Changes in Iron Metabolism in Early Chloramphenicol Toxicity12

Rubin, David; Weisberger, Austin S.; Botti, Robert E.; Storaasli, John P.

doi:10.1172/jci103716

Cited by 69 publications

(14 citation statements)

References 11 publications

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“…Since uremic patients are usually also anemic, further bone marrow depression that might result from chloramphenicol or its products may be difficult to detect. Of interest in this regard is a recent report of 15 patients observed during chloramphenicol administration in which five patients showed a reduced incorporation of iron into hemoglobin on the basis of which it was suggested that this drug may produce subclinical bone marrow depression (33). Although the possible role of renal impairment in these cases was not discussed, three of the five patients were listed as having renal disease, and two of the remaining 10 who showed no adverse effect from chloramphenicol are also listed as having some disease of the kidney.…”

Section: Discussionmentioning

confidence: 99%

Persistence of Antibiotics in Blood of Patients With Acute Renal Failure. Ii. Chloramphenicol and Its Metabolic Products in the Blood of Patients With Severe Renal Disease or Hepatic Cirrhosis*†

Kunin¹,

Glazko²,

Finland³

1959

J. Clin. Invest.

159

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Section: Discussionmentioning

confidence: 99%

Persistence of Antibiotics in Blood of Patients With Acute Renal Failure. Ii. Chloramphenicol and Its Metabolic Products in the Blood of Patients With Severe Renal Disease or Hepatic Cirrhosis*†

Kunin¹,

Glazko²,

Finland³

1959

J. Clin. Invest.

159

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“…Chloramphenicol-mediated hematotoxicity manifests as either a reversible (41), predictable, dose-dependent, early-onset, mild anemia characterized by reticulocytopenia with occasional leukopenia and thrombocytopenia observed during therapy (80,92,104) or a posttreatment pancytopenia that is unpredictable, irreversible, dose independent, and occasionally fatal (103,104). The early-onset myelosuppression primarily affects erythropoiesis, whereby the bone marrow exhibits an essentially normal landscape of cell types with reduced numbers of maturing erythroid cells (8,76). The latent aplastic anemia manifests as a severe pancytopenia related to an absence of myeloid constituents in the marrow (32,99,102).…”

Section: Chloramphenicol and Aplastic Anemiamentioning

confidence: 99%

Adverse Effects of Antimicrobials via Predictable or Idiosyncratic Inhibition of Host Mitochondrial Components

Barnhill

Brewer

Carlson

2012

Antimicrob Agents Chemother

107

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This minireview explores mitochondria as a site for antibiotic-host interactions that lead to pathophysiologic responses manifested as nonantibacterial side effects. Mitochondrion-based side effects are possibly related to the notion that these organelles are archaic bacterial ancestors or commandeered remnants that have co-evolved in eukaryotic cells; thus, this minireview focuses on mitochondrial damage that may be analogous to the antibacterial effects of the drugs. Special attention is devoted to aminoglycosides, chloramphenicol, and fluoroquinolones and their respective single side effects related to mitochondrial disturbances. Linezolid/oxazolidinone multisystemic toxicity is also discussed. Aminoglycosides and oxazolidinones are inhibitors of bacterial ribosomes, and some of their side effects appear to be based on direct inhibition of mitochondrial ribosomes. Chloramphenicol and fluoroquinolones target bacterial ribosomes and gyrases/topoisomerases, respectively, both of which are present in mitochondria. However, the side effects of chloramphenicol and the fluoroquinolones appear to be based on idiosyncratic damage to host mitochondria. Nonetheless, it appears that mitochondrion-associated side effects are a potential aspect of antibiotics whose targets are shared by prokaryotes and mitochondria-an important consideration for future drug design. SIDE EFFECTS OF ANTIBACTERIAL DRUGST he desired activity of an antibiotic is to kill or prevent the growth of offending pathogenic bacteria, and yet these drugs may impact the host in an injurious manner. Generalized adverse events are common to most antibiotics (e.g., gastrointestinal distress with any oral antibacterial drug), but certain antibiotics are associated with specific effects (Table 1). Some adverse events are mild, e.g., yellowing of the teeth for tetracyclines (77, 79), increased intestinal peristalsis related to erythromycin therapy (7, 67), and reversible orange discoloration of skin and body fluids as observed with rifampin treatment (23, 31). Altered drug metabolism (106) is a common side effect that, in the absence of co-drug therapy, could also be considered mild. More serious side effects include photosensitivity (44) and anaphylactoid reactions (34) observed with many agents, ototoxicity (27, 83) following aminoglycoside therapy, chondrotoxicity (85, 88) and retinopathy (95) with fluoroquinolones, neuropathies associated with metronidazole (30, 107) and linezolid (15), and lactic acidosis and serotonin syndrome attributed to linezolid (21, 61). Other consequences can be severe or even devastating such as: the dermonecrolytic Stevens-Johnson syndrome associated with sulfonamide antimicrobial agents (74, 81); nephrotoxicity related to aminoglycosides (63, 73); aplastic anemia due to chloramphenicol (9, 91); hepatitis caused by many drugs, including isoniazid (72, 89); neuromuscular blockade related to aminoglycoside (64, 65) or lincosamide (4, 70) therapy; myopathies due to ionophores (5, 28, 75); and neoplasia related to metronidazole (19)....

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“…K rakoff et al (6) and O zer et al (7) showed that the administration of large doses (8-12 gms. a day) to patients induced in all a reversible bone marrow suppression and both R ubin et al (8,9) and Saidi et al (5) have found a reversible erythropoietic suppression in a high percentage of treated cases. …”

mentioning

confidence: 85%

“…In view of the findings that chloramphenicol impairs iron up take and iron utilization in vitro, it seems probable that the early ferrokinetic changes observed in vivo after the administration of chloramphenicol (8,9) are caused by a direct action of the drug on the erythroid tissue. The concentrations met in vivo are ad mittedly much lower than the concentrations utilized here.…”

mentioning

confidence: 99%

In vitro Action of Chloramphenicol and Chloramphenicol-Analogues on the Metabolism of Human Immature Red Blood Cells

Erslev¹,

Iossifides²

1962

Acta Haematol

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Changes in Iron Metabolism in Early Chloramphenicol Toxicity12

Cited by 69 publications

References 11 publications

Persistence of Antibiotics in Blood of Patients With Acute Renal Failure. Ii. Chloramphenicol and Its Metabolic Products in the Blood of Patients With Severe Renal Disease or Hepatic Cirrhosis*†

Persistence of Antibiotics in Blood of Patients With Acute Renal Failure. Ii. Chloramphenicol and Its Metabolic Products in the Blood of Patients With Severe Renal Disease or Hepatic Cirrhosis*†

Adverse Effects of Antimicrobials via Predictable or Idiosyncratic Inhibition of Host Mitochondrial Components

In vitro Action of Chloramphenicol and Chloramphenicol-Analogues on the Metabolism of Human Immature Red Blood Cells

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