Probiotics use for antibiotic-associated diarrhea: a pragmatic participatory evaluation in nursing homes.

BACKGROUND: Antibiotic-associated diarrhea (AAD) occurs in 2-25% of nursing home residents, which may lead to dehydration, malnutrition, severe complications and hospitalizations. Research shows that probiotics can be effective and safe in reducing AAD. However, probiotics are not routinely used in Dutch nursing homes. The objectives of this evaluation were to develop a procedure for the implementation of probiotics to prevent AAD in nursing homes, to evaluate effects on AAD occurrence, and to evaluate the implementation process of probiotics in daily care. METHODS: A pragmatic participatory evaluation (PPE) design was chosen, as it seemed a suitable approach for implementation of probiotics, as well as for evaluation of its effectiveness in daily nursing home practice. Probiotics administration was implemented in three nursing homes of the Rivas Zorggroep for residents with somatic and/or psychogeriatric conditions. Ninety-three residents provided data on 167 episodes of antibiotics use, of which 84 episodes that included supplementation with probiotics and 83 episodes with no probiotics supplementation. A multispecies probiotics was administered twice daily upon start of antibiotic treatment, up to 1 week after completing the antibiotics course. The occurrence of AAD was monitored and a process evaluation was conducted to assess facilitators and barriers of probiotics implementation. RESULTS: The number of episodes with AAD when using probiotics was significantly lower than when no probiotics was used (20% vs 36%; p = 0,022, Chi-square). No significant differences in the occurrence of AAD were found between the residents taking amoxicillin/clavulanic acid or ciprofloxacin. Reported facilitators for implementation were perceived benefits of probiotics and prescription by medical staff. Reported challenges were probiotics intake by residents and individual decision-making as to which resident would benefit from it. CONCLUSION: Successful implementation of probiotics demonstrated the prevention of AAD in nursing home residents. TRIAL REGISTRATION: ISRCTN 94786163, retrospectively registered on 3 February 2020.

High-dose versus standard-dose amoxicillin/clavulanate for clinically-diagnosed acute bacterial sinusitis: A randomized clinical trial.

BACKGROUND: The recommended treatment for acute bacterial sinusitis in adults, amoxicillin with clavulanate, provides only modest benefit. OBJECTIVE: To see if a higher dose of amoxicillin will lead to more rapid improvement. DESIGN, SETTING, AND PARTICIPANTS: Double-blind randomized trial in which, from November 2014 through February 2017, we enrolled 315 adult outpatients diagnosed with acute sinusitis in accordance with Infectious Disease Society of America guidelines. INTERVENTIONS: Standard-dose (SD) immediate-release (IR) amoxicillin/clavulanate 875 /125 mg (n = 159) vs. high-dose (HD) (n = 156). The original HD formulation, 2000 mg of extended-release (ER) amoxicillin with 125 mg of IR clavulanate twice a day, became unavailable half way through the study. The IRB then approved a revised protocol after patient 180 to provide 1750 mg of IR amoxicillin twice a day in the HD formulation and to compare Time Period 1 (ER) with Time Period 2 (IR). MAIN MEASURE: The primary outcome was the percentage in each group reporting a major improvement-defined as a global assessment of sinusitis symptoms as "a lot better" or "no symptoms"-after 3 days of treatment. KEY RESULTS: Major improvement after 3 days was reported during Period 1 by 38.8% of ER HD versus 37.9% of SD patients (P = 0.91) and during Period 2 by 52.4% of IR HD versus 34.4% of SD patients, an effect size of 18% (95% CI 0.75 to 35%, P = 0.04). No significant differences in efficacy were seen at Day 10. The major side effect, severe diarrhea at Day 3, was reported during Period 1 by 7.4% of HD and 5.7% of SD patients (P = 0.66) and during Period 2 by 15.8% of HD and 4.8% of SD patients (P = 0.048). CONCLUSIONS: Adults with clinically diagnosed acute bacterial sinusitis were more likely to improve rapidly when treated with IR HD than with SD but not when treated with ER HD. They were also more likely to suffer severe diarrhea. Further study is needed to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02340000.

Antibacterial Efficacy and Discoloration Potential of Endodontic Topical Antibiotics.

INTRODUCTION: The optimal concentration for the use of endodontic topical antibiotics is not known. The aims of this study were to determine the minimum bactericidal concentrations (MBCs) and minimum inhibitory concentrations (MICs) of metronidazole, ciprofloxacin, minocycline, Augmentin (GlaxoSmithKline, Research Triangle Park, NC), and tigecycline against common endodontic pathogens and to evaluate ex vivo the antibacterial efficacy and discoloration effect of triple antibiotic paste (TAP), Augmentin, and tigecycline at different concentrations using a slow-release hydrogel scaffold. METHODS: Using the Epsilometer test method (Etest; bioMérieux USA, St Louis, MO), MICs and MBCs of selected antibiotics were determined against Fusobacterium nucleatum, Porphyromonas gingivalis, Streptococcus intermedius, and Enterococcus faecalis. Biofilms of these bacterial species were then grown in extracted single-rooted teeth anaerobically for 3 weeks. Root canals were filled with TAP, Augmentin, and tigecycline at concentrations of 1 or 0.1 mg/mL in a degradable hydrogel scaffold or pure TAP at 1 g/mL for 7 days. Coronal discoloration was evaluated spectrophotometrically at 1, 2, and 3 weeks after dressing. RESULTS: MIC/MBC data showed significant efficacy of tigecycline, Augmentin, and minocycline compared with the other antibiotics (P < .05). Significant differences were found when comparing the log10 colony-forming units of all experimental groups (P < .05). TAP at 1 g/mL had no bacterial growth but caused the greatest discoloration. Hydrogel mixtures with TAP, Augmentin, or tigecycline at 1 mg/mL significantly reduced bacterial growth and the number of positive samples compared with those at 0.1 mg/mL (P < .05) with minimal discoloration. CONCLUSIONS: TAP, Augmentin, and tigecycline in a hydrogel at 1 mg/mL reduced bacterial growth significantly with minimal color change.

Moxifloxacin in Pediatric Patients With Complicated Intra-abdominal Infections: Results of the MOXIPEDIA Randomized Controlled Study.

BACKGROUND: This study was designed to evaluate primarily the safety and also the efficacy of moxifloxacin (MXF) in children with complicated intra-abdominal infections (cIAIs). METHODS: In this multicenter, randomized, double-blind, controlled study, 451 pediatric patients aged 3 months to 17 years with cIAIs were treated with intravenous/oral MXF (N = 301) or comparator (COMP, intravenous ertapenem followed by oral amoxicillin/clavulanate; N = 150) for 5 to 14 days. Doses of MXF were selected based on the results of a Phase 1 study in pediatric patients (NCT01049022). The primary endpoint was safety, with particular focus on cardiac and musculoskeletal safety; clinical and bacteriologic efficacy at test of cure was also investigated. RESULTS: The proportion of patients with adverse events (AEs) was comparable between the 2 treatment arms (MXF: 58.1% and COMP: 54.7%). The incidence of drug-related AEs was higher in the MXF arm than in the COMP arm (14.3% and 6.7%, respectively). No cases of QTc interval prolongation-related morbidity or mortality were observed. The proportion of patients with musculoskeletal AEs was comparable between treatment arms; no drug-related events were reported. Clinical cure rates were 84.6% and 95.5% in the MXF and COMP arms, respectively, in patients with confirmed pathogen(s) at baseline. CONCLUSIONS: MXF treatment was well tolerated in children with cIAIs. However, a lower clinical cure rate was observed with MXF treatment compared with COMP. This study does not support a recommendation of MXF for children with cIAIs when alternative more efficacious antibiotics with better safety profile are available.

Effectiveness of Lactobacillus helveticus and Lactobacillus rhamnosus for the management of antibiotic-associated diarrhoea in healthy adults: a randomised, double-blind, placebo-controlled trial.

Broad-spectrum antibiotic use can disrupt the gastrointestinal microbiota resulting in diarrhoea. Probiotics may be beneficial in managing this type of diarrhoea. The aim of this 10-week randomised, double-blind, placebo-controlled, parallel study was to investigate the effect of Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011 supplementation on antibiotic-associated diarrhoea in healthy adults. Subjects were randomised to receive 1 week of amoxicillin-clavulanic acid (875 mg/125 mg) once per day, plus a daily dose of 8×109 colony-forming units of a multi-strain probiotic (n 80) or placebo (n 80). The probiotic or placebo intervention was maintained for 1 week after completion of the antibiotic. Primary study outcomes of consistency and frequency of bowel movements were not significantly different between the probiotic and placebo groups. The secondary outcomes of diarrhoea-like defecations, Gastrointestinal Symptoms Rating Scale scores, safety parameters and adverse events were not significantly different between the probiotic intervention and the placebo. A post hoc analysis on the duration of diarrhoea-like defecations showed that probiotic intervention reduced the length of these events by 1 full day (probiotic, 2·70 (sem 0·36) d; placebo, 3·71 (sem 0·36) d; P=0·037; effect size=0·52). In conclusion, this study provides novel evidence that L. helveticus R0052 and L. rhamnosus R0011 supplementation significantly reduced the duration of diarrhoea-like defecations in healthy adults receiving antibiotics.

Comparative evaluation of cariogenic and erosive potential of commonly prescribed pediatric liquid medicaments: an in vitro study.

INTRODUCTION: Liquid oral medicines being the most accepted form of medication in children are frequently prescribed. The harmful effects of these liquid medicaments on a child's dental health are not known to many. The present study aimed to evaluate and compare the cariogenic and erosive potential of 5 most commonly prescribed pediatric liquid medicaments (PLM) in Pimpri Chinchwad and Pune city, Pune district. MATERIALS AND METHODS: Most commonly prescribed PLM in Pune district were selected as opined by 50 pediatricians. The selected medicaments were Syr. Augmentin® Duo, Syr. Valparin®, Syr. Combiflam®, Syr. Visyneral and Syr. Orofer®. An estimation of pH, percentage of sucrose concentration and calcium dissolving capacity of these preparations was carried out. The results as obtained were subjected to statistical analysis using SPSS v 17.0 for windows. The statistical test as undertaken was Pearson's correlation coeffcient(r). RESULTS: Sucrose was seen to be present in Syr. Combiflam® (35.75% ± 0.25%) and Syr. Visyneral (18.48% ± 0.43%). Acidic pH was observed for Syr. Visyneral (mean pH 3.63 ± 0.04), Syr. Combiflam®(mean pH 5.03 ± 0.02) and Syr. Augmentin® (mean pH 6.22 ± 0.02). Highest calcium dissolution was seen with Syr. Combiflam®(295.86 mg/ml) and the least with Syr. Orofer® (25.51 mg/ml). No statistical significant correlation was observed with calcium dissolution potential of PLM in comparison with their respective pH. CONCLUSION: Syr. Combiflam® can be regarded as the highest cariogenic and erosive potential medicament among the compared and tested PLM. CLINICAL SIGNIFICANCE: Considering syrups with high cariogenic and erosive potential should always follow with proper oral hygiene practices or search for an alternative drugs void of such detrimental effects.

[Infectious exacerbation of chronic obstructive pulmonary disease: prospects for high-dose levofloxacin therapy].

This open comparative randomized study of efficacy, safety, and pharmacoeconomic characteristics of hilifox-750 (750 mg daily for 5 days) and amoxiclav 2X (875/125 mg twice daily for 10 days) included 60 patients with chronic obstructive pulmonary disease (COPD). Duration of the study was 6 months. Medians of age and smoking index in the group treated with hilifox-750 were 63.5 yr (59, 67) and 30 packs/yr (15, 60) respectively. The treatment reduced cough, apnea, sputum volume and pyoptysis with comparative rates of normalization of body temperature and peripheral leukocyte counts in both groups. Helifox-750 promoted decrease in coughing and apnea within the first three days of therapy. 28 (93%) and 26 (87%) patients recovered by day 4 of helifox and amoxiclav therapy (F-test p = 0.67). Both drugs showed comparable bacteriological efficacy. They were not different in terms of side effect frequency that were mild, resolved spontaneously and did not require withdrawal of therapy. Helifox had advantages over amoxiclav in that it reduced duration of antibacterial therapy to 5 days and of temporary incapacity to 12 days (vs 14); moreover, it needs to be taken only once daily.

Moxifloxacin versus amoxicillin/clavulanic acid in outpatient acute exacerbations of COPD: MAESTRAL results.

Bacterial infections causing acute exacerbations of chronic obstructive pulmonary disease (AECOPD) frequently require antibacterial treatment. More evidence is needed to guide antibiotic choice. The Moxifloxacin in Acute Exacerbations of Chronic Bronchitis TriaL (MAESTRAL) was a multiregional, randomised, double-blind non-inferiority outpatient study. Patients were aged ≥ 60 yrs, with an Anthonisen type I exacerbation, a forced expiratory volume in 1 s < 60% predicted and two or more exacerbations in the last year. Following stratification by steroid use patients received moxifloxacin 400 mg p.o. q.d. (5 days) or amoxicillin/clavulanic acid 875/125 mg p.o. b.i.d. (7 days). The primary end-point was clinical failure 8 weeks post-therapy in the per protocol population. Moxifloxacin was noninferior to amoxicillin/clavulanic acid at the primary end-point (111 (20.6%) out of 538, versus 114 (22.0%) out of 518, respectively; 95% CI -5.89-3.83%). In patients with confirmed bacterial AECOPD, moxifloxacin led to significantly lower clinical failure rates than amoxicillin/clavulanic acid (in the intent-to-treat with pathogens, 62 (19.0%) out of 327 versus 85 (25.4%) out of 335, respectively; p=0.016). Confirmed bacterial eradication at end of therapy was associated with higher clinical cure rates at 8 weeks post-therapy overall (p=0.0014) and for moxifloxacin (p=0.003). Patients treated with oral corticosteroids had more severe disease and higher failure rates. The MAESTRAL study showed that moxifloxacin was as effective as amoxicillin/clavulanic acid in the treatment of outpatients with AECOPD. Both therapies were well tolerated.

A randomized trial of the efficacy and safety of sequential intravenous/oral moxifloxacin monotherapy versus intravenous piperacillin/tazobactam followed by oral amoxicillin/clavulanate for complicated skin and skin structure infections.

OBJECTIVES: The primary aim of the RELIEF study was to evaluate the efficacy and safety of two sequential intravenous (iv)/oral regimens: moxifloxacin iv/oral versus piperacillin/tazobactam (TZP) iv followed by oral amoxicillin/clavulanate (AMC). PATIENTS AND METHODS: The study had a prospective, randomized, double-dummy, double-blind, multicentre design. Patients ≥18 years were prospectively stratified according to complicated skin and skin structure infection (cSSSI) subtype/diagnosis (major abscess, diabetic foot infection, wound infection or infected ischaemic ulcer), surgical intervention and severity of illness. Diagnoses and disease severity were based on predetermined criteria, documented by repeated photographs, and confirmed by an independent data review committee. Patients were randomized to receive either 400 mg of moxifloxacin iv once daily followed by 400 mg of moxifloxacin orally once daily or 4.0/0.5 g of TZP iv thrice daily followed by 875/125 mg of AMC orally twice daily for 7-21 days. The primary efficacy variable was clinical response at test of cure (TOC) for the per-protocol (PP) population. Clinical efficacy was assessed by the data review committee based on repeated photographs and case descriptions. Clinical trials registry number: NCT 00402727. RESULTS: A total of 813 patients were randomized. Clinical success rates at TOC were similar for moxifloxacin and TZP-AMC in the PP [320/361 (88.6%) versus 275/307 (89.6%), respectively; P = 0.758] and intent-to-treat (ITT) [350/426 (82.2%) versus 305/377 (80.9%), respectively; P = 0.632] populations. Thus, moxifloxacin was non-inferior to TZP-AMC. Bacteriological success rates were high in both treatment arms [moxifloxacin: 432/497 (86.9%) versus TZP-AMC: 370/429 (86.2%), microbiologically valid (MBV) population]. Moxifloxacin was non-inferior to TZP-AMC at TOC in both the MBV and the ITT populations. Both treatments were well tolerated. CONCLUSIONS: Once-daily iv/oral moxifloxacin monotherapy was clinically and bacteriologically non-inferior to iv TZP thrice daily followed by oral AMC twice daily in patients with cSSSIs.

A novel study design for antibiotic trials in acute exacerbations of COPD: MAESTRAL methodology.

Antibiotics, along with oral corticosteroids, are standard treatments for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The ultimate aims of treatment are to minimize the impact of the current exacerbation, and by ensuring complete resolution, reduce the risk of relapse. In the absence of superiority studies of antibiotics in AECOPD, evidence of the relative efficacy of different drugs is lacking, and so it is difficult for physicians to select the most effective antibiotic. This paper describes the protocol and rationale for MAESTRAL (moxifloxacin in AECBs [acute exacerbation of chronic bronchitis] trial; www.clinicaltrials.gov: NCT00656747), one of the first antibiotic comparator trials designed to show superiority of one antibiotic over another in AECOPD. It is a prospective, multinational, multicenter, randomized, double-blind controlled study of moxifloxacin (400 mg PO [per os] once daily for 5 days) vs. amoxicillin/clavulanic acid (875/125 mg PO twice daily for 7 days) in outpatients with COPD and chronic bronchitis suffering from an exacerbation. MAESTRAL uses an innovative primary endpoint of clinical failure: the requirement for additional or alternate treatment for the exacerbation at 8 weeks after the end of antibiotic therapy, powered for superiority. Patients enrolled are those at high-risk of treatment failure, and all are experiencing an Anthonisen type I exacerbation. Patients are stratified according to oral corticosteroid use to control their effect across antibiotic treatment arms. Secondary endpoints include quality of life, symptom assessments and health care resource use.

Moxifloxacin for the treatment of patients with complicated intra-abdominal infections (the AIDA Study).

This prospective, randomized, open, international, multicenter study of adults with complicated intra-abdominal infections (cIAI) compared the efficacy and safety of sequential intravenous (i.v.) to oral (p.o.) moxifloxacin 400 mg once daily, with that of i.v. ceftriaxone 2 g once daily, plus metronidazole 500 mg three times daily, followed by p.o. amoxicillin/clavulanate 625 mg three times daily. The primary efficacy variable was clinical cure at test of cure (TOC) (day 28-42 after study entry) in the per protocol (PP) population. Of 595 patients in the study, 511 patients were valid for PP analysis (246 moxifloxacin, 265 ceftriaxone/metronidazole). Sequential moxifloxacin was noninferior to the comparator regimen--clinical cure rates at TOC were 80.9% versus 82.3% (moxifloxacin versus ceftriaxone/metronidazole; 95% CI -8.9, 4.2%). The incidence of adverse events was comparable between the two treatment groups. Therefore, sequential moxifloxacin monotherapy is as effective and safe as combination therapy with i.v. ceftriaxone plus i.v. metronidazole followed by oral amoxicillin/clavulanate for the treatment of cIAI.

Comparison of two oral regimens for the outpatient treatment of low-risk cancer patients with chemotherapy-induced neutropenia and fever: ciprofloxacin plus cefuroxime axetil versus ciprofloxacin plus amoxicillin/clavulanate.

The objective of this investigation was to assess retrospectively the safety and the efficacy of oral ciprofloxacin plus cefuroxime axetil compared to the combination of oral ciprofloxacin plus amoxicillin/clavulanate, as initial outpatient treatment, in low-risk cancer patients with fever and neutropenia. We analysed retrospectively 120 episodes of febrile neutropenia, treated on an outpatient basis at 2 different oncology units; 63 episodes were treated with the oral regimen of ciprofloxacin plus amoxicillin/clavulanate and 57 were treated with the combination of oral ciprofloxacin plus cefuroxime. 20 treatment failures were recorded-2 of them among patients receiving ciprofloxacin plus amoxicillin/clavulanate and 18 in the ciprofloxacin plus cefuroxime group. Univariate analysis showed that the administration of ciprofloxacin plus cefuroxime was associated with a worse outcome compared to the regimen ciprofloxacin plus amoxicillin/clavulanate (OR 11, CI 2.42-49.9, p =0.002). In the multivariate model, after adjusting for the absolute number of neutrophils and the duration of neutropenia, the effect of the antibiotic regimen on the outcome disappeared, and no significant differences between the 2 regimens were noted, although the regimen of ciprofloxacin plus cefuroxime was associated with a trend to a worse outcome (OR 4.74, CI 0.72-31.1, p =0.10). In conclusion, the 2 regimens appeared equally safe and effective but prospective studies are needed to confirm these results.

Treating diabetic foot infections with sequential intravenous to oral moxifloxacin compared with piperacillin-tazobactam/amoxicillin-clavulanate.

OBJECTIVES: Complicated skin and skin structure infections (cSSSIs), including diabetic foot infections (DFIs), are often polymicrobial, requiring combination or broad-spectrum therapy. Moxifloxacin, a broad-spectrum fluoroquinolone, is approved for cSSSI and can be administered by either intravenous (iv) or oral routes. To assess the efficacy of moxifloxacin for treating DFIs, we analysed a subset of patients with these infections who were enrolled in a prospective, double-blind study that compared the efficacy of moxifloxacin with piperacillin-tazobactam and amoxicillin-clavulanate. METHODS: Patients>or=18 years of age with a DFI requiring initial iv therapy were randomized to either moxifloxacin (400 mg/day) or piperacillin-tazobactam (3.0/0.375 g every 6 h) for at least 3 days followed by moxifloxacin (400 mg/day orally) or amoxicillin-clavulanate (800 mg every 12 h orally), if appropriate, for 7-14 days. DFI was usually defined as any foot infection plus a history of diabetes. Our primary efficacy outcome was the clinical response of the infection at test-of-cure (TOC), 10-42 days post-therapy. RESULTS: Among 617 patients enrolled in the original study, 78 with DFIs were evaluable for treatment efficacy. Clinical cure rates at TOC were similar for moxifloxacin and piperacillin-tazobactam/amoxicillin-clavulanate (68% versus 61%) for patients with investigator-defined infection (P=0.54). Overall pathogen eradication rates in the microbiologically-valid population were 69% versus 66% for moxifloxacin and comparator, respectively (P=1.00). CONCLUSIONS: Intravenous+/-oral moxifloxacin was as effective as iv piperacillin-tazobactam+/-amoxicillin-clavulanate in treating moderate-to-severe DFIs. Moxifloxacin may have potential as a monotherapy regimen for DFIs.

The comparison of single-dose ceftriaxone, five-day azithromycin, and ten-day amoxicillin/clavulanate for the treatment of children with acute otitis media.

The aim of the study was to evaluate the efficacy of short-course antimicrobial therapies [single intramuscular dose of ceftriaxone (50 mg/kg, not exceeding 1 g), 5 days of azithromycin (10 mg/kg on day 1, then 5 mg/kg daily on days 2-5) and the traditional 10-day course of amoxicillin/clavulanate (90/6.4 mg/kg/day in 2 doses)] in children with acute otitis media (AOM). The study was conducted as a prospective, comparative, open randomized trial between February 2001 and April 2003, and 104 children were enrolled, with a mean age of 3.8 (2.3) years. The clinical and otoscopic assessments of the children were made on days 0, 3, 11 and 30 after admission, and tympanometry was performed on day 30. The patients were diagnosed and followed with a scoring system. Clinical success was achieved in 29/34 patients (85.3%) in the ceftriaxone group, 27/31 patients (87.1%) in the azithromycin group and 34/39 children (87.2%) in the amoxicillin/clavulanate group. The rate of persistence of middle-ear fluid did not differ between the three groups (p>0.05). During the one-month period, no recurrent case was observed. The most common drug-related adverse effects were associated with the gastrointestinal system. In conclusion, for the treatment of children with AOM, the clinical success of single-dose intramuscular ceftriaxone and of five-day azithromycin treatments was comparable to that of the traditional 10-day therapy with high-dose amoxicillin/clavulanate.

Efficacy, tolerability, and parent reported outcomes for cefdinir vs. high-dose amoxicillin/clavulanate oral suspension for acute otitis media in young children.

OBJECTIVES: To compare efficacy, tolerability, and parental satisfaction of cefdinir and high-dose amoxicillin/clavulanate oral suspensions given to young children with non-refractory acute otitis media (AOM) based on clinical endpoints and outcomes measures. RESEARCH DESIGN AND METHODS: This was an investigator-blinded, multicenter study in which 318 children 6 months through 6 years of age with a clinical diagnosis of AOM were randomized to receive 10 days of either cefdinir (14 mg/kg divided BID) or high-dose amoxicillin/clavulanate (90/6.4 mg/kg divided BID). MAIN OUTCOME MEASURES: Investigators evaluated clinical response at an end-of-therapy (EOT) office visit conducted on day 12-15. Outcomes of satisfaction, tolerability, and adherence were also assessed at that visit using an Otitis Parent Questionnaire. RESULTS: The treatment groups were similar at baseline with respect to patient demographics. At the EOT visit, for cefdinir and amoxicillin/clavulanate, respectively, intent-to-treat (ITT) clinical cure rates were 82% (129/158) and 85% (134/158) (p = 0.547; 95% confidence interval [CI] -11.7 to 5.4) and per-protocol cure rates were 82% (123/150) and 90% (129/143) (p = 0.045; 95% CI -16.4 to 0.0). This difference was driven primarily by reduced cefdinir response in patients with recurrent AOM (p = 0.010) and those younger than 24 months (p = 0.039). Comparing cefdinir with amoxicillin/clavulanate, parents more often reported significantly better ease of use (89% vs. 57%; p < 0.0001), better taste (85% vs. 39%; p < 0.0001), and better adherence (at least 95% of doses) (82% vs. 61%; p < 0.0001). Diarrhea/loose stools were more common in the amoxicillin/clavulanate group than in the cefdinir group (28% vs. 18%, respectively; p = 0.0341). One patient in the cefdinir group and eight patients in the amoxicillin/clavulanate group withdrew from the study prematurely due to at least one adverse event (p = 0.0364). Study limitations included assessment of clinical recurrence by telephone call rather than office visit, exclusion of children with refractory AOM, and no assessment of middle ear microbiology. CONCLUSIONS: Among young children with non-refractory AOM, cefdinir was as efficacious as high-dose amoxicillin/clavulanate in the ITT group, but somewhat less effective in per-protocol analysis. From the parental perspective, cefdinir was easier to administer, had a better taste, caused less diarrhea, and resulted in higher treatment adherence than high-dose amoxicillin clavulanate.

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.

Neutropenia secundaria a betalactámicos. Una vieja compañera olvidada / Beta-lactam-induced neutropenia. An old forgotten companion

La neutropenia provocada por los betalactámicos es un problema conocido desde que se utiliza la penicilina. Aparece por lo general tras tratamientos con más de 10 días con betalactámicos a dosis altas, aumentando su incidencia al incrementarse la dosis acumulativa del antibiótico. Con frecuencia está precedida de fiebre o exantema que sirven de señales de alarma. A diferencia de la neutropenia provocada por otros fármacos no quimioterápicos, la neutropenia por betalactámicos no suele durar más de 10 días, y excepcionalmente conlleva complicaciones infecciosas o muerte. Aunque cualquier betalactámico puede provocar neutropenia, las publicaciones en los últimos años se han centrado en la neutropenia causada por piperacilina-tazobactam o por cefepima, demostrando que la incidencia de neutropenia durante tratamientos prolongados con ellos es elevada. La aparente contradicción con los resultados de los ensayos clínicos con estos antibióticos, que no habían detectado esta complicación, se debe a que en estos ensayos los tratamientos eran menores de 2 semanas. En el desarrollo de nuevos betalactámicos se debe tener presente la posible aparición de neutropenia durante tratamientos intravenosos prolongados (AU)

Beta-lactam-induced neutropenia has been a well-recognized problem since the initiation of penicillin use. It generally develops following high-dose beta-lactam treatment lasting longer than 10 days, and its frequency rises with increases in the cumulative antibiotic dose. Beta-lactam-induced neutropenia is frequently preceded by fever or rash, which can be considered alarm signs. Unlike neutropenia induced by other nonchemotherapy drugs, beta-lactam-induced neutropenia usually lasts less than 10 days and infrequently causes infectious complications or death. Although any beta-lactam agent can cause neutropenia, recent studies have focused on cases of piperacillin-tazobactam- or cefepime-induced neutropenia; a high incidence of neutropenia has been demonstrated during prolonged treatment with these antibiotics. The apparent contradiction with the results of clinical trials that did not detect this complication is due to the fact that they involved treatments shorter than two weeks. The potential for the development of neutropenia during lengthy intravenous treatment should be borne in mind in the development of new beta-lactams (AU)

Moxifloxacin monotherapy compared to amoxicillin-clavulanate plus roxithromycin for nonsevere community-acquired pneumonia in adults with risk factors.

The objective of this study was to assess the efficacy and safety of moxifloxacin versus amoxicillin-clavulanate plus roxithromycin (comparator) in adult community-acquired pneumonia (CAP) patients with risk factors. In this comparative, randomized, multicenter, open-label study, patients hospitalized for CAP received a 10-day oral treatment with either moxifloxacin (400 mg o.d.) or amoxicillin-clavulanate (1,000/125 mg t.i.d.) plus roxithromycin (150 mg b.i.d.). Clinical and bacteriological outcomes were assessed during test of cure and follow-up visits (5-7 days and 21-28 days after the end of treatment, respectively). Of 349 randomized patients, 346 were included in the intent-to-treat analysis and 289 in the per-protocol analysis. Their baseline characteristics were comparable. The most frequent risk factors for mortality were age >65 years (50.0%), alcoholism (23.1%), and comorbidities (50.6%); chronic obstructive pulmonary disease (COPD) (25.4%) and diabetes mellitus (13.6%) were the most common associated comorbidities. A causative pathogen was documented in 66 of 346 (19.1%) of the patients (including 21 with positive blood cultures). Respective per-protocol clinical success rates at test-of-cure (primary efficacy endpoint) for moxifloxacin and comparator were 131 of 151 (86.8%) and 120 of 138 (87.0%), with a 95% confidence interval (CI) of -8.0-7.6 for the difference. Bacteriological success rates (eradication) were 23 of 30 (76.7%) and 23 of 31 (74.2%); rates for patients with positive blood cultures were 10 of 14 and 4 of 6. Persistent clinical success rates at follow-up were 118 of 120 (98.3%) and 102 of 106 (96.2%), with a 95%CI of -2.2-6.4 for the difference. The intent-to-treat analysis confirmed these results. Adverse events associated with moxifloxacin and the comparator drug were reported for 42 of 171 (24.6%) and 50 of 175 (28.6%) of the patients, respectively, and comprised predominantly digestive disorders, which occurred in 9.4% and 21.1%. On the basis of these results, once-daily oral moxifloxacin alone is as effective as amoxicillin-clavulanate plus roxithromycin for the treatment of CAP in patients with risk factors.

Five-day moxifloxacin therapy compared with 7-day co-amoxiclav therapy for the treatment of acute exacerbation of chronic bronchitis.

In this randomized, non-blinded study, the efficacy and safety of a 5-day course of moxifloxacin (one 400 mg tablet daily) was compared with that of co-amoxiclav (one 625 mg tablet every 8h) for 7 days, for the treatment of acute exacerbations of chronic bronchitis (AECB). A total of 162 patients with clear signs of an acute exacerbation of chronic bronchitis were enrolled. Of these, 153 could be studied. Seventy-nine patients were randomized in the moxifloxacin arm and 74 in the co-amoxiclav arm of the study. The primary efficacy parameter was clinical response at 14 days in the evaluable population. A clinical success was classified as resolution or improvement of symptoms. Variables used to assess clinical response included wheeze, cough, dyspnoea, sputum volume, rales and ronchi. The success rate in the moxifloxacin group was 88.6% (70 of 79) and that for co-amoxiclav group was 89.2% (66 of 74). At follow-up (28-35 days post-treatment), the continued clinical cure rates were 90.0% (63 of 70) for moxifloxacin and 89.4% (59 of 66) for co-amoxiclav. No significant differences were detected between the two groups. A total of 78 pathogenic bacteria were isolated from the sputum samples of the patients, with Moraxella catarrhalis, Haemophilus influenzae and Streptococcus pneumoniae being the most frequently isolated pathogens. The eradication rate at 14 days in the valid patients was similar for both groups, 90.9% (20 of 22) for the moxifloxacin group and 90.0% (18 of 20) for the co-amoxiclav group. Both drugs were well tolerated with no differences in the drug-related adverse effects or the patients withdrawing because of an adverse event. These results and the good spectrum of antibacterial activity make moxifloxacin a promising and also safe alternative for the empirical treatment of AECB.

High-dose azithromycin versus high-dose amoxicillin-clavulanate for treatment of children with recurrent or persistent acute otitis media.

Infants and young children, especially those in day care, are at risk for recurrent or persistent acute otitis media (AOM). There are no data on oral alternatives to high-dose amoxicillin-clavulanate for treating AOM in these high-risk patients. In this double-blind, double-dummy multicenter clinical trial, we compared a novel, high-dose azithromycin regimen with high-dose amoxicillin-clavulanate for treatment of children with recurrent or persistent AOM. Three hundred four children were randomized; 300 received either high-dose azithromycin (20 mg/kg of body weight once a day for 3 days) or high-dose amoxicillin-clavulanate (90 mg/kg divided twice a day for 10 days). Tympanocentesis was performed at baseline; clinical response was assessed at day 12 to 16 and day 28 to 32. Two-thirds of patients were aged < or =2 years. A history of recurrent, persistent, or recurrent plus persistent AOM was noted in 67, 18, and 14% of patients, respectively. Pathogens were isolated from 163 of 296 intent-to-treat patients (55%). At day 12 to 16, clinical success rates for azithromycin and amoxicillin-clavulanate were comparable for all patients (86 versus 84%, respectively) and for children aged < or =2 years (85 versus 79%, respectively). At day 28 to 32, clinical success rates for azithromycin were superior to those for amoxicillin-clavulanate for all patients (72 versus 61%, respectively; P = 0.047) and for those aged < or =2 years (68 versus 51%, respectively; P = 0.017). Per-pathogen clinical efficacy against Streptococcus pneumoniae and Haemophilus influenzae was comparable between the two regimens. The rates of treatment-related adverse events for azithromycin and amoxicillin-clavulanate were 32 and 42%, respectively (P = 0.095). Corresponding compliance rates were 99 and 93%, respectively (P = 0.018). These data demonstrate the efficacy and safety of high-dose azithromycin for treating recurrent or persistent AOM.