chloramphenicol
Regulatory sources consulted
Approved indications
- Serious infections due to susceptible organisms when less toxic alternatives are ineffective or contraindicated, including typhoid fever, H. influenzae meningitis, and serious Salmonella, rickettsial, or other gram-negative infections.
Contraindications
Absolute
- Previous hypersensitivity or toxic reaction to chloramphenicol. Do not use for trivial infections, colds, influenza, sore throat, or bacterial prophylaxis.
Clinical warnings
- Boxed warning · It may cause severe bone-marrow suppression and irreversible, fatal aplastic anemia, even after short courses. Reserve for serious infections without alternatives and obtain serial blood counts; discontinue for reticulocytopenia, leukopenia, thrombocytopenia, or anemia. — FDA, set_id aed29594-211d-49ef-813f-131975a8d0e3
- Major warning · In neonates it may cause gray syndrome with abdominal distension, vomiting, cyanosis, circulatory collapse, and death. Follow neonatal dosing and monitor concentrations. — FDA, set_id aed29594-211d-49ef-813f-131975a8d0e3
Drug interactions
- HighMyelotoxic drugs
Mechanism: They may increase bone-marrow suppression.
Recommendation: Avoid the combination and monitor blood counts if no alternative exists.
FDA, set_id aed29594-211d-49ef-813f-131975a8d0e3
Adverse events
Common (≥1%)
Nausea, vomiting, diarrhea, and injection-site reaction
Rare but serious
Aplastic anemia, pancytopenia, gray syndrome, optic neuritis, and anaphylaxis
Pregnancy and lactation
Use during pregnancy only if clearly needed. During breastfeeding, decide whether to discontinue breastfeeding or discontinue the drug because of the risk of serious infant toxicity.
Recent literature (PubMed)
This paper discusses the mechanisms of S. aureus drug resistance including: (1) introduction. (2) resistance to beta-lactam antibiotics, with particular emphasis on the mec genes found in the Staphylococcaceae family, the structure and occurrence of SCCmec cassettes, as well as differences in the presence of some virulence genes and its expression in major epidemiological types and clones of HA-MRSA, CA-MRSA, and LA-MRSA strains. Other mechanisms of resistance to beta-lactam antibiotics will also be discussed, such as mutations in the gdpP gene, BORSA or MODSA phenotypes, as well as resistance to ceftobiprole and ceftaroline. (3) Resistance to glycopeptides (VRSA, VISA, hVISA strains, vancomycin tolerance). (4) Resistance to oxazolidinones (mutational and enzymatic resistance to linezolid). (5) Resistance to MLS-B (macrolides, lincosamides, ketolides, and streptogramin B). (6) Aminoglycosides and spectinomicin, including resistance genes, their regulation and localization (plasmids, transposons, class I integrons, SCCmec), and types and spectrum of enzymes that inactivate aminoglycosides. (7). Fluoroquinolones (8) Tetracyclines, including the mechanisms of active protection of the drug target site and active efflux of the drug from the bacterial cell. (9) Mupirocin. (10) Fusidic acid. (11) Daptomycin. (12) Resistance to other antibiotics and chemioterapeutics (e.g., streptogramins A, quinupristin/dalfopristin, chloramphenicol, rifampicin, fosfomycin, trimethoprim) (13) Molecular epidemiology of MRSA.
Antibiotics are molecules that can kill bacteria or inhibit their growth by targeting essential cellular functions. They act by inhibiting peptidoglycan synthesis (β-lactams, glycopeptides and fosfomycin); protein synthesis (aminoglycosides, macrolides lincosamides and streptogramins -tetracyclines, tetracyclines, chloramphenicol, fusidic acid, oxazolidinones-); or nucleic acid synthesis (quinolones/ fluoroquinolones and rifamycins) or interfering with key metabolic pathways such as folate biosynthesis (cotrimoxazole). However, the extensive and sometimes inappropriate use of antibiotics has led to the emergence of resistance, progressively reducing their efficacy and highlighting the need for the development of new antibacterial agents. This review presents the origin, structure, mechanism of action, main clinical agents, and spectrum of activity of each class of antibiotic. Mécanismes d’action des antibiotiques. Les antibiotiques sont des molécules capables de détruire les bactéries ou d’inhiber leur croissance en ciblant des fonctions cellulaires essentielles. Ils peuvent agir en inhibant la synthèse du peptidoglycane (α-lactamines, glycopeptides, fosfomycine), la synthèse protéique (aminosides, macrolides-lincosamides-streptogramines, cyclines, chloramphénicol, acide fusidique, oxazolidinones), la synthèse des acides nucléiques (quinolones et fluoroquinolones, rifamycines) ou certaines voies métaboliques comme la biosynthèse de l’acide folique (cotrimoxazole). Cependant, l’usage massif et parfois inapproprié des antibiotiques a favorisé l’émergence de résistances, réduisant progressivement leur efficacité et nécessitant le développement continu de nouvelles molécules antibactériennes. Cette synthèse décrit pour chaque classe d’antibiotique leur origine, leur structure, leur mécanisme d’action ainsi que les principales molécules utilisées en clinique, et leur spectre d’activité.
Due to the increasing emergence of antibiotic resistance in Enterococcus faecalis (E. faecalis), it indicated as potentially opportunistic pathogen causing various healthcare-associated and life-threatening diseases around the world. The aim of this meta-analysis was to evaluate the weighted pooled resistance rates in clinical E. faecalis isolates based on over time, areas, antimicrobial susceptibility testing (AST), and infection source. We searched the studies in PubMed, Scopus, and Web of Science (November 30, 2022). All statistical analyses were carried out using the statistical package R. The analysis encompassed a total of 74 studies conducted in 28 countries. According to the meta-regression, the chloramphenicol, fosfomycin, imipenem, linezolid, minocycline, norfloxacin, quinupristin-dalfopristin, and tetracycline resistance rate increased over time. Analysis revealed statistically significant differences in antibiotic resistance rates for ampicillin, chloramphenicol, erythromycin, gentamicin, penicillin, rifampicin, teicoplanin, tetracycline, and vancomycin across various countries. Globally, the prevalence of drug resistant E. faecalis strains are on the increase over time. Daptomycin and tigecycline can be an effective agent for the treatment of clinical E. faecalis infections. Considering the low prevalence of antibiotic resistance in continents of Europe and Australia, it is suggested to take advantage of their preventive strategies in order to obtain efficient results in other places with high prevalence of resistance.
Typhoid and paratyphoid (enteric fever) are febrile bacterial illnesses common in many low- and middle-income countries. The World Health Organization (WHO) currently recommends treatment with azithromycin, ciprofloxacin, or ceftriaxone due to widespread resistance to older, first-line antimicrobials. Resistance patterns vary in different locations and are changing over time. Fluoroquinolone resistance in South Asia often precludes the use of ciprofloxacin. Extensively drug-resistant strains of enteric fever have emerged in Pakistan. In some areas of the world, susceptibility to old first-line antimicrobials, such as chloramphenicol, has re-appeared. A Cochrane Review of the use of fluoroquinolones and azithromycin in the treatment of enteric fever has previously been undertaken, but the use of cephalosporins has not been systematically investigated and the optimal choice of drug and duration of treatment are uncertain. To evaluate the effectiveness of cephalosporins for treating enteric fever in children and adults compared to other antimicrobials. We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, the WHO ICTRP and ClinicalTrials.gov up to 24 November 2021. We also searched reference lists of included trials, contacted researchers working in the field, and contacted relevant organizations. We included randomized controlled trials (RCTs) in adults and children with enteric fever that compared a cephalosporin to another antimicrobial, a different cephalosporin, or a different treatment duration of the intervention cephalosporin. Enteric fever was diagnosed on the basis of blood culture, bone marrow culture, or molecular tests. We used standard Cochrane methods. Our primary outcomes were clinical failure, microbiological failure and relapse. Our secondary outcomes were time to defervescence, duration of hospital admission, convalescent faecal carriage, and adverse effects. We used the GRADE approach to assess ce