Liver International ISSN 1478-3223
CIRRHOSIS AND LIVER FAILURE
Risk factor of community-onset spontaneous bacterial peritonitis caused by fluoroquinolone-resistant Escherichia coli in patients with cirrhosis Jungok Kim1, Cheol-In Kang1, Eun-Jeong Joo1, Young Eun Ha1, Sun Young Cho1, Geum-Youn Gwak2, Doo Ryeon Chung1, Kyong Ran Peck1 and Jae-Hoon Song1 1 Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Keywords fluoroquinolone-resistant E. coli – spontaneous bacterial peritonitis – cirrhosis
Correspondence Cheol-In Kang, MD, Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-ro 81, Gangnam-gu, Seoul 135-710, Korea Tel: + 82 2 3410 0324 Fax: + 82 2 3410 0064 e-mail: [email protected] Received 25 April 2013 Accepted 31 October 2013 DOI:10.1111/liv.12374 Liver Int. 2014: 34: 695–699
Abstract Background & Aims: Despite the high prevalence of antimicrobial-resistant Escherichia coli in hospital-acquired infections, the clinical epidemiology of fluoroquinolone (FQ) resistance in community-onset spontaneous bacterial peritonitis (SBP) in patients with cirrhosis is not well understood. This study was performed to evaluate clinical features and risk factors for communityonset SBP caused by FQ-resistant E. coli. Methods: A case-control control study was performed using cases of community-onset SBP from June 2000 to August 2011 at Samsung Medical Center (Seoul, Korea). Patients with FQresistant E. coli were designated as case patients. A control group I (CG I) patient was defined as a person whose clinical sample yielded FQ-susceptible E. coli, and a control group II (CG II) patient was defined as a person with a negative culture result. Results: A total of 82 subjects with community-onset SBP caused by E. coli were identified, of which 26 (31.7%) were FQ-resistant E. coli infection. Fifty-seven matched subjects were randomly selected for CG II. Compared with CG I, previous SBP episodes (OR, 4.91; 95% CI, 1.50– 16.53; P = 0.010), prior use of FQ within 30 days (OR, 7.05; 95% CI, 1.17– 42.38; P = 0.033), and third-generation cephalosporin resistance (OR, 17.68; 95% CI, 1.67–187.26; P = 0.017) were significantly associated with FQ-resistant E. coli. Compared with CG II, a previous SBP episode was significantly associated with FQ-resistant E. coli (OR, 4.20; 95% CI, 1.50–11.80; P = 0.006). Conclusion: FQ-resistant E. coli is a significant cause of community-onset SBP, with relation to previous SBP episodes, recent FQ use and third-generation cephalosporin resistance.
Spontaneous bacterial peritonitis (SBP) is one of the serious complications that occurs in advanced cirrhosis and has a high mortality. Primary and secondary prophylaxis with flouroquinolones (FQ) has reduced the incidence of bacterial infections and improved survival in cirrhotic patients. However, the widespread use of FQ has resulted in changes in intestinal flora and has influenced antibiotic susceptibility patterns. Consequently, FQ-resistant Escherichia coli has been emerged in cirrhotic patients undergoing prophylaxis with Norfloxacin (1, 2). Although the prevalence of FQ-resistant E. coli is increasing, risk factors and clinical implications are still not well understood in community-onset SBP in patients with cirrhosis. Therefore, we conducted a casecontrol control study to evaluate risk factors associated with FQ-resistant E. coli in community-onset SBP by comparison of resistant cases to susceptible controls and culture negative controls. Liver International (2014) © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Methods Study design and population
A case-control control study was performed at Samsung Medical Center, a 1950-bed tertiary care university hospital in South Korea. Patients with cirrhosis were eligible for inclusion in the study if they experienced an episode of community-onset SBP from June 2000 to August 2011. Patients aged older than 18 years were enrolled in the study, and all SBP episodes were included. E. coli isolates from ascitic fluid and/or blood were abstracted from the clinical microbiology laboratory database of patients with community-onset SBP. We identified three groups: one case and two control groups. Patients with SBP caused by FQ-resistant E. coli were assigned to the case group. Patients with SBP caused by FQ-susceptible E. coli were assigned to the control group I (CG I), and selected patients with
695
SBP caused by FQ-resistant E. coli
Kim et al.
culture-negative SBP were assigned to the control group II (CG II). CG II patients were randomly selected among those patients with negative cultures and matched with case patients based on gender and date of SBP diagnosis.
profiles of ascites and serum, empirical antibiotic regimen within 24 h, previous history of SBP, antibiotics exposure in the 30 days prior to the SBP episode and 30-day mortality. Definitions
Data collection
Data were obtained from the electronic medical records including age, gender, aetiology of cirrhosis, Child-Pugh score, concomitant hepatocellular carcinoma (HCC), septic shock, acute kidney injury (AKI), laboratory
SBP was defined as an elevated absolute polymorphonuclear neutrophil count ≥250 cells/mm3 in ascitic fluid and a positive culture of ascites and/or blood (3). Community-onset SBP was defined as an infection that occurred within 48 h of admission to the hospital.
Table 1. Clinical characteristics and factors associated with community-onset spontaneous bacterial peritonitis caused by fluoroquinoloneresistant E. coli strains Variable Age in years ± SD Male gender Cause of cirrhosis HBV HCV Alcohol Others Child-Pugh classification Mean score ± SD Class B Class C Concomitant HCC Diabetes mellitus Septic shock Acute kidney injury Laboratory finding Serum Na (mmol/L) Serum creatinine (mg/dl) Ascites PMN (103 cells/ll) Ascites protein (g/L) Antibiotic resistance Trimethoprim/sulfamethoxazole Third generation cephalosporins ESBL producer Appropriate antibiotics within 24 h Previous SBP episodes Previous antibiotics within 30 days* FQ† Third-generation cephalosporins‡ Other b-lactams§ Previous hospitalization within 90 days All cause 30-day mortality
FQ-resistant (n = 26) 58.2 ± 9.6 19 (73.9) 15 (57.7) 5 (19.2) 3 (11.5) 3 (11.5) 11.0 ± 1.6 4 (15.4) 22 (84.6) 9 (34.6) 3 (11.5) 9 (34.6) 15 (57.7) 130 ± 1.88 ± 7236.1 ± 968.8 ±
5 1.15 9061.2 564.9
13 (50.0) 5 (19.2) 4 (15.4) 23 (88.5) 17 (65.4) 12 (46.2) 9 (34.6) 9 (34.6) 5 (19.2) 19 (73.1) 11 (42.3)
FQ-susceptible (n = 56)
P-value
Culture-negative (n = 57)
P-value
57.8 ± 10.4 40 (71.4)
0.854 0.958
58.1 ± 9.7 41 (71.9)
0.938 0.914
39 (69.6) 8 (14.3) 5 (8.9) 4 (7.1)
0.324 0.746a 0.704a 0.673a
43 (75.4) 5 (8.8) 6 (10.5) 3 (5.3)
11.3 ± 1.4 5 (8.9) 51 (91.1) 33 (58.9) 11 (19.6) 16 (28.6) 28 (50.0)
0.423 0.455a
10.6 ± 1.6 15 (26.3) 42 (73.7) 39 (68.4) 13 (22.8) 6 (10.5) 21 (36.8)
129 ± 1.66 ± 8169.5 ± 989.7 ±
0.057 0.531a 0.613 0.636
6 0.96 10274.8 669.1
15 (26.8) 1 (1.8) 1 (1.8) 55 (98.2) 11 (19.6) 4 (7.1) 2 (3.6) 3 (5.4) 1 (1.8) 30 (53.6) 23 (41.1)
0.616 0.359 0.693 0.894 0.048 0.011a 0.033a 0.092a
CIRRHOSIS AND LIVER FAILURE
Risk factor of community-onset spontaneous bacterial peritonitis caused by fluoroquinolone-resistant Escherichia coli in patients with cirrhosis Jungok Kim1, Cheol-In Kang1, Eun-Jeong Joo1, Young Eun Ha1, Sun Young Cho1, Geum-Youn Gwak2, Doo Ryeon Chung1, Kyong Ran Peck1 and Jae-Hoon Song1 1 Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Keywords fluoroquinolone-resistant E. coli – spontaneous bacterial peritonitis – cirrhosis
Correspondence Cheol-In Kang, MD, Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-ro 81, Gangnam-gu, Seoul 135-710, Korea Tel: + 82 2 3410 0324 Fax: + 82 2 3410 0064 e-mail: [email protected] Received 25 April 2013 Accepted 31 October 2013 DOI:10.1111/liv.12374 Liver Int. 2014: 34: 695–699
Abstract Background & Aims: Despite the high prevalence of antimicrobial-resistant Escherichia coli in hospital-acquired infections, the clinical epidemiology of fluoroquinolone (FQ) resistance in community-onset spontaneous bacterial peritonitis (SBP) in patients with cirrhosis is not well understood. This study was performed to evaluate clinical features and risk factors for communityonset SBP caused by FQ-resistant E. coli. Methods: A case-control control study was performed using cases of community-onset SBP from June 2000 to August 2011 at Samsung Medical Center (Seoul, Korea). Patients with FQresistant E. coli were designated as case patients. A control group I (CG I) patient was defined as a person whose clinical sample yielded FQ-susceptible E. coli, and a control group II (CG II) patient was defined as a person with a negative culture result. Results: A total of 82 subjects with community-onset SBP caused by E. coli were identified, of which 26 (31.7%) were FQ-resistant E. coli infection. Fifty-seven matched subjects were randomly selected for CG II. Compared with CG I, previous SBP episodes (OR, 4.91; 95% CI, 1.50– 16.53; P = 0.010), prior use of FQ within 30 days (OR, 7.05; 95% CI, 1.17– 42.38; P = 0.033), and third-generation cephalosporin resistance (OR, 17.68; 95% CI, 1.67–187.26; P = 0.017) were significantly associated with FQ-resistant E. coli. Compared with CG II, a previous SBP episode was significantly associated with FQ-resistant E. coli (OR, 4.20; 95% CI, 1.50–11.80; P = 0.006). Conclusion: FQ-resistant E. coli is a significant cause of community-onset SBP, with relation to previous SBP episodes, recent FQ use and third-generation cephalosporin resistance.
Spontaneous bacterial peritonitis (SBP) is one of the serious complications that occurs in advanced cirrhosis and has a high mortality. Primary and secondary prophylaxis with flouroquinolones (FQ) has reduced the incidence of bacterial infections and improved survival in cirrhotic patients. However, the widespread use of FQ has resulted in changes in intestinal flora and has influenced antibiotic susceptibility patterns. Consequently, FQ-resistant Escherichia coli has been emerged in cirrhotic patients undergoing prophylaxis with Norfloxacin (1, 2). Although the prevalence of FQ-resistant E. coli is increasing, risk factors and clinical implications are still not well understood in community-onset SBP in patients with cirrhosis. Therefore, we conducted a casecontrol control study to evaluate risk factors associated with FQ-resistant E. coli in community-onset SBP by comparison of resistant cases to susceptible controls and culture negative controls. Liver International (2014) © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Methods Study design and population
A case-control control study was performed at Samsung Medical Center, a 1950-bed tertiary care university hospital in South Korea. Patients with cirrhosis were eligible for inclusion in the study if they experienced an episode of community-onset SBP from June 2000 to August 2011. Patients aged older than 18 years were enrolled in the study, and all SBP episodes were included. E. coli isolates from ascitic fluid and/or blood were abstracted from the clinical microbiology laboratory database of patients with community-onset SBP. We identified three groups: one case and two control groups. Patients with SBP caused by FQ-resistant E. coli were assigned to the case group. Patients with SBP caused by FQ-susceptible E. coli were assigned to the control group I (CG I), and selected patients with
695
SBP caused by FQ-resistant E. coli
Kim et al.
culture-negative SBP were assigned to the control group II (CG II). CG II patients were randomly selected among those patients with negative cultures and matched with case patients based on gender and date of SBP diagnosis.
profiles of ascites and serum, empirical antibiotic regimen within 24 h, previous history of SBP, antibiotics exposure in the 30 days prior to the SBP episode and 30-day mortality. Definitions
Data collection
Data were obtained from the electronic medical records including age, gender, aetiology of cirrhosis, Child-Pugh score, concomitant hepatocellular carcinoma (HCC), septic shock, acute kidney injury (AKI), laboratory
SBP was defined as an elevated absolute polymorphonuclear neutrophil count ≥250 cells/mm3 in ascitic fluid and a positive culture of ascites and/or blood (3). Community-onset SBP was defined as an infection that occurred within 48 h of admission to the hospital.
Table 1. Clinical characteristics and factors associated with community-onset spontaneous bacterial peritonitis caused by fluoroquinoloneresistant E. coli strains Variable Age in years ± SD Male gender Cause of cirrhosis HBV HCV Alcohol Others Child-Pugh classification Mean score ± SD Class B Class C Concomitant HCC Diabetes mellitus Septic shock Acute kidney injury Laboratory finding Serum Na (mmol/L) Serum creatinine (mg/dl) Ascites PMN (103 cells/ll) Ascites protein (g/L) Antibiotic resistance Trimethoprim/sulfamethoxazole Third generation cephalosporins ESBL producer Appropriate antibiotics within 24 h Previous SBP episodes Previous antibiotics within 30 days* FQ† Third-generation cephalosporins‡ Other b-lactams§ Previous hospitalization within 90 days All cause 30-day mortality
FQ-resistant (n = 26) 58.2 ± 9.6 19 (73.9) 15 (57.7) 5 (19.2) 3 (11.5) 3 (11.5) 11.0 ± 1.6 4 (15.4) 22 (84.6) 9 (34.6) 3 (11.5) 9 (34.6) 15 (57.7) 130 ± 1.88 ± 7236.1 ± 968.8 ±
5 1.15 9061.2 564.9
13 (50.0) 5 (19.2) 4 (15.4) 23 (88.5) 17 (65.4) 12 (46.2) 9 (34.6) 9 (34.6) 5 (19.2) 19 (73.1) 11 (42.3)
FQ-susceptible (n = 56)
P-value
Culture-negative (n = 57)
P-value
57.8 ± 10.4 40 (71.4)
0.854 0.958
58.1 ± 9.7 41 (71.9)
0.938 0.914
39 (69.6) 8 (14.3) 5 (8.9) 4 (7.1)
0.324 0.746a 0.704a 0.673a
43 (75.4) 5 (8.8) 6 (10.5) 3 (5.3)
11.3 ± 1.4 5 (8.9) 51 (91.1) 33 (58.9) 11 (19.6) 16 (28.6) 28 (50.0)
0.423 0.455a
10.6 ± 1.6 15 (26.3) 42 (73.7) 39 (68.4) 13 (22.8) 6 (10.5) 21 (36.8)
129 ± 1.66 ± 8169.5 ± 989.7 ±
0.057 0.531a 0.613 0.636
6 0.96 10274.8 669.1
15 (26.8) 1 (1.8) 1 (1.8) 55 (98.2) 11 (19.6) 4 (7.1) 2 (3.6) 3 (5.4) 1 (1.8) 30 (53.6) 23 (41.1)
0.616 0.359 0.693 0.894 0.048 0.011a 0.033a 0.092a
