Use Of Levofloxacin Research Articles

Fluoroquinolone-Associated Tendinopathy: Does Levofloxacin Pose the Greatest Risk?

Fluoroquinolone antibiotics recently have gained increased national attention due to safety concerns. A well-described and serious adverse event associated with receipt of fluoroquinolones is tendinitis and tendon rupture. These tendon injuries can result in long-term sequelae, including chronic pain and mobility restrictions, and may warrant surgery. Due to the severity of these adverse events, a black box warning is included in the product labeling of all fluoroquinolones. In light of the mounting concerns surrounding fluoroquinolone-associated toxicities, the purpose of this clinical review is to provide a comprehensive summary of the risk of tendinopathy associated with levofloxacin, one of the most widely prescribed antibiotics in the United States, across in vitro, animal, and clinical studies, relative to other antibiotics. As part of this review, clinical presentation and onset, proposed mechanisms, patient-specific risk factors, and management of fluoroquinolone-induced tendon injury are summarized. Data were obtained from a comprehensive PubMed literature search and a review of U.S. Food and Drug Administration documents. Although tendinopathy is considered a fluoroquinolone class-wide toxicity, data from in vitro studies, animal studies, patient-level analyses, and large national and international surveillance reports suggest that levofloxacin, as well as its parent compound ofloxacin, possess higher propensities to cause tendon damage relative to other fluoroquinolones. Risk with ofloxacin and levofloxacin appears to be exposure dependent, with higher doses and longer durations being most commonly associated with tendinopathy. Other well-described patient risk factors for fluoroquinolone-associated tendinopathy include older age (older than 60 yrs), receipt of concomitant corticosteroid therapy, presence of renal dysfunction, and history of solid organ transplantation. Given widespread use of levofloxacin across patient care settings, knowledge of both patient- and drug-specific characteristics associated with increased risk of tendinitis and tendon rupture can promote safe use of levofloxacin and other fluoroquinolones.

МОЖЛИВОСТІ КОРЕКЦІЇ ДИСБІОЗУ КИШЕЧНИКА ПРИ ХРОНІЧНОМУ НЕКАЛЬКУЛЬОЗНОМУ ХОЛЕЦИСТИТІ У ХВОРИХ НА ЦУКРОВИЙ ДІАБЕТ ІІ ТИПУ

<p>РЕЗЮМЕ. У статті представлено комплексне обстеження та лікування 44 хворих на хронічний некалькульозний<br />холецистит при цукровому діабеті ІІ типу. У всіх хворих було виявлено больовий синдром з локалізацією в правому<br />підребер’ї, іноді – в епігастрії, ниючого характеру, з іррадіацією в поперек, праве плече та лопатку, який посилювався<br />після вживання жирної та смаженої їжі, а також диспептичний синдром у вигляді нудоти, відрижки повітрям,<br />постійного гіркого присмаку у роті, метеоризму, чергування проносів та запорів. Залежно від призначеного<br />лікування хворих поділили на дві клінічні групи. У І групу ввійшли 20 хворих, які в якості антибактеріальної<br />терапії отримували напівсинтетичний пеніцилін – ампіцилін. Хворі ІІ групи (24 хворих) отримували антимікробний<br />препарат з групи фторхінолонів – левофлоксацин. Усі хворі на ХНХ отримували пребіотик лактулозу. Застосування<br />левофлоксацину в поєднанні з лактулозою (Біофлоракс) є ефективнішим для корекції кишкового дисбіозу хворих<br />на ХНХ, ніж використання ампіциліну з відповідним пребіотиком.</p><p><br />Ключові слова : хронічний некалькульозний холецистит, цукровий діабет ІІ типу, дисбіоз кишечника, діагностика, лікування.</p>

Comparative in vitro efficacies of various antipseudomonal antibiotics based catheter lock solutions on eradication of Pseudomonas aeruginosa biofilms

Antibiotic lock technique (ALT) may be an adjunct therapy in treating catheter-related infections. The aim of this study was to determine the in vitro stability and efficacy of colistin, meropenem and levofloxacin alone or in combination with clarithromycin or heparin lock solutions against biofilm embedded Pseudomonas aeruginosa strains. The efficacy of antibiotic lock solutions was tested in an in vitro catheter biofilm model against P. aeruginosa isolated from catheter-related bacteremia. We observed that the use of meropenem, levofloxacin or colistin as a lock solution had potent bactericidal effects and could be prevented bacterial regrowth at 96 or 72 hours, respectively. When the tested antibiotics were used in combination with clarithromycin, the combinations were significantly more effective and rapid in eliminating P. aeruginosa colonization in biofilm than each of the antibiotics were used alone. Moreover, tested antibiotics in combination with heparin were not significantly different for killing effect against PA-1 and PA-27853 compared with that of each antibiotics alone. Tested catheter lock solutions may have promising adjuvants for treating infections caused by P. aeruginosa.

Rare Incidence of Ventricular Tachycardia and Torsades de Pointes in Hospitalized Patients With Prolonged QT Who Later Received Levofloxacin: A Retrospective Study

ObjectiveTo determine the incidence of ventricular tachycardia and ventricular fibrillation in patients with prolonged corrected QT interval (QTc) who received levofloxacin through retrospective chart review at a tertiary care teaching hospital in the United States. Patients and MethodsWe selected 1004 consecutive hospitalized patients with prolonged QTc (>450 ms) between October 9, 2009 and June 12, 2012 at our institution. Levofloxacin was administered orally and/or intravenously and adjusted to renal function in the inpatient setting. The primary outcome measure was sustained ventricular tachycardia recorded electrocardiographically. ResultsWith a median time from the start of levofloxacin use to hospital discharge (or death) of 4 days (range, 1-94 days), only 2 patients (0.2%; 95% CI, 0.0%-0.7%) experienced the primary outcome of sustained ventricular tachycardia after the initiation of levofloxacin use. ConclusionIn this study, the short-term risk for sustained ventricular tachycardia in patients with a prolonged QTc who subsequently received levofloxacin was very rare. These results suggest that levofloxacin may be a safe option in patients with prolonged QTc; however, studies with longer follow-up are needed.

Reduction of hospital levofloxacin use is associated with a decrease in hospital-acquired fluoroquinolone-resistant Pseudomonas aeruginosa rates: An 11 year study

Reduction of hospital levofloxacin use is associated with a decrease in hospital-acquired fluoroquinolone-resistant Pseudomonas aeruginosa rates: An 11 year study

Life-Threatening Metabolic Coma Caused by Levofloxacin

Patients with diabetes mellitus are often susceptible to hypoglycemic episodes while on therapy. Most of these are attributed to inappropriate dosing of hypoglycemic agents, dietary indiscretion, or acute illness. Medications being used concomitantly should be reviewed closely when the etiology of hypoglycemia is unclear. A fifty-six-year-old woman with a history of diabetes mellitus (on metformin monotherapy) was found unresponsive at home. Her fingerstick glucose was 15 mg/dL for which she received 50% dextrose intravenously. The patient never had any previous documented hypoglycemic episodes. She had recently been diagnosed with pneumonia and was prescribed oral levofloxacin therapy. The patient had taken 4 doses of levofloxacin before the onset of hypoglycemia. These episodes recurred over the next 2 days needing close intensive care unit monitoring, dextrose infusion, and glucagon administration. Basic blood/urine investigations, cortisol and thyroid profile were normal except for low blood glucose and renal insufficiency (serum creatinine 1.4 mg/dL and creatinine clearance 42 mL/min). HbA1c was 6.8% (4.4%-6.4%), insulin 51.3 μU/mL (2.6-24.9 μU/mL), IGF-1 301 ng/mL (27-223 ng/mL), and C peptide 9.3 ng/mL (0.8-3.5 ng/mL). These levels were elevated but were deemed nondiagnostic because of fluctuating glucose values after glucagon administration. A blood screen for sulfonylureas and metaglinides was negative. A seventy-two-hour fast was performed to rule out hyperinsulinemic hypoglycemic syndromes; however, blood glucose values remained consistently above 120 mg/dL during this period. Thus, after exclusion of other causes, we utilized the adverse drug reaction probability scale and concluded that hypoglycemia was probably related to recent use of levofloxacin.

Risk for uveitis with oral moxifloxacin: a comparative safety study.

Numerous case reports have suggested that the recent use of moxifloxacin may lead to uveitis. This epidemiologic study is, to our knowledge, the first to explore the relationship between oral moxifloxacin hydrochloride use and uveitis. We conducted a case-control study within a cohort of men aged 40 to 85 years followed up from January 2001 through December 2011. All cases with a new diagnosis of uveitis were identified. For each case, 10 control subjects were matched by age, cohort entry date, and follow-up duration. For identified uveitis cases, current use of moxifloxacin, levofloxacin, or ciprofloxacin hydrochloride was compared with nonuse. Rate ratios were adjusted for potential confounding variables. We identified 13,313 uveitis cases and 133,130 corresponding controls. Compared with nonusers of fluoroquinolones, current first-time users of moxifloxacin demonstrated the highest risk for uveitis (adjusted rate ratio, 2.98 [95% CI, 1.80-4.94]). Current first-time users of ciprofloxacin (adjusted rate ratio, 1.96 [95% CI, 1.56-2.47]) showed an increased risk for uveitis, while current first-time users of levofloxacin (adjusted rate ratio, 1.26 [95% CI, 0.90-1.77]) did not show a significant association with uveitis. Current use of moxifloxacin or ciprofloxacin appears to increase the risk for uveitis. A statistically significant association of current first-time use of levofloxacin with uveitis could not be identified. Levofloxacin may pose the least risk for uveitis compared with moxifloxacin and ciprofloxacin.

Levofloxacin for BK virus prophylaxis following kidney transplantation: a randomized clinical trial.

BK virus infection is a significant complication of modern immunosuppression used in kidney transplantation. Viral reactivation occurs first in the urine (BK viruria) and is associated with a high risk of transplant failure. There are currently no therapies to prevent or treat BK virus infection. Quinolone antibiotics have antiviral properties against BK virus but efficacy at preventing this infection has not been shown in prospective controlled studies. To determine if levofloxacin can prevent BK viruria in kidney transplant recipients. Double-blind, placebo-controlled randomized trial involving 154 patients who received a living or deceased donor kidney-only transplant in 7 Canadian transplant centers between December 2011 and June 2013. Participants were randomly assigned to receive a 3-month course of levofloxacin (500 mg/d; n = 76) or placebo (n = 78) starting within 5 days after transplantation. The primary outcome was time to occurrence of BK viruria (detected using quantitative real-time polymerase chain reaction) within the first year after transplantation. Secondary outcomes included BK viremia, peak viral load, rejection, and patient and allograft survival. The mean follow-up time was 46.5 weeks in the levofloxacin group and 46.3 weeks in the placebo group (27 patients had follow-up terminated before the end of the planned follow-up period or development of viruria because the trial was stopped early owing to lack of funding). BK viruria occurred in 22 patients (29%) in the levofloxacin group and in 26 patients (33.3%) in the placebo group (hazard ratio, 0.91; 95% CI, 0.51-1.63; P = .58). There was no significant difference between the 2 groups in regard to any of the secondary end points. There was an increased risk of resistant infection among isolates usually sensitive to quinolones in the levofloxacin group vs placebo (14/24 [58.3%] vs 15/45 [33.3%], respectively; risk ratio, 1.75; 95% CI, 1.01-2.98) as well as a nonsignificant increased risk of suspected tendinitis (6/76 [7.9%] vs 1/78 [1.3%]; risk ratio, 6.16; 95% CI, 0.76-49.95). Among kidney transplant recipients, a 3-month course of levofloxacin initiated early following transplantation did not prevent BK viruria. Levofloxacin was associated with an increased risk of adverse events such as bacterial resistance. These findings do not support the use of levofloxacin to prevent posttransplant BK virus infection. clinicaltrials.gov Identifier: NCT01353339.

Prophylactic use of levofloxacin during medicinal leech therapy

Medicinal leech therapy is effective in establishing venous outflow in congested flaps and replants. However, its use is also associated with infections, especially from Aeromonas species. To prevent this nosocomial infection, levofloxacin has been established as prophylaxis during leech therapy in our hospital. To study the implementation rate of a guideline, to study the effect of levofloxacin on possible Aeromonas infections, and to evaluate the financial impact of this preventive measure. A retrospective analysis on all patients treated with Hirudo medicinalis between July 2007 and March 2011 was performed at the Ghent University Hospital, Belgium. A list of patients treated with leeches was retrieved from the pharmacy database. Patient characteristics, date of start and stop of leech therapy were collected. Data on routine diagnostic cultures during leech therapy, date and type of clinical sample, while cultivated micro-organism with antibiotic susceptibility were obtained from the laboratory database. percentage implementation rate of a guideline, presence of Aeromonas infections, financial impact of levofloxacin prophylaxis. Fifty-one patients were treated with leeches. Forty-six (90.2 %) patients were treated according the guideline. Fourteen out of 51 patients (27.5 %) were suspected for postoperative wound infections. From them, 60 clinical samples were sent for microbiological analysis. These included exudates (26.7 %), peroperative samples (5.0 %), puncture fluid (1.7 %), blood cultures (3.3 %) or smears from burns (63.3 %). No Aeromonas species were cultivated. Comparison between period before and after implementation of levofloxacin prophylaxis revealed that levofloxacin prevents colonization or infection with Aeromonas species in relation to leech therapy. The direct cost for levofloxacin prophylaxis in the current study was 2,570 euro. Based on data obtained in a previous study, we presume that a minimum cost-saving of 20,500 euro was realised during the current study period by implementation of antimicrobial prophylaxis. This study demonstrates successful implementation of a guideline for levofloxacin prophylaxis during leech therapy. Following its introduction, no Aeromonas species related to the use of leeches were isolated as compared to 8.5 % in the baseline period.

Current and Future Insights in H. pylori Eradication Regimens: The Need of Tailoring Therapy

Treatment of Helicobacter pylori (H. pylori) infection is crucial for the management of prevalent digestive and more recently also extra-digestive disorders. Rising prevalence of clarithromycin resistance worldwide has accounted for a dramatic decline in the efficacy of standard triple therapies, which should not be prescribed, unless local clarithromycin-resistance is low (<20%) or culture confirms susceptibility to this antibiotic (i,e,; as tailored treatments). Bismuth-quadruple, sequential, non-bismuth quadruple (concomitant), dual-concomitant (hybrid), and levofloxacin-based regimens have been shown to overcome clarithromycin resistance and are now preferred empirical treatments achieving improved eradication rates (>90% in per protocol analysis). In the future, empiric use of both clarithromycin and levofloxacin is likely to become steadily more challenging as even these novel eradication therapies may be prone to the effect of increasing antibiotic resistance. Tailored treatment based on the individual characterization of H. pylori therapeutic susceptibility appears to be a reasonable future alternative, currently limited by the shortcomings of systematically performing H. pylori culture (invasive, expensive, time-consuming). However, recent advances in the genotypic detection of H. pylori susceptibility to antibiotics, and in pharmacogenomics, may represent a breakthrough in our future approach to tailored therapy. Until then, efforts to optimize empirical treatments should continue.

Refractory shock secondary to treatment with levofloxacin in an extremely low birth weight infant affected by Stenotrophomonas maltophilia pneumonia

Abstract Stenotrophomonas maltophilia is an important but rare cause of late onset neonatal sepsis in extremely low birth weight (ELBW) infants. These infections are difficult to treat due to the multiple drug resistance profile of the organism. One class of antibiotics available for use is the quinolones, such as ciprofloxacin and levofloxacin. However, the limited experience and known toxicity of levofloxacin raises further concerns regarding its use in this patient population. We present a case of refractory shock in an ELBW infant following the use of levofloxacin to treat S. maltophilia infection. The use of levofloxacin in ELBW infants may be associated with major hemodynamic compromise and, accordingly, we recommend caution for its use in this patient population.

Personalized therapeutics for levofloxacin: a focus on pharmacokinetic concerns

BackgroundPersonalized medicine should be encouraged because patients are complex, and this complexity results from biological, medical (eg, demographics, genetics, polypharmacy, and multimorbidities), socioeconomic, and cultural factors. Levofloxacin (LVX) is a broad-spectrum fluoroquinolone antibiotic. Awareness of personalized therapeutics for LVX seems to be poor in clinical practice, and is reflected in prescribing patterns. Pharmacokinetic–pharmacodynamic studies have raised concerns about suboptimal patient outcomes with the use of LVX for some Gram-negative infections. Meanwhile, new findings in LVX therapeutics have only been sporadically reported in recent years. Therefore, an updated review on personalized LVX treatment with a focus on pharmacokinetic concerns is necessary.MethodsRelevant literature was identified by performing a PubMed search covering the period from January 1993 to December 2013. We included studies describing dosage adjustment and factors determining LVX pharmacokinetics, or pharmacokinetic–pharmacodynamic studies exploring how best to prevent the emergence of resistance to LVX. The full text of each included article was critically reviewed, and data interpretation was performed.ResultsIn addition to limiting the use of fluoroquinolones, measures such as reducing the breakpoints for antimicrobial susceptibility testing, choice of high-dose short-course of once-daily LVX regimen, and tailoring LVX dose in special patient populations help to achieve the validated pharmacokinetic–pharmacodynamic target and combat the increasing LVX resistance. Obese individuals with normal renal function cleared LVX more efficiently than normal-weight individuals. Compared with the scenario in healthy subjects, standard 2-hour spacing of calcium formulations and oral LVX was insufficient to prevent a chelation interaction in cystic fibrosis patients. Inconsistent conclusions were derived from studies of the influence of sex on the pharmacokinetics of LVX, which might be associated with sample size and administration route. Children younger than 5 years cleared LVX nearly twice as fast as adults. Patients in intensive care receiving LVX therapy showed significant pharmacokinetic differences compared with healthy subjects. Creatinine clearance explained most of the population variance in the plasma clearance of LVX. Switching from intravenous to oral delivery of LVX had economic benefits. Addition of tamsulosin to the LVX regimen was beneficial for patients with bacterial prostatitis because tamsulosin could increase the maximal concentration of LVX in prostatic tissue. Coadministration of multivalent cation-containing drugs and LVX should be avoided. For patients receiving warfarin and LVX concomitantly, caution is needed regarding potential changes in the international normalized ratio; however, it is unnecessary to seek alternatives to LVX for the sake of avoiding drug interaction with warfarin. It is unnecessary to proactively reduce the dose of cyclosporin or tacrolimus when comedicated with LVX. Transporters such as organic anion-transporting polypeptide 1A2, P-glycoprotein, human organic cation transporter 1, and multidrug and toxin extrusion protein 1 are involved in the pharmacokinetics of LVX.ConclusionPersonalized LVX therapeutics are necessary for the sake of better safety, clinical success, and avoidance of resistance. New findings regarding individual dosing of LVX in special patient populations and active transport mechanisms in vivo are opening up new horizons in clinical practice.

Azithromycin and Levofloxacin Use and Increased Risk of Cardiac Arrhythmia and Death

Azithromycin use has been associated with increased risk of death among patients at high baseline risk, but not for younger and middle-aged adults. The Food and Drug Administration issued a public warning on azithromycin, including a statement that the risks were similar for levofloxacin. We conducted a retrospective cohort study among US veterans to test the hypothesis that taking azithromycin or levofloxacin would increase the risk of cardiovascular death and cardiac arrhythmia compared with persons taking amoxicillin. We studied a cohort of US veterans (mean age, 56.8 years) who received an exclusive outpatient dispensation of either amoxicillin (n = 979,380), azithromycin (n = 594,792), or levofloxacin (n = 201,798) at the Department of Veterans Affairs between September 1999 and April 2012. Azithromycin was dispensed mostly for 5 days, whereas amoxicillin and levofloxacin were dispensed mostly for at least 10 days. During treatment days 1 to 5, patients receiving azithromycin had significantly increased risk of death (hazard ratio [HR] = 1.48; 95% CI, 1.05-2.09) and serious arrhythmia (HR = 1.77; 95% CI, 1.20-2.62) compared with patients receiving amoxicillin. On treatment days 6 to 10, risks were not statistically different. Compared with patients receiving amoxicillin, patients receiving levofloxacin for days 1 to 5 had a greater risk of death (HR = 2.49, 95% CI, 1.7-3.64) and serious cardiac arrhythmia (HR = 2.43, 95% CI, 1.56-3.79); this risk remained significantly different for days 6 to 10 for both death (HR = 1.95, 95% CI, 1.32-2.88) and arrhythmia (HR = 1.75; 95% CI, 1.09-2.82). Compared with amoxicillin, azithromycin resulted in a statistically significant increase in mortality and arrhythmia risks on days 1 to 5, but not 6 to 10. Levofloxacin, which was predominantly dispensed for a minimum of 10 days, resulted in an increased risk throughout the 10-day period.

DI-011 Evaluation of the use of levofloxacin and moxifloxacin in the treatment of pneumonia

BackgroundCurrent recommendations for the management of pneumonia promote two important measures to optimise antibiotic treatment: start sequential treatment early and do not extend antibiotic treatment more than five days in...

Clinical Impact of Fluoroquinolone-Resistant Escherichia coli in the Fecal Flora of Hematological Patients with Neutropenia and Levofloxacin Prophylaxis

BackgroundFluoroquinolone prophylaxis in patients with neutropenia and hematological malignancies is said to be effective on febrile netropenia (FN)-related infection and mortality; however, the emergence of antibiotic resistance has become a concern. Ciprofloxacin and levofloxacin prophylaxis are most commonly recommended. A significant increase in the rate of quinolone-resistant Escherichia coli in fecal flora has been reported following ciprofloxacin prophylaxis. The acquisition of quinolone-resistant E. coli after levofloxacin use has not been evaluated.MethodsWe prospectively examined the incidence of quinolone-resistant E. coli isolates recovered from stool cultures before and after levofloxacin prophylaxis in patients with neutropenia from August 2011 to May 2013. Some patients received chemotherapy multiple times.ResultsIn this trial, 68 patients were registered. Levofloxacin-resistant E. coli isolates were detected from 11 and 13 of all patients before and after the prophylaxis, respectively. However, this was not statistically significant (P = 0.65). Multiple prophylaxis for sequential chemotherapy did not induce additional quinolone resistance among E. coli isolates. Interestingly, quinolone-resistant E. coli, most of which were extended-spectrum β-lactamase (ESBL) producers, were already detected in approximately 20% of all patients before the initiation of prophylaxis. FN-related bacteremia developed in 2 patients, accompanied by a good prognosis.ConclusionsLevofloxacin prophylaxis for neutropenia did not result in a significant acquisition of quinolone-resistant E. coli. However, we detected previous colonization of quinolone-resistant E. coli before prophylaxis, which possibly reflects the spread of ESBL. The epidemic spread of resistant E. coli as a local factor may influence strategies toward the use of quinolone prophylaxis.

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BackgroundThe emergence of resistance has been demonstrated in cancer treatment centers where prophylaxis with fluoroquinolone is used.ObjectiveConsidering the importance of epidemiological monitoring as a strategy in choosing protocols involving antibiotics, this study aimed to evaluate the emergence of quinolone resistance and changes in the local epidemiology in a hematopoietic stem cell transplant service.MethodsFor this study, 60 positive cultures before the prophylactic use of levofloxacin (period A: 2007-2008) and 118 cultures after starting the use of prophylactic levofloxacin (period B: 2010-2011) were evaluated.ResultsResistance increased for all the different types of bacteria isolated (from 46.0% to 76.5%; p-value = 0.0002). Among Gram-negative bacteria, resistance increased from 21.4% to 60.7% (p-value = 0.0163) and among Gram-positive bacteria, it increased from 55.6% to 82.9% (p-value = 0.0025). The use of levofloxacin increased from 19.44 defined daily doses per 1,000 patient-days in period A to 166.64 in period B. The use of broad spectrum antibiotics remained unchanged. Considering bacteria associated with infection, 72 and 76 were isolated in periods A and B, respectively. There was a reduction in the rate of Gram-negative bacteria in cultures associated with infection (3.81 vs. 2.00 cultures/1,000 patient-days; p-value = 0.008).ConclusionThe study of prophylaxis with levofloxacin demonstrated that there was a decrease in infections by Gram-negative bacteria; however, bacterial resistance increased, even though the use of broad-spectrum antibiotics remained unchanged. Constant monitoring of local epidemiology combined with research on clinical outcomes is needed to evaluate the effectiveness of prophylaxis.© 2014 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. All rights reserved.

Prospective analysis of adverse reactions with long-term levofloxacin use

The safety of the long-term use of levofloxacin as an antibiotic has not previously been reported via a prospective study. This lack of evidence acts as a barrier for its use as an anti-tuberculosis drug. Cases with long-term levofloxacin use were prospectively followed at member hospitals of Ryoken. The frequency of adverse events is reported. Of 91 total cases, 7 cases were reported to have adverse drug reactions that may or may not have been levofloxacin-related. Of these 7 cases, 5 reported arthralgia and muscle pain that occurred 37-157 days after starting levofloxacin. Of 49 bacillary-positive cases, 1 case died 1 month later, 1 case did not have a culture examination, and 47 cases showed culture conversion. Long-term levofloxacin use is likely to be safe; however, arthralgia should be monitored in these long-term users.

Quinolone-containing therapies in the eradication of Helicobacter pylori.

Fluoroquinolones, especially levofloxacin, are used in the eradication of Helicobacter pylori worldwide. Many consensus guidelines recommend that the second-line rescue therapy for H. pylori eradication consists of a proton pump inhibitor, a quinolone, and amoxicillin as an option. Unfortunately, quinolone is well associated with a risk of developing bacterial resistance. In this paper, we review quinolone-containing H. pylori eradication regimens and the challenges that influence the efficacy of eradication. It is generally suggested that the use of levofloxacin should be confined to “rescue” therapy only, in order to avoid a further rapid increase in the resistance of H. pylori to quinolone. The impact of quinolone-containing H. pylori eradication regimens on public health issues such as tuberculosis treatment must always be taken into account. Exposure to quinolone is relevant to delays in diagnosing tuberculosis and the development of drug resistance. Extending the duration of treatment to 14 days improves eradication rates by >90%. Tailored therapy to detect fluoroquinolone-resistant strains can be done by culture-based and molecular methods to provide better eradication rates. Molecular methods are achieved by using a real-time polymerase chain reaction to detect the presence of a gyrA mutation, which is predictive of treatment failure with quinolones-containing triple therapy.

Risk of hepatotoxicity associated with fluoroquinolones: A national case–control safety study

Results of a pharmacoepidemiologic evaluation of fluoroquinolone-associated hepatotoxicity using national hospital admissions data on Veterans Affairs (VA) patients are reported. In a retrospective case-control study, all adults with a primary diagnosis of hepatotoxicity on admission to a VA facility during a 6.5-year period (January 2002-June 2008) were identified. After the exclusion of patients whose records indicated known causes of hepatotoxicity or a history of liver disease, a subgroup of 7,862 patients with exposure to fluoroquinolone antibiotics in the six months prior to hospital admission were matched with nonexposed controls (n = 45,512). Conditional logistic regression was used to assess the overall and drug-specific risks of hepatotoxicity in the case group, controlling for comorbidities, concomitant use of known hepatotoxic medications, and other variables. After adjusting for confounders, logistic regression analysis indicated a significantly higher overall risk of hepatotoxicity development among fluoroquinolone users relative to controls (odds ratio [OR], 1.20; 95% confidence interval [CI], 1.04-1.38). Drug-specific risk analyses focused on three fluoroquinolone agents (ciprofloxacin, levofloxacin, and moxifloxacin) indicated a significant association between ciprofloxacin use and an increased risk of hepatotoxicity (OR, 1.29; 95% CI, 1.05-1.58); when considered as independent variables, levofloxacin use and moxifloxacin use were not significantly associated with hepatotoxicity risk. The findings of a national VA safety study suggested an increased hepatotoxicity risk asssociated with fluoroquinolone exposure in the study population.

Effects of awakening and the use of topical dexamethasone and levofloxacin on the cytokine levels in tears following corneal transplantation.

Objectives. To study the short-term effect of eye opening and use of topical dexamethasone phosphate 0.1% and levofloxacin 0.5% on the cytokine levels in human tears. Methods. Prospective experimental design was used for tear collection from eyes of 10 healthy controls and 20 patients four days after penetrating keratoplasty (PKP) at awakening and after instilling dexamethasone or levofloxacin. The concentrations of different cytokines were measured by cytometric bead array. Results. At eye opening, IL-6 levels were higher in the PKP group as compared to the controls. Thirty minutes later, the released levels of IL-10, IL-13, IL-17, IFNγ, and CCL5 increased in controls, while CXCL8 decreased in both control and PKP groups. The release of the cytokines remained stable after 30 mins except for IFNγ, which showed a decrease in the controls following levofloxacin instillation. No short-term effects of the topically used dexamethasone and levofloxacin could be detected on the cytokine levels in controls and after PKP. Conclusions. Evidence of changes in the levels and time course of tear cytokines after awakening or eye opening could be established and the short-term confounding effects of dexamethasone and levofloxacin on the levels of released cytokines in human tears could be excluded.