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Editorial Comment

Wrapping Our Heads Around Outpatient Parenteral Antimicrobial Therapy for Central Nervous System Infections

Mahoney, Monica V. PharmD, BCPS, BCIDP

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Infectious Diseases in Clinical Practice: March 2021 - Volume 29 - Issue 2 - p e65-e66
doi: 10.1097/IPC.0000000000000993
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There is a growing body of evidence supporting the treatment of various infections with oral medications1; however, there will always be patients for whom circumstances require intravenous (IV) therapy. Outpatient parenteral antimicrobial therapy (OPAT) is a structured method of delivering IV therapy to patients without the need for inpatient hospital stays.2 It is estimated that more than 250,000 patients annually receive OPAT in the United States.3 Although the use of OPAT for central nervous system (CNS) infections has been adopted in the pediatric population, there has been a lack of data in adult patients. A 2006 Emerging Infections Network survey from the Infectious Diseases Society of America (IDSA) found the top 5 indications for OPAT to be bone and joint infection, endocarditis, skin and soft tissue infection, bacteremia and sepsis, and prosthetic device or orthopedic infection. Central nervous system infection ranked as the eighth most common.4

One of the reasons for its lower popularity among OPAT treatment may be a numbers game. We simply see more frequent other types of infections. It is difficult to quantify how prevalent CNS infections are, as they can encompass a number of different bacterial and viral syndromes. The Centers for Disease Control and Prevention quotes that 1.2 million cases of bacterial meningitis occur worldwide, but this reference stems from a 30-year old publication.5,6 More contemporary data quote 6000 cases of pneumococcal meningitis and 2600 cases of meningococcal meningitis in the United States each year.7 Incidence and prevalence rates for viral infections are even less clear.

More likely, however, is that there is a fear driving us to keep patients with CNS infections admitted and under close observation. These are sick patients, oftentimes requiring intensive care unit–level care. They may have cerebral-spinal fluid (CSF) shunts or require multiple CSF sampling for pressure relief or to evaluate response to therapy. The thought of discharging the patient to their home or a care facility may paralyze clinicians to keep the patient in-house, where their level of observation is higher, until they complete their antimicrobial therapy.

In addition, the guidelines have not fully addressed the topic of whether patients with CNS infections should be considered for OPAT. In the very last section of the archived 2004 IDSA meningitis guidelines, the idea of OPAT is mentioned, but it is so heavily shrouded in doubt and warning that many clinicians may decline to pursue this.8 The updated 2017 IDSA healthcare-associated ventriculitis and meningitis guidelines do not mention the notion of OPAT or outpatient therapy anywhere in the document.9 In addition, this information is lacking in the 2018 IDSA OPAT guidelines as well. Although neonate meningitis is briefly discussed, the concept of adult CNS infections is entirely missing.10 Only in the IDSA OPAT e-handbook are CNS infections addressed and included in the discussion. Although the e-handbook comments that the initial workup should be completed as an inpatient, it concludes that once a diagnosis is established and patients are stable, they can complete treatment in an outpatient setting.11 The problem with this recommendation, however, is that most practicing clinicians are not looking in the e-handbook as a reference on how to treat CNS infections.

Therein lies the biggest problem. There is a lack of data regarding safety and efficacy of treating CNS infections in OPAT recipients or as outpatients. In the 45+ years that OPAT programs have been in existence,12 only 2 studies have reviewed the use of OPAT in adult CNS patients. The first was in 1999 by Tice et al,13 and the second is in this issue of Infectious Diseases in Clinical Practice by Cummins et al.14 Both reported high success rates.

Tice et al13 retrospectively reviewed 68 patients receiving OPAT for predominately gram-positive infections, mostly meningitis (n = 29) and brain abscesses (n = 19). The mean and median durations of OPAT therapy were 18 and 17 days, respectively, with a range of 2 to 89 days. Patients received inpatient therapy for an average of 9.5 days (range, 2–53 days) before being discharged, with ceftriaxone and penicillin as the most common agents used. Although the authors stated that cure was achieved in 100% of patients, 3 patients changed antibiotics because of slow clinical response (n = 1) and enlarging brain abscess (n = 2). If these 3 patients were considered failures, the success rate would change to 95.6%. Hospital readmission occurred in 11 patients: 5 for nonemergent surgical procedures and 6 for medical complications. Upward of 27.9% of patients could have experienced line-related complications, but this was not clearly detailed. Adverse reactions were noted in 9 patients.13

Similarly, Cummins et al14 retrospectively reviewed 47 patients receiving OPAT, also for mostly gram-positive infections, with meningitis (n = 21), neurosyphilis (n = 12), and brain abscess (n = 11) the most common. The mean and median durations of OPAT therapy were 21.4 and 12 days, respectively, with a range of 2 to 144 days. On average, patients received approximately two thirds of their therapy as outpatients. Compared with the previous study, overall durations of therapy were longer, and the proportion of outpatient therapy was larger. Ceftriaxone, vancomycin, and penicillin were the most common agents used. The authors concluded that 80.4% of patients achieved clinical cure, 15.2% achieved probable cure, and 4.3% failed therapy. Hospital readmission occurred in 5 patients: worsening infection (n = 1), line complications (n = 2), CSF leak repair (n = 1), and insurance issues (n = 1). Four patients overall (8.5%) experienced line-related complications. Adverse reactions were noted in 3 patients.14

Overwhelmingly, patients did well in both studies. Combined, these studies begin to paint a picture that in carefully selected patients, CNS infections can be managed with OPAT. However, selecting the ideal patients will be crucial. As no prospective studies are available to guide this selection, a patient profile can be constructed from the IDSA OPAT guidelines10 and recommendations from the pediatric literature.15,16 These include patients with an identified organism, who are responding to therapy and have been afebrile for 24 to 48 hours. They have the ability or family support to administer medications at home or a care facility, have the resources to store medications/supplies safely, and have the technology/access for follow-up appointments.

Both Tice et al13 and Cummins et al14 highlight the resources dedicated to OPAT patient follow-up visits. In the study by Tice et al,13 patients were seen by an infectious disease (ID) physician or IV therapy nurse once or twice weekly and had twice weekly laboratory blood draws.13 In the study by Cummins et al,14 patients were seen in the OPAT clinic within 2 weeks of their discharge and then periodically thereafter. Patients also had weekly laboratory parameters available.14 Unique to this study was that an ID pharmacist, via a collaborative practice agreement, was able to receive and interpret the results and adjust drugs or doses as needed. Both of these interventions—early initial outpatient follow-up and availability of regular laboratory parameters—have been shown to optimize patient outcomes.17,18 The study by Cummins et al14 also demonstrates the value and success of a pharmacist managing the latter.

The utilization of OPAT is growing. As inpatient reimbursement is tied to diagnosis-related groups and some pay-for-performance measures such as healthcare-associated infections, institutions are looking for ways to safely discharge patients and decrease their inpatient length of stay. Enrollment in OPAT helps achieve all of this. Combined, the 2 studies included 2282 OPAT days, most of which would otherwise be assumed to have been inpatient days. These studies provide additional support that patients with CNS infections can be managed via OPAT, although appropriate care must go into selecting eligible patients. In addition, OPAT programs should include safeguard best practices, such as early follow-up care, weekly laboratory values, practical antibiotic selection, and the incorporation of ID-trained clinicians. With the ongoing shortage of ID physicians, the study by Cummins et al14 also lends support that ID pharmacists can complement that of ID physicians.

Thus, where does that leave us? Is OPAT for CNS infections ready for prime time? Probably not. However, in the stable patient with appropriate resources, who is being kept inpatient simply to finish their course of IV antibiotics, maybe, it is time that we overcame our fear and transition them to OPAT.


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