Bacteriological Eradication Rates Research Articles

Moxifloxacin in acute exacerbations of chronic bronchitis and COPD.

To the editor, Liu and colleagues have conducted a systematic review and meta-analysis to evaluate the efficacy and safety of moxifloxacin in acute exacerbations of chronic bronchitis and chronic obstructive pulmonary disease (1). The searched databases were inconsistent. In the Methods subsection of Abstract, searched databases were PubMed, EMBASE, and the Web of Science; however, in the Data sources and search strategy subsection of Text, searched databases were PubMed, the Cochrane Central Database of Controlled Trials, and EMBASE. For the outcomes of clinical success and bacteriological eradication, it was inappropriate to use odds ratio for estimating the differences between moxifloxacin group and other antibiotics group, since the clinical success and bacteriological eradication rates were very high in both groups. In this case, relative risk should be used; In the Study selection subsection of Text, the authors stated that for this meta-analysis, we considered those randomized control trials (RCTs) that compared the clinical efficacy of moxifloxacin and another antibiotic in patients with AECB and AECOPD. In the Statistical analysis subsection of Text, the authors said that we computed pooled odds ratios (ORs) and 95% confidence intervals (CIs) from the adjusted ORs and 95% CIs reported in the observational studies. And then, I have to wonder why the authors computed pooled ORs from the observational studies rather than the included RCTs, even the adjusted ORs? In the Statistical analysis subsection of Text, there is no reason to select fixed-effects analysis when heterogeneity is less than 50% by I squared, since under those circumstances tau squared may still be greater than zero and random-effects models may still give wider confidence intervals. If there is zero heterogeneity (tau squared zero), then the random effects result will equal the fixed effects result; In the second figure of that article, Wilson R 1999 accounts for nearly one-third (29.7%) of the total weight. Also, Wilson R 2012 accounts for nearly half (45.3%) of the total weight in the fourth figure of that article. The authors should performed sensitivity analysis by omitting the trial to test the robustness of their results; In the Publication bias subsection of Text, the authors found evidence of publication bias upon visual inspection of the funnel plot. Strictly speaking, it was incorrect to describe the result like this. The most important one is that the asymmetry of funnel plot does not mean the existence of publication bias. It would be more appropriate that evidence of small trial bias was found upon visual inspection of the funnel plot.

小児科領域におけるCefteram pivoxilの基礎的・臨床的検討

Bacteriological, pharmacokinetic and clinical studies on cefditoren pivoxil (CDTR-PI, ME 1207) in granules, a new oral cephalosporin, were performed in the field of pediatrics. The results are summarized below. 1. Antibacterial activities: Antibacterial activities of CDTR were studied against Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Haemophilus parainfluenzae and Branhamella catarrhalis in comparison with those of cefteram (CFTM), cefixime (CFIX), cefaclor (CCL), cefpodoxime (CPDX) and cefotiam (CTM). MIC80's of CDTR against S. aureus, S. pneumoniae, S. pyogenes, H. influenzae, H. parainfluenzae and B. catarrhalis were 1.56, 0.39, < or = 0.025, < or = 0.025, 0.05 and 0.20 micrograms/ml, respectively. These results showed that CDTR has high antibacterial activities against these organisms. 2. Absorption and excretion: Serum concentrations and urinary recovery rates of CDTR-PI (administered in granules) were determined. Upon single oral doses of 3 mg/kg and 6 mg/kg, the peak serum concentrations were 0.5-2.45 micrograms/ml at 2 to 4 hours and 1.79-4.05 micrograms/ml at 1 to 4 hours, respectively, and T 1/2 was 1.07-9.67 hours and 0.99-3.00 hours, respectively. At 8 hours after dosing, serum concentrations were 0-0.87 micrograms/ml with a dose of 3 mg/kg and 0.27-0.73 micrograms/ml with 6 mg/kg. These values indicated that the drug has a dose-dependent pharmacokinetic behavior. Urinary recovery rates in the first 8 hours were 12.9-34.2% with a dose of 3 mg/kg and 11.8-26.9% with 6 mg/kg. 3. Clinical study: Clinical efficacies were examined in a total of 81 cases consisting of 20 cases of acute bronchitis, 13 of acute pneumonia, 21 of tonsillitis, 5 of pharyngitis, 7 of scarlet fever, 2 each of impetigo, otitis media and purulent cervical lymphadenitis, 1 of pertussis and 8 of UTI. The clinical efficacy rate was 97.5% (79/81), and bacteriological eradication rate was 100% (76/76). As for side effects, 2 cases of watery stools and 1 case of minor elevation of GPT were observed.

Clinical studies of BRL 28500 (clavulanic acid/ticarcillin) in the treatment of pelvioperitonitis and Douglas' abscess

Clinical studies were conducted on BRL 28500 (a formulation containing 15 parts ticarcillin plus 1 part clavulanic acid). BRL 28500 was administered at doses of 1.6 g or 3.2 g b.i.d., generally for 10 days by drip infusion to patients with pelvioperitonitis or Douglas' abscess. The results obtained were summarized as follows. 1. Clinical efficacy was evaluated in 18 patients (pelvioperitonitis 14, Douglas' abscess 4), but 8 patients out of a total of 26 patients were excluded. 2. In the evaluation of clinical improvement by doctors in charge, clinical improvement rates were 44.4% on day 3, 88.2% on day 5. 3. On the basis of committee judgement, the clinical efficacy rate was 100%. 4. The bacteriological eradication rate of causative organisms was 100% in 11 patients (15 strains). Five strains out of a total of 15 strains produced beta-lactamase. 5. As a side effect, nausea was observed in 1 case. In laboratory examination, liver function abnormalities were observed in 1 case. 6. Regarding usefulness as judged by doctors in charge, the satisfactory rate was 83.3%. From the above results, it has been concluded that BRL 28500 is very useful in the treatment of pelvioperitonitis and Douglas' abscess.

Efficacy of linezolid on gram-positive bacterial infection in elderly patients and the risk factors associated with thrombocytopenia

Objective : Linezolid is active against drug-resistant gram-positive bacteria. However, the efficacy and safety of linezolid in the treatment of the elderly have not been well characterized. The purpose of this study was to evaluate the efficacy of linezolid in the treatment of the elderly with gram-positive bacterial infection and to investigate the risk factors associated with the development of thrombocytopenia in these patients. This was a retrospective analysis of 50 elderly patients who were treated with intravenous linezolid for gram-positive bacterial infection. Clinical data and bacteriological responses were assessed. Risk factors associated with thrombocytopenia in elderly patients were analyzed. The overall clinical cure rate of linezolid was 74%, and the bacteriological eradication rate was 69%. Thrombocytopenia occurred in 24 patients, and thrombocytopenia was associated with both the duration of treatment (P = 0.005) and the baseline platelet count (P = 0.042). Based on a logistic regression analysis, the baseline platelet count <200×10(9)/L (OR = 0.244; 95% CI = 0.068- 0.874; P = 0.030) was identified as the only significant risk factor for linezolid-associated thrombocytopenia in elderly patients. The mean platelet count decreased significantly from the 7(th) day of treatment, and decreased to the lowest value 1-2 days after the end of therapy. Conclusions : Linezolid is effective and safe for the elderly with gram-positive bacterial infections. Adverse effects such as thrombocytopenia are of greater concern. Platelet counts should be monitored in patients who are treated with linezolid and that measures should be taken in advance to avoid hemorrhagic tendencies.

Prospective randomized comparison study of piperacillin/tazobactam and meropenem for healthcare-associated pneumonia in Japan

Healthcare-associated pneumonia (HCAP) may have a more severe course than community-acquired pneumonia (CAP); hence, it is more likely to be caused by drug-resistant bacterial pathogens and anaerobes involved in aspiration pneumonia. We compared the efficacy and safety of initial empiric therapy with piperacillin/tazobactam (PIPC/TAZ, 13.5g/day) with that of meropenem (MEPM, 1.5g/day) as single broad-spectrum regimens with gram-negative and anaerobic coverage in patients with HCAP in Japan. The clinical cure rate was 75.9% (22/29 cases) in the PIPC/TAZ group and 64.3% (18/28 cases) in the MEPM group. The clinical efficacy rate was 87.9% (29/33 cases) in the PIPC/TAZ group and 74.2% (23/31 cases) in the MEPM group. The bacteriological eradication rate was 94.4% (17/18) in the PIPC/TAZ group and 87.5% (14/16) in the MEPM group. Adverse drug reactions were seen in 22.4% (11/49 cases) of patients in the PIPC/TAZ group and 17.4% (8/46 cases) of patients in the MEPM group. Although not statistically different, the PIPC/TAZ group had a slightly higher efficacy rate than the MEPM group. Both treatment regimens are tolerable and might be appropriate to use as initial empiric therapy for HCAP in Japan. To investigate the differences in efficacy profiles of those two regimens, a further confirmatory study with a larger cohort as determined by a power analysis is recommended.

成人の中耳炎に対するメシル酸ガレノキサシン（ＧＲＮＸ）の有効性

Background: Garenoxacin mesilate (GRNX) is a novel oral des-fluoro(6) quinolone with potent antimicrobial activity against common respiratory pathogens, including resistant strains. Some researchers showed high efficacy of GRNX for acute otolaryngological infectious diseases. However, there are few reports on its efficacy in the treatment of adult otitis media. Objective: The aim of this study was to investigate the effectiveness of GRNX for adult otitis media. Material and Method: We reviewed thirty adult patients with acute exacerbation of chronic otitis media and seven adult patients with acute otitis media from June 2008 to July 2009. We examined the clinical efficacy and biological response of GRNX in these patients. Results: Clinical efficacy rates were 93% in acute exacerbation of chronic otitis media and 100% in acute otitis media. In acute exacerbation of chronic otitis media, bacteriological eradication rates were 9/12 in MSSA, 2/2 in MRSA, 1/2 in P. aeruginosa, 1/1 in P. mirabilis and 1/1 in S. marcescens. The overall eradication rate in acute exacerbation of chronic otitis media was 75%. In acute otitis media, four strains were isolated: CNS, S. pyogenes, M. catarrhalis and PSSP. These were all eradicated. Conclusion: The clinical efficacy of GRNX for adult otitis media in this study was superior to those of previous reports. GRNX is very useful for the treatment of acute exacerbation of chronic otitis media and acute otitis media in adults.

Effectiveness and Safety of Short-Course vs Long-Course Antibiotic Therapy for Group A β-Hemolytic Streptococcal Tonsillopharyngitis: A Meta-analysis of Randomized Trials

OBJECTIVE To evaluate the effectiveness and safety of short-course antibiotic treatment of group A β-hemolytic streptococcal (GAS) tonsillopharyngitis. METHODS We performed a meta-analysis of randomized controlled trials (RCTs) retrieved from PubMed and the Cochrane Central Register of Controlled Trials using a structured search strategy. The last date either database was accessed was November 14, 2007. We included RCTs that involved patients of any age with GAS tonsillopharyngitis, comparing short-course (≤7 days) vs long-course (at least 2 days longer than short-course) treatment with the same antibiotics. The primary analysis compared 5 to 7 days with 10 days of treatment, using a random effects model. RESULTS Eleven RCTs comparing short-course vs long-course treatment (5 with penicillin V, 4 with oral cephalosporins, 1 with intramuscular ceftriaxone, and 1 with clindamycin; 6 of the 11 were open label) were included. In the primary analysis, microbiological eradication rates of GAS were inferior for short-course vs long-course treatment (8 RCTs, 1607 patients; odds ratio [OR], 0.49; 95% confidence interval [CI], 0.32-0.74). This association was noted with penicillin V treatment (3 RCTs, 500 patients; OR, 0.36; 95% CI, 0.13-0.99) but was nonsignificant with cephalosporin treatment (4 RCTs, 1018 patients; OR, 0.62; 95% CI, 0.38-1.03). Microbiological eradication was less likely with short-course treatment in trials involving primarily children and adolescents (aged <18 years) (6 RCTs, 1258 patients; OR, 0.63; 95% CI, 0.40-0.98). Clinical success was inferior in patients who received short-course treatment (5 RCTs, 1217 patients; OR, 0.49; 95% CI, 0.25-0.96). Adverse events did not differ between compared groups. The above associations were consistent in the analyses involving all included RCTs. CONCLUSION Short-course treatment for GAS tonsillopharyngitis, particularly with penicillin V, is associated with inferior bacteriological eradication rates. To evaluate the effectiveness and safety of short-course antibiotic treatment of group A β-hemolytic streptococcal (GAS) tonsillopharyngitis. We performed a meta-analysis of randomized controlled trials (RCTs) retrieved from PubMed and the Cochrane Central Register of Controlled Trials using a structured search strategy. The last date either database was accessed was November 14, 2007. We included RCTs that involved patients of any age with GAS tonsillopharyngitis, comparing short-course (≤7 days) vs long-course (at least 2 days longer than short-course) treatment with the same antibiotics. The primary analysis compared 5 to 7 days with 10 days of treatment, using a random effects model. Eleven RCTs comparing short-course vs long-course treatment (5 with penicillin V, 4 with oral cephalosporins, 1 with intramuscular ceftriaxone, and 1 with clindamycin; 6 of the 11 were open label) were included. In the primary analysis, microbiological eradication rates of GAS were inferior for short-course vs long-course treatment (8 RCTs, 1607 patients; odds ratio [OR], 0.49; 95% confidence interval [CI], 0.32-0.74). This association was noted with penicillin V treatment (3 RCTs, 500 patients; OR, 0.36; 95% CI, 0.13-0.99) but was nonsignificant with cephalosporin treatment (4 RCTs, 1018 patients; OR, 0.62; 95% CI, 0.38-1.03). Microbiological eradication was less likely with short-course treatment in trials involving primarily children and adolescents (aged <18 years) (6 RCTs, 1258 patients; OR, 0.63; 95% CI, 0.40-0.98). Clinical success was inferior in patients who received short-course treatment (5 RCTs, 1217 patients; OR, 0.49; 95% CI, 0.25-0.96). Adverse events did not differ between compared groups. The above associations were consistent in the analyses involving all included RCTs. Short-course treatment for GAS tonsillopharyngitis, particularly with penicillin V, is associated with inferior bacteriological eradication rates.

Effectiveness and Safety of Short-Course vs Long-Course Antibiotic Therapy for Group A β-Hemolytic Streptococcal Tonsillopharyngitis: A Meta-analysis of Randomized Trials

To evaluate the effectiveness and safety of short-course antibiotic treatment of group A beta-hemolytic streptococcal (GAS) tonsillopharyngitis. We performed a meta-analysis of randomized controlled trials (RCTs) retrieved from PubMed and the Cochrane Central Register of Controlled Trials using a structured search strategy. The last date either database was accessed was November 14, 2007. We included RCTs that involved patients of any age with GAS tonsillopharyngitis, comparing short-course (< or =7 days) vs long-course (at least 2 days longer than short-course) treatment with the same antibiotics. The primary analysis compared 5 to 7 days with 10 days of treatment, using a random effects model. Eleven RCTs comparing short-course vs long-course treatment (5 with penicillin V, 4 with oral cephalosporins, 1 with intramuscular ceftriaxone, and 1 with clindamycin; 6 of the 11 were open label) were included. In the primary analysis, microbiological eradication rates of GAS were inferior for short-course vs long-course treatment (8 RCTs, 1607 patients; odds ratio [OR], 0.49; 95% confidence interval [CI], 0.32-0.74). This association was noted with penicillin V treatment (3 RCTs, 500 patients; OR, 0.36; 95% CI, 0.13-0.99) but was nonsignificant with cephalosporin treatment (4 RCTs, 1018 patients; OR, 0.62; 95% CI, 0.38-1.03). Microbiological eradication was less likely with short-course treatment in trials involving primarily children and adolescents (aged <18 years) (6 RCTs, 1258 patients; OR, 0.63; 95% CI, 0.40-0.98). Clinical success was inferior in patients who received short-course treatment (5 RCTs, 1217 patients; OR, 0.49; 95% CI, 0.25-0.96). Adverse events did not differ between compared groups. The above associations were consistent in the analyses involving all included RCTs. Short-course treatment for GAS tonsillopharyngitis, particularly with penicillin V, is associated with inferior bacteriological eradication rates.

Prulifloxacin in the treatment of acute exacerbations of COPD in cigarette smokers

Smoking is associated with an increased risk of respiratory tract infection in adults likely because components in the smoke might alter properties of the epithelial cell surface. In studies with smokers suffering from acute exacerbations of COPD (AECOPD), the most common bacterial pathogens found were mainly Haemophilus influenzae, but also Streptococcus pneumoniae, Staphylococcus aureus, and Moraxella catarrhalis. Therefore, antibiotics should be effective against such possible pathogens. Prulifloxacin has demonstrated in vitro activity against all these pathogens. We designed the present study to evaluate the efficacy of prulifloxacin in the treatment of AECOPD in cigarette smokers. We enrolled 61 consecutive smokers hospitalized or out-patients of either sex with symptoms and signs compatible with the usual diagnosis criteria for AECOPD. Haemophilus influenzae was the most common bacterial species isolated in the sputum (in 42.6% of the total sample), followed by S. pneumoniae (16.5%), S. aureus (14.7%), M. catarrhalis (11.5%), and others (14.7%). Prulifloxacin 600 mg was given orally once daily for 10 days. Clinical success was observed in 91.8% of patients (67.2% cured and 24.6% improved). Bacteriological eradication rate of H. influenzae was 100%. Persistent pathogens were S. pneumoniae (2 out of 10), S. aureus (1 out of 8), M. catarrhalis (1 out of 7), and P. aeruginosa (1 out of 3). This study seems to indicate that prulifloxacin is of particular value in the treatment of AECOPD in cigarette smokers.

Doripenem

Doripenem, a parenteral, broad-spectrum antibacterial agent of the carbapenem family, is indicated as empirical therapy in serious bacterial infections in adults. Doripenem is indicated in Japan for use as a single agent in intra-abdominal infections (IAIs), lower respiratory tract infections (including nosocomial pneumonia), complicated urinary tract infections (cUTIs) and a variety of other bacterial infections, such as complicated skin and skin structure infections (cSSSIs), obstetric and gynaecological infections, serious ear, nose and throat infections, sepsis and endocarditis, dental and oral surgical infection, and ophthalmic infection caused by various susceptible strains of Gram-negative, Gram-positive or anaerobic bacteria. Doripenem is indicated in the US for the treatment of complicated IAIs (cIAIs) or cUTIs, including pyelonephritis, caused by susceptible strains of designated pathogens, and in the EU for the treatment of nosocomial pneumonia (including ventilator-associated pneumonia [VAP]), cIAIs or cUTIs.Doripenem has a broad spectrum of in vitro activity against Gram-positive and Gram-negative bacteria, including extended-spectrum beta-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae, and anaerobic pathogens. The drug also has a low propensity to select for resistance and is suitable for the prolonged infusions that may be required to achieve pharmacodynamic/pharmacokinetic targets for bactericidal activity (and therefore efficacy) against pathogens with increased MICs (minimum concentrations required to inhibit the pathogens). Doripenem is no less effective than other antibacterial agents, including meropenem, imipenem/cilastin, piperacillin/tazobactam or levofloxacin in a wide range of serious bacterial infections, such as complicated lower respiratory infections, nosocomial pneumonia (including VAP), cIAIs and cUTIs, and is well tolerated. Thus, doripenem is a valuable addition to the options available for the empirical treatment of serious bacterial infections in hospitalized patients.

Complicated Urinary Tract Infections Treated with Extended-Release Ciprofloxacin with Emphasis on Pseudomonas aeruginosa

This report focuses on the role of Pseudomonas aeruginosa in complicated urinary tract infections in a prospective, open-label, multicenter study designed to evaluate the safety and efficacy of extended-release ciprofloxacin (ciprofloxacin XR) 1000 mg once daily for 7-14 days for the treatment of complicated urinary tract infections. A total of 204 patients were valid for intention-to-treat analysis, of whom 130 were included in the clinical efficacy population. In the 56 microbiologically valid patients the bacteriological eradication rate was 82.1% and the clinical cure rate was 94.6%. Patients with P. aeruginosa infections valid for microbiological efficacy (n = 7) had 100% bacteriological eradication and clinical cure rates. In the intention-to-treat population, the bacteriological and clinical cure rates were 42.1% (51/121) and 55.9% (114/204), respectively. These rates were 58.3% and 75.0% respectively, for patients with P. aeruginosa infections. To achieve the desired 10 patients with P. aeruginosa for analysis, these data were pooled with data from a previous study. Treatment failure correlated with pre-therapy P. aeruginosa isolates being resistant to ciprofloxacin. On exploratory multivariate regression analysis, presence of neurogenic bladder, urinary retention owing to benign prostatic hypertrophy, prior urinary tract infection, and ischemic heart disease predicted P. aeruginosa infection.

The use of pharmacokinetic/pharmacodynamic principles to predict clinical outcome in paediatric acute otitis media

Double tympanocentesis studies of children with acute otitis media, carried out over an 11-year period, were used to confirm that pharmacokinetic (PK) and pharmacodynamic (PD) parameters can be used as predictors of the bacteriological and clinical efficacy of antimicrobial agents. Predicted susceptibilities of common respiratory pathogens, such as Streptococcus pneumoniae and Haemophilus influenzae, were compared with the bacteriological outcome of treatment in which the high-dose formulation of amoxicillin/clavulanate (90 mg/kg/day) given twice daily achieved the greatest bacteriological eradication rates for an oral agent. Further analysis of the data has indicated that failure to eradicate bacteria from the middle ear fluid is strongly correlated with clinical failure.

Oral Garenoxacin in the Treatment of Acute Bacterial Maxillary Sinusitis: A Phase II, Multicenter, Noncomparative, Open-Label Study in Adult Patients Undergoing Sinus Aspiration

Background: Garenoxacin is a des-F(6)-quinolone with in vitro activity against key respiratory pathogens, including Streptococcus pneumoniae, Hemophilus influenzae, Staphylococcus aureus, and Moraxella catar-rhalis. Limited data are available regarding the effect of garenoxacin in the treatment of acute bacterial sinusitis. Objective: The aim of this study was to assess the efficacy and tolerability of garenoxacin in adults with acute bacterial maxillary sinusitis undergoing a pre-treatment diagnostic sinus aspirate. Methods: This Phase II, multicenter, noncomparative, open-label study was conducted at 30 centers in the United States, Mexico, Argentina, and Europe. Male and female patients aged 18 to 80 years with clinical signs and symptoms lasting ≥5 but ⩽ 28 days and radiologic signs (air-fluid level, opacification, mucosal thickening) of acute maxillary sinusitis were eligible. The entry criteria for the 5-day treatment regimen did not include mucosal thickening of ≥5 mm because it was believed that improvement in mucosal thickening might not be reliably measurable at the 5-day time point. All patients received garenoxacin 400 mg QD for 5 or 10 days. Maxillary sinus needle aspiration for Gram stain, routine culture, and susceptibility testing were performed before treatment, and, if clinically indicated, during and after treatment. Bacteriologic eradication (negative culture on repeat sinus aspiration) and cure rates (complete resolution of all signs and symptoms) were assessed at a test-of-cure visit 5 to 18 days after the end of treatment. The occurrence of adverse events was recorded by the investigators up to 30 days after the last administration of garenoxacin by questioning patients. Results: A total of 546 patients were enrolled and 543 were randomized (5-day cohort: mean age, 40 years; mean weight, 76 kg; 56% women; 10-day cohort: mean age, 41 years; mean weight, 77 kg; 58% women). Clinically evaluable patients included 253 in the 5-day cohort and 266 in the 10-day cohort. Cure rates were 93% (236/253; 95% CI, 89%–96%) and 91% (243/266; 95% CI, 87%–94%) for evaluable patients in the 5− and 10-day cohorts, respectively. Bacteriologic eradication rates in microbiologically evaluable patients were 94% in both cohorts (5 days, 204/217; 10 days, 182/193). Eradication rates in the 5− and 10-day cohorts were as follows: S pneumoniae, 94% (62/66) and 93% (39/42); H influenzae, 100% (30/30) and 93% (26/28); S aureus, 96% (23/24) and 91% (31/34); and M catarrhalis, 89% (8/9) and 86% (12/14). Of the 9 patients with acute bacterial sinusitis due to multidrug-resistant S pneumoniae, 8 achieved clinical cure with garenoxacin treatment. Adverse events (AEs) most frequently reported were diarrhea (<2%), nausea (2%–6%), headache (2%–6%), and dizziness (<2%). Two percent of patients withdrew because of an AE (allergic reaction, adverse gastrointestinal effects, dyspnea, dizziness, headache, or elevation in liver enzymes). Conclusion: In this population of patients with signs and symptoms of acute maxillary sinusitis, oral garenoxacin 400 mg QD for 5 or 10 days eradicated 94% of bacterial pathogens associated with acute bacterial sinusitis in this population and appeared to be well tolerated in adults.

Moxifloxacin vs amoxicillin/clavulanate in the treatment of acute sinusitis

Purpose The aim of this study was to compare the efficacy and safety of moxifloxacin with that of amoxicillin/clavulanate for the treatment of acute bacterial sinusitis in adults. Materials and methods Five hundred seventy-five patients from Latin American countries were randomized to receive oral moxifloxacin 400 mg once daily for 7 days, or oral amoxicillin/clavulanate 500/125 mg 3 times daily for 10 days, in a prospective, open study. Results At the test-of-cure visit (7-14 days after the end of therapy), the clinical success rate in the moxifloxacin group was 93.4% similar to that in the amoxicillin/clavulanate group (92.7%). Documented bacteriological eradication plus presumed eradication rates in the moxifloxacin (96.5%) and the amoxicillin/clavulanate (96.7%) groups were also similar. Drug-related adverse events were recorded in 32.2% of patients in the moxifloxacin group and 29.7% in the amoxicillin/clavulanate group. Patient discontinuation in the trial due to adverse events occurred for 10 patients in the moxifloxacin group and 6 in the amoxicillin/clavulanate group. Conclusions Overall, in terms of clinical and bacteriological response, moxifloxacin was equivalent to amoxicillin/clavulanate for the treatment of acute bacterial sinusitis in adults.

Clinical and bacteriological outcomes in hospitalised patients with community-acquired pneumonia treated with azithromycin plus ceftriaxone, or ceftriaxone plus clarithromycin or erythromycin: a prospective, randomised, multicentre study

This study compared patients with moderate-to-severe community-acquired pneumonia (CAP) requiring hospitalisation, who received initial therapy with either intravenous ceftriaxone plus intravenous azithromycin, followed by step-down to oral azithromycin (n = 135), with patients who received intravenous ceftriaxone combined with either intravenous clarithromycin or erythromycin, followed by step-down to either oral clarithromycin or erythromycin (n = 143). Clinical and bacteriological outcomes were evaluated at the end of therapy (EOT; day 12–16) or at the end of study (EOS; day 28–35). At baseline, mean APACHE II scores were 13.3 and 12.6, respectively, with >50% of patients classified as Fine Pneumonia Severity Index (PSI) category IV or V. Clinical success rates (cure or improvement) in the modified intent-to-treat (MITT) population at EOT were 84.3% in the ceftriaxone/azithromycin group and 82.7% in the ceftriaxone/clarithromycin or erythromycin group. At EOS, MITT success rates (cure only) were 81.7% and 75.0%, respectively. Equivalent success rates in the clinically evaluable population were 83% and 87%, respectively, at EOT, and 79% and 78%, respectively, at EOS. MITT bacteriological eradication rates were 73.2% and 67.4%, respectively, at EOT, and 68.3% vs. 60.9%, respectively, at EOS. Mean length of hospital stay (LOS) was 10.7 and 12.6 days, and the mean duration of therapy was 9.5 and 10.5 days, respectively. The incidence of infusion-related adverse events was 16.3% and 25.2% (p 0.04), respectively. An intravenous-to-oral regimen of ceftriaxone/azithromycin was at least equivalent in efficacy and safety to the comparator regimen and appeared to be a suitable treatment option for hospitalised patients with CAP.

Efficacy and safety of intravenous moxifloxacin versus cefoperazone with azithromycin in the treatment of community acquired pneumonia

To compare the efficacy, safety, and tolerability of intravenous moxifloxacin with those of a commonly used empirical antibiotic regimen, cefoperazone and azithromycin in the treatment of community acquired pneumonia (CAP) in adult patients requiring initial parenteral therapy, 40 patients with CAP were divided into two groups, a moxifloxacin group (n = 20) and a control group (n = 20), which were treated for 7 to 14 days. The patients in the moxifloxacin group were intravenously given 400 mg of moxifloxacin (Avelox) once a day. Patients in the control group were administered 2.0 g of cefoperazone twice a day and azithromycin 0.5 g once a day. Clinical, bacteriological, and laboratory examinations were performed before the treatment, and at the end of the treatment. Our results showed that there was no significant difference in the clinical efficacy rate between two treatment groups at end of therapy (90% for moxifloxacin, 95% for cefoperazone plus azithromycin) (P > 0.05). The bacteriologic eradication rate at the end of treatment was 90% in the moxifloxacin group and 80% in the cefoperazone-plus-azithromycin group, whereas there was no significant difference between the two groups (P > 0.05). In addition, both drugs were well-tolerated in this trial, with the number of drug-related adverse events being comparable. It is concluded that moxifloxacin is an effective and well-tolerated treatment for CAP and was equivalent to the commonly used empirical treatment of cefoperazone plus azithromycin. Moxifloxacin is likely to offer clinicians an alternative for reliable empirical CAP treatment in the face of increasing antibiotic resistance.

Comparison of Sequential Intravenous/Oral Ciprofloxacin Plus Metronidazole with Intravenous Ceftriaxone Plus Metronidazole for Treatment of Complicated Intra-abdominal Infections

Intra-abdominal infections are a substantial clinical problem and an important cause of morbidity and death in the hospital. Optimal treatment requires both source control and antibiotic therapy. Sequential intravenous (IV) to oral therapy may improve patient convenience and reduce total health care costs. In this randomized, double-blind trial, the efficacy of sequential IV-to-oral ciprofloxacin plus metronidazole was compared with ceftriaxone plus metronidazole in adult patients with complicated intra-abdominal infections. The trial enrolled 531 patients, who began with IV therapy. Patients who improved clinically were switched to oral therapy on day three or later. The clinical and bacteriological responses four to six weeks after the end of therapy and the safety of the two regimens were assessed. To maintain blinding, the patients received placebo IV in the ciprofloxacin group or placebo orally in the ceftriaxone group. A total of 475 patients (235 ciprofloxacin plus metronidazole, 240 ceftriaxone plus metronidazole) were valid for evaluation of efficacy. All patients were included in the safety analysis. Of the patients valid for efficacy, 78% of the ciprofloxacin plus metronidazole group and 81% of the ceftriaxone plus metronidazole group were eligible for a switch to oral therapy. The clinical success rates were 98.9% and 96.9%, respectively, which were statistically equivalent. The clinical success rates for all patients, including those on continuous IV therapy, were 90.6% and 87.9%. Source control was achieved in more than 90% of the patients. The bacteriological eradication rates were similar in the two groups. Bacterial complications (e.g., surgical site infections, abscesses) were encountered more often in the ceftriaxone plus metronidazole group. Sequential ciprofloxacin plus metronidazole IV-to-oral therapy was statistically equivalent to ceftriaxone plus metronidazole. The switch to oral therapy with ciprofloxacin plus metronidazole was as effective and safe as continued IV therapy in patients able to tolerate enteral feeding.

Comparison of European and U.S. results for cephalosporin versus penicillin treatment of group A streptococcal tonsillopharyngitis

The outcome of cephalosporin versus penicillin treatment of group A streptococcal tonsillopharyngitis may differ between Europe and the USA. In the present study, Medline, Embase, reference lists, and abstract searches were used to identify randomized, controlled trials of cephalosporin versus penicillin treatment of group A streptococcal (GAS) tonsillopharyngitis. The outcomes of interest were bacteriologic and clinical cure rates from investigations conducted in Europe versus those conducted in the USA. Forty-seven trials involving 11,426 patients were included in the meta-analyses. For the comparison of 10 days of treatment with cephalosporins versus 10 days of treatment with penicillin, there were ten European and 25 U.S. trials, all involving pediatric subjects. The overall odds ratio (OR) favored cephalosporins more strongly in bacteriologic cure rate in Europe (OR=4.27, p<0.00001) than in the USA (OR=2.70, p<0.00001). Studies of 4-5 days of cephalosporin treatment versus 10 days of penicillin treatment were also analyzed. For nine European trials, the OR significantly favored cephalosporins (OR=1.30, p=0.03) in bacteriologic cure rates, but not as strongly as in the USA, (OR=2.41, p<0.00001). When results for 4-5 days of cephalosporin treatment were divided into pediatric versus adult populations, the differences in bacteriologic eradication rates obtained with cephalosporins were more pronounced in children. The likelihood of bacteriologic and clinical failure of GAS tonsillopharyngitis treatment in both European and U.S. patients is significantly less if a 10-day course of oral cephalosporin is prescribed, and is at least similar, if not significantly less, with a 4- to 5-day course of oral cephalosporin compared with a 10-day course of oral penicillin.

The treatment of urinary tract infections and use of ciprofloxacin extended release

Urinary tract infections (UTIs) are one of the most common reasons people seek medical attention. There are > 50% of women who will have at least one UTI during their lifetime and most of these will require a physician visit and antibiotic treatment. The high prevalence continues to the in-patient setting where genitourinary infections are the most common nosocomial infection. The efficient diagnosis and effective treatment of UTIs is a major healthcare concern. Factors such as economic efficiency and emerging resistance are increasingly becoming more important considerations in providing patient care. In out-patient uncomplicated UTIs, Escherichia coli has been implicated in ≤ 75 – 90% of cases. Although the prevalence in the in-patient setting decreases, E. coli is still the most common bacteria identified and present in 21 – 54% of urinary isolates. Trimethoprim–sulfamethoxazole has been the preferred first-line agent for uncomplicated out-patient UTIs where local resistance is < 10 – 20%. In recent years, resistance has superseded this threshold in most regions of the US and Europe. In these areas with increased resistance, fluoroquinolones have become a common first-line agent. Ciprofloxacin has been one of the most widely used fluoroquinolones and has a well-known safety profile, as well as excellent activity against most of the common uropathogens. Ciprofloxacin extended release (ER) is a recently released once-daily formulation that has been increasingly used with good clinical success. The pharmacokinetic and pharmacodynamic parameters of ciprofloxacin ER are shown to be at least equal to twice-daily ciprofloxacin and may even confer superiority as ciprofloxacin ER achieves a higher maximum serum concentration. This is supported by clinical studies, which have shown at least as effective clinical cure and bacteriological eradication rates. These studies have also demonstrated similar tolerability and side-effect profiles. Ciprofloxacin ER combines traditional ciprofloxacin's proven track record of efficacy and safety with favourable pharmacokinetics and convenient once-daily dosing. Increased patient compliance is associated with decreased treatment failures and can help slow the development of antimicrobial resistance. Economic considerations are also increasingly important and providing convenient and effective treatment leading to high clinical success decreases overall costs.

Sequential intravenous/oral moxifloxacin versus intravenous piperacillin-tazobactam followed by oral amoxicillin-clavulanate for the treatment of complicated skin and skin structure infection

In this prospective, double-blind, multicentre trial, adult patients with complicated skin and skin structure infection (cSSSI) randomly received sequential intravenous (i.v.)/oral (p.o.) moxifloxacin (400 mg once a day) or a control regimen of i.v. piperacillin-tazobactam (3.0/0.375 g every 6 h) followed by p.o. amoxicillin-clavulanate (800 mg every 12 h), each for 7–14 days. Clinical cure rates at the test-of-cure visit (10–42 days post therapy) for the efficacy-valid population were 79% (143/180) for the moxifloxacin-treated group and 82% (153/187) for the control group (95% confidence interval, −12.04, 3.29). Bacteriological eradication rates for Staphylococcus aureus, the most prevalent organism, were 78% and 80%, respectively. The incidence of drug-related adverse events was similar for both groups (31% moxifloxacin, 30% control). Sequential i.v./p.o. moxifloxacin was as effective and well tolerated as i.v. piperacillin-tazobactam followed by p.o. amoxicillin-clavulanate in treating patients with cSSSI.