2022 Nov; 11(11): 1543, PMCID: PMC9686604 Published online 2022 Nov 3. doi: 10.3390/antibioties11111543 PMID: 36358198, Meta-Analysis of Clinical Trials Comparing Cefazolin to Cefuroxime, Ceftriaxone, and Cefamandole for Surgical Site Infection Prevention Nehad J. Ahmed, Conceptualization, Data curation, Formal analysis, Software, Writing — original draft"? Abdul Haseeb, Funding acquisition, Investigation, Software, Ahmad Alamer, Investigation, Methodology, Resources,' Ziyad S, Almalki, Project administration, Resources, Software," Abdullah K, Alahmari, Investigation, Software,' and Amer H. Khan, Supervision, Writing ~ review & editing?” Marc Maresca, Academic Editor Abstract Surgical site infections are among the most prevalent and costly healthcare-associated infec- tions, resulting in poor patient outcomes and even death. Cefazolin is a first-generation cephalosporin antibiotic that is widely used for surgical prophylaxis in a variety of surgical dis- ciplines, Although previous studies showed that cefazolin is effective in preventing surgical site infections, other agents, such as cefuroxime and ceftriaxone, were used excessively for surgical patients. The present analysis included only clinical trials comparing the efficacy of cefazolin to cefuroxime, ceftriaxone, and cefamandole in lowering SSIs using PubMed, Google Scholar, and ClinicalTrials gov. Review Manager software (RevMan version 5.4) was used to conduct the meta-analyses. A total of 12,446 patients were included in the study, Among these patients, 6327 patients received cefazolin and 6119 patients received cefamandole, cefuroxime, or cef- triaxone. Our analysis showed that cefazolin is as effective as cefuroxime, cefamandole, and ceftriaxone in preventing surgical site infections. Hence, our findings have provided evidence for the use of cefazolin before surgeries because of its efficacy, as previous studies showed that it is inexpensive and safer than other agents. Keywords: cefamandole, cefazolin, ceftriaxone, cefuroxime, clinical trials, prophylaxis, surgical site infections 1. Introduction hitpsslwwn.neb.nin.nih goulpmelartcles/PMC@686604 ans10103 2023/98/10 Meta-Analysis of Clinical Trials Comparing Cefazalin to Cefuroxime, Ceftriaxone, and Cofamanale for Surgical Site Infactio, ‘The surgical site infection (SSI) appears in a wound created by a surgical or post-operative procedure of any cavity, joint, bone, tissue, or prosthesis involved [1]. SSI is considered if it oc- curs within 30 days of the operation or within 90 days if prosthesis implantation is involved, and is classified according to the tissues involved into superficial incisional, which involves only skin or subcutaneous tissue at the site of incision; deep incisional, which covers deep soft tis- sues (fasciae and muscles); and infections in organs and spaces, which involves any part of the anatomy other than the incision that was opened or manipulated during the operation [2,3]. ‘These infections are among the most prevalent and costly healthcare-associated infections, re- sulting in poor patient outcomes and even death [4] It is generally acknowledged that antibiotic prophylaxis is necessary for clean-contaminated, contaminated, and unclean wounds [5]. One antibiotic dose is typically enough if the procedure lasts four hours or less; however, further antibiotic doses may be needed to maintain the con- centration, especially if the antibiotic has a short half-life [6]. Repeat intraoperative antibiotic administration is necessary when the surgery lasts more than four hours or there is an ex- pected blood loss of more than 1500 mL. Unless there is a known infection, prophylactic an- tibiotics should be stopped within 24 h [7] Cephalosporins are beta-lactam antimicrobials used to manage a wide range of infections from Gram-positive and Gram-negative bacteria. First-generation cephalosporins, such as cefazolin, cefadroxil, cephalothin, cephradine, cephapirin, and cephalexin, have active coverage against most Gram-positive cocci, such as streptococci spp. and staphylococci spp., while having minimal coverage against Gram-negative bacteria [8]. Second-generation cephalosporins include ce- furoxime, cefmetazole, cefprozil, cefoxitin, and cefotetan. Second-generation cephalosporins have less activity against Gram-positive cocci than first-generation cephalosporins; however, they have increased activity against Gram-negative bacilli. Third-generation cephalosporins in- clude cefotaxime, cefdinir, ceftazidime, ceftriaxone, cefixime, and cefpodoxime, Third-genera- tion cephalosporins have less coverage against most Gram-positive organisms; however, they have increased coverage against Enterobacteriaceae, Neisseria spp., and Haemophilus influenzae [3] Cefazolin is a first-generation cephalosporin antibiotic that is widely used for surgical prophy- laxis in a variety of surgical disciplines [9]. Because of its superior safety profile, low cost, and targeted activity against germs typically encountered during surgical operations, it remains the medication of choice for surgical prophylaxis in many procedures [10]. According to Geroulanos et al, cefazolin has been frequently recommended with success in surgical prophy- laxis, although broad-spectrum cephalosporins such as ceftriaxone are generally not recom- mended [11]. Maki et al. stated that studies and findings from the 1990s show that the first-generation cephalosporin cefazolin is just as effective as second-generation cephalosporins, such as cefamandole or cefuroxime, in preventing surgical site infections [12]. Surat et al, noted that a new local perioperative antibiotic prophylaxis guideline set first-generation cefazolin as the new standard prophylactic antibiotic rather than second-generation cefuroxime [13]. As a re- sult, we decided to identify clinical trials, pool the data, and conduct a meta-analysis to com- pare the efficacy of cefazolin in reducing SSIs to cefuroxime, ceftriaxone, and cefamandole, which were routinely used to prevent postoperative site infections, hitpsslwwn.neb.nin.nih goulpmelartcles/PMC@686604 26£10103 2023/9/10 Meta-Analysis of Cirical Trials Comparing Cefazalin to Cofuroxime, Ceftriaxone, and Cofamansdale for Surgical Site Infactio, 2. Materials and Methods ‘The analysis included the clinical trials that compare the efficacy of cefazolin to cefuroxime, ceftriaxone, and cefamandole in lowering SSIs that were identified using PubMed, Google Scholar, and ClinicalTrials.gov. The keywords “surgical site infections” AND “cefazolin” AND “ceftriaxone” OR “cefuroxime” OR “cefamandole” were used in the search. The analysis comprised only published human clinical studies and included all of the trials that were published from 1976 to 2022. The study excludes other sorts of studies. The data ob- tained comprised the overall number of surgical patients who had cefazolin as well as the number of surgical site infections in these patients. In addition to that, the study included the total number of surgical patients who had cefuroxime, ceftriaxone, or cefamandole, and the number of surgical site infections that occurred in these patients. The occurrence of surgical site infections in the cefazolin and other cephalosporin groups was the endpoint of our study. The occurrence of surgical site infections was compared between cefazolin and cefuroxime; between cefazolin and ceftriaxone; and between cefazolin and cefamandole, Following that, we divided the patients into two groups: one with cefazolin; and one with cefuroxime, ceftriaxone, and cefamandole to assess the rate of surgical site infection between cefazolin and the other agents in general. An odds ratio and a random effect model with 95% confidence intervals were used to compare the groups. A funnel plot was used to assess publication bias. The data were shown by creating a forest plot with OR. The I? statistic was used to examine the studies’ heterogeneity. An [2 score of 50% or higher indicated significant trial heterogeneity. A statistically significant p- value of 0.05 was used, Review Manager software (RevMan version 5.4) was used to conduct the meta-analyses. 3. Results The present analysis included twenty-nine studies. All of the included trials were clinical trials. Four studies compare cefazolin with cefamandole; eleven studies compare cefazolin and ceftri- axone; eleven studies compare cefazolin with cefuroxime; and three compare cefazolin with both cefuroxime and cefamandole (Table 1). A total of 12,446 patients were included in the study. Among these patients, 6327 patients received cefazolin and 6119 patients received cefamandole, cefuroxime, or ceftriaxone (Figure 1), hitpsslwwn.neb.nin.nih goulpmelartcles/PMC@686604 ans£10103 2029/9/10 Meta-Analysis of Cirical Trials Comparing Cefazalin to Cofuroxime, Ceftriaxone, and Cofamandole for Surgical Site Infactio, Records. dented tom The Databases =#08e) The study indaied only studien were removed (0 = 7084) | Cini screened (71034) “Thal wrten in languages other than English were exctded bares ‘Ta reovant cnc! tale In the lore cetabsses were nctdes (r-ean) ‘The suds at dt cde 8 ‘comparison between cxazon| fond other antibiotics ware excluded (0 *818) | Studies includ inthe anys (n=29) Figure Study Flow Chart, hitpsslwwn.neb.nin.nih goulpmelartcles/PMC@686604 ans.#10103 20289110 Table 1 ‘The studies that were included in the analysis. study Simatupang et al. [14] Marni etal. [15] Kalawar etal. [15] Nishant et al. [17] Phoolcharoen etal. [18] Wei et al. [19] Tang et al. [20] Ross et al [21] Wellens etal. [221 Mauerhan etal. [23] Curtis etal, [24] awards Jret a. [25] Galbraith etal. [2] Townsend etal, [27] Edwards Jret al. [28] Maki etal. [12] Borrero etal. [29] Cotogni etal. [30] Soteriow et al. [31] Bryan etal. [32] Conklin etal. [33] Gentry et al. [34] Kaiser etal. [35] Recker etal. [36] Geroulanos et al. [37] Slama etal. [38] Beam etal. [39] Hemsell etal. [40] Kellum Jret al (41) Year 202 2020 2018 2o1a 21 2008 2003 1997 1995 1994 1993 1993 1993 1993 1992 1992 1991 1990 1989 1988 1988 1988 1987 1987 1986 1986 1984 1984 1984 ‘Antibiotics Cefazalin vs. Cefazoin vs. Cefazoin vs. Cefazolin vs. Cefazoin vs. Cefazolin vs. Cefazolin vs. Cefazalin vs. Cefazoin vs, Cefazoin vs. Cefazolin vs, Meta-Analysis of Clinical Trials Comparing Cefazolin to Cefuroxime, Ceftriaxone, and Cafamandale for Surgical Site Infect, Ceftiaxone Ceftiaxone Cefwiaxone Cefuroxime Cefwiaxone Cefwiaxone Cefuroxime Cofeiaxone Cefuroxime Cefuroxime Cefuroxime Cefazolin vs, Cefamandole Cefazolin vs. Cefuroxime Gefazolin vs, Cefuroxime vs, Cefamandole Cefazolin vs, Cefuroxime Cofazolin vs. Cefamandole Cefazolin vs. Cefuroxime Cefazolin vs. Cefuroxime Cefazolin vs, Ceftriaxone cefazolin vs, Cefamandole Cefazolin vs, Cefuroxime Cefazolin vs, Cefuroxime vs, Cefamandole cefazolin vs, Cefamandole Cefazolin vs. Ceftriaxone Cefazolin vs, Cefuroxime Cefazolin vs, Cefuroxime vs, Cefamandole Cefazolin vs, Ceftriaxone Cofazolin vs, Ceftriaxone Cefazolin vs, Ceftriaxone The results of the present analysis showed that the rate of SSIs in the cefazolin group was 3.51% and the total rate of SSIs in the other cephalosporins group was 3.58%. The present meta-analysis showed these differences to be statistically not significant using the random-ef- fect model (OR 1.09, 95% Cl 0.83-1.44, p-value more than 0.05) (Figure 2). hitpsslwwn.neb.nin.nih goulpmelartcles/PMC@686604 515£10103 2023/98/10 Meta-Analysis of Cirical Trials Comparing Cefazalin to Cofuroxime, Ceftriaxone, and Cofamansdole for Surgical Site Infoctio, tS + ‘The rate of SSIs in the cefazolin group vs. other cephalosporins. The included studies were Beam et al. 1984 [39], Borrero etal. 1991 [23], Bryan etal. 1988 [32], Conklin etal. 1988 [33], Cotogni et al. 1990 [30], Curtis etal. 1993 [24], Edwards Jret al. 1992 [28], Edwards Jr etal. 1993 [25], Galbraith etal. 1993 [26], Gentry et al, 1988 [24], Geroulanos etal, 1986 [37], Hemsell et al, 1984 [0], Kaiser etal, 1987 [25], Kalawar etal 2018 [16], Kellum jr etal. 1984 [41], Maki etal. 1992 [12], Mami et al, 2020 [15], Mauerhan et al, 1994 [23], Nishant et a. 2013 [17], Phoolcharoen et al. 2012 [18], Recker et al. 1987 [36], Ross et al. 1997 [21], Simatupang etal. 2021 [14], Slama etal. 1986 [38], Soteriou etal. 1989 [31], Tang etal. 2003 [20], Townsend etal. 1993 [27], Wei et al. 2005 [19], Wellens etal. 1995 [22] The results of the present analysis showed that the rate of SSIs in the cefazolin group was 4.05% and the total rate of SSIs in the cefuroxime group was 4.15%. The present meta-analysis showed these differences to be statistically not significant using the random-effect model (OR 1.14, 95% Cl 0,80-1.64, p-value more than 0.05) (Figure 3). hitpsslwwn.neb.nin.nih goulpmelartcles/PMC@686604 ans:£10103 2023/9/10 Meta-Analysis of Cirical Trials Comparing Cefazalin to Cofuroxime, Ceftriaxone, and Cofamandole for Surgical Site Infactio, Figure3 ‘The rate of SSIs in the cefazolin group vs. cefuroxime group. The included studies were Borrero et al. 1991 [29}, Conklin et a, 1988 [33], Cotogni et al. 1990 [30], Curtis et al, 1993 [24], Edwards fret al. 1992 [28], Galbraith et al, 1993 [26], Gentry etal, 1988 [24], Geroulanos etal. 1986 [37], Mauerhan etal. 1994 [23], Nishant et al 2013 [17], Slama et al, 1986 [38], Tang et al. 2003 [20], Townsend etal. 193 [27], Wellens et al, 1995 [22]. The results of the present analysis showed that the rate of SSIs in the cefazolin group was 2.33% and the total rate of SSIs in the ceftriaxone group was 2.37%. The present meta-analysis showed these differences to be statistically not significant using the random-effect model (OR 0.97, 95% Cl 0,48-1.97, p-value more than 0.05) (Figure 4). ance om oe Hem, arma san > Figure ‘The rate of SSIs in the cefazolin group vs, ceftriaxone group, The included studies were Beam et al, 1984 [39], Hemsell et al. 1984 [40], Kalawar et al, 2018 [16], Kellum et al, 1984 [41], Mami et al. 2020 [15], Phooicharoen et al. 2012 [18], Recker et al. 1987 [36], Ross etal. 1997 [21], Simatupang et al. 2021 [14], Soteriou et al. 1989 [31], Wei et al. 2005 [19] The results of the present analysis showed that the rate of SSls in the cefazolin group was 3.92% and the total rate of SSIs in the cefamandole group was 3.54%. The present meta-analy- sis showed these differences to be statistically not significant using the random-effect model (OR 1.11, 95% Cl 0.78-1.56, p-value more than 0.05) (Figure 5) hitpsslwwn.neb.nin.nih goulpmelartcles/PMC@686604 718£10103 2023/9/10 Meta-Analysis of Cirical Trials Comparing Cefazalin to Cofuroxime, Ceftriaxone, and Cofamandole for Surgical Site Infactio, 13S a a Figures ‘The rate of SSIs in the cefazolin group vs. cefamandole group. The included studies were Bryan etal. 1988 [32], Edwards Jr etal, 1993 [25], Gentry et al, 1988 [34], Kaisar etal, 1987 [35], Maki etal, 192 [12], Slama etal, 1986 [38], Townsend etal, 1993 [27] The heterogeneity test p-value and the p-value of the overall effect test showed non-significant results in the present study. Moreover, our funnel plot shows the symmetrical distribution of the study, which suggests a low level of publication bias (Figure 6). So, the findings of the present study findings have good validity. Funnel plot (surgical site infections rate). 4, Discussion Postoperative healthcare-related infections, particularly surgical site infections, are associated with worsening general health status, and a greater social and economic cost [42,43]. An evi- dence-based approach is thought to prevent more than half of HAls and perioperative antibi- otic treatment may play a key role in infection prevention. Cefazolin is most commonly used for surgical prophylaxis in patients who do not have a history of beta-lactam allergy or methicillin- resistant Staphylococcus aureus infection [44,45,46} The results of our meta-analysis show that cefazolin is as effective as cefuroxime and cefaman- dole in preventing surgical site infections. Edwards Jr reported that cefazolin is still the best cost-effective antibiotic for prophylaxis in clean vascular surgical procedures [25]. According hitpsslwwn.neb.nin.nih goulpmelartcles/PMC@686604 ans:10:03 2023/9/10 _Mela-Analysis of Cnical Tals Comparing Cefazokn to Cefuroxime, Cefriaxone, and Cafamandale for Surgical Site Infect to Townsend et al, the locations of infection and level of tissue involvement were not substan- tially different among the cefamandole, cefazolin, and cefuroxime groups. Because no differ- ences in effectiveness in avoiding postoperative site infections were proven in a properly planned experiment, the drug costs, including the costs of preparation and delivery, may be the only criteria used to choose between these three antibiotic prophylaxis regimens [27]. Furthermore, Edwards Jr 1992 stated that the trend in infection rates implies that cefazolin is more effective than cefuroxime for perioperative prophylaxis, despite the fact that the differ- ence was not statistically significant [28]. Wellens et al, reported that short-term treatment of 3 g cefazolin or cefuroxime failed to establish a therapeutic advantage of one antibiotic over the other in terms of clinical outcome, incidence or site of infection, or organisms detected [22] When compared to the first-generation cephalosporin, cefazolin, Curtis et al. found that the second-generation cephalosporin, cefuroxime, did not reduce the incidence of wound infec- tion. Because institutional antibiotic purchase and administration costs vary, careful considera- tion of these aspects will allow the best cost-effective infection prophylaxis strategy in cardiac surgery to be determined [24]. According to Nishant et al, there was no difference in the oc- currence of surgical site infection between cefazolin and cefuroxime [17]. Furthermore, Gentry etal, stated that there are no differences in the efficacy of cefuroxime, cefamandole, and cefa- zolin in avoiding postoperative infections in patients undergoing open-heart surgery [35]. The results of our meta-analysis show that cefazolin is as effective as ceftriaxone in preventing surgical site infections. Phoolcharoen et al. found no difference in redu ity between single-dose preoperative ceftriaxone and cefazolin in patients having a hysterec- tomy [18]. According to Kalawar et al, there is no difference in the efficiency of cefazolin and ceftriaxone in the prevention of surgical site infection [16]. Simatupang et al. demonstrated that cefazolin and ceftriaxone have the same effectiveness in avoiding germ growth in surgical wounds [14]. Furthermore, Ross et al. stated that ceftriaxone is therapeutically equivalent to cefazolin in preventing postoperative wound infections in patients who had peripheral vascu- lar surgery [21]. Marni et al, found no difference in the prevention of postoperative infections between ceftriaxone and cefazolin [15]. According to Wei et al, there is no statistically signifi- cant difference in the incidence of peritonitis and wound infection between the ceftriaxone and cefazolin groups [19]. fectious morbid- Current studies reported that cefazolin is the recommended antibiotic for most surgical proce- dures. Jocum et al. reported that cefazolin is utilized for prophylaxis in most surgical opera- tions. Ithas been carefully researched and has proved efficacy [47]. According to Ahmed et al, cefazolin is the antibiotic of choice for prophylaxis in the majority of surgeries because it has been widely investigated and has established efficacy [48]. Wolfhagen et al. stated that cefa- zolin is the most commonly indicated drug for surgical antibiotic prophylaxis [49]. Furthermore, according to Isserman et al,, cefazolin, a first-generation cephalosporin, is the most often recommended antibiotic for perioperative prophylaxis to decrease surgical site in- fections [50]. Cefazolin has been used in clinical practice for about 40 years, according to Kusaba, and a considerable body of research has been collected; in addition, its efficacy and safety are well-established when compared to other antibiotics. As a result, cefazolin has been selected as a first-line anti-microbial for prophylaxis following several surgical operations, such as cardiovascular surgery, hysterectomy, and arthroplasty [51]. Bratzler et al. stated that because of its favorable safety profile, low cost, and focused activity against germs typically en- countered during surgical operations, cefazolin remains the medication of choice for surgical prophylaxis in numerous procedures [10]. Furthermore, Alemkere stated that the American Society of Health-System Pharmacists recommends ceftriaxone only for high-risk biliary tract hips hwn:nbinin.nh govlpmclartles/PMC9586605) ans10:03 2023/9/10 —_Mela-Analysis of Cinical Tals Comparing Cefazokn to Cefuroxime, Cefriaxone, and Cafamandale for Surgical Site Infect procedures and colorectal surgery. Because ceftriaxone is a broad-spectrum medicine, it is more likely to produce an emergency of resistance than cefazolin and other commonly used surgical preventive agents [52] Marano et al. reported that using antimicrobials such as cefazolin and cefuroxime during ‘esophagogastric surgery to reduce infections within the intraoperative period should not ex- ceed two antimicrobial agents, at the lowest efficacious and safe doses to avoid the emergence of multi-drug resistance [53]. They reported that further studies are needed to investigate the optimal antimicrobial regimen in esophageal surgery [53]. Ruol et al. stated that a single-dose prophylactic regimen provides adequate prophylaxis and significant cost-savings in compari- son with multiple-dose prophylactic regimens in patients undergoing major surgery for ‘esophageal cancer [54]. Mohri et al. stated that cefazolin is a first-generation cephalosporin that has been suggested for antimicrobial prophylaxis in gastric surgery and thata single dose of cefazolin or ampicillin-sulbactam is just as effective as numerous doses in preventing sur; cal-site infections after gastric cancer surgery [55]. According to the Antibiotic Expert Group, cefazolin is the most commonly recommended antimicrobial for surgical prophylaxis due to a variety of factors, such as its narrow Gram-positive and Gram-negative spectrum coverage for common pathogens, efficacy, safety profile, and low cost [56]. a single agent for most surgeries; however, for some surgeries such as colon surgeries, itis combined with another agent that is active against anaerobic pathogens. lerano et al. stated that metronidazole is prescribed for some surgeries in addition to cefazolin to give a longer coverage of anaerobic microorganisms [57]. cefazolin is recommended as ‘The first limitation of the study was that the timing and route of antibiotic administration were not standardized for all the trials included in the meta-analysis. The second limitation was that the study included old trials due to the small number of recent surgical prophylactic clinical tr als. The third limitation was that in some studies, the total number of cases in the intervention and control groups is much different, This would affect the odd ratio comparisons. 5. Conclusions Our analysis showed that cefazolin is as effective as cefuroxime, cefamandole, and ceftriaxone in preventing surgical site infections. Our findings provide evidence for the use of cefazolin be- fore surgeries because it has a similar efficacy to cefuroxime, cefamandole, and ceftriaxone. So, it is recommended to add the first-generation cephalosporin cefazolin instead of ceftriaxone and cefuroxime in the current effective clinical practice guidelines for antimicrobial prophylaxis. Funding Statement ‘The authors would like to thank the Deanship of Scientific research at the Umm Al-Qura University for supporting this work by grant code: 22UQU4290073DSR04, Author Contributions hitpsslwwn.neb.nin.nih goulpmelartcles/PMC@686604 sons:£10103 2023/98/10 Meta-Analysis of Clinical Trials Comparing Cefazalin to Cefuroxime, Ceftriaxone, and Cofamanole for Surgical Site infoctio, Conceptualization, N,J.A; methodology, A.K.A. and A.A,; software, NA, validation, NJ.A., AH.K. and A.K.A, formal analysis, A.A, and N.J.A, investigation, A.H.; resources, AH. and NJ.A,; data cu- ration, NJ.A, Z.S.A, and A.H.K, writing—original draft preparation, NJ.A; writing—review and editing, AH.K, visualization, NJ.A. supervision, A.H.K. and AH, project administration, NJ.A, A.K.A. and A.A, funding acquisition, AH.K., A.H. and NA. All authors have read and agreed to the published version of the manuscript, Institutional Review Board Statement Not applicable, Informed Consent Statement Not applicable. Data Availability Statement Not applicable. Conflicts of Interest ‘The authors declare no conflict of interest. Footnotes Publisher's Note: MDP! stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. References 1. Hall CA, Allen J, Barlow G, Antibiotic prophylaxis. Surgery: 2015;33:542-549, [Google Scholar] 2, Borchardt R.A., Tzizik D, Update on surgical site infections, JAPA, 2018;31:52- doi: 10,1097/01,JAA.0000531052.82007.42, [PubMed] [CrossRef] [Google Scholar] 3, Idris KJ, Bamoosa EM., Alsabbah R.S, Faidah G.I, Alharbi SJ, Bar A.A., AlAhdal A.M, Awareness and level of knowledge of surgical site infection among surgical staffin King Abdullah Medical City during Hajj 2019: A cross- sectional study. MDC. 2020;4:1873-1878, doi: 10.2491 /IJMDC.51-1601213972, [CrossRef] [Google Scholar] 4. Seldelman J, Anderson D.J. Surgical Site Infections. Infect. Dis. Clin. North Am. 2021;35:901-929. doi: 10,1016/}ide.2021.07.006, [PubMed] [CrossRef] [Google Scholar] 5. Surgical Treatment: Evidence-Based and Problem-Oriented, [(accessed on 18 October 2022)]; Available online: ispsi//Awww.ncbi nlm nih, gov /books/NBK6917. 6, Antibioties for Surgical Prophylaxis. [(accessed on 18 October 2022)]. Available online: hupsi//Awwwu.nps.org.au/australian-prescriber articles /antibloties-for-surpical prophylaxis hitpsslwwn.neb.nin.nih goulpmelartcles/PMC@686604 1s1008 202819/10 Meta-Analysis of Cricl Trials Comparing Cefazalin o Cafuroxime, Ceftriaxone, and Cefamandole for Surgical Ste Infectio, 7, Dehne M.G,, Miihling ], Sablotzki A., Nopens H., Hempelmann G, Pharmacokinetics of antibiotic prophylaxis in major orthopedic surgery and blood-saving techniques, Orthopedics. 2001;24:665~669, doi: 10,3928/0147-7447- 20010701-15. [PubMed] [CrossRef] [Google Scholar] 8, Cophalosporins, [(accessed on 18 October 2022)]; Available online: https://www:ncbi.nlm.nih, gov books /NBKSS1517 9, Peppard W],, Bberle 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, doi: 10,1089/sur.2016,182, [EMC free 10, Bratzler D.W,, Dellinger EP, Olsen K-M., Perl TM., Auwaerter PG, Bolon M.K,, Fish D.N., Napolitano LM., Sawyer RG, Slain D., etal. American Society of Health-System Pharmacists (ASHP) Infectious Diseases Society of America (IDSA) Surgical Infection Society (SIS) Society for Healthcare Epidemiology of America (SHEA) Clinical practice guidelines for antimicrobial prophylaxis in surgery. Surg. Infect. 2013;14:73-156, doi: 10.1089 /sur2013,9999. PubMed] [CrossRef] [Google Scholar] 11, Geroulanos S,, Marathias K, Kriaras J, Kadas B. Cephalosporins in surgical prophylaxis. J. Chemother. 2001;1:23-26, doi: 10.1179/joc.2001.13.Supplement-2.23. [PubMed] [CrossRef] (Google Scholar] 12, Maki D.G,, Bohn M,, Stolz SM,, dole, and vancomycin for surgical prophylaxis in cardiac and vascular operations, A double-blind randomized trial. J. Thorac. Cardiovasc. Surg. 1992;104:1423- 1434, doi: 10,1016/0022-5223(19)34639-2, [PubMed] [CrossRef] [Google Scholar roncke G.M., Acher CW, Myerowitz D,P Comparative study of cefazolin, cefaman- 13, Surat G, Meyer Sautter P, Rusch J, Braun-Feldweg |, Markus CX, Germer GT, Lock JF Cefazolin Might Be Adequate for Perioperative Antibiotic Prophylaxis in Inte Abdominal Infections without Sepsis: A Quality Improvement Study. Antibiotics. 2022;11:501. dot: 10.3390/antibfotics11040501, [PMC fice article] [PubMed {CrossRef} [Google Scholar} 14, Simatupang M.D,, Dusak LW, SuyasaX,, Wiratnaya 1G.E, Bacterial growth from the surgical wound base smear at the end of the operation and superficial surgcal site Infection in the administration of cefazolin single dose, ceftriaxone single dose, and ceftriaxone 3 days as prophylactic antibiotics in cases of. Intisari Sains Medis. 2021;12:183-186 {Google Scholar} 15, Marat H,, Djanas D., Bachtiar The Effect of Giving Prophylactic Antibiotic Ceftriaxone and Cefazolin and Giving Ceftriaxone Before and After Surgery to The Risk of Postoperative Wound Infection in Postoperative Patients. Andalas Obstet. Gynecol J. 2020;4:77-86, [Google Scholar] 16. Kalawar RPS, Shrestha B.P, Khanal G.P, Chaudhary P, Rijal R, Maharjan R,, Paneru S.R. Randomized controlled trial comparing cefazolin with ceftriaxon doi: 10.3126/bpkihs.v1i1,19752, [CrassRer} [Google Scholar] n perioperative prophylaxis in orthopaedic surgeries. JBPKIHS. 2018;1:36~43. 17. Nishant, Kailash KK, Vijayraghavan PV. Prospective randomized study for antibiotic prophylaxis in spine surgery: Choice of drug, dosage, and timing, Asian Spine J. 2013;7:196. doi: 10.4184/as}2013.7.3.196. [PMC fi ] [PubMed] [CrossRef] [Google Scholar] artic 18. Phoolcharven N., Nilgate S., Rattanapuntamanee 0., Limpongsanurak S, Chaithongwongwatthana S.A randomized controlled trial comparing ceftriaxone with cefazolin for antibiotic prophylaxis in abdominal hysterectomy, Int. J. Gynaecol. Obstet. 2012;119:11-13. dot: 10.1016/.jgo.2012.04.023, [PubMed] [CrossRef] [Google Scholar} 19. Chen W,, Jiang 7.P, Zheng XI, Chen WY, Guo Q-¥, Mao ILP, Ye XQ, Yang X, Yu XQ. Prospective randomized controlled trial of antibiotic prophylaxis for newly placed peritoneal dialysis catheter to prevent postoperative peritonitis and wound infection, Chin. Nephrol. 2006;22:601-604, [Google Scholar] hitpsslwwn.neb.nin.nih goulpmelartcles/PMC@686604 vans.£10103 2029/98/10 Meta-Analysis of Cirical Trials Comparing Cefazalin to Cofuroxime, Ceftriaxone, and Cofamandale for Surgical Ste Infoctio, 20, Tang WM., Chiu KY, Ng TP, Yau W. antibiotic in primary arthroplasty. J Arthroplast. 2003;18:714-718, doi: 10.1016 /S0883-+ [CrossRef] [Google Scholar] Ching PTY, Seto WH, Efficacy of a single dose of cefazolin as a prophylactic -03(03)00201-8, [PubMed] 21, Ross C.B., Wheeler W.G., 2nd, Jones M,),, Kerins C.A,, Peck T.E, Ceftriaxone versus cefazolin in peripheral arterial operations: A randomized, prospective trial. South. Med. J. 1997;90:16-22, doi: 10,1097 /00007611-199701000-00004, [LubMed] [Crossief] [Google Scholar] 22, Wellens F, Pirlet M., Larbuisson R,, De Meireleire F, De Somer P, Prophylaxis in cardiac surgery, A controlled. randomized comparison between cefazolin and cefuroxime, Eur J. Cardiothorac. Surg. 1995;9:325-329, doi: 10.1016/S1010-7940(05}80191-5, [PubMed] [CrossRef] [Google Scholar] 23, Mauerhan D.R,, Nelson CL, Smith D.L., Fitegerald RH., Jr, Slama T.., Petty R.W, Jones RE, Evans RP Prophylaxis against infection in total joint arthroplasty. One day of cefuroxime compared with three days of cefazolin J. Bone jt. Surg. Am, 1994;76:39-45, doi: 10.2106 /00004623-199401000-00006, [PubMed] [CrossRef] [Google Scholar] 24, Curtis JJ., Boley TM,, Walls 7. Hamory B., Schmaltz R.A, Randomized, prospective comparison of first-and. ssecond-generation cephalosporins as infection prophylaxis for cardiac surgery. Am. J. Surg. 1993;166:734-737, doi: 10,1016/S0002-9610(05)80689-0, [PubMed] [CrossRef] [Google Scholar} 25, Edwards WH, Jr, Kaiser A.B,, Tapper S,, Edwards W.H., Sr, Martin R.S, III, Mulherin [.L, Jr, Jenkins JAM., Roach A.C, Cefamandole versus cefazolin in vascular surgical wound infection prophylaxis: Cost-effectiveness and risk factors. Vase. Surg. 1993;18:470-476, doi: 10.1016 /0741-5214{93)90265-N, [PubMed] [Crossite [Google Scholar] 26, Galbraith U,, Schilling J, Von Segesser L.K., Carrel T, Turina M., Geroulanos S, Antibiotic prophylaxis in cardiovascular surgery: A prospective randomized comparative trial of one day cefazolin versus single dose cefuroxime. Drugs Exp. Clin, Res. 1993;19:229-234, [PubMed] [Google Scholar] 27, Townsend TR, Reitz B.A., Bilker W.B., Bartlett J.G, Clinical trial of cefamandole, cefazolin, and cefuroxime for antibiotic prophylaxis in cardiac operations. . Thorac. Cardiovasc. Surg. 1993;106:664~670. doi: 10.1016/S0022- 5223(19)33709-2, [PubMed] [CrossRef] [Google Scholar} 28, Edwards W.H, Jr, Kaiser AB,, Kernodle D.S,, Appleby T.C, Edwards WAH. Sr, Martin RS, Ill, Mulherin LL, Js, Wood GA, Jr Cefuroxime versus cefazolin as prophylaxis in vascular surgery. J. Vasc. Surg. 1992;15:35-42, oi: 10.1016/0741-5214(92)70011-9. [PubMed] [CrossRef] [Google Scholar] 29, Borrero E,, Rosenthal D. Comparison of cefuroxime and cefazolin: Prophylaxis against infection in arterial reconstructive surgery, Vasc. Surg. 1991;25:54-59, doi: 10.1177/153857449102500109, [CrossRef] [Google Scholar] 30, Doebbeling BN,, Pfaller M.A,, Kuhns K.R., Massanari RM, Bebrendt D.M,, Wenzel R.P, Cardiovascular surgery prophylaxis: A randomized, controlled comparison of cefazolin and cefuroxime, . Thorac. Cardiovasc. Surg 1990;99:981-989, dot: 10.1016/80022-5223(20)31454-9, [PubMed] [CrossRef] [Google Scholar] 31, Soteriou M., Recker F, Geroulanos S,, Turina M, Perioperative antibiotic prophylaxis in cardiovascular surgery: A prospective randomized comparative trial of cefazolin versus ceftriaxone, World J. Surg. 1989;13:798-801, doi: 10.1007/BF01658441, [PubMed] [CrossRef] [Google Scholar 32, Bryan CS, Morgan S.L., Caton R¥., Lunceford EM., Jz Cefazolin versus cefamandole for prophylaxis during total joint arthroplasty. Clin. Orthop, Relat, Res. 1988:228:117-122, doi: 10,1097 /00003086-198803000-00018, [PubMed] [CrossRef] [Google Scholar 33, Conklin CM., Gray RJ, Neilson D,, Wong P, Tomita D.., Matloff.M. Determinants of wound infection incidence after isolated coronary artery bypass surgery in patients randomized to receive prophylactic cefuroxime or cefazolin, ‘Ann. Thorac, Surg. 1988;46:172-177. dol: 10.1016/S0003-1975(10}65891-2, [PubMed] [CrossRef] [Google Scholar hitpsslwwn.neb.nin.nih goulpmelartcles/PMC@686604 1388.10/08 2028/9/10 Meta-Analysis of Cricl Trials Comparing Cefazalin to Cefuroxime, Cafriaxane, and Cefamandole for Surgical Ste Infectio, 34, Gentry 1.0,, Zeluff B,J, Cooley D.A. Antibiotic prophylaxis in open-heart surgery: A comparison of cefamandole, cefuroxime, and cefazolin, Ann. Thorac. Surg. 1988;46:167-171. doi: 10.1016/S0003-4975(10)65890-0, [PubMed] [CrossRef] [Google Scholar] 35, Kaiser AB,, Petracek M.R,, Lea .W., Kernodle DS, Roach A.C, Alford W.C, Jr, Burrus G.R,, Glassford D.M., Jr, ‘Thomas CS, Jr, Stoney W.S. Efficacy of cefazolin, cefamandole, and gentamicin as prophylactic agents in cardiac surgery, Results of a prospective, randomized, double-blind trial in 1030 patients. Ann. Surg. 1987;206:791, 36, Recker F, Geroulanos S, Turina M. Perioperative antibiotic prophylaxis in heart and vascular surgery. A prospective randomized comparative study with cefazolin and ceftriaxone, Dtsch. Med. Wochenschr: 1987;112:135-138, oi: 10.1058/s-2008-1068018, [PubMed [Crossitef] [Google Scholar] 37, Geroulanos S,, Oxelbark S,, Turina M, Perioperative antimicrobial prophylaxis in cardiovascular surgery: A prospective randomized trial comparing two day cefuroxime prophylaxis with four day cefazolin prophylaxis. Cardiovasc. Surg. 1986;27:300-306. [PubMed] [Google Scholar] 38, Slama TG, Sklar SJ., Misinski }., Fess SW. Randomized comparison of cefamandole, cefazolin, and cefuroxime prophylaxis in open-heart surgery. Antimicrob. Agents Chemother. 1986;29:744-747, doi: 10.1128/AAC.29.5.744. [PMC free article] [PubMed] [CrossRef] [Google Scholar] 39, Beam T,, Raab T, Spooner J, Balderman S,, Aldridge J, Bhayana J. Single-dose antimicrobial prophylaxis in open heart surgery. Eur. J lin. Microbiol 1984;3:598-604. dot: 10,1007/BF02013631. [PubMed] [CrossRef] [Google Scholar] 40, Hemsell D.L., Menon M.O,, Friedman A,). Ceftriaxone or cefazolin prophylaxis for the prevention of infection after vaginal hysterectomy. Am. J. Surg. 1984;148:22-26, [PubMed] [ ple Scholar] 41, Kellum J.M,, Jr, Gargano S,, Gorbach S.L., Talcof C, Curtis I.B,, Weiner B,, McCoobery M., Tan JS, Kelly T,, Wagner D. Antibiotic prophylaxis in high-risk biliary operations: Multicenter trial of single preoperative ceftriaxone versus multidose cefazolin, Am. J. Surg. 1984;148:15-18, [PubMed] [Google Scholar] 42, Magill SS, Edwards |.R., Bamberg W,, Beldavs Z.G., Dumyati G, Kainer M.A,, Lyntield R,, Maloney M,, McAl Hollod L,, Nadle J., etal. Emerging Infections Program Healthcare-Associated Infections and Antimicrobial Use Prevalence Survey ‘Team, Multistate point-prevalence survey of health care-associated infections. N. Engl. |. Med. 2014;370:1198-1208, doi: 10,1056/NEJMoa1306801. [PMC free article] [PubMed] [CrossRef] [Google Scholar] 43, Umscheid C.A,, Mitchell M.D., Doshi J.A., Agarwal R,, Williams K., Brennan Pj. 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, doi: 10,1086/657912. [PubMed] [CrossRef] [Google Scholar] 44, Bervios-Torres SL, Umscheid CA,, Bratzler D.W., Leas B, Stone E.C,, Kelz R.R., Reinke CE, Morgan S, Solomkin JS, ‘Mazuskt |B, et al. Healthcare Infection Control Practices Advisory Committee, Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection, 2017. JAMA Surg. 2017;152:784-791. doi: 10.1001 /jamasurg.2017.0904, [PubMed] [CrossRef] [Google Scholar} 45, Allegranzi B., Bischoff P, de Jonge S, Kubilay NZ, Zayed B., Gomes SM., Abbas M., Atema ],., Gans S,, van Rijen M., etal. WHO Guidelines Development Group. New WHO recommendations on preoperative measures for surgical site infection prevention: An evidence-based global perspective. Lancet Infect. Dis. 2016;16:¢276-e287. doi: 10.1016/S1473- 3099(16)30398-X, [PubMed] [CrossRef] [Google Scholar] 46, Crader M.R, Varacallo M. Preoperative Antibiotic Prophylaxis. [(accessed on 23 September 2022)]; Available online: hups://www.nebi nlm nih, gov books /NBK442032 [PubMed] 47. Jocum J. Surgical antibiotic prophylaxis: Are you doing it right. S. Afr: J. Anaesth. Analg. 2018;24:S49-S53. [Google Scholar hitpsslwwn.neb.nin.nih goulpmelartcles/PMC@686604 sans.1008 202819/10 Meta-Analysis of Cricl Trials Comparing Cefazalin o Cafuroxime, Ceftriaxone, and Cefamandole for Surgical Ste Infectio, 48, Ahmed Ni], Haseeb A, Alfaifi A.A., Alahmari AK, Alshehri A.A, Almalki Z.S,, Almatrafi B.H., Alghamdi FM, Khan AH, The Appropriateness of Using Cefazolin as a Surgical Prophylaxis Antibiotic, Lat, Am. J. Pharm. 2022;41:609-612, [Google Scholar] 49, Wolfhagen N, Boldingh QJ. de Lange M., Boermeester M.A., de Jonge SW. 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;275:10S0-1057, doi: 10,1097/SL.A.0000000000005436, [PubMed] [CrossRef] [Google Scholar} 50, Isserman RS, Cheung J, Varallo D., Cafone J, Lee J. Chiotos K,, Mubly W.T, Metjian T.A., Swami S, Baldwin K, etal. Increasing Cefazolin Use for Perioperative Antibiotic Prophylaxis in Penicillin-Allergic Children. Pediatrics. 2022;149:22021050694. doi: 10.1542/peds.2021-050694. [PubMed] [CrossRef] [Google Scholar] 51, Kusaba T, Safety and efficacy of cefazolin sodium in the management of bacterial infection and in surgical prophylaxis, Clin. Med. Ther: 2009;1:1607-1615. doi: 10.4137 /CMT.S2096. [CrossRef] [Google Scholar} 52, Alemkere G, Antibiotic usage in surgical prophylaxis: A prospective observational study in the su Nekemte referral hospital, PLoS ONE. 2018;13:00203523, doi: 10.1371 /journal,pone.0203523, [PM PubMed) [CrossRef] [Google Scholar] 53, Marano L., Carbone L,, Poto G.E., Calomino N., Neri A. Piagnerelli R., Fontani A,, Verre L., Savelli V, Roviello ,, etal Antimicrobial Prophylaxis Reduces the Rate of Surgical Site Infection in Upper Gastrointestinal Surgery: A Systematic Scholar 54, Ruol A, Bertiato G, Boscarino S, Cusinato R, Pascarella M., Tonin E.A, Santi S, Ancona E, Short-term prophylaxis with ceftriaxone plus metronidazole in esophageal cancer surgery. Chemother: 2000;12:23-28. doi: 10.1080/1120009X2000.11782304. [PubMed] [CrossRef] [Google Scholar] 55, Mohri ¥, Tonouchi H., Kobayashi M., Nakai K., Kusunoki M, Randomized clinical trial of single-versus multiple- dose antimicrobial prophylaxis in gastric cancer surgery. J. Br: Surg. 2007;94:683-688, doi: 10,1002/bjs.5837. PubMed) {CrossRef} [Google Scholar 56, Alam M., Bastakoti B, Therapeutic Guidelines: Antibiotic. Version 15, Aust. Prescr. 2015;38:137. doi: 10.18773/austprescr2015.049, [CrossRef] [Google Scholar] 57. lerano C, Thursky K, Peel T, Koning S, James R, Johnson S, Hall ., Worth Li, Marshall C. Factors associated with antimicrobial choice for surgical prophylaxis in Australia. JAC Antimicrob, Resist. 2020;2:dlaa036, oi: 10.1093/jacamr/dlaa036. (PMC fre article} [PubMed] [CrossRef] [Google Scholar hitpsslwwn.neb.nin.nih goulpmelartcles/PMC@686604 158.