Levofla — Levofla Side effects, indications, usage

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Levofla

Levofla is a bacterial medication or antibiotic that exhibits a bacteriostatic activity, they act by inhibiting the growth of bacteria. Levofla contains the active ingredient known as levofloxacin. It’s a brand-name form of the antibiotic levofloxacin.

Levofla is not effective against viral illnesses like the common cold or flu. Fluoroquinolone antibiotics, such as levofloxacin, belong to a group of medications called fluoroquinolones. These antibiotics function by inhibiting the growth of bacteria that are hazardous to humans. It is not an over-the-counter medication and it requires a prescription from your doctor.

Uses of Levofla

If you have been diagnosed with any of the following medical conditions, your doctor may prescribe Levofla to you:

Pneumonia

Pneumonia is a dangerous lung infection. The air sacs of one or both lungs become inflamed and may fill with fluids or pus if you have pneumonia and this makes it harder to breathe. Bacteria, fungi, viruses, and chemical irritants can all cause pneumonia. Some common symptoms of pneumonia are chest pain, a wet cough, a fever, and chills. If you have bacterial pneumonia, you may be prescribed Levofla to help you recover.

Infections of the Kidney

The bacteria that caused your kidney infection most likely came from your lower urinary tract, such as your bladder or urethra. One-sided or bilateral flank or lower back discomfort, nausea, fever, and chills are all signs of a kidney infection. If you have these symptoms and are diagnosed with a significant kidney infection, Levofla is a popular antibiotic that can help.

Infections of the Prostate

You may have a prostate infection or if you experience pain in your lower abdomen or pelvic, as well as urinary symptoms including pain when urinating, increased urgency or frequency, and murky or bloody urine. Prostate infections (also known as prostatitis) are caused by bacteria and require antibiotic treatment. The type of bacteria causing your infection will determine the antibiotic recommended and the length of treatment.

Infections of the Skin

You can have a skin infection if your skin is red, sensitive, scaly, or swollen. Some skin diseases, such as cellulitis, necessitate the use of either a topical or an oral antibiotic.

A fluoroquinolone, such as Levofla, may be used to treat severe skin infections. Bronchitis viruses are responsible for over 90% of all occurrences of acute bronchitis.

Antibiotics, on the other hand, may be required in some circumstances.

When a bacterial infection is suspected, such as when there is colored sputum or if a person has certain high-risk underlying medical conditions, Levofla is an effective treatment for severe, persistent upper respiratory tract infections.

Usage

Levofla is available in tablet form, as an oral solution, and as an injectable administered once every 24 hours in varying strengths. It is always advisable to read the drug label before taking it, and only take it as directed by your doctor.

Dosage

To avoid reinfection and bacterial resistance, take the whole prescription dose of levofla as directed by your health care practitioner. The amount and length of your Levofla treatment may be influenced by a number of factors.

There are several of them which include;

Your infection’s type and severity
Your body mass index
Your age
Pre-existing medical issues, such as kidney disease

It is possible that your antibiotic dosage won’t stay the same for the duration of your therapy. Your doctor may start you on a low dose and gradually increase it as needed. Unless your doctor tells you otherwise, take this medication at the same time every day for the remainder of your treatment.

The oral dosage of Levofla is available in 3 different strengths: 250 mg, 500 mg, and 750 mg. You can take this medication with or without food.

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Levofla Side Effects

Levofla has the potential to induce major adverse effects. Always discuss your medical history with your healthcare practitioner before taking this levofla.

When taking Levofla, you may experience the following side effects that include;

Nausea
Headache
Diarrhea
Constipation
Dizziness
Insomnia (difficulty sleeping), nightmares, and paranoia are all symptoms of paranoia
Muscle deterioration

In addition to the more typical adverse effects listed above, Levofla has been associated with the following more serious, long-term negative effects: Tendon rupture or inflammation can occur at any age, although the risk is higher in individuals over 60, those who are on steroids (corticosteroids), and those who have had a kidney, heart, or lung transplant.

Tendon rupture can happen while you’re using Levofla or months after you’ve stopped taking it.
Nerve damage (peripheral neuropathy): This medication can harm the nerves in your arms, hands, legs, or feet. Changes in sensation may occur as a result of the damage, and these changes may be permanent. Effects on the central nervous system: Convulsions, psychosis, increased pressure inside the head, agitation, anxiety, tremors, disorientation, delirium, and hallucinations are all possible symptoms. Suicidal thoughts are possible in extreme circumstances.

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Frequently Asked Question About Levofla

What happens if I forget to take a dose?

If you forget to take a dose of levofla, make sure you take the dose of levofla as soon as you remember. However, you need to understand that two doses of levofla should never be taken at the same time and make sure you continue your regular dosing plan and skip the missed dose if your next single dose is less than eight hours away. Stop taking Levofla immediately if you or someone else is suffering serious adverse effects like trouble breathing, passing out, or dizziness. Immediately call 9-1-1 or go to a poison control center. Residents of the United States can call 1-800-222-1222 to reach their local poison control center.

Abstract

Despite the fact that few studies have been undertaken to assess the use of levofloxacin in this population, its use in critically sick patients has steadily increased since its commercialization in 1999. The high interest in the drug for the treatment of various infectious diseases, including ventilator-associated pneumonia (VAP), and the recommendation of levofloxacin in guidelines developed by a number of scientific societies, can be attributed to its pharmacological characteristics, a broad spectrum of activity, and tolerability.

According to pharmacokinetic-pharmacodynamic data, it appears acceptable to believe that a higher dose leads to an increase in activity, therefore 500 mg/12 h is sufficient in patients with VAP. Levofloxacin monotherapy is appropriate for the empirical treatment of patients with early-onset pneumonia without risk factors for multi-resistant infections, as well as in combination therapy for late-onset VAP or patients at risk for multiresistant pathogens in critically sick patients with VAP.

Several factors support the use of levofloxacin in combination therapy, including increased empirical coverage in infections with suspected intracellular pathogens; substitution for more toxic antimicrobial agents (e.g., aminoglycosides) in patients with renal dysfunction or those at risk of renal insufficiency; and the severity of the systemic response to infection (septic shock), which justifies multiple treatments with better-tolerated antibiotics. The oral formulation’s availability enables sequential therapy, going from intravenous to oral administration.

Critically sick patients tolerate levofloxacin well, with only a few minor to moderate side effects.

Introduction

Treatment of pneumonia associated with mechanical ventilation (ventilator-associated pneumonia, VAP), as well as most nosocomial infections diagnosed in critically ill patients admitted to the intensive care unit (ICU), should begin as soon as the infection is suspected on clinical grounds and samples from the lower respiratory tract have been collected, using antimicrobial agents prescribed empirically.

The importance of empirical antibiotic selection has been addressed in several research [1-5]. Appropriate empirical antibiotic treatment is linked to a lower risk of morbidity and a better rate of survival. Levofloxacin was included for the first time in a recent set of guidelines [6] as one of the antimicrobial agents recommended for use in monotherapy for the empirical treatment of early-onset pneumonia in mechanically ventilated patients without known risk factors for multiresistant pathogen selection. For patients with late-onset VAP and pneumonia who have risk factors for multiresistant infections, levofloxacin has also been included in the combination antibiotic therapy.

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This antibiotic was chosen for a variety of reasons, including its pharmacological properties (spectrum of activity, pharmacodynamics, and adverse event profile) and clinical tolerability, which allows it to be safely administered to patients with renal failure or hemodynamic instability.

After the etiology of pneumonia has been determined, treatment should be adjusted based on the results of antibiotic susceptibility testing, selecting the most effective and well-tolerated medicine with a narrower spectrum of activity and less influence on the endogenous anaerobic gut flora. Directed treatment can usually be continued in monotherapy in the majority of patients.

Only in cases of polymicrobial infections, where Pseudomonas has been isolated, or in patients with a long clinical course should combined treatment be continued. Levofloxacin remains a viable therapeutic option among the numerous quinolones available in these circumstances.

The criteria utilized to choose levofloxacin as one of the antimicrobial drugs for treating VAP are described in this review, as well as new pharmacokinetic-pharmacodynamic concepts that explain the choice of levofloxacin and current evidence for its usage.

The use of levofloxacin in the treatment of vap is justified.
A broad enough spectrum of activity to cover VAP-causing pathogens
VAP-causing microorganisms vary a lot depending on the patient’s underlying condition, previous antibiotic usage, days on mechanical ventilation preceding respiratory infection, and the prevalence of epidemics or endemics for a particular pathogen in the hospital or service where the patient is admitted. In around 25% of patients, VAP is caused by several pathogens.

(a) Patients with early-onset VAP or those who have no risk factors for multidrug-resistant infections. Primary endogenous flora present in the patient at the time of admission (methicillin-sensitive Staphylococcus aureus[MSSA], Haemophilus influenzae, Streptococcus pneumonia, and enterobacteria) predominate in early-onset pneumonia that develops during the first 4 days of mechanical ventilation in patients without previous antibiotic exposure and in the absence of chronic underlying illnesses (diabetes mellitus, chronic obstructive pulmonary

Early-onset pneumonia in patients with altered consciousness or in the immediate postoperative period after elective surgery are common examples [8-11]. Levofloxacin has antibacterial action against all pathogens that are likely to be encountered in this clinical setting.

(b) Patients with late-onset VAP or those who are susceptible to multidrug-resistant infections. Late-onset pneumonia is caused by secondary endogenous flora and occurs in people who have already been admitted to the hospital, have previously used antibiotics for infection treatment or prevention, and/or have persistent underlying illnesses (Gram-negative bacteria, Acinetobacter baumannii, and Staph. aureus, often methicillin-resistant)

In general, bacteria that are common in the area where the patient was admitted predominate in the secondary endogenous flora, therefore knowing the ICU’s epidemiological map assists in the selection of an empirical antibiotic regimen [16].

The use of two or more antimicrobial medicines active against potential causal microorganisms in the empirical therapy of late-onset VAP has not been linked to a greater survival rate [17].

Although there is minimal evidence on the efficacy of antibiotic monotherapy for the treatment of P. aeruginosa pneumonia, it appears that this approach is linked to a lower rate of microbiological eradication and/or a greater likelihood of relapse [20]. As a result, antibiotic combinations containing a -lactam with antipseudomonal action, aminoglycosides, or quinolones are used to treat these instances. In this circumstance, levofloxacin could be beneficial.

Pharmacokinetic indications that are favorable
Levofloxacin is broadly spread throughout the body and easily penetrates most tissues and fluids. There is a bigger than one relationship between drug concentrations in lung tissue and sputum and those found in plasma [21]. In epithelial lining fluid and alveolar macrophages, oral levofloxacin, 500 or 750 mg once daily, attained considerably greater steady-state concentrations than ciprofloxacin, 500 mg twice daily [22], but lower than azithromycin following intravenous treatment.

The steady-state plasma and epithelial lining fluid concentrations of intravenous levofloxacin 500 mg given once or twice daily in critically ill patients with severe community-acquired pneumonia were determined in a recent study [24]. Levofloxacin peak concentrations in plasma and epithelium lining fluid were 12.6 and 11.9 mg/L in the 24 h regimen and 19.7 and 17.8 mg/L in the 12 h regimen, indicating lung percentage penetration of > 100 percent in both groups.

Pharmacokinetic studies were carried out on 28 patients who were given levofloxacin intravenously. Ten of these individuals were then shifted to oral levofloxacin and had their pharmacokinetics assessed again while on oral treatment. The sequential treatment group’s maximum and lowest serum concentrations (Cmax and Cmin) were much lower than the intravenous dosage group’s, but they appeared to be adequate for most pathogens encountered in critically sick patients with normal renal function. In-vitro studies, on the other hand, have revealed that levofloxacin penetrates actively into phagocytic cells, potentially facilitating action against intracellular bacteria and increasing drug concentration in infectious foci via phagocytic release mechanisms.

The mean ratios between intracellular and extracellular concentrations in neutrophils after exposure to 5 and 50 mg/L levofloxacin were 8.8 and 9.8, respectively [26].

The pharmacokinetics of levofloxacin are represented by a two-compartment open model with first-order elimination, in which Cmax and the area under the concentration-time curve (AUC) both increase linearly in a dose-proportional manner [21]. Although pharmacokinetic studies of levofloxacin with 500 mg and 750 mg doses have been conducted in healthy populations and patients with infectious diseases and/or renal dysfunction [27-30], there is little information on pharmacokinetics in critically ill patients with hemodynamic instability, or in patients taking inotropic drugs, furosemide, or mannitol, or in patients with high distribution volumes.

In research of ICU patients treated for early-onset VAP with intravenous levofloxacin 500 mg twice daily, AUC was 30–40% lower than in healthy volunteers across a 12-hour dose interval, indicating a high renal excretion of unaltered medication and a shorter elimination half-life [31, 32]. Co-administered medications for underlying disorders (dopamine, furosemide, mannitol) may explain this improved elimination in critically ill patients, at least in part. In patients with severe pneumonia and normal renal function, these changes should be taken into account in clinical practice, as they justify the twice-daily dosage.

Excellent tolerability in patients with renal failure or those who are at risk of developing renal impairment. Unexpected severe adverse effects necessitating a change of the technical form of the product were not documented in a pharmacy surveillance study conducted three years following the commercialization of levofloxacin in the United States [33]. However, there are no data on safety and tolerability in the unique population of critically sick patients, where organ failure is widespread. Adverse events in patients treated with levofloxacin at doses between 500 and 1000 mg/day were rare (c. 12.5 percent) and not necessarily attributed to the use of levofloxacin because all patients were given other drugs, half of which were from other antibiotic classes, according to an observational study conducted in Spanish ICUs [34].

There were no cases of therapy discontinuation or modification owing to adverse effects. However, the discovery of heart rhythm problems requiring medical treatment in 2% of patients should prompt closer monitoring to determine the drug’s connection with levofloxacin [34], especially in patients taking large doses of the antibiotic. Small increases in QTc were detected with the 1500 mg dose in a clinical experiment done on healthy volunteers to examine the effect of escalating levofloxacin doses on the QT and QTc intervals (500, 1000, and 1500 mg) [35]. Levofloxacin doses of 1000 mg increased heart rate for a short time without changing the uncorrected QT interval.

Pharmacodynamic characteristics that are favorable
Pharmacodynamic indicators relating microbiological and pharmacokinetic variables have shown a correlation between Cmax/MIC ratio and bactericidal effect in experimental models with fluoroquinolones, indicating that this class of antimicrobial agent is classified as concentration-dependent killing [36]. Clinical and microbiological outcomes were predicted by the ratio of peak plasma concentration to MIC (peak/MIC ratio) in levofloxacin pharmacodynamic trials [37]. In-vitro testing of two dosages of levofloxacin (500 mg every 12 and 24 hours, and 750 mg daily dose) against P. aeruginosa and Strep. pneumonia strains revealed that greater peak concentrations increased bactericidal activity.

The parameters determining the likelihood of a positive microbiological or clinical outcome following the administration of an infusion of levofloxacin (total dose, 750 mg) in patients with hospital-acquired pneumonia were investigated [40]. A second medicine was added for individuals with P. aeruginosa or methicillin-resistant Staph. aureus (MRSA). Levofloxacin had a Cmax of 15.0 mg/L and an AUC of 147.1 mg h/L. The achievement of an AUC/MIC ratio of 87 had a substantial effect on pathogen eradication, according to multivariate logistic regression analysis.

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The area under the inhibitory curve (AUIC) is a relatively new efficacy metric that is mostly utilized in fluoroquinolone research. An in-vitro investigation looked at the association between fluoroquinolone concentration and bactericidal power, as well as the impact on resistance selection [41]. Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Staph. aureus strains were given different medication dosages to imitate human two-compartment pharmacokinetics. Peak concentrations of MIC 10 or AUIC >125 resulted in improved bactericidal action and bacterial regrowth prevention.

AUIC values of at least 100 should be attained for optimal clinical and bacteriological activity against Gram-negative and intracellular infections, according to animal model studies [42]. AUIC values greater than 40 have been demonstrated to predict clinical and bacteriological efficacy in Gram-positive cocci [43]. A pharmacodynamic investigation of levofloxacin’s efficacy against Strep. pneumonia found that hospitalized patients attain an AUC/MIC >30 99 percent of the time. This suggests that, in the vast majority of cases, levofloxacin will be quite effective in treating strep. pneumoniae infections.

During treatment, resistance develops

Although there have been reports of therapeutic failures due to the development of bacterial resistance when using levofloxacin, particularly against Strep. pneumonia [45, 46], the risk is smaller than when using ciprofloxacin. Time-kill data for ciprofloxacin, clinafloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin were generated in a dynamic in-vitro model against three isolates of quinolone-susceptible Strep. pneumonia.

In terms of bactericidal effect, ciprofloxacin (least active) was followed by levofloxacin, grepafloxacin, trovafloxacin, clinafloxacin, and moxifloxacin (most active), while in terms of resistance selection, ciprofloxacin (most likely) was followed by grepafloxacin, moxifloxacin, and trovafloxacin > TRUST (Tracking Resistance in the United States Today) is a long-running project that began tracking antibiotic resistance among respiratory infections in 1996 and is still going strong today [48]. The TRUST study looked at 9499 Strep. pneumonia, 1934 H. influenza, and 1108 Moxarella catarrhalis isolate from 1999 to 2000. Nationally, 0.5 percent of people were resistant to levofloxacin (regional range: 0.1–1.0 percent).

A mathematical model was built using data from mice infected with P. aeruginosa and treated with a fluoroquinolone antibiotic to describe connections between antimicrobial drug exposure and changes in drug-susceptible and drug-resistant bacterial subpopulations [49]. The AUC/MIC ratio of 157:1 was thought to be the bare minimum for preventing the formation of resistance. Monte Carlo simulations were also run for 750 mg of levofloxacin once daily and 400 mg of ciprofloxacin IV every 8 hours; the overall predicted AUC/MIC target attainment rate for levofloxacin was 61.2 percent and 61.8 percent for ciprofloxacin, respectively. The use of this fluoroquinolone in monotherapy for the treatment of P. aeruginosa infection is not recommended based on these findings.

Clinical evidence of levofloxacin’s usage in the treatment of vap
Despite the fact that numerous studies on the efficacy and tolerability of levofloxacin in the treatment of various infections, particularly respiratory tract infections, were carried out during the preclinical phase [50-58] and with the marketed drug [59-65], few studies in patients with VAP have been conducted. Patients with VAP were only included in two trials [31, 32, 64], both of which had quite distinct goals. One study [31, 32] included ten patients with early-onset VAP who were treated with levofloxacin 500 mg/12 h in a prospective, noncomparative open study. The renal function of all of the individuals was normal.

The goal of this study was to determine the pharmacokinetic and pharmacodynamic features of levofloxacin in this patient population, and the results have previously been published. The study’s clinical findings showed that levofloxacin is effective in patients with early-onset VAP. Only eight patients were evaluable at the conclusion of treatment, which lasted an average of eight days. The overall success rate was 75%, with the initial causing pathogen being eradicated in every case. However, levofloxacin-resistant bacteria were found in three of the patients (A. baumannii in two, P. aeruginosa in one).

The second research [64] aimed to assess the efficacy and safety of levofloxacin 750 mg versus imipenem/cilastatin followed by ciprofloxacin in adult patients with nosocomial pneumonia, with half of the patients having VAP. This was a North American multicenter, prospective, randomized, open-label trial. Patients were randomly randomized to one of two treatment arms: intravenous levofloxacin 750 mg/24 h followed by oral ciprofloxacin 750 mg every 12 h for 7–15 days or intravenous imipenem/cilastatin 500 mg to 1 g followed by oral ciprofloxacin 750 mg every 12 h for 7–15 days.

Renal function was used to alter the doses. In patients with verified or suspected P. aeruginosa, adjunctive antibiotic therapy was required, using ceftazidime 2 g/8 h (or non carbapenem—lactam) in the levofloxacin arm and amikacin 7.5 mg/kg/12 h (or an alternative aminoglycoside) in the imipenem/cilastatin arm. Vancomycin was given to any of the groups suspected of having MRSA. The clinical response in microbiologically evaluable patients 3–15 days following the conclusion of medication was the major specified outcome measure. A total of 438 adult patients were included in the study, with 220 receiving levofloxacin and 218 receiving imipenem/cilastatin. The intent-to-treat and clinically evaluable populations had similar demographic and baseline clinical characteristics.

Clinical success (cure or improvement) was achieved in 58.1 percent of levofloxacin-treated patients, compared to 60.6 percent of patients who received the comparator regimen [95 percent confidence interval (CI) 12.0 to 17.2]. In patients evaluable for clinical efficacy as well as the intent-to-treat population, similar clinical results were seen. Eradication was achieved in 66.7 percent of patients receiving levofloxacin and 60.6 percent of patients receiving imipenem/cilastatin (95 percent CI, 20.3 to 8.3) of the 187 patients evaluated for microbiologic effectiveness. In this trial, levofloxacin was found to be at least as successful as imipenem/cilastatin and to be as well tolerated as ciprofloxacin in adult patients with nosocomial pneumonia, as evidenced by comparable clinical and microbiological success rates.

However, because a large percentage of patients were given mixed regimens because of suspected or confirmed P. aeruginosa infection, these findings do not support the use of levofloxacin alone in patients with VAP [66].

222 patients were included in a subanalysis of the VAP subgroup from the aforementioned multicentre, prospective, randomized trial comparing levofloxacin and imipenem/cilastatin [67], with half (n = 111) of the patients assigned to each treatment group. In terms of age, the severity of sickness (APACHE II score 14.8 vs. 15.1), and duration of mechanical ventilation prior to the commencement of VAP (7.8 vs. 9.8 days), the patients in both groups were identical.

Other severity markers, such as the use of vasopressor drugs (17.1 percent vs. 12.6%), pleural effusion (2.7 percent vs. 0%), multilobar radiologic involvement (1.8 percent vs. 4.5), bacteremia (6.3 percent vs. 2.7 percent), or serum creatinine concentration greater than 1.5 mg/dL (8.1 percent vs. 12.6%), were distributed similarly in both arms. In terms of MRSA isolates (10.8 percent vs. 9.9 percent), simultaneous use of vancomycin (11.7 percent vs. 9.9 percent), and administration of empirical antibiotic combinations for the treatment of suspected P. aeruginosa pneumonia, the research groups were evenly split (30.6 percent vs. 25.2 percent ).

MSSA (18 cases), P. aeruginosa (16 cases), Serratia marcescens (13 cases), and H. influenza(13 cases) were the main pathogens treated in the levofloxacin group, whereas H. influenza (21 cases), MSSA (19 cases), P. aeruginosa (18 cases), and Enterobacter cloacae (11 cases) were the pathogens isolated in the imipenem/cilastatin group. MRSA was cultivated in five cases in each group. Clinical success (between 3 and 15 days following the end of treatment) was obtained in 58.6% of patients getting levofloxacin compared to 63.1 percent of patients receiving imipenem/cilastatin (95 percent CI, 8.77 percent to 17.79 percent) in the intention-to-treat population. Patients with VAP caused by P. aeruginosa had similar results (87.5 percent vs. 61.1 percent, p = NS).

The results of the multivariate analysis revealed that the antibiotic treatments (levofloxacin vs. imipenem/cilastatin) were not predictive of outcomes. The overall mortality rate was less than 15%. Only four patients in the levofloxacin group and two patients in the imipenem group had medication stopped due to adverse events, and the frequency of adverse events was similar (30.6 percent vs. 32.4 percent).

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The study’s main difference between treatment arms was the development of P. aeruginosa superinfection, which occurred in ten patients in the imipenem/cilastatin group versus three patients in the levofloxacin group (p = 0.045). The results of this secondary investigation in a group of VAP patients reveal that levofloxacin and imipenem/cilastatin are similar in treating one of the most common and dangerous infections in ICU patients.

These findings are similar to those reported in prospective, randomized, and comparative studies for ciprofloxacin in the therapy of nosocomial pneumonia [20, 68-70]. In two trials [20, 68], imipenem was used as the comparative medicine, ceftazidime in one, and the comparator therapy was not standardized in another [70]. Quinolones and comparator antibiotics had similar efficacy in individual studies and in a meta-analysis of all quinolone trials for nosocomial pneumonia, with a pooled odds ratio for the clinical cure of 1.12 (95 percent confidence interval, 0.80–1.55).

There was a decreased tendency for the establishment of resistant infections, particularly P. aeruginosa, among levofloxacin-treated patients in studies that reported data on microbiological outcomes [20, 64, 68].

Despite the limited number of studies on critically sick patients, there has been a steady increase in the usage of levofloxacin in ICUs across Spain. In 2004, levofloxacin was the 10th most commonly prescribed antimicrobial agent, 11th among those used in patients with extra-ICU nosocomial infection, and 13th among antibiotics used to treat ICU-acquired illness (annual report ENVIN-UCI 2004, unpublished data).

In a study evaluating the use of levofloxacin in critically ill patients including 30 Spanish ICUs and a review of 543 prescriptions for this medicine, 32.2 percent of all indications corresponded to the treatment of nosocomial infections, particularly those acquired in the ICU [34]. In a subsequent review of data from this trial focusing on the use of levofloxacin for the treatment of pneumonia [72], levofloxacin was given to 39 patients with ICU-acquired pneumonia, the majority of whom had mechanical ventilation [87.2 percent]. Combined antibiotic treatment was given to 25 patients, and in 78.3 percent of the cases, the response was satisfactory.

Although the goal of this descriptive study was not to evaluate the efficacy of levofloxacin in VAP, data on its use show that it is a viable option in this clinical context.

Criteria to consider while selecting levofloxacin for vap treatment ( heading)

Regulatory agencies have approved a wide variety of antimicrobial medicines for use in the treatment of VAP based on clinical trials. The inclusion of one of these drugs in therapeutic guidelines recommended by prestigious scientific societies [6, 19]; characteristics of individual VAP patients (immunosuppression, allergy to -lactams, renal dysfunction, etc. ); risk factors for multidrug-resistant pathogens; possibility of switching to the oral route (sequential treatment); and cost (drug and monitoring of plasma concentrations). The US Food and Drug Administration (FDA) has approved levofloxacin for the treatment of nosocomial pneumonia, including those caused by P. aeruginosa[73].

The following are the criteria to consider while choosing levofloxacin over other antimicrobial drugs for the empirical and directed treatment of VAP:

1 Patient has a known or suspected b-lactam antibiotic allergy. -lactam antibiotics make up the majority of antibiotics used in the treatment of VAP, both empirical and directed. In this clinical setting, levofloxacin is the primary antibiotic of choice, either as monotherapy (early-onset VAP, no danger of multiresistant infections) or in combination with aminoglycosides and/or glycopeptides (late-onset VAP, risk for multiresistant pathogens).

When using levofloxacin as a monotherapy, keep in mind that resistance to levofloxacin and other quinolones against P. aeruginosa and Strep. pneumonia has been described in patients with repeated hospitalizations and previous exposure to fluoroquinolones [74, 75].

2 patients with a renal function impairment. In patients with renal impairment or at high risk of renal failure, levofloxacin is an option for aminoglycosides for empirical treatment with a combination of antibiotics (advanced age, hemodynamic instability). If many nephrotoxic medicines, such as vancomycin, amphotericin, or cyclosporine, are being used at the same time, levofloxacin is the antibiotic of choice.

Antibiotic coverage must be extended to intracellular infections. Patients who are immunocompromised due to an underlying condition or medications taken might develop VAP, which can be caused by a variety of bacteria, including Legionella pneumophila. Antibiotic coverage for this disease is especially important in hospitals where L. pneumophila is endemic or has been found in local water systems. Levofloxacin has adequate antibacterial action against this pathogen [76] and has been shown to be beneficial in endemic or outbreak situations [77].

Lung tissue and respiratory secretions have high amounts. The ability of levofloxacin to penetrate diverse tissues, particularly alveoli and lung tissue [21–23], is linked to high antibiotic concentrations in the infection site, as opposed to limited penetration and low levels in the lung tissue when aminoglycosides are used [78]. Levofloxacin concentrations in lung tissue are higher than ciprofloxacin concentrations when given at recommended levels according to product technical specifications [79].

As a result, despite the fact that higher inhibitory concentrations for P. aeruginosa are required with this antibiotic, levofloxacin has different pharmacodynamic interactions at 500 mg/12 h compared to ciprofloxacin at 400 mg/12 h [79, 80]. Both antibacterial medicines are equal in terms of pharmacodynamic indicators; however, no comparative study has been conducted to analyze the clinical differences between the treatments.

Sequential therapy may be possible in patients who have had a good clinical response. The availability of both intravenous and oral forms of the drug, as well as demonstration of sufficient bioavailability to assure plasma equal concentrations, are the minimal conditions for using sequential therapy. Levofloxacin, a novel quinolone that fits both conditions, has been proven to be effective in the treatment of hospitalized patients with a low degree of disease in many studies [49-57, 81].

Up to one-third of critically sick patients receiving levofloxacin, medication was converted to the oral route in the ICU environment [34]. These are patients who were treated with antibiotics as monotherapy while they had less severe clinical problems. When switching from the intravenous to the oral route of administration was possible, cost-effectiveness studies of levofloxacin compared to ceftriaxone for the treatment of community-acquired pneumonia found that oral administration of the drug was associated with lower resource consumption, primarily due to differences in hospitalization costs [82, 83]. T

However, in critically ill patients admitted to the ICU, this factor is less important.

6 Synergistic activity against P. aeruginosa in a combination therapy Treatment with a combination of antibiotics is recommended in the treatment of infections caused by P. aeruginosa in order to broaden the antibacterial spectrum of empirical treatment and improve the bactericidal power of directed therapy [6, 19], even though there is no evidence that combined antibiotic treatment is more effective than monotherapy with an active antimicrobial agent in the treatment of infections caused by this pathogen [84, 85].

When taken in combination with cefepime, ceftazidime, imipenem, and piperacillin/tazobactam, levofloxacin has exhibited varied rates of synergism, showing that combining these antibiotics boosts its efficacy against P. aeruginosa[80, 86-88]. Despite the fact that ciprofloxacin’s MIC for P. aeruginosa is four times lower than levofloxacin’s (0.124 mg/L vs. 0.5 mg/L), studies have shown that the percentage of strains sensitive to both antibiotics is quite similar [89-92].

Reduced ability to generate resistance in P. aeruginosa. In vitro testing revealed that the combination of imipenem and levofloxacin had a lesser ability to generate resistance against P. aeruginosa [93, 94]. Another in-vitro investigation with different strains of P. aeruginosa revealed that levofloxacin has a stronger bactericidal activity than ciprofloxacin [95]. These findings back up the findings of several comparative clinical studies on the use of quinolones (ciprofloxacin or levofloxacin) in the treatment of nosocomial pneumonia, in which quinolones were shown to reduce the selection of resistant strains.
There is no need to monitor drug concentrations in the plasma to ensure efficacy and minimize harm. According to pharmacodynamic data on levofloxacin, it is recommended to prescribe doses of 500 mg/12 h when the drug is given empirically for the treatment of nosocomial pneumonia, including the presence of P. aeruginosa[31, 32], though the new 750 mg formulation may possibly improve pharmacodynamic parameters related to greater effectiveness. Unlike aminoglycosides and vancomycin, there is no need to monitor plasma medication concentrations to limit the risk of toxicity.