September 29, 2016

Dr. Naeem Khan Consultant Surgeon   |   JPMC Karachi

Duration of Antibiotic Treatment

Acute appendicitis is still the most common intra-abdominal infection requiring surgical intervention. Definitions of severity can be assigned to acute appendicitis, but grossly the disease can be divided into two entities: uncomplicated or non-perforated, or complicated disease with perforation of the appendix or the presence of purulent peritonitis. Several randomized clinical trials have shown the feasibility of antibiotic treatment alone for uncomplicated appendicitis, although it is associated with considerable recurrences requiring appendicectomy within 1 year. Therefore, appendicectomy is still considered the treatment of choice for acute appendicitis. The most frequent complication after appendicectomy is an infection, seen as wound infection (3.6 percent for laparoscopic surgery and 7.3 percent for open surgery) and intra-abdominal abscess (1.6 and 0.6 per cent respectively). The latter is often associated with readmission and need for reintervention. As expected, these complications are more frequent after complicated appendicitis.
Perioperative administration of antibiotics has been proven to reduce the number of infectious complications in acute appendicitis. Complicated appendicitis is commonly treated by a prolonged antibiotic regimen, although there is no consensus on the exact duration. American guidelines advise restriction of postoperative antibiotic treatment of complicated intra-abdominal infections to 4-7 days. Continuing antibiotics for more than 5 days does not provide further benefit, although the available evidence is restricted mainly to children. Currently, many clinics continue treatment for between 3 and 5 days after surgery for complicated appendicitis depending on local protocols. However, there is only limited evidence available on the duration of antibiotic treatment after appendicectomy for complicated appendicitis in adults. This study compared outcomes between two hospitals practicing different durations of antibiotic treatment in adults with complicated appendicitis.

This was an observational cohort study of all adult patients who had an appendectomy between January 2004 and December 2010 at either one of the two hospitals less than 7 km apart at Hilversum and Blaricum (location A and B respectively) in the centre of the Netherlands. The original article was published in march 2014 in a british journal of surgery. At location A, the protocol included 3 days of postoperative antibiotic treatment, whereas at location B it specified 5 days. The primary outcome was the development of postoperative infections as either superficial wound infection or deep intra-abdominal infections.

All patients received a single intravenous dose of cefamandole (1000mg) and metronidazole (500mg) as antibiotic prophylaxis before induction of anaesthesia. For complicated appendicitis, defined as a perforation of the appendix before or during operation, or appendicitis in the presence of purulent peritonitis, antibiotic treatment was continued for 3 or 5 days after surgery, depending on hospital. The therapeutic antibiotic regimen was cefuroxime (750 mg 3 times daily) and metronidazole (500 mg 3 times daily), administered intravenously. During the study interval, the standard duration of antibiotic treatment was 3 days at location A and 5 days at location B.

Between January 2004 and December 2010, 1232 adult patients underwent surgery for suspected appendicitis. In 89 patients the appendix was not infected or another diagnosis was found as the primary cause; 1143 patients with an intraoperative diagnosis of acute appendicitis underwent ap appendicectomy. Of these, 597 procedures were performed at location A and 546 at location B. Half of the patients were men, mean age was 42 years and mean duration of hospital admission was 3.7 days.
An open appendicectomy was done frequently than a laparoscopic procedure (655 versus 488; 7.4% converted). The laparoscopic technique was introduced from the end of 2006, and this technique prevailed during the final years. Mean operating time 51 min, 43 min for open surgery and 61 min for laparoscopic surgery.
Infectious complications developed following appendicectomy in 4.6% of patients; 3.1% developed an intra-abdominal abscess and 2.0 per cent a wound infection. A laparoscopic approach was identified as a risk factor for development of an intra-abdominal abscess (OR 2.06, 95% confidence interval 1.04 to 4.10; P= 0.039). An open approach proved to be a risk factor for wound infections (OR 3.62, 1.22 to 10.69; P=0.020).

Table 1 Baseline characteristic of complicated appendicitis.




Complicated disease in 267 patients (23.4 per cent) was treated after surgery with either 3 or 5 days of antibiotics, according to the local protocol. Baseline characteristics of patients with complicated appendicitis are shown in table 1. Complicated appendicitis was a risk factor for infectious complications compared with uncomplicated disease (OR 3.59, 2.04 to 6.29; P< 0.001). In the event of complicated appendicitis, the antibiotic regimen was prolonged for 3 days in 135 patients (50.6 per cent) and 5 days or more in 123 patients (46.1%). Antibiotic treatment lasted longer than 5 days in seven patients at location B. In nine patients (3.4%) the exact duration of antibiotics could not be retrieved. The median duration of hospital admission was 4 and 6 days in patients who received antibiotics for 3 and 5 days respectively (P<0.001).
Among the patients with continued antibiotic treatment because of complicated disease, 21 (7.9%) developed an intra-abdominal abscess and nine (3.4 per cent) a wound infection. The intraoperative diagnosis in those who developed an abscess was perforation at the start of surgery in 20 patients and purulent peritonitis in one. No difference was found between antibiotic treatment for 3 or 5 days in terms of developing an infectious complication. This was the case for both intra-abdominal abscess (OR 1.77, 0.68 to 4.58; P=0.242) and wound infection (OR 2.74, 0.54 to 13.80; P= 0.223).
In univariable analysis, laparoscopy was identified as a statistically significant factor for abdominal abscess formation (P= 0.049). However, laparoscopy was not an independent risk factor for any infectious complications in multivariable analysis.
In 16 of 126 patients treated at location A, the specified 3-day antibiotic treatment period was prolonged for 2 days (total 5 days) because clinical findings were suggestive of infectious complications. Two of these patients developed an intra-abdominal abscess. Because the prolonged antibiotic treatment in these patients was not in accordance with the local protocol, these patients were excluded from a sensitivity analysis. In this analysis, comparable results were found for the effect of duration of antibiotic treatment (3 versus 5 days) for development of any infectious complication (OR 2.44, 0.48 to 6.30; P= 0. 168) or an intra-abdominal abscess (OR 2.17, 0.75 to 6.30; P= 0.153).
In addition, some patients at location B received antibiotics for a shorter or longer time (3 days or more than 5 days) than the 5 days specified in the protocol. These patients were excluded from the final analysis together with those who received prolonged antibiotic treatment at location A. No differences were found on the impact of duration of antibiotic treatment (3 versus 5 days) on development of any infectious complication (OR 1.92, 0.68 to 5.40; P= 0.219), a wound infection (OR 1.50, 0.25 to 9.18; P=0.661) or an intra-abdominal abscess ( OR 2.63, 0.80 to 8.71; P= 0.112).

Table 2 Univariable logistic regression analysis of risk factors for all infectious complications and intra-abdominal abscesses after appendicectomy for complicated appendicitis




This study found no difference in the rate of infectious complications between the antibiotic treatment of perforated appendicitis for 3 or 5 days. Available data on duration of treatment are limited, with only one randomized clinical trial in adults comparing the duration of antibiotic administration. That study reported no additional benefit from standard treatment with antibiotics for at least 5 days compared with antibiotic treatment based on the clinical course; the mean antibiotic duration was 5.9 versus 4.3 days, with infectious complication rates of 13 versus 12.5% respectively. Other investigations of the optimal duration of antibiotic treatment in perforated appendicitis are scarce and limited mainly to children. In most pediatric studies, a duration of more than 5 days has been compared with antibiotic treatment for 5 days.
Almost all patients who developed an intra-abdominal abscess after prolonged antibiotic treatment in this study (20 of 21) had perforation as an intraoperative diagnosis at the start of the surgery, rather than purulent peritonitis or gangrenous appendicitis with perforation on manipulation during surgery. This is in line with previous findings that patients with the perforated appendix are at a much higher risk of postoperative abscess formation than patients with a non-perforated, purulent or gangrenous appendix.
In the present cohort, patients who had a laparoscopic appendicectomy more frequently developed intra-abdominal abscess than those who underwent open appendicectomy. This confirms previous findings, although the cause is still not fully understood. However, for the subgroup of patients with complicated appendicitis, laparoscopy was not a risk factor in the multivariable analysis. This implies that a laparoscopic approach can still be used in patients with preoperative suspicion of complicated appendicitis without the risk of infectious complications.
The type of stump closure in laparoscopic appendicectomy has been shown to influence postoperative infectious complications with the evidence favoring end stapling. In the present cohort, all appendicular stumps were closed with the stapling device in laparoscopic procedures. The conversion rate among complicated cases attempted laparoscopically was relatively high, probably because the study was carried out at the time when the laparoscopic approach was introduced.
The study included only clinically relevant in-hospital infectious complications (intra-abdominal abscess and wound infection) that altered the treatment, such as readmission, re-intervention or antibiotic treatment.
Therefore, the number of such complications is probably under-reported; this applies specially to wound infections, which can often be treated in the outpatient clinic. However, any underestimation of the complication rate would be expected to apply equally to both groups. Moreover, reintervention such as percutaneous drainage without the need for readmission were registered, because these were recorded in the electronic patient database.
The length of hospital stay was significantly shorter in patients who received antibiotics for 3 days compared with the treatment for 5 days. Although no cost analysis was performed, lower costs can be expected with the 3-day antibiotic regimen. Some clinics switch their antibiotic regimen from intravenous to oral administration if possible, to reduce hospital stay. This was not done in the authors’ clinic owing to the choice of antibiotics, resulting in a longer hospital stay for 5-day group.
This is a retrospective study, which has its limitations and risk of bias. For example, the open and laparoscopic approaches were not divided equally between the two locations. On the other hand, a laparoscopic approach was a risk factor in the development of an intra-abdominal abscess and this approach was chosen more often at location A, where a 3-day antibiotic regimen was used. Despite the shorter regimen in this hypothetically high-risk group, infectious complications were not increased compared with the rate in the 5-day group.
At both locations, the duration of antibiotic treatment in some patients differed from that specified in the local protocol. The sensitivity analysis carried to account for both protocol violations (either lengthening or shortening of antibiotic regimen) yielded results comparable to those of the main analysis. Finally, owing to the proximity of the two hospitals, the study groups were well matched. During the time of this study, the surgical departments of the two hospitals already worked together on many levels, although each department still had its own protocols. Those hospitals and their surgical departments have now merged, resulting in an antibiotic treatment for 3 days for complicated appendicitis.

The authors declare no conflict of interest.

British journal of surgery.
C. C. van Rossem, M. H. F. Schreinemacher, K. treskes, R. M. van Hogezand and A. A. W. Geloven