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Biomedical subjects

S E Holm

Publications and source records attributed to S E Holm.

At least 19 recordsLinked to original sources
PubMed1992

Resistance to erythromycin in group A streptococci.

BACKGROUND: The use of erythromycin in Finland nearly tripled from 1979 to 1989. In 1988, we observed an unusually high frequency of resistance to erythromycin in group A streptococci in one geographic region. Because routine testing does not detect the sensitivity of these organisms to antibiotics, we initiated a national study to evaluate the extent of this resistance. METHODS: We studied 272 isolates of group A streptococci obtained from blood cultures from 1988 through 1990. In 1990 we collected from six regional laboratories 3087 consecutive isolates from throat swabs and 1349 isolates from pus samples. Resistance was indicated by growth on blood agar containing 2 micrograms of erythromycin per milliliter after incubation in 5 percent carbon dioxide. We also evaluated the clinical importance of erythromycin resistance in a retrospective study of consecutive patients with pharyngitis. RESULTS: The frequency of resistance to erythromycin in group A streptococci from blood cultures increased from 4 percent in 1988 to 24 percent in 1990. From January to December 1990, the frequency of resistance in isolates from throat swabs increased from 7 percent to 20 percent, and resistance in isolates from pus increased from 11 percent to 31 percent. In four communities within 50 km of each other, the frequency of erythromycin resistance ranged from 2 to 5 percent to 26 to 44 percent. Several distinct DNA restriction profiles and serotypes were found among resistant isolates from the same area, suggesting a multiclonal origin. The treatment of pharyngitis with erythromycin failed in 9 of 19 patients infected with erythromycin-resistant group A streptococci, as compared with 1 of 26 patients with erythromycin-susceptible isolates (47 percent vs. 4 percent, P = 0.008). CONCLUSIONS: In Finland since 1988 there has been a rapid and substantial increase in resistance to erythromycin in group A streptococci. The extent of this resistance is particularly serious since there are only a few alternative antibiotics available for peroral treatment of group A streptococcal infections.

Blood↗
PubMed1992

Virulence properties of erysipelas-associated group A streptococci.

Group A streptococcal isolates (n = 53) recovered from 38 erysipelas patients in 1988 and 1990 in Sweden were analysed with respect to serotype, erythrogenic toxin production and polymorphism in the emm gene region. Serotype determination showed a dominance of type T1M1 (28.6% of the strains), but T type 8 was also prevalent (14.3%). In the majority of the strains only a low production of erythrogenic toxin A was demonstrated, while both toxin B and C production were high. Polymorphism was detected in the emm gene region of T1M1 strains at a frequency of 64%. These erysipelas associated group A streptococci were more heterogenic with respect to serotype distribution and polymorphism in the emm gene region compared to previously studied group A streptococci isolated during an outbreak of serious streptococcal infections in Sweden in 1988/1989. The material included isolates from two cases of recurrence, and typing of the isolates indicated that the patients had been infected by the same serotype as in the primary infection.

Adult↗
PubMed1992

Aspects of pathogenesis of serious group A streptococcal infections in Sweden, 1988-1989.

Serotypes of serious, sometimes fatal, streptococcal infections in Sweden during 1988-1989 were analyzed. The T1M1 type totally dominated, representing almost 70% of all group A streptococci from serious and uncomplicated infections at the peak of the outbreak. Immunoblots of isolates from various patient groups showed that all isolates produced high amounts of erythrogenic toxin (ET) B and high amounts of ET-C, whereas ET-A was released only in small amounts and from few isolates. ELISAs showed high antibody levels to these toxins and to the M1 antigen in patients with uncomplicated infections. Low antibody levels against M1 were seen in patients with bacteremia and in fatal cases; the latter also had low antibody levels against ET-B. It seems likely that a combination of production of large amounts of toxin and low antibody titers to it and to the M antigen of the infecting isolate are determining factors for the outcome of the infection. No signs of primary immune deficiency were noted.

Adolescent↗
PubMed1992

Genetic diversity in T1M1 group A streptococci in relation to clinical outcome of infection.

Genetic diversity was found at high frequency downstream of the emm1 gene among T1M1 group A streptococci (GAS) isolated in Scandinavia during a recent epidemic. Clonal variation was also seen in the speA and speB genes but at much lower frequency; no variation was detected in the speC gene. Erythrogenic toxin A was found to be expressed at low levels in all strains; erythrogenic toxins B and C were produced in high amounts. All strains were found to harbor the speA, speB, and speC genes, regardless of the amount of toxin produced. No correlation was found between one specific T1M1 clone and the more serious infections when isolates from bacteremic patients (fatalities or survivors), those with uncomplicated infections, and healthy carriers were compared. Similar results were obtained in a family study in which 3 family members were found to be asymptomatic carriers of the same GAS T1M1 clone as in the bacteremic patient, defined by genotypic and phenotypic experiments.

Base Sequence↗
PubMed1992

Novel coagglutination method for serotyping group B streptococci.

A group G streptococcal strain was coated with antibody against six different serotypes (Ia, Ib, II, III, IV, and V) of group B streptococci. The coagglutination patterns of 114 strains of group B streptococci were compared with the serotypes determined after immunoprecipitation. The specificity of the method was 100% and the sensitivity 97%. It was used for the typing of 89 invasive and 101 colonizing isolates. The new method is swift, specific, and highly sensitive. It consumes only minute amounts of antibody.

Agglutination Tests↗
PubMed1992

Influence of phenoxymethylpenicillin on the vaginal ecosystem.

The effects of phenoxymethylpenicillin on the bacterial flora of the vagina were investigated in 6 women who fulfilled the criteria of 'normality': predominance of lactobacilli, and absence of Enterobacteriaceae and fungi. Fourteen healthy women were enrolled and followed longitudinally; 8 of these were subsequently excluded because of divergence from normality. Following penicillin treatment, Gram-negative rods appeared in 4 of the remaining 6 women, and in 1 subject heavy growth of Candida albicans resulted. In 5 of the women there was no change in the lactobacillus count and a rise in pH was found in 4 subjects. In 1 woman, lactobacilli disappeared completely and were replaced by Escherichia coli. Concomitantly, high concentrations of endotoxins were found in the vaginal fluid. Treatment with penicillin may interfere with the normal vaginal bacterial flora and provide an environment favorable for Enterobacteriaceae and fungi.

Administration, Oral↗
PubMed1991

Neutralizing effect of zinc oxide on dehydroabietic acid-induced toxicity on human polymorphonuclear leukocytes.

The cytotoxic effect of dehydroabietic acid (DHAA), a resin acid found in rosin, was studied on human polymorphonuclear leukocytes (PMN) using leakage of 51Cr from prelabeled cells, supravital staining, and transmission electron microscopy. DHAA caused a strong dose-related release of 51Cr, a high uptake of trypan blue, and total cell necrosis as seen in transmission electron microscopy. Albumin slightly reduced the toxic effects, whereas the addition of zinc in various forms strongly inhibited these toxic effects of DHAA in the concentration range 10-500 micrograms/mL. In the presence of albumin, zinc oxide as a suspension inhibited the damage of the cell membranes more than a filtrate of zinc oxide, indicating a subsequent slow release of zinc from the zinc oxide.

Abietanes↗
PubMed1991

Neutralizing effect of zinc oxide on dehydroabietic acid-induced toxicity on human polymorphonuclear leukocytes.

The cytotoxic effect of dehydroabietic acid (DHAA), a resin acid found in rosin, was studied on human polymorphonuclear leukocytes using leakage of 51Cr from prelabeled cells, supravital staining, and transmission electron microscopy. DHAA caused a strong dose-related release of 51Cr, a high uptake of trypan blue, and total cell necrosis, as seen in transmission electron microscopy. Albumin slightly reduced the toxic effects, whereas the addition of zinc in various forms strongly inhibited these toxic effects of DHAA in the concentration range of 10-500 micrograms/mL. In the presence of albumin, zinc oxide as a suspension inhibited the damage of the cell membranes more than a filtrate of zinc oxide, indicating a subsequent slow release of zinc from the zinc oxide.

Abietanes↗
PubMed1991

Beta-lactamase production and bacterial tolerance in recurrent acute otitis media.

Different reasons for treatment failure or relapse of acute otitis media (AOM) have been suggested. In this study 38 children (8 treatment failures, 13 relapses of AOM within one month and 17 with a new AOM) were compared to 25 matching healthy children, regarding beta-lactamase producing bacteria and tolerance to penicillin V and ampicillin. Branhamella catarrhalis was the most common bacteria found in the nasopharynx and was isolated in 60% of children with AOM and in 48% of the control group. Fifty-two percent of the children classified as treatment failure or relapse of AOM had aerobic beta-lactamase producing bacteria in NPH. No bacteria tolerant to penicillin or ampicillin were found. Thus, beta-lactamase-producing bacteria seem to play a decisive role in treatment failure and relapse of AOM. On the other hand, tolerance to penicillin V or ampicillin does not seem to have any impact on healing of AOM.

Acute Disease↗
PubMed1990

Hypothesis on the pathogenesis of post-streptococcal glomerulonephritis based on recent clinical and experimental research.

The current theories on the pathogenesis of post streptococcal glomerulonephritis are reviewed. Clinical findings during the last decades have indicated the involvement of an immune mechanism. However, the lack of adequate animal models has hampered a thorough understanding of the development of the disease from the initiating infection to the final glomerulonephritic sequelae. Several facts point to the presence of a special nephritogenic streptococcal factor which is directly or indirectly involved in the pathogenesis. There seems to be a plasminogen activator (PA) with unique properties. Data on animals experiments using streptococci producing this factor as well as on injections of the pure substance are presented and correlated to the finding in post streptococcal glomerulonephritis in man.

Animals↗
PubMed1990

Demonstration and characterization of buoyant-density subpopulations of group B Streptococcus type III.

Group B Streptococcus (GBS) type III (18 strains) was investigated for the presence of buoyant-density subpopulations; 10 strains originated from invasive isolates causing early-onset septicemia, and 8 were colonizing isolates from pregnant women. By repeated processing in hypotonic density gradients of Percoll, high- (HD) and low-density (LD) subpopulations were recovered from all strains. Synthesis of type-specific polysaccharide (TPS) was increased in the invasive isolates and their respective LD variants compared with the colonizing strains and their LD subpopulations. Production of capsular TPS correlated directly with synthesis of soluble TPS; there was an inverse exponential relationship between soluble TPS production and buoyant density. LD variants were more resistant to phagocytic killing by human polymorphonuclear leukocytes (PMNL) than were the original strains and HD variants. In a luminol-enhanced chemoluminescence assay, LD variants elicited a weak, slow response. In contrast, the HD subpopulations evoked a prompt, strong respiratory burst in the PMNL.

Centrifugation, Density Gradient↗
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

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↗
PubMed1990

Accumulation of penicillin in vaginal fluid.

The excretion of phenoxymethylpenicillin in vaginal fluid was determined in five women after intake of a single dose of 1 g phenoxymethylpenicillin and in five women on a 10-day medication scheme with 1 g twice daily. After the single dose, there was a steady increase of penicillin in vaginal secretion during the following 3 hours. During the same period, the concentrations in serum and saliva peaked and started to decline. Fifteen hours after intake, vaginal fluid contained more than 1 mg/L, whereas no activity was found in serum or saliva. During the 10-day course of treatment, vaginal concentrations ranged between 2-3 mg/L. The drug was not eliminated from the vagina until the second day after ceasing medication. The accumulation and slow pharmacokinetics of phenoxymethylpenicillin in the vagina may be explained by the countercurrent vascular system supplying the internal genitalia and upper vagina. The effect of the high concentrations of penicillin on the vaginal microflora is discussed.

Adult↗