Combination Of Levofloxacin Research Articles

Activity of levofloxacin in combination with colistin against Acinetobacter baumannii: Invitro and in a Galleria mellonella model.

Treatment of Acinetobacter baumannii infections is challenging owing to widespread multidrug-resistant A. baumannii (MDR-AB) and the lack of novel agents. Although recent data suggest that levofloxacin (LVX) may have unique activity against MDR-AB in combination with colistin (CST), further preclinical work is needed. We used a A. baumannii type strain ATCC19606, a CST-resistant strain AB19606R, and two clinical isolates (GN0624 and GN1115) of MDR-AB to investigate the invitro and invivo efficacy of LVX-CST combination. Synergy studies were performed using the microtiter plate chequerboard assay and time-kill methodology. Inhibitory activity of antibiotics against biofilms and the mutant prevention concentrations were also studied invitro. A simple invertebrate model (Galleria mellonella) has been used to assess the invivo activity of antimicrobial therapies. The LVX-CST combination was bactericidal against the CST-susceptible clinical isolate (GN0624). In checkerboard assays, synergy (defined as a fractional inhibitory concentration index of < 0.5) was observed between CST and LVX in GN0624. The combination had antibiofilm properties on the preformed biofilms of four tested strains and could prevent the emergence of CST-resistant A. baumanni. Treatment of G. mellonella larvae infected with lethal doses of A. baumannii resulted in significantly enhanced survival rates when LVX was given with CST compared with CST treatment alone (p<0.05). In summary, a synergistic or additive effect between CST and LVX was observed invitro and invivo against CST-susceptible A. baumannii strains, although not against CST-resistant ones.

S-thanatin functionalized liposome potentially targeting on Klebsiella pneumoniae and its application in sepsis mouse model.

S-thanatin (Ts) was a short antimicrobial peptide with selective antibacterial activity. In this study, we aimed to design a drug carrier with specific bacterial targeting potential. The positively charged Ts was modified onto the liposome surface by linking Ts to the constituent lipids via a PEG linker. The benefits of this design were evaluated by preparing a series of liposomes and comparing their biological effects in vitro and in vivo. The particle size and Zeta potential of the constructed liposomes were measured with a Zetasizer Nano ZS system and a confocal laser scanning microscope. The in vitro drug delivery potential was evaluated by measuring the cellular uptake of encapsulated levofloxacin using HPLC. Ts-linked liposome or its conjugates with quantum dots favored bacterial cells, and increased the bacterial uptake of levofloxacin. In antimicrobial assays, the Ts and levofloxacin combination showed a synergistic effect, and Ts-LPs-LEV exhibited excellent activity against the quality control stain Klebsiella pneumoniae ATCC 700603 and restored the susceptibility of multidrug-resistant K. pneumoniae clinical isolates to levofloxacin in vitro. Furthermore, Ts-LPs-LEV markedly reduced the lethality rate of the septic shock and resulted in rapid bacterial clearance in mouse models receiving clinical multidrug resistant (MDR) isolates. These results suggest that the Ts-functionalized liposome may be a promising antibiotic delivery system for clinical infectious disorders caused by MDR bacteria, in particular the sepsis related diseases.

Retrospective investigation of combination therapy with clarithromycin and levofloxacin for pulmonary Mycobacterium avium complex disease.

BackgroundFluoroquinolones are often used for the treatment of refractory Mycobacterium avium complex (MAC) disease when the clinical efficacy of the recommended regimen, which includes clarithromycin (CAM), rifampicin (RFP), and ethambutol (EB), is insufficient. However, recent in vitro and in vivo studies have suggested that fluoroquinolones decreased the antibacterial activity of CAM when they were administered in combination. In this study, we retrospectively investigated the influence of the combination of CAM and levofloxacin (LVFX) on clinical outcomes for pulmonary MAC disease patients.MethodsPulmonary MAC disease patients from 2010 to 2012 were divided into two groups, those who received LVFX together with CAM (LVFX group) and those who received CAM without LVFX (control group). The number of patients who showed improvement was evaluated at 1, 3, 6 and 12 months after the start of therapy based on bacteriological examination (culture and smear examination) and the bacilli negative conversion rate.ResultsThere were no significant differences between the LVFX group (n = 18, 64.5 ± 6.5 years old) and the control group (n = 57, 71.0 ± 7.0 years old) in terms of gender, age, etiologic agent, baseline culture examination score, concomitant medication, and dosage of each drug. The clinical outcomes in the LVFX group were inferior to those in the control group at all endpoints and observational periods, and we found a significant difference in the percent improvement of the smear examination by fluorescence microscopy method (38 % vs. 83 %) and the bacilli negative conversion rate (38 % vs. 79 %) at 3 months. Our study suggests that the combination of CAM and LVFX causes unfavorable clinical outcomes for pulmonary MAC disease treatment. There was no significant difference between both groups in terms of frequency of adverse events.ConclusionThe possibility that combined administration of CAM and LVFX causes unfavorable clinical outcomes for pulmonary MAC disease treatment was suggested.

In vitro susceptibility of a penicillin-resistant and tolerable isolate of Streptococcus pneumoniae to combination therapy.

Preference for combination therapy to treat infection due to multidrug-resistant S. pneumoniae (MDRSP) has not been well elucidated in previous studies. In the present study, 19 antibiotics in combinations were tested against an MDRSP isolate. In vitro susceptibility studies including minimum inhibitory concentration (MIC), minimal bactericidal concentrations (MBC) and disk agar diffusion (DAD), tolerance to resistant antibiotics, checkerboard assay, time-kill curve, hemolytic assay, and autolysis assay were performed on the test strain to study its in vitro susceptibility to combination therapy. From the checkerboard assay and time-kill curve, it was observed that a combination of levofloxacin (MIC, 16 µg/mL) and ceftriaxone (MIC, 2 µg/mL), at sub-MIC concentration was synergistic and most effective against the MDRSP isolate (penicillin MIC, > 64 µg/mL). Hemolytic activities also increased significantly with combination therapy compared to monotherapy (p < 0.05). Moreover, the hemolytic activity of levofloxacin in combination with ceftriaxone was better than ciprofloxacin plus ceftriaxone or cefepime. The autolysis rate was also found to increase rapidly within one hour of exposure to levofloxacin plus ceftriaxone, and this was found to be significantly different from the other combinations at the fifth and sixth hour post incubation (p < 0.05). This data suggests that this combination is bactericidal in vitro, and requires further studies in in vivo models for treatment against MDRSP infections.

Enhanced efficacy of putative efflux pump inhibitor/antibiotic combination treatments versus MDR strains of Pseudomonas aeruginosa in a Galleria mellonella in vivo infection model.

The objectives of this study were to compare the antibiotic susceptibility of Pseudomonas aeruginosa strains with increased efflux pump expression in vitro and in vivo and to use these same strains to evaluate the efficacy of combinations of antibiotics with putative efflux pump inhibitors in vivo. A collection of P. aeruginosa strains that overexpress three efflux pumps (MexAB-OprM, MexCD-OprJ and MexEF-OprN), in addition to a strain with all three Mex pumps deleted, were used. The virulence of these strains and their antibiotic susceptibility was measured in vivo using a Galleria mellonella larval infection model. The inhibitory effect of combinations of putative efflux pump inhibitors (trimethoprim and sertraline) with antibiotics on the strain overexpressing MexAB-OprM was also measured in vitro and compared with their efficacy in vivo in terms of larval survival and bacterial burden. Increased expression of the individual efflux pumps, or deletion of all three, had no significant effect on the virulence of P. aeruginosa in vivo. Expression levels of the efflux pumps clearly influenced antibiotic efficacy in vivo. The efficacy of levofloxacin, piperacillin and meropenem against larvae infected with the efflux pump mutants reflected susceptibility to the same drugs in vitro. Treatment of G. mellonella larvae infected with a strain that overexpressed MexAB-OprM with a combination of putative efflux pump inhibitors and levofloxacin resulted in enhanced therapeutic benefit compared with the constituent monotherapies. This study has demonstrated the utility of using G. mellonella to screen for novel therapeutic options for MDR P. aeruginosa and has shown that antibiotic/efflux pump inhibitor combinations should be further investigated for clinical application.

Exploration of a standard treatment for Buruli ulcer through a comprehensive analysis of all cases diagnosed in Japan.

Buruli ulcer (BU) is a refractory skin ulcer caused by Mycobacterium ulcerans or M.ulcerans ssp. shinshuense, a subspecies thought to have originated in Japan or elsewhere in Asia. Although BU occurs most frequently in tropical and subtropical areas such as Africa and Australia, the occurrence in Japan has gradually increased in recent years. The World Health Organization recommends multidrug therapy consisting of a combination of oral rifampicin (RFP) and i.m. streptomycin (SM) for the treatment of BU. However, surgical interventions are often required when chemotherapy alone is ineffective. As a first step in developing a standardized regimen for BU treatment in Japan, we analyzed detailed records of treatments and prognoses in 40 of the 44 BU cases that have been diagnosed in Japan. We found that a combination of RFP (450mg/day), levofloxacin (LVFX; 500mg/day) and clarithromycin (CAM; at a dose of 800mg/day instead of 400mg/day) was superior to other chemotherapies performed in Japan. This simple treatment with oral medication increases the probability of patient adherence, and may often eliminate the need for surgery.

Synergy of drug combinations in treating multidrug-resistant Pseudomonas aeruginosa.

With the emergence of metallo-betalactamases (MBL) in Pseudomonas aeruginosa (P. aeruginosa), the value of carbapenem, the drug of last resort, is being severely compromised. Curtailing the use of carbapenems becomes paramount if resistance is to be reined in. To study the role of synergy between combinations of drugs as an alternative treatment choice for P. aeruginosa. Synergy was studied between combinations of levofloxacin with piperacillin-tazobactam and levofloxacin with cefoperazone-sulbactam by time-kill and chequerboard techniques. P. aeruginosa were tested for antibiotic susceptibility by the disc diffusion assay (260 isolates) and E-test (60 isolates). Synergy testing by chequerboard and time-kill assays was performed with combinations of piperacillin-tazobactam with levofloxacin (11 isolates) and cefoperazone-sulbactam with levofloxacin (10 isolates). Nearly all isolates were susceptible to piperacillin-tazobactam (96.1 per cent), followed by piperacillin (78.5 per cent). Seventy-one isolates (27.3 per cent) were found to be multidrug resistant and 19.6 per cent were ESBL producers. MIC50 of amikacin was 32μg/ml and MIC90 was 64μg/ml. MIC50 and MIC90 of cefoperazone-sulbactam was 32μg/ml and 64μg/ml, and for levofloxacin it was 10μg/ml and 240μg/ml, respectively. Piperacillin-tazobactam had MIC50 and MIC90 of 5μg/ml and 10μg/ml, respectively. Synergy was noted in 72.7 per cent isolates for levofloxacin and piperacillin-tazobactam combination, the remaining 27.3 per cent isolates showed addition by both chequerboard and time-kill assay. For levofloxacin and cefoperazone-sulbactam, only 30 per cent isolates had synergy, 40 per cent showed addition, 20 per cent indifference, and 10 per cent were antagonistic by the chequerboard method. The combination of levofloxacin and piperacillin-tazobactam is a good choice for treatment of such strains.

Combination treatment with meropenem plus levofloxacin is synergistic against Pseudomonas aeruginosa infection in a murine model of pneumonia.

Meropenem plus levofloxacin treatment was shown to be a promising combination in our in vitro hollow fiber infection model. We strove to validate this finding in a murine Pseudomonas pneumonia model. A dose-ranging study with meropenem and levofloxacin alone and in combination against Pseudomonas aeruginosa was performed in a granulocytopenic murine pneumonia model. Meropenem and levofloxacin were administered to partially humanize their pharmacokinetic profiles in mouse serum. Total and resistant bacterial populations were estimated after 24 hours of therapy. Pharmacokinetic profiling of both drugs was performed in plasma and epithelial lining fluid, using a population model. Meropenem and levofloxacin penetrations into epithelial lining fluid were 39.3% and 64.3%, respectively. Both monotherapies demonstrated good exposure responses. An innovative combination-therapy analytic approach demonstrated that the combination was statistically significantly synergistic (α = 2.475), as was shown in the hollow fiber infection model. Bacterial resistant to levofloxacin and meropenem was seen in the control arm. Levofloxacin monotherapy selected for resistance to itself. No resistant subpopulations were observed in any combination therapy arm. The combination of meropenem plus levofloxacin was synergistic, producing good bacterial kill and resistance suppression. Given the track record of safety of each agent, this combination may be worthy of clinical trial.

Levofloxacin-ceftriaxone combination attenuates lung inflammation in a mouse model of bacteremic pneumonia caused by multidrug-resistant Streptococcus pneumoniae via inhibition of cytolytic activities of pneumolysin and autolysin.

In this study, our objective was to determine whether a synergistic antimicrobial combination in vitro would be beneficial in the downregulation of pneumococcal virulence genes and whether the associated inflammation of the lung tissue induced by multidrug-resistant Streptococcus pneumoniae infection in vivo needs to be elucidated in order to consider this mode of therapy in case of severe pneumococcal infection. We investigated in vivo changes in the expression of these virulence determinants using an efficacious combination determined in previous studies. BALB/c mice were infected with 10(6) CFU of bacteria. Intravenous levofloxacin at 150 mg/kg and/or ceftriaxone at 50 mg/kg were initiated 18 h postinfection; the animals were sacrificed 0 to 24 h after the initiation of treatment. The levels of cytokines, chemokines, and C-reactive protein (CRP) in the serum and lungs, along with the levels of myeloperoxidase and nitric oxide the inflammatory cell count in bronchoalveolar lavage fluid (BALF), changes in pneumolysin and autolysin gene expression and COX-2 and inducible nitric oxide synthase (iNOS) protein expression in the lungs were estimated. Combination therapy downregulated inflammation and promoted bacterial clearance. Pneumolysin and autolysin expression was downregulated, with a concomitant decrease in the expression of COX-2 and iNOS in lung tissue. Thus, the combination of levofloxacin and ceftriaxone can be considered for therapeutic use even in cases of pneumonia caused by drug-resistant isolates.

Propionibacterium acnesprosthetic valve endocarditis with abscess formation: a case report

BackgroundEndocarditis due to Propionibacterium acnes is a rare disease. Scant data on treatment of these infections is available and is based on case reports only. If the disease is complicated by abscess formation, surgical intervention combined with an antibiotic therapy might improve clinical outcome. In some cases, cardiac surgeons are reluctant to perform surgery, since they consider the intervention as high risk. Therefore, a conservative therapy is required, with little, if any evidence to choose the optimal antibiotic. We report the first case of a successfully treated patient with P. acnes prosthetic valve endocarditis without surgery.Case presentationWe report the case of a 29-year-old patient with a prosthetic valve endocarditis and composite graft infection with abscess formation of the left ventricular outflow tract due to P. acnes. Since cardiac surgery was considered as high risk, the patient was treated intravenously with ceftriaxone 2 g qd and rifampin 600 mg bid for 7 weeks and was switched to an oral therapy with levofloxacin 500 mg bid and rifampin 600 mg bid for an additional 6 months. Two sets of blood cultures collected six weeks after completion of treatment remained negative. The patient is considered to be cured based on absence of clinical signs and symptoms, normal laboratory parameters, negative radiology scans and negative blood cultures, determined at site visits over two years after completion of treatment.ConclusionTo our knowledge, this is the first successfully managed patient with P. acnes prosthetic valve endocarditis with abscess formation of the left ventricular outflow tract who was treated with antibiotics alone without a surgical intervention. A six month treatment with a rifampin and levofloxacin combination was chosen, based on the excellent activity against stationary-phase and adherent bacteria.

Synergistic effects of berberines with antibiotics on clinical multi-drug resistant isolates of methicillin-resistant Staphylococcus aureus (MRSA)

N-Methyl-dihydroberberine (M-Ber) was synthesized, and antibacterial activities of Berberine (Ber) and M-Ber alone and combined with antibiotics were studied against ten clinical MRSA isolates. MICs/MBCs (μg/ml, alone) ranges were 32–128/64–256 (Ber) and 64–128/256–1,024 (M-Ber) by a broth microdilution method. Significant synergies of Ber (M-Ber)/Azithromycin and Ber (M-Ber)/Levofloxacin combinations were observed by the chequerboard test. The Ber (M-Ber)/Ampicillin and Ber (M-Ber)/Cefazolin combinations showed indifference. These results demonstrated that Ber and M-Ber enhanced the in vitro inhibitory efficacy of Azithromycin and Levofloxacin, which had potential for combinatory therapy of patients infected with MRSA.

Tamsulosin alters levofloxacin pharmacokinetics in prostates derived from rats with acute bacterial prostatitis

The combination of levofloxacin and α1 adrenergic antagonist treatment is the current preferred choice for both bacterial and non-bacterial prostatitis. The aim of this study is to explore the influence of α1 adrenergic antagonists on the pharmacokinetics of levofloxacin using rat models with acute bacterial prostatitis (ABP) induced by direct injection with Escherichia coli (ATCC25922). A total of 96 model rats were randomly assigned into two groups: the experimental group (treated with both tamsulosin and levofloxacin, n=48) and the control group (treated with levofloxacin and solvents, n=48). Six rats from each group were euthanized to collect blood, liver, kidney and prostate samples at the time points of 0.125, 0.25, 0.5, 1, 2, 4, 8 and 12h after drug administration. The levofloxacin concentrations were detected by high performance liquid chromatography (HPLC), and the pharmacokinetic parameters were calculated using the 3p97 software program. There were no obvious differences (P>0.05) between the experimental and control groups in the major pharmacokinetic parameters of levofloxacin, including the halftime (t1/2), time to peak (tpeak), clearance rate (CL), maximum concentration (Cmax) and area under the curve (AUC0∼12), in the plasma or in the hepatic and kidney tissues of the model rats. However, in the prostatic tissues, tamsulosin increased the Cmax, prolonged the t1/2 and decreased the CL of levofloxacin (P<0.05). These results indicate that tamsulosin may enhance the effect of levofloxacin in the treatment of bacterial prostatitis without changing the drug concentration in the liver and kidney.

Assessment of Antimicrobial Combinations for Klebsiella pneumoniae Carbapenemase–Producing K. pneumoniae

The prevalence of bla(KPC) among gram-negative bacteria continues to increase worldwide. Limited treatment options exist for this multidrug-resistant phenotype, often necessitating combination therapy. We investigated the in vitro and in vivo efficacy of multiple antimicrobial combinations. Two clinical strains of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae were studied. The killing activities of six 2-agent combinations of amikacin, doripenem, levofloxacin, and rifampin were quantitatively assessed using a validated mathematical model. Combination time-kill studies were conducted using clinically relevant concentrations; observed bacterial burdens were modeled using 3-dimensional response surfaces. Selected combinations were further validated in a neutropenic murine pneumonia model, using human-like dosing exposures. The most enhanced killing effect in time-kill studies was seen with amikacin plus doripenem. Compared with placebo controls, this combination resulted in significant reduction of the bacterial burden in tissue at 24 hours, along with prolonged animal survival. In contrast, amikacin plus levofloxacin was found to be antagonistic in time-kill studies, showing inferior animal survival, as predicted. Our modeling approach appeared to be robust in assessing the effectiveness of various combinations for KPC-producing isolates. Amikacin plus doripenem was the most effective combination in both in vitro and in vivo infection models. Empirical selection of combinations against KPCs may result in antagonism and should be avoided.

Antibacterial and Synergy of Berberines with Antibacterial Agents against Clinical Multi-Drug Resistant Isolates of Methicillin-Resistant Staphylococcus aureus (MRSA)

Antibacterial activity of berberine (Ber) and 8-acetonyl-dihydroberberine (A-Ber) alone and combined uses with antibacterial agents ampicillin (AMP), azithromycin (AZM), cefazolin (CFZ) and levofloxacin (LEV) was studied on 10 clinical isolates of SCCmec III type methicillin-resistant Staphylococcus aureus (MRSA). Susceptibility to each agent alone was tested using a broth microdilution method and the chequerboard and time-kill tests for the combined evaluations, respectively. The alone MICs/MBCs (μg/mL) ranges were 32–128/64–256 (Ber) and 32-128/128-512 (A-Ber). Significant synergies were observed for the Ber (A-Ber)/AZM and Ber (A-Ber)/LEV combinations against 90% of the tested MRSA strains, with fractional inhibitory concentration indices (FICIs) values ranged from 0.188 to 0.500. An additivity result was also observed for the Ber/AZM combination by time-kill curves. These results demonstrated for the first time that Ber and A-Ber enhanced the in vitro inhibitory efficacy of AZM and LEV to a same extent, which had potential for further investigation in combinatory therapeutic applications of patients infected with MRSA.

Detection of Legionella pneumophila serogroup 1 in blood cultures from a patient treated with tumor necrosis factor-alpha inhibitor

A 65-year-old man was admitted to our hospital with a temperature of 39.3 °C, cough, sputum, and pharyngeal discomfort that had persisted for 3 days. He had been treated with methotrexate and adalimumab (a tumor necrosis factor-alpha [TNF-α] inhibitor) for rheumatoid arthritis for 2 years, and he had also been treated with S-1 (tegafur, gimeracil, and oteracil potassium) for pancreatic metastasis of gastric cancer for 2 months. Regardless of the underlying pathologies, his general condition was good and he had worked as an electrician until 2 days before admission. However, his appetite had suddenly decreased from the day before admission, and high fever and hypoxia were also evident upon admission. A chest X-ray and computed tomography scan revealed left pleural effusion and consolidation in both lungs. The pneumonia severity index score was 165 and the risk class was V. Accordingly, we started to treat the pneumonia with a combination of levofloxacin and meropenem. Thereafter, we received positive urinary antigen test findings for Legionella pneumophila. After hospitalization, hypoxia was progressed and hypotension was emerged. Despite the application of appropriate antibiotics, vasopressors, and oxygenation, the patient died 8 h after admission. Even after his death, blood cultures were continued to consider the possibility of bacterial co-infection. Although no bacteria were detected from blood cultures, Gimenez staining revealed pink bacteria in blood culture fluids. Subsequent blood fluid culture in selective medium revealed L. pneumophila serogroup 1. Recently, TNF-α inhibitors have been described as a risk factor for Legionnaires' disease. In consideration of the increased frequency of TNF-α inhibitors, we may need to recognize anew that L. pneumophila might be a pathogen of severe community-acquired pneumonia.

Comparison of Rifabutin- and Levofloxacin-based Third-line Rescue Therapies forHelicobacter pylori

There is increasing need for third-line therapy of Helicobacter pylori due to increasing level of antibiotics resistance. The aim of this study was to compare rifabutin and levofloxacin rescue regimens in patients with first- and second-line Helicobacter pylori eradication failures. Patients, in whom a first treatment with proton pump inhibitor-clarithromycin-amoxicillin and a second trial with proton pump inhibitor-bismuth-tetracycline-metronidazole had failed, received treatment with either rifabutin or levofloxacin, plus amoxicillin (1 g twice daily) and standard dose proton pump inhibitor. Eradication rates were confirmed with 13C-urea breath test or rapid urease test 4 weeks after the cessation of therapy. Eradication rates were 71.4% in the rifabutin group, and 57.1% in the levofloxacin group, respectively. Although there was no significant difference in Helicobacter pylori eradication rates between two groups (p=0.656), rifabutin based regimen showed relatively higher eradication rate. Helicobacter pylori eradication rates of rifabutin- or levofloxacin-based triple therapy could not achieve enough eradication rate. Further studies would be needed on combination of levofloxacin and rifabutin-based regimen or culture based treatment.

Staphylococcus simulans as an authentic pathogenic agent of osteoarticular infections

To evaluate the role of Staphylococcus simulans in bone and joint infections (BJI) and determine their main characteristics. A search of the database of the microbiology laboratories of Lille hospital and Tourcoing hospital was performed. Only results from blood, bone, and orthopedic device cultures were taken into account for hospitalized patients between January 2004 and January 2009. We considered cases in which S. simulans was the only bacteria isolated in all of the patients' biological samples with clinical and laboratory signs of infection. For patients with complete medical records, we recorded the clinical and epidemiological data. Six cases of BJI due to S. simulans were recorded, with five cases related to orthopedic devices infections. Three patients lived in rural areas. In four out of six patients, S. simulans was isolated in intraoperative biopsy material. In one patient, S. simulans grew in synovial fluid and in another in blood cultures only. The latter patient had a spondylodiscitis, and chronic foot ulcers due to gout disease were suspected to be the origin of the infection. All patients were healed after a mean follow up of 9±3months. Orthopedic devices were removed in four of the five patients concerned. The combination of rifampicin plus levofloxacin was used in four patients. The present data suggest that, even though S. simulans remains rarely observed in clinical pathology, its role in osteoarticular infections, especially in the case of infected orthopedic devices, is not exceptional. As for the antibiotic treatment, the combination of rifampicin and levofloxacin seems to be an effective strategy according to our clinical results.

Efficient Penetration into Aqueous Humor by Administration of Oral and Topical Levofloxacin

We investigated whether an optimized combination of oral and topical levofloxacin would lead to higher levofloxacin concentrations in aqueous humor. Fifteen patients with cataracts in both eyes began topical treatment at 1 week before the first surgery and oral treatment at 1 day before the first surgery. On the day of surgery, they received oral and topical levofloxacin at 4 h and 1 h before surgery, respectively. Two days after the first operation, we performed cataract surgery on the second eye with the same drug administration protocol. Postsurgery concentrations of levofloxacin in the aqueous humor of the first and second eyes were 2.87±0.89 μg/mL (mean±standard deviation, n=15) and 3.76±1.32 μg/mL, respectively; the levofloxacin level in the second eye was significantly higher than that in the first eye (P=0.0085). Our protocol to achieve high aqueous humor concentrations of levofloxacin may be favorable in preventing endophthalmitis after eye surgery.

Comparative evaluation of synergy of combinations of -lactams with fluoroquinolones or a macrolide in Streptococcus pneumoniae

Streptococcus pneumoniae has shown a great ability to develop efficacious mechanisms of resistance to the main drugs for the treatment of pneumonia, such as β-lactams, macrolides and fluoroquinolones. The present study aimed to compare the antipneumococcal activity of combinations of respiratory fluoroquinolones with cephalosporins (either parenteral or oral) or protected penicillin versus the standard combinations (i.e. a macrolide with a protected penicillin or cephalosporin) against 100 isolates with different susceptibilities to macrolides and/or penicillin. Chequerboard assays for all isolates and time-kill curves for nine isolates with different patterns of susceptibility were performed. Synergy between antibiotics at serum peak concentrations was also determined. The combination of levofloxacin with ceftriaxone produced the highest rate of synergy (54/100), mainly against macrolide-resistant strains (22/30). Antagonism was not observed for any tested combination apart from clarithromycin with amoxicillin/clavulanic acid (22/100 isolates). Although the killing activities of all antibiotics improved when they were tested in combination, synergy was observed only for some combinations after 12 and/or 24 h. Serum concentrations were effective in inhibiting the growth of the tested strains. Combinations of levofloxacin with parenteral cephalosporins were the most active among all the tested combinations, while antagonism occurred when clarithromycin and amoxicillin/clavulanic acid were tested.

Postantibiotic Effects of Tigecycline, Colistin Sulfate, and Levofloxacin Alone or Tigecycline-Colistin Sulfate and Tigecycline-Levofloxacin Combinations against Acinetobacter baumannii

Background: Colistin sulfate and levofloxacin, alone and in combination with tigecycline, were investigated for their in vitro activities and postantibiotic effects (PAEs) on6 meropenem-resistant Acinetobacter baumannii. Methods: The in vitro activities of colistin sulfate and levofloxacin in combination with tigecycline were determined using a microbroth checkerboard technique. The results were interpreted based on the fractional inhibitory concentration index. To determine the PAEs, A. baumannii strains in the logarithmic phase of growth were exposed for 1 h to antibiotics, alone and in combination. Recovery periods of test cultures were evaluated using viable counting after centrifugation. Results: One synergistic interaction was observed for each of the tigecycline-colistin sulfate and tigecycline-levofloxacin combinations. Colistin sulfate produced a strong PAE ranging from 2.50 to 7.0 h in a concentration-dependent manner. PAEs were induced by levofloxacin (ranging from 0.35 to 2.45 h) and tigecycline (ranging from 0.05 to 1.40 h). In combination, tigecycline slightly changed the PAE of colistin sulfate and levofloxacin against the studied strains. Conclusion: This study’s findings could have important implications for the timing of doses during antimicrobial therapy with tigecycline, colistin sulfate, and levofloxacin alone and in combination.