Oral Cephalosporin Research Articles

773. First National Survey of Antibiotic Use Prescribed by All Dentists in Japan from 2015 to 2017 using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB)

BackgroundThe surveillance of antimicrobial use (AMU) among medical doctors and dentists is a key component of the Japanese national plan on antimicrobial resistance (AMR). However, there are no epidemiological studies of AMU among dentists in Japan. We aimed to evaluate the epidemiology of AMU among dentists in Japan and investigate the factors affecting inappropriate prescribing.MethodsTotal AMU among dentists in Japan between 2015 and 2017 was analyzed by using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), from the Ministry of Health, Labor and Welfare of Japan, which accounted for 98% of total claim data in Japan. Antimicrobials were classified by the World Health Organization (WHO) Anatomical Therapeutic Chemical Classification. The WHO measures antimicrobial usage by using the Defined Daily Dose per 1,000 inhabitant-days (DID) parameter. The patterns of oral AMU in 2017 in outpatient settings were compared between in-house and outside prescriptions.ResultsDID values of total AMU in 2015, 2016, and 2017 were 1.23, 1.22, and 1.21, respectively (Figure 1). In 2017, the DID value of oral AMU in outpatient settings was 1.19 (98.4%), comprising cephalosporins (0.76, 63.6%), macrolides (0.23, 18.9%), penicillins (0.12, 10.2%), and quinolones (0.07, 5.5%). DID values of oral AMU in outpatient settings were compared for in-house (0.89, 74.4%) and outside (0.31, 25.6%) prescriptions; in-house resulted in a higher proportion of oral cephalosporins (0.60, 66.9% vs. 0.17, 54.1%), but a lower proportion of oral penicillins (0.08, 9.0% vs. 0.04, 13.8%) (Table 1).ConclusionOral AMU in outpatient settings comprised the highest proportion of antibiotic prescribing by dentists in Japan (98.4%). Oral cephalosporins, the predominant drug type and thought to result from inappropriate prescribing in general, were more frequently prescribed in-house than outside. To tackle AMR, further studies are needed to determine the patient and dentist characteristics encouraging cephalosporin prescription. Disclosures All authors: No reported disclosures.

1148. Antimicrobial Stewardship Program at a Long-term Care Hospital for Severely Handicapped Children and Adults

BackgroundAlthough antimicrobial stewardship program (ASP) is also recommended for a long-term care facility (LTCF), research on ASP in LTCFs is still limited. Our study was conducted at an LTCF offering chronic medical care for pediatric and adult patients with extensive medical needs since childhood. Our aim of this study was to evaluate the impacts of ASP in an LTCF.MethodsA quasi-experimental study was conducted at Tokyo Metropolitan Fuchu Ryoiku Medical Center (250 beds) in Japan. The pre- and post-intervention periods were from April 2013 to March 2017 and April 2017 to March 2019, respectively. Periodic educational interventions were conducted throughout study period. ASP in post-intervention period consisted of mandatory consultation with infectious diseases service at an outside children’s hospital for prescription of restricted drugs. Fluoroquinolones, cefepimes, carbapenems and vancomycin were listed as restricted drugs. Intravenous and oral antimicrobial use was calculated by day of therapy (DOT) per 1,000 patient-days. Interrupted time series analysis was used for level and trend change for pre- and post-intervention periods.ResultsOral agents comprised 89% of the total antimicrobial use. Oral antimicrobials were decreased by 39% in post-intervention with significant level change (P < 0.01) and without trend change (P = 0.61) (Figure 1). Among oral antimicrobials, macrolides, fluoroquinolones and third-generation cephalosporins were decreased by 72% in post-intervention with significant level change (P < 0.01) and without trend change (P = 0.42) (Figure 2). Intravenous antimicrobials were decreased by 40% without level change (P = 0.15) and trend change (P = 0.65) (Figure 3).ConclusionCombining education and mandatory consultation with infectious diseases service for restricted drug enhanced in decreasing total oral antimicrobials at an LTCF. Disclosures All authors: No reported disclosures.

1139. Multidisciplinary Initiative to Increase Guideline-Concordant Antibiotic Prescriptions at Discharge for Hospitalized Children with Uncomplicated Community-Acquired Pneumonia

BackgroundCommunity-acquired pneumonia (CAP) is the most common diagnosis in hospitalized children. The Pediatric Infectious Diseases Society and the Infectious Diseases Society of America published evidenced-based clinical practice guidelines for the management of CAP in children 3 months of age or older in 2011. These guidelines are not consistently followed. Our objective was to evaluate if quality improvement (QI) methods could improve guideline-concordant antibiotic prescribing, specifically addressing the use of oral third-generation cephalosporins, at hospital discharge for children with uncomplicated CAP.MethodsQI interventions, implemented at a single tertiary care children’s hospital in Washington, D.C., focused on key drivers targeting hospital medicine resident teams. Multiple plan-do-study-act (PDSA) cycles were performed. Initial interventions included educational sessions (in small group and lecture formats) aimed at pediatric resident physicians, as well as visual job aids (Figure 1) and guideline summaries posted in resident physician work areas. Interventions were implemented in series to allow for statistical analysis via run chart. Medical records of eligible patients were reviewed monthly after each intervention to determine the impact on appropriate discharge antibiotic prescribing.ResultsAt baseline, the median percentage of children with a diagnosis of uncomplicated CAP discharged with guideline-concordant antibiotics was 50%. Median rates of guideline-concordant antibiotic prescribing improved to 87.5% after initial interventions (Figure 2).ConclusionA fellow-led multidisciplinary QI initiative was successful in decreasing rates of non-guideline-concordant antibiotic prescribing at discharge. These interventions can be tailored for use at other institutions and for other infectious processes with established treatment guidelines. To ensure sustained improvement in guideline-concordant prescribing, future planned interventions include additional educational sessions with residents, faculty, and pharmacists, EMR order set modification and physician benchmarking. These tactics are intended to address the anticipated challenge of resident/faculty turnover and automate antibiotic choice for uncomplicated CAP. Disclosures All authors: No reported disclosures.

1453. Cephalexin and Cefadroxil Are Not Therapeutic Equivalents for Uncomplicated Cystitis (uUTI): Further Analysis of Cefazolin Surrogate Susceptibility Testing Criteria

BackgroundCephalexin (CLEX) and cefadroxil are first-generation oral cephalosporins (OC’s) with similar antimicrobial spectrums, side-effects, and high urine concentrations; and are US-FDA approved for uUTI. Some stewardship programs are replacing CLEX (4 × daily) with cefadroxil (2 × daily) for dosing convenience. The US Committee on Antimicrobial Susceptibility Testing (USCAST) and CLSI recommend a cefazolin (CZOL) UTI surrogate breakpoint (≤16 mg/L; ≥15 mm) to predict susceptibility (S) for 7 OC’s against indicated Enterobacteriaceae. Direct cefadroxil antimicrobial S testing (AST) does not exist in US breakpoint interpretive documents, limiting specific results.MethodsWe reanalyzed and compared the CZOL surrogate testing for cefadroxil, CLEX and 5 other OC’s using AST data previously reported (Schuetz et al., 2013; IHMA). Broth microdilution AST was used against 205 isolates: E. coli (92; 40% with β-lactamase), K. pneumoniae (62), P. mirabilis (31; 10% with β-lactamase), and other enteric bacilli (20). A CZOL surrogate S breakpoint (≤16 mg/L) was used to infer S for OC’s.ResultsCZOL X cefadroxil cross-S accuracy rate was only 91.6% (unacceptable; < 95%) and the false resistance was 1.0% (acceptable). Cross-S accuracy was ≥ 97.0% for all tested OC’s except cefadroxil and cephradine (80.1%). CZOL spectrum vs. tested, indicated species (81.0%) was essentially identical for CLEX, cefprozil, cefaclor and loracarbef (80.0–81.0%). In contrast, cefdinir, cefpodoxime, and cefuroxime axetil S rates were underestimated 5.3 to 10.7% by the surrogate test. CLSI and USCAST did not list cefadroxil or cephradine for CZOL surrogate uUTI prediction; however the current (2019) US-FDA website document states “cefadroxil may be deduced from testing CZOL” regardless of clinical indication.ConclusionCefadroxil -S for guiding uUTI therapy cannot be accurately predicted by CZOL results at ≤16 mg/L (unacceptable surrogate accuracy and compromised spectrum/potency). Furthermore, direct cefadroxil AST does not exist in United States due to lack of breakpoint criteria (CLSI, USCAST) and reagent materials (MIC products or disks). CLEX or other OC’s remain preferred, more active (table) uUTI treatment choices having quality direct or surrogate AST guidances. Disclosures All authors: No reported disclosures.

Efficacy of educational intervention on reducing the inappropriate use of oral third-generation cephalosporins.

This study aimed to evaluate the efficacy of an educational intervention on reducing the inappropriate use of oral third-generation cephalosporins, the prevalence of resistant bacteria, and clinical outcomes. A before-after study was conducted to compare the data for 1 year before and after intervention at a Japanese university hospital. Educational intervention included lectures for all medical staff on oral antibiotics and educational meetings with each medical department. The primary outcome was the use of oral third-generation cephalosporins in inpatients as measured by the monthly median days of therapy (DOTs) per 1000 patient days. Secondary outcomes included the use of each oral antibiotic in inpatients and outpatients, proportion of β-lactamase-nonproducing ampicillin-resistant Haemophilus influenzae (BLNAR), penicillin-resistant Streptococcus pneumoniae (PRSP) and extended-spectrum β-lactamase producing Escherichia coli (ESBLEC), the incidence of hospital-acquired Clostridioides difficile infection (HA-CDI), and hospital mortality. The use of oral third-generation cephalosporins in inpatients was significantly decreased after intervention [DOTs (interquartile range): 24.2 (23.5-25.1) vs. 3.7 (0.0-7.1), P < 0.001], and the value in outpatients was also decreased significantly. The use of fluoroquinolones and macrolides did not increase after intervention. The proportion of BLNAR, PRSP and ESBLEC did not change significantly during the study period. The incidence of HA-CDI was significantly decreased, and hospital mortality did not change after intervention. Educational intervention was effective in reducing the use of oral third-generation cephalosporins without increasing the use of broad-spectrum antibiotics and worsening clinical outcome. The prevalence of resistant bacteria did not change during the study period.

Estudio de sensibilidad de Escherichia coli productores de infecciones del tracto urinario comunitarias en Galicia. Período: 2016-2017

ObjectiveEscherichia coli (E. coli) is responsible for the majority of community urinary tract infections. The objective of the study is to know the sensitivity spectrum of E. coli in urinary tract infections to be able to recommend the appropriate empirical antibiotic treatment. DesignCross-sectional, multicentric, retrospective study. LocationGalician 8 public hospitals, practically the entire population of Galicia (Spain). Participants43,137 outpatients with urinary tract infection due to E. coli isolated in urine in 2016/2017. Main measurementsAnalyzed variables: demographic, minimum inhibitory concentration and interpretation of sensitivity according to CLSI criteria and resistance mechanisms. The antibiotics studied were: ampicillin, amoxicillin-clavulanic acid, ciprofloxacin, cefotaxime, cefepime, gentamicin, nitrofurantoin, fosfomycin, cotrimoxazole, imipenem and ertapenem. The identification and sensitivity were made mainly by automated methods. ResultsThe percentages of non-sensitivity of E. coli isolates were: ampicillin 49.2%, amoxicillin-clavulanic acid 17.8%, cefotaxime 6.7%, cefepime 5.7%, ertapenem 0.04%, imipenem 0.05%, gentamicin 9,1%, ciprofloxacin 26.2%, fosfomycin 3.3%, nitrofurantoin 2.4% and cotrimoxazole 23.9%. The non-sensitivities were higher in men and as age increases. Six percent of E. coli were producers of extended-spectrum beta-lactamases. ConclusionsThe empirical treatment in Galicia for uncomplicated cystitis produced by E. coli in women continues to be nitrofurantoin and fosfomycin. In men under 15 years of age, fosfomycin is indicated and in men older than 15 years, treatment in our environment should include culture and administer a 3rd generation oral cephalosporin empirically. Cotrimoxazole and ciprofloxacin are not recommended as empirical treatment because of their high resistance rates.

Relationship between drug formulary and frequently used cephalosporins, macrolides and quinolones in Japanese hospitals

In Japan, hospitals' pharmaceutical affairs committees freely select the drugs to be purchased depending on the regulations of each hospital. This system poses a risk of the absence of essential drugs or an excess of similar drugs, and may promote inappropriate use of third-generation cephalosporins (3GCs) and quinolones. Against this backdrop, we researched availability of antibacterial agents in Japanese hospitals. We conducted a questionnaire-based study in eastern Shizuoka Prefecture, Japan. Questionnaires were sent to 33 hospitals that had established an interactive regional partnership on infection control. We analyzed the number of available oral cephalosporins, macrolides, and quinolones in each hospital, and the correlation between the number of total available antibacterial agents and the hospital scale and cephalexin availability. Thirty-one hospitals participated in this study. First-generation cephalosporin (1 GC) was available in only 22.5% of them. In all participating hospitals, 3GCs were available, with more than one 3 GC available in 74.2%. Quinolones were available in all hospitals, and more than one quinolone in 67.7%. The numbers of hospital beds and total available antibacterial agents were positively correlated and hospitals that owned cephalexin available also significantly more often owned other available antibacterial agents. 1 GC were available in only a few hospitals, while multiple 3GCs and quinolones were available in most. This situation may lead to excess use of 3GCs or quinolones in Japan. A low number of available drugs was associated with cephalexin unavailability. Outpatient antimicrobial stewardship may focus not only on the quality of medicine, but also on the prescribing environment.

Levels of outpatient prescribing for four major antibiotic classes and rates of septicemia hospitalization in adults in different US states - a statistical analysis

BackgroundRates of sepsis/septicemia hospitalization in the US have risen significantly during recent years. Antibiotic resistance and use may contribute to those rates through various mechanisms, including lack of clearance of resistant infections following antibiotic treatment, with some of those infections subsequently devolving into sepsis. At the same time, there is limited information on the effect of prescribing of certain antibiotics vs. others on the rates of septicemia and sepsis-related hospitalizations and mortality.MethodsWe used multivariable linear regression to relate state-specific rates of outpatient prescribing overall for oral fluoroquinolones, penicillins, macrolides, and cephalosporins between 2011 and 2012 to state-specific rates of septicemia hospitalization (ICD-9 codes 038.xx present anywhere on a discharge diagnosis) in each of the following age groups of adults: (18-49y, 50-64y, 65-74y, 75-84y, 85 + y) reported to the Healthcare Cost and Utilization Project (HCUP) between 2011 and 2012, adjusting for additional covariates, and random effects associated with the ten US Health and Human Services (HHS) regions.ResultsIncrease in the rate of prescribing of oral penicillins by 1 annual dose per 1000 state residents was associated with increases in annual septicemia hospitalization rates of 0.19 (95% CI (0.02,0.37)) per 10,000 persons aged 50-64y, of 0.48(0.12,0.84) per 10,000 persons aged 65-74y, and of 0.81(0.17,1.40) per 10,000 persons aged 74-84y. Increase by 1 in the percent of African Americans among state residents in a given age group was associated with increases in annual septicemia hospitalization rates of 2.3(0.32,4.2) per 10,000 persons aged 75-84y, and of 5.3(1.1,9.5) per 10,000 persons aged over 85y. Average minimal daily temperature was positively associated with septicemia hospitalization rates in persons aged 18-49y, 50-64y, 75-84y and over 85y.ConclusionsOur results suggest positive associations between the rates of prescribing for penicillins and the rates of hospitalization with septicemia in US adults aged 50-84y. Further studies are needed to better understand the potential effect of antibiotic replacement in the treatment of various syndromes, including the potential impact of the recent US FDA guidelines on restriction of fluoroquinolone use, as well as the potential effect of changes in the practices for prescribing of penicillins on the rates of sepsis-related hospitalization and mortality.

Ilizarov external fixation without bone graft for atrophic femoral shaft nonunion

To explore the effectiveness of Ilizarov external fixation without bone graft in the treatment of atrophic femoral shaft nonunion. The clinical data of 12 patients with atrophic femoral shaft nonunion admitted between October 2010 and January 2017 were retrospectively analyzed. There were 8 males and 4 females, aged from 24 to 61 years, with an average age of 41.7 years. The nonunion sites located in the middle and upper femur in 7 cases and in the distal femur or supracondylar in 5 cases. The disease duration ranged from 1 to 9 years, with an average of 3.7 years. Previous operations ranged from 1 to 9 times, with an average of 2.8 times. The original fixator was removed, the fracture end of nonunion was debrided, and Ilizarov external fixator was installed. In patients with the length of bone defect less than 4 cm, direct compression fixation was performed during operation; in patients with limb shortening more than 2.5 cm, proximal femoral osteotomy and bone lengthening components were required to prepare limb lengthening after operation; all patients did not receive bone graft. The wearing time of external fixator, clinical bone healing time of nonunion fracture end, and complications were recorded. The effectiveness was evaluated by Paley's nonunion evaluation criteria. All patients were followed up 24-50 months, with an average of 30 months. Bony union was achieved in all 12 cases with a healing time of 6.0-23.5 months (mean, 11.5 months). The wearing time of external fixator ranged from 7 to 25 months, with an average of 13.5 months. At last follow-up, according to Paley's nonunion evaluation criteria, the results were excellent in 6 cases, good in 4 cases, and fair in 2 cases, with an excellent and good rate of 83.3%. Sagittal angulation deformity of femur more than 7° occurred in 4 cases, with no significant effect on knee extension function, and no special treatment such as osteotomy was performed. Two patients had shorter limbs (>2.5 cm) after operation and were replaced by high shoes; 4 patients with trans-knee fixation lost knee joint mobility of 10-30° after operation; 10 cases of needle tract infection occurred, of which 4 cases with infection and loosening of fixed needle were replaced and re-fixed after needle extraction, the remaining 6 cases of infection without loosening of fixed needle were controlled by local dressing change, needle nursing, and oral cephalosporin anti-inflammatory drugs. No complications such as deep infection and vascular nerve injury occurred. Ilizarov external fixation has a high healing rate for atrophic femoral shaft nonunion, which is relatively minimally invasive and can avoid bone grafting. Its preliminary effectiveness is exact, and it is also effective for patients who have experienced multiple failed operations. It is necessary to pay attention to the nursing and rehabilitation training after external fixation.

Treatment of community-acquired pneumonia in the outpatient setting: learning to fail forward to success

Due to increase in S. pneumonia resistance to penicillin, macrolides and oral cephalosporin, the treatment of community-acquired pneumonia in children has to be revised. The article presents current (Eurasian and WHO) recommendations on the choice of rational antibiotic therapy for pneumonia in the outpatient setting. The common mistakes in choosing an initial antibacterial drug, replacing an antibiotic, if it is ineffective, and prescribing inadequate dosage are shown by two clinical examples from real outpatient practice. Due to mistakes in the treatment, pneumonia may take a more protracted course and complicate the clinical situation, forcing the physicians to resort to additional tests.

In Vitro Pharmacodynamics of a Novel Ceftibuten-Clavulanate Combination Antibiotic against Enterobacteriaceae.

A novel antibiotic combination of the oral cephalosporin ceftibuten (CTB) and the β-lactamase inhibitor clavulanate (CLA) is currently in development for urinary tract infections, including those caused by extended-spectrum-β-lactamase (ESBL)-producing organisms. This study aimed to identify the pharmacodynamic index and magnitude of this index for CLA, when combined with a fixed CTB exposure (∼59% free time above the CTB-CLA MIC) against ESBL-producing Escherichia coli and Klebsiella pneumoniae (CTB-CLA MICs of 0.25/0.125 to 1/0.5 μg/ml) using the in vitro chemostat model. Dose fractionation studies identified the time that free CLA concentrations remained above a threshold concentration (fT>threshold) to be the best pharmacodynamic index (R2 = 0.85) compared with the free area under the curve (AUC)/threshold ratio (R2 = 0.62) and free maximum concentration/threshold ratio (R2 = 0.37). For E. coli isolates, stasis and 1-log10 CFU reductions were achieved at 30.9 and 47.9% fT>CTB concentrations of the 2:1 CTB-CLA MIC (fT>MIC here), respectively. For K. pneumoniae isolates, stasis and 1-log10 CFU reductions were achieved at 51.9 and 92.0% fT>MIC, respectively. These data inform exposure requirements for CLA combined with CTB for optimizing pharmacodynamics against Enterobacteriaceae and should be useful in designing dosage regimens for this combination antibiotic.

Effective Oral Combination Treatment for Extended-Spectrum Beta-Lactamase-Producing Escherichia coli.

Background: Extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) is increasing worldwide. The drugs of choice for treatment of ESBLs are parenteral carbapenems. The aim of this study was to evaluate the in vitro and in vivo efficacy of a new combination of oral cephalosporins and amoxicillin/clavulanate in treatment of ESBL-EC. Methods: A total of 150 ESBL-EC samples were collected over 1 year from two referral centers. Synergistic studies of cephalosporins and amoxicillin/clavulanate were performed in vitro using disk approximation and disk replacement methods. Combination treatment was assessed in vivo on 20 ESBL-EC urinary tract infection (UTI) patients. Results: ESBL-EC isolates were confirmed in 150 patients with a mean age of 46.67 years, 75.2% of them being women. Antibiotic susceptibility testing of isolates indicated high resistance rate to oral antibiotics. The frequency of positive synergy and mean distance of synergy between cephalosporins and amoxicillin/clavulanate was significantly higher with cefotaxime and cefixime compared with cefpodoxime, cefdinir, and ceftazidime using disk approximation and disk replacement methods (p < 0.05). Addition of amoxicillin/clavulanate enhanced the susceptibility rate with cefixime from 8.6% to 86.3%, significantly higher than with other cephalosporins (p < 0.0005). Cefixime and amoxicillin/clavulanate synergy was not affected by age, gender, hospital, department, sample type, or bacterial load. Eighteen of 20 ESBL-EC-positive UTI patients had a positive in vitro synergy test and complete clinical and microbiological resolution after completion of cefixime and amoxicillin/clavulanate oral treatment course. Conclusions: Cefixime and amoxicillin/clavulanate combination therapy could be an effective oral outpatient treatment option for ESBL-EC. In vitro synergistic testing is simple and predictive of successful treatment.

Efficacy and safety of cefditoren pivoxil for exacerbations of chronic obstructive pulmonary disease: A prospective multicenter interventional study

Oral antibiotic therapy for patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) usually involves an aminopenicillin with clavulanic acid, a macrolide, or a quinolone. To date, however, the clinical efficacy and safety of the oral cephalosporin cefditoren pivoxil has not been evaluated in Japanese patients with acute exacerbations of COPD. We conducted a prospective, multicenter, single arm, interventional study from January 2013 to March 2017 to determine the efficacy and safety of oral administration of 200 mg cefditoren pivoxil three times daily for 7 days in a cohort of 29 eligible patients from 15 hospitals. The mean age (SD) of participants was 73.1 (8.1) years and 28 had a smoking history (the mean [SD] of smoking index, 1426.7 [931.7]). The primary efficacy endpoint was clinical response (cure rate) at test of cure, which was set at 5–10 days after treatment ceased. Of the 23 patients finally analyzed, cure was achieved in 15 (65.2%), while 8 (34.8%) remained uncured. Previous experience of acute exacerbations significantly affected the cure rate: none of the three patients who had at least two prior exacerbations were cured, while 15 of the 20 patients with one or fewer prior exacerbations were cured (p = 0.032). The microbiological eradication rate was 88.9% at test of cure. During treatment, mild pneumonia was reported as an adverse event in one patient (3.4%) but resolved within 10 days of onset. We conclude that cefditoren pivoxil represents a viable alternative for antibiotic therapy in patients with few prior exacerbations.

The Role of Pharmacists in Antimicrobial Stewardship

Antimicrobial resistance (AMR) has been declared a global public health emergency, necessitating the involvement of the whole of society to address this increasingly serious threat. AMR causes prolonged illness, greater risk of infection spread, increased morbidity, and higher mortality rates, which result in increased expenses to the government, healthcare services, and individuals. Inappropriate use of antimicrobials has been indicated as the primary cause for the global expansion of AMR. Under these circumstances, various countries have formulated suitable national action plans to curb AMR. In Japan, the national action plan on AMR was announced in April 2016. Our previous study clarified that orally administered antimicrobials accounted for approximately 90% of total consumption: oral third-generation cephalosporins, macrolides, and fluoroquinolones accounted for approximately 77% of oral consumption. Therefore pharmacists must extend their support for the appropriate use of antimicrobials prescribed by attending physicians to not only hospitalized patients but also outpatients. "Choosing wisely," a US-based health education campaign, warns against unnecessary use of antimicrobials. Pharmacists should strive to disseminate the concept of "choosing wisely" in relation to other medicines, implement further interventions, and evaluate them. In this article, we present data on use of antimicrobials in Japan, and mention how pharmacists should be involved in enabling physicians choose antimicrobials wisely.

Oral Eruption Associated With Cefuroxime Axetil: An Unusual Complication

Cefuroxime Axetil is an oral cephalosporin class of antibiotic having broader gram negative activity and used in infective conditions caused by facultative bacteria and anaerobes such as respiratory tract infection, intra-abdominal infection, pelvic inflammatory disease and diabetic foot infection etc. Severe oral eruption associated with swelling on lips and mucosal erythemas are not described previously as ADR due to Cefuroxime. Here, we report a case of severe oral eruption induced by Cefuroxime Axetil. An adult male of 27 y of age received Cefuroxime Axetil with Paracetamol tablet for upper respiratory tract infection. Three days after ingestion of the above drugs, the patient developed severe oral eruption associated with swelling on lips, mucosal erythema and multiple whitish spots on face. This case was managed by withdrawal of cefuroxime with symptomatic therapy. Thus, it is important to recognize such type of reaction and manage it to prevent fatality. Keywords: Cefuroxime Axetil, paracetamol, respiratory tract infection, oral eruption, mucosal erythema Cite this Article Himanshu Bhusan Sahoo, Bandana Rath, Jayanti Prava Behera et al . Oral eruption associated with cefuroxime axetil: an unusual complication. Research & Reviews: Journal of Health Professions . 2015; 5(3): 16–18p.

Пероральные цефалоспорины III поколения при внебольничных инфекциях мочевых путей: современные аспекты применения

Пероральные цефалоспорины III поколения при внебольничных инфекциях мочевых путей: современные аспекты применения

Appropriate Prophylactic Antibiotic Use in Clean Wound Surgery Under Local Anesthesia.

BackgroundAlthough guidelines to prevent surgical site infections (SSIs) were published more than a decade ago, prophylactic antibiotics are still used subjectively in clinical practice. In this study, we evaluated the safety of single-dose preoperative intravenous antibiotics without postoperative antibiotics in the field of clean wound surgery performed under local anesthesia. We also surveyed the present clinical conditions for prophylactic antibiotic use in the plastic surgery departments of training hospitals in Korea.MethodsA total of 360 consecutive patients who underwent clean wound surgery under local anesthesia in an outpatient clinic from March 2018 to October 2018 were reviewed. In the study group, a single surgeon administered first-generation cephalosporins intravenously within 1 hour of skin incision and did not prescribe additional antibiotics. In the control group, 2 other surgeons prescribed oral first-generation cephalosporins postoperatively for 2 to 3 days without preoperative antibiotics. A telephone survey about perioperative antibiotic regimens was conducted at the departments of plastic surgery in training hospitals.ResultsThere were 128 patients in the study group and 232 patients in the control group. There were no significant differences between the 2 groups regarding SSIs and other surgical complications. A total of 41 training hospitals answered the survey and every hospital had protocols of prescribing postoperative oral antibiotics routinely at the time of discharge with a mean duration of 3.9 days. Only 11 hospitals (26.8%) prescribed parenteral antibiotics before surgery as well as postoperative oral antibiotics.ConclusionIntravenous injection of single-dose first-generation cephalosporins 1 hour before surgery without postoperative antibiotics did not increase the incidence of SSIs compared with the usual practice of giving only postoperative antibiotics prescription for 2 to 3 days in cases of clean wound surgery performed under local anesthesia. Proper antibiotic prophylaxis should be performed by surgeons in training hospitals without hesitation.

Regional Variation of Antimicrobial Use in Japan from 2013-2016, as Estimated by the Sales Data.

The National Action Plan on Antimicrobial Resistance in Japan aims to achieve a 50% reduction in the use of broad-spectrum oral antimicrobials (cephalosporins, macrolides, and quinolones) from 2013 to 2020. Based on the national sales data for antimicrobials, we estimated the regional antimicrobial use (AMU) from 2013-2016 and evaluated the differences in the use of broad-spectrum oral antimicrobials among three regions in which differences had been identified previously. The AMU was standardized based on the defined daily dose (DDD) and described as the DDDs/1,000 inhabitants/day (DID). Annual combined total oral and parenteral AMU during 2013-2016 was 14.9, 14.5, 14.7, and 14.6 DID, respectively. The change in mean ± standard deviation in the total AMU at the prefectural level was - 0.2 ± 0.8 DID. Among the 47 prefectures, decreasing trends were observed in 34, while in the remaining 13 prefectures increasing trends were recorded. In 2016, no significant differences in the mean usage of oral cephalosporins among the three regions were observed. The mean usage of oral macrolides in the eastern (4.1 DID) was significantly lower than that in the central region (4.7 DID) (p = 0.009) and the western (4.8 DID) (p = 0.002). The mean usage of oral quinolones in the western (3.2 DID) was significantly higher than that in the eastern (2.3 DID) (p ＜ 0.001) and central (2.7 DID) (p = 0.001) regions. To determine appropriate targets for the implementation of antimicrobial stewardship for reducting the use of broad-spectrum oral antimicrobials, further studies are required to identify the reasons underlying these differences.

Oral sitafloxacin vs intravenous ceftriaxone followed by oral cefdinir for acute pyelonephritis and complicated urinary tract infection: a randomized controlled trial.

BackgroundThe conventional antibiotic regimen for community-acquired upper urinary tract infections with moderate severity in Thailand is parenteral ceftriaxone (CTRX) for several days followed by oral cephalosporin for 7–14 days. The aim of this study was to compare the efficacy and safety of oral sitafloxacin (STFX) with that of intravenous CTRX followed by oral cefdinir (CFDN) for the therapy of acute pyelonephritis (APN) and complicated urinary tract infection (cUTI).MethodsThis open-label, randomized, controlled, noninferiority clinical trial included patients from nine centers across Thailand. Adult patients with APN or cUTI were randomly assigned to receive 100 mg of oral STFX twice daily for 7–14 days, or 2 g of intravenous CTRX for several days followed by 100 mg of oral CFDN three times per day for another 4–12 days.ResultsA total of 289 adult patients with APN or cUTI (141 in the STFX group and 148 in the CTRX/CFDN group) were included in the intent-to-treat (ITT) analysis, and 211 patients (108 in the STFX group and 103 in the CTRX/CFDN group) were included in the per-protocol (PP) analysis. The baseline characteristics of patients in both groups were comparable. The causative pathogen in most patients with APN or cUTI was Escherichia coli. The clinical success rates at the end of treatment revealed the STFX regimen to be noninferior to the CTRX/CFDN regimen (86.6% vs 83.8% for ITT analysis and 97.2% vs 99.0% for PP analysis, respectively). Adverse events with mild-to-moderate severity were similar between groups.ConclusionOral STFX is noninferior to intravenous CTRX followed by oral CFDN in adult patients with APN and cUTI. Lower rates of resistance compared to CTRX and/or CFDN and oral administration suggest STFX as a more attractive treatment option in this patient population.

Antibiotic-associated adverse drug events at a Japanese academic hospital.

To promote antimicrobial stewardship activity, an understanding of the incidence of antibiotic-associated adverse drug events (ADEs) is essential. In this study, we aimed to describe the occurrence of antibiotic-associated ADEs at our hospital. We retrospectively searched the ADE registration system in Osaka University Hospital between 2010 and 2017. Registrations of ADEs were dependent on the patients' drug history and clinical course after hospitalization. We classified the data according to types of ADEs (gastrointestinal, hepatobiliary, renal, cardiac, respiratory, hematologic, neurologic, dermatologic, and musculoskeletal) and antibiotic class. During the study period, we found 707 cases of antibiotic-associated ADEs, accounting for 22.3% of all the cases. Beta-lactam antibiotics constitute more than half of the cases (51.3%). The most common ADE was dermatologic abnormalities (53.4%), followed by liver dysfunction (9.7%) and gastrointestinal symptoms (8.9%). Among all antibiotics, oral third-generation cephalosporins were frequently reported as offending drugs (107 cases), accounting for 29.5% of beta-lactam ADEs and 46.3% of cephem ADEs. Antibiotic-associated ADEs covered approximately 20% of all the ADEs at our hospital. We believe that the data would be helpful in ensuring patient safety by promoting antimicrobial stewardship in hospitals.