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O Cars

Publications and source records attributed to O Cars.

At least 73 records · Page 4Linked to original sources

Effects of benzylpenicillin on Streptococcus pyogenes during the postantibiotic phase in vitro.

A postantibiotic effect (PAE) for Streptococcus pyogenes M12, P1800 was induced by 10 x MIC of benzylpenicillin for 2 h in vitro. The PAE was found to be 2.4 h (range 1.75-3.0 h). No incorporation of 3H-thymidine by the streptococci occurred during the first hours of the postantibiotic phase (PA-phase), indicating that bacterial cell division was inhibited during this period. However, these bacteria showed the same killing rate as previously unexposed control cultures when 10 x MIC of benzylpenicillin was added during the PA-phase. When bacteria in PA-phase were re-exposed to penicillin at a concentration of 0.2 x MIC multiplication of the bacteria was inhibited for 6-7 h, while at a concentration of 0.3 x MIC slow killing was induced. In contrast, previously untreated controls exposed to 0.2 x MIC and 0.3 x MIC showed a growth rate corresponding to that of bacteria grown in the absence of penicillin. The effects of subinhibitory concentrations on streptococci previously exposed to penicillin may therefore be a more important factor in determining dosage intervals than the PAE.

Kinetics↗

Paradoxical effect of cloxacillin and benzylpenicillin against clinical isolates in Staphylococcus aureus.

The occurrence of a paradoxical effect of cloxacillin and benzylpenicillin in 7 strains of Staphylococcus aureus was studied with time killing curves in vitro. The isolates were exposed to 1, 2, 10 and 100 x MIC of the antibiotics. A paradoxical effect was found in 5/7 strains with cloxacillin and in 4/7 with benzylpenicillin. All strains were killed faster with 2 x MIC than with 100 x MIC. All strains that showed a paradoxical effect with cloxacillin did so already at 10 x MIC. For benzylpenicillin the effect occurred at 10 x MIC for 2 strains and at 100 x MIC for 2. A single MBC/MIC ratio will not reveal the paradoxical effect.

Cloxacillin↗

Bacteriological and serological aspects of group A streptococcal pharyngotonsillitis caused by group A streptococci.

Several bacteriological and serological variables were studied in connection with a clinical treatment trial in 212 patients with group A streptococcal pharyngotonsillitis. Anaerobic incubation was not superior to incubation in 5% CO2 in air for the detection of group A streptococci. Saliva cultures were inferior to conventional throat cultures in detecting group A streptococci. No strains from patients with recurrences were found to be tolerant to penicillin. In several patients (all asymptomatic), group C and G streptococci were found in follow-up cultures. Group A streptococci serology was more often positive after two months than after one month, also in patients without recurrence.

Adolescent↗

Throat carrier rates of beta-hemolytic streptococci among healthy adults and children.

In order to investigate the carrier rate of beta-hemolytic streptococci throat cultures were obtained every third month from 382 asymptomatic adults and schoolchildren during a 2-year period, altogether 2226 samples. In addition, 300 asymptomatic 4-year-olds were sampled once. The carrier rate of beta-hemolytic streptococci was 19.4%; group A streptococci alone 5.0%. There was no season-dependent variation. In the 3 age groups the carrier rates of group A streptococci were 0.8%, 5.9%, and 11.3%, respectively, with the highest rate among the 4-year-olds. Some of the individuals that were sampled repeatedly seemed to be pharyngeal carriers of group A streptococci, while others never became carriers. Group A streptococci were found significantly more often among 4-year-olds not attending day-care centres compared to those attending such institutions. For group C and G streptococci the influence of age on carrier rates was not similar to that found for group A streptococci. Throat carriership of beta-hemolytic streptococci does not result in clinical infections.

Adolescent↗

Five versus ten days treatment of group A streptococcal pharyngotonsillitis: a randomized controlled clinical trial with phenoxymethylpenicillin and cefadroxil.

216 patients aged greater than or equal to 7 years with febrile group A streptococcal pharyngotonsillitis were randomly assigned to 3 treatment groups receiving either phenoxymethylpenicillin for 5 days followed by placebo for 5 days, phenoxymethylpenicillin for 10 days, or cefadroxil for 10 days. 209 patients completed treatment, 70 subjects in each phenoxymethylpenicillin group and 69 in the cefadroxil group. Within 1 week after completion of the antibiotic treatment significantly more recurrences with the same T-type as the initial streptococcal strain occurred in the 5-day treatment group (27%) as compared with the two 10-day groups (6% and 3%, respectively). The cumulative rate of recurrences (irrespective of T-type) within 2 months from the start of therapy was 55% among patients treated with phenoxymethylpenicillin for 5 days, 24% among those treated for 10 days with this drug and 19% among patients receiving cefadroxil. Obviously, one important factor to avoid recurrence of group A streptococcal pharyngotonsillitis is the length of antibiotic treatment and, in our opinion, it is not advisable to change the current recommendation of 10 days treatment.

Adolescent↗

An in vivo model for evaluation of the postantibiotic effect.

A new experimental model to evaluate the postantibiotic effect (PAE) in vivo was developed using subcutaneously implanted tissue cages in rabbits with normal host defence mechanisms. The rabbits received benzylpenicillin i.v. in a dose giving a free penicillin concentration of 10 X MIC in the tissue cage fluid (TCF). A log-phase suspension of group A streptococci was injected into the tissue cages exposing them to penicillin in vivo. After 2 h bacterial samples were withdrawn, treated with penicillinase and transferred to 2 tissue cages in untreated rabbits. Simultaneously, unexposed streptococci were implanted in 2 other cages in the same animals. By repeated sampling of TCF, growth curves of the streptococci exposed to penicillin and the controls could be compared and a PAE of 1.6-2.4 h demonstrated. The PAE was of the same magnitude as that found in vitro. The model has several advantages for the demonstration of PAE in vivo: repeated samplings are easy to perform percutaneously, the effect of subinhibitory antibiotic concentrations are avoided, interindividual variations are eliminated since each animal is its own control, and the experiments can be performed in animals with undisturbed host defence mechanisms.

Animals↗

Concentrations of doxycycline in muscle tissue and muscle tissue fluid.

Doxycycline is known to have a marked tissue affinity, but there seems to be no previous studies where doxycycline levels have been compared in different compartments of a tissue. The purpose of the present investigation was to measure concentrations of doxycycline in serum, muscle and muscle tissue fluid using an experimental model in rabbits. After an intravenous infusion of doxycycline 10 mg/kg, samples were obtained at intervals for 4 h and concentrations were measured using microbiological methods. The levels of doxycycline in muscle tissue fluid followed closely the concentrations in serum and showed a similar rate of elimination. Doxycycline concentrations in muscle peaked later than the tissue fluid concentrations and were much higher than the corresponding serum level (mean ratio tissue/serum = 3.5).

Animals↗

Pharmacokinetics of intravenous cefuroxime during intermittent and continuous arteriovenous hemofiltration.

The pharmacokinetics of cefuroxime were determined in ten patients during intermittent hemofiltration (IHF) and in three patients during continuous arteriovenous hemofiltration (CAVH). All patients received a bolus dose of 1.5 g of cefuroxime intravenously and the concentrations of cefuroxime in serum and ultrafiltrate were followed during the hemofiltration period and up to 16 hours after injection of cefuroxime. During IHF the mean terminal half-life of cefuroxime was 1.6 +/- 0.3 hours compared with a terminal half-life of 21.7 +/- 5 hours after treatment. The total cefuroxime clearance was 120 +/- 22 ml/min. The hemofiltration clearance represented 86% of the total clearance and the hemofiltration process removed in average 63% of the dose. During CAVH the terminal half-life of cefuroxime was 7.9 +/- 2.2 hours. The total plasma clearance for cefuroxime was 32 +/- 7.5 ml/min where the CAVH-treatment represented only 34% of the total clearance. From these data we suggest that a full loading dose (1.5 g of cefuroxime) should be given after each intermittent hemofiltration treatment when performed every second day. In CAVH, where nonrenal clearance will influence the dosage scheme significantly, we suggest an initial dose of 1.5 g of cefuroxime to be followed by a supplementary dose of 750 mg every 20-24 h.

Aged↗

A micromethod for determination of antimicrobial agents in bone.

A microtechnique, requiring very small amounts of tissue material, was developed for assay of antimicrobial agents in bone. Without previous homogenization or extraction, small bone pieces (mean weight 0.014 g) from human subjects and pigs were placed into wells in agar plates preinoculated with the test strain. Round and distinct zones of inhibition were formed around the pieces. Standards for ampicillin and flucloxacillin were prepared from freeze-dried bone pieces from human subjects and pigs with known amounts of antibiotics as well as in human plasma and phosphate-buffered saline (PBS). Curves obtained from these standards were linear. Bone pieces from human and pig maxilla gave superimposable curves, but differed from curves obtained in plasma or PBS. The method was used in a pharmacokinetic study of bacampicillin in human maxillary bone and plasma. Bacampicillin tablets (2 X 400 mg) were given to patients before oral surgery. Standardized bone pieces and plasma samples were obtained at different times during surgery. The peak ampicillin concentrations estimated from the population curves were 8.0 mg/l in plasma and 1.1 mg/l in maxillary bone. The elimination half-life of ampicillin was similar in plasma and maxillary bone.

Ampicillin↗

Concentrations of phenoxymethylpenicillin and cefadroxil in tonsillar tissue and tonsillar surface fluid.

Thirty patients who underwent elective tonsillectomy were given phenoxymethylpenicillin (0.8 g) or cefadroxil (1 g) at different times before operation. The concentrations of the antibiotics were analysed in serum, tonsillar tissue, fluid from the surface of the tonsils, and mixed saliva. The concentrations in tonsillar tissue for both drugs were much lower than the corresponding serum concentrations. This apparently low tissue accessibility could be ascribed to the limited intracellular penetration of beta-lactam antibiotics. For both antibiotics the concentrations in the tonsillar surface fluid were higher than the levels in the tissue and well above the minimal inhibitory concentrations for streptococci. This was not due to antibiotics in saliva but probably a result of leakage from the interstitial fluid. Inability to reach active concentrations of phenoxymethylpenicillin or cefadroxil at the site of infection does not therefore seem to be a probable cause for relapse after treatment of streptococcal tonsillitis.

Adolescent↗

Effect of antibiotic protein binding on the killing rate of Staphylococcus aureus and on the paradoxical phenomenon.

The killing kinetics of Staphylococcus aureus, exposed to various concentrations of dicloxacillin in broth and in broth with 40 g/l human albumin was studied. When the free concentrations of dicloxacillin were identical in the two media, no difference in killing capacity could be demonstrated at concentrations above MIC, indicating that only the free antibiotic fraction is antibacterially active. However, at concentrations identical to the MIC, a better bactericidal effect in the medium containing albumin was found. In experiments where equal total concentrations were compared in the two media, an increasing bactericidal effect in the medium containing albumin could be demonstrated at concentrations between 10-100 X MIC. The most probable explanation for this was a prominent paradoxical effect with increasing antibiotic concentrations on the killing rate of S. aureus in broth. This effect was neutralized in the presence of albumin due to the lower free antibiotic concentration in this medium.

Dicloxacillin↗

Ceftazidime as prophylactic treatment in renal stone surgery. Clinical evaluation and pharmacokinetics in renal tissue.

The effect of ceftazidime in surgery of renal stones associated with urinary tract infection was investigated and its pharmacokinetics in serum and renal tissue was compared in 14 patients (15 kidneys) operated on for renal calculi associated with multiple urinary tract infection. Two to four days preoperatively ureteric catheterization was performed to localize the level of the infection and 2 g of ceftazidime was given intravenously twice daily for 10 days. Renal biopsy, serum samples and in one patient renal lymphatic fluid were taken simultaneously for antibiotic assay. Urine cultures were performed at regular intervals pre- and postoperatively. Ten patients had bacterial growth in the stone-carrying renal pelvis. The same strain was found in the bladder as in the pelvis. Nine patients had sterile urine after 3-5 days of treatment. One patient with bilateral stones did not get sterile urine until after seven days of treatment. Bacterial growth was found in two out of six cultured stones obtained from patients with bacterial growth in the pelvis. The decreases in concentration of ceftazidime in serum and renal tissue seemed to be parallel. Slight reversible elevation of liver transaminases was noted in 5/14 patients. It is concluded that the concentration of ceftazidime in serum parallels that in renal tissue. Ceftazidime seems to be an effective prophylactic in renal stone surgery and the preoperative dose should be given close to the operation.

Adult↗

The use of antibiotic serum levels to predict concentrations in tissues.

A review of the literature shows that antibiotic concentrations in tissues and tissue fluids are often quoted as being different in profile to concurrent serum levels. To study the relationship between serum and tissue concentrations we analysed published studies where different experimental models were tested simultaneously. In some models serum levels predicted tissue levels while in others they did not. The factors likely to be responsible for the differences were examined. The most important of these factors was tissue geometry (surface area to volume ratio; SA/V). Serum levels predicted tissue levels in models where the SA/V was high (greater than 60) but not where the SA/V's were low (less than 10); here the antibiotic concentrations were lower and more prolonged than serum levels. These observations can be extrapolated to the clinical situation. In most situations involving prophylaxis or treatment of infections in non-specialised tissues (naturally high SA/V), serum levels will closely reflect levels in extracellular tissue fluid where most bacterial infections are located.

Animals↗

Pharmacokinetics of dicloxacillin in serum and aortic wall during aneurysmal surgery.

Twenty-one patients undergoing elective surgery for abdominal aortic aneurysm were randomly assigned to receive 2 grams of dicloxacillin as an intravenous infusion either at the induction of anaesthesia, 3 hours or approximately 6 hours before surgery. Samples from serum and aortic tissue were simultaneously obtained so that antibiotic levels could be compared as a function of time. High concentrations of dicloxacillin in serum and aortic tissue were present already shortly after infusion and active levels were maintained in aortic tissue for approximately six hours. The kinetics of dicloxacillin was similar in serum and aortic tissue. These results support the need for antibiotic administration shortly before surgery to ensure adequate tissue levels of antibiotics.

Aged↗

Qualitative and quantitative bacteriological studies in infected surgical wounds treated with Debrisan or saline.

In a study of methods for the evaluation of clearing of wound infection, local treatment with Debrisan (10 wounds) or saline (11 wounds) was examined clinically and bacteriologically. No correlation was found between clinical course and numbers of bacteria found in wound biopsies or swabs. Biopsy results varied greatly between sites in the same wound. In wounds with established infection, biopsies or wet swabs yielded little more information than conventional dry swabs. Debrisan seemed to offer no advantage over saline as regards clearing of infection in this small patient group.

Bacteriological Techniques↗