Pleural Penetration Research Articles

Pleural penetration of amoxicillin and metronidazole during pleural infection: An ambispective cohort study

The pharmacokinetics of antibiotics in pleural fluid during pleural infections has been poorly described. This study aimed to explore amoxicillin and metronidazole diffusion into the pleural space. This was an ambispective, single-centre study that included patients with complicated parapneumonic effusion or pleural empyema managed with repeated therapeutic thoracentesis as first-line treatment between 2014 and 2022. Pleural steady-state or trough concentrations of amoxicillin and metronidazole were measured, with a lower limit of quantification of 5 mg/L. Seventy paired blood and pleural samples were analysed from 40 patients. The median (interquartile range) patient age was 55 years (45-67 years) and 88% were male. The median patient weight was 65.8 kg (57.3-82 kg) and median plasma albumin concentration was 29.7 g/L (23.7-33.9 g/L). Median creatinine clearance was 106 mL/min (95-117 mL/min). Median amoxicillin pleural concentrations in patients treated with oral, bolus and continuous intravenous administrations (6 g/day) were, respectively, 5.2 (<5-6.4), 9.4 (8-13.1) and 10.8 (7.1-13.1) mg/L. Pleural concentrations were <5 mg/L in 5/11 samples (45%) with oral treatment and 6/59 (10%) with intravenous treatment. Median metronidazole pleural concentrations were 18.4 (15.7-22.8) mg/L, with all patients being treated orally (1.5 g/day). Oral metronidazole (1.5 g/day) and intravenous amoxicillin (6 g/day) achieved therapeutic targets in pleural fluid in most cases, but oral amoxicillin did not.

Pleural fluid penetration of moxifloxacin and doripenem: An experimental model of empyema.

OBJECTIVE:This study aimed to evaluate the penetration of moxifloxacin and doripenem into the pleural fluid (PF) using a rabbit model of empyema.METHODS:An empyema was induced using the intrapleural injection of turpentine (1 mL), followed 24 h later by instillation of 5 mL Klebsiella Pneumoniae (ATCC 33495), Fusobacterium nucleatum (ATCC 25586) and Streptokok Pneumoniae (ATCC 6305) into the pleural space. After an empyema was corroborated, Moxifloxacin (25 mg/kg-1) and Doripenem (20 mg/kg-1) were administered intraperitoneally. To determine the levels of antibiotics measured by High-Performance Liquid Chromatography in pleural and blood samples were obtained serially at 8, 24, 48 and 72nd hour.RESULTS:The penetration of both antibiotics into the PF was very good. The penetration rate of doripenem (area under the curve (AUC) for PF/blood (AUCPF/AUCblood) ratio=1.68) was better than moxifloxacin (ratio=0.78). Equalization time between the PF and blood concentration of doripenem was more quickly than moxifloxacin. Peak PF concentration of moxifloxacin was 0,81 μg/mL-1 and occurred 8 h after infusion and then gradually decreased; at the beginning of the blood and pleural fluid concentrations of doripenem were equal. While the pleura concentration was increasing, blood concentration was almost the same. Doripenem reached a peak concentration (0.54 μg/ml) 24 h post-administration.CONCLUSION:Differences were found in the penetration of the two antibiotics. Doripenem had convenient penetration PF compared to moxifloxacin. Due to the differences between human and rabbit pleural thickness, doripenem’s pleural penetration should be examined in infection models in animals with equal pleura thickness and clinical trials.

Growth patterns of pulmonary metastases: should we adjust resection techniques to primary histology and size?

Safety margins in pulmonary metastasectomy are not yet well defined. We hypothesize that histological subtype, size of the lesion and local growth characteristics must be taken into consideration during metastasectomy. This study was conducted to examine and classify growth patterns at resection margins and define the relationships between aggressive local growth, metastasis size and local recurrence to direct metastasectomy. Histologic sections of pulmonary metastases were prospectively collected and haematoxylin-eosin stains were systematically evaluated and classified by their pattern of lung tissue infiltration. Logistic regression was used to model the association between the subgroups of colorectal, renal cell and epithelial cancers and melanomas and sarcomas. From 183 patients, 412 lung specimens were removed, which contained 459 pulmonary metastases. We found that 58% of all lesions had microscopic signs of aggressive local dissemination. The metastases showed histology-specific patterns of local growth: sarcoma was associated with pleural infiltration; colorectal metastases with interstitial spread and aerogenous spread of floating cancer cell clusters; and melanoma with perivascular growth and with lymph vessel involvement. Aggressive patterns of growth had an increasing probability of around 3% for each additional millimetre of metastasis diameter. Local intrapulmonary recurrence was significantly more common in association with interstitial growth and pleural penetration as well as safety margins <7 mm. Approximately 40% of all lung metastases have a smooth surface and might be resected with small margins. Growth characteristics within the lung differ with the histologic subtype and safety margins should generally increase with the size of the metastasis.

Pulmonary and pleural inflammation after intratracheal instillation of short single-walled and multi-walled carbon nanotubes.

Relationships between the physical properties of carbon nanotubes (CNTs) and their toxicities have been studied. However, little research has been conducted to investigate the pulmonary and pleural inflammation caused by short-fiber single-walled CNTs (SWCNTs) and multi-walled CNTs (MWCNTs). This study was performed to characterize differences in rat pulmonary and pleural inflammation caused by intratracheal instillation with doses of 0.15 or 1.5mg/kg of either short-sized SWCNTs or MWCNTs. Data from bronchoalveolar lavage fluid analysis, histopathological findings, and transcriptional profiling of rat lungs obtained over a 90-day period indicated that short SWCNTs caused persistent pulmonary inflammation. In addition, the short MWCNTs markedly impacted alveoli immediately after instillation, with the levels of pulmonary inflammation following MWCNT instillation being reduced in a time-dependent manner. MWCNT instillation induced greater levels of pleural inflammation than did short SWCNTs. SWCNTs and MWCNTs translocated in mediastinal lymph nodes were observed, suggesting that SWCNTs and MWCNTs underwent lymphatic drainage to the mediastinal lymph nodes after pleural penetration. Our results suggest that short SWCNTs and MWCNTs induced pulmonary and pleural inflammation and that they might be transported throughout the body after intratracheal instillation. The extent of changes in inflammation differed following SWCNT and MWCNT instillation in a time-dependent manner.

AB 25. Moxifloxacin pharmacokinetics and pleural fluid penetration in patients with pleural effusion

Background Moxifloxacin is widely used for the treatment of parapneumonic pleural effusion or empyema. However, data on moxifloxacin penetration and pharmacokinetics in pleural space have been reported are scarce. The aim of this study was to evaluate the kinetics and penetration of moxifloxacin in patients with various types of pleural effusion and degrees of inflammation.

Acute pulmonary dose–responses to inhaled multi-walled carbon nanotubes

This study investigated the in vivo pulmonary toxicity of inhaled multi-walled carbon nanotubes (MWCNT). Mice-inhaled aerosolized MWCNT (10 mg/m3, 5 h/day) for 2, 4, 8 or 12 days. MWCNT lung burden was linearly related to exposure duration. MWCNT-induced pulmonary inflammation was assessed by determining whole lung lavage (WLL) polymorphonuclear leukocytes (PMN). Lung cytotoxicity was assessed by WLL fluid LDH activities. WLL fluid albumin concentrations were determined as a marker of alveolar air–blood barrier integrity. These parameters significantly increased in MWCNT-exposed mice versus controls and were dose-dependent. Histopathologic alterations identified in the lung included (1) bronciolocentric inflammation, (2) bronchiolar epithelial hyperplasia and hypertrophy, (3) fibrosis, (4) vascular changes and (5) rare pleural penetration. MWCNT translocated to the lymph node where the deep paracortex was expanded after 8 or 12 days. Acute inhalation of MWCNT induced dose-dependent pulmonary inflammation and damage with rapid development of pulmonary fibrosis, and also demonstrated that MWCNT can reach the pleura after inhalation exposure.

Growth patterns of lung metastases from sarcoma: prognostic and surgical implications from histology

Pulmonary metastasectomy is firmly established in the multidisciplinary management of patients with advanced sarcomas. While the number of metastases, completeness of resection, disease-free interval and grading of the primary sarcoma are well established prognostic factors in metastatic surgery, histological parameters are not widely evaluated. The objective of the present study was to evaluate the prognostic impact of intrapulmonary growth patterns of sarcoma metastases. We retrospectively analysed the clinicopathological characteristics of 52 sarcoma patients who underwent surgical resection of lung metastases at our centre from January 2006 to January 2009. The histological growth characteristics of all 261 metastases have been categorized and published previously. 'Interstitial growth' was defined as a diffuse spread of the sarcoma cells into the alveolar septae at the transition of the metastasis to the normal lung tissue and was found to be prognostic. 'Pleural penetration' was defined as the infiltration and destruction of all visceral pleural layers by the tumour and was found to be a risk factor for local recurrence. The median post-metastasectomy overall survival was 50.3 months, and the corresponding 5-year survival rate was 44.7%. Age >55 years at metastasectomy (P = 0.02), the presence of interstitial growth (P = 0.008), size of the largest metastasis >35 mm (P = 0.023) and the presence of tumour recurrence at any site after metastasectomy (P < 0.001) were identified as risk factors for death. Pleural penetration (P = 0.007) and size of the metastasis >5 mm were found to be risk factors for local intrapulmonary recurrence. Interstitial tumour growth, which is easily detected by light microscopy, can serve as a strong predictor of survival following pulmonary metastasectomy in sarcoma patients. Obvious pleural infiltration indicates the need for larger margins.

Mouse pulmonary dose- and time course-responses induced by exposure to multi-walled carbon nanotubes

Carbon nanotubes (CNT) come in a variety of types, but one of the most common forms is multi-walled carbon nanotubes (MWCNT). MWCNT have potential applications in many diverse commercial processes, and thus human exposures are considered to be likely. In order to investigate the pulmonary toxicity of MWCNT, we conducted an in vivo dose-response and time course study of MWCNT in mice in order to assess their ability to induce pulmonary inflammation, damage, and fibrosis using doses that approximate estimated human occupational exposures. MWCNT were dispersed in dispersion medium (DM) and male C57BL/6J mice (7 weeks old) received either DM (vehicle control), 10, 20, 40 or 80 μg MWCNT by aspiration exposure. At 1, 7, 28 and 56 days post-exposure, MWCNT-induced pulmonary toxicity was investigated. Bronchoalveolar lavage (BAL) studies determined pulmonary inflammation and damage was dose-dependent and peaked at 7 days post-exposure. By 56 days post-exposure, pulmonary inflammation and damage markers were returning to control levels, except for the 40 μg MWCNT dose, which was still significantly higher than vehicle control. Histopathological studies determined that MWCNT exposure caused rapid development of pulmonary fibrosis by 7 days post-exposure, that granulomatous inflammation persisted throughout the 56-day post-exposure period, and also demonstrated that MWCNT can reach the pleura after pulmonary exposure. In summary, the data reported here indicate that MWCNT exposure rapidly produces significant adverse health outcomes in the lung. Furthermore, the observation that MWCNT reach the pleura after aspiration exposure indicates that more extensive investigations are needed to fully assess if pleural penetration results in any adverse health outcomes.

Minimally Invasive Cholecystostomy in the Dog: Evaluation of Placement Techniques and Use in Extrahepatic Biliary Obstruction

To evaluate 4 methods of cholecystostomy catheter placement and to report on laparoscopic (Lap) cholecystostomy for the management of extrahepatic biliary obstruction (EHBO) in 3 dogs. Experimental study and clinical report. Cadaveric dogs (n=20); 2 canine and 1 feline patient. Pigtail cholecystostomy catheters were inserted in 20 canine cadavers using ultrasound (US) or Lap guidance. Insertion routes were either transperitoneal or transhepatic. Methods studied included Lap-transperitoneal, US-transperitoneal, US-transhepatic, and US-Seldinger (n=5 dogs/group). Insertion success, pleural penetration, and insertion site leakage (Lap-transperitoneal group) were evaluated. Three clinical EHBO cases were treated by Lap-transperitoneal technique. Insertion success was 100% by Lap-transperitoneal but 0% with US-transperitoneal and US-Seldinger methods. US-transhepatic yielded 3 of 5 successful placements. The pleura was penetrated in all US-transhepatic and US-Seldinger insertions. Leakage pressure for Lap-transperitoneal catheters averaged 75 cm H2O (+/-20 cm H2O). Lap-transperitoneal cholecystostomy resulted in marked improvement in 2 dogs, but the catheter became obstructed in the cat. One dog spontaneously regained common bile duct patency and the remaining 2 animals had successful cholecystoenterostomy. In cadaver testing, the Lap-transperitoneal cholecystostomy method was superior based on high insertion success with no pleural penetration. In 2 clinical cases, Lap-transperitoneal placement successfully provided biliary drainage for patient stabilization. The role for temporary cholecystostomy has yet to be established, but may aid patient stabilization and mortality reduction in EHBO.

Spontaneous pneumothorax.

Pneumothorax is classified as spontaneous (not caused by trauma or any obvious precipitating factor), traumatic, or iatrogenic (Table 1). Primary spontaneous pneumothorax occurs in persons without clinically apparent lung disease; secondary spontaneous pneumothorax is a complication of preexisting lung disease. Iatrogenic pneumothorax results from a complication of a diagnostic or therapeutic intervention. Traumatic pneumothorax is caused by penetrating or blunt trauma to the chest, with air entering the pleural space directly through the chest wall; visceral pleural penetration; or alveolar rupture due to sudden compression of the chest. In this review we focus on spontaneous pneumothorax.Primary Spontaneous PneumothoraxEpidemiology . . .

Managing Complications of Posterior Spinal Instrumentation and Fusion

Complications of posterior spinal instrumentation for adolescent idiopathic scoliosis are often preventable. Preoperative planning helps to minimize intraoperative and postoperative problems. Late recurrence of rotational deformity (crankshaft) in skeletally immature patients can be prevented by adding anterior surgery. Intraoperative complications are minimized by controlled hypotensive anesthesia and sequencing of surgical steps to allow for autocoagulation, reducing blood loss. Use of spinal cord monitoring, Stagnara wakeup test, and careful distraction decreases the risk of neurologic deficit. Good hook-site preparation helps avoid dural tears. The incidence of postoperative pneumothorax and hemothorax is decreased by careful hook attachment, avoiding pleural penetration, judicious use of rib excision thoracoplasty, and roentgenographic verification of central venous pressure line position. Postoperative recommendations include bed position at 30 degrees, frequent log rolling, incentive spirometry, early sitting and standing, early Foley catheter and nasogastric tube removal, prophylactic antibiotics, and prompt attention to wound infections. Postoperative orthotic wear, prescribed exercise, and activity restriction decrease the risk of early instrumentation failure and help correct early postoperative trunk imbalance. The late complications include suspected pseudarthrosis; this should be surgically treated again if there is persistent pain or marked loss of curve correction.

Pleural Penetration of Ciprofloxacin in Patients with Empyema Thoracis

We evaluated the pharmacokinetics of a single 200-mg dose of ciprofloxacin, administered as a 30-minute infusion, into pleural exudate in five elderly patients with empyema thoracis. Ciprofloxacin was measured by HPLC and the pharmacokinetic parameters were determined by noncompartmental methods. Mean peak serum levels 30 minutes after administration were 1.98 +/- 0.07 mg/L. Terminal serum half-lives ranged from 3.9 to 5.1 h. Mean concentrations of ciprofloxacin in pleural exudate were 1.44 +/- 0.42 mg/L at a mean time of 4.5 +/- 2.5 h. After this time, the pleural exudate level exceeded the corresponding serum twofold to tenfold. The mean percentage penetration into the inflammatory compartment was approximately 210 percent. Our data suggested that ciprofloxacin penetrates well into the pleural fluid of patients with empyema thoracis. The concentrations achieved were well above the MIC90 of most pathogens normally found in patients with empyema thoracis for a period of approximately 12 h.

Penetration of ciprofloxacin into human pleural fluid

The concentrations of ciprofloxacin (1.5 mg/kg of body weight) in serum and in uninfected pleural exudates were studied after one and three intravenous injections had been given at 8-h intervals. The drug was assayed in serum and in pleural fluid by high-performance liquid chromatography. The peak concentrations in pleural fluid 1.5 h after one and three injections were (mean +/- standard error of the mean) 0.52 +/- 0.09 and 0.77 +/- 0.15 mg/liter, respectively; the corresponding 8-h concentrations were 0.19 +/- 0.05 and 0.39 +/- 0.10 mg/liter. At 1 and 8 h, the ratios of mean concentrations in pleural fluid to mean concentrations in serum were 112 and 158%, respectively, after one injection and 77 and 122% after three injections. This study suggested that there is a satisfactory pleural penetration of ciprofloxacin after intravenous injection.

Penetration of Aminoglycosides in Uninfected Pleural Exudates and in Pleural Empyemas

The concentrations of gentamicin, netilmicin, and amikacin were determined after one single intravenous injection in uninfected pleural fluid after thoracotomy and in purulent pleural empyemas. The mean peak concentrations in the pleural fluid after the injection of gentamicin (1.5 mg/kg), netilmicin (2.0 mg/kg), and amikacin (7.5 mg/kg) were 2.9 +/- 0.3 mg/L, 3.7 +/- 0.8 mg/L, and 11.0 +/- 3.1 mg/L, respectively. The pleural penetration of the drugs was very high (from 80.0 to 99.1 percent). By contrast, gentamicin and netilmicin were not detectable in empyema pus; in this exudate the mean peak level of amikacin was 5.7 +/- 2.2 mg/L, with the penetration of this drug being 31.0 percent. The concentrations of parenterally administered aminoglycosides are substantially lower in empyema pus than in sterile pleural fluid. The possibility of poor pleural penetration of some aminoglycosides, as well as the presence of local conditions in pleural empyema unfavorable to the bioactivity of these drugs, must be kept in mind when treating pleural infections.

Approaches to the management of shotgun injuries.

Shotgun wounds present specific challenges for the surgeon. Multiple penetrating wounds frequently involve large anatomic areas with potential multi-system injury. Experience with 121 patients sustaining shotgun wounds over the 5-year period ending 31 December 1981 was reviewed to assess results and evaluate treatment protocols. Sixty-six patients had chest wounds with pleural penetration. Twenty-four wounds were minor and were observed. Each had less than five pellets penetrating the pleura. Twenty-two patients had close-range injuries. Fourteen of these required chest tube drainage alone and eight patients required thoracotomy for control of bleeding. Eleven patients died, six as a direct result of the chest injury. In 55 patients with abdominal-retroperitoneal wounds exploratory operations were done if more than four pellets were thought to be lodged intraperitoneally or if signs of peritonitis were present, while lesser wounds without peritoneal findings were observed. In the 15 patients who did not have exploratory operations, there were no deaths or major complications. Thirty-five patients had exploratory operations. Two patients had five intraperitoneal missiles and no clinical evidence of peritonitis but were found to have significant intestinal perforations. Four patients died. Eighty-three patients with extremity wounds were classified according to location of injury. Forty-five had upper extremity wounds, with nine vascular injuries. Two patients died and one limb was amputated because of soft tissue infection. Thirty-eight patients had lower extremity wounds. Five had major vascular injuries. Preoperative arteriography was obtained in 13 patients with extremity injuries; the results of one of these were falsely negative. There were no deaths or amputations.(ABSTRACT TRUNCATED AT 250 WORDS)

A New Reliable Instrument for Pleural Biopsy

The Ballestero needle features an oval shaft with eccentric stylette, allowing 90° rotation of the cutting tip after pleural penetration. On withdrawal, the misaligned tip produces easily palpable hooking on the pleura. The tip is held against the pleura; the shaft-cutting jaw is rotated to alignment; the jaws are closed and the instrument is withdrawn. The Ballestero needle features an oval shaft with eccentric stylette, allowing 90° rotation of the cutting tip after pleural penetration. On withdrawal, the misaligned tip produces easily palpable hooking on the pleura. The tip is held against the pleura; the shaft-cutting jaw is rotated to alignment; the jaws are closed and the instrument is withdrawn.