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.     

回顾性分析本院抗菌药使用与G~-菌耐药率变化的相关性

目的 回顾性分析本院抗菌药使用与G-菌耐药率变化相关性.方法 用纸片法,测定每季度住院患者分离的常见G-菌对不同抗菌药的耐药率;统计全院住院患者第3,4代头孢菌素类、氨基糖苷类、含B内酰胺酶抑制剂复合物类、碳青霉烯类、氟喹诺酮类和复方磺胺甲恶唑抗菌药的使用情况,并进行季度限定日剂量(DDD)累积数和每千人出院患者所消耗的DDD数的计算.结果 大肠埃希菌对头孢吡肟的耐药率、鲍曼不动杆菌对亚胺培南的耐药率,与抗菌药的用量有显著正相关;耐亚胺培南鲍曼不动杆菌的耐药率与碳青霉烯类和第3,4代头孢菌素的用量均呈显著正相关(均P<0.01).结论 各种抗菌药使用情况的变化对医院内G-细菌的耐药率有较大影响.     

Association between Clostridium difficile infection and antimicrobial usage in a large group of English hospitals

Aims

This study aimed to determine the association between the reduction in the number of Clostridium difficile infection (CDI) cases reported by the English National Health Service (NHS) hospitals and concurrent antimicrobial use.

Methods

A retrospective ecological study for January 2005 to December 2008 was conducted using data from 26 of the 29 NHS trusts (i.e. a trust manages one or more hospitals) located in the North West Strategic Health Authority of England. Antimicrobial use data, for patients of all ages, were provided by IMS Health, and CDI case data for patients aged ≥65 years were provided by the Health Protection Agency. Antimicrobial use was converted into defined daily doses (DDDs). The overall association between antimicrobial use and CDI for the trusts was investigated using multilevel models.

Results

Our study shows a positive significant association between the CDI cases and the use of the following antimicrobials: ‘third-generation cephalosporins’ [11.62 CDI cases per 1000 DDDs; 95% confidence interval (CI), 5.92–17.31]; ‘fluoroquinolones’ (4.79 CDI cases per 1000 DDDs; 95% CI, 2.83–6.74); and ‘second-generation cephalosporins’ (4.25 CDI cases per 1000 DDDs; 95% CI, 1.66–6.83). The strength of this association was not significantly different (95% CI) among the antimicrobial groups.

Conclusions

This study shows that the reduction in the number of CDI cases reported by the English NHS hospitals is associated with concurrent reductions in antimicrobial use. This means that the number of CDI cases over time decreased in a similar fashion to the usage of various antimicrobials.     

Short- versus long-course antibacterial therapy for community-acquired pneumonia : a meta-analysis

BACKGROUND: The evidence for traditionally recommended 7- to 14-day duration of antibacterial therapy for community-acquired pneumonia (CAP) is not well established. OBJECTIVES: We endeavoured to assess the effectiveness and safety of shorter than traditionally recommended antibacterial therapy for CAP. METHODS: We performed a meta-analysis of randomized controlled trials (RCTs) comparing short- (/=2 days difference) course therapy for CAP with the same antibacterial regimens, in the same daily dosages. RESULTS: Five RCTs involving adults (including outpatients and inpatients who did not require intensive care) and two RCTs involving children (aged 2-59 months, residing in developing countries) were included. All RCTs were double-blind and assessed patients with CAP of mild to moderate severity. No differences were found between short- (adults 3-7 days; children 3 days) and long- (adults 7-10 days; children 5 days) course regimens (adults - amoxicillin, cefuroxime, ceftriaxone, telithromycin and gemifloxacin; children - amoxicillin) regarding clinical success at end-of-therapy (six RCTs; 5107 patients [1095 adults, 4012 children]; fixed-effect model [FEM]; odds ratio [OR] = 0.89; 95% CI 0.74, 1.07), clinical success at late follow-up, microbiological success, relapses, mortality (seven RCTs; 5438 patients; FEM; OR = 0.57; 95% CI 0.23, 1.43), adverse events (five RCTs; 3214 patients; FEM; OR = 0. 90; 95% CI 0.72, 1.13) or withdrawals as a result of adverse events. No differences were found in subset analyses of adults or children, and of patients treated with no more than 5-day short-course regimens versus at least 7-day long-course regimens. CONCLUSION: No difference was found in the effectiveness and safety of short- versus long-course antimicrobial treatment of adult and paediatric patients with CAP of mild to moderate severity.     

Impact of inappropriate drug use among hospitalized older adults

Objective Criteria for inappropriate drug use developed by Beers have been widely used in drug utilization reviews as the basis for educational materials and to assess the quality of prescribing. However, there is inconclusive evidence that these criteria can impact on patient outcomes. The objective of this study was to evaluate the impact of inappropriate drug use on all-cause mortality, adverse drug reactions (ADRs) and length of stay among in-hospital patients.Methods We performed a retrospective, cohort study on 5,152 patients aged 65 years or older admitted to 81 hospitals in Italy between 1997 and 1998. Inappropriate drug use was defined by 2003 Beers criteria. Outcomes of the study were: (a) in-hospital mortality; (b) incidence of ADR occurring during hospital stay; (c) length of hospital stay 13 days or more.Results The mean age of 5,152 participants was 78.8 years (standard deviation = 8.4 years), and 2,463 (47.8%) were men. During hospital stay, 1,475 (28.6% of the study sample) patients received one or more inappropriate drugs. After adjusting for potential confounders, use of inappropriate drugs was not associated significantly with either mortality [odds ratio (OR) 1.05; 95% confidence intervals (CI): 0.75–1.48], ADR (OR 1.20; 95% CI: 0.89–1.61) or length of stay 13 days or more (OR 1.09; 95% CI: 0.95–1.25).Conclusions This study did not show any significant effect of inappropriate drug use defined by Beers 2003 criteria on health outcomes among hospitalized older adults. Further studies conducted in different settings, using additional health outcomes and alternate measures of inappropriate drug use, are needed.     

Patient characteristics associated with prescribing of a newly introduced drug: the case of rofecoxib

Objective To identify socio-demographic characteristics of the first patients receiving a new drug—rofecoxib.Outcome measurement Patients starting on rofecoxib or another non-steroidal anti-inflammatory drug (NSAID) and who had not received any NSAIDs the 90 days prior to starting.Results Starting on rofecoxib was associated with an increasing age (OR in age 80 years and older 8.7; 95% CI 6.7–11.2), a poor self-perceived health (OR=2.4; 95% CI 1.8–3.3), female gender (OR=1.4; 95% CI 1.2–1.6), private insurance (OR=1.3; 1.1–1.5) and previous acetaminophen use (OR=1.3; 1.1–1.7).Conclusion This study noted that specific patient characteristics were associated with getting rofecoxib prescribed shortly after marketing. General practitioners should be aware of selectively prescribing new drugs to specific patients because it may place patients at unintentional and avoidable risk.     

Drug utilization in paediatrics: Non-medical factors affecting decision making by prescribers

Summary The study was done to show that in certain areas of paediatric pharmacotherapy unexpected discrepancies may arise between accepted therapeutic principles and the actual behaviour of a prescribing doctor. The first example was of a great reduction in penicillin use in a university teaching hospital after certain therapeutic accidents: in one year, there were 2 fatal cases of rhabdomyolysis due to use of procaine benzyl-penicillin. Other antimicrobial drugs inferior to penicillin, such as lincomycin and sulphonamides, replaced penicillins. The second example showed the inverse relationship between the use of antitussives and other drugs in symptomatic treatment of respiratory diseases in outpatients and inpatients; the pressure of unduly optimistic expectations of therapy imposes a high prescribing rate of these drugs in the outpatient population, in contrast to hospitalized patients, whose doctors, being spared such pressure, prescribe antitussives far less often. The third example demonstrates the possibility of inadequate education in the use of antimicrobial drugs. Although doctors from regional hospitals receive their training at an university hospital, they tend to prescribe chloramphenicol ten times more per bed-day than their colleagues in an university hospital. In terms of the cost/effectiveness ratio, a high prescribing rate of cephalosporins is not economically favourable in a university teaching hospital. It is also shown that studies of drug utilization in children are feasible if age — appropriate adaptation of the statistical value expressed as the defined daily dose is performed. The adaptation was evaluated by comparing pharmacy-based drug consumption data expressed in paediatric defined daily doses, with actual days of treatment with particular drugs, i.e. data from patient records for 244 beds in the University Teaching Hospital.     

Ceftriaxone/Amikacin vs Ceftazidime/Amikacin as Empirical Therapy for Fever in Patients with Haematological Malignancy and Severe Granulocytopenia: Clinical and Economic Outcomes

To assess the economic outcomes produced when a conventional antibiotic treatment regimen requiring three administrations per day was replaced with a treatment regimen requiring only one daily administration, the efficacy, tolerability and cost of ceftazidime was compared with that of ceftriaxone (both drugs in combination with amikacin) for the empirical treatment of febrile granulocytopenic patients with haematological malignancy. 102 febrile patient-episodes were randomly assigned to receive ceftazidime (6g in three divided doses) or ceftriaxone (2g as a single daily dose), both in combination with amikacin. The response was evaluable in 94 patients (47 in each group). 75 (80%) patients had an absolute granulocyte count lower than 100/mm(3) at the onset of fever or during the first week of antibiotic therapy. 61 (64.9%) were affected by acute leukaemia. Multiple daily ceftazidime plus amikacin was effective in 33 of 47 (70.2%) patients, and single daily ceftriaxone plus amikacin in 31 of 47 (66%) patients (p > 0.2). Among patients successfully treated, median time to defervescence was 3.3 days (range 1 to 11) for ceftazidime plus amikacin and 4.5 days for ceftriaxone plus amikacin (range 1 to 15) [p = 0.14]; study drugs were continued for 12 (range 7 to 26) and 12.3 days (range 7 to 28), respectively. Our study demonstrated that single daily administration of ceftriaxone was as effective and well tolerated as multiple daily administration of ceftazidime when both were administered in combination with amikacin. Cost analysis showed that compared with the thrice daily regimen, administration of single daily doses of ceftriaxone for a 12-day treatment period would result in a net cost saving of $US392 (626 940 Italian lire).     

Antimicrobial use in a critical care unit: a prospective observational study

Objective The purpose of this study was to describe antimicrobial utilization, consumption, indications and microbial resistance in a medical‐surgical‐trauma intensive care unit (ICU) of a teaching hospital to identify potential targets for antimicrobial stewardship. Methods This was a 30‐day prospective observational study enrolling adults admitted to the ICU for at least 24 h and having received antimicrobial therapy. Primary endpoints included utilization as percentage use of antimicrobials by class and agent, consumption measured as days of therapy per 1000 patient days (DOT/1000PD), indications for use and prescriber. Secondary endpoints included reasons for modifications to therapy and microbial resistance. Key findings Eighty‐three patients were screened and 61 enrolled, receiving 133 courses of antimicrobial therapy, mainly intravenously and prescribed by ICU staff. The most frequently prescribed agents were piperacillin/tazobactam (20%), cefazolin (17%) and vancomycin (13%). The indications for therapy were empirical (50%), directed (27%) and prophylactic (23%). Overall consumption was 1368.54 DOT/1000PD and was mainly attributed to empirical therapy (734.25). Prolonged durations were noted for carbapenems and for surgical prophylaxis. There were 86 therapy modifications involving indication (36), efficacy (25), safety (18) and route (7). Suboptimal or excessive dosing were common contributors to efficacy and safety modifications, respectively. Infections due to microorganisms with notable resistance included methicillin‐resistant Staphylococcus aureus (5), Pseudomonas aeruginosa (1) and Streptococcus pneumoniae (1). Conclusions Antimicrobial utilization and consumption based on DOT/1000PD were prospectively determined providing a comparator for other ICUs. Potential targets identified for antimicrobial stewardship initiatives include empirical therapy, treatment duration, dosing and route.