Generation Macrolide Research Articles

Results of a 5 year Antimicrobial Stewardship program in a North Italian Hospital

Abstract Issue A National Action Plan (PNCAR) to fight antimicrobial resistance has been launched in Italy in 2017, further revised in 2022. In order to reduce inappropriate exposure to antibiotics and infections from multidrug resistant bacteria, a structured system of surveillance and monitoring according to PNCAR standards has been set up in all Italian regions. In the Hospital of Cittadella (District of Padua, Veneto region), special focus has been given to the reduction of antibiotic consumption, in particular quinolones, third generation cephalosporins, carbapenems and macrolides. Description Multidisciplinary meetings have been monthly organized by the hospital Antimicrobial Stewardship Group, with the aim of coordinating the implementation of specific stewardship actions. A quantitative estimate of antibiotic consumption (defined daily dose - DDD - consumption per 100 days of hospitalization) has been provided by the Regional data warehouse from 2019 to 2023 regarding all classes of antibiotics. Results Between 2019 and 2023 a clear decrease in the consumption of quinolones (from 8 to 5,8 DDD, -28%) and carbapenems (from 2,5 to 1,3 DDD, -48%) was observed but, at the same time, an increase in the consumption of third generation cephalosporins (from 9 to 15,7 DDD, +74%) has been reported. This can be explained as a direct consequence of the correct application of therapy guidelines, which in several cases suggest the use of ceftriaxone instead of meropenem. Finally, after an increase in the consumption of macrolides during the first COVID-19 pandemic wave, the consumption of this class of antibiotics has returned to pre-pandemic level. Lessons Constant monitoring of antimicrobial consumption and the identification of warning situations that may need to implement specific actions are the cornerstone of Antimicrobial Stewardship programs. Targets must be defined analyzing data of bacterial resistance rates and infections from multidrug resistant bacteria. Key messages • In Antimicrobial Stewardship programs it is important to adopt constant monitoring of antimicrobial consumption. • Antimicrobial stewardship programs need to be adapted according to the characteristics of each hospital.

L’asthme, le cardiologue, les médicaments : questions soulevées par les macrolides

Erythromycin was discovered in the early 1950s, the development in the 1980s of new generation macrolides with an improvement in their pharmacokinetic properties and their tolerance led to a renewed interest in this family of antibiotics. They are indicated in respiratory tract infections, sexually transmitted diseases and gastrointestinal infections. In addition to their antibacterial property, macrolides would have antiviral and also immunomodulatory properties, which would have motivated the search for new therapeutic indications. After the discovery of the activity of erythromycin on diffuse panbronchiolitis with reduced symptoms and improved life expectancy, studies have shown that macrolides reduce exacerbations in patients with COPD, asthma, bronchiectasis and cystic fibrosis. Macrolides have also been proposed in the treatment of coronary heart disease. In severe asthma, azithromycin has been proposed in certain endotypes as prolonged treatment for several months, the efficacy would be related to an immunomodulatory effect. Prolonged prescription of macrolides, in addition to the risk of resistance development, increases adverse effects. Apart the frequent digestive side effects, macrolides can lead to a prolongation of the QT interval. There is then a risk of torsades de pointes, ventricular tachycardia and ventricular fibrillation. The highest risk is observed with erythromycin, the lowest with azithromycin. Patients with cardiac disorders, as well as those taking anti-arrhythmics or drugs known to cause interactions, should be carefully monitored.

WCK 4873 (INN: Nafithromycin): Structure–activity relationship (SAR) identifying a novel lactone ketolide with activity against Streptococcus pneumoniae (SPN) and Streptococcus pyogenes (SPY)

Ketolides are the fourth generation semisynthetic macrolides derived from erythromycin A, designed to address the limitations of currently available drug treatments including penicillins, macrolides and glycopeptides. Ketolides-the next generation macrolides antibiotics are deliberate to pass the issues of bacterial resistance by introducing keto function at C3 position of macrocycle through the replacement of l-cladinose sugar moiety and brings a broader spectrum of activity. The original research work reported here covers, structure activity relationship based design and synthesis of 34 novel ketolide molecules, are subsequently subjected to desired microbial evaluations. Through this exercise; WCK 4873 (Nafithromycin) has been emerged as clinical candidate among the four different series synthesized. Nafithromycin, consists of novel amidoxime function bearing 2-pyridine-1,3,4-thiadiazole biaryl side chain set apart through a four atom spacer containing a cis double bond and a chiral methyl. This non-flexible spacer possibly aligns the biaryl ring system resulting in a favorable interaction with dual 23S rRNA targets exhibiting better potency to treat gram positive infections. WCK 4873 emerged as preclinical candidate based on in vitro studies, and animal model studies, it had successfully accomplished phase 1 and phase 2 clinical studies in United States, Europe and India. Currently, nafithromycin has acquired the status as phase 3 drug candidate having potential to fulfill the unmet medical needs for treatment of CABP infections.

Derivation and validation of a risk assessment model for drug-resistant pathogens in hospitalized patients with community-acquired pneumonia.

To derive and validate a model for risk of resistance to first-line community-acquired pneumonia (CAP) therapy. We developed a logistic regression prediction model from a large multihospital discharge database and validated it versus the Drug Resistance in Pneumonia (DRIP) score in a holdout sample and another hospital system outside that database. Resistance to first-line CAP therapy (quinolone or third generation cephalosporin plus macrolide) was based on blood or respiratory cultures. This study was conducted using data from 177 Premier Healthcare database hospitals and 11 Cleveland Clinic hospitals. Adults hospitalized for CAP. Risk factors for resistant infection. Among 138,762 eligible patients in the Premier database, 12,181 (8.8%) had positive cultures and 5,200 (3.8%) had organisms resistant to CAP therapy. Infection with a resistant organism in the previous year was the strongest predictor of resistance; markers of acute illness (eg, receipt of mechanical ventilation or vasopressors) and chronic illness (eg, pressure ulcer, paralysis) were also associated with resistant infections. Our model outperformed the DRIP score with a C-statistic of 0.71 versus 0.63 for the DRIP score (P < .001) in the Premier holdout sample, and 0.65 versus 0.58 (P < .001) in Cleveland Clinic hospitals. Clinicians at Premier facilities used broad-spectrum antibiotics for 20%-30% of patients. In discriminating between patients with and without resistant infections, physician judgment slightly outperformed the DRIP instrument but not our model. Our model predicting infection with a resistant pathogen outperformed both the DRIP score and physician practice in an external validation set. Its integration into practice could reduce unnecessary use of broad-spectrum antibiotics.

Antibiotic Exposure during the Preceding Six Months Is Related to Intestinal ESBL-Producing Enterobacteriaceae Carriage in the Elderly

Intestinal carriage of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE carriage) poses a health risk to the elderly. It was aimed to study the prevalence and the risk factors of intestinal ESBL-PE carriage in the elderly. An observational study of a 921-elderly cohort was examined at health checkup for intestinal ESBL-PE carriage at a tertiary medical center in Shanghai. The prevalence and risk factors of intestinal ESBL-PE carriage, especially antimicrobial use in the preceding 9 months, were studied. The prevalence of intestinal ESBL-PE carriage was 53.3% (491/921) in community-dwelling elderly people. A total of 542 ESBL-producing isolates, including E. coli (n = 484) and K. pneumoniae (n = 58), were obtained. On genotyping, the CTX-M-9 ESBL was the most prevalent for 66.0% (358/542) of all isolates. Multivariate analysis showed that antibiotic exposure, age (61–70 years), and nursing home residence were independent risk factors of the ESBL-PE carriage. The analysis on the monthly use of antimicrobials showed that antibiotic exposure during the 6 months prior to sample collection contributed to the high prevalence of ESBL-PE carriage. A single exposure to an antimicrobial increased the risk of the carriage significantly, and the risk increased with the frequency of antimicrobial exposure (RR, 1.825 to 5.255). Prior use of second or third generation cephalosporins, fluoroquinolones, and macrolides increased the risk of the carriage. The results of this study indicate the importance of using antimicrobials judiciously in clinical settings to reduce antimicrobial resistance. Further studies with multiple center surveillance and with comparison of ESBL-PE carriage in the elderly and in the general population simultaneously are needed.

THERAPY OF POULTRY WITH ORNITHOBACTERIOSIS

Ornithobacteriosis, caused by Ornithobacterium rhinotracheale, belongs to the group of respiratory diseases that are currently one of the main problems in industrial poultry, as it leads to significant economic losses due to reduced productivity in commercial and reproductive herds, poor egg production, as well as reducing growth and increasing the death and culling of poultry, high treatment costs. Diagnosis of infections caused by Ornithobacterium rhinotracheale is often difficult because clinical symptoms and postmortem changes are not specific and can be easily confused with those of other infections. The difficulty also lies in the fact that Ornithobacterium rhino-tracheale can be isolated by bacteriological method only in the early stages of the disease. For effective prevention and treatment of ORT use veterinary medicines (VM), namely: tetracyclines; macrolides - tilmicosin, thiamulin; new generation macrolide – eulosin; semi-synthetic penicillin amoxicillin, amoxiclav; germacap - a mixture of aqueous solutions of citrates of zinc, germanium, silver, made on the basis of modern nanotechnology. In Ukraine, there are 29 names of VM for the treatment of poultry against ORT, consisting of one-, 2 and 3 components, namely: doxycycline hyclate, sarafloxacin hydrochloride, tiamulin, tylvalosin, tilmicosin, fluoropheniol; tilmicosin + bromhexine hydrochloride and gentamicin + fluorophenicol+ doxycycline. .Enzyme-linked immunosorbent assay (ELISA) is used to control the presence of ornithobacteriosis in poultry. The presence of antibodies to this pathogen in many species of poultry indicates its wide circulation. A total of 82 batches of broilers and 43 batches of laying hens were tested for ELT serum in ELISA. Positive average titers of antibodies to ORT were detected among meat crosses of 24 batches, which is 29.3%, and egg crosses of 35 batches, which is 81.4%, which indicates a wide circulation of ornithobacteria among poultry. When using Eulosin 625 mg / g at a dose of 25 mg / kg orally with water for 5 days for the treatment of ORT broilers found: high therapeutic effect of the medicine – 82 %, increase in average daily gain - by 2.7%, preservation - by 1.4%; and the efficiency index improved by 5.4 %. To successfully control ORT, it is necessary to carry out a set of veterinary and sanitary measures, as well as constant serological monitoring of blood sera from different age groups of poultry and turkeys in ELISA for specific antibodies, indicating its circulation, in order to conduct timely effective antibiotic therapy.

A nineteen-year report of serotype and antimicrobial susceptibility of enteric non-typhoidal Salmonella from humans in Southern India: changing facades of taxonomy and resistance trend

BackgroundThe steady increase in the proportion of Non-typhoidal Salmonella (NTS) infections in humans represents a major health problem worldwide. The current study investigated the serovar distribution and antimicrobial susceptibility trends of NTS isolated from faecal samples during the period 2000–2018.MethodsFaecal specimens of patients were cultured according to standard lab protocol. The isolates were serotyped and antimicrobial susceptibility testing (AST) were performed according to CLSI guidelines.ResultsA total of 1436 NTS isolates were obtained from faeces samples mostly comprising of S. Typhimurium (27.3%), S. Weltevreden (13%), S. Bareilly (11%), S. Newport (4.2%), S. Cholerasuis (4%), S. Infantis (3.4%), and S. Enteritidis (2.4%). Resistance to nalidixic acid (26%) was most common among the tested NTS, followed by ampicillin (18.5%), cotrimoxazole (13.5%), ciprofloxacin (12%), ceftriaxone (6.3%) and chloramphenicol (3.6%). Multidrug resistance was observed in 5% of NTS isolates with the highest rate (10.52%) in 2014. The incidence of NTS infection was maximum in children < 5 years of age with an average 19.3% of the total affected patients during the time period.ConclusionsBased on this study, the faecal NTS isolates have high resistance rates against first line antimicrobial agents except chloramphenicol. The gradual but consistent increase in resistance to fluoroquinolones, third generation cephalosporins and macrolide may restrict future treatment options. Hence periodic monitoring of NTS infections, serotype distribution and antimicrobial resistance trend is recommended.

Tildipirosin: An effective antibiotic against Glaesserella parasuis from an in vitro analysis

Tildipirosin is a latest generation macrolide that is used to battle infection diseases caused by Gram-negative bacteria. Recent studies have shown the effectiveness of this antimicrobial agent against Actinobacillus pleuropneumoniae; however, little information is available about Glaesserella parasuis, the etiological agent of Glässer's disease. In this study, the Tildipirosin activity to 100 Brazilian clinical isolates of G. parasuis was assessed using a broth microdilution assay. A total of 90% of G. parasuis isolates were sensitive at concentrations ≤ 4 µg/mL Tildipirosin, thus showing to be efficiently controlled by the therapeutic concentration recommended for pigs. On the other hand, a total of ten isolates have shown resistance to this antibiotic, with a minimal inhibitory concentration (MIC) ≥ 8 and ≤ 16 µg/ml. Notably, our findings highly support the use of Tildipirosin for treating Glässer's disease outbreaks, and it also advises the using of MIC approach to monitor the evolution of sensitivity or resistance exhibited by G. parasuis to this molecule, as well as to adjust therapeutic doses when necessary.

SIME: synthetic insight-based macrolide enumerator to generate the V1B library of 1 billion macrolides

We report on a new cheminformatics enumeration technology—SIME, synthetic insight-based macrolide enumerator—a new and improved software technology. SIME can enumerate fully assembled macrolides with synthetic feasibility by utilizing the constitutional and structural knowledge extracted from biosynthetic aspects of macrolides. Taken into account by the software are key information such as positions in macrolide structures at which chemical components can be inserted, and the types of structural motifs and sugars of interest that can be synthesized and incorporated at those positions. Additionally, we report on the chemical distribution analysis of the newly SIME-generated V1B (virtual 1 billion) library of macrolides. Those compounds were built based on the core of the Erythromycin structure, 13 structural motifs and a library of sugars derived from eighteen bioactive macrolides. This new enumeration technology can be coupled with cheminformatics approaches such as QSAR modeling and molecular docking to aid in drug discovery for rational designing of next generation macrolide therapeutics with desirable pharmacokinetic properties.

Evaluation of new generation macrolides for the treatment and metaphylaxis of contagious bovine pleuropneumonia (CBPP) in cattle experimentally infected with Mycoplasma mycoides subspecies mycoides

BackgroundContagious bovine pleuropneumonia (CBPP) caused by Mycoplasma mycoides subspecies mycoides (Mmm) is an important disease of cattle that causes serious economic losses. With the known effectiveness of new generation macrolides, tulathromycin and gamithromycin were assessed in comparison with oxytetracycline as a positive control and saline as a negative control for effectiveness in inhibiting lung lesion development, promoting resolution, preventing spread and bacteriological clearance in susceptible local cattle breeds in two separate studies in Kenya and Zambia. Animals were monitored for clinical signs, sero-conversion as well as detailed post-mortem examination for CBPP lesions.ResultsUsing the Hudson and Turner score for lesion type and size, tulathromycin protected 90%, gamithromycin 80%, and oxytetracycline 88% of treated animals in Kenya. In Zambia, all animals (100%) treated with macrolides were free of lung lesions, while oxytetracycline protected 77.5%. Using the mean adapted Hudson and Turner score, which includes clinical signs, post-mortem findings and serology, tulathromycin protected 82%, gamithromycin 56% and oxytetracycline 80% of the animals in Kenya whereas in Zambia, tulathromycin protected 98%, gamithromycin 94% and oxytetracycline 80%. The saline-treated groups had 93 and 92% lesions in Kenya and Zambia respectively, with Mmm recovered from 5/14 in Kenya and 10/13 animals in Zambia. Whereas the groups treated with macrolides were free from lesions in Zambia, in Kenya 5/15 tulathromycin-treated animals and 6/15 gamithromycin-treated animals showed lesions. Oxytetracycline-treated animals showed similarities with 3/14 and 4/15 showing lesions in Zambia and Kenya respectively and Mmm recovery from one animal in Kenya and six in Zambia. In both studies, lesion scores of saline-treated groups were significantly higher than those of the antibiotic treated groups (p < 0.001). In sentinel animals, CBPP lesions were detected and Mmm recovered from one and two animals mixed with the saline-treated groups in Kenya and Zambia respectively.ConclusionsThis study demonstrated that tulathromycin, a mycoplasmacidal, can achieve metaphylactic protection of up to 80%, while non-recovery of Mmm from sentinels suggests macrolides effectiveness in preventing spread of Mmm. It is recommended that further studies are conducted to evaluate strategies comparing vaccination alone or combining vaccination and antibiotics to control or eradicate CBPP.

Effectiveness of 3rd generation cephalosporin compare to 3rd generation cephalosporin - macrolides for community acquired pneumonia patients in PKU Muhammadiyah Yogyakarta Hospital

Pneumonia is a lung infection caused by bacteria with high fever symptoms accompanied by cough with phlegm, shortness of breath. According to Riskesdas 2013 results, the prevalence of pneumonia based on diagnosis at Yogyakarta Special Region is 1.7% and 4.6%. The researcher has founds 172 adult patients diagnosed pneumonia during 2011-2016 in PKU Muhammadiyah Yogyakarta hospital. This study aims to determine the level of effectiveness between 3rd generation cephalosporins with 3rd generation cephalosporins and macrolides on the outcome of adult patients with pneumonia in PKU Muhammadiyah Yogyakarta hospital period 2015-2017. It was a retrospective cohort study with an affordable population. There were two groups of 3rd generation cephalosporins (n = 24) compared to the 3rd generation cephalosporins and macrolide (n = 13) measured results in the form of body temperature, shortness of breath, leukocyte count, and length of hospitalization using univariate and bivariate analyzes. Based on the results of the study, 70.3% was dominated by men, and 51.4% was dominated by the age group &gt; 59 years. Both of groups showed a significant difference to the temperature where p=0.001 with difference of temperature decrease 0.79 ± 1.06 oC for single group while p=0.049 with difference of temperature decrease 0.65 ± 1.07 oC for combination group; as well as against leukocyte, both of groups had a value of p=0.001 where difference of leucocyte decrease was 4.80 ± 3.92 103/mm3 for single group and 5.43 ± 4.27 103 / mm3 combination group. While both of group showed no significant difference for shortness of breath p=0.638 with OR (95% CI) 2.4 (0.23 – 24.06) and p=0.435 for hospitalization, in single group was 5.88 ± 3.261 days while in combination group was 5.00 ± 1.826, this shows that the combination group had an average length of hospitalization of 0.88 days faster than the single group. The effectiveness between two groups showed a significant difference with p&lt;0.05 on body temperature and leukocyte count. While both groups did not show a significant difference with p&gt;0.05 to shortness of breath and length of stay.

Nationwide survey of indications for oral antimicrobial prescription for pediatric patients from 2013 to 2016 in Japan

BackgroundAntimicrobial resistance is a major public health concern. In 2016, the Japanese government launched a national action plan aimed at achieving a 33% and 50% reduction in the number of total and oral antimicrobial prescriptions (cephalosporins, macrolides, and quinolones) from the 2013 figures by 2020, respectively. The purpose of this study was to investigate the indications for recent antimicrobial prescriptions and to identify the primary targets for intervention to achieve the aims of the government's action plan. MethodsUsing the national health claims database, we retrospectively analyzed oral antibiotic prescriptions for Japanese children aged ≦ 15 years from 2013 to 2016. The trends were analyzed based on days of therapy (DOT) per infectious disease-related visit for each antibiotic. For patients whose chief diagnosis was an infectious disease, the number of antimicrobial prescriptions per diagnosis, their proportion, and the details of the type of antimicrobial were investigated. ResultsIn total, 297,197,328 infectious disease-related visits were identified during 2013–2016. Total antimicrobial prescriptions showed a 3.7% reduction from 1.519 DOT/visitor in 2013 to 1.463 DOT/visitor in 2016 (Ptrend < 0.001). Antimicrobials were prescribed for 31.7% and 36.9% of children with upper and lower respiratory tract infection, accounting for 54.6% and 26.2% of all antimicrobial prescriptions, respectively. Third generation cephalosporins and macrolides comprised the majority of these prescriptions. ConclusionsAntimicrobials were commonly prescribed for children with respiratory infections. Therefore, promoting appropriate antimicrobial use in this population is required to achieve the 2020 goals set by the action plan.

Solithromycin versus ceftriaxone plus azithromycin for the treatment of uncomplicated genital gonorrhoea (SOLITAIRE-U): a randomised phase 3 non-inferiority trial

Antibiotic-resistant gonorrhoea represents a global public health threat, and new therapies are needed. We aimed to compare the efficacy and safety of solithromycin, a fourth generation macrolide, with ceftriaxone plus azithromycin for the treatment of gonorrhoea. We did an open-label, multicentre, non-inferiority trial of patients aged 15 years or older with uncomplicated untreated genital gonorrhoea at two sites in Australia and one site in the USA. Patients were randomly assigned (1:1) to receive single dose oral solithromycin 1000 mg or intramuscular ceftriaxone 500 mg plus oral azithromycin 1000 mg. Neisseria gonorrhoeae cultures were obtained at baseline and test of cure (day 7 ± 2). The primary outcome was the proportion of patients with eradication of genital N gonorrhoeae based on culture at test of cure, assessed in the microbiological intention-to-treat (mITT) population, which included all randomly assigned patients who received any dose of study drug and had a positive genital culture for N gonorrhoeae at baseline. Non-inferiority of solithromycin was to be concluded if the lower limit of the 95% CI for the between-group differences was greater than -10%. Safety was analysed in all patients who received any dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02210325. Between Sept 3, 2014, and Aug 27, 2015, 262 patients were randomly assigned and 261 received treatment (130 in the solithromycin group and 131 in the ceftriaxone plus azithromycin group). In the mITT population, 99 (80%) of 123 patients in the solithromycin group and 109 (84%) of 129 patients in the ceftriaxone plus azithromycin group had N gonorrhoeae eradication at test of cure (difference -4·0%, 95% CI -13·6 to 5·5), thus solithromycin did not meet the criterion for non-inferiority at the prespecified -10% margin. The frequency of adverse events was higher in the solithromycin group than the ceftriaxone plus azithromycin group (69 [53%] of 130 patients vs 45 [34%] of 131 patients), the most common of which were diarrhoea (31 [24%] of 130 patients vs 20 [15%] of 131 patients), and nausea (27 [21%] of 130 patients vs 15 [11%] of 131 patients). Solithromycin as a single 1000 mg dose is not a suitable alternative to ceftriaxone plus azithromycin as first-line treatment for gonorrhoea. If insufficient duration of solithromycin exposure at the infection site in a subset of individuals was the reason for treatment failures, this might be adequately addressed with dose adjustment. However, any further trials with longer dosing need to consider the potential risk of gastrointestinal effects and liver enzyme elevations. Cempra Pharmaceuticals.

Tibola, Debonel ou Senlat, quèsaco ?

Tick-borne lymphadenopathy (Tibola) is an emerging disease caused by rickettsial agents transmitted by Dermacentor ticks.It is also known as Senlat syndrome or Debonel.Incubation is short and mute. The characteristic clinical features is an inoculation eschar at the site of the tick bite (scalp) with cervical or occipital lympnodes which may be painful in half of the cases. It’s a benign disease whose evolution is spontaneously favorable. The most common sequelae that may occur is residual alopecia at the site of tick bite (30% of cases). A chronic asthenia can also persist for several months.The diagnosis is based upon clinical features and epidemiologic signs : after tick bite an necrotic eschar with cervical lymphadenopathy, within the cold season.The diagnosis is based of rickettsia detection on eschar biopsy by PCR before any treatment.In the absence of treatment, the evolution is favorable but the use of cyclines in adults and children over eight years is recommended. Alternatively for children under eight and pregnant women, new generation macrolides can be used. Unfortunately, even started early, treatment does not prevent sequelae such alopecia.

Antibiotic use in emergency departments of class Ⅲ general hospitals in China

Objective: To investigate the utilization of antibiotics in emergency departments (EDs) of class Ⅲ general hospitals in China. Methods: Data from a national monitoring network for rational use of drugs was used. The data included prescriptions of EDs from 114 class Ⅲ general hospitals in 30 provinces (autonomous regions, municipalities) of China. A total of 10 260 595 prescriptions from October 1, 2014 to December 31, 2016 were extracted. The Anatomical Therapeutic Chemical Classification/Defined Daily Dose (DDD) system was used for the classification of antibiotics and calculation of antibiotic use intensity. An auto-regression model was used to analyze the trend over time and seasonal variation of antibiotic use in EDs. Results: The rate of antibiotic prescriptions was 27.82% in EDs, among the antibiotics prescribed, 25.58% were for the combination therapy with 2 or more antibiotic agents, and injectable antibiotic prescriptions accounted for 60.59%. Besides, the number of DDDs per 100 patient visits was 81.84. Broad-spectrum agents were the most commonly used antibiotics, among which the second and third generation cephalosporins, quinolones and macrolides accounted for 23.83%, 21.68%, 19.17% and 7.89% of all prescribed antibiotics, respectively. The use of antibiotics, including prescription frequency and use intensity, in EDs had a slight but significant increase tendency (P<0.05), and the seasonal variation of antibiotic use in EDs was obvious, characterized by the highest frequency and intensity of antibiotic use in winter, the differences were significant (P<0.05). Conclusion: The antibiotic prescription rate in EDs of classⅢ general hospitals in China was controlled at a low level, but the proportions of broad-spectrum antibiotics and injectable antibiotics were high, and a significant increase trend in antibiotic use in EDs was found.

Assessment of prescribing practices at the primary healthcare facilities in Botswana with an emphasis on antibiotics: Findings and implications.

Inappropriate drug prescribing has increased especially in developing countries where systems for monitoring medicine use are not well developed. This increases the rate of antimicrobial resistance. The study aim was to assess the prescribing patterns among urban primary health facilities in Botswana to provide future guidance including developing future quality indicators. Retrospective data from patients' records between January and December 2013 in 19 clinics were collected in a cross-sectional study. The WHO/International Network for Rational Use of Drugs indicators were used to assess prescribing patterns in the study clinics. Average number of drugs per prescription was 2.8; 78.6% of the prescribed antibiotics were by International Non-proprietary Name and 96.1% complied with the Botswana Essential Drugs List. Overall rate of antibiotic prescribing was high (42.7%) with 14.7%, 5.9% and 1.3% of prescriptions having two, three and four antibiotics, respectively. Systemic antibiotics (JO1C) accounted for 45.4% of prescribed antibiotics of which amoxicillin accounted for 28.4% and metronidazole 14.4% of all antibiotic prescriptions. There was low use of co-amoxiclav (0.3% of all antibiotic prescriptions). Third generation cephalosporins and macrolides accounted for 9.8% and 6.2% of antibiotic prescriptions respectively, with no prescribing of fluoroquinolones. The majority of indications (87%) for antibiotic prescriptions were according to ICD classification. While most indications for antibiotic prescriptions were based on signs and symptoms according to ICD, antibiotic prescribing rates were high with some conditions not requiring antibiotics because they are viral infections. There is a need to further improve prescribing practices through induction and training of in-service prescribers. An effective management tool for monitoring antibiotic prescribing practices at Primary Health Care facilities should be designed and implemented, including developing robust quality indicators.

Prescription of antibiotics to pre-school children from 2005 to 2014 in Japan: a retrospective claims database study.

Antibiotics are the most frequently prescribed medications for children but inappropriate antibiotic prescribing is prevalent. The purpose of our study was to access the nationwide trend in antibiotic prescriptions, and to ascertain inappropriate prescribing for upper respiratory infections (URIs) in pre-school children in Japan. Data from the administrative claims database from 2005 January to 2014 September in Japan were examined. We identified outpatient antibiotic prescription claims and described prescription patterns of subjects who were followed from birth to 6 years of age. Logistic regression analyses were performed to estimate odd ratios (ORs) and their 95% confidence intervals (CIs) for factors associated with inappropriate antibiotic prescriptions. Of 155 556 children in the database, 51.6% were male and 48.4% were female. Antibiotics were prescribed for 66.4% of the cohort, with third generation cephalosporin the most prescribed (38.3%), followed by macrolides (25.8%), and penicillin (16.0%). Antibiotic prescriptions for non-bacterial URIs were associated with male gender (OR = 1.06, CI: 1.05-1.07), facility scale, non-pediatrics (OR = 2.11, CI: 2.08-2.14) and out-of-hour visit (OR = 1.64, CI: 1.61-1.68). Third generation cephalosporins and macrolides are widely prescribed to Japanese pre-school children. Furthermore, inappropriate prescriptions for non-bacterial URIs are associated with increasing age, gender, facility characteristics, non-pediatrics and out-of-hour visits.

Next generation macrolides for community-acquired pneumonia: will solithromycin rise to the occasion?

Next generation macrolides for community-acquired pneumonia: will solithromycin rise to the occasion?

Next generation macrolides for community-acquired pneumonia: will solithromycin rise to the occasion?

Community-acquired pneumonia (CAP) remains the leading cause of death by an infectious disease (1). Although the aetiological agent varies by geographical location and population studied, in adults the most commonly isolated pathogens from adult CAP patients are bacteria.

The solithromycin journey—It is all in the chemistry

The macrolide class of antibiotics, including the early generation macrolides erythromycin, clarithromycin and azithromycin, have been used broadly for treatment of respiratory tract infections. An increase of treatment failures of early generation macrolides is due to the upturn in bacterial macrolide resistance to 48% in the US and over 80% in Asian countries and has led to the use of alternate therapies, such as fluoroquinolones. The safety of the fluoroquinolones is now in question and alternate antibiotics for the outpatient treatment of community acquired bacterial pneumonia are needed. Telithromycin, approved in 2003, is no longer used owing to serious adverse events, collectively called the ‘Ketek effects’. Telithromycin has a side chain pyridine moiety that blocks nicotinic acetylcholine receptors. Blockade of these receptors is known experimentally to cause the side effects seen with telithromycin in patients use. Solithromycin is a new macrolide, the first fluoroketolide, which has been tested successfully in two Phase 3 trials and is undergoing regulatory review at the FDA. Solithromycin is differentiated from telithromycin chemically and biologically in that its side chain is chemically different and does not significantly block nicotinic acetylcholine receptors. Solithromycin was well tolerated and effective in clinical trials.