Microbiota Assessment of Pediatric Simple and Complex Acute Appendicitis.

Background and Objectives. The aim of this study is to determine the prevailing microbiota in samples from pediatric patients with acute appendicitis, as well as evaluate the antibacterial sensitivity of the isolated microorganisms, comparing the data obtained with the clinic's antibacterial therapy guidelines. Materials and Methods. The study group consisted of 93 patients between the ages of 7 and 18. All patients underwent a laparoscopic or conventional appendectomy. The children were hospitalized with signs and symptoms suggestive of acute appendicitis. Microbiological cultures from the appendix and abdominal cavity were collected intraoperatively. Results. E. coli was identified in most cases irrespective of the clinical presentation of acute appendicitis. Most strains were susceptible to ampicillin and amoxicillin/clavulanic acid. Five strains of E. coli produced extended spectrum beta-lactamase (ESBL). Pseudomonas aeruginosa (P. aeruginosa) was the second most commonly isolated causative agent. Furthermore, it was common in cases of acute complex appendicitis. Most strains of P. aeruginosa were resistant to amoxicillin/clavulanic acid, ertapenem, ampicillin and cefotaxime, yet were susceptible to ceftazidime. Regardless of the clinical presentation, the samples yielded mixed isolates. Conclusion. E. coli is the main causative agent of acute appendicitis in the pediatric population displaying susceptibility to various antibiotics. P. aeruginosa was more prevalent in cases of acute complex appendicitis. P. aeruginosa isolates were susceptible to ceftazidime; however, they were resistant to cefotaxime, which should, therefore, be removed from guidelines for empirical antibacterial treatment of acute appendicitis due to phenotypic resistance of P. aeruginosa. We recommend antibiotics with distinct implementation to avoid antibiotic resistance.

Comparative Effectiveness and Harms of Antibiotics for Outpatient Diverticulitis : Two Nationwide Cohort Studies.

BACKGROUND: Outpatient diverticulitis is commonly treated with either a combination of metronidazole and a fluoroquinolone (metronidazole-with-fluoroquinolone) or amoxicillin-clavulanate alone. The U.S. Food and Drug Administration advised that fluoroquinolones be reserved for conditions with no alternative treatment options. The comparative effectiveness of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for diverticulitis is uncertain. OBJECTIVE: To determine the effectiveness and harms of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for outpatient diverticulitis. DESIGN: Active-comparator, new-user, retrospective cohort studies. SETTING: Nationwide population-based claims data on U.S. residents aged 18 to 64 years with private employer-sponsored insurance (2000 to 2018) or those aged 65 years or older with Medicare (2006 to 2015). PARTICIPANTS: Immunocompetent adults with diverticulitis in the outpatient setting. INTERVENTION: Metronidazole-with-fluoroquinolone or amoxicillin-clavulanate. MEASUREMENTS: 1-year risks for inpatient admission, urgent surgery, and Clostridioides difficile infection (CDI) and 3-year risk for elective surgery. RESULTS: In MarketScan (IBM Watson Health), new users of metronidazole-with-fluoroquinolone (n = 106 361) and amoxicillin-clavulanate (n = 13 160) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [95% CI, -0.3 to 0.6]), 1-year urgent surgery risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]), 3-year elective surgery risk (risk difference, 0.2 percentage points [CI, -0.3 to 0.7]), or 1-year CDI risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]) between groups. In Medicare, new users of metronidazole-with-fluoroquinolone (n = 17 639) and amoxicillin-clavulanate (n = 2709) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [CI, -0.7 to 0.9]), 1-year urgent surgery risk (risk difference, -0.2 percentage points [CI, -0.6 to 0.1]), or 3-year elective surgery risk (risk difference, -0.3 percentage points [CI, -1.1 to 0.4]) between groups. The 1-year CDI risk was higher for metronidazole-with-fluoroquinolone than for amoxicillin-clavulanate (risk difference, 0.6 percentage points [CI, 0.2 to 1.0]). LIMITATION: Residual confounding is possible, and not all harms associated with these antibiotics, most notably drug-induced liver injury, could be assessed. CONCLUSION: Treating diverticulitis in the outpatient setting with amoxicillin-clavulanate may reduce the risk for fluoroquinolone-related harms without adversely affecting diverticulitis-specific outcomes. PRIMARY FUNDING SOURCE: National Institutes of Health.

Medication as a risk factor for hospitalization due to heart failure and shock: a series of case-crossover studies in Swiss claims data.

PURPOSE: Heart failure is among the leading causes for hospitalization in Europe. In this study, we evaluate potential precipitating factors for hospitalization for heart failure and shock. METHODS: Using Swiss claims data (2014-2015), we evaluated the association between hospitalization for heart failure and shock, and prescription of oral potassium supplements, non-steroidal anti-inflammatory drugs (NSAIDs), and amoxicillin/clavulanic acid. We conducted case-crossover analyses, where exposure was compared for the hazard period and the primary control period (e.g., 1-30 days before hospitalization vs. 31-60 days, respectively). Conditional logistic regression was applied and subsequently adjusted for addressing potential confounding by disease progression. Sensitivity analyses were conducted and stratification for co-medication was performed. RESULTS: We identified 2185 patients hospitalized with heart failure or shock. Prescription of potassium supplements, NSAIDs, and amoxicillin/clavulanic acid was significantly associated with an increased risk for hospitalization for heart failure and shock with crude odds ratios (OR) of 2.04 for potassium (95% CI 1.24-3.36, p = 0.005, 30 days), OR 1.8 for NSAIDs (95% CI 1.39-2.33, p < 0.0001, 30 days), and OR 3.25 for amoxicillin/clavulanic acid (95% CI 2.06-5.14, p < 0.0001, 15 days), respectively. Adjustment attenuated odds ratios, while the significant positive association remained (potassium OR 1.70 (95% CI 1.01-2.86, p = 0.046), NSAIDs OR 1.50 (95% CI 1.14-1.97, p = 0.003), and amoxicillin/clavulanic acid OR 2.26 (95% CI 1.41-3.62, p = 0.001). CONCLUSION: Prescription of potassium supplements, NSAIDs, and amoxicillin/clavulanic acid is associated with increased risk for hospitalization. Underlying conditions such as pain, electrolyte imbalances, and infections are likely contributing risk factors. Physicians may use this knowledge to better identify patients at risk and adapt patient management.

RAIN study: a protocol for a randomised controlled trial evaluating efficacy, safety and cost-effectiveness of intravenous-to-oral antibiotic switch therapy in neonates with a probable bacterial infection.

INTRODUCTION: High morbidity and mortality rates of proven bacterial infection are the main reason for substantial use of intravenous antibiotics in neonates during the first week of life. In older children, intravenous-to-oral switch after 48 hours of intravenous therapy has been shown to have many advantages and is nowadays commonly practised. We, therefore, aim to evaluate the effectiveness, safety and cost-effectiveness of an early intravenous-to-oral switch in neonates with a probable bacterial infection. METHODS AND ANALYSIS: We present a protocol for a multicentre randomised controlled trial assessing the non-inferiority of an early intravenous-to-oral antibiotic switch compared with a full course of intravenous antibiotics in neonates (0-28 days of age) with a probable bacterial infection. Five hundred and fifty patients will be recruited in 17 hospitals in the Netherlands. After 48 hours of intravenous treatment, they will be assigned to either continue with intravenous therapy for another 5 days (control) or switch to amoxicillin/clavulanic acid suspension (intervention). Both groups will be treated for a total of 7 days. The primary outcome will be bacterial (re)infection within 28 days after treatment completion. Secondary outcomes are the pharmacokinetic profile of oral amoxicillin/clavulanic acid, the impact on quality of life, cost-effectiveness, impact on microbiome development and additional yield of molecular techniques in diagnosis of probable bacterial infection. ETHICS AND DISSEMINATION: This study has been approved by the Medical Ethics Committee of the Erasmus Medical Centre. Results will be presented in peer-reviewed journals and at international conferences. TRIAL REGISTRATION NUMBER: NCT03247920.

Prophylactic antibiotics reduce hospitalisations and cost in locally advanced head and neck cancer patients treated with chemoradiotherapy: A randomised phase 2 study.

BACKGROUND: Platinum-based chemoradiotherapy for locally advanced head and neck cancer (LAHNC) induces a high rate of acute toxicity, including dysphagia and aspiration pneumonia. We hypothesised that prophylactic antibiotics can prevent pneumonia and hospitalisations and can be cost-effective. PATIENT AND METHODS: In this multicentre randomised trial, patients with LAHNC treated with chemoradiotherapy received prophylactic amoxicillin/clavulanic acid from day 29 after the start of treatment until 14 days after completion of chemoradiotherapy or standard care without prophylaxis. The primary objective was to observe a reduction in pneumonias. Secondary objectives were to evaluate the hospitalisation rate, adverse events, costs and health-related quality of life. RESULTS: One hundred six patients were included; of which, 95 were randomised: 48 patients were allocated to the standard group and 47 patients to the prophylaxis group. A pneumonia during chemoradiotherapy and follow-up until 3.5 months was observed in 22 (45.8%) of 48 patients in the standard group and in 22 (46.8%) of 47 patients in the prophylaxis group (p = 0.54). Hospitalisation rate was significantly higher in the standard group versus the prophylaxis group, 19 of 48 pts (39.6%) versus 9 of 47 pts (19.1%), respectively (p = 0.03). Significantly more episodes with fever of any grade were observed in the standard group (29.2% vs 10.2%, p = 0.028). A significant difference in costs was found, with an average reduction of €1425 per patient in favour of the prophylaxis group. CONCLUSION: Although prophylactic antibiotics during chemoradiotherapy for patients with LAHNC did not reduce the incidence of pneumonias, it did reduce hospitalisation rates and episodes with fever significantly and consequently tended to be cost-effective.

Application of pharmacokinetic/pharmacodynamic analysis to evaluate the adequacy of antimicrobial therapy for pediatric acute otitis media in Spain before and after the introduction of the PCV7 vaccine.

OBJECTIVE: To evaluate, by applying pharmacokinetic/pharmacodynamic (PK/PD) analysis, if the change in antibiotic susceptibility after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in Spain had any influence on the usefulness of the antimicrobials more frequently used as empirical treatment of pediatric acute otitis media (AOM). METHODS: PK parameters and susceptibility of Streptococcus pneumoniae and Haemophilus influenzae were obtained from bibliography. Monte Carlo simulation was used to estimate the cumulative fraction of response (CFR), understood as the expected probability of therapy success. For amoxicillin and amoxicillin/clavulanate, the target was free antibiotic concentration remaining above the minimum inhibitory concentration (MIC) for ≥50% of the dosing interval (fT>MIC≥50%), whereas for cefuroxime axetil and cefotaxime, the target was fT>MIC≥60%. CFR values ≥90% were considered successful. RESULTS: When all serotypes of S. pneumoniae are considered, amoxicillin and cefotaxime turned out to reach a high probability of success, and difference before and after vaccination was scarce. For H. influenzae, CFR values were higher with amoxicillin/clavulanate than with amoxicillin. For both microorganisms, cefuroxime axetil resulted in low probability of success in the two periods of study. CONCLUSIONS: We have shown that the introduction of the PCV7 vaccination did not lead to changes in the probability of success of the current empiric treatments of the AOM. Integrated PK/PD analysis has demonstrated to be a useful tool to identify changes in antimicrobial activity after the implantation of a vaccination program, providing complementary information to the simple assessment of MIC values.

Non-prescribed sale of antibiotics for acute childhood diarrhea and upper respiratory tract infection in community pharmacies: a 2 phase mixed-methods study.

Background: Although prohibited by law and legal regulatory frameworks, non-prescribed sale of antibiotics in community medicine retail outlets (CMROs) remains a serious problem in Ethiopia. The aim of this study was to document the extent of and motivations behind non-prescribed sale of antibiotics among CMROs in Gondar town, Ethiopia. Methods: A 2 phase mixed-methods study (a simulated patient visit followed by an in-depth interview) was conducted among CMROs in Gondar town, Ethiopia. Two clinical case scenarios (acute childhood diarrhea and upper respiratory tract infection) were presented and the practice of non-prescribed sale were measured and results were reported as percentages. Pharmacy staff (pharmacists and pharmacy assistants) were interviewed to examine factors/motivations behind dispensing antibiotics without a valid prescription. Results: Out of 100 simulated visits (50 each scenarios) presented to drug retail outlets, 86 cases (86%) were provided with one or more medications. Of these, 18 (20.9%) asked about past medical and medication history and only 7 (8.1%) enquired about the patient's history of drug allergy. The most frequently dispensed medication for acute childhood diarrhoea simulation were oral rehydration fluid (ORS) with zinc (n = 16) and Metronidazole (n = 15). Among the dispensed antibiotics for upper respiratory infection simulation, the most common was Amoxicillin (n = 23) followed by Amoxicillin-clavulanic acid capsule (n = 19) and Azithromycin (n = 15). Perceived financial benefit, high expectation and/or demand of customers and competition among pharmacies were cited as the main drivers behind selling antibiotics without a prescription. Conclusions: A stringent law and policy enforcement regarding the sale of antibiotics without a valid prescription should be in place. This will ultimately help to shift the current pharmacy practices from commercial and business-based interests/practices to the provision of primary healthcare services to the community.

Azithromycin and Sensorineural Hearing Loss in Adults: A Retrospective Cohort Study.

OBJECTIVE: To examine whether short-term use of azithromycin increases the risk of sensorineural hearing loss (SNHL) in adults with uncomplicated infections. STUDY DESIGN: A retrospective cohort study using Medicaid claims data, 1999 to 2010. PATIENTS: Adults (18-64 years old) who had continuous enrollment in Medicaid for the 12 months (baseline) before the date of first dispensation (index date) of oral azithromycin or amoxicillin ±â€Šclavulanate for uncomplicated infections. MAIN OUTCOME DEFINITION: We operationalized sensorineural hearing loss (SNHL) by a charge for audiometry and followed by a diagnosis of SNHL within 30 days. ANALYSIS: We adjusted for the baseline covariates through propensity score matching. Adults were followed for up to 120 days after the index date. The hazard of SNHL in azithromycin-exposed adults was compared with those who had amoxicillin ±â€Šclavulanate using a Cox proportional hazard model. We performed several sensitivity analyses by varying the follow-up time, SNHL definition, adjusting for cumulative antibiotic use, and switching exposure status during the follow-up period. RESULTS: A total of 493,774 patients entered the study cohort. The unadjusted incidence rates of SNHL were 38 and 41 cases per 10,000 patient-years following exposure to azithromycin and amoxicillin ±â€Šclavulanate, respectively. The adjusted (matched) hazard ratio (HR) of SNHL for azithromycin versus amoxicillin ±â€Šclavulanate was 0.91 (95% confidence interval [CI], 0.77-1.07). The sensitivity analyses findings were consistent with the primary analysis. CONCLUSION: Azithromycin short-term use was not associated with an increased risk of SNHL in comparison to amoxicillin ±â€Šclavulanate.

Melioidosis.

Burkholderia pseudomallei is a Gram-negative environmental bacterium and the aetiological agent of melioidosis, a life-threatening infection that is estimated to account for ∼89,000 deaths per year worldwide. Diabetes mellitus is a major risk factor for melioidosis, and the global diabetes pandemic could increase the number of fatalities caused by melioidosis. Melioidosis is endemic across tropical areas, especially in southeast Asia and northern Australia. Disease manifestations can range from acute septicaemia to chronic infection, as the facultative intracellular lifestyle and virulence factors of B. pseudomallei promote survival and persistence of the pathogen within a broad range of cells, and the bacteria can manipulate the host's immune responses and signalling pathways to escape surveillance. The majority of patients present with sepsis, but specific clinical presentations and their severity vary depending on the route of bacterial entry (skin penetration, inhalation or ingestion), host immune function and bacterial strain and load. Diagnosis is based on clinical and epidemiological features as well as bacterial culture. Treatment requires long-term intravenous and oral antibiotic courses. Delays in treatment due to difficulties in clinical recognition and laboratory diagnosis often lead to poor outcomes and mortality can exceed 40% in some regions. Research into B. pseudomallei is increasing, owing to the biothreat potential of this pathogen and increasing awareness of the disease and its burden; however, better diagnostic tests are needed to improve early confirmation of diagnosis, which would enable better therapeutic efficacy and survival.

Assessment of the comparability of CLSI, EUCAST and Stokes antimicrobial susceptibility profiles for Escherichia coli uropathogenic isolates.

BACKGROUND: As many clinical laboratories convert between Stokes, Clinical and Laboratory Standards Institute (CLSI) and European Committee for Antimicrobial Susceptibility Testing (EUCAST) methods, the problem of comparing differently derived sets of antimicrobial susceptibility testing (AST) data with each other arises, owing to a scarcity of knowledge of inter-method comparability. The purpose of the current study was to determine the comparability of CLSI, EUCAST and Stokes AST methods for determining susceptibility of uropathogenic Escherichia coli to ampicillin, amoxicillin-clavulanate, trimethoprim, cephradine/cephalexin, ciprofloxacin and nitrofurantoin. METHODS: A total of 100 E. coli isolates were obtained from boric acid urine samples from patients attending GP surgeries. For EUCAST and CLSI, the Kirby-Bauer disc diffusion method was used and results interpreted using the respective breakpoint guidelines. For the Stokes method, direct susceptibility testing was performed on the urine samples. RESULTS: The lowest levels of agreement were for amoxicillin-clavulanate (60%) and ciprofloxacin (89%) between the three AST methods, when using 2017 interpretive guidelines for CLSI and EUCAST. A comparison of EUCAST and CLSI without Stokes showed 82% agreement for amoxicillin-clavulanate and 94% agreement for ciprofloxacin. Discrepancies were compounded by varying breakpoint susceptibility guidelines issued during the period 2011-2017, and through the inclusion of a definition of intermediate susceptibility in some cases. CONCLUSIONS: Our data indicate that the discrepancies generated through using different AST methods and different interpretive guidelines may result in confusion and inaccuracy when prescribing treatment for urinary tract infection.

Nonoperative treatment of acute appendicitis in children: A feasibility study.

PURPOSE: Nonoperative treatment of acute appendicitis appears to be feasible in adults. It is unclear whether the same is true for children. METHODS: Children 5-18 years with <48 h symptoms of acute appendicitis were offered nonoperative treatment: 2 doses of piperacillin IV, then ampicillin/clavulanate ×1 week. Treatment failure (worsening on therapy) and recurrence (after completion of therapy) were noted. Patients who declined enrollment were asked to participate as controls. Cost-utility analysis was performed using Pediatric Quality of Life Scale (PedsQL®) to calculate quality-adjusted life month (QALM) for study and control patients. RESULTS: Twenty-four patients agreed to undergo nonoperative management, and 50 acted as controls. At a mean follow-up of 14 months, three of the 24 failed on therapy, and 2/21 returned with recurrent appendicitis at 43 and 52 days, respectively. Two patients elected to undergo an interval appendectomy despite absence of symptoms. Appendectomy-free rate at one year was therefore 71% (C.I. 50-87%). No patient developed perforation or other complications. Cost-utility analysis shows a 0.007-0.03 QALM increase and a $1359 savings from $4130 to $2771 per nonoperatively treated patient. CONCLUSION: Despite occasional late recurrences, antibiotic-only treatment of early appendicitis in children is feasible, safe, cost-effective and is experienced more favorably by patients and parents.

Effectiveness of Patient Choice in Nonoperative vs Surgical Management of Pediatric Uncomplicated Acute Appendicitis.

IMPORTANCE: Current evidence suggests that nonoperative management of uncomplicated appendicitis is safe, but overall effectiveness is determined by combining medical outcomes with the patient's and family's perspective, goals, and expectations. OBJECTIVE: To determine the effectiveness of patient choice in nonoperative vs surgical management of uncomplicated acute appendicitis in children. DESIGN, SETTING, AND PARTICIPANTS: Prospective patient choice cohort study in patients aged 7 to 17 years with acute uncomplicated appendicitis presenting at a single pediatric tertiary acute care hospital from October 1, 2012, through March 6, 2013. Participating patients and families gave informed consent and chose between nonoperative management and urgent appendectomy. INTERVENTIONS: Urgent appendectomy or nonoperative management entailing at least 24 hours of inpatient observation while receiving intravenous antibiotics and, on demonstrating improvement of symptoms, completion of 10 days of treatment with oral antibiotics. MAIN OUTCOMES AND MEASURES: The primary outcome was the 1-year success rate of nonoperative management. Successful nonoperative management was defined as not undergoing an appendectomy. Secondary outcomes included comparisons of the rates of complicated appendicitis, disability days, and health care costs between nonoperative management and surgery. RESULTS: A total of 102 patients were enrolled; 65 patients/families chose appendectomy (median age, 12 years; interquartile range [IQR], 9-13 years; 45 male [69.2%]) and 37 patients/families chose nonoperative management (median age, 11 years; IQR, 10-14 years; 24 male [64.9%]). Baseline characteristics were similar between the groups. The success rate of nonoperative management was 89.2% (95% CI, 74.6%-97.0%) at 30 days (33 of 37 children) and 75.7% (95% CI, 58.9%-88.2%) at 1 year (28 of 37 children). The incidence of complicated appendicitis was 2.7% in the nonoperative group (1 of 37 children) and 12.3% in the surgery group (8 of 65 children) (P = .15). After 1 year, children managed nonoperatively compared with the surgery group had fewer disability days (median [IQR], 8 [5-18] vs 21 [15-25] days, respectively; P < .001) and lower appendicitis-related health care costs (median [IQR], $4219 [$2514-$7795] vs $5029 [$4596-$5482], respectively; P = .01). CONCLUSIONS AND RELEVANCE: When chosen by the family, nonoperative management is an effective treatment strategy for children with uncomplicated acute appendicitis, incurring less morbidity and lower costs than surgery. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01718275.

Augmented renal clearance implies a need for increased amoxicillin-clavulanic acid dosing in critically ill children.

There is little data available to guide amoxicillin-clavulanic acid dosing in critically ill children. The primary objective of this study was to investigate the pharmacokinetics of both compounds in this pediatric subpopulation. Patients admitted to the pediatric intensive care unit (ICU) in whom intravenous amoxicillin-clavulanic acid was indicated (25 to 35 mg/kg of body weight every 6 h) were enrolled. Population pharmacokinetic analysis was conducted, and the clinical outcome was documented. A total of 325 and 151 blood samples were collected from 50 patients (median age, 2.58 years; age range, 1 month to 15 years) treated with amoxicillin and clavulanic acid, respectively. A three-compartment model for amoxicillin and a two-compartment model for clavulanic acid best described the data, in which allometric weight scaling and maturation functions were added a priori to scale for size and age. In addition, plasma cystatin C and concomitant treatment with vasopressors were identified to have a significant influence on amoxicillin clearance. The typical population values of clearance for amoxicillin and clavulanic acid were 17.97 liters/h/70 kg and 12.20 liters/h/70 kg, respectively. In 32% of the treated patients, amoxicillin-clavulanic acid therapy was stopped prematurely due to clinical failure, and the patient was switched to broader-spectrum antibiotic treatment. Monte Carlo simulations demonstrated that four-hourly dosing of 25 mg/kg was required to achieve the therapeutic target for both amoxicillin and clavulanic acid. For patients with augmented renal function, a 1-h infusion was preferable to bolus dosing. Current published dosing regimens result in subtherapeutic concentrations in the early period of sepsis due to augmented renal clearance, which risks clinical failure in critically ill children, and therefore need to be updated. (This study has been registered at Clinicaltrials.gov as an observational study [NCT02456974].).

Cefepime combined with amoxicillin/clavulanic acid: a new choice for the KPC-producing K. pneumoniae infection.

OBJECTIVE: Clinical treatment for blaKPC-positive Klebsiella pneumoniae isolates is challenging because the recommended antibiotic options are limited and are extraordinarily expensive. This study aimed to explore a new therapy for infection caused by KPC-producing K. pneumoniae. METHODS: Patients with blaKPC-positive K. pneumoniae infection, were prospectively screened and were categorised into two groups: patients in the study group received a combination-based therapy of cefepime and amoxicillin/clavulanic acid and the control group received tigecycline-based therapy. The pathogen clearance rate, 28-day mortality and cost of the antibiotic treatment were compared between the two groups. Moreover, the checkerboard microdilution method was performed to determine the synergy between cefepime and amoxicillin/clavulanic acid in vitro. RESULTS: Twenty-six and 25 cases were enrolled in the study and control groups. The mortality and the overall pathogen clearance rate showed no significant differences (P=0.311 and P=0.447). Both the total cost and the portion of the cost not covered by insurance were higher for the control group compared to the study group (both P<0.001). Consistently, synergy (65.4%) and partial synergy (26.9%) were the main effects. CONCLUSIONS: In contrast to the currently recommended tigecycline-based therapy, cefepime and amoxicillin/clavulanic acid combination was an effective and economical option to KPC-KP infection in China.

Occurrence of otitis media in children and assessment of treatment options.

BACKGROUND: Otitis media is a more frequent occurrence in children, and the disease may progress from an acute to chronic state if appropriate and timely intervention is not initiated. METHODS: A total of 212 children aged 6 months to 10 years were examined and treated for otitis media, in a 13-month hospital-based study. RESULTS: Acute otitis media was diagnosed in 130 (61.3 per cent) of the patients. There were 82 (38.7 per cent) chronic suppurative otitis media cases. The incidence of acute otitis media and chronic suppurative otitis media in the first year of life was 54.6 per cent and 45.1 per cent respectively. Chronic suppurative otitis media patients were assigned to one of three treatment groups. Recovery occurred in 70.4 per cent of amoxicillin-treated patients, in 88.9 per cent of amoxicillin-clavulanic acid treated patients and in 96.4 per cent of culture and antibiotic sensitivity test patients. Relapses were seen only in the amoxicillin (five cases) and amoxicillin-clavulanic acid (two cases) groups. CONCLUSION: The success rate in patients treated with antibiotics makes this option mandatory for an established diagnosis.

[Modalities of management of cancer patients with febrile neutropenia in the oncology emergency unit of Gustave-Roussy and their related costs]. / Modalités de prise en charge des neutropénies fébriles chez les patients traités pour une néoplasie solide dans le service d'urgence de cancérologie Gustave-Roussy et leurs impacts économiques.

BACKGROUND: Febrile neutropenia (FN) is a severe chemotherapy side effect. Hospitalization is recommended for FN episode of high-risk (HR) of complications. Management of FN at lower risk of complications remains unclear. METHODS: This is a prospective observation study in patients with solid tumors admitted to the emergency department FN. Collected data included demographics, clinical, biological, therapeutic costs, MASCC score and complications. RESULTS: Hundred and thirty-seven consecutive FN were recorded in 128 patients. Twenty-six FN (19%) were managed at home (all of them had a MASCC score ≥ 21); 111 (81%) were treated at hospital of which 37 NF were at HR of complications based on clinical and biological parameters (all of them had a MASCC score < 21) and for 74 of them the admission could be discussed (MASCC < 20 or ≥ 20). This group of patients was considerate with intermediate risk (IR). All IR patients were treated with the same antibiotics than outpatients, i.e. ceftriaxone in 36 cases (49%) or amoxicillin/clavulanic acid and ciprofloxacin in 38 cases (51%). For these 74 cases, any severe complication was recorded. Antibiotics were adapted for only 12% of these patients according to bacteriology results. CONCLUSION: This study showed the limits of the MASCC score. We did not observe any severe complications in patients admitted to the hospital according to clinical and biological parameters and with the high risk score MASCC. This study had some methodological bias but it allowed us to estimate the cost of the different ways of management and the difficulties to decide the hospitalization in FN.

Payment analysis of two diagnosis and management approaches of acute otitis media.

We determined the cost of care for 2 diagnosis and management approaches for acute otitis media (AOM) among children 6 to 30 months old. A case-control design was used. Cases included 208 children diagnosed with AOM based on a bulging tympanic membrane (TM) and treated with amoxicillin/clavulanate. Controls (5:1 ratio) included 1020 children with AOM diagnosed not requiring bulging of the TM and treated with amoxicillin. Fewer cases (49%) than controls (69%) were diagnosed with AOM (P < .001), fewer were diagnosed with recurrent AOM or AOM treatment failure (0.34 vs 1.6/child; P < .0001), and fewer had insertion of tympanostomy tubes (6.3% vs 14.8%) due to recurrent AOM (P < .0001). The combined direct payments and indirect costs for management of AOM were $539/case versus $1,023/control. Using Rochester NY payments generalized to the US birth cohort, this case diagnosis and treatment strategy could save $1.008 billion per year.

The trends in antibiotic use by general dental practitioners in the Czech Republic (2006-2012).

We assessed antibiotic prescribing in practical dentistry in the Czech Republic, as antibiotics are widely prescribed by dental practitioners and warning signals of their overuse can be observed. The individual antibiotic prescriptions were extracted from the database of the General Health Insurance Company and further analysed. The proportion of dentists' prescription within the whole primary health-care sector and the rate of prescriptions of particular antibiotics were both in defined daily doses per 1,000 insurees and day (DID) and in number of prescriptions calculated. The proportion of antibiotic use in dentistry increased from 0.63 DID in 2006 to 0.75 DID. We found a decline in use of narrow-spectrum penicillins by 4.8%, tetracyclines by 3.5% and macrolides by 3.6%, accompanied by increasing rate of prescription of aminopenicillins combined with beta-lactamase inhibitor by 8.9% and lincosamides by 8.5%. The consumption of clindamycin and amoxicillin combined with clavulanate in DID has increased by approximately 60% since 2006 thanks to the exclusive prescribing of two commercial oral products only. Factors contributing to this unfavourable trend are commercial influence or defensive medicine practice.

Antibiotic therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) in non surgical wounds.

BACKGROUND: Non surgical wounds include chronic ulcers (pressure or decubitus ulcers, venous ulcers, diabetic ulcers, ischaemic ulcers), burns and traumatic wounds. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonisation (i.e. presence of MRSA in the absence of clinical features of infection such as redness or pus discharge) or infection in chronic ulcers varies between 7% and 30%. MRSA colonisation or infection of non surgical wounds can result in MRSA bacteraemia (infection of the blood) which is associated with a 30-day mortality of about 28% to 38% and a one-year mortality of about 55%. People with non surgical wounds colonised or infected with MRSA may be reservoirs of MRSA, so it is important to treat them, however, we do not know the optimal antibiotic regimen to use in these cases. OBJECTIVES: To compare the benefits (such as decreased mortality and improved quality of life) and harms (such as adverse events related to antibiotic use) of all antibiotic treatments in people with non surgical wounds with established colonisation or infection caused by MRSA. SEARCH METHODS: We searched the following databases: The Cochrane Wounds Group Specialised Register (searched 13 March 2013); The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2); Database of Abstracts of Reviews of Effects (2013, Issue 2); NHS Economic Evaluation Database (2013, Issue 2); Ovid MEDLINE (1946 to February Week 4 2013); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, March 12, 2013); Ovid EMBASE (1974 to 2013 Week 10); EBSCO CINAHL (1982 to 8 March 2013). SELECTION CRITERIA: We included only randomised controlled trials (RCTs) comparing antibiotic treatment with no antibiotic treatment or with another antibiotic regimen for the treatment of MRSA-infected non surgical wounds. We included all relevant RCTs in the analysis, irrespective of language, publication status, publication year, or sample size. DATA COLLECTION AND ANALYSIS: Two review authors independently identified the trials, and extracted data from the trial reports. We calculated the risk ratio (RR) with 95% confidence intervals (CI) for comparing the binary outcomes between the groups and planned to calculate the mean difference (MD) with 95% CI for comparing the continuous outcomes. We planned to perform the meta-analysis using both fixed-effect and random-effects models. We performed intention-to-treat analysis whenever possible. MAIN RESULTS: We identified three trials that met the inclusion criteria for this review. In these, a total of 47 people with MRSA-positive diabetic foot infections were randomised to six different antibiotic regimens. While these trials included 925 people with multiple pathogens, they reported the information on outcomes for people with MRSA infections separately (MRSA prevalence: 5.1%). The only outcome reported for people with MRSA infection in these trials was the eradication of MRSA. The three trials did not report the review's primary outcomes (death and quality of life) and secondary outcomes (length of hospital stay, use of healthcare resources and time to complete wound healing). Two trials reported serious adverse events in people with infection due to any type of bacteria (i.e. not just MRSA infections), so the proportion of patients with serious adverse events was not available for MRSA-infected wounds. Overall, MRSA was eradicated in 31/47 (66%) of the people included in the three trials, but there were no significant differences in the proportion of people in whom MRSA was eradicated in any of the comparisons, as shown below.1. Daptomycin compared with vancomycin or semisynthetic penicillin: RR of MRSA eradication 1.13; 95% CI 0.56 to 2.25 (14 people).2. Ertapenem compared with piperacillin/tazobactam: RR of MRSA eradication 0.71; 95% CI 0.06 to 9.10 (10 people).3. Moxifloxacin compared with piperacillin/tazobactam followed by amoxycillin/clavulanate: RR of MRSA eradication 0.87; 95% CI 0.56 to 1.36 (23 people). AUTHORS' CONCLUSIONS: We found no trials comparing the use of antibiotics with no antibiotic for treating MRSA-colonised non-surgical wounds and therefore can draw no conclusions for this population. In the trials that compared different antibiotics for treating MRSA-infected non surgical wounds, there was no evidence that any one antibiotic was better than the others. Further well-designed RCTs are necessary.