Management of Gram-Positive Multidrug-Resistant Infections: The Role of Long-Acting Lipoglycopeptides

Gram-positive multidrug-resistant infections may be managed effectively with a single dose of long-acting lipo­glycopeptide antibiotics in the outpatient setting, which can reduce hospital admissions and improve patient compli­ance. Careful patient selection is important for maximizing the cost benefit of these relatively expensive drugs, according to panelists who participated in a Contagion^® Peer Exchange panel.

Community-acquired and hospital health care—acquired gram-positive infections have become increasingly similar in recent years, according to Jason Pogue, PharmD, BCPS-AQID. He and panel moderator Peter L. Salgo, MD, also noted that multidrug-re­sistance is becoming increasingly prevalent in community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections. The results of an analysis of the 20-Year Multisite Emergency Department Emerging Infections Research Network (EMERGEncy ID NET) study that tracked patients who presented to emer­gency departments (EDs) in 11 cities showed that the overall prevalence of community-acquired MRSA infections was 59% over a 1-month period in 2004. Andrew Shorr, MD, predicted that the prevalence has likely increased since then.¹

“It’s a mess because it’s a very promiscuous bug, and these plasmids move back and forth, left and right,” said Dr. Shorr.

NOVEL LIPOGLYCOPEPTIDE THERAPIES FOR GRAM-POSITIVE INFECTIONS

According to Sandy J. Estrada-Lopez, PharmD, the long-acting lipoglycopeptides oritavancin and dalbavancin have been game-changing for the treatment of MRSA skin and soft tissue infections because they provide an option for patients to receive intravenous (IV) antibiotics as an outpatient or after early discharge from the hospital. She added that using these antibi­otics in the outpatient setting, most commonly the ED, allows the patient and health care system to avoid the high costs associated with hospitalization.

“The target is that patient who needs an IV antibiotic either due to the severity of the infection, having failed previous oral antibi­otics, [having] resistance to oral antibiotics, or perhaps where there’s significant concerns for adherence,” she said.

Dr. Estrada-Lopez also pointed out that past attempts to administer daily doses of a shorter-acting anti­biotic, such as vancomycin or daptomycin, in the outpatient setting in her health care system often led to greater financial and societal costs when the patient stopped showing up for infusions and had to be readmitted to the hospital.

“There’s a big cost associated with that [choice of treat­ment], if they get readmitted a week later, and now maybe we don’t want to give them that antibiotic again when moving further down the line,” she said.

Debra Goff, PharmD, FCCP, also pointed out that the single-dose long-acting antibiotics are useful for IV drug users because they do not require insertion of a peripherally inserted central catheter (PICC) line, which they could use for illicit purposes. However, she cautioned that assessing the individual and their home scenario is important for deciding whether to use this single-dose strategy. “Sometimes it’s almost an emotional decision of how you want to approach that IV drug user,” said Dr. Goff. “It’s very complex, [and] there are pros and cons of each decision.”

Dr. Estrada-Lopez also pointed out that the logistical convenience of a single dose could be useful for elderly patients who may travel frequently. “If they are saying, ‘I’m getting on a plane in 3 days, I can’t come for these infusions, I definitely don’t want to be in the hospital,’ we want to treat them with something that’s one-and-done, so to speak,” she said.

NUANCING LIPOGLYCOPEPTIDE THERAPY

Although long-acting lipoglycopeptides are convenient and may reduce the need for hospital admission in selected patients, Dr. Estrada-Lopez cautioned that they could be problematic for complex cases or those in whom bacteremia is missed.

“Let’s say that perhaps the patient is bacteremic and we didn’t realize that because they came into the ED. They looked like they just had an abscess, we drained it, but it was significant,” she said. “We felt like they needed antibiotics, but on day 3, their culture comes back positive and we can’t find the patient. They still have 7 days of antibiotics on board but maybe now we’re thinking they need 14 days or we need repeat blood cultures and we don’t have that patient in front of us.”

Dr. Estrada-Lopez also pointed out that even if they are able to get the patient to return, the strategy for additional treatment is unclear. “Would we consider that antibiotic active for 7 days and then give another dose, which would be off label, and switch to another antibiotic? At what point would you add another gram-positive agent that perhaps has a similar mechanism of action when this one is still active? There’s a lot of uncharted territory because we don’t have the clinical work to tell us.”

She added that providers should inform patients that it may take 48 to 72 hours to start seeing improvements and at least 7 days to see total improvement with long-acting lipoglycopeptides. “Just because you’re only going to get 1 dose does not mean you’re going to wake up tomorrow and [see a complete resolution of symptoms],” she said.

Dr. Shorr pointed out that providers also need to consider whether the long-acting glycopeptides are suitable for a given patient’s situation. “The novel long-acting glycopeptides are not better than the currently available therapies,” he said. “They have a different profile that may or may not offer a benefit to your patient or institution, but they’re not better in vitro [or] in clinical trials. They’re just different, and you have to decide if that distinction is a difference that matters to you or not.”

CONSIDERING THE COSTS OF LIPOGLYCOPEPTIDE THERAPY

Judicious patient selection for lipoglycopeptide therapy is especially important given their exponentially higher costs relative to other antibiotics. “You have to be fiscally responsible in how you decide to use them,” said Dr. Goff. “They can be the best spent money if they prevent a hospital admission or they could be a total waste of money.”

The panelists agreed that avoiding hospital admission and readmission within 30 days, as well as guaranteeing compliance, are the primary factors in cost savings. “If you can show that [the patient] didn’t get readmitted at 30 days because they either didn’t overdose on [illicit drugs] or they didn’t get a secondary complication from the PICC line, that’s cash in someone’s pocket at the hospital administrator level,” said Dr. Shorr.

Although estimating the costs of noncompliance is complicated, Dr. Estrada-Lopez stated that the basic cost is equivalent to that of a hospital admission that would have otherwise been unnecessary. Similarly, Dr. Goff noted that “the most expensive antibiotic is the one that doesn’t work,” and the costs from a lack of response can be estimated by the cost of the increase in length of hospital stay. However, she also pointed out that the associated societal costs are substantial and difficult to quantify.

“If you’re working for a living and you’re sitting in the hospital and you have children at home, [the costs to the patient start] escalating and snowballing,” she said.

The panelists concluded that the compartmentalization of the different hospital budgets remains a major challenge for justifying the overall cost-effectiveness of using long-acting lipoglycopeptides. “When we talk about antibiotics, it’s the pharmacy budget that’s getting hit for using more expensive antibiotics, and it’s the overall hospital budget that benefits from not having [an] extended length of stay,” said Dr. Estrada-Lopez.

Dr. Shorr added that breaking down this compartmentalization of the different budgets may introduce an opportunity to reassess the institutional protocols for treating these infections. “But you have to have a well-thought-out argument that shows it from a systems level [and present it] to the right person in the C-suite.”

Reference

1. Santibanez S, Fischer LS, Krishnadasan A, et al. EMERGEncy ID NET: review of a 20-year multisite emergency department emerging infections research network. Open Forum Infect Dis. 2017;4(4):ofx218. doi: 10.1093/ofid/ofx218.