Controversies in Perioperative Antimicrobial Prophylaxis

Brooke K. Decker, M.D.; Alexander Nagrebetsky, M.D.; Pamela A. Lipsett, M.D.; Jeanine P. Wiener-Kronish, M.D.; Naomi P. O'Grady, M.D.

Disclosures

Anesthesiology. 2020;132(3):586-597. 

In This Article

Controversies in Selected Cardiac Procedures

Cardiac Implantable Electrophysiologic Devices and Infection

Implantable cardiac electronic device infections continue to rise.[73] Infections can occur as an infection of the generator pocket, the leads, and/or involve endocardial structures. Cardiac implantable electrophysiologic device infections now constitute 10% of all endocarditis cases.[74] There has been an increase in the incidence of infectious endocarditis, in part because of the increased use of cardiac implantable electrophysiologic devices.[75] Surveys document that physicians frequently administer antibiotics to these patients in nonstandard ways.[76] Complete cardiac implantable electrophysiologic device hardware removal should be performed for definite infectious endocarditis cases. Parenteral antibiotics should be given, but optimal timing for reimplantation is unknown.[75]

Antibiotic Envelope for Cardiac Implantable Electrophysiologic Device Infections

A randomized controlled trial assessing the safety and efficacy of an absorbable, antibiotic-eluting envelope was completed, with 3,495 people in the envelope group and 3,488 people in the control group. A total of 25 patients in the envelope group and 42 patients in the control group developed an infection that required the removal or revision of the cardiac implantable electrophysiologic device pocket; major cardiac implantable electrophysiologic device–related infections occurred in 32 patients in the envelope group compared to 51 patients in the control group. The use of an antibacterial envelope led to a significantly lower rate of revisions caused by infection and significantly fewer major cardiac implantable electrophysiologic device infections.[77] Given that the trial was international, prospective, and randomized, these results suggest this needs to be considered when implanting cardiac implantable electrophysiologic devices. However, an accompanying editorial noted that the number of cases of bacteremia and endocarditis was higher in the intervention group, and this finding leads one to question the efficacy of the envelope.[78]

Extracorporeal Membrane Oxygenation

Survey data regarding antimicrobial prophylaxis and surveillance practice patterns were obtained from extracorporeal membrane oxygenation coordinators and directors internationally.[79] Of 556 surveys that were sent out to the 172 extracorporeal membrane oxygenation centers, 223 (41%) responded, and 198 completed the survey. There was marked variability between centers; the majority of centers administer prophylactic antibiotics. Given the lack of high-quality evidence and a lack of randomized trials, this variability should perhaps be expected. Surveillance tended to include routine blood cultures despite a lack of evidence for such practice.[79]

The relative incidence of infections and the efficacy of prophylactic regimens was evaluated in a systematic review that included Extracorporeal Life Support Organization registry studies, as well as data from individual centers. Rates of infection ranged from 7.6% in neonates to 20.9% in adults.[80] In two single-center studies, all subjects received prophylactic antibiotics and had a prevalence of infections of 16.1% and 18.4%, respectively.[80,81] Bloodstream infections were predominant in most of the studies, ranging from 2.6 to 19.5% prevalence, and rates of respiratory infections ranged from 1.4 to 15.8%.[80] One review did not find a benefit for prophylactic antibiotics in two retrospective studies.[80] Given changes in the care of these patients, multicenter randomized trials of prophylactic antibiotics are needed.

Drug Dosing in Patients Receiving Extracorporeal Membrane Oxygenation

The pharmacokinetics of drugs appear to be affected in at least three ways during extracorporeal membrane oxygenation: drug sequestration by the circuit, increased volume of distribution, and altered drug clearance.[82] Drug sequestration can occur by drug binding to the circuit, which may also lead to the circuit serving as a reservoir of certain drugs. The factors that seem important for these phenomena are the oxygenator materials, the types of conduit tubing, the circuit age, and the composition of the priming solutions.[82] Drug characteristics that influence drug sequestration are multiple and include the molecular size, the negative log of the acid dissociation constant (pKa), degree of ionization, lipophilicity, and predilection for plasma protein binding.[82]

Inflammatory and pharmacokinetic changes can lead to changes in the volume of distribution of drugs. Changes in blood pH also change the volume of distribution, and acidosis can be a common occurrence in patients on extracorporeal membrane oxygenation. Finally, drug clearance appears to be lower than normal when patients are on extracorporeal membrane oxygenation; drug accumulation can occur, but the use of inotropic support and increased cardiac outputs may counter this accumulation.[83]

The recommendations from a recent review are to use β-lactam antibiotics because they are utilized in other critically ill patients. The use of continuous vancomycin infusions during extracorporeal membrane oxygenation may help any extracorporeal membrane oxygenation-related pharmacokinetic changes. Recommendations for antifungal agents are sparse because of limited data. There are some data regarding voriconazole, suggesting a need for increased dosing because of sequestration.[82]

Bloodstream Infections in Extracorporeal Membrane Oxygenation Patients

Extracorporeal membrane oxygenation patients are at increased risk for bloodstream infections because they are in cardiogenic shock.[84] Large cannulae may be present for prolonged durations and are not easily exchanged if they become infected.[85] Finally, the presence of central lines and arterial catheters for prolonged periods may also increase the risk for bloodstream infection.[85]

Gram-negative rods were most frequently isolated from venous arterial–extracorporeal membrane oxygenation patients with bloodstream infection including Aeromonas hydrophilia/caviae, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa.[85] The venous venous–extracorporeal membrane oxygenation patients also had infections with Gram-negative rods including P. aeruginosa, A. baumannii, Burkholderia cepacia, and Enterobacter aerogenes, but they also had Candida infections. Notably, the venous arterial–extracorporeal membrane oxygenation patients in this study received prophylactic antimicrobial therapy with vancomycin and ceftriaxone for 48 h. All extracorporeal membrane oxygenation patients were bathed with chlorhexidine daily, and central lines are coated with minocycline/rifampin. Evaluation for infection was done if there was fever, leukocytosis, or purulence at an entry site.[85] Finally, bloodstream infection in extracorporeal membrane oxygenation patients was not associated with in-hospital mortality.[85]

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