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.     

Moxifloxacin 0.5% ophthalmic solution: in bacterial conjunctivitis

The fourth-generation 8-methoxyfluoroquinolone moxifloxacin is available as an 0.5% ophthalmic solution for use in the treatment of bacterial conjunctivitis. Moxifloxacin had good activity against various Gram-positive and -negative ocular isolates in vitro, and moxifloxacin 0.5% ophthalmic solution achieved good penetration into ocular tissues in healthy volunteers and patients undergoing ocular surgery. The efficacy of moxifloxacin 0.5% ophthalmic solution in the treatment of bacterial conjunctivitis has been shown in three randomized, double-blind, multicentre trials. In a trial in patients aged ≥1 year, the clinical success rate was significantly higher with moxifloxacin 0.5% ophthalmic solution than with placebo. In a trial in patients aged ≥12 years, moxifloxacin 0.5% ophthalmic solution was noninferior to levofloxacin 0.5% ophthalmic solution in terms of the clinical success rate. In a third trial, the clinical cure rate was significantly higher with moxifloxacin 0.5% ophthalmic solution than with trimethoprim 1.0%/polymixin B 10,000?IU/mL ophthalmic solution in paediatric patients aged ≤18 years. Moxifloxacin 0.5% ophthalmic solution was well tolerated in patients with bacterial conjunctivitis. Ocular adverse events (e.g. eye pain, eye irritation) were the most commonly reported treatment-related adverse events, with the majority being of mild severity.     

Moxifloxacin is non-inferior to combination therapy with ceftriaxone plus metronidazole in patients with community-origin complicated intra-abdominal infections

Management of community-origin complicated intra-abdominal infections (cIAIs) requires surgical intervention and antimicrobial therapy. This multinational, randomised, double-blind clinical trial carried out in Asia compared the efficacy and safety of moxifloxacin monotherapy and ceftriaxone/metronidazole combination therapy in adults with confirmed or suspected cIAI. Patients received surgical intervention and either intravenous (i.v.) moxifloxacin 400 mg once daily or i.v. ceftriaxone 2 g once daily plus i.v. metronidazole 500 mg twice daily. A total of 364 patients were randomised [intent-to-treat (ITT), moxifloxacin N = 180, comparator N = 181; per-protocol (PP), moxifloxacin N = 174, comparator N = 171]. The most common cIAI diagnosis was complicated appendicitis. Moxifloxacin was non-inferior to ceftriaxone/metronidazole in terms of clinical response at test-of-cure in the PP population [clinical cure, 90.2% for moxifloxacin vs. 96.5% for ceftriaxone/metronidazole; 95% confidence interval (CI) of the difference −11.7 to −1.7] and in the ITT population (87.2% for moxifloxacin vs. 91.2% for ceftriaxone/metronidazole; 95% CI −10.7 to 1.9). Bacteriological cure rates in the microbiologically evaluable population support the clinical results (89.4% for moxifloxacin vs. 95.9% for ceftriaxone/metronidazole; 95% CI −13.3 to −0.6). The incidence of treatment-emergent adverse events was similar for both treatment groups (moxifloxacin 31.7% vs. comparator 24.3%). These results confirm previous findings that moxifloxacin plus adequate source control is an appropriate treatment of cIAI.     

Sipuleucel-T: in metastatic castration-resistant prostate cancer

Sipuleucel-T is an autologous active cellular immunotherapy used in the treatment of men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (CRPC). It is the first therapeutic cancer vaccine to receive US FDA approval. Approximately 3 days prior to each infusion of sipuleucel-T, patients undergo a leukapheresis procedure for collection of autologous peripheral blood mononuclear cells. Preparation of sipuleucel-T involves enrichment for antigen-presenting cells from the leukapheresis product and activation ex vivo with a recombinant fusion protein (PA2024). In the randomized, double-blind, placebo-controlled IMPACT study in patients with metastatic CRPC, sipuleucel-T was associated with a 22% relative reduction in the risk of death (hazard ratio 0.78; p?=?0.03), which was the primary endpoint of the trial. After a median follow-up period of 34.1 months, median survival was 4.1 months longer with sipuleucel-T than placebo (25.8 vs 21.7 months). There was no significant between-group difference for the median time to objective disease progression (a secondary endpoint). Almost all patients treated with sipuleucel-T in clinical trials reported an adverse event, although these were mild or moderate in severity (grade 1 or 2) in most patients. The most common adverse events (e.g. infusion-related events, such as chills and fever) generally occurred within the first day after administration of sipuleucel-T and resolved within 2 days.     

Gefitinib in the adjuvant setting: safety results from a phase III study in patients with completely resected non-small cell lung cancer

Standard therapy for stage I-IIIA non-small cell lung cancer (NSCLC) is surgery, although adjuvant therapies are required to prevent disease recurrence and improve patient survival. This is the first study that planned to administer adjuvant gefitinib (Iressa) 250 mg/day or placebo to randomized patients with completely resected NSCLC (stage IB-IIIA) 4-6 weeks following surgery, for 2 years, until recurrence/withdrawal. However, recruitment was stopped after the randomization of 38 patients, because interstitial lung disease (ILD)-type events were being increasingly reported in Japan in the advanced disease setting. Finally, the trial was halted. Safety data for 38 recruited patients (18 gefitinib and 20 placebo) showed no unexpected adverse drug reactions (ADRs), with the most common being grade 1/2 gastrointestinal and skin disorders in 12 and 16 patients receiving gefitinib and in five and six patients receiving placebo, respectively. Grade 3/4 ADRs occurred in four patients receiving gefitinib and one patient receiving placebo. ILD-type events were reported in one patient receiving gefitinib (concomitantly with other ILD-inducing drugs) who died and two patients receiving placebo. Eight patients receiving gefitinib withdrew due to ADRs compared with three patients receiving placebo. Adverse events associated with surgical complications were reported for six patients receiving gefitinib and four patients receiving placebo. In the adjuvant setting there were no unexpected adverse events observed. Gefitinib had no impact on surgery-related complications when given within 4-6 weeks post-operatively.     

Moxifloxacin in uncomplicated skin and skin structure infections

Moxifloxacin is a fluoroquinolone antibacterial agent which attains good penetration into peripheral tissues and inflammatory fluids. The drug shows good in vitro activity against staphylococci and streptococci. Moxifloxacin is therefore a suitable option for the treatment of uncomplicated skin and skin structure infections of bacterial origin. In clinical trials, moxifloxacin was as effective as cephalexin in the treatment of uncomplicated skin and skin structure infections in patients aged >or=18 years. Moxifloxacin 400mg once daily or cephalexin 500mg three times daily for 7 days both resulted in clinical resolution in 84% of patients during a double-blind, randomised trial in 401 patients (intent-to-treat). The main infectious agent in this study was Staphylococcus aureus. Similar results were obtained in two other randomised, double-blind trials published as abstracts. The bioavailability of moxifloxacin is substantially reduced by coadministration with antacids or iron preparations. Moxifloxacin, however, does not show pharmacokinetic interaction with theophylline or warfarin. Dosage adjustments are not required in patients with renal impairment or in patients with mild to moderate hepatic insufficiency. The most common adverse events reported during moxifloxacin treatment are gastrointestinal disturbances. The potential for photosensitivity reactions during moxifloxacin treatment is low.     

High vancomycin minimum inhibitory concentration is a predictor of mortality in meticillin-resistant Staphylococcus aureus bacteraemia

Failure of vancomycin in the treatment of meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia has been reported despite full susceptibility of the organism to vancomycin. A retrospective observational cohort study including 137 patients with MRSA bacteraemia was performed at two centres in South Korea during 2009-2010. A total of 137 patients with MRSA bacteraemia receiving vancomycin therapy were enrolled during the study period. Isolates from 13 (9.5%) of the 137 patients had minimum inhibitory concentrations (MICs) ≥1 μg/mL. The 30-day cumulative survival was 53.8% for patients infected with isolates having a MIC≥1 μg/mL and 79.8% for patients infected with isolates having a MIC<1 μg/mL (log-rank test, P=0.026). Vancomycin MIC≥1 μg/mL [hazard ratio (HR)=7.0, 95% confidence interval (CI) 2.2-22.1; P=0.001], nosocomial acquisition of bacteraemia (HR=5.4, 95% CI 1.4-20.1; P=0.013), rapidly fatal underlying diseases (HR=20.5, 95% CI 3.9-106.4; P<0.001), presentation with septic shock (HR=8.4, 95% CI 3.0-23.3; P<0.001), presence of complicated infections (HR=5.6, 95% CI 2.0-15.8; P=0.001) and persistent MRSA bacteraemia for ≥3 days (HR=4.2, 95% CI 1.4-12.7; P=0.012) were independent predictors of 30-day mortality in patients with MRSA bacteraemia. In patients with high Pitt bacteraemia scores (Pitt score ≥2), the delay in initiation of vancomycin therapy was significantly different between non-survivors and survivors (2.4 days vs. 1.1 days; P=0.012). Vancomycin MIC≥1 μg/mL had a significant impact on mortality of patients with MRSA bacteraemia. These findings support early consideration of alternative anti-MRSA agents in patients with MRSA bacteraemia who have high vancomycin MICs as well as prompt initiation of anti-MRSA treatment in patients with MRSA bacteraemia, especially those with high Pitt scores.     

Efficacy and safety of a fixed combination phytomedicine in the treatment of the common cold (acute viral respiratory tract infection): results of a randomised, double blind, placebo controlled, multicentre study

OBJECTIVE: The common cold (acute viral respiratory tract infection) is one of the most frequent diseases in man, world-wide. Clinically relevant efficacy should include early improvement of all symptoms. Results of a clinical trial of a commercially available fixed combination herbal remedy (Radix echinaceae, Radix baptisiae, Herba thujae) are reported here. The aim of this study was to verify clinical efficacy shown in recent studies under (i) good clinical practice (GCP) quality assurance and (ii) common situations at family doctors. METHODS: Patients attending one of 15 study centres (practitioners) as a result of an acute common cold were randomised to the double-blind placebo-controlled study. Three tablets of study medication were applied t.i.d. for 7 to 9 days. Patients daily documented the intensity of 18 cold symptoms, as well as the cold overall, using a 10-point scale and estimated their general well-being using the Welzel-Kohnen colour scales. Additionally, the severity of illness was assessed by the physician on days 4 and 8 (CGI-1). The main and confirmatory outcome measure was expressed as a total efficacy value. This was gauged from the z-standardised AUC values of the primary endpoints (rhinitis score, bronchitis score, CGI-1 and general well-being). Adverse events, overall tolerability, vital signs and laboratory parameters were documented. RESULTS: 263 patients were included. For safety analysis, all patients were used. 259 patients were evaluable for primary efficacy analysis (ITT). Results were confirmed analysing only the 238 valid cases (VCs). The primary efficacy parameters showed the superiority of the herbal remedy over placebo (p < 0.05). Effect size was 20.6% of the standard deviation (90% CI: 0.04-41.1%; ITT) and 23.1% (1.7-44.5%; VC). In relation to the general well-being, the effect size was 33.9% of the standard deviation (12.5-55.3%; VC). Patients who suffered from at least moderate symptom intensity at baseline showed response rates (at least 50% improvement of the global score, day 5) of 55.3% in the herbal remedy group and 27.3% in the placebo group (p = 0.017; NNT = 3.5). In the subgroup of patients who started therapy at an early phase of their cold, the efficacy of the herbal remedy was most prominent (p = 0.014 for the primary efficacy parameter). The therapeutic benefit of the herbal remedy had already occurred on day 2 and reached significance (p < 0.05) on day 4, and continued until the end of the treatment in the totdl score of symptoms, bronchitis score and rhinitis score, as well as in the patients' overall rating of the cold intensity. At that time, equal levels of improvement were reached three days earlier in the verum group than in the placebo group. In 26 patients receiving the herbal remedy and 23 patients receiving placebo, adverse events were reported. Adverse drug reactions were suspected in two patients in the verum group and in four patients in the placebo group. Serious adverse events did not occur. CONCLUSIONS: This study shows that the herbal remedy is effective and safe. The therapeutic benefit consists of a rapid onset of improvement of cold symptoms. If patients with colds are able to start the application of the herbal remedy as soon as practical after the occurrence of the initial symptoms, the benefit would be expected to increase (e.g. self-medication).     

The VIOXX in prostate cancer prevention study: cardiovascular events observed in the rofecoxib 25 mg and placebo treatment groups

ABSTRACT

Background: A double-blind, randomized, placebo-controlled study was designed to determine the cumulative incidence of developing prostate cancer over 6 years of treatment with rofecoxib 25?mg/day versus placebo. Before completion, this trial was terminated following the voluntary withdrawal of rofecoxib. (On September 30, 2004, Merck & Co., Inc. announced the voluntary worldwide withdrawal of rofecoxib from the market.) Here we report the cardiovascular (CV) safety data collected from this study.

Methods: A total of 4741 men (44–81 years old) exhibiting prostate-specific antigen levels (PSA) between 2.5 and 10?ng/mL were enrolled. Patients were stratified by PSA level and use of low-dose aspirin (LDA), then randomized to rofecoxib 25?mg (n = 2369) or placebo (n = 2372). Safety data were analyzed in all patients receiving ≥1 dose of study medication. All reported thrombotic CV events occurring on-treatment or within 14 days after study drug discontinuation were adjudicated by an independent panel of clinical experts blinded to treatment assignment. Rates per 100 patient-years and relative risk (RR) of thrombotic CV events, rofecoxib vs. placebo, were determined.

Results: Approximately 36% of patients had ≥2 CV risk factors or LDA indicated. Median treatment duration was 4.14 (range: 0.03–15.90) months. Twenty-nine patients (14 rofecoxib, rate 1.27; 15 placebo, rate 1.36) experi­enced confirmed thrombotic CV events; RR 0.94 (95% CI: 0.45, 1.94) vs. placebo. Four patients (one rofecoxib; three placebo) died due to a confirmed thrombotic event. Significantly (?p = 0.002) more patients receiving rofecoxib (n = 20; 0.8%) experienced hypertension-related adverse events versus placebo (n = 2; 0.1%). There were no cases of congestive heart failure.

Conclusions: Rofecoxib 25?mg and placebo demon­strated similar risk of thrombotic CV events in this limited dataset.     

Impact of piperacillin/tazobactam on nephrotoxicity in patients with Gram-negative bacteraemia

Piperacillin/tazobactam (TZP) has been associated with nephrotoxicity in patients receiving vancomycin. Its impact on nephrotoxicity in patients with Gram-negative bacteraemia (GNB) is unclear. This study evaluated the impact of TZP on nephrotoxicity in patients with GNB. This retrospective cohort included patients aged ≥18 years receiving ≥48 h of therapy for bacteraemia due to Escherichia coli, Pseudomonas aeruginosa, Enterobacter, Klebsiella, Acinetobacter or Stenotrophomonas maltophilia from 1/01/2008–8/31/2011. Patients with baseline serum creatinine (SCr) ≥3.5 mg/dL, polymicrobial infection or recurrent bacteraemia were excluded. Nephrotoxicity was defined as a ≥0.5 mg/dL increase in SCr or ≥50% increase from baseline for ≥2 consecutive days. Any variable demonstrating a 10% change in exposure effect was retained in the final model. All variables biologically reasonable causes of nephrotoxicity were also considered for inclusion. The median age of the cohort (n?=?292) was 76 years; 38.0% had a cancer diagnosis and ICU residence was common (21.9%). There was no difference in nephrotoxicity incidence based on days of TZP received (0 days, 13.6%; 1–2 days, 14.7%; 3–4 days, 6.9%; ≥5 days, 16.7%; P?=?0.71). In multivariable analysis, baseline SCr, total body weight and vasopressor use were independently associated with nephrotoxicity. Duration of TZP was not associated with nephrotoxicity in multivariable analysis (1–2 days, OR?=?0.91, 95% CI 0.39–2.12; 3–4 days, OR?=?0.48, 95% CI 0.10–2.46; ≥5 days, OR?=?0.57, 95% CI 0.11–3.02). In this cohort of GNB patients, duration of TZP was not associated with nephrotoxicity.     

Clinical trial: effectiveness of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) in the prevention of antibiotic-associated diarrhoea in children

Background  Convincing evidence that probiotic administration can lower the risk of antibiotic-associated diarrhoea is limited to certain micro-organisms.
Aim  To determine the efficacy of administration of Lactobacillus rhamnosus (strains E/N , Oxy and Pen ) for the prevention of antibiotic-associated diarrhoea in children.
Methods  Children (aged 3 months to 14 years) with common infections were enrolled in a double-blind, randomized, placebo-controlled trial in which they received standard antibiotic treatment plus 2 × 10¹⁰ colony forming units of a probiotic ( n  = 120) or a placebo ( n  = 120), administered orally twice daily throughout antibiotic treatment. Analyses were by intention to treat.
Results  Any diarrhoea (≥3 loose or watery stools/day for ≥48 h occurring during or up to 2 weeks after the antibiotic therapy) occurred in nine (7.5%) patients in the probiotic group and in 20 (17%) patients in the placebo group (relative risk, RR 0.45, 95% confidence interval, CI 0.2–0.9). Three (2.5%) children in the probiotic group developed AAD (diarrhoea caused by Clostridium difficile or otherwise unexplained diarrhoea) compared to nine (7.5%) in the placebo group (RR 0.33, 95% CI 0.1–1.06). No adverse events were observed.
Conclusion  Administration of L. rhamnosus (strains E/N , Oxy and Pen ) to children receiving antibiotics reduced the risk of any diarrhoea, as defined in this study.     

Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: a randomized double-blind placebo-controlled trial

BACKGROUND: Co-treatment with Saccharomyces boulardii appears to lower the risk of antibiotic-associated diarrhoea in adults receiving broad-spectrum antibiotics. AIM: To determine whether S. boulardii prevents antibiotic-associated diarrhoea in children. METHODS: A total of 269 children (aged 6 months to 14 years) with otitis media and/or respiratory tract infections were enrolled in a double-blind, randomized placebo-controlled trial in which they received standard antibiotic treatment plus 250 mg of S. boulardii (experimental group, n = 132) or a placebo (control group, n = 137) orally twice daily for the duration of antibiotic treatment. Analyses were based on allocated treatment and included data from 246 children. RESULTS: Patients receiving S. boulardii had a lower prevalence of diarrhoea (> or =3 loose or watery stools/day for > or =48 h occurring during or up to 2 weeks after the antibiotic therapy) than those receiving placebo [nine of 119 (8%) vs. 29 of 127 (23%), relative risk: 0.3, 95% confidence interval: 0.2-0.7]. S. boulardii also reduced the risk of antibiotic-associated diarrhoea (diarrhoea caused by Clostridium difficile or otherwise unexplained diarrhoea) compared with placebo [four of 119 (3.4%) vs. 22 of 127 (17.3%), relative risk: 0.2; 95% confidence interval: 0.07-0.5]. No adverse events were observed. CONCLUSION: This is the first randomized-controlled trial evidence that S. boulardii effectively reduces the risk of antibiotic-associated diarrhoea in children.     

Palifermin: in myelotoxic therapy-induced oral mucositis

Palifermin, a recombinant human keratinocyte growth factor (KGF), mimics the actions of endogenous KGF and has shown efficacy in the management of myelotoxic therapy-induced oral mucositis in cancer patients. In a randomised, double-blind trial in patients with haemtaological malignancies receiving conditioning radiochemotherapy before undergoing autologous stem cell transplant, intravenous palifermin 60 microg/kg/day (two 3-day cycles, administered before myelotoxic therapy and after transplant) significantly reduced the median duration (primary endpoint) [3 vs 9 days] and incidence (63% vs 98%) of WHO grade 3 or 4 oral mucositis, compared with placebo. Patient-reported outcomes also showed significant improvement with palifermin treatment, which was associated with significant reductions in healthcare resource utilisation, compared with placebo. The drug was generally well tolerated, with skin/oral toxicities, pain/arthralgias and dysaesthesia being the most common palifermin-related adverse reactions.     

Extended-release intramuscular naltrexone

An extended-release intramuscular formulation of naltrexone that provides sustained release of the drug over a 28-day period has been developed with the aim of improving treatment adherence in patients treated with naltrexone for alcohol dependence. Biodegradable polylactide-co-glycolide polymer microspheres containing 34% w/w naltrexone are reconstituted in an aqueous suspension just prior to intramuscular administration. Extended-release intramuscular naltrexone 380 mg administered once every 4 weeks, in combination with psychosocial therapy, demonstrated superior efficacy to placebo plus psychosocial therapy in reducing the heavy drinking event rate (primary endpoint) in adult patients with alcohol dependence in a 6-month well controlled trial. Among the subset of patients who abstained completely from drinking during the 7 days prior to the first dose of medication (n = 53; 8% of the total study population), those treated with extended-release intramuscular naltrexone 380 mg had greater reductions in the number of drinking days and the number of heavy drinking days compared with placebo recipients. Treatment with extended-release intramuscular naltrexone 380 mg once every 4 weeks for up to 18 months was generally well tolerated, with infrequent treatment-related serious adverse events. The most common treatment-emergent adverse events leading to treatment discontinuation were nausea, injection site reaction and headache. The proportion of patients with clinically significant plasma transaminase elevations was not different between patients receiving extended-release intramuscular naltrexone and those receiving placebo.     

Update on the cardiac safety of moxifloxacin

Cardiac safety was compared in patients receiving moxifloxacin and other antimicrobials in a large patient population from Phase II-IV randomized active-controlled clinical trials. Moxifloxacin 400 mg once-daily monotherapy was administered orally (PO) or sequentially (intravenous/oral, IV/PO). Across 64 trials, 21,298 patients received PO therapy (10,613 moxifloxacin, 10,685 comparators) while 6846 received sequential IV/PO therapy (3431 moxifloxacin, 3415 comparators). Treatment-emergent cardiac adverse event (AE) rates were similar for moxifloxacin and comparators in PO (6.6% vs 5.8%) and IV/PO (11.0% vs 12.0%) trials. Treatment-emergent cardiac adverse drug reactions were rare in PO (moxifloxacin 3.2% vs comparators 2.4%) and IV/PO (moxifloxacin 1.4% vs comparators 1.5%) patients. There were five (<0.02%) treatment-emergent drug-related deaths due to cardiac events out of 28,144 patients; one PO patient died treated with comparators, one patient died treated with IV/PO moxifloxacin, and three patients died after treatment with IV/PO comparators. Only one case of treatment-related non-fatal torsade de pointes occurred in the comparator arm. Incidence rates of cardiac AEs remained low in populations at elevated risk of cardiac events predisposed to QTc prolongation (i.e. community-acquired pneumonia patients admitted to the intensive care unit and/or mechanical ventilation, patients with documented prolongation of baseline QTc interval, women, and patients ≥ 65 years old). There was no evidence of unexpected cardiac events. After moxifloxacin treatment, an expected small prolongation in QTcB and QTcF was found. This analysis of numerous clinical trials shows the favorable cardiac safety profile of moxifloxacin, when used appropriately and according to its label, versus other antibiotics.     

Fluoroquinolone-based versus β-lactam-based regimens for complicated intra-abdominal infections: a meta-analysis of randomised controlled trials

Complicated intra-abdominal infections (cIAIs) are common and confer significant morbidity, mortality and costs. In this era of evolving antimicrobial resistance, selection of appropriate empirical antimicrobials is paramount. This systematic review and meta-analysis of randomised controlled trials compared the effectiveness and safety of fluoroquinolone (FQ)-based versus β-lactam (BL)-based regimens for the treatment of patients with cIAIs. Primary outcomes were treatment success in the clinically evaluable (CE) population and all-cause mortality in the intention-to-treat (ITT) population. Subgroup analyses were performed based on specific antimicrobials, infection source and isolated pathogens. Seven trials (4125 patients) were included. FQ-based regimens included moxifloxacin (four studies) or ciprofloxacin/metronidazole (three studies); BL-based regimens were ceftriaxone/metronidazole (three studies), carbapenems (two studies) or piperacillin/tazobactam (two studies). There was no difference in effectiveness in the CE (2883 patients; RR = 1.00, 95% CI 0.95–1.04) or ITT populations (3055 patients; RR = 0.97, 95% CI 0.94–1.01). Mortality (3614 patients; RR = 1.04, 95% CI 0.75–1.43) and treatment-related adverse events (2801 patients; RR = 0.97, 95% CI 0.70–1.33) were also similar. On subset analysis, moxifloxacin was slightly less effective than BLs in the CE (1934 patients; RR = 0.96, 95% CI 0.93–0.99) and ITT populations (1743 patients; RR = 0.94, 95% CI 0.91–0.98). Although FQ- and BL-based regimens appear equally effective and safe for the treatment of cIAIs, limited data suggest slightly inferior results with moxifloxacin. Selection of empirical coverage should be based on local bacterial epidemiology and patterns of resistance as well as antimicrobial stewardship protocols.     

Continuous-infusion penicillin home-based therapy for serious infections due to penicillin-susceptible pathogens

To evaluate the feasibility of continuous-infusion (CI) penicillin in the treatment of serious bacterial infections, consecutive adult patients with deep-seated infections due to penicillin-susceptible pathogens were treated with CI aqueous penicillin G in a home-based programme, and their treatment outcomes were reviewed. Thirty-one patients with microbiologically proven infections completed the planned course of treatment. Twenty of 31 (65%) were followed for at least 2 months thereafter, and all remained free of relapse. One patient had fever attributable to penicillin hypersensitivity, two patients developed catheter-site infections and one patient developed catheter-related bacteraemia. Thus, CI penicillin is feasible for the home-based treatment of a variety of deep-seated infections with minimal toxicity.     

Adverse events with continuous doxapram infusion against late postoperative hypoxaemia

Objective: A randomized double-blind controlled trial of doxapram versus placebo against late postoperative hypoxaemia was planned to include 40 patients (2 × 20). Results: After inclusion of 18 patients a serious adverse event was encountered with development of a brain stem infarction in a 90-year-old woman receiving doxapram. At this point the randomization code was broken and we decided to terminate the trial. Three of nine patients receiving doxapram had had an adverse event whereas none of the patients receiving placebo had adverse events (P = 0.2). In the 18 patients studied, there was an insignificant trend towards higher mean oxygen saturation in the doxapram group, and a significantly higher minimum oxygen saturation and reduced number of hypoxaemic events on the first postoperative night. Conclusion: Although these preliminary data on the effect of doxapram on postoperative hypoxaemia seem promising, further studies on the effect of continuous nocturnal postoperative doxapram infusion on levels of arterial oxygen saturation should be postponed until more knowledge about the pharmacokinetics of doxapram in this particular clinical situation has been gathered. Received: 16 May 1995/Accepted in revised form: 18 October 1995     

Capecitabine in patients with breast cancer relapsing after high-dose chemotherapy plus autologous peripheral stem cell transplantation--a phase II study

Capecitabine, a tumor-selective, oral fluoropyrimidine, has demonstrated significant antitumor activity in patients with metastatic breast cancer. In this open-label monocenter phase II study the efficacy and safety of capecitabine in patients with metastatic breast cancer who relapsed after high-dose chemotherapy was examined. Female patients 18-65 years of age, with a histologically confirmed diagnosis of metastatic breast cancer, who relapsed after high-dose chemotherapy (adjuvant and/or metastatic) followed by autologous peripheral blood stem cell transplantation (PBSCT) and who had been treated in their course of the disease with an anthracycline and/or an anthracycline/taxane containing regimen were included into this clinical study. Capecitabine was applied as the first salvage chemotherapy at relapse after high-dose chemotherapy (1250 mg/m(2) b.i.d. p.o. for 14 days followed by 7 days rest period). Responding patients or those with stable disease after two treatment cycles were offered to continue treatment until tumor progression. Response rate, time to disease progression, survival, toxicity and quality of life were assessed. Fourteen patients between 35 and 60 years (median 45.5 years) entered this study and received a median number of 5 cycles (range 1-19) of capecitabine. All patients were evaluable for response. All patients had been pretreated with 1-2 cycles of high-dose chemotherapy plus PBSCT. Furthermore, 13 patients had additionally received local radiotherapy. On average, the patients showed metastatic disease in two organ sites (range 1-4 sites). One patient obtained a complete response and five patients a partial response, accounting for a response rate of 42.9% [95% confidence interval (17.7%; 71.1%)]. All responses were already achieved at the first observation time point 6 weeks after treatment initiation. Two further patients obtained stable disease for at least 12 weeks. At the time of final analysis all patients have progressed. Median time to progression was 2.8 months (range 0.4-13.3 months). No median survival time was reached (range 3.9-36.5 months, at the time of reporting eight patients were alive and six patients had died). Two patients developed grade III granulocytopenia. Five patients developed grade III hand-foot syndrome. One patient had the combination of nausea, fever and diarrhea grade III. All adverse events were considered manageable. We conclude that capecitabine as single-agent oral chemotherapy is active and well tolerated in heavily pretreated patients with breast cancer. It can be safely used in patients who have been intensively pretreated by myelotoxic chemotherapy or who have even relapsed after high-dose chemotherapy with PBSCT.     

莫西沙星治疗皮肤细菌感染随机双盲对照临床研究

目的：比较每日po1次莫西沙星400mg与每日po2次左旋氧氟沙星200mg，治疗轻中度急性无合并症皮肤细菌感染(包括蜂窝织炎、脓疱病，疖、单纯脓肿和伤口感染)的安全性和有效性。方法：用随机、双盲、平行研究，共入选88例患者，试验组和对照组各44例。疗程7～14天，主要疗效参数为治疗结束后第1，第7天的临床疗效。结果：在治疗结束后第1天，莫西沙星组与左旋氧氟沙星组临床有效率分别为84．6％(33／39)，85．0％(34／40)；细菌学清除率分别为93．8％(30／32)，93．9％(31／33)。在治疗结束后第7天莫西沙星组与左旋氧氟沙星组临床有效率分别为85.3％(29／34．)，90．0％(36，40)；细菌学清除率分别为92．9％(26／28)，93．9％(31／33)。莫西沙星组药物不良反应发生率为27．3％(12／44)，左旋氧氟沙星组为ll.4％(5／44)。两组差异均无统计学意义。结论：莫西沙星治疗轻中度急性无合并症皮肤细菌感染有效安全。