Search

This study aimed to clarify other diseases claimed simultaneously with acute upper respiratory infection (URI), antibiotic prescriptions, and examinations associated with infectious diseases in pediatric patients with acute URI insurance claims at otorhinolaryngology outpatient visits. Pediatric patients who visited an otolaryngology department between 2019 and 2021 and were definitively diagnosed with URI were selected using a large Japanese medical claims database. Patient backgrounds, antibiotic use, and examinations were descriptively evaluated. In total, 8010 patients were included in the analysis. The median number (interquartile range) of diseases claimed in the same month as acute URI was 4 (3–6). Only 519 (6.5 %) patients were claimed as acute URI alone. Regardless of the prescription of antibiotics, the most commonly redundantly claimed disease in these patients was allergic rhinitis, followed by acute bronchitis, acute sinusitis, and earwax impaction. The frequently prescribed antibiotics were third-generation cephalosporins, macrolides, and penicillins with extended-spectrum, including amoxicillin which was recommended by the Japanese manual; the proportion of patients with examinations was low (2.9–21.7 %). Among patients with acute URI, diagnoses requiring antibiotics were also claimed; therefore, when evaluating acute URI using the Japanese medical claims database, care must be taken in patient selection. Moreover, the implementation rate of examinations necessary for diagnosis was low, so there is an urgent need to develop an environment where examinations can be conducted in outpatient settings. [ABSTRACT FROM AUTHOR]

Background The choice of prophylactic antibiotics for use in endonasal transsphenoidal surgery (ETSS) lacks universal standards. This study aimed to investigate the effectiveness of cefazolin, ampicillin and third-generation cephalosporins for preventing postoperative meningitis and secondary outcomes (in-hospital death and the combination of pneumonia and urinary tract infection) in patients who have undergone ETSS. Methods The study used data from the Diagnosis Procedure Combination database in Japan. Data from 10 688 patients who underwent ETSS between April 2016 and March 2021 were included. Matching weight analysis based on propensity scores was conducted to compare the outcomes of patients receiving cefazolin, ampicillin or third-generation cephalosporins as prophylactic antibiotics. Results Of the 10 688 patients, 9013, 102 and 1573 received cefazolin, ampicillin and third-generation cephalosporins, respectively. The incidence of postoperative meningitis did not significantly differ between the cefazolin group and the ampicillin group (OR, 1.02; 95% CI, 0.14–7.43) or third-generation cephalosporins group (OR, 0.81; 95% CI, 0.10–6.44). Similarly, in-hospital death and the composite incidence of pneumonia and urinary tract infection did not differ between the cefazolin group and the ampicillin or third-generation cephalosporins group. Conclusions Cefazolin, ampicillin and third-generation cephalosporins as perioperative prophylactic antibiotics for ETSS do not differ significantly in terms of preventing meningitis. [ABSTRACT FROM AUTHOR]

• This is the first multicenter study on extended-spectrum beta-lactamase–related febrile urinary tract infections in Japanese children. • Risk factors include previous history of febrile urinary tract infections and recent antibiotic use. • Most patients who started on discordant antibiotics experienced clinical improvement. The incidence of infections caused by extended-spectrum beta-lactamase (ESBL)–producing bacteria has increased. This study aimed to clarify the risk factors and treatment strategies for febrile urinary tract infection (fUTI) caused by ESBL-producing bacteria in Japanese children. A retrospective observational study was conducted in 21 hospitals among children aged <16 years diagnosed with an fUTI between 2008 and 2017. Clinical data of children with fUTI caused by ESBL-producing and non-ESBL–producing bacteria were compared. Of the 2049 cases of fUTI, 147 (7.2%) were caused by ESBL-producing bacteria. Children in the ESBL group were more likely to have a history of recent antibiotic use or prophylactic antibiotic use, and experience recurrent UTIs (P <0.001) compared with those in the non-ESBL group. Of the 124 cases of fUTI due to ESBL-producing bacteria that were reviewed, 20 and 100 had concordant and discordant antibiotic use, respectively, and four had unknown antibiotic susceptibility. The median time from the start of treatment to fever resolution was 24 hours and did not differ significantly by therapy group (P = 0.39). ESBL-producing bacteria should be considered in children with recurrent UTIs and recent antibiotic use. Most children with fUTI experience clinical improvement regardless of the choice of antibiotic. [ABSTRACT FROM AUTHOR]

Oral antibiotic therapy is routinely administered when a third molar (M3) is extracted to prevent infectious complications after surgery. Oral third-generation cephalosporins are frequently used after M3 extraction in Japan but at the expense of an increased risk of antimicrobial resistance. Therefore, the infection control team (ICT) at our institution recommended a reduction in use of these agents after M3 extraction. In this study, we compared the types of antibiotic agents prescribed for patients undergoing M3 extraction before and after this recommendation. We investigated the relationship between type of antibiotic used and the likelihood of infectious complications as well as cost savings in patients who underwent M3 extraction in the 6 months before and after the ICT recommendation in July 2018. There was a marked reduction in use of oral third-generation cephalosporins after M3 extraction (P < 0.0001) and increased use of oral penicillins and first-generation cephalosporins after the ICT recommendation. Moreover, surgical site infection (SSIs) were significantly less common after the ICT recommendation (P = 0.0099); however, the SSI rate was higher in patients who received a third-generation cephalosporin than in those who received penicillin (8.8% vs 0.5%). There was also a significant saving in per-patient antibiotic costs after the ICT recommendation (269.5 ± 282.0 JPY vs 454.7 ± 376.6 JPY; P < 0.0001). These findings suggest that collaboration with an ICT promotes appropriate antibiotic use, decreases the risk of an SSI, and improves the cost-benefit ratio in patients undergoing M3 extraction. [ABSTRACT FROM AUTHOR]

Background: In this age of antimicrobial resistance, unnecessary use of antibiotics to treat non-bacterial acute respiratory tract infections (ARTIs) and inappropriate use of antibiotics in treating bacterial ARTIs are public health concerns.Purpose: Our aim is to identify the pattern of oral antibiotic prescriptions for outpatients with ARTIs in Japan.Methods: We analysed health insurance claims data of patients (aged ≤74 years) from 2013 to 2015, to determine the pattern of antibiotic prescriptions for outpatient ARTIs and calculated the proportion of each antibiotic.Results: Data on 4.6 million antibiotic prescriptions among 1559394 outpatients with ARTIs were analysed. The most commonly prescribed classes of antibiotics included cephalosporins (41.9%), macrolides (32.8%) and fluoroquinolones (14.7%). The proportion of first-, second- and third-generation cephalosporins was 1.0%, 1.7% and 97.3%, respectively. Fluoroquinolones accounted for a quarter of the prescriptions for ARTIs in patients aged >20 years. In contrast, penicillins accounted for just 8.0% of the total number of antibiotic prescriptions for ARTIs.Conclusions: According to clinical guidelines, penicillins are first-line antibiotics against ARTIs. However, third-generation cephalosporins, macrolides and fluoroquinolones are more frequently prescribed in Japan. Although we could not assess the extent to which appropriate antibiotics are selected, our results support the necessity of improving antibiotic choices in the treatment of ARTIs. [ABSTRACT FROM AUTHOR]

Cefiderocol is an injectable siderophore cephalosporin discovered and being developed by Shionogi & Co., Ltd., Japan. As with other β-lactam antibiotics, the principal antibacterial/bactericidal activity of cefiderocol occurs by inhibition of Gram-negative bacterial cell wall synthesis by binding to penicillin binding proteins; however, it is unique in that it enters the bacterial periplasmic space as a result of its siderophore-like property and has enhanced stability to β-lactamases. The chemical structure of cefiderocol is similar to both ceftazidime and cefepime, which are third- and fourth-generation cephalosporins, respectively, but with high stability to a variety of β-lactamases, including AmpC and extended-spectrum β-lactamases (ESBLs). Cefiderocol has a pyrrolidinium group in the side chain at position 3 like cefepime and a carboxypropanoxyimino group in the side chain at position 7 of the cephem nucleus like ceftazidime. The major difference in the chemical structures of cefiderocol, ceftazidime and cefepime is the presence of a catechol group on the side chain at position 3. Together with the high stability to β-lactamases, including ESBLs, AmpC and carbapenemases, the microbiological activity of cefiderocol against aerobic Gram-negative bacilli is equal to or superior to that of ceftazidime-avibactam and meropenem, and it is active against a variety of Ambler class A, B, C and D β-lactamases. Cefiderocol is also more potent than both ceftazidime-avibactam and meropenem versus Acinetobacter baumannii, including meropenem non-susceptible and multidrug-resistant (MDR) isolates. Cefiderocol's activity against meropenem-non-susceptible and Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriales is comparable or superior to ceftazidime-avibactam. Cefiderocol is also more potent than both ceftazidime-avibactam and meropenem against all resistance phenotypes of Pseudomonas aeruginosa and against Stenotrophomonas maltophilia. The current dosing regimen being used in phase III studies is 2 g administered intravenously every 8 h (q8 h) using a 3-h infusion. The pharmacokinetics of cefiderocol are best described by a three-compartment linear model. The mean plasma half-life (t½) was ~ 2.3 h, protein binding is 58%, and total drug clearance ranged from 4.6-6.0 L/h for both single- and multi-dose infusions and was primarily renally excreted unchanged (61-71%). Cefiderocol is primarily renally excreted unchanged and clearance correlates with creatinine clearance. Dosage adjustment is thus required for both augmented renal clearance and in patients with moderate to severe renal impairment. In vitro and in vivo pharmacodynamic studies have reported that as with other cephalosporins the pharmacodynamic index that best predicts clinical outcome is the percentage of time that free drug concentrations exceed the minimum inhibitory concentration (%fT > MIC). In vivo efficacy of cefiderocol has been studied in a variety of humanized drug exposure murine and rat models of infection utilizing a variety of MDR and extremely drug resistant strains. Cefiderocol has performed similarly to or has been superior to comparator agents, including ceftazidime and cefepime. A phase II prospective, multicenter, double-blind, randomized clinical trial assessed the safety and efficacy of cefiderocol 2000 mg q8 h versus imipenem/cilastatin 1000 mg q8 h, both administered intravenously for 7-14 days over 1 h, in the treatment of complicated urinary tract infection (cUTI, including pyelonephritis) or acute uncomplicated pyelonephritis in hospitalized adults. A total of 452 patients were initially enrolled in the study, with 303 in the cefiderocol arm and 149 in the imipenem/cilastatin arm. The primary outcome measure was a composite of clinical cure and microbiological eradication at the test-of-cure (TOC) visit, that is, 7 days after the end of treatment in the microbiological intent-to-treat (MITT) population. Secondary outcome measures included microbiological response per pathogen and per patient at early assessment (EA), end of treatment (EOT), TOC, and follow-up (FUP); clinical response per pathogen and per patient at EA, EOT, TOC, and FUP; plasma, urine and concentrations of cefiderocol; and the number of participants with adverse events. The composite of clinical and microbiological response rates was 72.6% (183/252) for cefiderocol and 54.6% (65/119) for imipenem/cilastatin in the MITT population. Clinical response rates per patient at the TOC visit were 89.7% (226/252) for cefiderocol and 87.4% (104/119) for imipenem/cilastatin in the MITT population. Microbiological eradication rates were 73.0% (184/252) for cefiderocol and 56.3% (67/119) for imipenem/cilastatin in the MITT population. Additionally, two phase III clinical trials are currently being conducted by Shionogi & Co., Ltd., Japan. The two trials are evaluating the efficacy of cefiderocol in the treatment of serious infections in adult patients caused by carbapenem-resistant Gram-negative pathogens and evaluating the efficacy of cefiderocol in the treatment of adults with hospital-acquired bacterial pneumonia, ventilator-associated pneumonia or healthcare-associated pneumonia caused by Gram-negative pathogens. Cefiderocol appears to be well tolerated (minor reported adverse effects were gastrointestinal and phlebitis related), with a side effect profile that is comparable to other cephalosporin antimicrobials. Cefiderocol appears to be well positioned to help address the increasing number of infections caused by carbapenem-resistant and MDR Gram-negative bacilli, including ESBL- and carbapenemase-producing strains (including metallo-β-lactamase producers). A distinguishing feature of cefiderocol is its activity against resistant P. aeruginosa, A. baumannii, S. maltophilia and Burkholderia cepacia. [ABSTRACT FROM AUTHOR]

Objectives: We examined four clinical strains of Neisseria gonorrhoeae (GU030113, GU110095, GU110332 and GU110362) isolated between 2000 and 2014 in Japan, exhibiting ceftriaxone MICs of 0.5 mg/L, for mutations of the genes associated with penicillin resistance.Methods: The penA, mtrR, porB1b (penB), ponA and pilQ genes of the strains were sequenced. PBP2s of the strains were aligned to the PBP2s associated with decreased susceptibility to oral cephalosporins, and PBP2s of previously reported strains with decreased susceptibility to ceftriaxone.Results: GU030113 had PBP2 pattern X with an additional substitution of A502T. GU110095 had PBP2 pattern XXVII. GU110332 had PBP2 pattern XXXIV with an additional substitution of P552S. GU110362 had PBP2 composed of pattern X (amino acid positions 1-291) and pattern V (amino acid positions 292-576). GU030113, GU110095 and GU110332 had deletion of A in the mtrR promoter, G120K and A121D or A121N in PorB1b and L421P in PBP1. GU110362 had A40D in the repressor of MtrR and L421P in PBP1. The strains did not have mutations of pilQ1 and pilQ2.Conclusions: Addition of A502T to PBP2 pattern X in GU030113 and of P552S to PBP2 pattern XXXIV in GU110332 would possibly contribute to decreased susceptibility to ceftriaxone. In GU110095 and GU110362, it was suggested that, in addition to their altered PBP2s, the enhanced efflux pump, reduced permeability in the outer membrane, another altered target of β-lactams and/or other mechanisms not identified in the present study might contribute to decreased susceptibility. [ABSTRACT FROM AUTHOR]

The article discusses a reports about the colistin-resistant Escherichia coli isolates from Japan, including a global-spreading pathogenic lineage. E. coli isolates obtained from clinical specimens taken at Sapporo Clinical Laboratory Inc. and Sapporo Medical University Hospital in Japan were tested and four E. coli isolates exceeded the colistin resistance breakpoint. The colistin-resistant isolates reported were resistant to fluoroquinolones, and one (SME296) was resistant to cephalosporins.

Bacterial meningitis is a serious problem in pediatric clinics and, therefore, needs urgent and empirical chemotherapy. We investigated 1,116 cases of empirical chemotherapy of patients aged older than 4 months from 1997 through 2008 by sending questionnaires. A single antibiotic treatment was carried out in less than 30% of the cases throughout the years, whereas the combination of two antibiotics had been practiced in more than 70% of the cases. The main antibiotics used were cephalosporins, carbapenems, and ampicillin. Combinatory use of ampicillin and cephalosporin was carried out in 74.7-82.7% of cases in 1997-2000, but sharply declined thereafter to 0-13.8% in 2004-2008. However, the combination of carbapenem and cephalosporin compensated for the decline, increasing from 3.8-6.6% in 1998-1999 to 79.5-89.9% in 2005-2008. The breakdown in the use of cephalosporins, carbapenems, and ampicillin in two-drug combinatory therapy was as follows. (i) Use of cefotaxime was 61.8-75.3% in 1997-2001, but decreased to nearly 50%, equivalent to the level of ceftriaxone use in 2003-2008. (ii) Use of ampicillin dropped from 74.7-92.3% in 1997-2000 to 4.6% in 2008, and this decreased level was compensated for by the use of carbapenems. Overall, combinatory chemotherapy of the third-generation cephalosporins and carbapenems seems to be practical. The discussion in this report includes the difference between Japan and the United States in the prevalence of the causative agents and the use of antibiotics. These studies provide information on trends in the treatment of children's meningitis in Japan and will be useful for the design of future empirical chemotherapy. [ABSTRACT FROM AUTHOR]

Background To manage antimicrobial resistance, both antimicrobial stewardship (AMS) and antifungal stewardship (AFS) are needed. However, limited data show AMS and AFS practices among hospitals in Japan. Methods We conducted a cross-sectional nationwide study using a questionnaire distributed to hospitals that participated in a hospital epidemiology workshop in Japan in July 2018. The questions addressed activities of preauthorization, notification, and intervention within 7 or 28 days about broad-spectrum antibiotics (third- and fourth-generation cephalosporins and piperacillin–tazobactam, carbapenem, intravenous quinolone) and antifungals. Interventions to use broad-spectrum antibiotics and antifungals were compared between large (≥501 beds) and small/medium-sized (≤500 beds) hospitals. Results Of 240 hospitals, 39 (16%; 18 large and 21 small/medium-sized) responded. Preauthorization of using broad-spectrum antibiotics and antifungals was found in 4 (10%) and 1 (3%) hospital(s), respectively. Notification of broad-spectrum antibiotics and antifungals was found in 37 (95%) and 2 (5%) hospitals, respectively. The numbers of hospitals that intervened in the use of broad-spectrum antibiotics within 7 and 28 days were 17 (44%) and 34 (87%), respectively; those of antifungals were 3 (8%) and 10 (26%), respectively (Table 1). Interventions to use broad-spectrum antibiotics within 7 days were statistically more frequent in small-/medium-sized hospitals than in large hospitals [13 (61.9%) vs. 4 (22.2%),odds ratio = 5.7, 95% confidence interval = 1.4–23.3, p = 0.023]. All hospitals had less-frequent interventions to use antifungals within 7 days than those for antibiotics[3 (14.3%) vs. 0 (0%)] (Table 2). Conclusion Small-/middle-sized hospitals had more frequent interventions within 7 days of broad-spectrum antibiotics than those of large hospitals, possibly because small-/medium-sized hospitals are agile and have few barriers against interventions to use broad-spectrum antibiotics. Compared with broad-spectrum antibiotics, interventions of antifungals were less frequently conducted in all hospitals. We need to emphasize the importance of AFS in Japan. Further studies on related factors are needed. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background The 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. Methods Total 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. Results DID 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). Conclusion Oral 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. [ABSTRACT FROM AUTHOR]

Background Antimicrobial resistance (AMR) is a global threat for both dentists and medical doctors. The Japanese national action plan on AMR targets a 50% reduction in the use of oral broad-spectrum antimicrobials by 2020 compared with its use in 2013. However, no study has compared the pattern of oral antimicrobial use (AMU) in outpatient settings between all dentists and medical doctors in Japan using the national database of health insurance claims and specific health checkups (NDB). Methods Data of oral AMU in outpatient settings prescribed by both all dentists (n = 104,533) and medical doctors (n = 319,480) in Japan in 2016 were evaluated using NDB collected by the Ministry of Health, Labor and Welfare of Japan; the data accounted for 98% of the total claim data in Japan. Antimicrobials were classified by the World Health Organization (WHO) defined Anatomical Therapeutic Chemicals Classification. WHO measures the number of AMU using defined daily dose per 1,000 inhabitant-days (DIDs). The pattern of oral AMU between all dentists and medical doctors in Japan in 2016 was compared. Results The values of oral AMU in outpatient settings among all dentists (n = 104,533) and medical doctors (n = 319,480) in Japan were 1.20 and 12.11, respectively. The proportions of AMU among dentists were cephalosporins, 65.1%; macrolides, 18.9%; quinolones, 5.5%; and penicillin, 8.7%. In contrast, the proportions of AMU among medical doctors were cephalosporins, 23.1%; macrolides, 36.9%; quinolones, 22.2%; and penicillin, 8.1%. There were differences in the pattern of oral AMU between dentists and medical doctors (P < 0.001) (Table 1). Conclusion Although the value of total oral AMU among dentists was 9.9% of medical doctors, the proportion of cephalosporin use, which was thought to be inappropriate prescribing, was higher among dentists than among medical doctors. Further studies that are adjusted to patients' characteristics are needed. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Uncomplicated cystitis (UC) imposes a large burden on antimicrobial use due to its high morbidity. IDSA/ESCMID guidelines recommend nitrofurantoin, sulfamethoxazole/trimethoprim (SMX/TMP), fosfomycin trometamol, and pivmecillinam for treating UC, but only SMX/TMP and fosfomycin calcium (FOM-C) are available in Japan. Therefore, we examined the antibiotics use to treat UC in Japan. Methods We obtained data from the JMDC Inc. claims database, which includes data of corporate employees and their family members. We extracted all records of oral antibiotic prescriptions for the treatment of acute cystitis (ICD-10 code: N300) between 2013 and 2016, and excluded prescriptions for male individuals and inpatients because they were considered to have complicated cystitis. Prescriptions for durations >7 days were also excluded because they were potentially prophylactic. Furthermore, we defined treatment failure as cases that required re-prescription within 13 days after the first prescription and estimated the treatment failure rate (TFR) of each antibiotic. Results Cephalosporins and quinolones accounted for 41.5% and 53.2% of the total number of antibiotic prescriptions (48,678). SMX/TMP and FOM-C only accounted for 0.7% and 0.8%. Third-generation cephalosporins accounted for 93.8% of total cephalosporins. TFR was less than 10% across almost all antibiotic categories, with the only exception being FOM-C. Conclusion Cephalosporins and quinolones accounted for 94.7% of oral antibiotic treatment for UC in Japan between 2013 and 2016. To avoid spreading antimicrobial resistance, approval of new antibiotics with good efficacy or an official recommendation for the use of narrower-spectrum antibiotics for treating UC may be required. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

The article focuses on occupational contact urticaria syndrome from cefotiam hydrochloride. Cefotiam hydrochloride (CTM) is a cephalosporin and one of the most common parenteral antibiotics in Japan in the last 10 years. Contact urticaria is classified as an immediate type of contact reaction and is further divided into 3 etiologic groups - non-immunologic, immunologic, and unknown. Contact urticaria related to antibiotics is usually accompanied by systemic symptoms, such as hypersensitivity reaction and is thus called contact urticaria syndrome.