The incidence of PUD is about 0.1%-0.3% per year with a prevalence that was about 5.7% in 1998, which has been progressively declining. 9 PPU in some studies account for more than 70% of deaths associated with PUD. The incidence of duodenal perforation (DP) is 7–10 cases/100,000 adults per year. 10 Factors associated with an adverse outcome in patients with complicated PPU include comorbid disease, poor general and medical status, sign of shock and sepsis (hypotensive shock, metabolic acidosis, acute renal failure, hypoalbuminemia), and delayed treatment. 11 Independent risk factors accounted for postoperative morbidity and mortality are elevated levels of serum creatinine and advanced age. Adequate resuscitation, sepsis control, addressing comorbidities and early access to hospital can minimize the risk of morbidity and mortality in patients with PPU. 12
Surgical intervention is the most widespread attitude practiced in cases of PPU. The postoperative outcome after surgical repair is influenced by delayed presentation, presence of pus in the peritoneal cavity, sepsis and shock. 13 The choice of the surgical approach (laparoscopy versus laparotomy) has an impact on the immune response in PPU. Schietroma et al., in a study on 119 patients with PPU, showed that 1 hour after the intervention, bacteraemia and the levels of endotoxin was significantly higher for the patients who undergo surgery by laparotomy. More, the laparotomy caused a significant increase in immune neutrophil concentration, neutrophil-elastase, IL-1 and IL-6, CRP and decrease of HLA-DR. 14 A conservative, non-operative attitude has equally been described. Asanasak et al., in a 9-year retrospective study on 38 patients with PPU who received non-operative treatment, concluded that for proper selected patients this attitude can be successful, with shorter hospital stay and decrease the number of patients that require an operation. 15 Whatever the attitude, the broad-spectrum antibiotics administration is essential for the treatment.
Bacteriology in PPU
The mortality rate in patients in case of intraabdominal sepsis can be as high as 185 % when gram-positive cocci are present. Along the years, due to the improved care of peritonitis, the mortality decreased from 9 % in 1900 to 15–2 % nowadays. The actual challenge is the increased microbial resistance and the administration of an appropriate empiric antibiotic treatment. 16 In case of anaerobic intra-abdominal contamination, there is a significant increase in septicaemia without a significant increase in mortality. Gowda et al., in a study on 275 consecutive patients with PPU, found that the factors that increase the risk of anaerobic infection were: age over 50 years, patients’ comorbidity, peritonitis of more than 48 hours, perforation diameter > 5 mm, peritoneal fluid > 1000 ml and purulent contamination. 17
Alwahed et al., in a study on PPU on 888 patients, found that 48.6% of the studied patients had positive cultures for Bacteroides spp., and that patients with increase age (> 50 years) had a higher prevalence of contamination (83.7%) 18 The review of Brook et al. sustained that anaerobic contamination in PPU was explainable by the fact that in the gastrointestinal tract flora, the ratio of anaerobe bacteria to aerobe bacteria was of 1,000–10,000 to 1. 19 Quantitative analyses of intestinal microbiota of the digestive tube revealed a non-homogeneous distribution. The number of bacterial cells in 1 g chime is lesser in the stomach and duodenum (101–103) and increase progressively until reaching their maximum in large intestine (1011–1012). 20 In terms of isolated species in PPU, Bhavin et al. in a study on 200 patients with PPU found that E. coli was the commonest organism isolated, and that the patients handled with antibiotics according to culture and sensitivity presented a reduces hospital stay and morbidity. 21 Lohith et al. in a study on 50 patients with different sites of perforation on the gastrointestinal tract found that E. coli was the most common organism isolated in all sites of perforation and that there was an increasing resistance against third generation cephalosporins. 22 Tayal et al. in a study on 43 intra-operative specimens from cases of perforated peptic ulceration, found that the bacterial culture in PPU revealed also gram-negative bacilli morphologically resembling H. pylori 41.86% specimens with an H. pylori culture positivity of 18.60%. 23
Initial empirical antibiotic therapy has to be adapted to the bacterial culture results and susceptibility, and it has been suggested that the most potent antibiotics should be used in cases of peritonitis, instead of the most commonly used antibiotics. 24 Empiric broad-spectrum antibiotic regimen against a mixture of Gram-negative, Gram positive and anaerobic bacteria should be administered, if possible, after the peritoneal fluid has been collected. According to WSES guidelines for perforated and bleeding peptic ulcers, in patients with PUP, a short-course (3–5 days) of antibiotic therapy is recommended (2C). 25
There is a controversy on the empirical administration of the anti-fungal agents (AF) in PPU. In most cases, fungal infections are present for surgical patients, especially intra-abdominal abscesses. The routine use of empiric AF is not sustained by the literature. 26 Barmparas et al., in a study of 554 patients with PPU, found that empiric use of AF presented no clinical advantage in preventing infections, even those due to Candida spp., thus its administration was unnecessary. 27 Nevertheless, Lee et al., in a study on 62 patients with PPU, found that 37.1% of patients presented positive culture to Candida spp. This study recommended that AF agents should be administered in all cases of fungal contamination to lower the mortality rate and shorten hospital stay. 28 Shan et al., in a taiwanese study on 145 patients with PPU, observed that 43% patients presented a positive fungal infection and Candida spp. was the most ordinary pathogen isolated from peritoneal fluid and wound cultures. This study recommended low-dose amphotericin B for critically ill surgical patients with intraperitoneal infection. 29
Strengths and limitations
One of the strengths of this study represents a well exhaustive description of the bacteria isolated in the peritonitis secondary to PPU. However, one of its limitations was a modest number of patients suitable for analysis, mainly due to the reduced prevalence of this clinical scenario compared to other entities such as colonic or appendicular peritonitis. Otherwise, there was a limitation during follow-up because of a reduced number of postoperative upper endoscopies, which prevented to analyse the true incidence of H. pylori as the aetiology of the PUD.