Double (vancomycin or teicoplanin with either levofloxacin or cefotaxime) and triple (vancomycin or teicoplanin + levofloxacin + one among amikacin, ceftazidime, cefepime, imipenem, piperacillin/tazobactam) combinations were evaluated by means of checkerboard assay and time kill curves. Mutational rates of single and combined drugs at antimicrobial concentrations equal to the resistance breakpoints were also calculated.
Aim. There is a paucity of data on the efficacy of empiric H. pylori treatment after multiple treatment failures. The aim of this study is to examine the efficacy of empiric salvage therapy as a second through sixth line treatment. Methods. In this single gastroenterology center prospective study in Montreal, Canada, patients with failed H. pylori treatment were offered empiric salvage therapy based on the patients' previous antibiotic exposure. Enrollment occurred after 1-5 previous failed attempts and eradication determined at least 4 weeks after completion of treatment. Results. 205 treatments were attempted in 175 patients using 7 different regimens. Eradication was achieved in 154 attempts (PP = 81% (154/191), ITT = 75% (154/205)). Bismuth quadruple therapy (BQT) had higher eradication success (PP = 91% (102/112), ITT = 84% (102/121)) when compared to all PPI triple therapies combined (PP = 66% (49/74), absolute risk reduction (ARR): 25% (95% CI: 13-37), ITT = 62% (49/79), ARR: 22% (95% CI: 10-35), and p < 0.001) and when compared to levofloxacin triple therapy (PP = 66% (40/61), ARR: 26% (95% CI: 13-39), ITT = 61% (40/66), and ARR: 24% (95% CI: 10-37)). Eradication was achieved in a high proportion with BQT on attempt two (PP = 94% (67/71), ITT = 91% (67/74)), three (PP = 85% (17/20), ITT = 71% (17/24)), four (PP = 100% (11/11), ITT = 92% (11/12)), and five (PP = 86% (6/7), ITT = 75% (6/8)). Patients with previous combined bismuth and tetracycline exposure had a lower proportion of eradication compared to patients without such an exposure (PP: 60% (6/10) versus 95% (94/99), ARR: 35% (95% CI: 11-64), and p < 0.001; ITT: 55% (6/11) versus 90% (94/105), ARR: 35% (95% CI: 10-62), and p < 0.01). Conclusions. Salvage therapy with a bismuth quadruple regimen is superior to triple therapies and is effective for second through fifth line empirical treatment (≥85% PP, ≥70% ITT). Successful eradication is significantly lower with BQT if a similar bismuth based regimen was used in the past.
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Subjects included patients within a managed care setting over 18 years of age with an initial diagnosis of community-acquired pneumonia from January 1995 to April 2002. Multivariate linear and logistic regression models were used to examine associations with treatment success rates and direct medical costs between antibiotic treatments after controlling for patient demographics and pneumonia risk factors.
Mutations in the QRDR of gyrA, gyrB, parC, and parE genes of 138 isolates of S epidermidis recovered from the human conjunctival flora were analysed. The minimal inhibitory concentrations (MICs) of four fluoroquinolones (levofloxacin, gatifloxacin, moxifloxacin and tosufloxacin) against these isolates were also determined using agar dilution methods.
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A 67-year-old woman with hypertension, hypothyroidism, and glaucoma was referred for jaundice and elevated liver function tests. She was treated for streptococcal endophthalmitis with 2 weeks of intravenous (IV) levofloxacin followed by 2 months of oral levofloxacin. The patient had no prior history of liver disease and denied alcohol intake. Her physical exam was remarkable for jaundice and scleral icterus without any stigmata of liver disease. Viral hepatitis serologies and antibodies, including myeloperoxidase, proteinase 3, and antinuclear, antimitochondrial, antiliver kidney microsome, antismooth muscle antibodies, were all within normal limits. The liver biopsy revealed severe cholestasis, extensive bile duct loss, and fibrosis. The patient had no known exposure to any other systemic medications or inciting factors other than levofloxacin. Although there are a few reported cases of drug-induced liver disease (DILI) related to levofloxacin, this case is believed to be the first reported case of ductopenia or vanishing bile duct syndrome (VBDS) associated with levofloxacin. Although fluoroquinolones, such as levofloxacin, are generally considered safe antibiotics, health practitioners must be aware of their association with DILI, as the diagnosis of DILI is one of exclusion and requires a high index of suspicion.
Using β-lactamase-negative ampicillin (ABPC)-susceptible (BLNAS) and β-lactamase-negative ABPC-resistant (BLNAR) nontypeable Haemophilus influenzae (NTHi) strains isolated from otological patients, colony biofilm was prepared on membrane filter substrates. Bactericidal activities of garenoxacin (GRNX), levofloxacin (LVFX), cefditoren (CDTR), and clavulanic acid/amoxicillin (CVA/AMPC) were examined by counting viable cells after drug exposure to biofilm cells for 6 and 24 h and by observation under a scanning electron microscope (SEM). After exposure of biofilm to the 100-fold MIC of GRNX or LVFX for 24 h, GRNX and LVFX showed potent bactericidal activity (∆log10 CFU/ml, ≥5.1). In this case, the drug-exposure AUC, exposure concentration × 24 μg h/ml, was 64-128 % for GRNX and 121 % for LVFX of free AUC at the clinical dosage in humans, respectively. CDTR and CVA/AMPC at 100-fold MIC exhibited little bactericidal activity against biofilm cells. Under an SEM, after exposure of BLNAS and BLNAR biofilms to GRNX or LVFX, most of the biofilm matrices were transformed. Quinolones such as GRNX show potent bactericidal activity against biofilm-forming NTHi at the usual clinical dosage.
Prospective, observational study.
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Breakthrough viridans streptococcal bacteremia (VSB) in patients with hematological malignancy receiving levofloxacin prophylaxis is a major blood stream infection (BSI) occurring during febrile neutropenia. However, clinical data focused on VSB in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are lacking.
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Overall, the minimum concentration inhibiting 50% of isolates (MIC50) and 90% of isolates (MIC90) for fosfomycin were 4 and 64 µg/mL, respectively. Of the 257 E. coli isolates, 99.6% were susceptible to fosfomycin. Ciprofloxacin, levofloxacin, SXT, and nitrofurantoin susceptibility rates were 65.4%, 65.8%, 59.9%, and 90.3%, respectively. The fosfomycin-susceptibility rate for E. faecalis (94.4%) was comparable with the nitrofurantoin-susceptibility rate (98.1%). Among the 144 ESBL-producing isolates, the fosfomycin MIC50 and MIC90 values were 2 and 32 µg/mL, respectively. Fosfomycin MIC50 and MIC90 values were 16 and 128 µg/mL for the 38 ceftazidime-nonsusceptible Enterobacter isolates and 64 and 128 µg/mL for the 15 ceftazidime-nonsusceptible P. aeruginosa isolates, respectively.
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A total of 116 clinical isolates collected in 2003 from a tertiary pediatric hospital and a primary pediatric department in Chicago, IL, were screened for reduced susceptibility to selected fluoroquinolones by disc diffusion. Correlation between reduced susceptibility and point mutations in the quinolone resistance-determining region of parC and gyrA genes was evaluated, and point mutations were compared with other reports of isolates derived from adult or mixed patient populations. Nine percent of isolates had reduced susceptibility to 1 or more of these fluoroquinolones by Etest: ciprofloxacin, levofloxacin, and moxifloxacin. A single point mutation (Ser-79) in parC seemed responsible for the reduced susceptibility. Resistant Streptococcus pyogenes isolates were compared using M/emm type, repetitive sequence-based PCR (rep-PCR), and pulsed-field gel electrophoresis (PFGE). Rep-PCR provided no more separation of strains than M/emm typing, and PFGE results with SgrAI were more discriminatory than with SmaI. The majority of these isolates were M/emm type 6. PFGE analysis using SgrAI demonstrated 2 different resistant strains among the M/emm type 6 isolates. The findings suggest that a population of S. pyogenes with an intrinsic reduced susceptibility to fluoroquinolones exists in pediatric clinical isolates. Monitoring of amino acid changes in both parC and gyrA will assist in the prediction of emergence of high-level fluoroquinolone resistance.
Outbreaks of urinary tract infections (UTIs) due to contaminated ureteroscopes have been rarely reported.