Journal of Infection and Chemotherapy最新文献

Treating disseminated cryptococcosis in people with human immunodeficiency virus (HIV) is challenging due to the limited availability of effective antifungals. Although isavuconazole has antifungal activity against Cryptococcus neoformans, clinical evidence is sparse because this new drug has not been approved for the treatment of cryptococcosis in the US or Europe. Here, we report a case of HIV-associated cryptococcal meningitis that relapsed during maintenance therapy with fluconazole. A Japanese man in his 20s was diagnosed with HIV-1 infection and cryptococcal meningitis. The patient was intolerant to flucytosine and was treated with liposomal amphotericin B monotherapy for 2 weeks as induction therapy, followed by fluconazole (400 mg/day) for 3 months as consolidation therapy. Four months after starting maintenance therapy with fluconazole (200 mg/day), the patient presented with fever and cough, leading to readmission to our hospital. Biopsies of a nodule in the left lung and a left cervical lymph node led to the diagnosis of disseminated cryptococcosis (pulmonary cryptococcosis and cryptococcal lymphadenitis). Although a combination of fluconazole and liposomal amphotericin B was ineffective, the patient was successfully treated with an induction therapy combining isavuconazole and liposomal amphotericin B, followed by a maintenance therapy with isavuconazole. The patient received isavuconazole orally except for loading doses, achieving stable blood concentration levels. Moreover, we observed that blood levels of amphotericin B increased gradually with repeated administration. Therefore, isavuconazole may have a potential role in the treatment of cryptococcosis, and clinical trials involving larger numbers of cases are needed to confirm its efficacy and safety.

Deep-seated mycoses are generally opportunistic infections that are difficult to diagnose and treat. They are expected to increase with the spread of advanced medical care and aging populations, thus highlighting the need for safe, effective, and rapid drug-based treatments. Depending on a patient's age, sex, underlying diseases, and immune system status, therapeutic drug monitoring (TDM) may be important for assessing variable pharmacokinetic parameters, as well as preventing drug-drug interactions, adverse events, and breakthrough infections caused by fungal resistance. Azole antifungal agents play an important role in the prevention and treatment of deep-seated fungal infections, with each azoles having its own unique pharmacokinetic properties and specific adverse events. Therefore, it is necessary to use national and international guidelines to build evidence for the expansion of TDM indications. This review focuses on the clinical utility and future perspectives of TDM using azole antifungal agents, in the context of recent evidence in the literature.

Objective: The mechanism of aminoglycoside resistance due to abnormal hemin synthesis remains unclear. We investigate an Escherichia coli strain with a single amino acid substitution at position 85 of HemC.

Methods: An aminoglycoside-resistant Escherichia coli DH5α was selected by passaging in Lysogeny Broth (LB) medium containing amikacin. Whole genome sequencing was performed to determine the genetic profile of the strain. An isogenic strain of E. coli DH5α was created. Growth rates, drug susceptibilities and expressions of the heme synthetic genes were compared between the original strain and the isogenic strain.

Results: Whole genome sequencing revealed a nucleotide substitution at position 254 of hemC from adenine (A) to thymine (T), resulting in an amino acid substitution at position 85 of HemC from histidine (H) to leucine (L). There were no mutations in other heme synthetic genes, including hemA, hemB, hemC, hemD, hemE, hemF, hemG, hemH, hemL, hemN, hemX and hemY. The isogenic strain of E. coli DH5α with H85L in HemC was less susceptible to aminoglycosides, and its growth was slower than that of E. coli DH5α before passage. Quantitative real-time PCR showed that the expression of hemA was higher and the expressions of hemL, hemG and hemX lower in the isogenic strain than before passage.

Conclusion: This is the first report of aminoglycoside resistance due to an amino acid substitution in HemC. These findings suggested that mutations in the heme synthetic genes may indirectly affect the growth rates of E. coli strains and their susceptibilities to aminoglycosides.

Background: A nationwide survey conducted by the Japanese Society of Chemotherapy and the Japanese Association for Infectious Diseases in 2020 provided insights into antimicrobial prescription practices among clinic doctors. This study aimed to investigate factors influencing changes in antimicrobial prescriptions post-implementation of the National Action Plan on Antimicrobial Resistance (NAPAR) and doctors' inclination to prescribe antimicrobials for common cold cases.

Methods: In September 2020, randomly selected questionnaires were distributed to 3000 community-based medical clinics in Japan. The primary objective was to assess the reduction in antimicrobial prescriptions post-NAPAR implementation. Multivariate linear regression analysis was employed to identify associated factors.

Results: Analysis of 632 responses (response rate: 21.1 %) revealed determinants of decreased antimicrobial prescriptions, including familiarity with the Guide to Antimicrobial Stewardship (β = .482, t = 3.177, p = 0.002) and awareness of NAPAR (β = .270, t = 2.301, p = 0.022).

Conclusion: Interventions such as the Guide to Antimicrobial Stewardship may have contributed to the reduction in antimicrobial prescriptions among Japanese physicians. However, targeted strategies are needed to address high-prescription groups. Enhancing awareness and education on appropriate antimicrobial use should be integral components of future initiatives to combat antimicrobial resistance effectively.

Introduction: This cross-sectional study assesses the prevalence of metronidazole resistance-associated mutations and virulence genotypes in Helicobacter pylori (H. pylori) strains isolated from the Egyptian population. H. pylori infection is a significant public health concern, with antibiotic resistance challenging its eradication.

Methods: Gastric biopsy samples were collected from symptomatic patients referred for upper gastrointestinal endoscopy at selected healthcare facilities. The study included 250 participants with symptoms suggestive of H. pylori infection and aged 18 years or older. Biopsy samples were obtained using standard endoscopic techniques, and H. pylori strains were isolated and identified in the laboratory. Antimicrobial susceptibility testing was conducted using standard methods. Molecular analysis, including polymerase chain reaction (PCR) and sequencing, was performed to identify metronidazole resistance-associated mutations (rdxA and frxA) and virulence genotypes (cagA and vacA).

Results: Antimicrobial susceptibility testing revealed that 43.6 % of the isolates were resistant to metronidazole, while 11.8 %, 4.5 %, and 55.4 % were resistant to clarithromycin, amoxicillin, and levofloxacin. Molecular analysis identified rdxA and frxA mutations in 36.3 % and 31.8 % of the isolates, respectively, indicating metronidazole resistance-associated mutations. Additionally, 60.0 % of the isolates were positive for the cagA gene, and 80.0 % had the vacA s1 type, both associated with increased virulence. A significant association was found between metronidazole resistance and the presence of cagA gene, vacA s1 type, rdxA mutation, and frxA mutation. Statistical analysis revealed associations between specific mutations and virulence genotypes with respective odds ratios, indicating higher likelihoods of metronidazole resistance in isolates exhibiting these genetic characteristics.

Conclusions: This study highlights the prevalence of metronidazole resistance and the association between specific mutations and virulence genotypes in H. pylori strains isolated from the Egyptian population. The findings underscore the importance of monitoring antibiotic resistance patterns and understanding the genetic determinants of virulence in H. pylori for effective management and treatment strategies.

Background: There are few reports detailing the prognostic factors of severe COVID-19 pneumonia requiring invasive ventilation. We investigated the long-term prognosis and evaluated which factors influenced outcomes in these patients.

Methods: Data was reviewed from severe adult COVID-19 cases admitted to our hospital and treated with mechanical ventilation between February 1, 2020, and October 30, 2021. On admission to our hospital, comorbidities and laboratory findings were collected from clinical records. Prognostic information for 90 days after diagnosis was also obtained from hospitals where patients were transferred after their conditions stabilized.

Results: Prognostic information was obtained in 133 patients, of which 106 were males (79.7 %). Of the 133 patients, 67 were discharged (51.5 %), 21 continued inpatient care (15.8 %), and 45 died (33.8 %). Age, Charlson Risk Index, and the number of patients on hemodialysis were significantly higher in the deceased group. There were no differences in therapeutic interventions between survivors and those who died except for a higher rate of muscle relaxant and vasopressor usage in the deceased group. Laboratory findings on admission showed significantly higher levels of BUN, creatinine, and serum Krebs von den Lungen 6 (KL-6), and significantly lower platelet counts, hemoglobin, and alanine aminotransferase in those who died. Multivariate analysis revealed that age, hemodialysis, lower platelet counts, and higher KL-6 were independent predictors for 90-day mortality.

Conclusions: Older age, hemodialysis, lower platelet counts and high KL-6 on admission were identified as independent predictors of 90-day mortality in patients with respiratory failure due to severe COVID-19 under invasive mechanical ventilation.

Background: Systemic baricitinib and corticosteroids play important roles in treating severely and critically ill patients with coronavirus disease 2019 (COVID-19). However, the efficacy of the combination of baricitinib and corticosteroids compared to that of corticosteroid monotherapy in severely and critically ill hospitalized patients with COVID-19 remains unclear.

Methods: We analyzed severely and critically ill hospitalized patients with COVID-19 aged >18 years between January 1, 2020 and May 31, 2023, using a Japanese multicenter inpatient database. We performed propensity score matching to analyze the effect of the combination of baricitinib and corticosteroids within 2 days of hospital admission (combination group) on the 28-day and in-hospital mortality rates compared with those of corticosteroid monotherapy within 2 days of hospital admission (control group). Sensitivity analysis was performed using inverse probability weighting analysis and the generalized estimating equation method.

Results: The eligible patients (n = 7433) were divided into a combination (n = 679) and a control group (n = 6754). One-to-four propensity score matching analyses included 566 combination and 2264 control group patients. There was no significant difference in 28-day (8.5 % vs. 8.8 %; risk difference, -0.3 % [95 % confidence interval, -2.9 to 2.3]) or in-hospital (11 % vs. 10 %; risk difference, 1.0 [-1.9 to 3.9]) mortality rates between 2 groups. The sensitivity analysis showed similar outcomes.

Conclusion: This observational study, using a Japanese multicenter inpatient database, found that the combination of baricitinib and corticosteroid therapy did not improve the 28-day or in-hospital mortality rates in severely and critically ill patients with COVID-19 compared to corticosteroid monotherapy.

We report a rare case of bacteremia with concomitant acute transverse myelitis (ATM) without evidence of a primary infectious focus or secondary localization due to Staphylococcus aureus in a 60-year-old man admitted for hyperpyrexia, quadriplegia, and respiratory failure. Bacterial ATM is a rare clinical entity with confusing clinical presentation and challenging diagnosis; isolated bacterial infections of the spinal cord without secondary localization or contiguous foci are exceptionally rare, as is S. aureus as the cause of infection. In this case, a rapid etiologic diagnosis was made possible by close collaboration between clinicians, infectious disease specialists and clinical microbiologists combined with extended molecular testing on CSF guided by incoming results.

Background: Coronavirus disease 2019 (COVID-19) is characterized by high interleukin-6 levels. Clinical data supporting tocilizumab, a monoclonal antibody that targets interleukin-6 receptor-alpha, for treating Japanese patients with severe COVID-19 pneumonia are needed.

Methods: This single-arm phase 3 study investigated tocilizumab (8 mg/kg) plus standard of care (SOC) in Japanese patients hospitalized with severe COVID-19 pneumonia. Clinical status was assessed using a 7-category ordinal scale on day 28 (primary endpoint) and day 14 (secondary endpoint). Other secondary endpoints were time to improvement (≥2 category improvement) and time to hospital discharge. Safety was assessed as the incidence of adverse events (AEs).

Results: Among 48 patients enrolled, 44 (91.7 %) scored ≥3 on the 7-category ordinal scale at baseline. At day 28, 35 patients (72.9 %) scored 1 and 5 (10.4 %) scored 7 on the 7-category ordinal scale; 36 (75.0 %, 95 % confidence interval [CI]: 60.40 %-86.36 %) and 39 (81.3 %, 95 % CI: 67.37 %-91.05 %) patients achieved ≥2- and ≥1-category improvement, respectively; 6 patients (12.5 %, 95 % CI: 4.73 %-25.25 %) demonstrated ≥1-category worsening. At day 14, 25 (52.1 %, 95 % CI: 37.19 %-66.71 %) and 33 patients (68.8 %, 95 % CI: 53.75 %-81.34 %) achieved ≥2- and ≥1-category improvement, respectively; 5 patients (10.4 %, 95 % CI: 3.47 %-22.66 %) demonstrated ≥1-category worsening. Median times (95 % CI) to improvement and hospital discharge were 11 (9-15) and 15 (11-18) days, respectively. Forty patients (83.3 %) experienced AEs; the incidence of ≥grade 3 AEs was 25 %.

Conclusion: Tocilizumab plus SOC may provide improved clinical status in Japanese patients with severe COVID-19 pneumonia; no new safety signals were identified.

Objectives: To evaluate the efficacy and patient outcomes of pharmacist-physician collaborative protocol-based antimicrobial treatment regimens for antimicrobial stewardship.

Methods: Patients treated for aspiration pneumonia due to stroke within 48 h after admission to Kochi Medical School Hospital (January 2019 to December 2022) were included. Primary outcomes were the cumulative number of days of antimicrobial treatment and length of hospital stay. Secondary outcomes included the percentage of patients under-dosed with first-choice antimicrobial agents and inpatient mortality.

Results: Group A (66 patients) did not receive the antimicrobial treatment protocol, whereas group B (46 patients) did. There were no differences in the patient backgrounds. Group B had a significantly lower percentage of patients who were undertreated with the first-choice antimicrobial agent (9.1 % vs. 42.9 %). There was no significant difference in inpatient mortality between group A and group B (6.1 % vs. 4.3 %). The cumulative number of days of antimicrobial administration and the length of hospital stay were significantly lower in group B: 7.0 days (95 % CI, 6.0-8.0) vs. 9.0 days (95 % CI, 8.0-11.0) for antimicrobial administration, and 28.5 days (95 % CI, 22.0-35.0) vs. 43.0 days (95 % CI, 28.0-55.0) for hospital stay.

Conclusions: Protocol-based antimicrobial treatment for aspiration pneumonia supports appropriate antimicrobial usage and improves patient quality of life. These findings will assist in the effective treatment of aspiration pneumonia in an aging society.