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Short-course therapy similarly effective to prolonged therapy for P. aeruginosa
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Adults receiving short-course therapy for the treatment of uncomplicated Pseudomonas aeruginosa bloodstream infections, or BSIs, experienced similar outcomes compared with those receiving prolonged-course therapy, according to findings from a multicenter, observational, propensity-score weighted cohort study.
Specifically, patients treated for a median of 9 days and those treated for a median of 16 days had similar odds of recurrent infection or death within 30 days, Valeria Fabre, MD, assistant professor of medicine at Johns Hopkins University School of Medicine, and colleagues reported.
Writing in Clinical Infectious Diseases, Fabre and colleagues highlighted rising rates of antibiotic resistance, antibiotic-related adverse events and the potential impact on the intestinal microbiome as reasons for re-evaluating the duration of antibiotic therapies.
They are not alone on this path. Last year, researchers presented findings that demonstrated the noninferiority of a 7-day antibiotic course compared with a 14-day course for the treatment of gram-negative bacteremia. Among numerous other studies, researchers have reported that a short-term antibiotic course to treat Enterobacteriaceae bloodstream infections does not increase the risk for mortality compared with prolonged therapy, and that shortened antibiotic courses are effective in treating community-acquired pneumonia.
“Due to P. aeruginosa’s propensity to develop resistance and affect patients who are immunocompromised, have indwelling hardware, or chronic underlying medical conditions, there has been a general acceptance that patients with P. aeruginosa bloodstream infections require more aggressive management than those with BSIs due to most other gram-negative organisms,” Fabre and colleagues wrote.
“To ensure our findings were generalizable to patient populations at greatest risk for P. aeruginosa BSIs, we elected to include high-risk patients who are frequently excluded from comparative effectiveness antibiotic studies,” including severely immunosuppressed patients, who made up 65% of the cohort, they wrote.
The study included 249 adults aged 18 years or older with a positive blood culture for P. aeruginosa who were admitted to five hospitals in the Johns Hopkins Health System between July 1, 2016, and Oct. 30, 2018. The primary exposure was a short-course of therapy, defined as 7 to 11 days of antibiotics. The primary outcome was a composite outcome of recurrent P. aeruginosa infection or death within 30 days of discontinuing antibiotic therapy, the researchers explained.
According to the study, 28% of patients received short-course therapy — a median of 9 days — and 72% received prolonged therapy — a median of 16 days. For both groups, the median duration of bacteremia was 1 day.
Of the antibiotics prescribed, 31% were piperacillin/tazobactam, 29% were cefepime, 24% were ciprofloxacin, 12% were meropenem, and 4% were ceftazidime. In the short-course group, 37% transitioned to oral fluoroquinolones during the treatment period compared with 35% in the prolonged group, with the median day of transition being 5 days and 6 days, respectively. The recommended treatment course was completed by 36% of patients in both groups.
A weighted analysis showed that 14% of patients in the short-course group experienced recurrent P. aeruginosa infection at any site or mortality within 30 days of completing therapy compared with 13% in the prolonged-course group (OR = 1.06; 95% CI, 0.24-2.68). Additionally, Fabre and colleagues observed that patients receiving shorter courses of therapy spent an average of 4.04 fewer days in the hospital compared with patients receiving prolonged courses (95% CI, 1.25-6.83).
“We found that patients with Pseudomonas BSIs who received approximately 10 days of antibiotic therapy had similar outcomes as patients receiving a prolonged course of therapy, with the potential added benefit of earlier hospital discharge if treated with a shorter course,” they wrote. “Further interventional studies are necessary to evaluate the reproducibility of our findings.” – by Marley Ghizzone
Disclosures: Fabre reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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Keith S. Kaye, MD, MPH
This manuscript suggests that some patients with P. aeruginosa bacteremia can be treated with short-course antibiotic therapy. Traditionally, gram-negative bacteremia has been treated for a minimum of 2 weeks. More recently, studies have suggested that in some cases of bacteremia due to Enterobacteriaceae, a shorter course of treatment is acceptable and possibly might be favorable (owing to decreased risks for adverse effects of the antibiotic and development of antimicrobial resistance). This study adds to the literature, particularly because it focused on P. aeruginosa. Of note, most subjects had a urinary, central venous catheter or skin source of infection, and almost all subjects had adequate source control. Clearly, in more deep-seated infections and in scenarios where there is a high-grade, persistent bacteremia and/or slow clinical response, short-course therapy should be avoided. Also of note, more than one-third of all subjects were switched to an oral fluoroquinolone at a median of 5 days after initiating therapy. Thus, regardless of total treatment duration, completing therapy with an oral fluoroquinolone should be considered in some patients with pseudomonal bacteremia.
Reference:
Yahav D, et al. Clin Infect Dis. 2018;doi:10.1093/cid/ciy1054.
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