tetracycline and Shock--Septic

Topics: Animals; Bacteroides Infections; Chloramphenicol; Enterobacter; Escherichia coli Infections; Gentamicins; Humans; Kanamycin; Klebsiella Infections; Polymyxins; Proteus Infections; Pseudomonas Infections; Sepsis; Serratia; Shock, Septic; Tetracycline

Topics: Anti-Bacterial Agents; Chloramphenicol; Dehydration; Diarrhea; Gastroenteritis; Humans; Kanamycin; Methicillin; Neomycin; Penicillin G; Polymyxins; Sepsis; Shock, Septic; Streptomycin; Sulfisoxazole; Tetracycline

The purpose of the present study was to study the synergy potential of gallic acid-based derivatives in combination with conventional antibiotics using multidrug resistant cultures of Escherichia coli. Gallic acid-based derivatives significantly reduced the MIC of tetracycline against multidrug resistant clinical isolate of E. coli. The best representative, 3-(3',4,'5'-trimethoxyphenyl)-4,5,6-trimethoxyindanone-1, an indanone derivative of gallic acid, was observed to inhibit ethidium bromide efflux and ATPase which was also supported by in silico docking. This derivative extended the post-antibiotic effect and decreased the mutation prevention concentration of tetracycline. This derivative in combination with TET was able to reduce the concentration of TNFα up to 18-fold in Swiss albino mice. This derivative was nontoxic and well tolerated up to 300 mg/kg dose in subacute oral toxicity study in mice. This is the first report of gallic acid-based indanone derivative as drug resistance reversal agent acting through ATP-dependent efflux pump inhibition.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Disease Models, Animal; Drug Synergism; Drug-Related Side Effects and Adverse Reactions; Enzyme Inhibitors; Escherichia coli; Gallic Acid; Indans; Macrophages; Mice; Microbial Sensitivity Tests; Molecular Docking Simulation; Shock, Septic; Tetracycline

We describe the laboratory-confirmed etiologies of illness among participants in a hospital-based febrile illness cohort study in northern Tanzania who retrospectively met Integrated Management of Adolescent and Adult Illness District Clinician Manual (IMAI) criteria for septic shock, severe respiratory distress without shock, and severe pneumonia, and compare these etiologies against commonly used antimicrobials, including IMAI recommendations for emergency antibacterials (ceftriaxone or ampicillin plus gentamicin) and IMAI first-line recommendations for severe pneumonia (ceftriaxone and a macrolide). Among 423 participants hospitalized with febrile illness, there were 25 septic shock, 37 severe respiratory distress without shock, and 109 severe pneumonia cases. Ceftriaxone had the highest potential utility of all antimicrobials assessed, with responsive etiologies in 12 (48%) septic shock, 5 (14%) severe respiratory distress without shock, and 19 (17%) severe pneumonia illnesses. For each syndrome 17-27% of participants had etiologic diagnoses that would be non-responsive to ceftriaxone, but responsive to other available antimicrobial regimens including amphotericin for cryptococcosis and histoplasmosis; anti-tuberculosis therapy for bacteremic disseminated tuberculosis; or tetracycline therapy for rickettsioses and Q fever. We conclude that although empiric ceftriaxone is appropriate in our setting, etiologies not explicitly addressed in IMAI guidance for these syndromes, such as cryptococcosis, histoplasmosis, and tetracycline-responsive bacterial infections, were common.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Ampicillin; Anti-Infective Agents; Bacterial Infections; Ceftriaxone; Child; Cohort Studies; Cryptococcosis; Emergencies; Female; Gentamicins; Histoplasmosis; Humans; Infections; Macrolides; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Bacterial; Respiratory Distress Syndrome; Shock, Septic; Tanzania; Tetracycline; Young Adult

An in vitro model was employed to study the potential role of streptococcal extra-cellular products, rich in streptolysin O, in cellular injury as related to streptococcal infections and post-streptococcal sequelae. Extra-cellular products (EXPA) rich in streptolysin O were isolated from type 4, group A hemolytic streptococci grown in a chemostat, in a synthetic medium. EXPA induced moderate cytopathogenic changes in monkey kidney epithelial cells and in rat heart cells pre-labeled with 3H-arachidonate. However very strong toxic effects were induced when EXP was combined with oxidants (glucose oxides generated H2O2, AAPH-induced peroxyl radical (ROO.), NO generated by sodium nitroprusside) and proteinases (plasmin, trypsin). Cell killing was distinctly synergistic in nature. Cell damage induced by the multi-component cocktails was strongly inhibited either by micromolar amounts of gamma globulin, and Evan's blue which neutralized SLO activity, by tetracycline, trasylol (aprotinin), epsilon amino caproic acid and by soybean trypsin inhibitor, all proteinase inhibitors as well as by a non-penetrating PLA2 inhibitor A. The results suggest that fasciitis, myositis and sepsis resulting from infections with hemolytic streptococci might be caused by a coordinated 'cross-talk' among microbial, leukocyte and additional host-derived pro-inflammatory agents. Since attempts to prolong lives of septic patients by the exclusive administration of single antagonists invariably failed, it is proposed that the administration of 'cocktails' of putative inhibitors against major pro-inflammatory agonizes generated in inflammation and infection might protect against the deleterious effects caused by the biochemical and pharmacological cascades which are known to be activated in sepsis.

Topics: Animals; Anti-Bacterial Agents; Antioxidants; Aprotinin; Arachidonic Acid; Cells, Cultured; Endopeptidases; Epithelial Cells; Erythrocytes; Evans Blue; gamma-Globulins; Haplorhini; Hemolysis; Humans; Hydrogen Peroxide; Myocardium; Oxidants; Phospholipases A; Phospholipases A2; Rats; Shock, Septic; Streptococcal Infections; Streptococcus pyogenes; Streptolysins; Tetracycline

We have tested whether tetracyclines (TETs) are able to protect mice from lipopolysaccharide (LPS)-induced shock, a cytokine-mediated inflammatory reaction. Mice, injected with a single dose of tetracycline base (TETb; 1.5, 10 and 20 mg/kg of body weight) or doxycycline (DOXY; 1.5 mg/kg), were significantly protected from a lethal intraperitoneal injection of LPS (500 micrograms per mouse). TETs acted in early events triggered in response to LSP; in fact, they were no longer significantly protective if injected more than 1 h after the injection of endotoxin. LPS-treated mice protected by TETs showed a significant inhibition of tumor necrosis factor alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), and nitrate secretion in the blood, events that were directly related with the survival. In mice treated with TETs a significant decrease of inducible nitric oxide synthase (iNOS) activity was observed in spleen and peritoneal cells compared with that detected in mice treated with LPS alone. Furthermore, TETs were found to inhibit NO synthesis by peritoneal macrophages stimulated in vitro with LPS. On the contrary, TETs were unable to decrease the ability of the macrophages to synthesize IL-1 alpha and TNF-alpha in vitro. These results indicate that TETs are not able to act directly on the synthesis of these cytokines, but they may modulate other pathways that could in turn be responsible for the inhibition of IL-1 alpha and TNF-alpha synthesis. Altogether, these results indicate that TETs are advantageous candidates for the prophylaxis and treatment of septic shock in mice, having both antimicrobial activity and the ability to inhibit endogenous TNF-alpha, IL-1 alpha, and iNOS, hence, exerting, potent anti-inflammatory effects.

Topics: Animals; Anti-Bacterial Agents; Cytokines; Down-Regulation; Doxycycline; Endotoxemia; Enzyme Induction; Female; Injections, Intraperitoneal; Interleukin-1; Lung; Macrophages, Peritoneal; Mice; Mice, Inbred BALB C; Nitrates; Nitric Oxide Synthase; Shock, Septic; Spleen; Tetracycline; Tumor Necrosis Factor-alpha

Septic shock results from excessive stimulation of host immune cells, particularly monocytes and macrophages, by lipopolysaccharide (LPS) released from gram-negative bacteria. Macrophage-derived cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1 beta), have been identified as central mediators in the pathogenesis of septic shock and the resultant mortality. Therefore, these cytokines were targets for experimental therapy for septic shock. Because of tetracycline's ability to intervene in cellular mechanisms involved in cytokine secretion, we tested the effect of tetracycline on LPS-induced septic shock and inflammatory lesions in mice. Tetracycline was found to protect mice against LPS-induced lethality and to abolish clinical signs of LPS-induced inflammatory lesions. This protection correlates with tetracycline's ability to reduce LPS-induced TNF-alpha levels in serum. Furthermore, tetracycline was found to inhibit LPS-induced TNF-alpha and IL-1 beta secretion, but not cytokine mRNA accumulation, in human monocytes in vitro. The results presented here suggest that tetracycline is a potent drug for LPS-induced pathology and that its mechanism of action involves blockage of posttranscriptional events of cytokine production.

Topics: Animals; Anti-Bacterial Agents; Cytokines; Female; Humans; Inflammation; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Shock, Septic; Tetracycline

Topics: Anaphylaxis; Gentamicins; Humans; Shock, Septic; Tetracycline

Topics: Aged; Chloramphenicol; Drug Resistance, Microbial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Pleuropneumonia; Shock, Septic; Tetracycline

The Jarisch-Herxheimer reaction is a complication that can follow treatment of several infectious diseases. Its most severe form is in louse-borne relapsing fever; in this syndrome the reaction can cause death. Information from studies in Ethiopia during the past eight years is presented, and clinical, physiological, pathological, and immunological features of the reaction are described. Possible causative mechanisms of the reaction are discussed, especially in relation to the role of endotoxin, and an attempt is made to consider this reaction in relation to other endotoxin-associated states.

Topics: Adult; Animals; Blood Gas Analysis; Blood Pressure; Body Temperature; Child; Endotoxins; Humans; Lung; Male; Myocardium; Penicillin G Procaine; Phagocytosis; Rabbits; Relapsing Fever; Respiration; Shock, Septic; Tetracycline; Vasomotor System

Topics: Aged; Ampicillin; Chloramphenicol; Drug Combinations; Dysentery; Humans; Male; Middle Aged; Oleandomycin; Salmonella Infections; Shock, Septic; Tetracycline

Topics: Animals; Haplorhini; Mice; Rabbits; Rats; Shock, Septic; Species Specificity; Tetracycline

Topics: Animals; Antigens, Bacterial; Chlortetracycline; Escherichia coli; Escherichia coli Infections; Intestinal Mucosa; Kidney; Lethal Dose 50; Liver; Lung; Macaca; Mice; Mice, Inbred A; Oxytetracycline; Rabbits; Rats; Shock, Septic; Tetracycline

Shock must be treated by correcting the cause, for any treatment of hypotension or shock, as such, is only an adjunctive measure; but the hemodynamic manifestations also need treatment. Vasopressors are helpful and effective under the right circumstances. Unless the blood volume is normal, the use of drugs that block the sympathetic nervous system (e.g., phenoxybenxamine) can be extremely hazardous and hasten death. However, the effect of adrenergic blocking drugs in endotoxic shock and other types of toxic shock is still to be determined; use of such drugs should be considered experimental until the results have been studied more extensively. Clinically, the most common forms of vascular shock are associated with blood loss, myocardial infarction, and endotoxemia. Characteristic hemodynamics of each situation are presented tabularly, and the physicians need to understand the differences is emphasized. The pharmacology of vasopressors, relating primarily to hemodynamic considerations and the response to vasopressors when severe reduction in blood pressure is associated with the shock syndrome is discussed. Drugs that stimulate the adrenergic receptors in the heart and blood vessels, with the exception of isoproteronol, are commonly referred to as vasopressors. The adrenergic stimulators may be classified into 3 groups: alpha (phenylephrine hydrochloride), beta (epinephrine), and alpha-beta (l-norepinephrine). Because alpha stimulators do not usually increase cardiac output, alpha-beta and beta-adrenergic stimulators are generally the most useful for treating shock. Routine use of adrenergic stimulators with the exclusion of other therapies, however, is generally unwarranted.

Topics: Bacteria; Chloramphenicol; Epinephrine; Humans; Isoproterenol; Metaraminol; Methoxamine; Morphine; Myocardial Infarction; Nalorphine; Norepinephrine; Phenoxybenzamine; Phenylephrine; Shock; Shock, Septic; Streptomycin; Tetracycline; Vasoconstrictor Agents

Topics: Animals; Endotoxins; Escherichia coli; Intestinal Mucosa; Kidney Cortex; Liver; Lung; Mice; Mice, Inbred Strains; Microscopy, Fluorescence; Shock, Septic; Tetracycline

Topics: Abortion, Septic; Adrenal Cortex Hormones; Bicarbonates; Blood Transfusion; Chloramphenicol; Digoxin; Escherichia coli Infections; Exchange Transfusion, Whole Blood; Female; Gentamicins; Humans; Hysterectomy; Isoproterenol; Kanamycin; Penicillins; Plasma Substitutes; Pregnancy; Puerperal Infection; Sepsis; Shock, Septic; Tetracycline

Topics: Adolescent; Adult; Age Factors; Aged; Child; Child, Preschool; Humans; Infant; Mannitol; Meningococcal Infections; Middle Aged; Penicillins; Shock, Septic; Sulfanilamides; Tetracycline

Topics: Adolescent; Adult; Aged; Ampicillin; Animals; Arteriovenous Anastomosis; Blood Pressure; Capillary Permeability; Cardiac Output; Cephalothin; Chloramphenicol; Dogs; Escherichia coli; Escherichia coli Infections; Female; Hemodynamics; Humans; Kanamycin; Klebsiella; Klebsiella Infections; Male; Methylprednisolone; Middle Aged; Penicillins; Polymyxins; Pseudomonas; Pseudomonas Infections; Shock, Septic; Tetracycline; Venous Pressure

The results of treatment have been analysed in 173 patients with septicaemia during 1962-8. Between 1962 and 1965 various antibiotics were used, and shock was treated with vasopressor agents. Between 1966 and 1968 kanamycin was given initially, and shock was treated with corticosteroids and with intravenous fluid therapy monitored with a central venous pressure manometer.The mortality rate in 1966-8 fell to half that of the earlier period in patients with Gram-negative infections, and in those with shock. The reduced mortality in the latter was clearly associated with the use of a central venous manometer to control intravenous fluid therapy, though whether the reduction resulted from specific improvement in intravenous therapy or from the necessary closer observation of the patient is not clear. Staphylococcal septicaemia was common during both periods, and its mortality rate did not fall; hence methicillin together with kanamycin is now given initially in all cases.

Topics: Adrenal Cortex Hormones; Adult; Aged; Chloramphenicol; Digitalis Glycosides; Female; Humans; Kanamycin; Male; Middle Aged; Sepsis; Shock, Septic; Staphylococcal Infections; Tetracycline; Vasoconstrictor Agents

Topics: Adult; Amnion; Birth Weight; Chloramphenicol; Female; Fetal Death; Hospitalization; Humans; Infant Mortality; Infant, Newborn; Inflammation; Injections, Intravenous; Labor Presentation; Maternal Mortality; Obstetric Labor, Premature; Penicillins; Pregnancy; Pregnancy Complications; Shock, Septic; Streptomycin; Tetracycline

Topics: Adrenal Cortex Hormones; Adult; Ampicillin; Anti-Bacterial Agents; Cephalothin; Chloramphenicol; Colistin; Enterobacter; Enterobacteriaceae; Escherichia coli; Female; Humans; Kanamycin; Klebsiella; Middle Aged; Polymyxins; Proteus; Pseudomonas; Pseudomonas aeruginosa; Sepsis; Shock, Septic; Streptomycin; Tetracycline; Vasoconstrictor Agents

Topics: Ampicillin; Angina Pectoris; Anti-Bacterial Agents; Bacteriological Techniques; Diagnosis, Differential; Drug Therapy; Emergencies; Genital Diseases, Female; Humans; Hydrocortisone; Hypoxia; Metaraminol; Sepsis; Shock; Shock, Septic; Surgical Wound Infection; Tetracycline

Bacteremic shock is second in frequency only to myocardial infarction as a cause of hypotension and death in hospitalized medical patients. The clinical course is marked by fever, usually with chills, and hypotension with a full pulse and warm extremities, followed by shock, often resistant to treatment. Anticipation of this complication in patients with certain predisposing diseases or factors facilitates early recognition of the symptoms and signs of bacteremic shock and prompt treatment. Early and effective treatment of the offending infection often prevents progression of hypotension to the stage of frank vascular collapse.

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Emergencies; Humans; Hypotension; Metaraminol; Methicillin; Myocardial Infarction; Norepinephrine; Phenoxybenzamine; Sepsis; Shock; Shock, Septic; Streptomycin; Tetracycline

Topics: Adrenocorticotropic Hormone; Aminosalicylic Acid; Aminosalicylic Acids; Anaphylaxis; Anti-Bacterial Agents; Aspirin; Body Constitution; Chloramphenicol; Cortisone; Drug Hypersensitivity; Otolaryngology; Penicillins; Physiology; Procaine; Shock; Shock, Septic; Skin Tests; Streptomycin; Surgical Procedures, Operative; Tetracycline; Toxicology