Top Articles Published in Contagion® in 2019

We are taking a look back at the top articles published in Contagion®’s print journal in 2019.

#5: Emergence of Ceftazidime-Avibactam Resistance: What Have We Learned in the Past 4 Years?

By: Ryan K. Shields, PharmD, MS

The US Food and Drug Administration (FDA) approved ceftazidime-avibactam for clinical use in February 2015, effectively changing the landscape for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infec­tions. Compared with traditional salvage agents (including aminoglycosides, colistin, and tigecycline), treatment with ceftazidime-avibactam is safer and more effective.^1-3 Despite these encouraging findings, the emergence of ceftazidime-avi­bactam resistance has been reported and may pose a serious threat to patients. Over the past 4 years, new insights into the molecular mechanisms and predisposing factors associated with ceftazidime-avibactam resistance have been described.

Avibactam is a novel diazabicyclooctane β-lactamase inhib­itor that reversibly inhibits Ambler classes A, C, and some class D β-lactamases. Avibactam does not inhibit class B metallo-β-lactamases (MBLs). In surveillance studies, the combination of ceftazidime-avibactam demonstrated potent in vitro activity against a wide spectrum of gram-negative pathogens, including multidrug-resistant Enterobacteriaceae and CRE.^4-6 Categorized by the FDA-approved susceptibility breakpoint (≤8/4 μg/mL), ceftazidime-avibactam was active against 97.5% of contemporary CRE isolates.⁶ In a subsequent study, 99.3% of Klebsiella pneumoniae carbapenemase (KPC)- producing CRE were susceptible.5 Against OXA-48 producing CRE, ceftazidime-avibactam was active against 100% of isolates in a recent clinical study.⁷

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#4: The Case for On-Demand PrEP

By: Christina M. Madison, PharmD, FCCP, BCACP, AAHIVP, and John Phoenix, ARPN, FNP-C

Although the incidence of HIV is declining, the prevalence of HIV infection and those living with the virus remains an issue. In the United States, approximately 1.1 million people are currently living with HIV/AIDS, and 38,739 new cases of HIV infection were reported in 2017.^1,2 A majority of those cases are in men, aged 25 to 45 years, and men who have sex with men (MSM) and are disproportionately prevalent in communities of color, specifically black and African American. Worldwide, there are 1 million new sexually transmitted infections (STIs) daily.³ Sexuality, race, ethnicity, age, sex/gender identity, and geographic location have a direct impact on the risk of HIV acquisition.^1,2

HIV PREVENTION: THE ACCESS ISSUE

Understanding an individual’s risk helps to make the right decision regarding HIV prevention strategies. Pre-exposure prophylaxis (PrEP) therapy includes taking an antiretroviral medication used in conjunction with harm reduction strategies to prevent HIV. PrEP is a vital component of the HIV care continuum that can help drastically reduce the number of new HIV infections.

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#3: Biktarvy: A Regimen of Choice for HIV Therapy

By: Brionna Matt, DO

Integrase strand transfer inhibitors (INSTIs), when combined with 2 nucleoside analogue reverse transcriptase inhibitors (NRTIs), make up the bulk of first-line HIV therapy regimens. With over 30 drugs approved for the treatment of HIV infection, the regimen choice is often determined by concerns over pill burden, tolerability and/or toxicity, and barrier to resistance.

Biktarvy is a fixed-dose, single-tablet regimen of bictegravir, emtricitabine, and tenofovir alafenamide. It received FDA approval on February 7, 2018, for treatment-naïve patients with HIV or those already virologically suppressed on an antiretroviral therapy regimen for at least 3 months with no known resistance to any of the drug components. Two of the 3 drug components, emtricitabine and tenofovir alafenamide, are already part of other first-line therapy regimens and are known to be safe and well tolerated by most patients. Biktarvy is a new, highly active INSTI with both a high barrier to resistance and few drug—drug interactions. These advantages have allowed Biktarvy to quickly become a regimen of choice among HIV health care providers.

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#2: Duration of Antibiotic Therapy for Uncomplicated Gram-Negative Bacteremia: Seven Is the New Fourteen

By: Christian Cho, PharmD

The treatment duration for uncomplicated gram-negative bloodstream infections (BSIs) has traditionally ranged from 7 to 14 days.^1-2 However, recent retrospective studies and meta-analyses have observed no differences in clinical outcomes in patients treated with shorter courses compared with prolonged courses, especially with urinary sources of infection.^1-2 In addition, the role of oral stepdown for defini­tive therapy for gram-negative BSIs has been explored with similar clinical outcomes regard­less of duration.³ These recent studies have led to an increased interest in stewardship efforts to optimize antibiotic utilization and promote appropriate oral stepdown therapy for gram-negative BSIs.

Yahav and colleagues conducted the first prospective, randomized, controlled, noninfe­riority trial to compare short-course (7 days) versus long-course (14 days) antibiotic therapy for uncomplicated gram-negative BSIs.⁴ Patients were included if they were hemodynami­cally stable and normothermic for 48 hours by day 7 of effective antibiotic therapy and were excluded if an uncontrolled source of infection was present. Overall, 604 patients were random­ized to receive either short-course (n = 306) or long-course (n = 298) therapy. The primary outcome was a composite of all-cause mortality; clinical failure defined as relapse, suppurative, or distant complications; and re-admission or extended hospitalization by 90 days. The first day of effective empiric or definitive antibiotics was considered day 1 of therapy. Most patients (92%) received the protocol-specific treatment durations (± 2 days), and about 73% of patients were switched to oral stepdown therapy (fluo­roquinolones: 74%; β-lactams: 18%; sulfamethox­azole/trimethoprim: 8%). Patients were generally older than 65 years (67%) and immunocom­petent (75%). The most common pathogens identified were Enterobacteriaceae, and the primary sources of infection were urinary (68%) and intraabdominal (12%).

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#1: HIV Infection in 2019: A Cure Is Not the Real News

By: Jason C. Gallagher, PharmD, FCCP, FIDP, FIDSA, BCPS

The announcement of the London patient, the second person cured of HIV infection through hematopoietic stem cell transplant, sent waves through the media and spurred a series of inaccurate headlines that put HIV back into focus for people who do not think about it often. I personally received a series of text messages along the lines of “Did you hear about the HIV cure?” and “I heard there’s someone in Europe with a cure for AIDS.” Because these came from intelligent, nonmedical people, it led me to reflect on the paucity of knowledge that most people have about the breakthroughs in HIV management and therapies.

One-pill regimens have been a reality for HIV regimens since the approval of efavirenz, emtricitabine, and tenofovir disoproxil fumarate (Atripla) more than 10 years ago. This revolution has continued with integrase strand transfer inhibitor (INSTI)—based regimens earlier this decade. Regimens containing 3 drugs can be replaced with 2-drug regimens, sparing patients from exposure to a third agent. In many ways, therapy for HIV infection has become easier to manage than that of diabetes. However, this is not well known outside infectious diseases clinicians, and even many HIV care practitioners are hesitant to transition patients whose infection is undetectable on an older 3-drug regimen to a novel regimen that decreases antiretroviral exposure.

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