Analyzing the Role of Levofloxacin in Urinary Tract Infections-A review

Affecting 150 million people each year worldwide (1), urinary tract infections (UTIs) are regarded to be among the most common causes of sepsis presenting to hospitals. UTIs pose a global health issue and infer a significant quantity of societal cost (1). Based on categorization into complicated urinary tract infections (cUTIs) and uncomplicated urinary tract infections (including prostatitis, pyelonephritis, and cystitis), UTIs exhibit a wide variation in clinical features, ranging from uncomplicated infections manageable with outpatient antibiotic therapy to a fatal urosepsis in a comorbid patient. (1,2)

With research highlighting that approximately 40-50% of women worldwide suffer from UTIs at least once in their lifetime, the female gender remains more susceptible to UTIs (1). Nearly one in every three females requires antibiotic therapy for a UTI by age 24, coupled with high recurrence rates of 30%–44%, making UTIs a challenge for physicians (3).

UTIs can be complicated by several risk factors, ultimately causing treatment failures, repeat infections, or significant morbidity and mortality. Complicated UTIs (cUTIs) can be a result of indwelling urinary catheters, renal diseases, urinary tract obstruction, incomplete voiding due to detrusor muscle dysfunction, vesicoureteral reflux, diabetes, and immunosuppression. (2) It has further been affirmed that complicated UTIs are associated with significant morbidity and increased healthcare costs.

Considering such scenarios, timely and effective antibiotic treatment, can lead the way to manage UTIs successfully.

Empirical therapy with drugs like Levofloxacin is widely recommended for clinical application in UTIs (1,4). This article aims to review the drug profile of Levofloxacin while summarizing the currently available studies on the role of this drug in managing UTIs effectively.

Deciphering the drug characteristics-

Levofloxacin is a fluoroquinolone (FQ) antibacterial that is the L isomer of Ofloxacin.Since its introduction in the 1990s, this drug has become one of the cornerstones of antibiotic therapy in managing UTIs, owing to its exceptional pharmacokinetic and pharmacodynamic profile, broad-spectrum antibacterial action, and satisfactory tolerance levels among patients. (2)

Analyzing the pharmacodynamic properties of levofloxacin-How does the drug act?

Levofloxacin possesses significant activity against E. coli, the major micro-organism involved in UTI.(5,6) Levofloxacin is also active against a broad range of Gram-positive, Gram-negative, and atypical bacteria, by virtue of its interference with critical processes in the bacterial cell, such as DNA replication, transcription, repair, and recombination, via inhibition of type II topoisomerases. (2)

Levofloxacin has a twice renal excretion rate (84%) as ciprofloxacin (43%), thus possessing higher urinary bactericidal titers and long-lasting time (1).

Drusano et al. showed that the prostate/plasma ratio of more than 70% of the subjects exceeded 1.0, indicating that Levofloxacin was able to penetrate the prostate and was suitable for local infection (1).

Wagenlehner et al. reported that the blood concentration of Levofloxacin in healthy volunteers was higher than that of ciprofloxacin at a single dose, confirming the fact that its minimum inhibitory concentration for uropathogen was higher in disk diffusion, compared with ciprofloxacin. (1)

Quoting studies-

Efficacy of levofloxacin in uncomplicated UTIs-

● A study by Manshahia PS et al (5) concluded that the most preferred antibiotics prescribed as empirical therapy for uncomplicated UTIs were Levofloxacin (44.77%). This study further confirmed that Escherichia coli is the major causative organism of UTI, both in males and females, followed by Klebsiella, and Gram-positive organisms including CONS (coagulase-negative Staphylococcus), MRSA (methicillin-resistant Staphylococcus aureus), and Enterococcus.

● Another study(4) was undertaken with the objective was to determining whether alternative non-fluoroquinolone agents are as effective as fluoroquinolones in the treatment of UTIs, and concluded that fluoroquinolones were associated with fewer return outpatient visits (OR 0.89, 95%CI 0.87e0.92), emergency department visits (OR 0.74, 95%CI 0.61e0.89), hospitalizations (OR 0.83, 95%CI 0.77e0.88), and repeat antibiotic dispensations (OR 0.77, 95%CI 0.75e0.80) within 30 days; thus reaffirming the superiority of FQs.

Efficacy of Levofloxacin in cUTIs

● Research has exhibited Levofloxacin to be an attractive therapy for cUTIs (including pyelonephritis) because of their elevated urinary concentration and their proven clinical efficacy [2].

● The ASPECT-cUTI study aimed to evaluate the efficacy and safety of ceftolozane/tazobactam versus Levofloxacin for the treatment of adult hospital patients with cUTI. The research team noted high rates of clinical cure (90–100%) at Levofloxacin MICs ≤4 μg/ mL. Rates of microbiological eradication were also consistently high (>90%) at Levofloxacin MICs ≤0.06 μg/mL. (2)

● Yet another study on patients with cUTIs, aimed to investigate the efficacy of a short-course therapy group (intravenous levofloxacin (LVFX) at750 mg/day for 5 days) vs. a conventional therapy group (intravenous/oral regimen of LVFX at 500 mg/day for 7–14 days). Research data suggested that short-course therapy is a more convenient alternative to the conventional regimen, with potential implications for anti-resistance and cost-saving. (2)

Guidelines –As per recommendations by the Infectious Diseases Society of America (IDSA) and the European Society for Clinical Microbiology and Infectious Diseases (ESCMID), a 3-day course of FQ therapy is advocated, but only in regions where the resistance rate is lower than 10%. (2)

European Association of Urology (EAU) guidelines indicate that FQs can be recommended as an empirical treatment when the patient is not seriously ill and it is considered safe to start initial oral treatment, or if the patient has had an anaphylactic reaction to beta-lactam antimicrobials. (7)

Highlights-

● Urinary tract infections (UTIs) are one of the most common bacterial infections acquired both in the community and in hospitals. Levofloxacin is an FQ active against a broad range of Gram-positive, Gram-negative, and atypical bacteria and is widely used in treating UTIs.

● With antimicrobial resistance (AMR) on a rapid rise, recommendations for judicious use of antibacterial drugs, based on local surveillance data, are becoming more prevalent. (2)

● It is important to tailor the treatment regimens according to local antibiotic susceptibility patterns, availability, and cost of antibiotics in the area. (5)

● Rational use of Levofloxacin, with an appropriately high dose and minimization of the duration of therapy, should be encouraged.

Summary- The therapeutic effect of fluoroquinolones in UTIs has been proved by an ample wealth of studies. With Indian studies (5) affirming that 44.77% of patients with UTIs are managed empirically with fluoroquinolones, the potentiality of this drug cannot be more emphasized. Levofloxacin, backed up by a huge number of studies, has been and continues to be the crucial drug in managing UTIs timely.

REFERENCES

1. Cao D, Shen Y, Huang Y, Chen B, Chen Z, Ai J, Liu L, Yang L and Wei Q(2021) Levofloxacin Versus Ciprofloxacin in the Treatment of Urinary Tract Infections: Evidence- Based Analysis. Front. Pharmacol. 12:658095.doi: 10.3389/fphar.2021.658095

2. Riccardo Bientinesi, Rita Murri & Emilio Sacco (2020): Efficacy and safety of levofloxacin as a treatment for complicated urinary tract infections and pyelonephritis, Expert Opinion on Pharmacotherapy, DOI: 10.1080/14656566.2020.1720647

3. Rich SN, Klann EM, Almond CR, Larkin EM, Nicolette G, Ball JD (2019). Associations between antibiotic prescriptions and recurrent urinary tract infections in female college students. Epidemiology and Infection 147, e119, 1–7. https://doi.org/10.1017/ S0950268818003369

4. Daneman, N., Chateau, D., Dahl, M., Zhang, J., Fisher, A., Sketris, I. S., ... & Bugden, S. (2020). Fluoroquinolone use for uncomplicated urinary tract infections in women: a retrospective cohort study. Clinical Microbiology and Infection, 26(5), 613-618.

5. Manshahia PS, Bisht M, Mittal A, Bhatia M, Handu SS. A prospective, follow-up study to assess guidelines compliance in uncomplicated urinary tract infection. J Family Med Prim Care 2020;9:4292-7.

6. McGregor, J. C., Allen, G. P., & Bearden, D. T. (2008). Levofloxacin in the treatment of complicated urinary tract infections and acute pyelonephritis. Therapeutics and Clinical Risk Management, 4(5), 843.

7. Bonkat, G., Pickard, R., Bartoletti, R., Bruyère, F., Geerlings, S., Wagenlehner, F., ... & Veeratterapillay, R. (2018). Urological infections. Arnhem: European Association of Urology.