Chemical peritonitis in a patient treated with icodextrin and intraperitoneal vancomycin
Peritonitis química en un paciente tratado con icodextrina y vancomicina intraperitoneal
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Freitas, Cristina Freitas, A. Rodrigues, Anabela Rodrigues, M.J. Carvalho, Maria João Carvalho, A. Cabrita, António Cabrita" "autores" => array:8 [ 0 => array:4 [ "Iniciales" => "C." "apellidos" => "Freitas" "email" => array:1 [ 0 => "crislmf@yahoo.com.br" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 1 => array:4 [ "nombre" => "Cristina" "apellidos" => "Freitas" "email" => array:1 [ 0 => "crislmf@yahoo.com.br" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 2 => array:3 [ "Iniciales" => "A." "apellidos" => "Rodrigues" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 3 => array:3 [ "nombre" => "Anabela" "apellidos" => "Rodrigues" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 4 => array:3 [ "Iniciales" => "M.J." "apellidos" => "Carvalho" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 5 => array:3 [ "nombre" => "Maria João" "apellidos" => "Carvalho" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 6 => array:3 [ "Iniciales" => "A." "apellidos" => "Cabrita" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 7 => array:3 [ "nombre" => "António" "apellidos" => "Cabrita" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:3 [ "entidad" => "Unidad de Nefrología, Hospital Santo António, Porto, Portugal, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Peritonitis química en un paciente tratado con icodextrina y vancomicina intraperitoneal" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Tab. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "10989_108_17844_en_t1.10989.jpg" "Alto" => 326 "Ancho" => 600 "Tamanyo" => 142416 ] ] "descripcion" => array:1 [ "en" => "Evolution of effluent characteristics" ] ] ] "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Dear Editor:</span></p><p class="elsevierStylePara">Peritonitis is the principal cause of peritoneal dialysis (PD) catheter loss and the primary reason why patients switch from PD to hemodialysis<span class="elsevierStyleSup">1</span>. It causes death in 6% of patients, particularly when it is caused by <span class="elsevierStyleItalic">Staphylococcus aureus</span>, enteric organisms and fungus<span class="elsevierStyleSup">2</span>.</p><p class="elsevierStylePara">Prompt initiation of antibiotics is critical and they should be started as soon as a cloudy effluent is seen, even without confirmation of the cell count from laboratory<span class="elsevierStyleSup">3</span>. G<span class="elsevierStyleItalic">uidelines</span> recommend empirical treatment with an association of vancomycin or a cephalosporin with aminoglycoside or third-generation cephalosporin<span class="elsevierStyleSup">3</span>.</p><p class="elsevierStylePara">Chemical peritonitis, described as peritoneal inflammation caused by a non-infectious agent (such antibiotics and dialysis solutions) is a rarer condition.</p><p class="elsevierStylePara">Chemical peritonitis induced by vancomycin was first described in 1986<span class="elsevierStyleSup">4</span> and near 90 similar cases were reported in the 80-90th decade<span class="elsevierStyleSup">5,6</span>. Since then no other case was noted.</p><p class="elsevierStylePara">Icodextrin-induced peritonitis has first described in 1999<span class="elsevierStyleSup">7</span>, but its prevalence is not clear. An epidemic outbreak occurred in Europe in 2002, related to solution contamination<span class="elsevierStyleSup">8</span>. Few cases were reported after improving manufacturing process, all related to “sensibilization” during that period or to other contaminations<span class="elsevierStyleSup">8</span>.</p><p class="elsevierStylePara">We reported a case of chemical peritonitis in a patient treated with icodextrin and intraperitoneal vancomycin, in which vancomycin seems to be the offending agent.</p><p class="elsevierStylePara">A 34-year-old man, with renal failure secondary to diabetic nephropathy, was in PD since 2006. Icodextrin was introduced one year after PD initiation. No peritonitis episodes were detected in the following years.</p><p class="elsevierStylePara">In 2009, he came to hospital with mild abdominal pain with four hours of evolution. He hadn’t other symptoms, exit-site hadn’t inflammatory signs and effluent was clear. Effluent analysis revealed 26 cells/µl (table 1), abdominal radiography and ultrasound were normal.</p><p class="elsevierStylePara">Intraperitoneal vancomycin (2 g each 5 days) and ceftazidime (1 g each day) were administrated and patient was discarried, maintaining icodextrin.</p><p class="elsevierStylePara">In the next day, he returned with cloudy effluent (table 1). The same treatment was maintained and cloudy effluent disappeared in the two following days.</p><p class="elsevierStylePara">At the 5th day, he was asymptomatic and came for second vancomycin administration. Latter in that day, abdominal pain and cloudy effluent reappeared (table 1).</p><p class="elsevierStylePara">PD was suspended and hemodialysis was started. Vancomycin and ceftazidime were switch to intravenous route and an extra daily dose of intraperitoneal ceftazidime (500 mg) was maintained. He became asymptomatic and cloudy effluent disappeared in the following two days. All cultures, including fungus and <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> were sterile.</p><p class="elsevierStylePara">At the 9th day, he reassumed PD (with icodextrin) and at 10th day intraperitoneal vancomycin was delivered. Cloudy effluent reappeared after vancomycin administration. At 12th day, he was asymptomatic and discarried (table 1).</p><p class="elsevierStylePara">Three months later, he remains asymptomatic, with preserved ultrafiltration and clean effluent.</p><p class="elsevierStylePara">Patients with peritonitis usually present with cloudy fluid and abdominal pain. Effluent’s leukocytes superior to 100/ml (with 50% polymophonuclear cells) indicate the presence of inflammation, with infectious peritonitis being the most likely cause<span class="elsevierStyleSup">3</span>. However, in short dwell time leukocytes may not reach 100/ml<span class="elsevierStyleSup">3</span> and peritonitis may present with abdominal pain and no cloudy effluent<span class="elsevierStyleSup">3</span>.</p><p class="elsevierStylePara">In our patient, other causes of abdominal pain such as gastroenteritis, pancreatitis, appendicitis or pneumoperitoneum were excluded and empirical treatment for infectious peritonitis was started. The cloudy effluent present in the following day was assumed to be a late expression of peritonitis in fluid of a longer dwell time.</p><p class="elsevierStylePara">Abdominal pain and cloudy effluent reappeared after second vancomycin administration and he was admitted with suspicion of refractory peritonitis. If the suspicion was confirmed, peritoneal catheter should be removed and patient switched to hemodialysis<span class="elsevierStyleSup">9</span>. However, he didn’t present the typical evolution of a refractory infectious peritonitis and other causes of cloudy effluent, such as hemoperitoneum, malignancy, eosinophilic and chylous effluent were excluded<span class="elsevierStyleSup">10</span>. Chemical peritonitis related to icodextrin or vancomycin remained a plausible diagnosis<span class="elsevierStyleSup">5,6</span>.</p><p class="elsevierStylePara">Icodextrin induced-peritonitis seems to be caused by contamination of solution by peptidoglycans released from bacteria (<span class="elsevierStyleItalic">Alicylobacillus acidocaldarius</span>) during the manufacturing process<span class="elsevierStyleSup">8</span>. Improvement in the process decreased its frequency from a peak of 0.912% in 2002 to 0.013% in 2003<span class="elsevierStyleSup">8</span>.</p><p class="elsevierStylePara">Patients present with mild abdominal pain and cloudy effluent, without rebound, fever or rash<span class="elsevierStyleSup">11,12</span>. Effluent leukocytes vary from 100 to 6,000/µl<span class="elsevierStyleSup">11,13</span>, with mononuclear predominance<span class="elsevierStyleSup">11</span>. Culture is always sterile<span class="elsevierStyleSup">11</span>. </p><p class="elsevierStylePara">Delay between the initiation of the icodextrin and first symptoms varies from few hours to several years<span class="elsevierStyleSup">7,12</span>. Clinical course is undulating, with intermittent pain and dialysate cloudiness after each icodextrin dwell, without response to antibiotics<span class="elsevierStyleSup">12</span>. Discontinuation of icodextrin leads to relief of the symptoms and normalization of leukocytes within 24-48 hours, but relapse is invariably induced after rechallenge<span class="elsevierStyleSup">12</span>.</p><p class="elsevierStylePara">In our patient, neither temporal relation with icodextrin administration was detected nor was relapse noted after rechallenge.</p><p class="elsevierStylePara">A temporal relation with the vancomycin administration supported the diagnosis of vancomycin-induced chemical peritonitis.</p><p class="elsevierStylePara">The clinical presentation ranges from cloudy effluent alone to severe abdominal pain and fever. It begins 2-12 hours after vancomycin administration<span class="elsevierStyleSup">5</span> and resolves within 3 to 4 days after suspension<span class="elsevierStyleSup">6</span>. There is a predominantly of neutrophils, with eosinophils ranging from 0-10%<span class="elsevierStyleSup">5,6</span>.</p><p class="elsevierStylePara">The reported incidence of vancomicyn (Vancoled<span class="elsevierStyleSup">®</span>)-induced peritonitis was 23%<span class="elsevierStyleSup">6</span>. The underlying mechanism is unknown<span class="elsevierStyleSup">5,14</span>. Some patients experience recurrence of abdominal pain and/or effluent leukocytes elevations on re-exposure to intraperitoneal vancomycin, without complains when intravenous or intraperitoneal vancomycin from another manufacturer’s brand is administrated<span class="elsevierStyleSup">5</span>. These results support the suspicion that inflammation is not completely due to vancomycin itself but to another constituent of its preparation<span class="elsevierStyleSup">14,15</span>.</p><p class="elsevierStylePara">Vancomycin include 5.2-16.7% impurities, depending both on the brand and the lot of the preparation<span class="elsevierStyleSup">14,15</span>. The varying amount of impurities present in individual lots may determine whether inflammatory reaction occurs<span class="elsevierStyleSup">6</span>. </p><p class="elsevierStylePara">No fatalities were reported<span class="elsevierStyleSup">6,7</span> and no treatment is recommended except for suspension of offending agent<span class="elsevierStyleSup">7</span>.</p><p class="elsevierStylePara">Although it is clinically benign with spontaneous resolution, the long-term sequelae are still unknown. Moreover, it could be confused with infectious peritonitis and lead to unnecessary antibiotic prescription or to catheter removal and PD suspension<span class="elsevierStyleSup">7</span>.</p><p class="elsevierStylePara">In last 15 years, none case of vancomycin-induced peritonitis was reported, maybe due to progressive improvement in purifications. In a time where generic preparations are in increasing use, our case may alert physicians to the presence of this forgotten adverse effect.</p><p class="elsevierStylePara"><a href="grande/10989_108_17844_en_t1.10989.jpg" class="elsevierStyleCrossRefs"><img src="10989_108_17844_en_t1.10989.jpg" alt="Evolution of effluent characteristics"></img></a></p><p class="elsevierStylePara">Table 1. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 6 | 14 |
| 2024 October | 85 | 27 | 112 |
| 2024 September | 70 | 19 | 89 |
| 2024 August | 108 | 62 | 170 |
| 2024 July | 79 | 25 | 104 |
| 2024 June | 76 | 37 | 113 |
| 2024 May | 87 | 42 | 129 |
| 2024 April | 63 | 23 | 86 |
| 2024 March | 49 | 25 | 74 |
| 2024 February | 63 | 35 | 98 |
| 2024 January | 49 | 21 | 70 |
| 2023 December | 51 | 37 | 88 |
| 2023 November | 43 | 33 | 76 |
| 2023 October | 66 | 50 | 116 |
| 2023 September | 48 | 37 | 85 |
| 2023 August | 69 | 22 | 91 |
| 2023 July | 61 | 31 | 92 |
| 2023 June | 49 | 24 | 73 |
| 2023 May | 85 | 43 | 128 |
| 2023 April | 40 | 22 | 62 |
| 2023 March | 66 | 28 | 94 |
| 2023 February | 44 | 24 | 68 |
| 2023 January | 51 | 22 | 73 |
| 2022 December | 49 | 52 | 101 |
| 2022 November | 33 | 33 | 66 |
| 2022 October | 50 | 44 | 94 |
| 2022 September | 54 | 39 | 93 |
| 2022 August | 49 | 39 | 88 |
| 2022 July | 44 | 37 | 81 |
| 2022 June | 50 | 46 | 96 |
| 2022 May | 30 | 42 | 72 |
| 2022 April | 48 | 62 | 110 |
| 2022 March | 48 | 50 | 98 |
| 2022 February | 44 | 52 | 96 |
| 2022 January | 44 | 31 | 75 |
| 2021 December | 40 | 41 | 81 |
| 2021 November | 66 | 40 | 106 |
| 2021 October | 69 | 46 | 115 |
| 2021 September | 46 | 37 | 83 |
| 2021 August | 46 | 48 | 94 |
| 2021 July | 40 | 36 | 76 |
| 2021 June | 52 | 31 | 83 |
| 2021 May | 42 | 29 | 71 |
| 2021 April | 150 | 88 | 238 |
| 2021 March | 75 | 36 | 111 |
| 2021 February | 99 | 30 | 129 |
| 2021 January | 58 | 18 | 76 |
| 2020 December | 65 | 16 | 81 |
| 2020 November | 59 | 13 | 72 |
| 2020 October | 62 | 14 | 76 |
| 2020 September | 49 | 7 | 56 |
| 2020 August | 59 | 13 | 72 |
| 2020 July | 65 | 7 | 72 |
| 2020 June | 60 | 9 | 69 |
| 2020 May | 52 | 16 | 68 |
| 2020 April | 64 | 23 | 87 |
| 2020 March | 45 | 14 | 59 |
| 2020 February | 57 | 27 | 84 |
| 2020 January | 66 | 27 | 93 |
| 2019 December | 51 | 32 | 83 |
| 2019 November | 46 | 22 | 68 |
| 2019 October | 34 | 6 | 40 |
| 2019 September | 48 | 22 | 70 |
| 2019 August | 29 | 16 | 45 |
| 2019 July | 34 | 23 | 57 |
| 2019 June | 29 | 8 | 37 |
| 2019 May | 23 | 19 | 42 |
| 2019 April | 81 | 42 | 123 |
| 2019 March | 39 | 19 | 58 |
| 2019 February | 23 | 16 | 39 |
| 2019 January | 23 | 16 | 39 |
| 2018 December | 81 | 34 | 115 |
| 2018 November | 103 | 13 | 116 |
| 2018 October | 77 | 13 | 90 |
| 2018 September | 55 | 14 | 69 |
| 2018 August | 49 | 20 | 69 |
| 2018 July | 52 | 16 | 68 |
| 2018 June | 43 | 14 | 57 |
| 2018 May | 45 | 9 | 54 |
| 2018 April | 41 | 8 | 49 |
| 2018 March | 43 | 5 | 48 |
| 2018 February | 46 | 5 | 51 |
| 2018 January | 52 | 4 | 56 |
| 2017 December | 51 | 9 | 60 |
| 2017 November | 42 | 12 | 54 |
| 2017 October | 37 | 8 | 45 |
| 2017 September | 36 | 9 | 45 |
| 2017 August | 27 | 7 | 34 |
| 2017 July | 37 | 12 | 49 |
| 2017 June | 42 | 8 | 50 |
| 2017 May | 42 | 8 | 50 |
| 2017 April | 30 | 10 | 40 |
| 2017 March | 23 | 7 | 30 |
| 2017 February | 23 | 7 | 30 |
| 2017 January | 23 | 4 | 27 |
| 2016 December | 50 | 6 | 56 |
| 2016 November | 55 | 2 | 57 |
| 2016 October | 86 | 7 | 93 |
| 2016 September | 109 | 3 | 112 |
| 2016 August | 181 | 11 | 192 |
| 2016 July | 152 | 3 | 155 |
| 2016 June | 111 | 0 | 111 |
| 2016 May | 132 | 0 | 132 |
| 2016 April | 96 | 0 | 96 |
| 2016 March | 80 | 0 | 80 |
| 2016 February | 126 | 0 | 126 |
| 2016 January | 97 | 0 | 97 |
| 2015 December | 113 | 0 | 113 |
| 2015 November | 75 | 0 | 75 |
| 2015 October | 78 | 0 | 78 |
| 2015 September | 55 | 0 | 55 |
| 2015 August | 73 | 0 | 73 |
| 2015 July | 90 | 0 | 90 |
| 2015 June | 28 | 0 | 28 |
| 2015 May | 46 | 0 | 46 |
| 2015 April | 5 | 0 | 5 |
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