• 1.

    Kitzman D, Wei S-Y, Fleckenstein L, 2006. Liquid chromatographic assay of ivermectin in human plasma for application to clinical pharmacokinetic studies. J Pharm Biomed Anal 40: 10131020.

    • Search Google Scholar
    • Export Citation
  • 2.

    Chhonker YS, Edi C, Murry DJ, 2017. LC-MS/MS method for simultaneous determination of diethylcarbamazine, albendazole and albendazole metabolites in human plasma: application to a clinical pharmacokinetic study. J Pharm Biomed Anal 151: 8490.

    • Search Google Scholar
    • Export Citation
  • 3.

    Ceballos L, Krolewiecki A, Juárez M, Moreno L, Schaer F, Alvarez LI, Cimino R, Walson J, Lanusse CE, 2018. Assessment of serum pharmacokinetics and urinary excretion of albendazole and its metabolites in human volunteers. PLoS Negl Trop Dis 12: e0005945.

    • Search Google Scholar
    • Export Citation
  • 4.

    Marriner S, Morris D, Dickson B, Bogan J, 1986. Pharmacokinetics of albendazole in man. Eur J Clin Pharmacol 30: 705708.

  • 5.

    Rose CE, Paciullo CA, Kelly DR, Dougherty MJ, Fleckenstein LL, 2009. Fatal outcome of disseminated strongyloidiasis despite detectable plasma and cerebrospinal levels of orally administered ivermectin. J Parasitol Res 2009: 818296.

    • Search Google Scholar
    • Export Citation
  • 6.

    Barrett J, Broderick C, Soulsby H, Wade P, Newsholme W, 2016. Subcutaneous ivermectin use in the treatment of severe Strongyloides stercoralis infection: two case reports and a discussion of the literature. J Antimicrob Chemother 71: 220225.

    • Search Google Scholar
    • Export Citation
  • 7.

    Buonfrate D, Requena-Mendez A, Angheben A, Muñoz J, Gobbi F, Van Den Ende J, Bisoffi Z, 2013. Severe strongyloidiasis: a systematic review of case reports. BMC Infect Dis 13: 78.

    • Search Google Scholar
    • Export Citation
  • 8.

    Boggild AK, Libman M, Greenaway C, McCarthy A; CATMAT, 2016. CATMAT statement on disseminated strongyloidiasis: prevention, assessment and management guidelines. Can Commun Dis Rep 42: 1219.

    • Search Google Scholar
    • Export Citation
  • 9.

    Bogoch II, Khan K, Abrams H, Nott C, Leung E, Fleckenstein L, Keystone JS, 2015. Failure of ivermectin per rectum to achieve clinically meaningful serum levels in two cases of Strongyloides hyperinfection. Am J Trop Med Hyg 93: 9496.

    • Search Google Scholar
    • Export Citation
  • 10.

    Grein JD, Mathisen GE, Donovan S, Fleckenstein L, 2010. Serum ivermectin levels after enteral and subcutaneous administration for Strongyloides hyperinfection: a case report. Scand J Infect Dis 42: 234236.

    • Search Google Scholar
    • Export Citation
  • 11.

    de Moura EB, Maia M de O, Ghazi M, Amorim FF, Pinhati HM, 2012. Salvage treatment of disseminated strongyloidiasis in an immunocompromised patient: therapy success with subcutaneous ivermectin. Braz J Infect Dis 16: 479481.

    • Search Google Scholar
    • Export Citation
  • 12.

    Turner SA, Maclean JD, Fleckenstein L, Greenaway C, 2005. Parenteral administration of ivermectin in a patient with disseminated strongyloidiasis. Am J Trop Med Hyg 73: 911914.

    • Search Google Scholar
    • Export Citation
  • 13.

    Donadello K, Cristallini S, Taccone FS, Lorent S, Vincent J-L, de Backer D, Jacobs F, 2013. Strongyloides disseminated infection successfully treated with parenteral ivermectin: case report with drug concentration measurements and review of the literature. Int J Antimicrob Agents 42: 580583.

    • Search Google Scholar
    • Export Citation
  • 14.

    Leung V, Al-Rawahi GN, Grant J, Fleckenstein L, Bowie W, 2008. Failure of subcutaneous ivermectin in treating Strongyloides hyperinfection. Am J Trop Med Hyg 79: 853855.

    • Search Google Scholar
    • Export Citation
  • 15.

    Fusco DN, Downs JA, Satlin MJ, Pahuja M, Ramos L, Barie PS, Fleckenstein L, Murray HW, 2010. Non-oral treatment with ivermectin for disseminated strongyloidiasis. Am J Trop Med Hyg 83: 879883.

    • Search Google Scholar
    • Export Citation
  • 16.

    Marty FM, Lowry CM, Rodriguez M, Milner DA, Pieciak WS, Sinha A, Fleckenstein L, Baden LR, 2005. Treatment of human disseminated strongyloidiasis with a parenteral veterinary formulation of ivermectin. Clin Infect Dis 41: e5e8.

    • Search Google Scholar
    • Export Citation
  • 17.

    González Canga A, Sahagún Prieto AM, Diez Liébana MJ, Fernández Martínez N, Sierra Vega M, García Vieitez JJ, 2008. The pharmacokinetics and interactions of ivermectin in humans—a mini-review. AAPS J 10: 4246.

    • Search Google Scholar
    • Export Citation
  • 18.

    Mahanty S, Paredes A, Marzal M, Gonzalez E, Rodriguez S, Dorny P, Guerra-Giraldez C, Garcia HH, Nash T, 2011. Sensitive in vitro system to assess morphological and biochemical effects of praziquantel and albendazole on Taenia solium cysts. Antimicrob Agents Chemother 55: 211217.

    • Search Google Scholar
    • Export Citation
  • 19.

    Thomsen EK 2016. Efficacy, safety, and pharmacokinetics of coadministered diethylcarbamazine, albendazole, and ivermectin for treatment of bancroftian filariasis. Clin Infect Dis 62: 334341.

    • Search Google Scholar
    • Export Citation
  • 20.

    Skuhala T, Trkulja V, Desnica B, 2014. Albendazolesulphoxide concentrations in plasma and hydatid cyst and prediction of parasitological and clinical outcomes in patients with liver hydatidosis caused by Echinococcus granulosus. Croat Med J 55: 146155.

    • Search Google Scholar
    • Export Citation
  • 21.

    Paredes A, de Campos Lourenço T, Marzal M, Rivera A, Dorny P, Mahanty S, Guerra-Giraldez C, García HH, Nash TE, Cass QB; Peru the CWG, 2013. In vitro analysis of albendazole sulfoxide enantiomers shows that (+)-(R)-albendazole sulfoxide is the active enantiomer against Taenia solium. Antimicrob Agents Chemother 57: 944949.

    • Search Google Scholar
    • Export Citation
  • 22.

    Sarin R, Dash AP, Dua VK, 2004. Albendazole sulphoxide concentrations in plasma of endemic normals from a lymphatic filariasis endemic region using liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci 799: 233238.

    • Search Google Scholar
    • Export Citation
  • 23.

    Chhonker YS, Edi C, Murry DJ, 2018. LC–MS/MS method for simultaneous determination of diethylcarbamazine, albendazole and albendazole metabolites in human plasma: application to a clinical pharmacokinetic study. J Pharm Biomed Anal 151: 8490.

    • Search Google Scholar
    • Export Citation
  • 24.

    Jung H, Hurtado M, Sanchez M, Medina MT, Sotelo J, 1992. Clinical pharmacokinetics of albendazole in patients with brain cysticercosis. J Clin Pharmacol 32: 2831.

    • Search Google Scholar
    • Export Citation
  • 25.

    Bolfer L, Bandt C, Shih A, Buckley G, 2013. 1132: use of single pass lipid dialysis for the treatment of avermectin toxicity. Crit Care Med 41: A286A287.

    • Search Google Scholar
    • Export Citation
  • 26.

    Johnson CA, Simmons WD, 2000. Dialysis of Drugs. Thousand Oaks, CA: Nephrology Pharmacy Associates, Inc.

  • 27.

    Dzierba AL, Abrams D, Brodie D, 2017. Medicating patients during extracorporeal membrane oxygenation: the evidence is building. Crit Care 21: 66.

    • Search Google Scholar
    • Export Citation
  • 28.

    Shekar K 2012. Sequestration of drugs in the circuit may lead to therapeutic failure during extracorporeal membrane oxygenation. Crit Care 16: R194.

    • Search Google Scholar
    • Export Citation
  • 29.

    Venkatesan P, 1998. Albendazole. J Antimicrob Chemother 41: 145147.

  • 30.

    Dong MD, Karsenti N, Lau R, Ralevski F, Cheema K, Burton L, Klowak M, Boggild AK, 2016. Strongyloidiasis in Ontario: performance of diagnostic tests over a 14-month period. Travel Med Infect Dis 14: 625629.

    • Search Google Scholar
    • Export Citation
  • 31.

    Gattinoni L, Carlesso E, Langer T, 2011. Clinical review: extracorporeal membrane oxygenation. Crit Care 15: 243.

  • 32.

    Fardet L, Généreau T, Poirot J-L, Guidet B, Kettaneh A, Cabane J, 2007. Severe strongyloidiasis in corticosteroid-treated patients: case series and literature review. J Infect 54: 1827.

    • Search Google Scholar
    • Export Citation

 

 

 

 

Case Report: Ivermectin and Albendazole Plasma Concentrations in a Patient with Disseminated Strongyloidiasis on Extracorporeal Membrane Oxygenation and Continuous Renal Replacement Therapy

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  • 1 Department of Medicine, University of British Columbia, Vancouver, Canada;
  • 2 University of Nebraska Medical Centre, Omaha, Nebraska;
  • 3 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada;
  • 4 J. D. MacLean Centre for Tropical Diseases, McGill University, Montreal, Canada;
  • 5 Department of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada

Disseminated strongyloidiasis is often fatal, despite treatment with oral albendazole and parenteral ivermectin (IVM). Here, we report elevated plasma IVM and albendazole sulfoxide concentrations in the context of extracorporeal membrane oxygenation and continuous renal replacement therapy in a patient with disseminated strongyloidiasis treated with subcutaneous IVM and nasogastric albenzadole. Despite elevated drug plasma concentrations, live filariform larvae were detected in endotracheal aspirates after 2 weeks of treatment.

INTRODUCTION

It is estimated that between 30 and 100 million people are infected with Strongyloides. People with Strongyloides infection are increasingly exposed to immunosuppressive therapy, which is often administered without consideration of the risks for dissemination of the infection. The prognosis of disseminated strongyloidiasis is poor; even with recommended therapy, mortality rates are approximately 60%. No randomized controlled trials describe the optimal treatment regimen for disseminated strongyloidiasis. Ivermectin (IVM) and albendazole (ABZ) are recommended treatment, but it is not clear what dose or duration of therapy is optimal. Previous publications report tissue and plasma concentrations of IVM; however, none describe plasma ABZ concentrations in patients with disseminated strongyloidiasis or either drug in the context of advanced life support, specifically continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO). Patients with disseminated Strongyloides are often admitted to critical care with multiple organ failure, requiring multiple therapies that may affect treatment success. By describing IVM and ABZ plasma concentrations in the context of CRRT and venovenous ECMO, we hope to contribute to the understanding of the pharmacokinetics of medications used in the treatment of this often lethal yet preventable disease.

CASE PRESENTATION

A 62-year-old male with a recent diagnosis of granulomatous interstitial nephritis presented to the hospital with abdominal distension. Ten weeks before hospital admission, the patient had been started on 75 mg of prednisone daily followed by a slow taper. At the time of presentation, he was taking 35 mg of prednisone daily and was admitted for conservative treatment of gastric ileus. Three weeks earlier, the patient had been admitted for Klebsiella pneumoniae bacteremia and was discharged with ongoing abdominal pain. Past medical history was significant for poorly controlled type 2 diabetes, hypertension, and dyslipidemia. The patient was born and raised in Fiji and immigrated to Canada 41 years earlier. He had returned to Fiji on multiple occasions. His last visit was 20 years before presentation. In his youth, he occasionally walked around barefoot in rural Fiji. His travel history also included a visit to Saudi Arabia 3 years before presentation, and Malaysia and Singapore 10 months before presentation, where he walked barefoot on the beach.

Eight days after admission, the patient developed septic shock, Enterococcus faecium bacteremia, hypoxemic respiratory failure, and acute kidney injury. He was intubated and started on meropenem and vancomycin with norepinephrine, vasopressin, and CRRT support (continuous venovenous hemodiafiltration and ST150 filter). On day 9, Strongyloides stercoralis filariform larvae were seen on a Gram stain of an endotracheal tube aspirate. Anthelmintic therapy, including nasogastric IVM (15 mg daily), veterinary formulation of intramuscular IVM (30 mg daily, 353 μg/kg), and ABZ (400 mg via nasogastric tube daily) was initiated. Parenteral IVM was obtained through a veterinary clinic and oral IVM was obtained through Health Canada’s Special Access Program. The first doses of parenteral IVM were delivered intramuscularly rather than subcutaneously, as there was concern that peripheral edema would reduce the bioavailability of subcutaneous IVM. The patient had not taken oral IVM before receiving prednisone.

On day 11, the patient was transferred to a tertiary care hospital and was started on venovenous ECMO. Initial investigations on transfer demonstrated hemoglobin of 72 g/L, platelets of 100 × 109/L, and leukocytes of 9.1 × 109/L, with a differential demonstrating normal eosinophils (0.26 × 109/L). The patient’s albumin was 35 g/L. Serology tests for human T-lymphotrophic virus-1 and human immunodeficiency virus were negative. Computed tomography of the abdomen showed gastric, duodenal, and jejunal distension. The route of IVM administration was changed to subcutaneous 17 mg daily (200 mcg/kg), and nasogastric IVM was discontinued. On day 13, the nasogastric tube was advanced to a post-pyloric location to increase the delivery of ABZ to the small intestine. Throughout the admission, the patient received stress-dose hydrocortisone (50 mg IV q6h). On day 15, he received pulse steroids (methylprednisone 1 g IV daily × 3 days) because of radiographic findings suspicious for organizing pneumonia after brief radiographic improvement.

On day 19, the patient was decannulated from ECMO. On day 20, motile filariform larvae were again seen on wet mount of a tracheal aspirate. The detection of live larvae after 11 days of treatment prompted measurement of IVM and ABZ concentrations because of concerns that ECMO might alter the pharmacokinetics of the medications.

Stored plasma samples obtained from peripheral venipuncture from days 12 and 24 were sent for determination of IVM, ABZ, and ABZ metabolite concentrations (see Table 1). The day 12 sample was taken 5.5 and 17.5 hours after the last ABZ and IVM doses, respectively. The day 24 sample was taken 7.3 and 8.3 hours after the last ABZ and IVM doses, respectively. On day 12, the patient was on ECMO and CRRT and the nasogastric tube delivered ABZ to the stomach. On day 24, the patient had been decannulated from ECMO and the nasogastric tube delivered ABZ to the duodenum. Ivermectin concentrations were determined using a validated high-performance liquid chromatography (HPLC) method with fluorescent detection.1 Ivermectin concentrations from day 12 to day 24 were 68.5 ng/mL and 109.6 ng/mL, respectively. Albendazole, albendazole sulfoxide (ABZ-OX), and albendazole sulfone (ABZ-ON) were measured using a validated LC/MS/MS method.2 Albendazole is quickly oxidized to its active metabolite, ABZ-OX, in the liver, leaving low concentrations of the parent compound.3,4 On day 12, plasma ABZ and ABZ-OX measured 12.6 and 277.9 ng/mL, respectively. On day 24, ABZ and ABZ-OX measured 63.2 and 487.1 ng/mL, respectively.

Table 1

Concentration for IVM, ABZ, and ABZ metabolites in serum

Sample no.IdentificationIVM (ng/mL)ABZ (ng/mL)ABZ sulfoxide (ng/mL)ABZ sulfone (ng/mL)
1Day 12 sample (13:30)68.512.6277.916.4
2Day 24 sample (04:20)109.663.2487.15.5

ABZ = albendazole; IVM = ivermectin.

IVERMECTIN Concentrations.

For IVM, plasma concentrations were determined using HPLC with fluorescence detection as previously described.1 Albendazole, ABZ-OX, and ABZ-ON were determined using a validated liquid chromatography–mass spectrometric (LC-MS/MS) method.2

On day 26, as the patient remained hypotensive despite vasopressors, the patient’s family decided to transition therapy to comfort care measures only. The patient died soon after.

DISCUSSION

Clinical outcomes of disseminated strongyloidiasis remain poor with mortality rates around 60%.57 No randomized controlled trials exist to determine the optimal regimen for treating disseminated strongyloidiasis. The existing standard of care includes the combination of IVM with ABZ, as treatment failure has been described with IVM alone.5,8 Case reports clearly demonstrate that in patients with hyperinfection and ileus, subcutaneous IVM achieves higher serum concentrations than nasogastric or rectal administration.912 However, appropriate target concentrations for IVM and ABZ have not been established. A wide variation of serum IVM concentrations have been described.5,10,1315 Most successful treatments occur between plasma concentrations of 15 and 100 ng/mL; however, different studies describe concentrations drawn at different times after IVM administration.6,1216 Peak IVM concentration after oral administration (0.2 mg/kg) ranges from 20 to 54.4 ng/mL and occurs between 3.4 and 10.3 hours after administration.17 Time to peak concentration has not yet been demonstrated for subcutaneous IVM administration.

No case reports describe ABZ concentrations in the treatment of disseminated strongyloidiasis. Albendazole concentrations have instead been described in the treatment of neurocysticercosis, hydatid disease, and lymphatic filariasis.1820 In neurocysticercosis, the concentrations of ABZ’s active metabolite, ABZ-OX, vary considerably.21,22 Taenia solium activity was inhibited at an ABZ-OX concentration of 50 ng/mL.18 In uninfected humans, a mean peak concentration of 1,200 ± 440 ng/mL was achieved 4.75 hours after a single 400-mg oral dose of ABZ.3

The increased ABZ-OX concentration on day 24, despite being further from documented peak concentrations, suggests altered pharmacokinetics and accumulating concentrations.3,23 This is corroborated by the concomitant elevation of parent compound concentrations and ABZ-OX’s residence time between 14 and 20 hours.3,24 It is also conceivable that the post-pyloric drug delivery in our day 24 sample increased the concentrations of both ABZ and ABZ-OX.

The IVM and ABZ-OX concentrations taken when our patient was on ECMO and CRRT exceeded concentrations expected to have activity against Strongyloides. This finding confirms the known hepatic metabolism of these medications and complements a veterinary study demonstrating the failure of hemodialysis to decrease IVM levels.25 Despite inadequate data, supplemental dosing of ABZ and IVM is not recommended during hemodialysis.26

Both IVM and ABZ-OX concentrations increased after decannulation from ECMO. This suggests that both medications may be sequestered by ECMO’s membrane oxygenator. Ivermectin and ABZ’s lipophilic and protein-bound properties are consistent with other medications known to be sequestered by ECMO.2729 Although ECMO priming may decrease drug concentrations by increasing effective circulating volume, this is unlikely to be a large contributor to the difference in IVM and ABZ-OX concentrations as both drugs have large volumes of distribution.4,17,28 Studies are needed to understand how ECMO alters serum concentrations of anthelmintic medications.

It is unknown why larvae are able to survive prolonged exposure to presumably adequate treatment doses. Parasitologic cure rates have not yet been established for the treatment of disseminated strongyloidiasis. The time interval between initiation of IVM therapy and parasitologic clearance shows significant variability, ranging between 6 and 37 days11,15,16 In one study, mean duration of larval shedding from stool and sputum samples was 12.7 and 12 days, respectively.30 Thus, it has been recommended that treatment be continued until parasite clearance is achieved.8

It is unlikely that the live filariform larvae from the sputum reflect a failure of drug delivery to the respiratory tract. Previous reports document the efficacy of subcutaneous IVM at achieving measurable pulmonary concentrations.15 In addition, venovenous ECMO maintains normal circulation through the pulmonary vasculature and should not impede drug delivery to the lungs.31

Factors that may have contributed to our patient’s delay in parasitologic clearance include steroid administration, a high-parasitic body burden, and unknown free IVM concentrations. Corticosteroids are known to stimulate the Strongyloides autoinfection cycle32; thus, their continued use may reduce treatment success. We measured total IVM concentrations—which include free IVM and IVM bound to albumin and alpha-1-acid glycoprotein.1 It has been suggested that IVM’s antiparasitic activity is generated by its free form.14 Thus, adequate total IVM concentrations may not properly reflect the IVM activity.14

CONCLUSION

Despite our patient’s poor outcome, IVM and ABZ concentrations during ECMO and CRRT exceeded those expected to have activity against Strongyloides. An increase in drug concentrations after ECMO decannulation suggests that ECMO’s membrane oxygenator may sequester IVM and ABZ. In a world of increasingly mobile populations, individuals at risk for Strongyloides infection are frequently being treated in nonendemic regions where knowledge of this disease is limited. Immunosuppressed patients are not always screened for infection and remain at risk of complications. Patients with Strongyloides dissemination often present with multiple organ failure. Improved knowledge of the interplay between advanced life support and anthelmintic pharmacokinetics is needed to reduce the mortality of this preventable disease.

Table 2

IVM and ABZ dose and administration time

IVM dose and administration timeABZ dose and administration time
Days 9–1015 mg via nasogastric tube at 20h00 and 30 mg intramuscular injection at 20h00 daily400 mg via nasogastric tube at 16h00 daily
Days 11–2617 mg subcutaneous injection at 20h00400 mg via nasogastric tube at 08h00 and 21h00

ABZ = albendazole; IVM = ivermectin.

REFERENCES

  • 1.

    Kitzman D, Wei S-Y, Fleckenstein L, 2006. Liquid chromatographic assay of ivermectin in human plasma for application to clinical pharmacokinetic studies. J Pharm Biomed Anal 40: 10131020.

    • Search Google Scholar
    • Export Citation
  • 2.

    Chhonker YS, Edi C, Murry DJ, 2017. LC-MS/MS method for simultaneous determination of diethylcarbamazine, albendazole and albendazole metabolites in human plasma: application to a clinical pharmacokinetic study. J Pharm Biomed Anal 151: 8490.

    • Search Google Scholar
    • Export Citation
  • 3.

    Ceballos L, Krolewiecki A, Juárez M, Moreno L, Schaer F, Alvarez LI, Cimino R, Walson J, Lanusse CE, 2018. Assessment of serum pharmacokinetics and urinary excretion of albendazole and its metabolites in human volunteers. PLoS Negl Trop Dis 12: e0005945.

    • Search Google Scholar
    • Export Citation
  • 4.

    Marriner S, Morris D, Dickson B, Bogan J, 1986. Pharmacokinetics of albendazole in man. Eur J Clin Pharmacol 30: 705708.

  • 5.

    Rose CE, Paciullo CA, Kelly DR, Dougherty MJ, Fleckenstein LL, 2009. Fatal outcome of disseminated strongyloidiasis despite detectable plasma and cerebrospinal levels of orally administered ivermectin. J Parasitol Res 2009: 818296.

    • Search Google Scholar
    • Export Citation
  • 6.

    Barrett J, Broderick C, Soulsby H, Wade P, Newsholme W, 2016. Subcutaneous ivermectin use in the treatment of severe Strongyloides stercoralis infection: two case reports and a discussion of the literature. J Antimicrob Chemother 71: 220225.

    • Search Google Scholar
    • Export Citation
  • 7.

    Buonfrate D, Requena-Mendez A, Angheben A, Muñoz J, Gobbi F, Van Den Ende J, Bisoffi Z, 2013. Severe strongyloidiasis: a systematic review of case reports. BMC Infect Dis 13: 78.

    • Search Google Scholar
    • Export Citation
  • 8.

    Boggild AK, Libman M, Greenaway C, McCarthy A; CATMAT, 2016. CATMAT statement on disseminated strongyloidiasis: prevention, assessment and management guidelines. Can Commun Dis Rep 42: 1219.

    • Search Google Scholar
    • Export Citation
  • 9.

    Bogoch II, Khan K, Abrams H, Nott C, Leung E, Fleckenstein L, Keystone JS, 2015. Failure of ivermectin per rectum to achieve clinically meaningful serum levels in two cases of Strongyloides hyperinfection. Am J Trop Med Hyg 93: 9496.

    • Search Google Scholar
    • Export Citation
  • 10.

    Grein JD, Mathisen GE, Donovan S, Fleckenstein L, 2010. Serum ivermectin levels after enteral and subcutaneous administration for Strongyloides hyperinfection: a case report. Scand J Infect Dis 42: 234236.

    • Search Google Scholar
    • Export Citation
  • 11.

    de Moura EB, Maia M de O, Ghazi M, Amorim FF, Pinhati HM, 2012. Salvage treatment of disseminated strongyloidiasis in an immunocompromised patient: therapy success with subcutaneous ivermectin. Braz J Infect Dis 16: 479481.

    • Search Google Scholar
    • Export Citation
  • 12.

    Turner SA, Maclean JD, Fleckenstein L, Greenaway C, 2005. Parenteral administration of ivermectin in a patient with disseminated strongyloidiasis. Am J Trop Med Hyg 73: 911914.

    • Search Google Scholar
    • Export Citation
  • 13.

    Donadello K, Cristallini S, Taccone FS, Lorent S, Vincent J-L, de Backer D, Jacobs F, 2013. Strongyloides disseminated infection successfully treated with parenteral ivermectin: case report with drug concentration measurements and review of the literature. Int J Antimicrob Agents 42: 580583.

    • Search Google Scholar
    • Export Citation
  • 14.

    Leung V, Al-Rawahi GN, Grant J, Fleckenstein L, Bowie W, 2008. Failure of subcutaneous ivermectin in treating Strongyloides hyperinfection. Am J Trop Med Hyg 79: 853855.

    • Search Google Scholar
    • Export Citation
  • 15.

    Fusco DN, Downs JA, Satlin MJ, Pahuja M, Ramos L, Barie PS, Fleckenstein L, Murray HW, 2010. Non-oral treatment with ivermectin for disseminated strongyloidiasis. Am J Trop Med Hyg 83: 879883.

    • Search Google Scholar
    • Export Citation
  • 16.

    Marty FM, Lowry CM, Rodriguez M, Milner DA, Pieciak WS, Sinha A, Fleckenstein L, Baden LR, 2005. Treatment of human disseminated strongyloidiasis with a parenteral veterinary formulation of ivermectin. Clin Infect Dis 41: e5e8.

    • Search Google Scholar
    • Export Citation
  • 17.

    González Canga A, Sahagún Prieto AM, Diez Liébana MJ, Fernández Martínez N, Sierra Vega M, García Vieitez JJ, 2008. The pharmacokinetics and interactions of ivermectin in humans—a mini-review. AAPS J 10: 4246.

    • Search Google Scholar
    • Export Citation
  • 18.

    Mahanty S, Paredes A, Marzal M, Gonzalez E, Rodriguez S, Dorny P, Guerra-Giraldez C, Garcia HH, Nash T, 2011. Sensitive in vitro system to assess morphological and biochemical effects of praziquantel and albendazole on Taenia solium cysts. Antimicrob Agents Chemother 55: 211217.

    • Search Google Scholar
    • Export Citation
  • 19.

    Thomsen EK 2016. Efficacy, safety, and pharmacokinetics of coadministered diethylcarbamazine, albendazole, and ivermectin for treatment of bancroftian filariasis. Clin Infect Dis 62: 334341.

    • Search Google Scholar
    • Export Citation
  • 20.

    Skuhala T, Trkulja V, Desnica B, 2014. Albendazolesulphoxide concentrations in plasma and hydatid cyst and prediction of parasitological and clinical outcomes in patients with liver hydatidosis caused by Echinococcus granulosus. Croat Med J 55: 146155.

    • Search Google Scholar
    • Export Citation
  • 21.

    Paredes A, de Campos Lourenço T, Marzal M, Rivera A, Dorny P, Mahanty S, Guerra-Giraldez C, García HH, Nash TE, Cass QB; Peru the CWG, 2013. In vitro analysis of albendazole sulfoxide enantiomers shows that (+)-(R)-albendazole sulfoxide is the active enantiomer against Taenia solium. Antimicrob Agents Chemother 57: 944949.

    • Search Google Scholar
    • Export Citation
  • 22.

    Sarin R, Dash AP, Dua VK, 2004. Albendazole sulphoxide concentrations in plasma of endemic normals from a lymphatic filariasis endemic region using liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci 799: 233238.

    • Search Google Scholar
    • Export Citation
  • 23.

    Chhonker YS, Edi C, Murry DJ, 2018. LC–MS/MS method for simultaneous determination of diethylcarbamazine, albendazole and albendazole metabolites in human plasma: application to a clinical pharmacokinetic study. J Pharm Biomed Anal 151: 8490.

    • Search Google Scholar
    • Export Citation
  • 24.

    Jung H, Hurtado M, Sanchez M, Medina MT, Sotelo J, 1992. Clinical pharmacokinetics of albendazole in patients with brain cysticercosis. J Clin Pharmacol 32: 2831.

    • Search Google Scholar
    • Export Citation
  • 25.

    Bolfer L, Bandt C, Shih A, Buckley G, 2013. 1132: use of single pass lipid dialysis for the treatment of avermectin toxicity. Crit Care Med 41: A286A287.

    • Search Google Scholar
    • Export Citation
  • 26.

    Johnson CA, Simmons WD, 2000. Dialysis of Drugs. Thousand Oaks, CA: Nephrology Pharmacy Associates, Inc.

  • 27.

    Dzierba AL, Abrams D, Brodie D, 2017. Medicating patients during extracorporeal membrane oxygenation: the evidence is building. Crit Care 21: 66.

    • Search Google Scholar
    • Export Citation
  • 28.

    Shekar K 2012. Sequestration of drugs in the circuit may lead to therapeutic failure during extracorporeal membrane oxygenation. Crit Care 16: R194.

    • Search Google Scholar
    • Export Citation
  • 29.

    Venkatesan P, 1998. Albendazole. J Antimicrob Chemother 41: 145147.

  • 30.

    Dong MD, Karsenti N, Lau R, Ralevski F, Cheema K, Burton L, Klowak M, Boggild AK, 2016. Strongyloidiasis in Ontario: performance of diagnostic tests over a 14-month period. Travel Med Infect Dis 14: 625629.

    • Search Google Scholar
    • Export Citation
  • 31.

    Gattinoni L, Carlesso E, Langer T, 2011. Clinical review: extracorporeal membrane oxygenation. Crit Care 15: 243.

  • 32.

    Fardet L, Généreau T, Poirot J-L, Guidet B, Kettaneh A, Cabane J, 2007. Severe strongyloidiasis in corticosteroid-treated patients: case series and literature review. J Infect 54: 1827.

    • Search Google Scholar
    • Export Citation

Author Notes

Address correspondence to Carl Boodman, Department of Medicine, University of British Columbia, Laurel Street, 10th Floor, Vancouver, BC Canada V5Z 1M9. E-mail: carl.boodman@alumni.ubc.ca

Authors’ addresses: Carl Boodman, Department of Medicine, University of British Columbia, Vancouver, Canada, E-mails: carl.boodman@alumni.ubc.ca or carl.boodman@mail.mcgill.ca. Yashpal S. Chhonker and Daryl J. Murry, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, E-mails: y.chhonker@unmc.edu and dj.murry@unmc.edu. Allison Mah, Jennifer Grant, and Theodore Steiner, Division of Infectious Diseases, University of British Columbia, Vancouver, Canada, E-mails: allimah@mail.ubc.ca, Jennifer.Grant@vch.ca, and tsteiner@mail.ubc.ca. Michael Libman, J. D. MacLean Centre for Tropical Medicine, McGill University, Montreal, Canada, E-mail: michael.libman@mcgill.ca. Cesilia Nishi, Department of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada, E-mail: cesilia.nishi@vch.ca. Marthe Charles, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada, E-mail: marthe.charles@vch.ca.

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