mycoses
Diagnosis,Therapy and Prophylaxis of Fungal Diseases
Original article
Spontaneous fungal peritonitis: a devastating complication of cirrhosis Derek N. Bremmer,1 Jeffrey M. Garavaglia1 and Ryan K. Shields2 1 Department of Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, PA, USA and 2Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
Summary
Spontaneous bacterial peritonitis is a well-known complication of cirrhosis; however, spontaneous fungal peritonitis (SFP) is less well-recognised and described. Our objective was to determine the clinical characteristics, treatment outcomes and factors associated with death among patients with SFP. We performed a retrospective cohort study using the primary outcome of all-cause mortality at 28 days. Twenty-five patients were included; Candida species were the causative pathogen in all cases. At the onset of SFP, patients were critically ill, median APACHE II and MELD scores were 22 and 30.3, respectively. The 28-day mortality rate was 56%; six patients died prior to culture positivity. Among the remaining patients, there were no differences in rates of death by treatment regimen (P = 0.55). APACHE II score at the onset of SFP was an independent predictor of death (OR = 1.46, 95% CI = 1.02– 2.08, P = 0.04). In conclusion, SFP develops among critically ill patients with cirrhosis and is associated with high rates of death. Directed antifungal therapy did not improve patient outcomes. Future studies assessing the benefit of early or pre-emptive antifungal therapy are warranted.
Key words: spontaneous fungal peritonitis, peritonitis, invasive candidiasis, cirrhosis.
Introduction Spontaneous peritonitis is an important complication of cirrhosis that occurs in up to 12% of cirrhotic patients admitted to the hospital and is associated with mortality rates ranging from 10% to 40%.1–3 Enteric bacteria found in the gastrointestinal (GI) tract are the most common causes of peritonitis and spontaneous bacterial peritonitis (SBP) is well-recognised in the literature.1–4 Patients with SBP are typically treated with targeted antimicrobial therapy, and among those with recurrent infections, antimicrobial prophylaxis is Correspondence: R. K. Shields, Assistant Professor of Medicine, University of Pittsburgh, Falk Medical Building, Suite 3a, 3601 Fifth Avenue, Pittsburgh, PA 15213, USA. Tel.: +412-864-3745. Fax: +412-648-6399. E-mail: [email protected]
recommended.5–7 In line, the risk factors for SBP are well-defined and include an elevated serum bilirubin and low ascitic fluid protein concentration.4,5 Taken together, SBP is well-studied and patient management strategies are defined in consensus guidelines.5 In contrast, spontaneous fungal peritonitis (SFP) is less well-recognised.8,9 In fact, the clinical significance of isolating Candida from abdominal cultures is unknown in many cases.9 Nevertheless, SFP may be associated with higher mortality rates than SBP,2,3,8,9 but therapeutic approaches are largely undefined. To this end, the epidemiology and outcomes of patients with SFP have only been documented sporadically.8–12 Thus, the objective of this study was to describe the clinical characteristics, treatment outcomes and factors associated with death among patients with SFP.
Methods Submitted for publication 13 February 2015 Revised 11 March 2015 Accepted for publication 11 March 2015
© 2015 Blackwell Verlag GmbH Mycoses, 2015, 58, 387–393
We conducted a retrospective cohort study of patients with SFP. All patients with ascitic fluid cultures
doi:10.1111/myc.12321
D. N. Bremmer et al.
growing fungus from 2009 to 2013 were identified through microbiology records. Patients were excluded if they did not have a history of cirrhosis (n = 29), if an alternative explanation for peritonitis was identified (n = 25; gastrointestinal tract perforation, dialysis catheter, etc.), and if patient signs or symptoms of infection were absent prior to death (n = 5). Demographics and baseline characteristics were collected through electronic medical records. This study was approved by the institutional review board at the University of Pittsburgh (PRO 14030085). The primary outcome of the study was all-cause mortality at 28 days. Fisher’s exact and Mann–Whitney tests were used to compare categorical and continuous variables, respectively. Multivariate logistic regression analysis was performed by backward selection procedures to identify predictors of death using variables identified by univariate analysis (P ≤ 0.10). Significance was defined as a P-value ≤ 0.05 (twotailed).
Results Twenty-five patients were included in the study. Demographics and clinical characteristics are listed in Table 1. The median age was 54 years and 68% were male. The most common causes of cirrhosis were alcoholic hepatitis (36%; 9/25), hepatitis C (8%; 2/25) or both (16%; 4/25). Median Charlson Comorbidity Index and MELD score were 4 (inter-quartile range [IQR]: 3–5) and 30.3 (IQR: 21.3–35.1) respectively. Ninetytwo percent (23/25) of patients had exposure to broad spectrum antibiotics in the 30 days preceding SFP. At the onset of disease, the median APACHE II score was 22 (IQR: 16.5–24.5), 44% (11/25) of patients resided in the intensive care unit (ICU), and concomitant bacteria were present in 32% (8/25) of cases. Candida albicans (48%; 12/25) was the most common fungus isolated from ascitic fluid cultures, followed by C. glabrata (20%), C. parapsilosis (16%), C. tropicalis (12%) and C. zeylanoides (4%). Antifungal therapy was employed in 60% (15/25) for a median duration of 26 days (IQR: 15–43). Treatment was initiated due to the presence of yeast in ascitic fluid cultures (n = 11) or at the time of signs and symptoms of infection (i.e. empiric therapy, n = 4). Sixty-seven per cent (10/15) had serial ascitic fluid cultures and the median time to culture negativity was 16 days (IQR: 4–33). Three patients had persistent (n = 2, defined as positive ascitic fluid cultures for ≥10 days) or recurrent (n = 1, 40 days after initial infection) peritonitis despite antifungal therapy. Of the remaining patients,
388
six died prior to positive cultures and 4 were electively not treated with antifungal therapy. In the latter group, two were treated for SBP alone, one patient clinically improved with empiric antibiotics, and repeat ascitic fluid cultures were negative in the final patient. Overall, the 14 day, 28 day and in-hospital mortality rates were 44%, 56% and 60% respectively. SFP contributed to death in 73% of patients who died in the hospital; median time to death was 6 days (IQR: 3–7). There were no differences in mortality rates at 28 days among patients receiving caspofungin (38%), fluconazole (57%), or those electively not treated with antifungals (25%; P = 0.55). APACHE II scores were similar for patients who were and were not treated with antifungals (median 20 vs. 20, P = 0.76). However, MELD scores were significantly higher among those who were treated with antifungals compared to those who were not (median 30.6 vs. 17.1, P = 0.04). Risk factors for death by day 28 included older age, higher Charlson Comorbidity Index and higher MELD and APACHE II scores (Table 2). By multivariate logistic regression, APACHE II score was an independent predictor of death (P = 0.038, OR = 1.45, 95% CI 1.02–2.08). Receipt of antifungal therapy was not associated with survival. On the other hand, 100% (4/ 4) of patients who received a liver transplant survived compared to 33% (7/21) of patients who did not (P = 0.02).
Discussion To our knowledge, this is the largest study of patients with SFP reported. Our most ominous finding was the high rate of death among patients with SFP, which was associated with infection in most cases. Mortality rates for SFP have been shown to be higher than SBP,2,3,8,9 which may be associated with the late-onset of SFP relative to SBP.8 Overall, our mortality rate was comparable to prior studies,8,9 and highlights the critically ill population most likely to be affected. Indeed, 44% of patients were diagnosed with SFP in the ICU and the median APACHE II score was 22. Not surprisingly, APACHE II score was an independent predictor of death. Rates of death were not influenced by initiation of antifungal therapy, although six patients died prior to receiving any antifungals. Taken together, our data suggest that SFP is a complication of advanced cirrhosis among critically ill patients, and in some cases, is diagnosed too late for therapeutic measures to be implemented.
© 2015 Blackwell Verlag GmbH Mycoses, 2015, 58, 387–393
Age (sex)
63 (M)
71 (M)
50 (M)
63 (M)
46 (M)
56 (F)
57 (M)
54 (M)
59 (M)
57 (F)
50 (M)
71 (F)
53 (F)
Patient
1
2
3
4
5
© 2015 Blackwell Verlag GmbH Mycoses, 2015, 58, 387–393
6
7
8
9
10
11
12
13
Alcoholic cirrhosis and hepatitis C
Metastatic carcinoid tumour Alcoholic cirrhosis Metastatic colorectal cancer
Cryptogenic cirrhosis
Alcoholic cirrhosis Alcoholic cirrhosis Haemochromatosis Alcoholic cirrhosis
Metastatic pancreatic cancer Alcoholic cirrhosis Alcoholic cirrhosis and hepatitis C
Hepatitis C
Underlying disease
4
9
3
12
10
4
5
3
5
5
4
9
3
Charlson Comorbidity Index
33
12
19
20
28
43
35
31
47
22
35
39
44
MELD score
Beta-lactamase PCN (8)
Beta-lactamase PCN (15) Beta-lactamase PCN (15)
3rd Gen ceph (4); Beta-lactamase PCN (3) Beta-lactamase PCN (5)
None
Beta-lactamase PCN (8) Beta-lactamase PCN (6); Fluoroquinolone (5) Beta-lactamase PCN (5) Beta-lactamase PCN (12) None
Beta-lactamase PCN (5) Beta-lactamase PCN (12)
Recent antibiotic exposure (duration)1
Table 1 Clinical characteristics and outcomes of patients with SFP.
23
31
14
20
23
22
22
30
30
24
23
23
28
APACHE II score
C.albicans
C.zeylanoides
C.albicans
C. parapsilosis
C.tropicalis
C.albicans
C.albicans
C.tropicalis
C.albicans
C.parapsilosis
C.glabrata
C.albicans
C.tropicalis
Infecting fungus
Caspofungin (3)
None3
–
– –
– Positive culture(3) Empiric therapy(0) Empiric therapy(0)
Positive culture (4)
–
–
– –
– – – –
–
None
–
Positive culture (5)
E. faecalis, MRSA, P. mirabilis
–
Fluconazole (12)
Fluconazole (5)
Fluconazole (6); Caspofungin (1) Fluconazole (7)
Caspofungin (2)
None3
None3
None3
Positive culture (3)
E. faecium
P. mirabilis, CONS
None3
–
K. pneumoniae None3
Antifungal treatment (duration)
Concomitant bacteria
Indication for antifungal treatment (time to treatment2)
(continued)
Death – day 15 due to abdominal sepsis, treated with pipercillin/ tazobactam and vancomycin Death – day 17 due to cardiac arrest
Death – day 8
Death – day 7
Death – day 6; complicated by fungemia Death – day 7
Death – day 6
Death – day 5
Death – day 4
Death – day 3
Death – day 3
Death – day 3
Death – day 2
28 day survival4
Case series: spontaneous fungal peritonitis
389
390
32 (F)
63 (M)
55 (M)
23 (F)
39 (M)
14
15
16
17
18
19
49 (F)
40 (M)
Patient
20
Age (sex)
Autoimmune cirrhosis
Primary sclerosing cholangitis
APAP overdose
Hepatitis C
Cryptogenic cirrhosis
Alcoholic cirrhosis
Alcoholic cirrhosis
Underlying disease
Table 1 (continued)
5
3
3
3
5
5
3
Charlson Comorbidity Index
30
33
13
24
30
32
34
MELD score
14
25
3rd Gen ceph (5)
Tigecycline (7)
19
20
Cefepime (5)
Beta-lactamase PCN (5)
15
18
3rd Gen ceph (5)
Cefepime (5)
29
APACHE II score
Beta-lactamase PCN (9)
Recent antibiotic exposure (duration)1
C.albicans
C.glabrata
C.glabrata
C.parapsilosis
C.glabrata
C.albicans
C.albicans
Infecting fungus
–
Positive culture (16)
Empiric therapy(0)
Empiric therapy(0)
–
E. Faecium
Positive culture (7)
–
–
Positive culture(7)
–
Positive culture (3)
Positive culture(3)
Concomitant bacteria
E. Faecium
Indication for antifungal treatment (time to treatment2)
Caspofungin (2); Fluconazole (38)
Voriconazole (10) Caspofungin (15)
Caspofungin (36); Voriconazole (8)
Fluconazole (9)
Caspofungin (31); Voriconazole (6)
Fluconazole (28)
Caspofungin (2); Fluconazole (8)
Antifungal treatment (duration)
(continued)
Death – day 19; persistently positive ascitic fluid cultures until death Alive – death on day 48 due to septic shock Alive – death on day 92; recurrent peritonitis and breakthrough fungemia Alive – Patient received liver transplant on day 1 Alive – Patient received liver transplant on day 3; ascitic fluid cultures persistently positive 46 days after transplant Alive – Patient received a liver transplant on day 4 Alive – Patient received liver transplant on day 16
28 day survival4
D. N. Bremmer et al.
© 2015 Blackwell Verlag GmbH Mycoses, 2015, 58, 387–393
© 2015 Blackwell Verlag GmbH Mycoses, 2015, 58, 387–393
60 (M)
46 (M)
49 (F)
61 (M)
38 (M)
Patient
21
22
23
24
25
Cryptogenic cirrhosis
Alcoholic cirrhosis
Alcoholic cirrhosis and hepatitis C
Alcoholic cirrhosis
Alcoholic cirrhosis and hepatitis C
Underlying disease
4
3
3
1
5
Charlson Comorbidity Index
27
22
8
6
30
MELD score
Beta-lactamase PCN (8)
Cefepime (5)
15
19
21
15
14
3rd Gen ceph (14)
Beta-lactamase PCN (7); Fluoroquinolone (8) Beta-lactamase PCN (8)
APACHE II score
Recent antibiotic exposure (duration)1
Days represent time from positive fungal culture to event.
4
Death prior to initiation of antifungal therapy.
3
Time from ascitic fluid culture to start of antifungal therapy in days.
2
Within the 30 days of the onset of spontaneous fungal peritonitis.
1
APAP, acetaminophen; F, female; GI, gastrointestinal; M, male; PCN, penicillin.
Age (sex)
Table 1 (continued)
C.albicans
C.parapsilosis
C.glabrata
C.albicans
C.albicans
Infecting fungus
None
None
–
–
Bacteroides Thetaiotomicron and MRSA –
None
–
Fluconazole (14)
Caspofungin (5); Fluconazole (12); Caspofungin + Fluconazole (41)
–
–
Antifungal treatment (duration)
Positive culture (3)
Positive culture (2)
Concomitant bacteria
E. faecium, K. pneumoniae
Indication for antifungal treatment (time to treatment2)
Alive – Treatment with pipercillin/ tazobactam alone, repeat culture on day 2 negative for fungus Alive – Treatment with metronidazole and vancomycin Alive – Not treated
Alive – Ascitic fluid cultures persistently positive until day 29 despite antifungal therapy; patient improved with combination therapy Alive – Follow-up cultures negative on day 2
28 day survival4
Case series: spontaneous fungal peritonitis
391
D. N. Bremmer et al.
Table 2 Factors associated with 28 day mortality.
Factor Male (%) Median age – years (IQR) Median APACHE II score (IQR) Median MELD score (IQR) Median Charlson Comorbidity Index (IQR) Infection due to Candida albicans, n (%) Antifungal treatment, n (%) PMN Count >250 cells ml 1, n (%) Concomitant SBP, n (%) Broad spectrum antibiotics within 30 days, n (%)2
Total population (n = 25)
Alive (n = 11)
Dead (n = 14)
Univariate P-value
17 54 22.0 30.3 4 12 15 16 8 23
7 49.2 18.0 27.1 3 5 8 7 4 11
10 57.0 23.0 34.0 4.5 7 7 9 4 12
1.00 0.06
Diagnosis,Therapy and Prophylaxis of Fungal Diseases
Original article
Spontaneous fungal peritonitis: a devastating complication of cirrhosis Derek N. Bremmer,1 Jeffrey M. Garavaglia1 and Ryan K. Shields2 1 Department of Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, PA, USA and 2Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
Summary
Spontaneous bacterial peritonitis is a well-known complication of cirrhosis; however, spontaneous fungal peritonitis (SFP) is less well-recognised and described. Our objective was to determine the clinical characteristics, treatment outcomes and factors associated with death among patients with SFP. We performed a retrospective cohort study using the primary outcome of all-cause mortality at 28 days. Twenty-five patients were included; Candida species were the causative pathogen in all cases. At the onset of SFP, patients were critically ill, median APACHE II and MELD scores were 22 and 30.3, respectively. The 28-day mortality rate was 56%; six patients died prior to culture positivity. Among the remaining patients, there were no differences in rates of death by treatment regimen (P = 0.55). APACHE II score at the onset of SFP was an independent predictor of death (OR = 1.46, 95% CI = 1.02– 2.08, P = 0.04). In conclusion, SFP develops among critically ill patients with cirrhosis and is associated with high rates of death. Directed antifungal therapy did not improve patient outcomes. Future studies assessing the benefit of early or pre-emptive antifungal therapy are warranted.
Key words: spontaneous fungal peritonitis, peritonitis, invasive candidiasis, cirrhosis.
Introduction Spontaneous peritonitis is an important complication of cirrhosis that occurs in up to 12% of cirrhotic patients admitted to the hospital and is associated with mortality rates ranging from 10% to 40%.1–3 Enteric bacteria found in the gastrointestinal (GI) tract are the most common causes of peritonitis and spontaneous bacterial peritonitis (SBP) is well-recognised in the literature.1–4 Patients with SBP are typically treated with targeted antimicrobial therapy, and among those with recurrent infections, antimicrobial prophylaxis is Correspondence: R. K. Shields, Assistant Professor of Medicine, University of Pittsburgh, Falk Medical Building, Suite 3a, 3601 Fifth Avenue, Pittsburgh, PA 15213, USA. Tel.: +412-864-3745. Fax: +412-648-6399. E-mail: [email protected]
recommended.5–7 In line, the risk factors for SBP are well-defined and include an elevated serum bilirubin and low ascitic fluid protein concentration.4,5 Taken together, SBP is well-studied and patient management strategies are defined in consensus guidelines.5 In contrast, spontaneous fungal peritonitis (SFP) is less well-recognised.8,9 In fact, the clinical significance of isolating Candida from abdominal cultures is unknown in many cases.9 Nevertheless, SFP may be associated with higher mortality rates than SBP,2,3,8,9 but therapeutic approaches are largely undefined. To this end, the epidemiology and outcomes of patients with SFP have only been documented sporadically.8–12 Thus, the objective of this study was to describe the clinical characteristics, treatment outcomes and factors associated with death among patients with SFP.
Methods Submitted for publication 13 February 2015 Revised 11 March 2015 Accepted for publication 11 March 2015
© 2015 Blackwell Verlag GmbH Mycoses, 2015, 58, 387–393
We conducted a retrospective cohort study of patients with SFP. All patients with ascitic fluid cultures
doi:10.1111/myc.12321
D. N. Bremmer et al.
growing fungus from 2009 to 2013 were identified through microbiology records. Patients were excluded if they did not have a history of cirrhosis (n = 29), if an alternative explanation for peritonitis was identified (n = 25; gastrointestinal tract perforation, dialysis catheter, etc.), and if patient signs or symptoms of infection were absent prior to death (n = 5). Demographics and baseline characteristics were collected through electronic medical records. This study was approved by the institutional review board at the University of Pittsburgh (PRO 14030085). The primary outcome of the study was all-cause mortality at 28 days. Fisher’s exact and Mann–Whitney tests were used to compare categorical and continuous variables, respectively. Multivariate logistic regression analysis was performed by backward selection procedures to identify predictors of death using variables identified by univariate analysis (P ≤ 0.10). Significance was defined as a P-value ≤ 0.05 (twotailed).
Results Twenty-five patients were included in the study. Demographics and clinical characteristics are listed in Table 1. The median age was 54 years and 68% were male. The most common causes of cirrhosis were alcoholic hepatitis (36%; 9/25), hepatitis C (8%; 2/25) or both (16%; 4/25). Median Charlson Comorbidity Index and MELD score were 4 (inter-quartile range [IQR]: 3–5) and 30.3 (IQR: 21.3–35.1) respectively. Ninetytwo percent (23/25) of patients had exposure to broad spectrum antibiotics in the 30 days preceding SFP. At the onset of disease, the median APACHE II score was 22 (IQR: 16.5–24.5), 44% (11/25) of patients resided in the intensive care unit (ICU), and concomitant bacteria were present in 32% (8/25) of cases. Candida albicans (48%; 12/25) was the most common fungus isolated from ascitic fluid cultures, followed by C. glabrata (20%), C. parapsilosis (16%), C. tropicalis (12%) and C. zeylanoides (4%). Antifungal therapy was employed in 60% (15/25) for a median duration of 26 days (IQR: 15–43). Treatment was initiated due to the presence of yeast in ascitic fluid cultures (n = 11) or at the time of signs and symptoms of infection (i.e. empiric therapy, n = 4). Sixty-seven per cent (10/15) had serial ascitic fluid cultures and the median time to culture negativity was 16 days (IQR: 4–33). Three patients had persistent (n = 2, defined as positive ascitic fluid cultures for ≥10 days) or recurrent (n = 1, 40 days after initial infection) peritonitis despite antifungal therapy. Of the remaining patients,
388
six died prior to positive cultures and 4 were electively not treated with antifungal therapy. In the latter group, two were treated for SBP alone, one patient clinically improved with empiric antibiotics, and repeat ascitic fluid cultures were negative in the final patient. Overall, the 14 day, 28 day and in-hospital mortality rates were 44%, 56% and 60% respectively. SFP contributed to death in 73% of patients who died in the hospital; median time to death was 6 days (IQR: 3–7). There were no differences in mortality rates at 28 days among patients receiving caspofungin (38%), fluconazole (57%), or those electively not treated with antifungals (25%; P = 0.55). APACHE II scores were similar for patients who were and were not treated with antifungals (median 20 vs. 20, P = 0.76). However, MELD scores were significantly higher among those who were treated with antifungals compared to those who were not (median 30.6 vs. 17.1, P = 0.04). Risk factors for death by day 28 included older age, higher Charlson Comorbidity Index and higher MELD and APACHE II scores (Table 2). By multivariate logistic regression, APACHE II score was an independent predictor of death (P = 0.038, OR = 1.45, 95% CI 1.02–2.08). Receipt of antifungal therapy was not associated with survival. On the other hand, 100% (4/ 4) of patients who received a liver transplant survived compared to 33% (7/21) of patients who did not (P = 0.02).
Discussion To our knowledge, this is the largest study of patients with SFP reported. Our most ominous finding was the high rate of death among patients with SFP, which was associated with infection in most cases. Mortality rates for SFP have been shown to be higher than SBP,2,3,8,9 which may be associated with the late-onset of SFP relative to SBP.8 Overall, our mortality rate was comparable to prior studies,8,9 and highlights the critically ill population most likely to be affected. Indeed, 44% of patients were diagnosed with SFP in the ICU and the median APACHE II score was 22. Not surprisingly, APACHE II score was an independent predictor of death. Rates of death were not influenced by initiation of antifungal therapy, although six patients died prior to receiving any antifungals. Taken together, our data suggest that SFP is a complication of advanced cirrhosis among critically ill patients, and in some cases, is diagnosed too late for therapeutic measures to be implemented.
© 2015 Blackwell Verlag GmbH Mycoses, 2015, 58, 387–393
Age (sex)
63 (M)
71 (M)
50 (M)
63 (M)
46 (M)
56 (F)
57 (M)
54 (M)
59 (M)
57 (F)
50 (M)
71 (F)
53 (F)
Patient
1
2
3
4
5
© 2015 Blackwell Verlag GmbH Mycoses, 2015, 58, 387–393
6
7
8
9
10
11
12
13
Alcoholic cirrhosis and hepatitis C
Metastatic carcinoid tumour Alcoholic cirrhosis Metastatic colorectal cancer
Cryptogenic cirrhosis
Alcoholic cirrhosis Alcoholic cirrhosis Haemochromatosis Alcoholic cirrhosis
Metastatic pancreatic cancer Alcoholic cirrhosis Alcoholic cirrhosis and hepatitis C
Hepatitis C
Underlying disease
4
9
3
12
10
4
5
3
5
5
4
9
3
Charlson Comorbidity Index
33
12
19
20
28
43
35
31
47
22
35
39
44
MELD score
Beta-lactamase PCN (8)
Beta-lactamase PCN (15) Beta-lactamase PCN (15)
3rd Gen ceph (4); Beta-lactamase PCN (3) Beta-lactamase PCN (5)
None
Beta-lactamase PCN (8) Beta-lactamase PCN (6); Fluoroquinolone (5) Beta-lactamase PCN (5) Beta-lactamase PCN (12) None
Beta-lactamase PCN (5) Beta-lactamase PCN (12)
Recent antibiotic exposure (duration)1
Table 1 Clinical characteristics and outcomes of patients with SFP.
23
31
14
20
23
22
22
30
30
24
23
23
28
APACHE II score
C.albicans
C.zeylanoides
C.albicans
C. parapsilosis
C.tropicalis
C.albicans
C.albicans
C.tropicalis
C.albicans
C.parapsilosis
C.glabrata
C.albicans
C.tropicalis
Infecting fungus
Caspofungin (3)
None3
–
– –
– Positive culture(3) Empiric therapy(0) Empiric therapy(0)
Positive culture (4)
–
–
– –
– – – –
–
None
–
Positive culture (5)
E. faecalis, MRSA, P. mirabilis
–
Fluconazole (12)
Fluconazole (5)
Fluconazole (6); Caspofungin (1) Fluconazole (7)
Caspofungin (2)
None3
None3
None3
Positive culture (3)
E. faecium
P. mirabilis, CONS
None3
–
K. pneumoniae None3
Antifungal treatment (duration)
Concomitant bacteria
Indication for antifungal treatment (time to treatment2)
(continued)
Death – day 15 due to abdominal sepsis, treated with pipercillin/ tazobactam and vancomycin Death – day 17 due to cardiac arrest
Death – day 8
Death – day 7
Death – day 6; complicated by fungemia Death – day 7
Death – day 6
Death – day 5
Death – day 4
Death – day 3
Death – day 3
Death – day 3
Death – day 2
28 day survival4
Case series: spontaneous fungal peritonitis
389
390
32 (F)
63 (M)
55 (M)
23 (F)
39 (M)
14
15
16
17
18
19
49 (F)
40 (M)
Patient
20
Age (sex)
Autoimmune cirrhosis
Primary sclerosing cholangitis
APAP overdose
Hepatitis C
Cryptogenic cirrhosis
Alcoholic cirrhosis
Alcoholic cirrhosis
Underlying disease
Table 1 (continued)
5
3
3
3
5
5
3
Charlson Comorbidity Index
30
33
13
24
30
32
34
MELD score
14
25
3rd Gen ceph (5)
Tigecycline (7)
19
20
Cefepime (5)
Beta-lactamase PCN (5)
15
18
3rd Gen ceph (5)
Cefepime (5)
29
APACHE II score
Beta-lactamase PCN (9)
Recent antibiotic exposure (duration)1
C.albicans
C.glabrata
C.glabrata
C.parapsilosis
C.glabrata
C.albicans
C.albicans
Infecting fungus
–
Positive culture (16)
Empiric therapy(0)
Empiric therapy(0)
–
E. Faecium
Positive culture (7)
–
–
Positive culture(7)
–
Positive culture (3)
Positive culture(3)
Concomitant bacteria
E. Faecium
Indication for antifungal treatment (time to treatment2)
Caspofungin (2); Fluconazole (38)
Voriconazole (10) Caspofungin (15)
Caspofungin (36); Voriconazole (8)
Fluconazole (9)
Caspofungin (31); Voriconazole (6)
Fluconazole (28)
Caspofungin (2); Fluconazole (8)
Antifungal treatment (duration)
(continued)
Death – day 19; persistently positive ascitic fluid cultures until death Alive – death on day 48 due to septic shock Alive – death on day 92; recurrent peritonitis and breakthrough fungemia Alive – Patient received liver transplant on day 1 Alive – Patient received liver transplant on day 3; ascitic fluid cultures persistently positive 46 days after transplant Alive – Patient received a liver transplant on day 4 Alive – Patient received liver transplant on day 16
28 day survival4
D. N. Bremmer et al.
© 2015 Blackwell Verlag GmbH Mycoses, 2015, 58, 387–393
© 2015 Blackwell Verlag GmbH Mycoses, 2015, 58, 387–393
60 (M)
46 (M)
49 (F)
61 (M)
38 (M)
Patient
21
22
23
24
25
Cryptogenic cirrhosis
Alcoholic cirrhosis
Alcoholic cirrhosis and hepatitis C
Alcoholic cirrhosis
Alcoholic cirrhosis and hepatitis C
Underlying disease
4
3
3
1
5
Charlson Comorbidity Index
27
22
8
6
30
MELD score
Beta-lactamase PCN (8)
Cefepime (5)
15
19
21
15
14
3rd Gen ceph (14)
Beta-lactamase PCN (7); Fluoroquinolone (8) Beta-lactamase PCN (8)
APACHE II score
Recent antibiotic exposure (duration)1
Days represent time from positive fungal culture to event.
4
Death prior to initiation of antifungal therapy.
3
Time from ascitic fluid culture to start of antifungal therapy in days.
2
Within the 30 days of the onset of spontaneous fungal peritonitis.
1
APAP, acetaminophen; F, female; GI, gastrointestinal; M, male; PCN, penicillin.
Age (sex)
Table 1 (continued)
C.albicans
C.parapsilosis
C.glabrata
C.albicans
C.albicans
Infecting fungus
None
None
–
–
Bacteroides Thetaiotomicron and MRSA –
None
–
Fluconazole (14)
Caspofungin (5); Fluconazole (12); Caspofungin + Fluconazole (41)
–
–
Antifungal treatment (duration)
Positive culture (3)
Positive culture (2)
Concomitant bacteria
E. faecium, K. pneumoniae
Indication for antifungal treatment (time to treatment2)
Alive – Treatment with pipercillin/ tazobactam alone, repeat culture on day 2 negative for fungus Alive – Treatment with metronidazole and vancomycin Alive – Not treated
Alive – Ascitic fluid cultures persistently positive until day 29 despite antifungal therapy; patient improved with combination therapy Alive – Follow-up cultures negative on day 2
28 day survival4
Case series: spontaneous fungal peritonitis
391
D. N. Bremmer et al.
Table 2 Factors associated with 28 day mortality.
Factor Male (%) Median age – years (IQR) Median APACHE II score (IQR) Median MELD score (IQR) Median Charlson Comorbidity Index (IQR) Infection due to Candida albicans, n (%) Antifungal treatment, n (%) PMN Count >250 cells ml 1, n (%) Concomitant SBP, n (%) Broad spectrum antibiotics within 30 days, n (%)2
Total population (n = 25)
Alive (n = 11)
Dead (n = 14)
Univariate P-value
17 54 22.0 30.3 4 12 15 16 8 23
7 49.2 18.0 27.1 3 5 8 7 4 11
10 57.0 23.0 34.0 4.5 7 7 9 4 12
1.00 0.06
