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- Correction: HLA Alleles Influence the Clinical Signature of Amoxicillin-Clavulanate Hepatotoxicity. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e112165.
[This corrects the article DOI: 10.1371/journal.pone.0068111.].
- Diagnosis and Management of Urinary Tract Infections in the Outpatient Setting: A Review. [JOURNAL ARTICLE]
- JAMA 2014 Oct 22; 312(16):1677-1684.
Urinary tract infection is among the most common reasons for an outpatient visit and antibiotic use in adult populations. The increasing prevalence of antibacterial resistance among community uropathogens affects the diagnosis and management of this clinical syndrome.To define the optimal approach for treating acute cystitis in young healthy women and in women with diabetes and men and to define the optimal approach for diagnosing acute cystitis in the outpatient setting.Evidence for optimal treatment regimens was obtained by searching PubMed and the Cochrane database for English-language studies published up to July 21, 2014.Twenty-seven randomized clinical trials (6463 patients), 6 systematic reviews, and 11 observational studies (252 934 patients) were included in our review. Acute uncomplicated cystitis in women can be diagnosed without an office visit or urine culture. Trimethoprim-sulfamethoxazole (160/800 mg twice daily for 3 days), nitrofurantoin monohydrate/macrocrystals (100 mg twice daily for 5-7 days), and fosfomycin trometamol (3 g in a single dose) are all appropriate first-line therapies for uncomplicated cystitis. Fluoroquinolones are effective for clinical outcomes but should be reserved for more invasive infections. β-Lactam agents (amoxicillin-clavulanate and cefpodoxime-proxetil) are not as effective as empirical first-line therapies. Immediate antimicrobial therapy is recommended rather than delayed treatment or symptom management with ibuprofen alone. Limited observational studies support 7 to 14 days of therapy for acute urinary tract infection in men. Based on 1 observational study and our expert opinion, women with diabetes without voiding abnormalities presenting with acute cystitis should be treated similarly to women without diabetes.Immediate antimicrobial therapy with trimethoprim-sulfamethoxazole, nitrofurantoin, or fosfomycin is indicated for acute cystitis in adult women. Increasing resistance rates among uropathogens have complicated treatment of acute cystitis. Individualized assessment of risk factors for resistance and regimen tolerability is needed to choose the optimum empirical regimen.
- Free antibiotic and vaccination programmes in community pharmacies of Miami-Dade County, FL, USA. [JOURNAL ARTICLE]
- J Antimicrob Chemother 2014 Oct 19.
Some community pharmacies provide prescribed oral antibiotics for free to incentivize customers. This can influence prescribing practices and may increase inappropriate antibiotic use. Thus, pleas to incorporate education and/or vaccinations into these initiatives have been made by the CDC and IDSA. This study aims to investigate the prevalence and characteristics of free antibiotic programmes (FAPs) and free vaccination programmes (FVPs) offered by community pharmacies within a major US county. Additionally, we evaluated the association between FAP location and proximate socioeconomic status.A telephone survey was administered to all community pharmacies in operation and located in Miami-Dade County, FL, USA (n = 668). Population characteristics at the five-digit ZIP code level were acquired from the 2010 US Census and American Communities Survey. An independent t-test, Kruskal-Wallis and logistic regression were used for statistical analysis.A total of 660 community pharmacies agreed to the telephone survey (response rate = 98.8%). FAPs were present in 6.8% of pharmacies (n = 45) and none incorporated an educational component targeted at patients or prescribers. Ciprofloxacin and amoxicillin were offered by all FAPs and 84.4% provided up to a 14 day supply (n = 38). Thirty-four of 72 ZIP codes had an FAP and those with a programme had larger populations and higher incomes (P ≤ 0.05). Family income ≥$75 000 (P = 0.0002) was an independent predictor of FAP availability. None of the surveyed pharmacies offered a FVP.Frequently provided by chain pharmacies and located in areas of higher income, FAPs within Miami-Dade County offer broad-spectrum antibiotics for long durations without additional education to patients or prescribers.
- First- and second-line Helicobacter pylori eradication with modified sequential therapy and modified levofloxacin-amoxicillin-based triple therapy. [JOURNAL ARTICLE]
- Ann Gastroenterol 2014; 27(4):357-361.
Helicobacter pylori (H. pylori) treatment remains a challenge for physicians. Although highly effective, the standard sequential therapy fails in a certain number of patients. Moreover, the cure rate following a levofloxacin-amoxicillin second-line triple therapy seems to be decreasing. We tested the efficacy of modified 10-day sequential therapy, and an intensified levofloxacin-amoxicillin regimen as first- and second-line therapy respectively.In this prospective, open label, multicenter, pilot study H. pylori-infected patients received a first-line modified 10-day sequential therapy regimen including rabeprazole 20 mg, and amoxicillin 1 g for the first 3 days, followed by rabeprazole 20 mg, clarithromycin 250 mg, and metronidazole 250 mg, for the remaining 7 days, all drugs given thrice daily. An 8-day therapy regimen with rabeprazole 20 mg, levofloxacin 250 mg, and amoxicillin 1 g, all thrice daily, was administered a second-line therapy.A total of 99 and 15 patients were enrolled for first- and second-line therapy. The eradication rates were 85.9% (95% CI 80-93) and 93.4% (95% CI 88-98) according to ITT and PP analyses following modified sequential therapy, and 60% (95% CI 35-86) and 64.3% (95% CI 39-89) following the intensified second-line therapy.A modified sequential 3- plus 7-day regimen with thrice daily drug administration failed to achieve very high eradication rate at ITT analysis. The intensified second-line regimen achieved disappointingly low eradication rate. Novel levofloxacin-free second-line therapies are urged in Italy.
- Mode of delivery and other risk factors for Escherichia coli infections in very low birth weight infants. [JOURNAL ARTICLE]
- BMC Pediatr 2014 Oct 18; 14(1):274.
Infections in newborns remain one of the most significant problems in modern medicine. Escherichia coli is an important cause of neonatal bloodstream and respiratory tract infections and is associated with high mortality. The aim of our study was to investigate the epidemiology of E. coli infection in Polish neonatal intensive care units (NICUs) and resistance to antibiotics, with particular reference to the safety of very low birth weight infants.Continuous prospective infection surveillance was conducted in 2009-2012 in five NICUs, including 1,768 newborns whose birth weight was <1.5 kg. Escherichia coli isolates from different diagnostic specimens including blood, tracheal/bronchial secretions and others were collected. All isolates were tested using disk diffusion antimicrobial susceptibility methods. Pulsed-field gel electrophoresis was used to determine the possible horizontal transfer of E. coli among patients.The incidence of E. coli infections was 5.4% and 2.0/1,000 patient-days. The occurrence of E. coli infections depended significantly on the NICU and varied between 3.9% and 17.9%. Multivariate analysis that took into account the combined effect of demographic data (gender, gestational age and birth weight) and place of birth showed that only the place of hospitalisation had a significant effect on the E. coli infection risk. The highest levels of resistance among all E. coli isolates were observed against ampicillin (88.8%) and amoxicillin/clavulanic acid (62.2%). Among E. coli isolates, 17.7% were classified as multidrug resistant. Escherichia coli isolates showed different pulsotypes and dominant epidemic clones were not detected.Our data indicate that antibiotic prophylaxis in the presence of symptoms such as chorioamnionitis and premature rupture of membranes did not help reduce the risk of E. coli infection. Multivariate analysis demonstrated only one significant risk factor for E. coli infection among infants with a birth weight <1.5 kg, that is, the impact of the NICU, it means that both neonatal care and care during pregnancy and labour were found to be significant.
- [Dissolution testing combined with computer simulation technology to evaluate the bioequivalence of domestic amoxicillin capsule]. [English Abstract, Journal Article]
- Yao Xue Xue Bao 2014 Aug; 49(8):1155-61.
Re-evaluation of bioequivalence of generic drugs is one of the key research focus currently. As a means to ensure consistency of the therapeutic effectiveness of drug products, clinical bioequivalence has been widely accepted as a gold standard test. In vitro dissolution testing based on the theory of the BCS is the best alternative to in vivo bioequivalence study. In this article, the conventional dissolution method and flow-through cell method were used to investigate the dissolution profiles of domestic amoxicillin capsules in different dissolution media, and the absorption behavior of the drugs with different release rates (t85% = 15-180 min) in the gastrointestinal tract was predicted by Gastro Plus. The flow-through cell method was thought better to reflect the release characteristics in vivo, and amoxicillin capsules with regard to the release rates up to 45 min (t85% = 45 min) were having a satisfied bioequivalence with the oral solution according to the C(max) and AUC. Although two different dissolution profiles of domestic amoxicillin capsules were found by flow-through cell methods, prediction results revealed that domestic capsules were probably bioequivalent to each other.
- Value of prophylactic postoperative antibiotic therapy after bimaxillary orthognathic surgery: a clinical trial. [Journal Article]
- Iran J Otorhinolaryngol 2014 Oct; 26(77):207-10.
Antibiotic therapy before or after orthognathic surgery is commonly recommended by surgeons to minimize the risk of wound infection. This article evaluates the value of Prophylactic antibiotic therapy in order to diminish the incidence of postoperative wound infection after orthognathic surgery.Fifty candidates for bimaxillary orthognathic surgery were divided into cases and controls. Cefazolin (1g) was administered intravenously to all participants 30 mins prior to surgery followed by a similar dose 4 hours later. Case-group patients ingested amoxicillin (500 mg) orally for 7 days after surgery. Postoperative wound infection was assessed using clinical features, and the P-value significance was set at P<0.05.Both groups were similar according to gender, age, and operating time. During the follow-up period no infection was observed in either the case or control group.The results of this study suggest that long-term postoperative antibiotic therapy is not essential for the prevention of postoperative infection, and that application of aseptic surgical technique and hygiene instruction after surgery are sufficient.
- Concentration of amoxicillin in maternal serum, cord blood, amniotic fluid and the placenta after vaginal administration. [JOURNAL ARTICLE]
- J Matern Fetal Neonatal Med 2014 Oct 15.:1-14.
Abstract Objective The aim of this study was to assess the amoxicillin concentration in maternal serum, cord blood, amniotic fluid and the placenta, two hours following vaginal administration and the factors influencing the drug level. Methods Twenty-eight full-term pregnant women who qualified for elective cesarean delivery were included in the study. Vaginal suppositories containing 250 mg of amoxicillin were administered two hours prior to the operation. Amoxicillin levels were determined using the diffusion microbial assay. Results The amoxicillin level in amniotic fluid was significantly higher in comparison to that of maternal serum, cord blood or the placenta. Maternal age positively and gestational weight gain negatively correlated with the amoxicillin concentration in maternal serum. The maternal serum hemoglobin level and red blood cell count were positively correlated with amoxicillin concentration in the amniotic fluid. Neonatal birth weight was positively correlated with maternal serum and cord blood amoxicillin levels. Hypertensive women had significantly higher amoxicillin concentrations in amniotic fluid, and women with thrombocytopenia presented significantly higher cord blood amoxicillin concentrations. Conclusions Amoxicillin presented poor concentration in maternal-fetal compartments after vaginal administration, but the factors influencing the drug level in different compartments require further investigation.
- Treatment of Infections in Young Infants in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis of Frontline Health Worker Diagnosis and Antibiotic Access. [Journal Article]
- PLoS Med 2014 Oct; 11(10):e1001741.
Inadequate illness recognition and access to antibiotics contribute to high case fatality from infections in young infants (<2 months) in low- and middle-income countries (LMICs). We aimed to address three questions regarding access to treatment for young infant infections in LMICs: (1) Can frontline health workers accurately diagnose possible bacterial infection (pBI)?; (2) How available and affordable are antibiotics?; (3) How often are antibiotics procured without a prescription?We searched PubMed, Embase, WHO/Health Action International (HAI), databases, service provision assessments (SPAs), Demographic and Health Surveys, Multiple Indicator Cluster Surveys, and grey literature with no date restriction until May 2014. Data were identified from 37 published studies, 46 HAI national surveys, and eight SPAs. For study question 1, meta-analysis showed that clinical sign-based algorithms predicted bacterial infection in young infants with high sensitivity (87%, 95% CI 82%-91%) and lower specificity (62%, 95% CI 48%-75%) (six studies, n = 14,254). Frontline health workers diagnosed pBI in young infants with an average sensitivity of 82% (95% CI 76%-88%) and specificity of 69% (95% CI 54%-83%) (eight studies, n = 11,857) compared to physicians. For question 2, first-line injectable agents (ampicillin, gentamicin, and penicillin) had low variable availability in first-level health facilities in Africa and South Asia. Oral amoxicillin and cotrimoxazole were widely available at low cost in most regions. For question 3, no studies on young infants were identified, however 25% of pediatric antibiotic purchases in LMICs were obtained without a prescription (11 studies, 95% CI 18%-34%), with lower rates among infants <1 year. Study limitations included potential selection bias and lack of neonatal-specific data.Trained frontline health workers may screen for pBI in young infants with relatively high sensitivity and lower specificity. Availability of first-line injectable antibiotics appears low in many health facilities in Africa and Asia. Improved data and advocacy are needed to increase the availability and appropriate utilization of antibiotics for young infant infections in LMICs.PROSPERO International prospective register of systematic reviews (CRD42013004586). Please see later in the article for the Editors' Summary.
- Seasonal variation in penicillin use in Mexico and Brazil: an analysis of the impact of over-the-counter restrictions. [JOURNAL ARTICLE]
- Antimicrob Agents Chemother 2014 Oct 13.
During 2010, Mexico and Brazil implemented policies to enforce existing laws of restricting over-the-counter sales of antibiotics. We determined if the enforcement led to more appropriate use by measuring changes in seasonal variation of penicillin use.We used retail quarterly sales data in defined-daily-dose per 1000 inhabitants-day (DDD/TID) from IMS Health from the private sector in Mexico and Brazil from the first quarter of 2007 to the first quarter of 2013. This database contains information on volume of antibiotics sold in retail pharmacies using information from wholesalers. We used interrupted time-series models controlling for external factors with the use of antihypertensives with interaction terms to assess changes in trend, level and variation in use between quarters for total penicillin use and by active substance.The most used penicillin was amoxicillin, followed by amoxicillin-clavulanic acid, and ampicillin (minimal use in Brazil). Before the restrictions, the seasonal variation of penicillin use was 1.1 DDD/TID in Mexico and 0.8 DDD/TID in Brazil. In Mexico, we estimated a significant decrease in the seasonal variation of 0.4 DDD/TID after the restriction mainly due the changes in seasonal variation of amoxicillin and ampicillin. In Brazil, the seasonal variation did not change significantly, neither overall nor in the breakdown by individual active substances.For Mexico inappropriate penicillin use may have diminished after the restrictions were enforced. For Brazil increasing use and no change in seasonal variation suggests that further efforts are needed to reduce inappropriate penicillin use.