Chloramphenicol and Aplastic Anemia

Rheingold, Jack J.

doi:10.1001/jama.1952.02930310037008

Cited by 32 publications

(11 citation statements)

References 4 publications

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“…Chloramphenicol was discovered in 1947 10 and became widely used due its broad activity against many Gram-positive and -negative species; however, by the 1960s it had largely been abandoned in high-income countries due to its toxicity profile 11 . Despite this it remains a key drug in low- and middle-income countries due to its low price and ease of production.…”

Section: Introductionmentioning

confidence: 99%

ChloS-HRM, a novel assay to identify chloramphenicol-susceptible Escherichia coli and Klebsiella pneumoniae in Malawi

Williams

Musicha

Feasey

et al. 2019

Journal of Antimicrobial Chemotherapy

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Objectives Chloramphenicol is a broad-spectrum antimicrobial widely available in sub-Saharan Africa. With susceptibility re-emerging among Enterobacteriaceae in Blantyre, Malawi, we designed and evaluated a new high-resolution melt (HRM) RT-PCR assay, ChloS-HRM, to identify chloramphenicol-susceptible infections in a hospital setting. Methods Seventy-two previously whole-genome sequenced isolates of Escherichia coli and Klebsiella pneumoniae from the Queen Elizabeth Central Hospital, Malawi, were subjected to determination of chloramphenicol MICs. Primers were designed to detect 18 chloramphenicol resistance genes that produce seven distinct peaks correlating with different gene groups ( catA1, catA2, catA3, catB2, catB group 3, cmlA and floR ) following HRM analysis. ChloS-HRM results were compared with MIC and WGS results. Results ChloS-HRM correctly identified 15 of 17 phenotypically susceptible isolates and 54 of 55 resistant isolates, giving an accuracy of 88% in identifying susceptibility and 98% in identifying resistance. WGS identified 16 of 17 susceptible and 54 of 55 resistant isolates, giving an accuracy of 94% in identifying susceptibility and 98% in identifying resistance. The single false-susceptible result had no detectable gene by ChloS-HRM or WGS. Compared with WGS, ChloS-HRM had 100% sensitivity and specificity for catA ( catA1–3 ), cmlA and floR , and 96% specificity for catB ; sensitivity could not be estimated due to the lack of catB in the clinical sample collection. The overall agreement between MIC and HRM was 96% and between MIC and WGS it was 97%. Conclusions ChloS-HRM could support antimicrobial stewardship in enabling de-escalation from third-generation cephalosporins by identifying chloramphenicol-susceptible infections. This would be valuable in areas with chloramphenicol-susceptible MDR and XDR Enterobacteriaceae.

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Section: Introductionmentioning

confidence: 99%

ChloS-HRM, a novel assay to identify chloramphenicol-susceptible Escherichia coli and Klebsiella pneumoniae in Malawi

Williams

Musicha

Feasey

et al. 2019

Journal of Antimicrobial Chemotherapy

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“…Shortly thereafter, a flurry of case reports describing one or several individuals attributed aplastic anemia to chloramphenicol. 23,35,41,50,59,84,116,122,131,140,155,203,223,224,276,305,306 These case reports differed from Volini's and associates' observations in several ways. All of the patients had chronic, nonremitting, even fatal bone marrow suppression.…”

Section: Clinical Pharmacology and Therapeuticsmentioning

confidence: 67%

Drug‐induced leukopenia and aplastic anemia

Pisciotta

1971

Clin Pharma and Therapeutics

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Hematopoietic damage following treatment with certain medications remains a major problem of drug therapy. As long as drugs remain indispensable in the treatment of disease, this problem cannot be resolved simply by avoiding their use. Instead, development of information that pertains to the mechanism and prediction of drug‐induced blood dyscrasias must be acquired for the safe use of drugs. Forewarned is forearmed; if it were possible to identify a susceptible patient or a potentially dangerous drug, then the potential risk of producing a serious blood re action with treatment would be minimized. A precedent for this concept was established with the discovery that patients whose erythrocytes are deficient in glucose‐6‐phosphate dehydrogenase are unusually susceptible to hemolytic anemia if treated with oxidant drugs.41 For most of the other toxic blood dyscrasias, knowledge of the pathogenesis remains obscure because certain difficulties limit acquisition of such information. The mechanisms of a drug reaction produced by one drug may differ from that produced by another drug. Also, the rare incidence of druginduced blood dyscrasias has made very few patients available for studies. Few papers have appeared which deal with the mechanism of drug‐induced hematopoietic disease. In addition, the difficulties entailed in obtaining bone marrow and other specimens in sufficient quantity has restricted effective investigation. Since the technique required to study mechanisms of drug reactions may be complex and expensive, it may be logistically unsound for a laboratory to “tool up” and then sit back and wait for the first patient to arrive.

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“…The hepatotoxicity of chloramphenicol has previously been suggested by the frequent appearance of a hepatitislike syndrome in association with drug-induced aplastic anemia,8, 10, 11, 34 as weIl as case reports of fatty infiltration or hepatic necrosis following oral chloramphenicol. l1 , 18,20,25,34 Drug toxicity is the simplest explanation of the transient hyperbilirubinemia associated with delirium in our third patient.…”

Section: Discussionmentioning

confidence: 78%

Chloramphenicol‐associated encephalopathy

Levine

Regelson

Holland

1970

Clin Pharma and Therapeutics

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Three cases of toxic delirium associated with oral chloramphenicol are reported. In two of the cases, symptoms disappeared with cessation of chloramphenicol and reappeared when treatment was resumed. The appearance of chloramphenicol‐associated encephalopathy after oral but not after parenteral medication at the same dosage suggests that altered hepatic function related to higher‐portal drug concentration may be responsible. Such dysfunction may depend on inhibition of synthesis of hepatic enzymes involved in biochemical processes necessary for normal brain function. An alternative possibility is a direct effect on brain cells.

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Chloramphenicol and Aplastic Anemia

Cited by 32 publications

References 4 publications

ChloS-HRM, a novel assay to identify chloramphenicol-susceptible Escherichia coli and Klebsiella pneumoniae in Malawi

ChloS-HRM, a novel assay to identify chloramphenicol-susceptible Escherichia coli and Klebsiella pneumoniae in Malawi

Drug‐induced leukopenia and aplastic anemia

Chloramphenicol‐associated encephalopathy

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