Using antibiotics to treat the critically ill and injured is common. While most antibiotic use is therapeutic, it also is used for prophylaxis. Antibiotic prophylaxis may be encountered in several circumstances in the intensive care unit (ICU), including perioperative prophylaxis, prophylaxis of certain bedside procedures, and prophylaxis of infection that may complicate certain disease states. Considering that overuse of antibiotic prophylaxis has deleterious consequences for patients, it is crucial for critical care practitioners to utilize prophylactic antibiotics appropriately.

An antibiotic is indicated for prophylaxis of surgical site infection during clean-contaminated (e.g., elective colon surgery) or contaminated operations (e.g., penetrating abdominal trauma). Many operations can be “covered” by a single dose of a first- or second-generation cephalosporin, but administrating antibiotics for a longer period is commonplace. The notion that postoperative prophylaxis continues long after surgery is supported by data from the Surgical Infection Prevention Project (SIP) of the Centers for Medicare and Medicaid Services (CMS).

According to SIP, only 40% of patients in the United States have surgical prophylaxis discontinued within 24 hours of surgery.¹ According to CDC, there is high utilization of first-generation cephalosporins in surgical ICUs (which are of little therapeutic use in ICUs), which undoubtedly reflects prophylactic use.²

When to Use Antibiotic Prophylaxis
Only a few bedside procedures possibly need antibiotic prophylaxis; data are scant. One randomized open-label trial showed that single-dose prophylaxis with ceftriaxone decreased infection rates by more than 50% after percutaneous endoscopic gastrostomy.³ However, many experts consider the choice of a third-generation cephalosporin unjustifiable for prophylaxis. The Eastern Association for the Surgery of Trauma issued a level III recommendation for prophylaxis with cefazolin for 24 hours after emergency tube thoracostomy; the recommendation is not a strong one because the infection to be pre-vented (empyema thoracis) is rare, making all relevant trials underpowered.⁴ Cerebral ventriculostomy for monitoring of intracranial pressure or drainage of cerebrospinal fluid should receive single-dose prophylaxis with a first-generation cephalosporin; longer prophylaxis does not prevent infection but does increase the risk of infection caused by multi-drug-resistant (MDR) pathogens^.5 The open abdomen (after “damage control” trauma celiotomy or for management of the abdominal compartment syndrome) does not require antibiotic prophylaxis.⁶ Percutaneous arterial and central venous catheters do not require antibiotic prophylaxis for insertion or while indwelling. Indwelling drains should never receive antibiotic prophylaxis; it is not only ineffective, but it increases the risk of later infection caused by an MDR pathogen^.7 It is far better to remove any drains or cath¬eters from the patient as soon as they are no longer necessary. Some injuries benefit from antibiotic prophylaxis; most do not. Two meta-analyses have shown no benefit of antibiotic prophylaxis for the prevention of meningitis basilar skull fracture, even with cerebrospinal fluid leakage.^8,9 Closed and open long-bone fractures treat¬ed by open reduction and internal fixation should receive antibiotic prophylaxis.^10,11 Despite current practice of administering 24 hours of cefazolin prophylaxis for closed and Grade I-II open fractures and 72 hours of cefazolin/gentamicin prophylaxis for Grade III open fractures, the data support single-dose prophylaxis for the former. In cases of prolonged, broad-spectrum prophylaxis of high-grade open fractures, the current practice is based on 30-year-old retrospective data, and modern prospective trials are needed. It is well established that penetrating abdominal trauma with a perforated hollow viscus requires only 24 hours of prophylaxis with a second-generation cephalosporin if surgical intervention is prompt (within four hours).¹² Although injury of the colon increases the risk of infection, the said risk is not decreased by prolonged prophylaxis. Indeed, prolonged prophylaxis increases the risk of infection.^13,14

Antibiotic Prophylaxis and Improved Outcomes
Are outcomes of critical illness and injury improved by antibiotic prophylaxis? The answer is complex. At least seven meta-analyses have been published in the past 15 years on the effectiveness of antibiotic prophylaxis in ICU patients, but controversy persists.15 Selective digestive decontamination (SDD) with topical (to the pharynx and to the stomach by gavage) and parenteral antibiotics decreases the incidence of respiratory tract infections by 65% (OR, 0.35; 95% CI, 0.29-0.41) and death (OR, 0.80; 95% CI, 0.69-0.93).* However, topical antibiotics alone decrease respiratory tract infections (OR, 0.57; 95% CI, 0.46-0.69), but not mortality (OR, 1.01; 95% CI, 0.84-1.22).* However, SDD in any guise is not popular in practice, possibly because mortality is not decreased by topical prophylaxis alone, the technique is cumbersome and expensive, and there is justifiable concern about bacterial resistance with the overuse of antibiotic prophylaxis. Prolonged antibiotic prophylaxis has been associated with postoperative pneumonia,¹³ catheter sepsis and catheter-related blood stream infection,¹⁴ and surgical site infection caused by methicillin-resistant Staphylococcus aureus (MRSA).⁷ Prolonged antibiotic prophylaxis increases the risk of Clostridium difficile-related disease (antibiotic-associated colitis) fivefold.¹⁶ Organ transplantation is managed with both antibacterial and antifungal prophylaxis.¹⁷ Up to 48 hours of prophylaxis is standard, but longer courses clearly carry risks.¹⁴ Invasive fungal infection is preceded by colonization of critically ill patients. Some have advocated prophylaxis with fluconazole, but the prevalence of fluconazole-resistant Candida is increasing as well, and the role of general antifungal prophylaxis in the ICU requires further evaluation.^18,19 Hepatic cirrhosis with portal hypertension and variceal hemorrhage is one example of a disease entity where antibiotic prophylaxis is of clear benefit.20 Bacterial infection is an independent risk factor for failure to control variceal hemorrhage. Antibiotic prophylaxis reduces the risk of infection, recurrent hemorrhage and death. In the most recent meta-analysis of 19 trials, antibiotic prophylaxis reduced the risks of infection by 61% (RR, 0.39; 95% CI, 0.32-0.48) and death by 30% (RR, 0.70; 95% CI, 0.56-0.89).*21 Antibiotic prophylaxis of variceal hemorrhage should now be standard.

Ensuring Proper Treatment
Appropriate antibiotic prophylaxis in the ICU can reduce morbidity and mortality, but usage must be appropriate lest the risk of harm to the patient be increased. Unfettered antibiotic prophylaxis almost invariably results in overuse. Critical care professionals have a responsibility to their patients and to their institutions to use prophylactic antibiotics appropriately.

* Confidence Interval (CI), Relative Risk (RR), Odds Ratio (OR)

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