Amikacin Liposome Inhalation Suspension in the Real-World Management of Refractory Mycobacterium avium Complex Pulmonary Disease.

The increasing prevalence of Mycobacterium avium complex (MAC) pulmonary disease poses a significant therapeutic challenge, particularly due to the limited efficacy and systemic toxicity associated with conventional guideline-based therapy. Amikacin liposome inhalation suspension (ALIS) has been developed, yet its real-world application remains underreported. This retrospective analysis, conducted from March 2021 to February 2024, examined ALIS's clinical use in patients aged 20 years or older with refractory MAC pulmonary disease at our institution. The primary objective of this study is to describe the patient characteristics and clinical trajectories associated with the initiation of ALIS therapy in real-world settings for individuals diagnosed with MAC pulmonary disease. Of 11 patients initiated on ALIS, one was excluded due to financial constraints impacting continuation. The analysis proceeded with the remaining 10 subjects. The mean age of participants was 70.2 years, with a predominance of female patients (n = 7, 70%) and a higher incidence of M. avium infections (n = 6, 60%). Forty percent of the cohort (n = 4) had a history of ethambutol-induced optic neuritis leading to the cessation of the drug. The average interval from the initiation of guideline-based therapy to the start of ALIS was 8.5 ± 6.9 years (mean ± standard deviation). The majority (80%) presented with positive Gaffky scores at ALIS initiation, and a significant proportion exhibited resistance to clarithromycin and ethambutol. Comorbid conditions, including diabetes and previous cancer, were noted. The study also observed elevated anti-MAC antibody levels. Treatment duration varied, with fatigue leading to discontinuation in two cases. Treatment-emergent adverse events were documented in individual patients, each presenting with grade 1 severity: hemoptysis (n = 1, 10%), elevated creatinine levels (n = 1, 10%), and dysphonia (n = 2, 20%) were observed, respectively. Correlation analysis revealed a significant inverse relationship between body mass index (BMI) and ALIS discontinuation due to fatigue, and a positive correlation between Gaffky scores and C-reactive protein (CRP) levels. These results underscore the potential benefits and limitations of ALIS, suggesting that timely intervention and comprehensive healthcare support are crucial for optimal outcomes in the treatment of advanced MAC pulmonary disease.

Effective treatment of inhaled corticosteroid and bronchodilator for "lymphocytic interstitial pneumonia" in primary Sjögren's syndrome.

We present a case of an 86-year-old woman who visited our hospital with a one-year history of exertional dyspnea (modified medical research council dyspnea scale; mMRC grade 2). Despite the absence of any smoking or dust exposure history, multiple cystic lesions were apparent in both lungs on her CT scan. We suspected Sjögren's syndrome-associated lymphocytic interstitial pneumonia (LIP) due to her additional symptoms of dry mouth and eyes. Her respiratory function test showed a restrictive disorder with a forced vital capacity (FVC) of 1.23 L (70.3 % predicted), forced expiratory volume in 1 s (FEV1) of 0.88 L, and FEV1/FVC of 71.5 %. The flow-volume curve showed a downward convex, suggesting peripheral airway obstruction. We initiated a daily inhalation treatment regimen comprising vilanterol 25 µg and fluticasone furoate 200 µg. One month later, at the follow-up visit, the clinical diagnosis of Sjögren's syndrome with LIP was made by positive SS-A and SS-B antibodies in the initial blood work, a Saxon test that confirmed decreased salivary secretion, and a confirmed diagnosis of dry eyes by her ophthalmologist. We noted improvement in FVC of 1.45 L (+17.8 %) and FEV1 to 0.99 L (+12.5 %) in the subsequent respiratory function test, along with alleviation of her symptoms. The present case represents the first report of LIP treated exclusively with inhaled corticosteroids and bronchodilators, highlighting a potential therapeutic approach, particularly for elderly patients vulnerable to immunosuppressive therapies.

A Teaching Case: Persistent COVID-19 Pneumonia Resembling Cryptogenic Organizing Pneumonia in a Patient With Remitted Lymphoma.

We report a case of a female patient in her 50s, previously diagnosed with follicular lymphoma (now in complete remission), who was admitted to our hospital due to antibiotic-resistant pneumonia lasting a month. The patient had contracted coronavirus disease 2019 (COVID-19) pneumonia a year earlier and exhibited persistent hypogammaglobulinemia. Chest CT scans revealed wondering ground-glass opacities and consolidations initially suggestive of cryptogenic organizing pneumonia (COP). Despite repeatedly negative nasopharyngeal SARS-CoV-2 tests, the virus was detected in the bronchoalveolar lavage fluid (BALF) using the BioFire FilmArray Respiratory Panel 2.1. She was subsequently diagnosed with COVID-19 pneumonia and responded well to treatment with remdesivir (RDV) and intravenous immunoglobulin. The SARS-CoV-2 variant in the BALF was suspected as the Omicron variant (XBB.1.16), prevalent in the area at the admission, indicating a re-infection rather than a recurrence. This case underscores the protracted nature of COVID-19 pneumonia in immunocompromised patients and the risks of false negatives in nasopharyngeal SARS-CoV-2 tests. Direct SARS-CoV-2 measurement from BALF can be crucial in such cases. A COP diagnosis based solely on imaging and administering corticosteroids without antiviral treatment might exacerbate the situation by reactivating SARS-CoV-2. Given the current pandemic, clinicians should be aware of the potential for persistent or recurrent COVID-19, particularly in immunocompromised patients.

Acute Pneumonitis Associated With the Inhalation of Pyrethroid-Based Domestic Insecticides.

We report a 72-year-old female who presented to our hospital with a worsening cough and dyspnea that had emerged a week earlier following the accidental inhalation of a significant quantity of spray-type imiprothrin (a synthetic pyrethroid)-based insecticide in her bathroom. She exhibited acute respiratory failure necessitating 4 L/minute of nasal oxygen at maximum. Chest CT images showed diffuse centrilobular ground-glass opacities with mosaic attenuation and consolidation areas in the lower lobes of both lungs. The patient was diagnosed with acute pneumonitis due to insecticide inhalation, and her symptoms improved following methylprednisolone pulse and alpha-tocopherol therapy. Generally, the accidental inhalation of aerosolized pyrethroids does not induce significant respiratory symptoms, and case reports on pulmonary toxicity related to pyrethroid inhalation are scarce. This case report underscores the need to include inhaled pyrethroid insecticides in the differential diagnosis of patients with acute pneumonitis and suggests that methylprednisolone and alpha-tocopherol therapy can be beneficial for treating this condition.

An Unusual Case of Bilateral Lower Extremity Edema in the Elderly: Immunoglobulin A (IgA) Vasculitis.

We report a case of a 74-year-old male who exhibited bilateral lower extremity edema over three days. Examination revealed no signs of heart, renal, or hepatic failure, and hypothyroidism was also ruled out. An outpatient regimen of 40 mg furosemide was initiated. At a 12-day follow-up, although the edema had improved, the patient had developed pain in both lower limbs, especially ankles, accompanied by numerous petechiae and erythemas, some of which had formed papules. Skin biopsy of the rash displayed leukocytoclastic vasculitis with immunoglobulin A (IgA) deposition within the vascular walls, leading to a diagnosis of IgA vasculitis. Given the rarity of IgA vasculitis in elderly patients and the broad spectrum of potential diagnoses related to bilateral lower extremity edema in this population, IgA vasculitis can be easily overlooked. While this case did not present with glomerulonephritis, regular renal function monitoring is recommended due to the prognostic implications of renal involvement in adult-onset IgA vasculitis.

Successful treatment of relapsing polychondritis with circumferential bronchial wall thickening including the tracheomembranous area with tumor necrosis factor-α inhibitor.

This is a case of a 55-year-old man who presented with cough and anterior chest pain. Tracheal biopsy confirmed the diagnosis of relapsing polychondritis (RP). Although the patient had circumferential bronchial wall thickening extending to the tracheomembranous area and was positive foRPR3-ANCA, he did not meet the diagnostic criteria for granulomatosis with polyangiitis. The patient was refractory to prednisolone + methotrexate + azathioprine and responded to adalimumab, a biologic tumor necrosis factor-α inhibitor effective in RP refractory cases. Herein, we report a rare case of RP with circumferential bronchial wall thickening extending to the tracheomembranous area.

Association of serum antibodies against the Mycobacterium avium complex and hemoptysis: a cross-sectional study.

BACKGROUND: Hemoptysis is very common and can be life threatening in clinical practice for nontuberculous mycobacteria. The serum antibody against the Mycobacterium avium complex (MAC-Ab), the majority of nontuberculous mycobacteria species, is well known to reflect the activity of MAC lung disease; however, there is no study investigating the association between the MAC-Ab and hemoptysis in MAC patients. Therefore, we assessed whether the MAC-Ab is a good biomarker for hemoptysis among subjects with MAC lung disease. METHODS: This study was conducted as a five-year retrospective survey at the National Hospital Organization Fukuoka National Hospital. A total of 155 patients aged ≥20 years with MAC lung disease were enrolled and separated into seropositive and seronegative groups using the cutoff for MAC-Ab levels of 0.7 U/ml. The prevalence of hemoptysis and odds ratios for the presence of hemoptysis were estimated and compared between the groups. To investigate the linear trends in the relationship between MAC-Ab levels and hemoptysis, the subjects were classified into three groups using the tertile distribution of the MAC-Ab. RESULTS: The prevalence of hemoptysis was twice as high in the seropositive group than in the seronegative group (42.2 and 21.7%, respectively, P = 0.02). The multivariable-adjusted risk of hemoptysis was elevated in the seropositive group as compared with the seronegative group (odds ratio = 2.79 (95% confidence interval 1.15-7.44)). Likewise, when categorizing the subjects into three groups, the risk of hemoptysis increased with increasing MAC-Ab levels (P = 0.03 for trend). CONCLUSIONS: A positive MAC-Ab level was a significant risk factor for hemoptysis among patients with MAC lung disease. There were also positive trends in the association between the MAC-Ab titer and the likelihood of hemoptysis. Measuring the MAC-Ab may contribute not only to early detection of the risk of hemoptysis but also to early intervention with anti-NTM therapy and, as a result, to the prevention of hemoptysis in MAC patients.

Nintedanib treatment for pulmonary fibrosis after coronavirus disease 2019.

A 78-year-old Japanese woman with no smoking history suffered from near-fatal coronavirus disease 2019 (COVID-19) requiring four-week invasive mechanical ventilation, with subsequent radiological features of pulmonary fibrosis. Although methylprednisolone gradually improved her respiratory condition, her oxygenation and exercise tolerance had drastically deteriorated, necessitating high-flow nasal cannula oxygen therapy. In parallel with tapering systemic steroid, the patient was treated with nintedanib. Three months later, the patient was able to walk with a walking aid using oxygen at 4 L/min. The present case is an indication that nintedanib might provide a novel therapeutic approach for managing post-COVID-19 fibrosis, although further studies are warranted.

Rise in nocturnal respiratory rate during CPAP may be an early sign of COVID-19 in patients with obstructive sleep apnea.

None: A middle-aged man with obstructive sleep apnea who had been treated with continuous positive airway pressure developed COVID-19. An analysis of airflow records from the continuous positive airway pressure machine revealed a rise in his respiratory rate on the night before the onset of COVID-19-related symptoms, while his nocturnal respiratory rate had been stable during the 18-month period prior to the presently reported episode. The present case suggests that a rise in respiratory rate detected using continuous positive airway pressure machine data could be an important sign of impending acute illness, such as COVID-19. Studies to elucidate the usefulness of this method are warranted.

Disseminated Cryptococcosis with Marked Eosinophilia in a Postpartum Woman.

Disseminated cryptococcosis usually develops in immunosuppressed patients. A 33-year-old postpartum woman developed disseminated cryptococcosis with marked eosinophilia. She presented with a cough and a week-long fever. A computed tomography scan showed multiple pulmonary nodules randomly distributed. Eosinophils were observed to have increased in number in both her peripheral blood and bronchoalveolar lavage fluid. A transbronchial lung biopsy and cerebrospinal fluid specimens revealed findings consistent with cryptococcal infection. Disseminated cryptococcosis can present with marked eosinophilia of the peripheral blood and lung tissues. Additionally, the postpartum immune status may sometimes be involved in the development of opportunistic infections in previously healthy women.

[Disseminated Cryptococcosis with Eosinophilia and Elevated IgE in a Non-HIV-infected Patient].

In general, disseminated cryptococcosis usually occurs among immunocompromised patients, especially those with cell-mediated immunodeficiency, such as HIV-infected patients. We present herein a rare case of an apparently immunocompetent 33-year-old woman who developed disseminated cryptococcal diseases, which included meningitis and pneumonia with eosinophilia, and pulmonary tuberculosis during her disease course. Pneumonia with a diffuse micronodular pattern, immediately followed by meningitis, was diagnosed as disseminated cryptococcosis, because of the presence of yeast-like-fungi demonstrated by transbronchial lung biopsy and a positive cerebrospinal fluid (CSF) culture. In addition, the pneumonia exhibited eosinophilia in the peripheral blood and bronchoalveolar lavage fluid. Re-exacerbation of the pneumonia occurred approximately 3 weeks after onset, along with a sputum culture positive for Mycobacterium tuberculosis. Administration of anti-tuberculosis drugs resulted in recovery from the pulmonary tuberculosis. The treatment of cryptococcal meningitis was initiated using a standard induction regimen;however, an unrecovered status, highlighted by elevated CSF pressure, persisted. Finally, full recovery was induced by the addition of flucytosine treatment (100 mg/kg/day) and repeated daily via lumbar puncture. The allergic condition of this patient may have contributed to the onset of disseminated cryptococcosis.

[Candida catheter related-blood stream infection].

Candida catheter-related bloodstream infection (CRBSI) is a biofilm-related disease, which is usually refractory because antifungals show limited effect. With medical development and increase in number of compromised hosts, CRBSI became more frequent. Candida, which is one of the opportunistic pathogens, ranks the fourth causative organism of bacteremia. The onset of bacteremia is greatly associated with the presence of catheter. Repeated blood cultures and the central venous catheter (CVC) tip culture are done for the definitive diagnosis of Candida CRBSI. Additionally serological examinations such as (1 --> 3)-beta-D-glucan and mannan antigen are also useful for early diagnosis. It is important for the appropriate treatment to remove CVC, which is an artificial contaminated material, and administer antifungals promptly. As to the choice of antifungals, we should also take into account the ability of antibiofilm effect of antifungals as well as immunological state of host including neutropenia, prior administration of azoles, isolated or estimated Candida species, sensitivity against antifungals, administration route, pharmacokinetics (bioavailability, metabolic and excretion pathway, distribution) and drug interaction. As to complication of Candida bacteremia, first we should check endophthalmitis, which occurs frequently and leads to the loss of eyesight, as well as infective endocarditis, arthritis, metastatic infections such as embolic pneumonia and suppurative thrombotic phlebitis of catheter insertion site. Lastly we emphasize that the appropriate treatment based on the character of Candida bacteremia and biofilm leads to favorable prognosis.

Successful treatment of invasive zygomycosis based on a prompt diagnosis using molecular methods in a patient with acute myelogenous leukemia.

Zygomycosis is a lethal and invasive mold infection that is often associated with hematological malignancies. The keys for successful treatment include making a rapid diagnosis and appropriately administering antifungal agents. We herein report the early diagnosis of a case of zygomycosis in a patient with acute myeloid leukemia using a deoxyribonucleic acid sequence analysis. We successfully performed allogeneic hematopoietic stem cell transplantation with the use of high-dose liposomal amphotericin B and granulocyte transfusion.

Infective endocarditis caused by Listeria monocytogenes forming a pseudotumor.

A 73-year-old woman with breast cancer and metastasis under chemotherapy suffered from fever, pleural effusion and pericardial effusion. Despite the administration of treatment with cefozopran and prednisolone, the patient's fever relapsed. An electrocardiogram identified a new complete atrioventricular block and an echocardiogram revealed vegetation with an unusual pseudotumoral mass in the right atrium. Blood cultures grew Listeria monocytogenes. The patient was eventually diagnosed with right-sided infective endocarditis, which improved following the six-week administration of ampicillin and gentamicin. Homemade yoghurt was suspected to be the cause of infection in this case. Listeria endocarditis is rare; however, physicians should pay more attention to preventing this fatal disease in immunocompromised patients.

Nosocomial spread of meticillin-resistant Staphylococcus aureus with ß-lactam-inducible arbekacin resistance.

A meticillin-resistant Staphylococcus aureus (MRSA) strain with additional ß-lactam-inducible aminoglycoside resistance was previously reported by a group at the Kitasato University in Japan. In addition to gentamicin, the 'Kitasato strain' was resistant to arbekacin (ABK), which is primarily used as an anti-MRSA aminoglycoside. No further studies regarding the spread of MRSA strains with the newly identified resistance mechanism have been reported to date. To obtain epidemiological data on MRSA strains with the antagonistic resistance and to analyse their genetic features, we examined the emergence of ß-lactam-inducible ABK-resistant MRSA strains at our university hospital using longitudinal analysis. Among the 396 isolates, 35 (8.8 %) were found to be ABK-resistant MRSA strains (the resistance being induced by ß-lactams). Moreover, based on the pulsed-field gel electrophoresis profiles, the clonality of those MRSA strains changed at different time periods. In the Kitasato strain, the antagonistic mechanism was clearly demonstrated by the integration of transposable elements; a Tn4001-IS257 hybrid structure that contained an aminoglycoside resistance gene cointegrated into a region downstream of the ß-lactamase gene. In most of the MRSA strains detected in our study, the antagonistic interaction was explained by the same mechanism as that found in the Kitasato strain. Interestingly, sequence analysis showed that all of our strains carried IS257 insertion sites which were different from those of the Kitasato strain. This study shows that MRSA strains with the additional antagonistic resistance are not uncommon and have been increasingly disseminating in clinical settings.

Radial mycotic aneurysm complicated with infective endocarditis caused by Streptococcus sanguinis.

Peripheral mycotic aneurysm is a rare complication of infective endocarditis. We herein report the case of a 61-year-old man with a mycotic aneurysm in the left brachial artery, that appeared during treatment with antibiotics against infective endocarditis caused by Streptococcus sanguinis. After confirming the collateral blood flow on arteriography, we resected the aneurysm and performed valvuloplasty, annuloplasty and coronary artery bypass grafting. The patient has been in good condition without complications, such as motor dysfunction or neuropathy.

[Influence of inoculum size on MICs for methicillin-susceptible Staphylococcus aureus and methicillin-resistant Staphylococcus aureus].

Using 49 clinical methicillin-susceptible Staphylococcus aureus isolates (MSSA) and 54 clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates, we examined the change of MIC using five different inocula (2.5-4 x 10(2) cfu/spot-2.5-4 x 10(6) cfu/spot). We found the big change of the MIC with the increase of the inoculum size in ampicillin against MSSA, and the change was small in cefazolin, meropenem, ciprofloxacin. For anti-MRSA antibiotics, we found the small change with the increase of the inoculums size in vancomycin and arbekacin, and the middle change in teicoplanin and linezolid against MSSA and MRSA. The data from this study suggest that in serious and high inocula infections caused by S. aureus, the presence of an inoculum effect should be considered in curing.

[Hematological unit invasive aspergillosis epidemiology].

Invasive aspergillosis (IA) is a major cause of morbidity and mortality among the immunocompromised, especially those undergoing hematopoietic stem cell transplantation. With spore inhalation the usual infection route, such subjects must be protected from environmental spore contamination, necessitating measures such as high-efficiency particulate air (HEPA) filtration. In April 2006, we implemented a new transplantation unit with HEPA filtration. We retrospectively evaluated its efficacy for hospitalized transplantation unit subjects whose sera were tested for aspergillus galactomannan antigen between April 2004 and March 2007. Subjects numbered 265 (973 samples) categorized as definite, probable, or possible. The earliest IA onset date was when symptoms, positive radiological findings, or positive galactomannan antigen tests occurred, based on revised European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) definitions. We classified cases when IA occurred over 10 days after admission as hospital-acquired. No such cases were detected after November 2005 and IA incidence decreased significantly after the new unit began being used. Results suggest that the new unit and HEPA filtration helped eliminate nosocomial IA.

Geographic distribution of fluoroquinolone-resistant Escherichia coli strains in Asia.

Fluoroquinolone (FQ) resistance is usually caused by point mutations within the quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, parC and/or parE. However, little is known about the worldwide increase in FQ-resistant Escherichia coli or, more specifically, about the geographical distribution of QRDR mutations and the clonal spread of isolates. In this study, we analysed 68 FQ-resistant E. coli isolates from eight Asian countries using QRDR amino acid mutation patterns and examined their susceptibility to FQs. Of the isolates, 38% had mutations at S83 and D87 of GyrA and S80 of ParC (MM/-/M-/-) and 34% had mutations at S83 and D87 of GyrA, S80 of ParC and S458 of ParE (MM/-/M-/M). MIC(50) values (minimum inhibitory concentrations for 50% of the isolates) for isolates with at least mutation at S458 of ParE for ciprofloxacin and prulifloxacin were relatively higher than MIC(50) values of isolates without this mutation. Based on their geographic distribution and the QRDR mutation patterns, the isolates were divided into a common type in which the organisms were isolated from three or more countries, and a local type in which the isolates were from one or two countries. Mutation types at S83L and D87N in GyrA and S80I in ParC with no or another site in the QRDR were the most frequent among the FQ-resistant isolates, especially among the common type. Gene typing indicated that isolates in the common type were not similar between countries. These data suggest that the increase in FQ-resistant E. coli strains is mainly generated by mutations in the QRDR in each geographical area rather than through intercontinental spread.

Combination therapy with micafungin and amphotericin B for invasive pulmonary aspergillosis in an immunocompromised mouse model.

OBJECTIVES: Antifungal monotherapy with polyenes, azoles or echinocandins is not always effective for invasive pulmonary aspergillosis (IPA). The main purpose of this study was to evaluate the efficacy of a combination of micafungin and amphotericin B for the primary treatment of IPA in an immunocompromised mouse model. METHODS: Female ICR mice were used in all experiments. An immunosuppressive state was induced in mice by an intraperitoneal injection of cyclophosphamide. Mice were intratracheally inoculated with Aspergillus fumigatus conidia, treated with micafungin, amphotericin B or both for 7 days, and were tested for their survival 20 days after the Aspergillus inoculation. Fungal burden in lungs, serum galactomannan index (GMI) and histopathology of lungs, spleen and kidneys were also evaluated. RESULTS: Combination therapy with micafungin and amphotericin B gave excellent survival of infected mice compared with monotherapy with micafungin or amphotericin B alone. Combined therapy reduced the fungal burden in the lungs and the serum GM levels compared with monotherapy or untreated controls, resulting in a significant histological improvement with disappearance of fungi in the lungs. CONCLUSIONS: These findings suggest that combination therapy with micafungin and amphotericin B is more effective compared with monotherapy with either of them alone for IPA treatment.