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IDCM: Five Key Studies from IDWeek 2018
Natasha Chida, MD, MSPH
Five Key Studies from IDWeek 2018
This year’s IDWeek, the combined annual meeting of the Infectious Disease Society of America (IDSA), the Society of Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), and the Pediatric Infectious Diseases Society (PIDS), convened October 3-7th in San Francisco, California. The conference features the latest science in the prevention, diagnosis, treatment, and epidemiology of infectious diseases. More information about IDWeek2018 can be found on the conference website: www.idweek.org. Covered in this ID Clinical Minute are some key findings presented at the conference that are relevant to primary care providers or consulting physicians who see patients with ID issues.
More Experience with Bacteriophage Therapy (BT)
Bacteriophages are viruses that infect bacteria and lead to their death. BT was first utilized in the 1920s and 1930s to treat bacterial infections, but it became obsolete when antibiotics were discovered. Now, nearly 100 years later, interest in the use of BT has re-emerged with the rise in drug-resistant bacteria.
In 2017, physicians at the University of California San Diego reported using BT to treat a patient with multidrug-resistant Acinetobacter baumannii infection.1 In this case series presented at IDWeek,2 the same group reported the results of 8 patients treated with BT for Staphylococcus aureus and Pseudomonas auerginosa infections that did not respond to antibiotics. Patients received both intravenous and inhaled BT for a median duration of 14 days. Antibiotics were continued in all patients. BT was well tolerated, there were no adverse events reported, and 75% patients experienced treatment success.
The purpose of this study was not to evaluate if the addition of BT improved patient outcomes (we cannot know this, as there was no control); it was to report the experience of using this novel therapy. Based on these 8 patients, BT appears to be safe and well tolerated. If BT proceeds to clinical trials and is successful, it would be an important addition to the arsenal against drug-resistant infections.
Phase 2b Trial of New TB Vaccine Shows Significant Reduction in Disease among Patients with HIV and Latent TB
The bacille Calmette-Guerin TB vaccine (BCG) has been used in humans since 1921, and has been a part of the fight against TB for nearly a century. BCG vaccine is most efficacious in children who have not yet been exposed to TB; it is less effective in adults—particularly those who have been exposed (ie, in those who have latent TB). A more efficacious vaccine for persons who have prior TB exposure would be an important tool to reduce the incidence of active TB disease.
In a randomized, double-blind, placebo-controlled trial,3 HIV-negative adults with latent TB (defined by a positive interferon gamma release assay) received either a candidate vaccine against TB or placebo. A total of 3,573 patients were randomized. Efficacy against pulmonary TB disease was 54%. There were more symptoms after the vaccine (67.4% vs 45.4%), but they were not serious and included injection side reactions and flu-like symptoms. The rate of serious adverse events was consistent between the vaccine and placebo groups (1.6% and 1.8%, respectively). This exciting new vaccine appears to have reasonable safety profile and reduces pulmonary TB disease in HIV-negative adults with latent TB. We look forward to seeing the results of a phase 3 clinical trial.
20% of Outpatient Antibiotic Prescriptions Occur without an In-person Office Visit.
Given that antimicrobial resistance is an increasingly serious threat to global health, understanding antibiotic prescribing habits among health providers is of vital interest. The authors of this study4 queried the electronic health records of an integrated health system and measured the prevalence of antibiotic prescribing. For each prescription, they noted the visit type and the associated ICD-10 code.
Researchers found that between November 2015 and October 2017, 509,534 antibiotic prescriptions were made in 514 clinics. 20% of the prescriptions were issued without an in-person visit, and 10% occurred after a telephone call to the patient. Only 54% of the antibiotic prescriptions were associated with an ICD-10 code that signified an infection diagnosis. If we are to curtail the rise of antibiotic resistance, we must be more judicious about our antibiotic prescribing practices.
New Influenza Drug Shows Promise
In this double-blind phase 3 clinical trial,5 patients at high risk for influenza complications were randomized in a 1:1:1 fashion to receive Baloxavir marboxil (BXM), placebo, or oseltamivir. Time to improvement of influenza symptoms among those who had received BXM was significantly shorter than placebo (median 73.2 hours vs. 102.3 hours, p<0.0001) and numerically shorter than oseltamivir (81 hours, p=0.8347). Additionally, the median time to cessation of viral shedding was shorter for the BXM group: 48 hours to cessation versus 96 hours for both placebo and oseltamivir groups. There was no difference in serious adverse events among the groups.
This new drug was superior to oseltamivir in shortening duration of viral shedding, and had a non-statistically significant reduced time to symptom improvement. Many questions remain: Is BXM better than oseltamivir for patients at high risk for complications? Does a shorter duration of viral shedding have important clinical outcomes in this population? Perhaps so from a public health standpoint, but more studies are needed.
Azithromycin Resistance among Shigella Isolates in the U.S. Rising Quickly
Shigellosis is a bacterial infection that presents as a gastrointestinal illness. It can be spread between people, including through anal intercourse. Although most cases of shigellosis do not require antibiotics, in severe cases they are important. The most commonly used antibiotics to treat this bacteria are azithromycin and ciprofloxacin. This study6 examined rates of azithromycin resistance among Shigella isolates in the U.S. Centers for Disease Control and Prevention’s National Antimicrobial Resistance Monitoring System between 2011-2017 (health departments around the country send every 20th isolate of Shigella recovered to the CDC).
As of October 2018, 3,044 isolates had been tested. 3% of isolates in 2011 showed decreased susceptibility to azithromycin; in 2017 23% showed deceased susceptibility, indicating an alarming 7-fold rise in resistance. In addition, 16% of isolates were resistant to ciprofloxacin. This trend has been noted in other countries as well. If this trend continues, azithromycin may no longer be a sound empiric choice for Shigella infections.
Bottom line: These studies highlight the breadth of clinical ID seen by both ID and non-ID providers. The dynamic nature of ID makes it important for providers to stay abreast of the ID literature.
- Schooley RT, Biswas B, Gill JJ, Hernandez-Morales A, Lancaster J, Lessor L, Barr JJ, Reed SL, Rohwer F, Benler S, Segall AM, Taplitz R, Smith DM, Kerr K, Kumaraswamy M, Nizet V, Lin L, McCauley MD, Strathdee SA, Benson CA, Pope RK, Leroux BM, Picel AC, Mateczun AJ, Cilwa KE, Regeimbal JM, Estrella LA, Wolfe DM, Henry MS, Quinones J, Salka S, Bishop-Lilly KA, Young R, Hamilton T. Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant Acinetobacter baumannii infection. Antimicrob Agents Chemother. 2017 Sep 22;61(10). pii: e00954-17. doi: 10.1128/AAC.00954-17. Print 2017 Oct. PMID: 28807909; PMCID: PMC5610518.
- Aslam S, et al. Safety and Efficacy of Bacteriophage Therapy: Analysis of Clinical Case Series Data. Abstract 1642 presented at: IDWeek 2018; October 3-7, 2018; San Francisco, CA.
- Van Der Meeren O, et al. A Randomized Double-blind Trial Assessing the Efficacy of M72/AS01E Vaccine against Pulmonary Tuberculosis Disease in Adults with Latent Mycobacterium tuberculosis Infection. Abstract 120 presented at: IDWeek 2018; San Francisco, CA. October 3-7, 2018.
- Linder JA, et al. on-Visit-Based and Non-Infection-Related Ambulatory Antibiotic Prescribing. Abstract 1632 presented at: IDWeek 2018; San Francisco, CA, October 3-7, 2018.
- Ison MG, et al. Phase 3 Trial of Baloxavir Marboxil in High Risk Influenza Patients (CAPSTONE-2 Study). Late Breaker 16 presented at: IDWeek 2018; San Francisco, CA. October 3-7, 2018.
Friedman C, et al. Rapid Rise in Decreased Susceptibility to Azithromycin among Shigella Isolates in the United States: A Look at National Surveillance Data, 2011–2017. Late Breaker 11 presented at: IDWeek 2018; San Francisco, CA. October 3-7, 2018.