Project «Antibiotic Policy in Surgery 2003»
V. Antimicrobial Therapy of Surgical Infection
Distinction between antibiotic prophylaxis and antimicrobial treatment in surgery
It is important to distinguish prophylactic from therapeutic indications for antibiotics, because this will influence the duration of administration as well as the antibiotic selection. Antibiotic prophylaxis is only recommended for perioperative prophylaxis. Antibiotic prophylaxis should not be extended beyond 24 h following surgery, because it does not pertain to prevention of SSI caused by postoperative contamination. Inappropriately extended (prolonged) use of prophylactic antibiotics leads to the development of bacterial resistance and may also mask the signs of established infections, making diagnosis more difficult.
In contrast, therapeutic antimicrobial treatment usually begins preoperatively, lasts for more than 24 h after operation and aimed to treat established surgical infections.
Indications for antimicrobial treatment in surgical patients
Therapeutic antimicrobials should be administered to the patients with surgical site infection or established surgical infection, which occurred before the operation.
Decision about administration of therapeutic antimicrobials should be made based on traditional classification of SSI and clinical picture. Indeed, in most superficial incisional SSI without evidence of systemic inflammatory response, antimicrobial treatment is unnecessary. In contrast, deep incisional and organ/space SSI as well as any SSI with systemic signs of infection should be treated with therapeutic antimicrobials.
It is necessary to emphasize that the initial approach to an area of wound infection is to obtain a relevant clinical specimen. The only definitive treatment for an infected wound is to drain it. Antibiotics are indicated only as an adjunct to surgical drainage if there is evidence of systemic infection.
When therapeutic antimicrobial treatment rather than antibiotic prophylaxis should be performed?
The use of antibiotics in almost all «contaminated» and «dirty» operations is considered as therapeutic rather than prophylaxis. In these cases antimicrobial treatment is usually administered preoperatively and continues for more than 24 h following surgical intervention.
With regard to primary surgical infection, patients in whom infection has extended beyond the initial anatomic focus should be given therapeutic antimicrobials for greater than 24 h. In contrast, patients with a fully removable focus of infection or inflammation, i.e. localized limited infection, should be treated with prophylactic antimicrobials for 24 h or less. Intra-operative confirmation of the infection (e.g. patients who have intra-operative findings of purulent or infected peritoneal fluid) is an absolute indication for therapeutic antimicrobial therapy, since these patients considered as having established surgical infection.
Although the distinction between therapeutic and prophylactic use of antimicrobials is usually apparent, there are patients in whom antimicrobial use falls into a «gray area». For example, antimicrobials given for 24 h or less are adequate for many patients with traumatic bowel perforations, iatrogenic bowel perforations (endoscopic perforations of the colon or enterotomies occurring during surgical inter-ventions) and gastroduodenal perforations operated on immediately. However, the consensus opinion is that patients with small bowel or colon perforations greater than 12 h old, or gastroduodenal perforations greater than 24 h old, have established intra-abdominal infections and should be treated with therapeutic antimicrobials.
One of the main tasks of antibiotic committee is to make for different fields of surgery clear recommendations on indications for antimicrobial prophylaxis/treatment based on highly scientific evident data from well-designed clinical trials.
General principles of antimicrobial therapy of surgical infection
When prescribing therapeutic antmicrobials every surgeon should adhere to the following guidelines to treat patients effectively and contain antimicrobial resistance:
- Select an antibiotic to which the known pathogen is likely to be fully sensitive (it is more advantageous to use a narrow-spectrum antibiotic where available);
- Restrict the use of antibiotics to which resistance is developing (or has developed);
- Antibiotics used systemically should not be used topically;
- The antibiotic should be given in full dose by the appropriate route and at correct intervals;
- Side effects should be known and monitored;
- Expensive antibiotics should not be used if equally effective and cheaper alternatives are suitable.
Empirical and directed antimicrobial therapy
A distinction must be made between specific (directed) therapy and empirical therapy.
When the cause of the disease is unknown, an empirical therapy is guided by the site and type of infection and the anticipated range of pathogens. Antibiotics should be administered (alone or in combinations) which
- cover this range of pathogens;
- have the highest chances of success with a narrow range of activity and;
- from which minimal adverse reactions can be expected.
Once the germ and the antibiogram are known, changing to an antibiotic with a narrow range of activity becomes possible. This helps to minimize the side effects, to reduce the selection pressure and to save costs. With known causes of infection and possibly with a known antibiogram, the antibiotic will be selected for a specific therapy that has the highest chances of success, with a narrow range of activity and minimal side effects.
Route of administration
Parenteral (intramuscular and intravenous) and oral routes of administration of antimicrobials are only adequate in surgical patients.
Intravenous administration has the advantage that high blood and tissue levels can be achieved quickly. This is why serious and life-threatening surgical infections require intravenous antibiotic therapy.
As soon as the clinical situation permits, conversion from intravenous to oral administration should be the aim. Oral application is, however, not recommended in cases of unconsciousness, vomiting, dysphagia and gastrointestinal diseases.
Another routes of administration of antibiotics shows unreliable results and should therefore be avoided as far as possible.
Antibiotics irrigated into peritoneal cavity during the surgery will not achieve optimal tissue concentrations at the site of infection. Increasing their concentrations may lead to the development of systemic adverse effects.
Local use of antimicrobials
The use of topical antibiotics often effectively diminishes the incidence of infection in contaminated wounds. However, the combination of topical agents and parenteral agents is not more effective than either one alone, and topical agents alone are inferior to parenteral agents. As a general rule, topical agents do not cause any harm if one adheres to the following rules: (1) do not use any agent in wounds or in the abdomen that would not be suitable for parenteral administration; and (2) do not use more of the agent than would be acceptable for parenteral administration. In considering the amount used, any drug being given parenterally must be added to the amount being placed in the wound. Topical agents used for burn wounds may be used in large open wounds in selected patients.
With the exception of burn wounds, local application of antimicrobial agents (intra-incisional injection, injection into drainage tubes, intra-operative irrigation of the cavities, etc.) for prophylaxis or treatment of SSI is faulty surgical practice and inferior to antibiotics given parenterally. Most antimicrobials have been shown to be destroyed by debris and bacterial toxins and enzymes. When applied locally, systemic antibiotics are not establishing optimal bactericidial concentrations in the infected site and surrounding tissues, resulting in the development antimicrobial resistance.
De-escalation therapy is a treatment strategy that works on the principle that the best possible regimen for critically ill patients with serious infections is empiric therapy with a broad-spectrum agent that provides full coverage of all identified pathogens. This is done to avoid the high mortality associated with inadequate antibiotic therapy.
Inadequate initial antibiotic therapy is a major risk factor for mortality in serious bacterial infections, particularly in hospital-acquired ones. Initial appropriate therapy is therefore an important determinant of outcome in these patients. Appropriate therapy is defined as the use of at least one antibiotic to which all isolates were susceptible in vitro from the moment in which culture was obtained. De-escalation therapy is an approach «to balance the need to provide adequate initial antibiotic treatment of high-risk patients with the avoidance of unnecessary antibiotic use that promotes resistance».
There are two stages in the process of de-escalation therapy. The first stage involves administering the broadest-spectrum antibiotic. The concept is that a broad-spectrum antimicrobial that is effective against both gram-negative and gram-positive bacteria needs to be administered as soon as infection is suspected. This is done to decrease mortality, prevent organ dysfunction and decrease hospital length of stay. Of course, it is very important for every institution to have local, current microbiological data in order to assess the likely infecting pathogens and the susceptibility patterns.
The second stage focuses on de-escalating the antibiotic therapy in order to minimize the possibility of resistant pathogens developing and in order to provide a more cost-effective treatment. Once initial culture results and bacterial sensitivity profiles become available after a relatively short period of time (i.e. 24 to 72 h), it is possible to de-escalate (narrow) the regimen, or even discontinue it if necessary. Meanwhile, the economic burden, unnecessarily long duration of therapy, selective pressures, which can cause antibiotic resistance, morbidity, and mortality associated with inadequate antibiotic therapy can be avoided.
The general principles when considering de-escalating are:
- Identify the organism and know its susceptibilities;
- Assess and potentially modify initial selection of antibiotics based on organism susceptibility report;
- Make the decision in the context of patient improvement on the initial regimen;
- Individualize the duration of therapy based on patient's factors and clinical response.
Sequential therapy in surgery
The modern and promising approach to rationalize use of antimicrobials in hospital is sequential therapy. The aim of this strategy is to reduce costs associated with the use of antimicrobial and minimize length of hospital stay without detriment to efficacy and quality of medical care. Sequential therapy (step-down therapy, switch therapy, follow-on therapy) is defined as two-stage use of antibiotics when initial intravenous antimicrobial therapy is switched to the same or another oral antibiotic as soon as patient's condition improves and he/she is able to take medications orally.
Most infectious diseases should be treated orally, unless the patient is critically ill, cannot take antibiotics by mouth, or there is no equivalent oral antibiotic. If the patient is able to take/absorb oral antibiotics, there is no difference in clinical outcome using equivalent IV or PO antibiotics. It is more important to think in terms of antibiotic spectrum, bioavailability and tissue penetration, rather than route of administration. Nearly all non-critically ill patients should be treated in part or entirely with oral antibiotics. When switching from IV to PO therapy, the oral antibiotic chosen ideally should achieve the same blood and tissue levels as the equivalent IV antibiotic.
It is important not to have the conversion to oral therapy result in courses of antimicrobial therapy that extend longer than would otherwise have been done with parenteral therapy alone. Most patients can have their antibiotics stopped when they have demonstrated some clinical improvement and the temperature and white blood cell count have returned to normal or at least improved. Continuing antibiotics beyond this time is not necessary.
In spite of clear advantages of sequential therapy, it moves into clinical practice, especially surgery, very slowly. Up to 75% of hospitalized patients with different types of infection could be converted from parenteral to oral antibiotics. Controlled clinical trials of sequential therapy have confirmed its efficacy in patients with urinary tract infections, skin and soft tissue infections, and osteomyelitis. Thus, the use of oral antibiotics to complete the antimicrobial course in patients with intra-abdominal infections seems reasonable based on evident data from randomized prospective clinical studies. Conversion from intravenous to oral ciprofloxacin plus metronidazole was found equivalent to a mandatory intravenous regimen in some clinical trials of intra-abdominal infections.