Nontuberculous mycobacterial infections in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation.

BACKGROUND: The incidence of mycobacterial infections in patients with hematologic malignancies and hematopoietic stem cell transplant (HSCT) recipients is increasing, contributing to significant mortality and morbidity. This review explores the epidemiology, risk factors, clinical presentation, diagnosis, and treatment of nontuberculous mycobacteria (NTM) in this population. METHODS: A literature search was performed using PubMed with keywords and MeSH terms pertaining to the topics of nontuberculous mycobacteria, hematologic malignancies, hematopoietic stem cell transplant, cellular therapies, chimeric antigen therapies, epidemiology, diagnosis, and treatment. Additionally, we examined the reference lists of the included articles to identify other pertinent studies. RESULTS: Diagnosing mycobacterial disease among patients with hematologic disease and treatment-associated immunosuppressive conditions is challenging due to the lack of distinctive clinical, radiographic, and laboratory markers, as well as the atypical manifestations compared to immunocompetent patients. Treatment involves using a combination of antibiotics for extended durations, coupled with strategies to achieve source control and reduce immunosuppression when feasible. This is complicated by the absence of clear data correlating in-vitro drug susceptibility and clinical outcome for many antimicrobials use to treat NTM, adverse drug-drug interactions, and the frequent challenges related to poor medication tolerability and toxicities. CONCLUSION: The rising incidence and corresponding clinical challenges of mycobacterial infections in this unique patient population necessitate a heightened awareness and familiarity of NTM disease by clinicians to achieve timely diagnosis and favorable treatment outcomes.

Recurrent nocardiosis in solid organ transplant recipients: An evaluation of secondary prophylaxis.

BACKGROUND: Immunocompromised individuals are at risk for Nocardia infection, with a recurrence rate of approximately 5%. Solid organ transplant (SOT) recipients often receive secondary prophylaxis due to their requirement of lifelong immunosuppression. However, data supporting this practice is sparse. We sought to evaluate Nocardia recurrence in SOT recipients, specifically evaluating secondary prophylaxis. METHODS: We conducted a retrospective cohort study of SOT recipients diagnosed with nocardiosis from 2000 through 2020. We included adult SOT recipients who completed their course of Nocardia therapy and had at least 6 months of posttherapy follow-up. The primary outcome was Nocardia recurrence, which included relapse and reinfection. RESULTS: One hundred two patients met inclusion criteria. Sixty-six (64.7%) were male and mean age was 58.6 ± 11.7 years. Most common SOT types were kidney (46.1%), heart (18.6%), kidney-pancreas (11.8%), and lung (10.8%). Most common sites of infection were lung (85.3%), skin (17.6%), and brain (14.7%). Secondary prophylaxis was utilized in 53 (52.0%) patients. Trimethoprim-sulfamethoxazole (TMP-SMX) single-strength daily was the most common prophylaxis agent and dose. Five patients (4.9%) experienced Nocardia recurrence, three of which were receiving secondary prophylaxis at time of recurrence. Two recurrences were with the same Nocardia species. Factors associated with recurrence were lung transplantation (p = .011), chronic lung disease (p = .032), and treatment ≤120 days (p = .006). Time from treatment completion to recurrence ranged from 107 to 875 days. CONCLUSIONS: Nocardia recurrence in SOT recipients is an uncommon event. TMP-SMX secondary prophylaxis is incompletely protective and recurrence may be dependent upon other factors. Further study of secondary prophylaxis is warranted.

Mycobacterium septicum: a 6-Year Clinical Experience from a Tertiary Hospital and Reference Laboratory.

Mycobacterium septicum is a rarely identified nontuberculous mycobacterium capable of causing infections in both healthy and immunocompromised individuals. Only a few cases of M. septicum infections have been reported, which makes recognizing corresponding clinical disease more challenging for clinicians. Antimicrobial susceptibility profiles for this organism are not well described, and corresponding optimal therapeutic regimens have not been established. We report a tertiary care center's experience with M. septicum from 2014 to 2020. Twelve adult patients with positive cultures for M. septicum were identified. Most cases were identified from sputum samples of individuals with underlying lung disease. Most cases involving M. septicum isolation in culture were not felt to be clinically significant. Two cases were considered possible infections, while only one case was considered a definite infection that required antimicrobial treatment. All M. septicum isolates were susceptible in vitro to amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and trimethoprim-sulfamethoxazole. Isolates were universally resistant to clarithromycin and doxycycline. The isolation of M. septicum in culture is uncommon and requires clinical correlation to determine its clinical relevance and need for treatment. Susceptibility testing should be performed to guide therapy.

Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline.

Background: The American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America jointly sponsored this new practice guideline on the treatment of drug-resistant tuberculosis (DR-TB). The document includes recommendations on the treatment of multidrug-resistant TB (MDR-TB) as well as isoniazid-resistant but rifampin-susceptible TB.Methods: Published systematic reviews, meta-analyses, and a new individual patient data meta-analysis from 12,030 patients, in 50 studies, across 25 countries with confirmed pulmonary rifampin-resistant TB were used for this guideline. Meta-analytic approaches included propensity score matching to reduce confounding. Each recommendation was discussed by an expert committee, screened for conflicts of interest, according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.Results: Twenty-one Population, Intervention, Comparator, and Outcomes questions were addressed, generating 25 GRADE-based recommendations. Certainty in the evidence was judged to be very low, because the data came from observational studies with significant loss to follow-up and imbalance in background regimens between comparator groups. Good practices in the management of MDR-TB are described. On the basis of the evidence review, a clinical strategy tool for building a treatment regimen for MDR-TB is also provided.Conclusions: New recommendations are made for the choice and number of drugs in a regimen, the duration of intensive and continuation phases, and the role of injectable drugs for MDR-TB. On the basis of these recommendations, an effective all-oral regimen for MDR-TB can be assembled. Recommendations are also provided on the role of surgery in treatment of MDR-TB and for treatment of contacts exposed to MDR-TB and treatment of isoniazid-resistant TB.

Anxiety symptoms and risk of dementia and mild cognitive impairment in the oldest old women.

OBJECTIVES: Research is limited and findings conflict regarding anxiety as a predictor of future cognitive decline in the oldest old persons. We examined the relationship between levels of and changes in anxiety symptoms, and subsequent dementia and mild cognitive impairment (MCI) in the oldest old women. METHOD: We conducted secondary analyses of data collected from 1425 community-dwelling women (mean age = 82.8, SD ±3.1 years) followed on average for five years. The Goldberg Anxiety Scale was used to assess anxiety symptoms at baseline, and an expert clinical panel adjudicated dementia and MCI at follow-up. Participants with probable cognitive impairment at baseline were excluded. RESULTS: At baseline, 190 (13%) women had moderate/severe anxiety symptoms and 403 (28%) had mild anxiety symptoms. Compared with those with no anxiety symptoms at baseline, women with mild anxiety symptoms were more likely to develop dementia at follow-up (multivariable-adjusted odds ratio = 1.66, 95% confidence interval 1.12-2.45). No significant association was observed between anxiety symptoms and MCI. CONCLUSION: In the oldest old women, our findings suggest that mild anxiety symptoms may predict future risk of dementia, but not MCI. Future studies should explore potential biological mechanisms underlying associations of anxiety with cognitive impairment.

Electronic health records and online medical records: an asset or a liability under current conditions?

Objective The aim of the present study was to audit the current use of medical records to determine completeness and concordance with other sources of medical information. Methods Medical records for 40 patients from each of five Melbourne major metropolitan hospitals were randomly selected (n=200). A quantitative audit was performed for detailed patient information and medical record keeping, as well as data collection, storage and utilisation. Using each hospital's current online clinical database, scanned files and paperwork available for each patient audited, the reviewers sourced as much relevant information as possible within a 30-min time allocation from both the record and the discharge summary. Results Of all medical records audited, 82% contained medical and surgical history, allergy information and patient demographics. All audited discharge summaries lacked at least one of the following: demographics, medication allergies, medical and surgical history, medications and adverse drug event information. Only 49% of records audited showed evidence the discharge summary was sent outside the institution. Conclusions The quality of medical data captured and information management is variable across hospitals. It is recommended that medical history documentation guidelines and standardised discharge summaries be implemented in Australian healthcare services. What is known about this topic? Australia has a complex health system, the government has approved funding to develop a universal online electronic medical record system and is currently trialling this in an opt-out style in the Napean Blue Mountains (NSW) and in Northern Queensland. The system was originally named the personally controlled electronic health record but has since been changed to MyHealth Record (2016). In Victoria, there exists a wide range of electronic health records used to varying degrees, with some hospitals still relying on paper-based records and many using scanned medical records. This causes inefficiencies in the recall of patient information and can potentially lead to incidences of adverse drug events. What does this paper add? This paper supports the concept of a shared medical record system using 200 audited patient records across five Victorian metropolitan hospitals, comparing the current information systems in place for healthcare practitioners to retrieve data. This research identifies the degree of concordance between these sources of information and in doing so, areas for improvement. What are the implications for practitioners? Implications of this research are the improvements in the quality, storage and accessibility of medical data in Australian healthcare systems. This is a relevant issue in the current Australian environment where no guidelines exist across the board in medical history documentation or in the distribution of discharge summaries to other healthcare providers (general practitioners, etc).

Anxiety symptoms and risk of cognitive decline in older community-dwelling men.

BACKGROUND: Previous research regarding anxiety as a predictor of future cognitive decline in older adults is limited and inconsistent. We examined the independent relationship between anxiety symptoms and subsequent cognitive decline. METHODS: We included 2,818 community-dwelling older men (mean age = 76.1, SD ±5.3 years) who were followed on an average for 3.4 years. We assessed anxiety symptoms at baseline using the Goldberg Anxiety Scale (GAS; range = 0-9). We assessed cognitive function at baseline and at two subsequent visits using the Modified Mini-Mental State Examination (3MS; global cognition) and the Trails B test (executive function). RESULTS: At baseline, there were 690 (24%) men with mild anxiety symptoms (GAS 1-4) and 226 (8%) men with moderate/severe symptoms (GAS 5-9). Men with anxiety symptoms were more likely to have depressed mood, poor sleep, more chronic medical conditions, and more impairment in activities of daily living compared to those with no anxiety symptoms. Compared to those with no anxiety symptoms at baseline, men with any anxiety symptoms were more likely to have substantial worsening in Trails B completion time (OR = 1.56, 95% CI 1.19, 2.05). The association was attenuated after adjusting for potential confounders, including depression and poor sleep, but remained significant (OR = 1.40, 95% CI 1.04, 1.88). CONCLUSION: In cognitively healthy older men, mild anxiety symptoms may potentially predict future decline in executive functioning. Anxiety is likely a manifestation of an underlying neurodegenerative process rather than a cause.

Correlation of Pain and Fluoride Concentration in Allogeneic Hematopoietic Stem Cell Transplant Recipients on Voriconazole.

Supportive care guidelines recommend antimold prophylaxis in hematopoietic stem cell transplant (HSCT) recipients deemed to have high risk for invasive fungal infection, leading to long-term use of voriconazole after allogeneic HSCT in patients who remain immunocompromised. Voriconazole has been associated with periostitis, exostoses, and fluoride excess in patients after solid organ transplantation, HSCT, and leukemia therapy. The aims of this study were to describe the frequency and clinical presentation of patients presenting with pain and fluoride excess among allogeneic HSCT patients taking voriconazole, to identify when a plasma fluoride concentration was measured with respect to voriconazole initiation and onset of pain, and to describe the outcomes of patients with fluoride excess in the setting of HSCT. A retrospective review was conducted of all adult allogeneic HSCT patients receiving voriconazole at Mayo Clinic in Rochester, Minnesota, between January 1, 2009 and July 31, 2012. Of 242 patients included, 32 had plasma fluoride measured to explore the etiology of musculoskeletal pain. In 31 patients with fluoride measurement while on voriconazole, 29 (93.5%) had elevated levels. The median plasma fluoride was 11.1 µmol/L (range, 2.4 to 24.7). The median duration of voriconazole was 163 days (range, 2 to 1327). The median time to fluoride measurement was 128 days after voriconazole initiation (range, 28 to 692). At 1 year after the start of voriconazole after HSCT, 15.3% of patients had developed pain associated with voriconazole use and 35.7% developed pain while on voriconazole after 2 years. Of the patients with an elevated fluoride level, 22 discontinued voriconazole; pain resolved or improved in 15, stabilized in 3, and worsened in 4 patients. Ten patients continued voriconazole; pain resolved or improved in 7, was attributable to alternative causes in 2, and undefined in 1. Serum creatinine, estimated glomerular filtration rate, alkaline phosphatase, and voriconazole concentration did not predict for fluoride excess and associated pain. Periostitis due to fluoride excess is a common adverse effect of voriconazole that should be considered in patients presenting with pain and is often reversible after drug discontinuation. Alternative antifungal agents with a lower risk for fluoride excess should be considered in patients receiving voriconazole who develop fluoride excess and pain.

The use of simultaneous confidence bands for comparison of single parameter fluorescent intensity data.

Despite the utility of multiparameter flow cytometry for a wide variety of biological applications, comparing single parameter histograms of fluorescence intensity remains a mainstay of flow cytometric analysis. Even comparisons requiring multiparameter gating strategies often end with single parameter histograms as the final readout. When histograms overlap, analysis relies on comparison of mean or median fluorescence intensities, or determination of percent positive based on an arbitrary cutoff. Earlier attempts to address this problem utilized either simple channel-by-channel subtraction without statistical evaluation, or the Kolmogorov-Smirnov (KS) or Chi-square test statistics, both of which proved to be overly sensitive to small and biologically insignificant differences. Here we present a method for the comparison of two single-parameter histograms based on difference curves and their simultaneous confidence bands generated by bootstrapping raw channel data. Bootstrapping is a nonparametric statistical approach that can be used to generate confidence intervals without distributional assumptions about the data. We have constructed simultaneous confidence bands and show them to be superior to KS and Cox methods. The method constructs 95% confidence bands about the difference curves, provides a P value for the comparison and calculates the area under the difference curve (AUC) as an estimate of percent positive and the area under the confidence band (AUCSCB95), providing a lower estimate of the percent positive. To demonstrate the utility of this new approach we have examined single-color fluorescence intensity data taken from a cell surface proteomic survey of a lung cancer cell line (A549) and a published fluorescence intensity data from a rhodamine efflux assay of P-glycoprotein activity, comparing rhodamine 123 loading and efflux in CD4 and CD8 T-cell populations. SAS source code is provided as supplementary material.

Prevention and Treatment of Cancer-Related Infections, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

Infectious diseases are important causes of morbidity and mortality in patients with cancer. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prevention and Treatment of Cancer-Related Infections characterize the major pathogens to which patients with cancer are susceptible, with a focus on the prevention, diagnosis, and treatment of major common and opportunistic infections. This portion of the guidelines highlights the sections on antifungal and antiviral prophylaxis. Antifungal and antiviral prophylaxis recommendations have expanded over the past few years. New agents for the treatment of fungal infections and incorporation of therapeutic drug monitoring are presented. Antiviral prophylaxis for hepatitis B and management considerations for hepatitis C and HIV have been further developed.

Physical activity participation by adults with cystic fibrosis: An observational study.

BACKGROUND AND OBJECTIVE: Studies in children with cystic fibrosis (CF) suggest greater physical activity (PA) is associated with a slower rate of decline in respiratory function. In adults with CF, objectively measured PA time and its relationship to long-term clinical outcomes of respiratory function and need for hospitalization are unknown. METHODS: PA measured objectively (SenseWear armband), pulmonary function, exercise capacity (Modified Shuttle Test-25) and CF-related quality of life (CFQ-R) were assessed in 65 adults (34 male; mean age 28 years) with CF during a stable phase. A sub-group of these participants undertook additional measurement of PA at hospital discharge for a respiratory exacerbation. RESULTS: Median daily habitual moderate-vigorous PA (MVPA) time was 31-min (IQR:15-53). Participants who accumulated ≥30-min MPVA daily experienced fewer hospital days (P = 0.04), better exercise capacity and higher FEV1 at 12 months (P ≤ 0.001). Daily, fewer females than males accrued ≥30-min MVPA (P = 0.02). Compared with those who did not, participants who accumulated 30-min MVPA in bouts ≥10-min (n = 21) recorded better FEV1 (P = 0.02) and exercise capacity (P = 0.006), and reduced hospital admissions (P = 0.04) and hospital days (P = 0.04) at 12 months. MVPA participation declined significantly 1 month post-hospital discharge (median 12 min (4-34); P = 0.04). CONCLUSION: Adults with CF are able to achieve recommended MVPA targets of 30mins/day; however, a significant gender difference in activity time is apparent. Greater time in MVPA is related to more positive clinical outcomes over 12 months. Whether increasing PA levels can improve clinical outcomes in adults with CF warrants further investigation. See Editorial, page 404.

Exchange transfusion for babesiosis when, how, and how long?

Babesiosis is a zoonotic disease transmitted by Ixodes ticks seen in the United States and parts of Europe. Because of the typically mild course of most infections, the disease is uncommonly seen in clinical practice. However, asplenic patients can develop a life-threatening infection. The first line of therapy for Babesia infections is antiparasitic medications; however, red blood cell (RBC) exchange transfusion has been described as an adjunct therapy. We describe a severe case of babesiosis in an asplenic patient and review the evidence, indications, and protocols for RBC exchange transfusion in this setting.

Metronidazole- and carbapenem-resistant bacteroides thetaiotaomicron isolated in Rochester, Minnesota, in 2014.

Emerging antimicrobial resistance in members of the Bacteroides fragilis group is a concern in clinical medicine. Although metronidazole and carbapenem resistance have been reported in Bacteroides thetaiotaomicron, a member of the B. fragilis group, they have not, to the best of our knowledge, been reported together in the same B. thetaiotaomicron isolate. Herein, we report isolation of piperacillin-tazobactam-, metronidazole-, clindamycin-, ertapenem-, and meropenem-resistant B. thetaiotaomicron from a patient with postoperative intra-abdominal abscess and empyema. Whole-genome sequencing demonstrated the presence of nimD with at least a portion of IS1169 upstream, a second putative nim gene, two ß-lactamase genes (one of which has not been previously reported), two tetX genes, tetQ, ermF, two cat genes, and a number of efflux pumps. This report highlights emerging antimicrobial resistance in B. thetaiotaomicron and the importance of identification and antimicrobial susceptibility testing of selected anaerobic bacteria.

The activin A antagonist follistatin inhibits cystic fibrosis-like lung inflammation and pathology.

Cystic fibrosis (CF) is the most common life-limiting genetically acquired respiratory disorder. Patients with CF have thick mucus obstructing the airways leading to recurrent infections, bronchiectasis and neutrophilic airway inflammation culminating in deteriorating lung function. Current management targets airway infection and mucus clearance, but despite recent advances in care, life expectancy is still only 40 years. We investigated whether activin A is elevated in CF lung disease and whether inhibiting activin A with its natural antagonist follistatin retards lung disease progression. We measured serum activin A levels, lung function and nutritional status in CF patients. We studied the effect of activin A on CF lung pathogenesis by treating newborn CF transgenic mice (ß-ENaC) intranasally with the natural activin A antagonist follistatin. Activin A levels were elevated in the serum of adult CF patients, and correlated inversely with lung function and body mass index. Follistatin treatment of newborn ß-ENaC mice, noted for respiratory pathology mimicking human CF, decreased the airway activin A levels and key features of CF lung disease including mucus hypersecretion, airway neutrophilia and levels of mediators that regulate inflammation and chemotaxis. Follistatin treatment also increased body weight and survival of ß-ENaC mice, with no evidence of local or systemic toxicity. Our findings demonstrate that activin A levels are elevated in CF and provide proof-of-concept for the use of the activin A antagonist, follistatin, as a therapeutic in the long-term management of lung disease in CF patients.

Printing-based assembly of quadruple-junction four-terminal microscale solar cells and their use in high-efficiency modules.

Expenses associated with shipping, installation, land, regulatory compliance and on-going maintenance and operations of utility-scale photovoltaics can be significantly reduced by increasing the power conversion efficiency of solar modules through improved materials, device designs and strategies for light management. Single-junction cells have performance constraints defined by their Shockley-Queisser limits. Multi-junction cells can achieve higher efficiencies, but epitaxial and current matching requirements between the single junctions in the devices hinder progress. Mechanical stacking of independent multi-junction cells circumvents these disadvantages. Here we present a fabrication approach for the realization of mechanically assembled multi-junction cells using materials and techniques compatible with large-scale manufacturing. The strategy involves printing-based stacking of microscale solar cells, sol-gel processes for interlayers with advanced optical, electrical and thermal properties, together with unusual packaging techniques, electrical matching networks, and compact ultrahigh-concentration optics. We demonstrate quadruple-junction, four-terminal solar cells with measured efficiencies of 43.9% at concentrations exceeding 1,000 suns, and modules with efficiencies of 36.5%.

Human herpesvirus 8 seroconversion in a population-based cohort of men in Tobago.

Human herpesvirus 8 (HHV-8) is the causal agent of Kaposi's sarcoma (KS). In Tobago, KS is not common; however, HHV-8 seropositivity has been reported to be 39.9% in men with prostate cancer compared to <22.9% in healthier women and men. To understand HHV-8 transmission, we examined HHV-8 seroconversion and seroreversion, and risk factors for these changes in Tobago men. Serum specimens from a sub-cohort of Tobago Prostate Survey men, aged 40-81 years (n = 381/442), were collected at baseline and a subsequent visit between 3 and 9 years and tested for HHV-8 seropositivity using an immunofluorescence assay for antibodies against HHV-8 lytic antigens. Poisson distribution was used to calculate HHV-8 seroconversion and seroreversion rates and their 95% confidence intervals. Differences in baseline characteristics between HHV-seroconverters versus persistent HHV-8 seronegative men and HHV-8 seroreverters versus HHV-8 seropositive men were examined. HHV-8 seropositivity was 12.3% (N = 381) at baseline, with HHV-8 seropositivity significantly higher in increasing age groups, 40-49 (4.0%) to 70-81 (37.5%) years (P-value trend <0.0001). HHV-8 seroconversion and seroreversion rates were 0.23 per 100 person-years (95% C.I., 0.06-0.58) and 2.42 per 100 person-years (95% C.I., 0.89-5.26), respectively. There were significantly more HHV-8 seroconverters who reported "ever smoked cigarettes of >6 months" at baseline compared to HHV-8 persistent seronegative men (P-value = 0.03). Baseline characteristics of HHV-8 seroreverters did not differ from persistent seropositive men. Low HHV-8 seroconversion and seroreversion rates were found. Data suggest that HHV-8 transmission occurred at earlier ages, <40 years, in Tobago men.

Pulmonary and systemic pharmacokinetics of inhaled and intravenous colistin methanesulfonate in cystic fibrosis patients: targeting advantage of inhalational administration.

The purpose of this study was to define the pulmonary and systemic pharmacokinetics of colistin methanesulfonate (CMS) and formed colistin following intravenous (i.v.) and inhaled administration in cystic fibrosis (CF) patients. Six CF subjects were administered nebulized CMS doses of 2 and 4 million IU and an i.v. CMS infusion of 150 mg of colistin base activity. Blood plasma, sputum, and urine samples were collected for 12 to 24 h postdose. To assess the tolerability of the drug, lung function tests, blood serum creatinine concentrations, and adverse effect reports were recorded. All doses were well tolerated in the subjects. The pharmacokinetic parameters for CMS following i.v. delivery were consistent with previously reported values. Sputum concentrations of formed colistin were maintained at <1.0 mg/liter for 12 h postdose. Nebulization of CMS resulted in relatively high sputum concentrations of CMS and formed colistin compared to those resulting from i.v. administration. The systemic availability of CMS was low following nebulization of 2 and 4 million IU (7.93% ± 4.26% and 5.37% ± 1.36%, respectively), and the plasma colistin concentrations were below the limit of quantification. Less than 2 to 3% of the nebulized CMS dose was recovered in the urine samples in 24 h. The therapeutic availability and drug targeting index for CMS and colistin following inhalation compared to i.v. delivery were significantly greater than 1. Inhalation of CMS is an effective means of targeting CMS and formed colistin for delivery to the lungs, as high lung exposure and minimal systemic exposure were achieved in CF subjects.

Bacterial pathogens.

Bacterial infections are frequent complications among patients treated for cancer. The type, severity, and treatment of bacterial infections vary and depend upon the specific malignancy, associated chemotherapies, and transplantation. This chapter discusses commonly encountered bacterial pathogens as well as Nocardia and mycobacteria in patients with cancer and addresses the clinical syndromes and management. Drug-resistant bacteria are becoming an increasingly recognized problem in patients with cancer. Antimicrobial resistance in select gram-positive and gram-negative bacteria are discussed along with the mechanisms of resistance and recommended therapies.

Proximal and distal gastro-oesophageal reflux in chronic obstructive pulmonary disease and bronchiectasis.

BACKGROUND AND OBJECTIVE: The aims of this observational study were (i) to examine the prevalence of symptomatic and clinically silent proximal and distal gastro-oesophageal reflux (GOR) in adults with chronic obstructive pulmonary disease (COPD) or bronchiectasis, (ii) the presence of gastric aspiration, and (iii) to explore the possible clinical significance of this comorbidity in these conditions. METHODS: Twenty-seven participants with COPD, 27 with bronchiectasis and 17 control subjects completed reflux symptom evaluation and dual-channel 24 h oesophageal pH monitoring. In those with lung disease, pepsin levels in sputum samples were measured using enzyme-linked immunosorbent assay, with disease severity (lung function and high-resolution computed tomography) also measured. RESULTS: The prevalence of GOR in COPD was 37%, in bronchiectasis was 40% and in control subjects was 18% (P = 0.005). Of those diagnosed with GOR, clinically silent reflux was detected in 20% of participants with COPD and 42% with bronchiectasis. While pepsin was found in 33% of COPD and 26% of bronchiectasis participants, the presence of pepsin in sputum was not related to a diagnosis of GOR based on oesophageal pH monitoring in either condition. Neither a diagnosis of GOR nor the presence of pepsin was associated with increased severity of lung disease in COPD or bronchiectasis. CONCLUSIONS: The prevalence of GOR in COPD or bronchiectasis is twice that of the control population, and the diagnosis could not be based on symptoms alone. Pepsin was detected in sputum in COPD and bronchiectasis, suggesting a possible role of pulmonary aspiration, which requires further exploration.