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O Cars

Publications and source records attributed to O Cars.

At least 55 records · Page 3Linked to original sources
PubMed1995

Postantibiotic effects and postantibiotic sub-MIC effects of roxithromycin, clarithromycin, and azithromycin on respiratory tract pathogens.

Pharmacodynamic parameters have become increasingly important for the determination of the optimal dosing schedules of antibiotics. In this study, the postantibiotic effects (PAEs), the postantibiotic sub-MIC effects (PA SMEs), and the sub-MIC effects (SMEs) of roxithromycin, clarithromycin, and azithromycin on reference strains of Streptococcus pyogenes group A, Streptococcus pneumoniae, and Haemophilus influenzae were investigated. The PAE was induced by 2x MICs (S. pneumoniae) or 10x MICs of the different drugs for 2 h, and the antibiotics were eliminated by washing and dilution. The PA SMEs were studied by addition of 0.1, 0.2, and 0.3x MICs during the postantibiotic phase of the bacteria, and the SMEs were studied by exposition of the bacteria to the drugs at the sub-MICs only. Growth curves were followed by viable counts for 24 h. The SMEs were generally very short. A PAE of 2.9 to 8 h was noted for all antibiotics against all strains. Clarithromycin induced a statistically significantly shorter PAE on S. pneumoniae than did roxithromycin and azithromycin and did so also against H. influenzae in comparison with azithromycin. The PA SMEs were long and varied at 0.3x MIC between 6.4 19.6 h. This pronounced suppression of regrowth of bacteria which are first treated with a suprainhibitory concentration of antibiotics and then reexposed to sub-MIC levels indicates that long dosing intervals for macrolides and azalides can be allowed.

Azithromycin↗
PubMed1993

Treatment of brain abscess with cefotaxime and metronidazole: prospective study on 15 consecutive patients.

The aim of the present investigation was to prospectively study the clinical and bacteriologic outcome of 15 consecutive patients with brain abscesses who were treated with surgical excision and cefotaxime (3 g every 8 hours) plus metronidazole (0.5 g every 8 hours) for at least 3 weeks. The patients were followed clinically and with computed tomographic (CT) examinations. All patients survived, and there were no recurrences within 1 year. CT scans showed an exponential decrease in the size of enhancement. Cultures of all six specimens obtained after < 24 hours of treatment with cefotaxime and metronidazole were positive compared with cultures of three of nine specimens obtained later (P = .017). Anaerobic bacteria were isolated from 2 of 3 patients given two doses of metronidazole or less compared with none of 12 given three doses or more (P = .029). Reversible side effects occurred in nine patients. It is concluded that cefotaxime plus metronidazole is an alternative treatment for brain abscess in addition to surgical excision because of their good abscess penetration, their ability to eradicate bacteria, and a good clinical outcome.

Adult↗
PubMed1993

The post-antibiotic sub-MIC effect in vitro and in vivo.

The post-antibiotic effect (PAE) has been recognized as a pharmacodynamic parameter which may influence optimal dosage intervals. During the post-antibiotic phase, various bacteria have been shown to be very sensitive to a repeated exposure to the same antibiotic. A long period of growth suppression may be obtained when a low concentration (< or = 0.3 x MIC) is added to bacteria previously exposed to a supra-inhibitory concentration. This phenomenon has been named the post-antibiotic sub-MIC effect (PA SME). Since a period with sub-inhibitory concentrations will often exist between the doses when intermittent dosing of antibiotics is used, the PA SME probably reflects the in-vivo situation more closely than the PAE. The published literature on the PA SME is reviewed and its possible role in antibiotic dosing discussed.

Animals↗
PubMed1993

A new method to determine postantibiotic effect and effects of subinhibitory antibiotic concentrations.

It has been shown that bacteria in a postantibiotic (PA) phase exposed to subinhibitory concentrations (sub-MICs) of antibiotics show a long delay before regrowth. This effect has been named the PA sub-MIC effect (PA SME). In the present study, we have used a new method to demonstrate this phenomenon. A computerized incubator for bacteria, Bioscreen C (Lab Systems, Helsinki, Finland), which incubates the bacteria, measures growth continuously by vertical photometry, processes the data, and provides a printout of the results was used. With this method, one may easily test several antibiotics against different bacteria for PA effects (PAEs), PA SMEs, and SMEs. In this study, the effects of benzylpenicillin against beta-hemolytic streptococci and pneumococci were examined. The bacteria were exposed to 2, 10, or 50x MIC for 2 h, washed and diluted, incubated in the Bioscreen C incubator, and then exposed to 0.1 to 0.9x MIC. The regrowth was monitored for 20 h. The PAE was calculated as the difference in the time required for the exposed and unexposed bacteria to grow to a defined point (A50) on the absorbance curve. A50 was defined as 50% of the maximum absorbance for the control cultures. The PA SMEs were calculated as the difference in the time required for the reexposed cultures and the unexposed controls to reach A50. The PAEs ranged between 0.6 and 3.2 h and varied little with the concentration used for the induction of the PAEs. At 0.2x MIC, the PA SMEs were 2 to 3 h longer than the PAEs. Higher sub-MICs increased this delay before regrowth. Most cultures exposed to sub-MICs alone were only slightly affected compared with the controls.

Anti-Bacterial Agents↗
PubMed1992

Postantibiotic sub-MIC effects of vancomycin, roxithromycin, sparfloxacin, and amikacin.

The sub-MIC effects (SMEs) and the postantibiotic sub-MIC effects (PA SMEs) of vancomycin, roxithromycin, and sparfloxacin for Streptococcus pyogenes and Streptococcus pneumoniae and of amikacin for Escherichia coli and Pseudomonas aeruginosa were investigated. A postantibiotic effect was induced by exposing strains to 10x the MIC of the antibiotic for 2 h in vitro. After the induction, the exposed cultures were washed to eliminate the antibiotics. Unexposed controls were treated similarly. Thereafter, the exposed cultures (PA SME) and the controls (SME) were exposed to different subinhibitory concentrations (0.1, 0.2, and 0.3x the MIC) of the same drug and growth curves for a period of 24 h were compared. In general, the PA SMEs were much more pronounced than the SMEs. However, for amikacin and E. coli the SME of 0.2 and 0.3x the MIC also had an initial bactericidal effect. The longest PA SMEs were demonstrated for the combinations with the most pronounced killing during the induction and for the combinations which exhibited the longest PAEs.

Amikacin↗
PubMed1992

First documented case of human babesiosis in Sweden.

A 34-year-old splenectomized man presented with fever, myalgia and dysuria. His condition rapidly deteriorated, he became anuric and developed severe haemolytic anaemia, thrombocytopenia and fibrinolysis. Peripheral blood smears revealed intra-erythrocytic parasites consistent with Babesia divergens in 40% of the erythrocytes. The diagnosis was confirmed by gerbil inoculation and by a significant rise in antibody titer. Blood exchange transfusion reduced the number of babesia infected erythrocytes to 1%. Parenteral therapy with a combination of quinine and clindamycin eradicated parasitaemia after 10 days of treatment and the patient rapidly improved. Renal failure necessitated haemodialysis for one month, whereafter the patient made a full recovery. Human babesiosis is a rare disease, but with a potential fatal outcome and should be considered as a diagnostic alternative in splenectomized and otherwise immunocompromised individuals with severe febrile illnesses.

Adult↗
PubMed1991

Neurotoxicity of beta-lactam antibiotics: predisposing factors and pathogenesis.

Neurotoxic reactions caused by beta-lactam antibiotics occur frequently following direct application of antibiotic to the brain surface or into the cerebral cisterns. Epileptogenic reactions have also been observed after administration of very high systemic doses. There seem to be considerable differences in the neurotoxic potential of the various beta-lactams; benzylpenicillin, cefazolin and, lately, imipenem/cilastatin appear to be drugs with higher neurotoxic potential than other compounds. There is now strong evidence that the concentration of beta-lactam in the brain, and not that in the cerebrospinal fluid, is the decisive factor for the risk of neurotoxic reactions. Factors known to increase the risk of neurotoxicity are excessive doses, decreased renal function, damage to the blood-brain barrier, preexisting diseases of the central nervous system, old age and concurrent use of drugs that are nephrotoxic or that may lower the seizure threshold. Another factor that may be of importance is blockage of the transport system that is responsible for transport of beta-lactams out of the central nervous system.

Animals↗
PubMed1991

Penetration of cefotaxime and desacetylcefotaxime into brain abscesses in humans.

Since clinical trials comparing the efficacies of different antibiotic regimens for treatment of brain abscesses are difficult to perform, the choice of antibiotics must rely on the antibacterial spectrum and the ability of the drug to penetrate into the abscess fluid. The aim of this investigation was to study the ability of cefotaxime and its active metabolite desacetylcefotaxime to penetrate into brain abscesses. Eight patients were given 3 g of cefotaxime intravenously every 8 h. Abscess fluid samples, obtained at surgery at various times after dosing, and blood samples were analyzed for their concentrations of cefotaxime and desacetylcefotaxime by using a newly developed microbiological assay. The brain abscess concentrations of cefotaxime and desacetylcefotaxime were 1.9 +/- 1.7 and 4.0 +/- 2.2 mg/liter, respectively. Simultaneous concentrations in plasma were 2.0 +/- 1.0 and 3.9 +/- 1.8 mg/liter, respectively. With increasing time following cefotaxime dosing there was a significant increase in the abscess:plasma concentration ratio of desacetylcefotaxime. Since both cefotaxime and desacetylcefotaxime penetrate well into the brain abscess, reaching concentrations above the MIC for probable bacteria except gram-negative anaerobes, it is concluded that cefotaxime in combination with metronidazole may be used as an alternative in the treatment of brain abscesses.

Adult↗
PubMed1991

Pharmacodynamic effects of subinhibitory concentrations of beta-lactam antibiotics in vitro.

The pharmacodynamic effects of subinhibitory concentrations of different beta-lactam antibiotics were investigated. A postantibiotic effect (PAE) was induced for different bacterial species by exposure to 10x MIC of several beta-lactam antibiotics for 2 h in vitro. The antibiotic-bacterial combinations used in this study were imipenem-Pseudomonas aeruginosa, benzylpenicillin-Streptococcus pneumoniae and -Streptococcus pyogenes, cefcanel-S. pyogenes, ampicillin-Escherichia coli, and piperacillin-E. coli. After the induction of the PAE, the exposed cultures as well as the unexposed controls were washed and diluted. Thereafter, the cultures in the postantibiotic phase (PA phase) and the cultures not previously treated with antibiotics were exposed to 0.1, 0.2, and 0.3x MIC of the relevant drug and the growth curves were compared. When bacteria in the PA phase were exposed to sub-MICs, a substantial prolongation of the time before regrowth was demonstrated, especially in antibiotic-bacterial combinations for which a PAE was found. In contrast, sub-MICs on cultures not previously exposed to suprainhibitory antibiotic concentrations yielded only a slight reduction in growth rate compared with the controls. Thus, it seems important to distinguish the direct effects of sub-MICs on bacteria not previously exposed to suprainhibitory concentrations from the effects of sub-MICs on bacteria in the PA phase.

Anti-Bacterial Agents↗
PubMed1990

Pharmacokinetics of intravenous imipenem/cilastatin during intermittent haemofiltration.

The pharmacokinetics of a single iv dose of imipenem/cilastatin (500/500 mg) were studied during and after intermittent haemofiltration (IHF) treatment in six patients with chronic renal failure. The elimination half-lives of imipenem and cilastatin during the IHF treatment were almost identical, 1.4 +/- 0.3 and 1.5 +/- 0.3 h, respectively. Accordingly, approximately 75% of the given dose was eliminated during a 3-h IHF session. However, there was a great difference between the elimination half-lives of the two drugs in the post-treatment period, 3.4 +/- 1.0 and 16 +/- 10 h for imipenem and cilastatin, respectively. The haemofiltration clearance of imipenem was 134 +/- 41 ml/min and that of cilastatin 109 +/- 8 ml/min. On the basis of our results, we suggest that a supplementary dose of imipenem/cilastatin (500/500 mg) should be given directly after the IHF treatment. This dose should be the starting dose for a period of 12-h dosing intervals until the next IHF procedure.

Adult↗
PubMed1990

Effects of supra- and sub-MIC benzylpenicillin concentrations on group A beta-haemolytic streptococci during the postantibiotic phase in vivo.

A postantibiotic effect (PAE) in vivo was induced in group A streptococci established in a tissue cage model in rabbits. The bacteria were exposed to 10 x MIC of benzylpenicillin in tissue cage fluid (TCF) for 2 h. TCF was then aspirated, penicillin was eliminated by washing and the bacteria were transferred to tissue cages in other rabbits in order to study the in-vivo killing kinetics of streptococci in the postantibiotic phase. In these latter rabbits the concentration of benzylpenicillin in TCF corresponded to 10 or 0.3 x MIC. Bacteria not previously exposed to penicillin were used as controls. Streptococci in postantibiotic phase were killed as effectively after re-exposure to 10 x MIC in vivo as the growing controls. Although the concentration of penicillin fell below the MIC after 12 h, no regrowth was seen during the following 12 h in either culture. When only subinhibitory concentrations in TCF were used in the second phase, a killing of approximately 1 log10 cfu/ml was noted both in the previously exposed cultures and in controls. Both cultures started to multiply first after 6-7 h.

Animals↗
PubMed1990

Paradoxical effects of antibiotics.

The paradoxical effect of antibiotics is defined as a substantially reduced bacterial killing at antibiotic levels above the minimal bactericidal concentration in vitro. This phenomenon which was originally described for beta-lactam antibiotics in their reactions against Gram-positive bacteria has later been noted with aminoglycosides against Gram-negatives and other antibiotic-microorganism combinations, indicating a multifaceted background. The clinical significance of the paradoxical effect is unknown. However, the phenomenon can be demonstrated in vitro at levels easily achievable in clinical situations, as illustrated in our own experiments, where clinical isolates of Staphylococcus aureus were tested for a paradoxical effect versus several penicillins. In most strains exhibiting a paradoxical effect, this effect occurred at concentrations as low as 10xMIC. The relationship between paradoxical effect and tolerance is discussed.

Animals↗
PubMed1990

The postantibiotic effect of cefcanel on beta-hemolytic streptococci group A in vitro and in vivo.

The postantibiotic effect (PAE) of cefcanel, a new oral cephalosporin with high in vitro activity against Gram-positive bacteria, was investigated. Ten clinical isolates of Streptococcus pyogenes group A and one reference strain (M12, P1800) were exposed to 5 X MIC of cefcanel for 2 h in vitro. The PAE was found to be 2.3 (range 1.7-3.2) h. To investigate the PAE in vivo, a newly developed animal model with implanted tissue cages in rabbits was used. The rabbits received different doses of cefcanel i.v. and unbound concentrations in the tissue cage fluid (TCF) were measured. The protein binding of cefcanel in TCF was approximately 98%. Above a certain dose level, unexpectedly high TCF concentrations were found, indicating that the albumin binding capacity for the drug was surpassed. A PAE in vivo of 0.9-2.6 h was confirmed for cefcanel when the free drug concentration in TCF exceeded 3 X MIC.

Albumins↗
PubMed1990

Pharmacokinetics of antibiotics in tissues and tissue fluids: a review.

The majority of bacterial infections occur outside the vascular compartment and, thus, considerable interest has been devoted to studies of antibiotic concentrations in different tissues. This review deals with the pharmacokinetics of antibiotics in tissues where the drug is distributed by passive diffusion. It is not always recognized that tissue levels of antibiotics represent the means of different concentrations in the major tissue compartments: interstitial fluid, cells and blood capillaries. Non-lipophilic drugs, such as beta-lactam antibiotics, which do not penetrate cells, are confined to the extracellular fluid volume, which constitutes approximately 20% of the tissue. Consequently, whole tissue levels are low. Conversely, drugs that penetrate and accumulate in cells may well yield tissue levels exceeding the serum levels. Since most bacterial infections start and progress in the interstitial fluid, whole tissue levels are therapeutically meaningless, but are nevertheless often compared to the MICs of bacteria. For protein-bound drugs, the lower albumin concentrations in extracellular fluids is another important factor that may lead to erroneous conclusions regarding the ability of an antibiotic to distribute into tissues. Different models have been developed to study antibiotic levels in the interstitial fluid. The geometry of the tissue fluid compartment (ratio of surface area to volume: SA/V) has been recognized as one of the most important determinants of antibiotic pharmacokinetics in these models. In healthy tissues (high SA/V) similar concentrations are found in serum and tissue fluid. Although limited information is available regarding antibiotic pharmacokinetics in infected tissues, it seems that in acute bacterial infections, the most relevant concentrations to relate to pharmacodynamic parameters are the unbound levels of the drug in serum.

Albumins↗
PubMed1990

Pharmacodynamic effects of subinhibitory antibiotic concentrations.

The pharmacodynamic effects of subinhibitory antibiotic concentrations (sub-MICs) on bacteria can be evaluated in different ways. A direct effect in vitro can be expressed as the minimum antibiotic concentration that produces a structural change in the bacteria seen by light or electron microscopy, or as the concentration that produces one log10 decrease in a bacterial population compared to controls. A direct effect of sub-MICs has also been reported in vivo, both in animals with normal host defenses and in humans. In these cases, it has been shown that subinhibitory antibiotic concentrations can be sufficient to clear an infection. Another effect of sub-MICs can be seen when bacteria are pretreated with suprainhibitory antibiotic concentrations and then exposed to subinhibitory concentrations. Here, sub-MICs may produce a long period of delay before regrowth and even yield a bactericidal effect, especially in antibiotic/bacterial combinations where a postantibiotic effect is present. It seems that subinhibitory antibiotic concentrations may be of great importance for the success of intermittent dosing in certain combinations of antibiotics and bacteria.

Animals↗
PubMed1989

Postantibiotic and bactericidal effect of imipenem against Pseudomonas aeruginosa.

The postantibiotic effect of imipenem on Pseudomonas aeruginosa was studied at different inocula using one ATCC strain and four clinical isolates. The postantibiotic effect was measured using two different methods: viable counts and bioluminescence assay of intracellular bacterial ATP. The postantibiotic effect could be demonstrated with both methods (viable counts 1-2 h, ATP assay 3-5 h) for all strains at an inoculum of 10(6) CFU/ml. When the inoculum was raised to 10(8) CFU/ml, no postantibiotic effect could be observed with either method using routine growth conditions. This disappearance of the postantibiotic effect coincided with a loss of bactericidal effect of imipenem when high inocula were used. Improved oxygenation of the cultures restored the bactericidal and postantibiotic effects of imipenem at high inocula.

Dose-Response Relationship, Drug↗