The effect of amikacin and imipenem alone and in combination against an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain.

In vitro and in vivo activities of amikacin and imipenem alone, and in combination, were studied against an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain. The strain was in vitro susceptible to both antimicrobials at 10(5) and 10(7) CFU/mL. In time-kill studies amikacin, imipenem, and amikacin plus imipenem decreased the bacterial counts; difference between the bactericidal effects was not observed.

The effect of different doses of cisplatin on the pharmacokinetic parameters of cefepime in mice.

The simulation of human serum levels is essential in animal models to extrapolate the experimental results to clinical practice. Administration of a nephrotoxic drug such as cisplatin can be used to cause renal dysfunction as an approach to mimic human serum levels of renally excreted drugs. We aimed to determine the dose of cisplatin that did not affect the survival rate of mice and to achieve human-like serum concentrations of cefepime.

In vitro and in vivo activities of ciprofloxacin and levofloxacin against an SHV-5 extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain.

Activities of ciprofloxacin and levofloxacin against an SHV-5 extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae strain were studied in vitro and in vivo in septic mice using a high inoculum. Susceptibility to ciprofloxacin and levofloxacin was independent of the inoculum size. In killing curve studies, after 24 hours the initial 7.

[Biological effects of microorganisms, their substances and immunosuppressive agents in mice].

The author provide evidence from several aspects that the normal microbial flora has a permanent and life-long immune modulating role in conventional organisms and a stimulating effect both on specific and non-specific defence. However, in case of artificial interventions (stress, drugs) affecting the organism, existence of the normal flora may have an adverse effect (endotoxin effect, bacterial translocation). The immunomodulants show a stimulating affect mainly in organisms with undeveloped immune system, and their effects are independent from the presence or absence of the microbial flora.

In vitro and in vivo activities of amikacin, cefepime, amikacin plus cefepime, and imipenem against an SHV-5 extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain.

The in vitro and in vivo effectiveness of amikacin, cefepime, and imipenem was studied using a high inoculum of an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain. An in vitro susceptibility test at the standard inoculum predicted the in vivo outcome of amikacin or imipenem while it did not do so for cefepime due to the inoculum effect.

Interaction of immunosuppressive drugs in mouse experiments with special regards to bacterial translocation.

Following intraperitoneally (i.p.) applied treatment with 12.

[Interaction of immunosuppressive drugs in mice with special regard to bacterial translocation].

Following intraperitoneally (i.p.) applied treatment with 12.

[Effect of immunosuppressive agents and antilymphocyte serum on bacterial translocation in mice].

Following intraperitoneally applied treatment with 0.5 ml of ana partes diluted antilymphocyte serum (ALS) of immunosuppressive effect no bacterial translocation (BT) was observed in mice. The ALS treatment applied in combination with other immunosuppressive agents such as lymphotropic cytostatics as dianhydrogalactitol (30 mg/kg) or chlorpromazine (75 mg/kg) did not increase the mice drug sensitivity to used agents.

Modulation of the cellular immune response to intracerebral lymphocytic choriomeningitis virus (LCMV) infection in mice.

Certain viruses do not kill the cells they infect. The immunological response of the host in such situations may be involved in the development of pathologic changes and clinical illness. Pioneering work by Rowe has shown that death associated with acute LCMV infection in the mouse is resulted from the immune response.

Biological effects of microorganisms and their substances in mice.

In our experiments we evidence from several aspects that the normal microbial flora has a permanent and life-long immune modulating role in conventional organisms and a stimulating effect both on specific and non-specific defense. However, in case of artificial interventions (stress, drugs) affecting the organism, existence of the normal flora may have an adverse effect on it (endotoxin effect, bacterial translocation). The immunomodulants show a stimulating effect mainly in organisms with undeveloped immune system, and their effects are independent from the presence or absence of the microbial flora.

Outlines of the immunological research in the Institute of Microbiology; Semmelweis Medical University.

The working group on immunology under the leadership of Pál Földes began its activity with poliovirus studies during the severe epidemics of 1957. It was he who first in Hungary isolated poliovirus strain from patients [1]. His colleague was Ilona, Szeri who had gained her first experiences in virology at József Sinkovics's virus laboratory.

Effect of antilymphocyte serum on bacterial translocation in mice.

Following intraperitoneally applied treatment with antilymphocyte serum (ALS) of immunosuppressive effect no bacterial translocation (BT) was observed in mice. The ALS treatment applied in combination with other immunosuppressive agents such as lymphotropic cytostatics as dianhydrogalactitol or chlorpromazine did not increase the mice's drug sensitivity to the used agents. According to our results, ALS can be suitable for combined application with other immunosuppressive agents as it can increase immunosuppression without side-effects such as those induced by bacterial translocation.

[Role of the thymus and normal microbial flora on plasma fibronectin concentration in mice treated with immunomodulatory drugs].

The plasma fibronectin (pFN) concentration (cc)-determined by electro-immunodiffusion method-of untreated genetically or artificially athymic mice, or treated with TP-4 (thymus hormone sequence analog synthetic preparation) showed no significant difference from their euthymic or untreated controls. In contrast, the pFN cc in mice with different microbiological state showed significant alterations; the highest level occurred in conventional mice. The lower level in germfree mice was increased by bacterial monocontamination.

[Interaction between Bordetella pertussis vaccine and chlorpromazine in mice].

In acute toxicity experiments authors observed increased mortality on the first day following 75 mg/kg chlorpromazine (CPZ) treatment in mice pretreated with Bordetella pertussis vaccine (9 x 10(9) killed bacterium/mouse) compared to control animals treated with CPZ alone. Initially, the increased drug sensitivity observed after combined treatment was attributed to summation of the toxic effects. However, the cumulation of mortality did not cease on the following days; furthermore, an increase of bacterial translocation (translocation index of P-CPZ group: 4.

Interaction between Bordetella pertussis vaccine and chlorpromazine in mouse experiments.

In acute toxicity experiments the mortality of mice pretreated with Bordetella pertussis vaccine increased on the first day following chlorpromazine (CPZ) treatment, compared to control animals treated with CPZ alone. Initially, the increased drug sensitivity observed after combined treatment was attributed to summation of the toxic effects. However, the cumulation of mortality did not cease on the following days, furthermore, an increase of bacterial translocation was observed on days 6 and 7, i.

Interaction of immunomodulant substances in mouse experiments with special regard to drug sensitivity and bacterial translocation.

In acute toxicity experiments changes in drug sensitivity and in the rate of bacterial translocation (BT) were investigated in mice treated with immunomodulatory drugs: dianhydrogalactitol (DAG) in doses 20 and 30 mg/kg, chlorpromazine (CPZ) in doses 60 and 75 mg/kg and Mannozym (M) in dose equivalent to 40 mg per kg zymosan. The drugs were used separately or in combination. The sensitivity of mice to immunosuppressive DAG or CPZ was higher in the case of combined treatment than that of separately treated ones.

[Interaction between immunomodulatory drugs in mice with special regard to changes of drug sensitivity and rate of bacterial translocation].

In acute toxicity experiments the changes in drug sensitivity and in the rate of bacterial translocation (BT) were investigated in mice treated with immunomodulatory drugs: dianhydrogalactitol (DAG) in doses 20 and 30 mg/kg, chlorpromazine (CPZ) in doses 60 and 75 mg/kg and Mannozym (M) in dose 40 mg/kg for zymosan content. The drugs were used separately or in combination. The sensitivity of mice to immunosuppressive DAG or CPZ was higher in the case of combined treatment, than that of separately treated ones.

Influence of the thymus and the normal microflora on the plasma fibronectin concentration in mice.

The plasma fibronectin (pFN) concentration (cc) of untreated genetically or artificially athymic mice, or treated with TP-4 (thymus hormone sequence analog synthetic preparation) showed no significant difference from their euthymic or untreated controls. In contrast, the pFN cc in mice with different microbiological state showed significant alterations; the highest level occurred in conventional mice and the lower level in germfree mice was increased by bacterial monocontamination. The alternation from SPF into conventional state in nude mice also resulted in the increase of the pFN cc.

[Effect of pretreatment with immunomodulating agents on the outcome of lymphocytic choriomeningitis virus infection in athymic (nude) and euthymic mice].

Balb/c (euthymic) and nu/nu (athymic) mice were treated intraperitoneally with TP-4 (a synthetic tetrapeptide, thymopoietin sequence analog, Pharmaceutical Product's Factory Gedeon Richter, Budapest, Hungary) or with Mannozym (0.1% zymosan suspension, Institute for Serobacterological Production and Research, HUMAN, Budapest, Hungary), and were infected intracerebrally with LCM virus. Both of the agents contributed to the development of fatal choriomeningitis, consequently they stimulated the cellular immune response in euthymic mice, but the athymic mice, either treated or not, survived the infection, consequently the agents had no effect on the course of LCM virus infection.

Effect of Mannozym on the course of LCMV infection in mice with undeveloped and normal immune system.

Adult germfree (Gf) mice with undeveloped immune system due to antigen deficient environment, conventional (Cv) mice with normal immune system and Cv suckling mice with undeveloped immune system due to age were treated intraperitoneally with Mannozym (M, 0.1% zymosan suspension) 4 days or 4 days and 1 day before the intracerebral inoculation with lymphocytic choriomeningitis virus (LCMV). One dose of M was equal to 40 mg/kg of zymosan.

Effect of microbial immunomodulants on the course of LCMV infection in old mice with thymus involution.

Old mice with thymus involution were treated intraperitoneally with a live vaccine containing a mesogenic strain of attenuated Newcastle Disease Virus or with Mannozym (M, 1% zymosan suspension). One day after the treatments mice were infected with lymphocytic choriomeningitis virus (LCMV) intracerebrally. The fatal course of the consequent LCMV infection was stimulated by each of the pretreatments, indicating that the cellular immune response was stimulated.

The course of LCMV infection in euthymic and athymic mice pretreated with immunomodulatory agents.

Balb/c (euthymic) and nu/nu (athymic) mice were treated intraperitoneally with TP-4 (a synthetic tetrapeptide, thymopoietin sequence analog) or with Mannozym (1% zymosan suspension), and were infected intracerebrally with LCM virus. Both of the agents contributed to the development of fatal choriomeningitis, consequently stimulated the cellular immune response in euthymic mice, but the athymic mice either treated or not, survived the infection, consequently the agents had no effect on the course of LCM virus infection. Both agents exerted a thymus-dependent cellular immune response stimulating effect.

[Effect of microbial immunomodulators on the course of lymphocytic choriomeningitis virus infection in old mice with physiological thymus involution].

Aged mice with physiological thymus involution were treated intraperitoneally with 0.2 ml of live Newcastle Disease Virus (NDV) containing attenuated NDV vaccine (HA titre: log 2(16)/ml) one day before or with Mannozym (0.1% zymosan suspension) four days and one day before intracerebral inoculation with 100 LD50 dose of LCMV.

Effect of chlorpromazine (CPZ) on the course of LCM virus infection in mice with developed and undeveloped immune system.

The cellular immune response to lymphocytic choriomeningitis (LCM) virus in germfree adult and conventional (Cv) suckling mice with undeveloped immune systems and in Cv adult mice with developed immune systems was suppressed by a single large, sublethal dose of the calmodulin antagonistic chlorpromazine and stimulated by a 100-times smaller dose administered intraperitoneally one day before the intracerebral virus infection. CPZ thus exerted a two-directional dose-dependent immunomodulatory effect in mice with both undeveloped and developed immune system.