In this episode I’ll:
1. Discuss an article about the duration of therapy in gram-negative bacteremia.
2. Answer the drug information question “Can cefazolin sensitivity be used to predict cephalexin sensitivity?”
3. Share a tip for responding to inpatient medical emergencies.
Seven versus fourteen Days of Antibiotic Therapy for uncomplicated Gram-negative Bacteremia: a Non-inferiority Randomized Controlled Trial
Lead author: Dafna Yahav
Published in the journal Clinical Infectious Disease December 2018
Most studies attempting to identify the shortest possible course of antibiotic therapy to successfully treat an infection exclude patients with bacteremia. A meta-analysis of studies suggested no difference between short and long courses for patients with bacteremia but only 89 adult patients were analyzed. The authors of this study sought to determine whether a 7 or 14-day course of antibiotics for uncomplicated gram-negative bacteremia were non-inferior to each other.
The study was a randomized, multicenter, open-label, non-inferiority trial of inpatients with gram-negative bacteremia. To be included, patients had to have successful source control and be afebrile and hemodynamically stable for at least 48 hours. They were then randomized to receive 7 or 14 days of appropriate antibiotic therapy. The primary outcome was a composite of all-cause mortality; relapse, suppurative or distant complications; and re-admission or extended hospitalization (>14 days) at 90 days.
Approximately 300 patients in each group were enrolled in three centers in Israel and Italy. The source of the infection was urinary in 68% of patients and the causative bacteria was Enterobacteriaceae in 90% of patients. The composite outcome occurred in 45.8% of patients in the short course group and 48.3% in the long course group. This difference was not statistically significant and met the non-inferiority margin. No significant differences were observed in all other outcomes and adverse events, except for one interesting difference: There was a shorter time to return to baseline functional status in the short therapy arm.
The authors concluded:
In patients hospitalized with Gram-negative bacteremia achieving clinical stability before day 7, an antibiotic course of 7 days was non-inferior to 14 days. Reducing antibiotic treatment for uncomplicated Gram-negative bacteremia to 7 days is an important antibiotic stewardship intervention.
While reducing the use of unnecessary antibiotics is an important goal, so is adequately treating the patient’s infection. I think it is important to keep in mind the limitations of this study before applying it in practice.
Most notably, patients in the study almost entirely had an infection caused by Enterobacteriaceae. Applying the results to patients with other gram-negative organisms is risky in my opinion.
The inclusion criteria for the study is also very important to keep in mind when applying the results to practice. Many elderly and immunocompromised patients were included in the study, which makes translating it to real-world practice easier. However, it must be noted that to be included the patient needed to have adequate source control AND achieve hemodynamic stability for at least 48 hours before the 7th day of antibiotic therapy was reached.
To members of my Hospital Pharmacy Academy that have been listening to my weekly literature digests, the fact that patients with a shorter antibiotic course had a more rapid regain of baseline functional capacity is not surprising, given the study we recently reviewed about antimicrobial exposure and the risk of delirium in critically ill patients. To get access to the archive of over 110 weekly literature digests, as well as all future ones, go to pharmacyjoe.com/academy.
Drug information question
Q: Can cefazolin sensitivity be used to predict cephalexin sensitivity?
A: It depends on the infection being treated.
The CLSI guidelines for oral cephalosporin prediction state:
For uncomplicated urinary tract infections, cefazolin results predict results for oral cephalexin, cefaclor, cefdinir, cefpodoxime, cefprozil, and cefuroxime.
The restriction to uncomplicated urinary infections is likely due to the 11% chance that a bacteria that is sensitive to cefazolin is resistant to cephalexin. The thought being due to concentrations achieved in the urine, the clinical success rate is likely not affected by the chance of resistance.
Tip for responding to inpatient medical emergencies
When a patient is unstable or ‘crashing’ the team usually doesn’t feel like the time it takes to check IV compatibility is worth delaying treatment to a patient. That’s why I keep in mind two basic IV compatibility rules for common critical medications that hold up according to Y-site compatibility data from Trissel’s.
Rule #1: With the exception of propofol and vasopressin (which have never been tested together) all the usual sedatives and vasopressors are compatible with each other at Y-site. This includes norepinephrine, epinephrine, phenylephrine, vasopressin, dopamine, fentanyl, midazolam, propofol, and dexmedetomidine.
Rule #2: When adding sodium bicarbonate to sedatives and vasopressors, care must be used to avoid incompatibilities. Sodium bicarbonate at Y-site is not compatible with midazolam, and it inactivates catecholamine based vasopressors such as norepinephrine, epinephrine, and dopamine. Sodium bicarbonate is compatible with fentanyl, propofol, dexmedetomidine, phenylephrine, and vasopressin.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.