Ceftriaxone-induced Hemolytic Anemia

Northrop, Michael S; Agarwal, Hemant

doi:10.1097/mph.0000000000000181

Cited by 19 publications

(10 citation statements)

References 29 publications

(63 reference statements)

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“… 1 Of note, children may be more vulnerable to ceftriaxone-induced hemolytic anemia than adults, and reactions in children can be severe and often fatal. 13 However, the condition is rare, and affected children commonly have underlying chronic hematologic or immunologic disorders or chronic/recurrent infections (reviewed by Northrop and Agarwal 14 ). Since 2008, piperacillin has superseded cefotetan and ceftriaxone as the leading cause of DIIHA.…”

Section: Introductionmentioning

confidence: 99%

<p>No Evidence for Ceftobiprole-Induced Immune Hemolytic Anemia in Three Phase 3 Clinical Trials</p>

Hamed

Wiktorowicz

Gehr

2020

IDR

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Purpose Drug-induced immune hemolytic anemia (DIIHA) is a rare but serious adverse event associated with a number of drugs, including second- and third-generation cephalosporins. A positive direct antiglobulin test (DAT) is a reliable finding in DIIHA, but positive results without evidence of hemolysis can occur, particularly in hospitalized patients. There have been no reports of hemolytic anemia in four previous Phase 3 trials or from post-marketing surveillance of the advanced-generation, broad-spectrum cephalosporin, ceftobiprole. The aim of this analysis was to review the incidence of positive DAT results and any evidence of hemolytic anemia from three recent Phase 3 trials of ceftobiprole. Patients and Methods Patients were enrolled in three Phase 3 randomized controlled trials: 94 pediatric patients with pneumonia received ceftobiprole in the BPR-PIP-002 trial; 335 adults with acute bacterial skin and skin structure infections received ceftobiprole in the TARGET trial; and 201 adults with Staphylococcus aureus bacteremia have been randomized 1:1 to ceftobiprole or daptomycin ± aztreonam in the ongoing ERADICATE trial. In all three trials, DAT results were obtained at baseline, and follow-up tests were performed either at the test of cure (TOC) visit (BPR-PIP-002), end-of-treatment (EOT) visit (TARGET), or both EOT and post-treatment Day 70 visits (ERADICATE). Results In the BPR-PIP-002 trial, five patients (all ceftobiprole treated) had a documented negative DAT result at baseline followed by a positive result at the TOC visit. One patient in the ongoing, blinded ERADICATE trial had a positive DAT result at both baseline and EOT. Results from other laboratory investigations showed no evidence of hemolytic anemia in these patients. No positive DAT results were reported in the TARGET trial. Conclusion No evidence of hemolytic anemia associated with ceftobiprole was observed in either adults or children across several indications in this analysis of three large Phase 3 trials.

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Section: Introductionmentioning

confidence: 99%

<p>No Evidence for Ceftobiprole-Induced Immune Hemolytic Anemia in Three Phase 3 Clinical Trials</p>

Hamed

Wiktorowicz

Gehr

2020

IDR

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“…In children with ceftriaxone-induced IHA, 8 of 9 patients, whose ceftriaxone therapy was stopped immediately, survived. In contrast, children without cessation of ceftriaxone treatment after diagnosis had a mortality of 50% [ 8 ]. DIIHA patients should be admitted to an intensive care unit to provide optimal supportive care and if required circulatory support.…”

Section: Discussionmentioning

confidence: 99%

“…However, the question remains open whether the positive outcome of the patient was due to IVIG therapy or due to cessation of ceftriaxone. In some cases, plasmapheresis/plasma exchange has been used for treating DIIHA [ 3 , 7 , 8 ]. It could be speculated that removing drug-induced antibodies from the patient’s serum actively via plasmapheresis could be helpful in patients with “ drug adsorption-type ” DIIHA or with severe renal failure, where the causative drug is not eliminated within its normal half-time and might therefore trigger a prolonged hemolysis as well as an intensified immunologic stimulation.…”

Section: Discussionmentioning

confidence: 99%

“…During the last years, ceftriaxone has been one of the most important drugs that were shown to be responsible for drug-induced immune hemolytic anemia (DIIHA) [ 3 – 6 ]. Ceftriaxone-induced immune hemolytic anemia (IHA) is characterized by sharp decrease of hemoglobin, a high rate of organ failure and a mortality of at least 30% [ 2 , 3 , 6 – 8 ], whereas children present with a more severe clinical picture and have a worse prognosis than adults [ 2 , 5 – 7 ]. Here, we present the case of a 76-year-old patient with ceftriaxone-induced IHA who was treated in our department and could be managed to survive without persistent physical impairment.…”

Section: Introductionmentioning

confidence: 99%

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Ceftriaxone-induced hemolytic anemia with severe renal failure: a case report and review of literature

Leicht

Weinig

Mayer

et al. 2018

BMC Pharmacol Toxicol

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BackgroundDrug induced immune hemolytic anemia (DIIHA) is a rare complication and often underdiagnosed. DIIHA is frequently associated with a bad outcome, including organ failure and even death. For the last decades, ceftriaxone has been one of the most common drugs causing DIIHA, and ceftriaxone-induced immune hemolytic anemia (IHA) has especially been reported to cause severe complications and fatal outcomes.Case presentationA 76-year-old male patient was treated with ceftriaxone for cholangitis. Short time after antibiotic exposure the patient was referred to intensive care unit due to cardiopulmonary instability. Hemolysis was observed on laboratory testing and the patient developed severe renal failure with a need for hemodialysis for 2 weeks. Medical history revealed that the patient had been previously exposed to ceftriaxone less than 3 weeks before with subsequent hemolytic reaction. Further causes for hemolytic anemia were excluded and drug-induced immune hemolytic (DIIHA) anemia to ceftriaxone could be confirmed.ConclusionsThe case demonstrates the severity of ceftriaxone-induced immune hemolytic anemia, a rare, but immediately life-threatening condition of a frequently used antibiotic in clinical practice. Early and correct diagnosis of DIIHA is crucial, as immediate withdrawal of the causative drug is essential for the patient prognosis. Thus, awareness for this complication must be raised among treating physicians.

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“…The time to onset may vary from a few hours, especially in children with severe clinical presentations, to several days. Its clinical features are characterized by a sharp decrease in hemoglobin, leading to organ failure and severe complications such as shock, circulatory arrest, organ ischemia, disseminated intravascular coagulation and acute respiratory distress syndrome with a potentially high mortality rate up to 30-50% [60,61]. Children present with more severe and quickly-occurring clinical features associated with worse prognosis [58][59][60].…”

Section: Nephropathy Associated With Hemolytic Anemiamentioning

confidence: 99%

Beta-Lactams Toxicity in the Intensive Care Unit: An Underestimated Collateral Damage?

Roger

Louart

2021

Microorganisms

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Beta-lactams are the most commonly prescribed antimicrobials in intensive care unit (ICU) settings and remain one of the safest antimicrobials prescribed. However, the misdiagnosis of beta-lactam-related adverse events may alter ICU patient management and impact clinical outcomes. To describe the clinical manifestations, risk factors and beta-lactam-induced neurological and renal adverse effects in the ICU setting, we performed a comprehensive literature review via an electronic search on PubMed up to April 2021 to provide updated clinical data. Beta-lactam neurotoxicity occurs in 10–15% of ICU patients and may be responsible for a large panel of clinical manifestations, ranging from confusion, encephalopathy and hallucinations to myoclonus, convulsions and non-convulsive status epilepticus. Renal impairment, underlying brain abnormalities and advanced age have been recognized as the main risk factors for neurotoxicity. In ICU patients, trough concentrations above 22 mg/L for cefepime, 64 mg/L for meropenem, 125 mg/L for flucloxacillin and 360 mg/L for piperacillin (used without tazobactam) are associated with neurotoxicity in 50% of patients. Even though renal complications (especially severe complications, such as acute interstitial nephritis, renal damage associated with drug induced hemolytic anemia and renal obstruction by crystallization) remain rare, there is compelling evidence of increased nephrotoxicity using well-known nephrotoxic drugs such as vancomycin combined with beta-lactams. Treatment mainly relies on the discontinuation of the offending drug but in the near future, antimicrobial optimal dosing regimens should be defined, not only based on pharmacokinetics/pharmacodynamic (PK/PD) targets associated with clinical and microbiological efficacy, but also on PK/toxicodynamic targets. The use of dosing software may help to achieve these goals.

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Ceftriaxone-induced Hemolytic Anemia

Cited by 19 publications

References 29 publications

<p>No Evidence for Ceftobiprole-Induced Immune Hemolytic Anemia in Three Phase 3 Clinical Trials</p>

<p>No Evidence for Ceftobiprole-Induced Immune Hemolytic Anemia in Three Phase 3 Clinical Trials</p>

Ceftriaxone-induced hemolytic anemia with severe renal failure: a case report and review of literature

Beta-Lactams Toxicity in the Intensive Care Unit: An Underestimated Collateral Damage?

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