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Biomedical subjects

L Sörén

Publications and source records attributed to L Sörén.

At least 19 recordsLinked to original sources

Acute glomerulonephritis associated with streptococcus pyogenes with concomitant spread of streptococcus constellatus in four rural families.

We studied history, renal histopathology and microbiology of an epidemic of acute glomerulonephritis associated with throat infections and uncommon culture results in four neighbour families. A 40-year-old man (index patient) was referred to a university hospital for dialysis and kidney biopsy due to a suspected acute glomerulonephritis. An acute tonsillitis had preceded the condition. Penicillin treatment had been started four days before the discovery of renal failure. Throat swabs were positive for beta-hemolytic streptococci, group C (GCS). GCS were also found in throat cultures from his wife and two of their children. The bacteria were typed as Streptococcus constellatus. A third child had S. constellatus expressing Lancefield antigen group G. A neighbour and two of his children fell ill the following week with renal involvement. Throat swabs from both these children were positive for S. constellatus. His third child had erythema multiforme and S. constellatus in the throat while a fourth child had beta-hemolytic streptococci group A; Streptococcus pyogenes. Kidney biopsies on the index patient and his neighbour showed an acute diffuse prolipherative glomerulonephritis compatible with acute post-streptococcal nephritis and microbiological analysis of renal tissue revealed in both cases S. pyogenes and S. constellatus. The families had had much contact and had consumed unpasteurized milk from our index patient's farm. In four of seven persons in two additional neighbouring families S. constellatus was found in throat swabs during the same month while two persons carried Streptococcus anginosus expressing the Lancefield C antigen. In conclusion spread of S. constellatus coincided with the occurrence of four cases of acute glomerulonephritis. The two biopsied patients had both S. pyogenes and S. constellatus present in renal tissue. The epidemic either suggested that the outbreak of glomerulonephritis was due to S. pyogenes but coincided with the transmission and colonization of S. constellatus or that the S. constellatus strains were highly pathogenic or nephritogenic and that this organism can be transmitted in such cases.

Acute Disease↗

Surveillance of antibiotic resistance in ICUs in southeastern Sweden. ICU Study Group of the South East of Sweden.

BACKGROUND: A study was designed to assess a computer-based program for continuous registration of antibiotic resistance, statistics concerning severity of illness, and consumption of antibacterial drugs. METHODS: The frequency of antibiotic resistance among bacteria in eight ICUs in southeastern Sweden was investigated yearly from 1995 through 1997. The antibiotic consumption in the ICUs was registered as defined daily doses (DDD) and compared to severity of illness (APACHE-II scores). RESULTS: There was a statistically significant increase in ampicillin resistance among Enterococcus spp. between 1996 and 1997, which was due to a shift from Enterococcus faecalis to Enterococcus faecium. A high prevalence of resistance among coagulase-negative staphylococci to oxacillin (approximately 70%), ciprofloxacin (approximately 50%), fucidic acid (approximately 50%) and netilmicin (approximately 30%) was seen in all ICUs during the whole study period. There was a statistically significant increase in ciprofloxacin resistance among Escherichia coli and Enterococcus spp. The resistance among Enterobacter spp. to cefotaxime decreased but this change was not statistically significant. Efforts were made to avoid betalactam antibiotics, except carbapenems, for treatment of infections caused by Enterobacter spp. and the consumption of cephalosporins decreased whereas the consumption of carbapenems increased. The total antibiotic consumption decreased by 2.5% during the study period. There was no correlation between APACHE II scores and antibiotic consumption. CONCLUSIONS: Each ICU within a hospital ought to have a program for "on-line" antibiotic resistance surveillance of drugs used in that unit so that changes in empirical treatment can be made when there is an increase in antibiotic-resistant isolates within that unit.

APACHE↗

New species-related MIC breakpoints for early detection of development of resistance among gram-negative bacteria in Swedish intensive care units.

The frequency of decreased antibiotic susceptibility among 534 Gram-negative aerobic bacilli from patients admitted to intensive care units at eight hospitals in Sweden during 1997 was evaluated. MICs of cefepime, ceftazidime, ceftriaxone, ciprofloxacin, gentamicin, imipenem and piperacillin-tazobactam were determined using Etest. Reduced susceptibility (resistant and intermediate/indeterminate susceptible strains) was defined according to the MIC breakpoints of the British Society for Antimicrobial Chemotherapy (BSAC), the National Committee for Clinical Laboratory Standards (NCCLS) and the new species-related breakpoints of the Swedish Reference Group for Antibiotics (SRGA). The BSAC/NCCLS/SRGA breakpoints for susceptible category (mg/L) of Enterobacteriaceae are: cefepime, not available (NA)/8/0.5; ceftazidime, 2/8/2; ceftriaxone, NA/8/0.5; ciprofloxacin, 1/1/0.12; gentamicin, 1/4/2; imipenem, 4/4/1; and piperacillin-tazobactam, NA/16/16. The most frequently isolated organisms were Escherichia coli (n = 160; 30%), Klebsiella spp. (n = 84; 16%), Enterobacter spp. (n = 77; 14%), Pseudomonas aeruginosa (n = 64; 12%) andProteus spp. (n = 28; 5%). Decreased susceptibility among E. coliusing the BSAC/NCCLS/SRGA respective breakpoints (%) were: cefepime, NA/0/2; ceftazidime, 2/2/2; ceftriaxone, NA/1/2; ciprofloxacin, 2/2/8; gentamicin, 21/0/3; imipenem, 0/0/2; and piperacillin-tazobactam, NA/4/4. Corresponding levels of decreased susceptibility (%) among Klebsiellaspp. were: cefepime, NA/0/5; ceftazidime, 2/1/2; ceftriaxone, NA/1/10; ciprofloxacin, 4/4/19; gentamicin, 25/2/5; imipenem, 0/0/0; and piperacillin-tazobactam, NA/10/10; and among Enterobacter spp. were: cefepime, NA/1/19; ceftazidime, 30/29/30; ceftriaxone, NA/30/36; ciprofloxacin, 3/3/15; gentamicin,18/0/0; imipenem, 0/0/5; and piperacilllin-tazobactam, NA/27/27. In conclusion, the species-related SRGA breakpoints detected Gram-negative isolates with decreased susceptibility in comparison with the native population with higher frequency than did the NCCLS breakpoints. The BSAC breakpoints for susceptible organisms were similar to NCCLS for ciprofloxacin and imipenem, and similar to SRGA for ceftazidime but lower than both NCCLS and SRGA for gentamicin, causing a much higher frequency of decreased susceptibility to gentamicin.

Anti-Bacterial Agents↗

Quantitation of antibiotic effects on bacteria by bioluminescence, viable counting and quantal analysis.

Discrepant results are obtained when antibiotic-induced bacterial killing is quantitated by viable counting or bioluminescence assay of intracellular ATP. In this study the killing of bacteria exposed to amikacin or imipenem was quantitated by viable counting and bioluminescence assay of intracellular ATP and also by quantal analysis. The results of quantal analysis and viable counting agreed very well, whereas a much lower degree of bacterial killing was recorded by bioluminescence.

Amikacin↗

Frequencies of subpopulations of aminoglycoside- and vancomycin-resistant variants in Staphylococcus aureus and Staphylococcus epidermidis.

Selection and regrowth of resistant variants, which are present in low frequencies in the initial inoculum, were seen when large inocula of five strains of Staphylococcus aureus and four strains of Staphylococcus epidermidis were incubated in broth with amikacin, gentamicin, netilmicin and tobramycin. Statistical analysis showed no significant difference between the aminoglycosides in the selective growth of resistant variants (P > 0.5). Vancomycin differed significantly from the aminoglycosides in both the frequency of, and selection of resistant variants (P < 0.001). No bacteria resistant to > 1 x MIC was seen in the vancomycin-exposed cultures of S. aureus and S. epidermidis, while in most aminoglycoside-exposed cultures, bacteria resistant to 4-16 x MIC were seen.

Aminoglycosides↗

A new diagnostic approach to the patient with severe pneumonia.

36 patients with severe community-acquired pneumonia, treated in an intensive care unit (ICU), were examined in a prospective study using a comprehensive diagnostic program to establish an early etiological diagnosis. The resulting prompt and adequate antimicrobial therapy may have decreased the number of fatal cases. Special emphasis was placed on the use of a method incorporating fiberoptic bronchoscopy, together with protected brush sampling and bronchial lavage. An etiological diagnosis was established in 81% (29/36) of the cases. This etiological diagnosis was established within 48-72 h in 53% (19/36) of the patients, S. pneumoniae being the most frequent agent found (12 patients). This information, however, was poorly utilized since in only 11/19 of these patients was the antimicrobial therapy changed from a broad-spectrum antibiotic to a more specific narrow spectrum agent. The overall mortality rate was 22% (8/36). 7/8 patients who died had compromising factors. Most deaths in community-acquired pneumonia are still associated with pneumococcal infection. We conclude that fiberoptic bronchoscopy with brush samples via a plugged double lumen catheter provides the least misleading information concerning the etiological agent in pneumonia; sampling should be done as soon as possible after admission to the hospital, ideally before the need for ICU treatment; factors other than prompt antimicrobial therapy may influence the outcome of severe community-acquired pneumonia.

Adult↗

Postantibiotic effect of aminoglycosides on gram-negative bacteria evaluated by a new method.

The in-vitro postantibiotic effect (PAE) of amikacin, gentamicin, netilmicin and tobramycin was investigated by a bioluminescent assay of bacterial ATP. Two strains each of Escherichia coli and Pseudomonas aeruginosa were exposed for 1 h to different concentrations of the aminoglycosides. The aminoglycoside was removed by a 10(-3) dilution, and regrowth of bacteria was followed at hourly intervals by monitoring bacterial ATP. This method simplified the PAE studies and made such studies possible at high aminoglycoside concentrations. The length of the PAE was dose-dependent for all the aminoglycosides studied. The PAEs ranged between three and seven hours for all four strains at the aminoglycoside concentrations normally reached in serum during standard dosing. The long PAE of aminoglycosides, especially after exposure to high drug concentrations, constitutes an argument in favour of administering aminoglycosides in higher-than-usual doses with longer intervals between doses. This proposal is also supported by recent pharmacokinetic, bacteriological and toxicity data.

Adenosine Triphosphate↗

A study of amikacin given once versus twice daily in serious infections.

Forty-five mostly elderly patients with serious infections were treated in a prospective, comparative and randomized pharmacokinetic study with amikacin 11.0 or 15.0 mg/kg administered in a single daily dose as an intravenous, short-term infusion or with amikacin 7.5 mg/kg administered twice daily in the same way. The results indicate that administration of amikacin 15 mg/kg in a single daily dose should be a practical and safe principle of administration. However elderly patients often have reduced creatinine clearance and should preferably be given a lower dose of 11 mg/kg bw. The risk of nephrotoxicity did not increase, but conclusions on ototoxicity and clinical efficacy cannot be drawn from this limited study. This should be considered as an initial part of a future multicentre trial.

Aged↗

Frequencies of variants resistant to different aminoglycosides in Pseudomonas aeruginosa.

The MICs of aminoglycosides for Pseudomonas aeruginosa are higher than those for Enterobacteriaceae and the number of variants resistant to high concentrations of aminoglycosides is greater in P. aeruginosa than in Escherichia coli. However, when the frequencies of resistant variants at different multiples of the MIC were calculated, these frequencies were similar in P. aeruginosa and E. coli. When large inocula of strains of P. aeruginosa, which were classified as sensitive in conventional MIC determinations, were incubated with amikacin, gentamicin, netilmicin or tobramycin at the break-point concentrations between sensitivity and resistance, 82%, 90%, 90% and 15%, respectively, of the strains regrew. The corresponding percentages for Enterobacteriaceae were much lower. The clinical relevance of this pronounced regrowth of P. aeruginosa is discussed.

Aminoglycosides↗

Selective growth of resistant variants during incubation of Enterobacteriaceae with four aminoglycosides.

The selective growth of resistant variants, present at low frequencies, varied with different strains of Enterobacteriaceae and different aminoglycosides. This phenomenon was more pronounced during incubation with amikacin than with gentamicin, netilmicin and tobramycin. Selective growth of the resistant variants resulted in an inoculum effect and an increase in MIC with longer incubation. In-vitro evaluation of this phenomenon may be justified when choosing an aminoglycoside for therapy.

Adenosine Triphosphate↗

Subclinical rubella reinfection in vaccinated women with rubella-specific IgM response during pregnancy and transmission of virus to the fetus.

This report concerns 2 cases of documented rubella reinfection during pregnancy in previously vaccinated women. The antibody response at reinfection comprised not only anti-rubella IgG but also IgM. In the first case the reinfection occurred between the 13th and 19th week of pregnancy and was followed by transmission of virus to the fetus (anti-rubella IgM in cord blood and persisting antibody activity). The child had no clinical signs of congenital rubella and is normally developed without hearing impairment at 41/2 years of age. In the second case the reinfection resulted from exposure in the 15th week of pregnancy; there were neither serological nor clinical signs of congenital rubella in the child. The reported case of fetal infection in spite of previous rubella vaccination of the mother does not discourage the use of rubella vaccine. Rubella vaccine induces long lasting immunity and protection from viremia in the vast majority of individuals.

Adult↗

Regrowth of aminoglycoside-resistant variants and its possible implication for determination of MICs.

Regrowth of aminoglycoside-resistant variants was seen when large inocula of two strains of Escherichia coli were incubated with gentamicin in concentrations well above their MICs (0.5 micrograms/ml). The extent of the selection of resistant variants was proportional to the concentration of gentamicin during incubation; after incubation with gentamicin (greater than or equal to 2 micrograms/ml for 24 h), all bacteria were resistant to at least 8 micrograms/ml. Bacteria resistant to these concentrations always formed small colonies, whereas variants resistant to lower concentrations (1 to 2 micrograms/ml) could form both small and normal colonies. The regrowth of resistant variants could be monitored by luciferase assay of intracellular ATP in cultures incubated with gentamicin (less than or equal to 2 micrograms/ml). In cultures incubated with higher concentrations, regrowth did occur, although this did not result in viability (CFU per milliliter) or ATP levels above those of the initial inocula. The implications of this regrowth for MIC determinations in broth and the possible clinical revelance of the resistant variants are discussed.

Aminoglycosides↗

Restimulation of PPD-stimulated lymphocytes: decreased responsiveness of prestimulated cells to a second challenge with PPD and PHA.

Lymphocytes stimulated with purified protein derivative (PPD) were inhibited in their response to a second stimulation with PPD or phytohaemagglutinin (PHA). The degree of inhibition was related to the PPD concentration during prestimulation, the dose-response curve for inhibition resembling very much that of stimulation. The decreased reactivity was neither due to a toxic effect of PPD nor to altered proliferation kinetics of the prestimulated cells. Lymphocytes preincubated for 6 h or 16 days with PPD were equally refractory, and the non-reactivity persisted even if the cells were incubated without stimulant for 1 week or more. The prestimulated cells were able to suppress the PHA stimulation of fresh lymphocytes. These results indicate that the decreased reactivity of the prestimulated lymphocytes is due to the action of suppressor lymphocytes, generated during the primary stimulation.

Cell Division↗

Suppressor cells induced by purified protein derivative of tuberculin (PPD): the suppression is mediated by cells that proliferate in response to stimulation with PPD.

Lymphocytes stimulated with purified protein derivative of tuberculin (PPD) were found to inhibit the PPD stimulation of fresh, autologous lymphocytes. This suppressor effect was exerted after preincubation with both high and low concentrations of PPD. Optimal suppression occurred after preincubation with PPD in concentrations of 5 micrograms/ml and higher, the same concentrations that gave optimal stimulation of DNA synthetsis in primary cultures. The suppressor effect was abolished completely by 'hot pulse' treatment and partly by treatment with colchicine during PPD preincubation, showing that the PPD-induced suppressr cells are generated by cell division. When fresh lymphocytes were incubated together with PPD-pretreated cells in cultures that were not stimulated with PPD, the PPD-stimulated lymphocytes exerted a stimulatory effect on the fresh lymphocytes. This effect was maximal for cells preincubated for 1 h with PPD, decreasing with increasing duration of preincubation with PPD. Possible explanations of this observation are discussed.

Cell Division↗

Mitogen stimulation and distribution of T- and B-lymphocytes during natural rubella infection.

The phytohaemagglutinin (PHA) response of lymphocytes from seven patients with natural rubella infection was investigated during the acute, early and late convalescence stages of disease. When the lymphocytes were cultured in autologous serum, a moderate depression of the response, following stimulation with PHA in both optimal and suboptimal concentrations was obtained two weeks after the onset of exanthema (early convalescence). Two months later (late convalescence), the lymphocyte stimulation response had returned to almost normal values. On the other hand, lymphocytes incubated in pooled homologous serum reacted normally to PHA in optimal concentrations at all three stages. Determination of T- and B-lymphocytes did not reveal any change in the relative proportion of T-lymphocytes during the course of the disease. However, in late convalescence, a significant decrease in the relative number of B-lymphocytes was recorded.

Adolescent↗

Brief report. In vitro effects of Rubella virus, strain RA 27/3, on human lymphocytes. III. Inhibition of mitogen stimulation transferred by supernatants from virus-infected cultures.

When lymphocytes from humans with serological immunity against rubella were incubated with live rubella virus, supernatants were obtained which when added to non-infected lymphocytes gave a significant inhibition of phytohaemagglutinin (PHA)-induced proliferation. In contrast, supernatants from virus-infected lymphocytes from donors lacking immunity against rubella gave no inhibition of the PHA response.

Cells, Cultured↗