Tazobactam‐induced haemolytic anaemia, possibly caused by non‐immunological adsorption of IgG onto patient's red cells

Abstract

A patient with pneumonia was treated with Tazocin (piperacillin/tazobactam). However, the expected haemoglobin (Hb) increment after transfusion was not achieved. Plasma bilirubin and lactate dehydrogenase were raised. The direct antiglobulin test (DAT) was positive (4+) for immunoglobulin G (IgG) only, but no RBC antibodies were demonstrable in the plasma or an eluate from the patient's RBCs. Drug-induced haemolysis was suspected. After discontinuing Tazocin administration, Hb and bilirubin levels returned to expected values. The patient's plasma gave a positive (3+) indirect antiglobulin reaction only with RBCs pretreated with tazobactam. However, random patient plasmas also gave weak (+/- to 1+) reactions, indicating non-immunological adsorption of IgG onto RBCs rather than specific anti-tazobactam antibodies. Subsequently, plasma samples with varying IgG levels (0.8-89.7 g L(-1)) were tested against RBCs pretreated with tazobactam. The amount of plasma IgG non-immunologically adsorbed onto the drug-coated RBCs was found to correlate directly with the plasma IgG level. The patient had a high plasma IgG level (41.6 g L(-1)) which explains why the antiglobulin test was stronger with the patient's plasma than with random plasma samples. Previous reports (Garratty & Arndt, (1998) British Journal of Haematology, 100, 777-783; Arndt & Garratty (2000) Transfusion, 40, 29S) suggested that non-immunological coating of RBCs with IgG may affect RBC survival; our results would support that suggestion. This is the first reported case of haemolytic anaemia associated with tazobactam.

Meropenem tolerance in a patient with probable fulminant piperacillin-induced immune hemolytic anemia

“…Although the presence of drug-specific antibodies would have been supportive of DIIHA, a negative result should not exclude the diagnosis. Tazobactam has been reported to cause a positive DAT result secondary to nonimmunologic red cell adsorption of proteins, 5 and there are reports of decreased RBC survival in patients taking beta-lactamase inhibitors 6 ; however, it is unlikely to be the cause of this patient's severe hemolysis. Piperacillin is a semisynthetic penicillin that is often combined with tazobactam to achieve broad activity against Gram-positive and Gram-negative bacteria.…”

Drug-induced immune hemolytic anemia

“…We now believe NIPA can cause hemolytic anemia. [20][21][22] RBCs having IgG on their membrane caused by nonimmunologic adsorption yield positive monocyte monolayer assays (MMA), suggesting that the macrophages would interact with these coated RBCs, leading to decreased RBC survival. 21,22 We have published data suggesting that the NIPA mechanism can be the cause of decreased RBC survival in patients taking drugs that contain β-lactamase inhibitors (clavulanate, sulbactam, tazobactam) [20][21][22] and drugs in the platinum family 23 without any drug antibodies being involved.…”

Drug-induced immune haemolytic anaemia caused by levofloxacin

“…(1, 6) Our reported case satisfied the diagnostic criteria for AIHA, as it met the clinical and serological criteria of haemolysis (indirect hyperbilirubinaemia, decreasing haemoglobin level, elevated lactate dehydrogenase level, low haptoglobin level, and peripheral blood smear consistent with haemolysis) along with a positive Coombs test and an autoantibody screen showing IgG autoantibodies (warm antibodies). (4) This was likely due to the induction of drug-independent antibodies (which are indistinguishable from RBC autoantibodies in AIHA) by levofloxacin.…”