Levofloxacin scientific update |
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2010 Jun;19(2):131-4.
Zullo A, De Francesco V, Manes G, Scaccianoce G, Cristofari F, Hassan C.
Gastroenterology and Digestive Endoscopy, "Nuovo Regina Margherita" Hospital, Rome, Italy; Email: zullo66@yahoo.it.
Second-line and rescue therapies for Helicobacter pylori eradication in clinical practice.
BACKGROUND AND AIMS. A levofloxacin-based triple therapy and a rifabutin-based regimen are advised as second-line and rescue therapies in the current Italian guidelines for H. pylori eradication. However, no data are available for the efficacy of these treatments in clinical practice. METHODS. A total of 86 consecutive patients who failed a standard, first-line, triple therapy for H. pylori infection were treated with a 10-day triple therapy including omeprazole 20 mg, amoxycillin 1 g, and levofloxacin 250 mg or 500 mg, each given twice daily. Eradication failure patients received a 10-day rescue therapy with omeprazole 20 mg, amoxycillin 1 g, and rifabutin 150 mg, each given twice daily. A further therapeutic attempt was performed with a 14-day, high-dose dual therapy (esomeprazole 40 mg and amoxicillin 1 g, each thrice daily). RESULTS. Following the second-line therapy, H. pylori infection was cured in 76.4% (95% CI = 67.8-85.0) and 79.5% (95% CI = 70.8-88.2) at intention-to-treat (ITT) and per-protocol (PP) analysis, respectively. After the rescue therapy, bacterial eradication was achieved in 84.6% (95% CI = 65-100). Two patients with persistent infection were successfully cured with the high-dose dual therapy. CONCLUSION. The efficacy of levofloxacin-based second-line therapy seems to be decreasing, whilst rescue therapy with rifabutin would appear a valid third-line therapy, and a high-dose dual therapy may be used as a further rescue therapy.
2010 Jun 30. [Epub ahead of print]
Schelleman H, Bilker WB, Brensinger CM, Wan F, Hennessy S.
Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Anti-Infectives and the Risk of Severe Hypoglycemia in Users of Glipizide or Glyburide.
The objective of this study was to evaluate whether orally administered anti-infectives increase the risk of severe hypoglycemia in users of glipizide or glyburide. We performed two case-control studies and two case-crossover studies using US Medicaid data. All the anti-infectives examined were associated with an elevated risk of severe hypoglycemia. Using cephalexin as the reference category, in glipizide users, statistically significant associations were found with co-trimoxazole (odds ratio (OR) = 3.14; 95% confidence interval (CI): 1.83-5.37); clarithromycin (OR = 2.90; 95% CI: 1.69-4.98); fluconazole (OR = 2.53; 95% CI: 1.23-5.23); and levofloxacin (OR = 2.09; 95% CI: 1.35-3.25). In glyburide users, with cephalexin as the reference, statistically significant associations were found with clarithromycin (OR = 5.02; 95% CI: 3.35-7.54); levofloxacin (OR = 2.83; 95% CI: 1.73-4.62); co-trimoxazole (OR = 2.68; 95% CI: 1.59-4.52); fluconazole (OR = 2.20; 95% CI: 1.04-4.68); and ciprofloxacin (OR = 2.08; 95% CI: 1.23-3.52). In conclusion, exposure to all studied anti-infective agents were associated with subsequent severe hypoglycemia. Using cephalexin as the reference, drug-drug interactions were evident with ciprofloxacin (in glyburide users only), clarithromycin, co-trimoxazole, fluconazole, and levofloxacin.
2010 Jul;23(3):245-249.
Iffat W, Shoaib MH, Muhammad IN, Rehana, Tasleem S, Gauhar S.
Dow College of Pharmacy, Dow Medical University, Karachi.
Antimicrobial susceptibility testing of newer quinolones against gram positive and gram negative clinical isolates.
Antibiotic resistance development is an ongoing process associated with irrational antibiotic use. WHO recommends regular surveillance programs for monitoring of antibiotic resistance. The present study is a step in this direction. A total of 124 clinical isolates of Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa were collected from different hospitals in Karachi. In vitro antimicrobial susceptibility studies were carried out by agar dilution method using newer quinolones that included Gatifloxacin and Levofloxacin. It was observed that 50% (n=30) isolates of Staphylococcus aureus were resistant to gatifloxacin. Gatifloxacin was more active against Pseudomonas aeruginosa (n=23) and showing complete susceptibility with MIC 1mg/L except for three very resistant strains that shown resistance at even higher concentrations. Escherichia coli (n=45) has shown 15.5% and Klebsiella pneumoniae (n=26) 34.61% resistance to gatifloxacin. Levofloxacin was more active against Staphylococcus aureus and Escherichia coli showing complete susceptibility at 0.5 mg /L concentration. Pseudomonas aeruginosa and Klebsiella pneumoniae were found to be resistant to Levofloxacin showing 36.36% and 23.08% resistance respectively. The study strongly recommends the adherence to the antibiotic policy and regular susceptibility testing to overcome the problem associated with antimicrobial resistance.
2010 Jun;22(3):153-9.
Tempera G, Furneri PM, Carlone NA, Cocuzza C, Rigoli R, Musumeci R, Pilloni AP, Prenna M, Tufano MA, Tullio V, Vitali LA, Nicoletti G.
Department of Microbiological and Gynecological Sciences, University of Catania, Italy. tempera@unict.it
Antibiotic susceptibility of respiratory pathogens recently isolated in Italy: focus on cefditoren.
The aim of this study was to evaluate the in vitro antibiotic susceptibility of respiratory pathogens recently isolated in Italy to commonly used antibiotics including cefditoren. Six clinical microbiological laboratories collected, between January and September 2009, a total of 2,510 respiratory pathogens from subjects with community-acquired respiratory tract infections (CARTI). Ceftditoren, out of all the beta-lactams studied, had the lowest MIC(90 )against 965 strains of Streptococcus pneumoniae examined, followed by cefotaxime and ceftriaxone (2% resistance in penicillin-resistant S. pneumoniae (PRSP)). Against 470 Haemophilus influenzae , independently of their production of beta-lactamases or ampicillin resistance, cefditoren was the oral cephalosporin with the best in vitro activity, comparable to that of the injectable cephalosporins and levofloxacin. Higher MIC(90)s were found for the macrolides (4 - 16 mg/l) and cefaclor (4 - 32 mg/l). As was foreseeable, Streptococcus pyogenes (225 strains) was uniformly sensitive to all the beta-lactam antibiotics, but the elevated MIC(90 )values reduced (<75%) susceptibility of this pathogen to macrolides. Beta-lactamase-negative Moraxella catarrhalis (100 strains) had reduced susceptibility only to the macrolides, while the 250 beta-lactamase-producing strains also had reduced susceptibility to cefuroxime. Levofloxacin showed the lowest MIC(50)/MIC(90 )values in the producing strains, whereas cefditoren, cefotaxime and ceftriaxone in the non-producers. As regards the enterobacteriaceae, cefditoren and levofloxacin had the lowest MIC(90)s against Klebsiella pneumoniae. Cefditoren and the third-generation injectable cephalosporins had the lowest MIC(90)s against Escherichia coli (100% susceptibility) while levofloxacin was less active (86% susceptibility).In conclusion, cefditoren's wide spectrum and high intrinsic activity, as well as its capacity to overcome most of the resistance that has become consolidated in some classes of antibiotics widely used as empiric therapy for CARTI, allows us to suggest that cefditoren might be included in the european guidelines as one of the first-choice antibiotics in the treatment of CARTI.
2010 Apr-Jun;53(2):276-80.
Ramakrishnan R, Ramesh S, Bharathi MJ, Amuthan M, Viswanathan S.
Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Tirunelveli, Tamil Nadu- 627 001, India.
Comparative in-vitro efficacy of fluoroquinolones against Streptococcus pneumoniae recovered from bacterial keratitis as determined by E-test.
BACKGROUND AND OBJECTIVES: The advent of new fluoroquinolones has drawn the attention for reliable methods on the in-vitro susceptibility testing of Streptococccus pneumoniae. This study attempts to determine the minimum inhibitory concentration (MIC) of second-generation (ciprofloxacin and ofloxacin), third-generation (levofloxacin) and the fourth-generation (moxifloxacin and gatifloxacin) fluoroquinolones against S. pneumoniae recovered from bacterial keratitis. MATERIALS AND METHODS: In retrospect, the MICs of 50 strains of S. pneumoniae isolated from the corneal scrapes of patients with bacterial keratitis were determined against ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin and moxifloxacin using E-tests. The National Committee of Clinical Laboratory Standards (NCCLS) susceptibility patterns and the potencies of the MICs were statistically compared. RESULTS: The median MIC of ciprofloxacin (0.25microg/ml) was found to be lower than the median MICs of ofloxacin (0.5microg/ml) (P < 0.449) and levofloxacin (1.0microg/ml) (P < 0.001). The median MICs of gatifloxacin (0.1microg/ml) was lower than the median MICs of ciprofloxacin (0.25microg/ml) (P < 0.001), ofloxacin (0.5microg/ml) (P < 0.001) and levofloxacin (1.0microg/ml) (P < 0.001). Moxifloxacin (0.06microg/ml) had showed lower median MICs than gatifloxacin (0.1microg/ml) (P < 0.001) levofloxacin (1.0microg/ml) (P < 0.001), ofloxacin (0.5microg/ml) (P < 0.001) and ciprofloxacin (0.25microg/ml) (P < 0.001). Moxifloxacin (0.06microg/ml) had a lower MIC50 (microg/ml) than gatifloxacin (0.1microg/ml), levofloxacin (1.0microg/ml), ciprofloxacin (0.25microg/ml) and ofloxacin (0.5microg/ml). MIC90 (microg/ml) of moxifloxacin (0.06microg/ml) was found to be lower than the MIC90 (microg/ml) of gatifloxacin (0.5microg/ml), levofloxacin (1.0microg/ml), ofloxacin (0.5microg/ml) and ciprofloxacin (0.5microg/ml). CONCLUSION: Based on in-vitro testing, the five portrayed fluoroquinolones 100% sensitivity to S. pneumoniae. However, the fourth-generation fluoroquinolone, moxifloxacin appeared to be more effective against S. pneumoniae than gatifloxacin, levofloxacin, ofloxacin and ciprofloxacin.
2009 Nov 17;89(42):2983-7.
Sun HL, Yang QW, Xu YC, Wang H, Xie XL, Chen MJ, Zhang XZ, Liu Y, Ye HF, Sun ZY, Duan Q, Ni YX, Yu YS, Zhao WS, He L, Wang J, Ji P, Liu PP, Zhang LX.
Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
[Resistance study of community respiratory pathogens isolated in China from 2005 to 2007] [Article in Chinese]
OBJECTIVE: To investigate the antimicrobial resistance of community respiratory pathogens isolated in China. METHODS: The strains of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, S. pyogenes were isolated from patients with community-acquired respiratory tract infections at 14 Chinese hospitals from 2005 to 2007. Etest and disk diffusion methods were used to survey the susceptibility of 14 antibiotics against these strains. These antibiotics included penicillin G, ampicillin, amoxicillin/clavulanic acid, cefaclor, cefprozil, ceftriaxone, cefepime, levofloxacin, gatifloxacin, ciprofloxacin, tetracycline, clindamycin, erythromycin and trimethoprim/sulfamethoxazole (SXT). RESULTS: A total of 1870 strains were collected including S. pneumoniae (n = 997), S. pyogenes (n = 176), H. influenzae (n = 499) and M. catarrhalis (n = 198). The 2005 - 2007 prevalence of penicillin-susceptible S. pneumoniae (PSSP) were 92.6%, 73.9%, 74.1% and penicillin-intermediate S. pneumoniae (PISP) 4.5%, 9.5%, 14.3% and penicillin-resistant S. pneumoniae (PRSP) 2.9%, 16.6%, 11.6% respectively. 36.9% of S. pneumoniae strains isolated from or= 92.9%. CONCLUSIONS: Antimicrobial resistance in S. pneumoniae is rising. The prevalence of PNSSP isolated from children < or = 6 years old is higher than other age groups. Amoxicillin-clavulanic acid, ceftriaxone, cefepime, gatifloxacin and levofloxacin remain highly active against common community respiratory pathogens.
2009 Nov 5;3(11):843-8.
Moehario LH, Tjoa E, Kiranasari A, Ningsih I, Rosana Y, Karuniawati A.
Department of Microbiology, Faculty of Medicine University of Indonesia. Indonesia. luckyhmoehario@gmail.com
Trends in antimicrobial susceptibility of gram-negative bacteria isolated from blood in Jakarta from 2002 to 2008.
BACKGROUND: This study examined the susceptibility of Gram-negative bacteria in the bloodstream to antimicrobials with the aim of providing information relevant to the guidance of therapy. METHODOLOGY: Blood specimens received by the Laboratory of Clinical Microbiology, Faculty of Medicine, University of Indonesia, from 2002 to 2008, were analyzed for the presence of Gram-negative bacteria and their susceptibility to four antibiotic groups frequently administered in hospitals and community settings. RESULTS: During the seven-year period leading up to 2008, approximately 68% of Gram-negative bacteria were identified among all positive isolates from blood specimens. The eight most frequent species found were Acinetobacter anitratus (25.8%), Pseudomonas aeruginosa (19.5%), Klebsiella pneumoniae subsp. pneumoniae (14.5%), Enterobacter aerogenes (8%), Salmonella Typhi (7.5%), Escherichia coli (6.2%), Alcaligenes faecalis (5.6%) and Klebsiella oxytoca (3.2%). At 80% susceptibility or greater, Ceftriaxone and Cefotaxime were active only on E. coli and S. Typhi. Cefepime demonstrated activity on all eight species tested except K. pneumonia while Amikacin showed activity against five species, A. faecalis, E. aerogenes, E. coli, K. pneumoniae subsp. pneumoniae and S. Typhi. Gentamycin was active against three species: E. aerogenes, K. oxytoca and S. Typhi. Ciprofloxacin and Levofloxacin significantly differed in their spectrum: while Ciprofloxacin was active against four of the eight species tested (E. aerogenes, E. coli, K. oxytoca, and S. Typhi ), Levofloxacin was similar to Cefepime and was active against all eight species except K. pneumoniae subsp. pneumonia. CONCLUSIONS: Since antimicrobials are broadly used in Jakarta, it is important that the information captured in this study be disseminated.
2009 Oct;62(5):452-9.
Kashimoto Y, Kurosaka Y, Karibe Y, Uoyama S, Fujikawa K, Namba K, Otani T, Yamaguchi K.
Daiichi Sankyo Co. Ltd., Biological Research Laboratories IV.
[Therapeutic efficacy of levofloxacin against a model of replicable Legionella pneumophila lung infection in DBA/2 mice] [Article in Japanese]
The in vitro and in vivo antibacterial activities of levofloxacin (LVFX), a quinolone antibacterial, against clinically isolated Legionella pneumophila were investigated in comparison with those of existing antimicrobial agents approved for legionnaires disease. The minimum inhibitory concentrations (MICs) of the agents against 42 strains of L. pneumophila isolated in Japan were determined using agar dilution methods with buffered starch yeast extract agar. MIC90 of LVFX was 0.03 microg/ml and this activity was similar to ciprofloxacin and pazufloxacin, and higher than telithromycin and minocycline. Therapeutic efficacy of LVFX was studied against a pneumonia model induced by intranasal of L. pneumophila strain suzuki serogoup 1 in DBA/2 mice. Therapeutic doses in mice were selected that would closely match human exposure profile, area under the concentration-time curve (AUC) for a human oral dose of LVFX at 500 mg once a day. LVFX decreased significantly the bacterial burden in the lungs from the next day of commencing treatment. These results, including in vitro antibacterial activity against clinical isolates and therapeutic efficacy of a humanized dosing regimen, provide good evidence to support the use of LVFX at 500 mg once a day for treating patient with legionnaires disease.
2009 Dec;21(12):722-5.
Gao XL, Liu B, Jin K, Cheng J, Li JB, Zhou SS.
Intensive Care Unit, Anhui Province Hospital, Affiliated to Anhui Medical University, Hefei 230032, Anhui, China.
[A study on the active efflux system in methicillin-resistant Staphylococcus aureus] [Article in Chinese]
OBJECTIVE: To explore the status of methicillin-resistant Staphylococcus aureus (MRSA) infection in an intensive care unit (ICU), and investigate the active efflux mechanism of MRSA. METHODS: Eighty isolates were identified as MRSA among 102 strains of Staphylococcus aureus collected, and then the minimal inhibitory concentration (MIC) were determined. The 4 primers of active efflux gene were designed to amplify the 80 clinical isolates respectively by polymerase chain reaction (PCR). The PCR products were analyzed by electrophoresis in order to grasp the situation of the existence of the four genes (norA, qacA, qacB and qacJ). Omeprazole inhibition test was used to observe the changes in the susceptibility of MRSA to antibiotics. RESULTS: The detection rate of MRSA was 78.4%. The sensitivity rate of MRSA to both vancomycin and teicoplanin was 100.0%, while to other antibiotics (oxacillin, benzylpenicillin, cefuroxime, cefotaxime, ceftazidime, ceftiaxone, cefepime, cefoxitin, imipenem, piperacillin and tazobactam, azithromycin, erythromycin, chloramphenicol, clindamycin, amikacin, gentamicin, levofloxacin, gatifloxacin, ciprofloxacin) MRSA was multi-drug resistant. The detection rates of norA, qacA, qacB and qacJ were 67.5% (54/80), 15.0% (12/80), 21.2% (17/80) and 11.2% (9/80), respectively. Combined use of omeprazole and levofloxacin could lower MIC value. CONCLUSION: The infection of MRSA in ICU is serious. MRSA is multi-drug resistant and possesses active efflux genes norA, qacA, qacB and qacJ. Omeprazole can inhibit the activity of the active efflux genes.
2009 Jul 28. [Epub ahead of print]
Inoshita A, Yokoi H, Matsumoto F, Yao T, Kawano K, Furukawa M, Ikeda K.
Department of Otorhinolaryngology, Juntendo University School of Medicine, Tokyo, Japan.
A randomized prospective study of oral levofloxacin vs intravenous flomoxef prophylaxis in postoperative infection after endoscopic sinus surgery.
OBJECTIVE: The clinical efficacy and cost effectiveness of oral antimicrobial prophylaxis with levofloxacin (LVFX) on endoscopic sinus surgery (ESS) was evaluated. MATERIALS AND METHODS: Ninety-three patients undergoing ESS were prospectively enrolled in the present study. The patients were randomly divided into 2 groups, LVFX and flomoxef (FMOX). Two hundred milligrams of LVFX was orally given 2 hours before the start of surgery and 6 hours after the end of surgery, which was followed by the administration of 200 mg every 12 hours for 2 days. One gram of FMOX was dissolved in 100 ml of physiological saline and given intravenously at the induction of anesthesia and 6 hours after the end of surgery, followed by infusion twice daily for 2 days. RESULTS: There were no statistically significant differences between 2 groups in terms of age, sex, systemic complications, surgical procedures, the duration of the operation, the length of hospitalization, the amount of blood loss, body temperature, or the number of white blood cells or C-reactive protein. Although no statistical significance was observed in the bacterial resistance between the two antibiotics, LVFX seems to show a low rate of resistance pattern change as compared to FMOX. The present study demonstrated that no patients treated with LVFX or FMOX were afflicted with postsurgical infection. CONCLUSION: Oral administration of LVFX is a simple, cost-effective and safe alternative to intravenous prophylaxis in ESS based on clinical efficacy and bacteriological study.
2008 May;19(3):243-9.
Zhanel GG, Decorby M, Nichol KA, Baudry PJ, Karlowsky JA, Lagace-Wiens PR, McCracken M, Mulvey MR, Hoban DJ.
Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba.
Characterization of methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and extended-spectrum beta-lactamase-producing Escherichia coli in intensive care units in Canada: Results of the Canadian National Intensive Care Unit
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and vancomycin-resistant enterococci (VRE) are important hospital pathogens in Canada and worldwide. OBJECTIVES: To genotypically and phenotypically characterize the isolates of MRSA, VRE and ESBL-producing E coli collected from patients in Canadian intensive care units (ICUs) in 2005 and 2006. METHODS: Between September 1, 2005, and June 30, 2006, 19 medical centres participating in the Canadian National Intensive Care Unit (CAN-ICU) study collected 4133 unique patient isolates associated with infections in ICUs. Isolates of MRSA underwent mecA polymerase chain reaction (PCR) and Panton-Valentine leukocidin analysis; they were typed using pulsed-field gel electrophoresis. All isolates of E coli with ceftriaxone minimum inhibitory concentrations greater than or equal to 1 mug/mL were tested for the presence of an ESBL using the Clinical Laboratory Standards Institute double-disk diffusion method. Subsequently, PCR and sequence analysis were used to identify bla(SHV), bla(TEM) and bla(CTX-M). Isolates of VRE were tested for the presence of vanA and vanB genes by PCR. RESULTS: Of the 4133 ICU isolates collected, MRSA accounted for 4.7% (193 of 4133) of all isolates. MRSA represented 21.9% (193 of 880) of all S aureus collected during the study; 90.7% were health care-associated MRSA strains and 9.3% were community-associated MRSA strains. Resistance rates for the isolates of MRSA were 91.8% to levofloxacin, 89.9% to clarithromycin, 76.1% to clindamycin and 11.7% to trimethoprim-sulfamethoxazole; no isolates were resistant to vancomycin, linezolid, tigecycline or daptomycin. ESBL-producing E coli accounted for 0.4% (18 of 4133) of all isolates and 3.7% (18 of 493) of E coli isolates. All 18 ESBL-producing E coli were PCR-positive for CTX-M, with bla(CTX-M-15) occurring in 72% (13 of 18) of isolates. All ESBL-producing E coli displayed a multidrug-resistant phenotype (resistant to third-generation cephalosporins and one or more other classes of antimicrobials), with 77.8% of isolates resistant to ciprofloxacin, 55.6% resistant to trimethoprim-sulfamethoxazole, 27.8% resistant to gentamicin and 26.3% resistant to doxycycline; all isolates were susceptible to ertapenem, meropenem and tigecycline. VRE accounted for 0.4% (17 of 4133) of all isolates and 6.7% (17 of 255) of enterococci isolates; 88.2% of VRE had the vanA genotype. Isolated VRE that were tested were uniformly susceptible to linezolid, tigecycline and daptomycin. CONCLUSIONS: MRSA isolated in Canadian ICUs in 2005 and 2006 was predominately health care-associated (90.7%), ESBL-producing E coli were all CTX-M producers (72% bla(CTX-M-15)) and VRE primarily harboured a vanA genotype (88.2%). MRSA, ESBL-producing E coli and VRE were frequently multidrug resistant.
2008 Oct;20 Suppl 1:28-35.
Dartois N, Castaing N, Gandjini H, Cooper A; Tigecycline 313 Study Group.
Wyeth Research, Paris, France. dartoin@wyeth.com
Tigecycline versus levofloxacin for the treatment of community-acquired pneumonia: European experience.
Tigecycline (TGC), a first-in-class glycylcycline that has been approved for treating complicated skin and skin structure infections and complicated intra-abdominal infections, has an expanded spectrum of activity against Gram-positive, Gram-negative, anaerobic, and atypical bacteria, including resistant strains. The purpose of this study was to compare the efficacy and safety of TGC with levofloxacin (LEV) in adult hospitalised patients with community-acquired pneumonia (CAP) in a randomised, doubleblind, phase 3 multinational trial. This analysis evaluated TGC efficacy and safety in the European region. Hospitalised patients from 53 centres in 18 countries received 7-14 days of i.v. TGC (100-mg loading dose followed by 50 mg every 12 hours) or i.v. LEV (500 mg once or twice daily). Co-primary efficacy endpoints were clinical response in clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure (TOC). Results indicated that 358 patients received at least 1 dose of study medication (mITT: TGC 177, LEV 181), 245 were CE (TGC 125, LEV 120). Demographics were similar in both groups and the majority of patients had a Fine Pneumonia Severity Index of II to IV (84.4% TGC, 78.2% LEV, mITT). At TOC (CE), TGC cured 112/125 patients (89.6%; 95% CI 82.9, 94.3) and LEV cured 103/120 patients (85.8%; 95% CI 78.3, 91.5), absolute difference of TGC-LEV 3.8% (95% CI -5.3, 12.8; test for noninferiority p<0.001). For those CE patients with a Fine score of
2008 Oct;4(5):843-53.
McGregor JC, Allen GP, Bearden DT.
Oregon State University College of Pharmacy, Portland, OR, USA.
Levofloxacin in the treatment of complicated urinary tract infections and acute pyelonephritis.
Levofloxacin is a widely used fluoroquinolone approved for the treatment of complicated urinary tract infections and acute pyelonephritis. A comprehensive review of the medical literature identified five publications evaluating levofloxacin for the treatment of either complicated urinary tract infections or acute pyelonephritis. All trials, although variable in their inclusion criteria and levofloxacin dosing strategies, reported microbiologic, clinical, and safety-related outcomes. High microbiologic eradication rates, ranging from 79.8% to 95.3%, were observed in all studies. Escherichia coli was the most commonly isolated uropathogen. Data on levofloxacin resistance, both at baseline and after therapy, were limited. Clinical success was observed to range from 82.6% to 93% when measured after the completion of therapy. These clinical and microbiologic results were comparable to the fluoroquinolone comparators in all trials. Insufficient data are available to evaluate the outcomes in any meaningful patient subgroups, including catheterized patients, and those with other specific complicating factors. Levofloxacin was well tolerated in these studies, with headache, gastrointenstinal effects, and dizziness being the most commonly reported adverse events. The published data support the use of levofloxacin in complicated urinary tract infections and acute pyelonephritis. Further trials are necessary to evaluate levofloxacin within specific patient sub-populations.
2008 Oct;42(10):758-61.
Shen JL, Yang BW, Zhi S, Cui SH, Xi ML, Yang PF, Meng JH.
College of Food Science and Engineering, Northwest Agriculture and Forestry University, Yangling Shaanxi 712100, China.
[Detection and analysis of antibiotic resistance of Salmonella from retail meats in some districts of Shaanxi province] [Article in Chinese]
OBJECTIVE: Salmonella isolates recovered from retail meats that were collected in supermarkets and free markets in Xi'an and Yangling areas of Shaanxi province were studied to determine antibiotic susceptibility. METHOD: Antimicrobial susceptibility to 14 antibiotics of 193 salmonella isolates were determined by using agar dilution method, which was recommended by National Committee of Clinical Laboratory Standard (NCCLS), and E.coli ATCC25922 and E.faecalis ATCC29212 as standard control strains. RESULTS: The 44.6% of the salmonella isolates were resistant to sulfamethoxazole, followed by resistance to kanamycin (40.9%), tetracycline (37.8%), amoxicillin (26.9%), ampicillin (25.4%), gentamicin (23.3%) and chloramphenicol (21.8%). Some isolates also showed resistance to fluoroquinolones, the rates for ciprofloxacin, enrofloxacin, levofloxacin and gatifloxacin were 22.3%, 21.8%, 20.8% and 21.2%, respectively. 55 isolates (28.5%) were multidrug resistant (MDR) strains, 28 of 193 isolates (14.5%) could resist at least 13 antibiotics, 24 isolates (12.4%) were resistant to from 4 to 12 antibiotics. CONCLUSION: Salmonella isolates recovered from retail meats in Xi'an district of Shaanxi province were seriously resistant to antimicrobials commonly used as human and veterinary medicine.
2008 Dec;13(6):572-6.
Sanches B, Coelho L, Moretzsohn L, Vieira G Jr.
Instituto Alfa de Gastroenterologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
Failure of Helicobacter pylori treatment after regimes containing clarithromycin: new practical therapeutic options.
Failure of Helicobacter pylori treatment is a growing problem in daily practice. AIM: To evaluate the efficacy of two new regimes as second-line options in a randomized and prospective study. METHODS: Patients in whom a first eradication regime containing clarithromycin had failed were included. After performing gastroscopy and a 13C-urea breath test (UBT), the patients were randomized to receive a combination of 20 mg of rabeprazole, 500 mg of levofloxacin, and 200 mg (two tablets) of furazolidone administered once daily for 10 days (RLF) or the combination of 20 mg of rabeprazole, 120 mg (two tablets) of bismuth subcitrate, 100 mg of doxycycline, and 200 mg of furazolidone, administered twice daily for 10 days (RBDF). Clinical examinations and new UBT were performed 60 days after therapy. RESULTS: Sixty patients were included (mean age, 46 years, 57% females). Two patients were excluded: one because of adverse effects and another as a result of protocol violation. Compliance was similar in both groups (90% took all medications correctly). Side-effects (96% mild) were observed in 87% of the patients and were comparable between groups, except diarrhea, which was more frequent in group RLF (p= .025). Intention-to-treat cure rates were 77% (95% confidence interval (CI): 62-93%) in the RLF group and 83% (95% CI: 68-97%) in the RBDF group (p= .750). Per-protocol cure rates were 80% (95% CI: 65-95%) in the RLF group and 82% (95% CI: 67-96%) in the RBDF group (p= 1.0). CONCLUSIONS: Both once-daily triple (rabeprazole, levofloxacin, and furazolidone) and twice-daily quadruple therapy (rabeprazole, bismuth subcitrate, doxycycline, and furazolidone) for 10 days achieved encouraging results. Subsequent studies should be performed to evaluate antibiotic resistance, doses, dosing intervals, duration of treatment, and safety of these two regimes.
2007;52(1-2):10-7.
Malakhova MV, Vereshchagin VA, Il'ina EN, Govorun VM, Filimonova OIu, Grudinina SA, Sidorenko SV.
[MALDI-ToF mass-spectrometry in analysis of genetically determined resistance of Streptococcus pneumoniae to fluoroquinolones] [Article in Russian]
New fluoroquinolones with higher antipneumococcal activity are considered promising in the treatment of respiratory tract infections. Still, their wide use in clinical practice is connected with possible selection and rapid distribution of the resistance, requiring constant monitoring. Development of resistance to fluoroquinolones results from step-wise accumulation of mutations in the genes of DNA-gyrase and topoisomerase IV, the mutations of the first step being not always accompanied by a significant increase of the MIC of the new fluoroquinolones. Therefore, to detect the first signs of the resistance development, it is necessary not only to detect the susceptibility of the circulating Streptococcus pneumoniae strains phenotypically, but also to detect the genetic changes. In the present study the minisequent reaction followed by detection of the reaction products by MALD-ToF mass-spectrometry was used to reveal the mutations in the genes of the fluoroquinolone targets of 38 S. pneumoniae strains with different levels of the resistance to ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin. In the strains with high resistance to all the three fluoroquinolones (MIC 4-16 mcg/ml) there were detected mutations in GyrA (Ser81Tyr or Glu85Zys) and as well in ParC (Ser79Phe or Ser79Tyr). In the strains resistant to ofloxacin and ciprofloxacin (MIC 4-8 mcg/ml) with preserved susceptibility to levofloxacin and moxifloxacin, the mutations were detected only in GyrA (Ser114Gly). In the moderately resistant strains (MICs 4 and 2-4 mcg/ml respectively for ofloxacin and ciprofloxacin) there were detected the known mutations in ParC (Ser79Tyr or Ser79Phe or Asp83Tyr) and in GyrB (Glu475Lys) as well as the earlier not described mutations in ParE (ins Asn381a) and in Gyr B (Thr329Ala or Va1355Ile). The described method can be used in mass screening of S. pneumoniae strains for the presence of mutations in the genes of the fluoroquinolone targets.
2007 Oct;23(5):349-51.
Zhang LQ, Su F, Liu HY, Wu XT, Zhao HT.
Department of Burns and Plastic Surgery, Weifang People's Hospital, PR China.
[Survey on the distribution of burn pathogens and their antibiotic resistance in burn unit] [Article in Chinese]
OBJECTIVE: To investigate the distribution of burn pathogens and their antibiotic resistance in a burn unit, so as to provide reference for clinical practice. METHODS: Three hundred and forty-eight burn patients hospitalized in our department were enrolled in this study. The pathogens isolated from the wounds, blood, venous catheter, sputum, urine, purulent discharge of wounds in these patients, and their antibiotic resistance were surveyed by retrospective analysis from Jan, 2001 to Dec, 2006. RESULTS: Total-ly 464 strains were isolated, among which Gram negative (G-) bacilli accounted for 52.6%, Gram positive microorganisms (G+) accounted for 40.5%, and fungi accounted for 6.9%. The main pathogens were Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter species and Escherichia coli, among which Staphylococcus aureus (MRSA) was predominant (93.5%). MRSA was 100% resistant to levofloxacin, penicillium, oxacillin, and it was also resistant to other antibiotics except Vancomycin. The resistance rate of Pseudomonas aeruginosa to Cefoperazone/Sulbactam, Imipenem and cefepime were 15.8%, 36.8%, 33.3%, respectively. CONCLUSION: Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter species and Escherichia coli were predominant in the burn unit,among them Staphylococcus aureus and Acinetobacter were more resistant to antibiotics.
2007 Jun;3(2):309-17.
Giordano P, Weber K, Gesin G, Kubert J.
Skin and skin structure infections: treatment with newer generation fluoroquinolones.
Skin and skin structure infections (SSSI) are an emerging issue in healthcare. They are responsible for increasing heathcare utilization, both in hospitalizations and intravenous antibiotic use. SSSI are caused by an evolving variety of pathogens, including Gram-positive, Gram-negative, and anaerobic bacteria. In combination with mounting resistance patterns, this diverse range of bacteria mandate empiric broad-spectrum antibiotic coverage. Historically, cephalosporins and penicillins have been the mainstay of treatment, but recent data suggest newer generation fluoroquinolones are being used with increasing frequency. In 2005, moxifloxacin joined gatifloxacin and levofloxacin as newer generation fluoroquionolones with Food and Drug Administration indications for SSSIs. Even within this group there exist subtle differences that impact optimal management. This paper offers the clinician a comparative review of the antimicrobial spectrum, pharmacodynamics, pharmacokinetics, and clinical efficacy data to support the appropriate use of fluoroquinolones in SSSIs.
2007;2(4):551-9.
Blasi F, Aliberti S, Tarsia P.
Institute of Respiratory Diseases, University of Milan, IRCCS Fondazione Policlinico-Mangiagalli-Regina Elena Milano, Italy.
Clinical applications of azithromycin microspheres in respiratory tract infections.
Few adequately designed clinical trials have addressed optimal treatment duration in lower respiratory tract infections. Drugs possessing favourable pharmacokinetic and pharmacodynamic profiles may obtain early bacterial eradication allowing shorter treatment duration. This may be associated with a number of advantages including reduced resistance induction, increased compliance, lesser adverse events, and cost containment. Recently, a novel 2.0 g single dose of azithromycin microspheres has been compared with 7-day levofloxacin 500 mg or extended release clarithromycin in over 400 patients with community-acquired pneumonia. Clinical cure and bacteriological eradication rates, hospitalizations, and deaths were similar between azithromycin and comparators. Azithromycin 2.0 g microspheres proved as effective as 7 days of levofloxacin 500 mg in acute exacerbation of chronic bronchitis patients across all degrees of obstruction severity. In both settings Azithromycin microspheres obtained clinical cure in most patients harbouring macrolide-resistant Streptococcus pneumoniae strains. The drug was well tolerated in clinical studies and in healthy volunteers with modest and transitory adverse events. An undoubted advantage of single-dose azithromycin administration is the facility in ensuring that patients complete their prescribed course of therapy. A further advantage of single-dose therapy is the potential for use as directly-observed therapy, which may be useful in specific clinical conditions.
2007 Dec;82(12):891-6.
Kazumi Y, Itagaki N, Ohmori M, Wada M, Hoshino H, Mitarai S, Sugawara I, Ishikawa N, Mori T.
Pathology Division, Mycobacterium Reference Center, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo. kazumi@jata.or.jp
[Frequency of MDR-TB/XDR-TB strains isolated from chronic pulmonary tuberculosis patients in Japan] [Article in Japanese]
PURPOSE: To observe the frequency of MDR-TB/XDR-TB strains isolated from chronic pulmonary tuberculosis patients in Japan. OBJECT: Ad hoc National Tuberculosis Survey 2000 on frequency of MDR-TB and XDR-TB strains. MATERIALS AND METHOD: Four hundred and thirty four clinical isolates were collected by the Ad hoc National Tuberculosis Survey 2000, the drug susceptibility testings (proportion method, MGIT Middlebrook, and BrothMIC NTM) were conducted on these strains. These clinical isolates were obtained from patients registered at Health Centers in Japan by the end of 1999 who were culture-positive in 1999 and were registered before January 1st, 1998. The isolates used in this study were selected from patients who were culture-positive at shortest 2 years after the registration. RESULT: The clinical isolates resistant to both INH and RFP were 321 out of 434 (74.0%). The 180 MDR-resistant clinical isolates were also resistant to levofloxacin and amikacin and/or kanamycin. These phenotypes are XDR-TB. No previously registered cases were 165, and previously registered cases were 143 and unknown cases were 13 out of 321 MDR-TB. In 180 XDR-TB cases, no previously registered cases were 95, previously registered cases were 78 and unknown cases were 7. In no previously registered cases, more than 50% cases started treatment in 1990s. Approximately 50% of previously registered patients started treatment in 1960s and 1970s. CONCLUSION: We performed drug susceptibility testing for 434 clinical isolates which were culture-positive at shortest 2 years after registration. No. of MDR-TB patients was 321 and that of XDR-TB patients was 180. The treatment outcome of these patients have to be followed up carefully at Health Centers. The frequency of amikacin resistance was relatively high. This may be due to either common use of amikacin or cross-resistance against streptomycin and kanamycin.
J Ocul Pharmacol Ther. 2009 Oct;25(5):425-31.
Choi JA, Chung SK.
Department of Ophthalmology and Visual Science, St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Safety of intracameral injection of gatifloxacin, levofloxacin on corneal endothelial structure and viability.
PURPOSE: To investigate the safety of intracameral injection of gatifloxacin, levofloxacin in a rabbit model as prophylaxis against endophthalmitis. METHODS: Twenty-four eyes of New Zealand white rabbits were randomly divided into 3 treatment groups: levofloxacin, gatifloxacin, and balanced salt solution (BSS) control groups. After 100 microL of each was injected into the anterior chamber, endothelial toxicity was evaluated by measuring the central corneal thicknesses and the clinical toxicity scores using a slit-lamp at post-procedure days 3 and 7. The percent of dead cells was determined by vital staining with alizarin red and trypan blue at 7 days after injection. Finally, in each group, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were performed for the evaluation of structural integrity. RESULTS: The toxicity scores were increased at post-procedure days 3 and 7, but the difference among the groups was not statistically significant (P = 0.661, 0.216, respectively). With regard to baseline corneal thickness, only the levofloxacin group exhibited a significant increase from baseline (P = 0.028), whereas the other treatment groups showed no difference from baseline (P = 0.128 in gatifloxacin, 0.161 in BSS group). The mean corneal endothelial damage was 0.81 +/- 0.31% in the levofloxacin group, 0.56 +/- 0.47% in the gatifloxacin group, and 0.53 +/- 0.52% in the BSS group, with no statistically significant difference noted among the groups (P = 0.582). SEM revealed a well-preserved hexagonal endothelial cell mosaic and normal microvilli on the endothelial cell surface in the gatifloxacin and control groups. However, the levofloxacin group showed slightly disintegrated cellular borders. TEM revealed that each group maintained normal intracellular organization, whereas the levofloxacin group exhibited slightly flat cell configuration with irregular folds on the apical cell surface. CONCLUSIONS: Intracameral injection of gatifloxacin and levofloxacin was nontoxic in terms of clinical toxicity score, corneal thickness, and viability. However, there were changes on electron microscopy in the levofloxacin group, which may indicate microstructural damage to corneal endothelial cells.
J Infect Chemother. 2009 Oct;15(5):293-300. Epub 2009 Oct 24.
Zhang J, Xu JF, Liu YB, Xiao ZK, Huang JA, Si B, Sun SH, Xia QM, Wu XJ, Cao GY, Shi YG, Zhang YY.
Institute of Antibiotics, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Lu, Shanghai 200040, China.
Population pharmacokinetics of oral levofloxacin 500 mg once-daily dosage in community-acquired lower respiratory tract infections: results of a prospective multicenter study in China.
This study aimed to explore the pharmacokinetic features of levofloxacin (LVFX) in Chinese patients with infections and to confirm oral LVFX 500 mg once daily as an optimal treatment regimen based on pharmacokinetic-pharmacodynamic (PK-PD) analysis. A total of 1052 plasma samples from 164 Chinese adult patients with community acquired lower respiratory tract infections (CALRTIs) and 18 healthy volunteers were used for population PK analysis. LVFX 500-mg tablets were given once daily. A nonlinear mixed effects model (NONMEM) program was used for population PK model-building and a two-compartment model with first-order absorption process was established. Creatinine clearance (CL(cr)) and body weight were identified as intrinsic factors which significantly affected oral clearance (CL(t)/F) and the apparent volume of distribution of the central compartment (V1/F), respectively. The final model is described as follows: CL(t)/F (l/h) = (8.97 + 0.917 x (CL(cr) (ml/min)-100.92) x 60/1000) x exp (eta(CLt/F)). V1/F (l) = (85.3 + 1.22 x (weight (kg)-60.75)) x exp (eta(V1/F)). Q/F (l/h) = 0.351. V2/F (l) = 6.81. k(a) (h(-1)) = 1.44 x exp(eta(ka)). Based on the population PK model, mean C(max) and AUC(0-24h) in CALRTI patients were estimated as 5.13 microg/ml and 58.98 microg.h/ml, respectively. A subgroup analysis showed that patients with mild renal dysfunction (50 ml/min < or = CL(cr) < 80 ml/min) had 34% higher AUC(0-24h) values compared to patients with normal renal function (CL(cr) > or = 80 ml/min). Postmodeling simulation using final population PK estimates also showed that C(max) and AUC(0-24h) increased markedly in patients with severe renal dysfunction. The results indicate that LVFX dosage adjustment should be individualized on the basis of the CL(cr), especially in those with CL(cr) less than 50 ml/min. None of the PK parameters had any correlation with the occurrence of adverse events. PK-PD analysis indicated that, in patients treated with LVFX 500 mg once daily, the AUC(0-24h)/MIC ratio exceeded the target for those major CALRTI pathogens isolated. In addition, the C(max)/MIC ratio reached 5 for Streptococcus pneumoniae, indicating that the emergence of LVFX-resistant S. pneumoniae could be prevented during the therapy with this dosage regimen. These results demonstrate that oral LVFX 500 mg once daily has favorable PK parameters and PK-PD features in patients with CALRTIs, and the results strongly support this dosage regimen for the treatment of CALRTI.
J Infect Chemother. 2009 Oct;15(5):301-11. Epub 2009 Oct 24.
Zhang YY, Huang HH, Ren ZY, Zheng HG, Yu YS, Lü XJ, Xiao ZK, Yang HF, Xiu QY, Chen BY, Yue HM, Hao QL, Huang JA, Ma H, Xiao W, Guo DY, Si B, Sun SH, Zhang W, Li QH, Shen HH, Duan J, Li HY, Yao WZ, Gu JM, Xia QM, Ying KJ, Liu A, Yang HP, Shi MH, Sun T
Institute of Antibiotics, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Lu, Shanghai 200040, China.
Clinical evaluation of oral levofloxacin 500 mg once-daily dosage for treatment of lower respiratory tract infections and urinary tract infections: a prospective multicenter study in China.
Levofloxacin (LVFX), a fluoroquinolone agent, has a broad spectrum that covers Gram-positive and -negative bacteria and atypical pathogens. It demonstrates good clinical efficacy in the treatment of various infections, including lower respiratory tract infections (LRTIs) and urinary tract infections (UTIs). To evaluate the efficacy and safety of oral LVFX 500 mg once daily, a large open-label clinical trial was conducted in 1266 patients (899 with LRTIs and 367 with UTIs) at 32 centers in China. In the per-protocol population, the clinical efficacy rate (cure or improvement) at 7 to 14 days after the end of treatment was 96.4% (666/691) for LRTIs and 95.7% (267/279) for UTIs. In 53 patients diagnosed with atypical pneumonia the treatment was effective. The bacteriological efficacy rate was 96.6% (256/265) for LRTIs and 93.3% (126/135) for UTIs. The eradication rate of the causative pathogens was 100% (33/33) for Haemophilus influenzae and 96.0% (24/25) for Streptococcus pneumoniae in LRTIs, and 94.1% (80/85) for Escherichia coli in UTIs. The overall efficacy rates were 89.3% (617/691) for LRTIs and 87.8% (245/279) for UTIs. The incidence of drug-related adverse events (ADRs) was 17.3% (215/1245), and the incidence of drug-related laboratory abnormalities was 15.7% (191/1213). Common ADRs were dizziness, nausea, and insomnia. Common laboratory abnormalities included "WBC decreased", "alanine aminotransferase (ALT) increased", "aspartate aminotransferase (AST) increased", and "lactate dehydrogenase (LDH) increased". All of these events were mentioned in the package inserts of fluoroquinolones including LVFX, and most events were mild and transient. Thirty-four patients (2.7%) were withdrawn from the study because of the ADRs. No new ADRs were found. This study concluded that the dosage regimen of LVFX 500 mg once daily was effective and tolerable for the treatment of LRTIs and UTIs.
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