Expectorated Sputum Research Articles

Distribution of ESBL-producing and non-ESBL-producing Klebsiella pneumoniae isolated from sputum specimens in the Zainoel Abidin General Hospital, Banda Aceh, Indonesia

Abstract. Suhartono S, Hayati Z, Mahdani W, Andini F. 2024. Distribution of ESBL-Producing and Non-ESBL-Producing Klebsiella pneumoniae isolated from sputum specimens in the Zainoel Abidin General Hospital, Banda Aceh, Indonesia. Biodiversitas 25: 3247-3254. Klebsiella pneumoniae, a significant nosocomial pathogen, particularly in the case of strains producing extended-spectrum beta-lactamase (ESBL), was the focus of this study. The study aimed to determine the distributions stratified by patients’ age, sex, hospital wards, and the antimicrobial susceptibility pattern of ESBL and non-ESBL K. pneumoniae isolated from expectorate sputum at Zainoel Abidin General Hospital (RSUD dr. Zainoel Abidin), Banda Aceh, Indonesia, from January 2021 to January 2024. The prevalence of ESBL-producing K. pneumoniae was 79.84% (103/129 isolates), with the highest incidence found in patients aged >45 years (74.76%) and males (67.96%). The prevalence of non-ESBL-producing K. pneumoniae was 20.16% (26 isolates), with the highest incidence in patients aged >45 years (76.92%) and males (62.23%). The surgical ward had the highest incidence of ESBL-producing K. pneumoniae (14.56%), followed by the cardiopulmonary ward (14.56%). The cardiopulmonary ward also had the highest incidence of non-ESBL-producing K. pneumoniae (38.47%). The ESBL-producing K. pneumoniae isolates were more sensitive to amikacin than non-ESBL isolates, while the non-ESBL-producing K. pneumoniae isolates were sensitive to cefotaxime, amikacin, and tobramycin. The increasing prevalence of ESBL-producing K. pneumoniae underscores the significance of the study's findings, providing valuable insights into the epidemiology and antibiotic susceptibility profiles of K. pneumoniae in this clinical setting and the importance of reasonable antibiotic use.

The diagnostic yield of nasopharyngeal aspirate for pediatric pulmonary tuberculosis: a systematic review and meta-analysis

BackgroundTuberculosis (TB) is a leading cause of death in children, but many cases are never diagnosed. Microbiological diagnosis of pulmonary TB is challenging in young children who cannot spontaneously expectorate sputum. Nasopharyngeal aspirates (NPA) may be more easily collected than gastric aspirate and induced sputum and can be obtained on demand, unlike stool. However, further information on its diagnostic yield is needed.MethodsWe systematically reviewed and meta-analyzed the diagnostic yield of one NPA for testing by either culture or nucleic acid amplification testing (NAAT) to detect Mycobacterium tuberculosis from children. We searched three bibliographic databases and two trial registers up to 24th November 2022. Studies that reported the proportion of children diagnosed by NPA compared to a microbiological reference standard (MRS) were eligible. Culture and/or WHO-endorsed NAAT on at least one respiratory specimen served as the MRS. We also estimated the incremental yield of two NPA samples compared to one and summarized operational aspects of NPA collection and processing. Univariate random-effect meta-analyses were performed to calculate pooled diagnostic yield estimates.ResultsFrom 1483 citations, 54 were selected for full-text review, and nine were included. Based on six studies including 256 children with microbiologically confirmed TB, the diagnostic yield of NAAT on one NPA ranged from 31 to 60% (summary estimate 44%, 95% CI 36–51%). From seven studies including 242 children with confirmed TB, the diagnostic yield of culture was 17–88% (summary estimate 58%, 95% CI 42–73%). Testing a second NPA increased the yield by 8–19% for NAAT and 4–35% for culture. NPA collection procedures varied between studies, although most children had NPA successfully obtained (96–100%), with a low rate of indeterminate results (< 5%). Data on NPA acceptability and specifically for children under 5 years were limited.ConclusionsNPA is a suitable and feasible specimen for diagnosing pediatric TB. The high rates of successful collection across different levels of healthcare improve access to microbiological testing, supporting its inclusion in diagnostic algorithms for TB, especially if sampling is repeated. Future research into the acceptability of NPA and how to standardize collection to optimize diagnostic yield is needed.

A Retrospective Assessment of Sputum Samples and Antimicrobial Resistance in COVID-19 Patients.

Data on bacterial or fungal pathogens and their impact on the mortality rates of Western Romanian COVID-19 patients are scarce. As a result, the purpose of this research was to determine the prevalence of bacterial and fungal co- and superinfections in Western Romanian adults with COVID-19, hospitalized in in-ward settings during the second half of the pandemic, and its distribution according to sociodemographic and clinical conditions. The unicentric retrospective observational study was conducted on 407 eligible patients. Expectorate sputum was selected as the sampling technique followed by routine microbiological investigations. A total of 31.5% of samples tested positive for Pseudomonas aeruginosa, followed by 26.2% having co-infections with Klebsiella pneumoniae among patients admitted with COVID-19. The third most common Pathogenic bacteria identified in the sputum samples was Escherichia coli, followed by Acinetobacter baumannii in 9.3% of samples. Commensal human pathogens caused respiratory infections in 67 patients, the most prevalent being Streptococcus penumoniae, followed by methicillin-sensitive and methicillin-resistant Staphylococcus aureus. A total of 53.4% of sputum samples tested positive for Candida spp., followed by 41.1% of samples with Aspergillus spp. growth. The three groups with positive microbial growth on sputum cultures had an equally proportional distribution of patients admitted to the ICU, with an average of 30%, compared with only 17.3% among hospitalized COVID-19 patients with negative sputum cultures (p = 0.003). More than 80% of all positive samples showed multidrug resistance. The high prevalence of bacterial and fungal co-infections and superinfections in COVID-19 patients mandates for strict and effective antimicrobial stewardship and infection control policies.

Efficacy of three sputum specimens for the diagnosis of Mycobacterium avium complex pulmonary disease

BackgroundIn Mycobacterium avium complex pulmonary disease (MAC-PD), diagnosis requires a positive culture from at least two separate expectorated sputum specimens. The optimal number of sputum examinations remains unclear.ObjectiveThis study sought to elucidate the diagnostic yield of acid-fast bacilli in MAC-PD using 3 sputum specimens and to clarify the clinical characteristics of patients with MAC-PD diagnosed using 3 sputum specimens. Furthermore, we investigated the correlation between increased number of sputum specimens and diagnostic yield.MethodsWe reviewed the medical records of 139 patients with MAC-PD diagnosed at Toho University Omori Medical Center for whom at least three sputum specimens were examined before treatment from November 2014 through June 2021. Patients were classified into the 3-sputum diagnosed and the non-3 sputum diagnosed groups based on diagnostic procedure; clinical and radiological characteristics were compared. We also assessed diagnostic yield with the increased number of sputum specimens.ResultsDiagnostic yield with 3 sputum specimens was 16.5% (23/139). The 3-sputum diagnosed group had a lower body mass index [18.6(17–19.5) vs. 19.5(18–21.5); p = 0.014], and higher chest CT score [9(6.5–13) vs. 6(4–9); p = 0.011] including cavitary lesions (39.1% vs. 19%; p = 0.037) compared with the non-3 sputum diagnosed group. When the number of sputum specimens was increased to 6, the diagnostic yield increased to 23.7% (33/139).ConclusionDiagnostic yield with 3 sputum specimens was 16.5%. Patients diagnosed using 3 sputum specimens had more severe chest CT findings including cavitary lesions. Increasing the number of sputum specimens to 6 improved diagnostic yield by 7.2%.

Effects of High-Frequency Chest Wall Oscillation on Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This study aimed to evaluate the efficacy of high-frequency chest wall oscillation for sputum expectoration and hospital length of stay in patients with acute exacerbations of chronic obstructive pulmonary disease. The improvements in pulmonary function and oxygenation were also investigated. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviewand Meta-analyses (PRISMA) guidelines. Automated literature database searches were conducted from the earliest records to March 31, 2022. The methodological quality of the included studies was assessed using the Cochrane Risk of Bias tool (RoB 2.0), and meta-analysis software (RevMan 5.4) was used to analyze the data. From 5439 identified articles, 13 studies (with 756 patients) were included in this meta-analysis. Compared to other airway clearance techniques, HFCWO significantly increased expectorated sputum volume by 6.18 mL (95% CI: 1.71 to 10.64; I2 = 87%), shortened hospital stay by 4.37 days (95% CI: -7.70 to -1.05; I2 = 84%). However, FEV1 (%), PaO2, and PaCO2 did not improve significantly. AECOPD patients may benefit from HFCWO therapy. HFCWO enables AECOPD patients to excrete more sputum and shorten their hospital stays. However, due to heterogeneity among the included research, these results should be interpreted with caution.

Clinical Aspects of Pulmonary Nontuberculous Mycobacteriosis

Nontuberculous mycobacterial (NTM) infections are an emerging problem. Common organisms include Mycobacterium avium, M. intracellulare, and M. kansasii, along with the M. avium intracellulare complex (MAC), which includes both M. avium and M. intracellulare. Typically, NTM infections affect the lungs and subsequently demonstrate a chronic course. Therefore, persistent respiratory symptoms generally indicate of the presence of pulmonary NTM diseases, and chest radiography, along with a sputum examination, are essential for its diagnosis. Because NTM are ubiquitous environmental organisms, a positive culture from a minimum of two separate expectorated sputum samples are required to make a diagnosis. The repertoire of effective drugs for treatment is considerably limited, indicating the need for long-term management with multiple drugs. Establishing a treatment regimen with high therapeutic efficacy and safety is an important issue for the future.

Which sample type is better for Xpert MTB/RIF to diagnose adult and pediatric pulmonary tuberculosis?

Objective: This review aimed to identify proper respiratory-related sample types for adult and pediatric pulmonary tuberculosis (PTB), respectively, by comparing performance of Xpert MTB/RIF when using bronchoalveolar lavage (BAL), induced sputum (IS), expectorated sputum (ES), nasopharyngeal aspirates (NPAs), and gastric aspiration (GA) as sample.Methods: Articles were searched in Web of Science, PubMed, and Ovid from inception up to 29 June 2020. Pooled sensitivity and specificity were calculated, each with a 95% confidence interval (CI). Quality assessment and heterogeneity evaluation across included studies were performed.Results: A total of 50 articles were included. The respective sensitivity and specificity were 87% (95% CI: 0.84–0.89), 91% (95% CI: 0.90–0.92) and 95% (95% CI: 0.93–0.97) in the adult BAL group; 90% (95% CI: 0.88–0.91), 98% (95% CI: 0.97–0.98) and 97% (95% CI: 0.95–0.99) in the adult ES group; 86% (95% CI: 0.84–0.89) and 97% (95% CI: 0.96–0.98) in the adult IS group. Xpert MTB/RIF showed the sensitivity and specificity of 14% (95% CI: 0.10–0.19) and 99% (95% CI: 0.97–1.00) in the pediatric ES group; 80% (95% CI: 0.72–0.87) and 94% (95% CI: 0.92–0.95) in the pediatric GA group; 67% (95% CI: 0.62–0.72) and 99% (95% CI: 0.98–0.99) in the pediatric IS group; and 54% (95% CI: 0.43–0.64) and 99% (95% CI: 0.97–0.99) in the pediatric NPA group. The heterogeneity across included studies was deemed acceptable.Conclusion: Considering diagnostic accuracy, cost and sampling process, ES was a better choice than other sample types for diagnosing adult PTB, especially HIV-associated PTB. GA might be more suitable than other sample types for diagnosing pediatric PTB. The actual choice of sample types should also consider the needs of specific situations.

Predictive value of C-reactive protein for tuberculosis, bloodstream infection or death among HIV-infected individuals with chronic, non-specific symptoms and negative sputum smear microscopy.

C-reactive protein (CRP) is an inflammatory biomarker that may identify patients at risk of infections or death. Mortality among HIV-infected persons commencing antiretroviral therapy (ART) is often attributed to tuberculosis (TB) or bloodstream infections (BSI). In two district hospitals in southern Malawi, we recruited HIV-infected adults with one or more unexplained symptoms present for at least one month (weight loss, fever or diarrhoea) and negative expectorated sputum microscopy for TB. CRP determination for 452 of 469 (96%) participants at study enrolment was analysed for associations with TB, BSI or death to 120 days post-enrolment. Baseline CRP was significantly elevated among patients with confirmed or probable TB (52), BSI (50) or death (60) compared to those with no identified infection who survived at least 120 days (269). A CRP value of >10 mg/L was associated with confirmed or probable TB (adjusted odds ratio 5.7; 95% CI 2.6, 14.3; 87% sensitivity) or death by 30 days (adjusted odds ratio 9.2; 95% CI 2.2, 55.1; 88% sensitivity). CRP was independently associated with TB, BSI or death, but the prediction of these endpoints was enhanced by including haemoglobin (all outcomes), CD4 count (BSI, death) and whether ART was started (death) in logistic regression models. High CRP at the time of ART initiation is associated with TB, BSI and early mortality and so has potential utility for stratifying patients for intensified clinical and laboratory investigation and follow-up. They may also be considered for empirical treatment of opportunistic infections including TB.

A systematic approach to diagnosing intra-thoracic tuberculosis in children

Children suffer a huge and often underappreciated burden of disease in tuberculosis (TB) endemic countries. Major hurdles include limited awareness among health care workers, poor integration of TB into maternal and child health approaches, diagnostic difficulties and a lack of child-friendly treatment options. Accurate disease diagnosis is particularly difficult in young and vulnerable children who tend to develop paucibacillary disease and are unable to produce an expectorated sputum sample. In addition, access to chest radiography is problematic in resource-limited settings. Differentiating between TB exposure and M. tuberculosis infection, and especially between M. tuberculosis infection and TB disease is crucial to guide clinical management. TB represents a dynamic continuum from well-contained "latent" infection to incipient and ultimately severe disease. The clinical spectrum of disease in children is broad and can be confused with a myriad of common infections. We provide a pragmatic 4-step approach to diagnose intra-thoracic TB in children and demonstrate how classifying clinical, radiological and laboratory findings into recognised clinical syndromes may provide a more refined diagnostic approach, even in resource-limited settings.

Molecular Identification of Staphylococcus aureus in Airway Samples from Children with Cystic Fibrosis.

BackgroundStaphylococcus aureus is a common and significant pathogen in cystic fibrosis. We sought to determine if quantitative PCR (qPCR) and 16S rRNA gene sequencing could provide a rapid, culture-independent approach to the identification of S. aureus airway infections.MethodsWe examined the sensitivity and specificity of two qPCR assays, targeting the femA and 16S rRNA gene, using culture as the gold standard. In addition, 16S rRNA gene sequencing to identify S. aureus directly from airway samples was evaluated. DNA extraction was performed with and without prior enzymatic digestion.Results87 samples [42 oropharyngeal (OP) and 45 expectorated sputum (ES)] were analyzed. 59 samples (68%) cultured positive for S. aureus. Using standard extraction techniques, sequencing had the highest sensitivity for S. aureus detection (85%), followed by FemA qPCR (52%) and 16SrRNA qPCR (34%). For all assays, sensitivity was higher from ES samples compared to OP swabs. Specificity of the qPCR assays was 100%, but 21.4% for sequencing due to detection of S. aureus in low relative abundance from culture negative samples. Enzymatic digestion increased the sensitivity of qPCR assays, particularly for OP swabs.ConclusionSequencing had a high sensitivity for S. aureus, but low specificity. While femA qPCR had higher sensitivity than 16S qPCR for detection of S. aureus, neither assay was as sensitive as sequencing. The significance of S. aureus detection with low relative abundance by sequencing in culture-negative specimens is not clear.

Diagnostic performance of measuring antibodies to the glycopeptidolipid core antigen specific to Mycobacterium avium complex in patients with rheumatoid arthritis: results from a cross-sectional observational study.

IntroductionThe aim of this study was to investigate the diagnostic performance of measuring antibodies to the glycopeptidolipid (GPL) core antigen specific to Mycobacterium avium complex (MAC) in patients with rheumatoid arthritis (RA).MethodsWe cross-sectionally investigated anti-GPL antibodies and radiographs of 396 patients with RA. A diagnosis of MAC pulmonary disease (MAC-PD) was made according to the criteria by the American Thoracic Society and the Infectious Diseases Society of America. Serum immunoglobulin A antibodies to MAC-specific GPL core antigen were measured by an enzyme immunoassay. All patients with RA with abnormal shadows on chest x-rays underwent chest computed tomography (CT). Bronchoscopy was performed on patients with negative cultures for MAC by expectorated sputum and positive CT findings compatible with MAC-PD.ResultsTen patients were newly diagnosed with MAC-PD. Eight individuals who already had diagnoses of MAC-PD at the time of enrollment and nineteen who had negative expectorated sputum cultures for MAC and positive CT images compatible with MAC-PD and who refused bronchoscopy were excluded from the following analysis. Anti-GPL antibodies were detected in 12 of 369 patients. Eight of the ten patients with MAC-PD and 4 of 359 patients without MAC-PD tested positive for the anti-GPL antibodies. The specificity and sensitivity were 99 % and 80 %, respectively. Positive and negative predictive values were 67 %, and 97 %, respectively. When we analyzed diagnostic performance of the antibodies in 57 patients with RA who had abnormal shadows on chest x-rays, the positive and negative predictive values were 100 %, and 96 %, respectively. Twelve patients underwent bronchoscopy. Bronchoalveolar lavage fluid (BALF) samples from six patients were positive for MAC, and BALF samples from the remainder were negative. Anti-GPL antibodies were detected in the sera of all six patients with positive results for MAC by BALF sampling, whereas the antibodies were not detected in the sera from the remainder with negative results for MAC by BALF sampling.ConclusionsThe measurement of anti-GPL antibodies is useful as a supplementary diagnostic tool for MAC-PD in patients with RA and may provide a new strategy, in combination with chest x-ray and CT, for differentiating MAC-PD from other pulmonary comorbidities in patients with RA.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0787-y) contains supplementary material, which is available to authorized users.

Assessment of airway microbiota and inflammation in cystic fibrosis using multiple sampling methods.

Oropharyngeal (OP) swabs and induced sputum (IS) are used for airway bacteria surveillance in nonexpectorating children with cystic fibrosis (CF). Molecular analyses of these airway samples detect complex microbial communities. However, the optimal noninvasive sampling approach for microbiota analyses and the clinical relevance of microbiota, particularly its relationship to airway inflammation, is not well characterized. The goals of this study were to compare molecular analyses of concurrently collected saliva, OP swabs, IS, and expectorated sputum (ES) from children with CF and to determine the association between microbiota, lung function, and airway inflammation. Saliva, OP swabs, IS, and ES were collected from 16 children with CF. Spirometry was performed. Respiratory and saliva samples (n = 61) were sequenced for bacterial microbial communities, and total and CF-specific bacterial quantitative PCR assays were performed. Airway samples underwent conventional culture for CF-specific pathogens. Neutrophil elastase, IL-1β, IL-1ra, IL-6, Il-8, TNF-α, and vascular endothelial growth factor were measured in ES and IS. Sequencing results from individual subjects were similar across samples, with greater between-subject than within-subject variation. However, Pseudomonas and Staphylococcus were detected in higher relative abundance from lower airways (ES and IS) compared with paired upper airway samples (OP and saliva). Pseudomonas, Staphylococcus, and Enterobacteriaceae correlated with increased airway inflammation. Divergence between microbiota in upper airway compared with lower airway samples, indicating greater differences between communities, was associated with increased sputum neutrophil elastase. Bacteria detected in IS samples resemble ES samples, whereas OP samples may underrepresent bacteria associated with airway inflammation. Divergence of lower airway communities from upper airway was associated with airway inflammation and may portend disease progression.

Sputum induction improves detection of pathogens in children with cystic fibrosis.

Sputum induction is a safe, well tolerated means of obtaining lower airway secretions from children with cystic fibrosis (CF), particularly for assessment of airway inflammation but the clinical value in diagnosing outpatient infections has not been extensively studied. Investigate the success rate and microbiologic yield of induced sputum (IS) compared to oropharyngeal swabs (OP) and expectorated sputum (ES) samples in children with CF, and determine if IS culture results impact treatment. Two cohorts were included in this prospective, longitudinal comparative study. In one cohort, simultaneously collected OP, ES, and IS specimens were obtained from 17 CF children at three visits over 1 year. In the second group, sputum induction was performed in 35 CF subjects at four annual visits, and culture results were compared to their nearest respiratory culture within 4 months. Antimicrobial treatment regimens were captured retrospectively. Sputum induction was successful in 149 of 158 (94%) visit encounters. Polymicrobial infection (combined P = 0.005) and gram negative organisms (combined P = 0.003) were detected more frequently in IS samples compared to OP, as were the individual pathogens Pseudomonas aeruginosa (combined P = 0.04) and Stenotrophomonas maltophilia (combined P = 0.05). The microbiologic yield of serial IS samples collected over 1 year was stable. IS culture results led to antibiotic changes in 6% of visit encounters. However, based on current practice 13% of visits could have resulted in treatment changes. Sputum induction is feasible in the outpatient setting and appears to improve pathogen detection in children with CF.

Analysis of Lung Flute-collected Sputum for Lung Cancer Diagnosis.

Molecular analysis of sputum can help diagnose lung cancer. We have demonstrated that Lung Flute can be used to collect sputum from individuals who cannot spontaneously expectorate sputum. The objective of this study is to further evaluate the performance of the Lung Flute by comparing the characteristics of parallel samples collected with and without the Lung Flute and the usefulness for diagnosis of lung cancer. Fifty-six early-stage lung cancer patients (40 current smokers and 16 former smokers) and 73 cancer-free individuals (52 current smokers and 21 former smokers) were instructed to spontaneously cough and use Lung Flute for sputum sampling. Sputum cytology and polymerase chain reaction analysis of three miRNAs (miRs-21, 31, and 210) were performed in the specimens. All 92 current smokers and 11 (28.7%) of 37 former smokers spontaneously expectorated sputum and also produced sputum when using the Lung Flute. Twenty-seven former smokers (70.3%) who could not spontaneously expectorate sputum, however, were able to produce sputum when using the Lung Flute. The specimens were of low respiratory origin without contamination from other sources, eg, saliva. There was no difference of sputum volume and cell populations, diagnostic efficiency of cytology, and analysis of the miRNAs in the specimens collected by the two approaches. Analysis of the sputum miRNAs produced 83.93% sensitivity and 87.67% specificity for identifying lung cancer. Therefore, sputum collected by the Lung Flute has comparable features as spontaneously expectorated sputum. Using the Lung Flute enables former smokers who cannot spontaneously expectorate to provide adequate sputum to improve sputum collection for lung cancer diagnosis.

Evaluation of lung flute in sputum samples for molecular analysis of lung cancer

BackgroundMolecular analysis of sputum provides a promising approach for lung cancer diagnosis, yet is limited by the difficulty in collecting the specimens from individuals who can’t spontaneously expectorate sputum. Lung Flute is a small self-powered audio device that can induce sputum by generating sound waves and vibrating in the airways of the lungs. Here we propose to evaluate the usefulness of Lung Flute for sputum sampling to assist diagnosis of lung cancer.MethodsForty-three stage I lung cancer patients and 47 cancer-free individuals who couldn’t spontaneously cough sputum were instructed to use Lung Flute for sputum sampling. Expressions of two microRNAs, miRs-31 and 210, were determined in the specimens by qRT-PCR. The results were compared with sputum cytology.ResultsSputum was easily collected from 39 of 43 (90.7%) lung cancer patients and 42 of 47 (89.4%) controls with volume ranges from 1 to 5 ml (median, 2.6 ml). The specimens had less than 4% oral squamous cells, indicating that sputum was obtained from low respiratory tract. Expressions of miRs-31 and 210 in sputum were considerably higher in cancer patients than cancer-free individuals (8.990 vs. 4.514; 0.6847 vs. 0.3317; all P <0.001). Combined use of the two miRNAs produced a significantly higher sensitivity (61.5% vs. 35.9%, P = 0.002) and a slightly lower specificity (90.5% vs. 95.2%, p = 0.03) compared with cytology for lung cancer diagnosis.ConclusionLung Flute could potentially be useful in convenient and efficient collection of sputum for molecular diagnosis of lung cancer.

Characterization of Candida Species Isolated from Cases of Lower Respiratory Tract Infection among HIV/AIDS Patients in Calabar, Nigeria

This study was designed to identify and characterize the Candida species isolated from lower respiratory tract infections among HIV positive patients and to determine the prevalence rates of Candida infections among these subjects. Two early morning expectorate sputum samples were collected from 272 HIV positive subjects visiting the ART clinics and DOTS centre with cases of lower respiratory tract infection, over a period of 14 months from May 2009 to July 2010 in Calabar. Subjects were recruited for this study upon approval by the Ethical Research Committee of the University of Calabar Teaching Hospital and obtaining written informed consent from the patients. Samples were processed by standard methods for isolation of Candida. Speciation was done by a germ tube test, chlamydospore production on corn meal agar and sugar fermentation and assimilation tests using the Microexpress Candida identification kit (Tulip, India). Out of the 544 sputum samples collected from 272 subjects, Candida species were isolated from 40 (14.7%) and identified after confirming the growth in the second sample. The majority of Candida species among the Candida isolates were Candida albicans (80%) followed by Candida tropicalis 5 (12.5%), Candida dubliniensis 2 (5.0%) and Candida guilliermondii 1 (2.5%). The isolation rate of Candida species from sputum samples was found to be highest among subjects aged 25 - 34 years, followed by those aged 15 - 24 years. Twenty (7.3%) HIV seropositive subjects had bacterial infections, while 4 (1.5%) subjects had mixed fungal and bacterial infections. This study is the first of its kind to be carried out in Calabar and the South-South geopolitical region of Nigeria, and has shown that pulmonary candidiasis is a health problem among HIV positive patients in Calabar.

Cost effectiveness of a lung cancer screening protocol based on 3D cell cytology antecedent to helical thoracic computed tomography (CT).

e16534 Background: Despite decades of progress in treatment and prevention, lung cancer mortality remains frustratingly high. Better survival prognosis for early stage cases, along with the occult nature that keeps lung cancer hidden from clinical observation in those early stages have combined to make early detection an appealing public health strategy. The National Lung Screening Trial (NLST) provides the first conclusive evidence that lung cancer screening with helical computed tomography (CT) can produce a significant mortality reduction for a high-risk population cohort. Because improved clinical outcomes are discounted by factors of test uncertainty, test cost, and the effects of elective radiation exposure, we sought to explore the value of preceding the CT exam with a non-invasive, highly specific and sensitive diagnostic test. Methods: Using a disease progression model based upon clinical evidence from published studies, we simulate a 15 year probabilistic experience for a high-risk patient cohort under the proposed protocol of pretesting followed by CT exam if positive, and periodic retesting if negative. The pretest is based upon the LuCED technology (Lung Cancer Evaluation Device) that compares patient cells from expectorate sputum to 3D morphometric biosignatures from a cancerous cell line. Results: The introduction of the LuCED technology to the screening protocol for a high-risk patient population resulted in increased early detection of stage I and Stage II NSCLC, reduced overall false positive and false negative detection rates, reduced unnecessary post-CT procedures and morbidity, and increased the number of life years saved by the program. The cost effectiveness ratio (CER) of this protocol ranged from $17,800 to $74,900 per life year saved with variation dependent on sensitivity, specificity and disease prevalence assumptions. Conclusions: The introduction of LuCED technology to the standard screening protocol for a high-risk population is comparable to other national cancer screening protocols such as breast and colorectal cancers in terms of CER.

Non-tuberculous mycobacterium infection after lung transplantation is associated with increased mortality

Pulmonary non-tuberculous mycobacterial (NTM) infection is relatively common after lung transplantation, but the effect on mortality remains undetermined. Herein we describe our experience with pulmonary NTM infection after lung transplantation and hypothesized that non-tuberculous mycobacterial infection after lung transplantation would be associated with increased mortality. We retrospectively evaluated 201 primary lung transplant recipients transplanted between January 2000 and August 2006. Serial bronchoscopies with bronchoalveolar lavage and transbronchial biopsy were performed according to a surveillance protocol and when clinically indicated. The diagnosis NTM infection was established by a positive NTM culture in a bronchoalveolar lavage sample or in at least two separate expectorated sputum samples. NTM infections were further classified as "disease" or "colonization," based on whether or not NTM infection patients developed symptoms and characteristic radiographic findings. Thirty-six (18%) recipients were diagnosed with pulmonary NTM infection at a median of 97 days post-transplantation: 9 were classified as NTM disease and the remaining 27 as NTM colonization cases. Single lung transplant was a significant risk factor for NTM infection (HR 2.25, p = 0.02). NTM colonization was a risk factor for NTM disease (HR 8.39, p = 0.003). NTM infection significantly increased the risk of death after lung transplantation (HR 2.61, p = 0.001) and persisted in multivariate models controlling for single lung transplant and bronchiolitis obliterans syndrome. The increased risk was seen for both NTM colonization and NTM disease. Among the patients who died, non-NTM infection was a more common contributing factor in the cause of death for the NTM infection group (44% vs 12%, p = 0.04). Non-tuberculous mycobacterial infection is common after lung transplantation. NTM colonization and treated acute rejection are risk factors for NTM disease. NTM infection is associated with increased risk of mortality independent of bronchiolitis obliterans syndrome.

Sputum Induction in Routine Clinical Care of Children with Cystic Fibrosis

To determine the microbiological yield of induced sputum (IS) samples compared with conventional airway samples, spontaneously expectorated sputum and throat swabs, in children with cystic fibrosis (CF) attending an outpatient clinic. Ninety-five children with CF (75 able to spontaneously expectorate sputum) were included in this prospective cross-sectional comparative study. After obtaining expectorated sputum or throat swabs samples, IS was obtained by performing the sputum induction procedure using an eFlow device (PARI, Starnberg, Germany). CF bacterial culture results were compared between the two procedures. Differences in culture results between samples were observed in 25 of 94 (27%) patients. IS had a significantly higher yield for CF pathogens, with 80% of the differences being due to detection of additional organisms in IS samples. Overall, SI was well tolerated, but 12 of 95 cases had a >20% postinduction decline in forced expiratory volume in 1 second. The whole SI procedure took 30 to 85 minutes of clinic time, and its estimated additional cost was $150 (US)/patient. Induced sputum has a higher microbiological yield compared with the conventional samples in children with CF, even in patients capable of expectorating sputum spontaneously. Although sputum induction is safe and tolerable, it is time-consuming and expensive in routine clinical settings.

Nontuberculous Mycobacteria in Solid Organ Transplant Recipients

Nontuberculous Mycobacteria in Solid Organ Transplant Recipients