Pharmacokinetics of antibiotics for pleural infection.

INTRODUCTION: Pleural infection causes significant morbidity and mortality. An important aspect in the treatment of pleural infection is the pharmacokinetics of antibiotics, an area often neglected. AREAS COVERED: Pathophysiology of pleural infection and the importance of antibiotic therapy in the treatment of pleural infection are discussed. After reviewing all available literature on pharmacokinetics of antibiotics for pleural infection, the scarcity of data and knowledge gaps are highlighted. EXPERT OPINION: This review aims to heighten awareness of the limited pharmacokinetic data of commonly used antibiotics for pleural infection. It serves to remind clinicians that choice of antibiotics for pleural infection should be based not only on bacterial sensitivity but also adequate delivery of antibiotics to the infected pleural cavity. Antibiotic pharmacokinetics may vary with agents used, pleural thickness and individual characteristics. Consideration must be given to insufficient pleural delivery of systemic antibiotics in patients lacking clinical improvement. Pleural infection research has disproportionately focused on fluid drainage. Optimizing delivery of effective antibiotic therapy to the pleural cavity must be regarded a key priority to progress clinical care. Large comprehensive cohort studies on pharmacokinetic variability are the essential next step. The possibility of intrapleural administration is also an area that warrants additional research.

Clinical utility of 16S rRNA PCR in pleural infection.

Pleural infections cause major morbidity and mortality, particularly amongst paediatric and elderly populations. The aetiology is broad, but pleural culture fails to yield a causative pathogen in approximately 40 % of cases. Alternative pathogen identification methods are therefore required. The aim of the study was to investigate the yield from and impact on patient care when performing 16S rRNA PCR on culture-negative pleural fluid specimens and to determine whether any individual laboratory parameters were associated with a positive 16S rRNA PCR result. We conducted a study on 90 patients with suspected pleural infection, who had a culture-negative pleural fluid specimen, which underwent 16S rRNA PCR analysis between August 2017 and June 2019. This study was undertaken at a large NHS Trust in London, UK. Thirty-one per cent of culture-negative pleural fluid specimens tested by 16S rRNA PCR yielded a positive PCR result. Our data demonstrated that 16S rRNA PCR detected a significantly higher proportion of Streptococcus pneumoniae (P<0.0001) and fastidious, slow-growing and anaerobic pathogens (P=0.0025) compared with culture-based methods. Of the 25 16S rRNA PCR results that were positive for a causative pathogen, 76 % had a direct impact on clinical management. No single laboratory variable was found to be associated with a positive 16S rRNA PCR result. The findings from our real-world evaluation highlight the importance of 16S rRNA PCR in confirming pleural infection when the aetiology is unknown, and its direct, positive impact on clinical management.

Cumulative radiation dose incurred during the management of complex pleural space infection.

BACKGROUND: Complex pleural space infections are commonly managed with antibiotics, pleural drainage, intrapleural fibrinolytic therapy, and surgery. These strategies often utilize radiographic imaging during management, however little data is available on cumulative radiation exposure received during inpatient management. We aimed to identify the type and quantity of radiographic studies along with the resultant radiation exposure during the management of complex pleural space infections. METHODS: Retrospective review of community network healthcare system from January 2015 to July 2018. Patients were identified through billing databases as receiving intrapleural fibrinolytic therapy and/or surgical intervention. Patient demographics, clinical outcomes, and inpatient radiographic imaging was collected to calculate cumulative effective dose. RESULTS: A total of 566 patients were identified with 7275 total radiographic studies performed and a median cumulative effective dose of 16.9 (IQR 9.9-26.3) mSv. Multivariable linear regression analysis revealed computed tomography use was associated with increased cumulative dose, whereas increased age was associated with lower cumulative dose. Over 74% of patients received more than 10 mSv, with 7.4% receiving more than 40 mSv. CONCLUSIONS: The number of radiographic studies and overall cumulative effective dose in patients hospitalized for complex pleural space infection was high with the median cumulative effective dose > 5 times normal yearly exposure. Ionizing radiation and modern radiology techniques have revolutionized medical care, but are likely not without risk. Additional study is warranted to identify the frequency and imaging type needed during complex pleural space infection management, attempting to keep ionizing radiation exposure as low as reasonably possible.

Pleural infection-an indicator of morbidity and increased burden on health care.

OBJECTIVES: Patients with pleural infections frequently have several comorbidities and inferior long-term survival. We hypothesized that these patients represent a vulnerable cohort with high rates of hospitalization and frequent use of healthcare services. This study aims to ascertain the need for and causes of treatment episodes after pleural infections during long-term follow-up. METHODS: Patients treated for pleural infections at Tampere University Hospital between January 2000 and December 2008 (n = 191, 81% males, median age 58 years) were included and compared to a demographically matched population-based random sample of 1910 controls. Seventy percent of the pleural infections were caused by pneumonias and 80% of the patients underwent surgery. Information regarding later in-hospital periods and emergency room and out-patient clinic visits, as well as survival data, was obtained from national registries and compared between patients and controls. RESULTS: Patients treated for pleural infections had significantly higher rates of hospitalizations (8.19 vs 2.19), in-hospital days (88.5 vs 26.6), emergency room admissions (3.18 vs 1.45), out-patient clinic visits (41.1 vs 11.8) and procedures performed (1.26 vs 0.55) per 100 patient-months when compared to controls during 5-year follow-up, in addition to having increased mortality (30% vs 11%), P-value <0.00001 each. Particularly, episodes due to respiratory and digestive diseases, malignancies and mental disorders were more frequent. The patients' comorbidities, such as alcoholism or chronic pulmonary disease, were associated with more frequent use of healthcare services. CONCLUSIONS: Patients treated for pleural infections have high rates of hospitalizations, emergency room admissions and out-patient clinic visits during follow-up.

Factors associated with variations in the rate of referrals and microbiology of pleural infection.

OBJECTIVES: Invasive pneumococcal disease is seasonal and associated with influenza, but the same is uncertain for pleural infection. We set out to investigate whether pleural infection referrals similarly correlate with the seasonal variation in influenza burden and whether the microbiologic etiology varies according to certain factors. METHODS: Cases of pleural infection were retrieved from the database of a Pleural Unit in a tertiary hospital in the UK. The rate of referrals for pleural infection was compared to contemporary national rates of influenza hospitalizations and primary care presentation with influenza like illnesses. RESULTS: Between August 2015 and December 2019, 157 cases of pleural infection were diagnosed. The monthly rate of referrals with pleural infections was 3.8 cases/month, but this varied between months [range 0-6 cases]. No clear increase in pleural infection referrals coinciding or falling after peak influenza diagnosis was observed. However, the rate of infection referrals correlated positively with the overall monthly volume of pleural referrals (ß 0.035, p = 0.004). Gram negative bacteria seemed more common during the hotter months, in hospital-acquired infections and in younger adults. Young adults were more commonly infected with pneumococci than older adults, who were more vulnerable to anaerobic infections. CONCLUSION: Direct association between the rate of pleural infection cases and influenza activity was not identified. Pleural infection microbiology appears to differ according to age and environmental temperatures.

A systematic review of comorbidities and outcomes of adult patients with pleural infection.

BACKGROUND: Pleural infection remains an important cause of mortality. This study aimed to investigate worldwide patterns of pre-existing comorbidities and clinical outcomes of patients with pleural infection. METHODS: Studies reporting on adults with pleural infection between 2000 and 2017 were identified from a search of Embase and MEDLINE. Articles reporting exclusively on tuberculous, fungal or post-pneumonectomy infection were excluded. Two reviewers assessed 20 980 records for eligibility. RESULTS: 211 studies met the inclusion criteria. 134 articles (227 898 patients, mean age 52.8 years) reported comorbidity and/or outcome data. The majority of studies were retrospective observational cohorts (n=104, 78%) and the most common region of reporting was East Asia (n=33, 24%) followed by North America (n=27, 20%). 85 articles (50 756 patients) reported comorbidity. The median (interquartile range (IQR)) percentage prevalence of any comorbidity was 72% (58-83%), with respiratory illness (20%, 16-32%) and cardiac illness (19%, 15-27%) most commonly reported. 125 papers (192 298 patients) reported outcome data. The median (IQR) length of stay was 19 days (13-27 days) and median in-hospital or 30-day mortality was 4% (IQR 1-11%). In regions with high-income economies (n=100, 74%) patients were older (mean 56.5 versus 42.5 years, p<0.0001), but there were no significant differences in prevalence of pre-existing comorbidity nor in length of hospital stay or mortality. CONCLUSION: Patients with pleural infection have high levels of comorbidity and long hospital stays. Most reported data are from high-income economy settings. Data from lower-income regions is needed to better understand regional trends and enable optimal resource provision going forward.

The microbiology of pleural infection in adults: a systematic review.

BACKGROUND AND OBJECTIVES: Pleural infection is a major cause of morbidity and mortality among adults. Identification of the offending organism is key to appropriate antimicrobial therapy. It is not known whether the microbiological pattern of pleural infection is variable temporally or geographically. This systematic review aimed to investigate available literature to understand the worldwide pattern of microbiology and the factors that might affect such pattern. DATA SOURCES AND ELIGIBILITY CRITERIA: Ovid MEDLINE and Embase were searched between 2000 and 2018 for publications that reported on the microbiology of pleural infection in adults. Both observational and interventional studies were included. Studies were excluded if the main focus of the report was paediatric population, tuberculous empyema or post-operative empyema. STUDY APPRAISAL AND SYNTHESIS METHODS: Studies of ≥20 patients with clear reporting of microbial isolates were included. The numbers of isolates of each specific organism/group were collated from the included studies. Besides the overall presentation of data, subgroup analyses by geographical distribution, infection setting (community versus hospital) and time of the report were performed. RESULTS: From 20 980 reports returned by the initial search, 75 articles reporting on 10 241 patients were included in the data synthesis. The most common organism reported worldwide was Staphylococcus aureus. Geographically, pneumococci and viridans streptococci were the most commonly reported isolates from tropical and temperate regions, respectively. The microbiological pattern was considerably different between community- and hospital-acquired infections, where more Gram-negative and drug-resistant isolates were reported in the hospital-acquired infections. The main limitations of this systematic review were the heterogeneity in the method of reporting of certain bacteria and the predominance of reports from Europe and South East Asia. CONCLUSIONS: In pleural infection, the geographical location and the setting of infection have considerable bearing on the expected causative organisms. This should be reflected in the choice of empirical antimicrobial treatment.

Clinical profile of tuberculosis in patients with chronic kidney disease: A report from an endemic Country.

The objective is to study the clinical profile of tuberculosis (TB) in chronic kidney disease (CKD). This is retrospective study of CKD patients who were diagnosed to have TB over a period of seven years at a tertiary care hospital. TB was diagnosed in 115 patients with an incidence of 4200/100,000. Mean age of the patients was 46.9 ± 16 years. Sixty-two patients (53.9%) were male. Causes of CKD were diabetic nephropathy and hypertension in 11.3% each, chronic glomerulonephritis in 31.3%, chronic tubulointerstitial nephritis in 39.1%, autosomal dominant polycystic kidney disease, and post-renal transplant CKD in 3.5% each. About 68.7% of patients with TB had advanced CKD stage of 4-5D, whereas 31.3% of patients had early CKD stage 1-3. Twenty percent of patients were on dialysis. Three-fourths of the patients had extrapulmonary TB. Pleuropulmonary (41.8%), kidney and urinary tract (20%), and abdomen and lymph node (13% each) were the most common sites for TB. The main clinical presentation of TB was: fever/pyrexia of unknown origin in 24.3%, constitutional symptoms of anorexia, fever, night sweats, and weight loss in 27.8%, abnormal chest radiograph in 31.2%, ascites/peritonitis in 13.9%, pleural effusion in 25.2%, lymphadenopathy in 20%, and sterile pyuria/hematuria/chronic pyelonephritis in 13%. Microbiological and/or histopathological diagnoses were made in 45.2% and in the other 54.8%, diagnosis of TB was made on clinical grounds. Adverse effects of anti-TB drugs were seen in 9.6% of patients. Ninety-three percent completed the treatment and survived. Eight patients (7%), all in CKD stage 5D, died. The incidence of TB was high among CKD stages 4 and 5 and in those receiving dialysis. Extrapulmonary disease such as pleuropulmonary, renal, peritoneal, and lymph node were the common forms of TB.

Pleural infection: a closer look at the etiopathogenesis, microbiology and role of antibiotics.

INTRODUCTION: Pleural infection is a condition that continues to pose a significant challenge to respiratory physicians. We hypothesize that the main barriers to progress include limited understanding of the etiopathogenesis, microbiology,and role of antibiotics in the pleural space. Areas covered: PubMed was searched for articles related to adult pleural infection using the terms 'pleural infection', 'empyema' and 'parapneumonic'. The search focused on relevant literature within the last 10 years, with any older citations used only to display context or lack of progress. Tuberculous pleural infection was excluded. We chose to give specific attention to the etiopathogenesis of pleural infection, including recent advances in diagnostics and biomarkers. We discuss our understanding of the pleural microbiome and rationalize the current use of antibiotics in treating this condition. Expert commentary: Understanding of key events in the development of this condition remains limited. The microbiology is unique compared to the lung, and highly variable. Higher culture yields from pleural biopsy may add new insights into the etiopathogenesis. There is little evidence into achievable effective antibiotic concentration within the pleura. Research into issues including the relevance of biofilm formation and significance of pleural thickening is necessary for treatment progress.

Bacteriology and clinical outcomes of patients with culture-positive pleural infection in Western Australia: A 6-year analysis.

BACKGROUND AND OBJECTIVE: Pleural infection is a clinical challenge; its microbiology can be complex. Epidemiological and outcome data of pleural infection in adult Australians are lacking. We describe the bacteriology and clinical outcomes of Australian adults with culture-positive pleural infection (CPPI) over a 6-year period. METHODS: Cases with CPPI were identified through Western Australian public hospitals electronic record. Culture isolates, admission dates, vital status, co-morbidities, radiology, blood and pleural fluid tests were extracted. RESULTS: In total, 601 cases (71.4% males; median age: 63 years (IQR: 50-74); median hospital stay 13 days) involving 894 bacterial isolates were identified. Hospital-acquired (HA)-CPPI was defined in 398 (66.2%) cases, community-acquired (CA)-CPPI in 164 (27.3%) cases and the remaining classified as oesophageal rupture/leak. Co-morbidities, most frequently cancer, were common (65.2%). Radiological evidence of pneumonia was present in only 43.8% of CA-CPPI and 27.3% of HA-CPPI. Of the 153 different bacterial strains cultured, Streptococcus species (32.9%) especially viridans streptococci group were most common in CA-CPPI, whereas HA-CPPI was most often associated with Staphylococcus aureus (11.6%) and Gram-negative (31.9%) infections. Mortality was high during hospitalization (CA-CPPI 13.4% vs HA-CPPI 16.6%; P = 0.417) and at 1 year (CA-CPPI 32.4% vs HA-CPPI 45.5%; P = 0.006). CONCLUSION: This is the first large multicentre epidemiological study of pleural infection in Australian adults and includes the largest cohort of HA-CPPI published to date. CPPI is caused by a diverse range of organisms which vary between CA and HA sources. CPPI is a poor prognostic indicator both in the short term and in the subsequent 12 months.

Pleuropulmonary tuberculosis with spinal lesions due to metastatic malignancy differentiated definitively on imaging.

A healthy 31-year-old man presenting with back pain was found to have multiple spinal enhancing lesions on MRI. An incidental asymptomatic large pleural effusion was identified on investigations for the back pain and pleural and pulmonary tuberculosis (TB) was subsequently diagnosed. The radiographical features on MRI spine were not typical of spinal TB and a Ga68 DOTATATE Positron Emission Tomography (PET)/CT confirmed metastatic paraganglioma with multiple bone metastases. Although metastatic paraganglioma is rare, this case highlights that even in young patients dual pathology needs to be considered. Most importantly, it is a reminder to physicians managing TB of the clues that help distinguish spinal TB from important alternative causes, including metastatic malignancy.

Identification of Streptococcus pneumoniae lytA, plyA and psaA genes in pleural fluid by multiplex real-time PCR / Identificación de los genes lytA, plyA y psaA de Streptococcus pneumoniae en líquido pleural mediante una técnica de PCR múltiple en tiempo real

INTRODUCTION: The aim was to evaluate the utility of a multiplex real-time PCR to detect Streptococcus pneumoniae lytA, plyA and psaA genes in pleural fluid (PF). METHODS: A collection of 81 PF samples was used. Sixty were considered positive for S. pneumoniae according to previous results (54 by an in-house lytA gene PCR and eight by universal rRNA PCR). RESULTS: The sensitivity for detection of the lytA, plyA and psaA genes by multiplex PCR was 100% (60/60), 98.3% (59/60) and 91.7% (55/60), respectively. The detection of all three genes was negative in 21 samples formerly confirmed as negative for S. pneumoniae (100% specificity) by the other procedures (9 by in-house lytA PCR and 12 by rRNA PCR). CONCLUSIONS: The use of this multiplex PCR may be a useful option to identify S. pneumoniae directly in PF samples

INTRODUCCIÓN: El objetivo fue evaluar la utilidad de una técnica de PCR múltiple para detectar los genes lytA, plyA y psaA de Streptococcus pneumoniae en líquido pleural. MÉTODOS: Se empleó una colección de 81 muestras de líquido pleural. Sesenta habían sido consideradas positivas para S. pneumoniae según resultados previos (54 por una prueba casera de PCR para el gen lytA y 8 por una PCR universal rRNA). RESULTADOS: La sensibilidad de la técnica para la detección de los genes lytA, plyA y psaA fue respectivamente 100% (60/60), 98,3% (59/60) y 91,7% (55/60). La detección de los tres genes resultó negativa en 21 muestras negativas (especificidad 100%) por los otros procedimientos (9 por la prueba casera de PCR para lytA y 12 por la PCR rRNA). CONCLUSIONES: El uso de esta técnica de PCR múltiple puede ser una opción útil para la detección directa de S. pneumoniae en líquido pleural

Clinical and microbiologic characteristics of pleuro-pulmonary infection due to Streptococcus intermedius / Características clínicas y microbiológicas de la infección pulmonar causada por Streptococcus intermedius

The clinical and microbiological characteristics of pleuro-pulmonary infection (PPI) caused by Streptococcus intermedius is described, including 6 cases in the literature and 9 cases handled at the present centre. Out of the 15 patients, 12 were male; mean age at diagnosis was 62.06 ± 15 years. Twelve had risk factors for S. intermedius infection such as alcoholism in 5 (35.7%) patients, periodontal disease in 3 (24.6%) cases, chronic obstructive pulmonary disease in 3 (24.6%), and diabetes mellitus in 2 (14.2%). Cough was present in 12 (80%) patients and chest pain and dyspnea in 9 (60%). The mean diagnosis interval was 34 days. The diagnosis was obtained from pleural fluid aspirate in 13 (86.6%) cases and from biopsy/tissue samples in 2. The most frequently antimicrobials used for treatment were ceftriaxone + levofloxacin. Ten patients cured with a combination of medical and surgical treatment and 2 patients died as a consequence of infection. The incidence of PPI caused by S. intermedius is increasing in our health area; drainage along with antibiotic therapy is recommended for treatment

Se describen las características clínicas y microbiológicas de la infección pleuro-pulmonar producida por Streptococcus intermedius , incluyendo 6 casos de la literatura y 9 casos diagnosticados en nuestro centro. De los 15 pacientes, 12 eran varones; la media de edad al diagnóstico fue de 62,02 ± 15 años. Doce tenían factores de riesgo para la infección por S. intermedius , tales como alcoholismo en 5 (35,7%) pacientes, enfermedad periodontal en 3 (24,6%) casos, enfermedad pulmonar obstructiva crónica en 3 (24,6%), y diabetes mellitus en 2 (14,2%). Se presentó tos en 12 (80%) pacientes y dolor torácico y disnea en 9 (60%). La media del intervalo diagnóstico fue de 34 días. El diagnóstico se obtuvo de aspirado de líquido pleural en 13 (86,6%) casos y de muestras de biopsia/tejido en 2. Los antimicrobianos más frecuentemente utilizados fueron ceftriaxona + levofloxacino. Diez pacientes curaron con una combinación de tratamiento médico y quirúrgico y dos pacientes fallecieron como consecuencia de la infección. La incidencia de infección pleuro-pulmonar causada por S. intermedius se ha incrementado en nuestra área de salud; el tratamiento recomendado es el drenaje junto con la terapia antibiótica

A rare case of pleural infection due to Propionibacterium acnes (Cutibacterium acnes) / Un caso raro de infección pleural producida por Propionibacterium acnes (Cutibacterium acnes)

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Clinical and microbiologic characteristics of pleuro-pulmonary infection due to Streptococcus intermedius.

The clinical and microbiological characteristics of pleuro-pulmonary infection (PPI) caused by Streptococcus intermedius is described, including 6 cases in the literature and 9 cases handled at the present centre. Out of the 15 patients, 12 were male; mean age at diagnosis was 62.06 ± 15 years. Twelve had risk factors for S. intermedius infection such as alcoholism in 5 (35.7%) patients, periodontal disease in 3 (24.6%) cases, chronic obstructive pulmonary disease in 3 (24.6%), and diabetes mellitus in 2 (14.2%). Cough was present in 12 (80%) patients and chest pain and dyspnea in 9 (60%). The mean diagnosis interval was 34 days. The diagnosis was obtained from pleural fluid aspirate in 13 (86.6%) cases and from biopsy/tissue samples in 2. The most frequently antimicrobials used for treatment were ceftriaxone + levofloxacin. Ten patients cured with a combination of medical and surgical treatment and 2 patients died as a consequence of infection. The incidence of PPI caused by S. intermedius is increasing in our health area; drainage along with antibiotic therapy is recommended for treatment.

Marked cachexia in probable invasive pulmonary aspergillosis with bronchopleural fistula.

A 49-year-old man with a medical history of diabetes and heavy smoking was admitted to intensive care with severe bilateral pneumonia associated with marked cachexia. He developed a complex right-sided bronchopleural fistula and was transferred to our tertiary centre for consideration of surgical intervention.Despite escalation of antibiotic therapy, he did not improve and further investigations led to a diagnosis of invasive pulmonary aspergillosis. Definitive treatment plans required a right pneumonectomy; however, given the severity of cachexia, he remained unable to undergo such a large operation. This case demonstrates an atypical presentation of invasive pulmonary aspergillosis in a mildly immunodeficient individual. It highlights the challenges in assessment and management of critically ill patients' nutrition as well as optimal timing for surgical intervention.

The Utility of Ultrasound to Diagnose Tunnel-Tract Infection Related to Indwelling Pleural Catheters.

Indwelling pleural catheter (IPC) infections lead to increased morbidity and treatment failure in patients with chronic recurrent pleural effusions. Ultrasonography is a readily available diagnostic tool used by pulmonologists on a daily basis. Ultrasonography has been used to identify the etiology of indwelling peritoneal catheter obstruction, including infection of the exit site and tunnel tract. The use of ultrasonography to identify tunnel-tract infection involving IPC has not been reported. We describe the ultrasonographic characteristics of 3 cases of confirmed tunnel-tract infection and compared them with noninfected chronic IPCs. Ultrasonographic evaluation of the soft tissue tunnel tract can accurately identify fluid collections around the catheter and cuff, which is highly suggestive of tunnel-tract infection.