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[Antibiotic resistance of anaerobic bacteria (author's transl)].

Reference data on the overall resistance patterns of anaerobic bacteria are needed since in individual clinical cases susceptibility testing is complicated by the long generation time and difficulties of test conditions. Benzylpenicillin and tetracyclines are the drugs of choice against Clostridium perfringens. Newer cephalosporins are also active, whereas other Clostridium species have been found resistant. Beta-lactam antibiotics show high activity against Peptococcaceae; resistance to clindamycin should be noted, however. The good in vitro activity of tetracyclines, clindamycin and erythromycin against Propionibacterium acnes could be confirmed in the systemic and local therapy of acne vulgaris. In contrast to gram-positive anaerobic bacteria, only some penicillin and cephalosporin derivatives are sufficiently active against gram-negative rods of the Bacteroides group. Sporadic resistance is seen to the newer tetrayclines, nitroimidazole compounds and to lincomycins. Nevertheless, these substances must be considered as standard therapeutics for infections caused by anaerobic gram-negative bacteria. It should be mentioned that cefoxitin may offer new therapeutic possibilities.

Actinomyces↗

In vitro-activity of clavulanic acid and amoxicillin combined against amoxicillin-resistant bacteria.

The ability of clavulanic acid to inactivate beta-lactamase was investigated using 47 amoxicillin-resistant bacteria. In the presence of 10 mg/l clavulanic acid most strains of staphylococci, Escherichia coli, Klebsiella and Proteus mirabilis became fully amoxicillin-sensitive. This effect of clavulanic acid was in most instances not observed with Serratia marcescens, Proteus inconstans, Pseudomonas aeruginosa, Enterobacter and indole-positive Proteus species.

Amoxicillin↗

In vitro and in vivo inhibition of lectin mediated adhesion of Pseudomonas aeruginosa by receptor blocking carbohydrates.

In vitro and in vivo experiments with Balb/c mice and Pseudomonas aeruginosa ATCC 27853 supported our hypothesis that bacterial lectins play an important role in the organotropy of infectious diseases. In vitro and in vivo adhesion of P. aeruginosa was mediated by N-acetylneuraminic acid (NANA) receptors. Blocking of the binding sites (lectins) on the bacterial surfaces with competitive specific carbohydrates (NANA) completely prevented the bacterial adhesion process in vitro. In vivo the number of adherent organisms in various organs decreased dramatically in the presence of NANA, whereas non-related carbohydrates (e.g. D-galactose) just showed negligible effects. Additionally, the application of NANA-treated organisms protected the animals from septicemia and death. Therefore, blocking of bacterial lectin receptors with specific carbohydrates might be of clinical relevance to prevent bacterial attachment to organ cells.

Animals↗

Chemiluminescence response of human polymorphonuclear and mononuclear phagocytic cells induced by Staphylococcus saprophyticus, lectinophagocytosis versus opsonophagocytosis.

Two strains of Staphylococcus saprophyticus with well characterized cell surface structures were studied to determine the contribution of lectinophagocytosis versus opsonophagocytosis exerted by human phagocytic cells from five healthy donors. The luminol specific chemiluminescence assay was used to evaluate the response of phagocytes. Human polymorphonuclear leukocytes (PMNL) were demonstrated to have surface lectin receptors, since the chemiluminescence response towards both S. saprophyticus strains was inhibited by lectin-specific glycoconjugates for those organisms. Phagocytosis of S. saprophyticus by mononuclear cells was not inhibited by microbial lectin-specific glycoconjugates but was inhibited by D-mannose, suggesting that human monocytes express D-mannose specific lectins on their surface.

Hemagglutination Tests↗

[Animal experiment studies on the modification of the immune system by ofloxacin].

Ofloxacin, one of the new group of quinolone antibiotics, was investigated with respect to its possible interactions with different parameters of the immune system. The study was performed in vivo on Balb/c-mice treated for seven days with different doses of the antibiotic and in vitro on human phagocytes from peripheral blood. It was found that ofloxacin does not affect cellular or humoral immune responses in mice. Moreover, human phagocytic cells exposed in vitro even to high concentrations of the drug did not show any significant changes in their function. On the other hand, it was observed that subinhibitory concentrations of ofloxacin induced an increased susceptibility of Staphylococcus aureus 511-Jena to the bactericidal activity of phagocytes.

Animals↗

The role of staphylococcal lectins in human granulocyte stimulation.

The anti-staphylococcal activity spectrum of human polymorphonuclear leucocytes (PMN) is widely ranged. Using chemiluminescence measurements, the opsonin-independent stimulation of PMNs from eight healthy humans towards two Staphylococcus saprophyticus strains (S 1 and S 35) was investigated. Strain S 1 was shown to have surface lectins with N-acetylgalactosamine specificity, whereas strain S 35 had N-acetyl-neuraminic acid specificity. Three different PMN-reaction patterns could be demonstrated: PMN stimulation was either sensitive to N-acetylgalactosamine-or N-acetylneuraminic acid-blocking, or resistant to both. These results point to the importance of lectins for staphylococcal-PMN interactions.

Acetylgalactosamine↗

Investigations on ofloxacin: antibacterial activity and influence on the immune system.

The in vitro activity of ofloxacin was tested against freshly isolated strains, from clinical material, of Pseudomonas aeruginosa, Staphylococcus aureus, and coagulase-negative staphylococci, including strains that were resistant to methicillin and/or novobiocin. 97% of the Pseudomonas strains were inhibited by ofloxacin concentrations in the range of 0.78 to 6.25 mg/l, with 55% of the strains being inhibited by concentrations up to 1.56 mg/l. All of the staphylococci strains, including those resistant to novobiocin and/or methicillin, were sensitive to ofloxacin in the range 0.19 to 1.56 mg/l. The influence of ofloxacin on cellular and humoral host immunity was evaluated both in vivo and in vitro. The influence of the compound on phagocytic activity of human polymorphonuclear leucocytes was evaluated by luminol-enhanced chemiluminescence. Ofloxacin did not influence cell-mediated immunity. It had no effect on chemotaxis. The use of sub-inhibitory concentrations of ofloxacin enhanced the phagocytic kill rate.

Animals↗

Effects of cefodizime and cefotaxime on cellular and humoral immune responses.

Cefodizime is a new cephalosporin antibiotic which has shown some remarkable immunomodulating activities. To mimic possible immunopharmacological effects of prolonged chemotherapy in vivo, we investigated the influence of a seven-day treatment with cefodizime on cellular and humoral parameters of the immune system in BALB/c mice. The dosages (0.4, 0.8 and 1.8 mg cefodizime per day) were calculated on a per kg bodyweight basis according to therapy recommendations for humans. Delayed type hypersensitivity (oxazolone test) as well as the production of IgM and IgG antibodies (direct and indirect plaque forming test) were investigated in BALB/c mice. Leukocyte and monocyte activities were measured using human cells. The results are discussed using cefotaxime as comparable reference drug.

Animals↗

Bacteremia due to Acinetobacter species other than Acinetobacter baumannii.

The objective of this study was to describe the clinical features, possible predisposing factors and treatment outcomes associated with bacteremia du to Acinetobacter species other than Acinetobacter baumannii. A review of laboratory and medical charts over a period of 18 months revealed 61 cases of bacteremia due to Acinetobacter species other than A. baumannii occurring in 59 patients. Six of these were considered not significant. Fifty cases represented catheter-related bacteremia, one case was associated with meningitis following brain surgery, and four cases could not be classified. Clinical courses wre usually benign: all but four patients were cured, but death was not related to Acinetobacter bacteremia in any case. Therapy included catheter removal alone (32.8%), appropriate antimicrobials alone (12.7%), or both (49.1%). Plasmid analysis showed distinct patterns in all strains isolated from different patients and did not reveal any epidemiological relationship among cases. Acinetobacter species other than A. baumannii are clinically significant organisms with limited pathogenic potential. They are almost exclusively involved in devise-related bacteremia. Clinical and epidemiological features of infections due to these organisms are clearly distinct from infections due to A. baumannii.

Acinetobacter↗

Inhibition of liver tumor cell colonization in two animal tumor models by lectin blocking with D-galactose or arabinogalactan.

Repeated administration of the hepatic lectin blocking agents D-galactose or arabinogalactan completely prevented the settling of metastatic cells of sarcoma L-1 tumor in the liver of Balb/c mice and greatly reduced the colonization process of highly metastatic ESb lymphoma cells of the liver of DBA/2 mice. Therefore, when hepatic lectins were blocked with competitive glycoconjugates, tumor cell colonization of the liver could be prevented in two different model systems.

Animals↗

Small-cell lung cancer and immunochemotherapy with Propionibacterium granulosum KP 45.

Seventy-nine patients with small-cell lung cancer were treated with vincristin, methotrexate, and cyclophosphamide in inductive therapy and with methotrexate, cyclophosphamide, and procarbazine in maintenance therapy. Patients were divided at random into two groups: one group received chemotherapy alone and the second group was additionally subjected to systemic immunotherapy with Propionibacterium granulosum strain KP-45. In general, differences in the frequency of therapy response and in duration of remission could not be stated between the two groups of patients, but patients responding to chemotherapy showed a significantly longer remission time and lower complication rates. This benificial effect of chemoimmunotherapy is not related to a direct antitumor activity of the immunomodifier used, but to the lowered risk of myelosuppression and infections. Immunomodulation in combination with chemo- and/or radiotherapy can be recommended for the treatment of small-cell lung cancer.

Adult↗

Prevention of experimental liver metastases by D-galactose.

The metastasis of malignant tumors from a primary site to near and distant secondary sites is probably the most important event in the pathogenesis of cancer and it accounts for most cancer deaths. Whereas advances in the treatment of primary cancer have led to increased patient survival, metastatic cancers are still the most difficult group of diseases to treat successfully. As organ-characteristic lectins play an important role in the organ manifestation of metastatic islets, it might be possible (e.g. during surgical operations on malignant tumors) to block those organ-characteristic lectins with the appropriate receptor-bearing glycoconjugates in order to inhibit the metastatic spread. Recent experiments have demonstrated that neuraminidase treatment of tumor cells (mouse sarcoma-1) alters in vivo (Balb/c-mice) the organotropic distribution of metastases; instead of being found exclusively in the lung, they are found both in lung and liver. However, pre-injection and regular application of D-galactose--the same holds for arabinogalactan--prevents the setting of metastases in the liver but does not influence the metastatic process to the lung, whereas mannan--as a galactose-free control substance--does not alter the initial pattern of metastasis to lung and liver.

Animals↗

Hepatocellular injury inhibits lectin-mediated tumor colonization into BALB/c-mice livers.

Acute (hepatitis) and chronic (cirrhosis) liver injuries were experimentally induced in BALB/c-mice by administration of D-galactosamine and carbon tetrachloride, respectively. In both experimental liver diseases the incidence of hepatic tumor colonization of sarcoma L-1 was significantly reduced as compared to non-treated control animals. Thus, it seems that either dysfunction or loss of organ-characteristic lectins (galactosyl-specific hepatic lectins) prevented liver colonization. Histochemical staining of liver sections from D-galactosamine or carbon tetrachloride-treated mice with appropriate galactose-containing (neo)glycoproteins supported this hypothesis, since the lectin-dependent binding was greatly reduced as compared to sections from non-treated animals.

Animals↗

Typing of coagulase-negative staphylococci isolated from foreign body infections.

Twenty-six coagulase-negative staphylococci isolated from patients with various foreign body infections were characterised using different typing systems. Staphylococcus epidermidis was the most predominant species found. Phage typability was below 50% in all strains. The strains showed differences in surface properties--relative hydrophobicity or hydrophilicity--and ability to adhere to polystyrene with subsequent slime production (adherence tube test). Protein and polypeptide profiles as well as plasmid profiles demonstrated the heterogeneity of the strains. Thus, this preliminary study indicates that all coagulase-negative staphylococci of human origin may become involved in foreign body infections.

Bacterial Adhesion↗

Blocking of lectin-like adhesion molecules on pulmonary cells inhibits lung sarcoma L-1 colonization in BALB/c-mice.

Adhesion and inhibition experiments with pulmonary cells of BALB/c-mouse origin and syngeneic sarcoma L-1 cells indicated that L-fucose specific lectin-like adhesion molecules, presumably situated on pulmonary cell surfaces are (at least partly) responsible for the specificity of this cell-cell interaction. Addition of specific sugars and glycoconjugates (L-fucose and fucoidan, respectively) to the incubation medium evidently inhibited the adhesion process as quantified using radiolabelled tumor cells. Unspecific carbohydrates (e.g. D-galactose) did not affect the cellular interaction. In vivo, repeated administration of fucoidan (but not of unspecific glycoconjugates) significantly inhibited the settling of metastatic sarcoma L-1 cells in the lungs of BALB/c-mice. Therefore, when lectin-like adhesion molecules on pulmonary cells were blocked with competitive glycoconjugates, tumor cell colonization of the lung could be significantly inhibited.

Animals↗

Lectin-mediated bacterial adhesion to human tissue.

In vitro experiments with frozen sections of human lung and kidney demonstrated that adhesion of Streptococcus pneumoniae Pn 629 Type 14 and Pseudomonas aeruginosa ATCC 27853 to human cells was mediated by bacterial lectins (adhesins) with N-acetyl-D-glucosamine/D-galactose or N-acetyl-neuraminic acid specificity. Blocking of the lectin binding sites on bacterial surfaces with competitive carbohydrates completely prevented the bacterial adherence, whereas non-specific carbohydrates (D-mannose, D-xylose) did not inhibit adherence.

Acetylglucosamine↗

Enterotoxigenicity of Staphylococcus aureus strains from clinical isolates.

The enterotoxigenicity of 208 strains of Staphylococcus aureus isolated from clinical specimens and four strains isolated from food was investigated. All strains were examined for production of enterotoxins A, B, C, D, and E in cellophane-over-agar cultures using a modified optimum-sensitivity-plate method. Strains from systemic infections were also examined for production of toxic-shock toxin. The overall frequency of enterotoxigenic strains among the clinical isolates was 42%. Enterotoxin A was the predominant enterotoxin found among positive strains (45/88). Enterotoxins B to E were found in decreasing order of frequency. Twenty-three strains produced two enterotoxins and one strain three toxins. A significant association was observed between multi-resistance of strains (defined as resistance against penicillin and at least two other antibiotics) and enterotoxin B production. Strains from phage groups I and III produced predominantly enterotoxin A. Four of the five strains producing toxic shock toxin belonged to phage group I; one was not classifiable.

Bacteriophage Typing↗