Minimum Inhibitory Concentrations Of Levofloxacin Research Articles

In vitro susceptibility test of Xiao'er Feire Kechuan Oral Solution to Mycoplasma pneumoniae.

The aim of this study was to evaluate the inhibitory effect of antibiotics and Xiao’er Feire Kechuan Oral Solution on Mycoplasma pneumoniae (MP) clinical isolates.Twenty clinical isolates containing A-to-G transition at position 2063 and 10 clinical isolates without mutations in 23S rRNA V regions were randomly selected. The international standard strain FH was chosen as control strain. The minimum inhibitory concentration (MIC) of macrolide, quinolones, tetracycline, and Xiao’er Feire Kechuan Oral Solution to MP clinical isolates were performed using broth microdilution method.In vitro antibiotic susceptibility test of MP clinical isolates showed that MP showed high resistance to macrolide antibiotics (erythromycin and azithromycin); MIC of both were more than 64 μg/mL. The MICs of erythromycin and azithromycin for clinical isolates without mutations in 23S rRNA V regions were ≤0.5 μg/mL. The MICs of tetracycline and levofloxacin for all clinical isolated strains were ≤2.0 μg/mL and ≤1.0 μg/mL, respectively. The MIC of Xiao’er Feire Kechuan Oral Solution was 13.828∼6.914 mg/mL.In vitro, the drug resistance of MP to macrolide antibiotics is higher, MP clinical isolates are sensitive to tetracycline and levofloxacin, and Xiao’er Feire Kechuan Oral Solution also has a certain inhibitory effect on the macrolide-resistant MP.

<p>A novel mechanism of action of ketoconazole: inhibition of the <em>NorA</em> efflux pump system and biofilm formation in multidrug-resistant <em>Staphylococcus aureus</em></p>

Background: The rapid emergence of antimicrobial resistance among Gram-positive organisms, especially staphylococci, has become a serious clinical challenge. Efflux machinery and biofilm formation are considered two of the main causes of antimicrobial resistance and therapy failure.Aim: Our study aims to evaluate the antibiofilm and efflux pump inhibitory activity of the antifungal ketoconazole against multidrug-resistant (MDR) Staphylococcus aureus.Methods: Ketoconazole was tested for its effect on the following: minimum inhibitory concentrations (MICs) of ciprofloxacin, norfloxacin, levofloxacin, and ethidium bromide (EtBr) by the broth microdilution method, the efflux of EtBr by NorA-positive MDR S. aureus, and the relative expression of NorA, NorB, and NorC efflux pump genes. Docking studies of ketoconazole were performed using 1PW4 (glycerol-3-phosphate transporter from Escherichia coli which was the representative structure from the major facilitator superfamily).Results: Ketoconazole significantly decreased the MICs of levofloxacin, ciprofloxacin, norfloxacin, and EtBr (a substrate for efflux pump) by 8 to 1024-fold (P<0.01) and decreased the efflux of EtBr. Furthermore, a time-kill assay revealed that combinations of levofloxacin with ketoconazole or carbonyl cyanide m-chlorophenylhydrazone showed no growth for the tested strains after 24 h in comparison to the effect of levofloxacin alone. Docking studies and the ability of ketoconazole to diminish the relative expression of NorA gene in comparison to control (untreated strains) confirmed its action as an efflux pump inhibitor. Conclusion: The findings showed that the antifungal ketoconazole has no antibacterial activity but can potentiate the activity of the fluroquinolones against MDR S. aureus via inhibiting efflux pump and biofilm formation in vitro.

Evaluating Minimum Inhibitory Concentration Values of Levofloxacin and Azithromycin on Haemophilus Influenzae

Background: Community Acquired Pneumonia (CAP) is leading cause of morbidity and mortality in all age groups globally. 4 million cases of Community Acquired Pneumonia occur annually. Haemophilus influenzae is a causative organism of CAP. Empirical treatment with antibiotics like levofloxacin and azithromycin is recommended in these cases. Objectives: This study was conducted to evaluate the minimum inhibitory concentration of levofloxacin and azithromycin in H. influenzae isolates from respiratory specimens. Design: Minimum inhibitory concentrations of levofloxacin and azithromycin in 40 clinically significant H.influenzae isolates were tested using E-test method after the approval of Institutional Ethics committee. The results were analyzed according to 2019 CLSI guidelines. Result: MIC50 for levofloxacin was 0.008 µg/ml, MIC90 1.5 µg/ml and the 3 resistant isolates had MIC ranging between 8 and 12 µg/ml. Azithromycin MIC50 was 0.047µg/ml, MIC90 6.4 µg/ml and 5 resistant isolates had MIC between 6 and 32µg/ml. Conclusion: The rising MIC of levofloxacin and azithromycin in H.influenzae emphasizes the need to monitor the antibiotic susceptibility pattern on a regular basis. It is also advisable to restrain the use of fluoroquinolones to make it available for use in the tuberculosis treatment and also to avoid any adverse effects.

Long-term effects of cataract surgery with topical levofloxacin on ocular bacterial flora

To clarify the long-term effect of topical antibiotics on the ocular bacterial flora after cataract surgery. Miyata Eye Hospital, Miyazaki, Japan. Prospective case series. Patients who had cataract surgery between November 2014 and January 2015 were included. Levofloxacin 1.5% was administered 4 times a day by topical instillation from 3days before surgery to 1month postoperatively. The conjunctival sacs of patientswere scraped before the procedure and 0, 3, 6, 9, and 12months after the last instillation. The samples were cultured, and minimum inhibitory concentrations (MICs) of levofloxacin for Staphylococcus epidermidis and Propionibacterium acnes were evaluated using mixed-effects models. The study evaluated 50 patients. Diverse bacterial species, predominantly S epidermidis and P acnes, were isolated before the application of topical levofloxacin. Bacterial diversity was substantially reduced after the final topical levofloxacin application and subsequently increased after 3months. However, the geometric mean levofloxacin MICs for S epidermidis isolates were still significantly higher at 0months and 3months than before treatment (P<.01 and P=.03, respectively) and reached pretreatment levels 6months and 12months after the last application. Propionibacterium acnes did not show significant changes in the geometric mean levofloxacin MIC over time. The restoration of the bacterial flora required more than 6months after cataract surgery and topical levofloxacin.

Conjunctival Bacteria Flora of Glaucoma Patients During Long-Term Administration of Prostaglandin Analog Drops

To investigate the effects of the long-term use of prostaglandin analogs for glaucoma treatment on the indigenous flora of the conjunctiva. Bacterial isolates were collected from the conjunctival sacs of 68 patients at Miyata Eye Hospital from February to September 2014, who had been receiving continuous monotherapy with prostaglandin analogs for glaucoma for at least 1 year. Minimum inhibitory concentrations of levofloxacin, gatifloxacin, moxifloxacin, cefmenoxime, tobramycin, chloramphenicol, and erythromycin against the isolates were measured to determine susceptibility. The positive culture rate in all cases was 90.5% (57/63 eyes), and a total of 79 bacterial strains were isolated. The isolated bacteria included aerobic gram-positive cocci (8% Staphylococcus aureus and 41% Staphylococcus epidermidis), coagulase-negative staphylococci (5%), Streptococcus spp. (1%), Corynebacterium spp. (4%), gram-negative bacteria (4%), and the facultative anaerobe Propionibacterium acnes (33%). The positive culture rates for patients using 0.005% latanoprost (Xa group) and 0.004% travoprost (Tz group) were 88.9% and 92.6%, respectively, with no statistically significant difference in the composition of isolated bacteria between groups. Methicillin-resistant S. epidermidis (MRSE) was significantly more frequently isolated in the Xa group. The antimicrobial susceptibility rates of S. epidermidis were significantly lower in the Xa group for levofloxacin, gatifloxacin, moxifloxacin, and tobramycin. The indigenous flora may be affected by the long-term use of prostaglandin analogs. The higher incidence of MRSE in the Xa group should be considered during the long-term, continuous administration of eye drops, such as in glaucoma treatment.

Antimicrobial susceptibilities of Chlamydia trachomatis isolated from the urethra and pharynx of Japanese males.

Sexually transmitted infections due to Chlamydia trachomatis (C.trachomatis) are a worldwide public health problem. The aim of this study was to investigate the drug susceptibilities of C.trachomatis strains isolated from the urethra and pharynx of Japanese males. Urethral and pharyngeal swabs were collected between 2013 and 2014 from Japanese males with urethritis. Using a McCoy cell line, 18 chlamydial strains were isolated from urethra in 18 patients and 7 from the pharynx in 7 of the 18 patients. The minimum inhibitory concentrations (MICs) of levofloxacin (LVFX) and azithromycin (AZM) were measured using the standard method of the Japanese Society of Chemotherapy. The MICs of LVFX and AZM against urethral chlamydial strains were 0.125-0.5μg/mL and 0.125-0.25μg/mL, respectively. In pharyngeal strains, the MICs of LVFX and AZM were 0.125-0.25μg/mL and 0.125-0.25μg/mL, respectively. In 7 patients with chlamydial strains isolated from both the urethra and pharynx, the MICs of LVFX between these strains were identical in 3 of 6 patients (no growth was observed for one pharyngeal strain), while the MICs of AZM between these strains were identical in all 6 patients (not performed for one patient). Our data suggest that C.trachomatis strains isolated from the urethra and pharynx of Japanese males are susceptible to LVFX and AZM. Although measuring the MICs of chlamydial strains is labor intensive, it is a significant surveillance tool for treating chlamydial infections and preventing the spread of STIs.

Pefloxacin as a surrogate marker for quinolone susceptibility in Salmonella enterica serovars Typhi & Paratyphi A in India.

Background & objectives:The emergence of resistance to fluoroquinolones in enteric fever despite the pathogen being susceptible by in vitro laboratory results, led to repeated changes in Clinical and Laboratory Standard Institute (CLSI) guidelines for this class of antibiotics to have specific and sensitive interpretative criteria. In 2015, CLSI added pefloxacin disk diffusion criteria as a surrogate marker for fluoroquinolone susceptibility. This study was carried out to evaluate the use of pefloxacin as a surrogate marker for ciprofloxacin, ofloxacin and levofloxacin susceptibility in clinical isolates of Salmonella Typhi and S. Paratyphi A.Methods:A total of 412 strains of S. Typhi and S. Paratyphi A were studied for pefloxacin disk diffusion test as a surrogate marker for susceptibility to ciprofloxacin, ofloxacin and levofloxacin as per CLSI and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Molecular mechanisms of resistance to fluoroquinolones were also determined and correlated with pefloxacin susceptibility breakpoints.Results:Of the total 412 strains, 34 were susceptible to ciprofloxacin and 33 each to levofloxacin and ofloxacin using CLSI minimum inhibitory concentration (MIC) breakpoints. There was a positive correlation between MICs with correlation coefficients 0.917, 0.896 and 0.958 for the association between ciprofloxacin and ofloxacin, ciprofloxacin and levofloxacin and ofloxacin and levofloxacin, respectively (P <0.001). The sensitivity, specificity and positive predictive value of pefloxacin as a surrogate marker using ciprofloxacin MIC as a gold standard were 100, 99.5 and 94.4 per cent, while 100, 99.2 and 91.7 per cent taking ofloxacin and levofloxacin MIC as gold standard. Mutations in target genes correlated with the pefloxacin susceptibility results.Interpretation & conclusions:Our results showed that pefloxacin served as a good surrogate marker for the detection of susceptibility to ciprofloxacin, ofloxacin and levofloxacin in S. Typhi and S. Paratyphi A. Further studies are required to confirm these findings.

Bactericidal activity and post-antibiotic effect of ozenoxacin against Propionibacterium acnes.

Ozenoxacin, a novel non-fluorinated topical quinolone, is used for the treatment of acne vulgaris in Japan. We investigated bactericidal activity and post-antibiotic effect (PAE) of ozenoxacin against Propionibacterium acnes, a major causative bacterium of acne vulgaris. The minimum inhibitory concentrations (MICs) of ozenoxacin against 3 levofloxacin-susceptible strains (MIC of levofloxacin; ≤4μg/mL) and 3 levofloxacin-resistant strains (MIC of levofloxacin; ≥8μg/mL) ranged from 0.03 to 0.06μg/mL and from 0.25 to 0.5μg/mL, respectively. These MICs of ozenoxacin were almost the same or lower than nadifloxacin and clindamycin. The minimum bactericidal concentrations (MBCs) of ozenoxacin against the levofloxacin-susceptible and -resistant strains were from 0.06 to 8μg/mL and from 0.5 to 4μg/mL, respectively. These MBCs were lower than those of nadifloxacin and clindamycin. In time-kill assay, ozenoxacin at 1/4, 1 and 4 times the respective MIC against both levofloxacin-susceptible and -resistant strains showed a concentration-dependent bactericidal activity. Ozenoxacin at 4 times the MICs against the levofloxacin-susceptible strains showed more potent and more rapid onset of bactericidal activity compared to nadifloxacin and clindamycin at 4 times the respective MICs. The PAEs of ozenoxacin at 4 times the MICs against the levofloxacin-susceptible strains were from 3.3 to 17.1h, which were almost the same or longer than nadifloxacin and clindamycin. In contrast, the PAEs were hardly induced by any antimicrobial agents against the levofloxacin-resistant strains. The present findings suggest that ozenoxacin has a potent bactericidal activity against both levofloxacin-susceptible and -resistant P.acnes, and a long-lasting PAE against levofloxacin-susceptible P.acnes.

Haemophilus influenzae Isolated From Men With Acute Urethritis: Its Pathogenic Roles, Responses to Antimicrobial Chemotherapies, and Antimicrobial Susceptibilities.

There have been few comprehensive studies on Haemophilus influenza-positive urethritis. In this retrospective study, we enrolled 68 men with H. influenzae-positive urethritis, including coinfections with Neisseria gonorrhoeae, Chlamydia trachomatis, and/or genital mycoplasmas: 2, 3, 20, and 43 treated with ceftriaxone, levofloxacin, sitafloxacin, and extended-release azithromycin (azithromycin-SR), respectively. We assessed microbiological outcomes in 54 men and clinical outcomes in 46 with H. influenzae-positive monomicrobial nongonococcal urethritis. We determined minimum inhibitory concentrations (MICs) of 6 antimicrobial agents for 59 pretreatment isolates. H. influenzae was eradicated from the men treated with ceftriaxone, levofloxacin, or sitafloxacin. The eradication rate with azithromycin-SR was 85.3%. The disappearance or alleviation of urethritis symptoms and the decreases in leukocyte counts in first-voided urine were significantly associated with the eradication of H. influenzae after treatment. For the isolates, ceftriaxone, levofloxacin, sitafloxacin, azithromycin, tetracycline, and doxycycline MICs were ≤0.008-0.25, 0.008-0.5, 0.001-0.008, 0.12-1, 0.25-16, and 0.25-2 μg/mL, respectively. The azithromycin MICs for 3 of 4 strains persisting after azithromycin-SR administration were 1 μg/mL. H. influenzae with an azithromycin MIC of 1 μg/mL increased chronologically. H. influenzae showed good responses to the chemotherapies for urethritis. The significant associations of the clinical outcomes of the chemotherapies with their microbiological outcomes suggested that H. influenzae could play pathogenic roles in urethritis. All isolates, except for one with decreased susceptibility to tetracyclines, were susceptible to the examined agents. However, the increase in H. influenzae with an azithromycin MIC of 1 μg/mL might threaten efficacies of azithromycin regimens on H. influenzae-positive urethritis.

Rise in Haemophilus influenzae With Reduced Quinolone Susceptibility and Development of a Simple Screening Method.

β-Lactamase-nonproducing ampicillin-resistant Haemophilus influenzae are prevalent in Japan. Resistance has increased as a consequence of the expanded use of antimicrobial agents, raising concerns about the rise of multidrug (macrolide and fluoroquinolone)-resistant H. influenzae. In this study, we investigated susceptibility to fluoroquinolones in H. influenzae clinical isolates from 2013 to 2014 and identified the amino acid substitutions in quinolone resistance-determining regions of gyrA and parC. All isolates (n = 145) were susceptible to fluoroquinolones; however, some showed reduced susceptibility. The minimum inhibitory concentration of levofloxacin for these strains was 0.063-0.5 µg/mL, and the strains harbored the amino acid substitution S84L in GyrA. Such strains have seen a significant increase. Importantly, all mutants from 2014 were isolated from pediatric patients. In addition, we developed a simple polymerase chain reaction-based screening method for detecting isolates with reduced fluoroquinolone susceptibility. The mutation in GyrA is important as a first step in the development of fluoroquinolone resistance. Hence, detection of reduced susceptible strains may influence the choice of antimicrobial treatment.

Effect of the administration period of perioperative topical levofloxacin on normal conjunctival bacterial flora

To assess the long-term and short-term effects of post-cataract surgery antibiotic therapy on the drug-resistance profile of normal conjunctival bacterial flora. Miyata Eye Hospital, Miyazaki, Japan. Randomized prospective clinical trial. Patients aged 20years or older who had cataract surgery between May and September 2015 were given levofloxacin 1.5% ophthalmic solution for 3days preoperatively. The patients were randomly assigned to a 1-week postoperative group or a 1-month postoperative group according to postoperative administration duration. Conjunctival sacs were scraped for bacterial culturing before administration, 1week postoperatively, at the completion of administration, and 1, 3, and 6months after administration completion. The bacterial culture growth and minimum inhibitory concentrations (MICs) of levofloxacin against recovered strains of Staphylococcus epidermidis were assessed. The study enrolled 104 patients. The MICs of levofloxacin against S epidermidis increased during levofloxacin administration compared with before administration in both groups and then declined after administration completion. However, by 3months, the MICs in the 1-month group were approximately twice those in the 1-week group. Antibiotic susceptibility before administration, at completion of administration, and at 3months was 73.6%, 20.2%, and 38.5%, respectively, in the 1-week group and 63.0%, 0.0%, and 19.3%, respectively, in the 1-month group. The results indicate that from completion of administration to 3months, the susceptible strains were approximately 20% lower in the 1-month postoperative group than in the 1-week postoperative group. Administration duration of perioperative levofloxacin 1.5% influenced the MICs and susceptibility of S epidermidis isolated from the conjunctival sac.

Expression of the Fluoroquinolones Efflux Pump Genes acrA and mdfA in Urinary Escherichia coli Isolates.

Escherichia coli is one of the most frequent causes of urinary tract infections. Efflux system overexpression is reported to contribute to E. coli resistance to several antibiotics. Our aim in this study was to investigate the relation between antibiotic resistance and the expression of the efflux pump genes acrA and mdfA in E. coli by real-time reverse transcription-PCR. We tested the in vitro susceptibilities to 12 antibiotics in 28 clinical isolates of E. coli obtained from urine samples. We also determined the minimum inhibitory concentrations of levofloxacin to these samples. We then revealed significant correlations between the overexpression of both mdfA and acrA and MICs of levofloxacin. In conclusion, we demonstrated that the increased expression of efflux pump genes such as mdfA and acrA can lead to levofloxacin resistance in E. coli. These findings contribute to further understanding of the molecular mechanisms of efflux pump systems and how they contribute to antibiotic resistance.

Outcomes of high-dose levofloxacin therapy remain bound to the levofloxacin minimum inhibitory concentration in complicated urinary tract infections

BackgroundFluoroquinolones are a guideline-recommended therapy for complicated urinary tract infections, including pyelonephritis. Elevated drug concentrations of fluoroquinolones in the urine and therapy with high-dose levofloxacin are believed to overcome resistance and effectively treat infections caused by resistant bacteria. The ASPECT-cUTI phase 3 clinical trial (ClinicalTrials.gov, NCT01345929 and NCT01345955, both registered April 28, 2011) provided an opportunity to test this hypothesis by examining the clinical and microbiological outcomes of high-dose levofloxacin treatment by levofloxacin minimum inhibitory concentration.MethodsPatients were randomly assigned 1:1 to ceftolozane/tazobactam (1.5 g intravenous every 8 h) or levofloxacin (750 mg intravenous once daily) for 7 days of therapy. The ASPECT-cUTI study provided data on 370 patients with at least one isolate of Enterobacteriaceae at baseline who were treated with levofloxacin. Outcomes were assessed at the test-of-cure (5–9 days after treatment) and late follow-up (21–42 days after treatment) visits in the microbiologically evaluable population (N = 327).ResultsTest-of-cure clinical cure rates above 90% were observed at minimum inhibitory concentrations ≤4 μg/mL. Microbiological eradication rates were consistently >90% at levofloxacin minimum inhibitory concentrations ≤0.06 μg/mL. Lack of eradication of causative pathogens at the test-of-cure visit increased the likelihood of relapse by the late follow-up visit.ConclusionsResults from this study do not support levofloxacin therapy for complicated urinary tract infections caused by organisms with levofloxacin minimum inhibitory concentrations ≥4 μg/mL.Trial registrationClinicalTrials.gov, NCT01345929 and NCT01345955 Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-2057-2) contains supplementary material, which is available to authorized users.

Study of Multidrug Resistance Pattern among Escherichia coli isolated from patients with Urinary tract infection

Objective: Urinary tract infections (UTIs) are some of the most common bacterial infections encountered in community and cause of significant morbidity and high medical cost. Escherichia coli is the most common pathogen belongs to Enterobacteriaceae family responsible for majority of UTI infections. Antimicrobial drugs have been routinely prescribed for empirical treatment of UTIs which has led to a dramatic increase in antibiotic resistance pattern of E. coli. The aim of present study was to analyse the multidrug resistance patterns (MDR) of E. coli isolated from UTI patients.Methods: A total of 80 urine samples collected from the patients suspected of having UTI attending Maharishi Markandeshwar Institute of Medical Sciences and Research (MMIMSR), Mullana, Ambala were cultured using standard microbiological techniques. Antibiotic susceptibility testing of E.coli was done by using minimum inhibitory concentration (MIC). MIC of tetracycline, doxycycline, azithromycin, erythromycin, ciprofloxacin, levofloxacin, ampicillin, amoxicillin and amikacin was done by agar dilution method.Results: Of the total 46 isolates contributing 33 females and 13 males were confirmed as E. coli. About 51.34% of the female patients belonged to the age group 21-40 yr and 53.84% of the male population belonged to 41-80 yr were found to be more susceptible to UTI infection. All isolates confirmed as E.coli were found to be multidrug resistant. 80% of the isolates exhibited MICs higher than 1000mg/L against β-lactams. 20% of the E. coli isolates exhibited MICs higher than 1000mg/L against ciprofloxacin, amikacin and erythromycin. 23% and 95% of E. coli isolates exhibited MICs less than 128 mg/L against doxycycline and levofloxacin respectively.Conclusion: The present study revealed the decreased susceptibility of the E.coli to all drugs. E. coli resistance profile to beta lactams, quinolones, macrolides, tetracyclines and aminoglycosides were also found to be quite high in this study emphasizing the need to educate public about appropriate use of antibiotics.NA

Changes in minimum inhibitory concentration of levofloxacin for Escherichia coli strains isolated from urine samples in mainland China, 2004 to 2014.

Eschrichia coli urinary isolates were collected from 20 Chinese hospitals during five 1-year periods from 2004 to 2014. The susceptibility of E. coli to levofloxacin has remained stable during the past 11years, and 90% of strains had minimum inhibitory concentrations of ≤32mg/L. The urine-specific susceptibility breakpoints for levofloxacin should be reset based on more relevant clinical studies and the current pharmacokinetic/pharmacodynamic considerations in this field.

Nationwide surveillance of the antimicrobial susceptibility of Chlamydia trachomatis from male urethritis in Japan.

Genital chlamydial infection is a principal sexually transmitted infection worldwide. Chlamydia trachomatis can cause male urethritis, acute epididymitis, cervicitis, and pelvic inflammatory disease as sexually transmitted infections. Fortunately, homotypic resistant C.trachomatis strains have not been isolated to date; however, several studies have reported the isolation of heterotypic resistant strains from patients. In this surveillance study, clinical urethral discharge specimens were collected from patients with urethritis in 51 hospitals and clinics in 2009 and 38 in 2012. Based on serial cultures, the minimum inhibitory concentration (MIC) could be determined for 19 isolates in 2009 and 39 in 2012. In 2009 and 2012, the MICs (MIC90) of ciprofloxacin, levofloxacin, tosufloxacin, sitafloxacin, doxycycline, minocycline, erythromycin, clarithromycin, and azithromycin were 2μg/ml and 1μg/ml, 0.5μg/ml and 0.5μg/ml, 0.125μg/ml and 0.125μg/ml, 0.063μg/ml and 0.063μg/ml, 0.125μg/ml and 0.125μg/ml, 0.125μg/ml and 0.125μg/ml, 0.016μg/ml and 0.016μg/ml, and 0.063μg/ml and 0.063μg/ml, respectively. In summary, this surveillance project did not identify any resistant strain against fluoroquinolone, tetracycline, or macrolide agents in Japan.

Pharmacodynamically Guided Levofloxacin Dosing for Pediatric Community-Acquired Pneumonia

Oral levofloxacin is recommended as a preferred treatment for infection with Streptococcus pneumoniae with a penicillin minimum inhibitory concentration (MIC) of ≥4 µg/mL and as an alternative for infection with S pneumoniae with a penicillin MIC of ≤2 µg/mL. To investigate the current dosing recommendations and create a pharmacodynamically guided regimen, a Monte Carlo simulation was performed. The simulation included a previously published 1-compartment model, and incorporated a formula that takes into account age-appropriate weights for hospitalized patients. Three different dosing regimens, including community-acquired pneumonia guideline dosing, inhalational anthrax dosing, and a pharmacodynamically guided regimen, were assessed. The probability of target attainment was described as the proportion of patients who achieve an unbound-drug area under the concentration-time curve over 24 hours divided by the MIC above 33.7 µg/mL per hour. Microbiologic data from 2 stand-alone pediatric tertiary care centers were included. Guideline-recommended doses of levofloxacin seem to produce suboptimal exposure in patients aged 5-14 years for pneumococci with an MIC of 1 µg/mL. Anthrax dosing was suboptimal in patients aged <5 years and in those aged >15 years. The pharmacodynamically guided regimen maintained a probability of target attainment of >90% for all age groups without producing peak concentrations higher than those previously described. None of the regimens attained the pharmacodynamic targets for a levofloxacin MIC of 2 µg/mL. Current dosing recommendations were found to be suboptimal for specific age groups. A pharmacodynamically guided levofloxacin dosing regimen was determined, but it will need to be studied clinically for safety and tolerability.

In vitro time–kill curves study of three antituberculous combinations against Mycobacterium tuberculosis clinical isolates

The objective of this study was to examine the in vitro synergism of three-drug combinations against Mycobacterium tuberculosis (levofloxacin/linezolid/ethambutol, levofloxacin/amikacin/ethambutol and levofloxacin/linezolid/amikacin) using the time–kill curves method. In total, 8 multidrug-resistant and 12 drug-susceptible M. tuberculosis isolates were used. Minimum inhibitory concentrations (MICs) of the isolates for each drug were determined by the proportions method. Time–kill curves were studied for the three combinations proposed over 14 days using two different protocols. In protocol 1, 0.5× MIC for each drug was used. In protocol 2, 0.5× MIC for levofloxacin and linezolid and 0.25× MIC for amikacin and ethambutol were used. The MICs for all of the isolates studied were 0.5mg/L for levofloxacin and linezolid and 2.5mg/L for ethambutol and amikacin. All of the combinations displayed an additive activity compared with the most active individual drug. In conclusion, these results demonstrate that the three combinations tested were equally effective against M. tuberculosis isolates. The study of antituberculous combinations using in vitro methods is an excellent first step to predict their effect in clinical development phases as well as to test new regimens of the antituberculous drugs currently available.

Inhibitory effects of emodin, baicalin, schizandrin and berberine on hefA gene: treatment of Helicobacter pylori-induced multidrug resistance.

To investigate the inhibitory effects of emodin, baicalin, etc. on the hefA gene of multidrug resistance (MDR) in Helicobacter pylori (H. pylori). The double dilution method was used to screen MDR H. pylori strains and determine the minimum inhibitory concentrations (MICs) of emodin, baicalin, schizandrin, berberine, clarithromycin, metronidazole, tetracycline, amoxicillin and levofloxacin against H. pylori strains. After the screened MDR stains were treated with emodin, baicalin, schizandrin or berberine at a 1/2 MIC concentration for 48 h, changes in MICs of amoxicillin, tetracycline, levofloxacin, metronidazole and clarithromycin were determined. MDR strains with reduced MICs of amoxicillin were selected to detect the hefA mRNA expression by real-time quantitative PCR. A total of four MDR H. pylori strains were screened. Treatment with emodin, baicalin, schizandrin and berberine significantly decreased the MICs of amoxicillin and tetracycline against some strains, decreased by 1 to 2 times, but did not significantly change the MICs of clarithromycin, levofloxacin, and metronidazole against MDR strains. In the majority of strains with reduced MICs of amoxicillin, hefA mRNA expression was decreased; one-way ANOVA (SPSS 12.0) used for comparative analysis, P < 0.05. Emodin, baicalin, schizandrin and berberine significantly decreased the MICs of amoxicillin and tetracycline against some H. pylori strains, possibly by mechanisms associated with decreasing hefA mRNA expression.

Serotype distribution and resistance genes associated with macrolide and fluoroquinolone resistance in Streptococcus agalactiae isolates from a hospital in southern Taiwan.

Antimicrobial resistance of Streptococcus agalactiae (Group B Streptococcus, GBS) has been emerging worldwide. We aimed to examine the correlation of drug-resistant genes with serotypes and with the mutations of the quinolone resistance-determining region (QRDR) in GBS isolates. A total of 323 human GBS isolates were collected from a hospital in southern Taiwan. Laboratory investigation included serotyping by a multiplex polymerase chain reaction (PCR) method, antimicrobial susceptibility testing by a disc diffusion method, and mechanism analysis of the resistance to macrolides and fluoroquinolones by PCR and sequencing methods. Multiplex PCR showed that the most prevalent serotypes were Ib, III, V, and VI, mostly isolated from urine. The ermB gene was highly prevalent in serotypes Ib and V and was associated with clindamycin and macrolide resistance. GBS with a serine-to-leucine mutation at codon 81 in GyrA and with a serine-to-phenylalanine or -tyrosine mutation at codon 79 in ParC had a higher minimum inhibitory concentration of levofloxacin than isolates with only an aspartic acid-to-tyrosine mutation at codon 83 (>32 μg/ml vs. 16 μg/ml) in GyrA. The most prevalent GBS serotypes were Ib, III, V, and VI. The ermB and mefE genes carried in serotypes Ib and V were highly associated with the resistance to macrolides and clindamycin. Mutations at codon 79 and codon 83 of ParC were the major determining factors for high-level fluoroquinolone resistance.