Pediatr Surg Int (2014) 30:323–326 DOI 10.1007/s00383-014-3477-y
ORIGINAL ARTICLE
Ceftriaxone-induced pseudolithiasis in children treated for perforated appendicitis Hanna Alemayehu • Amita A. Desai • Priscilla Thomas • Susan W. Sharp • Shawn D. St. Peter
Accepted: 13 January 2014 / Published online: 28 January 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose Ceftriaxone has been associated with development of pseudolithiasis. In our institution, it is used for treatment of perforated appendicitis in children. This study evaluated the occurrence of ceftriaxone-related pseudolithiasis in this population. Methods After obtaining IRB approval, we performed a retrospective chart review over 51 months. We included patients undergoing laparoscopic appendectomy for perforated appendicitis. All patients were treated with ceftriaxone post-operatively. Patients without initial or posttreatment gallbladder imaging available for review were excluded. Results There were 71 patients who met inclusion criteria with a mean (±SD) age of 10.8 ± 3.8 years. Of these, 14 % (n = 10) developed stones or sludge in the gallbladder. The mean duration of ceftriaxone therapy was 8.7 ± 3.8 days. The average time to post-antibiotic imaging was 11.5 ± 10.3 days from initiation of antibiotics. There was no significant difference in duration of ceftriaxone therapy in the children that developed pseudolithiasis or sludge (10.0 ± 4.9 days) compared to those that did not (8.5 ± 3.6, p = 0.26). One child (10 %) with pseudolithiasis went on to become symptomatic, requiring a laparoscopic cholecystectomy.
H. Alemayehu A. A. Desai P. Thomas S. W. Sharp S. D. St. Peter (&) Department of Surgery, Center for Prospective Clinical Trials, Children’s Mercy Hospital, 2401 Gillham Road, Kansas City, MO 64108, USA e-mail: [email protected] S. D. St. Peter Pediatric Surgery Training Program, Children’s Mercy Hospital, 2401 Gillham Road, Kansas City, MO 64108, USA
Conclusions In our experience, ceftriaxone use for perforated appendicitis is associated with a significant incidence of biliary pseudolithiasis, and is unrelated to duration of ceftriaxone therapy. Keywords Ceftriaxone Adverse effects Pseudolithiasis Perforated appendicitis
Introduction Ceftriaxone is a commonly used third-generation cephalosporin due to its broad spectrum coverage and convenience of daily dosing; however, gallbladder and urinary precipitation resulting in pseudolithiasis and sludge have been described in the pediatric and adult literature [1, 2], having first been described in 1986 [3]. Pseudolithiasis commonly occurs shortly after institution of therapy with the antibiotic and resolves after discontinuation of the medication [1]. It has been suggested that biliary pseudolithiasis is more common in the use of ceftriaxone to treat biliary tract infections, than non-biliary tract infections [4]. In our institution, it is used per protocol in children with perforated appendicitis as we have conducted several prospective, randomized trials in this population [5–9]. This study evaluated the occurrence of ceftriaxone-related pseudolithiasis in this population and the incidence of symptomatic presentation.
Methods After obtaining IRB approval, we performed a retrospective chart review over a 51 month period of all patients undergoing laparoscopic appendectomy for perforated
123
324
appendicitis who subsequently developed intra-abdominal abscesses. All patients were treated with ceftriaxone postoperatively for perforated appendicitis. The protocol to treat perforated appendicitis in our institution is once daily dosing of ceftriaxone, 50 mg/kg with a maximum dose of 2 g, infused over 10 min. This patient population had both initial diagnostic computed tomography (CT) scans, and post-treatment CT scans for diagnosis of intra-abdominal abscesses. Both initial and post-treatment CT scans were reviewed for the presence of gallstones or gallbladder sludge as determined by a staff radiologist at the time of the study, and confirmed by the research personnel. Gallstones and gallbladder sludge were, respectively, defined as visually detectable high attenuation stones or visually detectable high attenuation material layering in the gallbladder. Patients without initial or post-treatment gallbladder imaging available for review were excluded. Means are expressed with standard deviation. Comparative analysis was performed using the two-tailed student t test, and a p value \0.05 was deemed significant.
Results There were 71 patients who met inclusion criteria, with a mean age of 10.8 ± 3.8. Ten patients (14 %) developed stones or sludge in the gallbladder. The mean duration of ceftriaxone therapy was 8.7 ± 3.8 days. The average time to post-antibiotic imaging was 11.5 ± 10.3 days from initiation of antibiotics. There was no significant difference in duration of ceftriaxone therapy in the children that developed pseudolithiasis or sludge compared to those that did not (10.0 ± 4.9 vs. 8.5 ± 3.6 days, respectively, p = 0.26). There was also no difference in mean age, which was 10.4 ± 4.2 with pseudolithiasis and 10.8 ± 3.8 without (p = 0.76). Only one child with biliary pseudolithiasis became symptomatic, and underwent a laparoscopic cholecystectomy. Pathology in this patient showed chronic cholecystitis on microscopic exam, and gross examination showed the gallbladder to be filled with dark green bile admixed with yellow, grainy appearing material.
Discussion Ceftriaxone was introduced to the market in the United States in 1984, which was shortly followed by the first description of biliary precipitations associated with the antibiotic [3]. The pathophysiology is thought to relate to the biliary excretion of ceftriaxone and the calcium–ceftriaxone salt precipitation in the gallbladder secondary to a significantly higher biliary concentration than serum concentration [10, 11]. An early prospective cohort study
123
Pediatr Surg Int (2014) 30:323–326
described the incidence and transient nature of the problem in 37 patients [1]. Several prospective studies have since looked at the problem of ceftriaxone-associated biliary pseudolithiasis in children, which are summarized in Table 1 [1, 4, 12–22]. Evident from this table is that ceftriaxone-related pseudolithiasis is not uncommon, ranging from 3 to 56 %. Also apparent from these studies is the transient nature of the finding, and the low likelihood of producing a clinical impact. Our occurrence rate of 14 % was lower than many of the series in Table 1; however, when looking at the studies evaluating patients treated with the same dose we use (50 mg/kg/d), our occurrence rate was similar (3–17 %). This may indicate that the higher incidences seen in the other studies using higher doses may in fact be secondary to a dose-dependent increased occurrence rate as shown by some studies [10, 22]. This, however, has not been shown in other studies [13]. Another explanation for our relatively low occurrence rate is the fact that we performed repeat imaging 11.5 ± 10.3 days from initiation of antibiotics. The mean duration of ceftriaxone therapy was 10.0 ± 4.9 days, and in some patients, repeat imaging was performed after the cessation of antibiotics so we may have missed the window to capture them since the majority resolve within 3 weeks (Table 1). Our study also did not demonstrate the association with older age that has been shown by other studies [1, 3, 12, 14, 22]; implying that in children with perforated appendicitis, age plays less of a role than in the other disease models studied. We found that duration of ceftriaxone therapy was not a predictive factor for the development of pseudolithiasis, and this is in agreement with previous studies [1, 13, 15, 20, 21]. In our series, 1 patient underwent cholecystectomy 18 days after cessation of ceftriaxone, comprising 10 % of the patients that developed pseudolithiasis, which fits nicely within the range of symptomatic cases previously reported (Table 1). The symptomatic patients in these studies typically resolved symptoms when the biliary imaging normalized. Since the reported range of resolution of pseudolithiasis is 2–150 days, it is reasonable to manage these cases expectantly provided their severity of symptoms will allow observation. The major limitation of our study was the lack of uniformity in timing of repeat imaging after initiation of antibiotics as it was not the primary objective to track for development and resolution of pseudolithiasis; this was a secondary investigation. The protocol for repeat imaging in post-operative patients with perforated appendicitis at our institution includes the performance of a CT scan on postoperative day 7 for patients that have not shown clinical improvement while in the hospital. For patients who meet
100 (25) 7–54 (every 3 days)
Conclusions In our experience, ceftriaxone use for perforated appendicitis is associated with a significant incidence of biliary pseudolithiasis and/or sludge. The development of pseudolithiasis is unrelated to duration of ceftriaxone therapy. The finding is usually asymptomatic requiring no further intervention.
2–7 (NA) 30–80
43 (25)
NA
References
Median value
Mean value
Range in years c
b
a
NA not available
58 Meng [4]
2.8
0 (0)
19 (5) 10–30 (weekly)
4–21 (every 4–6 days) 4–8 (7.2a)
3–7 (6.4a) 6.0a
6.7a 56 (19)
17 (27) C50
100 6.35
4.5
33
156
Ozturk [21]
50 Ceran [20]
criteria for discharge prior to post-operative day 7, a repeat CT scan is performed only if they return to the Emergency Department for clinical deterioration with signs and symptoms of intra-abdominal abscess, on post-operative day 7 or later. As a result, we likely did not capture many patients.
Conflict of interest The authors declare that they have no conflicts of interest or relevant financial relationships to disclose.
Biner [22]
2.6 (1)
NA \7 (weekly) (7.9a) 6.8a 26 (13) 100
38 Bor [19]
NA
40 (2) 7–19 (every 3–5 days)
30–90 (monthly) all checked on day 10
35 Acun [18]
5.2
100
36.8 (14)
NA
4–9 (5.4a) 5.4a 14 (5) 100
33 (NA) 70a NA Herek [17]
NA
34 Bonnet [16]
4.08
0 (0)
NA 2–63 (NA) 4–22 (9a)
0 (0)
15 (5) 100
NA
30–150 (monthly) 3–5 (NA) b
18 (2)
6b
7
3–15 (every 3 days) 5–11 (9.1a) 5.3a 118 Palanduz [15]
17 (20) 100 0.25–14c
0 (0)
8–23 (weekly)
4–11 (every 3–5 days) 3–7 (NA)
2–9 (3.8a) 7.5a
NA 3 (5) 151
44
Kong [13]
25 (11) 100
C50
325
Papadopoulou [14]
1.6
NA
19 (3)
19 (3)
2–63 (every 3–7 days)
11–63 (NA) 3–10 (6a)
4–22 (9a) 7.8a
4.4a 46 (16)
43 (16) 60–100 NA
3.1
37
35
Schaad [1]
Schaad [12]
100
Age with pseudolithiasis (years) % Pseudolithiasis (n) Ceftriaxone dose (mg/kg/day) Mean age (years) Number of children Study
Table 1 Prospective cohort studies evaluating ceftriaxone-associated biliary pseudolithiasis
Range of days to pseudolithiasis formation
Days to resolution of pseudolithiasis (frequency of follow up ultrasound)
% Symptomatic (n)
Pediatr Surg Int (2014) 30:323–326
1. Schaad UB, Wedgwood-Krucko J, Tschaeppeler H (1988) Reversible ceftriaxone-associated biliary pseudolithiasis in children. Lancet 2:1411–1413 2. Pigrau C, Pahissa A, Gropper S, Sureda D, Martinez-Vazquez JM (1989) Ceftriaxone-associated biliary pseudolithiasis in adults. Lancet 2:165 3. Schaad UB, Tschaeppeler H, Lentze MJ (1986) Transient formation of precipitations in the gallbladder associated with ceftriaxone therapy. Pediatr Infect Dis 5:708–710 4. Meng D, Cao Y, Fu J, Chen R, Lu L, Tu Y (2010) Sonographic assessment of ceftriaxone-associated pseudolithiasis in Chinese children. J Int Med Res 38:2004–2010 5. St. Peter SD, Little DC, Calkins CM, Murphy JP, Holcomb GW, Sharp RJ, Snyder CL, Ostlie DJ (2006) A simple and more cost effective antibiotic regimen for perforated appendicitis. J Pediatr Surg 41(5):1020–1024 6. St. Peter SD, Tsao K, Spilde TL, Sharp SW, Holcomb GW III, Murphy JP, Snyder CL, Sharp RJ, Andrews WS, Ostlie DJ (2008) Single daily dosing ceftriaxone and flagyl versus standard triple antibiotic regimen for perforated appendicitis in children: a prospective, randomized trial. J Pediatr Surg 43(6):981–985 7. Fraser JD, Aguayo P, Leys CM, Keckler SJ, Newland J, Sharp SW, Murphy JP, Snyder CL, Sharp RJ, Andrews WS, Holcomb GW III, Ostlie DJ, St. Peter SD (2010) A complete course of intravenous antibiotics versus a combination of intravenous and oral antibiotics for perforated appendicitis in children: a prospective, randomized trial. J Pediatr Surg 45(6):1198–1202 8. St. Peter SD, Adibe OO, Iqbal CW, Fike FB, Sharp SW, Juang D, Lanning D, Murphy JP, Andrews WS, Sharp RJ, Snyder CL, Holcomb GW III, Ostlie DJ (2012) Irrigation versus suction alone during laparoscopic appendectomy for perforated appendicitis: a prospective randomized trial. Ann Surg 256(4):581–585 9. St. Peter SD, Aguayo P, Fraser JD, Keckler SJ, Sharp SW, Leys CM, Murphy JP, Snyder CL, Sharp RJ, Andrews WS, Holcomb GW III, Ostlie DJ (2010) Initial laparoscopic appendectomy upon presentation versus initial non-operative management and interval appendectomy for perforated appendicitis with abscess: a prospective, randomized trial. J Pediatr Surg 45(1):236–240
123
326 10. Schiffman ML, Keith FB, Moore EW (1990) Pathogenesis of ceftriaxone-associated biliary sludge. In vitro studies of calcium ceftriaxone binding and solubility. Gastroenterology 99(6):1772–1778 11. Park HZ, Lee SP, Schy AL (1991) Ceftriaxone-associated gallbladder sludge. Identification of calcium-ceftriaxone salt as a major component of gallbladder precipitate. Gastroenterology 100(6):1665–1670 12. Schaad UB, Suter S, Gianella-Borradori A, Pfenninger J, Auckenthaler R, Bernath O, Cheseaux J, Wedgwood J (1990) A comparison of ceftriaxone and cefuroxime for the treatment of bacterial meningitis in children. New Engl J Med 322(3):140–147 13. Kong M, Chen C (1996) Risk factors leading to ceftriaxoneassociated biliary pseudolithiasis in children. Chang Gung Med J 19(1):50–54 14. Papadopoulou F, Efremidis S, Karyda S, Badouraki M, Karatza E, Panteliadis C, Malaka K (1999) Incidence of ceftriaxone-associated gallbladder pseudolithiasis. Acta Paediatr 88:1352–1355 15. Palanduz A, Yalcin I, Tonguc E, Guler N, Ones U, Salman N, Somer A (2000) Sonographic assessment of ceftriaxone-associated biliary pseudolithiasis in children. J Clin Ultrasound 28(4):166–168 16. Bonnet JP, Abid L, Dabhar A, Levy A, Soulier Y, Blangy S (2000) Early biliary pseudolithiasis during ceftriaxone therapy for
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17. 18.
19.
20.
21.
22.
acute pyelonephritis in children: a prospective study in 34 children. Eur J Pediatr Surg 10:368–371 Herek O, Pakdemirli E, Kocer N (2001) Ceftriaxone-associated biliary pseudolithiasis in children. Eur Radiol 11:902 Acun C, Erdem LO, Sogut A, Erdem CZ, Tomac N, Gundogdu S, Cavuldak S (2004) Gallbladder and urinary tract precipitations associated with ceftriaxone therapy in children: a prospective study. Ann Trop Paediatr 24:25–31 Bor O, Dinleyici EC, Kebapci M, Aydogdu SD (2004) Ceftriaxone-associated biliary sludge and pseudocholelithiasis during childhood: a prospective study. Pediatr Int 46:322–324 Ceran C, Oztoprak I, Cankorkmaz L, Gumus C, Yildiz T, Koyluoglu G (2005) Ceftriaxone-associated biliary pseudolithiasis in paediatric surgical patients. Int J Antimicrob Agents 25:256–259 Ozturk A, Kaya M, Zeyrek D, Ozturk E, Kat N, Ziylan Z (2005) Ultrasonographic findings in ceftriaxone: associated biliary sludge and pseudolithiasis in children. Acta Radiol 1:112–116 Biner B, Oner N, Celtik C, Bostancioglu M, Tuncbilek N, Guzel A, Karasalihoglu S (2006) Ceftriaxone-associated biliary pseudolithiasis in children. J Clin Ultrasound 34(5):217–222
ORIGINAL ARTICLE
Ceftriaxone-induced pseudolithiasis in children treated for perforated appendicitis Hanna Alemayehu • Amita A. Desai • Priscilla Thomas • Susan W. Sharp • Shawn D. St. Peter
Accepted: 13 January 2014 / Published online: 28 January 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose Ceftriaxone has been associated with development of pseudolithiasis. In our institution, it is used for treatment of perforated appendicitis in children. This study evaluated the occurrence of ceftriaxone-related pseudolithiasis in this population. Methods After obtaining IRB approval, we performed a retrospective chart review over 51 months. We included patients undergoing laparoscopic appendectomy for perforated appendicitis. All patients were treated with ceftriaxone post-operatively. Patients without initial or posttreatment gallbladder imaging available for review were excluded. Results There were 71 patients who met inclusion criteria with a mean (±SD) age of 10.8 ± 3.8 years. Of these, 14 % (n = 10) developed stones or sludge in the gallbladder. The mean duration of ceftriaxone therapy was 8.7 ± 3.8 days. The average time to post-antibiotic imaging was 11.5 ± 10.3 days from initiation of antibiotics. There was no significant difference in duration of ceftriaxone therapy in the children that developed pseudolithiasis or sludge (10.0 ± 4.9 days) compared to those that did not (8.5 ± 3.6, p = 0.26). One child (10 %) with pseudolithiasis went on to become symptomatic, requiring a laparoscopic cholecystectomy.
H. Alemayehu A. A. Desai P. Thomas S. W. Sharp S. D. St. Peter (&) Department of Surgery, Center for Prospective Clinical Trials, Children’s Mercy Hospital, 2401 Gillham Road, Kansas City, MO 64108, USA e-mail: [email protected] S. D. St. Peter Pediatric Surgery Training Program, Children’s Mercy Hospital, 2401 Gillham Road, Kansas City, MO 64108, USA
Conclusions In our experience, ceftriaxone use for perforated appendicitis is associated with a significant incidence of biliary pseudolithiasis, and is unrelated to duration of ceftriaxone therapy. Keywords Ceftriaxone Adverse effects Pseudolithiasis Perforated appendicitis
Introduction Ceftriaxone is a commonly used third-generation cephalosporin due to its broad spectrum coverage and convenience of daily dosing; however, gallbladder and urinary precipitation resulting in pseudolithiasis and sludge have been described in the pediatric and adult literature [1, 2], having first been described in 1986 [3]. Pseudolithiasis commonly occurs shortly after institution of therapy with the antibiotic and resolves after discontinuation of the medication [1]. It has been suggested that biliary pseudolithiasis is more common in the use of ceftriaxone to treat biliary tract infections, than non-biliary tract infections [4]. In our institution, it is used per protocol in children with perforated appendicitis as we have conducted several prospective, randomized trials in this population [5–9]. This study evaluated the occurrence of ceftriaxone-related pseudolithiasis in this population and the incidence of symptomatic presentation.
Methods After obtaining IRB approval, we performed a retrospective chart review over a 51 month period of all patients undergoing laparoscopic appendectomy for perforated
123
324
appendicitis who subsequently developed intra-abdominal abscesses. All patients were treated with ceftriaxone postoperatively for perforated appendicitis. The protocol to treat perforated appendicitis in our institution is once daily dosing of ceftriaxone, 50 mg/kg with a maximum dose of 2 g, infused over 10 min. This patient population had both initial diagnostic computed tomography (CT) scans, and post-treatment CT scans for diagnosis of intra-abdominal abscesses. Both initial and post-treatment CT scans were reviewed for the presence of gallstones or gallbladder sludge as determined by a staff radiologist at the time of the study, and confirmed by the research personnel. Gallstones and gallbladder sludge were, respectively, defined as visually detectable high attenuation stones or visually detectable high attenuation material layering in the gallbladder. Patients without initial or post-treatment gallbladder imaging available for review were excluded. Means are expressed with standard deviation. Comparative analysis was performed using the two-tailed student t test, and a p value \0.05 was deemed significant.
Results There were 71 patients who met inclusion criteria, with a mean age of 10.8 ± 3.8. Ten patients (14 %) developed stones or sludge in the gallbladder. The mean duration of ceftriaxone therapy was 8.7 ± 3.8 days. The average time to post-antibiotic imaging was 11.5 ± 10.3 days from initiation of antibiotics. There was no significant difference in duration of ceftriaxone therapy in the children that developed pseudolithiasis or sludge compared to those that did not (10.0 ± 4.9 vs. 8.5 ± 3.6 days, respectively, p = 0.26). There was also no difference in mean age, which was 10.4 ± 4.2 with pseudolithiasis and 10.8 ± 3.8 without (p = 0.76). Only one child with biliary pseudolithiasis became symptomatic, and underwent a laparoscopic cholecystectomy. Pathology in this patient showed chronic cholecystitis on microscopic exam, and gross examination showed the gallbladder to be filled with dark green bile admixed with yellow, grainy appearing material.
Discussion Ceftriaxone was introduced to the market in the United States in 1984, which was shortly followed by the first description of biliary precipitations associated with the antibiotic [3]. The pathophysiology is thought to relate to the biliary excretion of ceftriaxone and the calcium–ceftriaxone salt precipitation in the gallbladder secondary to a significantly higher biliary concentration than serum concentration [10, 11]. An early prospective cohort study
123
Pediatr Surg Int (2014) 30:323–326
described the incidence and transient nature of the problem in 37 patients [1]. Several prospective studies have since looked at the problem of ceftriaxone-associated biliary pseudolithiasis in children, which are summarized in Table 1 [1, 4, 12–22]. Evident from this table is that ceftriaxone-related pseudolithiasis is not uncommon, ranging from 3 to 56 %. Also apparent from these studies is the transient nature of the finding, and the low likelihood of producing a clinical impact. Our occurrence rate of 14 % was lower than many of the series in Table 1; however, when looking at the studies evaluating patients treated with the same dose we use (50 mg/kg/d), our occurrence rate was similar (3–17 %). This may indicate that the higher incidences seen in the other studies using higher doses may in fact be secondary to a dose-dependent increased occurrence rate as shown by some studies [10, 22]. This, however, has not been shown in other studies [13]. Another explanation for our relatively low occurrence rate is the fact that we performed repeat imaging 11.5 ± 10.3 days from initiation of antibiotics. The mean duration of ceftriaxone therapy was 10.0 ± 4.9 days, and in some patients, repeat imaging was performed after the cessation of antibiotics so we may have missed the window to capture them since the majority resolve within 3 weeks (Table 1). Our study also did not demonstrate the association with older age that has been shown by other studies [1, 3, 12, 14, 22]; implying that in children with perforated appendicitis, age plays less of a role than in the other disease models studied. We found that duration of ceftriaxone therapy was not a predictive factor for the development of pseudolithiasis, and this is in agreement with previous studies [1, 13, 15, 20, 21]. In our series, 1 patient underwent cholecystectomy 18 days after cessation of ceftriaxone, comprising 10 % of the patients that developed pseudolithiasis, which fits nicely within the range of symptomatic cases previously reported (Table 1). The symptomatic patients in these studies typically resolved symptoms when the biliary imaging normalized. Since the reported range of resolution of pseudolithiasis is 2–150 days, it is reasonable to manage these cases expectantly provided their severity of symptoms will allow observation. The major limitation of our study was the lack of uniformity in timing of repeat imaging after initiation of antibiotics as it was not the primary objective to track for development and resolution of pseudolithiasis; this was a secondary investigation. The protocol for repeat imaging in post-operative patients with perforated appendicitis at our institution includes the performance of a CT scan on postoperative day 7 for patients that have not shown clinical improvement while in the hospital. For patients who meet
100 (25) 7–54 (every 3 days)
Conclusions In our experience, ceftriaxone use for perforated appendicitis is associated with a significant incidence of biliary pseudolithiasis and/or sludge. The development of pseudolithiasis is unrelated to duration of ceftriaxone therapy. The finding is usually asymptomatic requiring no further intervention.
2–7 (NA) 30–80
43 (25)
NA
References
Median value
Mean value
Range in years c
b
a
NA not available
58 Meng [4]
2.8
0 (0)
19 (5) 10–30 (weekly)
4–21 (every 4–6 days) 4–8 (7.2a)
3–7 (6.4a) 6.0a
6.7a 56 (19)
17 (27) C50
100 6.35
4.5
33
156
Ozturk [21]
50 Ceran [20]
criteria for discharge prior to post-operative day 7, a repeat CT scan is performed only if they return to the Emergency Department for clinical deterioration with signs and symptoms of intra-abdominal abscess, on post-operative day 7 or later. As a result, we likely did not capture many patients.
Conflict of interest The authors declare that they have no conflicts of interest or relevant financial relationships to disclose.
Biner [22]
2.6 (1)
NA \7 (weekly) (7.9a) 6.8a 26 (13) 100
38 Bor [19]
NA
40 (2) 7–19 (every 3–5 days)
30–90 (monthly) all checked on day 10
35 Acun [18]
5.2
100
36.8 (14)
NA
4–9 (5.4a) 5.4a 14 (5) 100
33 (NA) 70a NA Herek [17]
NA
34 Bonnet [16]
4.08
0 (0)
NA 2–63 (NA) 4–22 (9a)
0 (0)
15 (5) 100
NA
30–150 (monthly) 3–5 (NA) b
18 (2)
6b
7
3–15 (every 3 days) 5–11 (9.1a) 5.3a 118 Palanduz [15]
17 (20) 100 0.25–14c
0 (0)
8–23 (weekly)
4–11 (every 3–5 days) 3–7 (NA)
2–9 (3.8a) 7.5a
NA 3 (5) 151
44
Kong [13]
25 (11) 100
C50
325
Papadopoulou [14]
1.6
NA
19 (3)
19 (3)
2–63 (every 3–7 days)
11–63 (NA) 3–10 (6a)
4–22 (9a) 7.8a
4.4a 46 (16)
43 (16) 60–100 NA
3.1
37
35
Schaad [1]
Schaad [12]
100
Age with pseudolithiasis (years) % Pseudolithiasis (n) Ceftriaxone dose (mg/kg/day) Mean age (years) Number of children Study
Table 1 Prospective cohort studies evaluating ceftriaxone-associated biliary pseudolithiasis
Range of days to pseudolithiasis formation
Days to resolution of pseudolithiasis (frequency of follow up ultrasound)
% Symptomatic (n)
Pediatr Surg Int (2014) 30:323–326
1. Schaad UB, Wedgwood-Krucko J, Tschaeppeler H (1988) Reversible ceftriaxone-associated biliary pseudolithiasis in children. Lancet 2:1411–1413 2. Pigrau C, Pahissa A, Gropper S, Sureda D, Martinez-Vazquez JM (1989) Ceftriaxone-associated biliary pseudolithiasis in adults. Lancet 2:165 3. Schaad UB, Tschaeppeler H, Lentze MJ (1986) Transient formation of precipitations in the gallbladder associated with ceftriaxone therapy. Pediatr Infect Dis 5:708–710 4. Meng D, Cao Y, Fu J, Chen R, Lu L, Tu Y (2010) Sonographic assessment of ceftriaxone-associated pseudolithiasis in Chinese children. J Int Med Res 38:2004–2010 5. St. Peter SD, Little DC, Calkins CM, Murphy JP, Holcomb GW, Sharp RJ, Snyder CL, Ostlie DJ (2006) A simple and more cost effective antibiotic regimen for perforated appendicitis. J Pediatr Surg 41(5):1020–1024 6. St. Peter SD, Tsao K, Spilde TL, Sharp SW, Holcomb GW III, Murphy JP, Snyder CL, Sharp RJ, Andrews WS, Ostlie DJ (2008) Single daily dosing ceftriaxone and flagyl versus standard triple antibiotic regimen for perforated appendicitis in children: a prospective, randomized trial. J Pediatr Surg 43(6):981–985 7. Fraser JD, Aguayo P, Leys CM, Keckler SJ, Newland J, Sharp SW, Murphy JP, Snyder CL, Sharp RJ, Andrews WS, Holcomb GW III, Ostlie DJ, St. Peter SD (2010) A complete course of intravenous antibiotics versus a combination of intravenous and oral antibiotics for perforated appendicitis in children: a prospective, randomized trial. J Pediatr Surg 45(6):1198–1202 8. St. Peter SD, Adibe OO, Iqbal CW, Fike FB, Sharp SW, Juang D, Lanning D, Murphy JP, Andrews WS, Sharp RJ, Snyder CL, Holcomb GW III, Ostlie DJ (2012) Irrigation versus suction alone during laparoscopic appendectomy for perforated appendicitis: a prospective randomized trial. Ann Surg 256(4):581–585 9. St. Peter SD, Aguayo P, Fraser JD, Keckler SJ, Sharp SW, Leys CM, Murphy JP, Snyder CL, Sharp RJ, Andrews WS, Holcomb GW III, Ostlie DJ (2010) Initial laparoscopic appendectomy upon presentation versus initial non-operative management and interval appendectomy for perforated appendicitis with abscess: a prospective, randomized trial. J Pediatr Surg 45(1):236–240
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