The Widely Used Antimicrobial Triclosan Induces High Levels of Antibiotic Tolerance In Vitro and Reduces Antibiotic Efficacy up to 100-Fold In Vivo.

The antimicrobial triclosan is used in a wide range of consumer products ranging from toothpaste, cleansers, socks, and baby toys. A bacteriostatic inhibitor of fatty acid synthesis, triclosan is extremely stable and accumulates in the environment. Approximately 75% of adults in the United States have detectable levels of the compound in their urine, with a sizeable fraction of individuals (>10%) having urine concentrations equal to or greater than the minimal inhibitory concentration for Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). Previous work has identified connections between defects in fatty acid synthesis and accumulation of the alarmone guanosine tetraphosphate (ppGpp), which has been repeatedly associated with antibiotic tolerance and persistence. Based on these data, we hypothesized that triclosan exposure may inadvertently drive bacteria into a state in which they are able to tolerate normally lethal concentrations of antibiotics. Here we report that clinically relevant concentrations of triclosan increased E. coli and MRSA tolerance to bactericidal antibiotics as much as 10,000-fold in vitro and reduced antibiotic efficacy up to 100-fold in a mouse urinary tract infection model. Genetic analysis indicated that triclosan-mediated antibiotic tolerance requires ppGpp synthesis but is independent of growth. These data highlight an unexpected and certainly unintended consequence of adding high concentrations of antimicrobials in consumer products, supporting an urgent need to reevaluate the costs and benefits of the prophylactic use of triclosan and other bacteriostatic compounds.

Mixed effects of restriction strategies in antimicrobial stewardship programs on antimicrobial use in 121 tertiary hospitals in China, 2013-2017.

Background: The research evaluated the impact of intravenous antimicrobial restriction strategy (IARS) on different types of hospitals in China for evidence-based management, for outpatients implemented in 2016. Methods: Based on panel data on antimicrobial use in 121 tertiary hospitals in Zhejiang, China, segmented regression analysis was used to evaluate the impact of IARS in children's hospitals (CHs), obstetrics and gynecology hospitals (OGHs), women's and children's hospitals (WCHs), traditional Chinese medicine hospitals (TCMHs) and general hospitals (GHs). Antimicrobial use was measured using the percentage of total encounters with prescribing and the percentage of total drug expenditure relating to antimicrobials (APP and AEP). Results: There was a downward baseline slope of APP in all types of hospitals and AEP in WCHs, TCMHs and GHs (P < 0.01). After IARS, a level reduction in AEP in CHs (-3.14%, 95% CI = -6.21 to 0.06), WCHs (-1.33%, 95% CI = -2.44 to 0.22) and TCMHs (-0.85%, 95%CI = -1.51 to 0.18). After IARS, the slope of AEP changed significantly in OGHs (-0.42%, 95%CI = -0.81 to 0.03) and WCHs (0.29%, 95% CI = 0.08 to 0.49), and the slope of APP changed significantly in CHs (2.35%, 95%CI = 1.20 to 3.49). Conclusions: IARS had the mixed effects including positive effect in AEP and no significant change in APP, and an unexpected rise in APP in CHs needs further study.

Clinical and economic impact of the taurolidine lock on home parenteral nutrition.

INTRODUCTION: catheter-related bloodstream infections (CRBSI) are one of the most serious concerns in patients on home parenteral nutrition (HPN) which involve high morbidity and cost for the healthcare system. In the last years, taurolidine lock has proven to be beneficial in the prevention of CRBSI; however, the evidence of its efficiency is limited. OBJECTIVE: to determine if taurolidine lock is a cost-effective intervention in patients on HPN. MATERIALS AND METHODS: retrospective study in patients on HPN with taurolidine lock. We compared the CRBSI rate and cost of its complications before and during taurolidine lock. RESULTS: thirteen patients, six (46%) males and seven (54%) females, with a mean age of 61.08 (SD = 14.18) years received taurolidine lock. The total days of catheterization pre and per-taurolidine were 12,186 and 5,293, respectively. The underlying disease was benign in five patients (38.5%) and malignant in eight (61.5%). The CRBSI rate pre vs per-taurolidine was 3.12 vs 0.76 episodes per 1,000 catheter days (p = 0.0058). When the indication was a high CRBSI rate, this was 9.72 vs 0.39 (p < 0.001) in pre and per-taurolidine period respectively. No differences have been observed in the occlusion rates. None of the patients reported any adverse effects. The total cost of CRBSI in the pre-taurolidine period was 151,264.14 euros vs 24,331.19 euros in the per-taurolidine period. CONCLUSIONS: our study shows that taurolidine lock is a cost-effective intervention in patients on HPN with high risk of CRBSI.

Antimicrobial consumption, costs and resistance patterns: a two year prospective study in a Romanian intensive care unit.

BACKGROUND: Due to the vulnerable nature of its patients, the wide use of invasive devices and broad-spectrum antimicrobials used, the intensive care unit (ICU) is often called the epicentre of infections. In the present study, we quantified the burden of hospital acquired pathology in a Romanian university hospital ICU, represented by antimicrobial agents consumption, costs and local resistance patterns, in order to identify multimodal interventional strategies. METHODS: Between 1st January 2012 and 31st December 2013, a prospective study was conducted in the largest ICU of Western Romania. The study group was divided into four sub-samples: patients who only received prophylactic antibiotherapy, those with community-acquired infections, patients who developed hospital acquired infections and patients with community acquired infections complicated by hospital-acquired infections. The statistical analysis was performed using the EpiInfo version 3.5.4 and SPSS version 20. RESULTS: A total of 1596 subjects were enrolled in the study and the recorded consumption of antimicrobial agents was 1172.40 DDD/ 1000 patient-days. The presence of hospital acquired infections doubled the length of stay (6.70 days for patients with community-acquired infections versus 16.06/14.08 days for those with hospital-acquired infections), the number of antimicrobial treatment days (5.47 in sub-sample II versus 11.18/12.13 in sub-samples III/IV) and they increased by 4 times compared to uninfected patients. The perioperative prophylactic antibiotic treatment had an average length duration of 2.78 while the empirical antimicrobial therapy was 3.96 days in sample II and 4.75/4.85 days for the patients with hospital-acquired infections. The incidence density of resistant strains was 8.27/1000 patient-days for methicilin resistant Staphylococcus aureus, 7.88 for extended spectrum ß-lactamase producing Klebsiella pneumoniae and 4.68/1000 patient-days for multidrug resistant Acinetobacter baumannii. CONCLUSIONS: Some of the most important circumstances collectively contributing to increasing the consumption of antimicrobials and high incidence densities of multidrug-resistant bacteria in the studied ICU, are represented by prolonged chemoprophylaxis and empirical treatment and also by not applying the definitive antimicrobial therapy, especially in patients with favourable evolution under empirical antibiotic treatment. The present data should represent convincing evidence for policy changes in the antibiotic therapy.

Antimicrobial activity of pomegranate peel extracts as affected by cultivar.

BACKGROUND: Some studies have reported that different parts of the pomegranate fruit, especially the peel, may act as potential antimicrobial agents and thus might be proposed as a safe natural alternative to synthetic antimicrobial agents. The high tannin content, especially punicalagin, found in pomegranate extracts, has been reported as the main compound responsible for such antimicrobial activity. Because the pomegranate peel chemical composition may vary with the type of cultivar (sweet, sour-sweet and sour), pomegranates may also differ with respect to their antimicrobial capacity. RESULTS: The extract from PTO8 pomegranate cultivar peel had the highest antimicrobial activity, as well as the highest punicalagins (α and ß) and ellagic acid concentrations. In the results obtained from both antibacterial and antifungal activity studies, the sour-sweet pomegranate cultivar PTO8 showed the best antimicrobial activity, and the highest ellagic acid concentrations. CONCLUSION: The results of the present study suggest that ellagic acid content has a significant influence on the antimicrobial activity of the pomegranate extracts investigated. The pomegranate peel of the PTO8 cultivar is a good source of antifungal and antibacterial compounds, and may represent an alternative to antimicrobial agents of synthetic origin. © 2016 Society of Chemical Industry.

Evaluation of dedicated infectious diseases pharmacists on antimicrobial stewardship teams.

PURPOSE: Patient care improvements and cost savings achieved by a large integrated health system through the implementation of antimicrobial stewardship programs (ASPs) at two hospitals are reported. METHODS: A pre-post analysis was conducted to evaluate cost and quality outcomes at the two ASP sites and three similar sites within the same health system not included in the ASP initiative. The utilization of 15 targeted antimicrobials and associated costs at the five sites during designated preimplementation and postimplementation periods were compared; changes in Hospital Standardized Mortality Ratio (HSMR) values for specific infections among Medicare patients were also assessed. RESULTS: In the year after ASP implementation, aggregate direct antimicrobial acquisition costs at the two study sites decreased 17.3% from prior-year levels and increased by 9.1% at the three comparator sites. Significant decreases in the consumption of targeted antimicrobial classes (antipseudomonals, quinolones, and agents active against methicillin-resistant Staphylococcus aureus) were observed at the ASP sites. Among the 2446 ASP interventions recorded, 72% involved discontinuing or narrowing the use of broad-spectrum antimicrobials. Although rates of health care-associated Clostridium difficile infection were little changed at both study sites after ASP implementation, HSMR data indicated substantial gains in combating sepsis and C. difficile and respiratory infections. CONCLUSION: After implementation of ASPs at two study sites, the utilization of all classes of antibiotics decreased and antimicrobial costs per 1000 patient-days decreased. While HSMR values for sepsis (including C. difficile-associated cases) and respiratory infections improved, the rate of C. difficile infections stayed the same.

Integrating rapid pathogen identification and antimicrobial stewardship significantly decreases hospital costs.

CONTEXT: Early diagnosis of gram-negative bloodstream infections, prompt identification of the infecting organism, and appropriate antibiotic therapy improve patient care outcomes and decrease health care expenditures. In an era of increasing antimicrobial resistance, methods to acquire and rapidly translate critical results into timely therapies for gram-negative bloodstream infections are needed. OBJECTIVE: To determine whether mass spectrometry technology coupled with antimicrobial stewardship provides a substantially improved alternative to conventional laboratory methods. DESIGN: An evidence-based intervention that integrated matrix-assisted laser desorption and ionization time-of-flight mass spectrometry, rapid antimicrobial susceptibility testing, and near-real-time antimicrobial stewardship practices was implemented. Outcomes in patients hospitalized prior to initiation of the study intervention were compared to those in patients treated after implementation. Differences in length of hospitalization and hospital costs were assessed in survivors. RESULTS: The mean hospital length of stay in the preintervention group survivors (n = 100) was 11.9 versus 9.3 days in the intervention group (n = 101; P = .01). After multivariate analysis, factors independently associated with decreased length of hospitalization included the intervention (hazard ratio, 1.38; 95% confidence interval, 1.01-1.88) and active therapy at 48 hours (hazard ratio, 2.9; confidence interval, 1.15-7.33). Mean hospital costs per patient were $45 709 in the preintervention group and $26 162 in the intervention group (P = .009). CONCLUSIONS: Integration of rapid identification and susceptibility techniques with antimicrobial stewardship significantly improved time to optimal therapy, and it decreased hospital length of stay and total costs. This innovative strategy has ramifications for other areas of patient care.

Application of proanthocyanidins from peanut skins as a natural yeast inhibitory agent.

UNLABELLED: Proanthocyanidins were extracted from peanut skins and investigated for their antimicrobial activity against Saccharomyces cerevisiae, Zygosaccharomyces bailii, and Zygosaccharomyces bisporus in traditional growth media (Sabouraud Dextrose and Maltose broth) and a simulated apple juice beverage. Peanut skins extracts (PSE) were prepared through a multisolvent extraction procedure. The PSE extended the lag phase growth of the 3 yeasts studied at a concentration of 1 mg/mL and at 10 mg/mL yeast growth was totally inhibited for 120 h. PSE was fractionated by normal phase high performance liquid chromatography and the active components/fractions were determined. Compounds present in the fractions were identified by liquid chromatography-mass spectrometry to determine the compounds responsible for inhibition. Fractions consisting mostly of A-type proanthocyanidin dimers, trimers, and tetramers showed the highest percent inhibition toward the yeasts tested in this study. Both optical density (OD) and standard enumeration plating methods were performed in this study. The OD method led to an overestimation of the inhibitory effects of PSE, the 2 methods agreed in respect to treatment effects but not the severity of the inhibition. PRACTICAL APPLICATION: There is a growing consumer demand for "fresh like" products containing reduced amounts of chemical preservatives without compromising food safety and quality. Therefore, the goal of this study was to determine if an extract of peanut skins containing flavonoid rich compounds could function as a natural antimicrobial in a model beverage system. Proteins were removed through the process of producing the peanut skin extract, thus it is unlikely to contain peanut allergens. The antimicrobial compounds mentioned in this study were successfully integrated into a model beverage system, and were found to have antimicrobial effect. However, the incorporation of these compounds would likely lead to negative sensory attributes at the concentration needed to achieve an appreciable antimicrobial effect alone.

Antimicrobial activity of Chinese bayberry extract for the preservation of surimi.

BACKGROUND: Chemical preservatives such as sodium nitrite and potassium sorbate have been widely used to keep surimi products fresh. However, the potential harmfulness to human health cannot be ignored. This study was conducted to develop natural preservatives for the storage of Collichthys surimi. RESULTS: Among the eight Chinese traditional herbs and fruits, Chinese bayberry extract showed the greatest inhibitory effect against surimi spoilage bacteria Serratia marcescens and Pseudomonas aeruginosa. Moreover, N-butanol phase extract of bayberry (NB) showed the greatest activity among the different phases of bayberry extract. When Chinese bayberry extract was combined with tea polyphenol, an additive inhibitory effect was observed on growth of Hansenula anomala, Micrococcus luteus, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. Our results further indicated that the shelf life of surimi products stored at room temperature can be extended when supplemented with Chinese bayberry extract. CONCLUSION: Our results suggest that Chinese bayberry extract can be used as a natural preservative for the storage of Collichthys surimi.

Antioxidant, antimicrobial, 15-LOX, and AGEs inhibitions by pineapple stem waste.

UNLABELLED: Pineapple stem has been extensively used for bromelain extraction; however, almost no attention has been given to the waste obtained during bromelain manufacturing. In this regard, antioxidant, antimicrobial, and inhibitions against 15-lipoxygenase and advanced glycation end product formations by pineapple stem waste (PSW) obtained during bromelain manufacturing process were studied. The PSW had moderate bioactivities in all the performed assays. It also showed a considerable inhibition against fungal growth, probably due to high amounts of the benzoic acid present in the sample. These results indicate that PSW could be utilized as an economic source of preventive or therapeutic agent in disease and in different functional food industries. PRACTICAL APPLICATION: A large amount of wastes are generated during bromelain manufacturing from pineapple stem. So far, these wastes are not utilized and are often considered as a burden while disposing them. However, we found some important phytochemicals with considerable bioactivities in these wastes. We believe that these wastes may have a promising usage as a cheap source of one of the ingredients in functional food based industries.

[Clinical aspects of antimicrobial therapy used in patients with urogenital infections].

AIM: To study the clinical aspects of using the furasidine potassium in combination with basic magnesium carbonate (furamag) and phosphomycin trometamol (monural) as antimicrobial agents most frequently used in outpatient practice during combination therapy for acute and chronic urinary tract (UT) diseases. SUBJECTS AND METHODS: To study the specific features of therapy for UT infections, 60 patients were randomized to 2 groups: 1) 30 patients received a course therapy with furasidine potassium (furamag) in a dose of 50 mg t.i.d. for 7 days (a study group) and 2) 30 had phosphomycin trometamol (monural) in a single dose of 3 g for pulse therapy (a comparison group). The clinical efficacy of the drugs, symptom disappearance rates, bacterial changes, and laboratory and instrumental findings were assessed. The patient's opinion was mainly used to evaluate outpatient pharmacoeconomic efficiency. Patient compliance with the given therapy was estimated by taking into account the specific features of prehospital care. RESULTS: During therapy, both groups showed positive clinical changes. In the study group, the symptoms of dysuria resolved 0.5 days more quickly and a complete clinical remission was achieved 0.8 days more promptly; the latter within the first 72 hours was achieved by 7.5% more of the patients; the symptoms of bacteriuria resolved 0.6 days more rapidly. With the similar average price of the packs of furasidine potassium (furamag) 50 mg (30 capsules) and phosphomycin trometamol (monural) 1 g (a sachet) being 350 and 370 rubles, the average costs of required treatment were 482 and 546 rubles, respectively. No case of adverse reactions was recorded during the study. CONCLUSION: Patients with infectious and inflammatory diseases of UT should be given furasidine potassium in the standard dose of 50 mg t.i.d for 7 days.

Antioxidant enrichment and antimicrobial protection of fresh-cut fruits using their own byproducts: looking for integral exploitation.

Fresh-cut fruit consumption is increasing due to the rising public demand for convenience and awareness of fresh-cut fruit's health benefits. The entire tissue of fruits and vegetables is rich in bioactive compounds, such as phenolic compounds, carotenoids, and vitamins. The fresh-cut fruit industry deals with the perishable character of its products and the large percentage of byproducts, such as peels, seeds, and unused flesh that are generated by different steps of the industrial process. In most cases, the wasted byproducts can present similar or even higher contents of antioxidant and antimicrobial compounds than the final produce can. In this context, this hypothesis article finds that the antioxidant enrichment and antimicrobial protection of fresh-cut fruits, provided by the fruit's own byproducts, could be possible.

Hospital visits and costs following outpatient treatment of CAP with levofloxacin or moxifloxacin.

BACKGROUND: Hospital admissions (inpatient and emergency room) are a major source of medical costs for community-acquired pneumonia (CAP) initially treated in the outpatient setting. Current CAP treatment guidelines do not differentiate between outpatient treatment with levofloxacin and moxifloxacin. OBJECTIVE: Compare health care resource use and medical costs to payers for CAP outpatients initiating treatment with levofloxacin or moxifloxacin. RESEARCH DESIGN AND METHODS: CAP episodes were identified in the PharMetrics database between 2Q04 and 2Q07 based on: pneumonia diagnosis, chest X-ray and treatment with levofloxacin or moxifloxacin. Subsequent 30-day risk of pneumonia-related hospital visits and 30-day health care costs to payers for levofloxacin vs. moxifloxacin treatment were estimated after adjusting for pre-treatment demographics, health care resource use and pneumonia-specific risk factors using propensity score and exact factor matching. RESULTS: A total of 15,472 levofloxacin- and 6474 moxifloxacin-initiated CAP patients were identified. Among 6352 matched pairs, levofloxacin treatment was associated with a 35% reduction in the odds of pneumonia-related hospital visits (odds ratio = 0.65, P = 0.004), lower per-patient costs for pneumonia-related hospital visits (102 dollars vs. 210 dollars, P = 0.001), lower pneumonia-related total costs (medical services and prescription drugs, 363 dollars vs. 491 dollars, P < 0.001) and lower total costs (1308 dollars vs. 1446 dollars, P < 0.001) vs. moxifloxacin over the 30-day observation period. LIMITATIONS: Although observational analyses of claims data provide large sample sizes and reflect routine care, they do have several inherent limitations. Since randomization of subjects is not possible, adequate statistical techniques must be used to ensure that patient characteristics are well-balanced between treatment groups. In addition, data may be missing or miscoded. CONCLUSIONS: CAP outpatients initiated with levofloxacin generated substantially lower costs to payers compared to matched patients initiated with moxifloxacin. The cost savings for patients initiated with levofloxacin were largely attributable to reduced rates of pneumonia-related hospitalization or ER visits.

Comparative analysis of length of stay, total costs, and treatment success between intravenous moxifloxacin 400 mg and levofloxacin 750 mg among hospitalized patients with community-acquired pneumonia.

OBJECTIVE: This study aimed to evaluate the length of stay (LOS), costs, and treatment consistency among patients hospitalized with community-acquired pneumonia (CAP) initially treated with intravenous (IV) moxifloxacin 400 mg or IV levofloxacin 750 mg. METHODS: Adults with CAP receiving IV moxifloxacin or IV levofloxacin for > or =3 days were identified in the Premier Perspective comparative database. Primary outcomes were LOS and costs. Secondary outcomes included treatment consistency, which was defined as 1) no additional IV moxifloxacin or levofloxacin after > or =1 day off study drug; 2) no switch to another IV antibiotic; and 3) no addition of another IV antibiotic. RESULTS: A total of 7720 patients met inclusion criteria (6040 receiving moxifloxacin; 1680 receiving levofloxacin). Propensity matching created two cohorts (1300 patients each) well matched for demographic, clinical, hospital, and payor characteristics. Before the patients were matched, mean LOS (5.87 vs. 5.46 days; P = 0.0004) and total costs per patient ($7302 vs. $6362; P < 0.0001) were significantly greater with moxifloxacin. After the patients were matched, mean LOS (5.63 vs. 5.51 days; P = 0.462) and total costs ($6624 vs. $6473; P = 0.476) were comparable in both cohorts. Treatment consistency was higher for moxifloxacin before (81.0% vs. 78.9%; P = 0.048) and after matching (82.8% vs. 78.0%; P = 0.002). CONCLUSIONS: In-hospital treatment of CAP with IV moxifloxacin 400 mg or IV levofloxacin 750 mg was associated with similar hospital LOS and costs in propensity-matched cohorts.

A prospective, controlled, randomized, non-blind, comparative study of the efficacy and safety of a once daily high dose of ceftriaxone plus ciprofloxacin versus thrice daily ceftazidime plus amikacin in empirical therapy for febrile neutropenic patients.

BACKGROUND: Empirical antibiotic treatment for febrile neutropenia is well established. The best regimen is still controversial. The purpose of this study was to evaluate the efficacy, safety, and cost of a once daily high dose of ceftriaxone plus ciprofloxacin versus thrice daily ceftazidime plus amikacin in neutropenic febrile patients. METHODS: Ninety-five patients with febrile neutropenia were included in a prospective, controlled, randomized, non-blind, comparative study. Patients were randomly assigned to one of the treatment groups (63 to the ceftriaxone/ciprofloxacin group and 32 to the ceftazidime/amikacin group) and evaluated as successes or failures according to defined criteria. Daily assessments were made of all patients and all adverse events were recorded. RESULTS: The overall incidence of documented infections was 45.9%: 24/47 (51.1%) in the ceftriaxone/ciprofloxacin group and 10/27 (37%) in the ceftazidime/amikacin group. There was a significant difference in clinical efficacy between the groups (p=0.011) at the end of therapy. The ceftriaxone/ciprofloxacin group had an overall incidence of resolution and improvement of 95.7% in comparison to 75% in the ceftazidime/amikacin group. Thirty-nine organisms were isolated, 26 (66.67%) gram-negative and 13 (33.33%) gram-positive. There was a low incidence of adverse events in both groups. CONCLUSION: The combination of a single, high dose of ceftriaxone plus ciprofloxacin daily was more effective than the standard combination of thrice daily ceftazidime plus amikacin with no significant adverse events in either group.

A comparison of levofloxacin and moxifloxacin use in hospitalized community-acquired pneumonia (CAP) patients in the US: focus on length of stay.

OBJECTIVE: Length of stay (LOS) and hospitalization costs were compared among patients admitted for community-acquired pneumonia (CAP) and initially treated with either levofloxacin 750 mg intravenous (IV) or with moxifloxacin 400 mg IV. Hospital-related complications and relationship of LOS and comorbidities were descriptively examined. METHODS: A retrospective database study was conducted of adult patients admitted for CAP and given levofloxacin 750 mg IV or moxifloxacin 400 mg IV through the first 3 days of hospitalization, using the Premier Perspective comparative database. Cohorts were matched 1:1 by hospital geographic location, by coarse caliper propensity scores using all baseline covariates, and by Mahalanobis metric matching based on age and severity (All Patient Refined-Diagnosis-related Groups Severity of Illness (APR-DRG SOI) index). Comparisons between groups were further adjusted for characteristics that remained imbalanced after matching using generalized estimating equation methodology. RESULTS: The initial sample of 3868 patients (levofloxacin = 827; moxifloxacin = 3041) was reduced to 1594 (797 patients per treatment group) after matching. Analyses of matched cohorts showed that the mean hospital LOS was significantly shorter for patients treated with levofloxacin 750 mg IV than for those patients treated with moxifloxacin 400 mg IV (5.8 vs. 6.4 days, respectively; least squares mean difference = 0.54 days; p = 0.020). Hospitalization costs were also lower for the levofloxacin 750 mg IV-treated patients (least squares mean difference = US$129; p = 0.753). There were no significant differences in the percentage of patients experiencing complications. LIMITATIONS: Although claims databases provide large sample sizes and reflect routine care, they do have several inherent limitations. Since randomization of subjects is not possible, adequate statistical techniques must be used to ensure treatment groups are balanced with respect to patient and clinical characteristics. In addition, data may be missing or miscoded. CONCLUSIONS: This retrospective study suggests that among patients hospitalized with CAP, initial treatment with levofloxacin 750 mg IV is associated with a significantly shorter mean hospital LOS compared with treatment with moxifloxacin 400 mg IV. The clinical implications of a shorter hospital LOS include improved patient and economic outcomes.

Topical ophthalmic fourth-generation fluoroquinolones: Appropriate use and cost considerations.

PURPOSE: The utilization and refill rates of topical ophthalmic fourth-generation fluoroquinolones among physicians, as well as the associated costs, were studied. METHODS: A large data set of retrospective pharmacy prescription claims was obtained from multiple plans, including commercial managed care organizations, Medicaid, and Medicare. The data included the number and cost of all new and refill prescriptions for six months for gatifloxacin 0.3% and moxifloxacin 0.5% by physician specialty. New prescription and refill data were also analyzed from a state Medicaid plan to determine if similar trends existed. RESULTS: Primary care physicians wrote approximately 7,000 (7.7%) gatifloxacin and 84,000 (92.3%) moxifloxacin prescriptions, with pediatricians accounting for 4,000 (5.1%) gatifloxacin and 75,000 (94.9%) moxifloxacin prescriptions. Eye care physicians accounted for a similar amount of prescriptions for each antibiotic during the same period. The total cost of prescriptions for all primary care practitioners was approximately $170,000 for gatifloxacin and $2.5 million for moxifloxacin; prescriptions written by pediatricians accounted for $110,000 for gatifloxacin and $2.2 million for moxifloxacin. CONCLUSION: Prescription drug claims from payers using pharmacy benefit management companies during a six-month period indicated that the numbers of prescriptions written for gatifloxacin and moxifloxacin were similar among eye care physicians, but primary care physicians wrote a greater number of prescriptions for moxifloxacin. Analysis of claims to a Medicaid database revealed an increase in the prescriptions written by primary care physicians for moxifloxacin after its addition to the drug formulary.

[Good clinical practices and inpatient antibiotics: optimization of fluoroquinolone switch therapy]. / Bon usage des antibiotiques: optimisation du relais per os des fluoroquinolones.

OBJECTIVE: Intravenous-to-oral switch therapy is strongly recommended in the medical literature. The aim of this study was to assess how we can improve fluoroquinolone switch therapy. METHODS: In this comparative prospective study, we analyzed 243 intravenous ciprofloxacin treatments and assessed the impact of promoting a switch to oral step-down therapy. RESULTS: This study found that switches from intravenous to oral therapy increased, mainly in medical wards, and led to significant savings in direct costs. DISCUSSION: Promoting switch therapy has improved clinical practices in antibiotic use and led to lower direct and probably indirect drug-related costs. CONCLUSION: Our findings will help define the role of switch therapy in improving clinical practices in inpatient antibiotic use.

The impact of an intensive antimicrobial control program in a Taiwanese medical center.

OBJECTIVE: The study evaluates the short term impacts of an intensive control program for the appropriate us of antimicrobials, and to provide a novel strategy for antimicrobial control in inpatient wards in Taiwan. METHOD: In September 2002, a dual intensive antimicrobial control program was implemented within a 921-bed medical center in Taiwan. The study sample included all patients admitted to the medical center during the basal period (October-December 2001) and the intervention period (October-December 2002), where at least one type of parenteral antimicrobial was administered. The sample comprised of 5046 patients during the basal period and 5054 patients during the intervention period. MAIN OUTCOME MEASURE: Analysis of the impact of the intensive antimicrobial control program was undertaken by comparing clinical outcomes, parenteral antimicrobial consumption and bacterial susceptibilities, before and after the establishment of the intensive antimicrobial control program. RESULTS: No statistical differences were found between the basal and intervention periods with regard to either the demographic variables, such as age and gender, or the incidence of nosocomial infections. The clinical outcomes, including length of stay in the medical center, mortality and readmission rates, were also similar for both periods. As compared to the basal period, the consumption of parenteral antimicrobials--in defined daily doses (DDDs) per 100 patient days (PDs)--declined by 13.2% during the intervention period (71.2 vs. 61.8). There were significant increases in the susceptibilities of Pseudomonas aeruginosa to both amikacin and ciprofloxacin, and Serratia spp. to ciprofloxacin (P < 0.05), while all others remained stable. CONCLUSION: This study reports positive responses to intensive antimicrobial control measures among health professionals within a Taiwanese medical center. Following the implementation of the intensive control program, both prescriptions and consumption levels of parenteral antimicrobials were reduced without compromising the clinical outcomes of patients, while the susceptibility patterns of bacterial organisms mostly remained stable. Long-term control of parenteral antimicrobials under such a program may well produce significant benefits for inpatients through the overall rationalization of antimicrobial usage, leading to potential reductions in both the incidence of adverse effects and the burden of resistant organisms. A method of incorporating this intensive control program into a computerized prescription order system is currently under construction.