Stimulation of cellular function by thymopentin (TP-5) in three AIDS patients.
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Biomedical subjects
Publications and source records attributed to N Clumeck.
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Ceftazidime was administered intravenously in doses of 1 to 6 g/day to 21 patients with serious Pseudomonas aeruginosa infections (12 pulmonary, 6 septicaemias, 3 urinary tract infections). Mean MIC was 1.0 mg/l. Eighteen (86%) of the 21 patients responded satisfactorily (cured or improved). The selection or emergence of resistant organisms during treatment (mostly Candida, Staphylococcus aureus, and enterococci) was noted in 6 patients. Toxicity was minimal (eosinophilia and reversible mild liver function abnormalities).
Ceftazidime was administered intravenously or intramuscularly or both in doses of 1 to 6 g per day to 33 patients with serious gram-negative bacillary infections (12 pulmonary, 10 urinary tract, 4 soft tissue, 4 intraabdominal, and 3 miscellaneous infections). Twenty-one patients were septicemic. We identified 20 isolates of members of the family Enterobacteriaceae and 13 isolates of Pseudomonas aeruginosa. Seventeen patients had failed to respond to previous antimicrobial therapy. A total of 23 patients were clinically cured, 7 patients improved, and 3 patients failed to respond to therapy. The selection or emergence of resistant organisms during treatment (mostly Candida spp., Staphylococcus aureus, and enterococci) was noted in 11 patients. Toxicity was minimal (reversible mild liver function abnormalities and eosinophilia). The results of this study suggest that ceftazidime is an effective and well-tolerated new cephalosporin for the therapy of serious infections due to susceptible gram-negative organisms.
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The severity of an infection is related to the disequilibrium in the complex relationship between the infected host and the pathogenic agent. The bacterial factors include the size of the inoculum, the pathogenicity and particular virulence of certain strains which, because of their antigenic structures (capsular antigen, lipopolysaccharide, exotoxins), may escape the bactericidal defence mechanisms of the serum, phagocytosis and intracellular bacterial destruction. The principal host factor, which also determines the prognosis of the infection, is the subject's immune status which can be affected in its non-specific elements (complement system) and in its specific elements (humoral and cellular immunity). Thus, in the normal host, only extremely virulent bacteria are capable of causing severe infections, while in the immunodepressed patient, even non-pathogenic organisms which are usually commensual are capable of being invasive.
33 patients with serious gram-negative bacillary infections were treated with cefotaxime. In patients with normal renal function the dose varied between 1.5 to 4 g/day. 17 patients had urinary tract infections, 5 respiratory tract infections, 1 combined urinary tract infection and respiratory tract infection, and 10 miscellaneous infections. 16 patients had septicemia. 25 infections were due to pathogens resistant in vitro to ampicillin, cephalothin, gentamicin and/or tobramycin. 15 infections had failed to respond to ampicillin, cefazolin, gentamicin or tobramycin therapy. 32/33 patients responded favourably to cefotaxime (cure or improvement) but 4 patients developed superinfection with cefotaxime-resistant bacteria. No evidence of nephrotoxicity was observed except for a transient moderate rise in creatinine in one patient.
The sensitivity of blood culture isolates to the bactericidal activity of normal human serum (NHS) has been studied in 101 patients with gram-negative sepsis. These results were compared with clinical status and outcome, and to the presence of specific IgG or IgM antibodies to O antigens of bacteraemic strains in autologous serum. 23% of the strains were markedly resistant, 27% markedly sensitive and 50% intermediately sensitive to the bactericidal activity of NHS. Shock or death occurred more frequently in immunocompromised patients and those infected with serum-resistant strains. IgG antibody titres to O antigens were significantly lower in patients with serum-resistant organisms regardless of their immune status. Resistance to natural bactericidal antibodies and low immunogenicity of the infecting organism, plus immunodeficiency in the host, may account for apparent increased virulence of some gram-negative bacilli.
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Cefotaxime was used to treat 33 patients with serious Gram-negative bacillary infections. The dosage varied between 1.5 g and 4 g/day in patients without renal failure. Eighteen patients had urinary tract infections, 6 had pulmonary infections and 10 had miscellaneous infections. Sixteen patients were also bacteremic. Twenty-five infections were due to pathogens resistant to ampicillin, cephalothin, gentamicin and/or tobramycin, in vitro. Fifteen infections had failed to resolve during ampicillin, cefazolin, gentamicin or tobramycin therapy. Thirty-two patients responded favourably (cure or improvement). Four patients developed superinfection with cefotaxime-resistant bacteria. One patient developed mild reversible renal insufficiency. Cefotaxime is a very active cephalosporin with potential use in serious multi-resistant enterobacteria infections.
In spite of discovery of new antibiotics and regular progress in intensive care, mortality from severe bacterial sepsis remains high. In this review the importance of cellular and humoral immunity in the pathogenesis and the outcome of severe infection is delineated. Immunological evaluation of patients in Intensive Care Units should be performed almost routinely in order to detect "high risk" patients with acquired defect in host-defence mechanisms. For these patients in addition to nutritional care, passive or active immunotherapy will help to restore resistance to bacterial infection.
The diagnostic value of several investigations which may demonstrate bacteria or bacterial products in cerebrospinal fluid (CSF) samples from patients with meningitis are discussed. Estimation of CSF lactate and lactate dehydrogenase levels was found to be of value in the differential diagnosis of viral, bacterial and fungal meningitis and the detection of endotoxin by the Limulus amoebocyte lysate test was shown to be strongly suggestive of Gram-negative meningitis. The demonstration of bacterial capsular polysaccharides in CSF by counterimmuno-electrophoresis, latex agglutination and ELISA was of value in establishing a precise aetiological diagnosis, but the usefulness of these methods was limited by the lack of general availability of specific high-potency antisera which determine the sensitivity of the procedure. These screening tests do not replace standard analysis of CSF but provide useful ancillary evidence of meningitis. Negative results obtained from screening tests should not exclude a diagnosis of bacterial meningitis and a decision to withhold treatment should only be made after all available CSF results are evaluated in conjunction with the clinical features.
Studies of coagulation were performed prospectively in 41 patients with mild to moderately severe acute pancreatitis. Six patients (15%) presented with coagulation data suggestive of defibrination; two of them had clinical signs of bleeding. No other cause than pancreatitis was found in these 6 patients to account for coagulation abnormalities. Comparing the patients who presented defibrination to those who did not, no difference was observed in clinical course and admission values of serum amylase, fibrinogen, urea, calcium, glucose, transaminase levels, white blood cell count and arterial partial pressure of oxygen. Platelets counts and serum creatinine levels were respectively lower and higher in the first group of patients.
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