Fluoroquinolones As Alternate Therapy Option for Bloodstream Infections in Some Patients

Empiric use of fluoroquinolones looks to be an alternate option for the treatment of gram-negative bloodstream infections, when risk factors for antimicrobial resistance are not present, according to research presented at the 2018 ASM Microbe conference in Atlanta, Georgia.

Fluoroquinolones are highly effective broad-spectrum antibiotics; however, the risk of serious side effects and a rise in antimicrobial resistance against these agents have limited their use.

“Fluoroquinolones have a bad reputation because of their side effects and the potential for resistance, but they do have very good bioavailability, orally,” shared Chelsea Drennan, PharmD candidate from the University of South Carolina School of Pharmacy and lead investigator on the study when she spoke with Contagion®. “If the pathogen is susceptible to fluoroquinolones, they typically are always going to eradicate that bacteria pretty quickly. And, so, they are still really good drugs for use when indicated and for susceptible organisms.”

In the absence of risk of factors for resistance—such as prior antimicrobial use, residence in skilled nursing facilities, or recent ambulatory gastrointestinal or genitourinary procedures—the results of recent studies suggest that fluoroquinolones can be effective treatment options against bloodstream infections (BSIs).

To test this theory, Drennan and her team performed a matched cohort study examining the clinical outcomes of patients receiving empirical fluoroquinolones or beta-lactam monotherapy for gram-negative BSI, in the absence of risk factors for antimicrobial resistance at initial presentation.

“We knew going into the study that the US Food and Drug Administration has said to reserve fluoroquinolones for more serious infections and not use them for more minor infections such as acute cystitis, acute sinusitis, etc. This is why we chose to study the more serious bloodstream infections,” Drennan said.

The team identified adult patients who were hospitalized for gram-negative BSI between January 1, 2010, and June 30, 2015, at Palmetto Health hospitals located in Columbia, South Carolina. Those patients who were determined to be without risk factors for antimicrobial resistance and who were receiving empiric fluoroquinolone therapy, “were matched to those receiving beta-lactam monotherapy in 1:2 fashion based on age, sex, and bloodstream infection mortality risk score,” according to the study abstract.

Drennan explained what classified as risk factors for resistance (see video).

A total of 74 patients received empiric fluoroquinolone therapy and 148 patients received beta-lactam monotherapy for gram-negative BSI. The mean age of the patients was 68 years. Seventy-two percent of the patients (159) were women and 71% (157) had community-acquired BSI. Sixty-eight percent (152) had a urinary source of infection and Escherichia coli was the most common pathogen.

Using multivariable logistic regression, the team examined early treatment failure, which was defined as, “mortality or persistence of ≥2 of the following criteria by 96 hours: fever/hypothermia, hypotension, mechanical ventilation, altered mental status, and leukopenia/leukocytosis. Cox proportional hazards regression was used to examine 28-day mortality and hospital length of stay (HLOS).”

The results of the study indicated that, empirical antimicrobial therapy was appropriate in 93% of patients (69) in the fluoroquinolone group and 98% (145) in the group receive beta-lactam monotherapy. Both groups had comparable early treatment failure rates: 12% for patients on fluoroquinolone versus 16% for beta-lactam monotherapy (odds ratio (OR) .70, 95% confidence intervals [CI] 0.30-1.62, P = .41) and 28-day mortality: .9% for patients on fluoroquinolone versus 9.7% for beta-lactam monotherapy (hazards ratio [HR] .74, 95% CI 0.26-1.90, P = .54). The median HLOS was 6.1 days for patients on empiric fluoroquinolone therapy and 7.1 days for beta-lactam monotherapy (HR .73, 95% CI 0.54-0.99, P = .04).

Drennan shared more about the findings on HLOS (see video).

Some of the limitations of the study include that the data is from 1 health system and so it is difficult to generalize the results out to the global population; however, the study provides good evidence for physicians that empiric use of a fluoroquinolones can be an alternative option over a beta-lactam in patients who are at low risk of resistance. This may be welcome news for physicians looking to be able to prescribe an alternative to a beta-lactam for reasons such as intolerability and not wanting to require the patient be hospitalized.

“One example where a physician might not want to prescribe a beta-lactam would be for a patient who has a severe cephalosporin allergy,” explained Drennan. “For those patients, instead of expanding on their therapy and giving them piperacillin and tazobactam or a carbapenem, we found it to be a viable option to use a fluoroquinolone instead of opening the patient up to nephrotoxicity.”

“Or, another example would be in a patient who is clinically stable, looks great, no leukocytosis, etc, and we think that the patient can be discharged,” she continued. “We found that it could be a viable option to give them an oral fluoroquinolone and send them home (as long as the bug they are infected with is susceptible.) This option introduces a cost-savings for the patient and enables them to have a shorter length-of-stay.”

As with any antibiotic therapy option, Drennan stated that a physician is still going to use the institution’s antibiogram to help guide therapy, but “working to try and give the patient the most individualized treatment based of their own specific risk-factors is better for patient outcomes.”