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Peers and Perspectives

1rem

This study revealed a significant decline in MSSA and a corresponding rise MRSA, particularly linked to COVID-19 social isolation measures.

Shifting Patterns of Staphylococcus aureus Infections in Pediatric Patients

A comparative study presented MAD-ID, The Antimicrobial Stewardship Meeting examining the effectiveness of ceftaroline and vancomycin in addressing this challenge.

Similar Efficacy of Ceftaroline and Vancomycin in Treating Complicated Skin and Soft Tissue Infections

Phase 3 study reveals exebacase combined with standard antibiotics in treating methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis did not meet its primary endpoints.

Exebacase Combined With Antibiotics Fails to Improve MRSA Bacteremia Outcomes

Rates of in-hospital mortality and days with bacteremia were similar between the two study cohorts.

Evaluating the Efficacy of Daptomycin and Ceftaroline for the Treatment of MRSAB

The antibacterial is efficacious in a majority of patients in a small study.

Eravacycline Realizes Successful Clinical Endpoint in OPAT Facilities

Investigators have observed an association between the prevalence of 

 in higher hospital levels, and greater rates of antibiotic use, suggesting the need for improved anti-MRSA antibiotic prescribing benchmarks.

, showed that across 122 Veterans Health Administration (VHA) hospitals during 2016, median days of therapy (DOT) with anti-MRSA antibiotics 96.5 (IQR, 81.1 - 116.9) per 1000 days present, versus 562.1 (IQR, 505.9 - 631.6) DOT with total antibiotics per 1000 days present.

A hospital-level risk-adjusted analysis showed hospital MRSA prevalence was significantly associated with monthly anti-MRSA and total antibiotic prescribing (IRR, 1.05 and 1.02, respectively).

“A 5% increase in the hospital’s MRSA prevalence was associated with an increase in the monthly use of anti-MRSA antibiotics and total antibiotics by 23.6 and 8.3 DOT per 1,000 days-present, respectively,” investigators wrote.

 during IDWeek, study author Daniel J. Livorsi, MD, MSc, Assistant Professor at the University of Iowa Carver College of Medicine, discussed his team’s findings and their implication for antibiotic stewardship needs.

“I think the other challenge is the way that stewardship teams generally interact with prescribers has changed as well,” he said. “We’re trying to discourage face-to-face conversations, and that’s often a good way to give feedback. If we’re trying to minimize doing that, we have to reconsider how we do stewardship.”

Watch the full interview with Livorsi in the video above.

The study, “Association of MRSA Prevalence and Hospital-level Antibiotic Use: A Retrospective Study Across 122 Acute-care Hospitals,” was presented at IDWeek 2020.

New data suggest collaboration between hospital prescribers and stewardship teams is still not perfected.

Conferences

Hospital Antibiotic Prescribing Linked to MRSA Prevalence

 showed various risk factors—both those known and under-acknowledged—can commonly drive MDRO contamination between patients, surfaces, and particular departments of a hospital.

The data, presented by study author Matthew J. Ziegler, MD MSCE,Assistant Professor of Medicine at University of 

, showed an observed group of 45 patients admitted to the intensive care unit (ICU) presented with a variety of MDROs:

Carbapenem-resistant organisms (CRO) (9%)

Vancomycin-resistant Enterococci (VRE) (9%)

Ziegler and colleagues reported that patient colonization during serial sampling was common among ESBLE, CRO, and VRE. MDRO detection via environmental surfaces was common among all subtypes aside from C. diff.

They also observed patient-to-environment transmission in 40% of patient rooms, and foreign MDRO contamination in 29% of rooms—with the most common being CRO.

Bathrooms and sinks, as well as surfaces near patients were the most frequently-contaminated MDRO environments.

 during IDWeek, Ziegler discussed these findings and their implication for contamination mitigation, as well as current clinical understanding of contaminated environments.

Watch the full interview with Ziegler in the video above.

The poster, “Patient to Environment Transmission of Multidrug-resistant Bacteria Within Intensive Care Units,” was presented by IDWeek 2020.

Multidrug-Resistant Infection is Diverse, Frequent in Hospital Setting

 Bruce Jones, PharmD, BCPS, clinical pharmacy specialist, infectious disease, St. Joseph’s/Candler Health System, discusses the growing burden of ABSSSI and why there have been an influx of MRSA cases.

Interview Transcript (modified slightly for readability)

“I think acute bacterial skin and skin structure infections (ABSSSI) is something we are all dealing with and the issue is with patients being hospitalized. We’re seeing greater than 3 million emergency department visits on a given year. Many of these patients are being treated as outpatients but more and more we’re seeing linear growth of how many are being treated as in-patients.

What we see with ABSSSI is mainly Gram-positive in nature; you know, 

 (MRSA); it’s becoming more and more difficult to treat. We’re seeing more issues with certain first-line antibiotics, so that’s probably our biggest issue we currently deal with right now, the MRSA-specific patients.

I think we’re seeing an increase [in ABSSSI cases], you know we can look to our local antibiogram, and we’re seeing more and more MRSA patients. We’re doing a better job at diagnosing them—I think that’s part of it&mdash;and we’re seeing a lot more recurrence as well. And so, as these become harder and harder to treat, it’s a bigger burden on us and health care systems.”

Bruce Jones, PharmD, BCPS, discusses the growing burden of ABSSSI and why there have been an influx of MRSA cases.

The Growing Burden of ABSSSI

Yoav Golan, MD, attending physician at Tufts Medical Center in Boston, Massachusetts, discusses trends in the incidence of acute bacterial skin and skin structure infections, standard protocols for treatment, and the challenges clinicians continue to face.

“One of the trends with ABSSSIs and the risk factors or the drivers of it, no question, we’ve seen a huge increase in skin infections both in the community and in the emergency department and admissions related to skin infections over the past 15 to 20 years. I think that there were 2 main drivers for that. One is that the bacteria that caused that particular 

; [for example], 1 clone in particular that’s known as USA-300—and it circulates now to the communities and hospitals in the United States&mdash;is known to be more virulent than other 

that we used to see in the past. In other words, many people are colonized, on average, about one-third of adults are colonized with this bacteria but the likelihood of infection if you are colonized with this particular bacteria is higher, and so, that’s one driver of the increased frequency of those infections. The other is obviously the fact that we see people who get older—life expectancy is going up, and more people have diabetes and other risk factors for skin infections, [such as being] overweight, [having a] sedentary lifestyle&mdash;and become more vulnerable to develop skin infections. And so, both on the treatment side and the risk factors for the infection we see an increase and I think the expectation is that skin infections will continue to increase with the aging population.

What are the standard protocols for treating those infections and challenges? Standard protocols involved antibiotic use and follow-up in drainage of an abscess. The skin infections that we see typically are divided into redness, painful redness, infected redness— which is usually cellulitis or erysipelas&mdash;or an abscess, and those abscesses need to be drained, with or without antibiotics, depending on their size, or wounds that got infected, for example, trauma wounds or surgical wounds that get infected.

Of course, the main step is choosing the right antibiotic because those infections are almost, almost always caused by gram-positive bacteria, such as 

; these are the bacteria you want to cover. And because methicillin-resistant 

 (MRSA), which is the more antibiotic-resistant variant of 

, is now so prevalent everywhere, including communities, you need to make sure that at least in patients who are sick you want to cover MRSA, as well. One of the challenges is for that many of the patients, we don’t actually have any guidance coming from the microlab because there are no cultures when you have cellulitis or erysipelas and you have to treat based on your understanding of what types of pathogens cause this and what is their susceptibility.

Challenges are the resistance, of course. It was much easier to treat skin infections 10, 20 years ago, particularly in the community because they would be responsive to many of our narrow-spectrum, best antibiotics like cephalosporins and the penicillins like oxacillin, dicloxacillin, [or] cephalexin, antibiotics that are not just very active but also very safe. And with increasing resistance we have lost most of the antibiotics that could be used for skin infections and the ones that we have [now] are not as good as the ones that we did have. So, you have 2 issues here, 1 is that you may give a patient an antibiotic for which the bacteria that is causing his infection is resistant to and even if the bacteria is susceptible, the response may not be as good as it used to be in the past, and this is, of course, a major challenge.

Another challenge is that many people do not have health insurance and skin infections are seen very often, in particular they’re seen in some populations more often than other populations, like people with the heavy drug use and so forth. Some of those people don’t have good insurance, and so, they don’t have good access to care and very often they find themselves in the emergency department as their first stop for care and that has been a major challenge as well.”

Yoav Golan, MD, discusses trends in the incidence of acute bacterial skin and skin structure infections, standard protocols for treatment, and the challenges clinicians continue to face.

Treatment Challenges Remain as ABSSSI Incidence Continues to Grow

Patrick Horn, MD, PhD, chief medical officer at Tetraphase Pharmaceuticals explains why eravacycline is a unique antibiotic and how it stands up against many different types of pathogens, including those that are multidrug-resistant.

Patrick Horn, MD, PhD, explains why eravacycline is a unique antibiotic and how it stands up against many different types of pathogens, including those that are multidrug-resistant.

What Makes Eravacycline a Unique Antibiotic?

Daniel Pilch, PhD, associate professor, Rutgers Robert Wood Johnson Medical School, explains which patients would not make good candidates for MRSA prodrug TXA709. Dr. Pilch shares that TXA709 is capable of treating life-threatening bloodstream infections as well as skin and soft tissue infections. MRSA is also known for infecting bone; although distribution studies suggest that the drug can treat bone infections, more research still needs to be done.

Daniel Pilch, PhD, explains which patients would not make good candidates for MRSA prodrug TXA709.

Who is Not a Good Candidate for MRSA Prodrug TXA709?

Daniel Pilch, PhD, associate professor in the Department of Pharmacology at Rutgers Robert Wood Johnson Medical School, co-founder of TAXIS Pharmaceuticals, discusses the three choices that developers have when it comes to the approach they can take for developing a new antibiotic. Dr. Pilch shares the two areas in which he and his team's approach to treating drug-resistant bacteria has been focused.

Daniel Pilch, PhD, discusses the approach that he and his team took to develop a new drug to fight MRSA.

Developing New Antibiotics: What's the Best Approach to Take?

Edmond LaVoie, PhD, professor and chair, Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, co-founder of TAXIS Pharmaceuticals, explains how the initial drug discovery process for MRSA drug TX709 evolved. The vision was to develop a drug that could be orally bioavailable, but still have a sustained effect. Dr. LaVoie explains how TXA709 has "necessary properties" that allow for it to be formulated for infusion. TXA709 has proved efficacious by the intravenous and oral routes in animal model studies, which offers significant clinical advantages.

Edmond LaVoie, PhD, describes the properties of prodrug TXA709.

What Are the Special Properties of MRSA Prodrug TXA709?

Daniel Pilch, PhD, associate professor in the Department of Pharmacology at Rutgers Robert Wood Johnson Medical School, co-founder of TAXIS Pharmaceuticals, breaks down the process of how 

) is able to gain resistance to methicillin. Dr. Pilch also explains if the pathogen can gain resistance to a new prodrug he helped develop: TXA709. 

Daniel Pilch, PhD, discusses the potential of Staphylococcus aureus to develop resistance to TXA709.

Rutgers Researchers Develop New MRSA Prodrug: Can the Pathogen Gain Resistance?

Prof. Josh Davis, MBBS, PhD, Principle Research Fellow, Menzies School of Health Research, Australia, discusses the role of combination therapy when it comes to treating invasive 

Interview Transcript (slightly modified for readability)

“The role of combination therapy in invasive 

] infections is really not completely defined yet, though a lot of research has been done on [multiple] different combinations. At present, none of those combinations has been shown to be clinically superior to just standard monotherapy.

However, there is one promising set of combination therapies that we are working on further, and that’s combining beta-lactam antibiotics with standard therapy, and the standard therapy being either vancomycin or daptomycin.

So, for the other combination therapies apart from beta-lactam, they’ve all been shown either not to work or to cause more harm than good. An example is adding gentamicin to nafcillin—it does shorten the duration of bacteremia by about a day, but it doesn’t improve mortality and it causes more renal failure. So, that’s not recommended. Rifampicin, a recent trial has just been finished, called the ARREST trial, which [found] absolutely no benefit in adding rifampicin to standard therapy, and then there are several other agents, which also have not been shown to be of any benefit.

Beta-lactams, in vitro, in the laboratory, nearly all beta-lactams show synergy against MRSA, [methicillin-] resistant 

 and [heterogenous vancomycin-intermediate 

] hVISA, when combined with either vancomycin or daptomycin, and there is some limited human data, but not enough yet to say that it’s superior to monotherapy. We’re currently running a large, randomized trial to try to answer that question.”

Prof. Josh Davis, MBBS, PhD, discusses the role of combination therapy when it comes to treating invasive Staphylococcus aureus infections.

What is the Role of Combination Therapy in Treating S. aureus Infections?

 Thomas Lodise, PharmD, PhD, professor, Albany College of Pharmacy, reviews the 2019 CAP guidelines and highlights areas that could be improved in future updates.

Interview transcript: (modified slightly for readability)

The question is, how can the guidelines be improved? I’ve served on guidelines committees. It’s challenging, you have to rely on available evidence to make decisions within certain criteria.

I appreciate them maintaining a current stratification. I think this is something we're all familiar with, and thinking about outpatients, whether or not they have comorbidities, and treatment selection, whether they're in the inpatient ward or within the ICU, and providing some guidance on how to handle patients at risk for MRSA and 

So I think their overall structure and stratification really provides a good framework for identifying what drugs could potentially be considered for your patient and also to provide some clarity even though they may not make a strong recommendation of one recommendation over another, because they usually give a few options some of the guiding evidence and principles which may lead you to take one drug combination over another for example, in patients within the ICU.

I appreciate the move away from HCAP, and, to streamline clinicians to check prior culture data. Given the importance of getting it right the first time, I wish they were a bit more aggressive. They do recommend empirically covering MRSA and 

 in patients with risk factors for those if they have severe pneumonia, which is basically pneumonia in septic shock. However, my fear is we may undertreat a few patients who could potentially progress to septic shock. I think their recommendation for this was based on the best available evidence showing that we overtreat drug-resistant pathogens. But I still think we have to have a bit more in a bit more work in that area, because there's a recommendation to rely on institute validated risk factor scores. And this is something that a lot of institutions do not have.

So I do think there's an opportunity to better clarify who is our CABP patients at risk for MRSA, pneumonia and 

 pneumonia, more than just having it on a prior culture or current culture or PCR nares test. The other thing I think they could have done is provided a bit more clarity on the role of new drugs. As I mentioned before we have lefamulin and omadacycline. Omadacycline is mentioned twice in the document lefamulin is mentioned once and both in the future research direction section, citing limited experience.

Why this is true? These 2 agents have gone through recent FDA guidance for approval. There’s a focus on patient-reported outcomes, symptomatic improvement. So these are all things that are of value and they moved away from a lot of test to cure assessment, which was a clinician assessment of the patient's response.

Lefamulin has 2 phase 3 clinical trials and omadacycline has 1. So I think we could add defining their roles in therapy, perhaps not as first-line therapy but for patients at high risk for a fluoroquinolone associated adverse event. If you just look at the packet insert of the fluoroquinolones, there's a lot of class effects listed, you know, aortic aneurysm, patients over 65 [years of age], cardiac conditions, hypertension, patients with renal failure; these are all at increased risk of certain adverse events associated with fluoroquinolones.

So I think there was an opportunity there within the guidelines to better perhaps define the use of our newer drugs in those patients. Alternatively, they can say in those patients, maybe there should be preferential use of a β-lactam with a macrolide. I think these are opportunities, but recognizing that the guideline committee relies on best available agents and with the newer agents, you only have phase 3 clinical data, 2 clinical trials with lefamulin, 1 with omadacycline.

So I appreciate the need for further data, but I think in clinical practices we have these fluoroquinolones which are our go-to CABP drugs, they have tremendous efficacy, you'll never have a more efficacious drug class than fluoroquinolones in patients with CABP; however, from our federal government—and this is also with the EU as well&mdash;they identify a number of serious adverse events.

Looking at overall fluoroquinolones use, these adverse events are low, but they do identify some high-risk patient populations. So in the next iteration of the guidelines now it's taken us 12 years to get this one. When will this occur? I do not know. But I think all clinicians would benefit from better clarity on what drugs we should use in patient populations at high risk for fluoroquinolone adverse events, given that they have historically been one of our go-to agents for patients with community-acquired bacterial pneumonia.

IDWeek 2019 News Network: Areas of Improvement for CAP Guidelines

 Thomas Lodise, PharmD, PhD, professor, Albany College of Pharmacy, shares his initial reactions to the updated CAP guidelines.

. They only became available this week, so I haven't been able to do a very deep dive. My overall impression is, this is largely consistent with the previous guidelines. They still stratify patients, either outpatient or inpatient. In the outpatient setting, they provide treatment recommendations in the presence of or absence of comorbid conditions like heart failure, renal disease, and things of that nature. And then for the inpatient setting, they stratify patients by hospital ward versus the ICU [intensive care unit], and the ICU is your typical ICU patient patients, septic sepsis or septic shock.

Across those different stratifications, there are a few differences. First, as I mentioned before, macrolides should not be used in monotherapy with regions greater than 25% macrolide resistance in 

, which is the No. 1 cause of CABP. Unfortunately, we don’t have a lot of good surveillance data, with 

 in different regions. And when we do look at it, most regions have 40%.

So really the guidelines indicate that macrolides should not be used alone, which is a new recommendation and contrasted to [the 2007 guidelines]. For patients with comorbidities, they recommend using β-lactams or fluoroquinolones. However, they make mention of some of the concerns with the fluoroquinolones within the guidelines. There's been a number of boxed warnings over the past few years. In years past we had issues with QTC prolongation, tendinitis and tendon rupture. More recently, the most recent update is the increased risk of aortic aneurysm, particularly among patients with cardiac risk factors.

I think from that standpoint, we have a few different iterations. But largely the treatment choices are the same. Inpatient, it's still a beta-lactam with the macrolides or respiratory fluoroquinolones for your hospital ward patients. And for our critically ill patients in the ICU, it’s a β-lactam with a macrolide or a β-lactam with a fluoroquinolone. They do discuss that there appears to be some advantage in our ICU patients using a β-lactam with a macrolide over with a fluoroquinolone. However, they said either one is an acceptable recommendation.

Another big difference with the guidelines is the whole idea of HCAP. So actually HCAP is health care-associated pneumonia. This was from the previous ATS IDSA [American Thoracic Society and Infectious Diseases Society of America] pneumonia guidelines. So they make mention of this and said that this designation should be avoided. And rather what they added is the treatment of community-acquired pneumonia and patients at risk for MRSA or 

. So, what they did in this circumstance with someone who's at risk, prior 

 or MRSA infection, or was colonized with MRSA or 

, those individuals should be empirically treated if they're in septic shock, or if they have a positive culture at presentation among our hospital ward patients. So this is a recommendation primarily for your inpatients. Because if patients do have risk factors for MRSA or 

, those are the ones that tend to be admitted who have high acute disease severity.

Interestingly, for our hospital ward patients, they indicated to only add MRSA or 

 coverage if the pathogen is identified. For MRSA, it could be PCR for 

 on a clinical culture or the patient has history of MRSA or 

infection. In that circumstance, if MRSA is previously recovered, to use vancomycin or linezolid, if Pseudomonas was previously identified, then consider an anti-Pseudomonal β-lactam.

And then again, those in septic shock, [the committee] recommend to use those drugs empirically and de-escalate if they’re not recovered. So I think these are some of the biggest differences, you know, still largely the same, but they did provide greater clarity on that HCAP designation which we all struggle with. They do mention about patients at risk for MRSA, within a hospital, the risk of MRSA should be predicated on some validated institution-specific clinical prediction rules, they acknowledge those are not readily available. So this is something that will need further clarification as we move forward in practice.

I think the biggest thing is that if they had MRSA in the past, you should probably cover MRSA. 

. If you have it on culture, personally, I think I would probably cover them empirically and in a high-risk patient, perhaps coming from a nursing home, or as a health care frequent flyer with a lot of prior antibiotic exposures. However, this recommendation that’s made is in conflict for patients who are sick with pneumonia admitted but not treated within the ICU. So these are the patients without severe pneumonia.

IDWeek 2019 News Network: Initial Reactions to Updated CAP Guidelines

 Thomas Lodise, PharmD, PhD, professor, Albany College of Pharmacy, provides an overview of new agents for treating CABP and discusses reducing the costs of treatment.

MRSA

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