The World Antimicrobial Awareness Week is a good reminder that we must all work together to slow the spread of antimicrobial resistance (AMR).

AMR has emerged as one of the principal public health problems of the 21st century. This has resulted in a public health crisis of international concern, which threatens the practice of modern medicine, animal health and food security. Combating resistance has become a top priority for global policy makers and public health authorities. New mechanisms of resistance continue to emerge and spread globally, threatening our ability to treat common infections. Antibacterial and antifungal use in animal and agricultural industries aggravates selective pressure on microbes. A One Health approach is urgently required. The burden of AMR is difficult to quantify in some regions of the world because enhanced surveillance requires personnel, equipment and financial resources that are not always available. However, the worldwide impact of AMR is significant  in terms of economic and patient outcomes; due to untreatable infections or those requiring antibiotics of last resort (such as colistin) leading to increased length of hospital stay, morbidity, mortality and treatment cost. Antibiotics can be life-saving when treating bacterial infections but are often used inappropriately, specifically when unnecessary or when administered for excessive durations or without consideration of pharmacokinetic principles. Large variations in antibiotic consumption exist between countries and whilst excessive use remains a major problem in some areas of the world, elsewhere there is lack of access to many antimicrobial agents. AMR is a natural phenomenon that occurs as microbes evolve. However, human activities have accelerated the pace at which bacteria develop and disseminate resistance. Inappropriate use of antibiotics in humans and food-producing animals, as well as poor infection prevention and control practices, contribute to the development and spread of AMR.

Efforts must be aimed at the general public, healthcare professionals, food producing farmers, civil society organizations and policy makers. An effective and cost-effective strategy to reduce AMR should involve a multi-faceted approach aimed at optimizing antimicrobial use, strengthening surveillance and infection prevention and control, and improving patient and clinician education regarding the appropriate use of antibiotics.

AMR poses a global challenge. No single country, however effective it is at containing resistance within its boundaries, can protect itself from the importation of antibiotic resistance through travel and trade.

The global nature of AMR calls for a global response, both in the geographic sense and across the whole range of sectors involved. Nobody is exempt from the problem.

Although the current magnitude of the problem, healthcare workers play a central role in preventing the emergence and spread of resistance. Appropriate use of antibiotics should be integral to good clinical practice and standards of care. Healthcare workers should be aware of their role and responsibility for maintaining the effectiveness of current and future antibiotics specifically by:

•  Following locally-developed customized antibiotic guidelines and clinical pathways

•  Supporting and enhancing IPC including correct hand hygiene protocols

•  Supporting and enhancing surveillance of ABR and antibiotic consumption

•  Prescribing and dispensing antibiotics only when they are truly required

•  Identifying and controlling the source of infection

•  Prescribing and dispensing appropriate antibiotics(s) with adequate dosages i.e.   administration of antibiotics according to pharmacokinetic-pharmacodynamic   principles

•  Reassessing treatment when culture results are available

•  Using the shortest duration of antibiotics based on evidence

•  Educating healthcare workerss and staff how to use antibiotics wisely

Acute appendicitis is the most common cause of intra-abdominal infections worldwide. Acute appendicitis encompasses a wide spectrum of clinical presentations, from the uncomplicated form to the one with diffuse peritonitis.

Since McBurney advocated early surgical intervention, appendectomy has been the gold standard for the treatment of appendicitis. This view was based on the assumption that, in the absence of a surgical intervention, acute appendicitis always lead to perforation. This has been recently challenged by the hypothesis that perforated and non-perforated appendicitis may be distinct entities rather than sequential events, just like in acute diverticulitis. Therefore in recent years there has been increased interest in antibiotic therapy as primary treatment, and several studies have indicated that perforated appendicitis can be treated with antibiotics

Unfortunately, the clinical presentation of appendicitis is often inconsistent. While the clinical diagnosis may be clear in patients presenting with classic signs and symptoms, atypical presentations may result in delay in treatment. Besides many patients with pain in the right lower quadrant do not have acute appendicitis. Imaging is an important part in the diagnosis of acute appendicitis as well. CT-scan is classically considered the best radiological modality for acute appendicitis. It can distinguish complicated from uncomplicated appendicitis. However, the radiation exposure, the possible delay in performing CT-scan and the difficult access to CT-scan in some areas of the world are concerns associated with its widespread application. Despite of the role of imaging tools in diagnosing acute appendicitis, clinical assessment remains the key in the decision-making process.

In the last years, the conservative treatment with antibiotics alone has been proposed for treating uncomplicated appendicitis. The term of acute uncomplicated appendicitis is vague. It was defined as the presence of peritonitis, perforation and abscess. However, this diagnosis is often difficult, and the most suitable tool for differentiating complicated from uncomplicated appendicitis is CT-scan.

In 2015 the APPAC trial enrolling 350 patients with uncomplicated appendicitis confirmed by a CT-scan (257 antibiotic therapy, 273 appendectomy) was published. Patients aged 18 to 60 years admitted to the emergency department with a clinical suspicion of uncomplicated acute appendicitis confirmed by a CT scan were enrolled in the study. Patients with complicated appendicitis, which was defined as the presence of an appendicolith, perforation, abscess, or suspicion of a tumor on the CT scan, were excluded. Of 257 patients in the antibiotic group, 15 (5.8%; 95% CI, 3.3%-9.4%) underwent appendectomy during the initial hospitalization. Of these 15 patients, 7 (2.7%; 95% CI, 1.1%-5.5%) had complicated acute appendicitis at surgery and 8 (3.1%; 95% CI, 1.4%-6.0%) had uncomplicated appendicitis. Of the 7 patients with complicated acute appendicitis, there were 5 with perforated appendicitis. Of these 5 patients, 1 had an appendicolith not visible on a CT scan, 2 presented with severe gangrene of the inflamed appendix, and 1 underwent right hemicolectomy based on an intraoperative suspicion for a tumor with lymphadenopathy. However, histopathology of the resected specimen revealed only perforated appendicitis. The 1-year recurrence rate and appendectomy in the antibiotic group was reported as 27%. Ertapenem was the antibiotic of choice in this study. It was preferred due to its efficacy as a single agent for abdominal infections.

To determine the late recurrence rate of appendicitis after antibiotic therapy for the treatment of uncomplicated acute appendicitis five-year observational follow-up of patients in APPAC study was recently published. The cumulative incidence of appendicitis recurrence was 34.0% (95% CI, 28.2%-40.1%; 87/256) at 2 years, 35.2% (95% CI, 29.3%-41.4%; 90/256) at 3 years, 37.1% (95% CI, 31.2%-43.3%; 95/256) at 4 years, and 39.1% (95% CI, 33.1%-45.3%; 100/256) at 5 years. At 5 years, the overall complication rate (surgical site infections, incisional hernias, abdominal pain, and obstructive symptoms) was 24.4% (95% CI, 19.2%-30.3%) (n = 60/246) in the appendectomy group and 6.5% (95% CI, 3.8%-10.4%) (n = 16/246) in antibiotic group (P < .001), which calculates to 17.9 percentage points (95% CI, 11.7-24.1) higher after surgery. There was no difference between groups for length of hospital stay.

Although antibiotic therapy alone can be successful in selected patients with uncomplicated appendicitis, some concerns remain. Arguments against the non-operative approach include the difficult diagnosis of uncomplicated appendicitis needing CT-scan, the possible need and subsequent delay in surgery, the high risk for recurrence of acute appendicitis up to 38% within 1 year, and missing of other diagnosis when CT-scan is not performed.

Antibiotics seem to be a safe and effective treatment in certain subsets of patients with uncomplicated acute appendicitis, possibly reducing the number of unnecessary surgeries and hence their associated morbidity. However, the present data are not sufficient to definitively recommend conservative management. Randomized controlled trials and systematic reviews have shown conflicting results with regard to the safety and efficacy of non-surgical treatment by antibiotics.

For these reasons, I believe that appendectomy remains the gold-standard treatment for the patients with a very high suspicion of acute uncomplicated appendicitis, reserving conservative treatments in selected patients, such as those with equivocal clinical picture or equivocal imaging.

Massimo Sartelli

References

Salminen P, Paajanen H, Rautio T, et al. Antibiotic therapy vs appendectomy for treatment of ncomplicated acute appendicitis: the APPAC randomized clinical trial. JAMA. 2015;313:2340–8.

Salminen P, Tuominen R, Paajanen H, Rautio T, Nordström P, Aarnio M, Rantanen T, Hurme S, Mecklin JP, Sand J, Virtanen J, Jartti A, Grönroos JM. Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial. JAMA. 2018 Sep 25;320(12):1259-1265.

Antimicrobial resistance (AMR) has emerged as one of the principal public health problems of the 21st century. This has resulted in a public health crisis of international concern, which threatens the practice of modern medicine, animal health and food security. The substantial problem of antimicrobial resistance is especially relevant to antibiotic resistance, although antifungal resistance is increasing at an alarming rate.

Antibiotics can be life-saving when treating bacterial infections but are often used inappropriately, specifically when unnecessary or when administered for excessive durations or without consideration of pharmacokinetic principles. Large variations in antibiotic consumption exist between countries and whilst excessive use remains a major problem in some areas of the world, elsewhere there is lack of access to many antimicrobial agents. AMR is a natural phenomenon that occurs as microbes evolve. However, human activities have accelerated the pace at which bacteria develop and disseminate resistance. Inappropriate use of antibiotics in humans and food-producing animals, as well as poor infection prevention and control practices, contribute to the development and spread of AMR.

The webinar meeting will be free and will be accessible to all in all parts of the world. After your registration we will send you the invitation letter with links to access the free platform.

The web meeting will highlight the threat posed by antimicrobial resistance and the need for appropriate use of antibiotics and antifungal agents in hospitals worldwide with particular reference to surgical infections. As such it is our intent to raise awareness amongst healthcare workers and to improve antibiotic prescribing.

The Global Alliance for Infections in Surgery, the World Society of Emergency Surgery (WSES), the Surgical Infection Society (SIS), the Surgical Infection Society Europe (SIS-E), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) the World Alliance Against Antibiotic Resistance (WAAR), the British Society for Antimicrobial Chemotherapy (BSAC) and the Italian Society of Anti-Infective Therapy (SITA) have joined the webinar meeting.

JOIN US!

Massimo Sartelli