By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

Dr. Deresinski reports no financial relationships relevant to this field of study.

SYNOPSIS: Approximately one-fifth of outpatient parenteral antimicrobial therapy recipients developed a clinically significant antimicrobial-related adverse drug event.

SOURCE: Keller SC, Williams D, Gavgani M, et al. Rates of and risk factors for adverse drug events in outpatient parenteral antimicrobial therapy. Clin Infect Dis 2018;66:11-19.

Keller and colleagues addressed the issue of adverse drug-related events (ADE) that occurred in 339 adults discharged on outpatient antimicrobial therapy (OPAT) from one of two tertiary care academic medical centers in Baltimore. All the patients had peripherally inserted central venous catheters and all had assistance from a home health agency. Most cases were managed by an infectious disease specialist. The primary outcome measure was clinician-documented clinically significant ADEs ones resulting in hospital admission, a change in the antimicrobial administered, antimicrobial discontinuation, or the development of Clostridium difficile infection (CDI).

Clinically significant ADEs occurred in 49 (14.5%) patients, at an incidence of 2.24/1,000 patient-days. Independent risk factors for the occurrence of clinically significant ADEs were female gender and receipt of vancomycin or daptomycin, while both uncomplicated bacteremia and empiric (as opposed to targeted) therapy were associated with lower incidences of ADEs.

Sixty-one (18%) vancomycin recipients suffered an ADE, 19 (21.3%) of which were clinically important; 11 (18.0%) experienced nephrotoxicity. Three (37.5%) of eight daptomycin recipients developed elevated serum creatine kinase levels. No ceftriaxone recipient suffered a significant ADE. The incidence of ADE was highest in the first two weeks of OPAT.


This study found that approximately one in every five patients undergoing OPAT will suffer an ADE, a result not greatly different from that reported in inpatients. Thus, in a study of hospitalized patients at one of the institutions included in the analysis by Keller and colleagues, 298 (20%) of 1,488 experienced at least one antimicrobial-associated ADE, most frequently gastrointestinal, renal, and hematologic.1 There was a 3% increased risk of ADE for each additional 10 days of antimicrobial therapy. The incidence of identified CDI (0.47%) was even less than that reported by Keller et al (1.5%) but both seem remarkably low.

It is important to acknowledge that this OPAT evaluation only examined ADEs attributed to receipt of antimicrobials. Some serious adverse events not directly related to antibiotic therapy that may occur in OPAT patients include venous thrombosis and vascular access infections, including bloodstream infections.

Safe and effective OPAT requires a systematic approach. There should be a special focus on the transition from the inpatient to the outpatient setting, a time when error frequency is likely to be greatest. In fact, Keller et al found that the frequency of ADEs was greater in the first two weeks of OPAT than in subsequent weeks.

Muldoon and colleagues have proposed an OPAT bundle with six elements: “patient selection, infectious disease (ID) consultation, patient/caregiver education, discharge planning, outpatient monitoring/tracking, OPAT program review.”2 Appropriate patient selection includes, among other things, determining that the patient’s status is acceptable for management outside the acute care facility in a conducive environment with adequate support and resolution of financial aspects of care. ID consultation (or stewardship team consultation) should be performed prior to discharge and prior to placement of a central vascular catheter. The ID consultant must assess the feasibility and need for OPAT and explicitly delineate the therapeutic course as well as the necessary laboratory and clinical monitoring. The use of checklists can be a very important element of a successful OPAT program.3

The OPAT program must provide an individual responsible for monitoring visit adherence and laboratory results. The plan must be documented and accessible and the patient/family/caregiver appropriately educated regarding their responsibilities.

Finally, it is critical that the process, outcomes, adverse events, and patient satisfaction be audited on an ongoing basis. All of this requires a comprehensive structure and dedicated personnel, and, thus, must have the support of the institution’s administration. One solution is the provision of a clinical pharmacist or advanced practitioner to provide day-to-day oversight.

Many patients receiving OPAT do not require parenteral antibiotic administration and, in fact, some do not require any antibiotic therapy. Others can be treated with oral antibiotics alone. Furthermore, the role of the long half-life drugs dalbavancin and oritavancin may need to be taken into consideration.


  1. Tamma PD, Avdic E, Li DX, et al. Association of adverse events with antibiotic use in hospitalized patients. JAMA Intern Med 2017;177:1308-1315.
  2. Muldoon EG, Snydman DR, Penland EC, Allison GM. Are we ready for an outpatient parenteral antimicrobial therapy bundle? A critical appraisal of the evidence. Clin Infect Dis 2013;57:419-424.
  3. Gilchrist M, Seaton RA. Outpatient parenteral antimicrobial therapy and antimicrobial stewardship: Challenges and checklists. J Antimicrob Chemother 2015;70:965-970.