Complicated intra-abdominal infections represent a widespread problem, encountered worldwide, with appendicitis alone affecting 300,000 patients/year and consuming >1 million hospital days in the United States [1]. The lifetime risk is estimated to be 8.6% in men and 6.7% in women [2].

This pathology is well-known and the etiology is related usually with an obstruction of the appendix lumen. Other pathologies that can produce an inflammation of the appendix are tumors (carcinoid tumors and adenocarcinoma), intestinal parasites, and hypertrophied lymphatic tissue [3].

Acute appendicitis is treated by appendectomy and is usually followed by additional antibiotic treatment. In case of necrosis or perforation of the appendix with secondary peritonitis, the antibiotherapy is important for the treatment and prevention of the postoperative infectious complications. Antibiotic use can be considered as an adjunct to surgical intervention, and their appropriate use remains a critical aspect [4]. The bacteriological sample in case of presence of intra-abdominal free fluid is necessary to adapt the antibiotherapy and to prevent the development of resistance. In case of simple appendicitis, restriction of antibiotic treatment can be considered.

The bacterial flora in the appendix consists of a mixture of aerobes and anaerobes bacteria. In the literature, Escherichia coli and Bacteroides fragilis are most commonly associated with appendicitis, and the first-line empiric antibiotic therapy is typically selected to target these bacteria [5]. Nevertheless, acute appendicitis is habitually a polymicrobial infection, with up to 14 different bacteria reported [6].

The aim of the study is to evaluate the differences between uncomplicated acute appendicitis (UAA) and complicated acute appendicitis (CAA) in terms of bacterial culture results and antibiotic resistance. The secondary outcome was to evaluate the predictors for complicated appendicitis. The study also evaluates the clinical implication of the bacterial culture results of UAA and CAA in term of antibiotic resistance, and the risk factor of CAA.

A total of 834 patients were operated for acute appendicitis during the period of the study. We included 268 patients (161 with UAA and 107 with CAA) after excluding 566 patients according to the exclusion criteria, mainly due to the absence of sufficient free fluid for bacteriological analysis.

The demographic analysis (Table 1) revealed that patients in the CAA group were older (38.5 years [IQR, 27.0–52.0 years] vs. 33.5 years [IQR, 25.3–41.0 years]), and there was a higher proportion of male patients in this group (71.0% vs. 56.5%). These differences were statistically significant. There were no statistically significant differences in the nationality between groups.

Patients in the UAA group presented more personal history of abdominal surgeries (26 [16.1%] vs. 14 [13.1%]) and more personal history of other surgeries (18 [11.2%] vs. 10 [9.3%]), with no statistical significance.

Although the median CCI was 0 for both groups, the IQR was discretely higher in the CAA group (0–1 vs. 0–0), thus there was a statistically significant difference (P=0.017).

Acute appendicitis is the most common cause of acute peritonitis, with 7% of cases of secondary diffuse peritonitis. In case of complicated appendicitis, perforated appendicitis with peritonitis, the morbidity is increased. Diffuse peritonitis represents the most severe grade of CAA, and it is still considered an important cause of morbidity (10%) and mortality (1%–2.5%) [10].

In some studies, gram-negative bacteria are more common in acute appendicitis compared to gram-positive [11, 12]. García-Marín et al. [13] found that the culture-positive rate was higher in CAA than in UAA, identifying a higher frequency of gram-positive cocci and anaerobic bacteria with different isolates and susceptibilities. Parthiban and Harish [14] in a microbiology study of the appendicectomy specimen showed that anaerobes acted as the commonest organism involved in appendicitis and postoperative wound infection. Moreover, the presence of anaerobes caused a higher incidence of complicated appendicitis. Lafi et al. [15] found that the most common bacteria found in a bacteriological study of acute appendicitis were E. coli, B. fragilis, and Staphylococcus aureus. For Chen et al. [3], the most commonly involved bacteria were E. coli, followed by Klebsiella pneumoniae, Streptococcus spp., Enterococcus spp., and P. aeruginosa. The presence of P. aeruginosa was associated with wound infection, despite antibiotic prophylaxis, highlighting that special consideration for the clinical and biological evolution of these patients was necessary when this pathogen was found [16]. In our study, the most frequently identified bacteria were gram-negative, especially in the setting of CAA, without statistically significant differences between groups in the presence of gram-positive or anaerobes. However, there was no association between the group of bacterial isolation or the specific isolated bacteria and the presentation of a CAA.

In recent years, multiple studies revealed that in case of UAA, the antibiotics only can be a reliable treatment. APPAC (Appendicitis Acuta) randomized clinical trial found that in case of UAA, the antibiotic treatment for did not require appendectomy during the 1-year follow-up period, and those who required appendectomy did not experience significant complications [17, 18]. In case of simple appendicitis, the inferiority of nonoperative therapy vs. appendectomy could equally be related to the type of antibiotic used. Current evidence show that resistance of E. coli to amoxicillin plus clavulanic acid is increasing [19].

There is a real concern about the antibiotic resistance of the bacteria. The resistant and virulent microorganisms might be a result of antibiotic exposure or the application of invasive and prolonged medical and surgical treatment [20]. The presence of multidrug-resistant bacteria can contribute to additional morbidity [21]. In a study from 2010, 25% of children with gangrenous or ruptured appendicitis were insensitive to the antimicrobial regime used [22]. E. coli and mixed anaerobes are the predominant organisms identified in secondary peritonitis from appendicitis in children. In case of an inadequate empirical antibiotic and amoxicillin/clavulanate resistance of the bacteria, postoperative infectious complications might increase [23].

The initial empirical therapy should target all of the microorganisms likely to be involved, on the basis of the suspected risk factors [24]. Empiric antibiotic treatment is effective in most patients, early (blood or intra-abdominal) culturing is very useful to guide antibiotic modification in abdominal infection [25]. If the postoperative evolution of the patient is not optimal, the results of the bacterial culture are critical, especially in the actual tendency of increased occurrence of multidrug-resistant bacterial strains [26].

Andersen et al. [27] in a review of literature found that the antibiotic prophylaxis is effective in the prevention of postoperative complications in appendectomies patients, whether the administration is given preoperatively, perioperatively, or postoperatively. Kimbrell et al. [28] in a study on postoperative antibiotic administration in CAA suggest that the use of postoperative prophylactic antibiotics more than 24 hours in patients does not prevent the development of an abscess. Obinwa et al. [23] in a study on the microbiology of secondary bacterial peritonitis due to appendicitis found that inadequate initial empirical antibiotic and amoxicillin/clavulanate resistant E. coli may contribute to increased postoperative infectious complications. The study recommended a triple antibiotic combination of amoxicillin/clavulanate, gentamicin, and metronidazole as an empiric treatment in CAA.

The prospective multicenter study MUSTANG (Multicenter Study of the Treatment of Appendicitis in America: Acute, Perforated, and Gangrenous) on the duration of antibiotherapy found that there was no evidence of an association between the duration of 24 hours versus 96 hours for CAA and an increased rate of SSI [29]. A study from the Netherlands (2014) concluded that 3 days of antibiotics led to a similar rate of infectious complications of 5 days or more [30, 31]. In a meta-analysis by van den Boom et al. [32] revealed that there were no differences in the incidence of intra-abdominal abscess with ≤3 days versus >3 days of antibiotic treatment, but there was a reduction with >5 days of treatment. Xu et al. [33] in a retrospective analysis of 93 patients who underwent appendectomy found that the average stay of patients receiving fluoroquinolones was 2.6 days shorter than patients who received cephalosporins. In our study, the median duration of the antibiotic treatment was 5 days for UAA and 5.5 days for CAA. Therefore, the duration could have been optimized in the UAA but might have been optimal for the CAA group. In our institution, the antibiotics were discontinued, in concertation with the infectiology team accordingly to the type of bacteria culture and type of antibiotic.

In conclusion, the bacterial culture allows for not only evaluating the immediate impact of the antibiotics treatment and evaluating the resistance, but also evaluating the preoperative empirical treatments in order to reduce patients’ morbidity. CAA presented a higher rate of positive cultures with increased identification of gram-negative bacteria. E. coli, bacteria from the S. anginosus group, and Bacteroides spp. were the most commonly isolated bacteria, without relevant differences in terms of antibiotic resistance. The predictors for complicated appendicitis were preoperative or intraoperative variables, while the culture results, the group of bacterial isolation or the specific isolated bacteria did not predict complicated appendicitis.