Negative Sputum Cultures Research Articles

Evaluation of Fraction of Exhaled Nitric Oxide (FeNO) in CF Children and its Association with Sputum Culture

Background: Exhaled nitric oxide (FeNO) in cystic fibrosis (CF) patients is reduced when compared with healthy people, and it has now been found that FeNO has a relative association with airway clearance index. Studies have shown the role of some infections in changing the FeNO level; however, the role of respiratory infections in FeNO has not yet been thoroughly studied. Objectives: The objective of this study was to investigate the possibility of FeNO usage to monitor the infections in CF patients. Methods: This cross-sectional case-control study was conducted on CF patients between the age of five to 18 with positive sputum culture, through simple non-random census method. FeNO levels were measured in 30 healthy children and 30 CF children with positive sputum culture. CF patients were treated by antibiotic therapy for two weeks; in the case offending negative sputum culture, the FeNO level was re-measured. FeNO levels were re-evaluated in 13 patients after four weeks. Results: There was no statistical difference between both groups in terms of age and weight. The level of FeNO in CF patients was significantly lower than in healthy children (22.1 ± 10.1 versus 30.0 ± 11.0 in the control group and P = 0.003). In 27 children, two weeks after administration of antibiotic therapy, sputum culture was negative. The mean of FeNO in these patients was 16.4 ± 5.5 at the time of the negative sputum culture, which was significantly lower than FeNO before starting the treatment. (P: 0.003). The mean FeNO was 13.0 ± 7.41 in 13 patients who were re-measured four weeks after starting the treatment. There was no significant difference between FeNO level two weeks after treatment and four weeks after starting treatment (P: 0.292). Patients with pseudomona sputum culture were not significantly different from those with non-pseudomona sputum culture in terms of primary FeNO and FeNO changes after the treatment (P value: 0.084 and 0.094, respectively). Conclusions: However, in our study, FeNO was decreased after administration of antibiotic treatment in CF patients, but according to the sample size and conflicting or similar results in other studies, currently, FeNO levels cannot be used as a way of monitoring the treatment of infection in CF patients.

51. An atypical case of GCA: an innocuous presentation ending with ophthalmic complications and cerebral vasculitis

IntroductionDespite being the most common form of primary systemic vasculitis in adults, giant cell arteritis (GCA) remains a difficult diagnosis to make due to the breadth and versatility of presenting symptoms and signs. Many patients present with a myriad of symptoms which don’t fit neatly into the American College of Rheumatology criteria (1990) often with a negative or absent temporal artery biopsy. Here we describe an atypical and aggressive presentation of a patient with GCA.Case descriptionA 77-year old male with a background of pertussis was initially referred to the medical take with 2 weeks of lethargy, raised C-reactive protein (343) and white cell count (27.8). He admitted to fevers, myalgia and sweats but denied any GCA symptoms. Examination revealed no abnormalities. He was treated for an infection of unknown source with broad spectrum antibiotics. A CT chest, abdomen and pelvis showed bibasal consolidation in the lungs with small effusions. He went on to have negative blood, sputum and urine cultures. Despite antibiotic escalations, his inflammatory markers remained high. An echocardiogram showed no vegetations. His pleural effusions were aspirated and revealed a transudative lymphocytic fluid with no acid-fast bacilli. He was then referred to rheumatology. He denied GCA or connective tissue disease symptoms. He had a persistently raised CRP (>150) and WCC (>15) with no fevers. Examination revealed present temporal artery pulses and no abnormalities. Immunology was negative (ANA, ENA, ANCA and CCP). A PET scan showed no changes consistent with a malignancy, large vessel vasculitis or infection. He was labelled as an undifferentiated autoimmune disorder by the medical team and given a trial of prednisolone 30mg to which his CRP fell from 265 to 41. He was discharged with general medical follow-up and a prednisolone weaning regime. After 1 month he re-presented to the medical take with acute bilateral visual loss (on 15mg prednisolone). This was preceded by a 2-week history of bitemporal headaches. There was no history of polymyalgia, jaw claudication or scalp tenderness. Ocular examination revealed bilateral swollen optic discs. He was admitted and treated with pulsed intravenous methylprednisolone. An MRA of his head and neck showed intracranial irregularities consistent with a cerebral vasculitis. He was started on methotrexate alongside prednisolone and referred to the regional GCA centre for tocilizumab therapy. DiscussionThe frequency of ophthalmic complications in GCA is quoted to be as high as 30%. The case above presented with non-specific symptoms and extremely raised inflammatory markers. Despite numerous investigations including a PET scan, a definitive diagnosis was not made without the final presentation of permanent bilateral visual loss. The patient had appropriate and timely investigations for his symptoms at initial admission (blood tests, cultures, CT and PET imaging). Positive findings were appropriately investigated further. Ultimately, he was trialled with prednisolone when infection and malignancy were excluded by the medical team and discharged with follow up. Unfortunately, he was then readmitted with a dramatic relapse. The British Society for Rheumatology recommends starting methotrexate following recurrent relapses in GCA, but we decided to start methotrexate due to the aggressive nature of his disease (sudden onset visual loss and cerebral vasculitis on MRA).Few randomised controlled studies, case-control studies and meta-analyses have looked at the efficacy and steroid-sparing effects of methotrexate introduction at diagnosis of GCA to conflicting results. Jover et al. (2001) showed that low dose methotrexate (10mg) was effective in controlling GCA disease activity. This was supported by a meta-analysis (Mahr et al., 2007) and most recently in a retrospective case-control study (Koster et al., 2019). The larger and well-designed Hoffman et al. (2002) trial showed a small benefit from methotrexate introduction but no statistical significance. There has been no large-trial convincing evidence of methotrexate efficacy in GCA at introduction or for relapses and this is reflected in the national guidance. However, the trials above used relatively low doses of methotrexate. Some of the trial also had short follow-up times and with slow steroid weans possibly masking a positive methotrexate effect. Key learning pointsDespite the vague and nondescript presentation of this patient, focusing on subtleties from the history and having a high index of suspicion are vital to making a diagnosis of GCA.The patient had a negative PET scan despite progression to severe disease within 1 month. PET studies have shown high sensitivity and specificity values for the diagnosis of large vessel inflammation in GCA (90% and 98% respectively – Soussan et al., 2015). However, the lack of large vessel involvement on this scan was falsely reassuring. Conflicts of interestThe authors have declared no conflicts of interest.

The Relationship Between Bacterial Pattern with Degree of Airflow Limitation FEV1 in Acute Exacerbation of COPD at Adam Malik General Hospital and Pirngadi Hospital

Background: Respiratory tract infections are the leading cause of acute exacerbation of COPD (AECOPD). The aim of this study was to investigate the relationship between bacterial pattern and the degree of airflow limitation (FEV1) in patients with acute exacerbation of COPD at Adam Malik General Hospital and Pirngadi Hospital, also the sensitive antibiotics according to the susceptibility test.
 Methods: This was a cross sectional study of all patients admitted to Adam Malik and Pirngadi Hospital with AECOPD from September 2015 until September 2016. In all 45 subjects who fulfilled the inclusion criteria, the spirometry was examination undergone to evaluate the degree of severity of COPD according to GOLD 2017. In each sample sputum expectoration, the gram smear was made. Barttlet criteria was used to calculate the amount of epithelial cells and PMN. The sample was then grown on blood agar medium. Bacterial susceptibility test to antibiotics was conducted using VITEC 2 methods.
 Results: From 45 patients, 30 patients (66,7%) had positive sputum cultures. The most frequently isolated pathogen was Streptococcus pneumonia (26,7%). The most sensitive antibiotic was Amikacin (100%). There were no correlation between the in degree of airflow limitation FEV1 and bacterial sputum culture result. There were no significant differences between gram positive or negative bacteria with the degree of airflow limitation.
 Conclusion: The incidence of bacterial infection based on positive sputum culture in AECOPD was about 66,7% Streptococcus pneumonia was the most common pathogen and Amikacin was the most sensitive antibiotic. There were no significant correlation between the degree of airflow limitation FEV1 with the positive or negative sputum culture and also with the result of gram staining. (J Respir Indo. 2019; 39(3):204-9)

Potential false-positive urine Legionella enzyme immunoassay test results.

The objective of this study was to identify potential false-positive urine Legionella pneumophila (Legionella) enzyme immunoassay test results. A total of 107 consecutive patients with positive EIA tests were retrospectively analyzed over a 34-month period. Concurrent blood, urine, and sputum cultures, as well as chest radiographic findings, were reviewed in these patients. Twenty patients (19%) had no radiographic evidence of pulmonary disease despite a positive EIA test. In those 20 patients, 14 also had growth of non-Legionella bacteria. Of patients with an infiltrate or opacity on chest imaging, only 27 had Legionella sputum cultures obtained, with Legionella culture growth occurring in 7 (26%). Nine other patients had negative Legionella sputum cultures but the growth of another pathogenic organism in blood, sputum, and/or urine cultures. Pseudomonas aeruginosa was the most common organism isolated, found in 20% of patients in the entire cohort. Twenty-five patients (23%) were characterized as having probable false-positive Legionella urinary antigen EIA testing, and an additional 17 patients (16%) were characterized as having possible false-positive Legionella EIA tests. Our findings suggest that urine Legionella EIA tests may lead to a substantial number of cases being misdiagnosed as Legionaries' disease in patients with non-Legionella bacterial colonization or infection.

Sitafloxacin-Containing Regimen for the Treatment of Refractory Mycobacterium avium Complex Lung Disease.

BackgroundSitafloxacin (STFX) exhibits potent activity against Mycobacterium avium complex (MAC) in both in vitro and in vivo experiments. However, limited data are available for the clinical efficacy and adverse effects of STFX and the susceptibility of refractory MAC lung disease (MAC-LD) to the drug. Therefore, this study was aimed at evaluating the clinical efficacy and safety of an STFX-containing regimen for the treatment of refractory MAC-LD.MethodsWe retrospectively evaluated treatment outcomes of 31 patients with refractory MAC-LD, who received an STFX-containing regimen for ≥4 weeks between January 2010 and July 2017. Refractory MAC-LD was defined as persistent positive sputum cultures for >6 months of macrolide-based standard therapy.ResultsClarithromycin resistance (minimum inhibitory concentration [MIC] ≥32 μg/mL) was identified in 15 patients (48%). Twelve months after receiving the STFX-containing regimen, 26% and 19% of patients showed symptomatic and radiological responses, respectively. Although STFX-associated adverse effects were noted in 9 patients, their severity was grade 1 (National Cancer Institute Common Terminology Criteria); only 1 patient discontinued STFX because of suspected gastrointestinal disturbance. Negative sputum culture conversion was achieved in 7 patients (23%). Both univariate and multivariate logistic regression analyses revealed that surgery, low STFX MIC (≤1 μg/mL), and macrolide resistance were significant predictors of negative sputum culture conversion.ConclusionsOur results demonstrate that STFX may be effective in one-fourth of patients with refractory MAC-LD. Prospective larger studies that include the analyses of MAC are needed to determine the clinical efficacy of STFX against refractory MAC-LD.

Bronchial Washing to Diagnose Smear-Negative Pulmonary Tuberculosis

Introduction: Bronchoscopy with bronchial washing is useful for the diagnosis of pulmonary tuberculosis (TB) when sputum smears are negative. However, its indication has not been standardized. Therefore, we conducted a retrospective study to assess the diagnostic value of bronchial washing in patients suspected with pulmonary TB. Methodology: A retrospective analysis was performed on patients diagnosed with pulmonary TB in Kosin university gospel hospital, a tertiary hospital with 969 beds in South Korea, from March 2017 to December 2018. We obtained three serial sputum samples for acid-fast bacilli (AFB) smear and culture, and all patients underwent bronchoscopy with bronchial washing for AFB smear and culture. Results: Fifty-six patients were enrolled in the study. Smear-negative pulmonary TB (SNPT) was diagnosed in 42/56 (75%) patients. Among the patients with smear-positive sputum, 14/14 (100%) showed culture-positive sputum, while smear- and culture-positive bronchial washing were seen in 7/14 (50%) and 12/14 (85.7%) patients, respectively. Among the patients with SNPT, 17/42 (40.47%) had culture-negative sputum and were diagnosed using the bronchoscopic washing. Conclusions: For patients with smear-negative sputum, it is necessary to perform bronchoscopic washing to increase the diagnostic rate of pulmonary TB. To control the transmission of pulmonary TB, it is necessary to use a fast and accurate examination method.

Correlation between Gene Xpert Negative and AFB Sputum Culture Among Patients with Cavitary PTB by Chest X-Ray

Correlation between Gene Xpert Negative and AFB Sputum Culture Among Patients with Cavitary PTB by Chest X-Ray

Treatment of Mycobacterium avium Complex Pulmonary Disease.

The pathogen Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial pulmonary disease worldwide. The decision to initiate long-term antibiotic treatment is difficult for the physician due to inconsistent disease progression and adverse effects associated with the antibiotic treatment. The prognostic factors for the progression of MAC pulmonary disease are low body mass index, poor nutritional status, presence of cavitary lesion(s), extensive disease, and a positive acid-fast bacilli smear. A regimen consisting of macrolides (clarithromycin or azithromycin) with rifampin and ethambutol has been recommended; this regimen significantly improves the treatment of MAC pulmonary disease and should be maintained for at least 12 months after negative sputum culture conversion. However, the rates of default and disease recurrence after treatment completion are still high. Moreover, treatment failure or macrolide resistance can occur, although in some refractory cases, surgical lung resection can improve treatment outcomes. However, surgical resection should be carefully performed in a well-equipped center and be based on a rigorous risk-benefit analysis in a multidisciplinary setting. New therapies, including clofazimine, inhaled amikacin, and bedaquiline, have shown promising results for the treatment of MAC pulmonary disease, especially in patients with treatment failure or macrolide-resistant MAC pulmonary disease. However, further evidence of the efficacy and safety of these new treatment regimens is needed. Also, a new consensus is needed for treatment outcome definitions as widespread use of these definitions could increase the quality of evidence for the treatment of MAC pulmonary disease.

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Assessing Treatment Response of Pulmonary Multidrug-Resistant Tuberculosis.

Background: The purpose of this prospective study was to evaluate the role of 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for assessing treatment response in patients with pulmonary multidrug-resistant tuberculosis (MDR-TB). Methods: The study subjects were four patients diagnosed with pulmonary MDR-TB who underwent MDR-TB treatment and serial 18F-FDG PET/CT at baseline and 6 and 12 months after treatment. The highest lung maximum standardized uptake value (SUVmax), average SUVmean (average of all hypermetabolic parenchymal lesions), total metabolic lung volume (TMLV, sum of metabolic volumes from the hypermetabolic parenchymal lesions), and total lung glycolysis (TLG, sum of lesion glycolysis from the hypermetabolic parenchymal lesions) were determined as representative quantitative PET parameters for each patient. Results: All patients except one had negative sputum culture conversion after one month of treatment and achieved successful treatment outcomes. Baseline TMLV and TLG PET parameters were much higher in the single patient with treatment failure than in the remaining three patients with treatment success. No other PET parameters at baseline or follow-up were associated with the treatment results. Conclusions: Pretreatment volume-based 18F-FDG PET/CT lung parameters were associated with the final therapeutic response in patients with pulmonary MDR-TB. Our preliminary results warrant a larger study.

Eradication of persistent methicillin-resistant Staphylococcus aureus infection in cystic fibrosis

BackgroundThe prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in individuals with cystic fibrosis (CF) has increased significantly. While studies demonstrate that persistent MRSA infection in CF is associated with poor clinical outcomes, there are no randomized controlled studies informing management. MethodsThe Persistent MRSA Eradication Protocol was a double-blind, randomized, placebo-controlled study investigating a comprehensive 28-day treatment regimen with or without inhaled vancomycin for eradication of MRSA. Eligible participants had CF and documented persistent MRSA infection. All participants received oral antibiotics, topical decontamination, and environmental cleaning and were randomized to receive inhaled vancomycin or inhaled placebo. The primary outcome was the difference in MRSA eradication rates one month after completion of the treatment protocol. Results29 participants were randomized. Four subjects in the inhaled vancomycin group required withdrawal from the study for bronchospasm before outcome data were collected and were excluded from analysis. There was no difference in the primary outcome: 2/10 (20%) of subjects in the intervention group and 3/15 (20%) in the placebo group had a MRSA negative sputum culture one month after treatment. There were no statistically significant differences in the rates of MRSA eradication at the end of treatment or three months after treatment completion. ConclusionsThis study suggests that persistent MRSA infection is difficult to eradicate, even with multimodal antibiotics. The use of a single course of inhaled vancomycin may not lead to higher rates of MRSA eradication in individuals with CF and may be associated with bronchospasm. FundThis trial was financially supported by the Cystic Fibrosis Foundation.

Amikacin Inhalation as Salvage Therapy for Refractory Nontuberculous Mycobacterial Lung Disease.

Although guidelines recommend amikacin (AMK) inhalation therapy for difficult-to-treat nontuberculous mycobacterial lung disease (NTM-LD), data are limited regarding the safety and clinical efficacy of this salvage therapy. We retrospectively evaluated the treatment outcomes of 77 patients with refractory NTM-LD caused by Mycobacterium abscessus complex (MABC) or M. avium complex (MAC) who initiated AMK inhalation therapy between February 2015 and June 2016. MABC was the most common etiology (n = 48, 62%), followed by MAC (n = 20, 26%) and mixed infections (n = 9, 12%). Isolates with macrolide resistance and baseline AMK resistance were identified in 63 (82%) patients and 5 (6%) patients, respectively. At 12 months after AMK inhalation therapy, 49% of patients had symptomatic improvement, whereas 42% had radiological improvement. Conversion to a negative sputum culture occurred in 14 (18%) patients, and the culture conversion rate was higher in patients infected with macrolide-susceptible isolates (7/14, 50%) than in those infected with macrolide-resistant isolates (7/63, 11%) (P = 0.003). Significant decreases in sputum semiquantitative culture positivity occurred after AMK inhalation therapy (P < 0.001). On multivariate analysis, conversion to a negative sputum culture was associated with mixed infections (P = 0.009), a forced expiratory volume in 1 s of greater than 60% (P = 0.008), and the absence of macrolide resistance (P = 0.003). Thirty-eight percent of patients experienced adverse effects, with ototoxicity (n = 15) being the most common. AMK inhalation salvage therapy may improve the treatment responses in some patients with refractory NTM-LD. However, considering the common adverse effects, further evaluation of the optimal dosage and intervals for AMK inhalation therapy is needed.

Infección crónica por Pseudomonas aeruginosa en pacientes con bronquiectasias no fibrosis quística

Introduction: Chronic airways infection with Pseudomonas aeruginosa (PA) is a common situation in patients with Bronchiectasis (BQ) and constitutes a breakdown in the natural history of the latter. Moreover, BQ is also associated with a poor prognosis and an increased severity of the disease. Objective: To describe the characteristics of the population diagnosed with non-Cystic Fibrosis Bronchiectasis (non-CFB) who are chronically infected with PA, and to perform a comparison with patients with negative sputum cultures. Methodology: We performed a retrospective analysis of the clinical files of patients diagnosed with non-CFB who were attended at the ‘Instituto Nacional del Torax’ (Chile) between July 2007 and April 2017. The characteristics of the population were described and the FACED scores and other severity indexes were compared. Results: The average age of patients was 55 ± 17.3 years-old, and 81% of them were female. According to PA isolation in sputum culture, they were classified as “chronically infected” (non-CFB with PA, n = 61) and “not infected with PA” (non-CFB without PA, n = 59). There were no differences in age and gender between the two groups. On the other hand, FEV1 was lower in the non-CFB PA group. The calculated FACED score was higher in colonized patients. The most frequent etiology was post-infectious, mainly TB sequels, with a 30.8% unidentified etiology. Conclusions: Patients with bronchiectasis chronically infected with Pseudomonas aeruginosa show increases in the severity of the disease, with a lower FEV1 and a higher FACED score. The postinfectious etiology is highlighted in our group.

A study on multi drug resistant tuberculosis at Sree Mookambika Institute of Medical Sciences

Background: Tuberculosis (TB) is one of the major causes of morbidity and mortality worldwide. Resistance to antitubercular drugs has been noted since the drugs were first introduced, and occasionally outbreaks of drug-resistant tuberculosis have been reported worldwide. WHO emphasizes that good TB control prevents the emergence of drug resistance in the first place and that the proper treatment of multi-drug resistant tuberculosis prevents the emergence of XDR-TB. The objectives of the study were to examine the sputum samples regarding MDR-TB, to study the grading regarding sputum positive and to study the multi-drug resistance tuberculosis in Sree Mookambika Institute of Medical sciences.Methods: Study design was cross-sectional, Study duration was January 2016-March 2017. Study place was Sree Mookambika Institute of Medical Sciences Hospital, Kulasekharam. Sample size was 400. Data entered in MS-Office Word- 2016. Institutional ethical committee clearance was obtained. Results: In present study 54.86% patient had sputum AFB positive, 45.13% had sputum AFB negative smears. 75% of the sputum AFB positive pulmonary TB came under the age group between 20-60 and 25% above 60 yrs. 78.24% males, 21.75% females had sputum AFB smear positive pulmonary tuberculosis and 43.73% patients had positive sputum culture, 56.26% patients had negative sputum culture and the most common strain found was Mycobacterium tuberculosis. Conclusions: So from our study we found that Mycobacterium tuberculosis is the major strain isolated from sputum samples. The resistance is more to Isoniazid and Rifampicin and is more in the rural parts of India. Early screening and drug susceptibility test of culture positive and MTB cases will help in initiating treatment of MDR-TB.

The efficacy, safety, and feasibility of inhaled amikacin for the treatment of difficult-to-treat non-tuberculous mycobacterial lung diseases

BackgroundIn multidrug regimens, including an intravenous aminoglycoside (e.g. amikacin [AMK]) is recommended for difficult-to-treat non-tuberculous mycobacterial (NTM) lung diseases. We aimed to evaluate the efficacy, safety, and feasibility of inhaled AMK therapy in patients with difficult-to-treat NTM lung diseases in a retrospective chart review.MethodsThe study population consisted of patients with NTM lung diseases who received combination therapy, including inhaled AMK therapy, at Keio University Hospital (Tokyo, Japan), from January 2014 through May 2016. A total of 26 cases, consisting of 23 Mycobacterium avium complex (MAC) and three Mycobacterium abscessus complex (MABC) infections cases, were included in this study. The efficacy, safety, and feasibility of inhaled AMK therapy were retrospectively investigated. The Research Ethics Committee of Keio University Hospital approved this study, and informed consent was obtained from all patients.ResultsAll 26 patients were culture-positive at enrolment. Twenty-three of the 26 patients (88.5%), including 21/23 MAC patients (91.3%) and 2/3 MABC patients (66.7%), were administered inhaled AMK therapy for >3 months. The proportion of patients who had clinical symptoms, including, cough and sputum, declined after inhalation AMK therapy. Ten of the 23 patients (43.5%) who received AMK inhalation, including 8/21 MAC (38.1%) and 2/2 MABC patients (100%), showed sputum conversion, defined as at least three consecutive negative sputum cultures. Seven of the 23 patients, including, 5/21 MAC and 2/2 MABC patients, showed improvements in high-resolution computed tomography imaging of the chest. In addition, the serum AMK trough levels before the second inhalation were <1.2 μg/mL in all 26 patients, with no occurrence of severe adverse events, such as renal toxicity. One patient (3.8%) experienced auditory toxicity, in the form of tinnitus. However, this symptom was reversible, after temporary interruption of AMK, the patient was able to safely resume the therapy.ConclusionsInhaled AMK therapy is an effective and feasible therapy for difficult-to-treat NTM lung disease.

Extracorporeal Membrane Oxygenation Support for Rituximab-Induced Acute Respiratory Distress Syndrome in an ABO-Incompatible Living Donor Liver Transplant Recipient: Successful Management of a Rare Complication and a Review of the Literature

BACKGROUND Rituximab is commonly used to reduce the agglutinin titer in ABO-incompatible liver transplant recipients. Although well-tolerated, rituximab infusion therapy may result in severe pulmonary adverse effects such as drug-induced pneumonitis, leading to acute respiratory distress syndrome (ARDS), which has a high mortality rate. Management of such rare cases in an ABO-incompatible patient has never been described before. Herein, we present successful use of extracorporeal membrane oxygenation (ECMO) support for rituximab-induced ARDS in an ABO-incompatible living donor liver transplantation (LDLT) recipient. CASE REPORT A 57-year-old man patient presented with acute-on-chronic hepatic failure. Due to worsening clinical condition and unavailability of a deceased donor organ, ABO-incompatible LDLT was considered. The patient received rituximab therapy and plasmapheresis 1 week before the transplantation to reduce the B cell count. However, he suddenly developed acute respiratory distress-like symptoms, with a chest X-ray suggesting organized pneumonia. Infectious etiology was excluded as evidenced from negative sputum and blood culture, which were repeated after 48 h. LDLT was performed and ECMO support was instituted in the immediate postoperative period due to worsening of the ARDS. The pulmonary signs improved, with a chest X-ray showing clear lung fields on the 5th postoperative day. The patient recovered well and was discharged with normal liver functions in the 4th postoperative month. CONCLUSIONS This is first reported experience of successful use of ECMO in an ABO-incompatible liver transplant recipient with rituximab-induced ARDS. This experience shows the feasibility and effectiveness of ECMO support in liver transplant recipients with poor respiratory functions.

Efficacy of Mycobacterium vaccae immunotherapy for patients with tuberculosis: A systematic review and meta-analysis

ABSTRACTTuberculosis (TB) is a significant cause of illness and death worldwide. Immunotherapy has been investigated in the treatment of TB. The purpose of this study was to perform a meta-analysis investigating the effectiveness of the M. vaccae vaccine. Medline, Cochrane, EMBASE, and Google Scholar were searched until November 5, 2015 using the keywords: tuberculosis, pulmonary TB, therapeutic vaccines, immunotherapy, M. vaccae, sputum smear. Randomized controlled trials (RCTs) or 2-arm prospective studies were included. The primary outcome was the sputum smear clearance rate at 1 or 2 months and 6 months after treatment. Secondary outcomes were improvement of chest X-ray findings, sputum culture negative rate at 1 or 2 months and 6 months, erythrocyte sedimentation rate (ESR), hemoglobin, and leukocyte count, weight gain, and mortality. Of 89 records identified, 13 RCTs were included in the meta-analysis. The number of patients ranged from 22 to 1337, and the mean age ranged from 26.4 to 44.3 y. Patients treated with M. vaccae were more likely to have negative sputum smear results at 1–2 months (pooled OR = 2.642, 95% CI: 1.623–4.301, P < .001) and at 6 months (pooled OR = 2.111, 95% CI: 1.141–3.908, P = .017), and have a negative sputum culture at 1 or 2 months (pooled OR = 2.660, 95% CI: 1.978–3.578, P < .001). The results of this meta-analysis suggest that M. vaccae immunotherapy may be effective in the treatment of pulmonary TB.

Clofazimine-Containing Regimen for the Treatment of Mycobacterium abscessus Lung Disease.

Patients with lung disease caused by Mycobacterium abscessus subsp. abscessus (here M. abscessus) typically have poor treatment outcomes. Although clofazimine (CFZ) has been increasingly used in the treatment of M. abscessus lung disease in clinical practice, there are no reported data on its effectiveness for this disease. This study sought to evaluate the clinical efficacy of a CFZ-containing regimen for the treatment of M. abscessus lung disease. We performed a retrospective review of the medical records of 42 patients with M. abscessus lung disease who were treated with CFZ-containing regimens between November 2013 and January 2015. CFZ was administered in combination with other antibiotics as an initial antibiotic regimen in 15 (36%) patients (initial treatment group), and it was added to an existing antibiotic regimen for refractory M. abscessus lung disease in 27 (64%) patients (salvage treatment group). Overall, there was an 81% treatment response rate based on symptoms and a 31% response rate based on radiographic findings. Conversion to culture-negative sputum samples was achieved in 10 (24%) patients after CFZ-containing antibiotic treatment, and during treatment, there were significant decreases in the positivity of semiquantitative sputum cultures for acid-fast bacilli in both the initial (P = 0.018) and salvage (P = 0.001) treatment groups. Our study suggests that CFZ-containing regimens may improve treatment outcomes in patients with M. abscessus lung disease and that a prospective evaluation of CFZ in M. abscessus lung disease is warranted.

Same-Day Diagnostic and Surveillance Data for Tuberculosis via Whole-Genome Sequencing of Direct Respiratory Samples.

ABSTRACTRoutine full characterization of Mycobacterium tuberculosis is culture based, taking many weeks. Whole-genome sequencing (WGS) can generate antibiotic susceptibility profiles to inform treatment, augmented with strain information for global surveillance; such data could be transformative if provided at or near the point of care. We demonstrate a low-cost method of DNA extraction directly from patient samples for M. tuberculosis WGS. We initially evaluated the method by using the Illumina MiSeq sequencer (40 smear-positive respiratory samples obtained after routine clinical testing and 27 matched liquid cultures). M. tuberculosis was identified in all 39 samples from which DNA was successfully extracted. Sufficient data for antibiotic susceptibility prediction were obtained from 24 (62%) samples; all results were concordant with reference laboratory phenotypes. Phylogenetic placement was concordant between direct and cultured samples. With Illumina MiSeq/MiniSeq, the workflow from patient sample to results can be completed in 44/16 h at a reagent cost of £96/£198 per sample. We then employed a nonspecific PCR-based library preparation method for sequencing on an Oxford Nanopore Technologies MinION sequencer. We applied this to cultured Mycobacterium bovis strain BCG DNA and to combined culture-negative sputum DNA and BCG DNA. For flow cell version R9.4, the estimated turnaround time from patient to identification of BCG, detection of pyrazinamide resistance, and phylogenetic placement was 7.5 h, with full susceptibility results 5 h later. Antibiotic susceptibility predictions were fully concordant. A critical advantage of MinION is the ability to continue sequencing until sufficient coverage is obtained, providing a potential solution to the problem of variable amounts of M. tuberculosis DNA in direct samples.

Comparison of Sputum-Culture Conversion for Mycobacterium bovis and M. tuberculosis.

Current US guidelines recommend longer treatment for tuberculosis (TB) caused by pyrazinamide-resistant organisms (e.g., Mycobacterium bovis) than for M. tuberculosis TB. We compared treatment response times for patients with M. bovis TB and M. tuberculosis TB reported in the United States during 2006–2013. We included culture-positive, pulmonary TB patients with genotyping results who received standard 4-drug treatment at the time of diagnosis. Time to sputum-culture conversion was defined as time between treatment start date and date of first consistently culture-negative sputum. We analyzed 297 case-patients with M. bovis TB and 30,848 case-patients with M. tuberculosis TB. After 2 months of treatment, 71% of M. bovis and 65% of M. tuberculosis TB patients showed conversion of sputum cultures to negative. Likelihood of culture conversion was higher for M. bovis than for M. tuberculosis, even after controlling for treatment administration type, sex, and a composite indicator of bacillary burden.

Oral Macrolide Therapy Following Short-term Combination Antibiotic Treatment of Mycobacterium massiliense Lung Disease

Although Mycobacterium massiliense lung disease is increasing in patients with cystic fibrosis and non-cystic fibrosis bronchiectasis, optimal treatment regimens remain largely unknown. This study aimed to evaluate the efficacy of oral macrolide therapy after an initial 2-week course of combination antibiotics for the treatment of M massiliense lung disease. Seventy-one patients received oral macrolides, along with an initial 4-week (n=28) or 2-week (n= 43) IV amikacin and cefoxitin (or imipenem) treatment. These patients were treated for 24months (4-week IV group) or for at least 12months after negative sputum culture conversion (2-week IV group). Total treatment duration was longer in the 4-week IV group (median, 23.9months) than in the 2-week IV group (15.2months; P< .001). The response rates after 12months of treatment were 89%for symptoms, 79%for CT scanning, and 100%for negative sputum culture results in the 4-week IV group. In the 2-week IV group, these values were 100%(P=.057), 91%(P= .177), and 91%(P= .147), respectively. Acquired macrolide resistance developed in two patients in the 2-week IV group. Genotyping analyses of isolates from patients who did not achieve negative sputum culture conversion during treatment and from those with positive culture results after successful treatment completion revealed that most episodes were due to reinfection with different genotypes of M massiliense. Oral macrolide therapy after an initial 2-week course of combination antibiotics might be effective in most patients with M massiliense lung disease. ClinicalTrials.gov; No.: NCT00970801; URL: www.clinicaltrials.gov.