625

Outpatient Parenteral Antimicrobial

53  Therapy
Kevin Hsueh and Jeffrey Bruce Greene

SHORT VIEW SUMMARY

• Outpatient parenteral antimicrobial therapy
(OPAT) refers to the intravenous treatment of
infections outside of the acute or subacute
health care setting. Developed in the 1970s,
OPAT has many theoretical advantages over
inpatient intravenous therapy, including lower
cost, greater patient satisfaction, and lower
risk of nosocomial infections. The downside is
that outcomes are comparatively less well
studied. The data most supportive of OPAT are
for its use in treating infections that require
prolonged therapeutic courses where oral
therapy is inappropriate, most notably bone
and joint infections and select cases of
infective endocarditis. However, it has also
been used with some success in skin, soft
tissue, pulmonary, and genitourinary infections.
Anecdotal evidence even reports success in
treating central nervous system, chronic
fungal, viral, and opportunistic infections by
OPAT, although the body of literature definitely
cannot be said to support its use as standard
of care.
• Consideration for OPAT must be made on a
case-by-case basis. Optimally, clearly defined
culture and sensitivity data for the infective
organism(s) should be available, as should
easily monitored parameters to confirm
response to therapy. Caution should be taken
with cases where either the infective
organism, source of infection, or most
appropriate avenue of management is unclear,
because these types of cases can often fare
poorly in less-monitored settings. Similarly,
every effort should be made to ensure patients
are entirely stable, that all surgical or
radiologic interventions have been completed,
and that the home environment is appropriate
before starting OPAT. The infectious disease
physician plays a key role, both in selecting
cases for OPAT and managing treatment
during the therapeutic course. They provide
expertise on which diseases and organisms are
amenable to outpatient therapy, which
patients can tolerate said therapy, and which
antibiotics are both effective, practical, and
minimize complications. They also help monitor
disease response and side effects and can
alter regimens in response to new issues.
• It is likely that OPAT will continue to play a
larger and larger role in anti-infective therapy
in the years to come. Forces both within and
without the medical community continue to
advocate further minimization of the hospital
stay, and technologic and pharmacologic
advances are making OPAT an easier and
cheaper option of care. This growth should be
met with a corresponding growth in outcomes
tracking and literature, to make OPAT use as
safe and practical as possible.

Outpatient parenteral antimicrobial therapy (OPAT) refers to the treat-
ment of infections by intravenous therapy in settings other than acute-
care hospitals or subacute health care facilities. The earliest published
report of OPAT was in 1974 by Rucker and Harrison,1 who treated
children with cystic fibrosis for exacerbation of lung infections. This
came 40 years after the discovery of sulfonamides and 30 years after
the parenteral antibiotic therapy era began with the availability of
penicillin and chloramphenicol. Until that point, hospitals had been
considered the preferred site for the management of complicated infec-
tions. Using parenteral antibiotics in settings other than a hospital is
not simply a matter of choosing an alternative venue of care. The deci-
sion to treat and monitor a patient outside a hospital requires specific
skill sets, along with a firm foundation in the management of infectious
disease therapies.
A number of nearly concurrent developments served to propel the
use of parenteral antibiotics in outpatient settings. The first was the
development, in the late 1970s, of elastomeric venous access devices
with complication rates low enough to serve as stable antibiotic deliv-
ery platforms.2 In the early 1980s, antimicrobials such as ceftriaxone,
having pharmacokinetic, clinical efficacy, and safety profiles advanta-
geous for outpatient administration, started to be widely used.3,4
Finally, in addition to the clinical advances, financial incentives devel-
oped that encouraged earlier discharge from the hospital. In 1983,
diagnostic-related group (DRG) models for payment of clinical ser-
vices were adopted nationally in the United States by the Health Care
Financing Administration, now called the Centers for Medicare and
Medicaid Services (CMMS). Other third-party payers subsequently
adopted the DRG system, in which compensation to hospitals for
inpatient care was no longer remitted on a fee-for-service manner but
instead as a lump-sum payment based on a weighted estimate of cost
for specific diagnoses multiplied by a fixed average length of stay. It
was quickly understood that prolonged hospital stays represented
financial liability, and means were sought to transfer patients from the
acute-care setting earlier.5
There are many theoretical advantages to OPAT. Studies comparing
parenteral antimicrobial treatment in the outpatient setting with hos-
pital care have repeatedly shown significantly lower costs of OPAT
across a wide range of infections. Although there is a reimbursement
disparity for OPAT among different types of payers, daily costs are in
the range of 25% of the daily costs of in-hospital treatment.6-8 Of
importance, there appears to be an acceptably high rate of successfully
completed courses of therapy compared with inpatient treatment.9-13
Furthermore, there is theoretically a lower risk of secondary nosoco-
mial infections, such as Clostridium difficile colitis, methicillin-resistant
Staphylococcus aureus (MRSA) or infection by multiple drug-resistant
bacteria, which some studies have indicated.14-16 From the patient and
family’s point of view, OPAT allows treatment of serious infections in
familiar surroundings, with loved ones present, and in some cases,
affords the ability to remain gainfully employed during the course of
therapy. This is especially important for particularly sensitive popula-
tions, such as children and the elderly, where the unfamiliar and often
frightening inpatient setting can actively hamper or obstruct therapy.17,18
Despite the continued growth of OPAT in the United States and
around the world, there is still a paucity of well-designed studies com-
paring it with hospital-based antimicrobial therapy. There are few ran-
domized controlled outcomes trials in the literature. The focus has
instead been on cost and not efficacy. Even then, much of the recent
cost savings data comes from cost-controlled health care systems, such
as Canada and the United Kingdom. Therefore, these studies may not
be representative of costs of OPAT in the less-regulated U.S. health care
system. As OPAT became more commonly used in the United States,
the diversity of infections and the case severity of patients treated
increased in parallel. By the late 1990s, the organic growth of OPAT in
the United States begged for a comprehensive database, similar to ones
that those countries with national health services compile, so as to
better analyze the risks, benefits, and outcomes. An attempt to address
this issue in the United States came in the form of the OPAT Outcomes
Registry (1997 to 2000), which studied more than 11,000 patients from
625
 625.e1
KEYWORDS
antibiotic; antimicrobial; arthritis; bacterial; endocarditis; infection;
infective; intravenous; IV; joint; management; OPAT; osteomyelitis;

Chapter 53  Outpatient Parenteral Antimicrobial Therapy

outpatient; parenteral; prosthetic; septic
 626
TABLE 53-1  Types of Infections Treated by OPAT
(% of Total Courses)
OPAT Outcomes Registry 1996-2002
Part I  Basic Principles in the Diagnosis and Management of Infectious Diseases
Skin and soft tissue (23%)
Osteomyelitis (15%)
Septic arthritis/bursitis (5%)
Bacteremia (5%)
Wound infection (4%)
Pneumonia (4%)
Pyelonephritis (3%)
OPAT, outpatient parenteral antimicrobial therapy.
Data from Tice AD, Rehm SJ, Dalovisio JR, et al. Practice guidelines for
outpatient parenteral antimicrobial therapy. Clin Infect Dis. 2004;38:1651-1671.
TABLE 53-2  Types of Antibiotics Used in OPAT (%
of Total Courses)
OPAT Outcomes Registry 1996-2002
Ceftriaxone (33%)
Vancomycin (20%)
Cefazolin (6%)
Oxacillin/nafcillin (5%)
Aminoglycosides (5%)
Clindamycin (3%)
Ceftazidime (3%)
OPAT, outpatient parenteral antimicrobial therapy.
Data from Tice AD, Rehm SJ, Dalovisio JR, et al. Practice guidelines for
outpatient parenteral antimicrobial therapy. Clin Infect Dis. 2004;38:1651-1671.
24 contributing medical centers, providing important clinical data.19
The registry reported critical information, such as the number and
types of infections treated, the antimicrobial usage frequency, any inci-
dence of antimicrobial side effects, and the percentage of treatment
regimens completed versus those that were terminated early for toxic-
ity or other reasons (Tables 53-1 and 53-2). Unfortunately, the registry
could not be maintained for lack of resources, leaving an ever-widening
gap in data collection that has yet to be filled.
DECISION MAKING IN CHOOSING
PATIENTS FOR OPAT
Despite decades of growth in OPAT use, the number of patients treated
yearly in this manner still represents a small percentage of total patient-
days of intravenous antibiotic use. This is because not every patient is
suitable for OPAT, and not every physician has the skills or resources
necessary for its use. To assess a patient for appropriateness for OPAT,
it is necessary to consider a wide range of issues. This requires the input
of a clinician who is versed in the principles of infectious diseases and
who has experience in managing patients in the outpatient setting
(Table 53-3).
Outpatient parenteral therapy may be considered when an infection
requires treatment and no oral antimicrobial is appropriate, usually in
the context of prolonged therapeutic courses. Ideally, most referrals for
OPAT are for patients who have already begun their therapy in the
hospital setting and have demonstrated a clear laboratory and clinical
response to the planned therapeutic agent. Most patients receive the
remainder of their antibiotic infusions at home after being taught how
to self-administer, or, occasionally, entirely from a trained infusion
nurse. In recent years, there has also been a modest growth in the
numbers of patients referred for OPAT directly from physician clinics
or emergency departments.
Making an accurate infectious disease diagnosis is the first key step
in determining the suitability of OPAT. Conditions for which there is
a clear standard of care, with available culture and sensitivity data, and
for which there are easily obtainable clinical, laboratory, or radiologic
parameters with which to assess the response to therapy are the pre-
ferred situations for application of OPAT (Table 53-4). For example, an
appropriate referral to OPAT would be a patient with subacute bacte-
rial endocarditis caused by a viridans strain of Streptococcus, which is
TABLE 53-3  Decision Making in Outpatient
Parenteral Antimicrobial Therapy
Determine the clinical Bacteremia/fungemia, bacterial endocarditis, soft
syndrome tissue/joint/bone/hardware, pulmonary,
genitourinary, Lyme disease,* HIV-associated
opportunistic infections, intra-abdominal abscess,
CNS infections
Consider the pathogen Organism(s) identified, predictable pathogen(s),
sensitivities identified, demonstrable response to
therapy
Choose an Good therapeutic index, drug levels predicted
antimicrobial adequate for the infected site, expense/payer
preference, ability or need to monitor drug levels
Weigh OPAT-limiting Advanced age, comorbid diseases (DM,
host factors hepatic/renal failure, neutropenia, cancer,
immunodeficiency states), co-administered
immunosuppressive therapies (corticosteroids,
TNF inhibitors, chemotherapy), history of
multiple antibiotic allergies, history of recurrent
Clostridium difficile infection
Assess the outpatient Stable home, adequate clean treatment space, safe
treatment setting location for nursing visits, access to phone/
Internet communication, patient/family able to
self-treat or cooperate with caregivers
Recognize and manage Indispensable components for care need to be
payer restrictions, covered; antimicrobial provision, infusion
and assume a supplies, intravenous catheter care, nursing,
leadership role for physician oversight. Concrete assignment of who
patient’s care is monitoring patient for therapeutic efficacy and
side effects, and who is the contact person
responsible for regimen changes is necessary
*Use of intravenous antibiotic therapy for treatment of Lyme syndromes other
than neuroborreliosis or carditis is controversial. Please refer to Chapter 243 for
more specific recommendations regarding Lyme disease.
CNS, central nervous system; DM, diabetes mellitus; HIV, human
immunodeficiency virus; OPAT, outpatient parenteral antimicrobial therapy; TNF,
tumor necrosis factor.
without evidence of embolic complications, valvular dysfunction or
large vegetations, and whose fever and bacteremia have resolved.20,21
However, not all cases successfully managed in the outpatient setting
are so ideal. Frequently, OPAT is used in soft tissue or bone infections,
where the identification of the causative pathogen(s) is not known, or
in patients previously treated with antimicrobials, making isolation of
a pathogen difficult.22 The literature is also rife with anecdotal case
reports where OPAT has been used for virtually every conceivable kind
of infection. However, there are clearly some infections for which
OPAT should not be recommended. Patients with hemodynamic insta-
bility, hyperpyrexia, altered mental status, or poor performance status
should never be discharged for home therapy.23,24 Similarly, patients on
empirical or multiple antimicrobial agents for what would be predicted
to be polymicrobial infections pose special challenges. Higher risks of
drug toxicity or breakthrough bacteremia with resistant organisms
should generally exclude such persons from outpatient treatment. The
most prudent advice is to limit referrals for OPAT to those infections
that do not pose imminent or likely threats to patient survival and have
demonstrated a clear response to the class of antibiotics that will be
used at home.
Infections that demand combined antimicrobial and surgical man-
agement should not be referred for OPAT until both modes of treat-
ment are well underway. This might entail such interventions as
percutaneous drainage of a liver abscess or empyema, stenting of an
obstructed ureter, débridement of infected bone, or incision and drain-
age of a soft tissue abscess.
Identification of the causative organism(s) may influence the deci-
sion to consider outpatient therapy. In general, bacteremia demands
an exhaustive evaluation to understand the source, pathogenesis, and
potential effects before a patient is referred for OPAT. Polymicrobial
bacteremia is especially worrisome. Patients infected with more patho-
genic bacteria, such as MRSA, the Enterobacteriaceae, and clostridial
species, are more likely to experience poor outcomes.25-28 Especially
challenging are those patients in whom no causative organisms are
recovered. An adequate period of observation on the intended home
antibiotic therapy is essential before discharge from the hospital.
 627

TABLE 53-4  Infections That May Be Referred for Outpatient Parenteral Antimicrobial Therapy
Bacteremia SBE (excluding Staphylococcus aureus, large vegetation, CHF, perivalvular abscess, conduction defects)
IV device–associated (excluding cases where removal of device and/or needed débridement not performed

Chapter 53  Outpatient Parenteral Antimicrobial Therapy

Pulmonary
Bone/soft tissue
Intra-abdominal/retro-peritoneal
Central/axial nervous system
AIDS opportunistic infections
AIDS, acquired immunodeficiency syndrome; CHF, congestive heart failure; CMV, cytomegalovirus; CNS, central nervous system; GI, gastrointestinal; IV, intravenous; SBE,
subacute bacterial endocarditis.
Neutropenic sepsis (after resolution of absolute neutropenia)
Community-acquired pneumonia (excluding multilobar, gram-negative pathogen, hypoxemia, undrained empyema)
Lung abscess
Acute/chronic osteomyelitis
Septic arthritis
Cellulitis (after excluding necrotizing fasciitis, pyomyositis, synergistic anaerobic infection)
Diabetic foot infection
Surgical/nonsurgical wound infections
Periappendiceal or diverticular abscess/phlegmon
Liver abscess (after drainage)
Pelvic inflammatory disease
Pyelonephritis/renal carbuncle
Pyogenic discitis
Brain abscess (after clear response to therapy and assessment of seizure risk)
Meningitis (after clear response to therapy and assessment of seizure risk)
CMV disease (retina, skin, GI tract)
Atypical mycobacterial infection
CNS toxoplasmosis

Host factors figure prominently in predicting successful antimicro-
bial therapy outcomes. Having patients of advanced age; those with
comorbidities, such as diabetes mellitus, malignancy, chronic liver, or
renal disease; those co-administered corticosteroids or other immuno-
suppressant agents; or those with neutropenia are but some of the
factors that should argue against OPAT. In addition, patients with
multiple medication allergies are more likely to experience OPAT com-
plications, as are patients who have had recurrent Clostridium difficile
infection.
The choice of antibiotic for OPAT is influenced by the isolated or
suspected pathogen, the site of infection and the drug level achievable
at those sites, pharmacokinetics of the drug, the patient’s renal and
hepatic function, allergy history, and any anticipated toxicity of long-
term therapy (Table 53-5).29 Although use of the narrowest-spectrum
agent is usually advisable, in OPAT, selection of antimicrobials is often
influenced by convenience of administration and the therapeutic
margin of safety. For example, an infection caused by a methicillin-
sensitive Staphylococcus aureus might be treated with ceftriaxone in the
OPAT setting, rather than a narrower-spectrum drug such as oxacillin
or nafcillin.30 Ceftriaxone has once-daily dosing (because of a longer
half-life), is more stable at room temperature, and is less likely to cause
phlebitis than the semisynthetic penicillins. Aminoglycosides may
be used daily at higher doses (5 mg/kg), and extended intervals to
provide improved bactericidal activity and postantibiotic effect with
less toxicity.31 Knowledge of drug stability characteristics is crucial
when reconstituted agents are stored for days in the home for patient
self-administration. Drugs such as the penicillin derivatives might be
administered by intermittent administration via a compact program-
mable pump worn by the patient.32,33 Unfortunately, despite their great
clinical utility and safety enhancement, many payers will not authorize
the use of these devices because of their added expense.
Some technologically advanced home-care vendors permit first-
dose antimicrobial administration at home. However, it is preferable
that first doses of antimicrobials be administered in more monitored
settings, such as the hospital or clinical offices, so that acute allergic
reactions can be promptly recognized and treated.
The “hospitalization” of the home setting demands a suitable area
for nurse assessment and intravenous infusion. The home should be
clean, have adequate storage space for supplies, proper refrigeration
when necessary, and should be in a safe location for needed home visits
by the clinical and technical staff. Easy contact by telephone or Internet
is a must. Inadequate home environment is one of the more common
obstacles to OPAT.23
There are many nuances in OPAT that set it apart from inpatient
care. With OPAT, day-to-day patient needs are typically provided
by specialist infusion companies, often combined with an infusion
pharmacy and a nursing agency.34 A responsible physician is typically
designated as the care coordinator, but he or she is dependent on the
information and observations of others. Care can be fragmented, and
communication between the various providers is not always efficient.
This places increased responsibility upon the physician, who is in the
difficult position of making clinical recommendations without the
benefit of firsthand information. Ideally, the physician should be an
infectious diseases specialist who has been involved in the initiation of
parenteral therapy in the hospital and who has experience in OPAT.
Beyond the physician’s challenges in managing a patient’s care from
afar, there are nonmedical factors that require consideration. Under-
standing which services are covered by the patient’s payer, whether
co-pays apply, and which medications are on the payer’s formulary
are but a few of the areas that impact a patient’s appropriateness for
OPAT.35 Patients or their caregivers must also be physically capable of
performing the intricate tasks required of them. If they are receiving
infusions at home, they must cognitively be able to comprehend the
technologies they are using. Physically, they must also be able to
manipulate the complicated packs and infusion devices provided by
the infusion companies, often a difficult task for aged, neuropathic, or
rheumatic fingers.
EVIDENCE-BASED DATA FOR OPAT
As previously described, the most frequent referrals for OPAT are in
patients with infective endocarditis, complicated skin and soft tissue
infection, and osteoarticular infections with or without hardware
involvement. These indications for OPAT have the greatest representa-
tion in the literature, and there are data to support the conclusion that
for most cases outpatient management of infection produces outcome
results comparable to hospital-based therapies. For example, OPAT-
managed infective endocarditis caused by viridans streptococci has
been shown to have a greater than 95% cure rate when ceftriaxone is
used.36,37 Infective endocarditis caused by other organisms, such as
Staphylococcus aureus, has lower cure rates and higher readmission
rates.28,38,39
The most frequent use of OPAT is in the treatment of bone and
joint infections, including prosthetic joint infections, and there is a
sizable experience reported in the literature. In the largest published
study, OPAT treatment of chronic osteomyelitis had a 70% overall cure
rate.25 This is equivalent to that expected in patients completing their
 628

TABLE 53-5  Properties of Commonly Used OPAT Antimicrobials (Modified from 2004 IDSA Guidelines)
HALF-LIFE STABILITY PHLEBITIS
DRUG (hr) AT 5° C/25° C RISK* ISSUES OF CONCERN DURING OPAT
Part I  Basic Principles in the Diagnosis and Management of Infectious Diseases

Caspofungin >48 24 hr/24 hr 1

Cefazolin 1-2 10 days/1 day 1
Ceftazidime 1.4-2 21 days/2 days 1
Ceftriaxone 5.4-10.9 10 days/3 days 1
Clindamycin 2-3 32 days/16 days 1
Daptomycin 8.1 12 hr/48 hr 1 Occasional myopathy; CPK should be checked weekly.
Can falsely prolong INR without changing anticoagulation; INR should be checked
at least 24 hr after daptomycin dosing.
Ertapenem 4 24 hr/6 hr 2 LFTs should be checked weekly.
Gentamicin 2.3 30 days/30 days 1 Ototoxicity and nephrotoxicity common.
Drug levels, kidney function must be checked twice weekly.
Hearing and vestibular function must be monitored frequently.
Meropenem 1.5 24 hr/4 hr 1 LFTs should be checked weekly.
Nafcillin 0.5-1.5 3 days/1 day 3 Occasional hepatotoxicity; LFTs should be checked weekly.
Oxacillin 0.3-0.8 7 days/1 day 2 Higher risk of thrombophlebitis and DVTs.
Frequent dosing requires advanced continuous infusion systems.
Penicillin G 0.4-0.9 14 days/2 days 2
Tobramycin 2-3 4 days/2 days 1 Ototoxicity and nephrotoxicity common.
Drug levels, kidney function must be checked twice weekly.
Hearing and vestibular function must be monitored frequently.
Vancomycin 4-6 63 days/7 days 2 Occasional nephrotoxicity; kidney function should be checked weekly.
Drug level monitoring recommended.
Initial infusions must be monitored for red man syndrome.
*Degree of tendency to cause phlebitis: 1, mild; 2, moderate; 3, high.
CPK, creatine phosphokinase; DVTs, deep vein thromboses; IDSA, Infectious Disease Society of America; INR, international normalized ratio; LFTs, liver function tests;
OPAT, outpatient parenteral antimicrobial therapy.
Data from Tice AD, Rehm SJ, Dalovisio JR, et al. Practice guidelines for outpatient parenteral antimicrobial therapy. Clin Infect Dis. 2004;38:1651-1671.

course in an inpatient setting.40 Different pathogens clearly influence
the treatment outcomes. Pseudomonal osteomyelitis has a much lower
rate of cure and a higher rate of limb amputation when compared with
Staphylococcus aureus. MRSA has a poorer outcome than methicillin-
sensitive strains, and vancomycin may have a lower cure rate than
infections treated with semisynthetic penicillins or ceftriaxone.25
The longer the duration of therapy, often 6 to 8 weeks or more, the
higher the rate of adverse drug- and catheter-related complications. In
one recent study, 20% of patients experienced a catheter-related com-
plication, and 16% had an adverse drug reaction.41 Given the compa-
rable outcome results and the long duration of therapy that is necessary,
most experts recommend OPAT for patients with serious bone and
joint infection.
Skin and soft tissue infections, such as cellulitis, erysipelas, cutane-
ous abscesses, and surgical wound infections requiring parenteral
therapy, are a common cause for emergency room visits or admission
to a hospital. For complicated infections, standard treatment usually
entails initial use of parenteral antimicrobials for 3 to 4 days, with the
remainder of the course completed orally. Outpatient parenteral
therapy has been extensively studied.12,42,43 Certain clinical signs,
including leukocytosis, elevated band count, fever, tachycardia, tachy-
pnea may be harbingers of more serious soft tissue infection, such as
necrotizing fasciitis, and should prompt initial therapy to be instituted
in a hospital setting. Similarly, comorbidities such as diabetes and
peripheral vascular disease should prompt caution before referring a
patient for OPAT.26
There are many other infectious diseases for which OPAT has been
used and reported in the literature. Community-acquired pneumonia
has been considered for early OPAT. In a randomized control study in
Australia, patients referred for OPAT were visited daily by physicians
and twice daily by nurses. Clinical outcomes (resolution of symptoms)
were identical between patients receiving OPAT versus inpatient care,
although patients receiving OPAT had overall longer intravenous regi-
mens when compared with a randomly assigned inpatient control
group. The study’s authors believed this effect was due to the OPAT
group adhering more stringently to oral step-down criterion (need for
48 hours afebrile before oral antibiotic conversion).44
Multidrug-resistant organisms have resulted in an increasing
number of infections in otherwise healthy adults. Uncomplicated
genitourinary infections requiring parenteral antimicrobials can be
successfully treated outside of the hospital by using the carbapenems
or aminoglycosides.31,45
The use of OPAT for consolidation therapy in central nervous
system (CNS) infections, such as meningitis or brain abscess, has been
described in the literature. The experience suggests a relatively high
rate of readmission for neurologic complications such as stroke or
seizures.46 Further study is needed before routine use of OPAT can be
recommended for CNS infection.
Carefully selected neutropenic patients have been treated by OPAT.
Although studies of these carefully chosen and monitored patients
report good outcomes, there is abundant evidence that empirical oral
antimicrobials are equivalent to parenteral agents in these patients.47-50
Chronic fungal infections, viral infections, deep tissue abscess,
empyema, human immunodeficiency virus (HIV)-associated opportu-
nistic infections, and Lyme disease are some of the infections treated
with OPAT, despite a paucity of convincing efficacy and safety data.
Note that prolonged intravenous therapy for Lyme disease is a hotly
contended issue (see Chapter 243 for details).
ANTIMICROBIAL CONSIDERATIONS
IN OPAT
In theory, almost any antibiotic can be used in the outpatient setting.
Some of the first case reports of OPAT used agents such as oxacillin,
cefazolin, and penicillin G at infusion frequencies up to every 4 hours.51
For most patients, however, multiple infusions each day offset the
benefits of leaving the hospital early. The development of antimicrobi-
als with long half-lives and postantibiotic effects has propelled the use
of OPAT for a variety of infectious diseases. Ceftriaxone provided the
first safe, broad-spectrum, effective once-daily alternative to the older
β-lactam antimicrobials.
The most important characteristic that determines whether a drug
lends itself to OPAT is its frequency of administration. Except in
unusual situations, most OPAT regimens should use a maximum of
twice daily infusions. An antimicrobial’s pharmacokinetic features and
its kill properties determine the frequency of administration.29,52 For
example, drugs that display time-dependent kill properties, such as the
β-lactams, glycopeptides, and oxazolidinones, will need serum half-
lives of at least 6 to 8 hours in order to exceed the minimal inhibitory
concentration (MIC) in the serum throughout the day for the pathogen
being treated. For drugs that have concentration-dependent killing

characteristics (e.g., aminoglycosides, fluoroquinolones, metronida-
zole, and daptomycin), higher post dosing serum peak levels permit
longer dosing intervals. However, concentration-dependent toxicity
may limit their usefulness. Few available drugs are ideal for outpatient
629
rightly should be a meaningful team leader and advocate for the
patient’s well-being. It is the authors’ opinion that the onus falls upon
the hospital systems to ensure access to an OPAT specialist who will
be involved in each aspect of care until the infection is deemed cured.

Chapter 53  Outpatient Parenteral Antimicrobial Therapy

use. Ceftriaxone has a long (5- to 10-hour) half-life that allows once-
daily infusion. Ertapenem has a shorter (4-hour) half-life, but because
of a long postantibiotic effect (continued antimicrobial effect even after
drug levels are below the MIC), it too can be used once daily.
Vancomycin has a half-life of 4 to 6 hours in patients with normal
glomerular filtration rates, allowing twice-daily dosing. In the elderly
or in patients with chronic kidney disease, therapeutic plasma levels
of vancomycin may be achieved with less-than-daily dosing. A
vancomycin-related antimicrobial, teicoplanin, has an extraordinary
70- to 100-hour half-life, allowing administration at frequencies of
daily or less and making it a potentially useful OPAT drug, although
currently, it is only available outside the United States. High-dose
extended-interval dosing of aminoglycosides also allow once-daily
dosing, although their ototoxicities and nephrotoxicities make pro-
longed usage risky in all but the most stable patients. Last, medications
such as linezolid or the fluoroquinolones have excellent oral bioavail-
ability and may supplant the need for OPAT in some patients.
Consideration must be given to medication side effects and the use
of therapeutic drug monitoring in OPAT, particularly because regi-
mens tend to be prolonged. Antimicrobial plasma level monitoring can
be rendered difficult because it requires a timed specimen to be drawn
in relation to the last dose of medication. Nonetheless, it is important
to insist that samples be documented to have been drawn at the pre-
scribed times. Vancomycin, a drug with a narrow therapeutic window,
should always be used with once- or twice-weekly drug levels and
assessment of renal function. Amphotericin B, the aminoglycosides,
and semisynthetic penicillins previously were used much more fre-
quently but have now fallen out of favor because of alternative thera-
peutic strategies.53 The OPAT registry documented that up to 10% of
patients using these agents had medication-induced complications
requiring the cessation of therapy.54
Knowledge of drug stability is crucial in OPAT. Unless delivered in
an infusion center or doctor’s office, reconstituted infusate must often
be stored either at room temperature or in a refrigerator (ideally) for
several days (see Table 53-5).
THE INFECTIOUS DISEASES
PHYSICIAN ROLE AND OPAT
The decision to discharge the patient from a hospital setting for OPAT
is often initiated by providers other than infectious diseases (ID) spe-
cialists. If called at all, the ID specialist may be asked on the day of
discharge for medication recommendations. Discharge planning ser-
vices or hospitalists may not have the depth of knowledge or experience
necessary to safely transition a patient to OPAT. Furthermore, the
patient will need to have ongoing monitoring for therapy-related
complications as well as cure of infection. Rather than being a medical-
legal partner for the other elements of the care team, the physician
Formal OPAT programs have developed in a growing number of medi-
cal centers around the United States. Ideally, an OPAT team should
actively identify patients who might benefit from OPAT and begin their
involvement early in the hospital course.55,56 Close working relation-
ships with nursing and infusion device vendors is the key to ensuring
a team approach. Follow-up with the patient and the OPAT team in
the form of telephone communications, interim office visits, and home
visits would likely improve infection outcomes and prevent adverse
events, although dedicated study on this topic has not yet been done.
THE FUTURE OF OPAT
The use of OPAT has increased since its inception in 1974, and there
is every reason to expect its growth to continue into the future. There
will be continued financial pressures on hospital systems to move
patients to alternative care. On the horizon, experts in health care
financing are expecting payments to hospitals for patient care to be
bundled, which has already caused anticipatory changes in the way
care is rendered in hospital settings. The roll-out of the Affordable Care
Act in 2014, in particular, will greatly increase federal oversight of
private insurers and health care vendors. Regulators will require hos-
pitals to collect increasing amounts of quality-of-care data, and com-
parison metrics will start being analyzed and reported to the public.
Because OPAT is a multi–billion-dollar industry, it is likely to receive
increasing scrutiny. On a positive note, these data may begin to fill the
gaps in knowledge left after the OPAT registry was terminated in 2002.
The development of new pharmaceutical agents aimed at infections
will also influence OPAT programs. New drugs with suitable dosing
frequencies and unique antimicrobial spectra are entering the market.
Ceftaroline fosamil, a next-generation cephalosporin with broad-
spectrum activity against gram-positive bacteria (most notably MRSA),
gram-negative organisms, and a dosing frequency of every 12 hours is
expected to find a niche in the outpatient setting, pending further
study.57,58 As hospital lengths of stay for infections decrease and OPAT
use expands, pharmaceutical companies are likely to start investing in
boutique antimicrobial designs, with a specific eye on the OPAT
market.
Last, the information technology revolution has already started to
change the ways in which OPAT is performed. Telemedicine is likely
to reduce the number of hands-on visits needed for routine monitoring
and troubleshooting, potentially decreasing even further the cost of
OPAT per patient.59
ACKNOWLEDGMENT
The authors would like to recognize Alan D. Tice, MD, whose breadth
of work and advancements in the field of OPAT, including his chapters
in prior editions of this text, provided a guiding light for our field and
whose passing is a great loss.

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