Antimicrobial approach of abdominal post-surgical infections

Table 1 Definitions and clinical characteristics of surgical site infections according to Centers for Disease Control and Prevention and National Healthcare Safety Network criteria

Distinction	Superficial incisional SSI	Deep incisional SSI		Organ/space infections
Localization	Subcutaneous tissue and/or skin	Fascial and muscle layers		Organ manipulated during surgery
Timing	Within 30 d post-surgery		Within 30 or 90 d post-surgery/1 yr (implant in place)
Diagnosis at least one of the following
Pain	Yes	Yes		Yes
Swelling	Yes	Inconstant		Inconstant
Erythema or heat	Yes	Inconstant		Inconstant
Purulent drainage	Yes (superficial)	Yes (from deep incision)		No
Wound dehiscence	Yes (superficial)	Yes		No
Culture	Yes	Recommended		Recommended
Abscess	No	Yes		Yes
Fever (temperature > 38 °C)	Inconstant	Yes		Yes

SSI: Surgical site infection.

Table 2 Geographical distribution of the surgical site infections’ incidence

Continent	Country	Period	SSIs incidence	Ref.
Africa	Cameroon	2013-2014	Overall: 15.25%	[23]
	Egypt	2013-2017	CSEC: 5.34%	[24]
		2016-2018	Overall: 2.3%, CSEC: 2.8%	[25]
	Ethiopia	2015	Overall: 19.1%	[26]
		2019	Overall: 21.1%; ABDS: 49.06%	[27]
	Ghana	2017-2018	Overall: 10%; APPY: 13.4%; GAST: 12.7%; HER: 5.9%; ABDS: 13.7%	[28]
	Kenya	2015	CSEC: 4%	[29]
	Morocco	2018-2019	Overall: 6.3%	[30]
	Rwanda	2019-2020	CSEC: 5.7%	[31]
	Sierra Leone	2019-2020	CSEC: 10.3%; HER: 1.2%	[32]
		2021	Overall: 11.5%; ABDS: 79.5%	[33]
	South Africa	2017	APPY: 25%	[34]
	Tanzania	2009-2010	Overall: 26%; APPY: 15%; CHOL: 14.3%; XLAP: 27.9%	[35]
		2018-2020	CSEC: 14%	[36]
	Tunisia	2015-2016	CSEC: 5%	[37,38]
		2015	APPY: 9.8%; CHOL: 1.1%; BILI: 13.6%
America	Brazil	2008-2011	Overall: 3.4%	[39]
		2008-2018	BAR open: 3%; BAR VLP: 0.5%	[40]
	Canada	2015-2016	CSEC: 5.9%	[41]
		2015-2019	COLO: 10.28%; BILI: 16.13%	[42]
	Colombia	2008-2010	APPY: 3.9%; HYST: 5.5%; SPLE: 4.5%; CHOL: 3%	[43]
		2022	HER: 7.9%; CHOL: 8.3%; CSEC: 22.2%	[44]
	Cuba	2017-2018	APPY: 13.8%; HER: 5.7%	[45]
	Ecuador	2018	CSEC: 1.35%	[46]
	Honduras	2017-2018	CSEC: 5.1%	[47]
	Mexico	2011-2012	Overall: 12.1%; COLO: 5.2%; APPY: 4.9%; CHOL: 0.8%; HER: 0.9%	[48]
		2013-2015	CHOL: 5.5%	[49]
	Peru	2005-2010	APPY: 2.9%; CHOL: 2.8%; CSEC: 2.2%	[50]
		2015-2018	CSEC: 2.4%	[51]
		2019-2020	CSEC: 0.88%; CHOL: 0.18%; HER: 0.38%	[52]
	Uruguay	2012-2013	APPY: 3.2%; CHOL: 6.2%; COLO: 15.4%	[53]
		2021	CSEC: 1.74%; CHOL open: 1.85%; CHOL VLP: 0.23%	[54]
	Venezuela	2019-2021	Overall: 9.7%; APPY: 10.42%; BILI 3.79%	[55]
	United States	2011-2014	Overall: 0.9%; COLO: 3.99%-9.47%; CHOLO: 0.23%-1.72%; HER: 0.74%-5.25%; REC: 3.47%-26.67%; SB: 3.44%-6.75%	[16,17,56]
		2015-2019	COLO: 6.82%; BILI: 12.72%	[42]
		2016-2017	CHOL: 0.96%	[57]
Asia	China	2020	ABDS: 2.9%; COLO 7.1%	[58,59]
		2018	GAST: 5.2%	[60]
		2017-2020	CSEC: 23.30%	[61]
	India	2011-2017	Appendix: 35.3%	[62]
		2016	CSEC: 10.3%	[63]
		2005-2011	XLAP: 6%; HER: 3.8%	[64]
	Iran	2018	Overall: 0.29%	[65]
		2021	Overall: 5.2% surveillance	[66]
	Japan	2008-2010	COLO: 15%; REC: 17.8%	[67,68]
		2009-2019	APPY: VLP 4.19%, OPEN 6.60%	[69]
			CHOL: VLP 1.91%, OPEN 7.42%
			SB: VLP 8%, OPEN 15%
			COLO: VLP 7.27%, OPEN 15.5%
			REC: VLP 11.3%, OPEN 8.8%
	Kuwait	2016	SB: 6.5%; GAST: 0.7%	[70]
	Nepal	2019	CSEC: 8.54%	[71]
	Pakistan	2014-2019	BILI: 40%	[72]
		2016-2017	APPY: 32.7%; CHOLO: 20.7%; HER: 37.6%	[73]
	Philippines	2018-2019	Overall: 9.7%	[74]
	Republic of Korea	2008-2012	GAST: 3.12%	[75]
	Saudi Arabia	2016	Overall: 16.3%; open surgery: 34.8%; VLP surgery: 3.5%	[76]
	Taiwan	2021	Overall: 4.0%; regional hospital: 4.7% medical center	[77]
	Thailand	2007-2016	Overall: 2.98%	[78]
	Turkey	2005-2011	CHOL: 1.3%; COLO: 11.4%; CSEC: 3%; GAST: 4.3%; HYST: 3.1%; SPLE: 5%; XLAP: 2.6%	[79]
	United Arab Emirates	2016-2017	CSEC: 1.4%	[80]
Europe	Austria	2018-2020	CHOL: 0.4%; COLO: 3.6%; CSEC: 0.5%	[19]
	England	2017-2022	HYST: 1.7%; BILI: 15.4%; CHOL: 9.7%; GAST: 1.9%; COLO: 8.6%	[81]
	Estonia	2018-2020	CSEC: 2.0%	[19]
	France	2018-2020	CHOL: 0.7%; CSEC: 1.7%	[19]
	Germany	2018-2020	CHOL: 0.9%; COLO: 8.9%; CSEC: 0.6%	[19]
	Hungary	2018-2020	CHOL: 1.1%; COLO: 10.4%; CSEC: 1.3%	[19]
	Italy	2018-2020	CHOL: 0.7%; COLO: 5.9%; CSEC: 0.7%	[19]
	Lithuania	2018-2020	CHOL: 0.2%; COLO: 10.6%; CSEC: 0.6%	[19]
	Malta	2018-2020	COLO: 26.8%	[19]
	Netherlands	2018-2020	CHOL: 2.6%; COLO: 16.1%; CSEC: 1.5%	[19]
	Norway	2018-2020	CHOL: 2.8%; COLO: 11.7%; CSEC: 3.6%	[19]
	Portugal	2018-2020	CHOL: 2.3%; COLO: 14.5%; CSEC: 1.6%	[19]
	Slovakia	2018-2020	CHOL: 2.9%	[19]
	Spain	2016	COLO: 10.6%	[82]
		2013-2016	REC: 11.9%	[83]
		2009-2016	CHOL: 1.96%	[84]
	Switzerland	2017-2018	APPY: 3.1%; CHOL: 2.2%; HER: 0.9%; COLO: 13.5%; REC: 17.7%; GAST: 3.1%; CSEC: 1.8%	[85]
Oceania	Australia	2002-2013	Overall: 2.8%	[86]

ABDS: Abdominal surgery (miscellany); APPY: Appendix surgery; BAR: Bariatric surgery; BILI: Bile duct, liver or pancreatic surgery; CHOL: Gallbladder surgery; COLO: Colon surgery; CSEC: Caesarean section; GAST: Gastric surgery; HER: Herniorrhaphy; HYST: Abdominal hysterectomy; REC: Rectal surgery; SB: Small bowel surgery; SPLE: Spleen surgery; SSI: Surgical site infection; XLAP: Exploratory laparotomy.

Table 3 Microorganisms distributions for different type of abdominal surgery

Microorganism	Type of surgery
	Laparoscopic CHOL	Open CHOL	Laparoscopic COLO	Open COLO	CSEC
Gram-positive cocci	52.9	39	34.8	70.4	78.8
Staphylococcus aureus	23.9	7.6	4.3	25	38.4
Coagulase-negative staphylococci	9.2	6.2	2.2	27	22.6
Enterococcus species	11.1	18.9	24.5	9.3	5.6
Streptococcus species	4.8	1.9	2.3	3.7	5.7
Other Gram-positive cocci	3.9	4.4	1.4	5.4	6.5
Gram-positive bacilli	1.5	0.8	0.1	2	2.7
Gram-negative bacilli Enterobacterales	27.5	44.4	48.7	18.3	10.6
Escherichia coli	13.2	21.7	30.4	6.2	3.5
Citrobacter species	0.5	2.4	1.1	0.7	0.4
Enterobacter species	2.3	5.6	5.5	3.3	2.8
Klebsiella species	5	9.8	6.2	2.1	1.4
Proteus species	3.5	2.1	2.1	3.8	1.3
Serratia species	1.1	0.3	0.9	1	0.8
Other Enterobacteriaceae	2.1	2.5	2.5	1.1	0.4
Gram-negative nonfermentative bacilli	4.2	2.1	6	3.8	3.3
Acinetobacter species	0.5	0.3	0.4	0.6	0.6
Hemophilus species	0.2	0.1	0	0	0.1
Pseudomonas aeruginosa	2.1	0.9	5.3	2.9	1.6
Pseudomonadaceae family, other	0.2	0	0	0.2	0.6
Stenotrophomonas maltophilia	0	0.3	0.1	0.1	0.3
Other Gram-negative nonfermentative bacilli	1.4	0.5	0.2	0.1	0
Anaerobes	12	8.7	6.3	4.8	3.8
Bacteroides species	1.8	1.2	4.4	0.2	0.1
Other anaerobes	10.2	7.5	2	4.6	3.7
Other bacteria	1.8	3.5	1	0.4	0.6
Fungi, parasites	0.2	1.5	3.2	0.3	0.1
Candida species	0.2	1.5	3.2	0.3	0.1
Other fungi or parasites	0	0	0	0	0

Data obtained from the ECDC’s Annual Epidemiological Report for 2018-2020 on surgical site infections. CHOL: Cholecystectomy; COLO: Colon surgery; CSEC: Caesarean section.

Table 4 Ongoing trials

Study name	ClinicalTrial.gov identifier	Design	Status	Type of surgery	Intervention(s)	Country
Iodine-Povidone Alcohol Compared to Chlorhexidine Alcohol as Preoperative Antiseptics in Major Abdominal Elective Clean Contaminated Surgery	NCT03859908	Single blind RCT	Terminated	Elective surgery categorized as clean contaminated surgery	Drug: Iodine povacrylex/isopropyl alcohol	El Salvador
					Drug: Chlorhexidine gluconate/isopropyl alcohol
Examination of the Effect of Skin Antisepsis with Pre-heated Povidone Iodine on Surgical Site Infections: A Quasi-Experimental Study	NCT04969302	Single blind RCT	Completed	NS	Experimental: Povidone-iodine will heat to 37 °C using a gel warmer	Greece
					Control: Povidone-iodine will heat to 20 °C using a gel warmer
Study to Assess the Safety & Efficacy of Oral Ciprodiazole Versus Currently Used Ciprofloxacin & Metronidazole (CIPRO-001)	NCT05863832	Open label RCT	Recruiting	Pelvi-abdominal surgery	Experimental	Egypt
					Ciprodiazole
					Active comparator: Ciprofloxacin 500 mg
PVP Iodine vs Chlorhexidine in Alcohol for Disinfection of the Surgical Site (PICASSo)	NCT03685604	Single blind RCT	Completed	Colorectal surgery, cholecystectomy, herniotomy, appendectomy and bariatric surgery	Active comparator: Braunoderm®	Switzerland
					Comparator
					Softasept®
Delafloxacin IV and OS Administration Compared to Best Available Therapy in Patients with Surgical Site Infections (DRESS)	NCT04042077	Single blind RCT	Terminated	Abdominal surgery	Drug: Delafloxacin	Rome
					Drug: Vancomycin
					Drug: Linezolid
					Drug: Piperacillin/tazobactam
					Drug: Tigecycline
A Randomized, Blinded, Placebo and Standard of Care Controlled Efficacy, Safety, and Tolerability Study of up to 20 mL of DFA-02 in Patients Undergoing Abdominal Surgery	NCT01888367	Triple blind RCT	Completed	Abdominal surgery	Drug: DFA-02 Antibiotic Gel	United States
					Drug: DFA-02 Placebo Gel
Reduction of Postoperative Wound Infections by Antiseptica? (RECIPE)	NCT04055233	Double blind RCT	Completed	Laparotomy for visceral surgery	Drug: Polihexanide; Serasept	Germany
					Drug: NaCl; saline
Study of Chlorhexidine Gluconate as a Preoperative Antisepsis (CHG)	NCT01495117	Quadruple blind RCT	Completed	Resection surgery (clean-contaminated open surgery)	Drug: Povidone-Iodine	Republic of Korea
					Drug: Chlorhexidine gluconate
A Randomized Controlled Trial of 2% Chlorhexidine Gluconate Skin Preparation Cloths for the Prevention of Post-Operative Surgical Site Infections in Colorectal Patients	NCT02385708	Open label RCT	Completed	Colorectal surgery	Drug: 2% chlorohexidine gluconate standard of care	United States
					Drug: 2% chlorohexidine gluconate chin to toe
Effect of Peritoneal Lavage with Clindamycin-gentamicin Solution on Postoperative Colorectal Cancer Infection in Elective Surgery	NCT01378832	Open label RCT	Completed	Colorectal surgery	Procedure: Intra-peritoneal antibiotic lavage	No location data
Collagen-Gentamicin Implant in the Treatment of Contaminated Surgical Abdominal Wounds - A Randomized Controlled Trial	NCT00977405	Double blind RCT	Terminated	Abdominal surgery	Device: Collatamp gentamicin implant	Singapore
CLinical Evaluation of Adults UNdergoing Elective Surgery Utilizing Intraoperative Incisional Wound Irrigation: A Randomized Controlled Trial (CLEAN Wound)	NCT04548661	Double blind RCT	Not yet recruiting	Laparotomy (clean-contaminated or contaminated incision). Laparoscopy (clean-contaminated or contaminated incision)	Procedure: Intraoperative incisional wound irrigation with povidone-iodine solution	Canada
					Procedure: Intraoperative incisional wound irrigation with saline
Randomized Controlled Trial to Evaluate the Optimal Timing of Surgical Antimicrobial Prophylaxis	NCT01790529	Quadruple blind RCT	Completed	Colorectal surgery	Procedure: Cefuroxime + metronidazole 75 to 30 min prior to skin incision	Switzerland
					Procedure: Cefuroxime + metronidazole within 30 min prior to skin incision)
A Pilot Clinical Evaluation of the Antimicrobial Effectiveness of Topically Applied ZuraPrep™	NCT02221232	Open label pilot study	Terminated	NS	Drug: Chloraprep	United States
					Drug: ZuraPrep
					Drug: ZuraPrep Vehicle
ROSSINI 2 - Reduction of Surgical Site Infection Using Several Novel Interventions (ROSSINI 2)	NCT03838575	Double blind RCT	Recruiting	Colorectal, hepatobiliary, upper GI, urological, vascular, or gynecological	Drug: 2% alcoholic chlorhexidine skin prep (SKIN PREP)	United Kingdom
					Device: Iodophor Antimicrobial Incise Drapes (DRAPE)
					Device: Gentamicin-impregnated implants/sponges (SPONGE)
					Other: None (control)
D-PLEX 311: Safety and Efficacy of D-PLEX in the Prevention of Post Abdominal Surgery Incisional Infection (SHIELD I)	NCT04233424	Triple blind RCT	Completed	Elective colorectal surgery	Drug: D-PLEX (new formulation of extended release of doxycycline)	United States
					Other: SoC
D-PLEX 312 - Safety and Efficacy of D-PLEX in the Prevention of Post Abdominal Surgery Incisional Infection (SHIELD II)	NCT04411199	Triple blind RCT	Recruiting	Elective colorectal surgery	Drug: D-PLEX + SoC	United States, Hungary, Serbia, Poland, Israel
					Other: SoC
Abdomen Closure Using Triclosan Coated Absorbable Suture vs Uncoated Sutures of the Same Base Material	NCT01620294	Double blind RCT	Completed	Elective colorectal surgery	Procedure: Abdominal wall closure	Hungary
					Procedure: Surgical site infection
Prophylaxis of Surgical Wound Infection with Topical Antibiotics	NCT04476212	Triple blind RCT	Recruiting	Elective abdominal wall surgery	Drug: Amoxicillin-clavulanate for topical prophylaxis	Spain
				Elective and emergency colorectal surgery	No intervention: Control
D-PLEX 310: Safety and Efficacy of D-PLEX in the Prevention of Post Abdominal Surgery Incisional Infection	NCT03633123	Single blind RCT	Completed	Elective colorectal surgery	Drug: D_PLEX	Israel
					Other: SoC
Antibiotic Prophylaxis in the Prevention of Surgical Site Infections After Selected Urgent Abdominal Surgical Procedures	NCT01524081	Double blind RCT	Completed	Emergent surgery for: Acute appendicitis/perforated gastric or duodenal ulcer/small bowel obstruction	Drug: Metronidazole, cefuroxime	Czech Republic
					Drug: Amoxicillin (+ clavulanic acid) and fluconazole
					Drug: Placebo
					Drug: Placebo
Study the Efficacy of Topical Antibiotherapy in the Prophylaxis of Incisional Surgical Infection in Colorectal Surgery (PROTOP)	NCT03574090	Triple blind RCT	Completed	Colorectal surgery	Drug: Amoxicillin clavulanate	Spain
					Drug: Physiological saline
Parenteral Antibiotics Compared to Combination of Oral and Parenteral Antibiotics in Colorectal Surgery Prophylaxis (ORALEV)	NCT02505581	Quadruple blind RCT	Completed	Colorectal surgery	Drug: Extra dosage - cefuroxime (750 mg) intravenous	Spain
					Drug: Ciprofloxacin 750 mg oral
					Drug: Metronidazole 250 mg oral
					Drug: Cefuroxime 1.5 g intravenous
					Drug: Metronidazole 1 g intravenous
Impact of Triclosan-coated Suture on Surgical Site Infection After Colorectal Surgery	NCT01869257	Single blind RCT	Completed	Colorectal surgery	Device: Triclosan coated suture	Italy
					Device: Regular suture
Intravenous Versus Combined Oral and Intravenous Antimicrobial Prophylaxis for the Prevention of Surgical Site Infection in Elective Colorectal Surgery (COMBINE)	NCT02618720	Double blind RCT	Completed	Elective colorectal surgery	Drug: Ornidazole	France
					Drug: Placebo
Prophylactic Effect Preoperative Antibiotics with Mechanical Bowel Preparation in SSIs	NCT03856671	Open label RCT	Completed	Laparoscopic colorectal surgery	Drug: Neomycin, metronidazole	China
Frequency of Surgical Site Infection in Abdominal Hernia with Gentamycin Spray on Mesh Versus no Spray	NCT04164524	Case-Control trial	Completed	Elective surgery; Para umbilical hernia, umbilical and epigastric hernia,	Drug: Gentamycin 160 mg spray applied over the mesh	Pakistan
Antibiotic Instillation in Acute Complex Appendicitis for Prevention of Deep Space Surgical Site Infections	NCT05470517	Single blind RCT	Recruiting	Appendectomy	Drug: Ceftriaxone	United States
					Procedure: Intra-peritoneal fluid aspiration
Prophylaxis of Surgical Wound Infection in Incisional Hernia Repair With Topical Antibiotics (PROTOP-PAR)	NCT05508152	Triple blind RCT	Recruiting	Elective surgical procedure due to an abdominal wall incisional hernia	Drug: Wound irrigation with amoxicillin-clavulanate in saline solution	Spain
					Drug: Wound irrigation with a saline solution
Orally Administered Trimethoprim-sulfamethoxazole and Metronidazole as Prophylaxis of Infection Following Elective Colorectal Surgery	NCT00613769	Triple blind RCT	Completed	Colorectal surgery	Drug: Trimethoprim-sulfamethoxazole + metronidazole	Sweden
					Drug: Cefuroxime and metronidazole
The Effect of Intraoperative Peritoneal Lavage With Super-Oxidized Solution on Surgical Site Infections and Mortality in Patients With Secondary Peritonitis: A Randomized Controlled Trial	NCT05050253	Open label RCT	Recruiting	Emergency abdominal surgery by laparotomy	Device: Super-oxidized solution	Switzerland
					Device: Ringer’s solution
Reducing INfection at the Surgical SitE With Antibiotic Irrigation During Ventral Hernia Repair (RINSE Trial)	NCT03945357	Open label RCT	Completed	Elective, open ventral hernia repair	Drug: Gemcitabine/clindamycin	United States
					Drug: Normal saline
Preoperative Oral Antibiotics With vs Without Mechanical Bowel Preparation to Reduce Surgical Site Infections Following Colonic Resection: an International Randomized Controlled Trial. (ORALEV2)	NCT04161599	Single blind RCT	Recruiting	Colectomy	Drug: Cefuroxime (750 mg) intravenous	China
					Drug: Cefuroxime 750 mg oral	Italy
					Drug: Metronidazole 250 mg oral tablet	Spain
					Drug: Metronidazole 1 g intravenous	Russia
					Drug: Cefuroxime 1.5 g intravenous	Greece
					Drug: Sodium picosulfate, light magnesium oxide, anhydrous citric acid 10 mg/3.5 g/10.97 g oral	United Kingdom
Standard Versus Pre-emptive Antibiotic Treatment to Reduce the Rate of Infectious Outcomes After Whipple’s Procedure (SPARROW): a Multicenter, Randomized Controlled Trial	NCT05784311	Open label RCT	No yet recruiting	Elective pancreatoduodenectomy	Drug: Cefuroxime	Netherlands
					Drug: Metronidazole

NS: Not specified; RCT: Randomized controlled trial; SoC: Standard of care.