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Chronic obstructive pulmonary disease (COPD) is a respiratory and systemic disease affecting more than 300 million people globally every year, and it also becomes a substantial economic burden. COPD is commonly comorbid with various underlying diseases such as cancer, cardiovascular diseases, cerebrovascular diseases, diabetes mellitus, osteoporosis, etc. It has been shown that statins can improve a significant decline in pulmonary function among COPD patients due to their pleiomorphic effect. Some systematic reviews also reported that statins reduced the risk of COPD-related events such as cancer and cardiovascular events, eventually resulting in more favorable outcomes than for non-statin user COPD patients. However, the physiological mechanism is still elucidated. Recently, it has been reported that statins influence the gut microbial composition with increased relative abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii and act with pleiomorphic effects such as anti-inflammatory and anti-cancer effects through modulating gut dysbiosis. We described this review to focus on whether statins can be a useful preventive option for COPD.

Background. While prognostic guidelines for pneumonia have widely allowed clinicians to treat patients, poor prognostic factors for 1- or 2-year survival times have never been mentioned to our knowledge. Patients and methods. We conducted this retrospective study to evaluate whether malnutrition according to the GLIM criteria is a poor prognostic factor for 1- or 2-year survival among patients with aspiration pneumonia. All patients with community-onset aspiration pneumonia who were admitted to Aichi Medical University and had intervention from our nutrition support team (NST) in 2019 and 2020 were enrolled in this study. Results. A total of 56 patients were enrolled in the study. The mean age was 86 ± 6.5 and 25 (45%) were male. Thirty-one patients died during this observational period. Comparing the survival and death group, higher respiratory rate (RR) and malnutrition were seen more frequently in the death group than in the survival group. Then, the patients were divided into the following three groups: those with an RR ≥ 22 and malnutrition, those with malnutrition, and a control group [patients who were not malnourished and had a low RR (p = 0.009 by Log-Rank test) for 1-year prognosis. The result of 2-year prognosis displayed a statistical significance that was the same as that for 1-year prognosis (p = 0.004 by Log-Rank test). The Cox hazard regression model showed that a higher RR was an independent poor prognostic factor for 1- and 2-year survival among aspiration pneumonia patients. Conclusions. This pilot study showed that combined scores of higher RR and malnutrition according to the GLIM criteria (modified R-GLIM score) was an independent poor prognostic factor for 1 or 2-year survival among super-elderly patients (aged over 80 years) with aspiration pneumonia.

The present study aimed to evaluate the impact of prospective audit and feedback (PAF) on the use of inpatient broad-spectrum antibiotics for more than 10 days using days of therapy (DOT) and a novel metric called days of antibiotic spectrum coverage (DASC) to assess whether the antimicrobial spectrum was narrowed. Conducted at Aichi Medical University Hospital in Japan, the study compared a six-month baseline period (April to September 2022) with a six-month intervention period (April to September 2023). The primary outcome measures were changes in DOT/patient and DASC/patient for broad-spectrum antibiotics. Propensity score matching was performed between two periods and a total of 172 patients were included in the study (pre-intervention, n = 86; intervention, n = 86). The DASC/patient of broad-spectrum antibiotics was statistically decreased in the intervention period compared to that in the baseline period (153.3 vs. 122.7, p < 0.05). Additionally, our PAF intervention led to a switch to narrow-spectrum antimicrobial therapy without increasing all-cause 30-day mortality (5.8% vs. 5.8%, p = 1.0). However, the DOT/patient, DASC/patient, and DASC/DOT of all antimicrobials were not significantly changed. Our study concluded that we should reconsider the timing of PAF intervention by evaluating the effort of PAF by using DOT and DASC.

In 2016, Tosei General Hospital, a tertiary emergency medical facility with 633 beds in Japan, experienced a large nosocomial outbreak of carbapenemase-producing Enterobacterales (CPE) that had spread to numerous sink outlets. Based on our experience with using steam cleaners to suppress CPE on environmental surfaces, we report the efficacy of steam cleaners in the disinfection of sink outlets. Steam cleaners were used to disinfect 22 target areas. CPE disappeared in 90.9% of the sink outlets within the first two months after disinfection, and, after 12 months, 54.5% of the sink outlets remained negative throughout the remainder of the study period. This study demonstrates the effectiveness of using steam cleaners to disinfect sink outlets contaminated with CPE.

The coronavirus disease (COVID-19) pandemic continues to threaten global public health. Remdesivir and monoclonal antibodies have shown promise for COVID-19 treatment of patients who are immunocompromised, including those with cancer, transplant recipients, and those with autoimmune disorder. However, the effectiveness and safety of this combination therapy for patients who are immunosuppressed remain unclear. We compared the efficacy and safety of combination therapy and remdesivir monotherapy for patients with mild-to-moderate COVID-19 who were immunosuppressed. Eighty-six patients treated in July 2021–March 2023 were analyzed. The combination therapy group (CTG) showed a statistically significant reduction in viral load compared with the monotherapy group (MTG) (p < 0.01). Patients in the CTG also experienced earlier resolution of fever than those in the MTG (p = 0.02), although this difference was not significant in the multivariate analysis (p = 0.21). Additionally, the CTG had significantly higher discharge rates on days 7, 14, and 28 than the MTG (p < 0.01, p < 0.01, and p = 0.04, respectively). No serious adverse events were observed with combination therapy. These findings suggest that combination therapy may improve the clinical outcomes of immunosuppressed COVID-19 patients by reducing the viral load and hastening recovery. Further studies are required to fully understand the benefits of this combination therapy for immunocompromised COVID-19 patients.

Clostridioides difficile infection (CDI) has significant implications for healthcare economics. Although clinical trials have compared fidaxomicin (FDX) and vancomycin, comparisons of FDX and oral metronidazole (MNZ) are limited. Therefore, we compared the therapeutic effects of FDX and oral MNZ. Patients diagnosed with CDI between January 2015 and March 2023 were enrolled. Those treated with oral MNZ or FDX were selected and retrospectively analyzed. The primary outcome was the global cure rate. Secondary outcomes included factors contributing to the CDI global cure rate; the rate of medication change owing to initial treatment failure; and incidence rates of clinical cure, recurrence, and all-cause mortality within 30 days. Of the 264 enrolled patients, 75 and 30 received initial oral MNZ and FDX treatments, respectively. The corresponding CDI global cure rates were 53.3% and 70% (p = 0.12). In multivariate analysis, FDX was not associated with the global cure rate. In the MNZ group, 18.7% of the patients had to change medications owing to initial treatment failure. The FDX group had a higher clinical cure rate and lower recurrence rate than the MNZ group, although not significant. However, caution is necessary owing to necessary treatment changes due to MNZ failure.

Fungemia is a fatal systemic infection that can occur in immunocompromised patients. Despite that, antifungal stewardship is spreading widely, but the mortality rate is extremely high, showing 40–60%. Loderomyces elongiporus is a newly morphologically detected pathogen, first described in 1994, followed by isolation in humans in 2008. It has been misrecognized as Candida parapsilosis. Recently, fever attributable to L. elongisporus fungemia cases has been reported, and the etiology and clinical features are still unknown. Here, we present three successfully treated L. elongisporus fungemia cases by echinocandin. In total, 11 cases were reviewed, including ours. Six of the eleven cases (55%) had external devices. All cases had some immunocompromised conditions or underlying diseases, such as diabetes mellitus, lung cancer, etc. Six patients survived, and the remaining five died. Seven patients who had received echinocandin initially survived. Risk factors for L. elongiporus fungemia overlap with those of candidemia. Even though there is no breakpoint for L. elongiporus, echinocandin can be a helpful treatment regimen for L. elongiporus fungemia.

Linezolid (LZD) and Tedizolid (TZD) are oxazolidinone antibiotic for meticillin-resistant Staphylococcus aureus (MRSA). Severe hyponatremia after LZD administration have been reported. Severe hyponatremia cause seizures, unconsciousness, and even death. Therefore, we conducted a study to assess the change of serum sodium level after LZD and TZD therapy. We enrolled 67 patients treated with LZD and 28 treated with TZD. We monitored the serum sodium level from the administration to 14 days after administration of oxazolidinone drug. Hyponatremia was defined a sodiuln level ≤134 mmol/L after the initiation of oxazolidinone drug. The frequency of hyponatremia in the LZD group was significantly higher than that in the TZD group (39.7% vs. 11.1%, p < 0.05). The rate of patients administered by injection was significantly higher than in the LZD group than in the TZD group (52.9% vs. 14.8%, p < 0.01). Multiple logistic regression analyses identified the albumin level before the oxazolidinone drug therapy as the independent variables associated with the development of hyponatremia. We revealed that TZD is safer than LZD in terms of hyponatremia. Therefore, cases that LZD is administered by injection should be used more carefully with hyponatremia in patients with low albumin level.

There are limited reports on the safety of remdesivir for patients with severe kidney disease. We investigated the safety of remdesivir administration for COVID-19 patients with estimated glomerular filtration rate (eGFR) 30 mL/min with remdesivir administration. The primary outcome was 30-day mortality after the first administration. Adverse events, including development of acute kidney injury (AKI), liver function disorder, anemia, and thrombocytopenia 48 h after the end of remdesivir administration, were evaluated. After propensity score matching, 23 patients were selected from each group. There were no differences in the 30-day mortality (risk ratio [RR] 1.00; 95% confidence interval [CI] 0.18–5.56). Development of AKI and liver function disorder was not statistically different between the two groups (RR 1.05; 95% CI 0.96–1.14 and RR 0.48; 95% CI 0.04–5.66, respectively). There was no trend toward a significant increase in adverse events in the eGFR < 30 mL/min group and severe renal dysfunction had little effect on the safety of remdesivir treatment.

Cefazolin (CFZ) is the first-line treatment for beta-lactamase-producing methicillin-sensitive Staphylococcus aureus (BP-MSSA) infection. In 2019, Japan experienced a CFZ shortage because of foreign object inclusion in a batch. Ampicillin/sulbactam (SAM) was preferred in many cases as definitive therapy for the treatment of BP-MSSA bacteremia to preserve broad-spectrum antibiotic stock. However, there are no previous studies reporting the clinical efficacy of SAM for BP-MSSA bacteremia. We aimed to compare the clinical efficacy and adverse effects of SAM versus CFZ in patients with BP-MSSA bacteremia. In total, 41 and 30 patients treated with SAM and CFZ, respectively, were identified. The baseline characteristics were similar in both groups. No significant differences were observed in length of hospital stay and all 30-day mortality between the two groups (p = 0.270 and 0.643, respectively). Moreover, no intergroup difference in 90-day mortality was found (hazard ratio 1.02, 95% confidential interval 0.227–4.53). Adverse effects, such as liver dysfunction, were less in the CFZ group than in the SAM group (p = 0.030). Therefore, in cases of poor CFZ supply or in patients allergic to CFZ and penicillinase-stable penicillins, SAM can be an effective therapeutic option for bacteremia due to BP-MSSA with attention of adverse effects, such as liver dysfunction.

Current guidelines recommend the use of ceftriaxone and sulbactam-ampicillin for the initial treatment of community-acquired pneumonia (CAP). However, there are no clear data on these guidelines. Therefore, this systematic review and meta-analysis aims to evaluate the effectiveness of ceftriaxone and sulbactam-ampicillin in the initial treatment of CAP. The Embase, Scopus, PubMed, Ichushi, and Cumulative Index to Nursing and Allied Health Literature databases were systematically searched from inception to July 2022. The studies included patients who received ceftriaxone or sulbactam-ampicillin as the initial antibiotic therapy for CAP. The mortality and clinical cure rates were evaluated. Of the 2152 citations identified for screening, four studies were included. Results of the pooled analysis indicated no significant differences in the mortality and clinical cure rates between patients treated with ceftriaxone and those treated with sulbactam-ampicillin (mortality, odds ratio [OR]: 1.85, 95% confidence interval [CI]: 0.57–5.96; clinical cure rate, OR: 1.08, 95% CI: 0.18–6.44). This study supports the guidelines for CAP treatment, though further studies are needed to obtain a deeper understanding.

Although a 2 g once daily administration of ceftriaxone remains the standard dosing regimen for the treatment of aspiration pneumonia, there are no studies to investigate the optimal dosing method. Hence, we retrospectively evaluated the effectiveness and safety of 1 g twice daily versus 2 g once daily administration of ceftriaxone in adult patients with aspiration pneumonia. Patients who received ceftriaxone for the treatment of aspiration pneumonia between 2015 and 2021 were included in this study. Clinical responses, inflammatory markers, and incidence of adverse events after completion of ceftriaxone therapy were investigated. In total, 33 patients received 1 g twice daily (group 1) and 28 received 2 g once daily (group 2) ceftriaxone for the treatment of mild-to-moderate aspiration pneumonia. Compared with that of group 1, group 2 demonstrated significantly improved clinical responses (group 1 vs. group 2, 84.8% vs. 100%, p = 0.0316). Although the safety profile was not significantly different between the two groups, the incidence of choleliths during ceftriaxone therapy in group 1 was higher than that in group 2 (31.3% vs. 9.1%, p = 0.174). Therefore, a 2 g once daily administration of ceftriaxone appeared to be a simple regimen adequate for the treatment of inpatients with mild-to-moderate aspiration pneumonia, which might not be heavily involved by anaerobes.

Vancomycin or daptomycin is administered to hemodialysis patients infected with methicillin-resistant Staphylococcus and Enterococcus species. Although serious concerns regarding nephrotoxicity due to vancomycin have been raised, it might not be a critical issue in hemodialysis patients. Moreover, very few studies have investigated the effectiveness of vancomycin versus daptomycin in patients undergoing hemodialysis. Hence, we retrospectively evaluated the effectiveness and safety of vancomycin and daptomycin in patients undergoing hemodialysis. We investigated the following measures: mortality, clinical and microbiological effectiveness, and incidence of adverse events in hemodialysis patients who received vancomycin or daptomycin from 2014 to 2019. Moreover, we evaluated the covariates related to 30-day mortality. We found that 73 patients received vancomycin, while 34 received daptomycin for the treatment of infections due to methicillin-resistant Staphylococcus aureus, methicillin-resistant coagulase-negative Staphylococci, and Enterococcus faecium. Mortality after vancomycin treatment was significantly lower than daptomycin treatment (4.1% vs. 26.5%, p < 0.01). The clinical and microbiological effectiveness as well as the safety were not significantly different between the two treatments. Although daptomycin treatment with a loading dose was associated with lower mortality, the mortality of the treatment (8.3%) did not differ significantly compared to that of the vancomycin treatment (4.1%). Therefore, our findings suggest that vancomycin remains the first-line treatment for hemodialysis patients; however, a loading dose may be beneficial for patients receiving daptomycin.

Although combination therapy using trimethoprim–sulfamethoxazole (TMP–SMX) plus echinocandins has been reported to reduce the mortality of patients with pneumocystis pneumonia (PCP), it remains unclear whether it is more effective than TMP–SMX monotherapy, the current first-line treatment for this disease. Hence, we performed a systematic review and meta-analysis to compare the efficacies of these treatment options for PCP. The Scopus, EMBASE, PubMed, CINAHL, and Ichushi databases were searched for studies (up to January 2022) reporting the mortality and positive response rates (fewer clinical symptoms, improved partial pressure of arterial oxygen, and resolution of pneumonitis on chest imaging) of PCP patients receiving monotherapy or combination therapy. Four studies met the inclusion criteria. All four presented mortality data and one had positive response rates. Compared with the monotherapy, the combination therapy resulted in significantly lower mortality and higher positive response rates (mortality: odds ratio (OR) 2.20, 95% confidence interval (CI) 1.46–3.31; positive response rate: OR 2.13, 95%CI 1.41–3.23), suggesting it to be an effective and promising first-line therapy for PCP. However, further safety evaluations are needed to establish this as a fact.

There is increasing evidence regarding the optimal therapeutic strategies for multidrug-resistant (MDR) bacteria that cause common infections and are resistant to existing antibiotics. Combination therapies, such as β-lactam combined with β-lactamase inhibitors or combination antibiotics, is a therapeutic strategy to overcome MDR bacteria. In recent years, the therapeutic options have expanded as certain combination drugs have been approved in more countries. However, only a handful of guidelines support these options, and the recommendations are based on low-quality evidence. This review describes the significance and efficacy of combination therapy as a therapeutic strategy against Gram-negative MDR pathogens based on previously reported meta-analyses.

Mycoplasma genitalium is recognized as a remarkable pathogen since azithromycin-resistant strains and treatment failure have been increasingly reported. Nevertheless, international guidelines still recommend azithromycin as a first-line treatment and moxifloxacin as a second-line treatment. We performed a systematic review and meta-analysis to validate the efficacy and safety of both drugs in the initial treatment of M. genitalium. We systematically searched the EMBASE, PubMed, Scopus, Ichushi, and CINAHL databases up to December 2021. We defined efficacy as clinical and microbiologic cure, and safety as persistent diarrhea. Overall, four studies met the inclusion criteria: one showed clinical cure (azithromycin treatment, n = 32; moxifloxacin treatment, n = 6), four showed microbiologic cure (n = 516; n = 99), and one showed safety (n = 63; n = 84). Moxifloxacin improved the microbiologic cure rate compared with azithromycin (odds ratio [OR] 2.79, 95% confidence interval [CI], 1.06–7.35). Clinical cure and safety did not show a significant difference between azithromycin and moxifloxacin treatments (OR 4.51, 95% CI 0.23–88.3; OR 0.63, 95% CI 0.21–1.83). Our meta-analysis showed that moxifloxacin was more effective than azithromycin at eradicating M. genitalium infections and supports its preferential use as a first-line treatment.

Clostridium butyricum is a human commensal bacterium with beneficial effects including butyrate production, spore formation, increasing levels of beneficial bacteria, and inhibition of pathogenic bacteria. Owing to its preventive and ameliorative effects on gastrointestinal infections, C. butyricum MIYAIRI 588 (CBM 588) has been used as a probiotic in clinical and veterinary medicine for decades. This review summarizes the effects of C. butyricum, including CBM 588, on bacterial gastrointestinal infections. Further, the characteristics of the causative bacteria, examples of clinical and veterinary use, and mechanisms exploited in basic research are presented. C. butyricum is widely effective against Clostoridioides difficile, the causative pathogen of nosocomial infections; Helicobacter pylori, the causative pathogen of gastric cancer; and antibiotic-resistant Escherichia coli. Accordingly, its mechanism is gradually being elucidated. As C. butyricum is effective against gastrointestinal infections caused by antibiotics-induced dysbiosis, it can inhibit the transmission of antibiotic-resistant genes and maintain homeostasis of the gut microbiome. Altogether, C. butyricum is expected to be one of the antimicrobial-resistance (AMR) countermeasures for the One-health approach.

We investigated the in vitro efficacy of combinations of carbapenems with clindamycin (CLDM) and minocycline (MINO) against Bacteroides fragilis and Peptostreptococcus species. We selected the carbapenems imipenem, meropenem, panipenem, doripenem, and biapenem. To evaluate the antibiotic efficacy of these combination regimens, the fractional inhibitory concentration index (FICI) was calculated against clinical isolates. Consequently, combination regimens of each carbapenem with CLDM or MINO showed synergistic or additive effects against 83.3–100.0% and no antagonistic effects against P. anaerobius isolates. However, against the B. fragilis group (B. fragilis, B. thetaiotaomicron, and Parabacteroides distasonis), although the combination with other carbapenems and CLDM or MINO did not show remarkable synergistic effects, the combination regimen of IPM with CLDM or MINO indicated mainly additive antibiotic efficacies (FICIs: >0.5 to ≤1.0) to B. fragilis groups. Then, antagonistic effects were admitted in only 5.6% of B. fragilis groups. The effectiveness of antibiotic combination therapy against pathogenic anaerobes has remained unclear. Then, our results can provide new insights to explore the effective combination regimens against multidrug-resistant anaerobic bacteria as empirical and definitive therapies, while this study used only carbapenem susceptible isolates. Hence, further studies are needed to use highly antibiotic-resistant anaerobic isolates to carbapenems.

Pneumococcal disease is one of the most common and severe vaccine-preventable diseases (VPDs). Despite the advances in antimicrobial treatment, pneumococcal disease still remains a global burden and exhibits a high mortality rate among people of all ages worldwide. The immunization program of the pneumococcal conjugate vaccine (PCV) in children has decreased pneumococcal disease incidence in several countries. However, there are several problems regarding the pneumococcal vaccine, such as indications for immunocompetent persons with underlying medical conditions with a risk of pneumococcal disease, the balance of utility and cost, i.e., cost-effectiveness, vaccine coverage rate, serotype replacement, and adverse events. Especially for individuals aged 19–64 at risk of pneumococcal disease, physicians and vaccine providers should make a rational decision whether the patients should be vaccinated or not, since there is insufficient evidence supporting it. We describe this review regarding topics and problems regarding pneumococcal vaccination from the clinician’s point of view.

Carbapenem-resistant Enterobacterales (CRE) and carbapenemase-producing Enterobacterales (CPE) have become global threats. CRE− and CPE− derived infections have been associated with high mortality due to limited treatment options. Nacubactam is a β-lactamase inhibitor and belongs to the new class of diazabicyclooctane. The agent has an in vitro antimicrobial activity against several classes of β-lactamase-producing Enterobacterales. This study evaluated antimicrobial activity of combination therapies including β-lactams (aztreonam, cefepime, and meropenem) and nacubactam against four Enterobacter cloacae and six Klebsiella pneumoniae isolates with murine pneumonia model. Based on changes in bacterial quantity, antimicrobial activities of some regimens were assessed. Combination therapies including β-lactams (aztreonam, cefepime, and meropenem) with nacubactam showed enhanced antimicrobial activity against CRE E. cloacae (−3.70 to −2.08 Δlog10 CFU/lungs) and K. pneumoniae (−4.24 to 1.47 Δlog10 CFU/lungs) with IMP-1, IMP-6, or KPC genes, compared with aztreonam, cefepime, meropenem, and nacubactam monotherapies. Most combination therapies showed bacteriostatic (−3.0 to 0 Δlog10 CFU/lungs) to bactericidal (10 CFU/lungs) activities against CRE isolates. This study revealed that combination regimens with β-lactams (aztreonam, cefepime, and meropenem) and nacubactam are preferable candidates to treat pneumonia due to CRE and CPE.

The gut microbiome is closely related to gut metabolic functions, and the gut microbiome and host metabolic functions affect each other. Clostridium butyricum MIYAIRI 588 (CBM 588) upregulates protectin D1 production in host colon tissue following G protein-coupled receptor (GPR) 120 activation to protect gut epithelial cells under antibiotic-induced dysbiosis. However, how CBM 588 enhances polyunsaturated fatty acid (PUFA) metabolites remains unclear. Therefore, we focused on the metabolic function alterations of the gut microbiome after CBM 588 and protectin D1 administration to reveal the interaction between the host and gut microbiome through lipid metabolism during antibiotic-induced dysbiosis. Consequently, CBM 588 modified gut microbiome and increased the butyric acid and oleic acid content. These lipid metabolic modifications induced GPR activation, which is a trigger of ERK 1/2 signaling and directed differentiation of downstream immune cells in the host colon tissue. Moreover, endogenous protectin D1 modified the gut microbiome, similar to CBM 588. This is the first study to report that CBM 588 influences the interrelationship between colon tissue and the gut microbiome through lipid metabolism. These findings provide insights into the mechanisms of prevention and recovery from inflammation and the improvement of host metabolism by CBM 588.

There are limited data of amikacin pharmacokinetics (PK) in the elderly population. Hence, we aimed to describe the population PK of amikacin in elderly patients (>70 years old) and to establish optimized initial dosing regimens. We simulated individual maximum concentrations in plasma (Cmax) and minimal concentrations (Cmin) for several dosing regimens (200–2000 mg every 24, 48, and 72 h) for patients with creatinine clearance (CCr) of 10–90 mL/min and analyzed efficacy (Cmax/minimal inhibitory concentration (MIC) ≥ 8) for MICs of 4, 8, and 16 mg/L and safety (Cmin < 4 mg/L). A one-compartment model best described the data. CCr was the only covariate associated with amikacin clearance. The population PK parameter estimates were 2.25 L/h for clearance and 18.0 L for volume of distribution. Dosing simulations recommended the dosing regimens (1800 mg) with dosing intervals ranging 48–72 h for patients with CCr of 40–90 mL/min based on achievement of both efficacy for the MIC of 8 mg/L and safety. None of the dosing regimens achieved the targets for an MIC of 16 mg/L. We recommend the initial dosing regimen using a nomogram based on CCr for an MIC of ≤8 mg/L in elderly patients with CCr of 40–90 mL/min.