Clinical Significance of Surveillance Culture in Liver Transplant Recipients

Clinical Significance of Surveillance Culture in Liver Transplant Recipients

Clinical Significance of Surveillance Culture in Liver Transplant Recipients Y.J. Kim, S.I. Kim, Y.H. Jun, J.Y. Choi, S.K. Yoon, Y.-K. You, and D.-G. K...

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Clinical Significance of Surveillance Culture in Liver Transplant Recipients Y.J. Kim, S.I. Kim, Y.H. Jun, J.Y. Choi, S.K. Yoon, Y.-K. You, and D.-G. Kim ABSTRACT Background. Routine microbiologic surveillance is a method of infection control, but its clinical significance in transplant recipients is not known. We analyzed microbiologic data to evaluate the influence of cultured microorganisms between the point of surveillance and infectious episodes in liver transplant recipients. Methods. We performed surveillance culture for sputum and peritoneal fluid in liver transplant recipients from January 2009 to December 2011, at the time of transplantation (T1), 5 days (T2), and 10 days (T3) postoperatively. Results. Of the 179 recipients, 32.9% had a positive sputum culture result and 37.4% had a positive peritoneal culture result during surveillance. In the culture surveillance of sputum, 37 organisms were isolated from 35 recipients at T1, and the most common organism was Staphylococcus aureus (n ¼ 13). At T2, 45 organisms were isolated from 39 recipients, including Klebsiella pneumoniae (n ¼ 10), S aureus (n ¼ 8), and Acinetobacter baumannii (n ¼ 6). At T3, 18 organisms were isolated from 15 patients, including Stenotrophomonas maltophilia (n ¼ 5) and K pneumonia (n ¼ 4). In the peritoneal fluid, 11 organisms were isolated from 10 recipients at T1, including Pseudomonas aeruginosa (n ¼ 2) and Enterococcus species (n ¼ 2). At T2, 39 organisms were isolated from 36 recipients, including coagulase-negative Staphylococcus species (CNS; n ¼ 8) and Enterococcus species (n ¼ 7). At T3, 54 organisms were isolated from 51 recipients, including CNS (n ¼ 17) and Candida species (n ¼ 8). Among the 59 patients with positive culture results for sputum surveillance, 16.9% developed pneumonia caused by the same organisms. Among the 67 patients with positive peritoneal fluid culture, 16.4% developed an intra-abdominal infection caused by the same organisms cultured. The recipients with positive surveillance culture had a higher risk of pneumonia (20.3% [12/59] vs 1.6% [2/120]; P < .001) and intra-abdominal infection (31.3% [21/67] vs 18.7% [21/112]; P ¼ .05). Conclusions. Periodic microbiologic surveillance may be useful in the prediction of posttransplantation pneumonia and intra-abdominal infection and could offer a potential target for empirical antimicrobial therapy in cases of infection.

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ESPITE advances in surgical techniques and postoperative care, infectious complications after organ transplantation remain important risk factors for morbidity and mortality. Bacterial infection is most common among recipients of liver transplants, and is responsible for 33%e68% [1]. The most common types of infection are intra-abdominal infections, primary bacteremia, and pneumonia [2]. Studies have reported that pneumoniarelated mortality after liver transplantation may be as high as 36.6%e53% [3]. 0041-1345/14/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2013.11.030 828

From the Division of Infectious Disease, Department of Internal Medicine (Y.J.K., S.I.K., Y.H.J., J.Y.C., S.K.Y.), and Department of Surgery (Y.-K.Y., D.-G.K.), Catholic University of Korea, Seoul, Korea. Address reprint requests to Sang Il Kim, MD, Division of Infectious Disease, Department of Internal Medicine, Seoul St Mary’s Hospital, Catholic University of Korea, 505 Banpodong, Seochogu, 137-701, Republic of Korea. E-mail: drksi@catholic. ac.kr ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 46, 828e831 (2014)

SURVEILLANCE CULTURE IN LIVER TRANSPLANT

Routine microbiologic surveillance is an infection control measure. Liver transplant recipients are at increased risk of colonization with multidrug-resistant organisms because of multiple admissions, prolonged hospitalization, broadspectrum antimicrobial use, and invasive procedures [4,5]. Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) colonization through active surveillance culture are associated with risk of infection [4,6]. However, data on the clinical significance of surveillance culture from sites except nasal or rectal swab, and its usefulness in liver transplant recipients, are limited. This study aimed to analyze microbiologic data to evaluate the clinical utility of surveillance culture and the influence of cultured microorganisms between the point of surveillance and infectious episodes in liver transplant recipients. METHODS This prospective observational study was conducted on 184 liver transplant recipients from a 1,200-bed tertiary hospital. We performed surveillance culture on sputum and peritoneal fluid samples from all liver transplant recipients from January 2009 to December 2011. Samples were taken at the time of transplantation (T1), 5 days after surgery (T2), and 10 days after surgery (T3). Sputum samples were obtained with the use of tracheal aspirate at T1 and sputum at T2 and T3. Peritoneal fluid samples were obtained from intraabdominal fluid with the use of a drainage catheter. Infection was defined with the use of previously reported criteria [7]. Infectious complications within 3 months after transplantation were investigated as clinical outcomes. Pneumonia was defined if patients had clinical symptoms or signs of respiratory tract infection, as well as laboratory and radiologic evidence of pneumonia. Intraabdominal infection was defined if patients had clinical symptoms or signs of intra-abdominal infection, as well as radiologic evidence of infection that involved any organ within the abdomen or that extended beyond the viscus of origin into the peritoneal space and was associated with either abscess formation or peritonitis [8].

Statistical Analysis Student t test was used to analyze continuous variables, and the c2 test was used for categoric variables. Results are presented as mean  SD.

RESULTS

Five patients who had a preexisting infection were excluded, and 179 patients (126 male, 53 female) were included in the

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final analysis. The mean age of the patients was 50.1  11.4 years. As the underlying diseases, viral hepatitis B was most prevalent (n ¼ 101; 56.4%), followed by alcoholic liver disease (n ¼ 31; 17.3%) and acute hepatic failure (n ¼ 14; 7.8%). The percentage of Child C was 44.7%. Sputum Culture Results and Their Clinical Significance

A total of 59 patients (32.9%) had positive results for sputum culture. At T1, 37 organisms were isolated from sputum samples from a total of 35 transplant recipients, and the most common organism was S aureus (n ¼ 13), followed by Klebsiella pneumonia (n ¼ 5), Stenotrophomonas maltophilia (n ¼ 5), and Aspergillus species (n ¼ 4). At T2, 45 organisms were isolated from 39 recipients, including K pneumoniae (n ¼ 10), S aureus (n ¼ 8), Acinetobacter baumannii (n ¼ 6), and Enterobacter species (n ¼ 4). At T3, 18 organisms were isolated from 15 recipients, including S maltophilia (n ¼ 5), K pneumonia (n ¼ 4), and S aureus (n ¼ 3; Table 1). Among the 59 patients with positive results for sputum culture, 16.9% (n ¼ 10) developed pneumonia caused by the same organisms isolated, including MRSA (n ¼ 5), A baumannii (n ¼ 3), K pneumonia (n ¼ 1), and Aspergillus fumigates (n ¼ 1). Recipients with positive sputum surveillance culture results experienced a higher incidence of pneumonia compared with recipients with negative sputum surveillance culture results (20.3% [12/59] vs 1.6% [2/120]; P < .001; Table 2). Overall mortality rate did not differ significantly between patients with positive results for sputum culture and those with negative results (13.5% [8/59] vs 8.4% [10/120]; P ¼ .27). Moreover, the infection-related mortality rate did not differ significantly between the two groups (10.1% [6/59] vs 4.1% [14/112]; P ¼ .11). Peritoneal Fluid Culture Results and Their Clinical Significance

A total of 67 patients (37.4%) had positive results for peritoneal fluid culture. At T1, 11 organisms were isolated from samples from 10 patients, including Pseudomonas aeruginosa (n ¼ 2) and Enterococcus species (n ¼ 2). At T2, 39 organisms were isolated from 36 recipients, including coagulase-negative Staphylococcus (CNS; n ¼ 8), Enterococcus species (n ¼ 7), Candida species (n ¼ 7), and

Table 1. Isolated Organisms According to Surveillance Results Peritoneal fluid

Sputum No of patients

No of organisms

T1

35

37

T2

39

45

T3

15

18

Organisms

S aureus (n ¼ 13) K pneumoniae (n ¼ 5) S maltophilia (n ¼ 5) Aspergillus (n ¼ 4) K pneumoniae (n ¼ 10) S aureus (n ¼ 8) A baumannii (n ¼ 6) Enterobacter species (n ¼ 4) S maltophilia (n ¼ 5) K pneumonia (n ¼ 4) S aureus (n ¼ 3)

No of patients

No of organisms

Organisms

11

10

P aeruginosa (n ¼ 2) Enterococcus species (n ¼ 2)

36

39

51

54

CNS (n ¼ 8) Enterococus species (n ¼ 7) Candida species (n ¼ 7) P aeruginosa (n ¼ 3) S aureus (n ¼ 3) CNS (n ¼ 17) Candida species (n ¼ 8) A baumannii (n ¼ 7) Enterobacter species (n ¼ 5) S aureus (n ¼ 4) S maltophilia (n ¼ 4)

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KIM, KIM, JUN ET AL Table 2. Infectious Episodes and Clinical Outcomes According to Surveillance Results Peritoneal fluid

Sputum

Pneumonia Intra-abdominal infection Overall mortality Infection-related mortaltiy

Positive (n ¼ 59)

Negative (n ¼ 120)

P value

Positive (n ¼ 67)

Negative (n ¼ 112)

P value

12 (20.3%) d 8 (13.5%) 6 (10.1%)

2 (1.6%) d 10 (8.4%) 5 (4.1%)

<.001 d .27 .11

d 21 (31.3%) 4 (5.9%) 3 (4.4%)

d 21 (18.7%) 14 (12.5%) 8 (7.1%)

d .05 .16 .47

Pseudomonas species (n ¼ 3). At T3, 54 organisms were isolated from 51 recipients, including CNS (n ¼ 17), Candida species (n ¼ 8), A. baumannii (n ¼ 7), and Enterobacter species (n ¼ 5; Table 1). Of the 67 patients with positive peritoneal fluid culture results, 16.4% (n ¼ 11) developed an intra-abdominal infection caused by the same organisms isolated, including Enterococcus species (n ¼ 5), Candida glabrata (n ¼ 1), P aeruginosa (n ¼ 2), A baumannii (n ¼ 1), MRSA (n ¼ 1), and Enterobacter cloacae (n ¼ 1). Transplant recipients with positive surveillance cultures had a higher incidence of intra-abdominal infection compared with recipients with negative surveillance cultures (31.3% [21/67] vs 18.7% [21/112]; P ¼ .05; Table 2). Overall mortality did not differ significantly between patients with positive results for peritoneal fluid culture and those with negative results (5.9% [4/67] vs 12.5% [14/112]; P ¼ .16). Moreover, infection-related mortality did not differ significantly between the 2 groups (4.4% [3/67] vs 4.1% [8/112]; P ¼ .47). DISCUSSION

Active surveillance culture is one method of infection control. Active surveillance culture programs have traditionally focused on monitoring the presence of VRE by rectal swab or MRSA by nasal swab [9], because colonization with VRE or MRSA acts as a reservoir for transmission to other patients and has been shown to be associated with infection and mortality. However, there have been limited data about on the clinical efficacy of periodic surveillance culture for sputum or peritoneal fluid samples in liver transplant recipients. In our study, liver transplant recipients with positive surveillance culture for sputum or peritoneal fluid were at increased risk of pneumonia and intra-abdominal infection compared with recipients whose results were negative. Hospital-acquired pneumonia can develop because of aspiration of oropharyngeal secretions, inhalation of aerosols, seeding via the bloodstream, and reactivation of latent infection. Johanson et al reported that nosocomial respiratory infection developed in 23% of patients with upper respiratory colonization, but in only 3% of noncolonized patients [10]. Our study showed that 32.9% of liver transplant recipients were colonized with bacteria according to sputum surveillance culture, and 20.3% of these colonized patients developed pneumonia. Furthermore, 16.9% of colonized patients developed pneumonia caused by the same organisms isolated. The major pneumonia-causing

pathogen in our study was S aureus, and this finding is similar to that of an earlier report in which patients with health careeassociated pneumonia had a higher portion of S aureus than those with community-associated pneumonia [11]. In particular, liver transplant recipients showed high rates of nasal carriage of MRSA because of prolonged hospitalization, invasive procedures, and use of broadspectrum antimicrobial therapy [12]. Nasal colonization could be a factor that precedes respiratory tract infection by aspiration. Our study suggests that the surveillance culture of sputum in liver transplant recipients offers a potential target for empirical antimicrobial therapy. In our study, 16.4% of transplant recipients with positive surveillance culture for peritoneal fluid developed an intraabdominal infection caused by the same organisms isolated, mainly Enterococcus species. Liver transplant recipients were at an increased risk of developing intra-abdominal infections because of mechanical disruption of barrier. Periodic peritoneal fluid surveillance culture after transplantation could provide useful data for identifying infected patients and choosing the optimal empirical antibiotics for the infected patients. In general, enterococci are endogeneous microorganisms with minimal pathogenic potential in the normal host, however in the immunocompromised patients or patients with a history of procedures, enterococci are important pathogens [8]. One study showed that Enterococcus species are more common in health caree associated intra-abdominal infections than in communityacquired intra-abdominal infection [13]. Our results show that Enterococcus species were the main pathogen causing intra-abdominal infection in liver transplant recipients, as previously reported [2,14]. Our study has some limitations. First, we included only a small number of patients from a single center. Second, our data were analyzed only based on phenotyping pattern. Molecular analysis, such as pulsed-field gel electrophoresis, was not applied. In conclusion, periodic microbiologic surveillance is useful for predicting post-transplantation pneumonia and intraabdominal infection and could be helpful in choosing optimal empirical antimicrobial agents to combat posttransplantation infections.

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SURVEILLANCE CULTURE IN LIVER TRANSPLANT [2] Kim YJ, Kim SI, Wie SH, et al. Infectious complications in living-donor liver transplant recipients: a 9-year single-center experience. Transpl Infect Dis 2008;10:316e24. [3] Golfieri R, Giampalma E, Morselli Labate AM, et al. Pulmonary complications of liver transplantation: radiological appearance and statistical evaluation of risk factors in 300 cases. Eur Radiol 2000;10:1169e83. [4] McNeil SA, Malani PN, Chenoweth CE, et al. Vancomycinresistant enterococcal colonization and infection in liver transplant candidates and recipients: a prospective surveillance study. Clin Infect Dis 2006;42:195e203. [5] Hashimoto M, Sugawara Y, Tamura S, et al. Acquisition of methicillin-resistant Staphylococcus aureus after living donor liver transplantation: a retrospective cohort study. BMC Infect Dis 2008;8:155. [6] Russell DL, Flood A, Zaroda TE, et al. Outcomes of colonization with MRSA and VRE among liver transplant candidates and recipients. Am J Transplant 2008;8:1737e43. [7] Garner JS, Jarvis WR, Emori TG, et al. CDC definitions for nosocomial infections, 1988. Am J Infect Control 1988;16:128e40. [8] Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the

831 Infectious Diseases Society of America. Clin Infect Dis 2010;50: 133e64. [9] Santos RP, Mayo TW, Siegel JD. Healthcare epidemiology: active surveillance cultures and contact precautions for control of multidrug-resistant organisms: ethical considerations. Clin Infect Dis 2008;47:110e6. [10] Johanson WG Jr, Pierce AK, Sanford JP, et al. Nosocomial respiratory infections with gram-negative bacilli. The significance of colonization of the respiratory tract. Ann Intern Med 1972;77: 701e6. [11] Kollef MH, Shorr A, Tabak YP, et al. Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia. Chest 2005;128: 3854e62. [12] Bert F, Galdbart JO, Zarrouk V, et al. Association between nasal carriage of Staphylococcus aureus and infection in liver transplant recipients. Clin Infect Dis 2000;31:1295e9. [13] Swenson BR, Metzger R, Hedrick TL, et al. Choosing antibiotics for intra-abdominal infections: what do we mean by “high risk”? Surg Infect (Larchmt) 2009;10:29e39. [14] Kim SI, Kim YJ, Jun YH, et al. Epidemiology and risk factors for bacteremia in 144 consecutive living-donor liver transplant recipients. Yonsei Med J 2009;50:112e21.