Lactic Acidosis with Chloramphenicol Treatment in a Child with Cystic Fibrosis.

Children with cystic fibrosis are commonly colonized with multi-resistant bacteria. In such patients, infectious exacerbation may require salvage therapy with uncommonly used antimicrobials, including chloramphenicol. Chloramphenicol is rarely used nowadays because of the associated severe adverse events. We describe the case of a 15-year-old female with terminal cystic fibrosis who required intravenous (IV) chloramphenicol treatment for a Burkholderia cepacia (B. cepacia) exacerbation. The child subsequently developed lactic acidosis and secondary respiratory compensation adding to her baseline respiratory distress. Based on the Naranjo scale, the probability of chloramphenicol being the cause of the hyperlactatemia and associated respiratory distress was rated as probable, as the adverse effects resolved upon discontinuation of the drug. Subsequent genotyping for mitochondrial polymorphism (G3010A) confirmed a possible susceptibility to lactic acidosis from mitochondrial RNA-inhibiting agents such as chloramphenicol. Hyperlactatemia is a rare but life threatening adverse effect that has been previously reported with chloramphenicol exposure, but is not generally thought of. Clinicians should be aware of this potentially life threatening, but reversible adverse event. Lactate should be monitored under chloramphenicol and it should be discontinued as soon as this complication is suspected, especially in patients with low respiratory reserve.

Inclusion complexes of chloramphenicol with ß-cyclodextrin and aminoacids as a way to increase drug solubility and modulate ROS production.

The aim of this study was to improve the solubility of chloramphenicol and reduce the production of reactive oxygen species (ROS) in leucocytes induced by this drug, using complexation. Multicomponent complexes were prepared by the addition of ß-cyclodextrin with glycine or cysteine. Nuclear magnetic resonance and phase solubility studies provided information at the molecular level on the structure of the complexes and their association binding constants, respectively. In the solid state, all systems were extensively characterized by Fourier-transform infrared spectroscopy, scanning electron microscopy, thermal analysis and X-ray powder diffraction. Antimicrobial activity of inclusion complexes was investigated by agar diffusion methods. Finally ROS determination by chemiluminescence was used to investigate the effect of complex formation on the potential toxicity in human leucocytes. These studies revealed that multicomponent complexes can increase the aqueous solubility of chloramphenicol as well as reducing the stress by ROS production in leucocytes and maintaining its microbiological activity.

High error rates in selenocysteine insertion in mammalian cells treated with the antibiotic doxycycline, chloramphenicol, or geneticin.

Antibiotics target bacteria by interfering with essential processes such as translation, but their effects on translation in mammalian cells are less well characterized. We found that doxycycline, chloramphenicol, and Geneticin (G418) interfered with insertion of selenocysteine (Sec), which is encoded by the stop codon, UGA, into selenoproteins in murine EMT6 cells. Treatment of EMT6 cells with these antibiotics reduced enzymatic activities and Sec insertion into thioredoxin reductase 1 (TR1) and glutathione peroxidase 1 (GPx1). However, these proteins were differentially affected due to varying errors in Sec insertion at UGA. In the presence of doxycycline, chloramphenicol, or G418, the Sec-containing form of TR1 decreased, whereas the arginine-containing and truncated forms of this protein increased. We also detected antibiotic-specific misinsertion of cysteine and tryptophan. Furthermore, misinsertion of arginine in place of Sec was commonly observed in GPx1 and glutathione peroxidase 4. TR1 was the most affected and GPx1 was the least affected by these translation errors. These observations were consistent with the differential use of two Sec tRNA isoforms and their distinct roles in supporting accuracy of Sec insertion into selenoproteins. The data reveal widespread errors in inserting Sec into proteins and in dysregulation of selenoprotein expression and function upon antibiotic treatment.

Reaction or infection: topical chloramphenicol treatment.

Chloramphenicol is a topical treatment that is used widely, especially in wounds around the eyes. In our practice there have been a number of cases of delayed hypersensitivity to chloramphenicol that has been mismanaged initially as an infective cellulitis. We hope to share some of our experience of this uncommon reaction to highlight the delayed reaction that can occur with topical application of this drug.

Chloramphenicol--not so innocuous: a case of optic neuritis.

The authors present a case of optic neuritis in an adult patient who had been self-prescribing extraordinarily large dosages of chloramphenicol for chronic prostatitis over several years. The visual symptoms resolved upon cessation of the drug and prescription of B group vitamins. Chloramphenicol optic neuritis has not been described in the literature for over 20 years and previously predominantly in children with cystic fibrosis.

[The treatment of MRSA colonized middle ear; case report and literature review]. / Die Behandlung des MRSA besiedelten Mittelohres; eine Fallbeschreibung und Literaturübersicht.

BACKGROUND: The treatment of MRSA (methocillin resistant staphylococcus aureus) colonized middle ear is difficult. According to the guidelines, a MRSA colonized Patient is not to be treated with systemic antibiotics. The topical treatment shows the problem of the ototoxicity of most of the used antiseptic as well as antibiotic substances. METHOD: Selective literature review and consideration of the author's own clinical experience. RESULTS AND CONCLUSIONS: Antibiotic treatment options include aequeous Tetracyclin drops, aequeous chloramphenicol drops and quinolon ear drops (unfortunately the MRSA is resistent mostly). Antiseptics without ototoxic effects are the Burow's solution, Povidone-iode, acetic acid solutions and aequeous dequalinium solutions.

Morphological characteristics and haematological studies in Wistar rats subjected to prolonged treatment of chloramphenicol / Características morfológicas y estudios hematológicos en ratas Wistar sometidas a un tratamiento prolongado con cloranfenicol

The morphological characteristics and haematological studies were studied in fifteen male albino rats (Wistar Strain) aged between 12 and 14 weeks and with a body weight of 150- 180g. The rats were allowed to feed on commercially prepared rat pellet and provided with fresh water ad libitum. The rats were divided into three groups; the rats were in groups A, B and C of 5 rats each. Group A served as control of the study; Group B was treated with Chloramphenicol at the dose rate of 25mg/kg body weight per os for 20 days; while Group C was treated for 25 days. Semen used in this study was obtained from the caudal epididymides while morphological aberrations were determined from spermatozoa counted after stained with Wells and Awa stain. Results of the spermiogram showed that the volume was decreasing as the prolonged dosage of chloramphenicol increases. The percentage motility in Group A (89.0 + 2.45 percent), differed significantly (p < 0.05) when compared to Group B (72.0 + 3.74 percent) and Group C (66.0 + 2.45 percent). The same pattern is observed in percentage liveability, morphological aberration and sperm concentration. This indicates that prolonged dosage of chloramphenicol will cause infertility in male animals. It is therefore concluded and recommended that prolonged dosage of chloramphenicol can cause infertility and or sterility. So it should not be used in male animals meant for mature breeding and artificial insemination programme.

Fueron estudiadas las características morfológicas y hematológicas de 15 ratas albinas Wistar, macho, entre 12 y 14 semanas y con un peso corporal de 150 - 180g. Las ratas fueron alimentadas con pellet preparado comercialmente y con agua fresca ad libitum. Las ratas fueron divididas en tres grupos de 5 ejemplares cada uno. El Grupo A sirvió como control; Grupo B fue tratado con cloranfenicol en dosis de 25mg/kg de peso corporal durante 20 días, mientras que el Grupo C recibió este tratamiento durante 25 días. El esperma utilizado en este estudio se obtuvo desde la cauda del epidídimo, donde las aberraciones morfológicas fueron determinadas a partir del conteo de espermatozoides, después de ser teñidos con la tinción de Wells y Awa. Los resultados del espermiograma puso de manifiesto que el volumen fue disminuyendo a medida que la dosis de cloranfenicol aumentaba. El porcentaje de motilidad en el grupo A (89,0 +/- 2,45 por ciento), fue diferente significativamente (p <0,05) en comparación con el Grupo B (72,0 +/- 3,74 por ciento) y Grupo C (66,0 +/- 2,45 por ciento). El mismo patrón se observó en los porcentaje de habitabilidad, aberración morfológica y la concentración de espermatozoides. Esto indica que la prolongación de la dosis de cloranfenicol puede causar infertilidad en los animales machos. Por lo tanto, se concluye y recomienda que una prolongada dosis de cloranfenicol puede causar infertilidad o esterilidad, así que no debe utilizarse en animales machos destinados a la cría y en los programas de inseminación artificial.

Chloramphenicol: screening and review to evaluate its potential beneficial effects in leukaemia.

Chloramphenicol is an antimicrobial agent having a very broad-spectrum of activity including Gram-positive bacteria, Gram-negative bacteria and anaerobes. However the use of chloramphenicol has reduced over a period of time due to the adverse effects of causing bone marrow depression or in some cases severe aplastic anaemia. As the effects are seen on the bone marrow cell, it was intended to find out if these adverse effects could be used for the benefits in leukaemia patients, using in-vitro study on leukaemic cell lines. The study showed inhibition of growth of the leukaemia cells by chloramphenicol which was comparable to or better than daunorubicin in some cell lines. The article also discusses the other adverse effect profile of chloramphenicol compared with anticancer drugs and its potential benefit in leukaemia and in neutropenic fever.

Anterior uveitis, poliosis, and skin hypopigmentation associated with topical chloramphenicol allergy following ptosis surgery.

The association of uveitis and vitiligo has long been established in specific disease entities: Vogt-Koyanagi-Harada syndrome and sympathetic ophthalmia. We report an unusual case of topical chloramphenicol allergy associated with an anterior uveitis with subsequent poliosis and periocular vitiligo, following anterior approach levator advancement surgery.

Cyclosporine-responsive thrombocytopenia in a patient with chloramphenicol-associated myelodysplastic syndrome.

A 64-yr-old patient with myelodysplastic syndrome (MDS), with refractory cytopenia with multilineage dysplasia subtype following chloramphenicol exposure received immunosuppressive treatment with antithymocyte globulin and cyclosporine (CsA). Complete remission was achieved and CsA was tapered after 2.5 yr. Shortly after CsA withdrawal, the patient relapsed with thrombocytopenia but responded to restoration of CsA. This case illustrates that immune-mediated mechanisms of cytopenia in MDS may be dependent on continued immunosuppressive treatment similar to aplastic anemia.

Linezolid-induced dyserythropoiesis: chloramphenicol toxicity revisited.

We report here two cases of dyserythropoietic anaemia associated with long-term linezolid use that share striking similarities to chloramphenicol-associated myelotoxicity.