Research Article
Intrapleural Antimicrobial Irrigation for Postpneumonectomy Empyema in Patients With Lung Cancer
Journal of Pharmacy Practice 1-4 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0897190014544787 jpp.sagepub.com
Heather Torbic, PharmD, BCPS1, Nicole Glasser, PharmD, BCPS2, Sara E. Rostas, PharmD, BCPS1, Mohammed Alquwaizani, PharmD1, and Gaspar Hacobian, BA, BS, PharmD1
Abstract Purpose: Postpneumonectomy empyema (PPE) is a possible complication after a pneumonectomy in patients with lung cancer. The use of intrapleural (IP) antibiotic irrigation to treat infections in the pleural space may be indicated after systemic antimicrobial therapy, and drainage of the pleural space has been insufficient. Methods: Adult patients 18 years old who received IP antibiotic irrigation between 2006 and 2011 were included. Demographic data, past medical history, surgical procedure, systemic antibiotics, and culture data were collected. Additionally, the IP antibiotic administered, the dose, and how it was prepared and administered were collected. Results: A total of 18 patients were evaluated in this retrospective descriptive analysis. The majority of patients underwent an extrapleural pneumonectomy (EPP; 72%). Most patients received systemic antibiotics before IP antibiotic administration (95%). Vancomycin was the most common antibiotic used for both systemic therapy (100%) and IP irrigation (94%). The median number of IP antibiotic doses received per patient was 5.5 (interquartile range [IQR] 1-9). Recurrence of PPE within 6 months of initial PPE resolution occurred in 28% of patients. Intrapleural antibiotic irrigation was well tolerated in all patients. Conclusion: Vancomycin is most commonly used for IP antibiotic irrigation at our institution after patients have undergone a thoracic surgery, which was most commonly an EPP. Keywords critical care, infectious disease, medication safety
Introduction According to the American Cancer Society, approximately 250 000 patients will be diagnosed in 2013 with lung cancer and 146 000 will die from this disease.1 The removal of diseased tissue in combination with chemotherapy and radiation is the most effective therapy to treat or slow the progression of this disease.2-4 The most common surgical procedures performed are pneumonectomy, extrapleural pneumonectomy (EPP), and pleurectomy. Patients who undergo thoracic surgical procedures have an increased risk of death with a 25% mortality rate.5 This increased risk of death is most likely due to postoperative complications. Postpneumonectomy empyema (PPE), one of many serious complications acquired after a pneumonectomy, has an incidence rate of 5% to 10%. About half of all PPEs occur within the first 4 weeks after pneumonectomy and 75% within the first 3 months.6,7 Management of PPEs may include thoracostomy, systemic antibiotics, surgical debridement, and irrigation of the pleural cavity with antibiotics.8-10 The combined approach of an open thoracostomy and antibiotic irrigation has been successful in up
to 92% of cases, although it results in prolonged hospitalization, repeated operative procedures, and significant morbidity.6 Surgical interventions to eradicate PPE are associated with a mortality rate of 9% to 13%.7 Although it is possible to reach an adequate antibiotic serum concentration in the pleural fluid with systemic administration, sterilization of the pleural fluid in PPE is extremely difficult due to damaged microcirculation, which impedes the ability to clear the infection.11 The use of intrapleural (IP) antibiotic irrigation to treat infections in the pleural space may be helpful, but the data evaluating the safety and efficacy of IP antibiotic administration are limited as are the procedures for preparing and administering these products. We conducted a single-center, retrospective descriptive analysis to assess and
1 2
Department of Pharmacy, Brigham and Women’s Hospital, Boston, MA, USA Department of Pharmacy, Crozer-Chester Medical Center, Upland, PA, USA
Corresponding Author: Heather Torbic, Department of Pharmacy, Brigham and Woman’s Hospital, 75 Francis Street, Boston, MA 02115, USA. Email: [email protected]
Downloaded from jpp.sagepub.com at SETON HALL UNIV on April 28, 2015
2
Journal of Pharmacy Practice
Table 1. Intrapleural Antimicrobial Preparation. Antibiotic Vancomycin Meropenem Voriconazole Metronidazole Ceftazidime
Dose, mg 1000 1000 1000 500 1000
Diluent 1000 1000 1000 500 1000
mL mL mL mL mL
NS NS NS NS NS
Abbreviation: NS, normal saline.
describe the practice of IP antibiotic irrigation at a tertiary academic medical center.
Methods This study was approved by the institutional review board at Brigham and Women’s Hospital. An internal pharmacy database was used to identify all patients who received IP antibiotics. Subjects were included in the study if they were 18 years old and received at least 1 dose of an IP antibiotic between December 2006 and December 2011. Patients were excluded if they were ordered for an IP antibiotic but never received a dose. Electronic medical records were utilized to obtain pertinent patient-specific information for this analysis. Data collected included baseline demographic information, including age, gender, race, type of lung cancer, type of thoracic surgery performed, systemic antibiotics received prior to IP antibiotics, and positive cultures prior to systemic antibiotics. We collected adverse event data by reviewing notes in the patient chart suggesting that there was an adverse event directly related to IP antibiotic administration (ie, pain with administration or evidence of irritation to the chest cavity). Data regarding pharmacy preparation of IP antibiotics were also collected. This included the antibiotic administered, dose, concentration, and the diluent used to compound the irrigation product. The administration procedures of IP antibiotics at our institution were also evaluated. Efficacy was assessed by examining the recurrence of PPE within 6 months of initial PPE resolution.
All patients had blood and sputum cultures collected prior to the start of IP antibiotics, and 95% of cultures were collected before systemic antimicrobial administration. Only 45% of cultures were positive for an organism before systemic antibiotic administration. A total of 5 (28%) patients completed a course of systemic antibiotics for the treatment of a pulmonary infection prior to developing a PPE. Most (95%) patients received systemic antibiotics prior to IP antibiotic administration. All patients who received systemic antibiotics received more than 1 systemic antibiotic. The most common systemic antibiotics patients received included vancomycin (100%), metronidazole (88%), ceftazidime (35%), and levofloxacin (35%). Other systemic antimicrobials utilized included meropenem, voriconazole, clindamycin, ceftriaxone, sulfamethoxazole/trimethoprim, fluconazole, cefepime, and gentamicin. The median duration of systemic antibiotic therapy prior to initiation of IP antimicrobials was 6 days (IQR 3-9). No patients received IP antibiotics or any other IP-administered therapies prior to evaluation in this analysis. The most common IP antibiotic prescribed was vancomycin, as it was received by 17 (94%) patients. Other IP antimicrobials administered to 1 patient each included ceftazidime, meropenem, voriconazole, and metronidazole. Of the 18 patients, 13 (72%) received more than 1 dose of IP antibiotics. The median number of IP antimicrobial doses received per patient was 5.5 (IQR 1-9). Recurrence of a PPE within 6 months of initial PPE resolution occurred in 28% of patients. There were no reports of adverse events associated with IP antibiotic administration. All IP antimicrobials were prepared in the pharmacy sterile products room, and our standard dilutions for these agents are listed in Table 1. Nurses administered IP antibiotics via a chest tube (not placed to suction), an angiocath via an infusion pump running at 42 mL/h, or directly into the chest tube via a stopcock device. The IP antibiotic was able to dwell in the thoracic cavity for a specific amount of time as determined by the physician (median 6.3 hours [IQR 4-10]) and was then drained. If additional doses of IP antibiotics were indicated, they were ordered every 24 hours.
Discussion Results Our pharmacy database identified 51 patients who had been ordered for IP antibiotics. Of the 51 patients, only 18 were found to have received IP antibiotics during their hospital admission and were subsequently included in the analysis. The majority (83%) of patients were male with a median age of 68 years old (interquartile range [IQR] 56-78). The majority of patients had a diagnosis of mesothelioma (14 [78%] patients), 3 (17%) patients had nonsmall cell lung cancer (adenocarcinoma), and 1 (5%) patient had nonsmall cell lung cancer (squamous cell). Of the thoracic surgeries performed, 13 (72%) patients underwent an EPP, 3 (17%) patients underwent a pleurectomy, and 2 (11%) patients underwent a pneumonectomy.
Empyema still remains as a common complication following a pneumonectomy. Based on previous studies, first-line therapy still involves chest tube drainage, systemic antimicrobials, and possible surgical intervention.6,7 Surgical management, using the Clagett procedure,12 which involves an open-chest window, continues to be a first-line therapy option for management of PPE. Surgical management has limitations and not all patients are able to tolerate a surgical procedure. Additionally, the open-chest window procedure can affect a patient’s quality of life and often results in a longer recovery time.10 Most antibiotics have been shown to reach adequate levels in pleural fluid when administered systemically. In patients with PPE, however, the ability of systemic antibiotics to reliably reach therapeutic levels in infected pleural fluid may be decreased due to changes in microcirculation.11 Our analysis, as well as other
Downloaded from jpp.sagepub.com at SETON HALL UNIV on April 28, 2015
Torbic et al
3
small reports, suggests that IP antimicrobials may be a reasonable treatment option when first-line therapies have failed. Although data regarding IP antimicrobials are limited, Bagan et al13 conducted a descriptive analysis of thoracoscopic debridement preceded by antibiotic irrigation. The analysis evaluated 18 patients with PPE. In this study, all patients received IP antibiotic irrigation and systemic parenteral antibiotics for 10 days followed by videothoracoscopic debridement. The success rate of IP antibiotics was 88.8% with no recurrence after a mean follow-up of 44.4 months. From this small, single-center study, Bagan and colleagues concluded that IP antibiotics followed by thoracoscopic debridement were effective in the management of PPE. The authors did not comment on the safety and tolerability of this practice. Ng et al14 conducted an analysis of 8 patients to determine the efficacy of continuous antibiotic irrigation following debridement in PPE. Most (88%) patients received IP vancomycin, no adverse events were associated with this practice, and there was no recurrence of empyema noted in patient follow-up. Ng and colleagues concluded that surgical debridement in combination with continuous IP antibiotic irrigation is a safe and effective management strategy for PPE. The IP antibiotic irrigation practices described by Bagan et al and Ng et al differ significantly than practices observed during our retrospective observational analysis. We observed a single IP antimicrobial instillation that remained in the chest cavity for a range of 4 to 10 hours and was then drained. This instillation was repeated in some, but not all, patients in our study. We do not have a standardized procedure of administration of IP antibiotics. Therefore, the dwell times, frequency, and duration of IP antibiotics at our institution are determined by the attending surgeon and inconsistent among the surgeons. Ng et al utilized a continuous irrigation of IP antibiotics for a minimum of 2 weeks. Bagan et al did not comment on the IP antibiotics dwell times used in their study. One commonality between Ng et al and our study was the frequency with which vancomycin was utilized in patients as the selected IP irrigation antibiotic. More data are needed before a recommendation for IP antibiotic dosing, preparation, and dwell time can be made. Given our small sample size, our study was not powered to determine efficacy nor did it have the lengthy follow-up period that other small studies have had. Due to the retrospective nature of our study, many patients were lost to follow-up beyond 6 months; and therefore, it was only feasible to assess PPE recurrence for a 6-month time period, thus limiting our ability to truly comment on the efficacy of IP antibiotic administration. Bagan et al and Ng et al had mean follow-up periods of 44.4 months and 580 days, respectively, and found a low incidence of PPE recurrence after IP antibiotic administration, suggesting this is an effective practice. Larger studies are needed to confirm these findings. The available literature examining IP administration of antibiotics has not reported adverse effects and has demonstrated that IP antibiotics are well tolerated. In our small study, we did not find any reports of adverse events associated with IP antibiotics. Due to the retrospective nature of the study, we had to rely on documentation of adverse events related to IP antibiotic
administration in the patient chart, thus a limitation of our data. Neither Ng et al nor Bagan et al reported any adverse events with IP antibiotic administration further supporting that this is likely a well-tolerated procedure. Our analysis has many limitations. It is a small, single-center, retrospective analysis. Due to the retrospective design, we were unable to control for other variables affecting the management of the PPE. It is unknown whether any concomitant therapies or any nonpharmacologic strategies affected the results of the study. Additionally, our study did not have a control group and therefore, we cannot compare the addition of IP antibiotics to standard care. The small sample size and limited follow-up period limit our ability to comment on the optimal IP antibiotic regimen, but given the data, we do have available; it appears the practice at our institution is effective and well tolerated. At our institution, the first-line management of PPE continues to be drainage and systemic antibiotics based on the greater abundance of available literature regarding the efficacy and safety of these practices.6,7,12 Based on the limited data available and the inconsistency in antibiotic selection, dosing, and administration techniques among the published literature, it is difficult at this time to recommend IP antimicrobial therapy as a first-line option for management of PPE. Intrapleural fibrinolysis therapy with and without IP recombinant human DNase therapy has also been studied for management of PPE, particularly in patients who are not surgical candidates.10,15,16 These IP therapies have been shown to help dissolve infected loculated areas of the lung resulting in increased drainage of the empyema.10,15,16 Pleurodesis using sclerosing agents, such as talc, bleomycin, tetracyclines, or povidone iodine, has only been shown to be effective in the management of pleural effusion or pneumothorax.17-20 We have implemented a safe procedure for instilling IP antimicrobials should patients not adequately respond to first-line PPE management options and warrant IP antimicrobial administration. Through a multidisciplinary effort with physician, nursing, and pharmacy leadership and the data from this analysis, we are working to standardize a procedure for IP antibiotic administration at our institution. Our goal is to standardize IP antibiotic dosing, preparation, administration techniques, and dwell times. Further studies are needed to evaluate the efficacy and safety of this practice in a larger subset of patients.
Conclusion Our analysis demonstrates that administration of IP antimicrobials for the management of a PPE is feasible and safe. Larger studies evaluating efficacy of IP antimicrobials for the management of PPE are needed. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Downloaded from jpp.sagepub.com at SETON HALL UNIV on April 28, 2015
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Journal of Pharmacy Practice
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11-30. 2. NCCN Small Cell Lung Cancer Guidelines. NCCN Guidelines Version 2.2013. National Comprehensive Cancer Network; Revised 2013. 3. NCCN Non-Small Cell Lung Cancer Guidelines. NCCN Guidelines Version 2.2013. National Comprehensive Cancer Network; Revised 2013. 4. NCCN Malignant Pleural Mesothelioma Cancer Guidelines. NCCN Guidelines Version 2.2013. National Comprehensive Cancer Network; Revised 2013. 5. Fuentes PA. Pneumonectomy: historical perspective and prospective insight. Eur J Cardiothorac Surg. 2003;20(4): 439-445. 6. Gharagozloo F, Trachiotis G, Wolfe A, et al. Pleural space irrigation and modified clagett procedure for the treatment of early postpneumonectomy empyema. J Thorac Cardiovasc Surg. 1998; 116(6):943-948. 7. Schneiter D, Cassina P, Korom S, et al. Accelerated treatment of early and late postpneumonectomy empyema. Ann Thorac Surg. 2001;72(5):1668-1672. 8. Karkhanis VS, Joshi JM. Pleural effusion: diagnosis, treatment, and management. Open Access Emergency Medicine. 2012;4(2012): 31-52. 9. Pairolero PC, Arnold PG, Trastek VF, et al. Postpneumonectomy empyema. The role of intrathoracic muscle transposition. J Thorac Cardiovasc Surg. 1990;99(6):958-968.
10. Ben-Nun A, Soudack M, Best LA. Non-surgical treatment for post-pneumonectomy empyema. Interact Cardiovasc Thorac Surg. 2003;2(4):616-619. 11. Falagas ME, Vergidis PI. Irrigation with antibiotic-containing solutions for the prevention and treatment of infections. Clin Microbiol Infect. 2005;11(11):862-867. 12. Clagett OT, Geraci JE. A procedure for the management of postpneumonectomy empyema. J Thorac Cardiovasc Surg. 1963;45:141-145. 13. Bagan P, Boissier F, Berna P, et al. Postpneumonectomy empyema treated with a combination of antibiotic irrigation followed by videothoracoscopic debridement. J Thorac Cardiovasc Surg. 2006;132(3):708-710. 14. Ng T, Ryder BA, Maziak DE, et al. Treatment of postpneumonectomy empyema with debridement followed by continuous antibiotic irrigation. J Am Coll Surg. 2008;206(3):1178-1183. 15. Tokuda Y, Matsushima D, Stein GH, et al. Intrapleural fibrinolytic agents for empyema and complicated parapneumonic effusions: a meta analysis. Chest. 2006;129(3):783-790. 16. Rahman NM, Phil D, Maskell NA, et al. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med. 2011;365(6):518-526. 17. Roberts ME, Neville E, Berrisford RG, et al. Management of a malignant pleural effusion: British Thoracic Society Pleural Disease Guideline 2010. Thorax. 2010;65(suppl 2):ii32-ii40. 18. Putnam JB Jr, , Light RW, Rodriguez RM, et al. A randomized comparison of indwelling pleural catheter and doxycycline pleurodesis in the management of malignant pleural effusions. Cancer. 1999;86(10):1992-1999. 19. Walker-Renard PB, Vaughan LM, Sahn SA. Chemical pleurodesis for malignant pleural effusions. Ann Intern Med. 1994; 120(1):56-64. 20. Heffner JE. Diagnosis and management of malignant pleural effusions. Respirology. 2008;13(1):5-20.
Downloaded from jpp.sagepub.com at SETON HALL UNIV on April 28, 2015
Intrapleural Antimicrobial Irrigation for Postpneumonectomy Empyema in Patients With Lung Cancer
Journal of Pharmacy Practice 1-4 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0897190014544787 jpp.sagepub.com
Heather Torbic, PharmD, BCPS1, Nicole Glasser, PharmD, BCPS2, Sara E. Rostas, PharmD, BCPS1, Mohammed Alquwaizani, PharmD1, and Gaspar Hacobian, BA, BS, PharmD1
Abstract Purpose: Postpneumonectomy empyema (PPE) is a possible complication after a pneumonectomy in patients with lung cancer. The use of intrapleural (IP) antibiotic irrigation to treat infections in the pleural space may be indicated after systemic antimicrobial therapy, and drainage of the pleural space has been insufficient. Methods: Adult patients 18 years old who received IP antibiotic irrigation between 2006 and 2011 were included. Demographic data, past medical history, surgical procedure, systemic antibiotics, and culture data were collected. Additionally, the IP antibiotic administered, the dose, and how it was prepared and administered were collected. Results: A total of 18 patients were evaluated in this retrospective descriptive analysis. The majority of patients underwent an extrapleural pneumonectomy (EPP; 72%). Most patients received systemic antibiotics before IP antibiotic administration (95%). Vancomycin was the most common antibiotic used for both systemic therapy (100%) and IP irrigation (94%). The median number of IP antibiotic doses received per patient was 5.5 (interquartile range [IQR] 1-9). Recurrence of PPE within 6 months of initial PPE resolution occurred in 28% of patients. Intrapleural antibiotic irrigation was well tolerated in all patients. Conclusion: Vancomycin is most commonly used for IP antibiotic irrigation at our institution after patients have undergone a thoracic surgery, which was most commonly an EPP. Keywords critical care, infectious disease, medication safety
Introduction According to the American Cancer Society, approximately 250 000 patients will be diagnosed in 2013 with lung cancer and 146 000 will die from this disease.1 The removal of diseased tissue in combination with chemotherapy and radiation is the most effective therapy to treat or slow the progression of this disease.2-4 The most common surgical procedures performed are pneumonectomy, extrapleural pneumonectomy (EPP), and pleurectomy. Patients who undergo thoracic surgical procedures have an increased risk of death with a 25% mortality rate.5 This increased risk of death is most likely due to postoperative complications. Postpneumonectomy empyema (PPE), one of many serious complications acquired after a pneumonectomy, has an incidence rate of 5% to 10%. About half of all PPEs occur within the first 4 weeks after pneumonectomy and 75% within the first 3 months.6,7 Management of PPEs may include thoracostomy, systemic antibiotics, surgical debridement, and irrigation of the pleural cavity with antibiotics.8-10 The combined approach of an open thoracostomy and antibiotic irrigation has been successful in up
to 92% of cases, although it results in prolonged hospitalization, repeated operative procedures, and significant morbidity.6 Surgical interventions to eradicate PPE are associated with a mortality rate of 9% to 13%.7 Although it is possible to reach an adequate antibiotic serum concentration in the pleural fluid with systemic administration, sterilization of the pleural fluid in PPE is extremely difficult due to damaged microcirculation, which impedes the ability to clear the infection.11 The use of intrapleural (IP) antibiotic irrigation to treat infections in the pleural space may be helpful, but the data evaluating the safety and efficacy of IP antibiotic administration are limited as are the procedures for preparing and administering these products. We conducted a single-center, retrospective descriptive analysis to assess and
1 2
Department of Pharmacy, Brigham and Women’s Hospital, Boston, MA, USA Department of Pharmacy, Crozer-Chester Medical Center, Upland, PA, USA
Corresponding Author: Heather Torbic, Department of Pharmacy, Brigham and Woman’s Hospital, 75 Francis Street, Boston, MA 02115, USA. Email: [email protected]
Downloaded from jpp.sagepub.com at SETON HALL UNIV on April 28, 2015
2
Journal of Pharmacy Practice
Table 1. Intrapleural Antimicrobial Preparation. Antibiotic Vancomycin Meropenem Voriconazole Metronidazole Ceftazidime
Dose, mg 1000 1000 1000 500 1000
Diluent 1000 1000 1000 500 1000
mL mL mL mL mL
NS NS NS NS NS
Abbreviation: NS, normal saline.
describe the practice of IP antibiotic irrigation at a tertiary academic medical center.
Methods This study was approved by the institutional review board at Brigham and Women’s Hospital. An internal pharmacy database was used to identify all patients who received IP antibiotics. Subjects were included in the study if they were 18 years old and received at least 1 dose of an IP antibiotic between December 2006 and December 2011. Patients were excluded if they were ordered for an IP antibiotic but never received a dose. Electronic medical records were utilized to obtain pertinent patient-specific information for this analysis. Data collected included baseline demographic information, including age, gender, race, type of lung cancer, type of thoracic surgery performed, systemic antibiotics received prior to IP antibiotics, and positive cultures prior to systemic antibiotics. We collected adverse event data by reviewing notes in the patient chart suggesting that there was an adverse event directly related to IP antibiotic administration (ie, pain with administration or evidence of irritation to the chest cavity). Data regarding pharmacy preparation of IP antibiotics were also collected. This included the antibiotic administered, dose, concentration, and the diluent used to compound the irrigation product. The administration procedures of IP antibiotics at our institution were also evaluated. Efficacy was assessed by examining the recurrence of PPE within 6 months of initial PPE resolution.
All patients had blood and sputum cultures collected prior to the start of IP antibiotics, and 95% of cultures were collected before systemic antimicrobial administration. Only 45% of cultures were positive for an organism before systemic antibiotic administration. A total of 5 (28%) patients completed a course of systemic antibiotics for the treatment of a pulmonary infection prior to developing a PPE. Most (95%) patients received systemic antibiotics prior to IP antibiotic administration. All patients who received systemic antibiotics received more than 1 systemic antibiotic. The most common systemic antibiotics patients received included vancomycin (100%), metronidazole (88%), ceftazidime (35%), and levofloxacin (35%). Other systemic antimicrobials utilized included meropenem, voriconazole, clindamycin, ceftriaxone, sulfamethoxazole/trimethoprim, fluconazole, cefepime, and gentamicin. The median duration of systemic antibiotic therapy prior to initiation of IP antimicrobials was 6 days (IQR 3-9). No patients received IP antibiotics or any other IP-administered therapies prior to evaluation in this analysis. The most common IP antibiotic prescribed was vancomycin, as it was received by 17 (94%) patients. Other IP antimicrobials administered to 1 patient each included ceftazidime, meropenem, voriconazole, and metronidazole. Of the 18 patients, 13 (72%) received more than 1 dose of IP antibiotics. The median number of IP antimicrobial doses received per patient was 5.5 (IQR 1-9). Recurrence of a PPE within 6 months of initial PPE resolution occurred in 28% of patients. There were no reports of adverse events associated with IP antibiotic administration. All IP antimicrobials were prepared in the pharmacy sterile products room, and our standard dilutions for these agents are listed in Table 1. Nurses administered IP antibiotics via a chest tube (not placed to suction), an angiocath via an infusion pump running at 42 mL/h, or directly into the chest tube via a stopcock device. The IP antibiotic was able to dwell in the thoracic cavity for a specific amount of time as determined by the physician (median 6.3 hours [IQR 4-10]) and was then drained. If additional doses of IP antibiotics were indicated, they were ordered every 24 hours.
Discussion Results Our pharmacy database identified 51 patients who had been ordered for IP antibiotics. Of the 51 patients, only 18 were found to have received IP antibiotics during their hospital admission and were subsequently included in the analysis. The majority (83%) of patients were male with a median age of 68 years old (interquartile range [IQR] 56-78). The majority of patients had a diagnosis of mesothelioma (14 [78%] patients), 3 (17%) patients had nonsmall cell lung cancer (adenocarcinoma), and 1 (5%) patient had nonsmall cell lung cancer (squamous cell). Of the thoracic surgeries performed, 13 (72%) patients underwent an EPP, 3 (17%) patients underwent a pleurectomy, and 2 (11%) patients underwent a pneumonectomy.
Empyema still remains as a common complication following a pneumonectomy. Based on previous studies, first-line therapy still involves chest tube drainage, systemic antimicrobials, and possible surgical intervention.6,7 Surgical management, using the Clagett procedure,12 which involves an open-chest window, continues to be a first-line therapy option for management of PPE. Surgical management has limitations and not all patients are able to tolerate a surgical procedure. Additionally, the open-chest window procedure can affect a patient’s quality of life and often results in a longer recovery time.10 Most antibiotics have been shown to reach adequate levels in pleural fluid when administered systemically. In patients with PPE, however, the ability of systemic antibiotics to reliably reach therapeutic levels in infected pleural fluid may be decreased due to changes in microcirculation.11 Our analysis, as well as other
Downloaded from jpp.sagepub.com at SETON HALL UNIV on April 28, 2015
Torbic et al
3
small reports, suggests that IP antimicrobials may be a reasonable treatment option when first-line therapies have failed. Although data regarding IP antimicrobials are limited, Bagan et al13 conducted a descriptive analysis of thoracoscopic debridement preceded by antibiotic irrigation. The analysis evaluated 18 patients with PPE. In this study, all patients received IP antibiotic irrigation and systemic parenteral antibiotics for 10 days followed by videothoracoscopic debridement. The success rate of IP antibiotics was 88.8% with no recurrence after a mean follow-up of 44.4 months. From this small, single-center study, Bagan and colleagues concluded that IP antibiotics followed by thoracoscopic debridement were effective in the management of PPE. The authors did not comment on the safety and tolerability of this practice. Ng et al14 conducted an analysis of 8 patients to determine the efficacy of continuous antibiotic irrigation following debridement in PPE. Most (88%) patients received IP vancomycin, no adverse events were associated with this practice, and there was no recurrence of empyema noted in patient follow-up. Ng and colleagues concluded that surgical debridement in combination with continuous IP antibiotic irrigation is a safe and effective management strategy for PPE. The IP antibiotic irrigation practices described by Bagan et al and Ng et al differ significantly than practices observed during our retrospective observational analysis. We observed a single IP antimicrobial instillation that remained in the chest cavity for a range of 4 to 10 hours and was then drained. This instillation was repeated in some, but not all, patients in our study. We do not have a standardized procedure of administration of IP antibiotics. Therefore, the dwell times, frequency, and duration of IP antibiotics at our institution are determined by the attending surgeon and inconsistent among the surgeons. Ng et al utilized a continuous irrigation of IP antibiotics for a minimum of 2 weeks. Bagan et al did not comment on the IP antibiotics dwell times used in their study. One commonality between Ng et al and our study was the frequency with which vancomycin was utilized in patients as the selected IP irrigation antibiotic. More data are needed before a recommendation for IP antibiotic dosing, preparation, and dwell time can be made. Given our small sample size, our study was not powered to determine efficacy nor did it have the lengthy follow-up period that other small studies have had. Due to the retrospective nature of our study, many patients were lost to follow-up beyond 6 months; and therefore, it was only feasible to assess PPE recurrence for a 6-month time period, thus limiting our ability to truly comment on the efficacy of IP antibiotic administration. Bagan et al and Ng et al had mean follow-up periods of 44.4 months and 580 days, respectively, and found a low incidence of PPE recurrence after IP antibiotic administration, suggesting this is an effective practice. Larger studies are needed to confirm these findings. The available literature examining IP administration of antibiotics has not reported adverse effects and has demonstrated that IP antibiotics are well tolerated. In our small study, we did not find any reports of adverse events associated with IP antibiotics. Due to the retrospective nature of the study, we had to rely on documentation of adverse events related to IP antibiotic
administration in the patient chart, thus a limitation of our data. Neither Ng et al nor Bagan et al reported any adverse events with IP antibiotic administration further supporting that this is likely a well-tolerated procedure. Our analysis has many limitations. It is a small, single-center, retrospective analysis. Due to the retrospective design, we were unable to control for other variables affecting the management of the PPE. It is unknown whether any concomitant therapies or any nonpharmacologic strategies affected the results of the study. Additionally, our study did not have a control group and therefore, we cannot compare the addition of IP antibiotics to standard care. The small sample size and limited follow-up period limit our ability to comment on the optimal IP antibiotic regimen, but given the data, we do have available; it appears the practice at our institution is effective and well tolerated. At our institution, the first-line management of PPE continues to be drainage and systemic antibiotics based on the greater abundance of available literature regarding the efficacy and safety of these practices.6,7,12 Based on the limited data available and the inconsistency in antibiotic selection, dosing, and administration techniques among the published literature, it is difficult at this time to recommend IP antimicrobial therapy as a first-line option for management of PPE. Intrapleural fibrinolysis therapy with and without IP recombinant human DNase therapy has also been studied for management of PPE, particularly in patients who are not surgical candidates.10,15,16 These IP therapies have been shown to help dissolve infected loculated areas of the lung resulting in increased drainage of the empyema.10,15,16 Pleurodesis using sclerosing agents, such as talc, bleomycin, tetracyclines, or povidone iodine, has only been shown to be effective in the management of pleural effusion or pneumothorax.17-20 We have implemented a safe procedure for instilling IP antimicrobials should patients not adequately respond to first-line PPE management options and warrant IP antimicrobial administration. Through a multidisciplinary effort with physician, nursing, and pharmacy leadership and the data from this analysis, we are working to standardize a procedure for IP antibiotic administration at our institution. Our goal is to standardize IP antibiotic dosing, preparation, administration techniques, and dwell times. Further studies are needed to evaluate the efficacy and safety of this practice in a larger subset of patients.
Conclusion Our analysis demonstrates that administration of IP antimicrobials for the management of a PPE is feasible and safe. Larger studies evaluating efficacy of IP antimicrobials for the management of PPE are needed. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Downloaded from jpp.sagepub.com at SETON HALL UNIV on April 28, 2015
4
Journal of Pharmacy Practice
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
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