Susceptibility of Ureaplasma urealyticum to Tetracycline,Doxycycline, Erythromycin,Roxithromycin, Clarithromycin,Azithromycin, Levofloxacin and Moxifloxacin

Abstract

The in vitro activity of tetracycline, doxycycline, erythromycin, roxithromycin, clarithromycin, azithromycin, levofloxacin and moxifloxacin was tested against 63 clinical isolates of Ureaplasma urealyticum. The minimal inhibitory concentrations (MICs) and the minimal bactericidal concentrations (MBCs) were determined by the broth microdilution method in A7 medium. The miC50 and miC90 of the tested agents after 24 h of incubation were as follows: Tetracycline, 0.5 and 2.0 μg/ml; doxycycline, 0.125 and 0.25 μg/ml; erythromycin, 2.0 and 8.0 μg/ml; roxithromycin, 2.0 and 4.0 μg/ml; clarithromycin, 0.25 and 1.0 μg/ml; azithromycin, 2.0 and 4.0 μg/ml; levofloxacin, 1.0 and 2.0 μg/ml; and moxifloxacin, 0.5 and 0.5 μg/ml, respectively. The MIC values after 24 h and 48 h incubation differed by no more than one dilution for all the agents with the exception of doxycycline (two dilution difference for MIC₉₀). Overall, moxifloxacin was the most active agent in vitro against U. Urealyticum, with the narrowest difference between MIC and MBC values, followed closely by levofloxacin. Clarithromycin was the most active macrolide.     

An ex-vivo pharmacodynamic study comparing bactericidal activity of amoxicillin/sulbactam, azithromycin, doxycycline and levofloxacin against Streptococcus pneumoniae

We designed a 4-way crossover, ex-vivo pharmacodynamic study to compare the bactericidal rate of amoxicillin/sulbactam (AMX-SUL), azithromycin (AZM), doxycycline (DOX) and levofloxacin (LVX) against Streptococcus pneumoniae ATCC 49619. Six volunteers were randomized to receive alternatively a single tablet of the above drugs. Venous blood samples were obtained immediately before and at 2, 4 and 6 h after dose to perform time-kill studies and to determine antibiotic levels in serum. AMX-SUL was the only drug showing bactericidal activity with the sera obtained at every time after dose, as defined by a > or = 3-log10 cfu/ml decrease in the viable cell counts compared to the original inoculum after a 24-h incubation. AZM was only inhibitory at 2h after dose (i.e. a 1.3-log10 cfu/ml decrease in the viable cell counts) and proved bactericidal at 4 and 6 h post-dose. LVX proved bactericidal with the 2-h serum, was only inhibitory with the 4-h serum (e.g. a 1.5-log10 cfu/ml decrease) and was unable to avoid bacterial growth at 6 h post-dose. Bacterial growth was observed with DOX at every time after dose. This study may shed light on the understanding of breakthrough pneumococcal bacteremia during the course of oral therapy with AZM in patients with community-acquired nia (CAP), as well as the increasing treatment failures observed with LVX, and the selection of bacterial resistance during therapy reported with both drugs. It also provides the basis for a "warning signal" on the use of oral DOX and confirms the efficacy of AMX-SUL.     

In vivo pharmacodynamic evaluation of clarithromycin in comparison to erythromycin

The efficacy of various dosing regimens of clarithromycin and erythromycin against recently isolated Streptococcus pneumoniae strains was determined in vivo using two animal infection models (mouse peritonitis and thigh infection). For the thigh infection model, mice received a total dose of 4 mg/Kg of either clarithromycin or erythromycin, as a single total dose or divided into 2, 4 or 8 doses/24h. After 24h of therapy S. pneumoniae organisms were killed at 2.06 to 4.03 log10 CFU/thigh by clarithromycin and the one- or two-dose regimens were significantly more effective than the four- or eight-dose regimens. Organism killing following 24h of therapy with erythromycin ranged from 1.13 to 2.31 log10 CFU/thigh, with the one- or two-dose regimens significantly less effective than the four- or eight-dose regimens. In the mouse survival study, the same dose of either clarithromycin or erythromycin was given as a single total dose or divided into two or four doses with dosing intervals of 4 and 2-times the t1/2 respectively. The results obtained in this model show that there is a significant difference in survival when clarithromycin is administered less frequently (4% deaths for the one-dose regimen in comparison to 40% deaths with the four-dose regimen, P < 0.01, Chi-square test). With erythromycin there was a trend for increased survival with the multiple-dose regimen, with significantly higher survival when concentrations exceeding the MIC were maintained for a longer time period. These results indicate that the time during which serum concentrations exceeding the MIC value of the pathogen is an important parameter for efficacy for erythromycin. On the contrary, results with both animal models demonstrate that bacterial killing and survival are significantly higher among clarithromycin-treated mice when the antibiotic is administered less frequently and the highest Cmax/MIC ratio is achieved.     

Effect of moxifloxacin on bacterial pathogenicity factors in comparison with amoxicillin, clarithromycin and ceftriaxone

Moxifloxacin is a recent fluoroquinolone with an antibacterial spectrum encompassing both aerobic Gram-negative and Gram-positive strains, as well as anaerobic bacteria. In this study the activity of moxifloxacin against Streptococcus pneumoniae, Staphylococcus aureus, Moraxella catarrhalis, Haemophilus influenzae, Escherichia coli, Proteus mirabilis and Pseudomonas aeruginosa, and effects of subinhibitory concentrations on bacterial morphology and adhesion properties were compared with those of amoxicillin, clarithromycin and ceftriaxone. The in vitro activity of moxifloxacin against Gram-positive and Gram-negative pathogens was equal to or better than that of comparators. Subinhibitory concentrations of moxifloxacin significantly affected bacterial morphology of S. pneumoniae, M. catarrhalis, H. influenzae and P. aeruginosa, leading to formation of spherical forms and filaments. Moreover, bacterial adhesion to buccal cells and fibroblasts was reduced after treatment with 1/4 and 1/8 X MIC of moxifloxacin. In conclusion, subinhibitory concentrations of moxifloxacin remarkably interfere with some bacterial pathogenic factors, thereby contributing to its antimicrobial activity.     

Prevalence of Ureaplasma urealyticum and Mycoplasma hominis infection in unselected infertile men

Abstract

In this study, we investigated the prevalence of Ureaplasma urealyticum and Mycoplasma hominis infection among 250 unselected infertile men, the presence of urogenital symptoms in infected men and the effects of these microorganisms on the conventional sperm parameters. Urethral samples were obtained using a swab inserted 3–4 cm into the urethral meatus. Ureaplasma urealyticum and Mycoplasma hominis were detected by the kit Mycofast R evolution 3 Elitech Microbiology (Elitech Microbiology, Signes, France). Ureaplasma urealyticum was detected in 15·6% of the cases and Mycoplasma hominis in 3·6%. One patients had a co-infection with both pathogens. About 41% of the infertile patients with mycoplasma infection had urogenital symptoms. A lower number of patients with mycoplasma infection had normal sperm parameters compared with non-infected infertile men, but this frequency showed only a trend compared to non-infected patients (Chi-square?=?3·61; P?=?0·057), and a significantly higher percentage of patients with oligo-astheno-teratozoospermia (Chi-square?=?127·3; P<0·0001), or asthenozoospermia alone (Chi-square?=?5·74; P<0·05) compared to non-infected infertile patients. In conclusion, this study showed an elevated prevalence of ureaplasma urealyticum and mycoplasma hominis infection in unselected men attending an infertility outpatient clinic and that the presence of these microorganisms is associated with a higher percentage of patients with abnormal sperm parameters.     

Penetration of moxifloxacin and levofloxacin into cancellous and cortical bone in patients undergoing total hip arthroplasty

Penetration of levofloxacin and moxifloxacin into cancellous and cortical bone was studied using high-performance liquid chromatography (HPLC) in 16 patients who underwent routine total hip arthroplasty. Our results demonstrate a good degree of penetration into bone for both quinolones. The mean cancellous penetration was 53.86% for moxifloxacin and 54.13% for levofloxacin. The penetration into cortical bone was 41.59% and 34.26% respectively. The concentrations for both quinolones were above the minimum inhibitory concentration (MIC(90s)) for the most common pathogens, so they can be used for the treatment of osteomyelitis.     

Bactericidal activity of moxifloxacin compared to grepafloxacin and clarithromycin against Streptococcus pneumoniae and Streptococcus pyogenes investigated using an in vitro pharmacodynamic model

The aim of the present investigation was to study and compare the killing activity of two new fluoroquinolone compounds, moxifloxacin and grepafloxacin, and a new generation macrolide, clarithromycin, against three clinical isolates of Streptococcus pneumoniae (penicillin-susceptible, -intermediate and -resistant) and two Streptococcus pyogenes (erythromycin-susceptible and -resistant) strains by simulating their human pharmacokinetics in a pharmacodynamic model. Results were achieved by measuring the reduction in viable bacterial count during the 24-h experimental period. All three antimicrobials led to a continuous reduction in the bacterial counts of penicillin-susceptible S. pneumoniae and erythromycin-susceptible S. pyogenes strains, the maximal reduction observed after 8-10 hours being 5-6 logs for moxifloxacin and 3 logs for grepafloxacin; clarithromycin exhibited a similar reduction of 5 logs only after 24 h. No regrowth was observed for any strain after 24 h with any of the antibiotics. The bactericidal activity of both the fluoroquinolones was not affected by penicillin resistance of S. pneumoniae and erythromycin resistance of S. pyogenes. In contrast, clarithromycin was not able to reduce the bacterial count of penicillin-resistant S. pneumoniae and erythromycin-resistant S. pyogenes strains. Moxifloxacin exhibited, within 24 h, higher and faster bactericidal activity than grepafloxacin and clarithromycin against S. pneumoniae, and was not affected by penicillin resistance. These results suggest that moxifloxacin is a promising new agent for treatment of streptococcal infections.     

In vitro induction of resistance by tissue concentrations of azithromycin, clarithromycin, cefixime and amoxicillin/clavulanate in clinical isolates of Streptococcus pyogenes

This study evaluated the effects of exposure to serum, tonsils and breakpoint drug concentrations of clarithromycin, azithromycin, cefixime and amoxicillin/clavulanate on Streptococcus pyogenes susceptibility. Frequency of mutation and development of resistance after ten passages on antibiotic gradient plates, followed by ten passages without antibiotic, were determined. Phenotypes of macrolide-resistant strains grown at the end of multi-step selection were also determined. Azithromycin induced a surge of resistant strains more rapidly and frequently than clarithromycin, particularly at tonsils concentrations. With amoxicillin/clavulanate no strains showed minimum inhibitory concentrations (MICs) higher than the susceptibility breakpoint. Mutational frequencies were higher for azithromycin, at serum and breakpoint drug concentrations, than for the other drugs. Most of the macrolide resistant strains showed an MLS(B) phenotype. In conclusion, the ability to prevent the occurrence of resistance in clinical isolates of S. pyogenes was similar for amoxicillin/clavulanate and clarithromycin followed by cefixime > azithromycin when tonsil drug concentrations were considered, and greater for amoxicillin/clavulanate followed by clarithromycin > cefixime> azithromycin, at breakpoint and serum concentrations.     

Comparative analysis of azithromycin and clarithromycin efficacy and tolerability in the treatment of chronic prostatitis caused by Chlamydia trachomatis

A total of 123 patients, older than 18 years of age, with symptoms of chronic prostatitis and inflammatory findings as well as the presence of Chlamydia trachomatis confirmed by DNA/RNA DIGENE hybridization method in expressed prostatic secretion or in voided bladder urine collected immediately after prostatic massage, were examined. The patients were randomized to receive a total of 4.5 g of azithromycin for 3 weeks, given as a 3-day therapy of 1 x 500 mg weekly or clarithromycin 500 mg b.i.d. for 15 days. Patients' sexual partners were treated at the same time. Clinical and bacteriological efficacy were evaluated 4-6 weeks after the end of therapy. In the group of patients with chronic chlamydial prostatitis the eradication rates (azithromycin 37/46, clarithromycin 36/45) and the clinical cure rates (azithromycin 32/46, clarithromycin 32/45) were not significantly different with regards to the administered drug (p > 0.05). In the group of patients with asymptomatic chlamydial prostatitis the eradication rates (azithromycin 11/16, clarithromycin 10/15) were not significantly different with regards to the administered drug (p = 1.00, OR = 1.1).     

Antimicrobial efficacy of gatifloxacin and moxifloxacin with and without benzalkonium chloride compared with ciprofloxacin and levofloxacin against methicillin-resistant Staphylococcus aureus

We compared the antimicrobial activity of gatifloxacin and moxifloxacin with and without benzalkonium chloride (BAK) against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). Minimum inhibitory concentrations (MICs) against clinical isolates of MRSA were evaluated. Approximately 10(5 )CFU/ml of methicillinresistant S. aureus was added to Mueller-Hinton broth containing two-fold concentration increments of drug. For the evaluation of gatifloxacin with BAK, 50 microg/ml of BAK were added to the first well of the plate with gatifloxacin or moxifloxacin and then serially diluted. The combination of gatifloxacin or moxifloxacin with BAK was more active than either fluoroquinolone without BAK. The MICs ranged from 相似文献   

Comparative Analysis of Azithromycin and Doxycycline Efficacy in the Treatment of Female Patients with Acute Urethral Syndrome Caused by Ureaplasma urealyticum

Abstract

Rifaximin, a poorly absorbed rifamycin derivative, exhibited time-dependent bactericidal activity and at concentrations as low as 1/32 of the minimum inhibitory concentration (MIC) caused morphological alterations in both susceptible and resistant bacterial strains. Spontaneous rifaximin-resistant clones appeared with an incidence of 2.6×10^?7. The percentage of Escherichia coli cells cured of various plasmids ranged from: 4.5-70% (Flac), 0-18% (pBP507), 7.7-43.8% (plasmid carrying ESBL genes) and 22.4-41.6% (plasmid encoding toxin from ETEC mex264). 8.4-18.2 and <0.1- 18% of Staphylococcus aureus cells were cured (plasmid-mediated penicillinase), 9.5-58.6% of Morganella morganii (ESBL), 10.6-47.1% Citrobacter freundii(ESBL), 2.3-38.7% of Proteus mirabilis (ESBL) and 14.3-66.6% of Klebsiella pneumoniae (ESBL). Rifaximin reduced plasmid transfer from donor to recipient strains by >99%. The MIC of ceftazidime was reduced (2-4 dilutions) in the presence of rifaximin (0.5xMIC) in ESBL producing strains. Rifaximin lowered the viability and virulence of the bacteria even though they developed resistance to the compound.

In conclusion, the present findings add new features to the microbiological characteristics of rifaximin and suggest that if in vivo pathogens are exposed to sub-MICs of the drug, not only are their physiological functions compromised, but gene virulence and antibiotic resistance are not fully expressed.     

Accumulation of azithromycin and roxithromycin in tracheal epithelial fetal cell lines expressing wild type or mutated cystic fibrosis transmembrane conductance regulator protein (CFTR)

Macrolides are accumulated in phagocytes, partially via an active transport system; the membrane carrier is not identified but many data indicate a link with the P-glycoprotein family which includes the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. We have used two epithelial cell lines which express either wild-type (N cells) or mutated (homozygous deltaF508) (F cells) CFTR to study the cellular accumulation of two macrolides (azithromycin and roxithromycin). Adherent cells were incubated with the radiolabeled drugs before extensive washings and counting. Azithromycin was better (about 2-fold) accumulated in F cells up to 60 min but then plateaued, whereas accumulation continued without saturation over 3 hours in N cells. Roxithromycin was also better (1.5-fold) accumulated in F cells at 15 and 30 min, but there were no differences at further incubation times. Macrolide efflux from loaded N and F cells, and the susceptibilities of the carrier systems (entry and efflux) to various pharmacologic agents were similar to those previously observed with phagocytes. These data suggest that the macrolide carriers (for entry and efflux) are not strictly specific for phagocytes and that the CFTR protein plays a role in macrolide uptake.     

Treatment of Waldenstrom's macroglobulinemia with clarithromycin,low-dose thalidomide,and dexamethasone

Twelve patients with Waldenstrom's macroglobulinemia (WM) underwent treatment with the nonmyelosuppressive combination regimen BLT-D: clarithomycin (Biaxin [BXN], Abbott Laboratories, Abbott Park, IL) 500 mg orally twice daily, low-dose thalidomide (THAL) 50 mg orally escalated to 200 mg daily, and dexamethasone (DXM) 40 mg orally once weekly all with modification for toxicity. Omepraxole 20 mgm orally twice daily for 2 days with the DXM, and enteric-coated aspirin 81 mg orally daily were also administered. Twelve patients have been evaluated. All had previously received at least one purine analogue or alkylating agent. Five had a reduction in either leukocytes and/or platelets prior to treatment, of which three were disease-related. Median age was 62 years. All patients received a minimum of 6 weeks of therapy. Of the 12 patients, 10 had a significant response (83%) consisting of three near complete, three major, four partial, and two minor responses. Four of five had restoration of reduced blood counts. Two with minor responses did not receive sufficient dose escalation due to toxicity. Median time on therapy was 7 months (range, 3 to 28 months). Patients were removed from therapy primarily due to neurotoxicity. Drug resistance occurred in three patients, with one transformation to large cell lymphoma. Toxicity was as follows: gastrointestinal (primarily constipation), 42%; neurological, 100%; endocrine, 42%, and thrombotic, 8%. Most toxicities were World Health Organization (WHO) grade 1 or 2; however, neurological toxicity was more prominent and severe in WM patients than in myeloma. BLT-D is effective in WM. Because of its toxicity, predominantly neurological, BLT-D may best serve as an induction regimen or to "rescue" patients with refractory disease or disease-related low counts.