Comparative study of imipenem in severe infections

Forty patients with severe bacterial infections due to micro-organisms known or presumed to be sensitive to both study antibiotics, were randomized to receive either imipenem with cilastatin, 500 mg/500 mg iv tid (20 patients), or cefotaxime, 2 g iv tid (20 patients). The types of infections observed were equally distributed between the 2 groups, and consisted of 18 complicated urinary tract infections, 9 pneumonia, 7 bone and soft tissue infections, 4 septicaemia of unknown origin and 2 intravenous-catheter-related septicaemia. In the imipenem group, 12 patients were bacteraemic, compared to 10 in the cefotaxime group. The micro-organisms observed were evenly distributed with Escherichia coli (22 cases) and Klebsiella pneumoniae (6 cases) being the most frequent. Sixteen patients were cured in the imipenem group and 15 in the cefotaxime group, while 2 and 2 improved, 2 and 1 relapsed and 0 and 2 did not respond to the therapy, respectively. In the imipenem group, no clinical side effects were observed while 5 patients had mild reactions in the cefotaxime group (2 fever, 1 skin rash, 1 oral candidiasis and 1 diarrhoea). Imipenem thus appeared as effective and well tolerated as cefotaxime in the treatment of severely infected patient

Controversies in the Use of Passive Immunotherapy for Bacterial Infections in the Critically Ill Patient

Several preparations of standard immunoglobulins for intravenous use have been tested as adjunctive therapy for bacterial infections in premature neonates and in critically ill adults after major surgery, trauma, and burn. The use of intravenous immunoglobulins in these settings is controversial because the efficacy and cost-effectiveness of this treatment are still not definitively established. Specific preparations of immunoglobulins against Pseudomonas aeruginosa for intramuscular administration have shown promising efficacy, and preparations for intravenous administration are now under investigation. Cross-protection against a wide range of gram-negative infections has been attempted by the administration of antiserum to the core glycolipid of lipopolysaccharide prepared from volunteers immunized with the J5 mutant of Escherichia coli 0111. Treatment with this preparation improved the survival rate of patients with gram-negative bacteremia and, when administered prophylactically to high-risk surgical patients, prevented shock and death related to gram-negative infections. The mechanism of protection of the J5 antiserum is not clearly understood because of our inability to measure the actual protective antibody in polyclonal J5 antiserum. Thus, the preparation of readily available cross-protective hyperimmune immunoglobulins is hampered because there is presently no method of selecting appropriate donors or high-titered plasma pool

Comparative imipenem treatment of Staphylococcus aureus endocarditis in the rat

The efficacy of imipenem alone or in association with gentamicin against Staphylococcus aureus experimental endocarditis was compared to the efficacy of cloxacillin alone or in association with gentamicin. Parenteral treatment was started 24 h after intravenous bacterial challenge of rats with catheter-induced aortic valve vegetations. The cloxacillin MIC and MBC for Staph. aureus were 0.125 and 32 mg/l and the imipenem MIC and MBC 0.008 and 8 mg/l, respectively. In-vitro killing curves showed a synergistic effect between cloxacillin and gentamicin, and an additive effect between imipenem and gentamicin. Only large doses of cloxacillin (400 mg/kg tid) (producing serum levels above those obtained after intravenous injection of 2 g in man) achieved results comparable to those of imipenem 80 mg/kg tid (producing serum levels similar to those obtained after an intravenous dose of 750 mg in man) in reducing the bacterial numbers in vegetations after 3 and 5 days of treatment. There was a significantly greater reduction of bacterial numbers in vegetations after treatment with the association of cloxacillin and gentamicin than with cloxacillin alone. In contrast, the addition of gentamicin to imipenem did not improve significantly the results of treatment with imipenem alone, but imipenem alone was as good as the combination cloxacillin and gentamicin after 5 days of treatment. We conclude that imipenem is a highly bactericidal drug in this animal model, worth considering for clinical trials in the treatment of Staph. aureus infection

Controversies in the use of passive immunotherapy for bacterial infections in the critically ill patient

Several preparations of standard immunoglobulins for intravenous use have been tested as adjunctive therapy for bacterial infections in premature neonates and in critically ill adults after major surgery, trauma, and burn. The use of intravenous immunoglobulins in these settings is controversial because the efficacy and cost-effectiveness of this treatment are still not definitively established. Specific preparations of immunoglobulins against Pseudomonas aeruginosa for intramuscular administration have shown promising efficacy, and preparations for intravenous administration are now under investigation. Cross-protection against a wide range of gram-negative infections has been attempted by the administration of antiserum to the core glycolipid of lipopolysaccharide prepared from volunteers immunized with the J5 mutant of Escherichia coli 0111. Treatment with this preparation improved the survival rate of patients with gram-negative bacteremia and, when administered prophylactically to high-risk surgical patients, prevented shock and death related to gram-negative infections. The mechanism of protection of the J5 antiserum is not clearly understood because of our inability to measure the actual protective antibody in polyclonal J5 antiserum. Thus, the preparation of readily available cross-protective hyperimmune immunoglobulins is hampered because there is presently no method of selecting appropriate donors or high-titered plasma pools

Mechanical concept of the neurosurgical robot ‘Minerva'

We describe a robot capable of performing all procedures necessary to carry out a complete stereotactic neurosurgical operation under the control and supervision of a surgeon. The operation consists of the introduction of a small probe with diameter 2-3 mm through a hole without trepanation. The robot has been built and is now being tested and evaluated. The accompanying control software as well as various medical probes are either in development or partially tested. The installation will be able to carry out a complete intervention under the surveillance of a computed tomography scanner. In this article we emphasize the design choices required to eliminate gearing backlash in a crucial degree of freedo

Pathogenesis and Potential Strategies for Prevention and Treatment of Septic Shock: An Update

Septic shock is mediated by complex interactions of cells, cytokines, and humoral pathways. Clinical therapeutic strategies aimed at inhibiting selected pathways have been efficacious in subsets of patients. Experimental studies focusing on the activities of single cytokines have contributed to the understanding of the complex pathophysiology of septic shock. More precise delineation of the roles of each mechanism contributing to pathogenesis will permit the identification of subsets of patients who might benefit from particular therapeutic strategies and will guide the development of additional approaches to prevention and treatmen

Antibodies to Lipopolysaccharides after Immunization of Humans with the Rough Mutant Escherichia coli J5

To investigate whether immunization with Escherichia coli J5 boiled cells induces antibodies directed at deep core structures, antibodies against JS lipopolysaccharide (LPS), Re LPSt and Iipid A were measured in the serum of 70 volunteers before and 2 weeks after immunization. To improve the sensitivity and the specificity ofELISAt complexes of core LPS with high-density lipoproteins were used instead of free core LPS as antigens. A median three-fold increase in antibodies directed against J5 LPS was observed, but no significant increase in the antibodies against Re LPS or lipid A was found. Since JS antiserum did not react with several smooth LPS or with Re LPS and lipid At cross-reactivity could not be demonstrated. Thus, immunization of volunteers with E. coli J5 produced a modest specific antibody response against J5 LPS. The mechanism of protection previously observed with J5 antiserum remains unclea

Antibodies to Core Lipopolysaccharide Determinants: Absence of Cross-reactivity with Heterologous Lipopolysaccharides

Using monoclonal antibodies directed against defined epitopes of endotoxin core, this study demonstrated that the presentation of lipopolysaccharide (LPS) to antibodies is critical for measuring the specific binding of antibodies to LPS structures. False cross-reactive reactions apparently were observed when free core LPS or lipid A were used as antigens in ELISA, whereas coating with complexes of high-density lipoproteins with core LPS increased both the sensitivity and the specificity of the test compared with coating with free core LPS, so that nonspecific binding of antibodies was largely avoided. Using this technique, it was not possible to find broadly cross-reactive core LPS antibodies after immunization of rabbits and humans with rough mutants of gram-negative bacteria. These observations underscore the need for careful evaluation of the potential for cross-reactivity of antisera and of monoclonal antibodies directed against endotoxin cor