What is the minimum effective dose of ciprofloxacin for treating uncomplicated urinary tract infections in women. How does short-course ciprofloxacin therapy compare to conventional 7-day treatment. Which ciprofloxacin regimen provides the best balance of efficacy and convenience for UTI patients.

Understanding Ciprofloxacin as a UTI Treatment

Ciprofloxacin is a widely prescribed antibiotic for treating urinary tract infections (UTIs). As a fluoroquinolone antibiotic, it targets the bacteria commonly responsible for UTIs, such as Escherichia coli. However, determining the optimal dosage and treatment duration is crucial for maximizing efficacy while minimizing side effects and the risk of antibiotic resistance.

A comprehensive study conducted by Iravani et al. aimed to identify the minimum effective dosing regimen of ciprofloxacin for acute, symptomatic, uncomplicated lower UTIs in women. This research provides valuable insights into optimizing UTI treatment protocols.

Why is optimizing ciprofloxacin dosage important?

• Minimizes unnecessary antibiotic exposure
• Reduces the risk of side effects
• Helps prevent the development of antibiotic resistance
• Improves patient compliance with shorter treatment courses
• Potentially lowers healthcare costs

Study Design: Evaluating Ciprofloxacin Efficacy

The research comprised three multicenter, prospective, randomized, double-blind trials involving a total of 970 evaluable patients diagnosed with UTIs. These studies compared various ciprofloxacin dosing regimens to each other and to norfloxacin, another commonly used antibiotic for UTIs.

Key aspects of the study design:

• Ciprofloxacin doses ranged from 200 mg to 500 mg daily
• Treatment durations varied from 1 to 7 days
• Norfloxacin was administered at 400 mg twice daily for 7 days as a comparison
• Primary efficacy measure: bacteriologic eradication at the end of therapy
• Secondary measure: clinical success rate

Ciprofloxacin Dosage Regimens: Comparing Efficacy

The study evaluated several ciprofloxacin dosing regimens to determine the most effective approach for treating uncomplicated UTIs. Here’s a breakdown of the key findings:

Study 1: Single-dose vs. 7-day treatment

• 500 mg single dose: 89% bacteriologic eradication, 94% clinical success
• 250 mg twice daily for 7 days: 98% bacteriologic eradication, 100% clinical success

Study 2: Comparing 3-day and 7-day regimens

• 100 mg twice daily for 3 days: 93% eradication, 97% clinical success
• 250 mg twice daily for 3 days: 90% eradication, 100% clinical success
• 250 mg twice daily for 7 days: 93% eradication, 98% clinical success

Study 3: Ciprofloxacin vs. Norfloxacin

• Ciprofloxacin 500 mg once daily for 3 days: 92% eradication, 97% clinical success
• Ciprofloxacin 500 mg once daily for 5 days: 90% eradication, 97% clinical success
• Norfloxacin 400 mg twice daily for 7 days: 94% eradication, 97% clinical success

Short-Course vs. Conventional Therapy: A Comparison

One of the most significant findings of this study was the comparison between short-course (3 or 5 days) and conventional (7-day) ciprofloxacin therapy. The results demonstrated that short-course treatment was statistically equivalent to the longer, conventional approach in terms of both bacteriologic eradication and clinical success rates.

Advantages of short-course therapy:

• Reduced overall antibiotic exposure
• Potentially fewer side effects
• Improved patient compliance
• Cost-effective approach
• Decreased risk of developing antibiotic resistance

These findings suggest that healthcare providers can confidently prescribe shorter courses of ciprofloxacin for uncomplicated UTIs without compromising treatment efficacy.

Single-Dose Ciprofloxacin: Efficacy Concerns

While the convenience of a single-dose antibiotic regimen is appealing, the study revealed that single-dose ciprofloxacin therapy was statistically less effective than conventional 7-day treatment. This finding highlights the importance of balancing convenience with clinical efficacy when determining optimal treatment protocols.

Factors to consider with single-dose therapy:

• Lower bacteriologic eradication rates
• Potential for incomplete symptom resolution
• Increased risk of recurrence or treatment failure
• Need for follow-up and possible retreatment

Despite these concerns, single-dose therapy may still be appropriate in certain clinical situations, such as for patients with mild symptoms or those at low risk for complications. However, healthcare providers should carefully weigh the benefits and risks before recommending this approach.

Identifying the Minimum Effective Dose

Based on the comprehensive analysis of various dosing regimens, the study concluded that ciprofloxacin at a dosage of 100 mg twice daily for 3 days was the minimum effective dose for treating uncomplicated UTIs in women. This finding has significant implications for clinical practice and antibiotic stewardship efforts.

Benefits of using the minimum effective dose:

• Reduces unnecessary antibiotic exposure
• Minimizes the risk of adverse effects
• Helps preserve antibiotic efficacy for future use
• Potentially improves patient adherence to treatment
• May lead to cost savings for patients and healthcare systems

By identifying this optimal dosing regimen, healthcare providers can tailor their prescribing practices to achieve the best possible outcomes for patients with uncomplicated UTIs while promoting responsible antibiotic use.

Clinical Implications and Best Practices

The findings of this study have several important implications for clinical practice in the treatment of uncomplicated UTIs. Healthcare providers should consider the following recommendations when prescribing ciprofloxacin:

1. Opt for short-course therapy: 3-day regimens offer comparable efficacy to 7-day treatments with potential additional benefits.
2. Use the minimum effective dose: 100 mg twice daily for 3 days is sufficient for most uncomplicated UTIs.
3. Avoid single-dose therapy: While convenient, it may lead to lower eradication rates and increased risk of treatment failure.
4. Consider patient factors: Tailor treatment based on individual patient characteristics, severity of symptoms, and risk factors for complications.
5. Monitor for side effects: Although short-course therapy may reduce the risk, patients should be informed about potential adverse reactions.
6. Emphasize compliance: Educate patients on the importance of completing the full course of antibiotics, even if symptoms improve quickly.
7. Follow up: Ensure patients understand when to seek further medical attention if symptoms persist or worsen.

By implementing these evidence-based practices, healthcare providers can optimize the use of ciprofloxacin for UTI treatment, improving patient outcomes while promoting antibiotic stewardship.

Future Directions in UTI Treatment Research

While this study provides valuable insights into ciprofloxacin dosing for uncomplicated UTIs, there are still areas that warrant further investigation:

Potential research topics:

• Long-term outcomes of short-course vs. conventional therapy
• Impact of different dosing regimens on antibiotic resistance patterns
• Efficacy of ciprofloxacin in specific patient populations (e.g., elderly, immunocompromised)
• Comparison of ciprofloxacin to newer antibiotics for UTI treatment
• Development of personalized treatment algorithms based on patient characteristics and bacterial susceptibility
• Exploration of non-antibiotic alternatives or adjunct therapies for UTI management

Continued research in these areas will help refine UTI treatment strategies, ensuring that patients receive the most effective and appropriate care while minimizing the risks associated with antibiotic use.

Antibiotic Stewardship and UTI Management

The findings of this study align well with the principles of antibiotic stewardship, which aims to optimize antibiotic use to improve patient outcomes, reduce adverse effects, and combat the growing threat of antibiotic resistance. By identifying the minimum effective dose and demonstrating the efficacy of short-course therapy, this research supports more judicious use of ciprofloxacin in UTI treatment.

Key aspects of antibiotic stewardship in UTI management:

• Accurate diagnosis: Ensure UTIs are properly diagnosed before initiating antibiotic therapy
• Appropriate antibiotic selection: Choose antibiotics based on local resistance patterns and patient factors
• Optimal dosing: Use the minimum effective dose to achieve desired outcomes
• Shortest effective duration: Implement short-course therapy when appropriate
• Regular monitoring: Track antibiotic prescribing patterns and resistance trends
• Education: Provide ongoing training for healthcare providers on best practices in UTI management
• Patient engagement: Educate patients on proper antibiotic use and UTI prevention strategies

By incorporating these principles into clinical practice, healthcare providers can contribute to more sustainable and effective UTI management while helping to preserve the efficacy of important antibiotics like ciprofloxacin for future use.

Short-course ciprofloxacin treatment of acute uncomplicated urinary tract infection in women. The minimum effective dose. The Urinary Tract Infection Study Group [corrected]

Clinical Trial

. 1995 Mar 13;155(5):485-94.

A Iravani 
¹
, A D Tice, J McCarty, D H Sikes, T Nolen, H A Gallis, E P Whalen, R L Tosiello, A Heyd, S F Kowalsky, et al.

Affiliations

Affiliation

• ¹ Central Florida Medical Research Center, Orlando.

• PMID:

  7864704

Clinical Trial

A Iravani et al.

Arch Intern Med.

1995.

. 1995 Mar 13;155(5):485-94.

Authors

A Iravani 
¹
, A D Tice, J McCarty, D H Sikes, T Nolen, H A Gallis, E P Whalen, R L Tosiello, A Heyd, S F Kowalsky, et al.

Affiliation

• ¹ Central Florida Medical Research Center, Orlando.

• PMID:

  7864704

Abstract

Background:

Three studies were undertaken to determine the minimum effective dosing regimen of ciprofloxacin for the treatment of acute, symptomatic, uncomplicated lower urinary tract infection.

Methods:

All studies were multicenter, prospective, randomized, double-blind trials. A total of 970 evaluable patients with a diagnosis of urinary tract infection received oral ciprofloxacin (200 mg to 500 mg daily in one or two divided doses for 1, 3, 5, or 7 days) or norfloxacin (400 mg twice daily [BID] for 7 days). The primary measure of efficacy was bacteriologic eradication at the end of therapy.

Results:

In study 1, bacteriologic eradication was reported in 95 (89%) and 101 (98%) of patients in the groups who received ciprofloxacin, 500-mg single dose and 250 mg BID for 7 days, respectively. Clinical success occurred in 101 patients (94%) who received a 500-mg single dose and in 103 patients (100%) who were administered 250 mg BID for 7 days. In study 2, eradication rates in the groups who received ciprofloxacin, 100 mg BID for 3 days, 250 mg BID for 3 days, and 250 mg BID for 7 days, were 98 (93%), 95 (90%), and 98 (93%), respectively. Clinical success was reported in 102 (97%), 105 (100%), and 104 (98%) of the patients, respectively. In study 3, the eradication rates in the groups who received ciprofloxacin in dosages of 500 mg once daily for 3 days and 500 mg once daily for 5 days and norfloxacin in a dosage of 400 mg BID for 7 days were 137 (92%), 134 (90%), and 133 (94%) of the women, respectively. Clinical success was the same (97%) in all three groups. Overall, short-course (either 3- or 5-day) therapy with ciprofloxacin was statistically equivalent to conventional (7-day) therapy with either ciprofloxacin or norfloxacin. Single-dose ciprofloxacin therapy was statistically less effective than conventional treatment.

Conclusions:

Ciprofloxacin at a dosage of 100 mg BID for 3 days was the minimum effective dose for the treatment of uncomplicated urinary tract infection in women.

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Uses, side effects, and alternatives

Cipro, or ciproflaxin, is an antibiotic that doctors use to treat urinary tract infections. However, it may not be suitable during pregnancy or for people with certain health risks. In these cases, a doctor will offer an alternative.

For many people, Cipro is a safe treatment for a urinary tract infection (UTI). But it is not the only option.

The United States Foods and Drug Administration (FDA) warns doctors about prescribing Cipro to certain people, as there is a potential for serious side effects.

Understanding how Cipro works and its possible side effects, can help a person make an informed choice about their UTI treatment.

This article looks at Cipro for UTIs, its potential side effects, and when a person should see a doctor.

Cipro is the brand name for ciprofloxacin, which is a type of antibiotic in the fluoroquinolone class.

Doctors use fluoroquinolones to treat various bacterial infections. The one they prescribe depends on the underlying infection, and if the bacteria are resistant to a specific drug.

Fluoroquinolones work by interfering with bacteria’s ability to replicate and grow. This action then kills the infection.

Cipro is a widely usedantibiotic because it is:

• effective at killing bacteria
• generally safe to use
• relatively affordable

It is a good choice for treating a wide variety of bacterial infections caused by both Gram-positive and Gram-negative bacteria. This means that doctors can prescribe it without waiting for test results to see what specific type of bacteria is causing an infection.

It is also available in multiple formats, such as:

• tablets
• liquids
• IV solutions

So, doctors can find an option for most people. As a result, medical professionals may prescribe it frequently.

Doctors often prescribe Cipro for people with UTIs, as these infections are often bacterial and respond well.

However, the FDA advises that the serious side effects may outweigh the benefits for people with uncomplicated UTIs who have other treatment options.

When a person takes Cipro for a UTI, they must follow the doctor’s instructions exactly. Usually, the medication is an oral tablet or liquid, and the course of treatment lasts for up to 14 days.

A person must complete the full course. Even if their symptoms start to ease, it is essential to finish all the medication to eliminate the infection completely. This is to prevent antibiotic resistance.

People should not stop treatment early unless a doctor tells them otherwise. Doing so may allow the infection to return and it could be worse.

When taking Cipro or any other antibiotic for a UTI, drinking extra fluids and urinating often can help flush out the infection and speed up recovery.

Side effects are usually mild with Cipro. They may include:

• nausea
• diarrhea
• vomiting
• abdominal pain
• rash
• abnormal liver function tests

They generally clear up without treatment once a person stops taking Cipro.

Less common side effects may include:

• headache
• abdominal pain
• pain in the extremities
• pain in the feet
• dizziness or fainting
• difficulty sleeping
• palpitations, flutters, or rapid heartbeat
• high or low blood pressure
• heart attack
• fever
• yellowing of the skin or eyes
• dark urine
• oral yeast infections
• intestinal tears
• gastrointestinal bleeding and blood in the stool

Rarely, Cipro can cause a severe allergic reaction. Anyone who experiences any of the following symptoms should seek immediate medical care:

• hives, forming an itchy or irritating skin rash
• trouble swallowing or breathing
• swelling of the tongue, lips, or face
• tightness in the throat

Fluoroquinolone antibiotics also carry a boxed warning. This is the most serious warning from the FDA, and it means that they consider the drug to be potentially dangerous in some capacity.

The boxed warning for Cipro is for three separate risks.

Tendinitis

Firstly, Cipro may increase the risk of tendinitis, tendon rupture, and peripheral neuropathy in people of all ages. This can lead to serious side effects, including:

• nerve pain and a sensation of pins and needles
• chronic pain
• burning, numbness, or weakness in the joints and muscles
• swelling and pain in the joints and tendons
• tendon rupture
• changes in the nerves of the hands, arms, feet, and legs

These symptoms may develop after just one or two doses and may continue for years. Doctors do not yet know if these issues are permanent.

The risk of tendinitis and tendon rupture is greater for people who are:

• more than 60 years of age
• taking corticosteroid drugs
• recipients of kidney, lung, or heart transplants

Muscle weakness

Secondly, fluoroquinolones may worsen muscle weakness in people who have myasthenia gravis. This is a chronic, neuromuscular condition that weakens the muscles in the body.

People who have myasthenia gravis should not take Cipro.

Nervous system

Finally, Cipro may cause side effects to the central nervous system (CNS), such as:

• nervousness
• agitation
• insomnia
• anxiety
• nightmares
• paranoia
• dizziness
• confusion
• tremors
• hallucinations
• depression
• suicidal thoughts

It is also important to understand that several other antibiotics have similar side effects, though they may affect a person in slightly different ways.

The FDA classifies Cipro as safe and effective for treating UTIs for most people, and that the risk of serious side effects is low. However, they are still possible and occur often enough for the FDA to warn that doctors should only use fluoroquinolones — such as Cipro — when they have no other treatment options.

Cipro may not be right for someone who is pregnant. Pregnant people should discuss all their treatment options with a doctor before deciding.

Some limited evidence suggests Cipro is excreted in breast milk. However, people who are nursing can use Cipro, but their doctor should monitor them for digestive upset and candidiasis. They should avoid breastfeeding for 3 to 4 hours after taking the medication. Doctors may also monitor the breastfed infants for signs of thrush and/or diarrhea.

People should discuss their options with a healthcare professional to find the best treatment.

Cipro can interact with other medications. This could change how Cipro works and may lead to serious side effects.

Many drugs may interact with fluoroquinolones, such as Cipro, including:

• warfarin
• theophylline
• phenytoin
• antiarrhythmic drugs, such as amiodarone and quinidine
• tricyclic antidepressants, such as imipramine and amitriptyline
• duloxetine
• cyclosporine
• drugs to treat diabetes, such as glimepiride and glyburide
• methotrexate
• clozapine
• corticosteroids

Again, people must always discuss current medications, vitamins, and supplements with a doctor before taking Cipro or another antibiotic.

The bacteria Escherichia coli, or E.coli, causes most cases of UTIs. Unfortunately, E. coli resistance to ciprofloxacin is increasing, meaning that the medical community may need to restrict the use of this antibiotic.

Therefore, doctors recommend other therapies for treating UTIs.

Other drugs that doctors may recommend for UTIs include:

• trimethoprim/sulfamethoxazole, or Bactrim- combo drug
• nitrofurantoin
• fosfomycin

However, some of these options may also have issues with bacterial resistance. Researchers are currently investigating new treatment options for UTIs and other bacterial infections, including combination drug therapy, vaccines, and small molecules that attack specific functions in the bacteria.

If someone suspects they have a UTI, they should see a doctor. While Cipro is an effective option for many people with uncomplicated UTIs, some doctors recommend other treatment options first.

Anyone concerned about taking Cipro, or its possible side effects, should discuss them with a doctor. By working directly with a medical professional, most people can find the right solution for their UTI.

Cipro, or ciprofloxacin, is a type of antibiotic. It belongs to the fluoroquinolone class. These antibiotics can treat a wide range of bacterial infections.

Cipro may be an option for people with urinary tract infections, or UTIs. However, the medication does come with a boxed warning from the FDA.

It may not be suitable to use in certain people, for example, those who have myasthenia gravis. Like all medications, using Cipro can come with some side effects. These can range from mild to more severe effects.

In some cases, doctors may prefer to use another antibiotic to treat UTIs.

New in the treatment of urinary tract infections: sustained release ciprofloxacin | Iremashvili V.V.

Urinary tract infections (UTIs) continue to be one of the most common infectious diseases. Thus, in Russia, the incidence of UTIs is about 1,000 cases per 100,000 population per year [1], and according to data obtained in the United States, this group of diseases annually causes 7 million visits and more than 1 million emergency visits to doctors [2]. The financial component of this problem is also significant, the cost of treatment of which in the United States alone reaches 2 billion dollars annually [3].

UTIs are also leading among nosocomial infections, accounting for about 40% of their total number. Bacteriuria develops in 25% of patients with a urethral catheter for more than a week, and thereafter the risk of its occurrence is 5% per day [4]. According to American data, the occurrence of nosocomial UTI increases the cost of treatment by 100–500 US dollars [5].
Contrary to a widespread misconception, the structure of the causative agents of most infectious diseases does not undergo significant changes over time. At the same time, the ongoing changes in the principles of treatment of such diseases are associated with various factors, including the deepening of knowledge about their pathogenesis, the identification of previously unknown pathogens, the emergence of new, more effective drugs, and the development of resistance of microorganisms to the antimicrobial agents used [6,7]. In the context of UTI, the latter factor is of the greatest importance.
The information obtained already in the first studies that Gram-negative microorganisms predominate in the structure of UTI pathogens is relevant to the present. According to current data, at least 80% of cases of community-acquired UTIs are caused by Escherichia coli, among other pathogens the most common are Staphylococcus saprophyticus, Klebsiella, Enterobacter and Proteus spp., as well as enterococci [8].
The frequency of nosocomial UTIs caused by Escherichia coli is significantly lower and ranges from 35 to 50%. At the same time, other pathogens are much more common, in addition, according to some studies, the prevalence of Escherichia spp. exceeds 10% [9-eleven].
If the microbiological structure of UTI pathogens remains stable, then the sensitivity of microorganisms to antibacterial drugs changes significantly over time. The latter greatly complicates the treatment of this widespread group of diseases, which in the vast majority of cases is carried out empirically. For a long time, drugs such as ampicillin and later co-trimoxazole (trimethoprim/sulfamethoxazole) were considered the first line in the treatment of UTIs, but in recent years enough data have been accumulated to state that in many regions of the world, including Russia, North and South America and Western Europe, the resistance of UTI pathogens to these antibacterial agents has reached a critical level – more than 15-20% [12-16]. When this level of resistance is reached, the use of drugs is considered inappropriate [17].
In connection with the above, drugs from the group of fluoroquinolones, characterized by a wide spectrum of antibacterial activity and convenient pharmacological properties, have now come to the fore in the treatment of UTIs.
According to both current European and North American clinical guidelines, fluoroquinolones are considered as first-choice drugs in the treatment of community-acquired UTIs in adults [17,18]. Despite a fairly long period of their widespread use, the resistance of pathogens of community-acquired UTIs to this group of drugs continues to be low (Table 1).
It should be noted that despite the fact that the sensitivity of pathogens of nosocomial UTIs to fluoroquinolones is significantly lower than that of community-acquired ones, fluoroquinolones, in particular, ciprofloxacin, still significantly outperform all other oral preparations in this respect [23].
Ciprofloxacin was the first fluoroquinolone with a broad spectrum of antibacterial activity, capturing most of both gram-positive and gram-negative microorganisms, including Pseudomonas aeruginosa. Due to its high efficiency and good tolerability, this drug has been widely used since the second half of the 80s of the last century in the treatment of not only UTIs, but also sexually transmitted infections, skin and skeletal infections, and gastrointestinal infections [24].
It should be noted that the above-described changes in the sensitivity of microorganisms to antibacterial drugs threaten the high effectiveness of fluoroquinolones, which is currently taking place. One of the important reasons for the development of resistance is non-compliance by patients with the rules for taking drugs, leading to fluctuations in their concentration in the blood, and as a result, antibacterial activity [7]. The latter contributes to the selection of resistant strains. One way to address this problem is to develop more patient-friendly sustained-release formulations. This review considers one such drug, sustained release ciprofloxacin.
When creating this form of the drug, the researchers faced several challenges. Firstly, the new form should at least not be inferior in its pharmacological parameters to the existing ones (standard ciprofloxacin, taken 2 times a day). The main pharmacokinetic parameters by which delayed-release ciprofloxacin was evaluated were the ratio of the area under the concentration-time curve (AUC) and the minimum inhibitory concentration (MIC) and the ratio of the maximum plasma concentration (MCP) to the MIC, and the latter parameter for the delayed form should exceed that for the standard. The importance of these indicators is determined by the fact that in the case of fluoroquinolones, including ciprofloxacin, their clinical efficacy is determined by the concentration in blood plasma [25].
In order to achieve these indicators, the developers needed to achieve stable absorption of the drug in the stomach, while not exceeding the safe level of the drug in blood plasma. This was achieved by combining two “layers” of different salts of the drug in the composition of the tablets, constituting 35 and 65% of the total dose, respectively. A smaller part is absorbed much faster, allowing early (1-4 hours after ingestion) to reach the MCP, while the majority is absorbed for a longer time, providing high AUC values ​​[26]. The drug is completely absorbed in the stomach. The presented data indicate the importance of taking the tablets in their original state and the impossibility of “dividing” one tablet into several doses.
The main pharmacokinetic parameters of sustained release ciprofloxacin are presented in Table 2. The AUC after a single dose of the new form of the drug at a dose of 500 or 1000 mg corresponds, and the MCP significantly exceeds that for a double dose of standard ciprofloxacin (2 tablets of 250 and 500 mg, respectively). It should be noted that the MCP after taking sustained release ciprofloxacin at a dose of 500 and 1000 mg does not go beyond safe values.
Food intake does not significantly affect the absorption of sustained release ciprofloxacin. In addition, this drug is safe and does not require dose adjustment in the elderly, patients with stable cirrhosis of the liver (for a dose of 500 and 1000 mg) and renal insufficiency (for a dose of 500 mg). In patients with renal insufficiency, dose adjustment is necessary when taking 1000 mg, similar to that when taking the standard drug at a dose of 500 mg 2 times a day. About 35% of the dose of both standard and sustained release ciprofloxacin is excreted unchanged in the urine [28].
The concentrations of the active substance in the urine and prostate when taking sustained release ciprofloxacin significantly exceed those necessary to inhibit the growth of uropathogenic microorganisms. In addition, these indicators also exceeded those for the standard drug, and this may indicate a potentially higher clinical efficacy of the new form, which was confirmed by computer simulation data [28].
The clinical efficacy of sustained-release ciprofloxacin in the treatment of UTIs has been extensively studied in many studies, many of which were compared with other antibacterial drugs, primarily with standard ciprofloxacin, whose high efficacy is well known.
In a randomized, double-blind, multicenter study that included 891 patients with uncomplicated UTI, the efficacy of sustained-release ciprofloxacin (500 mg 1 time per day for 3 days) was compared with that of the standard drug (250 mg 2 times a day for 3 days) [29]. The clinical and bacteriological efficacy of therapy was evaluated twice: 4–11 and 25–50 days after its completion. These rates were higher for extended release ciprofloxacin, although the differences did not reach statistical significance. Moreover, at follow-up, it was noted that patients treated with sustained-release ciprofloxacin were less likely to experience bacteriological and clinical relapses of the disease (1.7 and 5.0% compared with 4.9and 7. 4% among those receiving the standard drug), which seems to reflect the pharmacokinetic differences discussed above.
The high clinical efficacy of sustained release ciprofloxacin 500 mg in the treatment of uncomplicated UTIs was also confirmed in a large-scale open study that included 7360 women and conducted in the United States. The effectiveness of treatment was 91.3% and did not depend on age, race and social status [28].
The efficacy of sustained-release ciprofloxacin in patients with complicated UTIs and acute pyelonephritis was also studied in a randomized, double-blind, multicenter, phase III study that included 435 patients [30]. Treatment was with standard ciprofloxacin (500 mg twice daily) or sustained release ciprofloxacin (1000 mg once daily) for 7–14 days. The bacteriological and clinical efficacy of the treatment was assessed 5–11 and 28–42 days after the end of the drug intake.
In general, the results of this study were consistent with those obtained in a study on the effectiveness of ciprofloxacin with a sustained release in patients with uncomplicated UTI. This drug was more effective both clinically and bacteriologically, but the differences were not statistically significant. At re-examination (after 28–42 days), the persistence of the same or the appearance of new microorganisms in the urine was significantly less common among those receiving the sustained release form (5.6 and 11.7% compared with 90 and 19.1%, respectively), clinical relapses were also significantly more frequent among those receiving standard ciprofloxacin (4 and 9%, respectively). The high rate of bacteriological and clinical relapses noted in this study is explained by the significant number of patients with complicated UTIs, including patients with urethral catheter, acute urinary retention, and neurogenic bladder.
Sustained release ciprofloxacin, like the standard form of this drug, is well tolerated. Less than 1% of patients who took the drug at a dose of 500 mg and about 5% at a dose of 1000 mg stopped treatment due to the development of significant side effects, which does not exceed those for the standard form [28]. The most common side effects of ciprofloxacin are gastrointestinal disturbances (nausea, diarrhea) and headaches.
The interaction of sustained release ciprofloxacin with other pharmacological agents is not expected to differ from that of standard ciprofloxacin [31]. The absorption of this drug is slowed down when combined with omeprazole, didanosine, sucralfate, as well as substances containing di- and trivalent cations, including magnesium, calcium and iron. Ciprofloxacin inhibits the activity of hepatic microsomal enzymes, thus inhibiting the metabolism of theophylline, cyclosporine, glyburide and warfarin. When combining the intake of any form of ciprofloxacin with the latter, it is necessary to monitor the state of the blood coagulation system.
Thus, due to a significant increase in the resistance of UTI pathogens to previously used oral antibiotics, drugs from the fluoroquinolone group have now come to the fore in the treatment of this group of diseases. A new form of one of the most effective representatives of this group, sustained release ciprofloxacin (Ifitipro OD, etc. ), is a highly effective and well-tolerated drug that is part of the first choice antibacterial agents in the treatment of UTIs. The pharmacokinetic characteristics of sustained release ciprofloxacin are superior to those of the standard form of the drug, which is reflected in a slightly higher clinical efficacy. Given the ease of administration, it can be expected that the use of this form will prevent or slow down the development of resistance of UTI pathogens to ciprofloxacin.

Literature
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2. Schappert SM. Ambulatory care visits to physician offices, hospital outpatient departments, and emergency departments: United States, 1997. Vital Health Stat 13. 1999; 143:1–39.
3. Rosenberg M. Pharmacoeconomics of treating uncomplicated urinary tract infections. Int J Antimicrobial Agents. 1999; 11:247–251.
4. Stamm WE. Scientific and clinical challenges in the management of urinary tract infections. Am J Med 2002; 113 (1A): 1S–4S.
5. Tambyah PA, Knasinski V, Maki DG. The direct costs of nosocomial catheter–associated urinary tract infection in the era of managed care. Infect Control Hosp Epidemiol 2002; 23:27-31.
6. Iremashvili VV. Urinary tract infections – a modern view of the problem. Russian medical journal. 2007; 15 (29): 2231–2236.
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8. HoodonTM. Practice guidelines for urinary tract infections in the era of managed care. Int J Antimicrobial Agents. 1999; 11:241–245.
9. Mathai D, Jones RN, Pfaller MA. Epidemiology and frequency of resistance among pathogens causing urinary tract infections in 1,510 hospitalized patients: a report from the SENTRY Antimicrobial Surveillance Program (North America). Diagn Microbiol Infect Dis 2001; 40:129-136.
10. Bouza E, San Juan R, Munoz P, Voss A, Kluytmans J, on Behalf of the Co-operative Group of the European Study Group on Nosocomial Infections (ESGNI). A European perspective on nosocomial urinary tract infections I. Report on the microbiology workload, etiology and antimicrobial susceptibility (ESGNI–003 study). Clin Microbiol Infect 2001; 7:523-531.
11. Johansen T.E. Nosocomially acquired urinary tract infections in urology departments. Why an international prevalence study is needed in urology. Int J Antimicrob Agents 2004; 23 (Suppl. 1): S30-S34.
12. Wright SW, Wrenn KD, Haynes ML. Trimethoprim–sulfamethoxazole resistance among urinary coliform isolates. JG Intern Med. 1999; 14:606–609.
13. Gupta K, Sahm DF, Mayfield D, Stamm WE. Antimicrobial resistance among uropathogens that cause community acquired urinary tract infections in women: a nationwide analysis. Clin Infect Dis. 2001; 33:89–94.
14. Gordon KA, Jones RN. Susceptibility patterns of orally administered antimicrobials among urinary tract infection pathogens from hospitalized patients in North America: comparison report to Europe and Latin America. Results from the SENTRY Antimicrobial Surveillance Program (2000). Diagn Microbiol Infect Dis 2003; 45:295–301.
15. Rafalsky V.V., Strachunsky L.S., Krechikova O.I. et al. Resistance of causative agents of outpatient urinary tract infections according to multicenter microbiological studies UTIAP-I and UTIAP-II. Urology 2004; #2: 13–17.
16. Gobernado M, Valdes L, Alos JI, et al. Antimicrobial susceptibility of clinical Escherichia coli isolates from uncomplicated cystitis in women over a 1–year period in Spain. Rev Esp Quimioterap. 2007; 20:68–76.
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19. Karlowsky JA, Thornsberry C, Jones ME, et al. Susceptibility of antimicrobial-resistant urinary Escherichia coli isolates to fluoroquinolones and nitrofurantoin. Clin Infect Dis 2003; 36(2): 183–187.
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Ciprolet 500 tablets

Ciprolet® (Ciprolet)

tablets 250 and 500 mg

International generic name: Ciprofloxacin (Ciprofloxacine).
Dosage form: coated tablets
Pharmacotherapeutic group: antibacterial drugs – quinolone derivatives.
ATX code: J01MA06.
Chemical name: 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-liperazinyl)-3-quinoline carboxylic acid hydrochloride monohydrate

Composition
Ciprolet – 250: 1 coated tablet contains Ciprofloxacin 250.0 mg, Corn starch 57.87 mg, microcrystalline cellulose 7. 5 mg, croscaramellose sodium 10.0 mg, colloidal an silicon hydrate 5.0 mg, talc 7.0 mg, magnesium stearate 3.510 mg, hypromellose 6.0 mg, sorbic acid 0.1 mg, titanium dioxide 2.5 mg, macrogol 1.7 mg, polysorbate 0.1 mg, dimethicone 0.1 mg

Ciprolet – 500: 9006 9 1 coated tablet contains ciprofloxacin hydrochloride monohydrate at a dose equivalent to 500 mg of ciprofloxacin and excipients – microcrystalline cellulose 5.0 mg, croscaramelose sodium 20 mg, corn starch 37.25 mg, magnesium stearate 4.5 mg, colloidal silicon dioxide 5.0 mg, talc 8.5 mg, gi promellose 7.0 mg, sorbic acid 0.1 mg, titanium dioxide 2.5 mg, macrogol 1.7 mg, polysorbate 0.1 mg, dimethicone 0.1 mg

Pharmacological properties
Ciprolet is an antimicrobial agent of the fluoroquinolone group.

Pharmacodynamics
The mechanism of action of ciprofloxacin is associated with the effect on bacterial DNA gyrase (topoisomerase), which plays an important role in the reproduction of bacterial DNA. Ciprofloxacin has a rapid bactericidal effect on microorganisms that are both at the stage of rest and reproduction.
The spectrum of action of ciprofloxacin includes the following types of gram (-) and gram (-+-) microorganisms:
E. coli, Shigella, Salmonella, Citrobacler, Klebsiella, Enterobacter, Serratia, Hafnia, Edwardsiella Proteus (indole positive and indole negative), Providencia, Morganella, Yersinia, Vibrio. Aeromonas, Plesiomonas, Pasteurella, Haemophilus, Campylobacter, Pseudomonas, Legionella, Neisseria, Moraxella, Branhamella, Acinetobacter, Brucella, Staphylococcus, Sreptococcus agalactiae, Listeria, Corynebacterium, Chiamydia.
Ciprofloxacin is effective against beta-lactamase producing bacteria.
Sensitivity to ciprofloxacin varies in: Gardnerella, Flavobaclerium, Alcaligenes, Streptococcus faecalis, Streptococcus pyogenes, Streptococcus pneumonia, Streptococcus viridans, Mycoplasma hominis, Mycobacterium tuberculosis, Mycobacterium fortuitum.
Streptococcus faecium, Ureaplasma urealyticum, Nocardia asteroides are most often resistant.
Anaerobes, with some exceptions, are moderately susceptible (Peptococcus, Peptostreptococcus) or resistant (Bacteroides).
Ciprofloxacin has no effect on Treponema pallidum and fungi.
Resistance to ciprofloxacin develops slowly and gradually, plasmid resistance is absent. Ciprofloxacin is active against pathogens that are resistant to
, for example, beta-lactam antibiotics, aminoglycosides or tetracyclines.
Ciprofloxacin does not disturb the normal intestinal and vaginal microflora.

Pharmacokinetics
Cilrofloxacin is rapidly and well absorbed after taking the drug (bioavailability is 70-80%). Peak plasma concentrations are reached after 60-90 min. The volume of distribution is 2-3 l / kg. Plasma protein binding is negligible (20-40%). Ciprofloxacin penetrates well into organs and tissues. Approximately 2 hours after ingestion or intravenous administration, it is found in tissues and body fluids at many times higher concentrations than in blood serum.
Ciprofloxacin is excreted largely unchanged from the body, primarily via the kidneys.
The plasma half-life after both oral and intravenous administration is 3 to 5 hours.
Significant amounts of the drug are also excreted in the bile and feces, so only significant impairment of kidney function leads to a slowdown in excretion.

Indications
Treatment of uncomplicated and complicated infections caused by pathogens sensitive to the drug

• respiratory tract infections. In the outpatient treatment of pneumococcal pneumonia, ciprofloxacin is not a first-line drug, but it is indicated for pneumonia caused by, for example, Klebsiella, Enterobacter, bacteria of the genus Pseudomonas, Haemophilus influenzae, bacteria of the genus Branhamella, legionella, staphylococci;
• infections of the middle ear and paranasal sinuses, especially if caused by gram-negative bacteria, including bacteria of the genus Pseudomonas, or staphylococci;
• eye infections
• kidney and urinary tract infections
• skin and soft tissue infections
• bone and joint infections
• infections of the pelvic organs (including adnexitis and prostatitis)
• gonorrhea
• gastrointestinal infections
• infections of the gallbladder and biliary tract
• peritonitis
• sepsis;

Prevention and treatment of infections in immunosuppressed patients (eg, in immunosuppressant and neutropenic patients)
Selective bowel decontamination during treatment with immunosuppressants.

Dosage and administration

In severe infections, such as recurrent infections in patients with cystic fibrosis, infections of the abdominal cavity, bones and joints caused by Pseudomonas or staphylococci, as well as acute pneumonia caused by Streptococcus pneumoniae, the daily dose should be increased to 1.5 g (2×750 mg) orally if treatment is not carried out intravenously.
Acute gonorrhea and acute uncomplicated cystitis in women can be treated with a single dose of 250-500 mg. If the patient, due to the severity of the disease or due to other reasons, is unable to take coated tablets, it is recommended to start treatment with Ciprolet for intravenous infusion a day half the standard dose or 1 time per day the full standard dose.
Patients with impaired liver function:
No dose adjustment is required.

Patients on peritoneal dialysis:
In case of peritonitis, ciprofloxacin is administered orally at 0.5 g 4 times a day or the drug is added as a solution for infusion at a dose of 0.05 g 4 times a day for 1 p of dialysate intraperitoneally.

Duration of use
The duration of treatment depends on the severity of the disease, the clinical course and the results of bacteriological examination.
Availability of ciprolet in two dosage forms makes it possible to start treatment of severe infections intravenously and continue it orally.
It is recommended to continue treatment for at least 3 days after the normalization of temperature or the disappearance of clinical symptoms. The duration of treatment for acute uncomplicated gonorrhea and cystitis is 1 day. With infections of the kidneys, urinary tract and abdominal cavity – up to 7 days. With osteomyelitis, the course of treatment can be up to 2 months. For other infections, the course of treatment is 7-14 days. In patients with reduced immunity, treatment is carried out during the entire period of neutropenia.
Method of administration
Tablets should be swallowed without chewing with liquid. The drug can be taken regardless of food intake. Reception on an empty stomach accelerates the absorption of the active substance.

Side effects
Ciprofloxacin is well tolerated by patients.
During treatment with ciprofloxacin, the following, usually reversible, side effects may occur:
From the side of the cardiovascular system, in very rare cases – tachycardia, hot flashes, migraine, syncope
From the gastrointestinal tract and liver: nausea, vomiting, diarrhea, abdominal pain, flatulence, lack of appetite.
From the nervous system and psyche: dizziness, headache, fatigue, insomnia, agitation, tremor, in very rare cases, peripheral sensory disturbances, sweating, gait instability, seizures, seizures, fear and confusion, nightmares, depression, hallucinations, taste and smell disorders, visual disturbances (diplopia, chromatopsia), tinnitus, temporary hearing loss awn especially on high sounds. In the event of these reactions, you should immediately stop the drug and notify your doctor.
On the part of the hematopoietic system: eosinophilia, leukopenia, thrombocytopenia, very rarely – leukocytosis, thrombocytosis, hemolytic anemia.
Allergic and immunopathological reactions: skin rashes, itching, drug-induced fever, and photosensitivity; rarely – angioedema, bronchospasm, arthralgia, very rarely – anaphylactic shock, myalgia, Stevens-Johnson syndrome, Lyell’s syndrome, interstitial nephritis, hepatitis.
Musculoskeletal: There are isolated reports that the use of ciprofloxacin was accompanied by ruptures of the tendons of the shoulder, arms and Achilles tendon, requiring surgical intervention. If complaints appear, treatment should be discontinued.
Impact on laboratory parameters: especially in patients with impaired liver function, there may be a temporary increase in the level of transaminases and alkaline phosphatase; temporary increase in the concentration of urea, creatinine and bilirubin in the blood serum, hyperglycemia.

Contraindications

• hypersensitivity to ciprofloxacin and other quinolone drugs
• pregnancy
• lactation
• children and adolescence.

Caution
Ciprofloxacin should be used with caution in elderly patients. Patients with epilepsy, a history of seizures, vascular diseases and organic brain damage due to the threat of adverse reactions from the central nervous system, ciprofloxacin should be prescribed only for health reasons.
During treatment with ciprofloxacin, adequate hydration is necessary to prevent possible crystalluria.

Advice for road users
This medicinal product, even when used properly, may change the ability to concentrate to such an extent that the ability to drive a vehicle and operate machinery is reduced. This is especially true in cases of interactions with alcohol

Interaction with other drugs:
Simultaneous use of ciprofloxacin (by mouth) and drugs that affect the acidity of gastric juice (antacids) containing aluminum or magnesium hydroxide, as well as drugs containing calcium, iron and zinc salts, reduces the absorption of ciproflox cina. In this regard, Ciprolet should be taken 1-2 hours before or at least 4 hours after taking these drugs. With the simultaneous use of ciprofloxacin and theophylline, the concentration of theophylline in the blood plasma should be monitored and its dose adjusted, since an undesirable increase in the concentration of theophylline in the blood and the development of corresponding side effects may be observed.
With the simultaneous use of ciprofloxacin and cyclosporine in some cases, an increase in the concentration of serum creatinine was observed, therefore, in such patients, frequent (2 times a week) monitoring of this indicator is necessary.
Co-administration of ciprofloxacin and warfarin may increase the effect of warfarin. Animal studies have shown that very high doses of quinolones and some non-steroidal anti-inflammatory drugs (but not acetylsalicylic acid) can cause seizures. However, patients of this kind of drug interactions were not observed.
Ciprofloxacin may be used in combination with azlocillin and ceftazidime for Pseudomonas infections; with mezlocillin, azlocillin and other effective beta-lactam antibiotics – for streptococcal infections; with isoxazoylpenicillins, vancomycin – with staphylococcal infections, with metronidazole, clindamycin – with anaerobic infections.

Overdose
No specific antidote known. Routine emergency measures are recommended, as well as hemodialysis and peritoneal dialysis

Pharmaceutical information

Presentation
Blister containing 10 coated tablets (250 mg or 500 mg).
Storage conditions
In a dry, dark place at temperatures up to 25oC.