Perioperative Use of Antibiotics in Intra-Abdominal Surgical Infections

Abstract

Background:

We created a questionnaire with the aim of evaluating surgeon compliance with the guidelines for antibiotic use in the perioperative period in intra-abdominal surgical infections. We discuss the problems emerging from non-adherence to these guidelines.

Methods:

In the questionnaire, we tried to correlate the type of intra-abdominal infection with: (1) Time of antibiotic administration commencement; (2) type of antibiotic(s) administered; (c) duration of antibiotic administration; and (4) modification of antibiotic type/duration of administration in the presence of factors increasing the risk of treatment failure. In order to collect and process the data more easily, the patients were divided into four groups–Group A: Community patients with intra-abdominal surgical infections and simple contamination of the peritoneal cavity according to the Surgical Infection Society (SIS) guidelines; Group B: Community patients with an intra-abdominal surgical infection evolving to secondary peritonitis per SIS guidelines; Group C: Community patients with an intra-abdominal surgical infection with a high risk of surgical site infection; and Group D: Patients with recent hospitalization or nosocomial or postoperative intra-abdominal infection.

Results:

The questionnaire was sent to the directors of 43 surgical clinics in northern Greece, and 27 answered (63%). In 81.5% of the clinics (median 22; range 15–24), depending on the type of infection, empirical antibiotic treatment commenced preoperatively. In Group A, on average, 29.6% of the clinics (median 8; range 5–16) administer antibiotics for as long as 24 h, and 11.1% (median 3; range 1–10) use antibiotics not recommended in the SIS guidelines (e.g., third- and fourth-generation cephalosporins, ciprofloxacin, imipenem-cilastatin, meropenem, or piperacillin/tazobactam). In Group B, 22.2% of clinics (median 6; range 2–15) administer antibiotics for three to five days, and 14.8% (median 4; range 1–11) use antibiotics outside SIS guidelines. In Group C, 40.7% of clinics (median 11; range 1–14) administer antibiotics for more than five days, and 14.8% (median 4; range 1–14) use antibiotics that are outside the SIS guidelines. In Group D, 11.1% of clinics (median 3; range 2–5) do not cover Enterococcus with the antibiotics administered.

Conclusions:

There seems to be confusion in determining the situations with simple contamination of the peritoneal cavity, whose treatment requires short-duration antibiotic administration, and in the type of antibiotics administered to various patient groups, elements that lead to prolonged or erroneous administration of antibiotic drugs. Continuous discussion and surgeon training is imperative and may be the best choice to ensure familiarity with antibiotics and their proper use and thus to minimize serious adverse events and treatment failure.

The treatment of intra-abdominal surgical infections includes the reinforcement of the patient's general condition, appropriate source control, and complementary antimicrobial therapy. Treatment effects depend on the promptness of diagnosis, the correct timing of the operation, and the effectiveness and soundness of antimicrobial treatment.

The perioperative administration of antibiotics is complementary to surgical treatment of intra-abdominal infections, contributing substantially to the minimizing of complications, morbidity, and death. For a long time, the use of antibiotics was uncontrolled and chaotic. In 1992, the Surgical Infection Society–Europe (SIS-E), in an effort to reduce the adverse effects of antibiotic abuse, published specific guidelines, which were accepted, among others, by the Hellenic Society of Surgical Infections (HSSI). Unfortunately, despite these guidelines, antibiotic abuse did not abate, resulting in the emergence of multi-resistant microbial strains and infections caused by them, which are essentially non-treatable and life-threatening. As a result, in 2002, the SIS returned to the issue of antibiotic use and published new guidelines, with the necessary amendments required by recent data; and in 2003, the HSSI presented a similar guide [1 –7]. With the aim of evaluating the acceptance and application by surgeons of the guidelines regarding the use of antibiotics in the perioperative period and to discuss the problems arising from noncompliance with these guidelines, we asked the directors of the surgical clinics of northern Greece (Macedonia, Thrace, and Thessaly) to fill out a questionnaire (Table 1).

Table 1.

Number (%) of Surgical Clinics Using Various Durations of Treatment

	Gastric–duodenal perforation			Intestinal rupture–perforation			Acute cholecystitis			Acute appendicitis
Duration	Group A	Group B	Group C	Group A	Group B	Group C	Group A	Group B	Group C	Group A	Group B
≤24 h	8 (29.6)	–	1 (3.7)	8 (29.6)	–	–	5 (18.5)	–	–	16 (59.3)	2 (7.4)
2 days	–	–	–	1 (3.7)	–	–	–	–	–	1 (3.7)	–
2–3 days	1 (3.7)	–	–	–	–	–	–	–	–	1 (3.7)	–
2–4 days	1 (3.7)	–	–	–	–	–	–	–	–	–	–
3 days	5 (18.5)	5 (18.5)	5 (18.5)	2 (7.4)	2 (7.4)	3 (11.1)	3 (11.1)	3 (11.1)	3 (11.1)	4 (14.8)	2 (7.4)
3–4 days	1 (3.7)	–	–	2 (7.4)	–	–	2 (7.4)	–	–	–	–
3–5 days	1 (3.7)	11 (40.7)	8 (29.6)	5 (18.5)	10 (37.0)	8 (29.6)	7 (25.9)	6 (22.2)	9 (33.3)	1 (3.7)	15 (55.6)
4 days	–	–	–	–	–	–	–	–	–	1 (3.7)	–
4–5 days	2 (7.4)	–	–	2 (7.4)	–	–	–	–	–	–	–
5 days	3 (11.1)	–	–	2 (7.4)	–	–	3 (11.1)	–	1 (3.7)	–	–
5–7 days	2 (7.4)	10 (37.0)	11 (40.7)	1 (3.7)	14 (51.9)	14 (51.9)	1 (3.7)	15 (55.6)	12 (44.4)	–	7 (26.0)
7 days	–	–	–	3 (11.1)	1 (3.7)	1 (3.7)	1 (3.7)	2 (7.4)	1 (3.7)	1 (3.7)	1 (3.7)
8 days	1 (3.7)	1 (3.7)	–	–	–	–	–	–	–	–	–
≤48 h after signs of infection abate	–	–	–	1 (3.7)	–	1 (3.7)	1 (3.7)	1 (3.7)	1 (3.7)	–	–
>24 h	17 (63.0)	–	–	19 (70.4)	–	–	22 (81.5)	–	–	11 (40.7)	–
Not specified	2 (7.4)	–	2 (7.4)	–	–	–	–	–	–	–	–

Summary
Totals	Group A		Group B		Group C
≤24 h	Median 8 (29.6)	Range 5–16 (18.5–59.3)
>24 h	Median 22 (81.5)	Range 11–22 (40.7–81.5)
3–5 days			Median 26 (96.0)	Range 26–27 (96–100)	Median 26 (96.0)	Range 26–27 (96.0–100)

Materials and Methods

In a previous roundtable on the treatment of secondary peritonitis that was held during a symposium on surgical infections, it was apparent, from the speakers' presentations and the comments of the participants, that there was confusion regarding the usage of antibiotics in intra-abdominal surgical infections and ignorance of the relevant guidelines. After this, and in collaboration with the HSSI, we devised this questionnaire. We tried to correlate the type of intra-abdominal infection with the time antibiotic administration commenced, the type of antibiotic(s) administered, the duration of antibiotic administration, and modification of antibiotic type/duration of administration in the presence of factors increasing the risk of treatment failure. This questionnaire included an addendum where advanced age (>70 years old), metabolic diseases (diabetes mellitus, renal failure, obesity, cirrhosis, hypoalbuminemia <2 g/dL), immunosuppression (radiation therapy, chemotherapy, corticosteroids), long duration of operation (>3 h), foreign body use (e.g., mesh), tissue ischemia, and abuse of cautery were considered risk factors for surgical site infections (SSIs). Depending on the time of infection treatment and the type of infection and in accordance with the intra-abdominal surgical infection treatment guidelines, we divided the patients into four groups [8,9]:

Group A: Community patients with intra-abdominal surgical infections and simple contamination of the peritoneal cavity as described in the SIS guidelines (gastric or duodenal perforation treated within the first 24 h from symptom onset, intestinal perforation–rupture treated within the first 12 h from symptom onset, acute cholecystitis without gallbladder rupture, acute appendicitis without rupture);

Group B: Community patients with intra-abdominal surgical infections evolving to secondary peritonitis per SIS guidelines (gastric or duodenal perforation treated later than 24 h from symptom onset, intestinal perforation–rupture treated later than 12 h from symptom onset, acute cholecystitis with gallbladder rupture, acute appendicitis with rupture);

Group C: Community patients with intra-abdominal surgical infections at high risk for SSI.

Group D: Patients with recent hospitalization or nosocomial or postoperative intra-abdominal infections.

During this study, there was continuous communication by telephone with the directors of every clinic that participated in order to confirm proper completion. Additionally, after the data were processed, they were discussed with the participating clinic directors in two special surgical infection symposia.

The data are presented as percentages and medians and ranges, as this format is considered the simplest and easiest to understand.

Results

Twenty-seven (63%) surgical clinic directors responded (Appendix 1).

Gastric or duodenal perforation

Group A. In patients treated during the first 24 h from symptom onset, 29.6% of clinics (8/27) administer antibiotics during the first 24 h only, whereas 63% continue administration for two to eight days and 7% of the clinics did not provide the relevant data (Table 1). Second-generation cephalosporins with or without metronidazole and semisynthetic penicillins with a beta-lactamase inhibitor were used by all clinics (Table 2), although 7.4% of them (median 2; range 1–6) also used third- and fourth-generation cephalosporins with or without metronidazole, quinolones, piperacillin/tazobactam, imipenem-cilastatin, or meropenem, thereby deviating from the SIS guidelines.

Table 2.

Type of Antibiotic Given (Number [%] of Clinics)

	Gastric–duodenal perforation			Intestinal rupture–perforation			Acute cholecystitis			Acute appendicitis
Drug(s)	Group A	Group B	Group C	Group A	Group B	Group C	Group A	Group B	Group C	Group A	Group B
Second-gen. cephalosporin	7 (25.9)	3 (11.1)	4 (14.8)	6 (22.2)	3 (11.1)	3 (11.1)	14 (51.9)	8 (29.6)	7 (26.0)	16 (59.3)	3 (11.1)
Second-gen. cephalosporin + antianaerobic	15 (56.0)	12 (44.5)	6 (22.2)	13 (48.1)	12 (44.4)	8 (29.6)	7 (26.0)	8 (29.6)	5 (18.5)	8 (29.6)	16 (59.3)
Second-gen. cephalosporin + antianaerobic + aminoglycoside	3 (11.1)	1 (3.7)	3 (11.1)	1 (3.7)	2 (7.4)	2 (7.4)	1 (3.7)	–	2 (7.4)	–	1 (3.7)
Second-gen. cephalosporin + aminoglycoside	–	–	–	–	–	–	–	–	–	1 (3.7)	–
Ampicillin/sulbactam	8 (29.6)	4 (14.8)	2 (7.4)	4 (14.8)	2 (7.4)	2 (7.4)	3 (11.1)	2 (7.4)	4 (14.8)	7 (26.0)	3 (11.1)
Amoxycillin/clavulanic acid	4 (14.8)	3 (11.1)	1 (3.7)	3 (11.1)	1 (3.7)	3 (11.1)	3 (11.1)	1 (3.7)	–	3 (11.1)	1 (3.7)
Ticarcillin/clavulanic acid + aminoglycoside	–	1 (3.7)	–	–	–	–	–	–	–	–	–
Ticarcillin/clavulanic acid	2 (7.4)	7 (25.9)	3 (11.1)	7 (26.0)	9 (33.3)	10 (37.0)	6 (22.2)	6 (22.2)	7 (26.0)	4 (14.8)	5 (18.5)
Ertapenem	2 (7.4)	3 (11.1)	2 (7.4)	2 (7.4)	3 (11.1)	2 (7.4)	3 (11.1)	2 (7.4)	3 (11.1)	–	–
Aztreonam + clindamycin	1 (3.7)	1 (3.7)	2 (7.4)	1 (3.7)	–	2 (7.4)	–	1 (3.7)	2 (7.4)	–	2 (7.4)
Third-gen. cephalosporin	3 (11.1)	2 (7.4)	4 (14.8)	6 (22.2)	3 (11.1)	4 (14.8)	10 (37.0)	4 (14.8)	6 (22.2)	9 (33.3)	5 (18.5)
Third-gen. cephalosporin + antianaerobic	6 (22.2)	6 (22.2)	8 (29.6)	5 (18.5)	10 (37.0)	9 (33.3)	5 (18.5)	10 (37.0)	9 (33.3)	2 (7.4)	5 (18.5)
Third-gen. cephalosporin + antianaerobic + aminoglycoside	–	–	–	–	–	1 (3.7)	1 (3.7)	1 (3.7)	–	–	–
Fourth-gen. cephalosporin	1 (3.7)	–	3 (11.1)	4 (14.8)	2 (7.4)	3 (11.1)	8 (29.6)	3 (11.1)	5 (18.5)	8 (29.6)	2 (7.4)
Aminoglycoside + antianaerobic	1 (3.7)	6 (22.2)	5 (18.5)	2 (7.4)	4 (14.8)	4 (14.8)	–	–	–	2 (7.4)	4 (14.8)
Piperacillin/tazobactam	4 (14.8)	11 (40.7)	11 (40.7)	7 (26.0)	9 (33.3)	12 (44.4)	7 (26.0)	12 (44.4)	14 (51.9)	4 (14.8)	6 (22.2)
Piperacillin/tazobactam + aminoglycoside	–	1 (3.7)	–	–	–	–	–	–	–	–	–
Piperacillin/tazobactam + metronidazole	1 (3.7)	1 (3.7)	1 (3.7)	1 (3.7)	1 (3.7)	1 (3.7)	–	–	1 (3.7)	–	–
Ciprofloxacin + antianaerobic	2 (7.4)	5 (18.5)	4 (14.8)	2 (7.4)	5 (18.5)	9 (33.3)	3 (11.1)	5 (18.5)	8 (29.6)	1 (3.7)	6 (22.2)
Ciprofloxacin + antianaerobic + aminoglycoside	–	–	–	–	–	1 (3.7)	–	–	–	–	–
Imipenem-cilastatin	2 (7.4)	3 (11.1)	3 (11.1)	–	1 (3.7)	4 (14.8)	–	–	–	–	–
Meropenem	–	1 (3.7)	1 (3.7)	–	–	2 (7.4)	–	–	–	–	1 (3.7)

gen. = generation.

Group B. In patients treated later than 24 h from symptom onset, the duration of perioperative antibiotic administration was three to five days in 59.3% of clinics, five to seven days in 37%, and eight days in 3.7% (Table 1). Second- and third-generation cephalosporins, with or without an antianaerobic agent, semisynthetic penicillins with a beta-lactamase inhibitor, and ertapenem were used by all clinics, but 11.1% of them (median 3; range 1–11) also used third- and fourth-generation cephalosporins or quinolones combined with antianaerobic antibiotics or piperacillin/tazobactam, imipenem-cilastatin, or meropenem as monotherapy (Table 2).

Group C. In high-risk patients, 40.7% of surgical clinics administer antibiotics for five to seven days, whereas 14.8% (median 4; range 3–8) deviate from the SIS guidelines, as they do not cover patients for Enterococcus (Tables 1 and 2).

Intestinal rupture-perforation

Group A. In patients treated during the first 12 h from symptom onset, 29.6% of surgical clinics administer antibiotics in the first 24 h according to the SIS guidelines, 66.7% continue administration for two to eight days, whereas 3.7% discontinue antibiotic treatment 48 h after abatement of clinical and laboratory indicators of infection (Table 1). Also, 14.8% of the clinics (median 4; range 1–7) use third- and fourth-generation cephalosporins or quinolones singly or combined with antianaerobic antibiotics or piperacillin/tazobactam as monotherapy or combined with antianaerobic antibiotics, deviating from the SIS guidelines (Table 2).

Group B. In patients treated later than 12 h from symptom onset, 52% of clinics administer antibiotics for five to seven days (Table 1). Third- and fourth-generation cephalosporins with or without an antianaerobic agent, ciprofloxacin with an antianaerobic agent, or piperacillin/tazobactam or imipenem/cilastatin as monotherapy were administered in 14.8% of clinics (median 4; range 1–10), deviating from the SIS guidelines (Table 2).

Group C. In high-risk patients, 52% of surgical clinics administered antibiotics for five to seven days and 3.7% for as long as 48 h after clinical and paraclinical indicators of infection have abated. A total of 14.8% of clinics (median 4; range 1–9) deviate from the SIS guidelines, as they do not cover these patients for Enterococcus (Tables 1 and 2).

Acute cholecystitis

Group A: In patients without gallbladder rupture, 18.5% of surgical clinics administer antibiotics for the first 24 h, according to the SIS guidelines, whereas 81.4% administer antibiotics beyond the first 24 h postoperatively (Table 1). Third- and fourth-generation cephalosporins and piperacillin/tazobactam as monotherapy and third-generation cephalosporins and fluoroquinolones combined with antianaerobic agents, an aminoglycoside, or both were administered in 18.5% of clinics (median 5; range 1–10) (Table 2).

Group B: In patients with gallbladder rupture, 63% of surgical clinics administer antibiotics for five to seven days (Table 1). Third- and fourth-generation cephalosporins as monotherapy or in combination with antianaerobic agents, an aminoglycoside, or both or piperacillin/tazobactam or fluoroquinolones combined with antianaerobic agents, an aminoglycoside, or both were administered by 18.5% of clinics (median 5; range 1–12), deviating from the SIS guidelines (Table 2).

Group C: In high-risk patients, 51.8% of clinics administer antibiotics for five to seven days, whereas 22.2% (median 6; range 1–12) deviate from the SIS guidelines, as they do not cover patients for Enterococcus (Tables 1 and 2).

Acute appendicitis

Group A: In patients without rupture of the appendix, 59.3% of clinics administer antibiotics during the first 24 h, whereas 40.7% continue for two to seven days, thereby deviating from the SIS guidelines (Table 1). Third- and fourth-generation cephalosporins and quinolones as monotherapy or combined with metronidazole or piperacillin/tazobactam as monotherapy were administered by 14.8% of clinics (median 4; range 1–9), a deviation from the SIS guidelines (Table 2).

Group B: In patients with appendiceal rupture, 92.6% of clinics administer antibiotics for three to seven days (Table 1). Third- and fourth-generation cephalosporins and fluoroquinolones as monotherapy or combined with metronidazole and piperacillin/tazobactam were administered by 18.5% of clinics (median 5; range 1–6), deviating from the SIS guidelines (Table 2).

Group D: In patients with recent hospitalization or nosocomial or postoperative intra-abdominal infection, 74.1% of clinics administer antibiotics for five to seven days, whereas 11.1% (median 3; range 1–13) do not cover patients for Enterococcus, and 7.4% report that they followed instructions from an infectious disease specialist (Table 3). Preventive antifungal treatment was administered by 48.2% of the clinics in circumstances strongly suggesting fungal participation in the infection and was not administered by 33.3%, whereas 7.4% followed the instructions from infectious disease specialists in this regard (Table 4).

Table 3.

Treatment of Nosocomial or Postoperative Intra-Abdominal Infection (Number [%] of Surgical Clinics)

Duration (days)
3	1 (3.7)
3–5	1 (3.7)
5–7	19 (70.4)
7	1 (3.7)
>7	2 (7.4)
Not specified	3 (11.1)
Drug(s)
Second-generation cephalosporin	3 (11.1)
Third-generation cephalosporin	3 (11.1)
Fourth-generation cephalosporin	3 (11.1)
Ticarcillin/clavulanic acid	5 (18.5)
Piperacillin/tazobactam	11 (40.7)
Ertapenem	2 (7.4)
Imipenem-cilastatin	9 (33.3)
Meropenem	3 (11.1)
Aminoglycoside + antianaerobic	4 (14.8)
Aztreonam + clindamycin	3 (11.1)
Second-generation cephalosporin + antianaerobic	5 (18.5)
Third-generation cephalosporin + antianaerobic	13 (14.1)
Third-generation cephalosporin + antianaerobic + aminoglycoside	1 (3.7)
Ciprofloxacin + antianaerobic	12 (44.4)
Fourth-generation cephalosporin + antianaerobic + aminoglycoside	1 (3.7)
Piperacillin/tazobactam + antianaerobic	1 (3.7)
“Antibiotic combination” + anti-staphylococcal	2 (7.4)
Infectious disease specialist consulted	2 (7.4)

Table 4.

Coverage in Patients with Nosocomial or Postoperative Intra-Abdominal Infections (Number [%] of Clinics)

Coverage of Enterococcus
Yes	12 (45.0)
No	15 (55.0)
Prophylactic coverage of fungi
Yes	13 (48.1)
No	9 (33.3)
Infectious disease specialist consulted	2 (7.4)
No answer	3 (11.1)

In a mean of 81.5% of surgical clinics (median 22, range 15–24), antibiotic treatment commenced preoperatively. The commencement of perioperative antibiotics administration took place:

Immediately after the diagnosis of an intra-abdominal infection

For Group A patients, administration began immediately in 70.4% (median 19; range 15–20) (Table 5). For Group B, the figure was 81.5% (median 22; range 18–24). For Group C, this plan was used in 88.9% of clinics (median 24; range 22–24). For Group D, immediate treatment was used in 88.9% of clinics.

Table 5.

Timing of Commencement of Antibiotic Administration (Number [%] of Clinics)

Group		Preoperative	Induction of anesthesia	Intraoperatively
A	Gastric–duodenal perforation treated within 24 h	19 (70.4)	3 (11.1)	5 (18.5)
	Intestinal rupture treated within 12 h	20 (74.1)	4 (14.8)	3 (11.1)
	Acute cholecystitis without gallbladder rupture	19 (70.4)	3 (11.1)	5 (18.5)
	Acute appendicitis without appendiceal rupture	15 (55.6)	10 (37)	2 (7.4)
B	Gastric—duodenal perforation treated after 24 h	22 (81.5)	3 (11.1)	2 (7.4)
	Intestinal rupture treated after 12 h	24 (88.9)	2 (7.4)	1 (3.7)
	Acute cholecystitis with gallbladder rupture	22 (81.5)	2 (7.4)	3 (11.1)
	Acute appendicitis with appendiceal rupture	18 (66.7)	5 (18.5)	4 (14.8)
C	Gastric–duodenal perforation in high-risk patient	22 (81.5)	3 (11.1)	2 (7.4)
	Intestinal rupture treated after 12 h in high-risk patient	24 (88.9)	2 (7.4)	1 (3.7)
	Acute cholecystitis in high-risk patient	22 (81.5)	2 (7.4)	3 (11.1)
D	Nosocomial or postoperative intra-abdominal infection	24 (88.9)	2 (7.4)	1 (3.7)
	Median (range)	22 (15–24)	3 (2–10)	2 (1–5)

During induction to anesthesia

In Group A patients, antibiotics were delivered during induction in 14.8% of clinics (median 4; range 3–10). In Group B, this figure was 11.1% (median 3; range 2–5), whereas in Group C, it was 7.4% (median 2; range 2–3), and in Group D, it was 7.4% (n = 2).

Intraoperatively

In Group A patients, intraoperative administration was used in 18.5% of clinics (median 5; range 2–5). In Group B, such treatment was used in 7.4.1% of clinics (median 2; range 1–4). In Group C, intraoperative administration was applied in 3.7% of clinics (median 1; range 1–3). In Group D, it was used in 3.7% of clinics (Table 5).

Discussion

Antimicrobial agents, without doubt, are one of the greatest achievements of modern mankind. Their emergence, especially with the advent of penicillin, was met with great enthusiasm and excessive optimism. The quick emergence of resistant strains, initially staphylococcal and subsequently enterococcal and gram-negative ones, led to intense skepticism and reconsideration. It was understood that abuse and erroneous administration of these agents are the main elements that lead to resistance problems.

Today, despite many references in the literature to the appropriate use of antibiotics in the surgical patient during perioperative chemoprophylaxis and empirical or etiologic treatment of surgical and postoperative infections, the clinician often encounters difficulties in agent selection and administration. These difficulties are aggravated by the plethora of medications available with the same or similar effects and the vagueness of available information regarding the pharmaceutical value and use of the agents. We believe that every effort in setting guidelines on antimicrobial agent usage and reducing their abuse adds another page to the chapter on proper antibiotic usage.

According to the guidelines of both the SIS and the HSSI, gastric or duodenal perforation treated within 24 h of symptom onset, intestinal rupture or perforation treated within 12 h of symptom onset, acute or gangrenous appendicitis without appendiceal rupture, and acute or gangrenous cholecystitis without gallbladder rupture are considered localized inflammations that cause simple contamination of the peritoneal cavity, not an infection. Through the analysis of mostly Grade I studies, those experts recommend that perioperative antibiotic administration not exceed 24 h. The HSSI recommends that perioperative chemotherapy last five to seven days for biliary tract infection (acute cholecystitis/cholangiitis) and two or three days for gangrenous nonruptured appendicitis [10].

The HSSI first published its guidelines for antibiotic use in 2003. Taking into consideration the widespread use of antibiotics in Greek hospitals, the special conditions of the Greek area regarding multiresistant strains, and the confusion among surgeons about perioperative antibiotic use, the HSSI considered that some deviation from international guidelines should be included in the first organized step in perioperative antibiotic use, in light of the Greek reality; e.g., perioperative antibiotic administration for five to seven days in acute cholecystitis–cholangiitis and two or three days in gangrenous nonperforated appendicitis.

Gastric or duodenal perforation treated later than 24 h from symptom onset, intestinal perforation–rupture operated on later than 12 h from symptom onset, acute or gangrenous appendicitis with appendiceal rupture, and acute or gangrenous cholecystitis with gallbladder rupture are considered intra-abdominal infections that lead to generalized infection of the peritoneal cavity (secondary peritonitis). The guidelines for the perioperative use of antibiotics in these cases were based chiefly on Grade II studies, because the disease characteristics do not easily allow the planning of blinded randomized trials. The guidelines recommend that the duration of antibiotic treatment be four to seven days [8 –17]. However, there are studies recommending that the duration of perioperative chemotherapy be correlated with the intraoperative findings at the initial operation or the abatement of clinical and paraclinical indicators of infection. Despite the seeming divergence of the experts on this issue, it is stressed emphatically that the persistence of infection signs or their recurrence beyond four to six days after initial surgery is an indication for diagnostic re-evaluation of the extent of the initial infection or of the presentation of a new distant infection. Consequently, a change in antimicrobial therapy is called for.

Regarding the type of antibiotics that should be used in the perioperative period for proper coverage of patients with intra-abdominal infections, the SIS guidelines recommend the following:

1) Patients presenting from their homes with an intra-abdominal infection without recent hospitalization or antibiotic administration (community infection) have suffered infection by microorganisms from their own alimentary tracts. These infections usually are mixed, with aerobic microbial strains adequately covered by second-generation cephalosporins (cefuroxime, cefamandole, ceforadine, cefoxitin) or aminopenicillins with β-lactamase inhibitors (ampicillin/sulbactam, amoxicillin/clavulanic acid) and anaerobic strains covered by metronidazole, clindamycin, carboxypenicillins with β-lactamase inhibitors (ticarcillin/clavulanic acid), ureidopenicillins (piperacillin/tazobactam), and, to a lesser extent, by antianaerobic second-generation cephalosporins (cefoxitin, cefotetan). Aminoglycosides are considered in acute severe conditions, renal status permitting, and their blood concentrations can be controlled. Enterococci are not a particular problem for this group of patients, and not covering them with specific antibiotics does not alter the rates of successful treatment.

The surgical treatment of these infections can be augmented by the usual antibiotics in the perioperative period. This means that we can choose monotherapy with an antianaerobic second-generation cephalosporin (cefoxitin), ampicillin/sulbactam, amoxicillin/clavulanic acid, ertapenem, ticarcillin/clavulanic acid, or a combination of a second-generation cephalosporin plus metronidazole or aminoglycoside plus metronidazole in special cases.

2) Patients with a community intra-abdominal infection who are older or in poor general condition are in danger from postoperative enterococcal infection if not covered perioperatively by antibiotics effective against it. This means that these patients are not treated adequately by cephalosporins or aminoglycosides or a combination only. It is recommended to use ampicillin/sulbactam, amoxicillin/clavulanic acid, ertapenem, ticarcillin/clavulanic acid, or aztreonam plus clindamycin in cases of allergy to specific antibiotic groups.

3) Patients with an intra-abdominal infection and recent hospitalization or living in communal housing or with a postoperative infection should receive stronger antibiotics. Recommended as such are piperacillin/tazobactam, imipenem-cilastatin, meropenem as monotherapy, and aztreonam plus clindamycin, ciprofloxacin plus metronidazole, or third- and fourth-generation cephalosporin plus metronidazole or clindamycin as combination therapy. These patients also are in danger of enterococcal infection if not covered perioperatively with appropriate antibiotics. Patients with postoperative or tertiary peritonitis certainly need coverage against Pseudomonas and Staphylococcus, and frequently inability to control infection is attributable to fungi. So, if there is a high index of suspicion of a fungal contribution to the infection, early empiric (preemptive) antifungal therapy is necessary [18 –36].

As already mentioned, 27 surgical clinic directors (63% of the northern Greece surgical clinics) responded to the questionnaire. This percentage does not reduce the value of the conclusions, because in discussions in prior symposia, which the directors who did not participate in the study attended, it was agreed that the main reason for non-participation was their awareness of improper antibiotic use at their institutions and their fear of an audit. Their participation thus would simply have reinforced our conclusions.

To what extent is antibiotic management in northern Greek surgical clinics in compliance with these guidelines, which were adopted by the HSSI as well as the SIS? From the analysis of our data and comparison with the SIS guidelines, the following conclusions can be drawn.

Gastric-duodenal perforation

In patients treated within 24 h (Group A), the duration of perioperative chemotherapy does not comply with the SIS guidelines at 63% of the responding surgical clinics (duration two to eight days). Regarding the antibiotics used, 7.4% of clinics (median 2; range 1–6) deviate from the guidelines (administration of third- and fourth-generation cephalosporins, ciprofloxacin, or imipenem-cilastatin).

In patients treated after 24 h (Group B), the duration of perioperative chemotherapy is in accordance with the guidelines. Regarding the type of antibiotics, however, 11.1% of clinics (median 3; range 1–11) deviate from the guidelines by using third-generation cephalosporins as monotherapy or combined with antianaerobic agents and 33% of clinics by using ciprofloxacin plus metronidazole or imipenem-cilastatin.

In high-risk patients (Group C), 14.8% of surgical clinics (median 4, range 3–8) do not cover Enterococcus with the antibiotics administered.

Intestinal rupture

In Group A, only 29.6% of the surgical clinics administer antibiotics for 24 h. The remaining 70.4% deviate from the guidelines by treating patients for two to seven days. Regarding the type of antibiotic administered, 14.8% of clinics (median 4; range 1–7) do not comply with the guidelines, using third-generation cephalosporins as monotherapy or combined with metronidazole or clindamycin, the combination of ciprofloxacin/metronidazole or imipenem-cilastatin, or piperacillin/tazobactam with antianaerobic agents.

In Group B, the duration of perioperative chemotherapy is in accordance with the guidelines. A total of 14.8% of clinics (median 4; range 1–10) administered third- and fourth-generation cephalosporins with or without an antianaerobic agent, ciprofloxacin with an antianaerobic agent, or piperacillin/tazobactam or imipenem-cilastatin as monotherapy (Table 5).

In Group C, the duration of perioperative chemotherapy is in accordance with the guidelines, but 14.8% of clinics (median 4, range 1–9) do not cover Enterococcus with the antibiotics administered.

Acute cholecystitis

In patients without gallbladder rupture (Group A), 81.4% of surgical clinics administer antibiotics beyond the first 24 h, whereas 18.5% (median 5; range 1–10) administer third- and fourth-generation cephalosporins or piperacillin/tazobactam as monotherapy and third-generation cephalosporin or fluoroquinolones plus an antianaerobic agent, an aminoglycoside, or both.

In patients with gallbladder rupture (Group B), 18.5% of surgical clinics (median 5, range 1–12) administer third- and fourth-generation cephalosporins as monotherapy or combined with an antianaerobic agent or an aminoglycoside, piperacillin/tazobactam, or fluoroquinolone plus an antianaerobic agent, an aminoglycoside, or both. In Group C, 22.2% of surgical clinics (median 6; range 1–12) do not cover Enterococcus.

Acute appendicitis

In patients without appendiceal rupture (Group A), 40.7% of surgical clinics administer antibiotics for two to seven days, whereas 14.8% (median 4; range 1–9) administer third- and fourth-generation cephalosporins or fluoroquinolones as monotherapy or combined with metronidazole and piperacillin/tazobactam. In patients with appendiceal rupture (Group B), 18.5% of clinics (median 5; range 1–6) administer third- and fourth-generation cephalosporins or fluoroquinolones as monotherapy or combined with metronidazole and piperacillin/tazobactam.

In patients with recent hospitalization or nosocomial or postoperative intra-abdominal infection (Group D), 11.1% of clinics (median 3; range 1–13) do not cover patients for Enterococcus. Preemptive antifungal therapy on suspicion of fungal participation in the infection is employed by 48.2% of the clinics.

The time of antibiotic treatment commencement is important because the risk of a surgical infection rises two-fold to three-fold if the antibiotic is administered before the incision and six-fold if it is administered too early (e.g., more than 2 h before incision)[31,37]. From our study data, 7.4% (median 2; range 1–5) of surgical clinics administer antibiotics after the surgical incision; i.e., intraoperatively.

It seems from these data that:

The patient group with an intra-abdominal infection with simple contamination of the peritoneal cavity is not separated from the patient group with secondary peritonitis. In most surgical clinics, the patients of the first group are treated as if they suffered from a generalized peritoneal infection, and the duration of antibiotic treatment is two to seven days.

A high percentage of surgical clinics use advanced antibiotics, resulting in a higher treatment cost and a markedly higher likelihood of multiresistant strain emergence, as is already happening with Pseudomonas, Escherichia coli, Acinetobacter, and Klebsiella.

A high percentage of clinics do not consider Enterococcus as a potential participant in a postoperative infection and therefore do not cover patients for it.

A high percentage of surgical clinics do not appreciate the importance of fungi in infection in patients with postoperative or tertiary peritonitis.

Infectious disease specialists are consulted only rarely, particularly in special patient groups.

These data were discussed in the two surgical infections symposia under the auspices of HSSI, with the main subject being the management of antibiotics perioperatively during the treatment of intra-abdominal surgical infections. Additionally, the data were presented in the subsequent Pan-Hellenic Congress on Surgical Infections. Finally, the propositions evolved were included in a special HSSI issue with antibiotic use guidelines in surgical patients and a special issue of the Health Ministry Center for Disease Control.

It was also agreed to undertake a random, without warning, audit regarding antibiotic use in surgical clinics in a specific time frame. It is considered necessary for every surgical clinic to appoint a specific person to control antibiotic administration and to create a special form for using “restricted” antibiotic groups.

Conclusion

It must be accepted that in conditions characterized by simple contamination of the peritoneal cavity, surgical treatment must be accompanied by brief (≤24 h) administration of antimicrobial agents. There must be a continuous effort to minimize the duration of antibiotic treatment, in order to reduce the pressure of resistant strain emergence. The persistence or recurrence of the infection signs beyond three or four days from the initial operation means in all probability a recurrence of the original infection or a new infection site and mandates diagnostic re-evaluation of the patient, not continuation or immediate change of the antimicrobial treatment. Finally, the most potent and most specialized antibiotics should be reserved for cases in which they are absolutely necessary.

Continuous discussion and surgeon training by a specific scientific team is considered vital and probably is the best choice in order for surgeons to become connoisseurs of antibiotics and their proper use and thereby reduce serious adverse effects. The periodic update of the guidelines for antibiotic use should be the responsibility of this team, in addition to the continuous evaluation of their application, in order to increase the percentage of proper antibiotic management and to reduce the rate of emergence of multi-resistant strains, side effects, and overall cost.

Footnotes

Author Disclosure Statement

No conflicting financial interests exist.

Appendix. Surgical Clinics who responded to the questionnaire

*

Aristotle University of Thessaloniki.

**

Democritus University of Thrace.

References

Kambaroudis

. Secondary peritonitis and antibiotics. Surgical Infections: Modern Opinions on Their Treatment. Thessaloniki: University Studio Press Editions, 2004; 43–59.

Lafreniere

, Bohnen

, Spry

. Infection control in the operating room: Current practices or sacred cows? J Am Coll Surg, 2001; 193:407–416.

Merlino

, Yowler

, Malangoni

. Nosocomial infections adversely affect the outcomes of patients with serious intra-abdominal infections. Surg Infect, 2004; 5:21–27.

Struelens

, Byl

, Vincent

J-L

. Antibiotic policy: A tool for controlling resistance of hospital pathogens. Clin Microbiol Infect, 1999; 5:S19–S24.

Sigalas

. Nosocomial infections burdening by the abuse of antimicrobials. Treatment of Nosocomial Infections. Thessaloniki: Central Committee for Nosocomial Infections, 1992.

Charlaftis

. The prophylactic use of antibiotics and the nosocomial infections problem. Management of Nosocomial Infections. Thessaloniki: Central Committee for Nosocomial Infections, 1992.

Nikolaidis

. The policy for the use of antibiotics. Treatment of Nosocomial Infections. Thessaloniki: Central Committee for Nosocomial Infections, 1992.

Solomkin

, Mazuski

, Baron

et al. Guidelines for the selection of anti-infective agents for complicated intra-abdominal infections. Clin Infect Dis, 2003; 37:997–1005.

Mazuski

, Sawyer

, Nathens

et al. The Surgical Infection Society Guidelines on antimicrobial therapy for intra-abdominal infections: An executive summary. Surg Infect, 2002; 3:161–173.

10.

Voros

, Voutsinas

, Stergiopoulos

. The Use of Antibiotics in Surgery: Basic Principles. Athens: Parisianos Scientific Editions, 2003.

11.

Voros

. Surgical Infections. Athens: Parisianos Scientific Editions, 2002.

12.

Kirklant

, Briggs

, Trivette

et al. The impact of surgical-site infections in the 1990's: Attributable mortality, excess length of hospitalization, and extra costs. Infect Control Hosp Epidemiol, 1999; 20:725–730.

13.

Michalopoulos

, Tzelepis

, Geroulanos

. Antimicrobial Chemoprophylaxis and Therapy in Surgery and Emergency Medicine. Athens: H. Tzevelekakis Editions, 1997.

14.

Guide to Antimicrobial Therapy and Prophylaxis for the Hospitalized Patient. Athens: Central Committee for Surgical Infections, 2001.

15.

Bohnen

, Solomkin

, Dellinger

. Guidelines for clinical care: Anti-infective agents for intra-abdominal infections: A Surgical Infection Society policy statement. Arch Surg, 1992; 127:83–89.

16.

Smith

, Pierson

. The emergence of vancomycin resistance in Staphylococcus aureus. N Engl J Med, 1999; 340:493–501.

17.

Fridkin

, Jarvis

. Epidemiology of nosocomial fungal infections. Clin Microbiol Rev, 1996; 9:499–511.

18.

Schein

, Assalia

, Bachus

. Minimal antibiotic therapy after emergency abdominal surgery: A prospective study. Br J Surg, 1994; 81:989–991.

19.

Christou

, Turgeon

, Wassef

et al. Management of intra-abdominal infections: The case for intraoperative cultures and comprehensive broad-spectrum antibiotic coverage. Arch Surg, 1996; 131:1193–1201.

20.

Mercer-Jones

, Hadjiminas

, Heinzelmann

. Continuous antibiotic treatment for experimental abdominal sepsis: Effects on organ inflammatory cytokine expression and neutrophil sequestration. Br J Surg, 1998; 85:385–389.

21.

Roehrborn

, Wacha

, Schoeffel

et al. Coverage of enterococci in community-acquired secondary peritonitis: Results of a randomized trial. Surg Infect, 2000; 1:95–107.

22.

Wacha

, Hau

, Dittmer

et al. Risk factors associated with intra-abdominal infections: A prospective multicenter study. Langenbecks Arch Surg, 1999; 384:24–32.

23.

Burnett

, Haverstock

, Dellinger

et al. Definition of the role of enterococcus in intra-abdominal infection: Analysis of a prospective randomized trial. Surgery, 1995; 118:716–723.

24.

Lark

, Chenoweth

, Saint

. Four year prospective evaluation of nosocomial bacteremia: Epidemiology, microbiology and patient outcome. Diagn Microbiol Infect Dis, 2000; 38:131–140.

25.

Kamparoudis

, Karakantzas

, Kazdovasili

. Chemoprophylaxis: Is it necessary or not in appendectomy? Med Commun, 1990; 2:33–36.

26.

Taylor

, Dev

, Shah

et al. Complicated appendicitis: Is there a minimum intravenous antibiotic requirement? A prospective randomized trial. Am Surg, 2000; 66:887–890.

27.

Sakantamis

, Kamparoudis

, Metaxas

, Mavroudis

. Intraabdominal septic collection: Developments and questions. Hellenic Surg, 2001; 73:88–95.

28.

Eggiman

, Francioli

, Bille

et al. Fluconazole prophylaxis prevents intra-abdominal candidiasis in high-risk surgical patients. Crit Care Med, 1999; 27:1066–1072.

29.

Nathens

, Rotstein

, Marshall

. Tertiary peritonitis: Clinical features of a complex nosocomial infection. World J Surg, 1998; 22:158–163.

30.

Solomkin

. Antibiotic resistance in postoperative infections. Crit Care Med, 2001; 29,Suppl:N97–N99.

31.

Roy

. The Operating Room. Guide to Infection Control in the Hospital, 3rd Weuzel

, Bearman

GML

, Brewer

, Butzler

. Brookline, MA: ISID Publications, 2002.

32.

Cainzos

. Review of the guidelines for complicated skin and soft tissue infections and intra-abdominal infections—Are they applicable today? Clin Microbiol Infect, 2008; 14,Suppl 6:9–18.

33.

Dupont

. The empiric treatment of nosocomial intra-abdominal infections. Int J Infect Dis, 2007; 11,Suppl 1:S1–S6.

34.

Concia

, Viscoli

. Principles and application protocols in the treatment of intra-abdominal infections. Infez Med, 2008; 16:57–62.

35.

Swenson

, Metzger

, Hedrick

et al.

Choosing antibiotics for intra-abdominal infections: What do we mean by “high risk”?

Surg Infect, 2009; 10:29–39.

36.

Weigelt

. Empiric treatment options in the management of complicated intra-abdominal infections. Cleveland Clin J Med, 2007; 74:S29–S37.

37.

Esposito

, Carosi

, Leone

. Current guidelines for the treatment of intra-abdominal infections. Infez Med, 2008; 16:46–52.