Macrolide-Resistant Strains Identified in 40% of S. Pneumoniae Infections

About 40% of Streptococcus pneumoniae infections in the United States are macrolide-resistant strains, according to a new study.

The study, published in Open Forum Infectious Diseases, included isolates from 3,626 patients with S. pneumoniae blood or respiratory infections between October 2018 and September 2019 at 329 health care facilities in the United States.

Resistance varied by region but was greater than 25% in most areas and 39.5% overall, the study, led by Vikas Gupta, PharmD, BCPS, of Becton Dickinson and Company, found. It also was more common in ambulatory patients (45.3%) than inpatients (37.8%) and more common in respiratory isolates (47.3%) than blood isolates (29.5%).

“This is important because community physicians are even more unlikely to collect respiratory cultures on patients so this startling resistance rate may not be generally known prior to a physician empirically prescribing a regimen for a patient with pneumonia,” study co-author Jennifer Schranz, MD, chief medical officer at Nabriva Therapeutics told Contagion®.

“What’s concerning is that the IDSA guidelines discourage the use of macrolides — an example being azithromycin, commonly referred to as the “Z-pac” — when the resistance to the bacteria being targeted is above 25%,” Schranz added. “Essentially, that time is now, and these findings from a national sample underscore the need for new monotherapy alternatives to macrolides in the management of community-acquired pneumonia (CABP).”

The Infectious Diseases Society of American and the American Thoracic Society recommend macrolide antibiotics only be used to treat community-acquired bacterial pneumonia (CABP) if resistance is less than 25%.

The US Centers for Disease Control and Prevention has designated drug-resistant S. pneumoniae as a serious threat, and Schranz called the new research “a clarion call for action.”

Regions of the United States with the highest rates of macrolide resistance were the West North Central Region at 54.2%, followed by the South Atlantic at 48%. Regions with resistances rates below 25% were Mountain (13.9%), New England (18.2%), and Pacific (18.3%), but resistance in respiratory isolates was 25% or greater in all of those regions.

“This study demonstrates the importance of contemporary, local epidemiology data to optimize the selection of empiric therapy for patients with CABP,” Schranz said. “Based on current IDSA/ATS guidelines for pneumonia management, clinicians should consider alternatives to macrolide monotherapy for community-acquired pneumonia in the U.S. in areas with pneumococcal resistance rates greater than or equal to 25%.

“These data essentially remove one class from CAP treatment due to the demonstrated high resistance and current guidelines. The study results also underscore the urgent need for innovative antibacterial agents with a novel mechanism of action against drug-resistant S. pneumoniae that offer a short-course, monotherapy treatment option for patients with community-acquired pneumonia.”

Schranz said more research evaluating resistance trends is needed, but funding has decreased.

“It would be valuable if the CDC could reinstate their surveillance of such urgent threat bacteria,” she said.

“From a clinical perspective, having real world evidence data on the impact of antimicrobial resistance on clinical outcomes, such as ER visits, hospitalization rates, adverse events, cardiac complications, or mortality would be of value.”

The study results were “neither new nor surprising, but very much deserve repeating,” Daniel M. Musher, MD, FIDSA, of Baylor College of Medicine and the Michael E. DeBakey Veterans Affairs Medical Center in Houston, wrote in an associated commentary.

Musher recommended amoxicillin for healthy adults and amoxicillin/clavulanic acid in older adults with comorbid conditions and noted that two new drugs, lefamulin and omadacycline have been approved.

Lefamulin was approved in August 2019 and is the first systemic pleuromutilin antibiotic available for human use. Omadacycline is a tetracycline that was approved in October 2018.

“In summary, Gupta et al give us good reason not to treat outpatient pneumonia empirically with a macrolide,” Musher wrote. “My choice remains a beta-lactam, but fluoroquinolones are effective, and two new drugs are now available for consideration.”