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Background: Corneal cross-linking (CXL) with riboflavin is being used more frequently for the treatment of therapy-resistant microbial keratitis, since increasing drug resistance and specific pathogens, e.g. contact lens-associated Acanthamoeba, make this therapy appear as an attractive option to avoid a keratoplasty à chaud., Patients and Methods: This retrospective case series of 11 consecutive patients (4 women, 7 men, aged 24-82 years) who received standardised antimicrobial CXL for therapy-resistant keratitis to avoid a keratoplasty à chaud, included 4 cases with detection of bacterial pathogens, one case with proven fungal infection and 6 cases without pathogen detection. Analysed data comprised ophthalmic medical history, general risk factors for microbial keratitis, treatment before and after CXL. The characterisation of the corneal ulcer included photometric measurements of the infiltrates with a median of 16.2 mm² and four unmeasurable cases due to extended, not circumscribed lesions., Results: Within the follow-up period (mean 134 ± standard deviation 82 days), a penetrating keratoplasty was successfully avoided in 6 patients (55 %). After CXL 9 patients (82 %) received additionally amniotic membrane transplantation. After CXL treatment, topical antibiotic therapy was continued for a mean 27 ± 13 days postoperatively. Steroids were applied in 91 % of the patients. The cornea cleared at least to some extent in 9 patients (82 %). Patients with neurotrophic keratopathy or potentially compromised immune system showed no increased failure rate., Conclusion: These results suggest that antimicrobial CXL might be a useful option in patients with therapy-resistant corneal ulcer in order to avoid a perforating keratoplasty à chaud. For a comprehensive scientific assessment of this therapy, however, further, ideally prospective randomised interventional studies with large sample sizes are needed., (Georg Thieme Verlag KG Stuttgart · New York.)

The aim of this study was to assess the efficacy and pharmacokinetic profiles of gentamicin, vancomycin, and levofloxacin in a rat air pouch model, in which Staphylococcus aureus (ATCC 25293) was used as the test organism. Antibiotic treatments (i.p.) were started 1 hour after bacterial inoculation and continued for 5 days. Bacterial counts and antibiotic concentrations were determined in pouch exudates that were obtained on the 5th day of antibiotic treatment. The following observations were made: 1) The concentrations of gentamicin or vancomycin in the exudate were found to be below the detection limit. 2) Levofloxacin and ciprofloxacin exhibited a dose-dependent effect on bacterial counts in the exudate. 3) The antibacterial efficacy of levofloxacin was found to be enhanced when the total daily dose of 10 mg was divided into smaller parts. The present study also showed that the air pouch infection model was a valuable tool to assess the pharmacokinetic and pharmacodynamic properties of antibiotics.

Purpose: To examine the effect of levofloxacin prophylaxis on infection rates during chemotherapy with docetaxel plus carboplatin in elderly patients with advanced non-small cell lung cancer., Methods: In a randomized, double-blind, phase III study, patients (≥65 years) with untreated, histologically/cytologically proven stage IIIB/IV non-small cell lung cancer received docetaxel (75 mg/m) plus carboplatin (area under the curve 6) on day 1 every 3 weeks, plus once-daily levofloxacin (500 mg orally) or placebo on days 5 to 11. The primary end point was the rate of grade 3/4 infections or grade 1/2 infections treated with additional antibiotics. Secondary end points included overall infection rate, toxicity, overall survival, and progression-free survival., Results: In total, 187 patients were randomized to levofloxacin (n = 95) or placebo (n = 92). The rate of grade 3/4 infections or grade 1/2 infections treated with additional antibiotics (intent-to-treat population) was 27.5% (95% confidence interval, 19.3-39.0%) for levofloxacin versus 36.7% (95% confidence interval, 27.1-48.0%) for placebo. Median time to first infection was 67 days for levofloxacin versus 46 days for placebo. Grade 3/4 infections occurred in 8.8% of patients in the levofloxacin group versus 26.7% for placebo. There was one grade 5 infection in each group. Grade ≥3 toxicities (levofloxacin versus placebo) included leukopenia (63.2 versus 52.2%), neutropenia (62.1 versus 51.1%), dyspnea (12.6 versus 8.7%), and pain (10.5 versus 9.8%). There was no significant difference in overall survival or progression-free survival between groups., Conclusions: Levofloxacin prophylaxis reduces the rate of infection compared with placebo and is well tolerated in elderly patients receiving docetaxel plus carboplatin.

The aim of this prospective observational study was to present relevant data on the efficacy and safety of levofloxacin in the treatment of chronic bacterial prostatitis (NIH-II) in the daily clinical routine of urologists in their practices. In total, 243 patients were treated, including 62 patients with a microbiologically confirmed diagnosis -based on expressed prostatic secretion (EPS). The current evaluation is based on these patients. Their median age was 53 years. The patients were treated with levofloxacin 500 mg / day for 29 days (median) which is in accordance to the -registered recommendation for this indication. Clinical symptoms were assessed using a standardised questionnaire. The clinical symptoms dysuria, painful ejaculation, perineal pain, urinary obstruction, increased urgency, prostate pain during palpation as well as CRP and number of leukocytes showed statistically significant improvements at the end of therapy with levofloxacin as compared to baseline. At the end of treatment 93.5 % (n = 58 / 62, 95 % confidence interval: 84.5 %-97.8 %) of the patients were cured or improved. The patients were able to resume their regular activities after 10 days (median). 93.5 % (n = 58 / 62) of the patients and 95.2 % (n = 59 / 62) of the doctors were satisfied or very satisfied with this treatment. In all 62 patients the diagnosis was microbiologically confirmed based on EPS. In 39 patients (62.9 %) E. coli was identified. At the end of therapy microbiological testing was performed in 62.9 % (n = 39 / 62) of the patients, in 29 cases including EPS. In 37 of these 39 patients (94.9 %) no pathogen was identified. In 2 cases (5.1 %) a pathogen was identified (Proteus mirabilis and Staphylococcus species). In 181 patients without microbiological confirmation -based on EPS comparable clinical results were found. In the total population of 243 patients 5 adverse drug reactions were reported in 3 patients (incidence 1.2 %, n = 3 / 243), The results of this study confirm the efficacy and safety of levofloxacin in the treatment of chronic bacterial prostatitis in daily clinical practice., (Georg Thieme Verlag KG Stuttgart New York.)

Objective: To evaluate the clinical efficacy and safety of antofloxacin hydrochloride tablet for the treatment of acute bacterial infections., Methods: A multi-center randomized control, double blind and double dummy clinical trial was conducted; levofloxacin tablet was closed as controlled drug. The duration of treatment was 7-14 days in both groups., Results: A total of 719 patients were enrolled in the study, in which 359 patients treated with antofloxacin and 360 patients treated with levofloxacin were included. Three hundred and thirty and 337 patients completed the study and met with all the criteria for per-protocol analysis, respectively. By the end of chemotherapy, the cured rates in per protocol set (PPS) population were 79.7% and 77.4%, the effective rates were 95.2% and 96.7%, and the bacterial clearance were 96.7% and 97.5% for the treating and control group, respectively. The clinical and bacterial efficacy of antofloxacin and levofloxacin was comparable by the analysis of infectious sites. Three hundred and fifty-seven and 356 patients in antofloxacin and levofloxacin groups were evaluated the safety. The drug adverse events occurred both in 10.1%, and drug adverse reactions occurred in 7.8% and 7.9% patients in the two groups. The most common drug adverse reactions were mild gastroenteric symptoms. No QTc prolongation was detected in all the patients. One patient in each group had mild blood glucose increase at the end of therapy, but the glucose returned to normal level without any intervention. No statistic significant difference between the two groups in clinical efficacy and safety was detected (P > 0.05)., Conclusions: Antofloxacin hydrochloride tablet was effective and safe for the treatment of acute bacterial infections.

Background: Early, empiric, broad-spectrum antibiotics followed by de-escalation to pathogen-specific therapy is the standard of care for ventilator-associated pneumonia (VAP). In our surgical intensive care unit (SICU), imipenem-cilastatin (I-C) in combination with tobramycin (TOB) or levofloxacin (LEV) has been used until quantitative bronchoalveolar lavage results are finalized, at which time de-escalation occurs to pathogen-specific agents. With this practice, however, alterations in antimicrobial resistance remain a concern. Our hypothesis was that this strict regimen does not alter antimicrobial susceptibility of common gram-negative VAP pathogens in our SICU., Methods: After Institutional Review Board approval, a retrospective review of SICU-specific antibiograms was performed for the sensitivities of common gram-negative VAP pathogens. Time periods were defined as early (January-June 2005) and late (July-December 2006). Chart review of empiric and de-escalation antibiotic usage was obtained. Data were collated, and statistical significance was assessed with the chi-square test using the on-line Simple Interactive Statistical Analysis tool., Results: Imipenem-cilastatin was used 198 times for empiric VAP coverage (811 patient-days), whereas TOB and LEV were given a total of 149 (564 patient-days) and 61 (320 patient-days) times, respectively. Collectively, the susceptibility of gram-negative organisms to I-C did not change (early 91.4%; late 97%; p = 0.33). Individually, non-significant trends to greater sensitivity to I-C were noted for both Pseudomonas aeruginosa (early 85.7%; late 90.9%; p = 0.73) and Acinetobacter baumannii (early 80%; late 100%; p = 0.13). Further, both TOB (early 77.1%; late 70.0%; p = 0.49) and LEV (early 74.3%; late 70.0%; p = 0.67) were found to maintain their susceptibility profiles. The frequency of resistant gram-positive VAPs was unchanged during the study period. Our de-escalation compliance (by 96 h) was 78% for I-C, 77.2% for TOB, and 59% for LEV. When infections requiring I-C were removed from the analysis, de-escalation compliance was improved to 92%., Conclusions: In our SICU, early, empiric broad-spectrum VAP therapy followed by de-escalation to pathogen-specific agents did not alter antimicrobial resistance and is a valid practice. Further, our compliance with de-escalation practices was higher than published rates.

The aim of this research is to evaluate the recent changes in microorganisms causing spontaneous bacterial peritonitis in cirrhotic patients, antibiotic resistance, and response to empirical cephalosporin therapy. A total of 218 patients with ascites secondary to cirrhosis were enrolled. Parenteral cefotaxime or cefepime was given to patients who had a neutrophil count of 250/mm(3) or more or a positive bacterial culture of ascitic fluid. Antibiotic failure was defined by an absence of clinical improvement and an insufficient decrease in neutrophil count of ascites (<25% of initial value) by the third day of therapy. Of all the patients, 44.6% had culture-negative neutrocytic ascites, 24.8% had spontaneous bacterial peritonitis, and 10.1% had monomicrobial nonneutrocytic bacterascites. Growth in culture was observed in 76 patients (34.9%). The two most common isolated bacteria were Escherichia coli (33.8%) and coagulase-negative Staphylococcus (CoNS; 19.7%). The two cephalosporins were effective against E. coli (82%) and but not against CoNS (44%), while levofloxacin showed reasonable activity against both E. coli (71%) and CoNS (90%) in vitro. We confirmed a recent increased incidence of spontaneous bacterial peritonitis caused by Gram-positive bacteria. Levofloxacin seems to be a good alternative treatment for patients with uncomplicated spontaneous ascites infections.

Infection in chemotherapy-induced neutropenia (neutrophils < 500/mm3) is the main cause of death during the treatment of acute leukemia. Antibiotic prophylaxis is a controversial issue to prevent or delay this infection. This study assessed the efficacy of prophylaxis with oral levofloxacin in chemotherapy-induced febrile neutropenic patients. Eighty patients of acute leukemia was randomly assigned to had levofoxacin (500 mg/daily) or placebo from the starting of chemotherapy. Out of 80 patients 53 developed neutropenia and fever. The number of patients with fever (78% vs. 68%), isolation of the pathogenic bacteria (30.43% vs. 16%) was higher and mean starting day of the fever (11.1 vs. 13.2) was shorter in the placebo group than the levofloxacin group. Levofloxacin reduced the bacterial infections and delays the onset of fever in chemotherapy-induced neutropenia especially in short duration (< 7 days).

Levofloxacin possesses a wide antimicrobial spectrum which encompasses Gram positive (also including penicillin-resistant Streptococcus pneumoniae) and Gram negative, and atypical respiratory pathogens Chlamydia pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae) as well. Comparative clinical studies (macrolides, beta-lactams, and other fluoroquinolones), have evidenced bacteriological and clinical efficacy in community-acquired pneumonia (CAP), acute exacerbation of chronic bronchitis, urinary tract infections, and skin and soft tissue infections. In clinical practice, levofloxacin in sequential therapy allowed to reduce length of stay, the efficacy being maintained unaltered. In severe pneumonia, or when a pseudomonas aetiology is suspected, an association therapy is suggested, although a reliable body of clinical evidence is still lacking. Recent in vitro studies showed a synergism between levofloxacin and imipenem against multiresistant Pseudomonas aeruginosa strains. A recent Italian clinical study evidenced the good efficacy and tolerability profile of prophylactic use of levofloxacin in neutropenic patients with cancer. Such a prophylaxis reduced number of febrile episodes, at a statistically significant level, and mortality (although at a not statistically significant level).

According to data reported by Naber (2008), urinary tract infections (UTIs), represent the main nosocomial acquired infection (40%); these infections are second, in order of frequency, only to respiratory tract infections in ambulatory setting, and account for 20% of ambulatory uro-nephrologic disease. Nowadays, the UTI's classification recognizes five different groups, represented by acute, non complicated lower urinary tract infections (cystitis), acute non complicated pyelonephritis, complicated UTI's with/without pyelonephritis, urosepsis and special forms, such as prostatitis, epididimitis, and orchitis. With regard to therapy, and specifically to fluoroquinolones, the European urologists' scientific community is unanimous in considering that levofloxacin plays a very important activity in the urological field, its antimicrobial spectrum being extended to Gram positive and atypical microorganisms as well.

Objectives: To evaluate the combination of isepamicin and levofloxacin in the prophylaxis of infectious complications associated with prostate biopsy (PBX)., Methods: A total of 586 patients who underwent transrectal PBX in a single center were included in this retrospective analysis. They received 400 mg isepamicin once just before PBX plus 300 mg oral levofloxacin each day for three days as a rule. Clinical and laboratory data were evaluated., Results: A total of three (0.51%) patients presented a febrile complication after PBX. All of them were diagnosed as acute prostatitis. Serum white blood cell count and C-reactive protein in the 131 patients whose laboratory data were available for statistical analyses did not rise significantly after PBX., Conclusions: Isepamicin plus fluoroquinolone can be considered a valuable regimen for antibiotic prophylaxis of PBX.

This article reviews the characteristics of the main fluoroquinolones used in dentistry (ciprofloxacin, levofloxacin and moxifloxacin), including pharmacokinetic/ pharmacodynamic parameters, susceptibility profiles of oral bacteria and clinical trials on their efficacy in dental practice. It seems that some of these antibiotics might represent a safe alternative in patients with allergy, intolerance, or lack of response to beta-lactams.

Objective: To evaluate the clinical efficiency and safety of intravenous levofloxacin in the treatment of bacterial infections at a dose of 500 mg once a day., Methods: Randomized, prospective, multicenter, open-label study., Results: The total effective rate of levofloxacin was 90.8% (4103/4521). The effective rates of levofloxacin in the treatment of bacterial infections of respiratory tract, urinary tract, digestive tract and gynecologic infections and infections complicated with hematological disease were 90.2% (2884/3198), 92.3% (810/878), 91.9% (203/221), 94.5% (120/127), 88.7% (86/97), respectively. The bacterial eradication rate was 80.3% (677/843). The most common adverse drug reactions were gastrointestinal disorders (3.9%, 193/4888) and local irritation (1.7%, 84/4888), which were mild and disappeared after stopping administration., Conclusion: Intravenous levofloxacin with a dose of 500 mg once a day is effective and safe in treating bacterial infections with low adverse reactions.

Background: Topical antimicrobial therapy of infected diabetic foot ulcers can focus on the wound and avoid the adverse effects of systemic anti-infective agents. We compared the efficacy of outpatient treatment using an investigational topical antimicrobial peptide, pexiganan acetate cream, with the efficacy of systemic therapy using an oral fluoroquinolone antibiotic, ofloxacin, for mildly infected diabetic foot ulcers., Methods: In 2 consecutive, double-blind, controlled trials (study 303 and study 304), we randomized diabetic patients with a mildly infected diabetic foot ulcer to receive the active topical agent or active oral antibiotic, plus a respective inactive placebo. The primary outcome of interest was clinical cure or improvement of the infection. Secondary outcomes included eradication of wound pathogens and wound healing, which was documented by a semiquantitative scoring system., Results: Overall, 835 patients were randomized; those in each treatment arm were similar with regard to demographic and clinical characteristics. Although study 303 failed to demonstrate equivalence, study 304 and the combined data for the 2 trials demonstrated equivalent results (within the 95% confidence interval) for topical pexiganan and oral ofloxacin in clinical improvement rates (85%-90%), overall microbiological eradication rates (42%-47%), and wound healing rates. The incidence of worsening cellulitis (2%-4%) and amputation (2%-3%) did not differ significantly between treatment arms. Bacterial resistance to ofloxacin emerged in some patients who received ofloxacin, but no significant resistance to pexiganan emerged among patients who received pexiganan., Conclusions: Topical pexiganan might be an effective alternative to oral antibiotic therapy in treating diabetic patients with a mildly infected foot ulcer, and might reduce the risk of selecting antimicrobial-resistant bacteria.

The aim of this study was to confirm further the efficacy and safety of levofloxacin in patients with chronic bacterial prostatitis (CBP) in Europe. Men with a history of CBP were enrolled in a prospective, multinational (eight countries), open-label study to receive levofloxacin 500 mg once daily per os (p.o.) for 28 days. Patients were followed for 6 months. A total of 117 patients were treated. Gram-negative bacteria were identified in 57/106 patients (mainly Escherichia coli (n=37)) and Gram-positive bacteria in 60/106 patients (mainly Enterococcus faecalis (n=18) and Staphylococcus epidermidis (n=14)). Among the intention-to-treat population (n=116), the clinical success rate (cured and improved patients) was 92% (95% confidence interval (CI) 84.8-96.5%), 77.4% (95% CI 68.2-84.9%), 66.0% (95% CI 56.2-75.0%) and 61.9% (95% CI 51.9-71.2%) at 5-12 days, 1 month, 3 months and 6 months post treatment. The microbiological eradication rate according to evaluation scheme II was 82/98 (83.7%, 95% CI 74.8-90.4%) at 1 month and the continued eradication rate was 52/57 (91.2%, 95% CI 80.7-97.1%) at 6 months post treatment. Comparison of four classification schemes showed similar results. Thus, the present investigation is suitably comparable in methods and results to previous studies. Levofloxacin was well tolerated. Four patients (3.4%) discontinued therapy due to adverse events and 15 patients (12.8%) experienced at least one adverse event. Levofloxacin 500 mg p.o. once daily for 28 days is clinically and microbiologically effective in the treatment of CBP caused by susceptible pathogens and is well tolerated.

Objectives: To assess the efficacy of tosufloxacin as a prophylactic agent for transrectal biopsy of the prostate (TBP), we conducted a randomized prospective study comparing tosufloxacin versus levofloxacin., Methods: A randomized prospective study comparing tosufloxacin versus levofloxacin was performed. In group A, 124 patients received 300 mg tosufloxacin tosilate (including 204 mg tosufloxacin) twice daily for 2 days, with the initial dose being 2 h prior to biopsy. In group B, 119 patients received 200 mg levofloxacin in the same manner., Results: Infectious complications were reported equally in six cases in each group (4.8% in group A and 5.0% in group B). Each group included five cases of acute prostatitis and one of cystitis. Six patients suffering from prostatitis required hospitalization, while those with symptomatic urinary tract infection were treated as outpatients., Conclusions: Tosufloxacin was as effective as levofloxacin when administered twice daily for 2 days as prophylaxis for TBP, which suggests that this regimen is useful for reducing the clinical and febrile infection rate following TBP.

A total of 20 patients entered the clinical trial of efficacy and safety of Russian produced drug levofloxacin (floracid) in the treatment of chronic bacterial prostatitis (CBP). The drug was given in a single dose of 500 mg/day for 28 days. Antibacterial treatment of CBP with floracid killed sensitive to it bacteria in 18 of 20 (90%) CBP patients. Symptoms of the disease attenuated including pain syndrome and voiding disorders, quality of life assessed by NIH-CPSI scale improved. The absence of side effects points to good tolerance and safety of the drug.

Sinusitis remains 1 of the most common reasons for antimicrobial prescriptions in the United States, with health care costs approaching $4 billion annually. We utilized the serial sinus aspirate sampling (SSAS) technique to obtain daily specimens to evaluate the time course of drug effect in patients with acute maxillary sinusitis. Eighteen patients with a radiologically confirmed acute maxillary sinusitis were enrolled into a study evaluating the relationship between levofloxacin exposure and the time course of antimicrobial effect using SSAS. SSAS was performed daily during therapy for bacteriologic evaluation. Six steady-state levofloxacin concentrations were obtained. Levofloxacin plasma and sinus aspirate concentrations were modeled using Monte Carlo Parametric Expectation Maximization algorithm implemented in S-ADAPT 1.53. Endpoints evaluated included time to resolution of signs and symptoms and time to sinus sterilization. Among the 18 enrolled patients, 15 were clinically evaluable. From these, 1 Streptococcus pneumoniae, 3 Haemophilus influenzae, 1 Moraxella catarrhalis, 1 Corynebacterium spp., and 1 coagulase-negative Staphylococcus organisms were isolated, with the latter 2 organisms being likely contaminants. For the pathogens, levofloxacin MIC values ranged from 0.03 to 2 mg/L. All pathogens were eradicated by the 4th day of therapy. The median and mean time to sinus sterilization (pathogens only) was 1 and 1.4 days, respectively. The median time to resolution of each sign and symptom ranged from 1.5 to 12-19 days, with the 83% of total signs and symptoms resolved by the end of therapy (day 5). The mean plasma area under the concentration-time curve (AUC) (mg x h/L) was 100.1 (n = 14, %CV = 27). Plasma AUC/MIC ratios ranged from 33.9 to 1696 for isolated pathogens. In this pilot SSAS study, levofloxacin rapidly eradicated isolated pathogens from the maxillary sinus.

Levofloxacin (Levaquin) is a fluoroquinolone antibacterial that is the L-isomer of ofloxacin. A high-dose (750 mg) short-course (5 days) of once-daily levofloxacin is approved for use in the US in the treatment of community-acquired pneumonia (CAP), acute bacterial sinusitis (ABS), complicated urinary tract infections (UTI) and acute pyelonephritis (AP). The broad spectrum antibacterial profile of levofloxacin means that monotherapy is often a possibility in patients with CAP at times when other agents may require combination therapy, although levofloxacin can be used in combination therapy when necessary. The high-dose, short-course levofloxacin regimen maximizes its concentration-dependent bactericidal activity and may reduce the potential for resistance to emerge. In addition, this regimen lends itself to better compliance because of the shorter duration of treatment and the convenient once-daily administration schedule. Oral levofloxacin is rapidly absorbed and is bioequivalent to the intravenous formulation; importantly, patients can transition between the formulations, which results in more options in regards to the treatment regimen and the potential for patients with varying degrees of illness to be treated. Levofloxacin has good tissue penetration and an adequate concentration can be maintained in the urinary tract to treat uropathogens. Levofloxacin is generally well tolerated and has good efficacy in the treatment of patients with CAP, ABS, complicated UTI and AP. The efficacy and tolerability of levofloxacin 500 mg once daily for 10 days in patients with CAP, ABS and UTIs is well established, and the high-dose, short-course levofloxacin regimen has been shown to be noninferior to the 10-day regimen in CAP and ABS, and to have a similar tolerability profile. Similarly, the high-dose, short-course levofloxacin regimen is noninferior to ciprofloxacin in patients with complicated UTI or AP. Thus, levofloxacin is a valuable antimicrobial agent that has activity against a wide range of bacterial pathogens; however, its use should be considered carefully so that the potential for resistance selection can be minimized and its usefulness in severe infections and against a range of penicillin- and macrolide-resistant pathogens can be maintained.

Purpose: The SIGNIFICANT (Simple Investigation in Neutropenic Individuals of the Frequency of Infection after Chemotherapy +/- Antibiotic in a Number of Tumours) trial reported a reduction in febrile episodes (FEs) among 1,565 patients with solid cancers and lymphomas receiving cyclical, myelosuppressive chemotherapy (causing grade 4 neutropenia) in a randomized, placebo-controlled, double-blind trial of levofloxacin (P = .01). In response to concerns that increased antibacterial prescribing selects for microbial resistance, we examined our data to explore the rationale for more limited prophylaxis., Patients and Methods: The risk of FE was calculated for control patients on first versus nonfirst cycles, with or without first-cycle FE, and within subgroups defined by cancer type, performance status (PS), age, and treatment context (adjuvant v nonadjuvant). Using the randomized trial data, the prophylactic efficacy of levofloxacin was examined for the same subgroups., Results: The per-cycle FE incidence was much lower on nonfirst (3.3%) versus first cycles (8.0%). Prophylaxis was less effective for nonfirst (odds ratio [OR] = 0.78; P = .16) compared with first cycles (OR = 0.42; P < .001). However, FE on cycle 1 predicted a much higher risk of FE and a trend to continued prophylactic efficacy on subsequent cycles. FE rate was greatest for testicular cancer (27.9%), then small-cell lung cancer (17.3%), and lowest for breast cancer (11.5%). Prophylactic efficacy was consistent across age, sex, PS, treatment context, and disease type (except possibly non-Hodgkin's lymphoma)., Conclusion: Under pressure to limit antibacterial use, these exploratory data support offering prophylactic levofloxacin on cycle 1 only of myelosuppressive cancer chemotherapy and on subsequent cycles after a cycle-1 fever. Prophylactic levofloxacin is effective regardless of age, PS, or tumor type.

Bacterial septic sacroiliitis is an uncommon diagnosis that occurs most frequently in children and young adults. Nonspecific physical examination findings often make it difficult to diagnose the condition, thus delaying appropriate treatment. We review the case of middle-aged woman with sacroiliac joint (SIJ) pain after a torsional injury. Radiographic films showed the pelvis and left lower extremity to be normal. Despite anti-inflammatory medications, analgesics, a corticosteroid injection, and physical therapy, her pain persisted. Laboratory data showed an elevated erythrocyte sedimentation rate and C-reactive protein; otherwise, tests were normal, including negative blood cultures. Magnetic resonance imaging (MRI) revealed a left posteroinferior SIJ effusion and computed tomography (CT) showed an effusion and irregularity in the left SIJ. An SIJ biopsy revealed inflammation suggestive of osteomyelitis. After a course of intravenous antibiotics, the symptoms completely resolved, thus supporting our diagnosis of bacterial sacroiliitis. Repeat MRI and CT confirmed the complete resolution of the sacroiliitis.

The pharmacokinetics of levofloxacin and outcome of levofloxacin therapy in critically ill patients with ventilator-associated pneumonia (VAP) were assessed. Further theoretical considerations regarding the pharmacokinetic/pharmacodynamic (PK/PD) appropriateness of levofloxacin therapy were made. Twelve patients completed the study, all of whom were treated with a standard intravenous levofloxacin regimen (2x500 mg on Day 1, then 1x500 mg daily). The maximum free plasma levofloxacin concentration (fC(max,ss)) and the area under the free concentration-time curve (fAUC) were 8.13+/-1.64 mg/L and 49.63+/-15.60 mgh/L, respectively. Optimal PK/PD target parameters were achieved in 10 patients; clinical success was attained in 11 of the 12 patients who completed the study. Bacterial eradication was obtained in 9 of the 11 cases with microbiologically confirmed bacteriological aetiology. Intravenous levofloxacin therapy (500 mg/day) was proven to be an effective regimen in this limited number of patients with VAP. However, theoretical considerations based on PK/PD indices predict that, with the current susceptibility breakpoint of 2mg/L, even higher levofloxacin doses (e.g. 1000 mg) could result in treatment failures in infections caused by pathogens labelled as levofloxacin-susceptible in the microbiology report.

Objective: To examine study entry microbiology in patients stratified by disease severity in a clinical trial in acute bacterial exacerbation of chronic bronchitis (ABECB)., Methods: Patients were assigned to differing antibiotic therapies based on stratification by disease severity using parameters including forced expiratory volume in 1 second (FEV(1)) as a percentage of predicted value, number of exacerbations during the previous 12 months, and defined co-morbidities. All patients were required to have sputum Gram stain and culture at study entry., Results: There was no statistically significant difference in overall microbiology between patients with less severe and more severe clinical presentations. Typical ABECB pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) were found in 46.2% (147/318) of patients with less severe presentations and 41.9% (143/341) of patients with more severe presentations. Gram-negative organisms and Staphylococcus aureus were also found in both groups. Pneumococcal susceptibilities to the three antibiotics utilized in the trial revealed marked resistance to azithromycin. Limitations of this analysis include that the clinical trial was designed to examine clinical outcomes rather than microbiology, and that we do not correlate study entry microbiology with clinical outcomes., Conclusions: Stratification of patients by disease severity did not reveal a statistically significant difference in overall microbiological profile. Gram-negative organisms and S. aureus were recovered even from patients with less severe clinical presentations. Pneumococcal resistance varied with the agent tested. These findings may have implications for the selection of appropriate antibiotic therapy.

Background: Levofloxacin has excellent activity against common respiratory pathogens and therefore is likely to be effective in treating children with persistent or recurrent otitis media., Objective: The objective of this study was to assess the efficacy and safety of levofloxacin treatment in the eradication of bacterial pathogens from the middle ear fluid (MEF) of children with, or at high risk for, persistent or recurrent otitis media., Methods: An open-label multicenter trial was conducted that involved tympanocentesis at entry and selectively 3 to 5 days after starting levofloxacin (10 mg/kg twice a day for 10 days)., Results: : Two hundred five children (80% < or =2 years) were enrolled. One child did not have a confirmed diagnosis of acute otitis media and did not return for follow-up visits. Of the remaining 204 children, 94 (46%) had bilateral infection and 63 (31%) were receiving antimicrobials immediately before entry. One hundred five isolates of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus. pyogenes were recovered in pure or mixed cultures. All isolates were susceptible to levofloxacin. During-treatment bacterial eradication from MEF occurred in 88% (78 of 89) of bacteriologically evaluable patients, including 90% (65 of 72) of children < or =24 months of age. Bacteria initially isolated from MEF were eradicated in 31 of 37 (84%) children infected with S. pneumoniae and in 54 of 54 (100%) children infected with H. influenzae. Overall, clinical success rate after therapy was 94% for the total study population and 92% for the bacteriologically evaluable population. Levofloxacin was well tolerated. Vomiting (4%) was the most common treatment-limiting adverse event., Conclusions: Levofloxacin was safe and effective in treating and eradicating common bacterial pathogens from MEF in children with, or at risk for, recurrent or persistent otitis media.

The purpose of the study was to evaluate 90K/MAC-2BP, a glycoprotein member of the Scavenger Receptor Cystein Rich superfamily, in the seminal plasma of infertile male patients with male accessory gland infection in order to investigate a putative autoimmune pathogenesis. 90K seminal concentration and sperm parameters were evaluated in 50 patients with male accessory gland infection at baseline and after cycles of treatment with Levofluoxacin 500 mg daily for 15 days plus serratiopeptidase 10 mg daily for 30 days. Treatment was continued for up to 6 cycles in cases of persistant bacteriospermia and/or clinical and ejaculatory signs of the disease. Patients with persistant male accessory gland infection after 6 cycles were defined as nonresponders. The same parameters were evaluated at baseline and after a 2-month period in 30 healthy controls. Patients with male accessory gland infection showed impaired sperm parameters and had lower seminal 90K concentration compared to controls. After treatment, seminal 90K level significantly increased in patients compared to controls. Twenty-two patients responded to treatment (44%), while 28 were nonresponders (56%). No difference in pretreatment and posttreatment sperm parameters and seminal 90K was observed between the 2 subgroups. Thirteen patients (26%) had identifiable bacteriospermia: significantly less pretreatment seminal 90K was observed compared to patients without bacteriospermia. Seminal 90K is decreased in patients with male accessory gland infection, and may be restored by a treatment with quinolones. However, the clinical utility of a 90K assay in these patients remains uncertain, as its level is not predictive of response to treatment.

The best antibiotic regimen for acute prosthetic joint infection, treated without removal of the implant, has not been well-defined. This study describes the use of a protocol based on oral rifampicin combinations to treat 47 cases that were followed prospectively for a 2-year period. The regimen used most commonly was levofloxacin 500 mg/24 h plus rifampicin 600 mg/24 h for a mean duration of 2.7 +/- 1 months. The cure rate was 76.9%, and the only independent risk-factor associated with treatment failure was infection caused by methicillin-resistant Staphylococcus aureus or Enterococcus spp. (OR 17.6, p 0.003). Overall, the results suggested that use of oral antibiotics, including rifampicin, for 2-3 months was a good treatment option.

Traditional approaches to antimicrobial management of acute bacterial rhinosinusitis (ABRS) focus on courses of therapy of at least 10 days duration. The rationale for this length of therapy originated from studies in tonsillopharyngitis. Short-course antibiotic therapy for ABRS with 3-5 days of azithromycin has proved equally effective. Potential added benefits of short-course therapy include improved compliance, fewer adverse events as well as reduced risk of treatment failure, bacterial resistance and cost. Single-dose therapy is now possible with a novel microsphere formulation of azithromycin, which permits administration of a higher 2.0 g oral dose. This has proved as effective and well tolerated as 10 days levofioxacin 500 mg/day in patients with uncomplicated ABRS. High single-dose therapy has the potential to maximize adherence to prescribed therapy and thus to help in the battle to control rising antibiotic resistance among respiratory pathogens.

Background: The prophylactic use of fluoroquinolones in patients with cancer and neutropenia is controversial and is not a recommended intervention., Methods: We randomly assigned 760 consecutive adult patients with cancer in whom chemotherapy-induced neutropenia (<1000 neutrophils per cubic millimeter) was expected to occur for more than seven days to receive either oral levofloxacin (500 mg daily) or placebo from the start of chemotherapy until the resolution of neutropenia. Patients were stratified according to their underlying disease (acute leukemia vs. solid tumor or lymphoma)., Results: An intention-to-treat analysis showed that fever was present for the duration of neutropenia in 65 percent of patients who received levofloxacin prophylaxis, as compared with 85 percent of those receiving placebo (243 of 375 vs. 308 of 363; relative risk, 0.76; absolute difference in risk, -20 percent; 95 percent confidence interval, -26 to -14 percent; P=0.001). The levofloxacin group had a lower rate of microbiologically documented infections (absolute difference in risk, -17 percent; 95 percent confidence interval, -24 to -10 percent; P<0.001), bacteremias (difference in risk, -16 percent; 95 percent confidence interval, -22 to -9 percent; P<0.001), and single-agent gram-negative bacteremias (difference in risk, -7 percent; 95 percent confidence interval, -10 to -2 percent; P<0.01) than did the placebo group. Mortality and tolerability were similar in the two groups. The effects of prophylaxis were also similar between patients with acute leukemia and those with solid tumors or lymphoma., Conclusions: Prophylactic treatment with levofloxacin is an effective and well-tolerated way of preventing febrile episodes and other relevant infection-related outcomes in patients with cancer and profound and protracted neutropenia. The long-term effect of this intervention on microbial resistance in the community is not known., (Copyright 2005 Massachusetts Medical Society.)

Background: The role of prophylactic antibacterial agents after chemotherapy remains controversial., Methods: We conducted a randomized, double-blind, placebo-controlled trial in patients who were receiving cyclic chemotherapy for solid tumors or lymphoma and who were at risk for temporary, severe neutropenia (fewer than 500 neutrophils per cubic millimeter). Patients were randomly assigned to receive either 500 mg of levofloxacin once daily or matching placebo for seven days during the expected neutropenic period. The primary outcome was the incidence of clinically documented febrile episodes (temperature of more than 38 degrees C) attributed to infection. Secondary outcomes included the incidence of all probable infections, severe infections, and hospitalization but did not include a systematic evaluation of antibacterial resistance., Results: A total of 1565 patients underwent randomization (784 to placebo and 781 to levofloxacin). The tumors included breast cancer (35.4 percent), lung cancer (22.5 percent), testicular cancer (14.4 percent), and lymphoma (12.8 percent). During the first cycle of chemotherapy, 3.5 percent of patients in the levofloxacin group had at least one febrile episode, as compared with 7.9 percent in the placebo group (P<0.001). During the entire chemotherapy course, 10.8 percent of patients in the levofloxacin group had at least one febrile episode, as compared with 15.2 percent of patients in the placebo group (P=0.01); the respective rates of probable infection were 34.2 percent and 41.5 percent (P=0.004). Hospitalization was required for the treatment of infection in 15.7 percent of patients in the levofloxacin group and 21.6 percent of patients in the placebo group (P=0.004). The respective rate of severe infection was 1.0 percent and 2.0 percent (P=0.15), with four infection-related deaths in each group. An organism was isolated in 9.2 percent of probable infections., Conclusions: Among patients receiving chemotherapy for solid tumors or lymphoma, the prophylactic use of levofloxacin reduces the incidence of fever, probable infection, and hospitalization., (Copyright 2005 Massachusetts Medical Society.)

Episodes of acute rhinosinusitis are common among adults and are associated with a significant amount of morbidity. The symptoms of rhinosinusitis are nasal drainage, congestion, and sinus pressure. A bacterial sinus infection is more likely if these symptoms worsen after 5-7 days or do not improve after 10-14 days. The majority of bacterial episodes have been associated with Streptococcus pneumoniae and Haemophilus influenzae. In the current era of increasing resistance to beta -lactams and macrolides, treatment guidelines have been formulated worldwide to assist clinicians in the selection of antibacterials. According to one model, the following antibacterials are most likely to provide desired outcomes (90%-92% predicted clinical efficacy) for adults: respiratory fluoroquinolones (i.e., moxifloxacin, gatifloxacin, and levofloxacin), ceftriaxone, and high-dose amoxicillin-clavulanate (4 g of amoxicillin/day and 250 mg of clavulanate/day). Although the role of the fluoroquinolones in the treatment of this condition is evolving, fluoroquinolones are often recommended as second-line therapy or as first-line therapy for selected patients (e.g., those who received antibacterials in the previous 4-6 weeks or adults with moderate-to-severe disease).

Purpose: We compared baseline and post-therapy prostate specific antigen (PSA) in patients with chronic bacterial prostatitis who were treated with levofloxacin or ciprofloxacin., Materials and Methods: Subset analysis was done using a randomized, multicenter, double-blind, active control trial of 500 mg levofloxacin daily for 28 days vs 500 mg ciprofloxacin twice daily in 28 days in men with chronic bacterial prostatitis., Results: Of the 377 men in the intent to treat population, including 197 treated with levofloxacin and 180 treated with ciprofloxacin, 35 on levofloxacin and 37 on ciprofloxacin with baseline PSA greater than 4 ng/ml were included in this analysis. Excluded from analysis were 2 levofloxacin treated patients with extremely high PSA at baseline (62 and 103 ng/ml, respectively). Mean baseline PSA +/- SD in the patients analyzed was 8.33 +/- 4.46 ng/ml, which decreased to 5.36 +/- 3.82 ng/ml after therapy. There was no significant difference in the mean change in PSA between the levofloxacin and ciprofloxacin groups. Approximately 42% of patients with increased baseline PSA had a post-therapy PSA of 4 ng/ml or less. Of patients who were microbiologically evaluable and had normalized PSA after therapy levofloxacin eradicated the pathogen in 90.9% (10 of 11). However, of patients in whom post-therapy PSA remained increased the microbiological eradication rate was 69.2% (9 of 13). Similarly 93.3% of the ciprofloxacin group (14 of 15 patients) with normalized post-therapy PSA experienced microbiological eradication compared with 61.5% (8 of 13) with continued increased PSA after therapy., Conclusions: Approximately 20% of patients diagnosed with chronic bacterial prostatitis had increased PSA. A significant decrease in PSA was observed in these patients after treatment with levofloxacin or ciprofloxacin. An association was observed between bacterial persistence and the likelihood that PSA would return to normal.

Objectives: The authors had for aim to evaluate the efficacy and tolerance of oral levofloxacin (500 mg once a day during ten days), as a treatment for acute bacterial sinusitis at risk for complications in adult patients., Patients and Methods: This was a prospective, multicenter, open, non-comparative, efficacy and tolerance study of levofloxacin in acute sinusitis at risk for complications, radiologically confirmed, and with documentation of the bacterial origin by fiberoptic rhinoscopy., Results: Two hundred and thirty-one patients were included and 174 patients had an X ray confirmed sinusitis. The localization was frontal in 81% patients, sphenoidal in 9.2%, ethmoidosphenoidal in 2.3%, and 7.5% patients had a pansinusitis. One hundred and thirty-three patients had a probable or proven bacterial infection, involving: Streptococcus pneumoniae (26.0%), enterobacteriaceae (19.7%), Haemophilus influenzae (17.3%), Staphylococcus aureus (15.0%), streptococci other than S. pneumoniae (7.9%), and Branhamella catarrhalis (5.5%). One hundred and one patients constituted the per protocol population. Clinical success was observed in 94.1 % patients (95/101), and 85.1% (86/101), respectively 7 to 14 days and three to four weeks after the end of treatment, with consistent success rates according to the localization of the infection, and the various pathogens involved. The tolerance data was as expected for levofloxacin., Conclusions: The results of this study show that levofloxacin, (one 500 mg tablet QD during ten days) is efficient in over 94% patients with bacteriologically documented sinusitis at risk for complications.

Background: Fluoroquinolone prophylaxis during neutropenia in patients with cancer has been associated with decreased incidence of gram-negative bacteremia. Bacterial antimicrobial resistance is likely to cause a progressive lack of efficacy of fluoroquinolones, but no convincing evidence from clinicoepidemiologic observations has proved this hypothesis., Methods: This prospective observational study assessed the impact of discontinuing fluoroquinolone prophylaxis on the incidences of fever and bacteremia and on mortality among patients with neutropenia, after chemotherapy for hematologic malignancies., Results: After a 12-month baseline period of levofloxacin prophylaxis, a period of discontinuation of fluoroquinolone prophylaxis was planned but was stopped prematurely after 9 neutropenic episodes over 3 weeks, because the mortality rate (33.3%) was higher than that with routine fluoroquinolone prophylaxis (2.9%) (odds ratio [OR], 16.6; 95% confidence interval [CI], 3.6-77.2). Fewer patients had gram-negative bacteremia during the baseline period (4.8%; n=15) than during the discontinuation period (44.4%; n=4) (OR, 16.9; 95% CI, 4.1-70.0). After levofloxacin therapy was reintroduced, the incidence of gram-negative bacteremia and the mortality rate were comparable to those during the first period. Escherichia coli isolated during the discontinuation period was susceptible to levofloxacin in vitro, whereas all E. coli isolates isolated during both prophylaxis periods were resistant. Bloodstream infections were caused by a single agent when the patient had received levofloxacin prophylaxis, whereas most cases of gram-negative bacteremia were polymicrobial after discontinuation., Conclusions: These findings suggest that, despite increasing rates of antimicrobial resistance, levofloxacin prophylaxis during neutropenia may have a beneficial impact on morbidity and infection-related mortality. Continued monitoring of the rate of gram-negative bacteremia is warranted for timely detection of the loss of efficacy of fluoroquinolone prophylaxis.

The aim of this study was to evaluate the in vitro activity of levofloxacin (LVX) in comparison to nalidixic acid (NAL), ofloxacin (OFX), norfloxacin (NOR), amoxicillin (AMX), cefixime (CFM), cotrimoxazole (SXT) and nitrofurantoin (FT), against 402 strains recently isolated from urine specimens in outpatient women suffering from lower urinary tract infections for which short-term treatment was not indicated. MICs were determined by the agar dilution method on Mueller-Hinton medium (Bio-Rad) according to the recommendations of the Comite de l'Antibiogramme de la Societe Francaise de Microbiologie (CA-SFM). Strains were classified as susceptible (S), intermediate (I) or resistant (R) according to the CA-SFM recommended breakpoints. Quality control was carried out using three reference strains: Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853. For E. coli, the most prevalent species (345 isolates: 85.3%), susceptibilities were as follows: AMX: 60.6%, CFM: 99.1%, NAL: 94.8%, NOR: 97.4%, OFX: 97.4%, LVX: 97.4%, SXT: 84.5%, FT: 98%. This study confirms the good in vitro activity of LVX, OFX, and CFM against strains isolated from urinary tract infections in the community and particularly against E. coli, which is by far the most prevalent pathogen, 90% of strains, with more than 97% of strains being susceptible.

A rise of resistance in uropathogens to all agents used for the management of urinary tract infections has been observed in Moscow. However, because of the broad spectrum and favourable safety parameters, fluoroquinolones remain the drugs of choice for the treatment of community-acquired urinary tract infections. Among them levofloxacin is preferable. When the use of fluoroquinolones is contraindicated, the 1st-3rd generation cephalosporins are advisable. Nitrofurans are expedient in the treatment of acute and relapsing cystitis. By the antibacterial activity and bioavailability sodium furasidin is advantages among the nitrofurans.

Antibiotic treatment of bacterial exacerbation of chronic obstructive pulmonary disease (COPD) shows some immediate clinical benefits and may also minimise the frequency of further recurrences. Patients (n=511) were enrolled into a randomised double-blind multicentric study comparing the exacerbation-free interval (EFI), efficacy and safety of 7-day levofloxacin versus 10-day clarithromycin in patients with COPD exacerbation. Patients were monitored over a 1-yr period. A total of 434 patients (per protocol population) received the medication for > or =5 days. The median EFI in the per protocol population was 300 days for levofloxacin and 350 days for clarithromycin. For patients with a new documented exacerbation during follow-up (n=223), the median EFI was 100.5 days in the levofloxacin group and 95 days for clarithromycin. No significant differences in EFI between groups could be observed when stratifying the study population according to microbial aetiology and severity of bronchial obstruction. Levofloxacin and clarithromycin showed similar clinical success rates. The bacteriological success rate was significantly higher in the levofloxacin group. Both antibiotics were well tolerated. In summary, levofloxacin was associated with a significantly higher bacteriological eradication rate but similar exacerbation-free interval in patients with chronic obstructive pulmonary disease exacerbation compared to clarithromycin.