Success of susceptibility-guided eradication of Helicobacter pylori in a region with high secondary clarithromycin and levofloxacin resistance rates

BACKGROUND Resistance to clarithromycin(CLA)and levofloxacin(LFX)of Helicobacter pylori(H.pylori)is increasing in severity,and successful eradication is essential.Presently,the eradication success rate has greatly declined,leaving a large number of patients with previous treatment histories.AIM To investigate secondary resistance rates,explore risk factors for antibiotic resistance,and assess the efficacy of susceptibility-guided therapy.METHODS We recruited 154 subjects positive for Urea Breath Test who attended The First Affiliated Hospital of China Medical University between July 2022 and April 2023.Participants underwent a string test after an overnight fast.The gastric juice was obtained and transferred to vials containing storage solution.Subsequently,DNA extraction and the specific DNA amplification were performed using quantitative polymerase chain reaction(qPCR).Demographic information was also analyzed as part of the study.Based on these results,the participants were administered susceptibility-guided treatment.Efficacy was compared with that of the empiric treatment group.RESULTS A total of 132 individuals tested positive for the H.pylori ureA gene by qPCR technique.CLA resistance rate reached a high level of 82.6%(n=109),LFX resistance rate was 69.7%(n=92)and dual resistance was 62.1%(n=82).Gastric symptoms[odds ratio(OR)=2.782;95%confidence interval(95%CI):1.076-7.194;P=0.035]and rural residence(OR=5.152;95%CI:1.407-18.861;P=0.013)were independent risk factors for secondary resistance to CLA and LFX,respectively.A total of 102 and 100 individuals received susceptibility-guided therapies and empiric treatment,respectively.The antibiotic susceptibility-guided treatment and empiric treatment groups achieved successful eradication rates of 75.5%(77/102)and 59.0%(59/411)by the intention-to-treat(ITT)analysis and 90.6%(77/85)and 70.2%(59/84)by the per-protocol(PP)analysis,respectively.The eradication rates of these two treatment strategies were significantly different in both ITT(P=0.001)and PP(P=0.012)analyses.CONCLUSION H.pylori presented high secondary resistance rates to CLA and LFX.For patients with previous treatment failures,treatments should be guided by antibiotic susceptibility tests or regional antibiotic resistance profile.

Corrugated surface microparticles with chitosan and levofloxacin for improved aerodynamic performance

Corrugated surface microparticles comprising levofloxacin(LEV),chitosan and organic acid were prepared using the 3-combo spray drying method.The amount and the boiling point of the organic acid affected the degree of roughness.In this study,we tried to improve the aerodynamic performance and increase aerosolization by corrugated surface microparticle for lung drug delivery efficiency as dry powder inhaler.HMP175 L20 prepared with 175 mmol propionic acid solution was corrugated more than HMF175 L20 prepared with 175 mmol formic acid solution.The ACI and PIV results showed a significant increase in aerodynamic performance of corrugated microparticles.The FPF value of HMP175 L20 was 41.3%±3.9%compared with 25.6%±7.7%of HMF175 L20.Corrugated microparticles also showed better aerosolization,decreased x-axial velocity,and variable angle.Rapid dissolution of drug formulationswas observed in vivo.Lowdoses administered to the lungs achieved higher LEV concentrations in the lung fluid than high doses administered orally.Surface modification in the polymer-based formulation was achieved by controlling the evaporation rate and improving the inhalation efficiency of DPIs.

Levofloxacin体外抗菌活性研究

利用试管双倍稀释法及纸片法测定ｌｅｖｏｆｌｏｘａｃｉｎ（ＬＶＬＸ）体外抗菌活性，并与其它１０种药物比较。结果表明ＬＶＬＸ对革兰氏阴性菌具有良好抗菌作用，尤以对痢疾杆菌、伤寒杆菌、变形杆菌、肺炎杆菌、产气杆菌、大肠杆菌作用更为突出，ＭＩＣ５０≤０．０３～０．２８μｇ／ｍｌ，ＭＩＣ９０≤０．０３～１２８μｇ／ｍｌ，抑菌率６０％～１００％；其活性为氧氟沙星的１～４倍，比诺氟沙星、头孢呋辛强，与环丙沙星、庆大霉素及头孢噻肟相当。ＬＶＬＸ抗葡萄球菌活性为所测喹诺酮中最强，与头孢唑林相当，对肺炎球菌、溶血性及草绿色链球菌作用与头孢菌素相当。ＬＶＬＸ有较强抗铜绿假单胞菌活性，ＭＩＣ５０与ＭＩＣ９０分别为０．５与６４μｇ／ｍｌ，与阿米卡星及头孢哌酮相当。ＬＶＬＸ为一广谱高效抗菌药物。

健康受试者口服Levofloxacin的药动学研究

本文报道８例健康志愿者体内单次及多次给予３００ｍｇＬｅｖｏｆｌｏｘａｃｉｎ后的药代动力学研究。血药浓度及尿药浓度采用微生物和ＨＰＬＣ测定。单次及多次给药后的数据分别采用３ｐ８７及ＳＳＤ程序处理，药－时曲线符合二室模型。单次口服３００ｍｇＬｅｖｏｆｌｏｘａｃｉｎ，其微生物和ＨＰＬＣ测定结果分别为Ｔｍａｘ１．３１和１．４３ｈ，Ｃｍａｘ３．８４和４．２０ｍｇ／Ｌ，ｔ１／２２６．１２和６．０６ｈ。０～２４ｈ尿药回收率分别为６８．７９和６６．４３％。经ｔ检验两种方法的测定结果无显著性差异（ｐ＞０．０５）。在每日３００ｍｇｑ１２ｈ连续８天的多次口服给药实验中，第１天和第８天的药代动力学参数经ｔ－检验无显著性差异（ｐ＞０．０５），说明本品每日２次重复给药无明显蓄积现象。

Resistance of Helicobacter pylori to furazolidone and levofloxacin: A viewpoint

In their review, Arslan et al[1] did not describe the status of Helicobacter pylori(H. pylori) treatment with furazolidone and the resistance to this antibiotic. We have presented different surveys showing the resistance of H. pylori to furazolidone from Asia and South America. The resistance rates varied but were mostly low(< 5%). There are not enough data on its efficacy and resistance in the United States and Europe. H. pylori mutations occurring in the oor D gene, including A041 G, A122 G, C349A(G), A78 G, A112 G, A335 G, C156 T and C165 T, and in the por D gene, including G353 A, A356 G, C357 T, C347 T, C347 G and C346 A, have been indicated to be possibly related to the observed resistance. Additionally, to complete Arslan et al 's statement regarding levofloxacin resistance, it should be noted that compound mutations of N87 A, A88 N and V65 I at codon Asn-87 were recently observed in the gyr A gene for the first time. However, the results on these topics are not sufficient, and more worldwide studies are suggested.

Safety and efficacy of levofloxacin versus ciprofloxacin for the treatment of chronic bacterial prostatitis in Chinese patients

Levofloxacin is a synthetic fluoroquinolone that is usually used to treat chronic bacterial prostatitis. We investigated the safety and efficacy of levofloxacin compared with ciprofloxacin for the treatment of chronic bacterial prostatitis in Chinese patients. This was a multicenter, open-label, randomized controlled non-inferiority trial. Four hundred and seventy-one patients with clinical symptoms/ signs were enrolled into the study, and 408 patients were microbiologically confirmed chronic bacterial prostatitis, who were randomized to either oral levofloxacin （500 mg q,d.） or ciprofloxacin （500 mg b.i^d.） for 4 weeks. Bacterial clearance rate, clinical symptoms/signs, adverse reactions and disease recurrence were assessed. The clinical symptoms and signs （including dysuria, perineal discomfort or pain） and bacteria cultures in 209 patients treated with levofloxacin and 199 patients treated with ciprofloxacin were similar. The most common bacteria were Escherichia cofiand Staphylococcus aureus. One to four weeks after the end of 4 weeks treatment, the bacterial clearance rate （86.06% vs. 60.03%; P〈O.05） and the clinical efficacy （including clinical cure and clinical improvement（93.30% vs. 71.86%; P〈0.05）） were significantly higher in the levofloxacin-treated group than in the ciprofloxacin-treated group. The microbiological recurrence rate was significantly lower in the levofloxacin-treated group than in the ciprofloxacin-treated group （4.00% vs. 19.25%; P〈0.05）. Rates of adverse events and treatment-related adverse events were slightly lower in the levofloxacin-treated group than in ciprofloxacin-treated group. Levofloxacin showed some advantages over ciprofloxacin in terms of clinical efficacy and disease recurrence, with a low rate of adverse events, for the treatment of chronic bacterial prostatitis in Chinese patients.

Levofloxacin/amoxicillin-based schemes vs quadruple therapy for Helicobacter pylori eradication in second-line

Worldwide prevalence of Helicobacter pylori(H.pylori) infection is approximately 50%,with the highest being in developing countries.We compared cure rates and tolerability(SE) of second-line anti-H.pylori levofloxacin/amoxicillin(LA)-based triple regimens vs standard quadruple therapy(QT).An English language literature search was performed up to October 2010.A meta-analysis was performed including randomized clinical trials comparing 7-or 10-d LA with 7-d QT.In total,10 articles and four abstracts were identified.Overall eradication rate in LA was 76.5%(95% CI:64.4%-97.6%).When only 7-d regimens were included,cure rate was 70.6%(95% CI:40.2%-99.1%),whereas for 10-d combinations,cure rate was significantly higher(88.7%;95% CI:56.1%-109.9%;P < 0.05).Main eradication rate for QT was 67.4%(95% CI:49.7%-67.9%).The 7-d LA and QT showed comparable efficacy [odds ratio(OR):1.09;95% CI:0.63-1.87],whereas the 10-d LA regimen was significantly more effective than QT(OR:5.05;95% CI:2.74-9.31;P < 0.001;I 2 = 75%).No differences were reported in QT eradication rates among Asian and European studies,whereas LA regimens were more effective in European populations(78.3% vs 67.7%;P = 0.05).Incidence of SE was lower in LA therapy than QT(OR:0.39;95% CI:0.18-0.85;P = 0.02).A higher rate of side effects was reported in Asian patients who received QT.Our findings support the use of 10-d LA as a simple second-line treatment for H.pylori eradication with an excellent eradication rate and tolerability.The optimal second-line alternative scheme might differ among countries depending on quinolone resistance.

Comparison of the anti-inflammatory effects of fluorometholone 0.1% combined with levofloxacin 0.5% and tobramycin/dexamethasone eye drops after cataract surgery

AIM： To compare the combination of fluorometholone0.1% and levofloxacin 0.5% to tobramycin/dexamethasone eye drops in controlling inflammation and preventing infection after phacoemulsification with an intraocular lens implantation.METHODS： Sixty eyes from 60 patients undergoing cataract phacoemulsification were randomized into two groups; half of the patients were treated with fluorometholone（6 times/d） combined with levofloxacin（4 times/d）, while the other half were treated with tobramycin/dexamethasone（4 times/d） eye drops for one week. Preoperative and postoperative intraocular pressure, aqueous flare, corneal thickness, and signs and symptoms were recorded before the operation and1 wk following treatments. RESULTS： There were no statistically significant differences between the two groups in corneal thickness（P ≥0.629）, aqueous flare（P ≥0.398）, and signs and symptoms scores（P ≥0.350） at each time point. Ocular hypertension was only observed in two eyes in the tobramycin/dexamethasone group. CONCLUSION： Fluorometholone combined with levofloxacin treatment shows comparable efficacy but without the tendency to increase intraocular pressure;thus, it might be a better regimen for postoperative use.

Low efficacy of levofloxacin-doxycycline-based third-line triple therapy for Helicobacter pylori eradication in Italy

AIM:To evaluate a levofloxacin-doxycycline-based triple therapy with or without a susceptibility culture test in non-responders to Helicobacter pylori(H.pylori) eradication.METHODS:A total of 142(99 women,43 men; mean 53.0 ± 12.7 years) non-responders to more than two H.pylori eradication therapies underwent susceptibility culture tests or were treated with a seven-day triple therapy consisting of esomeprazole,20 mg b.i.d.,levofloxacin,500 mg b.i.d.,and doxycycline,100 mg b.i.d.,randomly associated with(n = 71) or without(n = 71) Lactobacillus casei DG.H.pylori status was checked in all patients at enrollment and at least 8 wk after the end of therapy.Compliance and tolerability of regimens were also assessed.RESULTS:H.pylori eradication was achieved in < 50% of patients [per prototol(PP) = 49%; intention to treat(ITT) = 46%].Eradication rate was higher in patients administered probiotics than in those without(PP = 55% vs 43%; ITT = 54% vs 40%).Estimated primary resistance to levofloxacin was 18% and multiple resistance was 31%.Therapy was well tolerated,and side effects were generally mild,with only one patient experiencing severe effects.CONCLUSION:Third-line levofloxacin-doxycycline triple therapy had a low H.pylori eradication efficacy,though the success and tolerability of this treatment may be enhanced with probiotics.

Development and validation of a simple UV spectrophotometric method for the determination of levofloxacin both in bulk and marketed dosage formulations

A rapid, specific and economic UV spectrophotometric method has been developed using a solvent composed of water：methanol：acetonitrile （9：0.5：0.5） to determine the levofloxacin content in bulk and pharmaceutical dosage formulations. At a pre-determined 2 of 292 nm, it was proved linear in the range of 1.0 12.0 μg/mL, and exhibited good correlation coefficient （R2=0.9998） and excellent mean recovery （99.0-100.07%）. This method was successfully applied to the determination of levofloxacin content in five marketed brands from Bangladesh and the results were in good agreement with the label claims. The method was validated statistically and by recovery studies for linearity, precision, repeatability, and reproducibility. The obtained results proved that the method can be employed for the routine analysis of levofloxacin in bulks as well as in the commercial formulations.

Standard triple versus levofloxacin based regimen for eradication ofHelicobacter pylori

AIM:To compare the eradication rates for Helicobacter pylori(H.pylori) and ulcer recurrence of standard triple therapy(STT) and levofloxacin based therapy(LBT).METHODS:Seventy-four patients with perforated duodenal ulcer treated with simple closure and found to be H.pylori infected on 3 mo follow up were randomized to receive either the STT group comprising of amoxicillin 1 g bid,clarithromycin 500 mg bid and omeprazole 20 mg bid or the LBT group comprising of amoxicillin 1 g bid,levofloxacin 500 mg bid and omeprazole 20 mg bid for 10 d each.The H.pylori eradication rates,side effects,compliance and the recurrence of ulcer were assessed in the two groups at 3 mo follow up.RESULTS:Thirty-four patients in the STT group and 32 patients in the levofloxacin group presented at 3 mo follow up.H.pylori eradication rates were similar with STT and the LBT groups on intention-to-treat(ITT) analysis(69% vs 80%,P = 0.425) and(79% vs 87%,P = 0.513) by per-protocol(PP) analysis respectively.Ulcer recurrence in the STT and LBT groups on ITT analysis was(20% vs 14%,P = 0.551) and(9% vs 6%,P = 1.00) by PP analysis.Compliance and side effects were also comparable between the groups.A complete course of STT costs Indian Rupees(INR) 1060.00,while LBT costs only INR 360.00.CONCLUSION:H.pylori eradication rates and the rate of ulcer recurrence were similar between the STT and LBT.The LBT is a more economical option compared to STT.

Intensification of levofloxacin sono-degradation in a US/H_2O_2 system with Fe_3O_4 magnetic nanoparticles

Fe3O4 magnetic nanoparticles(MNPs) were synthesised, characterised, and used as a peroxidase mimetic to accelerate levofloxacin sono-degradation in an ultrasound(US)/H2O2 system. The Fe3O4 MNPs were in nanometre scale with an average diameter of approximately 12 to 18 nm. The introduction of Fe3O4 MNPs increased levofloxacin sono-degradation in the US/H2O2 system. Experimental parameters, such as Fe3O4 MNP dose, initial solution p H, and H2O2 concentration, were investigated by a one-factor-at-a-time approach. The results showed that Fe3O4 MNPs enhanced levofloxacin removal in the p H range from 4.0 to 9.0. Levofloxacin removal ratio increased with Fe3O4 MNP dose up to 1.0 g·L-1and with H2O2 concentration until reaching the maximum. Moreover, three main intermediate compounds were identified by HPLC with electrospray ionisation tandem mass spectrometry, and a possible degradation pathway was proposed. This study suggests that combination of H2O2, Fe3O4 MNPs and US is a good way to improve the degradation efficiency of antibiotics.

High color rendering index white organic light-emitting diode using levofloxacin as blue emitter

Levofloxacin （LOFX）, which is well-known as an antibiotic medicament, was shown to be useful as a 452-nm blue emitter for white organic light-emitting diodes （OLEDs）. In this paper, the fabricated white OLED contains a 452-nm blue emitting layer （thickness of 30 nm） with 1 wt% LOFX doped in CBP （4,4＇-bis（carbazol-9-yl）biphenyl） host and a 584-nm orange emitting layer （thickness of 10 nm） with 0.8 wt% DCJTB （4-（dicyanomethylene）-2-tert-butyl-6-（1,1,7,7- tetramethyljulolidin-4-yl-vinyl）-4H-pyran） doped in CBE which are separated by a 20-nm-thick buffer layer of TPBi （2,2＇,2＂-（benzene-1,3,5-triyl）-tri（1-phenyl-lH-benzimidazole）. A high color rendering index （CRI） of 84.5 and CIE chromaticity coordinates of （0.33, 0.32）, which is close to ideal white emission CIE （0.333, 0.333）, are obtained at a bias voltage of 14 V. Taking into account that LOFX is less expensive and the synthesis and purification technologies of LOFX are mature, these results indicate that blue fluorescence emitting LOFX is useful for applications to white OLEDs although the maximum current efficiency and luminance are not high. The present paper is expected to become a milestone to using medical drug materials for OLEDs.

Comparative efficacy of levofloxacin and ceftriaxone in the treatment of community acquired pneumonia in children

Pneumonia is a common cause of mortality and morbidity in under-5 children throughout the world. Globally an estimated 156 million new episodes of pneumonia occur each year in children and 2 million children die from pneumonia each year which is 20 percent of all deaths of children under five years old. Ceftriaxone is a commonly used drug for empiric treatment of community acquired pneumonia (CAP) in children. Levofloxacin may be an adequate option for empiric therapy in treatment of CAP in children because it gives the broad spectrum activity against both bacterial and atypical pathogens causing CAP and studies suggest that it can be safely used in children. This open labeled, randomized, comparative clinical trial was carried out in the Department of Pediatrics, Sylhet MAG Osmani Medical College Hospital, Bangladesh during January, 2011 & December, 2012 to compare the efficacy of levofloxacin and ceftriaxone in the treatment CAP in children. A total 70 cases of CAP were enrolled. 35 cases were allocated to levofloxacin group and another 35 cases to ceftriaxone group. At first the study cases were selected by systematic random sampling. Group allocation to either levofloxacin or ceftriaxone group was done by lottery method. Total duration for receiving study drugs was seven days. Dose of levofloxacin was 10 mg/kg/day children ≥5 years, where as it was 10 mg/kg 12 hourly in 6 months to <5 years age groups. Dose of ceftriaxone was 75 mg/kg/day. Response to treatment was assessed initially after 3 days and also after 7 days by clinical symptoms and signs. Clinical cure rate was determined by disappearance of the clinical signs and symptoms of pneumonia and resolution of radiological findings reported at admission. Clinical responses were categorized as cured and treatment failure. 91.43% cases were cured in levofloxacin group, whereas cure rate of ceftriaxone group was 68.57% which was statistically significant (p = 0.0168). Adverse effects of levofloxacin were found as skin rash in 1 case and vomiting in 2 cases whereas skin rash was found in 1 case in ceftriaxone group. So it can be concluded that levofloxacin is more effective than ceftriaxone in the treatment of CAP in children.

QSAR Studies on the Inhibitory Activityof Levofloxacin-thiadiazole HDACi Conjugates to Histone Deacetylases

A molecular electronegativity distance vector(M)based on 13 atomic types has been used to describe the structures of 19 conjugates(LHCc)of levofloxacin-thiadiazole HDAC inhibitor(HDACi)and related inhibitory activities(pH,i=1,2,6)of LHCc against histone deacetylases(HDACs,such as HDAC1,HDAC2 and HDAC6).The quantitative structure-activity relationships(QSAR)were established by using leaps-and-bounds regression analysis for the inhibitory activities(pH)of 19 above compounds to HDAC1,HDAC2 and HDAC6 along with M.The correlation coefficients(R~2)and the leave-one-out(LOO)cross validation Rfor the pH,pHand pHmodels were 0.976 and 0.949;0.985 and 0.977;0.976 and 0.932,respectively.The QSAR models had favorable correlations,as well as robustness and good prediction capability by R~2,F,R~2,A,Fand Vtests.Validated by using 3876 training sets,the models have good external prediction ability.The results indicate that the molecular structural units:–CH–(g=1,2),–NH,–OH,=O,–O–and–S–are the main factors which can affect the inhibitory activity of pH,pHas well as pHbioactivities of these compounds directly.Accordingly,the main interactions between HDACs inhibitor and HDACs are hydrophobic interaction,hydrogen bond,and coordination with Znto form compounds,which is consistent with the results in reports.

Development and validation of microbial bioassay for quantification of Levofloxacin in pharmaceutical preparations

The aim of this study was to develop and validate a simple,sensitive,precise and cost-effective onelevel agar diffusion（5＋1） bioassay for estimation of potency and bioactivity of Levofioxacin in pharmaceutical preparation which has not yet been reported in any pharmacopoeia.Among 16 microbial strains.Bacillus pumilus ATCC-14884 was selected as the most significant strain against Levofioxacin.Bioassay was optimized by investigating several factors such as buffer pH,inoculums concentration and reference standard concentration.Identification of Levofioxacin in commercial sample Levoflox tablet was done by FTIR spectroscopy.Mean potency recovery value for Levofioxacin in Levoflox tablet was estimated as 100.90%.A validated bioassay method showed linearity（r^2 = 0.988）,precision（Interday RSD=1.05%,between analyst RSD=1.02%） and accuracy（101.23%,RSD=0.72%）.Bioassay was correlated with HPLC using same sample and estimated potencies were 100.90% and 99.37%.respectively.Results show that bioassay is a suitable method for estimation of potency and bioactivity of Levofioxacin pharmaceutical preparations.

A Single Blind Comparative Randomized Non-Inferior Multicenter Study for Efficacy and Safety of Levofloxacin versus Ciprofloxacin in the Treatment of Uncomplicated Typhoid Fever

Ciprofloxacin is currently the drug of choice for typhoid fever, but Salmonella typhi resistance to ciprofloxacin is increasing, while levofloxacin has been shown to be very effective in a few open studies. This study aimed to compare the efficacy, and safety of levofloxacin and ciprofloxacin for typhoid fever. From 110 patients with confirmed typhoid fever, 54 patients received oral levofloxacin 500 mg once daily with one drop out, while 56 received ciprofloxacin 500 mg twice daily for 7 days with two drop outs. Defervescence of fever was achieved on an average of 3 days after initiating levofloxacin and 5 days after starting ciprofloxacin and one microbiologically non confirmed typhoid fever relapse occurred in the levofloxacin group while two relapses with positive Salmonella microorganism occurred in the ciprofloxacin group. No carrier of Salmonella typhi was found in both groups at day 30. Adverse reactions were more pronounced in the ciprofloxacin group compared to the levofloxacin group. In conclusion, oral levofloxacin 500 mg once daily for one week showed faster fever clearance compared to ciprofloxacin 500 mg twice daily in typhoid fever in Indonesia, and less adverse reactions occurred with levofloxacin compared to ciprofloxacin. This electronic document is a “live” template. The various components of your paper (title, text, heads, etc.) are already defined on the style sheet, as illustrated by the portions given in this document.

Pharmacokinetic Prediction of Levofloxacin Accumulation in Tissue and Its Association to Tendinopathy

Objectives: We investigated pharmacokinetic tissue distributions of Levofloxacin to explain adverse tendon incidents. Methods: The pharmacokinetic profiles of single and multiple dosing of 500 mg Levofloxacin following oral and IV infusion administration were simulated. Monte Carlo simulation was used to simulate the drug concentration profiles in plasma and tissue after seven dosing regimens while varying the drug’s elimination and distribution rates to analyze the effects of changing those rates on Levofloxacin accumulation in tissue. Results: Simulated data following oral and IV administration reflect well the reported data (mean simulated plasma Cmax = 6.59 μg/mL and 5.19 μg/mL for IV and oral versus 6.4 μg/mL and 5.2 μg/mL for observed clinical IV and oral route, respectively). Simulations of seven repetitive doses are also in agreement with reported values. Low elimination rates affect the drug concentration in plasma and tissue significantly with the concentration in plasma rising to 35 μg/mL at day 7. Normal elimination rates together with escalation of distribution rates from plasma to tissue increase tissue concentration after 7 doses to 9.5 μg/mL, a value is more than twice that of normal. Conclusions: Simulation can be used to evaluate drug concentration in different tissues. The unexpectedly high concentrations in some cases may explain the reason for tendinopathy in clinical settings.

Comparative Study of the Mutant Prevention Concentrations of Sulfamethoxazole-Trimethoprim Alone and in Combination with Levofloxacin against <i>Stenotrophomonas maltophilia</i>

Objectives: To determine the mutant prevention concentration (MPC) of sulfamethoxazole-trimethoprim (SXT) alone and in combination with levofloxacin (LVX) against Stenotrophomonas maltophilia (S. maltophilia) and to determine if the combination may decrease the emergence of resistant mutants. Methods: The MPC with 20 S. maltophilia strains which were both susceptible to SXT and LVX were determined by inhibiting visible growth among 1010 CFU on four agar plates after 72 hours incubation at 37°C. Results: All except two strains (18/20) showed a mutant prevention concentration ≥ 152/8 μg/mL for SXT and the range of the mutant prevention concentration for the SXT in combination with LVX is 9.5/0.5~608/32 μg/mL, which demonstrates at least 2 fold reduction except one strain. There was a significant difference (P < 0.01) between SXT alone and in combination with LVX on the mutant prevention concentration and mutant prevention concentration/minimum inhibitory concentration values. Conclusions: The MPC/MIC values were narrowed for SXT by combining with LVX against the S maltophilia. The combination may decrease the enrichment of mutant bacterial populations. Much study is needed to verify whether the using of drug combinations may restrict or even block the selection of S. maltophilia mutants.

Al-Akidi Therapeutic Protocol for Severe Infections Associated with Covid-19:Potential and Effective Treatment by Levofloxacin and Vitamin D3 and Zinc(Part 1)

Background:The emergence of Coronavirus SARS-CoV-2 evoked an unprecedented threat globally.Ever since the spread of this pandemic research and clinical trials have concentrated on the repurposing of already exciting FDA drugs to find a successful candidate to combat Covid-19.Objective:The objective of this study is to propose a therapeutic protocol that may have a potential solution to treat the severe infections associated with coronavirus.The clinical application of this protocol(Al-Akidi Therapeutic Protocol,A-TP)is highly recommended,as there are several scientific evidences that support this trusted protocol to be of great potential.Methods and Materials:This A-TP includes the use of one of the respiratory Fluoroquinolones(Levofloxacin or Moxifloxacin)in doses of 500 mg twice daily for 7-10 days,together with high doses of Vitamin D3(10000 IU/day)and Zinc(50 mg daily)for few weeks.This protocol is based on the previous antiviral activity of those Fluoroquinolones towards few viruses,the potent antibacterial activity on respiratory infections and high available concentrations in the lungs.It is also based on molecular docking of Levofloxacin and Moxifloxacin on various viral enzymes.Results:Molecular docking showed encouraging and very interesting docking scores and binding affinity of Levofloxacin and Moxifloxacin to certain viral enzymes,such as,RNA dependent RNA polymerase(RdRp),3-Cysteine-Like protease,Neuraminidase,Replicase polyproteins and Trans-Membrane Protease Serine 2 inhibitor(TMPRSS2).The highly expected clinical results of using this protocol are:reduce infection,control of temperature,improve breathing with less dependent on supplemented oxygen,and remarkable reduction of the pro-inflammatory cytokine storm,and hence,reduce hospitalization and mortality.Conclusion:Levofloxacin is highly recommended in managing the severe infections associated with Corona virus and has a remarkable reduction of pro-inflammatory cytokine storm as an immuomodulating agent.Levofloxacin is superior in this protocol over Moxifloxacin,due to its high excretion(≤83%)as unchanged through the kidneys,while Moxifloxacin is only 20%is excreted unchanged.It is an extra advantage of Levofloxacin to manage coronavirus in the kidneys.High doses of Vitamin D3 and Zinc are very useful to provide additional effective measures to combat Corona virus.Therefore,the use of this A-TP is highly and strongly recommended,as it serves the full requirements for excellent and potential therapy for the severe infections associated with Covid-19.