Bacteremia is defined as the presence of bacteria within the bloodstream. Bacteremia could come from infections such as a urinary tract infection, pneumonia, even from dental or any kind of medical procedure.1 The symptoms one would experience when having bacteremia usually are non-existent, but when bacteria does accumulate in certain tissues or organs, this could cause serious infections. The immune system usually removes such bacteria from the body, but if one’s immune system is weakened, and the bacteria is present for an extended period of time within the blood stream, thus leading to other infections and could possibly trigger sepsis. Other examples of infections when bacteria accumulates in certain tissues are as followed: Meningitis, pericarditis, endocarditis, osteomyelitis, and infectious arthritis.1 Bacteremias are caused by gram-negative organisms 25-50% of the time, having the urinary tract being the most common source.2 However, there are only a limited amount of evidenced-based data on the efficaciousness of the transition of IV to oral therapy for Gram-negative BSI after discharge from the hospital.
Kutob and colleagues conducted a retrospective cohort study to evaluate the effect of oral antibiotics for definitive treatment for gram-negative bloodstream infections (BSI). Patients included in this study were those who had gram-negative BSI, hospitalized for <14 days, and discharged on oral antibiotics were included in the study.3 Patients were followed for 90 days from onset of BSI or until treatment failure. Patents included had a variety of comorbidities including ESRD, diabetes mellitus, liver cirrhosis, and cancer. The cohort was stratified in three different groups according to the bioavailability of oral antibiotics prescribed. High bioavailability was set at ≥95% (treated with levofloxacin 500 mg or 750 mg once daily), moderate bioavailability was set at 75-94% (treated with ciprofloxacin 500-750 mg every 12 hours or trimethoprim/sulfamethoxazole 800/160 mg every 12 hours), and low bioavailability was set at < 75% (beta-lactam antibiotics). 3 Treatment failure rates were shown to be 2%, 12%, and 14% for patients who took oral antibiotics with high, moderate, and low bioavailability, respectively.3 From the results, low and moderate bioavailability agents were significantly associated with failure in treatment when compared with agents with high bioavailability.3 During the 4-year study period, 362 patients with Gram-negative BSI were discharged on oral antimicrobial agents. The mean age of patients was 63, 217 were women (59.9%), and 243 (67.1%) had BSI due to Escherichia coli. 3 Other bacterial infections included Klebsiella spp., Proteus mirabilis, Pseudomonas aeruginosa, and AmpC-producing Enterobacteriaceae (CAE). 3 Overall, the patients received a mean of 4.7 days of IV therapy during hospitalization, followed by 9.1 days of oral therapy. Within 90 days of BSI, 27 patients had treatment failures, 233 survived without recurrences, and the remainder were censored on the last day of healthcare encounter.3 In the study, they discovered that there was no difference in treatment failure rates when comparing patients who received <5 days and ≥5 days of appropriate IV antibiotic treatment before switching to oral. 3 Therefore, results also demonstrated that duration of appropriate IV antimicrobial therapy before switching to oral therapy was not associated with treatment failure, suggesting that patients may be switched from IV to oral therapy with high bioavailability as soon as clinical improvement is seen in a patient who are able to tolerate oral medications. 3 Limitations in this study include that this study was not randomized, compliance couldn’t be assessed in these patients, and some patients who may have been lost to follow-up and could have presented treatment failure elsewhere.
Mercuro and colleagues conducted a study in order to compare and contrast the efficacy and safety between oral fluoroquinolone (ciprofloxacin, levofloxacin, and moxifloxacin) and beta-lactam (amoxicillin/clavulanate, cefalexin, amoxicillin, and cefdinir) stepdown therapy for adult patients with Enterobacteriaceae blood stream infections (EB-BSIs). Stepdown was defined as the switch to definitive oral antibiotic therapy following empirical IV antibiotics. 4 Stepdown therapy that occurred at three days or less was defined as early, while switching after 3 days was considered late stepdown. 4 Between January 2013 – July 2016, a total of 224 patients with Gram-negative bacteremia were screened and assessed regarding oral stepdown therapy. 4 The mean age was 70.8 years, 51.3% of the population being male. 4 Patients included had a variety of comorbidities including diabetes mellitus, CKD stage III or greater, cirrhosis, and cerebrovascular disease. Piperacillin/tazobactam was the most common IV antibiotic while ciprofloxacin was the most common oral stepdown medication utilized. 4 Escherichia coli and Klebsiella pneumoniae (71.4% and 17% respectively) were the most common isolates. 4 Approximately 46% of patients were transitioned from IV therapy to oral at least one day before discharge, while the others were transitioned on the day of discharge. 4 Most common sources of infection came from UTIs and intra-abdominal infections. From the study, they found that patients were more likely to tolerate beta-lactam medications without experiencing adverse effects in comparison to fluoroquinolones (91.7% vs 82.1%, P = 0.049). 4 A subgroup analysis shown that clinical success was similar between early and late stepdown displaying similar clinical success rates (86.7% vs 87.5% P > 0.05). 4 Therefore, as displayed in Kutob and colleagues’ study, this study reinforced that there is no statistical significance in clinical success rates between early or late stepdown to oral therapy. These results further argue for the initiation of oral therapy as soon as possible, whenever the patient could tolerate taking medications by mouth. Limitations to this study included utilized a single center to conduct research, in terms of following the adherence of outpatient medications (oral) they only were able to follow 67.5% of the patients.
Rieger and colleagues conducted a retrospective cohort study in which compared treatment failure associated with IV only vs. IV to PO antibiotic treatment utilized for bacteremic Enterobacteriaceae UTIs. The study assessed 241 adult patients who were hospitalized between July 1, 2010 – June 30, 2015 who had positive urine and blood cultures with the same pathogen (Enterobacter spp. , E. coli, Klebsiella spp., Proteus spp., Serratia marcescens, Citrobacter spp., Morganella morganii, or Providencia spp). 5 241 patients who met the inclusion criteria had the median age of 64 (54-74), 46% of the population were male, 53% African American and 46% were Caucasian. 5 Most of the patients had diabetes, often with comorbid renal diseases. 5 Other comorbidities include dementia, rheumatic disease, peptic ulcer disease, diabetes mellitus, past-MI, congestive heart failure, or peripheral vascular disease. 5 There were no statistically significance found in treatment failure in patients who received IV-only antibiotics versus IV-to-oral antibiotics for the treatment of bacteremic urinary tract infections (IV – 3.8% [95% CI: 1.0-9.4%] failure; intravenous/oral – 8.2% [95% CI: 4.1-14.1%] failure; p=0.19). 5 Although, there were less hospital days in those who were transitioned into oral therapy. The study concluded that transitioning from intravenous to oral antibiotic therapy is a viable decision to put into consideration for those who have bacteremic Enterobacteriaceae urinary tract infection. Again, these results argue for transitioning to oral therapy as soon as possible since it reflected less hospital stays in this case (save money in hospitals). Limitations of this study includes restrictions from the formulary which did not include ciprofloxacin or levofloxacin, and since these medications show many desirable characteristics such as high concentrations in the genitourinary system, similar concentrations with IV and PO dosing and cost, higher utility could have favored IV/PO treatment. Another limitation of this study is that it only focused on urinary tract infections, while being the most common source of infection, it is not the only one.