What’s New in ID? October-November 2019 / Listopad-Studeni 2019.

Lefamulin for the treatment of community-acquired pneumonia

Lefamulin is a novel antibiotic with activity against many common community-acquired pneumonia (CAP) pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and atypical pathogens. The agent was recently approved by the US Food and Drug Administration for the treatment of CAP based on two randomized trials. In one trial of >550 hospitalized adults with Pneumonia Severity indices ≥III, clinical response rates were similar with lefamulin compared with moxifloxacin (87 versus 89 percent). These two agents were also similarly effective in a second trial, which compared a five-day course of oral lefamulin with a seven-day course of oral moxifloxacin in >730 patients (88 versus 89 percent). Rates of adverse events leading to drug discontinuation were similar between groups, though diarrhea was more common with lefamulin. Based on these data, we have begun to adopt lefamulin into practice, specifically for otherwise healthy outpatients with CAP who cannot tolerate beta-lactams and wish to avoid the adverse effects associated with fluoroquinolones.

File TM Jr, Goldberg L, Das A, et al. Efficacy and Safety of IV-to-Oral Lefamulin, a Pleuromutilin Antibiotic, for Treatment of Community-Acquired Bacterial Pneumonia: The Phase 3 LEAP 1 Trial. Clin Infect Dis 2019.

Alexander E, Goldberg L, Das AF, et al. Oral Lefamulin vs Moxifloxacin for Early Clinical Response Among Adults With Community-Acquired Bacterial Pneumonia: The LEAP 2 Randomized Clinical Trial. JAMA 2019.

Duration of therapy for streptococcal pharyngitis

A 10-day course of a penicillin is standard therapy for streptococcal pharyngitis. To evaluate whether a shorter course using higher doses could be equally effective while reducing total antibiotic exposure, a randomized trial compared five days of penicillin V dosed at 800 mg four times daily with 10 days of penicillin V dosed at 1000 mg three times daily in 433 children and adults with microbiologically confirmed streptococcal pharyngitis. While clinical cure rates were similar (90 versus 93 percent), bacterial eradication rates were lower in the five-day treatment group (80 versus 91 percent). Because complications of streptococcal pharyngitis, particularly immune sequelae, can be severe and are likely related to the presence of group A Streptococcus (GAS) in the oropharynx, a 10-day course of therapy.

Skoog Ståhlgren G, Tyrstrup M, Edlund C, et al. Penicillin V four times daily for five days versus three times daily for 10 days in patients with pharyngotonsillitis caused by group A streptococci: randomised controlled, open label, non-inferiority study. BMJ 2019; 367:l5337.

Investigational maribavir for preemptive treatment of CMV in transplant recipients

Ganciclovir and its oral derivative, valganciclovir, are first-line options for treatment and prevention of cytomegalovirus (CMV) disease in transplant recipients, but their use is often limited by medication-related bone marrow suppression. A recent phase II, open-label trial of more than 150 solid organ or hematopoietic cell transplant recipients found that maribavir, an investigational novel CMV antiviral agent, achieved CMV viral suppression by six weeks at least as frequently as valganciclovir (79 versus 67 percent). Gastrointestinal adverse effects were more common with maribavir, whereas neutropenia was more common with valganciclovir. Although not yet available, maribavir may be a promising future option for transplant recipients whose care is limited by valganciclovir-related adverse effects.

Maertens J, Cordonnier C, Jaksch P, et al. Maribavir for Preemptive Treatment of Cytomegalovirus Reactivation. N Engl J Med 2019; 381:1136.

Community-wide screening for TB in high-incidence settings

The substantial proportion of individuals with tuberculosis (TB) who are never diagnosed and treated is a major barrier to reducing TB transmission in high-incidence settings; however, the optimal approach to identifying such individuals is uncertain. In a cluster-randomized trial in Vietnam, annual community-wide TB screening with sputum nucleic acid amplification testing (NAAT) was compared with standard passive case detection among individuals ≥15 years; all patients diagnosed with TB received treatment. After three years, the prevalence of pulmonary TB (as assessed by sputum NAAT) was lower among participants from the screening communities (126 versus 225 cases per 100,000 individuals). Although promising, further investigation is needed to assess the generalizability and durability of these findings prior to broad implementation of community-based screening.

Marks GB, Nguyen NV, Nguyen PTB, et al. Community-wide Screening for Tuberculosis in a High-Prevalence Setting. N Engl J Med 2019; 381:1347.

Sexually transmitted infections in the United States

According to annual surveillance through the Centers for Disease Control and Prevention, the incidence of the major sexually transmitted infections, chlamydia, gonorrhea, and syphilis, all increased dramatically from 2014 to 2018. In particular, the incidence of syphilis increased by 70 percent over this time frame, with over 35,000 cases of primary and secondary syphilis reported in 2018. Men who have sex with men (MSM) accounted for the majority of all reported cases, and of them, almost half were known to have HIV infection. Syphilis rates also increased among women, and the rate of congenital syphilis (1300 cases in 2018) has increased every year since 2012. These findings highlight the importance of sexually transmitted infection screening and treatment, especially in MSM and pregnant women.

Centers for Disease Control and Prevention. Sexually transmitted disease surveillance 2018. Atlanta: U.S. Department of Health and Human Services; 2019 https://www.cdc.gov/std/stats18/ (Accessed on October 24, 2019).

FDA approval of baloxavir for patients at high risk of influenza complications

The US Food and Drug Administration has expanded the approval of baloxavir for treatment of uncomplicated influenza to include patients who are at high risk of complications; the original approval included only otherwise healthy patients ≥12 years of age who have been symptomatic for ≤48 hours. This change was based on data from a randomized trial that showed that in high-risk adolescents and adults with laboratory-confirmed influenza infection, the median time to resolution of symptoms was 73 hours with baloxavir, 81 hours with oseltamivir, and 102 hours with placebo. The majority of patients had underlying asthma, chronic lung disease, diabetes mellitus, heart disease, or morbid obesity or were ≥65 years of age. Either baloxavir or a neuraminidase inhibitor (eg, oseltamivir, zanamivir, peramivir) is an option for treatment of uncomplicated influenza in patients ≥12 years of age.

Xofluza (baloxavir marboxil) for oral use, prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210854s001lbl.pdf (Accessed on October 17, 2019).

Eight weeks of glecaprevir-pibrentasvir for chronic HCV infection in treatment-naïve patients

The recommended duration for glecaprevir-pibrentasvir for treatment-naïve patients with chronic HCV infection has been revised to eight weeks. The previous recommended duration for treatment-naïve patients with compensated cirrhosis was 12 weeks, based on the duration used in initial trials. However, in a subsequent, as-yet-unpublished trial among such patients, eight weeks of glecaprevir-pibrentasvir resulted in sustained virologic response (SVR) rates of 98, 100, and 96 percent for genotype 1, genotype 2, and genotype 3 infections, respectively. Most other treatment options for previously untreated chronic HCV infection are given for 12 weeks.

Mavyret (glecaprevir-pibrentasvir). US FDA approved product information; North Chicago, IL; AbbVie Inc. Revised September 2019.

Brown RS, Hezode C, Wang S, et al. Preliminary efficacy and safety of 8-week glecaprevir/pibrentasvir in patients with HCV genotype 1-6 infection and compensated cirrhosis: The EXPEDITION-8 study. Presented at the AASLD Liver Meeting, San Francisco, CA. November 13, 2018.

Source: UpToDate, November 2019