Acute Kidney Injury in Non-Intensive Care and Intensive Care Patients Treated with Vancomycin and Piperacillin-Tazobactam.

BACKGROUND: We investigated the incidence of acute kidney injury (AKI) and risk factors associated with vancomycin (VAN) and piperacillin-tazobactam (TZP) combination therapy in non-intensive care unit (ICU) and ICU settings. METHODS: In this single-center retrospective cohort study, adults who received VAN for ≥48 h during the period from 1 January 2016 through 31 December 2017 were included. The primary endpoint was incidence of AKI. RESULTS: Data from 593 adults were analyzed. The incidence of AKI was 10.6% overall, 8.0% in the non-TZP group, and 19.8% in the TZP group. In univariate analysis, the odds ratio (OR) for AKI was higher in the TZP group than in the non-TZP group (2.84, 95% CI = 1.64-4.90). In both the non-ICU and ICU settings, the OR for AKI was higher in the TZP group than in the non-TZP group (non-ICU: OR = 3.04, 95% CI = 1.52-6.09; ICU: OR = 2.51, 95% CI = 1.03-6.08). Furthermore, in propensity score analysis, the OR for AKI was higher in the TZP group than in the non-TZP group (OR = 2.81, 95% CI = 1.52-5.17). In both the non-ICU and ICU settings, the OR for AKI was higher in the TZP group than in the non-TZP group (non-ICU: OR = 2.57, 95% CI = 1.17-5.64; ICU: OR = 3.51, 95% CI = 1.05-11.6). CONCLUSIONS: Combined use of TZP in patients receiving VAN increased AKI incidence in non-ICU and ICU settings.

Fatal fulminant Clostridioides difficile colitis caused by Helicobacter pylori eradication therapy; a case report.

A 74-year-old male was referred to our critical care department for refractory severe watery diarrhea with advanced leukocytosis (over 70,000/µl) after multiple administrations of eradication therapy against Helicobacter pylori (HP). He was diagnosed as having fulminant colitis due to Clostridioides difficile after antimicrobial eradication therapy. He was given intravenous metronidazole and oral vancomycin. He also received supportive therapy including continuous hemodiafiltration for severe metabolic acidosis. However, despite emergency open sigmoidectomy, he died. The C. difficile isolate recovered was PCR-ribotype 002, which was positive for toxins A and B but negative for binary toxin. HP eradication therapy for prevention of chronic gastritis and stomach cancer is now in widespread use. Although such secondary severe complications are rare, we consider it to be necessary to pay sufficient attention when administering HP eradication therapy.

Comparison between IMP carbapenemase-producing Enterobacteriaceae and non-carbapenemase-producing Enterobacteriaceae: a multicentre prospective study of the clinical and molecular epidemiology of carbapenem-resistant Enterobacteriaceae.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) are classified as carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE; the majority of CPE in Japan produce IMP carbapenemase. OBJECTIVES: We evaluated the clinico-epidemiological and microbiological information and effects of IMP-type carbapenemase production in CRE. METHODS: Patients with isolations of CRE (MICs of meropenem ≥2 mg/L, imipenem ≥2 mg/L or cefmetazole ≥64 mg/L) from August 2016 to March 2018 were included. Microbiological analyses and WGS were conducted and clinical parameters were compared between groups. Independent predictors for the isolation of CPE from patients were identified by logistic regression. For comparing clinical outcomes, a stabilized inverse probability weighting method was used to conduct propensity score-adjusted analysis. RESULTS: Ninety isolates (27 CPE and 63 non-CPE) were collected from 88 patients (25 CPE and 63 non-CPE). All CPE tested positive for IMP carbapenemase. Antibiotic resistance (and the presence of resistance genes) was more frequent in the CPE group than in the non-CPE group. Independent predictors for CPE isolation were residence in a nursing home or long-term care facility, longer prior length of hospital stay (LOS), use of a urinary catheter and/or nasogastric tube, dependent functional status and exposure to carbapenem. Although in-hospital and 30 day mortality rates were similar between the two groups, LOS after CRE isolation was longer in the CPE group. CONCLUSIONS: IMP-CPE were associated with prolonged hospital stays and had different clinical and microbiological characteristics compared with non-CPE. Tailored approaches are necessary for the investigational and public health reporting, and clinical and infection prevention perspectives for IMP-CPE and non-CPE.

Memory B cell pool of autoimmune pulmonary alveolar proteinosis patients contains higher frequency of GM-CSF autoreactive B cells than healthy subjects.

The IgG-type neutralizing GM-CSF autoantibody (GMAb) is known to be the causative agent for autoimmune pulmonary alveolar proteinosis (APAP). Previous studies report that serum levels of IgG-GMAb are approximately 50-fold higher in APAP patients than in healthy subjects (HS). Serum levels of IgM-GMAb are also higher in APAP patients than in HS, but this has been assumed to be an etiological bystander. However, the mechanism for the excessive production of IgG-GMAb in APAP remains unclear. To investigate this, we detected putative GMAb-producing B cells (PGMPB) by inoculated B cells from the peripheral blood of APAP patients, HS, and umbilical cord blood mononuclear cells (UCBMNs) with Epstein-Barr virus. Both ELISA and ELISPOT assays showed that IgM-type GMAb was consistently and frequently present in all three groups, whereas IgG-type GMAb was high only in APAP patients, in whom it was exclusively produced in memory B cells and not in naive B cells. Since PGMPB in UCBMNs produced IgM-GMAb, but not IgG-GMAb, to the same extent as in HS and APAP patients, most IgM-GMAb reacted with GM-CSF in a non-specific manner. The memory B cell pool of APAP patients contain higher frequency of PGMPB than that of healthy subjects.

Infective endocarditis caused by Cardiobacterium valvarum.

We report a case with infective endocarditis (IE) due to Cardiobacterium valvarum . The patient was a 57-year-old male, who was referred to our hospital based on suspected IE detected by transthoracic echocardiography at a neighbourhood clinic. Three sets of blood cultures obtained on admission yielded positive results, and revealed rather slender and linear Gram-negative bacilli with a rosette formation that dyed minimally, with a pale white appearance. Although no isolates were identified by conventional methods, C. valvarum was ultimately identified by 16 S ribosomal RNA genotyping. HACEK group strains are difficult to identify by conventional methods. Therefore, if Gram-negative bacilli are isolated from IE patients, 16 S ribosomal RNA genotyping will be necessary. Furthermore, IE due to C. valvarum is very rare. We thus discuss our case in comparison with previous reports.

Kodamaea ohmeri fungemia in severe burn: Case study and literature review.

Kodamaea ohmeri is a relatively rare yeast isolated form clinical specimens, and it is known to be a causative fungus of severe invasive infectious diseases in immunocompromised hosts. Herein, we describe fungemia due to K. ohmeri in a patient with a severe extended burn. The isolate was obtained from not only blood specimens but also skin lesions. We should be aware of risk for fungemia including K. ohmeri in case of severe burn.

Reduced incidence of lung cancer in patients with idiopathic pulmonary fibrosis treated with pirfenidone.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a disease with a worse prognosis than some types of cancer. In patients with IPF, lung cancer is critical because of the associated high mortality rate from its progression and fatal complications from anticancer treatments. Therefore, preventing lung cancer in patients with IPF is primordial. Pirfenidone is an anti-fibrotic agent that reduces the decline in forced vital capacity. This study aimed to assess the effect of pirfenidone in the development of lung cancer in patients with IPF. METHODS: Data from 261 patients with IPF with and without pirfenidone were retrospectively reviewed, and the incidence of lung cancer was analyzed. RESULTS: In the pirfenidone group, the incidence of lung cancer was significantly lower than in the non-pirfenidone group (2.4% vs. 22.0%, P < 0.0001). Multivariate Cox proportional hazards regression analysis demonstrated that pirfenidone decreased the risk of lung cancer (hazard ratio, 0.11; 95% confidence interval, 0.03 to 0.46; P = 0.003), whereas coexisting emphysema increased the incidence of lung cancer (hazard ratio, 3.22; 95% confidence interval, 1.35 to 7.70; P = 0.009). CONCLUSIONS: Pirfenidone might correlate with a decreased risk of lung cancer in patients with IPF. However, no definite conclusion can be drawn from this retrospective study, and a multicenter, prospective cohort study is still warranted to confirm the effect of pirfenidone on lung cancer in patients with IPF.

Neck abscess due to Salmonella Choleraesuis: case study and literature review.

Introduction. We herein describe a case with a neck abscess due to non-typhoidal Salmonella (NTS). NTS habitually reside in our environment and colonize all animals including mammals. Colonizations of pigs, chickens, cows and sheep are important because food poisoning episodes in human are often associated with meat. Extra-intestinal infection due to NTS has numerous presentations and complications, with aortic aneurysms being common. Case presentation. A 26-year-old Japanese male complaining of left-sided neck swelling was referred to our hospital for a suspected deep neck abscess. An enhanced computed tomography scan of the neck revealed a low density lesion in the left-sided deep neck area, and consequently the patient underwent urgent incision and drainage. After this urgent operation, Salmonella Choleraesuis was isolated from a greyish-white abscess. The patient ultimately recovered with antimicrobial administration, though re-incision for lymphadenectomy was necessary. The neck abscess may have developed because he had eaten raw meat. Furthermore, untreated diabetes mellitus was diagnosed at presentation. Conclusion.Salmonella enterica serovar Choleraesuis infections are rare in Japan. NTS are generally recognized as important pathogens in food poisoning globally, and attention is required to avoid the development of extra-intestinal infections. In Japan, the increasing lifestyle diversity in recent years highlights the importance of recognizing rare infections.

Risk factors of catheter-related bloodstream infection caused by Bacillus cereus: Case-control study in 8 teaching hospitals in Japan.

In this multicenter, matched case-control study, patients diagnosed with catheter-related bloodstream infection (CRBSI) caused by Bacillus cereus (n = 108) were matched to controls (n = 269). In the multivariable analysis, administration of an amino acid preparation and an indwelling peripheral catheter were significant variables for B cereus-related CRBSI.

A Semiquantitative Computed Tomographic Grading System for Evaluating Therapeutic Response in Pulmonary Alveolar Proteinosis.

RATIONALE: A useful semiquantitative method of using computed tomographic (CT) images to evaluate therapeutic response in pulmonary alveolar proteinosis (PAP) has not been established, although the extent score or grading score of ground-glass opacities has been used. OBJECTIVES: The purpose of this study was to establish a semiquantitative method for evaluating therapeutic response in PAP. METHODS: CT scans were obtained within 1 month before and after therapy from 32 patients with PAP who participated in a multicenter phase II trial of granulocyte-macrophage colony-stimulating factor inhalation therapy. The scans were evaluated by two chest radiologists independently. Increased parenchymal opacity was evaluated on the basis of its intensity and extent (CT grade), and the severity scores were compared with CT scores based on the extent alone (CT extent), as well as on the basis of physiological and serological results. RESULTS: CT grade score and CT extent score had significant correlation with diffusing capacity of the lung for carbon monoxide percent predicted (%DlCO), PaO2, VC percent predicted (%VC), Krebs von den Lungen (KL)-6, and surfactant protein D. The change in CT grade score between pre- and post-treatment examinations (ΔCT grade) correlated better with difference of PaO2 between pre- and post-treatment examinations (ΔPaO2) than ΔCT extent (difference of CT extent score between pre- and post-treatment examinations). In univariate analysis, ΔCT grade, ΔCT extent, ΔKL-6, Δ%DlCO, Δ%VC, and change in surfactant protein D correlated significantly with ΔPaO2. In multivariate analysis, ΔCT grade and ΔKL-6 correlated more closely with ΔPaO2. CONCLUSIONS: Although a number of CT variables were collected, the currently proposed grading system that correlates well with PaO2 should be viewed as a retrospective scoring system that needs future validation with another PAP cohort.

Body Mass Index and arterial blood oxygenation as prognostic factors in patients with idiopathic pleuroparenchymal fibroelastosis.

Background: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) was recently proposed as an entity to be included among rare idiopathic interstitial pneumonias (IIPs). However, the cause, clinical features and prognosis of this rare entity have not been elucidated. Objectives: We aimed to examine the clinical features, outcomes and prognostic factors for IPPFE in comparison to those of idiopathic pulmonary fibrosis (IPF). Methods: We retrospectively analyzed 20 patients with IPPFE and 71 with IPF. We compared clinical features, blood examination data, and respiratory functions at the time of diagnosis. Results: The IPPFE group had a significantly lower body mass index (BMI), percent forced vital capacity (%FVC), total lung capacity (%TLC) and expiratory reserve volume (%ERV), as well as a higher residual volume to TLC (RV/TLC) ratio than the IPF group. The annual FVC changes in the IPPFE group (-326ml/year) were significantly larger than those in the IPF group (-142ml/year). Survival was significantly poorer in the IPPFE than in the IPF group (P = 0.021). BMI and the partial pressure of oxygen in arterial blood (PaO2) were significantly related to the outcome of IPPFE. Conclusions: Our present results indicate the prognosis of IPPFE patients to be poorer than that of IPF patients. We advocate that BMI and arterial blood PaO2 be determined at the first visit as these parameters are closely related to patients' outcomes. Prospective evaluation of IPPFE starting in the subclinical phase is necessary to assure that appropriate measures are taken before progression. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 35-40).

Case Report: An Outbreak of Food-Borne Typhoid Fever Due to Salmonella enterica Serotype Typhi in Japan Reported for the First Time in 16 Years.

For the first time in 16 years, a food-borne outbreak of typhoid fever due to Salmonella enterica serotype Typhi was reported in Japan. Seven patients consumed food in an Indian buffet at a restaurant in the center of Tokyo, while one was a Nepali chef in the restaurant, an asymptomatic carrier and the implicated source of this outbreak. The multiple-locus variable-number tandem repeat analysis showed 100% consistency in the genomic sequence for five of the eight cases.

Acute Lung Injury Accompanying Alveolar Hemorrhage Associated with Flu Vaccination in the Elderly.

Flu vaccinations are administered worldwide every winter for prevention. We herein describe a case of acute lung injury resulting from a pathologically confirmed alveolar hemorrhage, which may have been closely related to a preceding vaccination for pandemic influenza A of 2009/10. The present patient had been hospitalized with an acute lung injury after flu vaccination one year prior to the present hospitalization, however, he received another flu vaccination. We should consider a vaccine-related adverse reaction as a potential cause of pulmonary disease if patients present with this illness during the winter season.

Streptobacillus moniliformis bacteremia in a rheumatoid arthritis patient without a rat bite: a case report.

BACKGROUND: Rat bite fever is a relatively rare infectious disease due to infection with Streptobacillus moniliformis or Spirillum minus mainly via directs bite by rats, mice, or other rodents. If there is no clear bite history, the diagnosis is difficult or may not be made. CASE PRESENTATION: A 72-year-old Asian female with rheumatoid arthritis was admitted for high grade fever and walking difficulty with severe lumbago. Initially, we suspected lumber compression fracture with deterioration of rheumatoid arthritis, but Gram-negative bacilli were isolated from blood culture during hospitalization. The isolated organism was identified as S. moniliformis by 16S ribosomal ribonucleic acid (rRNA) sequencing. S. moniliformis is well known to be a primary causative organism of rat bite fever, but this patient had no history of rat bite. Had S. moniliformis bacteremia not been detected, she might have been treated for rheumatic exacerbation. CONCLUSION: We emphasize the importance of performing appropriate microbial culture testing for identifying potential infectious diseases. We also conclude that S. moniliformis infection can become established with contaminated vehicle contact alone, not only as a direct result of a bite. We must keep mind that those working in places where rodents breed or are at risk of contact with rats or mice might be at risk for contracting this unusual disease.

Outcome of corticosteroid administration in autoimmune pulmonary alveolar proteinosis: a retrospective cohort study.

BACKGROUND: Although no report has demonstrated the efficacy of corticosteroid therapy for autoimmune pulmonary alveolar proteinosis (aPAP), we sometimes encounter patients who have received this therapy for various reasons. However, as corticosteroids can suppress alveolar macrophage function, corticosteroid therapy might worsen disease severity and increase the risk of infections. METHODS: For this retrospective cohort study, we sent a screening form to 165 institutions asking for information on aPAP patients treated with corticosteroids. Of the resulting 45 patients screened, 31 were enrolled in this study. We collected demographic data and information about corticosteroid treatment period, dose, disease severity score (DSS) over the treatment period, and complications. RESULTS: DSS deteriorated during corticosteroid therapy in 23 cases (74.1 %) and the estimated overall cumulative worsening rate was 80.8 % for the total observation period. The worsening rate was significantly higher in patients treated with high-dose prednisolone (>18.9 mg/day, n = 16) than treated with low-dose prednisolone (≤18.9 mg/day, n = 15) divided by median daily dose (p < 0.02). Of patients with worsening, one died of disseminated aspergillosis and another of respiratory failure. Infections newly emerged in 6 cases during corticosteroid therapy (p < 0.05). Median serum granulocyte/macrophage colony-stimulating factor (GM-CSF) autoantibody levels were similar to previously reported data in a large cohort study. CONCLUSION: The results demonstrate that corticosteroid therapy may worsen DSS of aPAP, increasing the risk for infections.

Pulmonary Nocardiosis due to Nocardia asiatica in an Immunocompetent Host.

We describe a case of pulmonary nocardiosis due to Nocardia asiatica in an immunocompent 64-year-old-female. Wadowsky-Yee-Okuda-α-ketoglutarate (WYOα) agar, a selective media for Legionella species, was useful for the detection based on the growth-inhibition of normal oral flora and growth-promotion of Nocardia species.

Two cases with bacteremia suspected to be due to relatively rare Pseudomonas (Flavimonas) oryzihabitans.

Pseudomonas oryzihabitans (formerly Flavimonas oryzihabitans) is a glucose non-fermentative, Gram-negative bacillus which is rarely isolated from human specimens. When isolated, it is on very rare occasion as a causative pathogen of catheter-related bloodstream infection in an immunocompromised patient. Herein, we describe two hematological malignancy patients suspected to have P. oryzihabitans bacteremia. We also review cases with bacteremia due to this pathogen and its microbiological characteristics.

Clinical experience with pirfenidone in five patients with scleroderma-related interstitial lung disease.

Interstitial lung disease is the most common complication and cause of death among patients with scleroderma. Scleroderma-related interstitial lung disease has usually been treated with cyclophosphamide; however, its effect was evaluated to be modest and long-term administration of this drug is associated with adverse effects. Herein, we report our clinical experience of administering pirfenidone, which is an antifibrotic agent, in five patients with scleroderma-related interstitial lung disease. All patients demonstrated an increase in vital capacity.

Pirfenidone inhibits fibrocyte accumulation in the lungs in bleomycin-induced murine pulmonary fibrosis.

BACKGROUND: Bone marrow-derived fibrocytes reportedly play important roles in the pathogenesis of idiopathic pulmonary fibrosis. Pirfenidone is an anti-fibrotic agent; however, its effects on fibrocytes have not been investigated. The aim of this study was to investigate whether pirfenidone inhibits fibrocyte pool size in the lungs of bleomycin-treated mice. METHODS: Bleomycin (100 mg/kg) was infused with osmotic pumps into C57BL/6 mice, and pirfenidone (300 mg/kg/day) was orally administered daily for 2 wk. The lungs were removed, and single-cell suspensions were subjected to fluorescence-activated cell sorter (FACS) analysis to detect fibrocytes, which were defined as CD45 and collagen-I double-positive cells. Immunohistochemistry was performed on the lung specimens to quantify fibrocytes. Chemokines in the lung digests were measured with enzyme-linked immunosorbent assay. The effect of pirfenidone on alveolar macrophages was evaluated with bronchoalveolar lavage (BAL). In a therapeutic setting, pirfenidone administration was initiated 10 days after bleomycin treatment. For chemotaxis assay, lung fibrocytes were isolated with immunomagnetic selection (CD45-positive mesenchymal cells) after culture and allowed to migrate toward chemokines in the presence or absence of pirfenidone. Moreover, the effect of pirfenidone on the expression of chemokine receptors on fibrocytes was evaluated. RESULTS: Pirfenidone significantly ameliorated bleomycin-induced pulmonary fibrosis as assessed with quantitative histology and collagen measurement. Fibrocyte pool size in bleomycin-treated mice lungs was attenuated from 26.5% to 13.7% by pirfenidone on FACS analysis. This outcome was also observed in a therapeutic setting. Immunohistochemistry revealed that fibrocytes were significantly decreased by pirfenidone administration compared with those in bleomycin-treated mice (P = 0.0097). Increased chemokine (CC motif) ligand-2 (CCL2) and CCL12 production in bleomycin-treated mouse lungs was significantly attenuated by pirfenidone (P = 0.0003 and P < 0.0001, respectively). Pirfenidone also attenuated macrophage counts stimulated by bleomycin in BAL fluid. Fibrocyte migration toward CCL2 and chemokine (CC motif) receptor-2 expression on fibrocytes was significantly inhibited by pirfenidone in vitro. CONCLUSIONS: Pirfenidone attenuated the fibrocyte pool size in bleomycin-treated mouse lungs via attenuation of CCL2 and CCL12 production in vivo, and fibrocyte migration was inhibited by pirfenidone in vitro. Fibrocyte inhibition is considered a mechanism of anti-fibrotic action of pirfenidone.

Duration of benefit in patients with autoimmune pulmonary alveolar proteinosis after inhaled granulocyte-macrophage colony-stimulating factor therapy.

BACKGROUND: Treatment of autoimmune pulmonary alveolar proteinosis (aPAP) by subcutaneous injection or inhaled therapy of granulocyte-macrophage colony-stimulating factor (GM-CSF) has been demonstrated to be safe and efficacious in several reports. However, some reports of subcutaneous injection described transient benefit in most instances. The durability of response to inhaled GM-CSF therapy is not well characterized. METHODS: To elucidate the risk factors for recurrence of aPAP after GM-CSF inhalation, 35 patients were followed up, monitoring for the use of any additional PAP therapies and disease severity score every 6 months. Physiologic, serologic, and radiologic features of the patients were analyzed for the findings of 30-month observation after the end of inhalation therapy. RESULTS: During the observation, 23 patients remained free from additional treatments, and twelve patients required additional treatments. There were no significant differences in age, sex, symptoms, oxygenation indexes, or anti-GM-CSF antibody levels at the beginning of treatment between the two groups. Baseline vital capacity (% predicted, %VC) were higher among those who required additional treatment (P<.01). Those patients not requiring additional treatment maintained the improved disease severity score initially achieved. A significant difference in the time to additional treatment between the high %VC group (%VC≥80.5) and the low %VC group was seen by a Kaplan-Meier analysis and a log-rank test (P<.0005). CONCLUSIONS: These results demonstrate that inhaled GM-CSF therapy sustained remission of aPAP in more than one-half of cases, and baseline %VC might be a prognostic factor for disease recurrence. TRIAL REGISTRY: ISRCTN Register and JMACCT Clinical Trial Registry; No.: ISRCTN18931678 and JMAIIA00013; URL: http://www.isrctn.org and http://www.jmacct.med.or.jp.