Antibiotic prophylaxis and infectious complications in surgery for acute cholecystitis

Abstract: The prevalence of gallstone disease in the world is 10-20%. Almost 20% of those with gallstone disease develop a complication during their lifetime. Acute cholecystitis (AC) is a common complication of gallstones, that is routinely managed with cholecystectomy. Technical developments have made it possible to use a minimally invasive laparoscopic technique for removing the gallbladder and stones. The postoperative complication rate, although seen after only a minority of procedures, is important due to the large number of cholecystectomies performed annually. The complication rate is lower in healthy patients and when the procedure is performed electively. The infectious complication rate may, however, reach 17% if surgery is performed for mild to moderately severe AC. Use of antibiotic prophylaxis (AP) has been firmly established as routine practice despite the lack of international guideline recommendations. There are many studies on low-risk patients showing minor or no impact of preoperative antibiotic prophylaxis (PAP) on postoperative infectious complications (PIC). Prior to this thesis, the benefit of AP in acute laparoscopic cholecystectomy (Lap-C) had not been studied. The aim of Study I was to explore the impact of AP on PIC in AC. In Study II the use of AP in Sweden was plotted at three different levels; county, hospital and surgeon. Study III aimed at exploring the impact of comorbidity on the risk for PIC. Study IV was a randomised controlled trial assessing the effectiveness of AP in reducing PIC. For the population-based cohort studies (I – III), we used Swedish Registry for Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks) and the National patient register (NPR) as sources of data. Study IV was conducted as a double-blinded randomised study between 2009 and 2017. Study I showed that there was no benefit of AP on PIC in acute cholecystectomy due to AC, even when adjusting for the most relevant confounders. Study II showed that AP usage differed between hospitals and surgeons, but not between counties. The difference was not related to the degree of inflammation or procedure difficulty. Study III explored patient-related risk factors. The risk for surgical site infection was increased in patients with connective tissue disease, diabetes, chronic kidney disease, cirrhosis and obesity. There was also a significantly higher risk for septicaemia in patients with chronic kidney disease or cirrhosis. In Study IV, there was no difference in the rate of PIC and bactibilia between the group receiving AP and those receiving placebo. Raised CRP and operation method were significantly associated with PIC. PIC is multifactorial and single dose AP preoperatively has no more than an additive effect on PIC. Patient-related risk factors should, however, be taken into consideration when deciding on AP. International guidelines based on well-designed studies are urgently needed so that the decision to administer AP during acute cholecystectomy for AC becomes more stringent and uniform.

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