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Peers and Perspectives

1rem

Skin and soft tissue infections (SSTIs) are an ongoing challenge that, like many 

 efforts, were exacerbated by the COVID-19 pandemic.

Bruce M. Jones, PharmD, FIDSA, BCPS, is an infectious diseases clinical pharmacy specialist at St. Joseph's/Candler Health System in Savannah, GA, and a self-proclaimed antimicrobial steward.

“When we talk about some of these newer novel agents, it’s how do we use them but use them for appropriateness, use them for the right patients, so that we maintain that stewardship type of mindset.”

Jones works primarily in the inpatient setting, and spoke frankly about the common problem of patients initially receiving unnecessary antibiotics. “A lot of what we see from a challenge standpoint is these patients come in, they’re on IV 

, it’s usually the main reason why they’re there,” he explained. “How do we transition them to the outpatient side?”

In this mini podcast, Jones breaks down the “very straightforward criteria” he uses to decide whether an SSTI patient should be inpatient or outpatient.

However, there is some nuance. “I always say, sometimes it’s things beyond the infection that will buy that ticket to admission,” Jones noted. “What we’ve found from our research is the number 1 reason why patients get admitted for these infections is failure of outpatient oral therapy.”

Jones emphasized the importance of including patients in the decision of whether they should be inpatient or outpatient. He strives to work with a patient, including them in their own treatment. Jones said, “We find that about 23-26% of the time, just by speaking to them, we can remove that allergy.”

Overall, Jones spoke positively about recent developments in antibiotics and efforts to use them vigilantly. “I feel optimistic about the agents that are out there and where we are with the science. The biggest barrier, I would say, is how do we get that information to the general clinician?”

Tune in to learn more about Jones’s methods and successes with antimicrobial stewardship, as well as a thorough explanation of the daily and overarching challenges he faces as a clinical pharmacist treating SSTI patients.

In this mini-podcast, infectious diseases clinical pharmacy specialist Bruce M. Jones, PharmD, FIDSA, BCPS, breaks down the “very straightforward criteria” he uses to decide whether a skin and soft tissue infection (SSTI) patient should be inpatient or outpatient.

How Do We Transition Patients on Heavy Antibiotics to Outpatient?

The effects of the COVID-19 pandemic continue to reverberate across other areas of health and medicine.

Notably, the US Centers for Disease Control and Prevention (CDC), reported 

 worsened by at least 15% during the pandemic.

“The biggest one that is concerning us is carbapenem-resistance among the gram-negatives, and that has increased,” said Christian Sandrock, MD, MPH, FCCP, vice chair for Quality and Safety, division vice chief of Internal Medicine, director of Critical Care, and professor of medicine at UC Davis Medical Center.

Assistant Managing Editor John Parkinson interviews Sandrock about how his institution is battling these bugs, the need for new therapies, and what we can all do to boost 

From the vantage point of his teaching hospital in Sacramento, Sandrock said, “We’ve actually seen things get a little bit worse, unfortunately.” Now is the time to renew the fight against the global threat of AMR.

Specifically, Sandrock discusses significant strides need takes to combat the rise in hospital-acquired bacterial pneumonia (HABP) and ventilator-acquired bacterial pneumonia (VABP).

In this podcast episode, Christian Sandrock, MD, MPH, FCCP, describes the need to make significant progress in antimicrobial stewardship.

COVID-19 Pandemic Drove Carbapenem Resistance in Gram-Negative Infections

“Usually for antibiotic awareness you have a week,” said Dr. Teena Chopra, “But for 

a whole month has been dedicated, for a reason.”

Awareness Month and Antimicrobial Awareness Week. As Chopra explains, too often the people most affected by a lack of vigilance in these areas already experience marginalization and discrimination.

“We are all global citizens, and having that uniform, consistent health care for all is where we need to move toward,” said Chopra.

Teena Chopra, MD, MPH is the Corporate Medical Director of Hospital Epidemiology at Detroit Medical Center, as well as a professor at the Wayne State University School of Medicine.

Chopra credits several mentors as inspiring her to specialize in infectious disease. Living and working in Detroit, MI, she has seen firsthand how infectious diseases can ravage underserved populations, moving her to practice where she’s most needed.

causes an estimated half a million infections a year and over a billion dollars in expenses in the US alone.

The Centers for Disease Control and Prevention (CDC) classifies 

However, until the disease touches their lives, the general public is largely unaware of its prevalence or even what 

 is. “We, as the health care community, need to raise more awareness for 

Listen in as Chopra discusses treatment regimens for 

 infection (CDI), as well as the populations disproportionately affected by this debilitating disease.

Missed Episode 6 of Contagion Community? 

Listen in on the conversation and feel free to offer your feedback on this episode, interest in participating in the podcast, or suggest ideas for future episodes. Please email your correspondence to Nina Cosdon: 

Dr. Teena Chopra discusses the global need to do more to prevent healthcare-associated infections like C difficile in vulnerable patient populations.

C difficile, Antimicrobials, and the Patients Most Affected

, where we delve into factors that create and widen health care disparities.

Although the development of antibiotics remains a challenge, there are some legislative strategies that could make it more attractive and get more players involved. 

On the fourth episode of the Contagion Community podcast, Evan Loh, MD, the CEO of Paratek Pharmaceuticals, discusses passing federal legislation to improve antibiotic development and reduce antimicrobial resistance.

Antimicrobial resistance (AMR) has been an ongoing public health problem for many years. A global analysis published in 

back in January estimated that antimicrobial resistance was the leading cause of death worldwide in 2019. Investigators estimated that resistance itself caused 1.27 million deaths that same year, and that antimicrobial-resistant infections played a role in 4.95 million deaths.

It has been something the medical community is quite aware of and has tried to do its part by developing antimicrobial stewardship programs at hospitals and medical centers to reduce the burden of AMR. Another issue within this public health concern has been antibiotic development. With it taking so many years to create new therapies, and reimbursement less attractive, larger pharmaceutical companies have left antibiotic development altogether. These life-saving medicines have become the domain of small, independent biopharmaceutical companies.

Combine those issues with 2 years of the COVID-19 pandemic, and this significant health topic has been shelved for some time.

Paratek Pharmaceuticals is a good example of a company in the antibiotic space. This smaller company has developed an FDA-approved tetracycline-class antibiotic for adult patients with community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. This antibiotic is also being studied for a variety of other potential indications.

, which has a mission to “improve the regulatory, investment, and commercial environment for antimicrobial drug and diagnostic device development to provide doctors and patients with innovative infectious disease treatment options.”

Paratek’s CEO Evan Loh, MD, is passionate about these life-saving medicines and has been active in his support of the Developing an Innovative Strategy for Antimicrobial Resistant Microorganisms Act of 2021 (DISARM) Act, which is a bill in Congress. “This bill requires additional payment under Medicare's inpatient prospective payment system for services that involve certain antimicrobial drugs, in accordance with specified limitations. Additionally, the Government Accountability Office must report on the barriers to developing such antimicrobial drugs and must recommend ways to address such barriers,” 

Along with governmental advocacy, Loh also sees the value in public and private partnerships to enable greater involvement in the antimicrobial space.

 about the challenges of developing antibiotics and providing incentives such as the DISARM act to attract more pharmaceutical companies to get involved in developing these vital medicines.

Forging an Evolutionary Regulatory Path for Antibiotic Development

The innovative antibiotic Xacduro has received FDA approval for its efficacy against ventilator-associated bacterial pneumonia caused by Acinetobacter baumannii-calcoaceticus. The intravenous therapy combines sulbactam and durlobactamto target multidrug-resistant and carbapenem-resistant strains. 

Xacduro, A New Weapon in the Fight Against Bacterial Pneumonia: Insights From Clinical Trials and Expert Interviews

Today, we celebrate the crucial role of infectious disease pharmacists in combating infectious diseases and promoting patient safety. 

Infectious Disease Pharmacists Day 2023: Our Top Stories

Empiric therapy for severe Salmonella disease remains effective, but fluoroquinolone resistance calls for a shift towards trimethoprim-sulfamethoxazole as the preferred oral treatment for non-severe cases.

Rising Threat: Evaluating Salmonella Treatment Options Amid Antimicrobial Resistance

Sulbactam-durlobactam is efficacious against carbapenem-resistant infections, and Innoviva is preparing for the antibiotic's PDUFA at the end of this month. 

Antibiotic Shows Noninferiority Vs Colistin for Acinetobacter infections

Antifungal therapy was frequently initiated before essential diagnostic elements confirmed invasive fungal infections in critically ill COVID-19 patients.

Invasive Fungal Infections in Critically Ill COVID-19 Patients

 What can be done for improving personalized medicine for treating complicated UTIs [urinary tract infections]? With the development of electronic health records, we should be able to develop systems that hospitals could use to communicate, especially between institutions for past medical history of resistance, isolation, and things along those lines. In Nevada, a patient transfer form is required to be filled out between patients being transferred from any types of institutions—from a rehab [facility] to a nursing home, from a nursing home to a hospital. One of the major requirements of this is [communicating] what multidrug-resistant organisms the patient has the patient been infected with or colonized with, so we have better communication about getting patients put in isolation as quickly as possible. If the patient is infected, this provides an idea of what empirical choices might be reasonable until we have cultures in definitive therapy. If we could work toward that as a group of health care professionals, then we’d be able to help interfere the spread much sooner in the process.

What’s the importance of antimicrobial stewardship? I’ve been doing stewardship at my institution [University Medical Center of Southern Nevada] for almost 15 years, and stewardship is 1 of the better ways, not only to monitor what’s going on in an institution but also to provide appropriate education on the changes in the environment, pathogens, and dosing and the different aspects that can directly impact patient care. Although stewardship doesn’t stand on its own, it needs to work closely with the infection preventionist for isolation and for appropriate cleanliness, and with the physicians and prescribers to optimize dosing, to encourage appropriate diagnostics, and to identify the actual infections of patients. It should be working with the microlaboratory so we can optimize information provided to the resources so it’s provided in a reasonable and quick amount of time. That way, we can focus everything on our patients. It’s the backbone for trying to improve and tackle resistance pathogens in our institutions.

How can we improve on antimicrobial stewardship? One of the biggest things is that we need to get better buy-in from individual physicians and practitioners to understand that stewardship isn’t the antibiotic police. Stewardship assists in making sure that patients are being treated optimally and that dosing is correct, and it encourages diagnostics. It’s not there just to interfere with what they’re trying to do. On the flip side, we need physicians to understand that not every fever is caused by an infection. Other things that would be optimal would be to improve the diagnostics, getting better idea of an infection that can be treated by antibacterials vs being a little more hesitant: “Maybe this is a virus or maybe it’s not, so we’re going to keep antibiotics.” Ultimately, we have the ability to improve these things so we can optimize patient care and decrease the impact on the microbiome. It’s tough, but it’s possible.

I’m very blessed that I work in a multidisciplinary group and that I work with some very good physicians. I have good microbiologists and infection preventionists, so we’re able to provide a lot of information and help our physicians quickly and collaboratively to hopefully prevent resistance. I have data at our institution. We’re doing pretty well, but we’ve also done it as colleagues. That’s going to be the key: not fighting one another but working together.

An expert in infectious diseases reviews best practices for improving personalized medicine when treating complicated urinary tract infections and highlights the importance of antimicrobial stewardship.

Optimizing Management of Complicated UTIs

 What were the effects of COVID-19 on the epidemiology of complicated UTIs [urinary tract infections]? Unfortunately, COVID-19 set back a lot of stewardship, infection prevention, and other practices that many institutions across the United States had been putting in place toward preventing the spread of multidrug-resistant infections. Some of the complications have to do with the supply chain issues, where we couldn’t put patients in appropriate isolation. That allowed for organisms to spread a little easier. We’re talking about patients who have to be hospitalized for significantly longer periods of time with a lot more antibiotic exposure, which alters the floor of the institutions, causing a higher risk for not only colonization but infection with multidrug-resistant bugs. It did us a disservice and set us up for almost having to start all over again.

What changes have there been in the use of antibiotics? At my institution [University Medical Center of Southern Nevada], we’ve tried to not let it affect as many places. Ours is a relatively focused—for lack of a better description—seek-and-destroy stewardship program that allows for empirical use but is proactive about de-escalating therapies based on cultures and sensitivities. Unfortunately, with the rise of overuse of antibiotics due to COVID-19, more patients are having infections with these agents and these multidrug-resistant pathogens; therefore, we have to allow for use of the broader-spectrum therapies for longer periods. I’m hoping that by getting back to normal and better infection-prevention practices, with supply chain improvements, we’ll get back on track and these numbers will go back down.

What changes have we seen in terms of positive pathogens and complicated UTIs since the COVID-19 pandemic? I’m happy to report that, at least at my institution, the organisms themselves haven’t changed. We’re still seeing our gram-negative causes, 

. It’s mostly the GI [gastrointestinal] flora resulting in these infections. The big difference is the prevalence of the resistant pathogens because of the higher incidence of antibiotic use and the change in the prevalence of resistant pathogens in all institutions—hospitals, nursing homes, rehab facilities. It’s still a reasonable choice…as are empirical cost pathogens. The gamble is whether this is going to be multidrug resistant or just slightly resistant?

Have there been any changes in multidrug resistance since the pandemic, and what are the potential causes? Unfortunately, we’re seeing more multidrug-resistant gram-negatives becoming a problem in institutions. This is directly driven by the continued use of antibiotics to try to treat a viral infection. COVID-19 was a complicated and unknown realm for a lot of practitioners. Because most of the information was developing as the pandemic was developing, we did our best to make sure patients were treated adequately and appropriately. Whenever you’re talking infections, many times that results in antibiotic use. Trying to de-escalate, trying to narrow therapy, became very difficult because these patients ultimately were hospitalized for long periods and developed multiple coinfections or secondary infections. Antibiotic use during this time frame probably skyrocketed in many institutions which can then select out for more of the resistant pathogens to stick around.

Kim Leuthner, PharmD, FIDSA, comments on the effect of COVID-19 on the epidemiology of complicated UTIs, the use of antibiotics, and antimicrobial resistance.

Impact of COVID-19 on Complicated UTIs

 What are some of the individual patient factors that need to be considered when picking therapy for a patient with a complicated UTI [urinary tract infection]? The biggest 1 is their own history. Hopefully, with the integration of better health care systems, it’s much easier to communicate between hospitals and find out what’s been going on with the patient. If that’s not a possibility, we need a thorough understanding of what antibiotics they’ve had, what cultures they’ve had, how long they’ve had the complications, and whether the complications are removable. That’s 1 big thing; if you can remove the source, you can treat patients much more effectively. The biggest thing is knowing the pathology, knowing the organisms that the patient has been exposed to, and knowing your own environment. If you’re in an institution that has high risk of ESBLs [extended-spectrum beta-lactamase], then it’s probably a reasonable thing to target in these patients, at least until you know individually.

In patients who have complicated UTIs, how do you choose empirical therapy before culture results and information is available, and when is antimicrobial therapy typically utilized? For us, the biggest thing is trying to understand the patient’s history. Our system has a record of previous antibiotics, cultures, and positive results. If we know that they’ve had resistant pathogens before, that’s our minimum coverage from that point on. For example, if they’ve had a history of an ESBL, then our starting drug would most likely be ertapenem. However, they may be coming from institutions that have higher risks of 

 in some of our institutions. Then we’ll start some of the more recently approved agents, such as ceftolozane, Avycaz [ceftazidime, avibactam], and things along those lines if they have a high enough risk. We try to individualize it. We don’t have a set protocol that mandates: “If it’s this, we do this therapy.” We try to make sure we take everything into consideration. In our institution these drugs are restricted for ID [identification], so that will typically be involved in the case very quickly.

What are the recommendations for treating a patient with a complicated UTI, and how is therapy modified for renal impairment? If the underlying condition is directly related to why the patient has the complicated UTI, we try to reverse it if at all possible. This is where the source control and the removal of the tubes and stents is feasible. If not, then unfortunately we’re stuck with longer treatment courses because now you have to deal with biofilm and additional drug penetration. When it comes to renal adjustment, I encourage treating a little higher on the break of the serum creatinine threshold. If the patients at borderline go with the higher of the 2 doses, we try to maintain our intervals. Especially if it’s a beta-lactam agent, if it’s at all possible, we try to optimize the time above the MIC [minimum inhibitory concentration]. If we need to do postdialysis dosing or whatever is recommended for the best pharmacokinetics of the drug, then we’ll adjust it based on the recommendations. At times, if we need to get levels, we will, but that’s a case-by-case basis.

What are the common pathogens associated with complicated UTIs from patients residing in long-term-care facilities, like nursing homes, and patients with catheter-related UTIs? The good news is the organisms themselves are still our most common ones. We’re going to see a lot of 

, klebsiellas, and even throwing in a little 

 in there. The problems come in when these patients are typically antibiotic experienced, so you’re going to start seeing many more of the ESBL and AmpC [AmpC beta-lactamase] producers. We’re even seeing patients coming in from the rehab facilities carrying CREs [carbapenem-resistant Enterobacterales] as part of their normal flora and infecting these catheters. Ideally, if possible, we try to remove the source of it, but it’s not uncommon for us to have to use some of the newer agents against the multidrug resistance. Throw in occasionally 

 in our problematic child, and we’ve got some very complicated patients.

How are complicated UTIs managed in patients coming from rehab facilities and nursing homes? Luckily, these patients can be treated similarly to standard therapy, if it’s at all possible to do source control—change out the catheter, change out any of the nephrostomy tubes. If those aren’t possible, then treatment durations become a lot more complicated. Unlike a standard UTI, where we’re talking a duration of 3 to 5 days, these patients are probably going to go with a minimum of 10-day therapy, assuming source control. If you can’t do source control, sometimes therapy has to get extended based on the radiological imaging and whether there’s going to be a removal of those sources. Unfortunately, it can become a very prolonged treatment course, which puts them at risk for even more nasty bugs.

What are the challenges that we face in treating these complicated UTIs, especially in nosocomial settings? One of the biggest is the length of therapy for most of these patients. If we’re talking about using some of our newer agents, most of these are multiple doses a day. They’re not a feasible option for OPAT [outpatient parenteral antibiotic therapy] or other home-health infusions. Plus, many of these patients unfortunately aren’t stable enough to go home or to some of the lesser step-down units. Some of these patients are going to be stuck for quite a bit of time in a health care environment, which brings in all the additional complications of further infections, further health care exposure, drug interactions, adverse effects, and a risk for poorer outcomes.

Which antimicrobial therapies are available for the treatment of complicated UTIs, focusing on the gram-negative causes of these infections? Fortunately, over the last several years, we’ve had an introduction of quite a few new agents that provide benefits against multidrug-resistant gram-negatives. On the simple side, we still have our ertapenem and meropenem, which are great options for ESBLs and some of our less multidrug-resistant pathogens. After that, we start getting into our carbapenemase-producing organisms which bring us options like ceftazidime-avibactam, imipenem-cilastatin-relebactam, and meropenem-vaborbactam. If you’ve got multidrug-resistant pseudomonas, you can also add ceftolozane-tazobactam as part of your treatment armamentarium. Finally, in our grouping is the siderophore cephalosporin, cefiderocol, which has activity against many of the multidrug-resistant gram-negatives. Although other newer agents are available, most of them have poor penetration into the urine and are probably not the best treatment options for this infection.

An infectious disease clinical specialist shares treatment considerations for patients with complicated urinary tract infections, including for patients with comorbidities and older patients, and reviews antimicrobial therapies for multidrug-resistant UTIs.

Approaching Treatment for Complicated UTIs

 What’s the difference between a complicated and an uncomplicated urinary tract infection [UTIs]? Unfortunately, complicated gets complicated, pardon the pun. You’ve got devices, surgical involvement, things that are abnormal from the human anatomy that result in a higher risk of complications and bacterial infection, which are more difficult to treat vs antibiotics. It can make it a bigger host, a bigger pathogen breeding ground—for lack of better terms—resulting in more difficult therapies needed for these patients.

Which patients are at high risk for developing complicated UTIs? There are a wide variety. On 1 side are male patients, who have complications because their anatomy is unique compared with female patients. They often have their own problems involving the prostate. On the opposite extreme, some transplant patients don’t have a typical kidney function and have bladder abnormalities due to the surgery. Patients who’ve had stents put in, who have drains because of hydronephrosis, bladder stones, or kidney stones, can make the source of bacteria difficult to eradicate.

How do you distinguish asymptomatic bacteria vs a complicated UTI and the importance of distinguishing the 2? It’s important because you don’t need to treat most patients with asymptomatic bacteria. Unfortunately, some forget that the urine and bladder aren’t sterile site and can be a home for a lot of bacteria that live there and enjoy the warm environment. Unfortunately, patients who have complicated devices have an opportunity for normal pathogens to move in and have a place to hide from the immune system and cause actual infections. The biggest difference is the presence or absence of symptoms. Most patients who have a complicated UTI have systemic symptoms, such as white blood cell count, fever, aches, chills, and back pain. They may have hesitancy or burning because of other issues that override those, but for asymptomatic patients, the only real presence you have is the bacteria in the urine.

Kim Leuthner, PharmD, FIDSA, provides insight on distinguishing between complicated and uncomplicated UTIs, and patients who are at high risk for developing complicated UTIs.

Overview of Urinary Tract Infections


Jasmine Marcelin, MD, FACP, FIDSA, associate professor, Department of Internal Medicine, associate medical director, Antimicrobial Stewardship Program, University of Nebraska Medical Center, says there are a number of instances where patients present with bacterial infections and their antibiotic regimens can be reduced.

“Shorter is better,” is a maxim being considered in clinical circles when it comes to thinking about antibiotic durations. Investigators are studying therapies that may have traditionally been used for 10-14 days and can be reduced by several days. Marcelin says there is more data supporting this decrease in duration and can be a strategy for stewardship.

She believes all clinicians can be stewards. “There are a lot of different ways we can all be antimicrobial stewards in the hospitals and clinical settings,” Marcelin said.

Marcelin presented a scientific session, Antibiotic Abuse: Making the Right Call With Antibiotics, at this week’s 

 being held in San Diego.

In addition, Marcelin says the delivery of therapies is another strategy that helps in this area. For example, transitioning inpatients from an IV administration to oral antibiotics  has a couple of distinct advantages including releasing patients earlier so they can be home in a comfortable setting as well as not expecting any complications with an early release. “There’s a lot of good data that for certain syndromes that we can switch a person to oral antibiotics and there isn’t going to be any increases in recurrences of those infections or adverse events.”

Another significant component to this stewardship strategy is counseling patients when they visit their providers, especially when the former is expecting to get a prescription for an antibiotic even though they may not have a bacterial infection. When a patient has a viral infection, Marcelin says this is an opportunity to explain to patients an antibiotic is not warranted but that watchful waiting is the best course of action.



spoke to Marcelin at the conference about her session, specific examples where therapy regimens can be reduced, and counseling patients when antibiotics should be withheld.

A paradigm shift is emerging when it comes to the clinical approach to prescribing antibiotics. One clinician weighs in on using this class of therapeutics more judiciously.

Conferences

‘We Can All be Antimicrobial Stewards’

Complicated intra-abdominal infections (cIAI) are challenging to treat because of the potential for high morbidity and mortality in these patients.

In addition, there can often be more variability in the number of clinicians involved in care as well as the types of patients who are experiencing these infections. “[cIAI] They are probably a little more heterogenous because the clinical decision-making comes from multiple areas; there are surgeons and there are emergency room physicians [involved],” Tony Hodges, MD, FACP, FCCP, Chief Medical Officer, La Jolla Pharmaceutical Company. “The ages of the patients may range from pediatric to the aged. The comorbidities that align with those age groups are also there and the risk factors for antimicrobial resistance also vary within those cohorts.”

Fortunately, there are treatment options for these infections. One particular antibiotic, eravacylcine (Xerava), which is produced by La Jolla, was FDA approved in August of 2018 for the treatment of cIAI in adults 18 years and older. 

 is a tetracycline-class antibacterial injection that has demonstrated potent activity against multidrug-resistant pathogens. In clinical trials, eravacycline was well tolerated and produced favorable results in curing patients with cIAI and demonstrated non-inferiority to ertapenem and meropenem.

The drug was assessed for cIAI in 2 Phase 3 studies called IGNITE (Investigating Gram-Negative Infections Treated with Eravacycline.) In the first trial, IGNITE1, 541 patients with cIAI were randomized to receive intravenous (IV) treatment with either eravacycline 1.0 mg/kg every 12 hours (n = 270) or ertapenem, 1.0 g every 24 hours (n = 271) for at least 4, 24-hour cycles. The primary endpoint was cure rates after about 1 month. The clinical cure was 86.8% and 87.6% in the eravacycline and ertapenem groups, respectively.

In the second trial, IGNITE4, a total of 499 patients with cIAIs were randomized to IV treatment with eravacycline 1.0 mg/kg twice-daily (n = 250) or meropenem 1 g every 8 hours (n = 249). The clinical cure rates evaluated about 1 month after the start of the treatments were comparable for eravacycline and meropenem whether evaluated according to the criteria set out by the FDA (90.8% vs 91.2%) and EMA (92.4% vs 91.6%).

One of the novel aspects of this therapy is its ability to withstand resistance that other tetracycline-class medications have not, explained Hodges. “It has withstood resistance to primarily historically tetracycline-resistant mechanisms that have degraded or caused resistance with others within the class.”

This is also the biggest takeaway about the therapy in its latest studies.

La Jolla is presenting four posters on eravacycline at the ongoing 

European Congress of Clinical Microbiology and Infectious Diseases (ECCMID)

 Surveillance of Eravacycline Against Enterobacterales and Non-Fermentor Clinical Isolates, Including Resistant Isolates, Collected in Europe During 2021, and 

surveillance of eravacycline against Gram-positive pathogens, including resistant isolates, collected In Europe during 2021, Hodges explains these studies are primarily looking at minimal inhibitory concentration (MIC) with regards to 

 data.

“What you’ll see is retention or lack of MIC drift over the last 5 to 6 years historically…across intra-abdominal pathogens,” Hodges stated. 

Hodges talked with 

 about these studies, an in-depth discussion on the treatment guidelines and breakpoints related to these infections, and the goal of reaching “target attainment” for better treatment for patients to reduce complications and obtain stewardship.

Several years after its FDA approval, this antibiotic continues to prove its efficacy in vitro across various pathogens related to these infections.

Eravacycline Remains Efficacious for Intra-Abdominal Infections

“We’re looking to find novel ways to treat resistant infections that have very high unmet medical needs,” said Alita Miller, PhD, senior vice president of research at Entasis Therapeutics.

Miller met with Contagion to discuss research slated to be presented at the 2023 European Congress of Clinical Microbiology & Infectious Diseases (

 is an intravenous investigational therapy that is a combination of sulbactam, an IV β-lactam antibiotic, and durlobactam, a novel broad-spectrum IV β-lactamase inhibitor. SUL-DUR targets 

 infections, including those caused by multidrug-resistant and carbapenem-resistant (CRAB) strains.

is recognized by the WHO and the CDC as a very high unmet medical need,” Miller said. “It’s actually the fifth leading cause of death across the world that’s attributed to drug resistance in nonbacteria.”

means that there are not many treatment options, and Miller noted there is no clear standard of care for these infections.

One poster presentation examined the efficacy of sulbactam-durlobactam versus colistin for the treatment of infections caused by 

(ABC). Miller and fellow investigators chose colistin as the comparator because it is known to have very low rates of resistance, about 4% worldwide.

However, in phase 3 trials, Miller said colistin resistance was found to be up to 17%. “The poster at ECCMID describes 3 different colistin-resistant outbreaks” Miller explained. “What we were pleased to see is the patients who had those colistin-resistant infections were effectively treated by sulbactam-durlobactam. The majority of them survived to 28 days and had favorable clinical and microbiological outcomes.”

The primary efficacy endpoints for this study were all-cause mortality at 28 days and reduction in nephrotoxicity; sulbactam-durlobactam performed better than colistin on both counts. SUL-DUR also met its secondary trial endpoints, including clinical cure and microbiological outcome.

Alita Miller, PhD, senior vice president of research at Entasis Therapeutics, discusses positive trial data for Sulbactam-durlobactam (SUL-DUR) slated to be presented at ECCMID 2023.

Antimicrobial Stewardship

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