Case Report
Candida Glabrata and Candida Tropicalis in an Immunocompetent Patient: A Case Report
Journal of Pharmacy Practice 1-4 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0897190014568387 jpp.sagepub.com
Leslie A. Hamilton, PharmD, BCPS1, Nicholas R. Lockhart, PharmD Candidate1, and Michael R. Crain, MD2
Abstract Objective: To report a case of Candida glabrata and tropicalis pneumonia in an immunocompetent patient. Case Summary: A 72-yearold male was transferred from an outside institution due to worsening respiratory status, acute kidney injury secondary to intravenous contrast media, sepsis, and pneumonia with fever and leukocytosis. Upon admission, he was initiated on treatment for hospital-acquired pneumonia, but was also concomitantly tested for many other opportunistic infections due to his recent month-long trip to Ecuador where he participated in a tribal treatment for neuropathy that involved direct exposure to dead guinea pigs. With completion of cultures and bronchoalveolar lavage, C. glabrata was identified in the blood culture and C. glabrata and C. tropicalis in the bronchoalveolar lavage specimen. One month later, he was admitted due to recurrent pneumonia. The patient unfortunately expired during the second admission, due to complications from chronic respiratory pulmonary disease and pneumonia. Discussion: Initially, this patient was treated for hospital-acquired pneumonia, but due to a recent trip to Ecuador, it was soon discovered that this patient had developed an invasive Candida pneumonia. His pulmonary biopsies showed growth of invasive C. glabrata and C. tropicalis, while his blood culture showed C. glabrata. Candida-related lower respiratory tract infections are exceptionally rare in immunocompetent patients and require histopathologic evidence to confirm the diagnosis. A second blood culture showed that the C. glabrata was still present and the patient had worsening leukocytosis, so micafungin was added to his antimicrobial therapy. Conclusion: It is understood that pneumonia is rarely caused by Candida species in patients who are admitted to the hospital. However, health care professionals should be aware that Candida pneumonia should be suspected as part of the differential diagnosis even in immunocompetent patients, particularly if they have recently traveled outside the United States. Keywords Candida, pneumonia, immunocompetent
Introduction/Objective/Literature Review A blood stream infection that is caused by a Candida species, candidemia, is the fourth most common bloodstream infection in the United States, and these fungi are responsible for approximately 9% of all health care-associated infections.1,2 The incidence of candidemia has been on the rise in the past few decades due to the increase in the number of patients in an immunocompromised state, such as patients undergoing treatment for human immunodeficiency virus (HIV) and transplantation, as well as the use of broad-spectrum antibiotics and chemotherapy.1 Candidemia also has the potential to invade other tissues and establish infection elsewhere in the body. In immunocompetent patients, isolation of Candida species is relatively frequent; however, this colonization is not considered an infectious process, regardless of the species, without biopsy showing true tissue invasion.3 Therefore, colonization of Candida species is not commonly treated in the clinical setting.
A true infection by Candida is a significant source of morbidity, mortality, and worsened clinical outcomes. The costs associated with a hospital visit with an episode of invasive fungal infection can be up to US$40 000, with mortality attributed to candidemia in the range of 15% to 47%.1,4 Clinical outcomes among patients who were colonized with Candida species in their respiratory tract secretions include longer
1 Department of Clinical Pharmacy, University of Tennessee Health Science Center College of Pharmacy, Knoxville, TN, USA 2 Department of Pulmonology, Princeton Baptist Medical Center, Birmingham, AL, USA
Corresponding Author: Leslie A. Hamilton, Department of Clinical Pharmacy, University of Tennessee Health Science Center College of Pharmacy, 1924 Alcoa Highway, Box 117, Knoxville, TN 37920, USA. Email: [email protected]
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intensive care unit (ICU) stays, longer hospital stays, and longer time on mechanical ventilation.5 According to the 2009 Infectious Disease Society of America Clinical Practice Guidelines for the Management of Candidiasis, for Candida glabrata fungemia, an echinocandin is the agent of choice for initial treatment in an immunocompetent patient and then changing therapy only based on sensitivities. There are presently 3 echinocandins on the market in the United States, which include micafungin, caspofungin, and anidulafungin, all of which have low minimum inhibitory concentrations for broadspectrum coverage for Candida species including C. glabrata. On the other hand, Candida tropicalis is generally considered to be sensitive to most antifungals, including azole antifungals, amphotericin B, and echinocandins.6 There are different patterns of opportunistic infections within different geographical areas of the world.7 Sometimes these patterns of epidemiology have to be taken into consideration for diagnostics and treatment strategies even for immunocompetent patients with infectious processes because of travel to an area outside of the United States. Within Latin America and across the globe, Candida is the most common cause of opportunistic infections; however, the incidence rates are significantly higher in the Southern Hemisphere. Candida albicans is by far the most common species followed by Candida parapsilosis and C. tropicalis in Latin America, which is in contrast to the United States where C. glabrata is second only to C albicans.7,8 The objective of this report is to explain an unusual case of an immunocompetent patient who developed an invasive fungal infection after participating in a tribal treatment with guinea pigs in Ecuador. A literature search was conducted in PubMed from 1950 to present with the following Medical Subject Headings terms in various combinations used, including Candida, C. tropicalis, C. glabrata, pneumonia, candidemia, Latin America, epidemiology, immunocompetent, nonneutropenic, and case report. Many of the results involved literature that either included or was exclusively focused on neutropenic patients with these types of infections. Multiple case reports were examined in an attempt to find more information about non-neutropenic patients with Candida infections. In the following case, an immunocompetent patient is treated for an invasive C. glabrata and C. tropicalis bloodstream infection and pneumonia.
Description of Case A 72-year-old white male initially presented to an outside hospital after a fall and was found to have a left hip fracture. While at this institution, he underwent an open reduction internal fixation (ORIF) procedure for the fracture. Approximately 2 days after the ORIF procedure, the patient was transferred to our facility due to worsening respiratory status, acute kidney injury (AKI), and pneumonia with low-grade fevers. The patient was retired after 26 years in the military and last worked as a recruiter. Significant past medical history includes chronic respiratory pulmonary disease (COPD), diet-controlled type II diabetes, Barrett’s esophagitis status postesophageal
resection and colonic transposition, peripheral artery disease, history of right renal injury secondary to motor vehicle accident, and right bundle branch block. The patient was not able to receive intravenous (IV) contrast media due to resulting AKI following administration. His family history is noncontributory and negative for known history of lung disease. This patient’s social history includes longstanding smoking and alcohol use, as well as a recent trip to Ecuador for approximately 1 month for alternative treatment for peripheral neuropathy. During this trip to Ecuador, the patient participated in a tribal treatment for peripheral neuropathy, which involved direct contact with dead guinea pigs that were rubbed on the patient’s legs and trunk. The patient received this treatment for 4 weeks, and he experienced a decline in pulmonary status, fatigue, and weakness upon his return to the United States, leading to his fall and left hip fracture. Upon admission, his height was 74 in and weight was 106 kg. His vital signs included the following: temperature 102.3 F, pulse 112 beats per minute, respirations 30 breaths per minute, and blood pressure 120/60. His initial laboratory data used at transfer was obtained from the initial institution. His blood counts showed significant leukocytosis with a white blood cell (WBC) count of 26.4 103 units/mm3 (4.5-10.5 103 units/mm3), hematocrit 29% (40%-51%), and platelets 193 103/mL (150-450 103/mL). Initial chemistry showed the following: sodium 135 mEq/L (136-144 mEq/L), potassium 6 mEq/L (3.7-5.2 mEq/L), chloride 109 mmol/L (96106 mmol/L), CO2 17 mmol/L (20-29 mmol/L), blood urea nitrogen (BUN) 51 mg/dL (7-20 mg/dL), serum creatinine 3.24 mg/dL (0.8-1.4 mg/dL), and glucose 79 mg/dL (70-100 mg/dL). Renal function had progressively worsened over the previous 4 days from a baseline of 0.99 mg/dL. Acute kidney injury and prerenal azotemia were likely secondary to IV contrast media administered prior to transfer, dehydration, and sepsis, and resolved during the patient’s hospital course. Home medications included albuterol 90 mcg inhaler q4h as needed, clopidogrel 75 mg daily, gabapentin 300 mg daily, and simvastatin 40 mg qHS. Upon admission to our institution, he was initiated on methylprednisolone 125 mg IV q6h, levofloxacin 750 mg IV q48h, piperacillin/tazobactam 3.375 g IV q8h, and vancomycin dosed intermittently based on levels. He was also initiated on heparin 5000 units SC q8h, levothyroxine 37.5 mcg IV daily, norepinephrine IV-titrated infusion, pantoprazole 40 mg IV daily, and sodium chloride 0.9% given via boluses and continuous infusion. He was emergently intubated and placed on mechanical ventilation. Arterial blood gases revealed severe respiratory acidosis. For complete list of antimicrobial medications and dosing that this patient received, refer to Table 1. Blood and urine cultures were also collected on day 1. Day 2 included a computed tomography (CT) scan of the chest revealed atypical pneumonia of probable fungal or viral origin with significant infiltrates in the right and left lobes. No pneumothorax was evident on chest CT. Possible tuberculosis (TB), histoplasmosis, and/or cryptococcus were the concerns because of recent trip to Ecuador. With the potential for these infections, liposomal amphotericin B and therapy for TB were initiated, including ethambutol, isoniazid,
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Table 1. Antimicrobial Medications and Laboratory Values during the Patient’s Hospital Stay.a Day
Medication
SCr
WBC
1
Levofloxacin 750 mg IV q48 hours, piperacillin/tazobactam (Zosyn) 3.375 g IV q8 hours, vancomycin 2000 mg IV 1 Isoniazid 300 mg PO daily, ethambutol 1600 mg q48 hours, rifampin 600 mg IV daily, pyrazinamide 2000 mg PO q48 hours, pyridoxine 100 mg IV daily, amphotericin B 500 mg IV daily, Zosyn 3.375 g IV q12 hours, vancomycin 2000 mg IV 1 Amphotericin B 500 mg IV daily, levofloxacin 500 mg IV q48 hours, Zosyn 3.375 g IV q12 hours Amphotericin B 500 mg IV daily, Zosyn 3.375 g IV q12 hours, vancomycin 2000 mg IV 1 Amphotericin B 500 mg IV daily, Zosyn 3.375 g IV q12 hours Amphotericin B 500 mg IV daily, Zosyn 3.375 g IV q8 hours, vancomycin 1750 mg IV 1 Amphotericin B 500 mg IV daily, meropenem 500 mg IV q6 hours, micafungin 100 mg daily, linezolid 600 mg IV q12 hours
3.24
26.4
2
3
4
5 6-7
Table 2. Cultures and Results Performed on This Patient During the Hospital Stay. Temp
102.3
Culture type
Growth
1
Blood Urine Bronchoalveolar lavage
Candida glabrata (2 of 4) No growth found C. glabrata, acid-fast bacilli (negative), Candida tropicalis Antigen not detected Antigen not detected Candida glabrata (2 of 4) No growth found No growth found Small amount yeast detected No growth found Negative No growth found
2 3.21
21.4
100.2 4 6 7 8
Histoplasmosis Cryptococcus Blood Urine Blood Sputum Blood, urine, sputum Clostridium difficile Hip fluid
2.72
24.7
Afebrile
12
2.33
36.6
Afebrile
2.07
33
Afebrile
1.62 1.32
27.9 32
Afebrile 100.9
ventricular response, and responded to therapy with diltiazem. He was initially managed under ICU care because of sepsis with significant hypotension, but later weaned off of the ventilator and was transferred to the floor. His renal function recovered by day 14 of the patient’s hospital stay and he was extubated on day 18. After he was transferred from the ICU, the patient experienced another episode of leukocytosis with increased infiltrates on chest radiography and was subsequently found to have worsening lymph nodes and organizing pneumonia upon chest CT. His antimicrobial therapy was adjusted at that time, with the discontinuation of levofloxacin, piperacillin/tazobactam, and vancomycin and the addition of linezolid and meropenem. Also, results from a second blood culture on day 4 showed the continued presence of C. glabrata, which constituted the addition of the micafungin to his antifungal therapy when it resulted on hospital day 8. The patient was then discharged from the hospital at day 33 after the course of antifungals was completed and he could be transferred to a rehabilitation facility. He was discharged on a prednisone taper. Within about a month of discharge, the patient was readmitted to the hospital because of fever (Tmax 101.1 F), hypotension (blood pressure 97/63), leukocytosis (WBC 22 103 units/mm3), and recurrent respiratory failure. Multiple bilateral pulmonary nodules were seen on CT scan. He was reinitiated on levofloxacin, micafungin, piperacillin/tazobactam, and vancomycin. Blood and urine cultures on this admission were sterile. This patient had a worsening respiratory status and ultimately died from COPD and pneumonia.
1.26 53 Afebrile 1.31 40.6 Afebrile 1.21 39.4 Afebrile 1.13 39.3 Afebrile 1.12 36.3 Afebrile 1.13 56 Afebrile 0.99 32.8 Afebrile 17-21 Meropenem 500 mg IV q6 hours, micafungin 100 mg daily, linezolid 600 mg IV q12 hours, amphotericin B 500 mg IV daily 8-16
Day
Abbreviations: SCr, serum creatinine; WBC, white blood cells; Temp, temperature; IV, intravenous. a Additional doses of meropenem 500 mg IV q6h, micafungin 100 mg daily, and linezolid 600 mg IV q12h were given for days 26 to 33; Amphotericin B 500 mg IV daily was given for days 30 to 33 of hospitalization before patient discharged on day 33.
pyrazinamide, pyridoxine, and rifampin. A right upper lung biopsy procedure showed benign lung tissue with histiocytic infiltrate and type II pneumocyte hyperplasia with probable yeast forms present.9 A bronchoalveolar lavage (BAL) performed showed evidence of heavy inflammation with fungal organisms suggestive of Candida. This BAL eventually grew out C. glabrata and C. tropicalis; however, there were no sensitivities performed on these organisms. Polymerase chain reaction tests were done to rule out Mycobacterium tuberculosis and Histoplasma/Blastomyces and a Mucicarmine stain to test for cryptococcus, all of which resulted negative, in addition to HIV. A summary of all cultures and results are shown in Table 2. Because of his chronic debility and esophageal resection with colonic transposition and difficulty placing an enteral feeding tube, he required a 21-day course of total parenteral nutrition, which was initiated on day 4 of hospitalization. During the hospital course, he had episodes of tachyarrhythmias, which was found to be paroxysmal atrial fibrillation with rapid
Discussion of Case/Literature Review Upon admission, this patient was treated for hospital-acquired pneumonia due to the recent hospitalization with broadspectrum antibiotics, but there was suspicion of other potential infectious processes because of a recent trip to Ecuador and participation in tribal treatment. He was subsequently tested for TB, histoplasmosis, blastomycosis, and cryptococcus but all were negative. He was found to have an invasive candidemia cultured from blood and respiratory specimens.
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The purpose of this case report is to describe a previously immunocompetent patient who developed an invasive fungal pneumonia with C. glabrata and C. tropicalis. It is widely seen in practice that respiratory cultures of critically ill patients will grow Candida species; however, this is almost always considered colonization and is not treated.3 Candida lower respiratory tract infections are rare; therefore, pathology studies are required to confirm the diagnosis of Candida pneumonia.6 This patient did have a lung biopsy that confirmed the invasive Candida species. On day 8 of the patient’s hospital course, micafungin was added to his antimicrobial therapy because of worsening leukocytosis and continued presence of C. glabrata in blood cultures. There is little available information concerning this type of Candida pneumonia in a nonimmunosuppressed patient. Most literature that has been published on this topic is in immunosuppressed patients, such as oncologic, transplant, or patients with acquired immunodeficiency syndrome. Other reports have focused on cutaneous, oropharyngeal, and skeletal manifestations of Candida infection. For patients with Candida pneumonia, there are limited case reports, one of an alcoholic patient who died from primary C albicans pneumonia and 5 cases of respiratory infections involving Candida krusei in 1 literature review.10,11 Another report describes a case of invasive C albicans pneumonia in an 83-year-old female who was not immunosuppressed.12 Another article reported probable C. glabrata pneumonia, but there was no histopathology performed.13 This case is unique in comparison to the others already published because this patient had spent an extended period of time outside the United States, which was most likely involved in the development of this unusual infection. There are no published reports of guinea pigs transmitting Candida infections to an immunocompetent human host.
Summary of Case/Conclusion This case depicts a patient who participated in an unusual tribal treatment for neuropathy in Ecuador that likely resulted in an invasive bloodstream C. glabrata infection and pneumonia. His BAL cultures showed histological evidence of C. glabrata and C. tropicalis. This is a rare case because these types of opportunistic organisms generally present themselves in immunocompromised patients; however, this patient was not considered immunosuppressed. Because of this and other case reports of these types of infections, health care providers should be made aware that there is a potential for Candida species to be the cause of sepsis and pneumonia, even in nonneutropenic patients, and should be considered as part of the differential diagnosis, particularly in patients with recent travel outside the United States. 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.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Giri S, Kindo AJ. A review of Candida species causing blood stream infection. Indian J Med Microbiol. 2012;30(3): 270-278. 2. Sievert DM, Ricks P, Edwards JR, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: Summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009-2010. Infect Control Hosp Epidemiol. 2013;34(1):1-14. 3. Garnacho-Montero J, Olaechea P, Alvarez-Lerma F, et al. Epidemiology, diagnosis, and treatment of fungal respiratory infections in the critically ill patient. Rev Esp Quimioter. 2013;26(2): 173-188. 4. Wisplinghoff H, Bischoff T, Tallent SM, et al. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004; 39(3):309-317. 5. Delisle MS, Williamson DR, Perreault MM, et al. The clinical significance of Candida colonization of respiratory tract secretions of critically ill patients. J Crit Care. 2008;23(1):11-17. 6. Pappas PG, Kauffman CA, Andes D, et al. Clinical guidelines for the management of candidiasis: 2009 update by the infectious disease society of America. Clin Infect Dis. 2009;48(5): 503-535. 7. Nucci M, Queiroz-Telles F, Tobon AM, et al. Epidemiology of opportunistic fungal infections in Latin America. Clin Infect Dis. 2010;51(5):561-570. 8. Falagas ME, Roussos N, Vardakas KZ. Relative frequency of albicans and various non-albicans Candida spp among candidemia isolates from inpatients in various parts of the world: a systematic review. Int J Infect Dis. 2010;14(11): e954-e966. 9. Stanley MW, MJ Henry-Stanley KJ, Gajl-Peczalska, et al. Hyperplasia of type II pneumocytes in acute lung injury. Cytologic findings of sequential bronchoalveolar lavage. Am J Clin Pathol. 1992:97(5):669-677. 10. Tamai K, Tachikawa R, Tomii K, et al. Fatal community acquired primary Candida pneumonia in an alcoholic patient. Intern Med. 2012;51(22):3159-3161. 11. Imtiaz T, Thomson F, Innes A, et al. Candida krusei bronchopneumonia with nodular infiltrates in a patient with chronic renal failure on haemodialysis—case report and review of literature. Mycoses. 2010;54(5):e611-e614. 12. Worthington M. Fatal candidemia pneumonia in a nonimmunosuppressed host. J Infect. 1983;7(2):159-161. 13. Kobayashi T, Miyazaki Y, Yanagihara K, et al. A probable case of aspiration pneumonia caused by Candida glabrata in a nonneutropenic patient with candidemia. Intern Med. 2005;44(11): 1191-1194.
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Candida Glabrata and Candida Tropicalis in an Immunocompetent Patient: A Case Report
Journal of Pharmacy Practice 1-4 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0897190014568387 jpp.sagepub.com
Leslie A. Hamilton, PharmD, BCPS1, Nicholas R. Lockhart, PharmD Candidate1, and Michael R. Crain, MD2
Abstract Objective: To report a case of Candida glabrata and tropicalis pneumonia in an immunocompetent patient. Case Summary: A 72-yearold male was transferred from an outside institution due to worsening respiratory status, acute kidney injury secondary to intravenous contrast media, sepsis, and pneumonia with fever and leukocytosis. Upon admission, he was initiated on treatment for hospital-acquired pneumonia, but was also concomitantly tested for many other opportunistic infections due to his recent month-long trip to Ecuador where he participated in a tribal treatment for neuropathy that involved direct exposure to dead guinea pigs. With completion of cultures and bronchoalveolar lavage, C. glabrata was identified in the blood culture and C. glabrata and C. tropicalis in the bronchoalveolar lavage specimen. One month later, he was admitted due to recurrent pneumonia. The patient unfortunately expired during the second admission, due to complications from chronic respiratory pulmonary disease and pneumonia. Discussion: Initially, this patient was treated for hospital-acquired pneumonia, but due to a recent trip to Ecuador, it was soon discovered that this patient had developed an invasive Candida pneumonia. His pulmonary biopsies showed growth of invasive C. glabrata and C. tropicalis, while his blood culture showed C. glabrata. Candida-related lower respiratory tract infections are exceptionally rare in immunocompetent patients and require histopathologic evidence to confirm the diagnosis. A second blood culture showed that the C. glabrata was still present and the patient had worsening leukocytosis, so micafungin was added to his antimicrobial therapy. Conclusion: It is understood that pneumonia is rarely caused by Candida species in patients who are admitted to the hospital. However, health care professionals should be aware that Candida pneumonia should be suspected as part of the differential diagnosis even in immunocompetent patients, particularly if they have recently traveled outside the United States. Keywords Candida, pneumonia, immunocompetent
Introduction/Objective/Literature Review A blood stream infection that is caused by a Candida species, candidemia, is the fourth most common bloodstream infection in the United States, and these fungi are responsible for approximately 9% of all health care-associated infections.1,2 The incidence of candidemia has been on the rise in the past few decades due to the increase in the number of patients in an immunocompromised state, such as patients undergoing treatment for human immunodeficiency virus (HIV) and transplantation, as well as the use of broad-spectrum antibiotics and chemotherapy.1 Candidemia also has the potential to invade other tissues and establish infection elsewhere in the body. In immunocompetent patients, isolation of Candida species is relatively frequent; however, this colonization is not considered an infectious process, regardless of the species, without biopsy showing true tissue invasion.3 Therefore, colonization of Candida species is not commonly treated in the clinical setting.
A true infection by Candida is a significant source of morbidity, mortality, and worsened clinical outcomes. The costs associated with a hospital visit with an episode of invasive fungal infection can be up to US$40 000, with mortality attributed to candidemia in the range of 15% to 47%.1,4 Clinical outcomes among patients who were colonized with Candida species in their respiratory tract secretions include longer
1 Department of Clinical Pharmacy, University of Tennessee Health Science Center College of Pharmacy, Knoxville, TN, USA 2 Department of Pulmonology, Princeton Baptist Medical Center, Birmingham, AL, USA
Corresponding Author: Leslie A. Hamilton, Department of Clinical Pharmacy, University of Tennessee Health Science Center College of Pharmacy, 1924 Alcoa Highway, Box 117, Knoxville, TN 37920, USA. Email: [email protected]
Downloaded from jpp.sagepub.com at FUDAN UNIV LIB on May 5, 2015
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intensive care unit (ICU) stays, longer hospital stays, and longer time on mechanical ventilation.5 According to the 2009 Infectious Disease Society of America Clinical Practice Guidelines for the Management of Candidiasis, for Candida glabrata fungemia, an echinocandin is the agent of choice for initial treatment in an immunocompetent patient and then changing therapy only based on sensitivities. There are presently 3 echinocandins on the market in the United States, which include micafungin, caspofungin, and anidulafungin, all of which have low minimum inhibitory concentrations for broadspectrum coverage for Candida species including C. glabrata. On the other hand, Candida tropicalis is generally considered to be sensitive to most antifungals, including azole antifungals, amphotericin B, and echinocandins.6 There are different patterns of opportunistic infections within different geographical areas of the world.7 Sometimes these patterns of epidemiology have to be taken into consideration for diagnostics and treatment strategies even for immunocompetent patients with infectious processes because of travel to an area outside of the United States. Within Latin America and across the globe, Candida is the most common cause of opportunistic infections; however, the incidence rates are significantly higher in the Southern Hemisphere. Candida albicans is by far the most common species followed by Candida parapsilosis and C. tropicalis in Latin America, which is in contrast to the United States where C. glabrata is second only to C albicans.7,8 The objective of this report is to explain an unusual case of an immunocompetent patient who developed an invasive fungal infection after participating in a tribal treatment with guinea pigs in Ecuador. A literature search was conducted in PubMed from 1950 to present with the following Medical Subject Headings terms in various combinations used, including Candida, C. tropicalis, C. glabrata, pneumonia, candidemia, Latin America, epidemiology, immunocompetent, nonneutropenic, and case report. Many of the results involved literature that either included or was exclusively focused on neutropenic patients with these types of infections. Multiple case reports were examined in an attempt to find more information about non-neutropenic patients with Candida infections. In the following case, an immunocompetent patient is treated for an invasive C. glabrata and C. tropicalis bloodstream infection and pneumonia.
Description of Case A 72-year-old white male initially presented to an outside hospital after a fall and was found to have a left hip fracture. While at this institution, he underwent an open reduction internal fixation (ORIF) procedure for the fracture. Approximately 2 days after the ORIF procedure, the patient was transferred to our facility due to worsening respiratory status, acute kidney injury (AKI), and pneumonia with low-grade fevers. The patient was retired after 26 years in the military and last worked as a recruiter. Significant past medical history includes chronic respiratory pulmonary disease (COPD), diet-controlled type II diabetes, Barrett’s esophagitis status postesophageal
resection and colonic transposition, peripheral artery disease, history of right renal injury secondary to motor vehicle accident, and right bundle branch block. The patient was not able to receive intravenous (IV) contrast media due to resulting AKI following administration. His family history is noncontributory and negative for known history of lung disease. This patient’s social history includes longstanding smoking and alcohol use, as well as a recent trip to Ecuador for approximately 1 month for alternative treatment for peripheral neuropathy. During this trip to Ecuador, the patient participated in a tribal treatment for peripheral neuropathy, which involved direct contact with dead guinea pigs that were rubbed on the patient’s legs and trunk. The patient received this treatment for 4 weeks, and he experienced a decline in pulmonary status, fatigue, and weakness upon his return to the United States, leading to his fall and left hip fracture. Upon admission, his height was 74 in and weight was 106 kg. His vital signs included the following: temperature 102.3 F, pulse 112 beats per minute, respirations 30 breaths per minute, and blood pressure 120/60. His initial laboratory data used at transfer was obtained from the initial institution. His blood counts showed significant leukocytosis with a white blood cell (WBC) count of 26.4 103 units/mm3 (4.5-10.5 103 units/mm3), hematocrit 29% (40%-51%), and platelets 193 103/mL (150-450 103/mL). Initial chemistry showed the following: sodium 135 mEq/L (136-144 mEq/L), potassium 6 mEq/L (3.7-5.2 mEq/L), chloride 109 mmol/L (96106 mmol/L), CO2 17 mmol/L (20-29 mmol/L), blood urea nitrogen (BUN) 51 mg/dL (7-20 mg/dL), serum creatinine 3.24 mg/dL (0.8-1.4 mg/dL), and glucose 79 mg/dL (70-100 mg/dL). Renal function had progressively worsened over the previous 4 days from a baseline of 0.99 mg/dL. Acute kidney injury and prerenal azotemia were likely secondary to IV contrast media administered prior to transfer, dehydration, and sepsis, and resolved during the patient’s hospital course. Home medications included albuterol 90 mcg inhaler q4h as needed, clopidogrel 75 mg daily, gabapentin 300 mg daily, and simvastatin 40 mg qHS. Upon admission to our institution, he was initiated on methylprednisolone 125 mg IV q6h, levofloxacin 750 mg IV q48h, piperacillin/tazobactam 3.375 g IV q8h, and vancomycin dosed intermittently based on levels. He was also initiated on heparin 5000 units SC q8h, levothyroxine 37.5 mcg IV daily, norepinephrine IV-titrated infusion, pantoprazole 40 mg IV daily, and sodium chloride 0.9% given via boluses and continuous infusion. He was emergently intubated and placed on mechanical ventilation. Arterial blood gases revealed severe respiratory acidosis. For complete list of antimicrobial medications and dosing that this patient received, refer to Table 1. Blood and urine cultures were also collected on day 1. Day 2 included a computed tomography (CT) scan of the chest revealed atypical pneumonia of probable fungal or viral origin with significant infiltrates in the right and left lobes. No pneumothorax was evident on chest CT. Possible tuberculosis (TB), histoplasmosis, and/or cryptococcus were the concerns because of recent trip to Ecuador. With the potential for these infections, liposomal amphotericin B and therapy for TB were initiated, including ethambutol, isoniazid,
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Hamilton et al
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Table 1. Antimicrobial Medications and Laboratory Values during the Patient’s Hospital Stay.a Day
Medication
SCr
WBC
1
Levofloxacin 750 mg IV q48 hours, piperacillin/tazobactam (Zosyn) 3.375 g IV q8 hours, vancomycin 2000 mg IV 1 Isoniazid 300 mg PO daily, ethambutol 1600 mg q48 hours, rifampin 600 mg IV daily, pyrazinamide 2000 mg PO q48 hours, pyridoxine 100 mg IV daily, amphotericin B 500 mg IV daily, Zosyn 3.375 g IV q12 hours, vancomycin 2000 mg IV 1 Amphotericin B 500 mg IV daily, levofloxacin 500 mg IV q48 hours, Zosyn 3.375 g IV q12 hours Amphotericin B 500 mg IV daily, Zosyn 3.375 g IV q12 hours, vancomycin 2000 mg IV 1 Amphotericin B 500 mg IV daily, Zosyn 3.375 g IV q12 hours Amphotericin B 500 mg IV daily, Zosyn 3.375 g IV q8 hours, vancomycin 1750 mg IV 1 Amphotericin B 500 mg IV daily, meropenem 500 mg IV q6 hours, micafungin 100 mg daily, linezolid 600 mg IV q12 hours
3.24
26.4
2
3
4
5 6-7
Table 2. Cultures and Results Performed on This Patient During the Hospital Stay. Temp
102.3
Culture type
Growth
1
Blood Urine Bronchoalveolar lavage
Candida glabrata (2 of 4) No growth found C. glabrata, acid-fast bacilli (negative), Candida tropicalis Antigen not detected Antigen not detected Candida glabrata (2 of 4) No growth found No growth found Small amount yeast detected No growth found Negative No growth found
2 3.21
21.4
100.2 4 6 7 8
Histoplasmosis Cryptococcus Blood Urine Blood Sputum Blood, urine, sputum Clostridium difficile Hip fluid
2.72
24.7
Afebrile
12
2.33
36.6
Afebrile
2.07
33
Afebrile
1.62 1.32
27.9 32
Afebrile 100.9
ventricular response, and responded to therapy with diltiazem. He was initially managed under ICU care because of sepsis with significant hypotension, but later weaned off of the ventilator and was transferred to the floor. His renal function recovered by day 14 of the patient’s hospital stay and he was extubated on day 18. After he was transferred from the ICU, the patient experienced another episode of leukocytosis with increased infiltrates on chest radiography and was subsequently found to have worsening lymph nodes and organizing pneumonia upon chest CT. His antimicrobial therapy was adjusted at that time, with the discontinuation of levofloxacin, piperacillin/tazobactam, and vancomycin and the addition of linezolid and meropenem. Also, results from a second blood culture on day 4 showed the continued presence of C. glabrata, which constituted the addition of the micafungin to his antifungal therapy when it resulted on hospital day 8. The patient was then discharged from the hospital at day 33 after the course of antifungals was completed and he could be transferred to a rehabilitation facility. He was discharged on a prednisone taper. Within about a month of discharge, the patient was readmitted to the hospital because of fever (Tmax 101.1 F), hypotension (blood pressure 97/63), leukocytosis (WBC 22 103 units/mm3), and recurrent respiratory failure. Multiple bilateral pulmonary nodules were seen on CT scan. He was reinitiated on levofloxacin, micafungin, piperacillin/tazobactam, and vancomycin. Blood and urine cultures on this admission were sterile. This patient had a worsening respiratory status and ultimately died from COPD and pneumonia.
1.26 53 Afebrile 1.31 40.6 Afebrile 1.21 39.4 Afebrile 1.13 39.3 Afebrile 1.12 36.3 Afebrile 1.13 56 Afebrile 0.99 32.8 Afebrile 17-21 Meropenem 500 mg IV q6 hours, micafungin 100 mg daily, linezolid 600 mg IV q12 hours, amphotericin B 500 mg IV daily 8-16
Day
Abbreviations: SCr, serum creatinine; WBC, white blood cells; Temp, temperature; IV, intravenous. a Additional doses of meropenem 500 mg IV q6h, micafungin 100 mg daily, and linezolid 600 mg IV q12h were given for days 26 to 33; Amphotericin B 500 mg IV daily was given for days 30 to 33 of hospitalization before patient discharged on day 33.
pyrazinamide, pyridoxine, and rifampin. A right upper lung biopsy procedure showed benign lung tissue with histiocytic infiltrate and type II pneumocyte hyperplasia with probable yeast forms present.9 A bronchoalveolar lavage (BAL) performed showed evidence of heavy inflammation with fungal organisms suggestive of Candida. This BAL eventually grew out C. glabrata and C. tropicalis; however, there were no sensitivities performed on these organisms. Polymerase chain reaction tests were done to rule out Mycobacterium tuberculosis and Histoplasma/Blastomyces and a Mucicarmine stain to test for cryptococcus, all of which resulted negative, in addition to HIV. A summary of all cultures and results are shown in Table 2. Because of his chronic debility and esophageal resection with colonic transposition and difficulty placing an enteral feeding tube, he required a 21-day course of total parenteral nutrition, which was initiated on day 4 of hospitalization. During the hospital course, he had episodes of tachyarrhythmias, which was found to be paroxysmal atrial fibrillation with rapid
Discussion of Case/Literature Review Upon admission, this patient was treated for hospital-acquired pneumonia due to the recent hospitalization with broadspectrum antibiotics, but there was suspicion of other potential infectious processes because of a recent trip to Ecuador and participation in tribal treatment. He was subsequently tested for TB, histoplasmosis, blastomycosis, and cryptococcus but all were negative. He was found to have an invasive candidemia cultured from blood and respiratory specimens.
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Journal of Pharmacy Practice
The purpose of this case report is to describe a previously immunocompetent patient who developed an invasive fungal pneumonia with C. glabrata and C. tropicalis. It is widely seen in practice that respiratory cultures of critically ill patients will grow Candida species; however, this is almost always considered colonization and is not treated.3 Candida lower respiratory tract infections are rare; therefore, pathology studies are required to confirm the diagnosis of Candida pneumonia.6 This patient did have a lung biopsy that confirmed the invasive Candida species. On day 8 of the patient’s hospital course, micafungin was added to his antimicrobial therapy because of worsening leukocytosis and continued presence of C. glabrata in blood cultures. There is little available information concerning this type of Candida pneumonia in a nonimmunosuppressed patient. Most literature that has been published on this topic is in immunosuppressed patients, such as oncologic, transplant, or patients with acquired immunodeficiency syndrome. Other reports have focused on cutaneous, oropharyngeal, and skeletal manifestations of Candida infection. For patients with Candida pneumonia, there are limited case reports, one of an alcoholic patient who died from primary C albicans pneumonia and 5 cases of respiratory infections involving Candida krusei in 1 literature review.10,11 Another report describes a case of invasive C albicans pneumonia in an 83-year-old female who was not immunosuppressed.12 Another article reported probable C. glabrata pneumonia, but there was no histopathology performed.13 This case is unique in comparison to the others already published because this patient had spent an extended period of time outside the United States, which was most likely involved in the development of this unusual infection. There are no published reports of guinea pigs transmitting Candida infections to an immunocompetent human host.
Summary of Case/Conclusion This case depicts a patient who participated in an unusual tribal treatment for neuropathy in Ecuador that likely resulted in an invasive bloodstream C. glabrata infection and pneumonia. His BAL cultures showed histological evidence of C. glabrata and C. tropicalis. This is a rare case because these types of opportunistic organisms generally present themselves in immunocompromised patients; however, this patient was not considered immunosuppressed. Because of this and other case reports of these types of infections, health care providers should be made aware that there is a potential for Candida species to be the cause of sepsis and pneumonia, even in nonneutropenic patients, and should be considered as part of the differential diagnosis, particularly in patients with recent travel outside the United States. 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.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Giri S, Kindo AJ. A review of Candida species causing blood stream infection. Indian J Med Microbiol. 2012;30(3): 270-278. 2. Sievert DM, Ricks P, Edwards JR, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: Summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009-2010. Infect Control Hosp Epidemiol. 2013;34(1):1-14. 3. Garnacho-Montero J, Olaechea P, Alvarez-Lerma F, et al. Epidemiology, diagnosis, and treatment of fungal respiratory infections in the critically ill patient. Rev Esp Quimioter. 2013;26(2): 173-188. 4. Wisplinghoff H, Bischoff T, Tallent SM, et al. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004; 39(3):309-317. 5. Delisle MS, Williamson DR, Perreault MM, et al. The clinical significance of Candida colonization of respiratory tract secretions of critically ill patients. J Crit Care. 2008;23(1):11-17. 6. Pappas PG, Kauffman CA, Andes D, et al. Clinical guidelines for the management of candidiasis: 2009 update by the infectious disease society of America. Clin Infect Dis. 2009;48(5): 503-535. 7. Nucci M, Queiroz-Telles F, Tobon AM, et al. Epidemiology of opportunistic fungal infections in Latin America. Clin Infect Dis. 2010;51(5):561-570. 8. Falagas ME, Roussos N, Vardakas KZ. Relative frequency of albicans and various non-albicans Candida spp among candidemia isolates from inpatients in various parts of the world: a systematic review. Int J Infect Dis. 2010;14(11): e954-e966. 9. Stanley MW, MJ Henry-Stanley KJ, Gajl-Peczalska, et al. Hyperplasia of type II pneumocytes in acute lung injury. Cytologic findings of sequential bronchoalveolar lavage. Am J Clin Pathol. 1992:97(5):669-677. 10. Tamai K, Tachikawa R, Tomii K, et al. Fatal community acquired primary Candida pneumonia in an alcoholic patient. Intern Med. 2012;51(22):3159-3161. 11. Imtiaz T, Thomson F, Innes A, et al. Candida krusei bronchopneumonia with nodular infiltrates in a patient with chronic renal failure on haemodialysis—case report and review of literature. Mycoses. 2010;54(5):e611-e614. 12. Worthington M. Fatal candidemia pneumonia in a nonimmunosuppressed host. J Infect. 1983;7(2):159-161. 13. Kobayashi T, Miyazaki Y, Yanagihara K, et al. A probable case of aspiration pneumonia caused by Candida glabrata in a nonneutropenic patient with candidemia. Intern Med. 2005;44(11): 1191-1194.
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