Pulmonary Infection In Patients Research Articles

Characterization of the genomically encoded fosfomycin resistance enzyme from Mycobacterium abscessus.

Mycobacterium abscessus belongs to a group of rapidly growing mycobacteria (RGM) and accounts for approximately 65-80% of lung disease caused by RGM. It is highly pathogenic and is considered the prominent Mycobacterium involved in pulmonary infection in patients with cystic fibrosis and chronic pulmonary disease (CPD). FosM is a putative 134 amino acid fosfomycin resistance enzyme from M. abscessus subsp. bolletii that shares approximately 30-55% sequence identity with other vicinal oxygen chelate (VOC) fosfomycin resistance enzymes and represents the first of its type found in any Mycobacterium species. Genes encoding VOC fosfomycin resistance enzymes have been found in both Gram-positive and Gram-negative pathogens. Given that FosA enzymes from Gram-negative bacteria have evolved optimum activity towards glutathione (GSH) and FosB enzymes from Gram-positive bacteria have evolved optimum activity towards bacillithiol (BSH), it was originally suggested that FosM might represent a fourth class of enzyme that has evolved to utilize mycothiol (MSH). However, a sequence similarity network (SSN) analysis identifies FosM as a member of the FosX subfamily, indicating that it may utilize water as a substrate. Here we have synthesized MSH and characterized FosM with respect to divalent metal ion activation and nucleophile selectivity. Our results indicate that FosM is a Mn2+-dependent FosX-type hydrase with no selectivity toward MSH or other thiols as analyzed by NMR and mass spectroscopy.

803. Overcoming β-Lactam Resistance in Mycobacterium abscessus

Background Mycobacterium abscessus (Mab) is an environmentally acquired nontuberculous mycobacterium (NTM) that causes severe pulmonary infections in patients with chronic lung disease, such as cystic fibrosis (CF). The incidence of drug-resistant Mab infections in CF patients in the United States is steadily rising, making it increasingly difficult to manage these often chronic and incurable infections. Mab requires two enzyme classes, l,d- and d,d-transpeptidases, to synthesize peptidoglycan (PG); an integral component of the bacterial cell wall. Each enzyme class is uniquely susceptible to different classes of β-lactam antibiotics. We hypothesize that a combination of two β-lactams, each specific for an enzyme class, will optimally inhibit PG synthesis and swiftly kill Mab, with potential to overcome drug-resistance.MethodsPaired antibiotic combinations were tested in vitro for synergy against the Mab reference strain ATCC 19977 at 106 CFU/mL, per CLSI guidelines. Combinations included two β-lactams, a β-lactam and a β-lactamase inhibitor, or a β-lactam and a rifamycin. The minimum inhibitory concentration (MIC) of each drug was initially confirmed via broth microdilution assay. A validated checkerboard assay was used to determine the fractional inhibitory concentration index (FICI) for each combination to identify pairs that exhibit synergistic activity against Mab.ResultsOf the initial 227 combinations screened, 18 pairs exhibited a high level of synergy (FICI ≤ 0.5). Half of these were combinations of two β-lactams. The average reduction in MIC for each drug in combination was at least fourfold, with 8/18 combinations exhibiting reductions greater than eightfold. Although MIC breakpoints against Mab have not been established for all of the antibiotics tested in this study, the MICs of at least seven combinations were within the therapeutic range.ConclusionComprehensive inhibition of essential enzymes involved in PG synthesis requires more than one β-lactam antibiotic, and this phenomenon is hypothesized to be the basis for observed synergy between β-lactams. Some of the combinations reduced MICs to within therapeutically achievable levels, potentially leading to vital new treatment options against drug-resistant Mab.Disclosures All authors: No reported disclosures.

Study of pulmonary infection in patients with diabetes Mellitus

Study of pulmonary infection in patients with diabetes Mellitus

Characteristics of pulmonary infection after mitral valve repair in patients with metabolic syndrome and its relationship with blood pressure, blood glucose and blood lipid.

Characteristics of pulmonary infection after mitral valve repair in patients with metabolic syndrome (MS) and its relationships with blood pressure, blood glucose and blood lipid were investigated. Clinical data of 126 patients were retrospectively analyzed, and patients were divided into infection group (n=19) and non-infection group (n=107). The differences of MS components in patients between the two groups were compared, and the distribution of pathogens and related factors of pulmonary infection were analyzed. The postoperative pulmonary infection rate was 15.08% (19/126); the body mass index (BMI), blood pressure, fasting blood glucose (FBG), triglyceride, total cholesterol, low-density lipoprotein cholesterol, the extubation time of trachea cannula, ventilator use time, rethoracotomy hemostasis rate, sternal dehiscence rate and incidence of low-cardiac-output syndrome were higher and high-density lipoprotein (HDL-C), left ventricular ejection fraction (LVEF) was lower in the infection group than that in the non-infection group (p<0.05). The rate of postoperative pulmonary infection in patients with MS was higher than in those without MS (p<0.05). Cardiac function, BMI, FBG, HDL-C, LVEF value, extubation time of trachea cannula, ventilator use time, sternal dehiscence, rethoracotomy hemostasis and low-cardiac-output syndrome were independent risk factors for pulmonary infection after mitral valve repair in patients with MS. In conclusion, pulmonary infection easily occurs in patients with MS after mitral valve repair. Taking intervention measures according to the characteristics of pulmonary infection pathogens and predisposing factors is expected to reduce the incidence of pulmonary infection.

Clinical Efficacy and Safety of Tanreqing Injection for Pulmonary Infection in Patients with Tuberculosis: A Meta-Analysis.

Tanreqing injection (TRQ) is often used in the treatment of pulmonary infection in patients with tuberculosis (TB). But its efficacy and safety are still unclear; to further reveal its efficacy and safety, the authors systematically evaluated all relevant trials. The authors searched published trials using the search strategy as (Tanreqing OR "Tanreqing injection") AND ("Tuberculosis" [MeSH] OR Tuberculosis OR TB) in Embase, PubMed, CNKI, VIP, Wanfang Database, CBM and CENTRAL, and ongoing trials in Chinese and U.S. clinical trials and World Health Organization International Clinical Trials Registry Platform (WHO-ICTRP) (established to January 2017). The authors evaluated the methodological bias risk of all included trials using the Cochrane evaluation handbook of randomized controlled trials (RCTs) (5.1.0), extracted data following the PICO principles, and synthesized the data using meta-analysis. Twenty-six RCTs involving 2404 patients were included. In TRQ alone versus antibiotics, the merged risk ratio (RR) values and their confidence interval (95% CI) of meta-analysis for overall efficacy, lesion absorption, and bacterial clearance were as follows: 1.05 (0.99-1.10), 0.98 (0.89-1.08), and 1.36 (1.09-1.70). All differences were not statistically significant. In TRQ plus antibiotics versus antibiotics, the RR values and their 95% CI of overall efficacy, lesion absorption, and bacterial clearance were as follows: 1.17 (1.10-1.25), 1.24 (1.11-1.38), and 1.61 (1.36-1.90). All differences were statistically significant. Except for the bacterial clearance, sensitivity analyses showed that the overall efficacy had good stability. TRQ may have the same overall efficacy as antibiotics in pulmonary infection in patients with TB. TRQ plus antibiotics may improve the clinical efficacy. TRQ may have synergistic effect to antibiotics through bacteriostatic activity and eliminating inflammatory mediators. Its antibacterial activity may be better than some antibiotics and does not increase adverse drug reaction. But all these need new evidences for further investigation.

Risk factors and treatment of pulmonary infection after liver transplantation

Objective To investigate the clinical characteristics and the related risk factors of pulmonary infection in patients after liver transplantation. Methods The clinical data of 298 patients who underwent liver transplantation in the Beijing Chaoyang Hospital between January 2013 and December 2017 were retrospectively studied. The patients were divided into the infection group (n=58) and the control group (n=240) according to whether they had pulmonary infection. The characteristics, diagnosis, treatment, prognosis and risk factors of pulmonary infection were analyzed. Results Pulmonary infection occurred in 58 patients (19.5%) after liver transplantation. Eight patients died in the infection group of pulmonary infection. The mortality rate was 13.8%. The most common pathogenic bacteria were Acinetobacter bauman, Pseudomonas aeruginosa and Klebsiella pneumoniae, which accounted for 28.8%, 20% and 13.8%, respectively for the pulmonary infection. Multivariate analysis showed that the neutrophil ratio, and intensive care unit (ICU) hospitalization time were independent risk factors of pulmonary infection (P<0.05). Conclusions Pulmonary infection was common after liver transplantation. The treatment strategy should be the use of rational antibiotics and intensive pulmonary management. The neutrophil ratio and ICU hospitalization time were the risk factors of pulmonary infection. Key words: Liver transplantation; Pulmonary infection; Risk factor; Treatment

Lund exhaust on hemodynamic parameters and inflammatory mediators in patients undergoing cardiac valve replacement under cardiopulmonary bypass.

The effect of Lund exhaust technique on hemodynamics and inflammatory mediators in patients undergoing cardiac valve replacement under cardiopulmonary bypass was evaluated. A total of 60 patients with heart disease undergoing elective heart valve replacement under elective cardiopulmonary bypass were randomly divided into Lund exhaust group (group A) and control group (group B), with 30 patients in each group. Group A underwent Lund exhaust during cardiopulmonary bypass, while group B was identical to group A except for not using the Lund exhaust technique during cardiopulmonary bypass. The hemodynamic parameters at different time-points showed that the indexes of MAP, PASP, CO, CI, PCWP, CVP and SVR in T1, T2, T3 and T4 moments between group A and group B were statistically significant (p<0.05). There was no statistical significance in IL-6, IL-8, IL-10, TNF-α and TIMP-1 between group A and group B patients at the T0 moment (p>0.05). The levels of IL-6, IL-8, IL-10, TNF-α and TIMP-1 in group B patients at T1, T2, T3 and T4 moments were statistically significant compared with those in group A (p<0.05). The IL-6, IL-8, TNF-α indexes of group B patients were statistically significant at the T5 moment compared with those in group A (p<0.05). The IL-10 and TIMP-1 of two groups were not statistically significant at the T5 moment. The operating time, CPB time, aortic clamp time, intraoperative blood loss, postoperative tube time, ICU stay time, hospital stay time and pulmonary infection of patients in group A were significantly less than those in group B. In conclusion, Lund exhaust technology can significantly reduce the fluctuation of hemodynamics, decrease the expression of inflammatory factors, improve lung function, and is conducive to the rehabilitation of patients.

The Study of Lophomonas Blattarum Infection in Children with Respiratory Symptoms: A Descriptive Clinical Study in North East of Iran

Background: Lophomonas blattarum is protozoan generally parasitizes in the intestinal tracts of some arthropods. It can infect adults and children with unspecific respiratory symptoms. We aimed to investigate the frequency of Lophomonas blattarum in children with respiratory symptoms in North East of Iran. Materials and Methods: One hundred fifty-six children with respiratory symptoms were investigated in a descriptive-analytical study using Bronchoalveolar lavage (BAL) according to enumeration method in March 2016 to March 2017.Data was collected via a check list, prospectively. All had Bronchoscopy and chest X-ray. The data were analyzed using SPSS program. Results: Of the 156 studied children,40.4% (n=63) of patients with the average age of 5.11±2.9 years were positive for L. blattarum infection. In positive cases, 42.9% (n=27) were male. There was a significant relationship between gender and Lophomonas infection (p=0.0006). The most common respiratory symptoms were cough, fever, wheeze and tachypnea. Radiography of infected patients showed pulmonary infiltration (16.7%), unilateral lung hyperinflation (23.1%), consolidation (19.9%), and lung collapse (14.7%). Underlying diseases were detected in 4 infected patients. Bronchoscopy showed abnormal results in 22 patients (14.1%). Most common abnormalities were in order: mucus plaque (22.7%), left bronchomalacia (18.2%), left bronchial stenosis (18.2%) and foreign body aspiration (13.6%). Conclusion: Generally, 40.4% of children with respiratory symptoms were positive for L. blattarum infection. It is suggested to consider L. blattarum as a cause of pulmonary infections in patients with pulmonary symptoms.

Amikacin Liposome Inhalation Suspension (ALIS) Penetrates Non-tuberculous Mycobacterial Biofilms and Enhances Amikacin Uptake Into Macrophages.

Non-tuberculous mycobacteria (NTM) cause pulmonary infections in patients with structural lung damage, impaired immunity, or other risk factors. Delivering antibiotics to the sites of these infections is a major hurdle of therapy because pulmonary NTM infections can persist in biofilms or as intracellular infections within macrophages. Inhaled treatments can improve antibiotic delivery into the lungs, but efficient nebulization delivery, distribution throughout the lungs, and penetration into biofilms and macrophages are considerable challenges for this approach. Therefore, we developed amikacin liposome inhalation suspension (ALIS) to overcome these challenges. Nebulization of ALIS has been shown to provide particles within the respirable size range that distribute to both central and peripheral lung compartments in humans. The in vitro and in vivo efficacy of ALIS against NTM has been demonstrated previously. The key mechanistic questions are whether ALIS penetrates NTM biofilms and enhances amikacin uptake into macrophages. We found that ALIS effectively penetrated throughout NTM biofilms and concentration-dependently reduced the number of viable mycobacteria. Additionally, we found that ALIS improved amikacin uptake by ∼4-fold into cultured macrophages compared with free amikacin. In rats, inhaled ALIS increased amikacin concentrations in pulmonary macrophages by 5- to 8-fold at 2, 6, and 24 h post-dose and retained more amikacin at 24 h in airways and lung tissue relative to inhaled free amikacin. Compared to intravenous free amikacin, a standard-of-care therapy for refractory and severe NTM lung disease, ALIS increased the mean area under the concentration-time curve in lung tissue, airways, and macrophages by 42-, 69-, and 274-fold. These data demonstrate that ALIS effectively penetrates NTM biofilms, enhances amikacin uptake into macrophages, both in vitro and in vivo, and retains amikacin within airways and lung tissue. An ongoing Phase III trial, adding ALIS to guideline based therapy, met its primary endpoint of culture conversion by month 6. ALIS represents a promising new treatment approach for patients with refractory NTM lung disease.

Perioperative treatment of patients with pheochromocytoma/paraganglioma combined catecholamine cardiomyopathy

Objective To discuss the diagnosis, perioperative treatment, cardiac function changing of pheochromocytoma/paraganglioma (PHEO/PGL)patients with catecholamine cardiomyopathy. Methods Fifteen PHEO/PGL patients with catecholamine cardiomyopathy were included in our hospital from Jan 2008 to Mar 2018. There were 8 males and 7 females with an average age of 32.8 years, ranging 13-64 years old.4 cases were found left PHEO. 4 cases were found right PHEO and 3 cases were bilateral PHEO, including 2 cases of VHL. One case was jugular PGL. 2 cases were lift PGL and 1 case was right PGL. The tumors diameter ranged from 2.3 to 7.2 cm. 14 patients were diagnosed as PHEO/PGL with catecholamine cardiomyopathy with typical clinical manifestations of PHEO/PGL, such as headache, palpitation and perspiration. Their 24 hours of urine catecholamines showed an average of 24.87 μg/24 h in epinephrine and 551.70 μg/24 h in norepinephrine. Their average value of dopamine was 395.41 μg/24 h. Among 7 cases, the octreotide scan and Iodine-131-meta-iodobenzylguanidine(131I-MIBG)s scan were positive in 6 and 1 case, respectively. Enhanced CT showed significantly heterogeneous enhancement tumors in adrenal or retroperitoneal area. Ischemia and necrosis area were found inside tumors. The blood flow of some tumors were extremely rich and irregular vascular network with a racemose distribution around the tumors could be observed. Echocardiography showed that the left ventricular ejection fraction (LVEF) ranged from 32% to 54%, mean (42.0±7.1) % during catecholamine cardiomyopathy. 5 cases were mild abnormal, which the LVEF ranged from 45% to 54%. 9 cases were moderate abnormal, which the LVEF ranged from 30% to 44%.Their catecholamine cardiomyopathy performance including left ventricular hypertrophy, myocardial echo enhancement and left ventricular enlargement.9 cases combined with acute left ventricular failure manifested as pulmonary edema and pink foamy phlegm. Sensitive antibiotics were given to suspected pulmonary infection patients. 14 cases accepted regular alpha blockers, beta blockers and calcium antagonists treatment for 1 to 3 months and underwent surgery after a significant improvement in cardiac function.1 non-functional PHEO patient was lack of typical clinical and imaging changing. Both of her 24 hours of urine catecholamines and octreotide scan were negative. Echocardiography showed that LVEF was 73% before operation. She was misdiagnosed as an adrenal non-functional adenoma. All patients underwent surgical treatment, including 13 laparoscopic surgery.One case switched to open surgery. 2 PGL patients all accepted open surgery. Rusults All cases accepted complete resection of the tumors. 1 case of non-functional PHEO had severe fluctuations in blood pressure during operation. Her BP were 190/130 to 80/50 mmHg (1 mmHg=0.133 kPa) and heart rate raised to 150 bpm. Catecholamine cardiomyopathy appeared in ICU ward after operation. Echocardiography showed that LVEF was 37%. The left ventricular enlargement and myocardial systolic function decreased. Fibrous bronchoscopy showed pink foamy phlegm in both sides of lungs. Chest X ray showed bilateral pulmonary edema which predominant in left side. The diagnosis was catecholamine cardiomyopathy of this patient. The LVEF was (55.9±7.6)% after treatment in 14 PHEO/PGL patients with catecholamine cardiomyopathy, and there was statistically significant difference between before and after treatment (P=0.041). The LVEF was (66.1±8.5)% postoperation, and there was statistically significant difference between postoperation and after treatment (P=0.013). The non-functional PHEO case occurred severe catecholamin cardiomyopathy after operation and cardiac function recovered after treatment. 15 cases were followed up from 1 months to 10 years without recurrence. Conclusions PHEO/PGL patients with catecholamine cardiomyopathy should have adequate medication. The abnormal cardiac function of patients would be reversed after surgical treatment. Cardiac function failure would be recovered after active treatment. Non-functional pheochromocytoma patients were extremely dangerous. Adequate medication should be given to any suspected non-functional pheochromocytoma patients. Key words: Pheochromocytoma; Paraganglioma; Catecholamines; Cardiomypathies; Nonfunctioning

Mixed Communities of Mucoid and Nonmucoid Pseudomonas aeruginosa Exhibit Enhanced Resistance to Host Antimicrobials.

ABSTRACTPseudomonas aeruginosa causes chronic pulmonary infections in patients with cystic fibrosis (CF). P. aeruginosa mucoid conversion, defined by overproduction of the exopolysaccharide alginate, correlates with accelerated decline in CF patient lung function. Recalcitrance of the mucoid phenotype to clearance by antibiotics and the immune response is well documented. However, despite advantages conferred by mucoidy, mucoid variants often revert to a nonmucoid phenotype both in vitro and in vivo. Mixed populations of mucoid isolates and nonmucoid revertants are recovered from CF lungs, suggesting a selective benefit for coexistence of these variants. In this study, cocultures of mucoid and nonmucoid variants exhibited enhanced resistance to two host antimicrobials: LL-37, a cationic antimicrobial peptide, and hydrogen peroxide (H2O2). Alginate production by mucoid isolates protected nonmucoid variants in consortia from LL-37, as addition of alginate exogenously to nonmucoid variants abrogated LL-37 killing. Conversely, nonmucoid revertants shielded mucoid variants from H2O2 stress via catalase (KatA) production, which was transcriptionally repressed by AlgT and AlgR, central regulators of alginate biosynthesis. Furthermore, extracellular release of KatA by nonmucoid revertants was dependent on lys, encoding an endolysin implicated in autolysis and extracellular DNA (eDNA) release. Overall, these data provide a rationale to study interactions of P. aeruginosa mucoid and nonmucoid variants as contributors to evasion of innate immunity and persistence within the CF lung.

P810 Serious pulmonary infections in patients with inflammatory bowel disease on treatment with anti-TNF

P810 Serious pulmonary infections in patients with inflammatory bowel disease on treatment with anti-TNF

Analysis of the effect of comprehensive nursing intervention on pulmonary infection in patients with severe neurosurgery

Objective: Investigated the effect of comprehensive nursing intervention on the prevention of pulmonary infection in severe patients in department of neurosurgery. Methods: Randomly divided 89 patients with neurosurgical intensive cases admitted in our hospital from April 2014 to September 2016 into two groups, 43 patients in the control group underwent routine neurosurgical care, and 46 cases in the observation group underwent comprehensive nursing intervention. Compared the Barthel index score, tracheotomy time, the length of ICU stay and hospital stay between the two groups before and after nursing care, and observed the lung infection and satisfaction. Results: There was no significant difference in daily living ability and Barthel index score between the two groups (P>0.05), which were significantly improved after treatment. And the observation group was significantly higher than that of the control group, the difference between the two groups was statistically significant (P<0.05), the incidence of lung infection, aspiration, expectoration and hypoxemia in the observation group were lower than those in the control group, and the differences were statistically significant (P<0.05). In addition, the overall satisfaction of the observation group was 95.65%, which was higher than that of the control group (79.07%), and the difference was significant (P<0.05). Conclusion: Comprehensive nursing intervention on the prevention of pulmonary infection in severe patients in department of neurosurgery can not only promote the recovery of patients, but also can effectively prevent complications such as lung infection, improve living ability.

Risk factor analysis and rehabilitation nursing of pulmonary infection in patients with stroke

Objective To explore the influencing factors of pulmonary infection in patient with stroke, in order to provide the basis for clinical rehabilitation nursing. Methods A total of 237 patients with stroke who were treated in hospitalsfrom January 2015 to December 2015, were enrolled in the study. To analysis the effect of several influencing factors such as age, sex, consciousnessdisorders, pulmonary diseases, swallowing disorder and the activities of daily living(ADL). Results Of the 237 patients, 66 were complicated with pulmonary infection, and the incidence rate of pulmonary infection was 27.8%. Thepulmonary infection in patients with stroke was associated with swallowing disorder, hypertension, pulmonarydiseases, albumin,stomach pipe retaining, proton pump, swallowing disorder, long bedridden and ADL. These results had significantly deference (P<0.05). The logistic regression analysis showed that the independent risk factors for sex, consciousnessdisorders, pulmonarydiseases, swallowing disorder and ADL. Conclusions The influencing factors were existed in pulmonary infection in patients with stroke. The independent risk factors for pulmonary infection in patient with stroke included sex, consciousnessdisorders, pulmonarydiseases, swallowing disorder and ADL. In the above some factors, nurse should be providingrehabilitation nursing measure to reduce the incidence rate of pulmonary infection. Key words: Stroke; Pulmonary infection; Influencing factors; Rehabilitation nursing

Pneumococcal vaccination and chronic respiratory diseases.

Patients with COPD and other chronic respiratory diseases are especially vulnerable to viral and bacterial pulmonary infections, which are major causes of exacerbations, hospitalization, disease progression, and mortality in COPD patients. Effective vaccines could reduce the burden of respiratory infections and acute exacerbations in COPD patients, but what is the evidence for this? This article reviews and discusses the existing evidence for pneumococcal vaccination efficacy and its changing role in patients with chronic respiratory diseases, especially COPD. Specifically, the recent Community-Acquired Pneumonia Immunization Trial in Adults (CAPITA) showed the efficacy of pneumococcal conjugate vaccine in older adults, many of whom had additional risk factors for pneumococcal disease, including chronic lung diseases. Taken together, the evidence suggests that pneumococcal and influenza vaccinations can prevent community-acquired pneumonia and acute exacerbations in COPD patients, while pneumococcal vaccination early in the course of COPD could help maintain stable health status. Despite the need to prevent pulmonary infections in patients with chronic respiratory diseases and evidence for the efficacy of pneumococcal conjugate vaccine, pneumococcal vaccine coverage and awareness are low and need to be improved. Respiratory physicians need to communicate the benefits of vaccination more effectively to their patients who suffer from chronic respiratory diseases.

Serum procalcitonin in patients with pulmonary infection and central nervous system injury

Objective: To evaluate the influence of serum procalcitonin in the diagnosis and treatment of pulmonary infection in patients with central nervous system injury. Methods: From October 2014 to February 2017, a retrospective study was performed. A total of 1 852 patients were screened in Department of Intensive Care Unite, First Affiliated Hospital of Sun Yat-sen University.Among them, 173 patients were identified with different kinds of infection. Finally, a total of 42 patients with pulmonary infection were enrolled. The clinical data of patients with pulmonary infection and central nervous system (CNS) injury was collected. A univariate and multivariate regression analysis was performed to study the correlation of serum procalcitonin (PCT) with clinical symptoms and signs of the pulmonary infection, body temperature(T), white blood cell count (WBC), percentage of neutrophils (NEU) and the severity of the pulmonary infection (CPIS). The relationship of serum PCT with type of CNS injury, GCS, and exogenous glucocorticoid was further studied. Results: During the period of pulmonary infection, the peak PCT was 0.83 (0.29, 2.79) μg/L and the CPIS was 5.50 (5.00, 7.00). In 9 of 42 patients, the peak PCT was less than 0.25 μg/L. In 7 of 42 patients, the peak PCT was ranged from 0.25 to 0.5 μg/L. In 12 of 42 patients, PCT was ranged from 0.5 to 2 μg/L. Only 10 patients had a PCT 2-10 μg/L and 4 patients had a PCT more than 10 μg/L. There is no correlation between serum PCT and body temperature, white blood cell, percentage of neutrophils and CPIS. There was no significant differences in patients with PCT<0.5 or ≥0.5 μg/L regarding the body temperature, white blood cell, percentage of neutrophils and CPIS. However, serum PCT in patients with pulmonary infection had independent correlation with the post CNS injury day (β=0.17, 95% CI (0.02, 0.32), P<0.05). The serum PCT was 1.26 (0.47, 2.7) μg/L and 29.41% patients with a PCT less than 0.5 μg/L within 3 days post CNS injury. Serum PCT level was 0.23 (0.16, 0.39) μg/L, and 77.78% patients with a PCT less than 0.5 μg/L at day 4 to day 7 post-injury. The PCT level was 0.52 (0.33, 1.12) μg/L, and 44.44% patients with a PCT less than 0.5 μg/L at day 8 to day 14. The PCT was 3.26 (2.07, 12.40) μg/L, and no patient with a PCT less than 0.5 μg/L after day 15 post-injury. There were no significant relationship found between serum PCT level and type of the disease and surgery, GCS, and use of exogenous glucocorticoid. Conclusions: Serum PCT had no significant increase and was not able to be used in guiding the antibiotics use in patients with CNS injury and pulmonary infection.

Clofazimine for Rapidly Growing Mycobacterial Infections

BackgroundRapidly growing mycobacteria (RGM) have high rates of antibiotic resistance and require prolonged therapy with considerable toxicity. Less toxic and more effective therapies are needed. One promising agent is clofazimine (CFZ), an antibiotic with favorable in vitro data but limited clinical data in RGM.MethodsWe performed a retrospective cohort study to assess outcomes of adult patients treated with CFZ for RGM infection. Primary outcome was cure, defined as no evidence of clinical, radiographic, or microbiologic recurrence within 1 year of follow-up after stopping treatment. If a patient was retreated for infection, only the index treatment was included in the analysis.ResultsWe treated 55 adults for RGM infection with CFZ in combination with a median of 5 other antibiotic classes over the entire course of treatment. Of these patients, 58% had pulmonary infection (81% nodular-bronchiectatic and 19% cavitary); 100% of pulmonary infections were M. abscessus. Non-pulmonary disease sites included skin (65%), bone (13%), intra-abdominal (9%), and other (13%); 48% were M. abscessus, 39% were M. chelonae, and 13% were M. fortuitum.Patients with pulmonary infection were treated for a median duration of 11.9 months and non-pulmonary for a median of 7.9 months. CFZ was well tolerated. There were 2 (4%) cases of hepatitis and 3 (5%) cases of QT prolongation. For patients who completed treatment for pulmonary infections (n = 27), 67% achieved symptomatic improvement, 65% achieved radiographic improvement, and 71% achieved negative cultures. For patients who completed treatment for non-pulmonary infection (n = 22), 100% achieved clinical improvement.For patients who had at least 1 year of follow up after stopping antibiotics (pulmonary n = 21, non-pulmonary n = 14), 43% of patients with pulmonary infections achieved clinical cure and 79% of patients with non-pulmonary infections achieved clinical cure. Within 1 year of follow-up 19% of pulmonary infection patients and none of the non-pulmonary patients had died.ConclusionAs a part of multidrug therapy, CFZ is useful in the in the treatment of drug-resistant RGM infections, particularly skin infections, and offers a better tolerated option compared with other available antibiotics.Disclosures All authors: No reported disclosures.

Dry powders for the inhalation of ciprofloxacin or levofloxacin combined with a mucolytic agent for cystic fibrosis patients

Objective: This study aimed to design and characterize an inhalable dry powder of ciprofloxacin or levofloxacin combined with the mucolytics acetylcysteine and dornase alfa for the management of pulmonary infections in patients with cystic fibrosis.Methods: Ball milling, homogenization in isopropyl alcohol and spray drying processes were used to prepare dry powders for inhalation. Physico-chemical characteristics of the dry powders were assessed via thermogravimetric analysis, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry and scanning electron microscopy. The particle size distribution, dissolution rate and permeability across Calu-3 cell monolayers were analyzed. The aerodynamic parameters of dry powders were determined using the Andersen cascade impactor (ACI).Results: After the micronization process, the particle sizes of the raw materials significantly decreased. X-ray and DSC results indicated that although ciprofloxacin showed no changes in its crystal structure, the structure of levofloxacin became amorphous after the micronization process. FT-IR spectra exhibited the characteristic peaks for ciprofloxacin and levofloxacin in all formulations. The dissolution rates of micro-homogenized and spray-dried ciprofloxacin were higher than that of untreated ciprofloxacin. ACI results showed that all formulations had a mass median aerodynamic diameter less than 5 μm; however, levofloxacin microparticles showed higher respirability than ciprofloxacin powders did. The permeability of levofloxacin was higher than those of the ciprofloxacin formulations.Conclusion: Together, our study showed that these methods could suitably characterize antibiotic and mucolytic-containing dry powder inhalers.

Recurrent Scedosporium apiospermum mycetoma successfully treated by surgical excision and terbinafine treatment: a case report and review of the literature

BackgroundScedosporium apiospermum is an emerging opportunistic filamentous fungus, which is notorious for its high levels of antifungal-resistance. It is able to cause localized cutaneous or subcutaneous infections in both immunocompromised and immunocompetent persons, pulmonary infections in patients with predisposing pulmonary diseases and invasive mycoses in immunocompromised patients. Subcutaneous infections caused by this fungus frequently show chronic mycetomatous manifestation.Case reportWe report the case of a 70-year-old immunocompromised man, who developed a fungal mycetomatous infection on his right leg. There was no history of trauma; the aetiological agent was identified by microscopic examination and ITS sequencing. This is the second reported case of S. apiospermum subcutaneous infections in Hungary, which was successfully treated by surgical excision and terbinafine treatment. After 7 months, the patient remained asymptomatic. Considering the antifungal susceptibility and increasing incidence of the fungus, Scedosporium related subcutaneous infections reported in the past quarter of century in European countries were also reviewed.ConclusionsCorticosteroid treatment represents a serious risk factor of S. apiospermum infections, especially if the patient get in touch with manure-enriched or polluted soil or water. Such infections have emerged several times in European countries in the past decades. The presented data suggest that besides the commonly applied voriconazole, terbinafine may be an alternative for the therapy of mycetomatous Scedosporium infections.

Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography.

We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. The aim was to compare both modalities for detection of pulmonary infections and to explore performance of low-dose computed tomography for early detection of invasive fungal disease. The low-dose computed tomography remained blinded during the study. A consensus diagnosis of the fever episode made by an expert panel was used as reference standard. We included 67 consecutive patients on the first day of febrile neutropenia. According to the consensus diagnosis 11 patients (16.4%) had pulmonary infections. Sensitivity, specificity, positive predictive value and negative predictive value were 36%, 93%, 50% and 88% for radiography, and 73%, 91%, 62% and 94% for low-dose computed tomography, respectively. An uncorrected McNemar showed no statistical difference (p = 0.197). Mean radiation dose for low-dose computed tomography was 0.24 mSv. Four out of 5 included patients diagnosed with invasive fungal disease had radiographic abnormalities suspect for invasive fungal disease on the low-dose computed tomography scan made on day 1 of fever, compared to none of the chest radiographs. We conclude that chest radiography has little value in the initial assessment of febrile neutropenia on day 1 for detection of pulmonary abnormalities. Low-dose computed tomography improves detection of pulmonary infiltrates and seems capable of detecting invasive fungal disease at a very early stage with a low radiation dose.