SAN DIEGO (FRONTLINE MEDICAL NEWS) Bacteria with favorable susceptibility profiles don’t always translate reliably into treatment successes, according to a detailed study of six isolates.

“Both patient and microbe factors can contribute to treatment failure, even involving pan-susceptible isolates,” Andrew Berti, PharmD, PhD, said in an interview prior to an annual scientific meeting on infectious diseases.

Although clinicians can employ suppressive antimicrobial therapy in patients with persistent or relapsing bacteremia, bacteria with favorable susceptibility profiles may be able to survive in high concentrations of antibiotics. “The antimicrobial tolerance phenotype can thwart efforts to prevent bacteremia recurrence with prolonged exposure to antimicrobials and may contribute to breakthrough bacteremias while the patient is receiving active therapy,” Dr. Berti, of the department of pharmacy practice at Wayne State University, Detroit, and his associates wrote in their abstract of the research they presented at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

The researchers presented the case of a patient who experienced multiple episodes of breakthrough Staphylococcus aureus bacteremia over a period of 5 years in the setting of appropriately dosed antimicrobial suppressive therapy. They recovered six clinical bloodstream isolates from the patient during distinct episodes of methicillin-susceptible S. aureus (MSSA) bacteremia, and it was determined that a central line infection was the source for each episode. Isolates recovered were susceptible to the individual therapies received, which included oxacillin, daptomycin, and dalbavancin. The researchers used Illumina technology to collect bacterial whole genome sequence data. “Relatively little is known about bacterial evolution during human infection as these tend to be acute, rapidly resolved events,” Dr. Berti said. “This case was unique in that we could observe changes to a pathogen over a more than 6 years period as it adapted to survive host defenses and multiple antibiotic interventions.”

The researchers discovered that the first two isolates (ST256) and the last four isolates (ST5) “represent distinct populations and suggest that a distinct MSSA strain displaced the previous population between bacteremia episodes 2 and 3,” they wrote in their abstract. “Of note, all of these strains were able to survive and establish breakthrough bacteremias despite favorable susceptibility profiles to the agents used as suppressive therapy. Although the MICs remain low and in the susceptible range to oxacillin, daptomycin, and dalbavancin, these isolates progressively developed significant antimicrobial tolerance phenotypes, which coincided with mutations in walK (yycG), htrA2, ftsW, ebh, and ileS that may be advantageous to survival under antibiotic pressure.”

Dr. Berti acknowledged certain limitations of the analysis, including the inability to test for heteroresistance to some antibiotics, which may also contribute to treatment failure. “Specific therapeutic interventions that coincide with bacterial population changes are not necessarily causative of those changes,” he said. One of the study authors, Warren Rose, PharmD, disclosed having received research grants, speaker honoraria, and/or consulting fees from Theravance, Merck, The Medicines Company and Visante, Inc. All other authors reported having no financial disclosures.