Top Infectious Disease News of the Week—August 12, 2018

#5: Antibiotic Development—We Gave It a Push, Now It Needs a Pull

After years of sounding the alarm about the dangers of limited antibiotic development, infectious diseases clinicians have been rewarded with multiple new antibiotics in the 2010s. To my shock, the Infectious Diseases Society of America’s “10x20” goal (10 new antibiotics before 2020) may actually be achieved. Changed regulatory pathways and “push” incentives that assist antibiotic development are partially responsible for the increased antibiotic throughput that we are benefitting from now.

However, the number of major pharmaceutical companies that invest in antibiotic development continues to decline, with AstraZeneca, Novartis, and Allergan recently announcing that they are leaving the anti-infective space. Allergan’s exit is particularly notable as the company markets several recently approved antibacterial agents that address critical needs. Antibiotics are a societal good that rely on private industry for production and the message that even selling approved, useful antibiotics that save patient lives is not enough to attract major drug developers to stay in the market is disheartening, to say the least.

Read more about antibiotic development.

#4: Controversies of Antimicrobial Transitions in Adults with Gram-Negative Bacteremia

Inevitably, most clinicians and antimicrobial stewards will encounter a challenging clinical decision: Can a patient with transient gram-negative bacteremia be treated with something other than 14 days of intravenous (IV) antimicrobial therapy? The potential disadvantages of a 2-week course of IV antibiotics (line infections, adverse effects, monitoring outpatient parenteral antimicrobial therapy [OPAT], prolonged hospital stay) are enough to cause second thoughts. Recent literature suggests that shorter courses of antibiotics and oral agents are reasonable alternatives for many patients, given several key considerations (see Sidebar).

Bloodstream infections (BSIs) due to gram-negative bacilli are typically manifestations of complicated urinary tract (UTI) or intra-abdominal infections. Some of the most common stewardship strategies for these infections include rapid organism identification and pharmacokinetic/ pharmacodynamic dose optimization of empiric and targeted therapy. However, practice guidelines offer little direction on the management of the bacteremic patient regarding antimicrobial transitions from IV therapy, selection of stepdown agents, and the duration of treatment.^1,2 Until recently, management strategies for gram-negative BSIs have only been examined in observational studies or subgroups of randomized trials.^3-5 Much of the available data are limited due to retrospective study designs, varying definitions of outcomes, differences in organisms studied, and a lack of complete antimicrobial administration information with follow-up.^6-9Given that each additional antimicrobial day/central-line day is associated with increased risk of Clostridium difficile infection, adverse effects, and reinfection, it is critical that antibiotic stewards critically evaluate each case individually.¹⁰

Read more about antimicrobial transitions in adults with gram-negative bacteremia.

#3: Infection Control Lacking in Outpatient Oncology

The US Food and Drug Administration (FDA) recently hosted an informational webinar drawing attention to the importance of infection control in the outpatient oncology setting. The webinar focused on infectious disease outbreaks that occurred in outpatient oncology areas, especially those related to failures in injection practices and sterile compounding standards.

In 2010, there were 1.5 million new cases of cancer diagnosed within the United States. Over 1 million cancer patients receive outpatient chemotherapy or radiation and with the focus on moving more and more services to outpatient centers, this number will likely increase. Moving oncology treatments to outpatient settings is beneficial for many reasons: 1) hospitalizations are avoided, which saves money; 2) treatment is scheduled around the patient’s needs and convenience; and 3) drug administration is performed under the supervision of an oncologist. Furthermore, with approximately 1.7 million health care-associated infections occurring in US hospitals each year, efforts to avoid hospitalization for chemotherapy or radiation are understandable.

Read more about the importance of infection control in outpatient oncology.

#2: CDC Issues New Guidance for Couples Trying to Conceive Following Exposure to Zika

The US Centers for Disease Control and Prevention (CDC) has released updated interim guidelines for the prevention of sexual transmission of Zika virus from men who have been exposed to Zika to their female partners who are planning to conceive or want to prevent sexual transmission of Zika.

The new recommendations, published in the latest issue of the CDC’s Morbidity and Mortality Weekly Report, suggest that men who have or have possibly been exposed to Zika wait at least 3 months after symptom onset or last possible Zika virus exposure before engaging in unprotected sex. Furthermore, the guidance suggests that couples who are not trying to conceive use condoms or abstain from sex for 3 months after last Zika exposure or symptom onset to minimize the risk of sexually transmitting the virus.

Read more about the new Zika guidance.

#1: What’s New from the CLSI Subcommittee on Antimicrobial Susceptibility Testing?

The latest Clinical and Laboratory Standards Institute’s (CLSI) Subcommit­tee on Antimicrobial Susceptibility Testing meeting was held June 3-5, 2018, in San Diego, California. Although new and revised break­points included in this article are approved by the subcommit­tee, they are subject to change prior to official approval of the meeting minutes at the January 2019 meeting.

REVISED BREAKPOINTS

Ceftaroline

Ceftaroline is a cephalosporin with a broad spectrum of activity, including methicillin-resistant Staphylococcus aureus (MRSA). Its high affinity for penicillin-binding proteins (PBPs), including PBP2a in MRSA, contributes to its activity against MRSA.¹ Ceftaroline is US Food and Drug Administration (FDA)-approved as a 600-mg dose every 12 hours (given over 5 to 60 minutes), while a high-dose regimen of 600 mg every 8 hours (given over 2 hours) has been approved for select indications in many countries outside the United States since 2017.

The in vitro activity of ceftaroline varies widely by geographic region, fueled by pandemic MRSA clones.² Data from the SENTRY Antimicrobial Surveillance Program presented by Helio S. Sader, MD, from JMI Laboratories show that ceftaroline minimal inhibitory concentrations (MICs) for MRSA rarely exceed 1 mg/L within the United States, while the proportion of MICs greater than or equal to 2 mg/L is near 30% in some Latin American countries. In regions with greater than 15% ceftaroline-nonsusceptible MRSA isolates, correlation between disk diffusion and broth microdilution MICs are poor, with elevated error rates. Although the current CLSI breakpoints appeared appropriate to reduce these discrepancy errors in the United States, CLSI breakpoints are often used outside the United States. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) has developed indication-specific breakpoints, with guidance surrounding dosing, but logistical implementation of these is often difficult.³ In light of all of the data presented, the Antimicrobial Susceptibility Testing (AST) Subcommittee approved revised breakpoints with a new susceptible-dose dependent (SDD) category based on the high-dose regimen (Table 1).

Read more about the new and revised breakpoints.