Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chloramphenicol is a unique antibiotic. The kinetics and efficacy of the oral and intravenous preparations are comparable. Chloramphenicol is usually bacteriostatic but is bactericidal against Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis, and chloramphenicol's clinical efficacy against these meningeal pathogens is well established. Chloramphenicol can be used to treat serious pediatric infections when Haemophilus influenzae is a likely pathogen, as well as typhoid fever, anaerobic infections, bacterial meningitis in patients allergic to penicillin, brain abscesses, and rickettsial infections. The use of chloramphenicol is limited because of its toxicity. Aplastic anemia is very rare but can occur after either oral or intravenous administration. The gray syndrome can be eliminated and marrow suppression minimized by using chloramphenicol at the recommended doses and monitoring levels. During the last decade the increased use of chloramphenicol has not resulted in increased resistance or in frequent reports of toxicity. Thus, chloramphenicol remains an important inpatient antibiotic that can be invaluable for treating certain life-threatening infections.
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PMID:Chloramphenicol: what we have learned in the last decade. 352 36

Chloramphenicol resistance in Haemophilus influenzae occurs most frequently via plasmid-mediated chloramphenicol acetyltransferase production. We studied four strains with high-level chloramphenicol resistance (MIC greater than 20 micrograms/ml) which did not have detectable chloramphenicol acetyltransferase activity. The chloramphenicol resistance determinant was transformed into a chloramphenicol-susceptible laboratory H. influenzae strain from each of the four wild-type strains, enabling isogenic comparisons. By thin-layer chromatography and a bioassay, there was no evidence of non-chloramphenicol acetyltransferase modification of chloramphenicol. In vitro protein synthesis in the presence of chloramphenicol was equivalently inhibited in the chloramphenicol-resistant transformants and in the susceptible recipient. Chloramphenicol uptake by these strains during logarithmic growth was compared by high-pressure liquid chromatographic quantitation; at chloramphenicol concentrations of 5, 10, and 20 micrograms/ml the four transformants showed a decreased rate of uptake of chloramphenicol compared with the isogenic chloramphenicol-susceptible recipient. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of outer membrane proteins revealed a markedly diminished 40-kilodalton protein in the resistant transformants. We propose that the mechanism of chloramphenicol resistance in these strains is a relative permeability barrier due to the loss of an outer membrane protein.
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PMID:A permeability barrier as a mechanism of chloramphenicol resistance in Haemophilus influenzae. 387 25

Spencer, Hugh T. (The Johns Hopkins University School of Hygiene and Public Health, Baltimore, Md.), and Roger M. Herriott. Development of competence of Haemophilus influenzae. J. Bacteriol. 90:911-920. 1965.-A chemically defined nongrowth medium was developed for the induction of competence of Haemophilus influenzae by a stepdown procedure. Cells grown logarithmically in Heart Infusion Broth became competent after being transferred to a medium which consisted of amino acids, sodium fumarate, and inorganic salts. Chloramphenicol (2 mug/ml) or l-valine (1 mug/ml) in the nongrowth medium inhibited development of competence. The inhibitory action of l-valine was reversed by comparable concentrations of l-isoleucine. Kinetic studies of the development of competence showed a variable capacity of competent cells to take up deoxyribonucleic acid and reaffirmed earlier findings that competence was not transmissible in H. influenzae. Addition of nicotinamide adenine dinucleotide, thiamine, calcium pantothenate, uracil, and hypoxanthine to the medium for competence resulted in a minimal growth medium in which reduced levels of competence were developed.
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PMID:Development of competence of Haemophilus influenzae. 529 17

Epiglottitis is a life-threatening infection due to Hemophilus influenzae causing respiratory obstruction. Commonly presenting in children under 5 years of age, the obstruction progresses rapidly with associated inspiratory stridor, muffled voice, fever and systemic toxicity. The epiglottis is markedly enlarged on lateral neck X-ray. Once the diagnosis is considered, the patient should always be accompanied by a clinician skilled in airway management, prepared to intervene should acute obstruction occur. Optimally, patients are intubated electively in the operating room by a team of specialized physicians. Nasal or oral tracheal intubation is commonly utilized although a tracheostomy is an alternative means of securing the airway. Positive pressure ventilation may be successful as a temporizing measure if obstruction occurs until the airway is stabilized. Chloramphenicol should be initiated once airway stabilization has been achieved.
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PMID:Epiglottitis. 633 47

It has been suggested that the therapeutic use of oral chloramphenicol in animals is liable to select resistance to antibiotics and that the resistance may jeopardise the treatment of infections in man. At present this risk appears minimal; resistance to chloramphenicol in animal bacteria may well be selected by the increasing use of semi-synthetic penicillins because of linkage between genes coding for production of beta-lactamase and resistance to chloramphenicol. Among salmonellae, the strains causing enteric fever have no animal reservoir and the few food poisoning incidents in man that require therapy can be treated with antibacterial agents such as trimethoprim. Chloramphenicol is not now the antibiotic of choice for any human infection except perhaps a few caused by Haemophilus influenzae. Resistance to antibiotics in 'human' cultures has largely been selected by the use of antibiotics in human medicine. Control of salmonellosis is essentially a public health, not a therapeutic problem.
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PMID:Does the use of chloramphenicol in animals jeopardise the treatment of human infections? 636 4

A kinetic killing-curve method, designed to mimic several aspects of clinical therapy in endocarditis, was used to test 10 strains of Haemophilus parainfluenzae against 28 antibiotic regimens. In an effort to simulate changing in vivo levels of antibiotic in serum, concentrations of three penicillins, three cephalosporins, gentamicin, and chloramphenicol were sequentially adjusted over a 12-hr period. Against six beta-lactamase-negative strains, gentamicin in combination with penicillin or cephalosporin invariably resulted in an additive or synergistic effect. Chloramphenicol and a penicillin or cephalosporin usually displayed an indifferent effect, but chloramphenicol was often antagonistic when combined with gentamicin. With four beta-lactamase-positive strains, variable responses were noted to penicillin-aminoglycoside combinations; cephalosporin-aminoglycoside combinations were usually synergistic. This dynamic approach to killing-curve studies may be more appropriate than a static system for in vitro examination of the effect of antimicrobial combinations against selected organisms.
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PMID:Antimicrobial susceptibility testing of Haemophilus parainfluenzae by a kinetic killing-curve method. 644 77

The bactericidal effects of chloramphenicol and three beta-lactams (ampicillin, cefamandole, and penicillin G) were measured for 27 strains of Haemophilus influenzae type b isolated from the blood or cerebrospinal fluid of infected infants. Of the ampicillin-susceptible strains, 75% were killed by less than 2.0 micrograms of each antibiotic per ml; however, the concentration of the beta-lactam agents required for bactericidal activity was higher than that required for inhibitory activity. Chloramphenicol was the only agent which had no marked discrepancy between inhibitory and bactericidal concentrations regardless of beta-lactamase production. Importantly, chloramphenicol was more rapidly bactericidal than either ampicillin or cefamandole. The bactericidal requirement of ampicillin was increased by the presence of chloramphenicol for about one-third of the isolates examined. Neither the inhibitory nor the bactericidal activity of chloramphenicol was influenced by ampicillin. Synergy occurred for only two beta-lactamase-positive isolates. The more rapid bactericidal action of chloramphenicol persisted even in the presence of ampicillin. The rapid bactericidal action of chloramphenicol with or without ampicillin supports the use of chloramphenicol alone or with ampicillin for H. influenzae infections.
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PMID:Chloramphenicol kills Haemophilus influenzae more rapidly than does ampicillin or cefamandole. 660 27

Three contemporary problems in antimicrobial susceptibility testing were assessed by the CAP-Microbiology Surveys Program in 1982. A penicillin-resistant Streptococcus pneumoniae was categorized correctly as resistant by nearly 78% of Infectious Disease Survey subscribers. This rate compares with a 15% accuracy in the 1981 Surveys challenge, and all results reported from the NCCLS recommended 1 microgram oxacillin screening test correctly found penicillin resistance. Further improvement in the microbiology laboratories' ability to recognize pneumococcal penicillin resistance is critical to good patient care. A methicillin-resistant Staphylococcus aureus (MRSA) strain was assessed accurately by 96.8% of NCCLS disk diffusion test users (methicillin, nafcillin, and oxacillin disks). The microdilution broth method using methicillin as the representative of the penicillinase-stable penicillins performed well. Only nafcillin and oxacillin broth microdilution tests and the automated MIC methods had reduced accuracy. Automated systems also failed to recognize an associated erythromycin resistance in the MRSA strain. Suggestions for improved microdilution test accuracy are made. Three survey challenges have evaluated the sensitivity and specificity of commercial and other beta-lactamase test methods. The false-positive rates for staphylococci range from 3.9 to 4.5%. The false-negative results on a Haemophilus paraphrophilus (beta-lactamase producer) were highest for the iodometric technic (8.7%) and lowest for the chromogenic cephalosporins (1.9%) such as nitrocefin and PADAC. Recommendations for their more limited use in generally emergent clinical settings are offered.
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PMID:Special topics in antimicrobial susceptibility testing: test accuracy against methicillin-resistant Staphylococcus aureus, pneumococci, and the sensitivity of beta-lactamase methods. 660 86

Recent developments (including more accurate assays) that have led to revised recommendations for route of administration, dosage, and indications for chloramphenicol are reviewed. Chloramphenicol is most bioavailable by the oral route; doses of 75 mg/kg/day provide adequate therapeutic concentrations for most clinical indications. Serum concentrations of the drug should be monitored to ensure adequate therapeutic concentrations and to avoid toxicity. This is particularly important in newborns, in patients with liver dysfunction, and in those receiving concomitant drugs that may influence free chloramphenicol concentrations. The indications for chloramphenicol therapy evaluated are: Haemophilus influenzae infections, anaerobic infections, salmonellosis, Rocky Mountain spotted fever, and eye infections. Chloramphenicol is useful in the treatment of invasive Haemophilus influenzae infections resistant to ampicillin, in selected anaerobic and ocular infections, and for rickettsioses in patients under the age of eight years. Because the rare but life-threatening complication of chloramphenicol (aplastic anemia) persists, indications for the drug's clinical use are narrowing once again with the advent of third-generation cephalosporins highly active against gram-negative bacilli including ampicillin-resistant H. influenzae. Similarly, metronidazole or clindamycin may be preferred for some anaerobic infections.
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PMID:Chloramphenicol: recent developments and clinical indications. 676 90

Chloramphenicol has certain notable characteristics: it penetrates reliably into the central nervous system; it is usually bacteriostatic, but is bactericidal for Hemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis; it is metabolized in the liver, and levels of drug in serum need to be monitored in patients with liver disease and in neonates. Potential toxicity limits the use of this drug. It has been estimated that death from aplastic anemia occurs in oe of 24,500-40,800 courses of treatment. The incidence of aplastic anemia after parenteral therapy is unknown; however, only a few cases have been reported. The gray baby syndrome occurred in premature and newborn infants receiving high or unmodified doses of chloramphenicol. This condition can be avoided by reduction of dosage and by monitoring levels of drug in the serum of these infants. The most common toxicity is a reversible, dose-related bone marrow suppression, which is identified by serial monitoring of reticulocyte and complete blood cell counts. Many of the indications for use of this drug are still controversial because studies comparing the toxicity and efficacy of chloramphenicol and of alternative antibiotics have not been done.
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PMID:Chloramphenicol: A review of its use in clinical practice. 679 81


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