High-Dose Levofloxacin Therapy for Community-onset Enterobacteriaceae Bacteraemia: A New Treatment Paradigm?

18 January, 2023

Prof. Tang Hung-Jen
Professor and Head of Infectious Disease, Section of Infectious Diseases, Department of Internal Medicine, Chi Mei Medical Center, Taiwan
Director of Infectious Disease Control Center, Chi Mei Medical Center, Taiwan


Community-onset bacteraemia or bloodstream infections (BSI) are associated with high morbidity and mortality, which leads to significant healthcare costs.1, 2 The Enterobacteriaceae family is the leading cause of community-onset bacteraemia.3, 4 The beneficial effects of high-dose, short course levofloxacin has been demonstrated in the treatment of community-acquired pneumonia (CAP), acute bacterial sinusitis (ABS), complicated urinary tract infections (UTI) and acute pyelonephritis (AP).5-10 However, clinical evidence supporting this treatment strategy for the empiric therapy of community-onset Enterobacteriaceae bacteraemia is limited thus far.

Professor Tang Hung-Jen from Taiwan discusses his experiences of treating community-onset Enterobacteriaceae bacteremia and shares his insights on the role of high-dose levofloxacin for this indication.


Q1: Please describe the prevalence of community-onset Enterobacteriaceae bacteraemia among the adult population of Taiwan.

In Taiwan, the prevalence of community-onset Enterobacteriaceae bacteraemia among the adult population is approximately 10% to 15%. Escherichia coli and Klebsiella pneumoniae remain the leading causes of community-onset Enterobacteriaceae bacteraemia among the adult population in Taiwan. Other common causative pathogens include Enterobacter spp., Proteus spp., Serratia spp. and Morganella spp.


Q2: What are the pathogen(s) that we should take note of when making treatment decisions regarding community-onset Enterobacteriaceae bacteraemia?

Klebsiella pneumoniae (K. pneumoniae) has been identified as an important common pathogen that is capable of causing severe organ and life-threatening disease, with a high propensity toward antimicrobial resistance. The increased incidence of extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae such as TEM and SHV types has been the predominant cause of nosocomial outbreaks worldwide.11 Recently, carbapenem resistance in community-onset Enterobacteriaceae bacteraemia such as K. pneumoniae carbapenemase (KPC)-producing bacteria, has emerged as an important cause of resistance.12


Q3: Pharmacokinetic/pharmacodynamic (PK/PD) studies in recent years have showed that levofloxacin is a concentration-dependent antimicrobial agent.13 What are your opinions on a high-dose, short-course regimen with levofloxacin for the empiric therapy of community-onset Enterobacteriaceae bacteraemia, while taking into account the emergence of resistance?

The emergence of ESBL-producing Klebsiella spp. and KCP as causative pathogens in patients with community-onset Enterobacteriaceae bacteraemia, means that the treatment options are reduced for clinicians. A high-dose, short-course levofloxacin regimen may play a potential role in addressing this issue. The therapeutic success of levofloxacin is linked to the ratio of the area under the concentration-time curve (AUC) to the minimum inhibitory concentration (MIC) for the organism, rather than time of concentration greater than the MIC.5 Therefore, a high dose of levofloxacin can increase the ratio of peak plasma concentration (Cmax) and AUC, leading to rapid bactericidal effect and shortened duration of treatment.5 Overall, the optimised high-dose, short-course levofloxacin regimen utilises its concentration-dependent bactericidal activity to maximise killing, reducing the total amount of drug to which pathogens are unnecessarily exposed. This high-dose, short-course regimen further helps to overcome the mutant prevention concentration (MPC), to prevent selection of resistant mutants, thereby reducing the likelihood of resistance developing.14


Q4: With regard to your clinical approach to community-onset Enterobacteriaceae bacteraemia, are there differences in the levofloxacin regimen you would use for patients with critical illness compared with stabilised illness?

Generally, a delay in appropriate antibiotic treatment of community-onset Enterobacteriaceae bacteraemia is associated to a higher risk of metastatic infection and mortality. Higher doses of antimicrobials such as 750 mg of levofloxacin, may allow the use of short-course regimens, owing to rapid and concentration-dependent bactericidal activity in eradicating bacteria from the bloodstream. For patients with critical illness, high-dose, short-course levofloxacin therapy is particularly beneficial for optimising clinical outcomes, by rapidly and completely killing bacteria and reducing the risk of selection of resistant organisms.14



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