Rapid detection of the plasmid-mediated quinolone resistance determinant AAC(6')-Ib-cr in Enterobacteriaceae by measuring acetyltransferase activity against fluoroquinolones by MALDI-TOF MS analysis.
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Strategies to eradicate Helicobacter pylori infection could be improved by suppressing acid and extending the duration of therapy (optimization). We compared the efficacy of 2 different optimized nonbismuth quadruple regimens in areas of high resistance to antimicrobial agents.
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Twenty-nine patients presented with endophthalmitis, of whom 20 were classified as having proven infective endophthalmitis. The absence of an intracameral cefuroxime prophylactic regimen at 1 mg in 0.1 mL normal saline was associated with a 4.92-fold increase (95% confidence interval [CI], 1.87-12.9) in the risk for total postoperative endophthalmitis. In addition, the use of clear corneal incisions (CCIs) compared to scleral tunnels was associated with a 5.88-fold increase (95% CI, 1.34-25.9) in risk and the use of silicone intraocular lens (IOL) optic material compared to acrylic with a 3.13-fold increase (95% CI, 1.47-6.67). The presence of surgical complications increased the risk for total endophthalmitis 4.95-fold (95% CI, 1.68-14.6), and more experienced surgeons were more likely to be associated with endophthalmitis cases. When considering only proven infective endophthalmitis cases, the absence of cefuroxime and the use of silicone IOL optic material were significantly associated with an increased risk, and there was evidence that men were more predisposed to infection (OR, 2.70; 95% CI, 1.07-6.8).
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Concerns have arisen regarding the equivalence of levofloxacin and some macrolides for treating community-acquired legionella pneumonia (LP). We aimed to compare the outcomes of current patients with LP treated with levofloxacin, azithromycin and clarithromycin.
In both groups, bacterial culture came from scrapings of the conjunctival sac, and the bacterial infection rate and pattern of drug resistance were determined. Findings were analyzed in various subgroups stratified by age, frequency of instillation, and concentration of antiseptic benzalkonium chloride in the eyedrops.
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Eradication was confirmed by a (13)C-urea breath test 8 weeks after therapy. Compliance with therapy was determined by questioning and the recovery of empty envelopes of medications. Incidence of adverse effects was evaluated by means of a specific questionnaire.
There was no significant interaction in healthy volunteers, however, when cystic fibrosis patients were given levofloxacin with 2-h spaced calcium, the maximum plasma concentration (Cmax) decreased by 19% and time to Cmax increased by 37% (p<0.05). This difference in peak concentrations resulted in a lack of bioequivalence (Cmax geometric mean ratio 81.6%, 90% confidence intervals: 71.8%, 91.4%) even when levofloxacin and calcium supplements were spaced by the standard 2h administration instruction in patients with cystic fibrosis.
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A novel sugar-based double-tailed surfactant containing renewable block was synthesized for preparing niosomal vesicles that could be exploited for Levofloxacin encapsulation, aiming to increase its oral bioavailability.
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Thirty-nine SD rats were randomly divided into normal control group, corneal suture model group, α9β1 group, and α9β1 suppression group, and in the latter 3 groups, the rats received topical administration of levofloxacin, levofloxacin + α9β1, and levofloxacin+ anti-α9β1 monoclonal antibody (Y9A2) twice daily after corneal suture, respectively. At 3, 5, 7, 14 days after the surgery, 3 rats were randomly selected from each group to observe corneal neovascularization (CNV) under slit lamp. RT-PCR and Western blotting were used to detect the expressions of VEGF-A.
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Levofloxacin pharmacokinetics were only partially comparable with those obtained from literature data for healthy volunteers. Area under the concentration-time curve (AUC(tau)) over the 12-hour dosage interval was about 30-40% lower than in healthy volunteers (33.90 vs 49.60 mg. h/L). The reduced exposure may be due to a greater clearance of levofloxacin (0.204 vs 0.145 L/h/kg [3.40 vs 2.42 mL/min/kg]), leading to a shorter elimination half-life (5.2 vs 7.6 hours). Cumulative urinary excretion during the 12-hour dosage interval confirmed the greater excretion of unchanged drug in these patients compared with healthy subjects (76% vs 68%). Coadministered drugs used to treat underlying diseases (dopamine, furosemide, mannitol) may at least partially account for this enhanced elimination in critically ill patients. Intravenous levofloxacin 500mg twice daily ensured a median C(max)/MIC (maximum plasma concentration/minimum inhibitory concentration) ratio of 102 and a median 24-hour AUC/MIC ratio of 930 SIT(-1). h (inverse serum inhibitory titre integrated over time) against methicillin-sensitive Staphylococcus aureus and Haemophilus influenzae. The overall success rate of the assessable cases was 75% (6/8). Bacterial eradication was obtained in all of the assessable cases (8/8), but a superinfection (Acinetobacter anitratus,Pseudomonas aeruginosa) occurred in three cases.
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A series of novel 1-[(1R,2S)-2-fluorocyclopropyl]naphthyridone derivatives 21-24 containing an oxime-functionalized pyrrolidine moiety were designed, synthesized and evaluated for their biological activity. Our results reveal that compounds 21a, 21e and 21j show considerable activity against MTB H37Rv ATCC 27294 (MICs: <0.25 μg/mL) and MDR-MTB 6133 (MICs: 0.03-0.054 μg/mL). The target compounds 21-24 are generally poor against the Gram-negative strains, but 21a-j and 22a-c have potent potency (MICs: <0.008-32 μg/mL) against all of the tested Gram-positive strains including MRSA and MRSE with a few exceptions, and the most active compounds 21d, 21e and 22a-c (MICs: <0.008-32 μg/mL) were found to be comparable to or better than moxifloxacin, and 2->250 times more potent than ciprofloxacin and levofloxacin.
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Levofloxacin is a synthetic broad-spectrum antibacterial agent for oral or intravenous administration. Chemically, levofloxacin is the levorotatory isomer (L-isomer) of racemate ofloxacin, a fluoroquinolone antibacterial agent. Quinolone derivatives rapidly and specifically inhibit the synthesis of bacterial DNA. Levofloxacin has in vitro activity against a broad range of aerobic and anaerobic Gram-positive and Gram-negative bacteria. However, formulation of combined poloxamers thermoregulated (as Pluronic® F127) and levofloxacin for use in multiresistant bacterial treatment were poorly described in the current literature. Thus, the aim of the present work is to characterize poloxamers for levofloxacin controlled release and their use in the treatment of multidrug bacterial resistance. Micelles were produced in colloidal dispersions, with a diameter between 5 and 100 nm, which form spontaneously from amphiphilic molecules under certain conditions as concentration and temperature. Encapsulation of levofloxacin into nanospheres showed efficiency and enhancement of antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae when compared with only levofloxacin. Furthermore, all formulations were not cytotoxic for NIH/3T3 cell lineage. In conclusion, poloxamers combined with levofloxacin have shown promising results, better than alone, decreasing the minimal inhibitory concentration of the studied bacterial multiresistance strains. In the future, this new formulation will be used after being tested in animal models in patients with resistant bacterial strains.
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The application of topical 0.5% levofloxacin for 1 or 3 days significantly reduced the number of eyes with positive conjunctival cultures. The addition of 5% povidone-iodine further eliminated bacteria from the conjunctiva. The application of levofloxacin for 1 day appears to be as effective as a 3-day application.
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In vitro, rifampin was the most effective drug overall. Moxifloxacin and trovafloxacin were as effective as the macrolides of which roxithromycin was the most active one.
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ML and HL showed similar activity against both MSSA and MRSA with MIC/MBC at 16 ~ 64 mg/L, with potency similar to amikacin (AMK) and gentamicin (GEN). When they were used in combination with conventional antibacterial agents, they showed bacteriostatic synergy with FICIs between 0.25 ~ 0.5, leading to the combined MICs decreasing to as low as 1 ~ 2 and 1 ~ 16 mg/L for ML (HL) and the agents, respectively. MIC50 of the combinations decreased from 16 mg/L to 1 ~ 4 mg/L for ML (HL) and 8 ~ 128 mg/L to 2 ~ 64 mg/L for the antibacterial agents, which exhibited a broad spectrum of synergistic action with aminoglycosides (AMK, etilmicin (ETM) and GEN), floroquinolones (levofloxacin (LEV), ciprofloxacin and norfloxacin), fosfomycin (FOS) and piperacillin. The times of dilution (TOD, the extent of decreasing in MIC value) were determined up to 16 for the combined MIC. A more significant synergy after combining was determined as ML (HL) with AMK, ETM, GEN and FOS. ML (HL) combined with antibacterial agents did not show antagonistic effects on any of the ten MRSA strains. Reversal effects of MRSA resistance to AMK and GEN by ML and HL were also observed, respectively. All the combinations also showed better dynamic bactericidal activity against MRSA than any of single ML (HL) or the agents at 24 h incubation. The more significant synergy of combinations were determined as HL (ML) + ETM, HL + LEV and HL + AMK (GEN or FOS), with △LC24 of 2.02 ~ 2.25.
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A sensitive, selective and simple method using a precipitation of protein with 10% perchloric acid, followed by high-performance liquid chromatography (HPLC) with fluorescence detection was developed for the determination of itopride hydrochloride in human plasma, using levofloxacin as the internal standard (IS). Chromatographic separation was obtained within 7.0 min using a reverse phase Hypersil BDS C(18) (250 mm x 4.6 mm, 5 microm) column and an isocratic mobile phase, constituting of a mixture of 0.1 mol/l ammonium acetate-methanol (30:70, v/v) flowing at 1.1 ml/min. The excitation and emission wavelengths were set at 304 and 344 nm, respectively. The method was validated over the concentration range of 5 ng/ml to 1000.0 ng/ml. The lower limit of quantitation (LLOQ) was 5 ng/ml. The extractive recovery of itopride hydrochloride from the biological matrix was more than 80.77%. The intra-day accuracy of the drug containing serum samples was more than 82.94% with a precision of 2.81-4.37%. The inter-day accuracy was 82.91% or more, with a precision of 6.89-9.54%. The limit we have used (70-143%) is based on the local regulatory authority (SFDA). The developed method was validated and successfully applied to bioequivalence studies of itopride hydrochloride in healthy male volunteers.
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Strains of group A streptococcus were collected from the Departments of Pediatrics in 36 hospitals at different Districts of Beijing, from May to July 2011. Minimal inhibitory concentrations (MIC) with ten antibiotics of these isolates were tested by VITEK 2 Compact method. All the Susceptibility rate (S%), Intermediate rate (I%) and Resistance rate (R%) were calculated according to their MIC values. The macrolides resistant phenotype of group A streptococcus was detected by D-test.
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E coli susceptibility for ED patients not requiring admission may not be accurately represented by hospital antibiograms that contain culture data from various patient types, sites of infection, or patients with varying illness severity. Separation of the ED population into CA-UTI and HA-UTI subgroups may be helpful when selecting empiric antibiotic therapy.
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In India, there is a high prevalence of ESBL producing organisms among intraabdominal isolates and in stool flora of 'normal' individuals. Hence, it may be presumed that unless antimicrobial therapy effective for ESBL flora is used perioperatively for abdominal surgery, the outcome will be adverse. We selected patients surgically treated for appendicitis as a model to explore the relevance of ESBL producing isolates in this retrospective observational study.
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Pneumococcal resistance to antimicrobials presents problems to physicians for empirical treatment of acute otitis media (AOM). Three hundred thirty-three isolates of Streptococcus pneumoniae selected for nonsusceptibility to penicillin (MIC >0.1 microg/ml) from the middle ear (n = 325) or mastoid (n = 8) of children seen between 1994 and 2000 at four children's hospitals in the United States were tested by broth microdilution for susceptibility to nine antibiotics. Using NCCLS 2002 breakpoints, resistance to the following drugs was as indicated: amoxicillin, 1%; azithromycin, 71%; cefprozil, 71%; ceftriaxone, 2%; cefdinir, 98%; erythromycin, 70%; levofloxacin, 0%; and trimethoprim-sulfamethoxazole, 93%. Of the penicillin- and erythromycin-nonsusceptible isolates, 97% were inhibited by cethromycin (ABT-773) and 83% were inhibited by telithromycin at a concentration of
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Probe substrates, phenacetin (CYP1A2), and tolbutamide (CYP2C9) were incubated with human liver microsomes and the metabolites were analyzed by liquid chromatography/mass spectrometry using electrospray ionization in positive or negative mode. Glipizide was used as the internal standard in both modes. The inhibitory potential of fluoroquinolones on CYP1A2 and CYP2C9 was investigated.
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Older people are often especially susceptible to pneumonia and bacteria may develop resistance to antibiotics quicker in the elderly, whose immune systems gradually diminish. This study analyses, retrospectively, resistance to antibiotics in high-risk elderly patients with fatal pneumonia. Records of all patients aged over 65 who did not survive a bout with pneumonia were gathered from the records of the Department of Pneumology of HELIOS Clinic in Wuppertal, Germany from the period of 2004-2014. Susceptibility testing was executed for the study population, whose pneumonia was triggered by various kinds of bacteria. We detected 936 pneumonia patients of the overall mean age of 68.0 ± 13.6 years, with the following pneumonia types: 461 (49.3 %) community-acquired, 354 (37.8 %) nosocomial-acquired, and 121 (12.9 %) aspiration pneumonia. There were 631 (67.4 %) males and 305 (32.6 %) females there. We identified 672 (71.8 %) patients who had a high risk for pneumonia, especially staphylococcal pneumonia (p < 0.0001). The elderly patients had a higher risk of dying from pneumonia (2.9 odds ratio, 95 % confidence interval 1.8-4.6; p < 0.0001); of the 185 pneumonia-related deaths, 163 (88.1 %) were in the elderly. In those with fatal staphylococcal pneumonia, a high antibiotic resistance rate was found for piperacillin-tazobactam (p = 0.044), cefuroxime (p = 0.026), cefazolin (p = 0.043), levofloxacin (p = 0.018), erythromycin (p = 0.004), and clindamycin (p = 0.025). We conclude that elderly patients with staphylococcal pneumonia show resistance to common antibiotics. However, no significant antibiotic resistance could be ascribed for other types of pneumonia in these patients.
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A total of 232 fecal samples were collected from Tibetan pigs, and the disk diffusion method was used to examine their antimicrobial resistance. Broth microdilution and agar dilution methods were used to determine minimum inhibitory concentrations for antimicrobial agents for which disks were not commercially available.
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Treatment of post-LASIK nontuberculous mycobacteria remains a challenge. Institution of combination therapy including fortified amikacin, clarithromycin 1%, and a fourth-generation fluoroquinolone appeared to be beneficial in this patient.
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The study comprised 579 patients (579 eyes) who underwent cataract surgery. Specimens were collected by lightly rubbing the inferior palpebral conjunctival sac with a sterile cotton swab 2 weeks before surgery, and then cultured for isolation of bacteria and antimicrobial sensitivity testing. The bacterial isolates and percentage of drug-resistant isolates were compared among age groups and according to whether or not patients had diabetes mellitus, hyperlipidemia, dialysis therapy, oral steroid use, dry eye syndrome, or allergic conjunctivitis.
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To evaluate the antimicrobial susceptibility of Gram-negative bacilli that caused hospital-acquired and community-acquired intra-abdominal infections (IAIs) in China between 2012 and 2013, we determined the susceptibilities to 12 antimicrobials and the extended-spectrum β-lactamase (ESBL) statuses of 3,540 IAI isolates from seven geographic areas in China in a central laboratory using CLSI broth microdilution and interpretive standards. Most infections were caused by Escherichia coli (46.3%) and Klebsiella pneumoniae (19.7%). Rates of ESBL-producing E. coli (P = 0.031), K. pneumoniae (P = 0.017), and Proteus mirabilis (P = 0.004) were higher in hospital-acquired IAIs than in community-acquired IAIs. Susceptibilities of enterobacteriaceae to ertapenem, amikacin, piperacillin-tazobactam, and imipenem were 71.3% to 100%, 81.3% to 100%, 64.7% to 100%, and 83.1% to 100%, respectively, but imipenem was ineffective against P. mirabilis (<20%). Although most ESBL-positive hospital-acquired isolates were resistant to third- and fourth-generation cephalosporins, the majority were susceptible to cefoxitin (47.9% to 83.9%). Susceptibilities of ESBL-positive isolates to ampicillin-sulbactam (<10%) were low, whereas susceptibilities to ciprofloxacin (0% to 54.6%) and levofloxacin (0% to 63.6%) varied substantially. The prevalences of cephalosporin-susceptible E. coli and K. pneumoniae were higher in the northeastern and southern regions than in the central and eastern regions, reflecting the ESBL-positive rates in these areas, and were lowest in the Jiangsu-Zhejiang (Jiang-Zhe) area where the rates of carbapenem resistance were also highest. Ertapenem, amikacin, piperacillin-tazobactam, and imipenem are the most efficacious antibiotics for treating IAIs in China, especially those caused by E. coli or K. pneumoniae. Resistance to cephalosporins and carbapenems is more common in the Jiang-Zhe area than in other regions in China.
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We investigated the contribution of the Na(+)/L-carnitine cotransporter in the transport of tetraethylammonium (TEA) by rat renal brush-border membrane vesicles. The transient uphill transport of L-carnitine was observed in the presence of a Na(+) gradient. The uptake of L-carnitine was of high affinity (K(m)=21 microM) and pH dependent. Various compounds such as TEA, cephaloridine, and p-chloromercuribenzene sulfonate (PCMBS) had potent inhibitory effects for L-carnitine uptake. Therefore, we confirmed the Na(+)/L-carnitine cotransport activity in rat renal brush-border membranes. Levofloxacin and PCMBS showed different inhibitory effects for TEA and L-carnitine uptake. The presence of an outward H(+) gradient induced a marked stimulation of TEA uptake, whereas it induced no stimulation of L-carnitine uptake. Furthermore, unlabeled TEA preloaded in the vesicles markedly enhanced [14C]TEA uptake, but unlabeled L-carnitine did not stimulate [14C]TEA uptake. These results suggest that transport of TEA across brush-border membranes is independent of the Na(+)/L-carnitine cotransport activity, and organic cation secretion across brush-border membranes is predominantly mediated by the H(+)/organic cation antiporter.
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In Europe, 4 inhaled antibiotics (tobramycin, colistimethate sodium, aztreonam, and levofloxacin) are currently approved for the treatment of chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis (CF). Levofloxacin inhalation solution (LIS) is the most recently approved inhaled antibiotic for adult patients with CF. A systematic literature review and Bayesian network meta-analysis (NMA) was conducted to compare the relative short-term (4 weeks) and long-term (24 weeks) outcomes of these inhaled antibiotics versus LIS.
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We surveyed the group B Streptococcus (GBS) strains isolated from four teaching hospitals during 1-year period to investigate the current serotypes and antimicrobial resistance status of these strains. A total of 231 non-duplicate colonizing GBS isolates were collected from pregnant women. Antimicrobial susceptibility of these isolates was tested by the disk diffusion method. Serotype was performed by a multiplex polymerase chain reaction (PCR) method. Analysis of the resistance mechanisms was performed by PCR amplification and DNA sequencing. Seven serotypes (Ia, Ib, II, III, V, VI, and VIII) were identified, and the prevalence ranged from 0.9 to 35.9%. All isolates were susceptible to the penicillin, ceftriaxone, and vancomycin. The resistance of all the isolates to erythromycin, clindamycin, and levofloxacin was 61.5, 51.9, and 35.5%, respectively. The erythromycin resistance was mainly associated with the genes ermB and ermB-mef(A/E) (69.8%). The most predominant phenotype was cMLSB (77.5%). Five gene panels, including gyrA, parC, parE, gyrA-parC, and gyrA-parC-parE, were detected. The most predominant genotype was gyrA-parC-parE triple mutation (69.5%). The S81L in gyrA gene, S79Y mutation in parC gene, and H225Y mutation in parE gene were discovered. The isolates with serotype III, V, and Ia were the most important clone concerning the prevalence and resistance.
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Pediatric tuberculous meningitis (TBM) is a highly morbid, often fatal disease. Standard treatment includes isoniazid, rifampin, pyrazinamide, and ethambutol. Current rifampin dosing achieves low cerebrospinal fluid (CSF) concentrations, and CSF penetration of ethambutol is poor. In adult trials, higher-dose rifampin and/or a fluoroquinolone reduced mortality and disability. To estimate optimal dosing of rifampin and levofloxacin for children, we compiled plasma and CSF pharmacokinetic (PK) and outcomes data from adult TBM trials plus plasma PK data from children. A population PK/pharmacodynamic (PD) model using adult data defined rifampin target exposures (plasma area under the curve (AUC)0-24 = 92 mg*h/L). Levofloxacin targets and rifampin pediatric drug disposition information were literature-derived. To attain target rifampin exposures, children require daily doses of at least 30 mg/kg orally or 15 mg/kg intravenously (i.v.). From our pediatric population PK model, oral levofloxacin doses needed to attain exposure targets were 19-33 mg/kg. Our results provide data-driven guidance to maximize pediatric TBM treatment while we await definitive trial results.