Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy
-
J. Infect. Chemother. · Oct 2013
Randomized Controlled Trial Multicenter StudyA Phase II study of polyclonal anti-TNF-α (AZD9773) in Japanese patients with severe sepsis and/or septic shock.
Because tumor necrosis factor-alpha (TNF-α) induces many of the pathophysiological signs and symptoms observed in sepsis, it is a potential therapeutic target for treatment. The primary objective of this study was to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple intravenous (i.v.) infusions of two doses of AZD9773 in Japanese patients with severe sepsis and/or septic shock. In this Phase II, double-blind, placebo-controlled, dose-escalation study (ClinicalTrials.gov Identifier: NCT01144624), Japanese patients were randomized to two successive treatment cohorts (cohort 1, loading/maintenance doses of 250/50 U/kg or placebo; cohort 2, loading/maintenance doses of 500/100 U/kg or placebo) for a 5-day treatment period, then a follow-up period to day 29. ⋯ Treatment with AZD9773 led to a decrease in TNF-α concentrations, which was more discernible in the AZD9773 cohort 2; TNF-α concentrations generally decreased with time in patients receiving placebo. A similar pattern of response was observed with interleukin-6 (IL-6) and IL-8. AZD9773 was generally well tolerated with dose-proportional pharmacokinetics in Japanese patients with severe sepsis/septic shock.
-
J. Infect. Chemother. · Aug 2013
Reevaluation of the Japanese guideline for healthcare-associated pneumonia in a medium-sized community hospital in Japan.
The Japanese guidelines for nursing- and healthcare-associated pneumonia (NHCAP) categorize patients by risk of resistant bacteria and defined antimicrobials to be used, similar to the healthcare-associated pneumonia (HCAP) guidelines of the United States. The data were collected in large-scale hospitals, possibly a cause of inconsistency with everyday practice in medium-sized community hospitals. To test the feasibility of this guideline based on a retrospective study performed in a medium-sized community hospital in Japan, the medical records of pneumonia patients were retrospectively studied [718 patients: NHCAP, 477, 66.4 %; community-acquired pneumonia (CAP), 241, 33.4 %). ⋯ For NHCAP, the success rate did not differ between those receiving and not receiving proper initial treatment (76.9 vs. 78.5 %) nor did mortality rate within 30 days differ (13.1 vs. 13.8 %). Risk factors for mortality within 30 days for NHCAP were diabetes [adjusted odds ratio (AOR) 2.394, p = 0.009], albumin <2.5 g/dl (AOR 2.766, p = 0.002), A-DROP very severe (AOR 1.930, p = 0.021), and imaging showing extensive pneumonia (AOR 2.541, p = 0.002). The severity of pneumonia rather than risk of resistant bacteria should be considered, in addition to ethical concerns, in initial treatment strategy in NHCAP to avoid excessive use of broad-spectrum antimicrobials.
-
J. Infect. Chemother. · Jun 2013
Nationwide surveillance of bacterial pathogens from patients with acute uncomplicated cystitis conducted by the Japanese surveillance committee during 2009 and 2010: antimicrobial susceptibility of Escherichia coli and Staphylococcus saprophyticus.
The Japanese surveillance committee conducted the first nationwide surveillance of antimicrobial susceptibility patterns of uropathogens responsible for female acute uncomplicated cystitis at 43 hospitals throughout Japan from April 2009 to November 2010. In this study, the causative bacteria (Escherichia coli and Staphylococcus saprophyticus) and their susceptibility to various antimicrobial agents were investigated by isolation and culturing of bacteria from urine samples. In total, 387 strains were isolated from 461 patients, including E. coli (n = 301, 77.8 %), S. saprophyticus (n = 20, 5.2 %), Klebsiella pneumoniae (n = 13, 3.4 %), and Enterococcus faecalis (n = 11, 2.8 %). ⋯ It is important to confirm the susceptibility of causative bacteria for optimal antimicrobial therapy, and empiric antimicrobial agents should be selected by considering patient characteristics and other factors. However, the number of isolates of fluoroquinolone-resistant or ESBL-producing strains in gram-negative bacilli may be increasing in patients with urinary tract infections (UTIs) in Japan. Therefore, these data present important information for the proper treatment of UTIs and will serve as a useful reference for future surveillance studies.
-
J. Infect. Chemother. · Jun 2013
Randomized Controlled Trial Multicenter StudyClinical dose findings of sitafloxacin treatment: pharmacokinetic-pharmacodynamic analysis of two clinical trial results for community-acquired respiratory tract infections.
The adequacy of sitafloxacin clinical dose regimens was assessed by comparing the efficacy of the administration of 100 mg sitafloxacin once daily (100 mg qd group) and 50 mg sitafloxacin twice daily (50 mg bid group). Patients with respiratory tract infections caused by pneumococci were orally treated with sitafloxacin (100 mg qd or 50 mg bid) for 7 days. The clinical efficacy, pneumococci eradication rate, safety, and pharmacokinetic and pharmacodynamic indices of the two groups were then assessed. ⋯ The incidences of adverse drug reactions were 33.7 % in the 100 mg qd group and 40.4 % in the 50 mg bid group. No obvious differences in the efficacy and safety were observed between the dosage groups. For cases in which a sufficiently high C peak is necessary to ensure the susceptibility of the pathogens to the drug, 100 mg sitafloxacin once daily should be administered.
-
J. Infect. Chemother. · Feb 2013
The use of ceftaroline fosamil in methicillin-resistant Staphylococcus aureus endocarditis and deep-seated MRSA infections: a retrospective case series of 10 patients.
There are many limitations to the current antibiotics used for the treatment of severe methicillin-resistant Staphylococcus aureus (MRSA) infections. Ceftaroline is a new fifth-generation cephalosporin approved for the treatment of skin and soft tissue infections caused by MRSA and community-acquired pneumonia. We propose that ceftaroline can also be used successfully in more severe MRSA infections, including endocarditis. ⋯ In most patients, ceftaroline was effective for treatment of MRSA bacteremia and other severe MRSA infections. Adverse effects seen included rash, eosinophilia, pruritus, and Clostridium difficile infection. Ceftaroline can be a safe and effective drug for treatment of severe MRSA infections, and further comparative studies are warranted.